厚生労働科学研究費補助金
新興・再興感染症及び予防接種政策推進研究事業

性感染症に関する特定感染症予防指針に基づく対策の推進に関する研究（Ｈ27 − 新興行政 − 一般 − 001）

平成27年度
総括・分担研究報告書

研究代表者

荒川

創一

平成28
（2016）
年３月―５―厚生労働科学研究費補助金
新興・再興感染症及び予防接種政策推進研究事業「性感染症に関する特定感染症予防指針に基づく対策の推進に関する研究」
研究班班員名簿
研究代表者

荒川

創一

神戸大学大学院医学研究科
ワーク学分野地域社会医学健康科学講座

地域医療ネット

特命教授／泌尿器科／感染制御部長

研究分担者

砂川

富正

国立感染症研究所感染症疫学センター中瀨

克己

岡山大学医療教育統合開発センター GI
Mセンター部門

小森

貴

濵砂

良一

産業医科大学医学部泌尿器科余田敬子

東京女子医科大学東医療センター耳鼻咽喉科

准教授

三鴨

廣繁

愛知医科大学大学院医学研究科臨床感染症学

主任教授

川名

敬

東京大学大学院医学系研究科産婦人科学講座

准教授

白井

千香

日本医師会

第二室長
教授

常任理事

神戸市保健福祉局

准教授

医務担当部長／大阪市立大学大学院医学研究科

公衆衛生学

田中

一志

神戸大学大学院医学研究科外科系講座

伊藤

晴夫

千葉大学

腎泌尿器科学分野

特命教授

名誉教授

研究協力者

山岸

拓也

国立感染症研究所感染症疫学センター

主任研究官

有馬

雄三

国立感染症研究所感染症疫学センター

主任研究官

高橋

琢理

国立感染症研究所感染症疫学センター

研究員

加納

和彦

国立感染症研究所感染症疫学センター

研究員

石金

正裕

国立感染症研究所感染症疫学センター

実地疫学専門家養成コース

協力研究員

金井

瑞恵

国立感染症研究所感染症疫学センター

実地疫学専門家養成コース

協力研究員

加藤

博史

国立感染症研究所感染症疫学センター

実地疫学専門家養成コース

協力研究員

安藤

美恵

国立感染症研究所感染症疫学センター
協力研究員

大西

真

国立感染症研究所細菌第一部

部長

実地疫学専門家養成コース

谷畑

健生

神戸市東灘区保健福祉部

医務担当課長五十嵐辰男

千葉大学フロンティア医工学センター

出口隆

岐阜大学医学部附属病院泌尿器科

教授

安田

満

岐阜大学医学部附属病院泌尿器科

講師

金山

博臣

教授

徳島大学大学院医歯薬学研究部泌尿器科学分野

教授

高野つる代

横浜市旭区福祉保健センター

川畑拓也

大阪府立公衆衛生研究所感染症部ウイルス課

細井舞子

大阪市保健所中谷友樹

立命館大学文学部地理学教室

教授

尾本由美子

豊島区池袋保健所健康推進課

課長

樫原

摩紀

株式会社エスアールエル八王子ラボ感染免疫部感染症特殊検査課

金谷泰宏

国立保健医療科学院健康危機管理研究部

山岸由佳

愛知医科大学病院感染症科

萩原真生

愛知医科大学病院感染制御部

岩室紳也

ヘルスプロモーション推進センター〔オフィスいわむろ〕 代表

種部恭子

女性クリニック We!TOYAMA 院長／産婦人科

センター長
主任研究員

係員

部長

准教授

野々山未希子自治医科大学看護学部

渡會

睦子

東京医療保健大学医療保健学部看護学科

秋元義弘

岩手県立二戸病院

産婦人科長

武島

仁

龍ケ崎済生会病院

副院長／泌尿器科科長

渡部享宏

NPO法人子宮頸がんを考える市民の会 事務局長

吉田弘之

神戸大学医学部附属病院感染制御部

教授
准教授

目

次

Ⅰ．総括研究報告書
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性感染症に関する特定感染症予防指針に基づく対策の推進に関する研究 .
７
荒川

創一

Ⅱ．分担研究報告書
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１．感染症発生動向調査から見たわが国の性感染症の動向、２０１５年.
１３
砂川

富正・他

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２．性感染症に関する特定感染症予防指針に基づく対策の推進に関する研究 .
― センチネルサーベイランスの施行について ―
谷畑

健生・他

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）サーベイランスの評価と改善に関する研究 .
７７３．性感染症（STI
中瀨

克己・他

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１４０
４．My
c
o
p
l
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s
mag
e
n
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t
a
l
i
u
m検査法に関する研究 .
濵砂

良一

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１４８
５．口腔・咽頭梅毒および淋菌・クラミジアの咽頭感染に関する検討 .
余田

敬子

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１５９
６．HPV関連子宮頸癌早期スクリーニングの啓発に関する研究 .
三鴨

廣繁・他

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１６４
７．性感染症、特に HPVと子宮頸癌についての啓発に関する研究 .
川名

敬

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１７７
８．感染予防行動、早期受診促進のための性感染症啓発スライドについて .
白井

千香・他

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１８７
Ⅲ．研究成果の刊行に関する一覧表 .
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１９１
Ⅳ．研究成果の刊行物・別刷 .

Ⅰ．総括研究報告書

平成２７年度厚生労働科学研究費補助金
新興・再興感染症及び予防接種政策推進研究事業

性感染症に関する特定感染症予防指針に基づく対策の推進に関する研究【研究代表者】 荒川

創一 （神戸大学大学院医学研究科）

総括研究報告書であり、男女とも増加が著しかった。

１．感染症発生動向調査から見たわが国の性感染症の動向、2015年
発生動向調査から見た５類定点把握疾患の２．センチネルサーベイランスの結果について

２０１５年の動向については、概ね例年並みで調査年別性別感染症別に観察すると、２０１５あった。例年同様、男女共に、性器クラミジ

年は男性に淋菌感染症が多く、女性に性器クア感染症の報告数が最も多かった。また、淋

ラミジア感染症、性器ヘルペスが非常に多菌感染症を除いて、男性と比べて女性症例のかった。性器クラミジアの感染が女性に極め

年齢分布の方が若かった。性器クラミジア感て多く目立った。また２０１２年より梅毒、淋菌染症の定点当たり報告数は、概ね横ばいで感染症、性器クラミジア感染症が増加した。

あった。性器ヘルペスウイルス感染症の定点調査年別性別年齢階級別感染症別に観察する

当たり報告数は、男女ともに概ね横ばいであと、各年とも男性では淋菌感染症及び性器クり、近年同様、女性の報告数が男性を若干上

ラミジア感染症とも２０～２４歳に多く、年次的回った。尖圭コンジローマの定点当たり報告に著増していた。同時に尖圭コンジローマも

数は、男性報告数が女性を上回る傾向が続い増加した。一方、女性での性器クラミジア感ており、男性においては微増した。淋菌感染

染症は１５～２９歳に非常に多く、年次ごとに増症の定点当たり報告数は、女性と比べ男性の加している。全体に女性性器クラミジア感染報告が例年通り多く、男女ともに低レベルで症は男性に比べて極めて多かった。また男性あった。より適切な性感染症発生動向把握、は淋菌感染症、性器クラミジア、女性は性器

若年者の人口減少を加味した指標、妊婦健診

クラミジア感染症、性器ヘルペスが全年齢階の結果を利用する仕組みづくり等がこれらの級で目立った。

疾患の動向を監視していくことにおいて重要
３．性感染症（STI）サーベイランスの評価とである。

改善に関する研究

梅毒は２０１１年以降急増しており、２０１５年は２，
６９２例（男 性１，
９３０、女 性７６２）で２０００年 以

わが国の性感染症（STI）に関するサーベ

降最多であった。２０１５年の人口１０万当たり報

イランスの改善を目的として本年度は以下の告数は全体で２．
１２、男性が３．
１３、女性が１．
１７研究を行った。まず、性感染症に関する特定―７―

感染症予防指針に基づく対策の現状把握とそ

４．Mycopl
asmagenitalium 検査法に関する研究の推進のために、１．「性感染症に関する特定感染症予防指針」への自治体の対応状況調査、

My
c
o
p
l
a
s
mag
e
n
i
t
a
l
i
u
m検出のための２つの２．地方自治体性感染症サーベイランス担当

検出法について、基礎的、臨床的研究を行っ者向け情報還元を行った。また、国の行う感た。旭化成ファーマ社のマイコプラズマ抗原

染症発生動向調査を補完する動向把握策等の検出キット「リボテストＲマイコプラズマ」

検討として、３．検査結果サーベイランスのを用いて M.g
e
n
i
t
a
l
i
u
m検出のための基礎的研試行と検討、４．STI
発生動向調査の報告情究 を 行 っ た。１７株 の M.g
e
n
i
t
a
l
i
u
mを 培 養 さ報の活用に関する検討を行った。

せた液体培地をそれぞれ段階希釈し、それぞ

その結果、梅毒を含めた性感染症のアウトれの希釈液を「リボテストＲマイコプラズマ」

ブレイクを１５自治体が把握し対応していた。

に滴下した。また、希釈液中の M.g
e
n
i
t
a
l
i
u
m

性感染症の報告は都市部に集中しており、病の DNAコピー数を r
e
a
l
t
i
me法にて測定し、原体サーベイランスや詳細データの共有を圏「リボテストＲマイコプラズマ」法の検出限域で進めると対策に有用と思われる。自治体

界を測定した。１７株中１６株が、その原液（希別（都道府県、保健所別）の情報が活用でき釈前）では「リボテストＲマイコプラズマ」

ると、自治体や医療機関での対策の推進に有は陽性を示した。しかし、１０倍希釈した液体用である。自治体を越えた発生動向の活用がでは陽性を示さず、「リボテストＲマイコプ

進まず、活用策が周知されていなかったり、ラズマ」の検出限界は４．
６×１０５コピー／㎖と高一部で利用に制約があることが理由ではない

く、臨床的には使用できない可能性が高い。

かと考えられた。中央感染症情報センターに集約されている報告データの利用要望があり、 ５．口腔・咽頭梅毒および淋菌・クラミジア
利用可能な範囲や許可等の手順の明確化が望の咽頭感染に関する検討まれる。自治体の施策担当者の担当年限は短口腔・咽頭梅毒と淋菌・クラミジアの咽頭く経験や知見の蓄積が十分でないと思われる。 感染について、今後の調査や対策を考察する
梅毒の増加を踏まえると、多発していない自目的で、前者は当科で経験した症例の臨床的治体向けの基本的な調査介入手順等の提供が特徴について後ろ向きに検討し、後者は当科必要である。梅毒は近年急増し、伝播経路とと研究協力施設において過去に実施した前向

して異性間性的接触が増加している。MSM

き研究の結果を比較検討した。

などの個別施策層に加え、対象者の特性の把

口腔・咽頭梅毒は、性器や皮膚に病変がな

握に基づく対策が必要でありパートナー健診

く口腔・咽頭の症状や病変が梅毒診断の契機の有用性が高まると考えられる。梅毒報告事になる場合が多かった。最近急激に患者数が項に現在含まれていない患者居住地情報を加増加している梅毒については、口腔・咽頭梅えることで、施策担当自治体が明確となり、毒の特徴を含めた情報を発信すること、現行自治体を越えた対策等の推進の基礎となる。

の梅毒発生届けに口腔咽頭梅毒の項目を追加することが望まれる。
特徴的な症状や所見に乏しい淋菌・クラミ―８―

ジアの咽頭感染については、性器と咽頭の同７．性感染症、特にHPVと子宮頸癌についての啓発に関する研究

日検査が保険で認められること、現行の感染症発生動向調査（STD定点）の調査票の項目

尖圭コンジローマの有無を層別化し、女性に「咽頭淋菌感染症」と「咽頭クラミジア感の子宮頸部における HPVタイプの分布を解染症」を別項目として加えることが望まれる。 析し、さらに尖圭コンジローマ不顕性感染の実態把握を行った。
６．HPV関連子宮頸癌早期スクリーニングの啓発に関する研究その結果、コンジローマの病変を認めない
女性でも、コンジローマタイプの不顕性感染

日本人健常女性２４０名における HPV
（h
u
ma
n

者が存在することが判明した。HPVタイピ）は、CSW（c
o
me
r
c
i
a
ls
e
x
p
a
p
i
l
l
o
ma v
i
r
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s

ングで検出されていることから、ウイルスを）では、非 CSW と比較して高率に HPV
wo
r
k
e
r

排出していると考えられ、新たな罹患者の感陽性であった（ p＜０．
００００１）。検討した対象

染源になりうる。尖圭コンジローマの実態把全体では HPV５２型が最多で、次いで５８型の握において、不顕性感染者の存在は無視でき順に多かった。non
CSW では５２型が多かっないと考えられた。

たが、CSW では５３型が多いもののハイリス
ク 型 全 体 が 万 遍 な く 検 出 さ れ た。特 に、

８．感染予防行動、早期受診促進のための性CSW では、複数のハイリスク型が同時に検

感染症啓発スライドについて出される率が高かった（ p＜０．
０１）。ローリス

スライド作成にあたって、中高生向け（特ク型 HPVのみが検出された症例は陽性者全に中学生）にわかるように以下の内容を盛り体の７．
６％であった。日本人健常女性におい込むことを考慮した。

ても高リスク型の HPV感染（保ウイルス）率①

は高く、子宮がん検診では細胞診に HPVスク
リーニング検査を併用することは臨床的意義

スライド一枚に示す情報は、できるだけ字数を少なくイラストや写真を活用する。

②

疾患については、無症状のもの、治るもの、生命の危険につながるものなどを説が高いと考えられた。
TM

を用いて、
An
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IHPV２８ d
e
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e
c
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i
o
nk
i
t
スワブ検体と尿検体を用いて検出された明する。
③

HPVジェノタイプの相同性を確認したとこ
ろ、全体の感度は６８．
４２％、特異度は９９．
８７％

性行動を分類し、性感染症がうつる行為とうつらない行為を明示する。

④

コンドームで予防できるものと必ずしもであった。細胞診と尿検体の検査で低い相同コンドームだけでは予防できないものを性を示した遺伝子型 HPVは単一もしくは複示す。

数の遺伝子型の HPVが同時に検出される場⑤

コンドームの使い方を詳しく説明する。

合でも検出率に影響はなかった。HPVスク

例えば、Q＆ A形式で中学生が間違いやリーニング検査において、尿検体は侵襲性が勘違いに気づくようにする。Yo
u
Tu
b
eに

低い検査であるが、尿検体による検査では感掲載されている動画を紹介する。

度が十分とは言えず、スクリーニング法とし⑥て使用するには注意する必要がある。

性に関するリスクのうち若年での妊娠に関するものは、今回のスライドでは具体

―９―

⑦

⑧

的な解説を除き、性感染症に焦点をあてる。

辰男・安田

HI
Vや性感染症にリスクのある状況は、

荒川創一：平成２５年７モデル県の性感染

性行動の相手との関係において、経済的症診療医療機関全数調査推計有病率と国優位、暴力、アルコール、薬物乱用など

立率感染症研究所の定点報告推計有病率の問題が考えられることを例示し、コンの比較～７県医療機関全数調査結果と定ドームを使えない関係性や、ドメスティッ

点調査報告結果の有病率はなぜ乖離した

クバイオレンスについても説明する。

のか？．日本性感染症学会誌 ２６（１），

医療機関への受診を促し、早期に検査治

１０９−１１６，２０１５．

療に結びつけるため、受診費用の概要を⑨

４

満・種部恭子・金山博臣・

荒川創一・井村裕夫（編）：第４版

提示する。

りやすい内科学

疾患の詳しい説明は、来年度以降の研究

Ⅰ髄膜炎菌感染症課題となる教師向けの資料に含める。

堂 ３９４−３９５，２０１４．

健康危機情報わか

グラム陰性球菌感染症
Ⅱ淋菌感染症．文光２．学会発表２．において、国・地方公共団体は性感染

１

荒川創一：性感染症を巡る最近の話題―症対策の基本であるコンドームの使用を強く様々な角度（排尿障害、……）から―．姫進めていく必要がある。一方で性感染症の感路皮膚科泌尿器科医会総会・講演会，２
０１５．

染源は明らかでないことも多いので，国民は２ 荒川創一：再び増加している性感染症

安全な環境にあるとは言えない危機的状況に（STI）の 現 状 と そ の 対 策．第 ６ 回 東 海あると考えられる。

研究会，２０１５．
STI
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3.
その他

仁・五十嵐

―１０―

なし

Ⅱ．分担研究報告書

感染症発生動向調査から見たわが国の性感染症の動向、
２０１５年【研究分担者】 砂川

富正 （国立感染症研究所感染症情報センター）【研究協力者】 山岸拓也 （国立感染症研究所感染症疫学センター）

砂川

富正 （同 上）有馬

雄三 （同 上）高橋琢理 （同 上）加納

和彦 （同 上）石金

正裕 （同 上）金井

瑞恵 （同 上）加藤博史 （同 上）安藤

美恵 （同 上）研究要旨
性感染症は近年国内での減少傾向が停滞、或は増加しており、その発生動向の把握と効果的な対策が重要である。対策の立案や評価に用いるための情報を提供するために、代表的な性感染症である性器クラミジア感染症、性器ヘルペスウイルス感染症、尖圭コンジ
ローマ、淋菌感染症及び梅毒について、２０００年以降の感染症発生動向調査の結果をまとめた。また、近年梅毒の報告が急増している為、梅毒の発生動向に注目した。
発生動向調査から見た５類定点把握疾患の２
０１５年の動向については、概ね例年並みであった。例年同様、男女共に、性器クラミジア感染症の報告数が最も多かった。また、淋
菌感染症を除いて、男性と比べて女性症例の年齢分布の方が若かった。性器クラミジア感
染症の定点当たり報告数は、概ね横ばいであった。性器ヘルペスウイルス感染症の定点当たり報告数は、男女ともに概ね横ばいであり、近年同様、女性の報告数が男性を若干上回った。尖圭コンジローマの定点当たり報告数は、男性報告数が女性を上回る傾向が続いており、男性においては微増した。淋菌感染症の定点当たり報告数は、女性と比べ男性の報告が例年通り多く、男女ともに低レベルであった。より適切な性感染症発生動向把握、若年者の人口減少を加味した指標、妊婦健診の結果を利用する仕組みづくり等がこれらの疾患の動向を監視していくことにおいて重要である。
梅毒は２
０１１年以降急増しており、２０１５年は２，６９２例（男性１，
９３０、女性７６２）で２０００年以
降最多であった。２０１５年の人口１０万当たり報告数は全体で２．
１２、男性が３．
１３、女性が１．
１７であり、男女とも増加が著しかった。２０１５年の病型別報告数は、無症候８３２例（３１％）、早期顕症Ⅰ期７８８例（２９％）、早期顕性Ⅱ期９６８例（３６％）、晩期顕症９１例（３％）、先天梅毒
１３例であり、２０１５年は男女ともに特に早期顕性が増加していた。性別は、男性では３５～３９―１３―歳の報告が最も多かった。２０１４年に引き続き幅広い年齢で増加しており、特に２０～４０歳代の増加が目立った。女性は２０～２４歳の報告が最も多く、２０１４年の倍以上の報告数であった。
感染経路は、男性では感染経路が報告されていた１，
７３９例（全体の９０％）でみると、１，７２２
例（９９％）が性的接触であり、内訳は同性間５８４例（性的接触による１，７２２例の中で３４％）、
異性間８３９例（同４９％）、異性間／同性間１２例（同１％）、性的接触の詳細不明２８７例（１７％）
であった。女性では感染経路が報告されていた６６７例（全体の８８％）の中で６６４例（９８％）
が性的接触であり、内訳は異性間５５４例（性的接触による６６４例の中で８３％）、同性間５例（同１％）、性的接触の詳細不明１０３例（同１６％）であった。２０１１年以降の梅毒急増、異性間性的接触による男性と若年女性での増加は緊急事態である。医療従事者や行政担当者の間で危機感を共有するために、それら関係者に対して梅毒増加について周知を図ること、
２０～４０歳代の男性と性交をする男性や２０歳代女性というハイリスク集団に対して梅毒増加と予防法について情報提供を行う、あるいは患者のパートナーに検査を進めるなどの対策
を、各関係者が行っていくことが急務である。

ており、その数は、保健所地域ごとに管内人

Ａ．研究目的口～７．
５万人までは０（ゼロ）、管内人口７．
５万

近年国内では淋菌感染症、性器クラミジア

人～では１＋（人口−７．
５万人）／１３万人とされ感染症など、いわゆる性感染症が減少してきている。また、梅毒は診断した医師が診断かているといわれているが、疾患や年齢によっら７日以内に報告することとされている。

ては増加に転じているものもあり１）梅毒等、性感染症対策の立案や評価に役立つ情報提顕著に増加しているものもある。これらの性供のために、感染症発生動向調査における性感染症対策をしていくうえで、その発生状況

感染症定点把握４疾患（性器クラミジア感染の把握が重要である。

症、性器ヘルペスウイルス、尖圭コンジロー

１９９９年４月に施行された「感染症の予防及マ、淋菌感染症）及び梅毒の動向を調べるこび感染症の患者に対する医療に関する法律」とにした。近年梅毒の急増を認めている為、（以下、感染症法）のもとで、性器クラミジ

梅毒を中心とした発生動向調査から見た性感ア感染症、性器ヘルペスウイルス感染症（以染症の動向について記述する。

下性器ヘルペス）、尖圭コンジローマ、淋菌感
染症は５類定点把握疾患として、梅毒は５類
全数把握疾患として、保健所を介して国に報Ｂ．研究方法告されることになった。定点把握４疾患は都感染症発生動向調査の１９８７～２０１５年の定点

道府県知事が定めた性感染症定点医療機関か把握４疾患と梅毒のデータ（２０１４年までのら毎月１回報告されている。性感染症定点医

データは感染症発生動向調査年報、２０１５年の療機関は、産婦人科、産科、産婦人科、性感データは２０１６年２月１０日現在の暫定報）と人染症を組み合わせた診療科名の診療科、泌尿

口動態統計（毎年１０月１日基準）を用いた。

器科、皮膚科を標榜する医療機関が指定されデータは国立感染症研究所において感染症―１４―

サーベイランスシステム（Na
t
i
o
n
a
lEp
i
d
e
mi
o
-

かった。また、例年同様、性器クラミジア感

l
o
g
i
c
a
l Su
r
v
e
i
l
l
a
n
c
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fI
n
f
e
c
t
i
o
u
s Di
s
e
a
s
e
:

染症の定点当たり報告数は、５月から１０月のNESID）から抽出し、同所内で解析をおこ

春～秋にかけて報告数が多い傾向が見られた。

なった。年齢群は５歳間隔とし、１０歳未満や性器クラミジア感染症の定点当たり報告数は、高齢者など、症例数が少ない年齢群は統合し男女ともに２００３年に減少に転じ、２０１１年以降た。なお、NESI
Dデータは今後各自治体の届

男性では概ね横ばい、女性では微減した。性出修正により変更される可能性がある。

器ヘルペスでは、男女ともに２００９年を最小に、横ばいの状況であった。尖圭コンジローマは、
近年女性は減少傾向だが、男性は２０１２以降微１．性感染症定点把握４疾患の動向
２０００年以降の性感染症定点把握４疾患の感染症発生動向調査の結果をまとめた。定点当増した。淋菌感染症は、男女ともに２００８年以降下がり止まった。

たり報告数の推移及び季節性、性別・年齢群
別定点当たり報告数の推移、定点数の推移、

２）性別・年齢群別定点当たり報告数推移（図２，３）

都道府県別定点数を調べた。

性器クラミジア感染症
２０１５年には、近年同様、男性と比べ女性の２．梅毒の動向
報告数の推移、人口１０万当たり報告数推移、

年齢分布の方が若く、男性は２５～２９歳、女性

年齢群別報告数推移、感染経路別報告数推移、は２０～２４歳の報告が最も多かった。１５～１９歳

年齢群別感染経路分布、都道府県別報告状況

では、男女共に２０１３年以降減少傾向であった。

を調べた。感染経路では性的接触を含む複数

性器ヘルペスの経路によるものを除いた。

２０１５年には、例年と変わらず、男性と比べ女性の年齢分布の方が若く、男性は３０代の報告が最も多いのに対して、女性は２０代が多倫理面への配慮
本研究で用いた感染症発生動向調査のデー

かった。また、定点当たり報告数は、女性のタには個人情報が含まれず、データ解析は国方が男性より多い傾向も近年と同様であった。

立感染症研究所内で行われ、倫理上の問題が尖圭コンジローマ発生する恐れはない。

２０１５年には、近年と同様に男性と比べ女性の年齢分布の方が若かった。男性は３０～３４歳

Ｃ．結の報告が最も多いのに対して、女性は２０～２４

果

歳の報告が最も多かった。男性は近年多くの

１．性感染症定点把握４疾患の動向

年齢群で微増しているが、女性は若干減少傾

１）定点当たり報告数推移（図１，２）

向である。１５～１９歳においては、男女共に発生動向調査から見た５類定点把握疾患の２０１３年以降微減した。

動向については、概ね例年並みであった。男

淋菌感染症

女ともに、例年通り性感染症の中では性器ク

２０１５年には、例年通り、男女ともに２０代のラミジア感染症の定点当たり報告数が最も多報告が最も多かった。また、定点当たり報告―１５―

数は、例年同様男性の方が高いが、近年男女（４％）であった。男性の早期顕症梅毒の報告

ともに横ばい・微減に転じている。

が増加し、特に１５歳～３４歳代が２０１４年より多かった。女性では無症候３２２例（４２％）、早期

３）性感染症定点医療機関数（図４，表１）

顕症Ⅰ期１１７例（１５％）、早期顕性Ⅱ期３０４例

２０１５年性感染症定点医療機関数の１２月平均（４０％）、晩期顕症１０例（１％）であった。女は９７７（１２月に報告された定点数も９７７）と過性の無症候症例は１０代～５０代の全ての年齢群

去よりも若干多く、その内訳は産婦人科（産で２０１４年よりも増加が見られたが、特に２０～科、婦人科、産婦人科の合計）４７７（４９％）、

２４歳代で約３倍（２０１４年：３３例、２０１５年：８９

泌尿器科４０４（４１％）、皮膚科８８（９％）、性例）の増加がみられた。また、早期顕症梅毒病科８（１％）であった。２０１５年１２月の定点も１５歳～４９歳代で増加しており、特に１５歳～

医療機関数を都道府県別にみると、産婦人科

２９歳代の増加が認められた。先天梅毒は２０１５系と泌尿器科との比率は岐阜県の３／９から年には男児４例、女児９例であった。

岡山県の１４／３まで幅広かった。
２）人口１０万当たり報告数の推移（図７）２０１５年の人口１０万当たり報告数は全体で２．梅毒の動向２．
１２、男性が３．
１３、女性が１．
１７であった。男

１）報告数推移（図５，６）
梅毒の総報告数は、２０００年以降減少してい女とも増加が著しかった。

たが、２００４年に増加に転じ、２００９～２０１０年の減少を挟んで再び増加し、２
０１５年は２，６９２例３）年齢群別報告数の推移（図８）で２０００年以降最も多かった。２０１１年以降の増

男性は４０～４４歳の報告が最も多く、２０１５年

加は男女ともに認められており、２０１５年は男は１５～６５歳の幅広い年齢で増加しており、特性では１，９３０例、女性では７６２例で、どちらもに３０～４０歳代の増加が目立った。女性は２０～

２０００年以降最も多かった。２０１５年の報告数で２４歳の報告が最も多かった。また、２０１５年も男女比（報告数の男性／女性）をみると、２．
５

２０１４年に引き続き１５～３４歳の年齢で増加してであり、過去４．
０前後で推移していたことをおり、特に２０代で２倍以上の増加があった。

踏 ま え る と、女 性 の 割 合 が 増 加 し て い る［２０１１年（３．
７）、２０１２年（３．
８）２０１３年（４．
２）、４）感染経路（図９，
１０）
男性では２
０１
５年の１，
９３０例の中で感染経路

２０１４年（３．
４）］ 。
２０１５年 の 病 型 別 報 告 数 は、無 症 候８３２例が報告されていた１７３９例（９０％）でみると、（３１％）、早期顕症Ⅰ期７８８例（２９％）、早期顕１，７２２例（９９％）が性的接触であり、内訳は

性Ⅱ期９６８例（３６％）、晩期顕症９１例（３％）、

同性間５８４例（性的接触による１，７２２例の中で先天梅毒１３例であった。２０１５年は早期顕性Ⅰ、 ３４％）、異性間８３９例（同４９％）、異性間／同性Ⅱ期の増加とともに、無症候の症例も増加が間１２例（同１％）、性的接触の詳細不明２８７例目立った。男女別にみると、男性では無症候（１７％）で あ っ た。感 染 経 路 不 明 は１９４例

５１０例（３１％）、早期顕症Ⅰ期６７１例（３５％）、（１０％）であった。３例が複数の感染経路を報早 期 顕 性 Ⅱ 期６６４例（３４％）、晩 期 顕 症８１例告していた。２０１１年以降、男性の同性間性的―１６―

性器クラミジア感染症は男女共に、依然と接触による感染が急増していたが、２０１５年はして最も多く報告される性感染症であった。

異性間性的接触による報告が増加した。
女性では２０１５年の感染経路が報告されてい２００９～２０１０年頃から減少が緩やかになり、概た６７７例（全体の８８％）の中で６６４例（９８％）

ね横ばいである。２０１３年には、１０歳代後半～

が性的接触であり、内訳は異性間５５４例（性的２０歳代前半等での微増が認められたが、その接触による６６４例の中で８３％）、同性間５例

後減少した。ただし、夏季にかけて報告数が（同 １ ％）、性 的 接 触 の 詳 細 不 明１０３例（同多い傾向が例年通り見られる為、季節的な啓１６％）であった。感染経路不明は８５例（全体発も検討する事が考えられる。性器ヘルペスの１１％）であった。また、複数の感染経路を及び淋菌感染症は、男女とも横ばいの状況で報告したものはなかった。２０１１年以降、女性あった。性器ヘルペスは、女性の方が男性よの異性間性的接触が急増していた。

り多い傾向が続いており、淋菌感染症におい

年齢群別にみると、男性ではこれまで同性ては、男性の方が多い傾向が続いていた。尖間性的接触による報告が異性間を上回ってい圭コンジローマは、２０１２以降、男性が微増したが２０１５年では異性間性的接触による感染がているのに対して、女性では概ね微減してい

同性間性的接触を上回り、特に２０歳代の増加る。２０１３年４月からヒトパピローマウイルスが著しかった。女性では１５歳～２０歳代の異性ワクチンの定期接種化による４価ワクチン接間性的接触による感染が多かった。

種の影響は今後尖圭コンジローマの報告数に

なお、感染経路の報告には確定以外に推定表れてくる可能性があり、特に若年者での動向を注意深く見ていく必要がある。その際は、が含まれていた。

若年者の人口減少を加味し、人口当たりの報告数でみていく必要がある。

５）都道府県別報告数（図１１）２０１５年の報告は東京都１０５５例、大阪府３２４

報告数の増減を考えるとき、現行の感染症

例、神奈川県１６５例、愛知県１２２例などであっ法のもとでの定点把握がどれだけ実態を反映た。２０１４年は東京都５０６例、大阪府２４０例、愛しているかが重要である。２０１１年２月に「性知県１１２例、神奈川県１０６例であった。２０１４年

感染症に関する特定感染症予防指針」が告示と比べ、東京都は２．
１倍、大阪府では１．
３倍、され、地方自治体での定点設定に各診療科の愛知県で１．
１倍、神奈川県では１．
６倍と、東京割合を反映させることや長期にわたって報告

都の報告が大きく増加していた。

実績のない医療機関についての見直しなどが求められた。その結果、２０１２年から２０１３年にＤ．考かけて、毎年１０を超す都道府県で性感染症定察点の変更が行われていた。今後も、地方自治体が地域で性感染症患者を多く診療している

１．性感染症定点把握４疾患の動向
例年同様、淋菌感染症を除いて、性器クラ医師や医療機関を把握し、より良い定点設定、ミジア感染症、性器ヘルペス、尖圭コンジ

或はその他の情報も用いた発生動向把握等にローマにおいては、女性症例の年齢分布の方

向けて地域医療機関や医師会と協議していくが若かった。

ことが期待される。

―１７―

感染症発生動向調査の結果を解釈する際にの間で梅毒が流行していると推定されていたは、いくつかの点に注意が必要である。まず、が、男女とも異性間性的接触の報告が急増し

性器クラミジア感染症、淋菌感染症は無症候ており、伝播の様相が変化している可能性がの症例が見逃されている可能性がある。両疾ある。

患とも咽頭感染が感染拡大の一つの原因とさ病期では、男女とも早期顕性Ⅰ、Ⅱ期と無れているが、本調査では把握が出来ない。ま症候が増加していた。早期顕性症例の増加はた、年齢群でみた定点当たり報告数の増減は

真の梅毒罹患率の増加を反映している可能性

各年齢群の人口構成を加味していないため、がある。無症候症例の増加は検査件数の動き

罹患率の評価は行えず、疾病負荷の概要の把を反映している可能性があるが、検査数、陽握にのみ有用である。罹患率の推移を検討す

性率の推移を把握していない為、発生動向調るためには、若年者人口の減少を加味し、若査では発見の契機が不明であり、原因は不明

年者だけでの解析、あるいは年齢調整が必要である。

である。また、定点当たり報告数は定点設定

年齢に関しては、男性では２０歳代から４０歳に大きく依存しているが、性感染症は居住地代が多く、女性では１５歳から２０歳代の増加が外のクリニックを受診することも多く、人口著しかった。米国でも２００１年から梅毒が増加

当たりで定められている定点は必ずしもそのしてきているが、流行の中心はＭＳＭで、年地域の住民の性感染症発生状況を反映してい齢は２０歳代である２）。欧州３，４）と日本では３０歳ない。更に、定点当たり報告数の診療科別内

代男性での梅毒増加が目立ち、ＭＳＭの年齢

訳は、都道府県によって大きく異なるので、分布あるいは自己申告の傾向が各地で異なる

都道府県別の比較等の解釈には制約が有る。

可能性がある。しかし、近年米国でも、女性

また、近年性感染症の郵送検査が普及してと先天梅毒の増加を認めており５）、若い女性

きており、その様な社会背景によって、検査・に増加がみられていることは緊急事態と捉え受診行動も影響を受けることが考えられる。

られる。

よって、感染症発生動向調査の年次推移等の男性の梅毒は感染経路が報告されたものの解釈については、注意が必要であり、その他

うち、２０１５年は３４％が同性間性的接触によるの調査や情報と合わせて解釈するのが重要でものであった。一方、異性間性的接触は約５あると考えられる。

割であった。２０１４年は同性間性的接触が約５割を占めており、異性間性的接触と同性間性

２．梅毒の動向

的接触の報告数において逆転現象が生じてい梅毒は２０１１年から男女ともに増加傾向である。異性間性的接触の動向を引き続き注意深

り、人口１０万当たりの報告数をみると、２０１３

く監視することが重要と考えられる。また、年までは男性での増加、２０１４年からは女性の引き続き MSMにおける伝播への注意が欠か増加が著しく、その傾向は加速度的である。

せないため、医療従事者や公衆衛生担当者は従来、感染経路として男性の同性間性的接触

男性梅毒患者を見た時には、多くが男性と性が多数を占めていたことから、男性と性交を交をする男性であることを意識し、丁寧なイ

する男性
（Me
nwh
oh
a
v
es
e
xwi
t
hme
n
:MSM）

ンタビューをもとに感染の可能性のあるパー―１８―

トナーへの医療の提供を図っていく必要があ

医療従事者や行政担当者の間で危機感を共有る。

するために、それら関係者に対して梅毒増加

検査方法に関しては、これまで行われてきについて周知を図ること、ハイリスク集団にた RPRカードテスト、凝集法、ガラス板法に対して梅毒増加と予防法について情報提供を代わり、自動化法（自動分析器による測定）

行う、あるいは患者のパートナーに検査を進を用いた測定値を採用する医療機関が増えつめるなどの対策を、各関係者が行っていくこ

つある。なお、ガラス板法、凝集法は検査とが急務である。

キットの国内流通最終ロットの使用期限が２０１４年１２月時点ですぎているため、信頼性に疑いが生じる。感染症発生動向調査では自動Ｅ．健康危機情報化法を用いた測定については、梅毒の正確な特になし

発生動向の把握のためには、多岐にわたる梅毒検査方法とその解釈を臨床医と行政担当者に適切に理解してもらうことが重要であり、届出基準の周知はその第一歩であると考えら

Ｆ．研究発表１．論文発表れた。

なし

小児の先天梅毒は２０１５年には１３例が報告された。先天梅毒の発生は、妊娠中の性感染対２．学会発表策の不備の表れとして重要である。男女とも

１

有馬雄三：国内外の梅毒の疫学的状況．

異性間性的接触による伝播が報告され、また、

日本性感染症学会第２８回学術大会．日本

女性の報告数が増加していることから、先天エイズ学会動向シンポジウム「梅毒を見梅毒に対する注意は欠かせない。妊婦の未受直す」．東京．２０１５年１２月．

診、妊娠中の感染の罹患率、適切な治療を受

２

金井瑞恵・有馬雄三・島田智恵・松井珠

け、治療効果判定がされているか、など先天乃・大石和徳：先天梅毒報告例の記述疫

梅毒の疫学情報の把握を行い、適切な対策を

学 ― 感染症発生動向調査（２０１１～２０１４

行っていく必要がある。また、児の母親の妊年）より．日本性感染症学会第２８回学術

娠前から妊娠中の梅毒感染・治療に関連する大会．東京．２０１５年１２月．

社会的背景についての情報も、先天梅毒の発生予防の為の対策立案に繋がる可能性もあり、検討すべきである。
梅毒の発生動向調査結果の解釈では過小評

Ｇ．知的所有権の所得状況
１．特許取得価の可能性を考える必要がある。梅毒は診断なし

した全症例の届出が法律で義務付けられているが、このことは全ての医師に周知されてい２．実用新案登録ない可能性がある。

なし

２０１１年以降の梅毒急増は緊急事態である。

―１９―

参考文献
１

岡部信彦・山岸拓也・多田有希：感染症
発生動向調査から見た我が国の性感染症の動向、２０１２年．性感染症に関する特定予防指針に基づく対策の推進に関する研究（研究代表者：荒川創一）平成２４年度
総括・分担研究報告書．２９−５５，２０１３．

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図１．性感染症定点把握４疾患の定点当たり報告数の月次推移、1987～ 2015年
男性

女性

2016年２月 10日現在―２１―

図２．性感染症定点把握４疾患の定点当たり報告数の年次推移、2000～ 2015年
男性

女性

―２２―

図３．性感染症定点把握４疾患の年齢群別定点当たり報告数の年次推移、2000～ 2015年
図３－１．性器クラミジア感染症
男性

女性

―２３―

図３－２．性器ヘルペスウイルス感染症
男性

女性

―２４―

図３－３．尖圭コンジローマ
男性

女性

―２５―

図３－４．淋菌感染症
男性

女性

―２６―

図４．性感染症定点医療機関数の年次推移、1999～ 2015年

1999～ 2013年は各月に報告のあった定点数の平均（切り捨て）で、2015年は 2015年 12月に報告された
定点数

―２７―

表１．診療科別・都道府県別 STD定点数、2015年 12月

都道府県
北海道
青森県
岩手県
宮城県
秋田県
山形県
福島県
茨城県
栃木県
群馬県
埼玉県
千葉県
東京都
神奈川県
新潟県
富山県
石川県
福井県
山梨県
長野県
岐阜県
静岡県
愛知県
三重県
滋賀県
京都府
大阪府
兵庫県
奈良県
和歌山県
鳥取県
島根県
岡山県
広島県
山口県
徳島県
香川県
愛媛県
高知県
福岡県
佐賀県
長崎県
熊本県
大分県
宮崎県
鹿児島県
沖縄県
総計

産婦人科
20
5
11
9
8
8
7
12
9
12
32
23
28
19
6
5
4
2
7
8
3
20
26
8
4
13
26
24
4
4
4
3
14
7
6
3
8
2
3
20
4
6
6
5
6
5
8
477

泌尿器科
19
7
4
8
6
2
8
7
7
11
21
11
20
33
6
4
5
3
2
4
9
9
33
5
5
4
26
21
5
2
3
3
3
15
4
3
7
6
3
13
3
4
10
3
4
10
3
404

皮膚科
2
1

3
1
1
3
9
6
6
3
1
1

性病科
1

1

2
3
2
6
4
6
10
1

4

2

1
2

3
4

1
2
1
1
88

1
1

8

総計
42
13
15
17
14
10
15
22
17
24
56
43
54
59
15
10
10
5
9
14
15
31
65
17
9
23
66
46
9
8
7
6
17
23
12
6
15
11
6
37
7
10
16
10
13
16
12
977
2016年１月 14日現在―２８―

図５．梅毒

報告数の推移、2000～ 2015年

2016年２月 10日現在

図６．梅毒

男女別報告数の推移、2004～ 2015年

男性

2016年２月 10日現在―２９―図６（続き）女性

2016年２月 10日現在

図７．人口 10万当たり報告数の推移、2001～ 2015年

2016年２月 10日現在の感染症発生動向調査と人口動態統計（毎年 10月１日基準）を使用―３０―

図８．梅毒の年齢群別報告数の推移、2006～ 2015年
男性

女性

2013年３月６日現在

2016年２月 10日現在―３１―

図９．梅毒の感染経路別報告数の推移、2006～ 2015年
男性

女性

2016年２月 10日現在―３２―

図１０．梅毒の年齢群別感染経路分布、2015年

2016年２月 10日現在

―３３―

―３４―

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



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ಧుਣ਩

2016年２月 10日現在

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図１１．梅毒の都道府県別・年別報告数、2013～ 2015年 （ｎ = 5581）

෭෼峼রੱ峒峁峉৅ে৿਱৹ਪ
岵峳ৄ峉ਙ૎ഉඪ峘৿਱峕峎岮峐૎ഉඪଢ଼஢ਚ૎ഉඪੲਾ崣嵛崧嵤ෛਆ୕ਫ岝৛഍ิื岝થ஝௟ਕ岝ৈଶማ৶岝ਸವਮ಻岝લসਫඥ岝স੩ၾ౩岝ਸઢ೗ఴ岝਍ઢ஖౩

ూବ嵣্১
ూବ
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਱৹ਪ峘崯嵤崧‫ ق‬ফ‫ڮ‬া঩ਠ૔‫ك‬峼ઞ৷峁峉岞যઠ峙যઠ৿ଙଁੑ‫ق‬൐ফা঩੦૆‫ك‬峼৷岮峉岞

―３５―ਙ૎ഉඪ৒ਡཔ඼
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―３６―

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―３７―෭෼岝ਾઔਯ岝୰஑શ岝੓ਙ岝ফશফ‫ع‬ফ
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੬ਙୃ৻

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‫ڸ‬

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෭෼‫؟‬૎ഉ৽ଡ଼શਾઔਯ
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ফ‫ك‬岤
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,':5岣ି৯峃峣岷૎ഉඪ岤‫؟‬ফা岝া ஶધ峬‫ك‬
LQFUHDVHG LQFLGHQFHਲਗ‫؟‬3URPHG 6XQDJDZD6\SKLOLV -DSDQLQFUHDVHGLQFLGHQFHFRPPHQWKWWSZZZSURPHGPDLORUJSRVW

―４０―ৌੁ嵣ৌૢ‫؟‬੘௜‫٭‬੒ଆ‫٭‬ཟ৅‫٭‬崝嵤嵁崌嵑嵛崡
• ෭෼૎ഉ峘৴ำ峼૵峋જ峵峉峫峕峙– ૎ഉ岶ઑ峹島峵ඪ૾岶峩峳島峉ৃ়峕峙岝ଫ਋峕ୢప峘൧૵嵣੘௜峼ਭ岻峵– ෭෼峒൧૵峁峉ৃ়峕峙岝ඍল峼ষ岰– ૑ਏ峕ૢ峂峉崹嵤崰崲嵤峕ৌ峃峵ઇ୘嵣ཟ৅岝ਫ਼ਪಉ– ્峕嵒崡崗岶ৈ岮ૐ੮峕ৌ峃峵ཟ৅ણ৿• ਂ્৒੗ਯ峘য峒峘ਙ৓மඡ峙嵒崡崗౤৕峑岬峴岝峇峘੠峕崛嵛 崱嵤嵈峼ిજ峕ઞ৷峁峔岮岽峒岶嵒崡崗峼ৈ峫峵岽峒岝崒嵤嵑嵓崣崫崗崡峮崊崲嵓崣崫崗崡峑峬 ૎ഉ峃峵岽峒岝෭෼峙ીেඊႵ峼੭峳島峄ગ૎ഉ峃峵– ঽ੘৬ಉ峒৴௚峁峔峳岶৅ে৿਱峕ିਔ峁岝嵊崳崧嵒嵛崘岝ৌૢ• ৎ岝ৃਚ岝崺崰岝嵒崡崗౤৕• ੔ଠ෭෼ੜਸ峘ೃ୛

―４１―੬੓શফೡীഘ‫ق‬ফা‫ك‬ਙஓ崗嵑嵇崠崊૎ഉඪ
੬ਙ

੓ਙ

―４２―

ਙஓ嵀嵓嵂崡૎ഉඪ
੬ਙ

੓ਙ

ቫ༳૎ഉඪ
੬ਙ

੓ਙ

―４３―

෭෼峘ਾઔਯ௓୎‫؟‬୰஑શ੬ਙ峘ੜਸଫ਋ႀਙ⋛਋岝⋜਋岝
૮ඪ౜ਙ

‫ڸ‬

੓ਙ峘ੜਸ
૮ඪ౜ਙ
ଫ਋ႀਙ⋛਋岝 ⋜਋‫ڸ‬෭෼岝ਾઔਯ岝୰஑શ岝 ୃਰৣ岝ফશ岝ফ‫ع‬ফ
㻝㻢
㻝㻠

↓⑕ೃᱵẘ
᪩ᮇ㢧⑕

㻝㻞

ඛኳᱵẘ

㻝㻜
ሗ
࿌
ᩘ

㻤
㻢
㻠
㻞
㻜
㻞㻜㻜㻝ᖺ 㻞㻜㻜㻞ᖺ 㻞㻜㻜㻟ᖺ 㻞㻜㻜㻠ᖺ 㻞㻜㻜㻡ᖺ 㻞㻜㻜㻢ᖺ 㻞㻜㻜㻣ᖺ 㻞㻜㻜㻤ᖺ 㻞㻜㻜㻥ᖺ 㻞㻜㻝㻜ᖺ 㻞㻜㻝㻝ᖺ 㻞㻜㻝㻞ᖺ 㻞㻜㻝㻟ᖺ 㻞㻜㻝㻠ᖺ 㻞㻜㻝㻡ᖺ
ሗ࿌ᖺ

―４４―

性感染症に関する特定感染症予防指針に基づく対策の推進に関する研究― センチネルサーベイランスの施行について ―【研究協力者】 谷畑健生 （神戸市東灘区保健福祉部・神戸市保健所）【研究代表者】 荒川

創一 （神戸大学大学院医学研究科）【研究協力者】 伊藤晴夫 （千葉大学）

五十嵐辰男 （千葉大学フロンティア医工学センター）
三鴨
安田
金山

廣繁 （愛知医科大学大学院医学研究科）
満 （岐阜大学医学部附属病院泌尿器科）
博臣 （徳島大学大学院医歯薬学研究部泌尿器科学）

研究要旨
平成２４～２６年をベースとし、医療機関全数調査を行った。対象疾患は梅毒、淋菌感染症、性器クラミジア感染症、非淋菌非クラミジア感染症、性器ヘルペス、尖圭コンジローマを対象として実測値を人年法により安定化させ、男女比較などあらゆる比較を可能とした。
本年の研究は、前３年と異なり、前３年で性感染症の多かった千葉県・兵庫県と岐阜県・徳島県を比較した。
また医療機関が梅毒については病期別に観察した。また検査を行った検体についての陽性率を算出し、陽性率に県の差があるかどうか、即ち県の意思の能力についても検討を行った。
本研究の最も特徴とすることは、国の感染症動向調査：定点動向調査報告をトレンドだけではなく、いろいろな比較が出来る自由度の効く調査報告にするための基礎的な疫学研究である。
性感染症定点動向調査は本研究に比べて感染者の推定値が低いことが明らかになったことから、定点の取り方について変更するべきであると考えられる。国は他の感染症と違えて新たな選定方法を考えるべき時期であると考えられる。
本研究は、感染症法の改正に伴う性感染症予防指針の改定のための基礎データを提供するものである。
を提供する。国立感染症研究所疫学情報セン

Ａ．研究目的ターで集計されている全国定点報告は、その第一の目標として、平成２４年から２７年の荒設計上、男女の比較、人口、性感染症同士の川班から性感染症の多い県と少ない県で、性比較が出来ないように設計されている。われ感染症がどう異なるのかを明らかにした。

われの本研究では、これらを比較可能とする

第二の目標として、感染症法の改正に伴う性感染症予防指針の改定のための基礎データ

ため、人年法を使用し、男女、年齢、疾患ごとの直接比較が出来るようにした。

―４５―

行い、回収率の向上を目指した。

Ｂ．研究方法医療機関への調査票の発送（９月初旬）及び本研究は平成２４年から２７年の荒川班を基礎

回収は各県の共同研究者が行った。回収率はとして、性感染症の多い千葉県・兵庫県、性千葉県７５．
２％、岐阜県６２．
９％、兵庫県９１．
１％、感染症の少ない岐阜県・徳島県の４県を調査

徳島県１００．
０％、４県で８０．
０％であった。
調査票の回収及び督促は地区責任者が行い、モデル県とした。
対象科は産婦人科（産科のみ、婦人科のみ

調査票に記載された記録を電子データ化し、を含む）、泌尿器科（皮膚泌尿器科を含む）、

データクリーニングは委託先の中央調査社が皮膚科、性病科を標榜する全ての医療機関を行った。疫学解析は谷畑が行い、調査の安定対象とした。調査対象とした性感染症は梅毒化を図るため人年法・９５％信頼区間を算出し（病期Ⅰ、病期Ⅱ、病期Ⅲ・無症候）、淋菌感

た。

染症、性器クラミジア感染症、非淋菌非クラ

９５％区間はその区間で真の値が確率的にあミジア感染症、性器ヘルペス、尖圭コンジることを示している。示されている推定値は、ローマとした。

最も近い代表値を示していている。この推定調査期間は平成２７年１０月１日から３１日まで

値はこの区間の代表とされる値であり、計算とし、対象医療機関の医師自らが期間中に対に用いられる。グラフの縦軸は人年を使用し象の５種性感染症と診断した全ての患者（氏ている。本研究では観察期間を１０月の１か月

名・住所等の個人が特定できる情報は収集し３１日間の調査としており、１年３５６日に換算ない）の受診日・性・年齢・また検査を行っしている。このことから縦軸は何人ではなく、た場合、検査検体数、検体陽性数を記入する

何人年になる。この方法の方が、一日だけのこととした。そして診断した性感染症名を調調査よりも、年間の感染者数という真の実際

査票に記録した。地区責任者（千葉大学・岐

受診値に近いため人年法を使用した。

阜大学・神戸大学・徳島大学）は督促を２回
データクリーニングについて（ア）診療科

無記入

→

入力せず

（イ）定点施設／非定点施設

無記入

→

入力せず

（ウ）感染症例有無

無記入＆

個別症例無記入→ 「なし」とする（エ）感染症例有無

無記入＆

個別症例記入あり→ 「あり」とする（オ）感染症例有無

なしに○（カ）女性に○男性尿道炎欄に記入は ERROR →＆（キ）男性尿道炎欄で

＆

非淋非ク

個別症例記入あり→ 「あり」に変更する
男性尿道炎欄に記入を削除のように○がついている場合は、非淋菌・非クラミ

ジアの両方に「１」を入力―４６―

Ｃ．研究結果
300

300

497.9

⏨

ዪ

765.8

250

250
ᱵẘ

ᱵẘ

᾿⳦ឤᰁ⑕

᾿⳦ឤᰁ⑕

䜽䝷䝭䝆䜰ឤᰁ⑕

䜽䝷䝭䝆䜰ឤᰁ⑕

ࠉ ேཱྀ

ࠉ ேཱྀ

㠀᾿⳦㠀䜽䝷䝭䝆䜰ឤᰁ⑕200

ᛶჾ䝦䝹䝨䝇
ᑤᆂ䝁䞁䝆䝻䞊䝬

୓ேᖺ

୓ேᖺ



ᛶჾ䝦䝹䝨䝇
ᑤᆂ䝁䞁䝆䝻䞊䝬


150

150

100

100

50

50

0

１

㠀᾿⳦㠀䜽䝷䝭䝆䜰ឤᰁ⑕200

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+ ᖺ㱋

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+ ᖺ㱋

調査年別性別感染症別に観察すると、男極めて多く目立った。また２０１２年より梅性に淋菌感染症が多く、女性に性器クラ

毒、淋菌感染症、性器クラミジア感染症

ミジア感染症・性器ヘルペスが非常に多が増加した。

かった。性器クラミジアの感染が女性に
2012ᖺ

2013ᖺ

2014ᖺ

2015ᖺ

2013ᖺ

2014ᖺ

2015ᖺ

（女）

吊呉吏呄呎吵
ᑤᆂᛶჾ启呂吱吐

ឤᰁ⑕
吆呀吶吏叹

᾿⳦ឤᰁ⑕

吊呉吏呄呎吵
ᑤᆂᛶჾ启呂吱吐

ឤᰁ⑕
吆呀吶吏叹

᾿⳦ឤᰁ⑕

―４７―

2012ᖺ

ᱵẘ

140
120
100
80
60
40
20
0

（男）

ᱵẘ

140
120
100
80
60
40
20
0

２

また梅毒は、近年定点調査で増加しているとされているが、本研究においても著

2012年（男）明に増加したと言えた。

200
150

梅毒（男）

5

250

100

4

50

3

0

2

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

ᖺ㱋

1
0

ᱵẘ
䜽䝷䝭䝆䜰ឤᰁ⑕᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2012ᖺ

2013ᖺ

2014ᖺ

250

2015ᖺ

䜽䝷䝭䝆䜰ឤᰁ⑕ᱵẘ᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2013年（男）
200
150

梅毒（女）

5

100

4

50

3

0

2

ᖺ㱋

1
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

2012ᖺ

2013ᖺ

2014ᖺ

250

2015ᖺ

䜽䝷䝭䝆䜰ឤᰁ⑕ᱵẘ᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2014年（男）200

３

調査年別性別年齢階級別感染症別に観察すると、各年とも男性では淋菌感染症及

150
100

び性器クラミジア感染症とも２０～２４歳に50

多く、年次的に著増していた。同時に尖0での性器クラミジア感染症は１５～２９歳に非常に多く、年次ごとに増加している。
全体に女性性器クラミジア感染症は男性に比べて極めて多かった。また男性は淋
菌感染症、性器クラミジア、女性は性器
クラミジア感染症、性器ヘルペスが全年

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+ᖺ㱋圭コンジローマも増加した。一方、女性

250䜽䝷䝭䝆䜰ឤᰁ⑕ᱵẘ᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2015年（男）
200
150
100
50

齢階級で目立った。

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

ᖺ㱋

―４８―

800

４

ᱵẘ
䜽䝷䝭䝆䜰ឤᰁ⑕᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

した。男性は配偶者無しが配偶者ありに

2012年（女）比べて、性感染症は圧倒的に多かった。

600

配偶者ありの男性は淋菌感染症、性器ク400

ラミジアが圧倒的に多かった。配偶者なしでは対象全ての性感染症が増加した。

200
015- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

ᖺ㱋

800

調査年別性別年齢階級別配偶者別を観察䜽䝷䝭䝆䜰ឤᰁ⑕ᱵẘ᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2013年（女）

2012ᖺ

2013ᖺ

2014ᖺ

2015ᖺ

配偶者あり
（男）

ᛶჾ启呂吱吐吊呉吏呄呎吵
ᑤᆂ

2014ᖺ

2015ᖺ

ឤᰁ⑕
吆呀吶吏叹

400

᾿⳦ឤᰁ⑕

ᱵẘ

600

140
120
100
80
60
40
20
0

200
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

ᖺ㱋

800

䜽䝷䝭䝆䜰ឤᰁ⑕ᱵẘ᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2014年（女）ᖺ㱋800䜽䝷䝭䝆䜰ឤᰁ⑕ᱵẘ᾿⳦ឤᰁ⑕ᑤᆂ䝁䞁䝆䝻䞊䝬
ᛶჾ䝦䝹䝨䝇

2015年（女）
600
400
200
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

ᖺ㱋

―４９―

吊呉吏呄呎吵
ᑤᆂ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+ᛶჾ启呂吱吐

0

配偶者なし
（男）

ឤᰁ⑕
吆呀吶吏叹

200

2013ᖺ

᾿⳦ឤᰁ⑕

400

2012ᖺ

ᱵẘ

600

140
120
100
80
60
40
20
0

女性は、配偶者ありに比べて配偶者無しの性感染症罹患率は、男性と同様に圧倒的に高かった。５種の疾患別に観察すると、性器クラミジアが他を圧倒している。
また梅毒も増加した。

6
4

2013ᖺ

2014ᖺ

吊呉吏呄呎吵
ᑤᆂᛶჾ启呂吱吐

ឤᰁ⑕
吆呀吶吏叹

᾿⳦ឤᰁ⑕

ᱵẘ

6
4
2
ᚨᓥ
ᒱ㜧呍

100

රᗜ
༓ⴥ呍

ᚨᓥ

2015ᖺ

配偶者なし
（女）

150

ᒱ㜧

2014ᖺ

රᗜ

2013ᖺ

༓ⴥ

2012ᖺ

2015ᖺ

梅毒（女）

8

0

淋菌感染症は、仮説通りであった。千葉
県・兵庫県が多かった。ただ兵庫県が突出し50ていることも分かった。
吊呉吏呄呎吵
ᑤᆂᛶჾ启呂吱吐

ឤᰁ⑕
吆呀吶吏叹

᾿⳦ឤᰁ⑕

ᱵẘ

５

2012ᖺ

ᚨᓥ
ᒱ㜧呍

10

රᗜ
༓ⴥ呍

0

配偶者あり
（女）

50

0

梅毒（男）

ᚨᓥ

2015ᖺ

100

200

2015ᖺ

2

2014ᖺ

150

0

2014ᖺ

8

ᒱ㜧

2013ᖺ

2013ᖺ

රᗜ

2012ᖺ

2012ᖺ

༓ⴥ

200

10

われわれは、２０１２～２０１４年までの前荒川

2013ᖺ

2014ᖺ

2015ᖺ

淋菌（男）

ᚨᓥ
ᒱ㜧呍

රᗜ
༓ⴥ呍

ᚨᓥ

ᒱ㜧

රᗜ

兵庫県は性感染症が多く、岐阜県と徳島

2012ᖺ

༓ⴥ

班調査結果を検討したところ、千葉県と

80
70
60
50
40
30
20
10
0

県が少ないことを観察した。この傾向も
今年度も続くことを仮説として、今年度
は前３年間と本年度の調査を合わせて、性感染症のそれぞれの県の傾向と、多い
県と少ない県の比較を行った。
梅毒は兵庫県・徳島県が０人であった

2014ᖺ

2015ᖺ

淋菌（女）

ᚨᓥ
ᒱ㜧呍

රᗜ
༓ⴥ呍

ᚨᓥ

ᒱ㜧

―５０―

2013ᖺ

රᗜ

は増加傾向にあった。

2012ᖺ

༓ⴥ

年があることから比較は難しいが、梅毒

80
70
60
50
40
30
20
10
0

淋菌は女性より男性が際立って多い感150染症であるが、兵庫県男性が際立って多ேཱྀ

増加傾向にある。また千葉県と兵庫県は



୓ேᖺ

く、２０
１４年に多くなったが、傾向として

多く、岐阜県と徳島県が少ないことを観察した。

察では千葉・兵庫県が多く、岐阜・徳島

100
50

アについては逆転していた。
2014ᖺ

2015ᖺ

ᐃⅬ᥎ᐃ᭷⑓⋡クラミジア（女）

୓ேᖺ

2014ᖺ

ᒱ㜧呍ᚨᓥ

༓ⴥ呍රᗜ

2013ᖺ

ᚨᓥ

ᒱ㜧

රᗜ

2012ᖺ

47㒔㐨ᗓ┴᥎ᐃ᭷⑓⋡

ேཱྀ

2013ᖺ

800
700
600
500
 400
300
200
100
0

性器クラミジア（男）

༓ⴥ20- 25- 30- 35- 40- 45- 50- 55- 60- 65+ᖺ㱋㝵⣭

女性クラミジア感染症について平成23年度47都道府県
医療機関推定有病率と定点推定有病率の比較（10万人年対）2015ᖺ

Ｄ．研究考察性器クラミジア（女）性感染症は決して少ない感染症とは言えない。男性は淋菌感染症が若い層で多く、女性は性器クラミジア感染症、性器ヘルペスが多いことがわかった。

ᒱ㜧呍ᚨᓥ

༓ⴥ呍රᗜ

ᚨᓥ

ᒱ㜧

රᗜ

༓ⴥ

180
160
140
120
100
80
60
40
20
0

2012ᖺ

20- 25- 30- 35- 40- 45- 50- 55- 60- 65+ᖺ㱋㝵⣭男性淋菌感染症について平成23年度47都道府県医療機関
推定有病率と定点推定有病率の比較（10万人年対）県で少ないとしていたが、性器クラミジ

180
160
140
120
100
80
60
40
20
0

ᐃⅬ᥎ᐃ᭷⑓⋡淋菌（男）0

性器クラミジア感染症はこれまでの観

47㒔㐨ᗓ┴᥎ᐃ᭷⑓⋡また配偶者別には、どの感染症についても配偶者無しが配偶者ありよりも多いことが改めて追認できた。しかしながら「配偶者あり」
であっても性感染症罹患者は現に存在してお次いで本研究と定点調査を比較した場合、り、どうして感染したのかを、行動学的に調定点は淋菌・性器クラミジア感染症で５５歳代査する必要がある。感染源は「浮気相手」なまで非常に低い値を示した。

のか、Co
なのか、また性
mme
r
c
i
a
lSe
xWo
r
k
e
r
感染症に罹患した配偶者からなのか、現状では何ら情報は無い。この点にスポットを当てた研究が必要であり、性感染症予防指針に、性についての人の行動・行為を入れる必要が―５１―

あると考えられる。「配偶あり」の場合、配偶者に避妊目的以外でコンドームをつけることはないと考えられるため、個々にスポットをＥ．結１

本研究は、国が行う感染症動向調査：定当てた指針の作成が必要と考えられる。 配
偶 者 あ り の 場 合「浮 気」「Co
mme
r
c
i
a
lSe
x

点調査に比べて感度が極めて良い。
２性感染症は前研究班のころよりも増加し」ともに家庭を壊すきっかけとなるの
Wo
r
k
e
r
で、人間行動学的アプローチによって、性感論た。
３ 「配偶者あり」であっても、性感染症患者
はおり、配偶者がありながら何故性感染

染症を減らす研究は必要であると考えられる。

症に罹患するかについて、人間行動学的に明らかにする必要が喫緊の課題である。

女性の性器クラミジア感染症は他の感染症を圧倒するものがあり、これについても、感４

本研究は調査設計が定点調査設計と全く染源を明らかにしない限り、性器クラミジア

異なり、独立した研究である。このため感染症を減少させることは出来ない。男性の定点調査の影響は受けない。
５

淋菌感染症も同様なことが言える。

定点調査に比べて自由度が高いことから、これまでの研究の積み重ねで、本年度の研解析結果を使って、男女別比較、性感染究において、これまで性感染症が多い県と少症間の比較を行うことが出来る。これらない県を定義した。しかしながら、４年間のは定点調査では出来ないことである。性性感染症の増加トレンドは、われわれの想定

感染症は他の感染症とは異なり、大々的を超えており、性感染症の多い県・少ない県に医療機関に罹ることの出来ない物であは無くなった可能性はある。今後本研究班のることから、定点の選定においては十分

活動によって追跡していきたい。

な配慮が必要である。本研究から性感染症のあり方について、国は他の感染症と違えて新たな選定方法を考えるべき時期

定点動向調査はあくまでもトレンドを追跡であると考えられる。

するのが目標であり、いろいろな比較ができないよう設計されている。一方本研究の特徴
は男女比較、男女別の年齢層比較、同性での感染症罹患率の比較、異性での感染症罹患率

Ｆ．健康危機情報の比較など、多様な比較が可能である。

国・地方公共団体は性感染症対策の基本でまた性感染症定点動向調査は本研究に比べあるコンドームの使用を強く進めていく必要て感染者の推定値が低いことが明らかになっがある。一方で性感染症の感染源は明らかでたことから、定点の取り方について変更するないことも多いので、国民は安全な環境にあべきであると考えられる。

るとは言えない危機的状況にあると考えられ
る。

―５２―

Ｇ．論文発表
谷畑健生・秋元義弘・武島男・安田仁・五十嵐辰満、種田恭子・金山博臣・荒川創一：平成２５年７モデル県の性感染症診察
医療機関全数調査推計有病率と国立感染症研究所の定点報告推計有病率の比較～７県
医療医官全数調査結果と定点調査報告結果の有病率は何故乖離したのか？

日本性感染症学会誌．２０１５；２６（１）：１０９−１１６．

Ｈ．知的所有権の取得状況
１．特許取得なし

２．実用新案登録なし

３．そ の 他
なし

―５３―

―５４―

検査数

︵

−

（

陽性（

（

陽性（

日

／

月

齢

年

別

性

）

無症候性（

）検体

）

）

うち、 症候性（）検体）

１．含まない

10

9

8

7

男・女
男・女
男・女

10/
10/
10/

男・女

男・女

10/

6
10/

男・女

10/

5

4
男・女

3
10/

男・女

10/

2

）検体

２．含む

男・女

10/

術前検査等を

男・女

10/

1

○○市 23 男・女

居︵
市
住郡
の
み
地︶

）

例 10/ 1

症
例
番
号

あり

症例件数
・

なし

有・無

有・無

有・無

有・無

有・無

有・無

有・無

有・無

有・無

有・無

有・無

者

偶

配

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅰ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

梅Ⅱ

毒

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

梅Ⅲ無症

Ⅲ期 以 上又は無症候

梅Ⅰ 期Ⅱ 期

ⓐ
ⓑ

淋

淋

淋

淋

淋

淋

淋

淋

淋

淋

淋

淋
菌
性

ク症

ク症

ク症

ク症

ク症

ク症

ク症

ク症

ク症

ク症

ク症

ク無症

ク無症

ク無症

ク無症

ク無症

ク無症

ク無症

ク無症

ク無症

ク無症

ク無症

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

非淋非ク

ヘ

ヘ

ヘ

ヘ

ヘ

ヘ

ヘ

ヘ

ヘ

ヘ

ヘ

コ

コ

コ

コ

コ

コ

コ

コ

コ

コ

コ

ⓔ
ⓕ
性ヘ 尖
ⓒクラミジア 性
ルⓓ非淋菌性
ペ症 候 性 無症候性 非クラミジア性
器ス 圭

男
性
尿
道
炎
女 性 子 宮 頸 管 炎

1 症例 1 行として該当疾患名の略語を○で囲む。重複感染例は複数疾患名を○で囲む。

2015年10月ひとつきに診断した性感染症症例

両方ご記入ください）

提出期限は、2015 年 11 月末日です。
該当患者がない場合でも、性感染症症例「なし」を○で囲むと共に、左欄に検査数を記入し、ご提出ください。 ※ 記載欄が足りない場合は、用紙をコピーしてご記入ください。

ク
ラ
ミ
ジ
ア

菌

淋

Ｐ
毒Ｒ
な 陽性（
血ど
清の
Ｓ （
反Ｔ
Ｓ
応法
︶

RPR では 16 倍（自動測定法
では 16 単位 /ml）以上（10 月1 日〜 31 日）

1 か月間の検査実施数

陽性数（一件も検査していない場合は、分母に（0）検体とご記入ください）梅Ｒ−

産婦人科 ・ 泌尿器科 ・ 皮膚科 ・ 性病科 ・ その他（

2015年10月ひとつきに検査した検体数と陽性数

科

FAX

榜

−

標

−

記 入
医師名

先

TEL

絡

連

地

在

所

県調査）
定点施設 ・ 非定点施設 （いずれかを○で囲む）

（

医療施設名

性 感 染 症 （ S T I ） 全 数 把 握 調 査 用 紙 （2015 年）

梅毒（縦軸：人口 10万人年、横軸：年齢階級）

100
90
80
70
60
50
40
30
20
10
0

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

182.0515- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―５５―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅

毒（縦軸：人口 10万人年、横軸：年齢階級）

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―５６―

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅毒Ⅰ期（縦軸：人口 10万人年、横軸：年齢階級）
100
90
80
70
60
50
40
30
20
10
0

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

182.0515- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―５７―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅 毒（縦軸：人口 1
梅毒Ⅰ期（縦軸：人口01
万人対・人年、横軸：年齢）
0万人年、横軸：年齢階級）
100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―５８―

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅毒Ⅱ期（縦軸：人口 10万人年、横軸：年齢階級）
100
90
80
70
60
50
40
30
20
10
0

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―５９―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅 毒（縦軸：人口 1
梅毒Ⅱ期（縦軸：人口01
万人対・人年、横軸：年齢）
0万人年、横軸：年齢階級）
100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―６０―

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅毒Ⅲ期以上・無症候（縦軸：人口 10万人年、横軸：年齢階級）
100
90
80
70
60
50
40
30
20
10
0

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―６１―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅 毒（縦軸：人口 1
梅毒Ⅲ期以上・無症候（縦軸：人口0万人対・人年、横軸：年齢）
10万人年、横軸：年齢階級）
100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

100
90
80
70
60
50
40
30
20
10
0

―６２―

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+淋菌性尿道炎・頸管炎（縦軸：人口 10万人年、横軸：年齢階級）300

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

0

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ300

0䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―６３―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅 毒（縦軸：人口 1
淋菌性尿道炎・頸管炎（縦軸：人口0万人対・人年、横軸：年齢）
10万人年、横軸：年齢階級）300

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

0

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

0

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

0

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―６４―

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

クラミジア性尿道炎・頸管炎（縦軸：人口 10万人年、横軸：年齢階級）䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1278.457874.87

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1095.284912.52

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
00

1965.821536.58
19836.96

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1092.32
1687.47

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
00

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

―６５―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅 毒（縦軸：人口 1
クラミジア性尿道炎・頸管炎（縦軸：人口0万人対・人年、横軸：年齢）
10万人年、横軸：年齢階級）䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

2392.19
18364.78

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1098.537952.0715- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

3373.38
23624.60

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

―６６―

1058.75

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

クラミジア性尿道炎・頸管炎（症候性）（縦軸：人口 10万人年、横軸：年齢階級）䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1312.48

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

6612.32

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

―６７―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

梅 毒（縦軸：人口 1
クラミジア性尿道炎・頸管炎（症候性）
0万人対・人年、横軸：年齢）（縦軸：人口 10万人年、横軸：年齢階級）䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

9182.39

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

―６８―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

クラミジア性尿道炎・頸管炎（無症候性）（縦軸：人口 10万人年、横軸：年齢階級）䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

6562.39

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

4912.52

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1608.401229.2713224.64

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1001.30
1687.47

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

―６９―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

クラミジア性尿道炎・頸管炎（無症候性）（縦軸：人口 10万人年、横軸：年齢階級）䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

1913.759182.39

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

7952.0715- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

3373.38
23624.60

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

1000
900
800
700
600
500
400
300
200
100
0

―７０―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

非淋菌非クラミジア性尿道炎・頸管炎（縦軸：人口 10万人年、横軸：年齢階級）300

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

300

656.24

250

250

200

200

150

150

100

100

50

50

0

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

300

818.75䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

250

200

200

150

150

100

100

50

50
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

300

250

250

200

200

150

150

100

100

50

50

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

300

250

0

䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―７１―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

非淋菌非クラミジア性尿道炎・頸管炎（縦軸：人口 10万人年、横軸：年齢階級）
200
180
160
140
120
100
80
60
40
20
0

300
250

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

269.33

180
160
140
120
100
80
60
40
20
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

312.491590.41

300

200

150

150

100

100

50

50

300

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

435.61

300

250

250

200

200

150

150

100

100

50

50

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

250

200

0

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―７２―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

366.4715- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

性器ヘルペス（縦軸：人口 10万人年、横軸：年齢階級）
200
180
160
140
120
100
80
60
40
20
0

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

200
180
160
140
120
100
80
60
40
20
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

200
180
160
140
120
100
80
60
40
20
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

200
180
160
140
120
100
80
60
40
20
0

200
180
160
140
120
100
80
60
40
20
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ඲ᅜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛺䛧䚷ዪ

200
180
160
140
120
100
80
60
40
20
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

200
180
160
140
120
100
80
60
40
20
0

200
180
160
140
120
100
80
60
40
20
0

―７３―

205.1415- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

性器ヘルペス（縦軸：人口 10万人年、横軸：年齢階級）
200
180
160
140
120
100
80
60
40
20
0

200
180
160
140
120
100
80
60
40
20
0

400

䕔 ᒱ㜧㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛒䜚䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛒䜚䚷ዪ

200
180
160
140
120
100
80
60
40
20
0

300

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 රᗜ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 රᗜ㓄അ⪅䛺䛧䚷ዪ

250
200
150
100
50
0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛒䜚䚷ዪ

400

350

350

300

300

250

250

200

200

150

150

100

100

50

50

0

䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―７４―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

407.21

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

尖圭コンジローマ（縦軸：人口 10万人年、横軸：年齢階級）300

䕔 ඲ᅜ㓄അ⪅䛒䜚䚷⏨䚷䚷䕔 ඲ᅜ㓄അ⪅䛒䜚䚷ዪ

300

656.24

250

250

200

200

150

150

100

100

50

50

0

0

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷⏨䚷䕔 ༓ⴥ䞉රᗜ㓄അ⪅䛒䜚䚷ዪ

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300

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15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䕔 ᒱ㜧䞉ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

300

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300

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15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―７５―

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ༓ⴥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ༓ⴥ㓄അ⪅䛺䛧䚷ዪ

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

尖圭コンジローマ（縦軸：人口 10万人年、横軸：年齢階級）300

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1590.41

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15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+―７６―䕔 ᒱ㜧㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᒱ㜧㓄അ⪅䛺䛧䚷ዪ

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15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+䕔 ᚨᓥ㓄അ⪅䛺䛧䚷⏨䚷䚷䕔 ᚨᓥ㓄അ⪅䛺䛧䚷ዪ

325.7715- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65+

性感染症（STI）
サーベイランスの評価と改善に関する研究【研究分担者】 中瀨克己 （岡山大学医療教育統合開発センター）【研究協力者】 高野つる代 （横浜市旭区福祉保健センター）

川畑

拓也 （大阪府立公衆衛生研究所）

細井

舞子 （大阪市保健所）

中谷友樹 （立命館大学）

尾本由美子 （豊島区池袋保健所）
砂川

富正 （国立感染症研究所）

有馬

雄三 （国立感染症研究所）

谷畑

健生 （神戸市保健所）

白井千香 （神戸市保健所）樫原摩紀 （株式会社エスアールエル）

金谷

泰宏 （国立保健医療科学院）

研究要旨
わが国の性感染症（STI）に関するサーベイランスの改善を目的として本年度は以下の研究を行った。まず、性感染症に関する特定感染症予防指針に基づく対策の現状把握とその推進のためにⅠ．
「性感染症に関する特定感染症予防指針」への自治体の対応状況調査、
Ⅱ．地方自治体性感染症サーベイランス担当者向け情報還元を行った。また、国の行う感染症発生動向調査を補完する動向把握策等の検討として、Ⅲ．検査結果サーベイランスの試行と検討、Ⅳ．
発生動向調査の報告情報の活用に関する検討を行った。
STI

Ｂ． 研究方法

Ⅰ．
「性感染症に関する特定感染症予防指針」への自治体の対応状況調査

サーベイランス活用を担う都道府県／保健所設置市の STD対策担当者および地方感染Ａ．研究目的症情報センター担当者を対象に２０１５年１２月に

平成２９（２０１８）年改訂が予想される「性感染症に関する特定感染症予防指針」（以降指電子メールあるいは郵送により質問紙を送付
回収した。
２０１３
（平成２５）年１２月にも同様の調査を行っ針）への反映を目的に、自治体における性感染症（STD）発生動向調査の運営と活用の状ており一部結果を比較した。

況を平成２４年度に改訂された点を中心に把握
する。

―７７―

なお、この纏めは公衆衛生情報研究協議会

倫理面への配慮
本研究には、個人情報および人や動物へのにて報告した。
また、指針の変更内容に対応した、情報提介入を行う内容は含まれていない。

供先やその内容、定点医療機関の変更、口腔Ｃ．研究結果及びＤ．考を介した感染の把握（耳鼻科定点の設定）等

察への対応に加え、耐性淋菌などの病原体定点

調査結果概要およびこれを踏まえた考察をへの考え方、性器ヘルペス動向把握の意義、
自治体検査での未返却割合、パートナー健診、別添１、２に示す。

アウトブレイクの把握とその際の対応など調
査結果の全体を別添３、４に示す。

対策担当課における対応の要約
・全国自治体の STD対策担当者を対象に調査した結果、指針にある口腔を介した感染について把握体制を変更した自治体は少な

Ⅱ．地方自治体性感染症サーベイランス
担当者向け情報還元い。一方で、全数調査など独自取り組みを行う自治体もある。
・梅毒を中心に性感染症のアウトブレイクをＡ．研究目的１５自治体で把握し、増加への対応や啓発が行われていた。

我が国の安定的な性感染症サーベイランスである感染症発生動向調査の運営を地方で担・担当者の経験年数は短く、保健師等の背景

う地方感染症情報センター職員および対策をを活かした関係機関や他自治体等との情報担う自治体性感染症対策担当者への情報還元

交換や的確な情報把握と効果的な還元のたを行うことによって、指針に示す拠点としてめの体制の充実が期待される。

の保健所を始めとして都道府県等地域からの情報発信を強化するとともにその結果に基づ発生動向担当者における対応のまとめ

く対策の推進を促す。

・定期情報の発信は、殆どが行っているが・臨時情報の発信が、地衛研（地方感染症情報センター）でバラツキがあった。

Ｂ．研究方法・若年女性層等、ターゲットに合わせた情報発信が課題。

地方感染症情報センター職員が集まる機会を捉えた情報還元を行うと伴に多様な媒体も・関係機関との連携も課題。

活用して情報提供を図る。

・性感染症罹患の指標として、性器ヘルペス
は課題がある。

倫理面への配慮・高度耐性淋菌に対する病原体定点等、疾患の流行に対応した新たな体制も必要か（そ本研究には、個人情報および人や動物への介入を行う内容は含まれていない。

の際は、都道府県一律ではなく、報告数の多い県等に限定するか）。

―７８―

Ｃ．研究結果及びＤ．考

１．梅毒届出医療機関に対する積極的疫学調

察査

多くの地方感染症情報センター職員が集ま

２．男性とセックスする男性への広報に加え、女性への啓発る地方衛生研究所全国協議会主催による公衆衛生情報研究協議会にて梅毒増加、自治体対

３．梅毒検査結果陽性者のパートナー向け資材の作成

応の現状、大阪市におけるサーベイランス活用手法の３演題を発表した。発表スライドを

４．他自治体と連携した普及啓発及び検査体
制整備

別添１、２、５に示す。
発表後の質疑や会場での質疑を踏まえ、研究Ⅰでの調査結果、Ⅳでの研究協力者間

サーベイランスの更なる活用への動機付
STIの協議等を踏まえると、以下のように考察さけや意義の理解に繋がったと推定される。参れた。

加者からの質問や意見等を別添１１に示す。

１．届け出時の適切な内容確認や必要時の積アンケート結果と考察は調査対象とした全

極的疫学調査が行われていることを自治

国自治体に対し、調査と同様にメールあるい体に周知する事が、対策の推進に有用とは郵送により還元した。

考えられる。今回も豊島区が用いている

全国の性感染症対策担当部門に配布され、Faxによる情報確認の様式を紹介した。

見ることが多いと想定されるニューズレター

２．HI
V感染も含め、異性間性交渉による感「性の健康」に寄稿し、特定感染症予防指針

染に関し改めて広い対象者に注意喚起すへの自治体対応の現状と考察を情報提供した。

る必要性が高い。

また、情報提供を目的としたホームページを

３．先天梅毒のような稀だが重要な事例では運営し、過去の研究成果や発生動向調査ガイ

積極的疫学調査により対象者の実情を把

ドラインなどを含め研究成果を還元した。

握する必要性が高い事の周知が必要であ（下図）る。増加しつつある新たな伝播への対応
として、パートナーへの働きかけによる感染防止と合わせた伝播に関する情報把握（パートナー健診）を強化することで、対象者の実情に合わせた予防対策を行え
ることの自治体担当者への情報提供が有用と思われる。
４．都市である大阪市では、梅毒報告の半数が市外での感染と報告されており、対策の基礎となる情報の共有が大阪市と近隣対策を担当する大阪市保健所感染症対策課

自治体で新たに個別に行われた。自治体

における梅毒の発生動向を踏まえた対応報告

間の発生動向情報共有が十分行われていでは、以下を今後の課題としている。

ない現状を踏まえ、① NESI
Dにおいて他
自治体への公開範囲の設定で情報提供が―７９―

可能な事をまず周知すると伴に、②事例行われる事があるので、重複の除外を依頼しの紹介や共有が進むような働きかけ③梅た。全国および大阪府における感染症発生動

毒届け出における居住地情報の追加など

向調査結果の詳細と比較し、未届け事例の可により情報の把握と共有の推進が必要と能性について検討した。

思われる。
倫理面への配慮
内容に個人情報は含まれず、各社内で提供に当たっての倫理等検討が行われた結果、３Ⅲ．検査結果サーベイランスの試行と検討

社から提供を受けた。
保健所 WB陽性数は公表データを用い、Ａ．研究目的２０１３年の近畿圏に関しては研究協力者が自治

感染症サーベイランスにおける動向把握方

体に問い合わせて数値を得た。

HPV、HSVについては大規模委託会社１

法の一つとして、検査結果によるものがある。
感染症発生動向調査を補完するサーベイラン社の委託に関する現状を把握した。

スとして検査結果サーベイランスの可能性を評価した。

上記のように本研究には、個人情報および人や動物への介入を行う内容は含まれていな

WB法による HI
V抗体確認検査は通常 HI
Vい。

感染の診断目的で用いられ、基本的に一人の感染者には１回の陽性結果と考えられる。そのため、HI
Vの WB陽性件数は HI
V感染症診

Ｃ．研究結果及びＤ．考察

WB法陽性数は２０１１年で約１５００件であった。

断動向の指標となる。未届けが高い割合であれば、発生動向調査の結果との乖離がみられ

主要な HI
Vの届出元と確認検査は、①自施設

ると考えられるので、HI
V確認検査陽性数ので WB検査が出来ない医療機関における委託意義を検討した。

検査、②保健所による地方衛生研究での確認

また、HPVと HSVに関する委託検査の現検査、③自医療機関内での確認検査、の３つ

状を問い合わせ、性感染症動向把握におけるであり、今回は③病院検査科における陽性数

活用の可能性を検討した。

は把握できていない。
都道府県ごとの重複を考慮した WB法陽性
数に保健所陽性分を加え、届出数とを比較しＢ．研究方法た結果、１４府県では両者の和が届け出数を上

大規模検査受託会社と試薬メーカーで構成
さるウイルス検査に関する連絡会（ウイルス

回った。診断された HI
V感染症例が届けられていない可能性が高い（別添６）。

検査技術連絡会）に２０１１年１月から２０１３年１２

HPVと HSVに関する大規模検査委託会社

月（検体提出時）に自施設で実施した WB法のコメントは以下のようであり、現在のとこによる HI
V抗体検査の集計値の提供を依頼しろ、委託検査結果から HPV，HSVについて動た。また、研究目的等で同一人の重複検査が向を把握するのは難しいと思われた。

―８０―

HPVは、女性の検診由来の検体が全てを占

倫理面への配慮
本研究には、個人情報および人や動物へのめており、男性由来の検体はない。

HSVは、依頼のある検査材料はほとんどが髄介入を行う内容は含まれていない。

液で、その他は眼科由来、血液で泌尿器由来の検体はない。

Ｅ．結

Ｃ．研究結果及びＤ．考察

指針では、引き続き「四．対象者の実情に論応じた予防対策を講ずるに当たっては、年齢

HI
V感染症診断例の報告の未届けは、かな

や性別等の対象者の実情に応じた配慮を行っりの数に上りそうであることが示唆された。

ていくことが重要である」としている。近年、今後は、病院内での WB法陽性診断数を把握

梅毒伝播経路において異性間性的接触によるし正確な未届け事例の評価をする必要性が高感染が増加していること、連携を図るべきとい。

される後天性免疫不全症候群においても異性

現在のところ、委託検査結果から HPV、間性的接触による感染が増加していること、

HSVについて動向を把握するのは難しいとを踏まえ感染の実情の把握に基づく効果的な思われた。

対策が重要と考えられる。罹患率の低い疾患対策としては、対象を特定しない啓発に加え、相手を特定した働きかけの有用性やこの際のⅣ．STI
発生動向調査の報告情報の活用に情報把握が効果的とされ、パートナーへの働関する検討

きかけが推奨されており１）、ヨーロッパ２）や米国の多くの州において梅毒等を対象に公的

Ａ．研究目的な働きかけがなされている１）。このようにサーベイランスに関わる中央感染症情STI

パートナー健診が無症候期や自発的な受診が報センター、地方自治体担当者、検査受託機

期待しにくい対象者への受診／加療の促進や関、研究者が協議する事によって、より性感

実情の把握に有用と考えられることを踏まえ、染症対策に資するサーベイランスの方策につ

我が国でも一層の推進が期待される。

いて検討する。

また、現状では中央情報センターに集約された発生動向調査結果の公開手順が示されていない。諸外国では情報公開の範囲や手順がＢ．研究方法公開され、その活用がすすんでいる。 今回本研究における自治体へのアンケート調査

は保健所で入手可能なデータを用いて地理的結果および他国における STI
サーベイランス

情報を加味して分りやすい情報提供の例を示の運用や活用の現状を踏まえ、研究協力者とした。NESI
Dシステムの制約から保健所か協議した。

らは、近隣であっても他自治体の年齢階級別データを得る事ができない。このため、自治体をまたいだ都市圏や地域において、指針に―８１―

示すような、性別年齢階級別の動向を踏まえ

自治体向けの基本的な調査介入手順等の提て、対象者の特性にあった対策を行う事に制供が必要である。
・梅毒は近年急増し伝播経路における異性間約がある。

性的接触が増加している。MSMなどの個結論に含まれる検討や今後の研究方向につ

別施策層に加え、対象者の特性の把握に基いて、非常に有用な議論が行われた。今後のづく対策が必要でありパートナー健診の有サーベイランスの方向として、性感染症
STI

用性が高まると考えられる。

サーベイランスの目的の明確化が議論され、・梅毒報告事項に現在含まれていない患者居アウトブレイク対応としての梅毒サーベイラ

住地情報を加えることで、施策担当自治体

ンス、蔓延疾患（STD）対策としての定点疾が明確となり自治体を越えた対策等の推進

患サーベイランスという、対策指向でサーベの基礎となる。

イランスの目的を区分するという考えかたが参提示された。

１

検討結果は結論のように要約される。

考
堀成美：公立性感染症クリニックにおける接触者検診拡大の試み．平成２５年度

Ｅ．結

厚生労働科学研究費補助金（新型インフ論

ルエンザ等新興・再興感染症研究事業）「自然災害時を含めた感染症サーベイラ

・梅毒を含めた性感染症のアウトブレイクをンスの強化・向上に関する研究」（研究代

１５自治体が把握し対応していた。

表者：松井珠乃）分担研究 STI
サーベ

・性感染症の報告は都市部に集中しており、病原体サーベイランスや詳細データの共有

イランスの評価と改善．報告書．

を圏域で進めると対策に有用と思われる。

２ CDC,Pa
r
t
ne
rSe
r
vi
c
e
s
,Se
xua
l
l
yTr
a
ns
mi
t
-

・自治体別（都道府県、保健所別）の情報が

t
e
dDi
s
e
a
s
e
sTr
e
a
t
me
n
tGu
i
d
e
l
i
n
e
s2
0
1
5
,

活用できると、自治体や医療機関での対策

MMWR,J
u
n
e5
,Re
c
o
mme
n
d
a
t
i
o
n
sa
n
d

の推進に有用。

Vo
l
.
6
4/
No
.
3
,p
p
.
8
9
,2
0
1
5
.
Re
p
o
r
t
s/

・自治体を越えた発生動向の活用が進まず、活用策が周知されていなかったり、一部で利用に制約があることが理由ではないか。

Ｇ．研究発表１．論文発表・中央感染症情報センターに集約されてい１

中瀨克己：特定感染症予防指針の変更をる報告データの利用要望があり、利用可

踏まえた自治体における性感染症発生動能な範囲や許可等の手順の明確化が望ま

向調査の活用．ニューズレター「性の健

れる。

康」，Vo
．
１５，No
．
１，１−３，２０１５．
l

・自治体の施策担当者の担当年限は短く経験

２

白井千香・古林敬一・川畑拓也・吉田弘

や知見の蓄積が十分でないとおもわれる。

之・荒川創一：性感染クリニック及び産梅毒の増加を踏まえると、多発していない科における口腔内性感染症に関するアン―８２―

ケートと検体検査の試み．日本性感染症

７

学会誌，Vo．
２６，No．
１，９１−９６，２０１５．
l

細井舞子・松本健二・高野つる代・金谷
泰 宏・尾 本 由 美 子・川 畑 拓 也・砂 川 富正・中瀨克己：大阪市における梅毒の発

２．学会発表生動向と取り組み．第２９回公衆衛生情報

１

研究協議会研究会，東京，２０１６年．

中瀨克己・中谷友樹・川畑拓也・中島一
敏・神谷信行・杉下由行・高野つる代・

２８

高野つる代・中谷友樹・細井舞子・尾本

尾本由美子・山内昭則・高橋裕明・樫原由 美 子・川 畑 拓 也・砂 川 富 正・中 瀨 克

摩紀・山岸拓也・白井千香：En
g
l
a
n
dと

己：地方感染症情報センターにおける比較した我が国の性感染症サーベイラン

サーベイランスの運用の現状．第２９STIスの特徴，日本性感染症学会，２０１５年１２

回公衆衛生情報研究協議会研究会，東京，月６日，東京．

２０１６年．

中谷友樹・安本晋也：地理情報システム

９中瀨克己・高野つる代・細井舞子・尾本（GIS）を用いた感染症流行の地理的視覚

由 美 子・川 畑 拓 也・砂 川 富 正・金 谷 泰

化・空間的モデリング．科学技術イノ

宏：特定感染症予防指針の期待する性感

ベーション政策のための科学研究開発プ

染症発生動向の活用．第２９回公衆衛生情

ログラム（RI
STEX）プログラムサロン

報研究協議会研究会，東京，２０１６年．

（第７回）エビデンスに基づいた政策形成
へ：医療における試み，政策研究大学院
大学（GRIPS）．（２０１６年２月２２日）
３

川畑拓也：大阪府における梅毒と HI
Vの発生動向について．大阪 STI
研究会

Ｈ．知的財産権の出願・登録状況
１．特許取得なし

第３８回学術集会，大阪，２０１５年．
４ 川畑拓也：HI
V検査･サーベイランスの２．実用新案登録

現状と課題．第８回近畿HI
VFRONTI
ER

なし

研究会，大阪，２０１５年．
５

川畑拓也・中山周一・古林敬一・亀岡

３．そ の 他

博・安本亮二・志牟田健・石原朋子・大西真：大阪府内で分離された淋菌株におけるアジスロマイシン感受性率の低下．
第２８回日本性感染症学会学術大会，東京，
２０１
５年．
６

川畑拓也・小島洋子・森之・中山周一・大西

治代・柴田敏真：大阪地域における梅毒感染拡大阻止の取組み（２０１３−
２０１５前半）．第２８回日本性感染症学会学術大会，東京，２０１５年．

―８３―

なし

〈別添１〉

බ⾗⾨⏕᝟ሗ◊✲༠㆟఍

≉ᐃឤᰁ⑕ண㜵ᣦ㔪䛾ᮇᚅ䛩䜛
ᛶឤᰁ⑕Ⓨ⏕ືྥ䛾ά⏝

2016.1.29.
୰ℨඞᕫ䠖ᒸᒣ኱Ꮫ་⒪ᩍ⫱⤫ྜ㛤Ⓨ䝉䞁䝍䞊䚸㧗㔝䛴䜛௦䠖ᶓ὾ᕷ᪫༊⚟♴ಖ೺䝉䞁䝍䞊䠄ඖᶓ὾ᕷ⾨⏕◊✲ᡤ䠅䚸䠖⣽஭⯙Ꮚ䠖኱㜰ᕷಖ೺ᡤ䚸 ᑿᮏ⏤⨾Ꮚ䠖㇏ᓥ༊ụ⿄ಖ೺ᡤ䚸 ᕝ⏿ᣅஓ䠖኱㜰ᗓ❧බ⾗⾨⏕◊✲ᡤ䚸◁ᕝᐩṇ䠖ᅜ❧ឤᰁ⑕◊✲ᡤ䚸㔠㇂Ὀᏹ䠖ᅜ❧ಖ೺་⒪⛉Ꮫ㝔┠ⓗ H29(2018)ᖺᨵゞ䛜ண᝿䛥䜜䜛䛂ᛶឤᰁ⑕䛻㛵䛩䜛≉ᐃឤᰁ⑕ண㜵ᣦ㔪䛃䠄௨㝆ᣦ㔪䠅䜈䛾཯ᫎ䜢䜑䛦䛧䚸⮬἞య䛻䛚䛡䜛ᛶឤᰁ⑕(STD)Ⓨ⏕ືྥㄪᰝ䛾ά⏝≧ἣ䜢ᢕᥱ䛩䜛䚹᪉ἲ 䝃䞊䝧䜲䝷䞁䝇ά⏝䜢ᢸ䛖㒔㐨ᗓ┴䠋ಖ೺ᡤタ⨨ᕷ䛾STDᑐ⟇ᢸᙜ⪅䜢ᑐ㇟䛻2015ᖺ12᭶䛻㟁Ꮚ䝯䞊䝹䛒䜛䛔䛿㒑㏦䛻䜘䜚㉁ၥ⣬䜢
㏦௜ᅇ཰䛧䛯䚹
 2013(H25)ᖺ12᭶䛻䜒ྠᵝ䛾ㄪᰝ䜢⾜䛳䛶䛚䜚୍㒊⤖ᯝ䜢ẚ㍑䛧䛯䚹

―８４―

ᅇ⟅⋡
㓄ᕸᩘ
㒔㐨ᗓ┴

㻠㻣

ᅇ⟅ᩘ

ᅇ⟅๭
ྜ

 ᅇ⟅⮬἞య䛾ෆヂ㻟㻡 㻣㻠㻚㻡㻑

13

㒔㐨ᗓ┴
35

ᣦᐃ㒔ᕷ

㻞㻜

㻝㻡 㻣㻡㻚㻜㻑

ಖ೺タ⨨
ᕷ

㻡㻞

㻡㻜 㻥㻢㻚㻞㻑≉ู༊㻞㻟㻝㻟 㻡㻢㻚㻡㻑඲య㻝㻠㻞㻝㻝㻟 㻣㻥㻚㻢㻑ᣦᐃ㒔ᕷಖ೺ᡤタ⨨ᕷ
50

15≉ู༊≉ᐃឤᰁ⑕ண㜵ᣦ㔪H24ᖺᨵゞ㏣ຍ ๓ᩥཱྀ⭍䜢௓䛧䛯ᛶⓗ᥋ゐ䛷ឤᰁ ཎᅉ㏣ཬ Ⓨ⏕ືྥ䛜ᐇែ䜢ⓗ☜䛻཯ᫎ䛧䛯䜒䛾䛸䛺䜛䜘䛖ᒆ䛡ฟ་⒪ᶵ㛵䛾ᇶ‽ᥦ♧ 㐃ᦠᙉ໬ ಖ೺ᡤ䛿ᬑཬၨⓎ䛾ᣐⅬ䛸䛧䛶䛾᝟ሗⓎಙᶵ⬟䛾ᙉ໬䜢ᅗ䜛

ឤᰁ⑕Ⓨ⏕ືྥㄪᰝ஦ᴗ䛾㊃᪨┠ⓗ Ⓨ⏕᝟ሗ䛾ṇ☜䛺ᢕᥱ䛸ศᯒ䚸䛭䛾⤖ᯝ䛾ᅜẸ䜔་⒪㛵ಀ⪅䜈䛾ⓗ☜䛺ᥦ౪䞉බ㛤䛻䛴䛔䛶䞉䞉యไ䜢ᵓ⠏䛧䛶䜖䛟
ᐇ᪋せ⥘

―８５―

Ⓨ⏕᝟ሗ䛾ṇ☜䛺ᢕᥱ䛸ศᯒཱྀ⭍䜢௓䛧䛶䛾ឤᰁືྥ䛾ᢕᥱᣦ㔪䛿ᛶឤᰁ⑕䜢ྲྀ䜚ᕳ䛟≧ἣ䛾ኚ໬䜢㋃䜎䛘
ぢ┤䛧䚸䛂ཱྀ⭍➼䜢௓䛧䛯ឤᰁ䛃䛜㏣ຍ䚹䠭䠊㈗⮬἞య䛷䛿ཱྀ⭍䜢௓䛧䛯ᛶឤᰁ⑕䛾ືྥᢕᥱ䛾ᚲせᛶ䜢ឤ䛨䜎䛩䛛
32
0%

48
20%

ᚲせᛶឤ䛨䛺䛔

38

5

60%

80%

100%

ุ᩿䛷䛝䛺䛔

ឤ䛨䜛

40%

―８６―

NA

ཱྀ⭍䜢௓䛧䛶䛾ឤᰁືྥ䛾ᢕᥱ䠭䠊ཱྀ⭍䜢௓䛧䛯ဗ㢌䛾ᛶឤᰁ⑕䛾ᢕᥱ䛾䛯䜑䛻䚸ᛶឤ
ᰁ⑕ᐃⅬ་⒪ᶵ㛵䛻⪥㰯⛉䜢㏣ຍ䛩䜛䛣䛸䛻
2 5

74

0%

20%

17

40%

60%

10

80%

100%

཯ᑐ

䛹䛱䜙䛛䛸ゝ䛘䜀཯ᑐุ᩿䛷䛝䛺䛔

䛹䛱䜙䛛䛸ゝ䛘䜀㈶ᡂ

㈶ᡂ

NA

H25ᖺᗘㄪᰝ
77䠭䠊ᑐ⟇䛻ά⏝䛷䛝䜛ᐃⅬ་⒪ᶵ㛵䛾ᣦᐃ䛻䛴 0%20%40%⌧ᅾ䛾ᣦᐃ䛷ၥ㢟䛺䛔䛔䛶᳨ウ䜢⾜䛔䜎䛧䛯௒ᚋ᳨ウணᐃ
䛛䚹

60%

5

80%

100%

ၥ㢟䛒䜛䛜᳨ウ䛧䛶䛔䛺䛔᳨ウ䛧䛯ᐃⅬ་⒪ᶵ㛵䛾ᣦᐃ䛾ᇶ‽ලయⓗ䛻♧䛩H䠎䠐ᨵゞᣦ㔪ᐃⅬ་⒪ᶵ㛵䛾㑅ᐃ᪉ἲ䛻䛴䛔䛶

೺ឤⓎ0301➨䠏ྕH24ᖺ3᭶1᪥
 ㊃᪨

ᛶឤᰁ⑕䛻䛴䛔䛶䛿䚸୍㒊䛾་⒪ᶵ㛵䛻ᝈ⪅䛜㞟୰䛩䜛ഴྥ䛜䛒䜛䛣䛸䛛䜙䚸་⒪ᶵ㛵䛾ᢳฟ䛾೫䜚䛻䜘䜛᥎ィ䛾㐣ᑠ䡡㐣኱ホ౯䛻୍ᒙ䛾␃ព䛜ᚲせ䛷䛒䜛デ⒪⛉䞉་⒪ᶵ㛵䛾✀ูẖ䛾ᐇ㝿䛾་⒪ᶵ㛵ᩘ䜢཯ᫎ䛩䜛䜘䛖䚸ྍ⬟䛺㝈䜚ᒙ໬䛧䛶ᢳฟ䛩䜛⏘፬ே⛉⣔䛸Ἢᒀჾ⛉⣔䚸⑓㝔䛸デ⒪ᡤ 㛗ᮇ䛻䜟䛯䛳䛶ሗ࿌䛜䛺䛔ᐃⅬ䚸ぢ┤䛧䜢᳨ウ

―８７―ᐃⅬ་⒪ᶵ㛵䛾タᐃ
་ᖌ఍䛻౫
㢗
⾜ᨻ䛜㑅ᐃ

1
24

40

39

9



་ᖌ఍䛸⾜
ᨻ䛷ㄪᩚ
䛭䛾௚

H25ᖺᗘㄪᰝ
ᛶឤᰁ⑕䛾ᐃⅬ་⒪ᶵ㛵䜢ᖹᡂ25ᖺᗘ䛻ኚ᭦䛧䜎䛧䛯
䛛

ኚ᭦䛧 䛯

15

3

98

NA

ኚ᭦䛧
䛶䛔䛺䛔
↓ᅇ⟅



ኚ᭦⌮⏤
䜔䜐䜢ᚓ䛪䛜᭱ከ⮬἞య⊂⮬䛾ᢕᥱ䛾ྲྀ䜚⤌䜏䠭䠊⮬἞య⊂⮬䛻䚸ᢕᥱ⑌ᝈ䛾✀㢮䜢ቑ䜔䛩䚸ሗ
࿌་⒪ᶵ㛵䜢ቑ䜔䛩䚸⮫᫬䛾ヲ⣽ㄪᰝ䜢⾜䛖䛺䛹ከᵝ䛺᪉ἲ䛷ືྥ䜢ᢕᥱ䛧䛶䛔䜛౛䛜䛒䜚䜎䛩䠄୕㔜┴䜔ᮾி㒔䛺䛹䠅䚹㈗⮬἞య䛿ᛶឤᰁ⑕䛾ືྥᢕᥱ䛾䛯䜑䛾㏣ຍ䜔ኚ᭦䛜䛒䜚䜎䛩䛛 䛒䜛 10⮬἞య㠀䜽䝷䝭䝆䜰㠀᾿⳦ᛶᒀ㐨⅖䚸┴ෆ඲་⒪ᶵ㛵䜢ᑐ㇟䛻ㄪᰝ䚸ᐃⅬ་⒪ᶵ㛵䛾㏣ຍ

―８８―ⓗ☜䛺ᥦ౪䞉බ㛤䛻䛴
䛴䛔䛶
యไ䜢
䜢ᵓ⠏

ᱵẘሗ࿌䛾ቑຍ䜈䛾ᑐᛂ ㏆ᖺ䛾ᱵẘ䛾ቑຍ䜢㋃䜎䛘ዷፎྍ⬟ᮇ䛾ዪᛶྥ䛡䛻ᱵẘ䛾ၨⓎ䜢᪂䛯䛻⾜䛳䛶䛔䜛䛛䠛

0%

20%

40%

⾜䛳䛶䛔䛺䛔

60%

௨๓䛛䜙⾜䛳䛶䛔䜛ᱵẘቑຍ䛻䛴䛔䛶䛾᳨ウ

39

0%

80%

10%

20%

᪂䛯䛻⾜䛳䛯

1130%ቑຍ䛧䛶䛔䛺䛔

40%

58

50%

᳨ウணᐃ

―８９―

100%

60%

70%

5

80%

ቑຍ䛧䛶䛔䜛

90%

100%

NA

ᱵẘሗ࿌䛾ቑຍ䜈䛾ᑐᛂ䠭䠊ᱵẘሗ࿌䛻㛵䛧䛶㏣ຍ᝟ሗ䜢ᚓ䜛䛯䜑䛻ၥ䛔ྜ䜟䛫䛯஦䛜
䛒䜛 41%䠄46⮬἞య䠅 䛭䛾ᑐ㇟䚸ෆᐜ䠖ඛኳᱵẘ7,ዷ፬8,ᑠඣ3,䛭䛾௚䛾ᕼᑡ䠋ᑐᛂ䛾᳨ウ䛜ᚲせ䛸ᛮ䜟䜜䛯౛7,ሗ࿌౛䛾ቑຍ䛻㛵㐃䛧䛶4,䛭䛾௚32䠄௚䛻ឤᰁ䛥䛫䛶䛔䛺䛔䛛☜ㄆ䛾䛯䜑䚸ᒆฟᇶ‽䜢‶䛯䛩䛛ุ᩿䛩䜛䛯䜑䠅
䠭䠊௚䛾STD䛾ၥ䛔ྜ䜟䛫䜢⾜䛳䛯஦䛜䛒䜛 45%䠄51⮬἞య䠅䠭䠊䜰䜴䝖䝤䝺䜲䜽䛾ᢕᥱ 䛒䜛 14%䠄16⮬἞య䠅ᱵẘ12䚸Aᆺ⫢⅖䠍

STD䛻㛵䛩䜛⑓ཎయ䛾ᢕᥱ䠭䠊⑓ཎయᐃⅬ䛻ᛶឤᰁ⑕䜢デ᩿䛩䜛་⒪ᶵ㛵䜢㏣ຍ䛩䜛ᚲせᛶ䜢ឤ䛨䜎䛩䛛
4

14

26

ᚲせᛶឤ䛨䛺䛔
ุ᩿䛷䛝䛺䛔
ឤ䛨䜛
NA

69

―９０―

ᆅ᪉⮬἞య䛻䛚䛡䜛STDᑐ⟇ᢸᙜ⪅䛾⫋✀䛸ᢸᙜᖺᩘ
ே 70

ே

60

70
60

50

50

40

40

30

64

0

34

30

20
10

58

20
16 11

8

8

10
2

2

17
3

0

⤖ㄽ
 ඲ᅜ⮬἞య䛾STDᑐ⟇ᢸᙜ⪅䜢ᑐ㇟䛻ㄪᰝ䛧䛯⤖ᯝ䚸ᣦ㔪䛻䛒䜛ཱྀ⭍䜢௓䛧䛯ឤᰁ䛻䛴䛔䛶ᢕᥱయไ䜢ኚ᭦䛧䛯⮬἞య䛿ᑡ䛺䛔䚹୍᪉䛷䚸඲ᩘㄪᰝ䛺䛹⊂⮬ྲྀ䜚⤌䜏䜢⾜䛖⮬἞య䜒䛒䜛䚹 ᱵẘ䜰䜴䝖䝤䝺䜲䜽䛾ᢕᥱ䚸ቑຍ䜈䛾ᑐᛂ䜔ၨⓎ䛜⾜䜟䜜䛶䛔䛯䚹 ᢸᙜ⪅䛾⤒㦂ᖺᩘ䛿▷䛟䚸ಖ೺ᖌ➼䛾⫼ᬒ䜢ά䛛䛧䛯㛵ಀᶵ㛵䜔௚⮬἞య➼䛸䛾᝟ሗ஺᥮䜔ⓗ☜䛺᝟ሗᢕᥱ䛸ຠᯝⓗ䛺㑏ඖ䛾䛯䜑䛾యไ䛾඘ᐇ䛜ᮇᚅ䛥䜜䜛䚹

―９１―

Exploring spao-temporal trendsof HIV/STI

Syphilis in Japan

Tomoki Nakaya, MSc, PhD
Professor, Department of Geography,
Ritsumeikan University, Japan
Research seminar on “Analysing geographic informaon
on STIs and sexual health”,
HIV/STI Department, Public Health England
12 Feb 2014

Geographic reference of thesurveillance data
HIV/AIDS• Reporting prefecture anddistrict: based on the locationof reporting clinics/hospitals• Living prefecture (from 2006)
Syphilis• Only reporting prefectureand district―９２―

47 Prefectures
ctures552 HealtheCentreDistrictts inDistricts
2013Annual trends of reported儴兠儥兇兠儬ซ౛
syphilis cases (perpopulaon)ᱵẘᖺ㛫ሗ࿌ᩘ凚୧ᛶ凛᥎⛣傍凚䢴䢲䢳䢲ᖺ⥲ேཱྀ储僅by prefecture, 2006-2013
30 per million
Total number of984
newly reported cases
622
523 497521

217 168

Miyagi

650 692 men

women

347
158 198

2006 2013183
124 177

236

Osaka

2006 2007 2008 2009 2010 2011 2012 2013

Men

Women

Tokyo

Fukuoka

Okinawa

Cartogram of syphilis SIR (Bayesian esmates),men, 2013
Hyper-endemic districts
Kita, Osaka
RR = 43.2

Shinjuku, Tokyo
RR = 67.9

1

8.

+
.1

.0
-8

1
4.

0

.0
-4

1
2.

Area x height = volume(pop) x (risk) = (incidence)

16

.0
-2

1
1.

6.

.0
-1

6
0.

-1

.5
-0
0
0.

ซ౛

―９３―

Comparison between sexes, syphilis
SIR (Bayesian esmates), 2013
men

Sendai, Miyagi
ซ౛

1

8.

+
.1

.0
-8

1
4.

0

.0
-4

1
2.

Cartogram The areal size is
proportional to the regional
population size

16

.0
-2

1
1.

6.

.0
-1

6
0.

-1

.5
-0
0
0.

women

Conclusion• In recent years, rapid increases in newly diagnosed syphilis cases
have been observed by the naonal surveillance system in Japan.
• Mapping the surveillance data suggested the existence of areas
with extremely high syphilis incidence rates in Japan, 2013.
– Shinjuku in Tokyo and Kita & Chuo in Osaka: possibly sustained byregional concentraon of MSM populaon and large agglomeraonof nightlife districts.
– Sendai in Miyagi: ‘rebuilding bubble’ eﬀects on increased heterosexual infecon?
GIS-based disease mapping should be beneficial for enhancing the valueof the surveillance data.

• Caveats: the following aspects need further aenons– Regional diﬀerences in age and mode of infecon– Reporng regions are not residenal regions– Eﬀects of late diagnosis and under-reporng

―９４―

―９５―

〈別添２〉

ᆅ᪉ឤᰁ⑕᝟ሗ䝉䞁䝍䞊䛻䛚䛡䜛
SIT䝃䞊䝧䜲䝷䞁䝇䛾㐠⏝䛾⌧≧බ⾗⾨⏕᝟ሗ◊✲༠㆟఍◊✲఍
ᖹᡂ28ᖺ
ᖺ1᭶
᭶29᪥
᪥

ᶓ὾ᕷ᪫༊⚟♴ಖ೺䝉䞁䝍䞊㧗㔝 䛴䜛௦

ㄪᰝᑐ㇟䛸ᅇ⟅⋡㒔㐨ᗓ┴47䜹ᡤ ᕷ28䜹ᡤ ィ75䜹ᡤ㏦௜
55䛛ᡤᅇ⟅(ᅇ⟅⋡73䠂䠅

―９６―

ឤᰁ⑕䝃䞊䝧䜲䝷䞁䝇䛾᰿ᣐἲ௧• ឤᰁ⑕ἲ ➨୕❶ ឤᰁ⑕䛻㛵䛩䜛᝟ሗ䛾཰㞟䛚䜘䜃බ⾲
➨༑஧᮲䠄་ᖌ䛾ᒆฟ䠅 ➨༑୕᮲䠄⋇་ᖌ䛾ᒆฟ䠅➨༑ᅄ᮲䠄Ⓨ⏕ືྥ䛾ᢕᥱ䠅 ➨༑஬᮲䠄ㄪᰝ䠅➨༑භ᮲䠄බ⾲䠅• ឤᰁ⑕Ⓨ⏕ືྥㄪᰝせ⥘㊃᪨䞉┠ⓗ䠖
ឤᰁ⑕Ⓨ⏕᝟ሗ䛾ṇ☜䛺ᢕᥱ䛸ศᯒ⤖ᯝ䛾ᅜẸ䜔་⒪㛵ಀ⪅䜈䛾ⓗ☜䛺ᥦ౪䞉බ㛤ᐃⅬ䛾㑅ᐃ䠗⏘፬ே⛉䚸⓶⭵⛉䚸Ἢᒀჾ⛉䚸ᛶ⑓⛉⟶ෆேཱྀ 䡚7.5୓ே䛆䝊䝻䛇
7.5୓ே䡚䛆䠍䠇(ேཱྀ䞊7.5୓ே/13୓ே䠅ᛶឤᰁ⑕䛾㢮ᆺ• ஬㢮ឤᰁ⑕䠖୍ 䜲䞁䝣䝹䜶䞁䝄䠄㫽䚸᪂ᆺ䜢㝖䛟䠅஧ 䜴䜲䝹䝇ᛶ⫢⅖䠄Eᆺ䚸Aᆺ䜢㝖䛟䠅୕ 䜽䝸䝥䝖䝇䝫䝸䝆䜴䝮⑕ᅄ ᚋኳᛶච␿୙඲⑕ೃ⩌஬ ᛶჾ䜽䝷䝭䝆䜰ឤᰁ⑕
භ ᱵẘ
୐ 㯞⑈
ඵ 䝯䝏䝅䝸䞁⪏ᛶ㯤Ⰽ䝤䝗䜴⌫⳦ឤᰁ⑕஑ ཌປ┬௧䛷ᐃ䜑䜛䜒䛾䠄᪋⾜つ๎䛷つᐃ䠅䠄ᛶᛶჾ䝦䝹䝨䝇䜴䜲䝹䝇ឤᰁ⑕䚸ᑤᆂ䝁䞁䝆䝻䞊䝬䚸᾿⳦ឤᰁ⑕➼䠅

―９７―ᛶឤᰁ⑕䛾≉ᐃឤᰁ⑕ண㜵ᣦ㔪䊠ཎཎᅉ✲᫂䠄ᚲせ䛺ㄪᰝ䚸Ⓨ⏕ືྥㄪᰝά⏝䚸㛵ಀᶵ㛵䛸㐃ᦠ➼䠅

䊡ⓎⓎ⏕ண㜵䞉䜎䜣ᘏ୰Ṇ䠄ⱝ⪅ᒙ䜢୰ᚰ䛻ᬑཬၨⓎ䚸䝁䞁䝗䞊䝮䛾ண㜵ຠᯝ䛾ᬑཬၨⓎ䚸᳨ᰝ䛾᥎ዡ䛸᳨ᰝᶵ఍䛾ᥦ౪䠅䊢 ་⒪యไ䠄㉁䚸䜰䜽䝉䝇ྥୖ䠅䊣 ◊✲㛤Ⓨ䛾᥎㐍䠄᳨ᰝ䚸἞⒪䚸Ⓨ⏕ືྥ䚸♫఍་Ꮫ㠃䛾ᛶ䛾⾜ືᵝᘧ➼䠅䊤 ᅜ㝿ⓗ㐃ᦠ䊥 㛵ಀᶵ㛵䛸䛾㐃ᦠ

STI᝟ሗ㑏ඖ≧ἣ• ᝟ሗ㑏ඖ95䠂᭷䜚53௳ / ↓䛧2௳
• 93䠂䛿ᐃᮇ㑏ඖ (51௳䠅
ᐃᮇ䛾䜏
ᐃᮇ䞉⮫᫬
• 29䠂䛿⮫᫬㑏ඖ (16௳)⮫᫬䛾䜏↓ᅇ⟅㒔┴ 10௳ / ᕷ 䠒௳31ᱵẘ䚷㻴㻵㼂
ᱵẘ䚷
㻴㻵㼂
ᐃⅬ
㐺ᐅ
↓グ㍕

㻢
㻟
㻞
㻝
㻟
㻝

15

36

―９８―

ᐃᮇ᝟ሗ

䈜 ⚟♴᪋タ䛿䚸ಖ⫱ᅬ䜔௓ㆤಖ㝤᪋タ䛭䛾௚䛿䚸Web䜔䝯䞊䝸䞁䜾䝸䝇䝖䛷ᗈ䛟ᥦ౪ ➼ᱵẘ䛾⮫᫬ሗ䜢ฟ䛧䛯㒔┴―９９―

ᆅ⾨◊ 䖩 ୺⟶ㄢᱵẘ䛸HIV䛾10ᖺ㛫䛾᥎⛣䈜2015ᖺ䛿ᬻᐃ್ຠᯝⓗ䛺᝟ሗ㑏ඖ䠛 ᆅ⌮ⓗ᝟ሗ䠄ᮍ䛰೫ᅾ䠛䠅
ሗ࿌ᩘ10ே
ே௨ୖ䛾ಖ೺ᡤᩘ䛸ሗ࿌ᩘྜ⟬

―１００―

10ᖺ
ᖺ㛫䛷䛾ሗ࿌ᩘቑຍಸ⋡䠄┴༢఩䠅

2015ᖺᱵẘᒆฟᩘ⏨ዪẚᒆฟᩘᖺ㛫30௨ୖ䛾㒔㐨ᗓ┴2006ᖺᱵẘ䛾ᖺ㱋ᒙูሗ࿌ᩘ

―１０１―

2015ᖺ

ຠᯝⓗ䛺᝟ሗ㑏ඖ䠛 ᛶ䞉ᖺ௧せ⣲ᱵẘ䛾10ᖺ㛫䛾ᖺ௧ᒙෆヂHIV䛾10ᖺ㛫䛾ෆヂ

⮫᫬᝟ሗ

⮫᫬᝟ሗ
⸆๣ᖌ
᳨ᰝᢏᖌ
⋇་ᖌ
ಖ೺ᖌ
⾨⏕┘ど

―１０２―

㻡
㻡
㻞
㻞
㻞

✚ᴟⓗ␿Ꮫㄪᰝ
୍㒊⾜䛳䛶䛔䜛ᆅ⾨◊䛿䠔䜹ᡤ䛾䜏஦ົ ་⒪䛻䛴䛺䛔䛰䛛⋇་ᖌ ឤᰁ◊䛛䜙䛾ᣦ♧┴ ᳨ᰝᢏᖌ ⱝᖺ㻛䝟䞊䝖䝘䞊᳨デ⸆๣ᖌ 㻴㻵㼂ᐇ᪋ಖ೺ᡤ
᳨ᰝᢏᖌ ಖ೺ᡤಖ೺ᖌ 㻴㻵㼂䚸ᱵẘ➼ᕷ ಖ೺ᖌ ⱝᖺ஦ົ ឤᰁ◊䛛䜙䛾ᣦ♧㞟ᅋⓎ⏕/䜰䜴䝖䝤䝺䜲䜽䛾ᢕᥱ• ᥈▱䛾ዎᶵ䝃䞊䝧᝟ሗ᝟ሗ䛆་⒪ᶵ㛵➼䛇
㏻▱䛆ᅜ➼䛇
䛭䛾௚
ᱵẘ
ᱵẘ➼
⣽⳦ᛶ㉥⑩
㻭ᆺ⫢⅖

―１０３―

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ᛶჾ䝦䝹䝨䝇䛻䛴䛔䛶䝦䝹䝨䝇䛾ᑐ㇟䛜ึឤᰁ▱䛳䛶䛔䛯㻞㻤▱䜙䛺䛛䛳䛯
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㒔㐨ᗓ┴ูᐃⅬሗ࿌ᩘ(2014ᖺ䠅• ᛶჾ䝦䝹䝨䝇௨እ䛿኱యືྥ䛿୍⮴䛧䛶䛔䜛―１０４―ᛶჾ䝦䝹䝨䝇䛸௚ᐃⅬ䠏⑌ᝈ䛾ᖺ௧ᒙẚ㍑⪏ᛶ⳦䛻䛴䛔䛶䠄᾿⳦䠅hp://idsc.nih.go.jp/iasr/31/362/kj3624.html
㧗ᗘ⪏ᛶ᾿⳦
▱䛳䛶䛔䛯㻞㻞▱䜙䛺䛛䛳䛯 㻟㻞↓ᅇ⟅㻝㻿㼀㻵⑓ཎయᐃⅬ䛾᪂タ㈶ᡂ
䛹䛱䜙䛛䛸ゝ䛘䜀㈶ᡂ
཯ᑐ䛹䛱䜙䛛䛸ゝ䛘䜀཯ᑐุ᩿䛷䛝䛺䛔
↓ᅇ⟅

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ṇ☜䛺᝟ሗᢕᥱ䛾䛯䜑⌧≧䜢ᢕᥱ䛷䛝䜛㼄㻞㈶ᡂ
㔜⑕໬㜼Ṇ䛾䛯䜑
᝟ሗᢕᥱ䛧䛯᪉䛜Ⰻ䛔཯ᑐ䝁䝇䝖䝟䝣䜷䞊䝬䞁䝇୺⟶ㄢ➼䛾ุ᩿
ண⟬䞉ேဨ䞉ἲ௧ᩚഛ⌧≧䛷䛿᳨ᰝ䛧䛶䜒↓⟇ண⟬䞉ேဨ୙㊊㼄㻞ุ᩿䛷䛝䛺䛔 ᳨య☜ಖᅔ㞴་⒪ᶵ㛵䛾☜ಖඃඛ㡰఩ప䛔
་⒪ᶵ㛵䞉ಖ೺ᡤ䛾䛤㒔ྜ㞴἞ᛶ᾿⳦䛾⌧≧୙᫂―１０５―ᅇ⟅⪅䛾ᒓᛶ

ᢸᙜᖺᩘ
㻞ᖺᮍ‶
㻞㻙㻠ᖺ
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䜎䛸䜑
• ᐃᮇ᝟ሗ䛾Ⓨಙ䛿䚸Ṥ䛹䛜⾜䛳䛶䛔䜛䛜• ⮫᫬᝟ሗ䛾Ⓨಙ䛜䚸ᆅ⾨◊䛷䝞䝷䝒䜻䛜䛒䛳䛯• ⱝᖺዪᛶᒙ➼䚸䝍䞊䝀䝑䝖䛻ྜ䜟䛫䛯᝟ሗⓎಙ䛜ㄢ㢟• 㛵ಀᶵ㛵䛸䛾㐃ᦠ䜒ㄢ㢟• ᛶឤᰁ⑕䛾ṇ䛧䛔཯ᫎ䛾㠃䛷䚸ᛶჾ䝦䝹䝨䝇䛿ㄢ㢟䛜䛒䜛• 㧗ᗘ⪏ᛶ᾿⳦䛾⑓ཎయᐃⅬ➼䚸⑌ᝈ䛾ὶ⾜䛻䜘䜛䛒䛯䜙䛧䛔యไ䜒ᚲせ䛛䠄䛭䛾㝿䛿䚸㒔㐨ᗓ┴୍ᚊ䛷䛿䛺䛟䚸ሗ࿌ᩘ䛾ከ䛔┴➼䛻㝈ᐃ䛩䜛䛛䠅

―１０６―

〈別添３〉

ᛶឤᰁ⑕䝃䞊䝧䜲䝷䞁䝇䛾㐠Ⴀ䛸⤖ᯝά⏝䛻㛵䛩䜛䜰䞁䜿䞊䝖⤖ᯝ䚷㻴㻞㻣ᖺ㻝㻞᭶ᐇ᪋䚷୺⟶ㄢྥ䛡䛂ᛶឤᰁ⑕䛻㛵䛩䜛≉ᐃឤᰁ⑕ண㜵ᣦ㔪䛻ᇶ䛵䛟ᑐ⟇䛾᥎㐍䛻㛵䛩䜛◊✲䛃㻔୺௵◊✲⪅䠖Ⲩᕝ㻌๰୍㻕ศᢸ◊✲䛂㻿㼀㻵䝃䞊䝧䜲䝷䞁䝇ᡓ␎䛃㻔ศᢸ◊✲⪅䠖୰℩ඞᕫ㻕

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㻞㻚㻌⾜䛳䛯ሙྜ䚸᝟ሗᥦ౪䛿ᐃᮇⓗ䛷䛩䛛䚸⮫᫬䛷䛩䛛䠄㻝㻚䛷䛂䛒䜛䛃䛸⟅䛘䛯ሙྜ䛾䜏䠅

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୧᪉

㻝㻜㻜㻑

㻟㻚㻌⾜䛳䛯ሙྜ䚸ឤᰁ⑕Ⓨ⏕ືྥㄪᰝ䛾≉ᛶ䜢⪃៖䛧䛶䛔䜎䛩䛛䠄㻝㻚䛷䛂䛒䜛䛃䛸⟅䛘䛯ሙྜ䛾䜏䠅㻟㻞㻝㻟⪃៖䛧䛶䛔䛺䛔

㻣⪃៖䛧䛶䛔䜛
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

㻠㻚㻌⮫᫬䛾᝟ሗᥦ౪ඛ䛻䛴䛔䛶䚷䛒䛶䛿䜎䜛䜒䛾඲䛶䛻䕿䜢䛴䛡䛶ୗ䛥䛔
㻞㻡
㻞㻜
㻝㻡
㻝㻜
㻡

㻞㻟

㻝㻤

㻝㻣
㻠

㻜

―１０７―

㻠

㻡㻚㻌㏆ᖺ䛾ᱵẘ䛾ቑຍ䜢㋃䜎䛘䚸ዷፎྍ⬟ᮇ䛾ዪᛶྥ䛡䛻ᱵẘ䛾ၨⓎ䜢᪂䛯䛻⾜䛳䛶䛔䜎䛩䛛⾜䛳䛶䛔䛺䛔㻤㻢㻠㻞㻞௨๓䛛䜙⾜䛳䛶䛔䜛㻝᪂䛯䛻⾜䛳䛯
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑
௨๓䛛䜙⾜䛳䛶䛔䜛䚸䛛䛴᪂䛯䛻⾜䛳䛯㻢㻚㻌㈗⮬἞య䛿ᛶឤᰁ⑕䛾ືྥᢕᥱ䛾䛯䜑䛾㏣ຍ䜔ኚ᭦䛜䛒䜚䜎䛩䛛
㻝㻜㻟

䛺䛔

㻝㻜

䛒䜛
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

䠘ᛶឤᰁ⑕Ⓨ⏕ືྥㄪᰝά⏝䛾䛯䜑䛾䜺䜲䝗䝷䜲䞁䛻䛴䛔䛶䠚㻣㻚㻌ᖹᡂ㻞㻠ᖺᗘ䛾ᙜ◊✲⌜䛻䜘䜛䛂ᛶឤᰁ⑕Ⓨ⏕ືྥㄪᰝά⏝䛾䛯䜑䛾䜺䜲䝗䝷䜲䞁䛃䜢䛤Ꮡ▱䛷䛩䛛
▱䜙䛺䛔
㻢㻤

㻠㻞

㻝㻝㻝

㻤㻜㻑

㻝㻜㻜㻑

▱䛳䛶䛔䜛䛜ᮍά⏝▱䛳䛶䛔䛶ά⏝
䛭䛾௚

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

↓ᅇ⟅

㻤㻚㻌ཧ⪃䛻䛺䛳䛯グ஦䜢ᩍ䛘䛶ୗ䛥䛔䠄」ᩘᅇ⟅ྍ䠅
㻞㻜
㻝㻡
㻝㻜

㻝㻥
㻝㻞

㻡

㻝㻣
㻝㻜

㻝㻞

㻥
㻜

㻜

㻥㻚㻌䜺䜲䝗䝷䜲䞁䛻᭦䛻ຍ䛘䛯᪉䛜Ⰻ䛔ෆᐜ䛜䛒䛳䛯䜙ᩍ䛘䛶ୗ䛥䛔䠄⮬⏤グ㏙䠅
㻝
㻞
㻟

ಖ೺⚟♴㒊
ᒆฟᇶ‽➼䛻䛴䛔䛶䛾ゎㄝᖺ௦ู䛛䜙䜏䛘䛶䛟䜛⑌ᝈ䛾≉ᚩ䛺䛹

―１０８―

㻟

䠘✚ᴟⓗ␿Ꮫㄪᰝ䛻䛴䛔䛶䠚㻝㻜㻚㻌ᱵẘሗ࿌䛻㛵䛧䛶䚸㏣ຍ᝟ሗ䜢ᚓ䜛䛯䜑䛻་⒪ᶵ㛵䛻ၥ䛔ྜ䜟䛫䛯஦䛜䛒䜚䜎䛩䛛᳨ウ㻛ᐇ᪋䛸䜒䛻䛺䛔
㻢㻣
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻜

㻠㻢

㻢㻜㻑

㻤㻜㻑

᳨ウ䛧䛯䛜ᐇ᪋䛿䛺䛔
㻝㻜㻜㻑

䛒䜛

㻝㻝㻚䚷䛭䛾ᑐ㇟䠋ෆᐜ䛿௨ୗ䛾䛹䜜䛻ᙜ䛯䜚䜎䛩䛛䠄㻝㻜㻚䛷䛂䛒䜛䛃䛸⟅䛘䛯ሙྜ䛾䜏䚸」ᩘᅇ⟅䠅
㻟㻡
㻟㻜
㻞㻡
㻞㻜
㻟㻞

㻝㻡
㻝㻜
㻡

㻤

㻣

㻣

㻟

㻠

㻜

㻝㻞㻚㻌⥲ㄪᰝ౛ᩘ䛿ఱ௳䛷䛩䛛䠄㻝㻜㻚䛷䛂䛒䜛䛃䛸⟅䛘䛯ሙྜ䛾䜏䠅
㻝௳
㻣

㻞㻝

㻢

㻞㻙㻡௳

㻤

㻢㻙㻥௳
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

㻝㻜௳௨ୖ

㻝㻟㻚㻌ୖグ䛾་⒪ᶵ㛵䜈䛾ၥ䛔ྜ䜟䛫䛿䚸ឤᰁ⑕ἲ䠍䠑᮲䛻䜘䜛✚ᴟⓗ␿Ꮫㄪᰝ䛸ぢ䛺䛧䛶䛔䜎䛩䛛䚷䚷䚷䠄㻝㻜㻚䛷䛂䛒䜛䛃䛸⟅䛘䛯ሙྜ䛾䜏䠅඲䛶䜏䛺䛧䛶䛔䜛
㻞㻡

㻠

㻣

㻥

㻝

୍㒊䜏䛺䛧䛶䛔䜛
඲䛶䜏䛺䛧䛶䛔䛺䛔ุ᩿䛧䛶䛔䛺䛔

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻝㻠㻚㻌ᱵẘ௨እ䛾ᛶឤᰁ⑕㻔㻴㻵㼂㻘㻮㻛㻭ᆺ⫢⅖㻘㉥⑩➼㻕䛻䛴䛔䛶་⒪ᶵ㛵䜈ၥ䛔ྜ䜟䛫䜢⾜䛳䛯஦䛜䛒䜚䜎䛩䛛᳨ウ䠋ᐇ᪋䛸䜒䛻䛺䛔
㻡㻡

㻞

㻡㻝

㻡

᳨ウ䛧䛯䛜ᐇ᪋䛿䛺䛔
䛒䜛

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

―１０９―

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻝㻡㻚㻌ᛶឤᰁ⑕䛾㏣ຍㄪᰝ䛜⾜䜟䜜䜛䛯䜑䛻᭷ຠ䛸ᛮ䜟䜜䜛ྲྀ䜚⤌䜏䛾䠍఩䛻䖂䜢䚸௚䛻䕿䜢䛴䛡䛶ୗ䛥䛔

㻝఩

㻢㻞

㻜㻑

㻝㻜

㻞㻜㻑

㻠㻜㻑

㻡

㻤

㻠㻞

㻢㻜㻑

㻞㻞

㻤㻜㻑

㻡✀㢮౵くᛶឤᰁ⑕䛾䜘䛖䛺ᅜ䛛䜙䛾㏻▱◊✲⌜➼䛻䜘䜛ᑐ㇟䠋ෆᐜ䛻㛵䛩䜛䜺䜲䝗䝷䜲䞁་⒪ᶵ㛵䜢ᑐ㇟䛸䛧䛯␿Ꮫㄪᰝ䛻㛵䛩䜛ㄝ᫂䚸◊ಟᶵ఍
↓ᅇ⟅

㻝㻜㻜㻑

ᢸᙜ⫋ဨ䛾◊ಟᶵ఍ㄪᰝ䛾ᵝᘧ䜔
ㄝ᫂ᩥ᭩䛾᱌
䛭䛾௚

㻡㻜
㻠㻜
㻟㻜
㻠㻣

㻞఩௨ୗ 㻞㻜

䠄」ᩘᅇ⟅䠅

㻝㻜

㻞㻡
㻠

㻡

㻜

㻞㻤

㻝㻥

㻝㻢

䠘㞟ᅋⓎ⏕䞉䜰䜴䝖䝤䝺䜲䜽䛸㛵㐃ㄪᰝ䛻䛴䛔䛶䠚㻝㻢㻚㻌㈗⮬἞య䛷䛿ᱵẘሗ࿌䛾ቑຍ䛻䛴䛔䛶᳨ウ䛥䜜䜎䛧䛯䛛
㻟㻤
㻜㻑

㻞㻜㻑

㻝㻝
㻠㻜㻑

㻡㻤
㻢㻜㻑

㻝㻡
㻤㻜㻑

㻝㻜㻜㻑

ቑຍ䛧䛶䛔䛺䛔
ቑຍ䛾᭷↓䜢᳨ウணᐃቑຍ䛧䛶䛔䜛ᶓ䜀䛔↓ᅇ⟅㻝㻣㻚㻌ᛶ⾜Ⅽ䛻䜘䜛ឤᰁ⑕䠄ᱵẘ䚸㻭㻛㻮ᆺ⫢⅖䚸䜰䝯䞊䝞䞊㉥⑩䜔㻴㻵㼂ឤᰁ⑕➼䠅䛾㞟ᅋⓎ⏕䜔㏻ᖖ௨ୖ䛾ቑຍ䠄䜰䜴䝖䝤䝺䜲䜽䠅ཬ䜃䛭䛾␲䛔䜢ᖹᡂ㻞㻢ᖺ䠍᭶䛛䜙ᖹᡂ㻞㻣ᖺ㻝㻝᭶ᮎ䜎䛷䛾㛫ᢕᥱ䛧䛯䛣䛸䛜䛒䜚䜎䛩䛛ᢕᥱ䛧䛶䛔䛺䛔
㻥㻠

㻞

㻝㻢

㻝

୙᫂
ᢕᥱ䛧䛯

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

―１１０―

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻝㻤㻚㻌䛭䛾㝿䚸ఱ䜙䛛䛾ᑐᛂ䜢⾜䛔䜎䛧䛯䛛䠄䛔䛟䛴䛷䜒䕿䜢䠅
㻝㻡
㻝㻜
㻝㻝

㻡
㻠

㻝

㻠

㻜

㻜

䠘䝟䞊䝖䝘䞊ᑐᛂ䛻䛴䛔䛶䠚㻝㻥㻚㻌ಖ೺ᡤ䞉≉タ᳨ᰝ䛷䛾ᛶឤᰁ⑕䠄㻿㼀㻰䠅㻛㻴㻵㼂᳨ᰝ䛷㝧ᛶ䛸䛺䛳䛯ཷ᳨⪅䛻䚸䝟䞊䝖䝘䞊䜈䛾᝟ሗᥦ౪䜢䚷䚷౫㢗䛧䛶䛔䜎䛩䛛䠄㻝䠅㻿㼀㻰㝧ᛶ⪅
඲ဨ䛻່ዡ
㻢㻥

㻞㻝

㻠 㻡

୍㒊䛻່ዡ

㻝㻠

່ዡ䛧䛶䛔䛺䛔
୙᫂

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

䠄㻞䠅㻴㻵㼂㝧ᛶ⪅
඲ဨ䛻່ዡ
㻣㻢

㻞㻞

㻢

㻣 㻞

୍㒊䛻່ዡ
່ዡ䛧䛶䛔䛺䛔
୙᫂

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻞㻜㻚㻌䝟䞊䝖䝘䞊䜈䛾ཷ᳨່ዡ䜢౫㢗䛧䛶䛔䜎䛩䛛䠄㻝䠅㻿㼀㻰㝧ᛶ⪅
඲ဨ䛻່ዡ
㻢㻢

㻞㻟

㻢 㻠

୍㒊䛻່ዡ

㻝㻠

່ዡ䛧䛶䛔䛺䛔
୙᫂

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

䠄㻞䠅㻴㻵㼂㝧ᛶ⪅
඲ဨ䛻່ዡ
㻣㻠

㻞㻞

㻤

㻢 㻟

୍㒊䛻່ዡ
່ዡ䛧䛶䛔䛺䛔
୙᫂

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻞㻝㻚㻌່ዡ䛾㝿䛻㈨ᩱ䜢⏝䛔䛶䛔䜎䛩䛛
㻠
㻜㻑

㻝㻤

㻢㻜
㻞㻜㻑

㻠㻜㻑

㻞㻡
㻢㻜㻑

―１１１―

㻤㻜㻑

㻢
㻝㻜㻜㻑

䛿䛔㻔㻿㼀㻰㻕
䛿䛔㻔㻴㻵㼂㻕
䛿䛔䠄୧᪉䠅
䛔䛔䛘↓ᅇ⟅㻞㻞㻚㻌່ዡ䛾ᡭ㡰䜔せ㡿䜢ᐃ䜑䛶䛔䜎䛩䛛䛿䛔㻔㻿㼀㻰㻕
㻞

㻝㻟

㻞㻝

㻣㻞

䛿䛔㻔㻴㻵㼂㻕

㻠䛿䛔䠄୧᪉䠅
䛔䛔䛘

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻞㻟㻚㻌່ዡ䛾⤖ᯝ䚸䝟䞊䝖䝘䞊䛾ឤᰁ䛜ศ䛛䛳䛯౛䛜䛒䜚䜎䛧䛯䛛ᢕᥱ䛧䛶䛔䛺䛔
㻤㻟

㻝

㻞㻢

㻟

ឤᰁ౛䛜䛒䛳䛯
▱䜛㝈䜚䛷䛿䛺䛛䛳䛯

㻜㻑

㻞㻜㻑

㻠㻜㻑

ᢕᥱ౛ᩘ䠄ィ䠅䠖㻴㻵㼂ឤᰁ⑕
௚䛾ᛶឤᰁ⑕

㻞㻜௳
㻟㻡௳

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

䠘ᛶჾ䝦䝹䝨䝇䛻䛴䛔䛶䠚㻞㻠㻚㻌ᛶჾ䝦䝹䝨䝇䛾ືྥᢕᥱ䛾⥅⥆䛻䛴䛔䛶䛹䛾䜘䛖䛻䛚⪃䛘䛷䛩䛛

㻣

㻞㻝

㻜㻑

㻝㻞

㻞㻜㻑

㻣㻟

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

ᛶჾ䝦䝹䝨䝇䛾ᢕᥱ䛭䛾䜒䛾䜢෌᳨ウ䛩䜛㐠⏝䛾ᨵၿ䛿ᚲせ䛰䛜ᢕᥱ䛿⥅⥆䛩䜛⌧≧䜢ኚ᭦䛩䜛ᚲせ䛿ឤ䛨䛺䛔≉䛻᫂☜䛺ពぢ䛿䛺䛔㻞㻡㻚㻌ᛶჾ䝦䝹䝨䝇䛾ືྥ䜢㈗⮬἞య䛻䛚䛡䜛ᑐ⟇䛻ά䛛䛧䛯⤒㦂䛜䛒䜚䜎䛩䛛
㻝㻜㻥
㻜㻑

㻞㻜㻑

㻠

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

䛺䛔
䛒䜛

㻝㻜㻜㻑

䠘ᐃⅬ་⒪ᶵ㛵䛻䛴䛔䛶䠚㻞㻢㻚㻌ᐃⅬ་⒪ᶵ㛵䛿䚸䛹䛾䜘䛖䛻タᐃ䛧䛶䛔䜎䛩䛛་ᖌ఍䛻᱌䜢౫㢗
㻟㻥

㻥

㻠㻜

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻞㻠

㻝

⾜ᨻ䛜㑅ᐃ
་ᖌ఍䛸⾜ᨻ䛷ㄪᩚ
䛭䛾௚

㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

㻞㻣㻚㻌㈗⮬἞య䛷䛿ཱྀ⭍䜢௓䛧䛯ᛶឤᰁ⑕䛾ືྥᢕᥱ䛾ᚲせᛶ䜢ឤ䛨䜎䛩䛛
㻟㻞

㻞㻤

㻠㻤

↓ᅇ⟅
༊ศ䛧䛶ᢕᥱ䛩䜛ᚲせᛶ䛿ឤ䛨䛺䛔

㻡ឤ䛨䜛ุ᩿䛷䛝䛺䛔

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

―１１２―

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻞㻤㻚㻌ཱྀ⭍䜢௓䛧䛯ဗ㢌䛾ᛶឤᰁ⑕䛾ᢕᥱ䛾䛯䜑䛻䚸ᛶឤᰁ⑕ᐃⅬ་⒪ᶵ㛵䛻⪥㰯⛉䜢㏣ຍ䛩䜛䛣䛸䛻䛴䛔䛶
㻝㻜

㻝㻣

㻜㻑

㻞 㻡

㻞㻜㻑

㻣㻠
㻠㻜㻑

㻡

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

㈶ᡂ
䛹䛱䜙䛛䛸䛔䛘䜀㈶ᡂ཯ᑐ䛹䛱䜙䛛䛸䛔䛘䜀཯ᑐุ᩿䛷䛝䛺䛔
↓ᅇ⟅㻞㻥㻚㻌㈗⮬἞య䛷⪥㰯⛉ᐃⅬ䜢ᣦᐃ䛩䜛䛸䛧䛯䜙ྍ⬟䛷䛩䛛
ẚ㍑ⓗᐜ᫆
㻝

㻝㻢

㻝㻞

㻣㻥

㻡

ྍ⬟
ᅔ㞴
୙᫂

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻟㻜㻚㻌⑓ཎయᐃⅬ䛻ᛶឤᰁ⑕䜢デ᩿䛩䜛་⒪ᶵ㛵䜢㏣ຍ䛩䜛ᚲせᛶ䜢ឤ䛨䜎䛩䛛
ឤ䛨䜛
㻝㻠

㻞㻢

㻢㻥

㻠

᪂䛯䛻ᣦᐃ䛩䜛ᚲせᛶ䛿ឤ䛨䛺䛔ุ᩿䛷䛝䛺䛔
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

䠘ᛶឤᰁ⑕䛾᳨ᰝ䛻䛴䛔䛶䠚㻟㻝㻚㻌ಖ೺ᡤ䞉≉タ᳨ᰝ➼䛷䛾ᛶឤᰁ⑕᳨ᰝ䛻䛚䛔䛶ཱྀ⭍䛷䛾ឤᰁ䛻䛴䛔䛶᳨ᰝ䛧䛶䛔䜎䛩䛛᳨ᰝ䛧䛶䛔䛺䛔㻝㻜㻣㻝㻞 㻟᳨ᰝ䛧䛶䛔䛺䛔䛜ᐇ᪋᪋タ䜢⤂௓᳨ᰝ䛧䛶䛔䜛

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

䛭䛾௚

㻟㻞㻚㻌ᛶឤᰁ⑕᳨ᰝ䛿┤Ⴀ䛷䛩䛛䠄ᕷ䚸≉ู༊䛜㒔㐨ᗓ┴䛾⾨◊䛻ጤク䛩䜛஦䜒ྵ䜐䠅䚸ጤク䛷䛩䛛
┤Ⴀ
㻢㻞

㻟㻞

㻝㻜

㒊ศⓗ䛻ጤク

㻥

඲ᩘጤク
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

㻟㻟㻚㻌㻴㻵㼂௨እ䛾ᛶឤᰁ⑕᳨ᰝ䛻䛴䛔䛶䚸⤖ᯝ䜢⪺䛝䛻᮶䛺䛔䛣䛸➼䛻䜘䜛ᮍ㏉༷䛾๭ྜ䛿䛹䜜䛟䜙䛔䛷䛩䛛
㻞㻠
㻜㻑

㻠㻣
㻞㻜㻑

㻠㻜㻑

㻞
㻢㻜㻑

㻝㻥

㻞

㻝㻤

㻤㻜㻑

㻝㻜㻜㻑

䜋䜌㻜㻑
㻝๭ᮍ‶
㻝㻙㻞๭
㻞㻙㻟๭
㻟๭௨ୖ
↓ᅇ⟅

㻟㻠㻚㻌་⒪ᶵ㛵䛻ᛶឤᰁ⑕䛾᳨ᰝᐇ᪋䜢ጤク䛧䛶䛔䜎䛩䛛
㻥㻜
㻜㻑

㻞㻜㻑

㻠㻜㻑

㻣
㻢㻜㻑

―１１３―

㻤㻜㻑

㻤

㻣 㻝
㻝㻜㻜㻑

ጤク䛧䛶䛔䛺䛔
㻴㻵㼂䜢ጤク㻴㻵㼂௨እ䛾ᛶឤᰁ⑕䜢ጤク㻴㻵㼂ཬ䜃௚䛾ᛶឤᰁ⑕䜢ጤク↓ᅇ⟅䠘䛤ᅇ⟅⪅䛸ᡤᒓ䛻䛴䛔䛶䠚㻟㻢㻚㻌⫋✀

㻤

㻤

㻜㻑

㻝㻝

㻝㻢

㻞㻜㻑
⸆๣ᖌ

㻢㻝

㻠㻜㻑

⋇་ᖌ

᳨ᰝᢏᖌ

㻢㻜㻑
஦ົ

㻟 㻞 㻟㻝

㻤㻜㻑

ಖ೺ᖌ

┳ㆤᖌ

㻝㻜㻜㻑
་ᖌ

䛭䛾௚

↓ᅇ⟅

㻟㻣㻚㻌㻞㻣ᖺᗘᮎ䛷䛾ᛶឤᰁ⑕ᢸᙜᖺᩘ
㻞ᖺᮍ‶
㻡㻤

㻟㻠

㻝㻣

㻟㻝

㻞㻙㻠ᖺ
㻡㻙㻥ᖺ
㻝㻜ᖺ௨ୖ

㻜㻑

㻞㻜㻑

㻠㻜㻑

㻢㻜㻑

―１１４―

㻤㻜㻑

㻝㻜㻜㻑

↓ᅇ⟅

〈別添４〉

ᛶឤᰁ⑕䝃䞊䝧䜲䝷䞁䝇䛾㐠Ⴀ䛸⤖ᯝά⏝䛻㛵䛩䜛䜰䞁䜿䞊䝖⤖ᯝ䚷㻴㻞㻣ᖺ㻝㻞᭶ᐇ᪋䚷ឤᰁ⑕᝟ሗ䝉䞁䝍䞊ྥ䛡䛂ᛶឤᰁ⑕䛻㛵䛩䜛≉ᐃឤᰁ⑕ண㜵ᣦ㔪䛻ᇶ䛵䛟ᑐ⟇䛾᥎㐍䛻㛵䛩䜛◊✲䛃㻔୺௵◊✲⪅䠖Ⲩᕝ㻌๰୍㻕ศᢸ◊✲䛂㻿㼀㻵䝃䞊䝧䜲䝷䞁䝇ᡓ␎䛃㻔ศᢸ◊✲⪅䠖୰℩ඞᕫ㻕

䚷ᐇ᪋⪅

ᅇ⟅๭ྜ
඲య
༊ศู

≉ู༊,
0, 0%

ಖ೺ᡤタ
⨨ᕷ, 3,
6%㓄ᕸᩘ ヱᙜᩘ ᅇ⟅ᩘ ᅇ⟅๭ྜ
㻣㻤
㻣㻝
㻡㻡
㻣㻣㻚㻡㻑
㒔㐨ᗓ┴
㻠㻤
㻠㻢
㻟㻤
㻤㻞㻚㻢㻑
ᣦᐃ㒔ᕷ
㻝㻥
㻝㻥
㻝㻠
㻣㻟㻚㻣㻑
ಖ೺ᡤタ⨨ᕷ
㻥
㻢
㻟
㻡㻜㻚㻜㻑
≉ู༊
㻞
㻜
㻜
㻙

ᣦᐃ㒔
ᕷ, 14,
25%
㒔㐨ᗓ┴, 38,69%ྛタၥ䠘䝃䞊䝧䜲䝷䞁䝇᝟ሗ䛾㑏ඖ≧ἣ䛻䛴䛔䛶䠚㻝㻚㻌ᛶឤᰁ⑕䛾ືྥ䠄ᩘ್䚸䜾䝷䝣䠅䛚䜘䜃ホ౯䞉䝁䝯䞁䝖䜢㑏ඖ䛧䛶䛔䜎䛩䛛䠛ᡈ䛔䛿䛧䛯஦䛜䛒䜚䜎䛩䛛㑏ඖ䜢⾜䛳䛶䛔䜛䠋⾜䛳䛯䛣䛸䛜䛒䜛
53

0%

20%

20

40%

60%

80%

㑏ඖ䛧䛶䛔䛺䛔
ุ䜙䛺䛔

100%㻞㻚㻌㑏ඖ䛿䚸ᐃᮇⓗ䛻⾜䛳䛶䛔䜎䛩䛛䠛⮫᫬䛷䛩䛛䠛୧᪉䛷䛩䛛䠛䚷
ᐃᮇⓗ
36

1

15

⮫᫬

3

୧᪉
0%

20%

40%

60%

80%

↓ᅇ⟅

100%

㻟㻚㻌ᐃᮇⓗ䛻⾜䛳䛶䛔䜛ሙྜ䚸䛭䛾㑏ඖ᪉ἲ඲䛶䛻䕿䜢䛴䛡䛶ୗ䛥䛔
HIV㸸ᖺホ౯

0 5

9HIV㸸ᖺືྥ

2 20
4 03

7

0 5

12

2

35

HIV㸸᭶ホ౯ 10

2

22

2

52

HIV㸸᭶ືྥ

4 1 1 4 10 4HIV㸸㐌ホ౯2 01 1 10 5HIV㸸㐌ືྥ

12

2

38

2

43

Web䛾䜏

ᱵẘ䠖ᖺホ౯

0 59ᱵẘ䠖ᖺືྥ

14

10

2 20

35
4 03

7

0 5

12

20

14

0

ᱵẘ䠖᭶ホ౯ 10

22

3

䝯䞊䝹䛾䜏

2

⣬䛾䜏

2

Web䛸䝯䞊䝹

2

52

Web䛸⣬
䝯䞊䝹䛸⣬

ᱵẘ䠖᭶ືྥ

3 01 4 10 4402ᱵẘ䠖㐌ホ౯

3 01 1 10 5422ᱵẘ䠖㐌ືྥ

11

ᐃⅬ⑌ᝈ䠖ᖺホ౯12඲䛶ᐃⅬ⑌ᝈ䠖ᖺືྥ

016

ᐃⅬ⑌ᝈ䠖᭶ホ౯ 1 1 1
ᐃⅬ⑌ᝈ䠖᭶ືྥ
0%

30

12

0

6

10 4

10

01

10%

20%

7

2

5 02

0

8

7

2

15

12

1

26
3 02

1

18

1

40
30

18
30%

40%

50%

60%

―１１５―

14
70%

80%

7

2

90%

100%

඲䛶䛺䛧
↓ᅇ⟅

㻠㻚㻌ᐃⅬⓗ㑏ඖ᪉ἲ䛾䚸㼃㼑㼎䚸䝯䞊䝹䚸⣬௨እ䛾᪉ἲ䛜䛒䜜䜀ᩍ䛘䛶ୗ䛥䛔䠄౛䠖෉Ꮚ䚸ᖺሗ䚸➼䠅
෉Ꮚ
ᖺሗ
䛭䛾௚

㻢௳
㻞㻠௳
㻠௳

㻡㻚㻌ᐃᮇ䛾㑏ඖඛ䛻䛴䛔䛶䚸䛒䛶䛿䜎䜛䜒䛾඲䛶䛻䕿䜢䛴䛡䛶ୗ䛥䛔䚷䚷䠄タၥ㻞㻚䛷䛂ᐃᮇⓗ䛃䛒䜛䛔䛿䛂୧᪉䛃䛸ᅇ⟅䛧䛯ሙྜ䛾䜏䠅
50
40
30
42

20

33
22

10

1

6

0

㻢㻚㻌ᐃᮇ䛾㑏ඖෆᐜ䛻䛴䛔䛶ᩍ䛘䛶ୗ䛥䛔䚹ヱᙜ䛩䜛䜒䛾䛻䕿䜢䛴䛡䛶䛟䛰䛥䛔䠄」ᩘᅇ⟅ྍ䠅
50
40
30
20

42
32

32

10

15
2

2

6

0

㻣㻚㻌⮫᫬䛾㑏ඖ᝟ሗ䛾㑏ඖ᪉ἲ䛻䕿䜢䛴䛡䛶䛟䛰䛥䛔䠄」ᩘᅇ⟅ྍ䠅
15
10
5

14

13
4

2

2

1

⣬
ᩥ
᭩

䛱
䜙
䛧

䝫
䝇
䝍

䛭
䛾
௚

0
W
e
b

䝯
䝹

―１１６―

㻤㻚㻌⮫᫬䛾㑏ඖඛ䜢䚸タၥ㻡䛾䠄㻝䠅䡚䠄㻡䠅䛾୰䛛䜙඲䛶㑅䜣䛷ୗ䛥䛔䠄」ᩘᅇ⟅ྍ䠅
15

10
14
11

5

10
0

2

0

㻥㻚㻌⮫᫬䛾᝟ሗ㑏ඖ䛻⮳䛳䛯≧ἣ䜢ᩍ䛘䛶ୗ䛥䛔䠄」ᩘᅇ⟅ྍ䠅
15
10
14
5
6

1

1

2

0

NPO

㻝㻜㻚㻌⮫᫬䛾᝟ሗ㑏ඖ䛜ᚲせ䛻䛺䛳䛯≧ἣ䜢ᩍ䛘䛶䛟䛰䛥䛔

2 3 3

0%

7

20%

21

37

40%

60%

80%

100%

㞟ᅋⓎ⏕䠋䜰䜴䝖䝤䝺䜲䜽㐃ᦠ఍㆟䛾㈨ᩱ
ၨⓎ➼㈨ᩱసᡂ䛾䛯䜑ୖグ඲䛶㞟ᅋⓎ⏕䛸㈨ᩱసᡂ䛾䛯䜑䛭䛾௚↓ᅇ⟅ᚲせ䛜䛺䛔䛛䜙

㻝㻝㻚㻌⮫᫬䛾㑏ඖ䜢䛧䛶䛔䛺䛔⌮⏤䜢ᩍ䛘䛶䛟䛰䛥䛔ᚲせ䛿䛒䜛䛜䚸
᪉ἲ䛜ศ䛛䜙䛺䛔䛛䜙

24

01

10

ᚲせ䛿䛒䜛䛜䚸
ண⟬䛜↓䛔➼ᡭẁ䛜↓䛔䛛䜙

20

䛭䛾௚

0%

20%

40%

60%

80%

100%

㻝㻞㻚㻌᝟ሗ㑏ඖ䛻㝿䛧䛶䚸ឤᰁ⑕Ⓨ⏕ືྥㄪᰝ䛾≉ᛶ䜢㓄៖䛧䛶䛔䜎䛩䛛↓ᅇ⟅㓄៖䛧䛶䛔䜛
≉ᛶ➼䛿ᢕᥱ䛧䛶䛔䜛䛜䚸㓄៖䛧䛶䛔䛺䛔

5

0%

15

20%

32

40%

60%

3

80%

―１１７―

100%

≉ᛶ䛻䛴䛔䛶≉䛻㓄៖䞉ᢕᥱ䛧䛶䛔䛺䛔↓ᅇ⟅㻝㻟㻚㻌ᛶឤᰁ⑕䛻䛴䛔䛶䚸⊂⮬䛷⾜䛳䛶䛔䜛ㄪᰝ䞉ྲྀ⤌䛿䛒䜚䜎䛩䛛䠄⮬⏤グ㏙䠅
㻭┴
㻮ᕷ
㻯┴
䠠┴
㻱ᕷ

⊂⮬䛾䝃䞊䝧䜲䝷䞁䝇䛸䛧䛶㠀᾿⳦ᛶ㠀䜽䝷䝭䝆䜰ᛶᒀ㐨⅖䜢ᐇ᪋ᢕᥱᑐ㇟⑌ᝈ䛻䛂㠀䜽䝷䝭䝆䜰ᛶ㠀᾿⳦ᛶᒀ㐨⅖䛃䜢ຍ䛘䛶䛔䜛ᱵẘᵝ⑌ᝈ䠄㻴㻞㻤㻛㻝㻛㻝䛷ㄪᰝᑐ㇟䛛䜙㝖እ䠅䚸⭼䝖䝸䝁䝰䝘䝇⑕
ᐃⅬ⑌ᝈ䛻䛚䛔䛶䚸┴⊂⮬䛾ᵝᘧ䜢సᡂ䛧䚸↓⑕≧⑓ཎయಖ᭷⪅䚸ཷデዎᶵ䚸㻯㻿㼃䛸䛾᥋ゐ➼䜢ㄪᰝ⾑ᾮ᳨ᰝ᫬䛾䜰䞁䜿䞊䝖䞉䜲䝧䞁䝖䛷䛾ၨⓎ䞉䜼䝱䝷䝸䞊䜈䛾ᥖ♧㻝㻠㻚㻌ᛶឤᰁ⑕Ⓨ⏕ືྥㄪᰝ䛾㞟ィ䛸䚸᝟ሗ㑏ඖ䛾ᢸᙜ⪅䛿ྠ䛨䛷䛩䛛」ᩘே䛷ཷ䛡ᣢ䛳䛶䛔䜛䛜䜋䜌ྠ䛨
25

23

5

2

ྠ୍ே
ᢸᙜ䛿␗䛺䜛

0%

20%

40%

60%

80%

100%

↓ᅇ⟅

䠘ᛶឤᰁ⑕Ⓨ⏕ືྥㄪᰝά⏝䛾䛯䜑䛾䜺䜲䝗䝷䜲䞁䛻䛴䛔䛶䠚㻝㻡㻚㻌ᖹᡂ㻞㻠ᖺᗘᙜ◊✲⌜䛻䜘䜛䛂ᛶឤᰁ⑕Ⓨ⏕ືྥㄪᰝά⏝䛾䛯䜑䛾䜺䜲䝗䝷䜲䞁䛃䜢䛤Ꮡ▱䛷䛩䛛
▱䜙䛺䛔
16
0%

32
20%

40%

7

60%

80%

0
100%

▱䛳䛶䛔䜛䛜ᮍά⏝▱䛳䛶䛔䛶ά⏝㻝㻢㻚㻌ཧ⪃䛻䛺䛳䛯グ஦䜢ᩍ䛘䛶䛟䛰䛥䛔䠄」ᩘᅇ⟅ྍ䠅
20

15

10
17

19

19

14
5
7

7
3

2

0

㻝㻣㻚㻌䜺䜲䝗䝷䜲䞁䛻᭦䛻ຍ䛘䛯᪉䛜Ⰻ䛔ෆᐜ䛜䛒䛳䛯䜙ᩍ䛘䛶ୗ䛥䛔䠄⮬⏤グ㏙䠅㻭ᕷ㑏ඖ᝟ሗ䛻䛴䛔䛶䚸ᩥᏐ䛰䛡䛷䛺䛟ᅗ⾲䜢౑䛳䛶౛♧䛧䛯᪉䛜Ⰻ䛔䠘✚ᴟⓗ␿Ꮫㄪᰝ䛻䛴䛔䛶䠚㻝㻤㻚㻌ᆅ᪉ឤᰁ⑕᝟ሗ䝉䞁䝍䞊䛸䛧䛶䛾ᛶឤᰁ⑕඲ᩘሗ࿌⑌ᝈ䛾✚ᴟⓗ␿Ꮫㄪᰝ䛾㛵䜟䜚䛻䛴䛔䛶⾜䛳䛶䛔䛺䛔
47
75%

80%

8
85%

90%

0
95%

―１１８―

100%

㒊ศⓗ䛻⾜䛳䛶䛔䜛䜋䜌඲ᩘ⾜䛳䛶䛔䜛㻝㻥㻚㻌✚ᴟⓗ␿Ꮫㄪᰝෆᐜ䜢ᩍ䛘䛶䛟䛰䛥䛔䠄」ᩘᅇ⟅ྍ䠅
10

5
7
5

5

4

4

1

3

0

㻞㻜㻚㻌ᒆฟ⏝⣬䛻䚸ᝈ⪅䠋ឤᰁ⪅䛾ఫᡤ䞉Ặྡḍ䛾᭷↓䛜䚸✚ᴟⓗ␿Ꮫㄪᰝ䛾䛧䜔䛩䛥䛻ᙳ㡪䛧䛶䛔䜎䛩䛛
䛧䛶䛔䜛
9

6

2

䛧䛶䛔䛺䛔

38

䛭䛾௚
0%

20%

40%

60%

80%

100%

↓ᅇ⟅

䠘㞟ᅋⓎ⏕䠋䜰䜴䝖䝤䝺䜲䜽䛻䛴䛔䛶䠚㻞㻝㻚㻌ᖹᡂ㻞㻢ᖺ䠍᭶䛛䜙ᖹᡂ㻞㻣ᖺ㻝㻝᭶ᮎ䜎䛷䛾㛫䛻䚸ᛶ⾜Ⅽ䛻䜘䜛ឤᰁ⑕䠄䝃䞊䝧䜲䝷䞁䝇⑌ᝈ䛾௚䚸㻮ᆺ⫢⅖䜔䚸㻭ᆺ⫢⅖䚸㉥⑩➼䠅䛾㞟ᅋⓎ⏕䜔䚸㏻ᖖ௨ୖ䛾ቑຍ䠄䜰䜴䝖䝤䝺䜲䜽䠅ཪ䛿䛭䛾␲䛔䜢ᢕᥱ䛧䛯஦䛜䛒䜚䜎䛩䛛
䛺䛔
36
0%

20%

2
40%

60%

17
80%

୙᫂
100%

䛒䜛

㻞㻞㻚㻌㞟ᅋⓎ⏕䠋䜰䜴䝖䝤䝺䜲䜽䜢ᢕᥱ䛧䛯ሙྜ䛾᥈▱䛾ዎᶵ䠄」ᩘᅇ⟅ྍ䠅
20
15
10

17

5
4

2

3

0

―１１９―

5

2

㻞㻟㻚㻌㞟ᅋⓎ⏕䠋䜰䜴䝖䝤䝺䜲䜽䚷䜢ᢕᥱ䛧䛯ሙྜ䛾ᑐ⟇䠄」ᩘᅇ⟅ྍ䠅
25
20
15
21

10

14

5

10

5

5

0

㻞㻠㻚㻌䛣䛾ᩘᖺ㛫䛷䚸ᅜෆ䛷䚸ᱵẘ䛾䜰䜴䝖䝤䝺䜲䜽䛜␲䜟䜜䛶䛔䜛䛾䜢䛤Ꮡ▱䛷䛩䛛
12

▱䜙䛺䛔

43

▱䛳䛶䛔䛯
0%

20%

40%

60%

80%

100%

㻞㻡㻚㻌㈗⮬἞య䛾ᱵẘᝈ⪅ᩘ䛿䚸㻝᭶䡚㻝㻝᭶ᮎ䛾ᮇ㛫䛷䚸௒ᖺ䛿๓ᖺ䛻ẚ䜉ቑຍ䛧䛶䛔䜎䛩䛛
35
0%

20%

12
40%

60%

6 02
80%

100%

ቑຍ䛧䛶䛔䜛
኱䛝䛺ኚ໬䛿䛺䛔
ῶᑡ䛧䛶䛔䜛
ุ᩿䛷䛝䛺䛔
↓ᅇ⟅㻞㻢㻚㻌㈗⟶ෆ䛷䛾ᱵẘ䛾ሗ࿌ᩘ䛾᥎⛣䜢ᩍ䛘䛶䛟䛰䛥䛔
ྜィ
㻣㻟㻞
㻥㻥㻝
㻞㻢㻢㻥

㻞㻜㻜㻥ᖺ௳ᩘ
㻞㻜㻝㻞ᖺ௳ᩘ
㻞㻜㻝㻡ᖺ௳ᩘ

䠘⑌ᝈẖ䛾≉␗ᛶ䛻䛴䛔䛶䠚㻞㻣㻚㻌ᛶჾ䝦䝹䝨䝇䛾ᒆฟᑐ㇟䛜ึឤᰁ䛾䜏䛸ゝ䛖䛣䛸䜢䛤Ꮡ▱䛷䛧䛯䛛
▱䛳䛶䛔䛯
28
0%

20%

25
40%

60%

2
80%

100%

▱䜙䛺䛛䛳䛯
↓ᅇ⟅㻞㻤㻚䚷䛤Ꮡ䛨䛾᪉䛿䚸୰㧗ᖺ⪅䛾ᒆฟ䛜᭷䛳䛯᫬䛻䚸ึឤᰁ䛛䚸෌Ⓨ䛛☜ㄆ䛧䛶䛔䜎䛩䛛䚷䚷䚷䠄タၥ㻞㻣㻚䛷䛂▱䛳䛶䛔䛯䛃䛸ᅇ⟅䛧䛯ሙྜ䛾䜏䠅
ẖᅇ☜ㄆ

1
0%

7
20%

㐺ᐅ☜ㄆ䠋
☜ㄆ䛧䛯䛣䛸䛜䛒䜛

20
40%

60%

80%

―１２０―

100%

☜ㄆ䛫䛪䚸་⒪ᶵ㛵䛾ᒆ䛡ฟ㏻䜚㞟ィ㻞㻥㻚㻌ᛶჾ䝦䝹䝨䝇ឤᰁ⑕䛾Ⓨ⏕ືྥ䛾⥅⥆䛻䛴䛔䛶䚸䛹䛾䜘䛖䛻䛚⪃䛘䛷䛩䛛
1

17

5

28

0%

20%

40%

60%

ᛶჾ䝦䝹䝨䝇䛾ᢕᥱ䛭䛾䜒䛾䜢෌᳨ウ㐠⏝䛾ᨵၿ䛿ᚲせ䛰䛜ᢕᥱ䛿⥅⥆⌧≧䜢ኚ᭦䛩䜛ᚲせ䛿ឤ䛨䛺䛔≉䛻᫂☜䛺ពぢ䛿䛺䛔
䛭䛾௚
↓ᅇ⟅

0 4

80%

100%

䠘ᛶឤᰁ⑕ᐃⅬ་⒪ᶵ㛵➼䛻䛴䛔䛶䠚㻟㻜㻚㻌ᐃⅬ་⒪ᶵ㛵䜢ኚ᭦䛧䛯ሙྜ䛾⌮⏤ᑐ㇟ᮇ㛫䛻ኚ᭦䛧䛶䛔䛺䛔་⒪ᶵ㛵䛾㎡㏥䞉ᗫṆ➼་⒪ᶵ㛵ഃ⌮⏤

28

17

03 1

ᆅ⌮ⓗ✵ⓑᆅ䜈䛾㏣ຍ䜔ኚ᭦➼⾜ᨻഃ䛾ពྥ

6

䛭䛾௚
0%

20%

40%

60%

80%

་⒪ᶵ㛵ഃ䞉⾜ᨻഃ୧᪉䛾⌮⏤

100%

↓ᅇ⟅

㻟㻝㻚㻌ᐃⅬ་⒪ᶵ㛵䛻䛴䛔䛶䚸ᅔ䛳䛶䛔䜛஦䛿䛒䜚䜎䛩䛛䠄」ᩘᅇ⟅ྍ䠅
30
25
20
15
26
10
13

5
6

6

6

2

0

㻟㻞㻚㻌ᛶឤᰁ⑕䛾Ⓨ⏕ືྥ䛾ᢕᥱ䛾䛯䜑䛻䚸ཱྀ⭍ဗ㢌䛾ᛶឤᰁ⑕䛾Ⓨ⏕ືྥ䜒ㄪᰝ䛩䜉䛝䛸ᛮ䛔䜎䛩䛛
䛭䛖ᛮ䛖
19

3

20%

40%

32

1

䛭䛖ᛮ䜟䛺䛔
ุ᩿䛷䛝䛺䛔

0%

60%

80%

100%

↓ᅇ⟅

㻟㻟㻚㻌ཱྀ⭍䜢௓䛧䛯ဗ㢌䛾ᛶឤᰁ⑕䛾ᢕᥱ䛾䛯䜑䛻䚸ᛶឤᰁ⑕ᐃⅬ་⒪ᶵ㛵䛻⪥㰯⛉䜢㏣ຍ䛩䜛䛣䛸䛻䛴䛔䛶
4
0%

9

1 4
20%

36
40%

60%

1
80%

―１２１―

100%

㈶ᡂ
䛹䛱䜙䛛䛸䛔䛘䜀㈶ᡂ཯ᑐ䛹䛱䜙䛛䛸䛔䛘䜀཯ᑐุ᩿䛷䛝䛺䛔
↓ᅇ⟅㻟㻠㻚㻌⪥㰯⛉ᐃⅬ䛾䛯䜑䛻ᚲせ䛺஦䛿䛺䜣䛰䛸ᛮ䛔䜎䛩䛛䠄」ᩘᅇ⟅ྍ䠅
30
25
20
15

26

10
12

5

16

12

14

0

㻟㻡㻚㻌ୡ⏺ⓗ䛻᾿⳦䛾⪏ᛶ⳦䛜ၥ㢟䛻䛺䛳䛶䛔䜎䛩䛜䚸ᅜෆ䛷䜒἞⒪⸆䛾㧗ᗘ⪏ᛶ᾿⳦䛜䜏䜙䜜䛶䛔䜛䛾䜢䚷䚷ᚚᏑ▱䛷䛧䛯䛛
▱䛳䛶䛔䛯
22
0%

32

20%

40%

60%

1
80%

▱䜙䛺䛛䛳䛯

100%↓ᅇ⟅㻟㻢㻚㻌㧗ᗘ⪏ᛶ᾿⳦䛾䝃䞊䝧䜲䝷䞁䝇䛾䛯䜑䛻䚸㞴἞ᛶ᾿⳦ᝈ⪅➼䜢ᑐ㇟䛸䛩䜛䛺䛹䛾䚸ᛶឤᰁ⑕⑓ཎయᐃⅬ
䚷䚷䜢㏣ຍ䛩䜛䛣䛸䛻䛴䛔䛶䛹䛖䛚⪃䛘䛷䛩䛛
9
0%

11
20%

11
40%

32
60%

1
80%

100%

㈶ᡂ
䛹䛱䜙䛛䛸䛔䛘䜀㈶ᡂ
䛹䛱䜙䛛䛸䛔䛘䜀཯ᑐ཯ᑐุ᩿䛷䛝䛺䛔
↓ᅇ⟅㻟㻣㻚㻌ᛶឤᰁ⑕䛾⾜ᨻ᳨デ䛿䚸ᆅ᪉⾨⏕◊✲ᡤ䛷᳨ᰝ䛧䛶䛔䜎䛩䛛඲䛶⮬๓䛷᳨ᰝ䛧䛶䛔䜛
7
0%

17
20%

30
40%

60%

1
80%

―１２２―

100%

඲䛟᳨ᰝ䛧䛶䛔䛺䛔㒊ศⓗ䛻᳨ᰝ䛧䛶䛔䜛䠘䛤ᅇ⟅⪅䛸ᡤᒓ䛻䛴䛔䛶䠚㻟㻥㻚㻌ᅇ⟅⪅䛾ᛶឤᰁ⑕௨እ䛾ᢸᙜᴗົ䠄」ᩘᅇ⟅ྍ䠅
50
40
30
20

45

45

44

10

16

15

0

㻠㻜㻚㻌⫋✀

13

0%

9

20%

16

40%

4

60%

5

10

7

80%

㻠㻝㻚㻌㻞㻣ᖺᗘᮎ䛷䛾ᛶឤᰁ⑕ᢸᙜᖺᩘ
2ᖺᮍ‶
17

23

13

2

2-4ᖺ
5-9ᖺ

0%

20%

40%

60%

80%

―１２３―

100%

10ᖺ௨ୖ

100%

⸆๣ᖌ
⋇་ᖌ
᳨ᰝᢏᖌ
஦ົ
ಖ೺ᖌ
┳ㆤᖌ
་ᖌ
䛭䛾௚

〈別添５〉➨29ᅇබ⾗⾨⏕᝟ሗ◊✲༠㆟఍⥲఍䞉◊✲఍
ᖹᡂ28ᖺ1᭶29᪥ ᅜ❧ಖ೺་⒪⛉Ꮫ㝔኱㜰ᕷ䛻䛚䛡䜛ᱵẘ䛾
Ⓨ⏕ືྥ䛸ྲྀ䜚⤌䜏⣽஭⯙Ꮚ䠍䚸ᯇᮏ೺஧䠍䚸㧗㔝䛴䜛௦䠎䚸㔠㇂Ὀᏹ䠏䚸ᑿᮏ⏤⨾Ꮚ䠐䚸ᕝ⏿ᣅஓ䠑䚸◁ᕝᐩṇ䠒䚸୰℩ඞᕫ䠓䠍 ኱㜰ᕷಖ೺ᡤ䚸䠎 ᶓ὾ᕷ᪫༊⚟♴ಖ೺䝉䞁䝍䞊䠄ඖᶓ὾ᕷ⾨⏕◊✲ᡤ䠅䚸䠏 ᅜ❧ಖ೺་⒪⛉Ꮫ㝔䚸䠐 ㇏ᓥ༊ụ⿄ಖ೺ᡤ䚸䠑䚷኱㜰ᗓ❧බ⾗⾨⏕◊✲ᡤ䚸䠒 ᅜ❧ឤᰁ⑕◊✲ᡤ䚸䠓 ᒸᒣ኱Ꮫᱵẘ䛸䛿 ᱵẘ䛿䚸ᱵẘ䝖䝺䝫䝛䞊䝬䛾ឤᰁ䛻䜘䛳䛶⏕䛨䜛ᛶឤᰁ⑕䛷䛒䜛䚹䠄ឤᰁ⑕ἲ䛷䛿5㢮ឤᰁ⑕䛻ศ㢮䛥䜜䚸඲ᩘሗ࿌䛜ᚲせ䠅 ⑓ᆺཬ䜃୺䛺⑕≧ 䈜ඛኳᱵẘ䜢㝖䛟
⑓ᆺ

⑕≧ฟ⌧
᫬ᮇ

୺䛺⑕≧

᪩ᮇ㢧⑕ᱵẘ ឤᰁᚋ
䠄䊠ᮇ䠅
䠏䡚䠒㐌㛫

◳⤖䚸◳ᛶୗ⑃䚸↓③ᛶ㰡ᚄ㒊䝸䞁䝟⠇⭘⬽᪩ᮇ㢧⑕ᱵẘ ឤᰁᚋ
䠄䊡ᮇ䠅
⣙䠏䛛᭶

⓶⭵䜔⢓⭷䛻ᱵẘᛶ䝞䝷⑈䚸ᡥᖹ䝁䞁䝆䝻䞊䝬ᬌᮇ㢧⑕ᱵẘ ឤᰁᚋ䠏ᖺ௨ୖ䝂䝮⭘䚸ᚰ⾑⟶⑕≧䚸⚄⤒⑕≧䚸║⑕≧↓⑕≧⑓ཎయ
ಖ᭷⪅

䛺䛧

2

―１２４―

἞⒪䛧䛺䛡䜜䜀⬻䛺䛹䛻㔜኱䛺ྜే⑕䜢ᘬ䛝㉳䛣䛩ྍ⬟ᛶ䛜䛒䜛䚹ዷ፬䛻ឤᰁ䛜䛒䜛䛸⫾ඣ䛻ឤᰁ䛩䜛䠄ඛኳᱵẘ䠅䛣䛸䛜䛒䜛䚹᪩ᮇⓎぢ䞉᪩ᮇ἞⒪䛜㔜せ3┠ⓗ኱㜰ᕷ䛻䛚䛡䜛ᱵẘ䛾Ⓨ⏕ືྥ䜢ศᯒ䛧䚸ᚲせ䛺ྲྀ䜚⤌䜏䜢᳨ウ䛩䜛䚹

4

―１２５―

ㄪᰝෆᐜ
2010ᖺ䡚2015ᖺ䛻኱㜰ᕷෆ䛷ឤᰁ⑕ἲ䛻ᇶ䛵䛝ᒆฟ䛾䛒䛳䛯ᱵẘ䛻䛴䛔䛶ศᯒ䛧䛯䚹䝕䞊䝍䛿㻞㻜㻝㻠ᖺ䜎䛷䛿㻞㻜㻝㻡ᖺ㻡᭶㻞㻝᪥⌧ᅾ䚸㻞㻜㻝㻡ᖺ䛿㻞㻜㻝㻢ᖺ㻝᭶㻝㻤᪥⌧ᅾ䛾䜒䛾䜢⏝䛔䛯䚹
5⤖ᯝ䠄ᖺḟู᥎⛣䠅

6

―１２６―

⏨ዪูᒆฟᩘ᥎⛣300 䠄ே䠅ඛኳᱵẘ1௳
䠄ዪඣ䠅

250

67

200

14
ዪᛶ

150

50

⏨ᛶ

5

100
10

3
39

3
54

65

2010ᖺ

2011ᖺ

2012ᖺ

182

185

2014ᖺ

2015ᖺ

110

0

2013ᖺ

7

⏨ዪูᒆฟ๭ྜ᥎⛣100.0%

7.1%

5.3%

13.3%

4.3%

7.1%
26.6%

80.0%
60.0%
40.0%

92.9%

94.7%

86.7%

95.7%

ዪᛶ๭ྜ

92.9%
73.4%

⏨ᛶ๭ྜ

20.0%
0.0%
2010ᖺ 2011ᖺ 2012ᖺ 2013ᖺ 2014ᖺ 2015ᖺ
8

―１２７―

ឤᰁ⤒㊰ูᒆฟ๭ྜ᥎⛣䠄ᛶⓗ᥋ゐ䛾䜏䠅
100%
80%

21.0%

21.2%

24.9%

35.3%
60%

୙᫂

␗ᛶ㛫

40%
20%

51.5%

41.7%
69.4%

67.3%

68.9%

ྠᛶ㛫

52.9%
39.1%

36.1%

0%
2010ᖺ

2011ᖺ

2012ᖺ

2013ᖺ

2014ᖺ

2015ᖺ
9

⤖ᯝ䠄2015ᖺ䠅

10

―１２８―

⏨ዪูᒆฟᩘཬ䜃๭ྜ
ᛶู

ᒆฟᩘ

ᒆฟ๭ྜ

⏨ᛶ

㻝㻤㻡

㻣㻟㻚㻠㻑

ዪᛶ

㻢㻣

㻞㻢㻚㻢㻑

ྜィ

㻞㻡㻞

㻝㻜㻜㻚㻜㻑

ᖹᆒᖺ㱋
䠄⠊ᅖ䠅
㻠㻜㻚㻡ṓ
䠄㻝㻣㻙㻥㻜䠅
㻞㻢㻚㻣ṓ䠄㻝㻤㻙㻠㻤䠅
㻟㻢㻚㻥ṓ䠄㻝㻣㻙㻥㻜䠅
11ឤᰁ⤒㊰ู๭ྜ䠄඲య䠅 N=252
୙᫂
6.7%
ᛶⓗ᥋ゐ
䠄୙᫂䠅
8.7%

ᛶⓗ᥋ゐ
䠄ྠᛶ䠅
36.6%

ᛶⓗ᥋ゐ
䠄␗ᛶ䠅
48.0%
12

―１２９―

ឤᰁ⤒㊰ู๭ྜ䠄⏨ዪู䠅
⏨ᛶ

ዪᛶ

n=185

୙᫂
8.1%
ᛶⓗ᥋ゐ
䠄୙᫂䠅
8.6%

ᛶⓗ᥋ゐ
䠄ྠᛶ䠅
49.8%

ᛶⓗ᥋ゐ
䠄୙᫂䠅
9.0%

n=67

୙᫂
3.0%

ᛶⓗ᥋ゐ
䠄␗ᛶ䠅
88.0%

ᛶⓗ᥋ゐ
䠄␗ᛶ䠅
33.5%

13

ᆺู๭ྜ䠄඲య䠅
↓⑕≧⑓
ཎయ
ಖ᭷⪅,
36.5%

N=252
᪩ᮇ㢧⑕
ᱵẘ䠄䊠ᮇ䠅,29.0%᪩ᮇ㢧⑕ᱵẘ䠄䊡ᮇ䠅,
32.1%

ᬌᮇ㢧⑕
ᱵẘ,
2.4%

14

―１３０―

ᆺู๭ྜ䠄⏨ዪู䠅
⏨ᛶ

ዪᛶ

n=185

↓⑕≧⑓
ཎయ
ಖ᭷⪅
31.9%

᪩ᮇ㢧⑕
ᱵẘ䠄Ϩᮇ䠅
31.4%

n=67
᪩ᮇ㢧⑕
ᱵẘ䠄Ϩᮇ䠅
22.4%

↓⑕≧⑓
ཎయ
ಖ᭷⪅
49.2%

᪩ᮇ㢧⑕
ᱵẘ䠄ϩᮇ䠅
28.4%᪩ᮇ㢧⑕ᱵẘ䠄ϩᮇ䠅
33.5%

ᬌᮇ㢧⑕
ᱵẘ
3.2%

15

ឤᰁᆅᇦ䠄඲య䠅 N=252
㒔㐨ᗓ┴
୙᫂
12.3%

ᅜእ
1.2%

ᅜෆ䠄኱㜰
ᗓ㝖䛟䠅
7.9%

ᕷෆ
53.2%

኱㜰ᗓ
25.4%

16

―１３１―

ឤᰁᆅᇦ䠄⏨ዪู䠅
⏨ᛶ
㒔㐨ᗓ┴
୙᫂
14.0%

ዪᛶ

n=185

㒔㐨ᗓ┴
୙᫂
7.5%

ᅜእ
1.0%

ᅜෆ䠄኱
㜰ᗓ㝖
䛟䠅
4.9%

ᕷෆ
50.9%

n=67
ᅜእ
1.5%

ᅜෆ䠄኱
㜰ᗓ㝖
䛟䠅
16.4%

ᕷෆ
59.7%

኱㜰ᗓ
14.9%

኱㜰ᗓ
29.2%

17

་⒪ᶵ㛵ูᒆฟᩘཬ䜃๭ྜ་⒪ᶵ㛵✀ู

ᒆฟᩘ

ᒆฟ๭ྜ

⑓㝔

㻝㻜㻡

㻠㻝㻚㻣㻑

デ⒪ᡤ

㻝㻠㻣

㻡㻤㻚㻟㻑

18

―１３２―

2015ᖺ䜎䛸䜑 ᒆฟ䛻༨䜑䜛⏨ᛶ䛾๭ྜ䛜㧗䛔䜒䛾䛾䚸ዪᛶ䛾ᒆฟᩘ䛚䜘䜃๭ྜ䛜ቑຍ䛧䛶䛔䛯䚹 ⏨ᛶ䛻䛚䛡䜛ឤᰁ⤒㊰䛿ྠᛶ㛫ᛶⓗ᥋ゐ䛜඲య䛾⣙༙ᩘ䛸᭱䜒ከ䛛䛳䛯䛜䚸␗ᛶ㛫ᛶⓗ᥋ゐ䜒⣙3๭䜢༨䜑䛯䚹 ⏨ᛶ䛿ዪᛶ䛸ẚ㍑䛧䛶᭷⑕≧䛷䛒䜛๭ྜ䛜㧗䛛䛳䛯䚹 ឤᰁᆅᇦ䛿኱㜰ᕷእ䛜⣙༙ᩘ䜢༨䜑䛯䚹 ᒆฟ་⒪ᶵ㛵✀ู䛿デ⒪ᡤ䛜㐣༙ᩘ䜢19༨䜑䛯䚹኱㜰ᕷ䛻䛚䛡䜛ྲྀ䜚⤌䜏ᱵẘ䛾Ⓨ⏕ືྥ䚸⑕≧䚸᳨ᰝ䚸἞⒪䛻

㛵䛩䜛᝟ሗⓎಙಖ೺⚟♴䝉䞁䝍䞊➼䛻䛚䛡䜛ᱵẘ᳨ᰝ⏨ᛶ䛸䝉䝑䜽䝇䛩䜛⏨ᛶ䜢ᑐ㇟䛸䛧䛯⮫
᫬HIV/ᱵẘ᳨ᰝᱵẘ᳨ᰝ⤖ᯝㄝ᫂㈨ᩱ䛻䝟䞊䝖䝘䞊䜈᳨ᰝ䜢່䜑䜛ᩥゝ䜢㏣グ௚⮬἞య䛸Ⓨ⏕ືྥㄪᰝ⤖ᯝ䛾ඹ᭷

20

―１３３―

௒ᚋ䛾᳨ウㄢ㢟ᱵẘᒆฟ་⒪ᶵ㛵䛻ᑐ䛩䜛✚ᴟⓗ␿Ꮫㄪᰝ⏨ᛶ䛸䝉䝑䜽䝇䛩䜛⏨ᛶ䜈䛾ᗈሗ䛻ຍ䛘䚸ዪᛶ䜈䛾ၨⓎᱵẘ᳨ᰝ⤖ᯝ㝧ᛶ⪅䛾䝟䞊䝖䝘䞊ྥ䛡㈨ᮦ䛾సᡂ
௚⮬἞య䛸㐃ᦠ䛧䛯ᬑཬၨⓎཬ䜃᳨ᰝయไᩚഛ

―１３４―

21

〈別添６〉

HIV䡷䞊䢉䢚䡮䢓䢙䡹䛾⌧≧䛸ㄢ㢟୺䛻WB㝧ᛶ஦౛(HIVឤᰁ)䛾
ᮍᒆ䛡஦౛䛾ྍ⬟ᛶ䛻䛴䛔䛶኱㜰ᗓ❧බ⾗⾨⏕◊✲ᡤឤᰁ⑕㒊䜴䜲䝹䝇ㄢ ୺௵◊✲ဨᕝ⏿ᣅஓ᪥ᮏ䛾HIV᳨ᰝ䞉䝃䞊䝧䜲䝷䞁䝇యไ
ᆅ᪉⾨⏕◊
◊✲ᡤ

ឤᰁ⑕ἲ䛻ᇶ䛵䛟䛂ឤᰁ⑕Ⓨ⏕ືྥㄪᰝ஦
ᴗ䛃
ᆅᇦ䛾ಖ
ಖ೺ᡤ
་ᖌ䛻䜘䜛ᒆฟ
ᑓ⏝ᅇ⥺↓ᩱ༏ྡHIV᳨᳨ᰝ䠄ಖ೺ᡤ䞉ጤク᳨ᰝሙ䠅⾡๓᳨ᰝ䞉ධ㝔๓᳨ᰝ
⑓㝔䞉
䞉デ⒪ᡤ

ᅜ❧ឤᰁ⑕◊✲ᡤឤᰁ⑕␿Ꮫ䝉
䝉䞁䝍䞊་ᖌ䛻䜘䜛ᒆฟ

䜶䜲䝈ືྥጤဨ఍䠄ཌ⏕ປാ┬䠅䠅Ẹ㛫⮫ᗋ᳨᳨ᰝ఍♫䠄⮫ᗋ᳨ᰝ䝉䞁䝍䞊䠅

⮬ᕫ᳨ᰝ

බ⾲䠄3䞄
䞄᭶ẖ䠅

㒑㏦᳨ᰝ

⊩⾑

―１３５―

᪥ᮏ䛻䛚䛡䜛HIV䡹䡴䢔䞊䢂䢙䡴䢚᳨ᰝᩘ(2013ᖺ)
ᆅ᪉⾨⏕◊
◊✲ᡤ

ឤᰁ⑕ἲ䛻ᇶ䛵䛟䛂ឤᰁ⑕Ⓨ⏕ືྥㄪᰝ஦
ᴗ䛃
ᆅᇦ䛾ಖ
ಖ೺ᡤ
་ᖌ䛻䜘䜛ᒆฟ
ᑓ⏝ᅇ⥺↓ᩱ༏ྡHIV᳨᳨ᰝ䠄ಖ೺ᡤ䞉ጤク᳨ᰝሙ䠅ᅜ❧ឤᰁ⑕◊✲ᡤឤᰁ⑕␿Ꮫ䝉
䝉䞁䝍䞊

136,400௳⾡๓᳨ᰝ䞉ධ㝔๓᳨ᰝ⑓㝔䞉䞉デ⒪ᡤ
⑓㝔ෆ᳨ᰝ⛉䠖䠛་ᖌ䛻䜘䜛ᒆฟ
᥎ᐃ620୓௳(ᅇ⟅⋡21.1%䛾䜰䞁䜿䞊䝖ㄪᰝ䛾᥎ィ)䜶䜲䝈ືྥጤဨ఍䠄ཌ⏕ປാ┬䠅䠅Ẹ㛫⮫ᗋ᳨᳨ᰝ఍♫䠄⮫ᗋ᳨ᰝ䝉䞁䝍䞊䠅

⮬ᕫ᳨
᳨ᰝ

㒑㏦᳨
᳨ᰝ

⊩⾑䠖5,205,819௳

73,863௳䠄11♫୰䛾10♫)

බ⾲䠄3䞄
䞄᭶ẖ䠅

2013ᖺ䛾䡹䡴䢔䞊䢂䢙䡴䢚᳨ᰝᩘ(㟷Ꮠ)䛸㝧ᛶ⪅ᩘ(㉥Ꮠ)

ᆅ᪉⾨⏕◊
◊✲ᡤ

ឤᰁ⑕ἲ䛻ᇶ䛵䛟䛂ឤᰁ⑕Ⓨ⏕ືྥㄪᰝ஦
ᴗ䛃
ᆅᇦ䛾ಖ
ಖ೺ᡤ
་ᖌ䛻䜘䜛ᒆฟ
ᑓ⏝ᅇ⥺↓ᩱ༏ྡHIV᳨᳨ᰝ䠄ಖ೺ᡤ䞉ጤク᳨ᰝሙ䠅ᅜ❧ឤᰁ⑕◊✲ᡤឤᰁ⑕␿Ꮫ䝉
䝉䞁䝍䞊

136,400(453)་ᖌ䛻䜘䜛ᒆฟ
⾡๓᳨ᰝ䞉ධ㝔๓᳨ᰝ⑓㝔䞉
䞉デ⒪ᡤ
᥎ᐃ620୓௳(ᅇ⟅⋡21.1%䛾䜰䞁䜿䞊䝖ㄪᰝ䛾᥎ィ)⑓㝔ෆ᳨ᰝ⛉䠖䠛(㝧ᛶ⪅ᩘ୙᫂)Ẹ㛫⮫ᗋ᳨᳨ᰝ఍♫䠄⮫ᗋ᳨ᰝ䝉䞁䝍䞊䠅
኱ᡭ6♫䛾ෆ䚸඲ᅜᒎ㛤䛧䛶䛔䜛4♫ศ(⣙1,500௳)
⮬ᕫ᳨
᳨ᰝ

㒑㏦᳨
᳨ᰝ

⊩⾑䠖5,205,819(63)73,863(192ͤ)86%:165(䡹䡴䢔䡬䢂䢙䡴䢚㝧ᛶ)―１３６―

䜶䜲䝈ືྥጤဨ఍䠄ཌ⏕ປാ┬䠅䠅
බ⾲䠄3䞄
䞄᭶ẖ䠅

1,590 (HIV:1106,AIDS:484)኱つᶍ᳨ᰝ఍♫䛻䛚䛡䜛HIVᢠయ
WB㝧ᛶᩘ䛸ᒆฟᩘ 㒔㐨ᗓ┴ู
2011ᖺ WB㝧ᛶn=1181* ᒆฟn=1529450*㝧ᛶ୰㒔㐨ᗓ┴୙᫂䛾䠐௳䜢㝖䛟
400
350
300
250

WB㝧ᛶᩘ
WB㝧ᛶ䠚ᒆฟ䛾 ┴㟷ᒾᐑ ᇸ༓ᮾ᳃ᡭᇛ ⋢ⴥி

㛗
㔝

⁠ிර
㈡㒔ᗜ

HIV + AIDS

ᒸ
ᒣ

⚟
ᒸ

200
150
100

0

໭ᾏ㐨
㟷᳃┴
ᒾᡭ┴
ᐑᇛ┴
⛅⏣┴
ᒣᙧ┴
⚟ᓥ┴
Ⲉᇛ┴
ᰣᮌ┴
⩌㤿┴
ᇸ⋢┴
༓ⴥ┴
ᮾி㒔
⚄ዉᕝ┴
᪂₲┴
ᐩᒣ┴
▼ᕝ┴
⚟஭┴
ᒣ᲍┴
㛗㔝┴
ᒱ㜧┴
㟼ᒸ┴
ឡ▱┴
୕㔜┴
⁠㈡┴
ி㒔ᗓ
኱㜰ᗓ
රᗜ┴
ዉⰋ┴
࿴ḷᒣ┴
㫽ྲྀ┴
ᓥ᰿┴
ᒸᒣ┴
ᗈᓥ┴
ᒣཱྀ┴
ᚨᓥ┴
㤶ᕝ┴
ឡ፾┴
㧗▱┴
⚟ᒸ┴
బ㈡┴
㛗ᓮ┴
⇃ᮏ┴
኱ศ┴
ᐑᓮ┴
㮵ඣᓥ┴
Ἀ⦖┴

50

HIVឤᰁ⑕Ⓨ⏕ᒆฟඖ䛸☜ㄆ᳨ᰝᐇ᪋ᶵ㛵
HIVឤ

ᣐⅬ⑓㝔䞉⑓㝔䠛(⮬᪋タෆ䛷WBἲྍ⬟) ⑓㝔ෆ᳨ᰝ⛉

᳨
᳨ᰝ
䝉 䝍䞊
䝉䞁䝍
䝉䞁䝍䞊
W
WB
㝧
㝧ᛶ
䠇
ಖ೺ᡤ
ᡤ
᳨ᰝ
㝧ᛶ

ᣐⅬ⑓㝔䞉⑓㝔䞉デ⒪ᡤ
(⮬᪋タෆ䛷WBἲ୙ྍ⬟) Ẹ㛫⮫ᗋ᳨ᰝ䝉䞁䝍䞊

Ⓨ⏕ᒆฟᩘ
Ⓨ⏕ᒆ
ᒆฟᩘ

ಖ೺ᡤ

ᆅ᪉⾨⏕◊✲ᡤᒆฟඖ☜ㄆ᳨ᰝᐇ᪋ᶵ㛵

―１３７―

኱つᶍ᳨ᰝ఍♫䛻䛚䛡䜛HIVᢠయWB㝧ᛶᩘ䛸ಖ೺ᡤ᳨ᰝ㝧ᛶᩘ䛾࿴䠄A䠅䛸
ᒆฟᩘ䠄B䠅䛾ẚ㍑ 㒔㐨ᗓ┴ู
600

2011ᖺ 䠄A䠅=1556* ᒆฟn=1529
炷A炸WB春⿏㔘(㮹攻㣄㞣⭌+ᾅ‍㇨)䠄B䠅ᒆฟᩘ

500
400
300

䠄A䠅䠚䠄B䠅䛾┴㟷ᒾᐑ ⩌ᇸ༓ᮾ᳃ᡭᇛ 㤿⋢ⴥி

㛗
㔝

⁠ிර
㈡㒔ᗜ

ᒸ
ᒣ

ᚨ
ᓥ

⚟
ᒸ

䠆㒔㐨ᗓ┴୙᫂䛾6௳䜢㝖䛟
200

0

໭ᾏ㐨
㟷᳃┴
ᒾᡭ┴
ᐑᇛ┴
⛅⏣┴
ᒣᙧ┴
⚟ᓥ┴
Ⲉᇛ┴
ᰣᮌ┴
⩌㤿┴
ᇸ⋢┴
༓ⴥ┴
ᮾி㒔
⚄ዉᕝ┴
᪂₲┴
ᐩᒣ┴
▼ᕝ┴
⚟஭┴
ᒣ᲍┴
㛗㔝┴
ᒱ㜧┴
㟼ᒸ┴
ឡ▱┴
୕㔜┴
⁠㈡┴
ி㒔ᗓ
኱㜰ᗓ
රᗜ┴
ዉⰋ┴
࿴ḷᒣ┴
㫽ྲྀ┴
ᓥ᰿┴
ᒸᒣ┴
ᗈᓥ┴
ᒣཱྀ┴
ᚨᓥ┴
㤶ᕝ┴
ឡ፾┴
㧗▱┴
⚟ᒸ┴
బ㈡┴
㛗ᓮ┴
⇃ᮏ┴
኱ศ┴
ᐑᓮ┴
㮵ඣᓥ┴
Ἀ⦖┴

100

⁠㈡┴䚸ி㒔ᗓ䚸රᗜ┴䛸኱㜰ᗓ䛻䛚䛡䜛ᒆฟᩘ䛸㔜」䜢⪃៖䛧䛯☜ㄆ᳨ᰝ㝧ᛶ௳ᩘ䛾ẚ㍑(2013)
236

250

223

200
150
100

46

45

50
13

22

⁠㈡┴

ி㒔ᗓ

12

51

0
䡢娵㣄㞣春⿏㔘

රᗜ┴

኱㜰ᗓ

ᒆฟᩘ

☜ㄆ᳨ᰝ㝧ᛶᩘ䠙ಖ೺ᡤศ䠇኱つᶍ᳨ᰝ఍♫ศ䠄⑓㝔ෆ᳨ᰝศ䜢㝖䛟䠅

―１３８―

• HIVឤᰁ⑕デ᩿౛䛾ሗ࿌䛾ᮍᒆ䛡䛿䚸䛛䛺䜚䛾ᩘ䛻ୖ䜚䛭䛖䛷䛒䜛䛣䛸䛜♧၀䛥䜜䛯䚹• ௒ᚋ䛿䚸䝰䝕䝹ᆅ༊䚸䛒䜛䛔䛿┴䜢㑅ᐃ䛧䚸䛭䛾┴䛾⑓㝔䜈䜰䞁䜿䞊䝖ㄪᰝ䜢ᐇ᪋䛩䜛䛣䛸䛷䚸⑓㝔ෆ䛷䛾WBἲ㝧ᛶデ᩿ᩘ䜢㞟ィ䛧䚸䛥䜙䛻ṇ☜䛺ᮍᒆ䛡஦౛䛾ホ౯䜢䛩䜛᪉ྥ䛷᳨ウ䛧䛯䛔䚹

―１３９―

My
c
o
p
l
a
s
mag
e
ni
t
a
l
i
um検査法に関する研究【研究分担者】 濵砂良一 （産業医科大学医学部泌尿器科）

研究要旨
My
c
o
p
l
a
s
mag
e
n
i
t
a
l
i
u
m検出のための２つの検出法について、基礎的、臨床的研究を行った。旭化成ファーマ社のマイコプラズマ抗原検出キット 「リボテストＲマイコプラズマ」
を用いて M.g
e
n
i
t
a
l
i
u
m検出のための基礎的研究を行った。１７株の M.g
e
n
i
t
a
l
i
u
mを培養さ
せた液体培地をそれぞれ段階希釈し、それぞれの希釈液を「リボテストＲマイコプラズマ」
させた。また、希釈液中の M.g
「リボ
e
n
i
t
a
l
i
u
mの DNAコピー数を r
e
a
l
t
i
me法にて測定し、テストＲマイコプラズマ」法の検出限界を測定した。１７株中１６株が、その原液（希釈前）では「リボテストＲマイコプラズマ」は陽性を示した。しかし、１０倍希釈した液体では陽性を示さず、「リボテストＲマイコプラズマ」の検出限界は４．
６×１０５コピー／㎖と高く、臨床的には使用できない可能性が高い。

Ａ．研究目的B．研究方法わが国で保険適用となっている M.g
e
ni
t
al
i
um

対 象 は 産 業 医 大 学 に て 保 存 し て い る M.

検出キットはなく、現在、数社から発売され

g
e
n
i
t
a
l
i
u
m株 １７株（標準株 G３７Tを含む）でている検出キットが臨床的に使用可能であるある。M.g４マイコプラズマ
e
n
i
t
a
l
i
u
m株は SP

かどうか、検討している。旭化成ファーマ社

培地（液体培地）で増殖、冷凍保存されていのマイコプラズマ抗原検出キット「リボテスる。保存株を再度、SP
４マイコプラズマ培地

トＲマイコプラズマ」は、My
c
o
p
l
a
s
map
n
e
u
-

にもどし増殖させ、その菌液をさらに本培地

mo
n
i
a
eの検出用に開発されたものであるが、を段階希釈した。段階希釈したそれぞれの菌

M.g
e
n
i
t
a
l
i
u
mと交差反応があり、初尿中の液を用いて、「リボテストＲマイコプラズマ」

M.g
e
n
i
t
a
l
i
u
mを検出できる可能性がある。本を 反 応 さ せ た。さ ら に、希 釈 し た 菌 液 をキットは約１５分で M.p
n
e
u
mo
n
i
a
eが検出可能

Mg
Paa
d
h
e
s
i
o
ng
e
n
eを 標 的 と す る r
e
a
l
t
i
me

であるため、M.g
e
n
i
t
a
l
i
u
mに応用できる場合、 PCR法にて、希釈菌液中の DNAコピー数を
来院当日および治療後判定にも使用できる可測定した。これにより本キットの検出限界

能性がある。本研究では本キットの検出限界（DNAコピー数）が推定できることとなる。

を測定し、臨床応用が可能かどうかの基礎試

本研究は、保存した M.g
e
n
i
t
a
l
i
u
m株を用い

験を行った。

た。これらの株はすべて番号化され、ヒトの検体由来であること以外に、個人情報を有しないため、倫理に関する問題は生じない。

―１４０―

C．研究結果

E．結論

標準株以外に、当科で保存している臨床分

旭化成ファーマ社のマイコプラズマ抗原検

離株１６株、計１７株を用いた。１７株中、１６株で、出キット「リボテストＲマイコプラズマ」の希釈する前の菌液で、「リボテストＲマイコ

M.g
e
n
i
t
a
l
i
u
mの検出限界を測定した。測定限プラズマ」で陽性を示した。１株は判定不能

界は１０５DNAコピー前後であり、本キットのであった。さらに１０倍希釈をすると、すべて臨床応用は困難である。

の株の１０倍希釈菌液で「リボテストＲマイコ
プラズマ」は陰性を示し、M.g
e
n
i
t
a
l
i
u
mは検
出できなかった。

Ｇ．研究発表「リボテストＲマイコプラズマ」が陽性を示なし

５した菌液の DNAコピー数は２．
０×１０ ±１．
１×
１０５コピーであった（最大値４．
６×１
０５、最小値
２．
７×１０４コピー）であった。

Ｈ．知的財産権の出願・登録状況
１．特許取得D．考なし

察

北 欧 で 検 査 の 中 心 と な っ て い る Mg
Pa

２．実用新案登録

ealtimePCR法（検査
a
d
h
e
s
i
nを標的とする rなし

室での検討）では、１０コピー以上の検体を陽性としており、我々の研究室でもこの基準に

３．そ の 他

従 っ て い る。こ れ ま で 我 々 が 検 討 し た M.

g
e
n
i
t
a
l
i
u
m陽性初尿検体の DNAコピー数は、
１０～２．
０×１
０７コピーであり、大半は１０～１０４コ
ピーである。「リボテストＲマイコプラズマ」
では１０５コピー以上でないと陽性を示さない
ことがわかった。陽性となる検体は、臨床検体のごく一部であり、これまでの検出を考慮すると、大半の尿道炎症例では M.g
e
n
i
t
a
l
i
u
m
は陰性と判断されることになる。従って、本キットの臨床使用は極めて困難であると言わざるをえない。

―１４１―なし

Mycoplasma genitalium
᳨ᰝἲ䜢
䜢୰ᚰ䛻
䛻
⏘ᴗ་⛉኱Ꮫ Ἢᒀჾ⛉ℊ◁Ⰻ୍ᖹᡂ 27ᖺᗘ䛾◊✲᪂䛧䛔M.genitalium᳨ฟἲ䠄䠎ἲ䠅䛻䛴䛔䛶䛾䚸ᇶ♏ⓗ䚸⮫ᗋⓗ◊✲䜢⾜䛳䛯1) ᪫໬ᡂ䝣䜯䞊䝬♫ 䝬䜲䝁䝥䝷䝈䝬ᢠཎ䜻䝑䝖 䛂䝸䝪䝔䝇䝖R 䝬䜲䝁䝥䝷䝈䝬䛃䛾M.genitalium᳨ฟ䛾䛯䜑䛾ᇶ♏ⓗ◊✲2) Seegene♫ AnyplexR䛾M.genitalium䛾⮫ᗋⓗ◊✲―１４２―䝬䜲䝁䝥䝷䝈䝬ᢠཎ䜻䝑䝖䝸䝪䝔䝇䝖R䝬䜲䝁䝥䝷䝈䝬• 䝸䝫䝌䞊䝮⺮ⓑ L7/L12䛾᳨ฟ䜻䝑䝖• Mycoplasma pneumoniae᳨ฟ⏝䛻㛤Ⓨ䛥䜜䛯• ဗ㢌䛼䛠䛔ᾮ䜢⏝䛔䛶䚸⣙15ศ䛷᳨ฟྍ⬟• Mycoplasma genitalium䛻஺ᕪ཯ᛂ䛜䛒䜚䚸⏨ᛶᒀ㐨䛾M.genitalium᳨ฟ䛻ᮇᚅ䛜䛷䛝䜛
┠ⓗM.genitalium䛾᳨ฟ㝈⏺䜢 ᐃ䛧䚸⮫ᗋᛂ⏝䛜ྍ⬟䛛䛹䛖䛛᳨ウ䛩䜛䠄⏘ᴗ་⛉኱Ꮫ೔⌮ጤဨ఍:H26-174䠅

M.pneumoniae䛻䛚䛡䜛ᇵ㣴䚸PCRἲ䛸䛾ẚ㍑:
ឤᗘ 57%, ≉␗ᗘ91-92%䚸㝧ᛶ୍⮴⋡ 85%―１４３―(᪫໬ᡂ䝣䜯䞊䝬 ㈨ᩱ䜘䜚䠅M.genitalium䛸஺ᕪ཯ᛂ䛒䜚→M.genitalium䛾᳨ฟ䛜ྍ⬟䛷䛿䛺䛔䛛䠛―１４４―䝬䜲䝁䝥䝷䝈䝬ᢠཎ䜻䝑䝖᳨ฟ㝈⏺䛾᳨ウ䛂䝸䝪䝔䝇䝖R䝬䜲䝁䝥䝷䝈䝬䛃 䛾ᑐ㇟
M.genitaliumᰴᰴ 17ᰴᰴᶆ‽ᰴ G37⮫ᗋศ㞳ᰴ

M2282 , M2300, M2321, M2341䠄䝕䞁䝬䞊䜽䠅 M6257, M6280, M6285, M6286, M6328, M6489 䠄䝇䜴䜵䞊䝕䞁䠅 M6090,
M6151䠄䝣䝷䞁䝇䠅 M6282, M6283, M6284, M6287 䠄᪥ᮏ䠅

᪉ἲ
䝇䝖䝑䜽䛧
䛧䛯ᰴ䛾ཎᾮ䜢10ಸಸᕼ㔘䛧䛧䚸䛭䜜䛮䜜䛾ᕼ㔘ᾮ䜢䛂䛂䝸䝪䝔䝇䝖R 䝬䜲䝁䝥䝷䝈䝬䛃䛻䛻䛶M.genitalium䜢䜢᳨ฟฟ䛩䜛ཎᾮ 䠄䠍ಸᕼ㔘䛸࿧䜆䠅 䜢10ಸᕼ㔘䛧䠄ཎᾮ0.4ml䠇DNA buﬀer 3.6ml䠅䚸108䜎䛷ᕼ㔘䛩䜛䛭䜜䛮䜜䛾ᕼ㔘ᾮ䛻䛂䝸䝪䝔䝇䝖R 䝬䜲䝁䝥䝷䝈䝬䛃䛾⥥Წ䜢1ศ㛫 ᾐ䛩ୖグ⥥Წ䜢䚸10ศ㛫ᢳฟᾮ䛻ᾐ䛩ୖグ䚸ᢳฟᾮ䛛䜙4᦬ 䝔䝇䝖䝥䝺䞊䝖䛻⁲ୗ䛧䚸30ศᚋ䛻ุᐃ䛩䜛䛭䜜䛮䜜䛾ᕼ㔘ᾮ䛾ṧᾮ䚸䛚䜘䜃ᕼ㔘ᾮ䜢౑⏝䛧䚸real-me PCR䛷M.genitalium䛾DNA 䝁䝢䞊ᩘ䜢⟬ᐃ䛩䜛⤖ᯝ䝸䝪䝔䝇䝖⤖ᯝ⳦ᰴ⳦ᾮ୰䛾DNA 䝁䝢䞊ᩘᢳฟ䝏䝳䞊䝤୰䛾DNA䝁䝢䞊ᩘ

1ಸ

10ಸ

100ಸ

1ಸ

10ಸ

100ಸ

1ಸ

10ಸ

100ಸ

G37㸦ᶆ‽ᰴ䠅

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

362980

40901

4058

28126

1780

291

M2282

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

118732

15233

1200

144463

549

72

M2300

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

243312

23336

5047

8136

1114

98

M2321

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

281078

24730

1870

11142

2112

160

M2341

ぢ䛘䛪䜙䛔

㝜ᛶ

㝜ᛶ

248401

27409

2365

14611

1220

225

M6257

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

156210

13940

945

5471

1112

48

M6280

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

258044

20088

1210

13539

1584

247

M6285

ẚ㍑ⓗ⃰䛔⥺

㝜ᛶ㝜ᛶ

304320

28557

3457

22623

2147

120

M6286

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

242903

12069

1208

15678

745

88

M6328

ᴟ䜑䛶ῐ䛔

㝜ᛶ

㝜ᛶ

199244

13991

1145

17567

734

107

M6489

ᴟ䜑䛶ῐ䛔

㝜ᛶ

㝜ᛶ

102323

6393

656

7955

790

196

M6090

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

467403

34197

2474

29632

2448

183

M6151

ᴟ䜑䛶ῐ䛔

㝜ᛶ

㝜ᛶ

27846

3009

217

841

147

35

M6282

ᴟ䜑䛶ῐ䛔

㝜ᛶ

㝜ᛶ

64160

6789

508

5157

469

73

M6283

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

97803

9789

534

13514

1885

102

M6284

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

125172

8387

663

5176

340

20

M6287

ῐ䛔⥺

㝜ᛶ

㝜ᛶ

131579

1073

800

9737

1668

112

17ᰴ
ᰴ୰16ᰴ
ᰴ䛷䚸⌧ᾮ䛷䛿㝧ᛶ2.0㽢
㽢105 㼼1.1 㽢105 DNA copies /ml(4.6㽢
㽢105䡚2.7㽢
㽢104 copies/ml)―１４５―⪃ᐹ䛚䜘䜃⤖ㄽ䛂䝸䝪䝔䝇䝖R䝬䜲䝁䝥䝷䝈䝬䛃䛿M.genitalium䛻ᑐ䛧䛶཯ᛂ䜢♧䛧䛯䛧䛛䛧䚸䛭䛾᳨ฟ㝈⏺䛿䛚䛚䜘䛭105 copies/ml䛷䛒䛳䛯ᡃ䚻䛜䛣䜜䜎䛷⾜䛳䛶䛝䛯M.genitalium㝧ᛶ᳨య䛾ᒀ୰⃰ᗘ䛿2㽢107䡚
108copies/ml䛷䛒䜛ᡃ䚻䛜⾜䛳䛶䛔䜛real-me PCRἲ䛾᳨ฟ㝈⏺䛿10copies/ml䛻タᐃ䛧䛶䛔䜛䚹ᚑ䛳䛶䚸኱༙䛾ᒀ᳨య䛷䛿䚸 䛂䝸䝪䝔䝇䝖R䝬䜲䝁䝥䝷䝈䝬䛃䛷䛿㝜ᛶ䛸ุᐃ䛥䜜䜛ྍ⬟ᛶ䛜㧗䛔ᚑ䛳䛶䚸ึᒀ᳨య䜢⏝䛔䛯䛂䝸䝪䝔䝇䝖R䝬䜲䝁䝥䝷䝈䝬䛃䛾M.genitalium䛾᳨ฟ䛿䚸ᅔ㞴䛷䛒䜛䛸⤖ㄽ௜䛡䛯AnyplexR䛾M.genitalium䛾⮫ᗋⓗ◊✲• Seegene♫ AnyplexR䛾M.genitalium䛾᳨ฟ㝈⏺䛾᳨ウ䛿᫖ᖺሗ࿌䛧䛯䚹 17ᰴ䛷䛿㻝㻝㻙㻠㻤 㼏㼛㼜㼕㼑㼟㻛㼙㼘㻘㻌㻝㻟ᰴ䛿㻝㻙㻢㻌㼏㼛㼜㼕㼑㼟㻛㼙㼘䛷᳨ฟྍ⬟䛷䛒䛳䛯䚹ሗ࿌ୖ䚸᳨ฟ㝈⏺䛿50 copies/ml䛸䛧䛯䛜䚸ከ䛟䛾ᰴ䛷10
copies/ml௨ୗ䛷᳨ฟྍ⬟䛷䛒䛳䛯• ಖᏑ⮫ᗋ᳨య㻔ึᒀ䠅䜢⏝䛔䛶䚸㻹㼓㻼㼍 㼞㼑㼍㼘㻙㼠㼕㼙㼑㻌㻼㻯㻾ἲ 㻔㻹㼓㻼㼍㼍㼐㼔㼑㼟㼕㼚䜢ቑᖜ䠅䛸㻭㼚㼥㼜㼘㼑㼤ἲ䛸䛾ẚ㍑䜢⾜䛳䛯䠄⏘ᴗ་⛉኱Ꮫ೔⌮ጤဨ఍:H25-158䠅

―１４６―

Seegene vs MgPa PCR for M.genitalium
MgPa

SeegeneConcordance

Positive

negative

Total

positive

27

1

28

Positive 96.4% (27/28)

negative

1

71

72

Negative 98.6% (71/72)

Total

28

72

100

⤖ᯝ䛚䜘䜃⤖ㄽAnyplexR䛸MgPa real-me PCRἲ䛸䛾㝧ᛶ୍⮴⋡䛿96.4%䚸㝜ᛶ୍⮴⋡䛿98.6%䛷䛒䜚䚸 AnyplexR䛿⮫ᗋ᳨య䛻䜒༑ศ౑⏝䛷䛝䜛᳨ᰝἲ䛷䛒䜛䛣䛸䛜ศ䛛䛳䛯௒ᚋ䚸AnyplexR䛿AllplexRἲ䜈ኚ᭦䛥䜜䛯䚹ᮏἲ䛿PCRἲ䛻ᐃ㔞ศᯒ䜢ຍ䛘䛯᪉ἲ䛷䛒䜚䚸Seegene♫䛷䛿Anyplexἲ䛸䛾ẚ㍑ヨ㦂䜒⤊஢䛧䛶䛔䜛䚹28ᖺᗘ䛻䛿䜟䛜ᅜ䛷⮫ᗋヨ㦂䜢ணᐃ䛧䛶䛔䜛䚹―１４７―

口腔・咽頭梅毒および淋菌・クラミジアの咽頭感染に関する検討【研究分担者】 余田敬子 （東京女子医科大学東医療センター耳鼻咽喉科）

研究要旨
口腔・咽頭梅毒と淋菌・クラミジアの咽頭感染について、今後の調査や対策を考察する
目的に、前者は当科で経験した症例の臨床的特徴について後ろ向きに検討し、後者は当科と研究協力施設において過去に実施した前向き研究の結果を比較検討した。
口腔・咽頭梅毒は、性器や皮膚に病変がなく口腔・咽頭の症状や病変が梅毒診断の契機になる場合が多かった。最近急激に患者数が増加している梅毒については、口腔・咽頭梅
毒の特徴を含めた情報を発信すること、現行の梅毒発生届けに口腔咽頭梅毒の項目を追加することが望まれる。
特徴的な症状や所見に乏しい淋菌・クラミジアの咽頭感染については、性器と咽頭の同日検査が保険で認められること、現行の感染症発生動向調査（STD定点）の調査票の項目に「咽頭淋菌感染症」と「咽頭クラミジア感染症」を別項目として加えることが望まれる。

A．研究目的Ｂ．研究方法性感染症のうち、患者数がこの数年で急増し口腔・咽頭の顕症梅毒については、当科でている梅毒と、従来から患者数が多いクラミジ

経験した症例の臨床的特徴について後ろ向き

アトラコマティス（Ch
；
l
a
my
d
i
at
r
a
c
h
o
ma
t
i
s

に検討する。淋菌・クラミジアの咽頭感染に以下クラミジア）感染症と淋菌感染症は、口ついては、当科と研究協力施設において過去

腔・咽頭に感染し病変を生じる場合があり、に実施した前向き研究の結果を比較検討する。

また口腔・咽頭が感染源ともなり得る。近年の性行動の多様化やオーラルセックスを提供

１．口腔・咽頭顕症梅毒する性風俗の増加を背景に、口腔・咽頭を介

１９８２年～２０１５年の間に当科で診断した口腔してこれらの性感染症に感染する人が増えて咽頭の顕症梅毒２７例について、その臨床所見いる一方で、口腔・咽頭への具体的な対策はや特徴を提示する。

遅れているといわざるを得ない。口腔・咽頭
梅毒と、淋菌・クラミジアの咽頭感染に対して、実際の感染者の特徴や臨床所見から、今後求められる対策について検討する。

２．淋菌・クラミジアの咽頭感染
２００５年～２０１５年の間に性感染症クリニック
および耳鼻咽喉科施設で実施した淋菌・クラ
ミジアの咽頭感染に関する前向き研究について、陽性者の結果を比較検討する。

―１４８―

性器の検査は、男性は初尿、女性は腟

１）性感染症クリニックにおける対象
神奈川県川崎市堀之内の性感染症（STI）

または子宮頸管スワブを検体として、淋

クリニック１施設にて性感染症検査を希望

菌・クラミジアともに SDA法で検出したして受診した人のうち、咽頭と性器から淋

②

耳鼻咽喉科

菌およびクラミジアの同日検査を受けた男

期間 cでは、上咽頭と咽頭からスワブ

女、２００５年１１月 １ 日 か ら２００６年 ７ 月 １ 日

を同日に採取し、SDA法を用いて淋菌と（期間 a）の５５５人と、２００８年９月１日から

クラミジアの検出を行った。期間 dでは、

２００９年１月１６日（期間 b）の２５０人。

上咽頭および咽頭スワブとうがい液を同日に採取し、スワブは SDA法を用いて、

２）耳鼻咽喉科施設における対象

うがい液は realt
imePCR法を用いて淋

全国１０箇所（表１）の耳鼻咽喉科施設において、口内炎、咽頭炎、扁桃炎、咽喉頭異常感などの患者、または咽頭の性感染症

菌とクラミジアの検出を行った。
４）倫理面での配慮

検査希望者のうち、同意の得られた１８歳～

研究開始前に、研究内容および研究に関

６５歳の男女、２０１０年１１月１８日から２０１２年３する事項について、本学倫理委員会にて承月６日（期間 c）の１８２人と、２０１３年１月７

認（東京女子医科大学倫理委員会承認１３５０

日から２０１５年２月２日（期間 d）の３６２人。

番および２０３０番）された説明文書を用いて口頭で説明を行い、文書にて研究参加の同

３）検査方法（表２）

意を得た。

咽頭スワブ、うがい液を検体とし、淋菌
培養と核酸増幅検査の PCR法（o
l
y
me
r
a
s
e

c
h
a
i
nr
e
a
c
t
i
o
nポリメラーゼ連鎖反応、アンプリコア STD−
１クラミジアトラコマティス）、

Ｃ．研究結果SDA法（s
t
r
a
n
dd
i
s
p
l
a
c
e
me
n
ta
mp
l
i
f
i
c
a
t
i
o
n、

１．口腔・咽頭顕症梅毒症例

鎖置換増幅、BDプローブテックETCT／ GC）、

１）男女比、年齢分布、年別患者数

TMA法（t
r
a
ns
c
r
i
pt
i
onmodi
a
t
e
da
mpl
i
f
i
c
a
t
i
on、

男性１５例、女性１２例で、年齢分布は１６～

転写介在増幅、アプティマコンボ２）
、r
e
a
l

７５歳、平均３７．
０歳で、男女とも各年齢層に

（r
t
i
mePCR
e
a
lt
i
mepol
yme
r
a
s
ec
ha
i
nr
e
a
c
t
i
on、

幅広く分布していた（図１）。経時的変化とコバスＲ４８００システム CT／ NG）を用いてして１９９７年以降男性例が多くなり、１９９９年検出した。

と２０００年に１例ずつ HI
V陽性の男性同性愛①

性感染症クリニック者が含まれていた。２００１年からは症例が途

期間 a、bともに、同日に採取した咽頭絶えていたが、２０１３年から１例ずつではあるが毎年患者がみられている（図２）。

スワブとうがい液を検体とし、淋菌は淋
菌培養、SDA法、TMA法の３検査を、咽２）主訴と口腔・咽頭所見（表３）

頭のクラミジア検査は核酸増幅法の受診時の主訴は咽頭痛が最も多く１５例

PCR法、SDA法、TMA法の３検査を実（５５％）、咽 頭 異 常 感 が 次 い で 多 く ６ 例

施し、いずれかの検査が２つ以上陽性（２２％）であった。当科初診時の口腔咽頭所だった人を陽性者と判定した。

見としては、第２期病変である粘膜斑が口―１４９―狭部粘膜、特に軟口蓋の後縁に沿って孤状

２）男女別咽頭陽性率（表５）に拡大して融合して蝶が羽を広げたような淋菌・クラミジアの咽頭陽性者それぞれ形を呈した b
u
t
t
e
r
f
l
ya
p
p
e
a
r
a
n
c
eが最も多くの割合は、性感染症クリニックの期間 aで１３例（４８％）、次いで粘膜斑が次いで多く１０

は男性１２．
８％・２．
６％、女性１２．
５％・８．
７％、

例（３
７％）、第１期病変である初期硬結・性 感 染 症 ク リ ニ ッ ク の 期 間 bで は 男 性

硬性下疳は２例（７％）であった。

２１．
０％・２．
５％、女 性１５．
４％・１
４．
８％、耳
鼻咽喉科施設の期間 cでは男性８．
７％・０％、

３）性器・皮膚病変の有無（表４）性器病変を認めたのは６例（２
２％）
、性器

女性７．
９％・１．
６％、性感染症クリニックの病変以外の皮膚病変を認めたのも６例

期 間 dで は 男 性７．
９％・１．
６％、女９．
９％・（２２％）であった。性器病変は扁平コンジ

４．
１％であった。性感染症クリニックでもローマが１例、他は詳細不明であるが性器

耳鼻咽喉科施設でも、a～ d全ての検討に病変に対して他院で精査・加療中が５例でおいて、陽性者の割合は淋菌の方がクラミあった。皮膚病変は梅毒性乾癬が２例、梅ジアを上回っており、そのうち性感染症ク

毒性脱毛が２例、梅毒性丘疹が１例、梅毒リニックでの男性では淋菌の咽頭陽性者が性膿疱疹が１例で、うち１例は乾癬・脱毛・

クラミジアの咽頭陽性より統計的に有意に膿疱疹、扁平コンジローマを合併していた。

多かった。

４）病

期（表５）

３）咽頭・性器の同日検査の陽性者の割合

第１期が２例、他はすべて第２期であっ性感染症クリニックで実施した咽頭・性た。第３～４期は認めなかった。

器の同日検査による陽性者の割合を図４、５）感染経路（表５）５に示す。

夫婦や交際相手など特定のパートナーか性器の陽性者の割合と咽頭の陽性者の割らが最も多く９例（３３％）、次いでソープラ合を比較すると、男性のクラミジアにおいンドなどの性風俗、水商売の女性からの感てのみ咽頭の陽性者の割合が性器の陽性者染が多かった。同性との性交渉で感染したの割合に比べて統計的に有意に少なかった

例はいずれも１９９８年以降の男性例で、３例

（Wi
l
c
o
c
x
o
n符号付順位検定）。男性の淋菌、中２例は HI
V感染を合併していた。

女性の淋菌およびクラミジア検査では咽頭の陽性者の割合は性器の陽性者の割合に比２．淋菌・クラミジアの咽頭感染

べて少ないものの有意差はなく、さらに女

１）男女別年齢分布

性の淋菌においてはやはり有意差はないも性感染症クリニックでの期間 a・b、耳鼻のの咽頭の陽性者の割合が性器の陽性者の咽喉科施設での期間 c・dにおける被験者の割合を上回っていた。

男女別年齢分を図３に示す。性感染症クリまた、淋菌もクラミジアも男女ともに性ニックと耳鼻咽喉科施設において、女性の器が陰性で咽頭のみの陽性者が存在した。

年齢分布はほぼ同じであった。性感染症ク４）耳鼻咽喉科施設における淋菌・クラミジ

リニックの男性被験者は耳鼻咽喉科に比べア陽性者の咽頭所見（表７）て２０歳代が少ない傾向がみられた。

耳鼻咽喉科施設の期間 c・dの計５４４人の―１５０―

咽頭からの淋菌・クラミジア検査の結果、受診する症例は少ないことが以前から指摘さ淋菌陽性者は４３例（７．
９％）、クラミジア陽

れ て い が、当 科 で も 第 １ 期 の 症 例 は ２ 例

性者は１１例（２．
０％）で、性感染症クリニッ（８％）に過ぎなかった。第２期の特徴的な粘クと同様にクラミジアは淋菌に比べて陽性

膜疹を生じていた症例も、多くは前医で難治者数が少なかった。

性咽頭炎・扁桃炎として診断に至らずに当科検査実施時の咽頭所見は、淋菌では所見へ紹介されていた。口腔・咽頭梅毒は第１期のない正常の咽頭が１６例、急性扁桃炎が１１

病変、第２期病変ともに他の疾患には見られ例、非特異的な咽頭炎が１１例、上咽頭炎がない梅毒独特の病変を呈するため、診断する

４例、慢性咽頭炎・扁桃炎が２例、舌炎・医療者側が口腔・咽頭梅毒病変の特徴を知っ

咽頭アフタが２例であった。このうち所見ていれば診断は決して難しくない。口腔・咽無しのうちの２例、急性扁桃炎のうちの２

頭梅毒は性器や皮膚病変を伴わないことが多例、慢性扁桃炎のうちの２例、咽頭アフタ

く、感染力のある早期梅毒であるため、口腔・の１例の計７例に反復する扁桃炎の既往が咽頭病変を適切に診断しないと、無症候に移あった。

行するなど診断を逸する可能性がある。ここ

クラミジアは所見のなしが３例、上咽頭数年の梅毒患者の増加に対して、「梅毒＝生炎が３例、急性扁桃炎・扁桃周囲炎が２例、殖器病変」というイメージを取り払い、口腔

非特異的な咽頭炎が１例、頸部リンパ節腫

咽頭病変のみの梅毒症例があることを広く周脹が１例、舌炎・咽頭アフタが２例であっ

知させることが望まれる。また、現行の梅毒た。このうち上咽頭炎の１例に反復する扁発生届けの「４．症状の欄」の「初期硬結・硬桃炎の既往があった。

性下疳」を「初期硬結・硬性下疳（部位：性器・口 腔・咽 頭・そ の 他（

Ｄ．考

）」と 部

位の記入欄を設け、さらに「４．症状の欄」の察

項目に「口腔・咽頭粘膜斑」を加えることも、
口腔・咽頭梅毒の認知につながると考える。

１．口腔・咽頭顕症梅毒
当科で経験した口腔・咽頭梅毒症例の特徴
は、第１期である初期硬結・硬性下疳を呈し

２．淋菌・クラミジアの咽頭感染て受診する症例は少なく、第２期の特徴的な性感染症検査希望者に性器と咽頭の同日検

粘膜疹である b
u
t
t
e
r
f
l
ya
p
p
e
a
r
a
n
c
eを呈して咽査を行うと、性器のみの陽性者、咽頭のみの頭痛などの咽頭症状で受診する症例が多いこ

陽性者がそれぞれ存在していた。淋菌・クラと、性器や皮膚病変を伴わない例が多く咽頭ミジア感染症は無症候性感染であっても不妊の症状や病変が診断の契機となっていたこと、の原因になるため、感染者数の多くを占める

同性愛男性では HI
V感染の可能性があること、

若い世代の感染者を早期に適切に診断するこが挙げられる。

とは重要である。性器も咽頭の特徴的な症状

第１期の初期硬結・硬性下疳は性器に次いや所見に乏しい淋菌・クラミジア感染症に対で口腔咽頭に好発し、痛みを伴わず数週間でして、受診の機会を逃さず適切に診断するた

自然消退するため第１期のうちに医療機関へ

めに、性性器と咽頭の同日検査が保険で認め―１５１―

ア感染症」を別項目として加えることを提案られることが求められる。
また、耳鼻咽喉科施設においては性感染症する。

と気づかず、咽頭炎や扁桃炎などの症状で耳鼻咽喉科を受診する人の中に淋菌やクラミジ
アの咽頭感染者が含まれていた。さらに淋

Ｆ．健康危険情報

菌・クラミジアの咽頭感染者のなかに反復性なし

扁桃炎の既往を持つ人が含まれていたことは、
淋菌・クラミジアが扁桃炎の診断で一般的に用いる細菌検査では検出できないために淋

Ｇ．研究発表菌・クラミジアによる扁桃炎と気づかれずに、

１．論文発表扁桃炎を繰り返している症例が含まれている１

余田敬子：口腔・咽頭に関連する性感染可能性が示唆された。性的活動期を過ぎて扁症

桃炎を反復するようになった症例においては、－８５３，２０１５．

淋菌・クラミジアの咽頭感染も除外診断に含２

日本耳鼻咽喉科学会会報 １１８：８４１

余田敬子：診断・治療に必要な耳鼻咽喉

めて対応するべきことを、耳鼻咽喉科の臨床科臨床検査 ― 活用の p
とp
―
o
i
n
t
i
t
f
a
l
l

現場に広く認知させることが必要と考えられ

咽喉頭炎の鑑別た。

１６４，２０１５．
３

Ｅ．結

MBENT１７９：１５６－

余田敬子：口腔粘膜疾患 ―特徴と治療の要点― 性感染症を疑う口腔粘膜疾患

論

MBENT１７８：６２－７２，２０１５．

の診療

口腔・咽頭の顕症梅毒患者の多くは、性器や皮膚に病変がなく口腔・咽頭の症状や特徴

２．学会発表なし的な病変が梅毒診断の契機になる場合が多い。
そのような口腔・咽頭梅毒の特徴を広く周知すべく情報を発信するとともに、現行の梅毒発生届けに口腔咽頭梅毒の項目を追加することを提案する。

Ｈ．知的所有権の取得状況
１．特許取得性器も咽頭も特徴的な症状や所見に乏しいなし

淋菌・クラミジア感染症に対して、受診の機会を逃さず適切に診断するために性器と咽頭２．実用新案登録の同日検査が保険で認められること、淋菌・なし

クラミジアについて現行の感染症発生動向調査（STD定点）の調査票の項目の「淋菌感染３．そのほか症」を「性器淋菌感染症」に改め（既にクラミジアは「性器クラミジア感染症」となっている）、「咽頭淋菌感染症」と「咽頭クラミジ

―１５２―

なし

⾲㻝㻌㻌᳨ᰝᐇ᪋᪋タAᮾிዪᏊ་⛉኱Ꮫᮾ་⒪䝉䞁䝍䞊ᮾி㒔Ⲩᕝ༊

Bᮡ⏣⪥㰯ဗႃ⛉༓ⴥ┴༓ⴥᕷ⨾὾༊

C䛛䜏䛷⪥㰯ဗႃ⛉䜽䝸䝙䝑䜽㟼ᒸ┴ᐩኈᕷ

D

ᯇཎ⪥㰯䛔䜣䛣䛖⛉་㝔

ᒱ㜧┴㛵ᕷ

E

Ώ㎶⪥㰯ဗႃ⛉䞉䜰䝺䝹䜼䞊⛉䜽䝸䝙䝑䜽* 㟼ᒸ┴⇕ᾏᕷ

F

䛸䜒⪥㰯⛉䜽䝸䝙䝑䜽*໭ᾏ㐨ᮐᖠᕷ୰ኸ༊

G

䛥䛟䜙⪥㰯ဗႃ⛉*໭ᾏ㐨ᮐᖠᕷⓑ▼༊Hすᒸ䛨䜃ဗႃ⛉䜽䝸䝙䝑䜽#໭ᾏ㐨ᮐᖠᕷ㇏ᖹ༊

I

ኳ⚄⪥㰯ဗႃ⛉#⚟ᒸ┴⚟ᒸᕷ୰ኸ༊

J

䜘䛧䛛䜟⪥㰯ဗႃ⛉#⚄ዉᕝ┴ᕝᓮᕷᖾ༊

↓༳ 2010ᖺ11᭶18᪥䛛䜙᳨ᰝ㛤ጞ䠆# 2011ᖺ8᭶1᪥䛛䜙᳨ᰝ㛤ጞ

2011ᖺ8᭶1᪥䛛䜙᳨ᰝ㛤ጞ

⾲2 ᮇ㛫ู ဗ㢌᳨య䛸᳨ᰝἲ
ᮇ㛫

2005ᖺ
ᖺ11᭶
᭶
䡚2006ᖺ
ᖺ7᭶
᭶
䠄ᮇ㛫a䠅
䠅

㻿㼀㻵
䡴䢔䢂䡫䡴
㻝᪋
᪋タ
2008ᖺ
ᖺ9᭶
᭶
䡚2009ᖺ
ᖺ1᭶
᭶
䠄ᮇ㛫b䠅
䠅

⪥㰯⛉
㻢᪋
᪋タ

2010ᖺ
ᖺ11᭶
᭶
䡚2012ᖺ
ᖺ2᭶᭶䠄ᮇ㛫c䠅䠅

⪥㰯⛉
㻝㻜᪋
᪋タ

2013ᖺ
ᖺ1᭶
᭶
䡚2014ᖺ
ᖺ2᭶
᭶
䠄ᮇ㛫d䠅
䠅

⑓ཎయ
᾿⳦

䜽䝷䝭䝆䜰

᾿⳦

䜽䝷䝭䝆䜰

᾿⳦䞉䜽䝷䝭䝆䜰᾿⳦䞉䜽䝷䝭䝆䜰

᳨య

᳨ᰝἲ

䝇䝽䝤

᾿⳦ᇵ㣴 SDA TMA䛖䛜䛔SDA TMA䝇䝽䝤PCR SDA TMA䛖䛜䛔PCR SDA TMA䝇䝽䝤᾿⳦ᇵ㣴 SDA TMA䛖䛜䛔SDA TMA䝇䝽䝤PCR SDA TMA䛖䛜䛔PCR SDA TMAୖဗ㢌䝇䝽䝤

SDA

ဗ㢌䝇䝽䝤

SDA

ୖဗ㢌䝇䝽䝤

SDA

ဗ㢌䝇䝽䝤

SDA

䛖䛜䛔

Real me PCR

―１５３―

⏨ዪẚ
ேᩘ

㻝㻥㻤㻞䡚㻞㻞㻜㻝㻡 ᖺ㱋ศᕸ

㻡

㻠㻠㻑

㻡㻢㻑

⏨ᛶ
ዪᛶ

㻠
㻟
㻞

⏨ᛶ

ዪᛶ

㻝
㻜
䡚㻝
㻝㻥 㻞㻜䡚
䡚 㻟㻜䡚
䡚 㻠㻜䡚
䡚 㻡㻜䡚
䡚 㻢㻜䡚
䡚 㻣㻜䡚
䡚

⏨ᛶ 15౛
ዪᛶ 12౛ᖺ㱋ᖺ㱋 16䡚75 䠄ᖹᆒ 37.0䠅ᅗ㻝 ᙜ⛉䛻䛚䛡䜛ཱྀ⭍䞉ဗ㢌㢧⑕ᱵẘ 㻞㻣⑕౛䛾⏨ዪẚ䞉ᖺ㱋ศᕸ

㻟㻜

㽢㻝㻜㻟

㻞㻡

ᝈ
⪅
ᩘ

4

ᙜ⛉⏨ᛶ⑕౛

㻞㻜ᙜ⛉ዪᛶ⑕౛
3

㻝㻡
2

㻝㻜
1

㻡
㻞㻜㻝㻡

㻞㻜㻝㻜

㻞㻜㻜㻡

㻞㻜㻜㻜

㻝㻥㻥㻡

㻝㻥㻥㻜

㻝㻥㻤㻡

㻝㻥㻤㻜

㻝㻥㻣㻡

㻝㻥㻣㻜

㻝㻥㻢㻡

㻝㻥㻢㻜

0

㻝㻥㻡㻡

㻜

ҽဃі΁ႾὉ‫׎‬ᇌज़௨ၐऴ‫إ‬ἍὅἑὊ ज़௨ၐႆဃѣӼᛦ௹‫إ‬ԓợụ

ᅗ2 ᪥ᮏ䛾ᱵẘⓎ⏕௳ᩘ䛾᥎⛣䛸ᙜ⛉ཱྀ⭍䞉ဗ㢌㢧⑕ᱵẘ⑕౛ᩘ

―１５４―

⾲3 ᙜ⛉䛻䛚䛡䜛ཱྀ⭍䞉ဗ㢌㢧⑕ᱵẘ27⑕౛䛾୺ッ䛸ཱྀ⭍ဗ㢌ᡤぢ౛ᩘ%ཱྀ⭍ဗ㢌ᡤぢ

౛ᩘ

%

ဗ㢌③

15

55

buerﬂy appearance

13

48

ဗ㢌␗ᖖឤ

6

22

ဗ㢌䞉⯉䛾⢓⭷ᩬ

10

37

ཱྀ၁䞉ཱྀゅ
䛾䜃䜙䜣

3

11

ึᮇ◳⤖䞉◳ᛶୗ⑃

2

7⯉③䞉ཱྀෆ③2

7

ཱྀゅ䛾䜃䜙䜣䞉ⓑᩬ

14㢕㒊䝸䞁䝟⠇
⭘⬽

1

4

ဗ㢌Ⓨ㉥

1

4

୺ッ

⾲4 ᙜ⛉䛻䛚䛡䜛ཱྀ⭍䞉ဗ㢌㢧⑕ᱵẘ27⑕౛䛾ᛶჾ䞉⓶⭵⑓ኚ䛾᭷↓
ᛶჾ⑓ኚ

౛ᩘ

%

⓶⭵⑓ኚ

౛ᩘ

%

䛒䜚

6

22

䛒䜚

5

19

䛺䛧

19

70

䛺䛧

22

81

୙ヲ

2

8

ᱵẘᛶ஝Ⓞ䠆
ᱵẘᛶ⬺ẟ䠆ᱵẘᛶୣ⑈ᱵẘᛶ⮋⑁⑈䠆

2౛
2౛
1౛
1౛

䠆䠍౛䛿஝Ⓞ䞉⬺ẟ䞉⮋⑁⑈䜢ྜే

―１５５―

⾲5 ᙜ⛉䛻䛚䛡䜛ཱྀ⭍䞉ဗ㢌㢧⑕ᱵẘ27⑕౛䛾⑓ᮇ䛸ឤᰁ⤒㊰

䠄ே䠅

⑓ᮇ

౛ᩘ

%

ឤᰁ⤒㊰

౛ᩘ

%

➨1ᮇ

2

8

䝟䞊䝖䝘䞊

9

33

➨2ᮇ

23

92

ᛶ㢼಑

5

19

Ỉၟ኎

3

11

ྠᛶឡ

3

11

䛭䛾௚

4

15

୙ヲ

3

11

䠄ே䠅

ᮇ㛫a 555ே

120
100
80
60
40
20
0

⏨ᛶ

ዪᛶ

ᮇ㛫b 250ே

50
40
30
20
10
0

⏨ᛶ

ዪᛶ

ᖺ㱋
䠄ṓ䠅
⏨ᛶ 272ே 18䡚69ṓ
ዪᛶ 283ே 17䡚55ṓ䠄ே䠅୰ኸ್ 37.0ṓ
୰ኸ್ 28.0ṓ

⏨ᛶ 81ே 20䡚60ṓ
ዪᛶ 169ே 18䡚57ṓ䠄ே䠅ᮇ㛫c 182ே

50
40
30
20
10
0

ᖺ㱋
䠄ṓ䠅

⏨ᛶ

ዪᛶ

ᮇ㛫d 362ே

50
40
30
20
10
0

⏨ᛶ

ᖺ㱋
䠄ṓ䠅
⏨ᛶ 92ே 19䡚59ṓ
ዪᛶ 90ே 57 䡚57ṓ

ᅗ3

୰ኸ್ 29.0ṓ
୰ኸ್ 28.0ṓ

ዪᛶ

ᖺ㱋
䠄ṓ䠅
⏨ᛶ 190ே 19䡚59ṓ
ዪᛶ 172ே 㻝㻣䡚57ṓ

ྛᮇ㛫䛾⿕㦂⪅䛾⏨ዪูᖺ㱋ศᕸ

―１５６―

୰ኸ್ 34.0ṓ
୰ኸ್ 29.0ṓ

୰ኸ್ 29.0ṓ
୰ኸ್ 28.0ṓ

⾲6 ⏨ዪู ဗ㢌㝧ᛶ⋡

㻿㼀㻵
䡴䢔䢂䡫䡴
㻝᪋タ

ᮇ㛫

⿕᳨⪅ᩘ

᾿⳦

䜽䝷䝭䝆䜰

2005ᖺ
ᖺ11᭶
᭶
䡚2006ᖺ
ᖺ7᭶᭶䠄ᮇ㛫a䠅䠅

⏨ᛶ 27212.8 %

2.6 %ዪᛶ 28312.5 %

8.7 %

2008ᖺ
ᖺ9᭶
᭶
䡚2009ᖺ
ᖺ1᭶᭶䠄ᮇ㛫b䠅䠅

⏨ᛶ

81

21.0 %

2.5 %ዪᛶ 16915.4 %

14.8 %

⪥㰯⛉
㻢᪋
᪋タ

2010ᖺ
ᖺ11᭶
᭶
䡚2012ᖺ
ᖺ2᭶᭶䠄ᮇ㛫c䠅䠅

⏨ᛶ

92

8.7 %

0%

ዪᛶ

90

4.4 %

1.1 %

⪥㰯⛉
㻝㻜᪋
᪋タ

2013ᖺ
ᖺ1᭶
᭶
䡚2014ᖺ
ᖺ2᭶᭶䠄ᮇ㛫d䠅䠅

⏨ᛶ 190

7.9 %

1.6 %

ዪᛶ 172

9.9 %

4.1 %

㻝㻣ே 㻣㻑

⏨ᛶ
272ே

㻝㻢㻥ே
㻢㻣㻑

᾿⳦

㻝㻤ே
㻣㻑

㻠㻥ே
㻝㻥㻑

㻡ே 㻞㻑 *
㻞ே 㻝㻑

*P<0.001

㻢㻥ே
㻞㻣㻑 *

䡴䢓䢌䡸䢚䡭

㻝㻤㻞ே 㻣㻜㻑

ዪᛶ
283ே

㻞㻡ே 㻝㻝㻑㻢ே 㻟㻑㻝㻟ே 㻢㻑᾿⳦䡴䢓䢌䡸䢚䡭 㻠㻡ே㻞㻣㻑㻝㻥㻝ே 㻤㻜㻑

ဗ㢌䛾䜏

ᅗ4

㻣ே 㻟㻑
㻝㻟ே
㻤㻑

ဗ㢌䠇ᛶჾ

㻥㻥ே 㻡㻤㻑

ᛶჾ䛾䜏

཮᪉㝜ᛶ

ᮇ㛫a ဗ㢌䞉ᛶჾ ྠ᫬᳨ᰝ䛾㝧ᛶ⪅ᩘ

―１５７―㻜ே 㻝ே 㻝㻑 *
㻞ே 㻞㻑

⏨ᛶ
81ே

㻝㻞ே
㻝㻡㻑 * *P<0.001

㻝㻡ே
㻝㻥㻑

㻟㻥ே
㻠㻤㻑

䡴䢓䢌䡸䢚䡭

᾿⳦
㻞㻡ே
㻟㻝㻑

ዪᛶ
169ே

㻢㻤ே 㻤㻠㻑
㻣ே 㻟㻑
㻝㻟ே㻢㻑

㻞㻡ே 㻝㻝㻑㻢ே 㻟㻑㻝㻟ே 㻢㻑᾿⳦䡴䢓䢌䡸䢚䡭 㻟㻞ே㻝㻠㻑㻝㻟㻡ே 㻤㻜㻑

ဗ㢌䛾䜏

ဗ㢌䠇ᛶჾ

㻝㻤㻟ே 㻣㻣㻑

ᛶჾ䛾䜏

཮᪉㝜ᛶ

ᅗ5 ᮇ㛫b ဗ㢌䞉ᛶჾ ྠ᫬᳨ᰝ䛾㝧ᛶ⪅ᩘ⾲㻣㻌㻌⪥㰯ဗႃ⛉᪋タ䛻䛚䛡䜛᾿⳦䞉䜽䝷䝭䝆䜰㝧ᛶ⪅䛾ဗ㢌ᡤぢ ᾿⳦㝧ᛶ 㻠㻟౛䠄㻣㻚㻥㻑䠅 䠄ᡤぢ䛾㔜」䛒䜚䠅
ᡤぢ↓䛧
ᛴᛶᡥ᱈⅖
㠀≉␗ⓗဗ㢌⅖
ୖဗ㢌⅖
៏ᛶဗ㢌⅖䞉ᡥ᱈⅖
⯉⅖䞉ဗ㢌䜰䝣䝍
㻔཯᚟ᛶᡥ᱈⅖䛾᪤ 䛒䜚

㻝㻢㻌౛
㻝㻝㻌౛
㻝㻝㻌౛
㻠㻌౛
㻞㻌౛
㻞౛
㻣㻌౛ 㻕

 䜽䝷䝭䝆䜰㝧ᛶ㻝㻝౛䠄㻞㻚㻜㻑䠅
ᡤぢ↓䛧
ୖဗ㢌⅖
ᛴᛶᡥ᱈⅖䞉࿘ᅖ⅖㠀≉␗ⓗဗ㢌⅖㻝㻌౛㢕㒊䝸䞁䝟⠇⭘⬽
㻔཯᚟ᛶᡥ᱈⅖䛾᪤ 䛒䜚

㻟㻌౛
㻟㻌౛
㻞㻌౛
㻞㻌౛
㻝㻌౛
㻝౛㻕

 ᾿⳦㻗䜽䝷䝭䝆䜰㝧ᛶ 㻝౛䠄㻜㻚㻞㻑䠅
ཱྀෆ⅖䊻ᡥ᱈⅖㻗ୖဗ㢌⅖―１５８―

HPV関連子宮頸癌早期スクリーニングの啓発に関する研究【研究分担者】 三鴨廣繁 （愛知医科大学大学院医学研究科）【研究協力者】 山岸由佳 （愛知医科大学病院感染症科）

萩原

真生 （愛知医科大学病院感染制御部）

研究要旨
日本人健常女性２
４０名における HPV（h）は、CSW（c
u
ma
np
a
p
i
l
l
o
mav
i
r
u
s
o
me
r
c
i
a
ls
e
x
）では、非 CSW と比較して高率に HPV陽性であった（ p＜０．
００００１）。検討した症例
wo
r
k
e
r
全体では HPV５２型が最多で、次いで５８型の順に多かった。nonCSW では５２型が多かった
が、CSW では５３型が多いもののハイリスク型全体が万遍なく検出された。特に、CSW では、複数のハイリスク型が同時に検出される率が高かった（ p＜０．
０１）。ローリスク型 HPVのみが検出された症例は陽性者全体の７．
６％であった。日本人健常女性においても高リス
ク型の HPV感染（保ウイルス）率は高く、子宮がん検診では細胞診に HPVスクリーニン
グ検査を併用することは臨床的意義が高いと考えられた。
TM
２８ dを用いて、スワブ検体と尿検体を用いて検出された
An
y
p
l
e
x
I
IHPV
e
t
e
c
t
i
o
nk
i
t

４２％、特異度は９９．
８７％でHPVジェノタイプの相同性を確認したところ、全体の感度は６８．
あった。細胞診と尿検体の検査で低い相同性を示した遺伝子型 HPVは単一もしくは複数の遺伝子型の HPVが同時に検出される場合でも検出率に影響はなかった。HPVスクリー
ニング検査において、尿検体は侵襲性が低い検査であるが、尿検体による検査では感度が十分とは言えず、スクリーニング法として使用するには注意する必要がある。

一 方、I
ARC（I
n
t
e
r
n
a
t
i
o
n
a
lAg
e
n
c
yf
o
rRe
-

Ａ．研究目的

s
e
a
r
c
ho
nCa
n
c
e
r
,国際がん研究機関）では、HPVの遺伝子型は１００種類以上存在するが、 ６６型を含む１４種をハイリスク型として提唱し癌化リスクが高い高リスク型群と低リスク型ていることから、大手検査会社（SRL等）で群に大別される。

は上記１３タイプに加えハイリスク型である６６

HPVジェノタイプ判定検査は２０１１年に新規型を加えた１４タイプの検出が可能としている

保険適用項目となっており、現在、クリニッ

が、１６，１８型以外は型別判定は実施されない。

チ HPV（２０１１年より）、MEBGENHPVキット

そこで、健常女性における HPV検出状況お（２０１３年より）が使用可能である。いずれもよび HPV検出にあたって子宮勁管スワブ検１３タイプ（１６，１８，３１，３３，３５，３９，４５，５１， 体と比較して侵襲性が低い尿検体は使用可能
５２，５６，５８，５９，６８型）の検出が可能である。 かについて検討した。

―１５９―

図１

Ｂ．研究方法

HPVが検出された１１８名における HPVの同時検出型

研究１：健常女性における HPV検出状況

HPV高リスク型１９種類、HPV低リスク型
９種類の計２８種類の型を検出できる Se
e
g
e
n
e
TM
社「An
」を用い、
y
p
l
e
x
I
IHPV2
8d
e
t
e
c
t
i
o
nk
i
t

既承認タイピングキットでは検出できない型も含めて日本人女性子宮頸部における HPV
検出状況を検討した。

研究２：HPV検出に尿検体は使用可能か？

HPVのスクリーニング検査の低侵襲化を目的として、スワブ検体の他に尿検体を用いた検査を行い、２種類の検体を用いた場合のHPV陽性１１８名の詳細な HPV血清型を図２
に示した。
図２

HPV陽性１１８名の詳細な HPV血清型

結果の相同性を調査した。

倫理面への配慮
本研究は、愛知医科大学病院倫理委員会の承認を得て実施した（承認番号１５－ H
０４４）。

Ｃ．研究結果ハイリスク型 HPVが検出された１０９例の研究１：健常女性における HPV検出状況

複数菌検出例数を図３に示した。

健常女性２４０名（CSW５４名（２３％）、非 CSW
１８６名（７７％））を対象とした。CSW 群には妊

図３

ハイリスク型 HPVが検出された１０９例の複数菌検出例数

婦 は 存 在 せ ず、非 CSW 群 で は 妊 婦 は６２名（３３％）であった。
健常女性１１８名（４９％）に何らかの HPVを検出した。HPV未検出例は１２０名（５０％）、測
定エラーが２名（１％）であった。

HPVが検出された１１８名における HPVの同時検出型について図１に示した。

HPVの検出状況を CSW群と非 CSW群に分けて示した（図４）。

―１６０―

図４

HPVの検出状況
CSW 群と非 CSW 群の比較

表２

ローリスク型 HPVの検出状況

56 58 59 68p* p

研究２：HPV検出に尿検体は使用可能か？

p

スワブ検体と尿検体を用いて検出された
ハイリスク型 HPV同時検出型数を CSW

HPVハイリスク型ジェノタイプの相同性

群と非 CSW 群にわけて表１に示した。

を表３に示した。

表１

表３

ハイリスク型 HPV同時検出型数
CSW 群と非 CSW 群の比較

スワブ検体と尿検体を用いて検出された
HPVハイリスク型ジェノタイプの相同性
Kappa data

No. of samples for each resultpp

Two-tailed
MacNemar’s P
value

NP

0.317

NP

1.000

NA

0.046

Risk

-/-

+/-

-/+

+/+

% agreement

Total no.
posive% posive
agreement

K

SD

16

High

220

1

0

17

99.6

18

94.4

0.969

0.030

18

High

226

1

1

10

99.2

12

83.3

0.905

0.067

26

High

234

4

0

0

98.3

4

0.0

0.000

0.000

31

High

221

1

0

16

99.6

17

94.1

0.967

0.032

NP

0.317

33

High

227

2

0

9

99.2

11

91.8

0.896

0.073

NP

0.157

35

High

231

3

0

4

98.7

7

57.1

0.721

0.154

ST

0.083

39

High

224

4

0

10

98.3

14

71.4

0.825

0.086

NP

0.046

45

High

232

0

0

6

100.0

6

100.0

1.000

0.000

PE

NA

51

High

228

2

0

8

99.2

10

80.0

0.885

0.081

NP

0.157

52

High

206

5

1

26

97.5

32

81.3

0.882

0.047

NP

0.103

53

High

221

3

0

14

98.7

17

82.4

0.897

0.059

NP

0.083

56

High

234

3

0

1

98.7

4

25.0

0.396

0.276

PO

0.083

58

High

216

2

0

20

99.2

22

90.9

0.948

0.037

NP

0.157

59

High

231

2

0

5

99.2

7

71.4

0.829

0.119

NP

0.157

66

High

229

2

0

7

99.2

9

77.8

0.871

0.090

NP

0.157

68

High

225

5

0

8

97.9

13

61.5

0.752

0.106

ST

0.025

69

High

231

3

0

4

98.7

7

57.1

0.721

0.154

ST

0.083

73

High

227

7

0

4

97.1

11

36.4

0.522

0.156

PO

0.008

82

High

228

8

0

2

96.6

10

20.0

0.324

0.173

PO

0.005

HPV検出１１８例の血清型別検出状況を図５

スワブ検体と尿検体を用いて検出された

HPVローリスク型ジェノタイプの相同性を

に示した。
図５

Int.

Genotype

表４に示した。

HPV検出１１８例の血清型別検出状況

表４

ローリスク型 HPVの検出状況について表２に示した。

―１６１―

スワブ検体と尿検体を用いて検出された
HPVローリスク型ジェノタイプの相同性尿検体を用いた場合の感度と特異度（スワブ検体との比較）を表５に示した。

ク型全体が万遍なく検出された。特に、CSW
では、複数のハイリスク型が同時に検出される率が高かった（ p＜０．
０１）。ローリスク型

表５

HPVのみが検出された症例は陽性者全体の尿検体を用いた場合の感度と特異度（スワブ検体との比較）

７．
６％であった。日本人健常女性においても高リスク型の HPV感染（保ウイルス）率は高
く、子宮がん検診では細胞診に HPVスクリー
ニング検査を併用することは臨床的意義が高
いと考えられる。
TM
を用いて、
An
y
p
l
e
x
I
IHPV2
8d
e
t
e
c
t
i
o
nk
i
t

スワブ検体と尿検体を用いて検出された

HPVジェノタイプの相同性を確認したところ、尿検体を用いて単一もしくは複数の遺伝子

全 体 の 感 度 は６８．
４２％、特 異 度 は９９．
８７％ で型の HPVが検出された場合の影響を表６にあった。細胞診と尿検体の検査で低い相同性示した。

を示した遺伝子型 HPVは単一もしくは複数の遺伝子型の HPVが同時に検出される場合

表６

尿検体を用いて単一もしくは複数の遺伝
子型の HPVが検出された場合の影響でも検出率に影響はなかった。尿検体は侵襲性が低い検査であるが、尿検体を用い多場合、

No. of cases
Single infecon

遺伝子検査であっても感度が十分とは言えず、

Mulple infecons

Genotype

Risk

26

High

0

0

3

39

High

0

2

68

High

1

73

High

5

82

High

42

p value*

スクリーニング法として使用するには注意す

0

1.000

3

9

1.000

る必要がある。

0

4

8

0.385

0

3

3

0.182

1

2

7

0

0.067

Low

2

1

2

5

0.500

43

Low

0

0

4

3

1.000

54

Low

1

1

9

5

1.000

70

Low

1

0

5

1

1.000

Discordant Concordant Discordant Concordant*: Fisherの正確確率検定

Ｅ．結論

日本人健常女性においても高リスク型のHPV感染（保ウイルス）率は高く、子宮がん
検診では細胞診に HPVスクリーニング検査

Ｄ．考を併用することは臨床的意義が高いことが明察らかになった。特に、CSW群では、HPV感染

日本人健常女性２４０名における HPV
（h
u
ma
n

率は高く、高リスク群に対する HPVスクリー）は、CSW（c
o
me
r
c
i
a
ls
e
x
p
a
p
i
l
l
o
ma v
i
r
u
s

ニングの意義はさらに高いものと推察された。

）では、非 CSW と比較して高率に HPV
wo
r
k
e
r

HPVスクリーニング遺伝子検査において陽性であった（ p＜０．
００００１）。検討した症例

尿検体は侵襲性が低い検査であるが、この方全体では HPV５２型が最多で、次いで５８型の法による検査では感度が十分とは言えず、ス順に多かった。non
CSW では５２型が多かっクリーニング法として使用するには注意する

たが、CSW では５３型が多いもののハイリス必要がある。

―１６２―

Ｇ．研究発表

Ｈ．知的所有権の出願・登録状況

１．論文発表１．特許取得（本研究班で得られた成果のみ。海外も該当なし

国内も含む。）
１

三鴨廣繁：淋菌感染症、今日の小児治療指針

２．実用新案登録

第１６版、p３８２－３８３、医学書院、
p
.

該当なし

東京、２０１５．
９．
１．（書籍）
２ MikamoH,Ma
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山岸由佳・三鴨廣繁：梅毒、日本母性衛生学会雑誌５６（２）：学６－学１２，２０１５．（総説）

２．学会発表（本研究班で得られた成果のみ。海外も国内も含む。）
１

山岸由佳・和泉孝治・宮﨑成美・鈴木隆
佳・末松寛之・西山直哉・小泉祐介・三
鴨廣繁：
「An
y
p
l
e
xI
IHPV2
8De
t
e
c
t
i
o
n」
キットの臨床現場での使用経験．日本性感 染 症 学 会 第２８回 学 術 大 会 O－１７、
２０１５．
１２．
６、東京．

―１６３―

該当なし

性感染症、特に HPVと子宮頸癌についての啓発に関する研究【研究分担者】 川名敬 （東京大学大学院医学系研究科産婦人科学講座）

研究要旨
尖圭コンジローマは日本における女性の第３番目の性感染症である。尖圭コンジローマ
は性器イボを形成する顕性感染とイボ形成を見ない不顕性感染があり、不顕性感染時にHPVを排出していることが性行為感染による蔓延を助長している。また子宮頸癌の原因ウイルスであるハイリスク HPVの同時感染も大きな問題である。本研究では、尖圭コンジ
ローマの有無を層別化し、女性の子宮頸部における HPVタイプの分布を解析し、さらに尖圭コンジローマ不顕性感染の実態把握を行った。
症する。コンジローマ合併妊婦から出生したＡ．研究目的児は、コンジローマ罹患歴のない妊婦から出尖圭コンジローマ（以下コンジローマ）の生した児と比較して、J
ORRPのリスクが２３１

罹患者数は近年漸増傾向にある。女性の罹患倍と言われている。J
ORRPのリスクとして、

年齢は２０歳前後がピークであり、その後に妊分娩時間や破水から出生までの時間の影響が娠・出産に与える影響が危惧される。HPV感示唆されている。一般的に、病変が小さい場染を予防する HPVワクチンが開発され、世界合、コンジローマ合併妊娠において帝王切開中で導入されている。尖圭コンジローマの主を選択する適応はない。広範囲またはかなりな原因となる HPV６／１１型感染に対して、海大きな病変がある場合は、HPVの母子感染を外では４価 HPVワクチンは高い予防効果が完全に防ぐことはできないだろうが、帝王切証明されている。国内においては、HPVワク

開を推奨する相対的適応がある。

チンの積極的勧奨が中止されており、現在にそこで、昨年度は、コンジローマ合併妊婦至っている。HPVワクチンの安全性が確認に焦点を絞り、その母体から出生する児へのされるまで、HPVワクチンによる HPV６／１１

母子感染について検討することとした。妊娠

感染予防は実質的に期待できない。

中のコンジローマの疫学調査とその児におけ

一方、HPV６／１１型の母子感染が起こると、る咽頭 HPV検査を実施した。

感染した児は再発性呼吸器乳頭腫症（JORRP）のリスクにさらされる。J
ORRPは HPV６／１１

本研究では、「尖圭コンジローマを有さな型によって引き起こされ、腫瘍が喉頭部や上いが、HPV６／１１／４２／４４のコンジローマタイ

気道で増大すると、嗄声や気道閉塞を生じうプの HPVDNAが検出される」場合を「不顕る。コンジローマ合併妊婦から出生した児の性感染」と定義している。海外の先行研究でうち、１４５人あたり１人の割合で J
ORRPを発は、コンジローマの不顕性感染者は、有病者―１６４―

の約３倍との報告がある。母子感染という観

ワブ中の擦過細胞が採取されていることを確点からは、不顕性感染者でも妊娠すると免疫認している。

制御能が落ちるために顕性（コンジローマを発症）になる。そのため、若年女性における（倫理面への配慮）
本研究にあたっては、厚生労働省の「ヒト不顕性感染者の把握は重要であった。
本年度は、女性における子宮頸部の不顕性

ゲノム解析研究に関する共通指針」に則り、東京大学医学部の医学部研究倫理審査委員会

感染の実態を把握することを目的とした。

の承認を得て研究を実施した。また、提供試料、個人情報をコード化したうえで厳格に管Ｂ．研究方法理・保存した。HPV検査は一般的な検査として一般診療で実施されている検査であるが、１．患者背景２０１０年～２０１５年に当科で HPVタイピングを実施した子宮頸部擦過細胞４６４検体につい

本研究では研究費によって i
nh
o
u
s
eで検査を
行っている。

て、尖圭コンジローマの有無を分けて、HPVタイプの分布を検討した。本研究に関しては東京大学医学部研究倫理委員会の承認を得ている。HPV検査は一般診療の中で実施されＣ．研究結果１．HPV感染率についてている。

視診によって、４１１例は尖圭コンジローマ－ 群）
無 し（CA、５３例 は 尖 圭 コ ン ジ ロ ー マ－群（CA+群）に分けた。HPV陽性者は、CA

２．ウイルス学的検討
外来受診の女性患者４６４例で、尖圭コンジ

では７２．
３％に対して、CA+群は９６．
２％であり、

ローマの有無を視診によって確認した。STD

CA+群では HPV感染者が多かった。本検体

クリニックを受診した患者も一部に含まれる。

は医療機関に受診している集団であり、一般

子宮頸部擦過細胞を採取し、その一部で HPV的な HPV陽性率よりも明らかに高かった。

検査を行った。

本調査の対象患者は、このような特殊性があることを加味しておく必要がある。CA+群

３．HPVタイピング

で HPV陰性が２例いたが、これは外陰コンジ

HPVタイピングを行うために、児の咽頭ス
ワブから t
（Qi
h
eDNe
a
s
yBl
o
o
dMi
n
iKi
t
a
g
e
n
,

ローマ患者で、子宮頸部には HPVが検出されなかった症例である。

Cr
a
wl
e
y
,UK）を 用 い て DNAを 抽 出 し た。
HPVタ イ ピ ン グ は PGMYCHUV法 に よ り

２．重複感染率について行った。本法は HPV６，１１，１６，１８，２６，３１，

複数の HPVタイプが検出される HPVの重３３，３４，３５，３９，４０，４２，４３，４４，４５，５１，－群では複感染率は、CA+群では約５０％、CA

５２，５３，５４，５５，５６，５７，５８，５９，６６，６８，

２６．
５％であり、CA+群では倍の重複感染者が６９，７０が検出できる方法である。全例で HLAいることが判明した。特に４タイプ以上の遺伝子が陽性であることを確認しており、ス

７％に対しHPV多重感染者は、CA+群で１２．

―１６５―

－ 群 で は３．
て、CA８％ で あ り、尖 圭 コ ン ジ

常成人女性）の HPV陽性率は約１０％である。

ローマ患者では、HPV感染・増殖が盛んに起－ 群の７本研究の CA
３％という HPV陽性率はこっていることが窺われる。

特殊な集団と考えるべきである。本検討では子宮頸部細胞診は全例には試行されていない

３．ハイリスク HPV感染についてために、細胞診異常の女性も含まれている。

子宮頸癌の関連するハイリスク HPVとは、細胞診の軽度異常（LSIL）の場合は、国内で４％の HPV陽性率であることから、これ
HPV１６，１８，３１，３３，３５，３９，４５，５１，５２，５６， は７９．
－ 群における
５８，６６，６８のことを指す。CAに近い集団であったと考えられる。細胞診異HPVタイプののべ検出数は、４７７タイプ（重複常者が多く含まれることが示唆された。

感染含）であり、そのうち２６４タイプ（５５．
３％）

重複感染率の検討では、CA+群では、ハイがハイリスクタイプであった。一方、CA+群

リスク HPVを含む複数の HPVタイプに感染

では、１０３タイプのうち３２タイプ（３１．
０％）－群に比して、子宮頸していることから、CAがハイリスクタイプであった。CA+群では、癌のリスクは高まると予想される。

コンジローマタイプが多くなるために、相対－群において、約半数がハイリスクタイ
CA

的にハイリスクタイプの割合は少なかった。

プであったことは、この集団においてハイリ
スク HPVが蔓延していることを示している。

４．コンジローマタイプの不顕性感染率

国内からの既報では、子宮頸部細胞診正常女

このような集団におけるコンジローマタイ

性のうち、約１０％にハイリスク HPVが検出さ

プ（HPV６／１１／４２／４４）の感染率を検討した。

れると言われる。また HPVワクチンの国内－群４１１例のうち、HPV６が４８例（１１．
６％）、 臨床試験の基礎データでは、約３０％の健常女
CA２％）、HPV４２／４４が７例
HPV１１が１３例（３．

性で HPV１６／１８抗体が陽性になっている。こ（１．
６％）であった。少なくとも約１５％の女性－群のうち７れと比べ、本検討では、CA
１検体が、コンジローマを発症していないにも関わ（約１５％）が HPV１６／１８であった。細胞診の正らず HPV６／１１の不顕性感染となっているこ

常・異常を考慮しない健常女性という集団にとが判明した。

－群は、一般集団
おいては、本検討対象の CA

一方、CA+群５３例のうち、３例のみコンジに近い可能性がある。

ローマタイプが検出されなかったが、これは－ 群において、HP
その CA
V６／１１の不顕性

外陰コンジローマのみで子宮頸部への感染は感染が５１例（約１５％）にみられたことは特記なかったためと考えられた。

すべきことである。以前の我々の研究（厚労省小野寺班）では、子宮頸部細胞診異常を認

Ｄ．考める女性のうち、不顕性感染率は約４～６％察であったことを考えると、今回の検討では明

本検討では、検討対象患者に医療機関受診らかに高い不顕性感染率であった。その原因と言うバイアスがかかっているため、HPV感として、コンジローマの既往患者（治療後の染率等のデータは先行研究と一致しない。国患者等）も含まれている可能性が考えられた。

内の既報では、子宮頸部細胞診正常女性（健サンプリング施設が限定されているため、本―１６６―

研究の結果がすぐに国内の実態を反映してい２．学会発表るとは言えなかったが、少なくとも本研究の１

敬：今どうなっているか、HPVワ

川名

HPVワクチン普及のためにな

結果に示されたような地域があることは言え

クチン

るだろう。

すべきことは？

第２８回日本性感染症学

会、教育講演、平成２７年１２月５日、神戸．

Ｅ．結

２

論

川名

敬：HPV予防ワクチンの光と影～接種の必要性と有害事象の可能性～、

HPVタイピングをベースとした疫学調査

中央区医師会学術講演会、平成２７年７月
２２日、東京．

を行った。コンジローマの病変を認めない女
性でも、コンジローマタイプの不顕性感染者が存在する。HPVタイピングで検出されていることから、ウイルスを排出していると考Ｈ．知的財産権の出願・登録状況

えられ、新たな罹患者の感染源になりうる。

１．特許取得

尖圭コンジローマの実態把握において、不顕

特になし

性感染者の存在は無視できないと考えられた。
２．実用新案登録
特になし

Ｇ．研究発表３．そ の 他

１．論文発表
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―１６７―

特になし

ͤࠝ‫ࣱڡ‬ỆấẬỦᵦᵮᵴज़௨ỉܱ७ிʮ‫ܖٻܖٻ‬ᨈ Ҕ‫ܖ‬ኒᄂᆮᅹဃ഻ႆᢋьᱫҔ‫ݦܖ‬ૌ ငۡʴᅹ‫ࡈᜒܖ‬
߷Ӹ ૟

Ꮡ ୎ ᾀ
‫⇞∙⇙סݴ‬∓∞∄↝ɼ↙Ҿ‫׹‣‣‡ ⁈⁂›↺↙↗׆‬ज़௨↚‫⅚↕ↆݣ‬ෙ‫↞∙⇧⇕∕⁈⁂›̖…↞↖ٳ‬᭗ⅳ
ʖ᧸јௐⅻᚰଢↄ↻↕ⅳ↺⅛‫׎‬ϋ↚ⅹⅳ↕↞⅚›⁂⁈∕⇕⇧∙↝ᆢಊႎѰ‫ڜ‬ⅻɶ
ഥↄ↻↕ⅹ↹⅚ྵ‫↚נ‬ᐱ→↕ⅳ↺⅛›⁂⁈∕⇕⇧∙↝‫ܤ‬μࣱⅻᄩᛐↄ↻↺↭↖⅚›⁂⁈∕⇕⇧∙↚↷↺›⁂⁈ ‡‣‣ज़௨ʖ᧸↞ܱឋႎ↚஖ࢳ↖ⅼ↙ⅳ⅛―１６８―

ᵐᆔ᫏ỉᵦᵮᵴὁἁἓὅ
ᾁ̖ὁἁἓὅ
ᵆἇὊἢἼἕἁἋᵇᾃ̖ὁἁἓὅ
ᵆỾὊἒἉἽᵇᵏᵔᵍᵏᵖ‫׹‬ᵏᵔᵍᵏᵖᵍᵔᵍᵏᵏ‫׹‬ỴἊἷἢὅἚᵟᵱᵎᵒỴἽἱἝỸἲ‫ط‬ᢘࣖ࠰ᱫᵏᵎബ῍‫ࣱڡ‬ᵗബ῍‫ࣱڡ‬੗ᆔ૾ඥ

ᵎᵊᴾᵏᵊᴾᵔὈஉᾂ‫ׅ‬ሂදᵎᵊᴾᵐᵊᴾᵔὈஉᾂ‫ׅ‬ሂදᢘࣖၐ‫ܷ܇‬ᫀầỮẆЭầỮ၏‫٭‬‫ܷ܇‬ᫀầỮẆЭầỮ၏‫٭‬Ẇ‫סݴ‬ἅὅἊἿὊἰ

ᵐᵎᵎᵗ࠰ႆ٥

ᵐᵎᵏᵏ࠰ႆ٥

ỽἢὊᵦᵮᵴἑỶἩᵐᵎᵏᵏ࠰ᵒஉ῍ μᐯ඙˳ẦỤỉπႎя঺ᵐᵎᵏᵑ࠰ᵒஉ῍ ‫ܭ‬஖੗ᆔ҄›⁂⁈∕⇕⇧∙↚᧙ↈ↺૎ሊ↝ਖ਼ᆆ‫ܷ܇‬ᫀⅻ⇂ሁ∕⇕⇧∙੗ᆔዬ࣯̟ᡶʙಅ᧏‫ڼ‬
․̖›⁂⁈
∕⇕⇧∙
ႆ٥

ોദʖ᧸੗ᆔඥ଀ᘍ
›⁂⁈∕⇕⇧∙‫ܭ‬஖੗ᆔ᧏‫ڼ‬

…̖›⁂⁈
∕⇕⇧∙
ႆ٥

ᆢಊႎѰ‫ڜ‬ɶഥⅺ↸ኖ․࠰Ҟኺᢅ․••‫࠰‫‬․••‫࠰•‣•․ ࠰‫‬․•‣•࠰ ․•‣‣࠰․•‣‣࠰ ․•‣․࠰․․•‣․•‣․࠰ ․•‣‥࠰․ • ‣ ‥࠰›⁂⁈∕⇕⇧∙੗ᆔࢸ↝ॸࣱ၊ၘႆၐ̊↚᧙ↈ↺‫إ‬ᢊ․•‣…࠰․ • ‣ …࠰․•‣‧࠰․ • ‣ ‧࠰ᇹ․‫ׅ‬иӒࣖ౨᚛ᢿ˟
›⁂⁈∕⇕⇧∙‫ܭ‬஖੗ᆔ↝ᆢಊѰ‫ڜ‬ɟ଺ࠀↆ੘ⅷ↝ᡫჷ≝›⁂⁈↚᧙ↆ⅚иӒࣖ౨᚛ᢿ˟↚↕‣•‫ׅ‬౨᚛

―１６９―

Ꮡ ୎ ᾁ
‫⇞∙⇙סݴ‬∓∞∄↝‫↝ࣱڡ‬፝ध࠰ᱫ↞․•ৗЭࢸⅻ⇺∞⇕↖ⅱ↹⅚↌↝ࢸ↚‫∝۔ک‬Јင↚ɨⅷ↺ࢨ
᪪ⅻүूↄ↻↺⅛›⁂⁈ ‡‣‣‫↝׹‬൐‫܇‬ज़௨ⅻឪↂ↺↗≏ज़௨ↆ↎δ↞ϐႆࣱԠԈ֥ʐ᪽ᏽၐ≋‼⁁⁄⁄⁂≌↝∐⇟⇕↚ↄ↸ↄ↻↺≑‼⁁⁄⁄⁂↞›⁂⁈ ‡‣‣‫ࡽ↕→↷↚׹‬ⅼឪↂↄ↻≏ᏽၨⅻձ᪽ᢿ↳ɥൢᢊ↖‫≏↗↺ↈٻف‬ք٣↳ൢᢊ᧍‫⇁ص‬ဃↇⅵ↺≑⇙∙⇞∓∞∄ӳ́‫ۡک‬ⅺ↸Јဃↆ↎δ↝ⅵ←≏‣…‧ʴⅱ↎↹‣ʴ↝лӳ↖‼⁁⁄⁄⁂⇁ႆၐↈ↺≑ମ࠰ࡇộỂỉᄂᆮỂỊὉὉὉɟᑍႎ↚≏၏‫٭‬ⅻ‫ↄݱ‬ⅳ‫ئ‬ӳ≏⇙∙⇞∓∞∄ӳ́‫↚۔ک‬ⅹⅳ↕ࠔྛЏ᧏⇁ᢠ৸ↈ↺ᢘࣖ↞↙ⅳ≑
࠼ር‫↞↎↭׊‬ⅺ↙↹‫ٻ‬ⅼ↙၏‫٭‬ⅻⅱ↺‫ئ‬ӳ↞≏›⁂⁈↝൐‫܇‬ज़௨⇁‫ܦ‬μ↚᧸ⅿↂ↗↞↖ⅼ↙ⅳⅻ≏
ࠔྛЏ᧏⇁ਖ਼‫↺ↈڜ‬Ⴛ‫ݣ‬ႎᢘࣖⅻⅱ↺⅛
ମ࠰ࡇ↞⅚‫۔ک‬ɶ↝⇙∙⇞∓∞∄↝၃‫ܖ‬ᛦ௹↗
↌↝δ↚ⅹↀ↺Թ᪽›⁂⁈౨௹⇁ܱ଀ↆ↎⅛―１７０―‫סݴ‬ἅὅἊἿὊἰểᚮૺẰủẺ‫۔ک‬ᡵૠி‫ٻ‬၏ᨈẆᵐᵎᵎᵎᵋᵐᵎᵏᵑ ίᶌᵛᵑᵐὸ

‫ٻ‬ᢿЎỊ᩼‫଺ک‬ỆỊ‫סݴ‬ἅὅἊἿὊἰầễẦẾẺ
7

6

6

5

5

5
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4

3

3

2

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2
1

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20

25

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35 ίᡵὸᏑ ୎ ᾂ ᵦᵮᵴᵔᵍᵏᵏज़௨ᎍỉạẼ‫סݴ‬ἅὅἊἿὊἰửஊẴỦஊ၏ᎍỊኖᵐᵓᵃỂẝụẆ‫ٶ‬ẪỊɧࣱ᫋ज़௨ểᚕỪủỦẇ ᵦᵮᵴὁἁἓὅỊଏज़௨ᎍὉஊ၏ᎍỆỊ໯јỂẝỦẇ‫ࣱڡ‬ỆấẬỦɧࣱ᫋ज़௨ỉܱ७ử৭੮ẴỦẮểỉ᣻ᙲࣱ

―１７１―

Ⴘ ႎ

‫⇞∙⇙סݴ‬∓∞∄⇁ஊↄ↙ⅳⅻ⅚›⁂⁈ ‡‣‣‡…․‡……
↝⇙∙⇞∓∞∄⇥⇊⇽↝›⁂⁈‟‶⁀″ⅻ౨Јↄ↻↺Ⅴɧ
ࣱ᫋ज़௨Ⅵ↝ܱ७⇁ჷ↺↎↰↚⅚‫↚ࣱڡ‬ⅹↀ↺‫ܷ܇‬ᫀᢿ↝ɧࣱ᫋ज़௨↝ܱ७⇁৭੮ↈ↺ↂ↗⇁Ⴘႎ↗ↆ↎૾ ඥ ᵱᵲᵧἁἼἝἕἁờẲẪỊி‫ٻ‬၏ᨈử˴ỤẦỉྸဌỂӖᚮẲẺ‫ࣱڡ‬धᎍỉạẼẆ‫סݴ‬ἅὅἊἿὊἰửஊẰễẟ ᾃᾀᾀ̊‫סݴ‬ἅὅἊἿὊἰửᛐỜẺᾄᾂ̊ ‫ܷ܇‬ᫀᢿờẲẪỊ‫ٳ‬ᨏẦỤરᢅኬᏘử੔ӕẲẆᵦᵮᵴἑỶἦὅἂ౨௹ửܱ଀ẲẺẇ ᵦᵮᵴỉ౨ЈỆỊẆᵮᵥᵫᵷඥίᵵᵦᵭỉᵦᵮᵴᴾᵥᶊᶍᶀᵿᶊᴾᵪᵿᶀᵬᶃᶒỆợụ೅แ҄ẰủẺᵦᵮᵴἑỶἦὅἂඥὸỂẝỦẇἡỶἼἋἁᵦᵮᵴᾉᵏᵔᵊᴾᵏᵖᵊᴾᵑᵏᵊᴾᵑᵑᵊᴾᵑᵓᵊᴾᵑᵗᵊᴾᵒᵓᵊᴾᵓᵏᵊᴾᵓᵐᵊᴾᵓᵔᵊᴾᵓᵖᵊᴾᵔᵔᵊᴾᵔᵖ
ἅὅἊἿὊἰᵆἿὊἼἋἁᵇᵦᵮᵴᾉ ᵔᵊᴾᵏᵏᵊᴾᵒᵐᵊᴾᵒᵑᵊᴾᵒᵒ
(zur Hausen, H. Nat Rev Cancer, 2002)ɶ᧓ἼἋἁᵦᵮᵴᾉ ᵓᵑᵊᴾᵓᵒᵊᴾᵖᵑ ễỄ―１７２―঺ጚᾀ ῍ᵦᵮᵴἑỶἩЎࠋᵦᵮᵴᶒᶗᶎᶃ
ᵔ
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ᶓᶌᶉᶌᶍᶕᶌ
ᶌᶃᶅᵿᶒᶇᶔᶃ
ᵲᶍᶒᵿᶊἅὅἊἿὊἰ໯Ẳίᵒᵏᵏ̊ὸ
ᵒᵖ
ᵏᵑ
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ᵐᵏ
ᵐ
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ᵐ
ᵗ
ᵒ
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ᵕ
ᵔ
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ᵏᵏᵒ
ᵓᵗᵏ

ἅὅἊἿὊἰஊụίᵓᵑ̊ὸ
ᵑᵕ
ᵏᵏ
ᵏᵎ
ᵐ
ᵎ
ᵎ
ᵎ
ᵎ
ᵎ
ᵎ
ᵏ
ᵐ
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ᵏ
ᵐ
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ᵓ
ᵏ
ᵎ
ᵎ
ᵏ
ᵏ
ᵐ
ᵐ
ᵏ
ᵐ
ᵏᵎᵓ

঺ጚᾀ ῍ᵦᵮᵴࣱᨗྙ
ἅὅἊἿὊἰᵆᵋᵇἅὅἊἿὊἰᵆᵉᵇ

ᵦᵮᵴᵋᶎᶍᶑᶇᶒᶇᶔᶃ

ᵐᵗᵕ̊ᵍᵒᵏᵏᵆᵕᵐᵌᵑᵃᵇᵓᵏ̊ᵍᵓᵑ
ᵆᵗᵔᵌᵐᵃᵇᵦᵮᵴᵋᶌᶃᶅᵿᶒᶇᶔᶃ

ᵏᵏᵒ̊ᵍᵒᵏᵏᵆᵐᵕᵌᵕᵃᵇᵐ̊ᵍᵓᵑᵆᵑᵌᵖᵃᵇἡỶἼἋἁἑỶἩᵐᵔᵒᴾἑỶἩᵑᵐ ἑỶἩ

ἅὅἊἿὊἰἑỶἩᵔᵖᴾ̊ᵍᵒᵏᵏᵆᵏᵔᵌᵓᵃᵇᵒᵗ ̊ᵍᵓᵑ
ᵆᵗᵐᵌᵓᵃᵇᵲᶍᶒᵿᶊᵓᵗᵏ ἑỶἩᵏᵎᵓᴾἑỶἩ

ᵲᶍᶒᵿᶊ

ᵒᵏᵏ̊

ᵓᵑ̊

―１７３―

঺ጚᾁ῍ἅὅἊἿὊἰἑỶἩỉЎࠋ
ᵡᵟᵆᵉᵇ

ᵡᵟᵆᵋᵇ
ᵎᵃ

6
31
44
54
66
82

ᵐᵎᵃ

ᵒᵎᵃ

11
33
45
55
68
83

16
35
51
56
69
84

ᵔᵎᵃ

ᵖᵎᵃ

18
39
52
58
70
unknown

ᵏᵎᵎᵃ

26
42
53
59
73
negative঺ጚᾂ῍ἡỶἼἋἁἑỶἩЎࠋ
ᵡᵟᵆᵉᵇ

ᵡᵟᵆᵋᵇ

ᵎᵃ

ᵐᵎᵃ

ᵏᵔ
ᵒᵓ
ᵔᵖ
ᵕᵎ
ᵏᵏ

ᵏᵖ
ᵓᵏ
ᵓᵑ
ᵕᵑ
ᵒᵐ

ᵒᵎᵃ
ᵑᵏ
ᵓᵐ
ᵓᵒ
ᵖᵐ
ᵒᵒ

ᵔᵎᵃ
ᵑᵑ
ᵓᵔ
ᵓᵓ
ᵖᵑ
ᵐᵔ

―１７４―

ᵖᵎᵃ
ᵑᵓ
ᵓᵖ
ᵓᵗ
ᵖᵒ
ᶓᶌᶉᶌᶍᶕᶌ

ᵏᵎᵎᵃ

ᵑᵗ
ᵔᵔ
ᵔᵗ
ᵔ
ᶌᶃᶅᵿᶒᶇᶔᶃ঺ጚᾃ῍᣻ᙐज़௨ྙ
㔜」ឤᰁ⋡䛾㐪䛔

ᵎᵌᵖ

CA(-)

ᵎᵌᵕ

CA(+)

ᵎᵌᵔ
ᵎᵌᵓ
ᵎᵌᵒ
ᵎᵌᵑ
ᵎᵌᵐ
ᵎᵌᵏ
ᵎ
ᶑᶇᶌᶅᶊᶃ

ᵐᶒᶗᶎᶃᶑ

ᵑᶒᶗᶎᶃᶑ

ᵒᶒᶗᶎᶃᶑ

ᵓᶒᶗᶎᶃᶑ

ᵔᶒᶗᶎᶃᶑ঺ጚᾄ῍ᵡᵧᵬधᎍửἫὊἋểẲẺἙὊἑ ኬᏘᚮီࠝửɼᚫỆӖᚮẲẺ‫ࣱڡ‬ᵏᵔᵓᵏ̊ử‫ݣ‬ᝋểẲềẆ‫ܷ܇‬ᫀᢿẦỤỉᵦᵮᵴử౨᚛ᵦᵮᵴᵔᵑᵏ̊ᵆᵡᵟᴾᵐᵐ̊ᵇᵦᵮᵴᵏᵏᵏᵓ̊ᵆᵡᵟ ᵏᵎ̊ᵇᵦᵮᵴᵒᵐᴾᴾᴾᴾᴾᴾᴾᴾᴾᴾᴾᴾᴾᵏᵎ̊ᵆᵡᵟ ᵎ̊ᵇᵦᵮᵴᵔᵉᶽᴾᴾᴾᴾᴾᴾᴾᴾᴾᴾ ᵐᵗ̊ ᵆᵡᵟ ᵏᵓ̊ᵇᵦᵮᵴᵏᵏᵉᶽᴾᴾᴾᴾᴾᴾᴾᴾᴾᴾᵏᵏ̊ ᵆᵡᵟ ᵖ̊ᵇᵦᵮᵴᵒᵐᵍᵒᵒᵉᶽᴾᴾᴾᴾᴾᴾᵖ̊ᵆᵡᵟ ᵏ̊ᵇἅὅἊἿὊἰἑỶἩ ᵏᵎᵒ ̊ ᵍᴾᵏᵔᵓᵏ ̊ ίᵔᵌᵑᵃὸ
ᵡᵟᵆᵉᵇ ᵓᵔ ̊ᵡᵟᵆᵋᵇ ᵒᵖ ̊ ᵍᴾᵏᵔᵓᵏ ̊ ίᵐᵌᵗᵃὸ

―１７５―

ộểỜ
 ஜ‫ݣ‬ᝋỆấẟềỊẆἅὅἊἿὊἰἑỶἩỉɧࣱ᫋ज़௨ྙỊᵏᵔᵌᵓᵃể᭗ẦẾẺẇᵡᵧᵬधᎍỆếẟềỊẆɧࣱ᫋ज़௨ྙỊኖᵑᵃể˯͌ỂẝẾẺẇ‫ࠀ؏ע‬ầẝỦẮểầᅆՐẰủẺẇ ౨ЈẰủẺᵦᵮᵴἑỶἩỉኖᵓᵎήỊἡỶἼἋἁᵦᵮᵴỂẝẾẺẇஜ‫ݣ‬ᝋỉ‫ܷ܇‬ᫀၶኬᏘᚮီࠝỉஊ໯ỊᎋॾẰủềẟễẟầẆ‫ݲ‬ễẪểờۡʴᅹӖᚮỉ࣏ᙲࣱầ᭗ẟᨼ‫ׇ‬ểᚕảỦẇ ᵡᵟᵆᵉᵇểᵡᵟᵆᵋᵇỉൔ᠋ỂỊẆᵡᵟᵆᵉᵇ፭ỂႻ‫ݣ‬ႎỆἡỶἼἋἁᵦᵮᵴầ˯ẪễẾềẟẺầẆᵦᵮᵴᵏᵔᵍᵏᵖỆᨂỦểẆᵡᵟᵆᵋᵇ፭ểӷሁỂẝẾẺẇ
ᵒ̖ᵦᵮᵴὁἁἓὅỊẆᫀၶểᵡᵟửјྙႎỆʖ᧸ỂẨỦӧᏡࣱầẝỦẇ ᣻ᙐज़௨ྙỊẆᵡᵟᵆᵉᵇỂଢỤẦỆ᭗ẪẆࣱ෇ѣỉ᭗ẰẆờẲẪỊ
ᵦᵮᵴỆ‫ݣ‬ẴỦβ၃ᛔ‫ݰ‬ỉ˯ẰửᅆՐẲềẟỦẇ

ʻࢸỉ‫ޒ‬ஓ ‫סݴ‬ἅὅἊἿὊἰӳ́‫ۡک‬ỉ‫ٶ‬ẪỊẆ᩼‫଺ک‬ỆỊီࠝửਦઇẰủềấỤẵɧࣱ᫋ज़௨ỂẝỦẇẲẦẲẆɧࣱ᫋ज़௨ᎍử‫۔ک‬ЭỆႆᙸẴỦẮểỊᩊẲẟẇ ᣻ᙐज़௨ỉợạỆẆ‫ٶ‬ૠỉᵦᵮᵴἑỶἩỆ୧ᩧẰủỦᨼ‫ׇ‬ỆấẟềỊẆᵦᵮᵴὁἁἓὅử੗ᆔẴỦॖ፯ầ‫ٻ‬Ẩẟẇ൐‫܇‬ज़௨ʖ᧸ὲၶʖ᧸ὲ ίɧࣱ᫋ज़௨ờԃỜềὸ࠼ẪᔯࡨẲềấụẆ൐‫܇‬ज़௨Ὁၶể᧙ᡲỉẝỦ၌धểẲềẆ࣬ବ஖ɭˊỆ‫סݴ‬ἅὅἊἿὊἰửᛐჷẰẶỦ࣏ᙲầẝỦểᎋảỦẇ

―１７６―

感染予防行動、早期受診促進のための性感染症啓発スライドについて【研究分担者】 白井千香 （神戸市保健福祉局）【研究協力者】 岩室紳也 （ヘルスプロモーション推進センター〔オフィスいわむろ〕）

種部

恭子 （女性クリニック We!TOYAMA）（自治医科大学看護学部）
野々山未希子渡會

睦子 （東京医療保健大学医療保健学部）

研究要旨
性感染症に関する特定感染症予防指針に示されている、若年層への情報提供について、性感染症の知識のみならず性感染症の予防を支援する環境づくりが必要であることから、予防行動や早期受診を促す情報提供を目的に、予防啓発資料をスライドで作成した。学校
では指導要領に沿って保健体育の教科書を使い、性感染症予防教育の授業がなされるべきだが、それを補い、中高生が自己学習できるスライドを厚生労働省のホームページから健康局結核感染症課のサイトに掲載可能とし、実際の普及を試みる。

Ａ．研究目的Ｂ．研究方法若年者の健康課題である性感染症について、思春期における１０代の若者を対象とした性『性感染症に関する特定感染症予防指針』に

感染症予防啓発スライド（PDF）を提供し、は「若年層に対しては、性感染症から自分の信頼できるサイト（厚生労働省健康局結核感

身体を守るための情報について、適切な人材

染症課のホームページ）から情報発信する。

の協力を得て、正確な情報提供を適切な媒体

スライド作成の資料収集等については、２０１２を用いて行い、広く理解を得ることが重要」

年に日本性感染症学会と日本思春期学会が共と示されている。若年者の感染予防行動を促編したスライド集「思春期の性の健康－性感し、感染を疑ったら医療機関に早期に適切に染症から身を守るために」の活用状況１）か受診できるよう、特に中高生向けの情報提供

らその見直しを踏まえ、研究協力者で議論をの方法を探る。

行い資料を収集し、実践的研究として新たなスライド集を研究協力
者の共同制作とした。

倫理面への配慮
個人情報を扱わないため特になし。

―１７７―

るか、であった。学校では指導要領に沿って

Ｃ．研究結果保健体育の教科書を使い、性感染症予防教育

スライド作成にあたって、中高生向け（特の授業が可能である。教科書や副読本にも性に中学生）にわかるように以下の内容を盛り感染症に関する知識の記述は丁寧で、高校生込むことを考慮した。

向けにはコンドームの使い方なども写真付き

・スライド一枚に示す情報は、できるだけ字で詳細に書かれている。ただし、それらの授数を少なくイラストや写真を活用する。

業の学習をさらに補うため、特に中高生がこ・疾患については、無症状のもの、治るもの、のスライドを一人で見ても、性感染症予防に

生命の危険につながるものなどを説明する。

ついて的確な情報を得られるようなスライド・性行動を分類し、性感染症がうつる行為と作成を意図した。
教科書とは違い、身近な自分自身のためのうつらない行為を明示する。
・コンドームで予防できるものと必ずしもコンドームだけでは予防できないものを示す。

情報提供を行うには、医学的な正確性より、伝える情報が簡潔でわかりやすいものであることを優先した。疾患の詳細や一般的治療、・コンドームの使い方を詳しく説明する。
例えば、Q＆ A形式で中学生が間違いや勘統計などは、講演会などで保健医療の専門家

違いに気づくようにする。Yo
u
Tu
b
eに掲載

から説明を得ながら理解することはできるかされている動画を紹介する。

もしれないが、自分自身の問題としてとらえ・性に関するリスクのうち若年での妊娠に関るための情報とはなりにくい。

するものは、今回のスライドでは具体的な

ただし、それぞれのスライドの補足説明や解説を除き、性感染症に焦点をあてる。

さらに詳細を知りたい者は、インターネット

・HI
Vや性感染症にリスクのある状況は、性やスマートフォンから情報を得るであろう。

行動の相手との関係において、経済的優位、

その検索の際に「性感染症」のうわさやガセ

暴力、アルコール、薬物乱用などの問題がネタにはつながらないよう、日本性感染症学考えられることを例示し、コンドームを使会の診療ガイドラインをホームページ上で会えない関係性や、ドメスティックバイオレ

員外にもオープンに閲覧可能にしておくことンスについても説明する。

は参考になると考える。

・医療機関への受診を促し、早期に検査治療

若年者向けとして作成したスライドが実際に結びつけるため、受診費用の概要を提示

どのような対象者に活用されるか、閲覧頻度する。

はどの程度か、啓発スライドの影響力などを・疾患の詳しい説明は、来年度以降の研究課推測して、評価することを今後検討したい。
診療の場では医療従事者、学校では教育関題となる教師向けの資料に含める。

係者が中高生の性の相談などにかかわる際に、Ｄ．考大人から若年者に伝える情報も重要であるの察

で、来年度はそれらの指導者向けにスライド

スライド作成にあたり、議論した点のひと集を作成することを計画する。

つは、若年者向けにどの程度の知識を提供す

―１７８―

Ｅ．結

論

作成したスライドが性感染症予防の一助となるよう、閲覧をオープンにして、実際に若年者（中高生）に情報が届いているか、今後、
スライドの周知や普及活用状況を評価し、さらなる改善を続ける。

Ｇ．研究発表１．論文発表なし

２．学会発表参考資料として
１性感染症予防における啓発教育用資料の活用について白井千香・荒川創一．日

本性感染症学会第２８回学術大会（一般演題）（東京）

Ｈ．知的財産権の出願・登録状況
なし

―１７９―

ɶ᭗ဃӼƚࣱज़ज़ ௨ၐƬƯƳƊƴ žࣱज़௨ၐſƬƯŴƲǜƳ၏ൢᲹ ᐯЎᢋƴƸŴ᧙̞Ƴƍ၏ൢƬƯ࣬ƬƯǔᲹƆ৷ቦǹȩǤȉ௏Ჩμ௏ƇዻᨼᲴɟᑍᅈ‫ׇ‬ඥʴ ଐஜࣱज़௨ၐ‫˟ܖ‬ҽဃі΁ᅹ‫ܖ‬ᄂᆮᝲᙀя᣿*࠰ࡇʙಅႸഏ ࣱƷȈȩȖȫ
ǹȩǤȉ0Q 3-4
 ज़௨ኺែᲢƏƭǓƔƨᲣᲷƲƏǍƬƯƏƭǔ Ố
5-7 ࣱज़௨ၐƸ඙ƞƳƍƱ ƲƏƳǔƷᲹ8-9 ၏ൢƷƳǇƑǛჷƬƯǔƔƳᲹ
10-15
 ࣱᘍໝƷƍǖƍǖ
16-17
 ǨǤǺƱƸᲹ18-22
 ൢƴƳƬƨǒӖᚮƠǑƏᲛ ౨௹ǛӖƚǑƏᲛ
23
 ʖ᧸૾ඥ Ჷ 5CHGT 5GZȷǳȳȉȸȠǛ̅ƓƏ
24-31
 ǳȳȉȸȠƷࠝᜤ᳋#32-36ǳȳȉȸȠƷᢋʴ37-39
 ǳȳȉȸȠǛბƚǒǕǇƢƔ㸽40-44
 ࠳ƤƳʴဃƸᐯЎưƭƔǉᲛ
45-46

―１８０―

ࣱ ज़௨ၐ

ƲƏǍƬƯƏƭǔᲛᲹ

ƨƱƑƹ
ƱƑƹ
ƹŴ*
Ŵ*+8
*+8
8ᲢǨǤǺ
ᲢǨǤǺƷҾ‫׆‬ᲣᲢǤǺǺƷҾ‫׆‬
ƕƍǔƱƜǖƸ
ƕ
Ƹȷȷȷ

ች෩

ᏺЎඣ
ඣ෩
ᘉ෩

൐ʐ

ࣱ ज़௨ၐƸŴᲫ‫ׅ‬඙Ƥƹ‫ٻ‬ɣ‫پ‬Ჹ‫ٻ‬ɣ‫پ‬Ჹ˴‫ׅ‬ưǋƔƔǔᲛࣱज़௨ၐƸŴƨƘƞǜᆔ᫏ƕƋǔŵǔŵɟࡇƴ ᙐૠƷ၏ൢƴƳǔƜƱƕƋǔŵ
ƕƋǔŵȑȸȈȊȸƱŴɟደƴ඙ƞƳƍƱŴ
ƱǋƏɟࡇǋǒƏƜƱƴƳǔŵ
ၐཞƕ໯ƘƳƬƯǋŴ඙ƬƨƱƸᨂǒƳƍŵ౨௹ǛƠƳƚǕƹǘƔǒƳƍ

―１８１―ၐཞƕ໯ƍǄƏƕ
᣻ƍ၏ൢƔǋ᣻ƍƓǋƳ၏ൢƷᆔ᫏ҮƸŴǄƔƷǹȩǤȉưᛟଢƋǓƋǓࣱ֥ȘȫȚǹ
ȈȪǳȢȊǹᏺ໒ǫȳǸȀᏺ໒

ǱǸȩȟၐ‫סݴ‬ǳȳǸȭȸȞప൒ǯȩȟǸǢȷ෱ᓏƴǑǔ໒ၐၐ‫ܷ܇‬ᫀၶ
ǦǤȫǹࣱᏁ໒
*+8ज़
ज़௨ၐȷ#+&5Ტ
ᲢǨǤǺᲣ
ǺᲣ

ప൒

ଥƷ၏ൢ
ưƸƳƍ

ǭǹǍࣱᘍໝưưज़௨ƢƢǔ ඙ ၲƠƳƘƯǋŴၐཞƸ໯ƘƳƬƨǓЈ ƨǓŴŴ Ƙ ǓᡉƠƯჷǒƳƍƏƪƴफ ҄ƢƢǔ ‫ۡک‬ƕज़௨ƢǔƱဃǇǕƨ‫܇‬ƲǋƴᨦܹƕƋƬƨǓŴ඙ၲƕ᡿ǕǔƱࢸᢡၐƕസǔƜƱƕƋǔŵ

―１８２―

ហƍ૮ໜ ƹǒ၉ᲣƲƜƔǒƕǢȖȊǤᲹƲƜƔǒƕǢȖȊǤᲹ၏ൢƕƏƭǔࣱᘍໝƱƸ၏ൢƕƏƭǔࣱᘍໝƱƸज़௨ẲởẴẟᾌạếỦࣱᘍໝज़௨ẲễẟᾌạếỤễẟࣱᘍໝज़௨ज़௨ ẲễẟᾌạếỤễẟࣱᘍໝἙỵὊἩỿἋ
Ἑ
ỵὊἩỿ
ὊἩỿἋ

᠉ƍǭǹ
᠉ƍǭǹ

ίᐾửӝỉɶộỂλủỦὸίίᐾửӝỉᐾửӝỉɶộỂλủᐾửӝỉɶộỂλủỦὸỦὸᲢ᪼ƬǃƨǍՑƷᘙ᩿ƴᴙᴅᴇᲣᲢ᪼ƬǃƨǍՑƷᘙ᩿ƴᴙᴅᴇᲣᙉưৼƖӳƏŴȚȃȆǤȳǰ
ᙉư
ᙉ
ᙉưৼ
ưৼƖӳ
ưৼ
ৼƖӳƏŴȚȃȆǤ
ৼƖӳƏŴȚȃȆ
ৼƖӳӳƏŴȚȃȆ
ƏŴȚȃȆ
ȆǤ
Ǥȳǰ

஌ǛბƯৼƖӳƏŴ৖ǛƭƳƙ஌ǛბƯৼƖӳƏŴ৖ǛƭƳƙ

ᏺࣱʩ
ᏺࣱʩ

ᏺࣱʩ
ᏺ
ࣱʩ
ȷƾƨǓƱǋዌ‫ݣ‬ƴИǊƯȷƾƨǓƱǋዌ‫ݣ‬ƴИǊƯȷƲƪǒǋࣱज़௨ၐǛȷƲƪǒǋࣱज़௨ၐǛਤƬƯƳƍज़௨ၐǛਤƬƯƳƍ
ƯƳƍȷИǊƯưƳƍ
ȷИǊƯưƳƍ
ȷǳȳȉȸȠǛƠƳƍ
ȷǳȳȉȸȠǛƠƳƍ

Ꮐᧉࣱʩ ᲢǢȊȫᲣ
Ꮐᧉࣱʩ
ᲢǢȊȫᲣ

ӝᏸࣱʩᲢȕǧȩȁǪȷǯȳȋȪȳ
ӝᏸࣱʩᲢȕǧȩȁǪȷǯȳȋȪȳ
ǰǹȷȪȟȳǰᲣǰǹȷȪȟȳǰᲣႻ৖ƷȞǹǿȸșȸǷȧȳǛႻ৖ƷȞǹǿȸșȸǷȧȳǛ
እ৖ưᘍƏ
እ৖ưᘍƏ

ᐯЎưᘍƏȞǹǿȸșȸǷȧȳᐯЎưᘍƏȞǹ
ưᘍƏƏȞǹǿȸșȸǷȧȞǹǿȸȸșȸǷȧȳșȸǷȧȳ᳂ ᳃᳐Ʒज़௨ኺែ
ࣱᘍໝᲤ

᳂
᳃
᳐

ᏺȷȚȋǹȷᏀᧉȷӝሁද‫ݧ‬Ʒ‫ׅ‬Ơ৙ƪȷХ᩷
Јငȷ੉ʐ

ज़
௨

᠞ᘉȷᘉ෩ᙌдྵ‫נ‬Ŵᘉ෩ᙌдƸ‫ܤ‬μưƢᲣĬࣱᘍໝᘍĭද‫ݧ‬Ʒ‫ׅ‬Ơ৙ƪ ĮЈငȷ੉ʐᲤဏࣱӷࣱ᧓ࣱႎ੗ᚑᎍưƷज़௨ƕ‫ٶ‬ƍ
᧓ࣱ
ࣱႎ

―１８３―

ưƖǔƩƚ
ࣱज़௨ၐǛ᧸ƙ૾ඥ

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―１８５―

Ⅲ．研究成果の刊行に関する一覧表

研究成果の刊行に関する一覧表
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秋元 義弘，
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金山 博臣，
荒川 創一

平成２５年７モデル県の性感染症診療医療機関全数調査推計
有病率と国立率感染症研究所
日本性感染症学の定点報告推計有病率の比較
２６
（１）
会誌
～７県医療機関全数調査結果と定点調査報告結果の有病率はなぜ乖離したのか？

中瀨

特定感染症予防指針の変更を
ニューズレター
踏まえた自治体における性感「性の健康」
染症発生動向調査の活用

白井 千香，
古林 敬一，
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今日の小児治
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第１６版

―１９０―

２０１４ ３９４−３９５

東京 ２０１５ ３８２−３８３

Ⅳ．研究成果の刊行物・別刷

Azithromycin Resistance and Its Mechanism in Neisseria gonorrhoeae
Strains in Hyogo, Japan
Katsumi Shigemura,a,b Kayo Osawa,b,c Makiko Miura,c,d Kazushi Tanaka,a Soichi Arakawa,a,b Toshiro Shirakawa,a,c,e Masato Fujisawaa
Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japana; Department of Infection Control
and Prevention, Kobe University Hospital, Kobe, Japanb; Division of Infectious Diseases, Department of International Health, Kobe University Graduate School of Health
Science, Kobe, Japanc; Department of Medical Technology, Kobe Tokiwa University, Kobe, Japand; Center for Infectious Diseases, Kobe University Graduate School of
Medicine, Kobe, Japane

Therapeutic options are limited for Neisseria gonorrhoeae infection, especially for oral drugs. The purpose of this study was toinvestigate the susceptibility of N. gonorrhoeae to oral azithromycin (AZM) and the correlation between AZM resistance-related
gene mutations and MIC. We examined the AZM MICs of clinical strains of N. gonorrhoeae, sequenced the peptidyltransferase
loop in domain V of 23S rRNA, and investigated the statistical correlation between AZM MIC and the presence and number ofthe mutations. Among 59 N. gonorrhoeae strains, our statistical data showed that a deletion mutation was seen signiﬁcantly
more often in the higher-MIC group (0.5 ␮g/ml or higher) (35/37; 94.6%) than in the lower-MIC group (0.25 ␮g/ml or less) (4/22; 18.2%) (P < 0.0001). However, a mutation of codon 40 (Ala¡Asp)¡
in the mtrR gene (helix-turn-helix) was seen signiﬁcantly
more often in the lower-MIC group (12/22; 54.5%) (P < 0.0001). In N. gonorrhoeae multiantigen sequence typing (NG-MAST)
analyses, ST4777 was representative of the lower-MIC group and ST1407, ST6798, and ST6800 were representative of the higherMIC group. NG-MAST type 1407 was detected as the most prevalent type in AZM-resistant or -intermediate strains, as previously described. In conclusion, a deletion mutation in the mtrR promoter region may be a signiﬁcant indicator for higher MIC(0.5 ␮g/ml or higher). ST4777 was often seen in the lower-MIC group, and ST1407, ST6798, and ST6800 were characteristic of
the higher-MIC group. Further research with a greater number of strains would help elucidate the mechanism of AZM resistancein N. gonorrhoeae infection.

Neisseria gonorrhoeae infection is often seen in male urethritis
and female cervicitis, and its diagnosis has historically led toprompt initiation of treatments with a single antibiotic (1, 2). In
the 1990s in most Asian countries, ﬂuoroquinolones (FQs) were
often used for this infection, partly because FQs have higher concentrations in the urinary tract. FQs showed good initial outcomes
for this infection, but the results were not enduring. This may bepartly due to the trend for single use of FQs for this infection, withno guidelines to recommend other choices (3–9).
In addition to the FQs, cephalosporins such as ceﬁxime werealso recommended as oral antibiotics until these drugs showeddecreased activity against N. gonorrhoeae (10). They are no longera recommended choice for this infection (11–13). Oral antibiotics
for outpatient treatment would be highly desirable for this kind of
infection. Azithromycin (AZM) is an oral antibiotic with medical
insurance approval for use against chlamydia infections (14), andthere are many reports of good activity against N. gonorrhoeae
infection (15). Other reports suggest that N. gonorrhoeae infectionis less susceptible to AZM and that AZM-resistant strains haveemerged (5). We investigated the AZM susceptibilities of N. gonorrhoeae strains and the correlation between mutations of macrolide resistance-related genes and the AZM MICs of clinically isolated strains of N. gonorrhoeae.
Three mechanisms of resistance to AZM are known: overexpression of the efﬂux pump, mutation in the peptidyltransferase
loop in domain V of 23S rRNA, and modiﬁcation of the ribosomal
target by methylase. Macrolides such as AZM and erythromycin(EM) bind to 4 alleles of the 23S rRNA component of the 50S
subunit of the bacterial ribosome and restrain protein synthesis by
inhibiting the elongation of peptide chains (16).
Overexpression of the MtrCDE pump is due to either the lackMay 2015 Volume 59 Number 5of repressor MtrR protein, which occurs by a single-base-pair deletion or TT insertion in the promoter region, or missense mutations in the mtrR coding region (17). Modiﬁcation of the ribosomal target by methylase or mutations reduces the afﬁnity of themacrolide antibiotics for ribosomes (18). Since the use of antimicrobial agents for treatment of gonococcal infections is different ineach country, the trend of drug resistance in gonococci is likely
different geographically (19). Hence, epidemiological investigations should be done in each country. Previous studies have reported a high use of N. gonorrhoeae multiantigen sequence typing(NG-MAST), which is based on limited DNA sequence analyses of
two highly polymorphic loci, porB and tbpB, in sequence type (ST)1407 N. gonorrhoeae, which is multidrug resistant and appears to
be disseminated basically worldwide (20). The selection andspread of AZM resistance are driven by inappropriate treatment ofpatients with suboptimal doses of AZM for gonococcal infection.
N. gonorrhoeae maintains its genetic resistance determinants evenafter the removal of antibiotic selection pressure.

Received 16 September 2014 Returned for modiﬁcation 9 December 2014
Accepted 14 February 2015
Accepted manuscript posted online 23 February 2015
Citation Shigemura K, Osawa K, Miura M, Tanaka K, Arakawa S, Shirakawa T,
Fujisawa M. 2015. Azithromycin resistance and its mechanism in Neisseria
gonorrhoeae strains in Hyogo, Japan. Antimicrob Agents Chemother
59:2695–2699. doi:10.1128/AAC.04320-14.
Address correspondence to Katsumi Shigemura, yutoshunta@hotmail.co.jp.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
doi:10.1128/AAC.04320-14

Antimicrobial Agents and Chemotherapy―１９３―

aac.asm.org

2695

Shigemura et al.

TABLE 1 Sequences for PCR primers for azithromycin resistance genes
Primer name

Target gene

Primer sequence (5= to 3=)

gonoRNA-F
allele1
allele2
allele3
allele4
mtrF1
mtr13Ra
ermA-F
ermA-R
ermB-F
ermB-R
ermC-F
ermC-RermF-FermF-R

23S rRNAACGAATGGCGTAACGATGGCCACA
TCAGAATGCCACAGCTTACAAACTGCGACCATACCAAACACCCACAGGGATCCCGTTGCAGTGAAGAAAGTCAACAGACTTACTATCCCATTCAGC
GCCAATCAACAGGCATTCTTA
GTTGGAACAACGCGTCAAAC
CTTCGATAGTTTATTAATATTAGTTCTAAAAAGCATGTAAAAGAAAGTAACGGTACTTAAATTGTTTACGAAAAGGTACTCAACCAAATAGCTAATATTGTTTAAATCGTCAATTCAAAACATAATATAGATAAACGGGTCAGCACTTTACTATTG
GGACCTACCTCATAGACAAG

mtrR
ermA
ermB
ermC
ermF

Size (bp)

Reference

2,054
2,240
2,217
1,847
380

16

645

18, 21, 22

17

639
642
466

Surveillance and characterization of the mechanisms of AZM
resistance are essential. In this study, we investigated the genetic
characteristics of N. gonorrhoeae strains with decreased susceptibility to AZM.

0.5 ␮g/ml or higher (higher-MIC group). Statistical analysis was conducted using Fisher’s exact test with the JSTAT (Java Virtual Machine
Statistics Monitoring Tool; Sun Microsystems, Inc., Santa Clara, CA).
Statistical signiﬁcance was established at a P value of 0.05.

MATERIALS AND METHODSRESULTS

Strains. N. gonorrhoeae strains were isolated from patients with male urethritis or female cervicitis and sent to Hyogo Rinsho Co. Ltd., Himeji,
Japan. Gonococcal strains were retrieved from storage at ⫺80°C by 48 h ofincubation (35°C, 5% CO2) on chocolate agar. The resulting colonies
were then subcultured.
MIC measurements. The MIC (␮g/ml) was determined using an Optopanel E212 dry plate (Kyokuto Pharmaceutical Industrial Co., Ltd., Tokyo, Japan) with the broth microdilution method. For AZM, the MIC
breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used (http://www.eucast.org). For quality
control, the N. gonorrhoeae reference strain ATCC 49226 was included ineach testing.
DNA extraction. DNA extracts were suspended in 500 ␮l of TrisEDTA (TE) buffer for 10 min and then boiled for 15 min and centrifuged
at 15,000 rpm for 10 min. The ﬁnal supernatant was retained for storage at⫺20°C.
PCR ampliﬁcation and sequencing of AZM resistance genes. To examine the mutations in the peptidyltransferase loop of domain V of the
23S rRNA gene, containing four copies, all four alleles were ampliﬁed by
PCR and sequencing as described previously (16). The mtrR promoter
region was examined by PCR and sequencing as described previously(17). DNA sequencing was performed after the PCR using PCR amplicons. Puriﬁcation of the PCR products was performed with the QIAquick
PCR puriﬁcation kit (Qiagen, Hilden, Germany), and the sequencing was
performed at Euroﬁns Genomics, Inc. (Tokyo, Japan) (Table 1).
PCR of the erm genes. The methylase genes ermA, ermB, ermC, andermF were detected using PCR with primers and conditions as described
previously (18, 21, 22). The PCR primers are shown in Table 1. The PCR
conditions were as follows: denaturing at 94°C for 30 s; annealing at 50°C
for 30 s (ermB and ermF), 48°C for 1 min (ermA), or 43°C for 1 min(ermC); and elongation at 72°C for 2 min. The cycle was repeated 35 times(18, 21, 22).
Molecular epidemiological typing. NG-MAST was performed by using PCR and sequencing of the more variable segments of porB and tbpB(23). The porB and tbpB allele numbers as well as NG-MAST STs wereassigned using the NG-MAST website (http://www.ng-mast.net/).
Statistical analyses. We investigated the statistical correlation between the AZM MIC and the presence and number of mutations under
the classiﬁcations of an MIC of 0.25 ␮g/ml or less (lower-MIC group) andAZM MICs. The AZM MICs of the 59 strains collected were 0.06,
0.12, 0.25, 0.5, 1, and 16 ␮g/ml. In detail, 2 strains (3.39%) had an
MIC of 0.06 ␮g/ml, 5 strains (8.47%) had an MIC of 0.12 ␮g/ml,
16 strains (27.1%) had an MIC of 0.25 ␮g/ml, 33 strains (55.9%)
had an MIC of 0.5 ␮g/ml, 4 strains (6.78%) had an MIC of 1
␮g/ml, and 1 strain (1.69%) had an MIC of 16 ␮g/ml. The MIC50
was 0.5 ␮g/ml, and the MIC90 was 0.5 ␮g/ml (Table 2).
Mutations in domain V of 23S rRNA. There were 2 strains
with C2214T (C204T) mutations in allele 3, one strain with a
G2209A (G199A) mutation in allele 4 and one strain (with thehighest MIC, 16 ␮g/ml) with C2599T (C589T) mutations in all 4
alleles in the peptidyltransferase loop in domain V of 23S rRNA.
mtrR mutations. There were 38 (64.4%) strains with an A deletion mutation in the promoter region of mtrR, and this was seen
signiﬁcantly more often in the higher-MIC group (0.5 ␮g/ml or
higher) (35/37; 94.6%) than the lower-MIC group (0.25 ␮g/ml orless) (4/22; 18.2%) (P ⬍ 0.0001). Conversely, mutations of codon
40 (Ala¡Asp)¡
in the mtrR gene (helix-turn-helix) were seen signiﬁcantly more often in the lower-MIC group (12/22; 54.5%)(P ⬍ 0.0001). In addition, except for deletion mutations, strains
with no mutation were seen signiﬁcantly more often in the higherMIC group (33/37; 89.2%) (P ⬍ 0.0001), and strains with one
mutation were seen signiﬁcantly more often in the lower-MIC
group (15/22; 68.2%) (P ⬍ 0.0001).
Detection of methylase genes. Of the 59 N. gonorrhoeae
strains, there were no strains with positive PCR detection of ermA,
ermB, ermC, or ermF (data not shown).
NG-MAST. N. gonorrhoeae multiantigen sequence typing(NG-MAST) results for porB and tbpB classiﬁed the 59 N. gonorrhoeae strains as ST3505, ST4015, ST4637, ST4777, ST5875,
ST6761, ST6773, ST6775, ST7382, and ST7806 in the lower-MIC
group and ST247, ST1407, ST3520, ST3588, ST4044, ST4163,
ST4186, ST5875, ST6764, ST6774, ST6798, and ST6800 in thehigher-MIC group. The highest MIC in our strains (16 ␮g/ml) was
found for ST1407. ST4777 was representative of the lower-MIC

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TABLE 2 MICs, mutations, and NG-MAST results for the N. gonorrhoeae strains
Mutationsa
mtrR promoter
regionAZM
MIC

No. ofstrains% ofstrainsA
deletion

16
1

1
4

100
100

⫻
⫻

0.5

28
2
1
1

88
6
3
3

⫻
⫻

8
3
2
1
1
1b

50
19
13
6
6
6

0.125

4

100

0.06

2

100

Total

59

0.25

ND
⫻

C¡T
mutation

mtrR gene
Helix-turn-helix
Codon 39
(Ala¡Thr)

Codon 40
(Ala¡Asp)¡

Codon 45
(Gly¡Asp)¡

Codon 29
(silent
mutation)

Codon 30
(silent
mutation)

NG-MAST type(s) (no. of strains)
ST1407 (1)ST6798 (3), ST1407 (1)

⫻

⫻

⫻
ND

⫻
ND

⫻
⫻
⫻
ND

ND

⫻

⫻

ST1407 (5), ST6800 (5), ST6798 (2),ST4044 (2), ST3588 (2), ST247(1), ST3520 (1), ST4163 (1),ST4186 (1), ST5875 (1), ST6764(1), ST6774 (1), nontypeable (9)

⫻
ND

⫻
ND

ST4777 (2), ST6761 (2), ST6775 (2),ST4015 (1), ST4637 (1), ST5875(1), ST7382 (1), ST7806 (1),nontypeable (5)

⫻
⫻

⫻

⫻

ST4777 (1), ST6773 (1),nontypeable (2)ST3505 (1), nontypeable (1)⫻, mutation present; ND, not determined.
b
100-bp insertion and mutation.
agroup, and ST1407, ST6798, and ST6800 were representative of
the higher-MIC group (Table 2).
DISCUSSION

The mechanism of resistance for the AZM-resistant N. gonorrhoeae phenotype is currently unknown in detail. AZM and othermacrolides exert a bacteriostatic effect by interacting directly withthe central loop of domain V, the site of peptide bond formation,
thereby inhibiting protein synthesis. Alteration in 23S rRNA isreported to contribute to low-level resistance. A 23S rRNA mutation (C2611T) has been proposed to contribute to the low-level
resistance observed in two Canadian gonococcal strains (24). Chisholm et al. showed that very-high-level resistance to AZM (MIC,
256 ␮g/ml) occurs in N. gonorrhoeae as a result of a single point
mutation in the peptidyltransferase region of domain V of the 23S
rRNA gene (24). Our study included a high-level AZM-resistantstrain (MIC, 16 ␮g/ml) with C2599T mutations in all the alleles(alleles 1 to 4) tested. This suggests that gonococcal strains fromJapan may have more mutations, even in strains with lower MICs,
than those from other countries, such as the United Kingdom.
We observed that all AZM-resistant strains contained several
mutated alleles and that highly resistant strains had at least 3 mutations, while sensitive and moderately resistant isolates had amaximum of one mutated allele. Mutation of A2059G in highly
resistant gonococci and C2611T mutations in the 23S rRNAs ofmoderately resistant gonococci were reported previously (16).
Our study found strains with mutations in one allele even instrains with low MICs (0.25 to 0.50 ␮g/ml), indicating that evengonococci with comparatively lower MICs harbor mutations.
Another mechanism of AZM resistance, the efﬂux pump, isMay 2015 Volume 59 Number 5well known to contribute to macrolide resistance. This pump excretes antibiotics, resulting in insufﬁcient intracellular accumulation. The MtrCDE efﬂux pump regulated by the MtrR repressor
protein is a representative efﬂux pump system. mtrR mutations in
the gene itself or in its promoter region have been reported in
low-level macrolide-resistant gonococcal strains (25, 26) becauseof decreased MtrR expression and upregulation of the MtrCDE
efﬂux pump. Clinical isolates or laboratory-derived mutants that
display resistance to hydrophobic agents frequently contain lossof-function mutations in the mtrR coding sequence or a singlebase-pair deletion in a 13-bp inverted repeat within the mtrR promoter (27–29).
The mtrR mutations in the clinical isolates described above
were identical to those reported for other strains of gonococci that
express resistance to multiple hydrophobic compounds (30, 31).
The combined genetic and molecular results obtained in this investigation implicate the mtrCDE-encoded efﬂux pump as amechanism by which gonococci can express decreased susceptibility to AZM. Through known mutations (27) that abrogatetranscription of the gene (mtrR) that encodes a transcriptional
repressor of mtrCDE or loss-of-function mutations in the repressor-encoding gene, gonococci can overproduce the MtrCDE efﬂux pump to increase their capacity to export hydrophobic
agents. Our data showed that a deletion mutation in the promoter
region of mtrR was seen signiﬁcantly more often in the higherMIC group (0.5 ␮g/ml or higher) compared with the lower-MIC
group (0.25 ␮g/ml or less) (P ⬍ 0.0001), and conversely, a mutation of codon 40 (Ala¡Asp)¡
in the mtrR gene (helix-turn-helix)
was seen signiﬁcantly more often in the lower-MIC group (P ⬍Antimicrobial Agents and Chemotherapy―１９５―

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Shigemura et al.

0.0001). These ﬁndings contribute to the current understandingof the mechanism of AZM resistance in N. gonorrhoeae. However,
the methylase genes were not detected in our tested N. gonorrhoeae
strains, indicating that our AZM-resistant strains did not have thesame mechanisms of macrolide resistance as seen in the study byRoberts et al. (18). The trend of AZM resistance has not yet become widespread, and thus we need to continue surveillance of
gonococcal sensitivity to AZM but also continue with mechanistic
studies.
As an epidemiological study tool, the NG-MAST method (32–36) is based on limited DNA sequence analyses of two highly polymorphic loci, porB and tbpB (23). There is public Internet accessfor sequence submission and assignment of sequence types, either
for porB or tbpB or for the assignment of STs using a combinationof these two loci (23). Our study clearly showed that STs could be
usefully classiﬁed according to high-level and low-level AZM
MICs. To our knowledge, there is no report of NG-MAST STs andAZM MICs. We identiﬁed ST1407 as a highly ASM-resistantstrain (MIC, 16 ␮g/ml) in Japan, suggesting that future epidemiological studies are needed for detecting the spread of this gonococcal antibiotic-resistant phenotype in order to prevent a repetition of the failure that resulted from continuous use ofquinolones, producing a high prevalence of quinolone-resistantgonococci.
This study has some limitations. First, the number of tested
gonococcal strains may not be enough for deﬁnitive conclusions.
Second, additional mechanistic investigation may be necessary forfurther understanding of gonococcal AZM resistance. These limitations should be overcome by our future studies.
In conclusion, a deletion mutation of the mtrR promoter region is a possible mechanism of AZM resistance and may be asigniﬁcant indicator for higher MICs (0.5 ␮g/ml or higher) in N.
gonorrhoeae infection. ST4777 was often seen in the lower-MIC
group and ST1407, ST6798, and ST6800 in the higher-MIC group,and this correlation with MIC was statistically signiﬁcant. Further
mechanistic studies are needed, including the use of a greaternumber of strains.
ACKNOWLEDGMENTS
We thank Masahiro Miyata for data analysis and Miki Fujiwara and Hiroyuki Yoshida for gonococcal samples.
We declare that we have no conﬂicts of interest.

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J Infect Chemother 21 (2015) 340e345

Contents lists available at ScienceDirect

Journal of Infection and Chemotherapy
journal homepage: http://www.elsevier.com/locate/jic

Surveillance

The second nationwide surveillance of the antimicrobial susceptibilityof Neisseria gonorrhoeae from male urethritis in Japan, 2012e2013
Ryoichi Hamasuna a, c, *, Mitsuru Yasuda a, d, Kiyohito Ishikawa a, e, Shinya Uehara a, f,
Hiroshi Hayami a, g, Satoshi Takahashi a, h, Tetsuro Matsumoto a, c, Shingo Yamamoto a, i,
Shinichi Minamitani a, Akira Watanabe b, Satoshi Iwata b, Mitsuo Kaku b, Junichi Kadota b,
Keisuke Sunakawa b, Junko Sato b, Hideaki Hanaki j, Taiji Tsukamoto h, Hiroshi Kiyota k,
Shin Egawa l, Kazushi Tanaka m, Soichi Arakawa m, Masato Fujisawa m, Hiromi Kumon f,
Kanao Kobayashi n, Akio Matsubara n, Seiji Naito o, Kentaro Kuroiwa o, Hideo Hirayama p,
Harunori Narita q, Takahide Hosobe r, Shin Ito s, Kenji Ito t, Shuichi Kawai u,
Masayasu Ito v, Hirofumi Chokyu w, Masaru Matsumura x, Masaru Yoshioka y,Satoshi Uno z, Koichi Monden aa, Kazuo Takayama ab, Shinichi Kaji ac,
Motoshi Kawahara ad, Toru Sumii ae, Hitoshi Kadena af, Takamasa Yamaguchi ag,
Shinichi Maeda ah, Shohei Nishi ai, Hirofumi Nishimura aj, Takeshi Shirane ak,
Mutsumasa Yoh al, Kikuo Akiyama am, Toshio Imai an, Motonori Kano aoa

The Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious
Diseases (JAID) and The Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japanb
The Surveillance Committee of JSC, JAID and JSCM, Tokyo, Japanc
Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japand
Department of Urology, Gifu University Hospital, Gifu, Japane
Department of Urology, School of Medicine, Fujita Health University, Toyoake, Japanf
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japang
Blood Puriﬁcation Center, Kagoshima University Hospital, Kagoshima, Japanh
Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japani
Department of Urology, Hyogo College of Medicine, Nishinomiya, Japanj
Research Center for Anti-infectious Drugs, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japank
Department of Urology, The Jikei University Katsushika Medical Center, Tokyo, Japanl
Department of Urology, The Jikei University School of Medicine, Tokyo, Japanm
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japann
Department of Urology, Institute of Biomedical & Health Sciences Hiroshima University, Hiroshima, Japano
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japanp
Hirayama Urology Clinic, Kumamoto, Japanq
Narita Clinic, Nagoya, Japanr
Hosobe Clinic, Tokyo, JapansiClinic, Sendai, Japant
Ito Urology Clinic, Kitakyushu, Japanu
Kawai Urology Clinic, Kitakyushu, Japanv
Gifu Urological Clinic, Gifu, Japanw
Chokyu Tenma Clinic, Himeji, Japanx
Matsumura Urology Clinic, Kato, Japany
Yoshioka Urology Clinic, Nishinomiya, Japanz
Hirajima Clinic, Okayama, Japanaa
Araki Urological Clinic, Kurashiki, Japanab
Department of Urology, Takayama Hospital, Chikushino, Japanac
Kaji Clinic, Fukuoka, Japanad
Kawahara Urology Clinic, Kagoshima, Japanae
Sumii Clinic, Hiroshima, Japanaf
Kadena Urological Clinic, Hiroshima, Japan* Corresponding author. Department of Urology, University of Occupational and Environmental Health Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyuhsu, 807-8555, Japan.
Tel.: þ81 93 692 7446; fax: þ81 93 603 8724.
E-mail address: hamaryo@med.uoeh-u.ac.jp (R. Hamasuna).
http://dx.doi.org/10.1016/j.jiac.2015.01.010
1341-321X/© 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

―１９８―

R. Hamasuna et al. / J Infect Chemother 21 (2015) 340e345

341

ag

Yamaguchi Dermatology and Urology Clinic, Munakata, Japan
Department of Urology, Toyota Memorial Hospital, Toyota, Japan
Nishi Urology and Dermatology Clinic, Kitakyushu, Japanaj
Nishimura Urology Clinic, Kitakyushu, Japanak
Shirane Urology Clinic, Aki-gun, Japanal
Yoh Urology and Dermatology Clinic, Inazawa, Japanam
Akiyama Urology Clinic, Nishinomiya, Japanan
Imai Urology Clinic, Akashi, Japanao
Department of Urology, Kano Hospital, Kasuya-gun, Japanahaia r t i c l e i n f o

a b s t r a c t

Article history:
Received 15 October 2014
Received in revised form
15 January 2015
Accepted 20 January 2015
Available online 31 January 2015

Worldwide, the most important concern in the treatment of sexually transmitted infections is the increase in antimicrobial resistant Neisseria gonorrhoeae strains including resistance to cephalosporins,
penicillins, ﬂuoroquinolones or macrolides. To investigate the trends of antimicrobial susceptibility
among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance
committee conducted the second nationwide surveillance study. Urethral discharge was collected frommale patients with urethritis at 26 medical facilities from March 2012 to January 2013. Of the 151
specimens, 103 N. gonorrhoeae strains were tested for susceptibility to 20 antimicrobial agents. None of
the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) 90% of ceftriaxone increased to 0.125 mg/ml, and 11 (10.7%) strains were considered less susceptible with an MIC of
0.125 mg/ml. There were 11 strains resistant to ceﬁxime, and the MICs of these strains were 0.5 mg/ml. The
distributions of the MICs of ﬂuoroquinolones, such as ciproﬂoxacin, levoﬂoxacin and tosuﬂoxacin, werebimodal. Sitaﬂoxacin, a ﬂuoroquinolone, showed strong activity against all strains, including strains
resistant to other three ﬂuoroquinolones, such as ciproﬂoxacin, levoﬂoxacin and tosuﬂoxacin. The azithromycin MICs in 2 strains were 1 mg/ml.
© 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
Published by Elsevier Ltd. All rights reserved.

Keywords:
Neisseria gonorrhoeae
Nationwide surveillance
Antimicrobial susceptibilities
Japan
2012
2013

1. Introduction
The antimicrobial resistance of Neisseria gonorrhoeae strains
against penicillins, tetracyclines, ﬂuoroquinolones, cephalosporins
and macrolides is increasing worldwide. Surveillance of the antimicrobial susceptibilities of N. gonorrhoeae provides important
information for treating gonococcal infections. We have reported
the antimicrobial susceptibilities of N. gonorrhoeae strains, whichwere collected at 2009e2010, in the ﬁrst national surveillance
study in Japan [1]. In summary, the rate of less susceptible strains toceftriaxone was 8.4%; the susceptibility rate to ceﬁxime according
to the criteria of the Clinical and Laboratory Standards Institutes(CLSI) [2] was 98.8%; the minimum inhibitory concentrations(MICs) of ﬂuoroquinolones, such as ciproﬂoxacin, showed abimodal distribution and resistance rates were 78.3%; sitaﬂoxacn
showed low MICs of 0.5 mg/ml against ciproﬂoxacin-resistantstrains; the proportion of strains with azithromycin MICs of morethan 0.5 mg/ml was 3.6%.
After a ceftriaxone-resistant N. gonorrhoeae strain was discovered in a pharyngeal specimen of a female commercial sex worker
in Kyoto, Japan [3], other ceftriaxone-resistant N. gonorrhoeae
strains were discovered in France [4] and Spain [5], but not otherwise in Japan [1,6].
Since 2009, a 2-g azithromycin dose has been accepted by Japanese national insurance for the treatment of both gonococcal andchlamydial urethritis. High-level azithromycin-resistant strains
have emerged in many sites worldwide [7e10], and a relationshipbetween the use of azithromycin and an increase in the azithromycin MIC has been described [11]. The Japanese Association of
Sexually Transmitted Infections [12] has not recommended the useof azithromycin for treating gonococcal infections. However, somephysicians prefer to use azithromycin to treat gonococcal infections, and we anticipate the emergence of high-level azithromycin-resistant strains of N. gonorrhoeae in Japan.

In this report, the antimicrobial susceptibility patterns of
N. gonorrhoeae strains collected from 2012 to 2013 are compared tothe patterns from 2009 to 2010 [1]. This national surveillance wasconducted by the surveillance committee of three Japanese societies including the Japanese Association of Infectious Diseases, theJapanese Society of Chemotherapy and the Japanese Society ofClinical Microbiology. The committee has previously performed
and published other surveillance studies regarding the antimicrobial susceptibilities of pathogens causing respiratory infections,urinary tract infections, urethritis and surgical site infections. The
present surveillance study was the second study performed on
N. gonorrhoeae strains collected from male patients with gonococcal urethritis.

2. Materials and methods
2.1. Patients and participating facilities
The targets were male patients older than 16 years with urethral discharge and symptoms of urethritis, such as pain upon
micturition, urethral pain or urethral discomfort. Included patientswere diagnosed with gonococcal urethritis by a clinician. The
period of specimen collection was between March 2012 andJanuary 2013. The 38 participating facilities included departmentsof urology in hospitals and private clinics that specialized in
urology or urology and dermatology in Japan. The clinicians who
participated in this study explained the purpose of the study to thepatients orally or through written documents and obtained thewritten consent of each patient. This study was approved by the
ethical committee of each facility. The facilities that did not havean ethical committee submitted this study to the ethical committee of the speciﬁc non-proﬁt organization CREC net, Kitakyushu, Japan, which approved it.

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R. Hamasuna et al. / J Infect Chemother 21 (2015) 340e345

2.2. Specimens and patient information
The discharge from the urethral meatus was collected with asterilized cotton swab, placed in transport agar (SEEDSWAB gNo2,
Eiken Chemical Co. Ltd., Tokyo, Japan) and sent at room temperature to the Infection Scientiﬁc Control Research Center, The Kitasato
Institution, Tokyo, Japan. Only one specimen was collected fromeach patient. The patient's information, including age, diagnosis
and the properties of the discharge were reported for each sample.
2.3. Isolation of N. gonorrhoeae strains and antimicrobial
susceptibility testingcollected from patients in their 20s and 30s, respectively. The
urethral discharge was described as purulent for 139 specimens
and serous for 11. Of the 151 specimens from 151 patients, 103
strains could be cultured and identiﬁed as N. gonorrhoeae. From the139 purulent specimens, 100 strains (71.9%) were isolated. Of these
103 strains, 36, 21, 16, 14, 9 and 7 strains were collected from the
Kyushu, Chugoku, Kinki, Chubu, Tohoku and Tokyo areas,
respectively.

3.2. Antimicrobial susceptibilities

The bacterial isolation and antimicrobial susceptibility testing
were performed in the Infection Scientiﬁc Control Research Center,
The Kitasato Institution, Tokyo, Japan. For each specimen,
N. gonorrhoeae strain isolation and identiﬁcation was attempted.
The antimicrobial susceptibility testing was performed according to the CLSI Document M100-S22 [2], and the minimum inhibitory concentrations (MICs) were determined by the agar dilution
method. Supplemented 1% GC agar (1.1 g L-cysteine, 0.03 g guanine
HCL, 3 mg thiamine HCL, 13 mg para-aminobenzoic acid, 0.01 g B12,
0.1 g cocarboxylase, 0.25 g nicotinamide adenine dinucleotide, 1 g
adenine, 10 g L-glutamine, 100 g glucose, and 0.02 g ferric nitrate
per liter) was used for determining the MICs. When the MIC ofcarbapenems or clavulanic acid was measured, cysteine was notincluded in the agar. The range of concentrations for testing
included 12 two-fold serial dilutions (128e0.063 mg/ml) of antimicrobials, but the starting concentration ﬂuctuated depending on
the particular type of antimicrobial used. The inoculum wasadjusted to a 0.5 MacFarland standard by the direct adjustment
method. The N. gonorrhoeae strains were cultured at 36 ± 1  C in 5%
CO2 atmosphere overnight. N. gonorrhoeae ATCC 49226 was used as
the standard control.
The MICs of the following 20 antimicrobial agents were
measured: penicillin G, ampicillin, amoxicillin, clavulanic acidamoxicillin, cefpodoxime, cefdinir, ceﬁxime, cefditoren, ceftriaxone, cefodizime, ﬂomoxef, aztreonam, meropenem, spectinomycin,
ciproﬂoxacin, levoﬂoxacin, tosuﬂoxacin, sitaﬂoxacin, minocycline
and azithromycin. The susceptibility or resistance of the isolate toeach antibiotic was determined according to CLSI Document M100S22 [2].The antimicrobial susceptibility data in this surveillance
were compared with those in the ﬁrst surveillance.
b-lactamase activity in the N. gonorrhoeae isolates was detectedby the nitroceﬁn method (Ceﬁnase Disk™; BD BBL™). The
N. gonorrhoeae strains that were resistant to penicillin G (MIC:2 mg/ml) and in which b-lactamase activity was detected were
determined to be penicillinase-producing N. gonorrhoeae (PPNG).
Among b-lactamase-non-producing strains, strains that wereresistant to penicillin G (MIC: 2 mg/ml) were determined to be
chromosomally mediated resistant N. gonorrhoeae (CMRNG).
The threshold MICs for antimicrobial resistance are assumed
according to the following criteria: 2 mg/ml of penicillin G, 2 mg/
ml of minocycline, 1 mg/ml of cefpodoxime, 1 mg/ml of ciproﬂoxacin or 0.5 mg/ml of azithromycin. The phenotypes of
N. gonorrhoeae strains were classiﬁed by their resistance to antimicrobial agents.
3. Results
3.1. Number of specimens and isolated strains
Of the 152 specimens from 26 medical facilities, one wasomitted because the patient's age was 14 years. The median age was
32 years (range: 18e65), and 39.7% and 33.8% of specimens were

Antimicrobial susceptibility testing was performed on all 103
isolated strains (Table 1). None was susceptible to penicillin G (MIC:0.06). Only two strains (1.9%) were determined to be PPNG, andthe MICs of penicillin G to these strains were 2 and 32 mg/ml. The
MIC of clavulanic acid-amoxicillin MIC to PPNG strains was 0.5 mg/
ml. Among b-lactamase-non-producing strains, 21 strains (20.8%)
had higher MICs to penicillin G (MIC 2 mg/ml, range: 2e4 mg/ml)
and were determined to be CMRNG. The MIC90 of four kinds of
penicillins including penicillin G, ampicillin, amoxicillin andamoxicillin-clavulanic acid for b-lactamase-non-producing strains
was 2 mg/ml.
The MICs of minocycline for two PPNG strains were also higher(8 and 16 mg/ml). The MIC range for minocycline in the b-lactamase-non-producing strains was 0.06e32 mg/ml and 3 strains(2.9%) were resistant to minocycline. (MIC: 16 or 32 mg/ml).
The susceptibility rates of all the strains to oral cephalosporins such as ceﬁxime and cefpodoxime were 89.3% and 59.2%
according to CLSI criteria [2], respectively. The susceptibility ofceﬁxime evidently decreased compared to the strains collectedin the ﬁrst surveillance study. The MICs of the parenteral cephalosporins ceftriaxone and cefodizime were relatively low. The
high-level ceftriaxone-resistant strains, such as Ohnishi's report[3], were not found in the surveillance. The MIC90 of ceftriaxone
increased from 0.06 mg/ml in the ﬁrst surveillance study to
0.125 mg/ml in this study. All 11 strains with a ceftriaxone MIC of
0.125 mg/ml had ceﬁxime MICs of 0.25 or 0.5 mg/ml. However, 3strains with cexiﬁme MIC of 0.5 mg/ml had a ceftriaxone MIC of0.06 mg/ml.
The MIC distribution for ﬂuoroquinolones, such as ciproﬂoxacin, levoﬂoxacin and tosuﬂoxacin, showed bimodal. The MICs ofthese three antimicrobials for the 21 susceptible strains were0.06 mg/ml. The MIC of sitaﬂoxacin was lower than that of theother ﬂuoroquinolones. Strains with ciproﬂoxacin MICs of0.06 mg/ml had also sitaﬂoxacin MIC of 0.06 mg/ml. Strains withciproﬂoxacin MICs between 0.5 and 32 mg/ml showed sitaﬂoxacin
MIC of 0.06, 0.125 or 0.25 mg/ml. Only one strains with sitaﬂoxacin MIC of 0.5 mg/ml and ciproﬂoxacin MIC of 64 mg/ml was
newly identiﬁed.
Strains with resistance to spectinomycin were not identiﬁed inthis study. No high-level azithromycin resistant strains were found,but two strains had an MIC of 1 mg/ml.

3.3. Phenotypes of antimicrobial resistance among N. gonorrhoeae
strains
Table 2 shows the antimicrobial resistance phenotypes of thestrains. Among the isolated strains, 83 (80.6%) met resistancecriteria to one or more tested antimicrobials and 34 were resistantto a single antimicrobial (ciproﬂoxacin: 33 azithromycin 1). Fortynine strains (47.5%) showed resistance to more than two types of
antimicrobials such as penicillins, cephalosporins, tetracyclines,
ﬂuoroquinolones and macrolides.

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R. Hamasuna et al. / J Infect Chemother 21 (2015) 340e345

343

Table 1
Antimicrobial MIC distribution for 103 N. gonorrhoeae strains.
MIC (mg/ml)

Antibacterial agent

0.06
Penicillin G
Ampicillin
Amoxicillin
Clavulanic acid-amoxicillin
Cefpodoxime
CefdinirCeﬁxime
Cefditoren
Ceftriaxone
Cefodizime
Flomoxef
Aztreonam
Meropenem
Spectinomycin
Ciproﬂoxacin
Levoﬂoxacin
Tosuﬂoxacin
Sitaﬂoxacin
Minocycline
Azithromycin

0.125

0.25

0.5

1

2

4

6
8

24
14
21
21
5
2
42
22

17
11
8
10
15
25
11
5

33
29
20
25
23
35

20
33
52
46
17

2
7
1

3
20
14

8
2

22
1

41
1

9
38

22

13
26
14

3
18
38
19

95
36
10
11

5
12

1
4

1
6
31

32
26
39

1
1
3
1
40
3

1

3

1

1
3

38
41
42
52
92
79

8
24
11
21
3
15
35

10
68
21
21
21
38
2
15

32
29
44

The guideline of the Japanese Association of Sexually Transmitted Infections recommends that gonococcal urethritis andcervicitis be treated with 1 g of ceftriaxone in a single intravenous
dose, 1 g of cefodizime in a single intravenous dose and 2 g ofspectinomycin in a single intramuscular dose [12]. This recommendation did not change during the ﬁrst and second surveillance
studies. The second surveillance study revealed that the patient
demographics and clinical features of the urethral discharges were
the same as in the ﬁrst study, although the antimicrobial susceptibility data were different.
The prevalence of PPNG decreased compared to the ﬁrst
surveillance data. Previous to 2009, the prevalence of PPNG in
Japan had been approximately 1% [13]. However, the prevalence
was 7.2% in the ﬁrst surveillance study. The second surveillancedata showed the prevalence of PPNG to be 0.2%, which is a return
to historic levels. We are not able to explain why the prevalence
was higher in 2009e2010. One explanation is that patients who
were infected in foreign countries were included in the ﬁrst
study. Penicillins are not available for the treatment of gonococcal
infections in Japan. No strain was sensitive to penicillin G in
this study. In addition, penicillin with a b-lactamase inhibitor

Table 2The phenotypes of antimicrobial resistance among N. gonorrhoeae strains.
Numbers

Penicillin G Minocycline Cefpodoxime Ciproﬂoxacin Azithromycin
R
R
R
R

R
R
R

R
R
R

R
R
R

R
R
R
R
R
R
R

R

R

33
1
1
1
22
3
1
17
1
3

R: Resistance to antimicrobial agents that was determined by the criteria below.
MICs of 2 mg/ml of penicillin G, 2 mg/ml of minocycline, 1 mg/ml of cefpodoxime,
1 mg/ml of ciproﬂoxacin or 0.5 mg/ml of azithromycin.

16

32

64

1
1
1

2

1
2

4. Discussion

Antimicrobials

8

1

128

256

MIC50

MIC90

1
1
2
1
0.5
0.5
0.25
0.06
0.06
0.06
1
4
0.06
16
8
4
2
0.125
0.25
0.125

2
2
2
2
2
1
0.5
0.25
0.125
0.125
2
8
0.125
16
32
8
16
0.25
0.5
0.25

cannot be recommended to treat gonococcal urethritis, because
the MICs of amoxicillin are relatively higher and the MIC
of clavulanic acid-amoxicillin was not low for PPNG strains(0.5 mg/ml).
The most serious problem for the treatment of gonococcal infections worldwide is the increase in cephalosporin-resistantstrains. We did not ﬁnd further evidence of high-level ceftriaxone-resistant strains in Japan. However, ceftriaxone-resistantstrains were reported from France and Spain [4,5] and there arereports of ceftriaxone treatment failure in patients with
N. gonorrhoeae strains isolated from the pharynx [14e17]. In
particular, Swedish case-report described a N. gonorrhoeae strain
with a ceftriaxone MIC of 0.25 mg/ml that was detected from thepharynx of a male patient after treatment with 250 mg and 500 mg
of ceftriaxone; this patient was most likely infected through unprotected oral sex with a female partner in Japan [14]. This indicatesthat some women in Japan have N. gonorrhoeae strains with a highceftriaxone MIC, but these strains were not found in any surveillance. Indeed, the MIC90 of ceftriaxone increased from 0.06 mg/ml
in the ﬁrst surveillance study to 0.125 mg/ml in this study. The
strains with a ceftriaxone MIC of 0.125 mg/ml, those are termed as“less susceptible strains,” increased. In addition, the strains sensitive to ceﬁxime with an MIC 0.06 mg/ml, which Deguchi recommended as the breakpoint MIC of ceﬁxime in Japan [18], decreased
from 55.4% to 40.8%. These resistance or those less susceptibility in
N. gonorrhoeae to cephalosporins are closely related to the mosaic
structure of penA gene which codes for PBP2 [4,5,19,20]. Our data
are evidence that this type of resistance has been spreading inJapan.
The MICs of ﬂuoroquinolones did not differ between the ﬁrst
and second surveillance studies. The ﬂuoroquinolone-resistantrates of strains have shown nearly the same level as in Tanaka'sreports [21]. This likely means that physicians treating gonococcal
infections are complying with the guidelines of the Japanese Society of Sexually Transmitted Infections. The activity of sitaﬂoxacin
remains stable in two our surveillances. As described previously [1],sitaﬂoxacin
has
activity
againstciproﬂoxacin-resistant
N. gonorrhoeae strains. Sitaﬂoxacin can be one of treatment options for untreatable N. gonorrhoeae strains. However, one strains
with sitaﬂoxacin MIC of 0.5 mg/ml was found and further observation or clinical study would be necessary.

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R. Hamasuna et al. / J Infect Chemother 21 (2015) 340e345

In both the ﬁrst and second surveillance study, high-level
resistant strains to azithromycin were not found. The main mechanism for azithromycin-resistance in N. gonorrhoeae is mutations of
the macrolide target, 23S rRNA as A2059G or C2611T mutations[7e10,20]. N. gonorrhoeae has four 23S rRNA alleles and the resistance to azithromycin depends on the numbers of alleles with
mutations [20]. Unemo described that the azithromycin MIC increase to 4,096 mg/ml in strains with A2059G mutations in three orfour alleles, but the MICs of strains with the mutation in one allele
are not changed as wild-type strains [10]. Through this theory, atleast two strains (1.9%) with an azithromycin MIC of 1 mg/ml havemutations in more than 2 alleles of the 23S rRNA. In other Japanesesurveillance data, 3.6% (7/193) of strains in the Kyoto and Osaka
areas or 6.6% (8/122) of strains in the Tokyo area were resistant toazithromycin (>0.5 mg/ml) [6,22]. In the Tokyo area, higherresistant strains were found (one and two strains with MIC 16
and 8 mg/ml, respectively). Yasuda et al. showed clinical study using
azithromycin 2g in Japan and strains with MIC 2 or 4 mg/ml ofazithromycin remained after the treatment [23]. Among strains
with MIC 1 or 0.5 mg/ml eradication rates were 58% (7/12) and 97%(31/32), respectively. Even if azithromycin 2g is used, a high dose ofazithromycin could covered only strains with MIC 0.5 mg/ml andwe wonder that azithromycin-resistance would increase.
Table 2 shows the numbers of strains according to the antimicrobial resistant phenotype. Among 103 strains, 20 were classiﬁed
as “not resistant” to all antimicrobials. These strains were 20 of 21
the strains with ciproﬂoxacin MIC 0.06 mg/ml (another one had anazithromycin MIC of 0.5 mg/ml). Regarding N. gonorrhoeae strains inJapan, the susceptibility for ﬂuoroquinolone, which are lessfrequently used now is important. According to Tapsall's criteria for
multi-drug resistant N. gonorrhoeae (MDR-NG) [24], 42 strains(40.1%) met the criteria of MDR-NG. In 2009e2010, 39.8% of thestrains were classiﬁed as MDR-NG, which was quite similar to the
proportion in 2011e2012.
The next Japanese antimicrobial surveillance initiative forN. gonorrhoeae is planned for 2016. The increase in cephalosporinresistance is more prominent worldwide. Dual therapies, such as
ceftriaxone plus azithromycin or ceftriaxone and effective quinolones are recommended and being used worldwide. The recommendation of Japanese Association of Sexually Transmitted
Infections for treating gonococcal infections has remained thesame. The purpose of the next surveillance study is to evaluate theappropriateness of the present recommendation for the treatmentof gonococcal infection and to determine whether the recommendation should be modiﬁed.
Conﬂicts of interest
Mitsuru Yasuda has received donation from Astellas Pharma Inc.
Akira Watanabe has received speaker's honorarium from MSD K.K.,
Glaxo SmithKline K.K., Shionogi & Co., Ltd., Daiichi Sankyo Co., Ltd.,Taisho Toyama Pharmaceutical Co., Ltd. and Pﬁzer Japan Inc.; grantsupport from Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Ltd.
Taisho Pharmaceutical Co., Ltd., Toyama Chemical Co., Ltd.,
Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.,
Taiho Pharmaceutical Co., Ltd. and Meiji Seika Pharma Co., Ltd.
Satoshi Iwata has received speaker's honorarium from Astellas
Pharma Inc., Pﬁzer Japan Inc., Taisho Toyama Pharmaceutical Co.,
Ltd., MSD K.K., Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd.
and Japan Vaccine Co., Ltd., donation from Taisho Toyama Pharmaceutical Co., Ltd. and supported, in part, by a fund from Nikon
Corporation. Mitsuo Kaku has received speaker's honorarium fromTaisho Toyama Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Pﬁzer
Japan Inc. and Sumitomo Dainippon Pharma Co., Ltd. and donationfrom Astellas Pharma Inc. Junichi Kadota has received speaker's

honorarium from Taisho Toyama Pharmaceutical Co., Ltd., Pﬁzer
Japan Inc., MSD K.K., Kyorin Pharmaceutical Co., Ltd., Daiichi SankyoCo., Ltd., Glaxo SmithKline K.K., payments for a manuscript draftingand editing from Nankodo Co., Ltd. and donation from Astellas
Pharma Inc. Keisuke Sunakawa has received speaker's honorariumfrom Taisho Toyama Pharmaceutical Co., Ltd., Toyama Chemical Co.,
Ltd. and Meiji Seika Pharma Co., Ltd. Hideaki Hanaki is a member ofa laboratory endowed chair from Kohjin Bio Co., Ltd. Taiji Tsukamoto has received speaker's honorarium from Astellas Pharma Inc.,and payments for a manuscript drafting and editing from RichHill
Medical Inc. Shin Egawa has received donation from Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Asahi Kasei Corp. andEuro Meditech Co., Ltd. Soichi Arakawa has received speaker's
honorarium from Taisho Toyama Pharmaceutical Co., Ltd.
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J Infect Chemother 21 (2015) 96e104

Contents lists available at ScienceDirect

Journal of Infection and Chemotherapy
journal homepage: http://www.elsevier.com/locate/jic

Original article

Efﬁcacy and safety of metronidazole injection for the treatment of
infectious peritonitis, abdominal abscess and pelvic inﬂammatory
diseases in Japan
Hiroshige Mikamo a, Miyako Matsumizu b, *, Yoshiomi Nakazuru c,
Masahito Nagashima a, b
a

Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Aichi, Japan
Clinical Research, Development Japan, Pﬁzer Japan Inc., Tokyo, Japanc
Clinical Statistics, Development Japan, Pﬁzer Japan Inc., Tokyo, Japanba r t i c l e i n f o

a b s t r a c t

Article history:
Received 18 June 2014
Received in revised form
6 October 2014
Accepted 7 October 2014
Available online 28 November 2014

Although metronidazole (MNZ) has been used worldwide for more than 4 decades as a standard therapy
for trichomoniasis, anaerobic and amebic infections, resistance to MNZ is still low. MNZ is available asoral, intravenous, and vaginal formulations, but the intravenous formulation of MNZ has not been
approved in Japan. We conducted a phase 3 study to evaluate the efﬁcacy and safety of intravenous MNZ
combined with ceftriaxone (CTRX) in Japanese subjects with infectious peritonitis, abdominal abscess orpelvic inﬂammatory diseases (PIDs) to obtain regulatory approval. A combination of MNZ/CTRX at dosesof 500 mg 3 or 4 times a day/1 or 2 g twice a day was administered intravenously to a total of 38
hospitalized subjects. MNZ/CTRX was well tolerated and exhibited excellent clinical and bacteriologicalefﬁcacy with clinical efﬁcacy rates of 100% (20/20) in infectious peritonitis or abdominal abscess subjects
and 90.0% (9/10) in PID subjects, and the eradication rates in infectious peritonitis or abdominal abscesssubjects and PID subjects were 100% (16/16) and 100% (4/4), respectively, at the test of cure. MNZ/CTRX
was effective in 1 subject in whom a metallo-b-lactamase-producing Bacteroides fragilis strain (MIC of
MNZ, 2 mg/ml) was identiﬁed. The most common treatment-related adverse event was diarrhea (23.7%),
followed by nausea (5.3%). No new safety signals were identiﬁed. MNZ/CTRX demonstrated excellent
efﬁcacy and was well tolerated in Japanese infectious peritonitis, abdominal abscess and PID subjects.
This treatment regimen can be useful for anaerobic infections.
Clinical registration number: NCT01473836.
© 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
Published by Elsevier Ltd. All rights reserved.

Keywords:
Metronidazole
Ceftriaxone
Infectious peritonitis
Abdominal abscessPelvic inﬂammatory diseases
Metronidazole/ceftriaxone combination
therapy

1. Introduction
Metronidazole (MNZ) is a nitroimidazole antimicrobial agent
with a potent anti-anaerobic, amebicidal, and antiprotozoal activity. Intravenous (IV) MNZ (MNZ-IV) has been used worldwide formore than 30 years as the standard therapy for the treatment oftrichomoniasis, anaerobic and amebic infections [1e5]. Harrison's
Principles of Internal Medicine and the Sanford Guide to Antimicrobial Therapy recommend the use of MNZ-IV for the treatment of
infections involving commonly encountered anaerobic gramnegative rods [6] and anaerobic infections [7] respectively. The* Corresponding author. Clinical Research, Development Japan, Pﬁzer Japan Inc.,
3-22-7 Yoyogi, Shibuya-ku, Tokyo 151-8589, Japan. Tel.: þ81 3 5309 7010; fax: þ81
3 5309 9060.
E-mail address: miyako.matsumizu@pﬁzer.com (M. Matsumizu).

guideline of the Infectious Diseases Society of America (IDSA) for
the Diagnosis and Management of Complicated Intra-abdominal
Infection in Adults and Children, the 2010 Sexually transmitted
disease treatment guidelines of the Centers for Disease Control andPrevention (CDC), and the IDSA practice guidelines for the diagnosis and management of skin and soft-tissue infections [8e10]also recommended the use of MNZ for various infections.
MNZ-IV has not been developed in Japan. Antimicrobial agents
presently used for the treatment of anaerobic infections in Japanare penicillins, b-lactam/b-lactamase inhibitor combination drugs,
and some cephalosporins, carbapenams, and clindamycin. However, the emergence of resistance to penicillins, cephalosporins andclindamycin among clinically isolated pathogenic anaerobes has
raised great concern [11e13]. In recent years, a high prevalence ofresistance to clindamycin has been observed among the Bacteroides

http://dx.doi.org/10.1016/j.jiac.2014.10.005
1341-321X/© 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

―２５４―

H. Mikamo et al. / J Infect Chemother 21 (2015) 96e104

fragilis group and non-fragilis Bacteroides spp., which are the mostcommon anaerobes isolated from intra-abdominal infections, aswell as Prevotella spp., a causative pathogen of aspiration pneumonia [14,15]. Decreased susceptibility and the emergence ofresistance to carbapenems among the B. fragilis group and nonfragilis Bacteroides spp. have also been reported [16].
Although MNZ has been used as a therapeutic drug for infections for longer than 45 years, the rate of resistance to MNZ
among anaerobes is still generally low. Therefore, MNZ is still
successfully used for the treatment of anaerobic infections causedby Bacteroides spp., Fusobacterium spp., and Clostridium spp [17].
Infectious anaerobic diseases often result in a serious condition
and treatment with appropriate antimicrobials is crucial, because
patients are highly compromised when the primary disease is severe. It is desirable that MNZ-IV would also be available in Japan for
the treatment of severe infectious diseases in hospitalized patients
who cannot take oral medication.
We planned this phase 3 study to evaluate the efﬁcacy andsafety of MNZ-IV administered at a dose of 500 mg 3 times a day(TID), or 4 times a day (QID) in severe cases, to Japanese adult patients with infectious peritonitis, abdominal abscess or PID in
combination with IV ceftriaxone (CTRX).
2. Subjects and methods
This study was conducted in accordance with the International
Conference on Harmonisation of Good Clinical Practice Guidelines,
the principle of the Declaration of Helsinki, and all applicable laws
and regulations at 15 medical centers nationwide in Japan between
November 2011 and October 2012. The protocol was reviewed andapproved by the Institutional Review Boards of all participating
study sites. All subjects provided written informed consent before
enrollment.
2.1. Study design
This multicenter, non-randomized, unblinded, non-comparative
phase 3 study was designed to investigate the safety and efﬁcacy
proﬁle of MNZ-IV in Japanese subjects with infectious peritonitis,
abdominal abscess or PID in combination with CTRX. A Data Review
Committee (DRC) was organized as an independent organization to
perform objective and uniﬁed efﬁcacy evaluation based on theclinical condition and diagnostic imaging ﬁndings. All subjects
received 500 mg MNZ administered by intravenous infusion over
20 min TID (or QID in subjects with refractory or severe infection)for 3e14 days in general. At the investigator's discretion, theduration of treatment could be prolonged for up to 21 days
depending on the subject's condition. All subjects received CTRX asa combination drug for the same period as MNZ-IV. CTRX, a 3rdgeneration cephalosporin with broad-spectrum activity against
aerobic bacteria is widely used in Japan and its efﬁcacy and safety
proﬁles are well established. Overseas textbooks and guidelines
recommend MNZ combined with agents that have antibiotic activity against aerobic pathogens, and for infectious peritonitis orabdominal abscess subjects, the target of this study, MNZ combinedwith 3rd generation cephalosporin antibacterial drugs, because
infections caused by anaerobic pathogens, the target diseases ofthis study, are often mixed infections including aerobic pathogens,and MNZ is not effective against them. Since CTRX can be given to
subjects once a day, it is considered useful in terms of decreasing
the burden on subjects. We therefore decided to use CTRX as the
combined drug. MNZ-IV was studied based on the following: (1)The safety and efﬁcacy of MNZ-IV has been demonstrated; and (2)the development of MNZ-IV was requested by the committee on“Unapproved Drugs and Indications with Unmet Medical Needs”

97

under the Ministry of Health, Labour, and Welfare of Japan, because
it is an unapproved drug with high medical needs. As a result of aconsultation with the Pharmaceutical and Medical Devices Agencyof Japan, the target number of subjects who meet the eligibility
criteria and receive the test drugs was set at 30, provided that we
could enroll at least 7 subjects in whom bacterial transition could
be evaluated with more than 80% probability, since the detection
rate of causative pathogens was assumed to be approximately 30%.
2.2. Eligibility criteria
Male and female subjects (for pelvic infections, subjects had to
be female) aged 16 years or older who had been diagnosed ashaving infectious peritonitis, abdominal abscess or PID, required
hospitalization, and initial IV antibacterial therapy were eligible.
The diagnostic criteria for infectious peritonitis or abdominal
abscess included: conﬁrmed infectious peritonitis or abdominal
abscess based on the presence of symptoms and signs of an inﬂammatory response (fever, increased white blood cell [WBC]count, CRP elevation), imaging ﬁndings, and the abdominal signs
and symptoms (lower abdominal pain, lower abdominal tenderness, upper abdominal pain, upper abdominal tenderness,
abdominal rebound, abdominal guarding, nausea, vomiting,decreased appetite, abdominal distension, diarrhea, constipation,
drainage, or abscess), and meeting either of the following criteria:
1) planned (or performed within the previous 24 h) drainage of
infective sites; and 2) for postoperative infectious peritonitis orabdominal abscess, conﬁrmed gastrointestinal tract secretion or
purulent discharge from an indwelling drain.
The diagnostic criteria for PID and related diseases (endometritis, myometritis, adnexitis, salpingitis, oophoritis, parametritis,
pelvic peritonitis, pelvic abscess, Douglas' abscess, perihepatitis,and perihepatic abscess) included: (1) one of the following symptoms should be observed: 1) lower abdominal pain or lower
abdominal tenderness; 2) uterus/uterine adnexa pain or uterus/
uterine adnexa tenderness; and 3) hypochondrial pain or hypochondrial tenderness; (2) negative for Chlamydia trachomatis; (3)once the above criteria are satisﬁed, one of the following 6 conditions should be observed: 1) fever 37  C (axillary); 2) WBC
count > upper limit of normal range; 3) CRP > upper limit of normal
range; 4) purulent discharge or pus observed by culdocentesis or
laparoscopy; 5) pelvic abscess conﬁrmed by ultrasonography; and6) positive for Neisseria gonorrhoeae.
Exclusion criteria included the following: subjects who had
undergone surgery for perforation of the digestive tract within 12 h,
or who had undergone surgery for perforation of gastroduodenal
ulcers within 24 h; subjects with suspected or conﬁrmed simple
appendicitis, necrotizing pancreatitis, infectious mononucleosis,
non-infectious peritonitis, or non-infectious endometriosis; subjects who did not undergo appropriate drainage; subjects expected
to be cured only by the surgical procedures (e.g., drainage) without
antimicrobial treatment; subjects who had open abdominal cavity
drainage; subjects with hypersensitivity to, intolerance of or
another contraindication to MNZ or CTRX or other cephem antibiotics; subjects with alcohol abuse; subjects with severe renal
dysfunction; subjects with hepatic dysfunction; subjects with severe underlying disease or other complications; subjects who
required additional systemic antibiotics; subjects who had received
treatment with systemic antibiotics within 7 days before the study;
subjects who had already received MNZ for the disease; subjects
whose causative pathogens were insusceptible to MNZ; and pregnant or lactating women.
The following concomitant medications were prohibited up to
the test of cure (TOC) assessment: systemic antibiotics (oral, injection); human immunoglobulin; colony-stimulating factor;

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H. Mikamo et al. / J Infect Chemother 21 (2015) 96e104

corticosteroids; continuous use of analgesic antipyretics; otherinvestigational drugs or medical devices; and anti-malignant tumor
agents.
2.3. Clinical and radiologic assessments
The primary efﬁcacy endpoint was the clinical response
assessed by the DRC at the end of treatment (EOT) and TOC (1 week
after EOT). Clinical efﬁcacy was mainly assessed based on theevaluation of clinical signs and symptoms, body temperature, WBC
count, CRP, and diagnostic radiographic imaging ﬁndings. The
clinical response was evaluated as “effective (cured or improved)” if
all of the following criteria were met: (1) resolution (cure) or
improvement of all inﬂammatory and abdominal ﬁndings, and/or
imaging abnormalities that were observed at the start of the study,
at the assessment time point, and (2) treatment with other antibiotics was not required during the study or after the assessment
time point. The clinical response was evaluated as “ineffective” ifeither of the following criteria were met: (1) the requirements for“effective” assessment were not satisﬁed; or (2) the treatment
failed and other systemic antibiotic therapy was applied to treat thetarget disease. The clinical response was evaluated as “indeterminate” if clinical efﬁcacy assessment was difﬁcult due to missing dataor other reasons.

2.6. Statistical analysis
Efﬁcacy analyses were mainly conducted on the Clinical Per
Protocol Set (CPPS) and the Bacteriologic Per Protocol Set (BPPS).
The CPPS consisted of all subjects in the Full Analysis Set (FAS) who
had no signiﬁcant protocol violations and who underwent theprescribed evaluations during the observation period as speciﬁed in
the protocol. The BPPS consisted of all subjects in the CPPS in whomcausative pathogens were identiﬁed by culture and antigen tests atbaseline.
The primary endpoint was the clinical efﬁcacy assessed by the
DRC at EOT and TOC. As the primary analysis of the primary
endpoint, the efﬁcacy rate and its 95% conﬁdence interval (CI) were
calculated at the TOC in the CPPS. The efﬁcacy rate and its 95% CI
were also calculated for infectious peritonitis or abdominal abscessand for PID.
For analysis of the bacteriological response, the secondary
endpoint, assessed by the DRC, the eradication rate and its 95% CI
were calculated for the BPPS.
Safety analysis was performed in the “Safety Analysis Set,” thepopulation of subjects who received at least 1 dose of the study
drug.

3. Results

2.4. Bacteriological assessment

3.1. Subject disposition

The secondary efﬁcacy endpoint was the bacteriologicalresponse assessed by the DRC on Day 4, EOT, and TOC. At thebaseline visit, all subjects provided clinical specimens (infection
sites), which were sent to a central laboratory for culture and theisolated pathogens were tested for susceptibility according to theprocedures of the Clinical and Laboratory Standards Institute atbaseline, Day 4, EOT, and TOC. The specimens from PID subjects(intrauterine materials, puncture ﬂuid from Douglas' pouch, or apurulent discharge) were also submitted for detection of
C. trachomatis, N. gonorrhoeae, or Mycoplasma genitalium,
M. hominis using antigen tests at baseline, EOT, and TOC.
The bacteriological response was assessed as “eradication” if theoriginal pathogen was not identiﬁed in the specimens; “presumed
eradication” if evaluable specimens were not obtained from a focus
of infection; “colonization” if an organism was isolated from asubject who had no signs or symptoms of infection; “persistence” if
the original pathogen remained in the specimens; “presumed
persistence” if a culture was difﬁcult or was not done in subjects
who were judged to be clinical failures and persistence of theoriginal pathogen was presumed; “replacement bacterium” if theoriginal pathogens were eradicated by treatment but other new
pathogens had appeared in the same specimen with symptoms orﬁndings of infection; “superinfection” if a pathogen other than theoriginal pathogens was isolated from a specimen taken while thesubject was on therapy and who had signs and symptoms ofinfection; “recurrence” if the original pathogen was isolated from a
specimen culture taken after the TOC visit; and “indeterminate” if a
specimen was not assessed according to the above-mentioned
criteria for various reasons.

A total of 38 subjects were enrolled at 15 medical centers inJapan and all of them received the study medication. Of these, 6
subjects (15.8%) discontinued the study (Table 1). Among the totalof 38 subjects, 23 were diagnosed as having infectious peritonitis orabdominal abscess and 13 with PID. Two subjects were judged tohave a disease not included in this study; 1 subject was diagnosed
as having lumbar disc herniation by the investigator after enrollment and the other as having suspected PID (non-infectious disease) by the DRC. Since 3 of the 23 infectious peritonitis orabdominal abscess subjects in the FAS were excluded because they
had received prohibited concomitant medications (2 subjects) orlacked the minimum 3 days of dosing (1 subject), the CPPS included
20 subjects with infectious peritonitis or abdominal abscess. The

2.5. Safety assessment
Safety data were obtained from the ﬁndings of clinical signs/
symptoms, physical examinations, vital signs, and laboratory data
up to TOC. The causality and severity of the adverse events were
evaluated by the investigators (or sub-investigators), based on the
MedDRA terminology.

Table 1
Subject disposition and analysis set.
Total

Subject
Enrolled and treatedCompleted
Discontinued
Deviation of inclusion criteria
Insufﬁcient efﬁcacy
Adverse event
Not related to the study drug
Related to the study drug

38a32b(84.2)
6 (15.8)
1c (2.6)
1 (2.6)4 (10.5)
3 (7.9)1 (2.6)

Diagnosis
Infectious
peritonitis orabdominal
abscess

PID

23
22 (95.7)
1 (4.3)00
1 (4.3)0
1 (4.3)13
9 (69.2)
4 (30.8)01 (7.7)
3 (23.1)
3 (23.1)
0

Values represent the number (%) of subjects.
PID: pelvic inﬂammatory disease.
aThirty-eight subjects included 2 subjects who were judged by the Data Review
Committee to have a disease not included in the study and who did not have infectious peritonitis, abdominal abscess or PID.
b
One subject was diagnosed as having suspected PID (non-infectious disease) by
the DRC and did not have infectious peritonitis, abdominal abscess or PID.
c
The subject was diagnosed as having lumbar disc herniation by the investigator
after enrollment and did not have infectious peritonitis, abdominal abscess or PID.

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H. Mikamo et al. / J Infect Chemother 21 (2015) 96e104

BPPS included 17 subjects with infectious peritonitis or abdominal
abscess in whom baseline causative pathogens were identiﬁed byculture. Since 3 of the 13 PID subjects in the FAS were excluded
because they met the exclusion criteria (2 subjects) or lacked theminimum 3 days of dosing (1 subject), the CPPS included 10 subjects with PID. The BPPS included 4 subjects with PID in whom thebaseline causative pathogens were identiﬁed by culture.
The baseline demographic characteristics of the subjects are
summarized in Table 2.
The details of the diagnoses in the CPPS are shown in Table 3.
Eleven of 20 infectious peritonitis or abdominal abscess subjects
had both abdominal abscess and infectious peritonitis. Among 10
PID subjects, 5 subjects had an abscess.
The average duration of treatment with MNZ-IV was 5.8 days
(range: 3e9 days) for infectious peritonitis or abdominal abscesssubjects and 8.3 days (range: 5e14 days) for PID subjects in the
CPPS. Most subjects received 500 mg of MNZ-IV TID. Only 2 subjects in the CPPS (1 subject with both infectious peritonitis andabdominal abscess and 1 subject with PID) received MNZ-IV QID.
At baseline, 29 causative pathogens were identiﬁed in 21 subjects (70.0%) in the CPPS (Table 4). Among infectious peritonitis orabdominal abscess subjects, 9 subjects had mixed infections withanaerobic and aerobic pathogens, 3 subjects had anaerobic infections, and 5 subjects had aerobic infections. For PID subjects, 2
subjects had mixed infections with anaerobic and aerobic pathogens and 2 subjects had aerobic infections. The major causative
anaerobic pathogens identiﬁed at baseline were B. fragilis (5strains), Parvimonas micra and Bacteroides thetaiotaomicron (2strains each) in the CPPS.

99

Table 3
Details of diagnosis in the CPPS.
Diagnosis
Infectious peritonitis orabdominal abscess
Abdominal abscess

Abdominal abscess,infectious peritonitis
Infectious peritonitis
PID
Douglas abscess, pelvic
peritonitis, tubo-ovarian
abscess
Adnexal abscess, adnexitis,
pelvic peritonitis
Adnexal abscess, pelvic
peritonitis
Adnexitis, endometritis,
pelvic peritonitis
Adnexitis, intrauterine
infection, pelvic peritonitis
Adnexitis, pelvic peritonitis
Pelvic peritonitis
Adnexitis, right adnexal
abscess
Right ovarian abscess

Infection site

N ¼ 3020

Appendix, peritoneal cavity,
mesentery, sigmoid colon,
perihepatic area, ascending colon
Appendix, peritoneal cavity,
peritoneum, douglas' pouch, small
intestine, colon, stomach, others
Peritoneum, small intestine,
sigmoid colon, appendix
Douglas' pouch, pelvic peritoneum,bilateral uterine, adnexia

6

11

3
10
1

Right adnexia, pelvic peritoneum

1

Left adnexia, pelvic peritoneum

1

Left adnexia, uterus, pelvic
peritoneum
Right adnexia, uterus, pelvic
peritoneum
Right adnexia, pelvic peritoneum
Pelvic peritoneum
Right adnexia

1

1
2
1

Right ovary

1

1

Values represent the number of subjects.
CPPS: clinical per protocol set; N: number of subjects evaluated; PID: pelvic inﬂammatory disease.

3.2. Efﬁcacy results
Table 2
Demographic characteristics.
Group

FAS

CPPS

Infectious peritonitis or abdominal abscess
Number of subjects
23
20
Sex
Male
14
12
Female98Age (years)
16  44
6 (26.1)
6 (30.0)45  64
8 (34.8)8 (40.0)65  74
5 (21.7)
4 (20.0)75  79
4 (17.4)
2 (10.0)
Mean ± SD
55.5 ± 16.3
52.7 ± 15.6
Range
25  78
25  78
Weight (kg)
45 kg2 (8.7)
2 (10.0)>45 kg21 (91.3)
18 (90.0)
Mean ± SD
64 ± 14.3
64.4 ± 14.8
Range
44.0e108.5
44.0e108.5
PID
Number of subjects
Sex
FemaleAge (years)
16e19
20e29
30e39
40
Mean ± SD
Range
Weight (kg)
45 kg>45 kgMean ± SD
Range

BPPS
17
11
6
4 (23.5)
8 (47.1)
4 (23.5)
1 (5.9)53.6 ± 13.7
25e75
1 (5.9)16 (94.1)
65.6 ± 14.945.0e108.5

13

10

4

13

10

4

1 (7.7)1 (7.7)5 (38.5)
6 (46.2)
39.4 ± 12.8
19  67

1 (10.0)04 (40.0)
5 (50.0)
41.3 ± 13.2
19  67002 (50.0)
2 (50.0)
39.0 ± 1.8
37  41

2 (15.4)
11 (84.6)
55.1 ± 13.2
40.0e90.5

2 (20.0)8 (80.0)
54.5 ± 14.5
40.0e90.5

0
4 (100)63.1 ± 19.3
45.3e90.5

FAS: full analysis set; CPPS: clinical per protocol set; BPPS: bacteriologic per protocol
set; PID: pelvic inﬂammatory disease.

For the clinical response assessed by the DRC in the CPPS (primary endpoint), the overall efﬁcacy rate was 96.7% (95% CI: 82.8%e
99.9%) at TOC (primary analysis) and 96.6% (95% CI: 82.2%e99.9%)
at EOT (secondary analysis) (Table 5). The efﬁcacy rate was 100% in
the subjects with infectious peritonitis or abdominal abscess and
90.0% in the subjects with PID, both at TOC and EOT. The therapy
failed only in 1 subject with PID (pelvic peritonitis).
For the clinical response by causative pathogen assessed by the
DRC in the BPPS, the efﬁcacy rate was 100% for all pathogens at EOT
and TOC.
For the bacteriological response in the BPPS overall assessed by
the DRC, the eradication rate was 100% on Day 4, EOT and TOC(Table 6). The eradication rates were also 100% in all subjects with
infectious peritonitis or abdominal abscess and PID on Day 4, EOT
and TOC (Table 6). The MICs of MNZ against the identiﬁed anaerobic
pathogens ranged from 0.06 to >128 mg/ml (Tables 7 and 8).
Among the 8 subjects with infectious peritonitis or abdominal
abscess who had 10 strains of anaerobic pathogens with resistanceto other antimicrobials than MNZ and CTRX, the clinical response
was assessed as cured or improved, except for 1 subject who was
judged as indeterminate at EOT, and the bacteriological response
was assessed as eradication or presumed eradication except in 2
subjects who were judged as colonization and indeterminate (1subject each) (Table 9).

3.3. Safety results
Among 38 subjects, 14 subjects (36.8%) experienced treatmentrelated adverse events during the entire treatment period. The
most common treatment-related adverse event was diarrhea (9subjects), followed by nausea (2 subjects), and vomiting andabdominal pain upper (1 subject each). The majority of adverse

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H. Mikamo et al. / J Infect Chemother 21 (2015) 96e104

which occurred after extubation following ileocecal resection surgery on Day 2. These adverse events were mild and moderate inseverity and resolved after discontinuation of the study medication.
There were no deaths or treatment-related serious adverse
events reported during the entire period.

Table 4
Number of subjects in the CPPS classiﬁed by identiﬁed pathogen.
Infectious peritonitis or abdominal abscessTotal number of subjects
Total number of subjects in whom pathogens were identiﬁed

20
17(85.0)
5(25.0)
2
1
2

Number of subjects in whom a single pathogen was identiﬁed
Bacteroides fragilis
Staphylococcus epidermidis*
Escherichia coli
Number of subjects in whom multiple pathogens were identiﬁed

Number of subjects in whom multiple pathogens were identiﬁed

Overall, MNZ-IV combined with CTRX exhibited excellent clinical and bacteriological efﬁcacy for the treatment of infectious
peritonitis, abdominal abscess and PID in Japanese subjects.
It is noted that MNZ-IV/CTRX was also effective in 1 subject who
had sepsis complicated by infectious peritonitis, indicating theeffectiveness of this dosing regimen in the treatment of patientswith severe complications of sepsis [18,19].
The combination therapy failed only in 1 subject with PID(pelvic peritonitis) who received MNZ-IV/CTRX for 8 days.
Although the spontaneous abdominal pain and tenderness, and thespontaneous pain of the uterus and its appendages improved,
tenderness of the uterus and its appendages remained, and a highWBC count (12,600/mm3) and CRP (8.5 mg/dl) as well as aggravation on computerized tomography and ultrasonic imaging wereobserved at EOT, the subject discontinued the study. This subject
recovered after administration of piperacillin, minocyline, andazithromycin. Since involvement of atypical microorganisms was
not conﬁrmed and no baseline causative pathogens were identiﬁed,
the clinical efﬁcacy in this subject at EOT and TOC was assessed asineffective.
MNZ is known to have high antimicrobial activity against anaerobes, including those identiﬁed in this study [5]. The MICs of
MNZ for most anaerobic pathogens identiﬁed in this study ranged
from 0.06 to 2 mg/ml, which may be associated with the highefﬁcacy for infectious peritonitis, abdominal abscess and PID.
Since MNZ has in vitro activity against most anaerobes including
Peptostreptococcus spp., Porphyromonas spp., Eubacterium spp.,
Veillonella spp., and Clostridium tetanii, which were not identiﬁed inthis study [5,20,21], MNZ-IV may be effective to treat infections
caused by these anaerobes. However, it is noted that MNZ is not
active in vitro against Actinomyces spp. or Propionibacterium acnes[22,23].
MNZ-IV/CTRX was also effective for mixed infections withanaerobic and aerobic pathogens, which may result due to theantibacterial activity of MNZ on anaerobes and the antibacterial
activity of CTRX on aerobes. When it is suspected that patients havemixed infections with anaerobic and aerobic pathogens, it isdesirable to use MNZ combined with an antibiotic drug that has
antibacterial activity on aerobes as recommended by many therapeutic guidelines.
For the treatment of anaerobic infections, the long-term use ofantianaerobic agents including b-lactam/b-lactamase-inhibitor

12(60.0)

2 pathogens identiﬁed
Parvimonas micra þ Escherichia coli
Bacteroides thetaiotaomicron þ Escherichia coli
Bacteroides vulgatus þ Escherichia coli
Enterococcus avium þ Escherichia coli
Escherichia coli þ Morganella morganii
3 pathogens identiﬁed
Bacteroides fragilis þ Streptococcus anginosus þ Escherichia coli
Bacteroides fragilis þ Streptococcus constellatus þ Escherichia coli
Bacteroides fragilis þ Enterococcus avium þ Klebsiella pneumoniae
4 or more pathogens identiﬁed
Eggerthella lenta þ Bacteroides xylanisolvens þ Escherichia coli þKlebsiella oxytoca
Parvimonas micra þ Bacteroides salyersiae þ Bacteroides
thetaiotaomicron þ Fusobacterium nucleatum þ Escherichia coli
Clostridium sp. þ Bacteroides ovatus þ Fusobacterium
necrophorum þ Streptococcus constellatus þ Escherichia coli
Streptococcus agalactiae þ Streptococcus constellatus þStreptococcus oralis þ Klebsiella pneumoniae þ Proteus
mirabilis þ Edwardsiella tarda
PID
Total number of subjects
Total number of subjects in whom pathogens were identiﬁed
Number of subjects in whom a single pathogen was identiﬁed

4. Discussion

1
1
1
1
1
1
1
1
1
1
1
1

10
4
(40.0)
04(40.0)

2 pathogens identiﬁed
Fusobacterium nucleatum þ Streptococcus agalactiae
Staphylococus haemolyticus þ Streptococus group G
Streptococcus agalactiae þ Citrobacter koseri
4 pathogens identiﬁed
Gemella morbillorum þ Prevotella intermedia þ Streptococcus
constellatus þ Streptococcus sanguis

1
1
1
1

Values represent the number (%) of subjects.
Underlined pathogens are anaerobic bacteria.
*: mutating into obligatory anaerobe.
CPPS: clinical per protocol set; PID: pelvic inﬂammatory disease.

events occurred within 6 days after starting the treatment, and was
mild to moderate in severity. There were no treatment-related
adverse events associated with intravenous injection.
One subject discontinued the study because of treatmentrelated adverse events (atrial ﬁbrillation and sinus tachycardia),

Table 5
Clinical response assessed by the Data Review Committee (CPPS).
Diagnosis

Overall
Infectious peritonitis or abdominal abscess
PID

Visit

EOT
TOC
EOT
TOC
EOT
TOC

N

30
30
20
20
10
10

Clinical response
Cure (%)

Improved (%)

Ineffective (%)

Ind (%)

4 (13.3)
25 (83.3)
1 (5.0)19 (95.0)
3 (30.0)
6 (60.0)24 (80.0)
4 (13.3)
18 (90.0)
1 (5.0)6 (60.0)
3 (30.0)

1 (3.3)1 (3.3)00
1 (10.0)
1 (10.0)

1 (3.3)0
1 (5.0)0
00

Efﬁcacy ratea (%)

95% CI

96.6
96.7
100
100
90.0
90.0

(82.2e99.9)(82.8e99.9)(82.4e100.0)(83.2e100)(55.5e99.7)(55.5e99.7)

Values represent the number (%) of subjects.
CPPS: clinical per protocol set; N: number of subjects evaluated; Ind: indeterminate; CI: conﬁdence interval; EOT: end of treatment; TOC: test of cure; PID, pelvic inﬂammatory
disease.
a
Efﬁcacy rate ¼ effective (cure þ improved)/(N  Ind)  100.

―２５８―

H. Mikamo et al. / J Infect Chemother 21 (2015) 96e104

101

Table 6Bacteriological response assessed by the Data Review Committee in the BPPS.
Diagnosis

Visit

Overall

Infectious peritonitis or abdominal abscess

PID

Day 4
EOT
TOC
Day 4
EOT
TOC
Day 4
EOT
TOC

n

13
21
21
9
17
17
4
4
4

Bacteriological response
Era

P Era

Col

Per

P per

Mic

Sup

Rec

Ind

11 (84.6)
12 (57.1)
4 (19.0)
7 (77.8)8 (47.1)
0
4 (100)4 (100)4 (100)2 (15.4)
6 (28.6)
17 (81.0)
2 (22.2)
6 (35.3)
17 (100)0000
2 (9.5)00
2 (11.8)
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
1 (4.8)00
1 (5.9)0000Eradication
ratea (%)

95% CI

100
100
100
100
100
100
100
100
100

75.3e100
83.2e100
83.9e100
66.4e10079.4e100
80.5e10039.8e10039.8e10039.8e100

Values represent the number (%) of subjects.
BPPS: bacteriologic per protocol set; n: number of subjects in whom infections were identiﬁed; Era: eradication; P Era: presumed eradication; Col: colonization; Per:
persistence; P Per: presumed persistence; Mic: microbial substitution; Sup: superinfection; Rec: recurrence of infection; Ind: indeterminate; CI: conﬁdence interval; EOT: endof treatment; TOC: test of cure; PID: pelvic inﬂammatory disease.
aEradication rate ¼ (Era þ P Era þ Col)/(n  Ind)  100.

Table 7
Clinical response by MIC for anaerobic pathogens assessed by the Data Review Committee in the BPPS.
Pathogen

MICa

Visit

n

(mg/ml)Infectious peritonitis or abdominal abscess
Eggerthella lenta
1/128
Parvimonas micra

0.5/0.06

Clostridium spp.

0.06/1

Bacteroides fragilis

1/>128
2/4
2/16
2/32
2/64

Bacteroides salyersiae
Bacteroides thetaiotaomicron

1/32
0.25/128
2/64

Bacteroides vulgatus

0.25/>128

Bacteroides xylanisolvens

1/32

Bacteroides ovatus

2/>128Fusobacterium nucleatum0.06/0.5

Fusobacterium necrophorum

NA

PID
Gemella morbillorum>128/0.5

Prevotella intermedia

0.5/0.06

Fusobacterium nucleatum0.06/1

Eradication rateb (%)

Clinical response
Cure

Improved

Ineffective

Ind

EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC
EOT
TOC

1
1
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1

0
1 (100)02 (100)0
1 (100)0
1 (100)0
1 (100)0
1 (100)000
1 (100)0
1 (100)0
1 (100)0
1 (100)1 (100)1 (100)0
1 (100)0
1 (100)0
1 (100)0
1 (100)1 (100)02 (100)0
1 (100)0
1 (100)0
1 (100)0
1 (100)0
1 (100)1 (100)1 (100)0
1 (100)000
1 (100)000
1 (100)0
1 (100)0
1 (100)0
1 (100)
0

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1 (100)
0
0
0
0
0
0
0
0
0
0
0
0
0

100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
e
100
100
100
100
100
100
100
100
100
100
100
100
100

EOT
TOC
EOT
TOC
EOT
TOC

1
1
1
1
1
1

0
1 (100)0
1 (100)00

1 (100)0
1 (100)0
1 (100)1 (100)

0
0
0
0
0
0

0
0
0
0
0
0

100
100
100
100
100
100

Values represent the number (%) of subjects.
BPPS: bacteriologic per protocol set; n: number of subjects in whom pathogens were identiﬁed; Ind: indeterminate; EOT: end of treatment; TOC: test of cure; NA: notapplicable; PID: pelvic inﬂammatory disease.
a
MIC of MNZ/MIC of CTRX.
b
Eradication rate ¼ (Cure þ Improved)/(n  Ind)  100.

―２５９―

102

H. Mikamo et al. / J Infect Chemother 21 (2015) 96e104

Table 8Bacteriological response by MIC for anaerobic pathogens assessed by the Data Review Committee in the BPPS.
PathogenMICa(mg/ml)Infectious peritonitis or abdominal abscess
Eggerthella lenta
1/128
Parvimonas micra

0.5/0.06

Clostridium spp.

0.06/1

Bacteroides fragilis

1/>128

2/4
2/16

2/32
2/64

Bacteroides salyersiae

1/32

Bacteroides thetaiotaomicron

0.25/128
2/64

Bacteroides vulgatus

0.25/>128

Bacteroides xylanisolvens

1/32

Bacteroides ovatus

2/>128Fusobacterium nucleatum0.06/0.5

Fusobacterium necrophorum

NA

PID
Gemella morbillorum>128/0.5

Prevotella intermedia

0.5/0.06

Fusobacterium nucleatum0.06/1

VisitnEradication rateb (%)

Bacteriological response
Era

P Era

Col

Per

P Per

Rec

Ind

EOT
TOC
Day 4
EOT
TOC
EOT
TOC
Day 4
EOT
TOC
EOT
TOC
Day 4
EOT
TOC
EOT
TOC
Day 4
EOT
TOC
Day 4
EOT
TOC
EOT
TOC
Day 4
EOT
TOC
Day 4
EOT
TOC
EOT
TOC
EOT
TOC
Day 4
EOT
TOC
EOT
TOC

1
1
1
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1

1 (100)001 (50.0)000
1 (100)1 (100)000
1 (100)1 (100)000
1 (100)1 (100)0000
1 (100)
0
0
0
0
0
0
0
1 (100)
0
0
0
0
0
0
0
0

0
1 (100)1 (100)1 (50.0)
2 (100)0
1 (100)00
1 (100)1 (100)1 (100)00
1 (100)0
1 (100)00
1 (100)1 (100)1 (100)1 (100)0
1 (100)1 (100)1 (100)1 (100)1 (100)1 (100)1 (100)0
1 (100)0
1 (100)1 (100)1 (100)1 (100)0
1 (100)

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1 (100)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

0
0
0
0
0
1 (100)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1 (100)0000
1 (100)
0

100
100
100
100
100
e
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
e
100
100
100
100
e
100

Day 4
EOT
TOC
Day 4
EOT
TOC
Day 4
EOT
TOC

1
1
1
1
1
1
1
1
1

1 (100)1 (100)1 (100)1 (100)1 (100)1 (100)1 (100)1 (100)1 (100)

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0

100
100
100
100
100
100
100
100
100

Values represent the number (%) of subjects.
BPPS: bacteriologic per protocol set; n: number of subjects in whom pathogens were identiﬁed; Era: eradication; P Era: presumed eradication; Col: colonization; Per:
persistence; P Per: presumed persistence; Rec: recurrence of infection; Ind: indeterminate; EOT: end of treatment; TOC: test of cure; NA: not applicable; PID: pelvic inﬂammatory disease.
a
MIC of MNZ/MIC of CTRX.
b
Eradication rate ¼ (Era þ P Era þ Col)/(n  Ind)  100.

combination, carbapenams, moxiﬂoxacin, garenoxacin, and sitaﬂoxacin resulted in the emergence of resistant pathogens and anincreased risk for Clostridium difﬁcile infection. Increased resistance
rates to clindamycin, which is used as an alternative antianaerobic
agent, have also been reported among anaerobic pathogens[11e13,16]. Therefore, MNZ-IV/CTRX can be useful to treat anaerobic infections as an antimicrobial therapy that prevents the
emergence of drug-resistant strains.
MNZ-IV/CTRX was effective in 1 subject with both infectious
peritonitis and abdominal abscess in whom a metallo-b-lactamaseproducing B. fragilis strain (MIC of MNZ, 2 mg/ml) was identiﬁed.
Since MNZ shows in vitro antimicrobial activity against metallo-b-

lactamase-producing carbapenem-resistant strains [24], MNZ may
provide a useful option for the treatment of infectious disease
involving metallo-b-lactamase-producing anaerobic pathogens.
The emergence rate of MNZ-resistant anaerobes is generally low,
but a slight decrease in susceptibility to MNZ among anaerobes
including Bacteroides spp. has been reported [24,25]. The appropriate use of MNZ is important for the treatment of anaerobic infections to prevent the emergence of MNZ-resistant anaerobes. It isthus desirable to not only administer MNZ, but also various antimicrobial classes equally for anaerobic infections to prevent theexcessive use of MNZ. Since clinicians frequently choose clindamycin for anaerobic infections, resistance to clindamycin is a growing―２６０―

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103

Table 9Anaerobic pathogens with resistance to antimicrobials other than MNZ and CTRX, MICs, and clinical and bacteriological responses to the pathogens when MNZ-IV combiniedwith CTRX was administered.
MIC of CTRX
(mg/ml)Subject ID

Anaerobic pathogen

MIC of MNZ(mg/ml)1Bacteroides xylanisolvens

1

32

Eggerthella lenta

1

128

2

Bacteroides vulgatus

0.25

3

Bacteroides thetaiotaomicron

264Bacteroides salyersiae

1

32

4

Bacteroides ovatus

2

>128

5

Bacteroides thetaiotaomicron

0.25

128

6

Bacteroides fragilis

2

32

7

Bacteroides fragilis

1

>128

8

Bacteroides fragilis

2

64

>128

MIC of other drugs(mg/ml)Clinical response

Bacteriological response

Clindamycin: >128
Cefepime: 128
Cefozopran: >64
Clindamycin: 0.12
Cefepime: 128
Cefozopran: 32
Sulbactam/Cefoperazone: 64
Clindamycin: >128
Cefepime: >128
Cefozopran: >64
Penicillin G: >128
Ampicillin: >128
Piperacillin: 128
Cefepime: >128
Cefozopran: >64
Cefepime: 64
Cefozopran: >64
Cefepime: >128
Cefozopran: >64
Penicillin G: >128
Ampicillin: >128
Piperacillin: >128
Cefepime: >128
Cefozopran: >64
Cefepime: 64
Cefozopran: 64
Penicillin G: 64
Cefepime: >128
Cefozopran: >64
Penicillin G: >128
Ampicillin: >128
Piperacillin: 128
Cefepime: 128
Cefozopran: >64
Penicillin G: >128
Ampicillin: >128
Piperacillin: >128

EOT: Improved
TOC: Cure

EOT: Era
TOC: P Era

EOT: Cure
TOC: CureDay 4: P Era
EOT: P Era
TOC: P Era

EOT: Improved
TOC: CureDay 4: P Era
EOT: P Era
TOC: P Era

EOT: Improved
TOC: Cure

EOT: Ind
TOC: P Era

EOT: Ind
TOC: Cure
EOT: Improved
TOC: Improved

EOT: Era
TOC: P Era
EOT: Col
TOC: P Era

EOT: Improved
TOC: CureDay 4: Era
EOT: Era
TOC: P Era

EOT: Improved
TOC: CureDay 4: Era
EOT: Era
TOC: P Era

MNZ: metronidazole; CTRX: ceftriaxone; IV: intravenous; EOT: end of treatment; TOC: test of cure; Era: eradication; P Era: presumed eradication; Col: colonization; Ind:
indeterminate.

issue in the treatment of anaerobic infections. Similarly, there might
be a possibility that the excessive use of MNZ for anaerobic infections may result in an increase in MNZ resistant anaerobes.
In this study, MNZ-IV in combination with CTRX was welltolerated, and demonstrated excellent clinical and bacteriological efﬁcacy in the treatment of hospitalized Japanese subjects
with infectious peritonitis, abdominal abscess or PID. These results indicate that MNZ-IV/CTRX therapy can be a reasonableoption for the empirical treatment of anaerobic infectious diseases involving antibiotic-resistant organisms in clinicalpractice.
The use of MNZ is recommended for the treatment of thevarious anaerobic infections referred to in textbooks and guidelines [7e10,26e31]. However, there has been little information on
the efﬁcacy and safety of MNZ-IV in Japanese patients with otheranaerobic infections than infectious peritonitis, abdominal abscess, or PID. Therefore, some clinical research will be needed forfurther evaluation of the efﬁcacy and safety of MNZ-IV in Japanesepatients.

Conﬂict of interest
H. Mikamo has received a consultant fee and a fee for participation in the Committee from Pﬁzer Japan Inc. M. Matsumizu, Y.
Nakazuru, and M. Nagashima are employees of Pﬁzer Japan Inc.

Acknowledgments
We wish to thank the investigators who have contributed to thisclinical study. This study was sponsored by Pﬁzer Japan Inc.

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J Infect Chemother 21 (2015) 520e526

Contents lists available at ScienceDirect

Journal of Infection and Chemotherapy
journal homepage: http://www.elsevier.com/locate/jic

Original article

Efﬁcacy and safety of a single oral 150 mg dose of ﬂuconazole for thetreatment of vulvovaginal candidiasis in Japan
Hiroshige Mikamo a, Miyako Matsumizu b, *, Yoshiomi Nakazuru c, Akifumi Okayama c,
Masahito Nagashima a, b
a

Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Aichi, Japan
Clinical Research, Development Japan, Pﬁzer Japan Inc., Tokyo, Japanc
Clinical Statistics, Development Japan, Pﬁzer Japan Inc., Tokyo, Japanba r t i c l e i n f o

a b s t r a c t

Article history:
Received 15 December 2014
Received in revised form
19 March 2015
Accepted 22 March 2015
Available online 30 March 2015

Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial
vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical(vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of ﬂuconazole has been
recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global
guidelines; however, in Japan oral ﬂuconazole therapy has not been approved. We conducted a phase 3
study to evaluate the efﬁcacy and safety of a single oral 150 mg dose of ﬂuconazole in Japanese subjects
with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral
150 mg dose of ﬂuconazole. Candida species (104 strains) were identiﬁed by fungal culture from 102
subjects at baseline, including Candida albicans (100 strains). The efﬁcacy rate for the therapeutic
outcome (assessed based on a comprehensive evaluation of the clinical and mycological efﬁcacy in eachsubject) was 74.7% (74/99) on Day 28 in the modiﬁed Intent-To-Treat (m-ITT) population. Concerning theclinical and mycological efﬁcacy on Day 28 in the m-ITT population, the cure, cure or improvement, anderadication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related
adverse events were diarrhea and nausea (1.9% for each). No clinically signiﬁcant safety issues werereported. A single oral 150 mg dose of ﬂuconazole demonstrated excellent therapeutic efﬁcacy and waswell tolerated in Japanese subjects with vulvovaginal candidiasis.
Clinical registration number: NCT01806623.
© 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
Published by Elsevier Ltd. All rights reserved.

Keywords:
Fluconazole
Single oral dose
Vulvovaginal candidiasis
Candidal vulvovaginitis

1. Introduction
Vulvovaginal candidiasis is an infection of the vulva and/or vagina caused by Candida species. Vulvovaginal candidiasis is thesecond most common cause of vaginal infections after bacterial
vaginosis, and is often diagnosed at primary care clinics for obstetrics and gynecology [1e3].
The most common causative pathogen of vulvovaginal candidiasis is Candida albicans, followed by Candida glabrata, which arepart of the indigenous ﬂora of the gastrointestinal tract and skin

* Corresponding author. Clinical Research, Development Japan, Pﬁzer Japan Inc.,
3-22-7 Yoyogi, Shibuya-ku, Tokyo 151-8589, Japan. Tel.: þ81 3 5309 7010; fax: þ81
3 5309 9060. .
E-mail address: miyako.matsumizu@pﬁzer.com (M. Matsumizu).

[1e3]. A positive vaginal culture for Candida species is found in
approximately 15% of non-pregnant adolescent women, and 30% ofpregnant women in Japan, but most women only have Candida
species in the vagina and are asymptomatic, but are not diagnosed
as having candidiasis, and do not require treatment. Treatment isrequired by approximately 35% of non-pregnant women withvaginal Candida species, and 15e30% of pregnant women withvaginal Candida species [1]. The infection caused by Candida affects
70e75% of women at least once during their lives, and is mostcommon in young women of childbearing age [1e3].
For the treatment of vulvovaginal candidiasis, antifungal agents,
either as topical (vaginal tablets and cream) or oral formulations,
are used. In European countries and the United States (US), for thetreatment of uncomplicated vaginal candidiasis, a single oral
150 mg dose of ﬂuconazole is recommended by the 2010 Sexually

http://dx.doi.org/10.1016/j.jiac.2015.03.011
1341-321X/© 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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H. Mikamo et al. / J Infect Chemother 21 (2015) 520e526

521

transmitted disease treatment guidelines of the CDC [3] and the
Sanford Guide to Antimicrobial Therapy 2014 [4].
In Japan, oral therapy with antifungal triazoles such as ﬂuconazole has not been approved for vulvovaginal candidiasis, andtopical therapies such as vaginal tablets and cream has been clinically used. In accordance with the Diagnosis and Treatment
Guidelines for Sexually Transmitted Diseases 2011 in Japan, 100 mg
of either clotrimazole, miconazole, isoconazole or oxiconazole isrecommended as a daily treatment with vaginal tablets or pessary
for uncomplicated acute vulvovaginal candidiasis, which in principle requires daily hospital visits and a vaginal douche prior toadministration. For patients who cannot visit the hospital daily,
vaginal administration of a weekly dose of 600 mg isoconazole oroxiconazole is recommended after vaginal douche [1]. However, it
is difﬁcult for patients to administer vaginal tablets or a pessary,
which is painful, by themselves, and therefore it often results inincompliance due to the burden of treatment [5e7].
Fluconazole, a triazole antifungal agent, has clinically been
widely used with the indication for deep mycosis as an oral drug
(capsules) and injection in Japan since it was launched in 1989. As
for the treatment of vulvovaginal candidiasis, a single oral 150 mg
dose of ﬂuconazole, if implemented in Japan, would be of clinicalsigniﬁcance as a new and satisfactory treatment option providing
better dose compliance than topical therapies.
The aim of this study was to investigate the efﬁcacy and safety
proﬁle of a single oral 150 mg dose of ﬂuconazole for the treatment
of Japanese subjects with vulvovaginal candidiasis for regulatory
submission.

redness of the vulva, and vaginal redness; and (B) property ofvaginal content scores: 0 ¼ normal, 1 ¼ mucoid, 2 ¼ paste-like, and
3 ¼ cottage cheese-like, cheese-like or granular.
Exclusion criteria included the following: a history of hypersensitivity to ﬂuconazole; diabetes; severe renal dysfunction; liver
disorder; heart disease or electrolyte abnormality; pregnancy orlactation; serious underlying diseases or complications; possible
accompanying trichomonas vaginitis or bacterial vaginosis, vaginitis caused by Chlamydia or Gonococcus, or herpes simplex;
chronic vulvovaginal candidiasis; vaginal pH  5.0; the previous
use of systemic antifungals within 4 weeks before starting thestudy medication, or the previous use of local (vulval or intravaginal) antifungals within 2 weeks before starting the study
medication; not willing to avoid sexual relations up to 28 days after
the dosing; menstruation at enrollment, or next menstruation expected to start within 1 week after the study medication; diagnosis
of being immunocompromised.
The following concomitant medications and therapy were prohibited up to Day 28: antifungals, antimicrobials, and antiallergic
drugs (oral, injection, topical [vulval or intravaginal] drugs); humanimmunoglobulin; colony stimulating factor; corticosteroids;
vaginal douching after the study medication; and other investigational drugs or medical devices. The use of antimicrobials wasallowed for subjects who turned out to have accompanying trichomonas vaginitis, bacterial vaginosis, vaginitis caused by Chlamydia or Gonococcus or herpes simplex after enrollment.

2. Subjects and methods

The primary endpoints included therapeutic outcomes determined by investigators on Days 7, 14, 28, and at discontinuation.
Primary evaluation was therapeutic outcome on Day 28.
Therapeutic outcome was assessed based on the comprehensive
evaluation of clinical and mycological efﬁcacy of each subject according to the criteria shown in Table 1.

This study was conducted in accordance with the International
Conference on Harmonisation of Good Clinical Practice Guidelines,
the principle of the Declaration of Helsinki, and all applicable laws
and regulations at 10 medical centers nationwide in Japan between
March 2013 and November 2013. The protocol was approved by theInstitutional Review Boards of all participating study sites. All
subjects provided written informed consent before enrollment. The
study was conducted in accordance with advice from the Pharmaceuticals and Medical Devices Agency (PMDA) after the appropriateness of the study design, endpoints, analysis set, inclusion
criteria, and so on were discussed with the PMDA.
2.1. Study design
This multicenter, open-label, non-comparative phase 3 study
was designed to evaluate the efﬁcacy and safety of a single oral
150 mg dose of ﬂuconazole in Japanese subjects with vulvovaginal
candidiasis. The target number of subjects was 99 who were in themodiﬁed Intent-To-Treat (m-ITT) population and whose therapeutic outcomes on Day 28 would be evaluated as effective or
ineffective. All the subjects took 3 ﬂuconazole 50 mg capsules orally
only once on the ﬁrst day of the treatment. The efﬁcacy and safety
were evaluated up to Day 28.

2.3. Assessments

2.3.1. Clinical efﬁcacy
Clinical efﬁcacy was assessed based on the evaluation of clinicalsigns and symptoms (vulvovaginal itching, vulvovaginal burning
sensation, excoriation of the vulva, vaginal discharge, vulval edema,
redness of the vulva, vaginal redness, property of vaginal content).
Clinical efﬁcacy was judged as “cured” or “improved” if the clinicalsymptoms at the start of treatment had resolved or improved at theassessment time point; “ineffective” if neither the criteria for“cured” nor “improved” were met, or the treatment failed and other
antifungals were administered for the treatment of vulvovaginal
candidiasis; “indeterminate” if efﬁcacy assessment was difﬁcult or
not determined because of missing data or failure to conduct the
test, or other antifungals were administered for the treatment ofother infections than vulvovaginal candidiasis.
2.3.2. Mycological efﬁcacy
The causative pathogen was identiﬁed by vaginal discharge
culture before the study medication on Day 1 and on Days 7, 14 and2.2. Eligibility criteria
Female Japanese subjects aged 18 years or older (<80 years inprinciple), who had clinical signs and symptoms of vulvovaginal
candidiasis with a total symptom severity scores of 4 or higher, andwere positive for Candida by fungal culture were eligible. Clinicalsigns and symptoms were evaluated as follows: (A) symptom
severity scores: 0 ¼ no symptoms, 1 ¼ mild, 2 ¼ moderate, and
3 ¼ severe, for vulvovaginal itching, vulvovaginal burning sensation, excoriation of the vulva, vaginal discharge, vulva edema,

Table 1
Criteria for determining the therapeutic outcomes.
Clinical efﬁcacy

Mycological efﬁcacy
Eradication

PersistentIndeterminate

Cure
Improvement
Ineffective
Indeterminate

Effective
Ineffective
Ineffective
Indeterminate

Ineffective
Ineffective
Ineffective
Ineffective

Indeterminate
Indeterminate
Ineffective
Indeterminate

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H. Mikamo et al. / J Infect Chemother 21 (2015) 520e526

28. Mycological response was assessed based on the results ofculture. Mycological efﬁcacy was judged as “eradication” if theoriginal pathogen was not identiﬁed in the vaginal discharge;“persistence” if the original pathogen remained in the specimens orother antifungals were administered for the treatment of vulvovaginal candidiasis; “indeterminate” if efﬁcacy assessment could
not be determined because of a failure to conduct the vaginal
discharge culture etc., or other antifungals were administered forthe treatment of other infections than vulvovaginal candidiasis.

Table 2
Baseline demographic and other characteristics of subjects with vulvovaginal candidiasis in the m-ITT population.
Variable

m-ITT population (N ¼ 102)

Age (years)
Mean (SD)Range

31.9 (8.2)
18e55

Body weight (kg)
Mean (SD)Range

53.9 (11.5)
40.0e136.8

2.4. Safety assessment
Severity of vulvovaginal candidiasis (n (%))
Mild
11 (10.8)
Moderate
73 (71.6)
Severe18 (17.6)

Safety data were obtained from the ﬁndings of clinical signs/
symptoms, physical examinations, vital signs, and laboratory data
up to Day 28. The causality and severity of the adverse events were
evaluated by the investigators (or sub-investigators), based on the
Medical Dictionary for Regulatory Activities terminology.

Number of occurrence of vulvovaginal candidiasis for the last 1 year (n (%))
080 (78.4)
1 or more
22 (21.6)
1e3
22
1
16
2
4
3
2
4 or more
02.5. Statistical analysis
Efﬁcacy analyses were mainly conducted of m-ITT subjects withvulvovaginal candidiasis who received the study drug, were positive for Candida by culture on Day 1 (before dosing), and whose
therapeutic outcome on Day 28 was evaluated as effective or
ineffective.
The primary endpoint was the efﬁcacy rate of the therapeutic
outcome in the m-ITT population on Day 28, and the efﬁcacy would
be conﬁrmed if the lower bound of the 95% conﬁdence interval (CI)of the therapeutic success rate was greater than 38% (pre-speciﬁed
threshold value).
The safety analysis set was deﬁned as all subjects who received
the study drug.
Assuming that the therapeutic success rate in this study would
be 54% based on the efﬁcacy results of 2 previous US phase 3
studies, and the lower bound of the 95% CI (threshold value) for the
success rate was set to be 38%, which was derived from themycological eradication rate in meta-analysis literature [8], 99
subjects were needed in the m-ITT population to ensure a statisticalpower of 90% at a one-sided signiﬁcance level of 0.025. Assumingthat Candida was detected in the vulva and/or vagina in 80% of thesubjects presenting with such symptoms as vulvovaginal itching
and increase in vaginal discharge, 130 subjects were needed to beenrolled.
3. Results
3.1. Subject disposition and demography
In this study, a total of 157 subjects were assigned and all ofthem received the study drug. Of these, 99 subjects completed thestudy, and 58 discontinued the study due to the following: (A) not
meeting the inclusion criteria in 56 subjects (55 were negative for
Candida by fungal culture, and 1 had abnormal values for liverfunction tests, which met the exclusion criteria); (B) voluntary
withdrawal from the study in 1 subject; and (C) adverse events not
related to the study drug (vulvovaginitis trichomonal) in 1 subject.
Of the 157 subjects who received the study medication, 55 were notincluded in the m-ITT population because they were negative for
Candida by fungal culture, and the remaining 102 subjects formed
the m-ITT population. The safety analysis set included all 157
subjects.
Table 2 summarizes the baseline demographic and other characteristics of the subjects.
At baseline, 104 strains of Candida were identiﬁed by fungal
culture in 102 of 157 subjects: C. albicans (100 strains), Candida

m-ITT, modiﬁed intent-to-treat.

parapsilosis (2 strains), C. glabrata, and Candida sp. (1 strain each)(multiple strains were identiﬁed in 2 subjects). The MICs50 andMICs90 of ﬂuconazole, oxiconazole, isoconazole, clotrimazole, andmiconazole for C. albicans, C. parapsilosis, and C. glabrata isolates areshown in Table 3. Severity scores assigned to each clinical symptom
at baseline are summarized in Fig. 1. More than half of the subjects
had moderate to severe vulvovaginal itching and vaginal discharge.
The property of vaginal content was paste-like, cottage cheese-like,or granular in most subjects.
3.2. Efﬁcacy results
The rate of “effective” for the therapeutic outcome in the m-ITT
population was 33.7% (95% CI: 24.2e44.3%) on Day 7, 54.2%(43.7e64.4%) on Day 14, and 74.7% (65.0e82.9%) on Day 28(Table 4). Efﬁcacy was conﬁrmed since the lower bound of the 95%
CI of the therapeutic success rate on Day 28 (65.0%) was greaterthan 38% (pre-speciﬁed threshold value).
For clinical efﬁcacy in the m-ITT population, the cure rate was
34.8% on Day 7, 57.3% on Day 14, and 81.6% on Day 28. The cure or
improvement rate was 100.0% on Day 7, 99.0% on Day 14, and 95.9%
on Day 28 (Table 5).
For the mycological efﬁcacy in the m-ITT population, themycological eradication rate was 95.7% on Day 7, 89.8% on Day 14,
and 85.9% on Day 28 (Table 6).
Most subjects whose therapeutic outcomes were assessed as“ineffective” showed “improvement” and “eradication” for clinicaland mycological efﬁcacy, respectively (57/61 on Day 7, 33/44 on
Day 14, and 10/25 on Day 28). Three subjects had “ineffective” forclinical efﬁcacy and “persistence” for mycological efﬁcacy on Day
28.
Changes in the percentages of subjects with some clinical signs
and symptoms are shown in Fig. 2. All the clinical signs andsymptoms improved from Day 3.
3.3. Safety results
Among the 157 subjects in the safety analysis set, 12 subjects(7.6%) experienced treatment-related adverse events (Table 7).

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523

Table 3
MICs of ﬂuconazole, oxiconazole, isoconazole, clotrimazole, and miconazole for C. albicans, C. parapsilosis and C. glabrata isolates.
C. albicans (N ¼ 100)

Fluconazole
Oxiconazole
Isoconazole
Clotrimazole
Miconazole

C. parapsilosis (N ¼ 2)

C. glabrata (N ¼ 1)

Range

MIC50

MIC90

Range

MIC50

MIC90

Range

MIC50

MIC90

0.12e40.06e0.25
0.06e0.25
0.06e0.06
0.06e1

0.25
0.06
0.06
0.06
0.06

0.25
0.06
0.06
0.06
0.06

1e1
0.25e0.5
0.5e0.5
0.06e0.06
0.5e0.5

e
e
e
e
e

e
e
e
e
e

8e8
0.06e0.06
0.5e0.5
0.5e0.5
0.5e0.5

e
e
e
e
e

e
e
e
e
e

Fig. 1. Percentage graphs of severity scores of clinical signs and symptoms at baseline in the m-ITT population. Clinical signs and symptoms: A ¼ vulvovaginal itching,
B ¼ vulvovaginal burning sensation, C ¼ vaginal discharge, D ¼ excoriation, E ¼ vulval edema, F ¼ redness of vulva, G ¼ vaginal redness, and H ¼ Property of vaginal content. Scores:
0 ¼ normal, 1 ¼ mild, 2 ¼ moderate, and 3 ¼ severe in A to G; and 0 ¼ normal, 1 ¼ mucoid, 2 ¼ paste-like, and 3 ¼ cottage cheese-like, cheese-like or granular in H.

The most common treatment-related adverse events werediarrhea and nausea (1.9% each). All adverse events were mild or
moderate in severity, and no deaths, serious adverse events, ordiscontinuations due to treatment-related adverse event werereported.
4. Discussion
Overall, in this non-comparative phase 3 study, a single oral
150 mg dose of ﬂuconazole was effective for the treatment of Japanese subjects with vulvovaginal candidiasis.

The efﬁcacy rate for the therapeutic outcome on Day 28 in the
m-ITT population in this study was comparable to the clinical efﬁcacy rates of a single oral 150 mg dose of ﬂuconazole (80% atshort-term assessment [Days 5e15] and 76% at long-term assessment [Days 30e60]) reported in previous clinical trials in Japanese
subjects with vulvovaginal candidiasis [9,10]. The mycological efﬁcacy on Day 28 in the present study was higher than 76% (shortterm assessment) and 70% (long-term assessment) in previous
Japanese studies. The difference in mycological efﬁcacy between
the current and previous studies may partly be due to the difference in the assessment time (Day 28 versus Days 5e15 or 30e60).

Table 4
Therapeutic outcome in the m-ITT population.
Assessment time point

Day 7
Day 14
Day 28

N

95
100
102

Therapeutic outcome
Effectiven (%)

Ineffectiven (%)

Indeterminaten (%)

31 (32.6)
52 (52.0)
74 (72.5)

61 (64.2)
44 (44.0)
25 (24.5)

3 (3.2)4 (4.0)3 (2.9)Efﬁcacy ratea(%)

95% CI (%)

33.7
54.2
74.7

24.2e44.3
43.7e64.4
65.0e82.9

m-ITT, modiﬁed intent-to-treat; CI, conﬁdence interval.
a
Efﬁcacy rate (%) ¼ (number of subjects considered effective/[number of evaluated subjects  number of subjects considered indeterminate])  100.

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H. Mikamo et al. / J Infect Chemother 21 (2015) 520e526

Table 5
Clinical efﬁcacy in the m-ITT population.
Assessment time point

Day 7
Day 14
Day 28

N

99
101
102

Clinical efﬁcacy
Cure
n (%)

Improvementn (%)

Ineffectiven (%)

Indeterminaten (%)

32 (32.3)
55 (54.5)
80 (78.4)

60 (60.6)
40 (39.6)
14 (13.7)

0
1 (1.0)4 (3.9)7 (7.1)5 (5.0)4 (3.9)Cure ratea

Cure or improvement rateb%

95% CI (%)%

95% CI (%)

34.8
57.3
81.6

25.1e45.4
46.8e67.3
72.5e88.7

100.0
99.0
95.9

96.1e100.0
94.3e100.0
89.9e98.9

m-ITT, modiﬁed intent-to-treat; CI ¼ conﬁdence interval.
aCure rate (%) ¼ (number of subjects considered cure/[number of evaluated subjects  number of subjects considered indeterminate])  100.
bCure or improvement rate (%) ¼ (number of subjects considered cure or improvement/[number of evaluated subjects  number of subjects considered
indeterminate])  100.

Table 6
Mycological efﬁcacy in the m-ITT population.
Assessment time point

Day 7
Day 14
Day 28

N

95
100
102

Mycological efﬁcacy
Eradicationn (%)

Persistencen (%)

Indeterminaten (%)

Eradication ratea(%)

95% CI (%)

90 (94.7)
88 (88.0)
85 (83.3)

4 (4.2)10 (10.0)
14 (13.7)

1 (1.1)2 (2.0)3 (2.9)

95.7
89.8
85.9

89.5e98.8
82.0e95.0
77.4e92.0

m-ITT, modiﬁed intent-to-treat; CI ¼ conﬁdence interval.
aEradication rate (%) ¼ (number of subjects considered eradication/[number of evaluated subjects  number of subjects considered indeterminate])  100.

Fig. 2. Changes in the percentages of subjects with clinical signs and symptoms. Percentage ¼ (number of subjects with clinical signs and symptoms/[N  NA])  100. NA, numberof subjects whose data were not available due to menstruation.

Similarly, in 2 global clinical studies of a single oral 150 mg dose of
ﬂuconazole, the clinical efﬁcacy rates (97 and 94%, respectively) at
the short-term follow-up visit (Day 7 and Days 5e16, respectively)
remained at a high level (87 and 84%, respectively) at the long-term
follow-up visit (Day 21 and Days 26e50, respectively), while themycological efﬁcacy rates were lower at the long-term follow-up
visit (76 and 59%, respectively) than those at the short-term followup visit (97 and 81%, respectively) [11,12]. This may reﬂect that theindigenous ﬂora of the vagina that was affected once by a single oral
dose of ﬂuconazole returned to normal after administration [5]. In
other words, mycological assessment at the long-term follow-up
visit detected Candida as normal vaginal ﬂora.
Mizuno et al. conducted 2 clinical studies of vaginal tablets[13,14]. They reported the cure rates and improvement rates at 3

weeks after the treatment were respectively 61.5% and 92.3% for 1day treatment with oxiconazole, 72.8% and 95.7% for 6-day treatment with oxiconazole, 63.3% and 90.8% for 1-day treatment withisoconazole, and 73.9% and 95.7% for 6-day treatment with clotrimazole. Mikamo et al. also reported the clinical efﬁcacy of clotrimazole was 58% on Days 30e60 [9,10]. Although the evaluation
methods and timing in these studies were different from those in
our study, the results of our study were generally consistent withthose of these studies.
A single oral 150 mg dose of ﬂuconazole is an easy-to-manage
dosing regimen and has many advantages. Research based on interviews with prescription doctors in the UK revealed that 27% of
patients complaint of pain and difﬁculties with insertion of vaginal
tablets and pessary, and 62% of prescription doctors also think there―２６７―

H. Mikamo et al. / J Infect Chemother 21 (2015) 520e526
Table 7
Treatment-related adverse events in the safety analysis set.
Preferred terma

Safety analysis set (N ¼ 157)
Treatment-related adverse eventn (%)

Palpitations
Abdominal distension
Diarrhea
NauseaPyrexia
Cystitis
Genital herpes
Hepatic enzyme increased
Genital hemorrhage
Urticariaa1 (0.6)
1 (0.6)3 (1.9)3 (1.9)1 (0.6)
1 (0.6)
1 (0.6)
1 (0.6)
1 (0.6)
1 (0.6)

Medical Dictionary for Regulatory Activities Terminology version 16.1.

is a problem with leakage of vaginal cream [6]. There are also some
reports stating easy-to-administer oral therapies are preferred to
topical vaginal therapies among patients [5,7]. In this study, vulvovaginal redness, irritation, tingling, itching, and pain were notreported as adverse events, suggesting that a single oral 150 mg
dose of ﬂuconazole had little adverse effect on the vulva and vagina
and the daily life of subjects compared with topical therapies, andthus provides the improved quality of life and satisfaction of patients besides resolving the difﬁculties with topical drug
administration.
Symptoms of vulvovaginal candidiasis often develop before
menstruation [15]. It is difﬁcult to apply topical vaginal therapies
before and during menstruation, when a sufﬁcient effect of treatment
cannot be expected because of leakage and reduction in drug contents
caused by menstrual bleeding. Single oral administration of ﬂuconazole can be used regardless of the menstrual status of patients.
It is known that 6-day topical vaginal therapies show problemsof early discontinuation of treatment for the reason of disappearance of symptoms and accidental dislodgement of inserted vaginal
tablets that are not in place, leading to reduce compliance. With asingle oral dose of ﬂuconazole, there is no concern about suchproblems.
A single oral 150 mg dose of ﬂuconazole can be prescribed atclinics of internal medicine as well as obstetrics and gynecology,
raising concern that some clinicians may make a diagnosis of vulvovaginal candidiasis based on the patient's complaints without
conﬁrming the vulvovaginal ﬁndings, and prescribe the drug,
resulting in delayed proper treatment of similar diseases such asvaginal trichomoniasis and bacterial vaginosis. To prevent inappropriate use, clinicians should make a deﬁnite diagnosis of thedisease giving the utmost care before prescribing the drug.
In this study, 4 subjects had complications of genital infection
caused by other pathogens than Candida (1 with Trichomonas
vulvovaginitis, 3 with chlamydial cervicitis) at baseline. These
complications were found in the microbiological tests conducted atbaseline after a single oral 150 mg dose of ﬂuconazole on Day 1. A
subject with trichomonas vulvovaginitis received tinidazole and 3
subjects with chlamydial cervicitis received azithromycin. The
investigator considered that it was possible to assess the efﬁcacy of
ﬂuconazole in these 4 subjects. For these 4 subjects, the clinicalefﬁcacy was assessed as either “cure” or “improvement,” and themycological efﬁcacy was assessed as either “eradication” or“persistence.” For 3 of the 4 subjects, the therapeutic outcomes
were assessed as “ineffective.” These ﬁndings suggest that a single
oral 150 mg dose of ﬂuconazole in combination with other antimicrobial agents is effective for the treatment of vulvovaginal
candidiasis complicated with genital infection caused by otherpathogens than Candida.

525

A subject had complications of diabetes mellitus in this study.
Although the subject was considered to have had them before
enrollment, the investigator considered that it was possible toassess the efﬁcacy of ﬂuconazole in the subject because the duration of diabetes mellitus was short, and the subject was considered
not to be immunocompromised. The therapeutic outcome of thesubject was assessed as “effective.” There were few studies
reporting the efﬁcacy of a single oral dose of ﬂuconazole in subjects
complicated with diabetes mellitus [16,17]. As diabetes mellitus is arisk factor for vulvovaginal candidiasis, the efﬁcacy in these subjects has to be studied further.
In this study, the most commonly identiﬁed pathogen was
C. albicans (100/104 strains), and all isolates were highly susceptible
to ﬂuconazole judging from the ﬂuconazole breakpoints for
C. albicans in the criteria of Clinical and Laboratory Standards
Institute (CLSI) (susceptible  2 mg/ml, susceptible-dose
dependent ¼ 4 mg/ml, resistant  8 mg/ml) [18], and the criteriaof the European Committee on Antimicrobial Susceptibility Testing(EUCAST) (susceptible  2 mg/ml, resistant  4 mg/ml) [19]. In thisstudy, C. glabrata was identiﬁed in a subject whose therapeutic
outcome was assessed as “effective” at all assessment time points.
This C. glabrata isolate (MIC of ﬂuconazole was 8 mg/ml) was notclassiﬁed into the category of resistant based on the ﬂuconazole
breakpoints for C. glabrata (susceptible-dose dependent 32 mg/ml,
resistant  64 mg/ml [CLSI criteria]; susceptible  0.002 mg/ml,
resistant > 32 mg/ml [EUCAST criteria]). C. glabrata, the second mostcommon pathogen of vulvovaginal candidiasis following C. albicans,
is however reported to be resistant to ﬂuconazole [20,21]. If ﬂuconazole is not effective, other topical drugs should be used instead.
The most common treatment-related adverse events occurring
in 1% or more of the subjects were only gastrointestinal-related
events (diarrhea and nausea), and there were no signiﬁcantsafety issues in this study. However, ﬂuconazole, even given as asingle oral dose, has more potential to produce side effects such as
gastrointestinal disorders and other systemic events comparedwith topical vaginal therapies, and subjects treated with ﬂuconazole should be monitored carefully. Since ﬂuconazole inhibits CYP
2C9 and 3A4, caution should be exercised when a single oral dose of
ﬂuconazole is applied in combination with other drugs to prevent
potential drug interactions.
There are 3 limitations to this study that should be consideredwhen these ﬁndings are interpreted. First, this was not a controlled
study. Second, there were not sufﬁcient other pathogens thanC. albicans to assess their efﬁcacy. Although further investigation,such as a large comparative study, accordingly needs to be performed to conﬁrm our study results, the methods of this study with
sufﬁcient clinical efﬁcacy will be useful for the treatment of patients with vulvovaginal candidiasis in Japan. Third, this was aclinical study led by the sponsor and the possibility of conﬂicts ofinterest between the authors and the sponsor could not be ruledout.
In conclusion, the results of this study demonstrated that asingle oral 150 mg dose of ﬂuconazole was effective for the treatment of vulvovaginal candidiasis in Japanese subjects, and no signiﬁcant safety issues were reported. A single oral 150 mg dose of
ﬂuconazole is recommended for the treatment of vulvovaginal
candidiasis in global guidelines. Therefore, a single oral 150 mg
dose of ﬂuconazole will be positioned as one of the ﬁrst-line
treatment options for vulvovaginal candidiasis in Japan.

Conﬂict of interest
H. Mikamo has received a consultant fee and a fee for participation in the Committee from Pﬁzer Japan Inc. M. Matsumizu, Y.

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526

H. Mikamo et al. / J Infect Chemother 21 (2015) 520e526

Nakazuru, A. Okayama, and M. Nagashima are employees of Pﬁzer
Japan Inc.
Acknowledgments
We wish to thank the investigators who have contributed to thisclinical study. This study was sponsored by Pﬁzer Japan Inc.
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[5] Pitsouni E, Iavazzo C, Falagas ME. Itraconazole vs ﬂuconazole for the treatmentof uncomplicated acute vaginal and vulvovaginal candidiasis in nonpregnant
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[6] Tooley P. Preferences in the treatment of vaginal candidosis. Practitioner
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[7] A comparison of single-dose oral ﬂuconazole with 3-day intravaginal clotrimazole in the treatment of vaginal candidiasis. Report of an international
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[10] Mikamo H, Kawazoe K, Sato Y, Hayasaki Y, Tamaya T. Comparative study on
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[11] De Punzio C, Garutti P, Mollica G, Nappi C, Piccoli R, Genazzani AR. Fluconazole
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[12] Rees T, Phillips R. Multicenter comparison of one-day oral therapy with ﬂuconazole or itraconazole in vaginal candidiasis. Int J Gynecol Obstet 1992;37:33e8.
[13] Mizuno S, Hashimoto M, Shimoya Y, Sagae S, Yajima A, Hamazaki Y, et al.
A double-blind comparative study of the efﬁcacy of one-day administration ofoxiconazole tablets for the treatment of vulvovaginal candidiasis. World
Obstet Gynecol (Sanfujinkanosekai) 1989;41:633e45 [in Japanese].
[14] Mizuno S, Hashimoto M, Shimoya Y, Sagae S, Yajima A, Hamazaki Y, et al.
A double-blind comparative study of the efﬁcacy of six-day administration ofoxiconazole tablets for the treatment of vulvovaginal candidiasis. World
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[15] Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK.
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[16] Gunther LS, Martins HP, Gimenes F, Abreu AL, Consolaro ME, Svidzinski TI.
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[17] Goswami D, Goswami R, Banerjee U, Dadhwal V, Miglani S, Lattif AA, et al.
Pattern of Candida species isolated from patients with diabetes mellitus andvulvovaginal candidiasis and their response to single dose oral ﬂuconazole
therapy. J Infect 2006;52:111e7.
[18] Clinical and Laboratory Standards Institute. Reference method for broth
dilution antifungal susceptibility testing of yeasts. Fourth Inf Suppl 2012;32:
1e28.
[19] European Committee on Antimicrobial Susceptibility Testing. Antifungal
agents breakpoint tables for interpretation of MICs. http://www.eucast.org/
ﬁleadmin/src/media/PDFs/EUCAST_ﬁles/AFST/Antifungal_breakpoints_v_6.1.
pdf; 2013.
[20] Kobayashi T, Muratani T. Drug susceptibilities of yeast-like fungi isolated fromvaginal discharge (proceedings). Jpn J Sex Transm Infect 2012;23:64 [inJapanese].
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梅毒

愛知医科大学病院感染症科
愛知医科大学病院感染制御部

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山岸

由佳

三鴨

廣繁

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Human leukocyte antigen class II DRB1*1302 allele
protects against cervical cancer: At which step ofmultistage carcinogenesis?
Koji Matsumoto,1 Hiroo Maeda,2 Akinori Oki,1 Naoyoshi Takatsuka,3 Toshiharu Yasugi,4 Reiko Furuta,5Ranko Hirata,2 Akira Mitsuhashi,6 Kei Kawana,4 Takuma Fujii,7 Takashi Iwata,7 Yasuo Hirai,8Masatoshi Yokoyama,9 Nobuo Yaegashi,10 Yoh Watanabe,11 Yutaka Nagai,12 Hiroyuki Yoshikawa1 and for theJapan HPV and Cervical Cancer (JHACC) Study Group1

Department of Obstetrics and Gynecology, University of Tsukuba, Tsukuba; 2Department of Transfusion Medicine and Cell Therapy, Saitama Medical
Center, Saitama Medical University, Saitama; 3Department of Health Economics, Gifu University Graduate School of Medicine, Gifu; 4Department of
Obstetrics and Gynecology, University of Tokyo, Tokyo; 5Department of Pathology, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo;
6
Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba; 7Department of Obstetrics and Gynecology, Keio University
School of Medicine, Tokyo; 8Departments of Gynecology and Cytopathology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo;
9
Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, Saga; 10Department of Obstetrics and Gynecology, Tohoku University
School of Medicine, Sendai; 11Department of Obstetrics and Gynecology, Kinki University School of Medicine, Osaka; 12Department of Obstetrics andGynecology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

Key words
cervical cancer, cervical intraepithelial neoplasia, humanleukocyte antigen, human papillomavirus, low-grade
squamous intraepithelial lesion
Correspondence
Koji Matsumoto, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba
305-8575, Japan.
Tel: +81 29 853 3073; Fax: +81 29 853 3072;
E-mail: matsumok@mui.biglobe.ne.jp
Funding Information
This work was supported by Ministry of Education,
Science, Sports and Culture of Japan (grant nos. 12218102
and 25462585).
Received May 7, 2015; Revised July 22, 2015; Accepted
July 29, 2015
Cancer Sci 106 (2015) 1448–1454

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association withcervical cancer included 1253 Japanese women: normal cytology (NL, n = 341),
cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2⁄ 3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher’s exact test or the v2-test. The Bonferroni
adjustment corrected for multiple comparisons. Among the study subjects, 454
women with low-grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3–4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLAclass II DRB1*1302 allele frequency was similar between women with NL (11.7%)
and CIN1 (11.9%), but signiﬁcantly decreased to 5.2% for CIN2 ⁄ 3 and 5.8% for
ICC (P = 0.0003). Correction for multiple testing did not change this ﬁnding. In
women with low-grade squamous intraepithelial lesion cytology, the cumulativerisk of CIN3 diagnosed within 10 years was signiﬁcantly reduced among
DRB1*1302-positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the
DRB1*1302 allele against progression from CIN1 to CIN2 ⁄ 3.

doi: 10.1111/cas.12760

C

ervical cancer is the third most common cancer in women
worldwide, with approximately 530 000 women developing the disease every year. (1) Virtually all cases of cervicalcancer are caused by persistent infection with carcinogenic
HPVs, speciﬁcally, HPV types 16, 18, 31, 33, 35, 39, 45, 51,
52, 56, 58, 59, and 68.(2) However, although carcinogenic
HPV infection is common among young women of reproductive age, only a small subset of infected women develop cervical cancer, implying the involvement of additional risk
factors.(3) Environmental factors such as smoking, parity, andOC use have been suggested as relevant to cervical carcinogenesis in numerous case–control studies.(4)Genetic linkage with cervical cancer has also been
implied.(5) There is a priori biological plausibility supporting
HLA involvement in the development of HPV-related cancer.(6) HLA molecules are responsible for the presentation ofviral antigens to the host immune system, thus playing a central role in immune recognition and subsequent clearance ofvirus-infected cells. Therefore, genetic variations in HLA
regions may inﬂuence the efﬁciency of HPV antigen presentation and condition the immune responsiveness to HPV infections.(7)It is known that rabbit MHC class II genes are associatedwith malignant conversion of cottontail rabbit papillomavirusinduced tumors.(8) To date, epidemiological studies have suggested that HLA class II DRB1*1501 and DQB1*03 may be
associated with an increased risk of cervical cancer, whereas
DRB1*13 may protect against cervical carcinogenesis.(7)However, results from these studies have not been entirely
consistent. In addition, very little is known about the step atwhich HLA class II alleles may play a central role in multistep cervical cancer pathogenesis from HPV infection to cancer development because most HLA data on cervical cancer
are based on case–control studies comparing HLA class II
allele frequencies between cancer patients and healthy controls. There are few prospective studies addressing HLA

Cancer Sci | October 2015 | vol. 106 | no. 10 | 1448–1454© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs License, which permits use and distribution
in any medium, provided the original work is properly cited, the use is noncommercial and no modiﬁcations or adaptations are made.

―２７７―

Original Article
Matsumoto et al.

www.wileyonlinelibrary.com/journal/cas

association with the development of cervical cancer andprecancer.
In the present study, we analyzed HLA class II data from1253 women with normal cytology, cervical precursor lesions,or invasive cervical cancer by using a cross-sectional study
design. To reduce the risk of chance ﬁndings, putative links
between cervical cancer and speciﬁc HLA class II alleles werealso examined in a prospective cohort study of 454 womenwith low-grade cervical lesions. By using cross-sectional andprospective study designs, we investigated the protective effectof the HLA class II DRB1*1302 allele against progression tocervical precancer.
Materials and Methods
Study design. Our study subjects consisted of 1253 Japanesewomen (341 with NL, 505 with CIN1, 86 with CIN2, 10 with
CIN3, and 311 with ICC) who visited 10 hospitals for cervicalcancer screening, treatment of cervical diseases, or other reasons between April 1998 and March 2011. These women were
included in the cross-sectional HLA class II analysis. Non-Japanese women were excluded from the present study based on
self-reported ethnicity. At enrolment, blood samples were collected for HLA genotyping. Histological specimens were
stained with H&E and reviewed by two pathologists (R. F.
[author] and Tomoyuki Kitagawa [Department of Pathology,
Cancer Institute Hospital, Japanese Foundation of Cancer
Research, Tokyo, Japan]).
Of the study subjects included in the cross-sectional analysis,
591 women with CIN1 or CIN2 were followed at 3–4-monthintervals and received cytology and colposcopic examinations
at each visit. Of these, 454 women with evident LSIL cytology
at baseline were included in the prospective analysis. This
prospective cohort study has been described elsewhere.(9)Brieﬂy, baseline cytology was reviewed by two cytopathologists(Y. H. [author] and Masafumi Tsuzuku [Department of
Cytopathology, Cancer Institute Hospital, Japanese Foundationof Cancer Research]). At the time of study entry, cervical HPV
DNA was determined by PCR-based methodology. In addition,
information about smoking, contraceptive and reproductive
history, and sexual behavior was also obtained from a selfadministered questionnaire. During follow-up, a cervical biopsy
was carried out only when Pap smears and colposcopic ﬁndings
were suggestive of progression to CIN3 or worse.
For women whose condition was regarded as progressing,based on cytology and histology examinations carried out inthe participating hospitals, the two cytopathologists and two
pathologists reviewed all cytological and histological specimens collected for diagnosis of disease progression. In theprospective study, the primary endpoint was histological CIN3
lesions or worse diagnosed after rigorous pathological review.
Occasionally a few difﬁcult cases were adjudicated by joint
review with consideration of cytology as well as histology. We
used the primary endpoint of CIN3 or worse because CIN3 isa more certain, rigorous histological diagnosis of precancer
than CIN2.(3)Women entered the study voluntarily only after giving theirsigned informed consent. The study protocol was approved by
the ethical and research review boards of the participating
institutions.
Genotyping of HLA class II. Blood leukocytes were used for
HLA genotyping. Total cellular DNA was extracted from these
specimens and ampliﬁed by PCR using locus-speciﬁc primers.
All samples were initially typed at the HLA-DRB1 and DQB1
Cancer Sci | October 2015 | vol. 106 | no. 10 | 1449

loci using a commercially available reverse sequence-speciﬁcoligonucleotide probe typing kit (Dynal RELI SSO; Dynal
Biotech, Oslo, Norway). For subtyping, group-speciﬁc ampliﬁcations were carried out as previously described.(10) DRB1 andDQB1 alleles were identiﬁed by SSCP and RFLP using the
PCR products. Laboratory staff who carried out the HLA class
II typing were blinded to the clinical data collected from thestudy subjects.
Genotyping of HPV. We detected HPV DNA in cervical samples by PCR-based methodology as described previously.(11) In
brief, HPV DNA was ampliﬁed by PCR using consensus primers (L1C1 ⁄ L1C2 + L1C2M) for the HPV L1 region. The
HPV types were identiﬁed by RFLP that has been shown to
identify at least 26 types of genital HPVs.(12) Laboratory staff
who carried out HPV genotyping were blinded to the clinicaldata collected from the study subjects.
Statistical analysis. In the cross-sectional study, HLA class II
allele frequencies were compared by Fisher’s exact test or thev2-test. When an expected cell value in the 2 9 2 tables was<5, Fisher’s exact test was used. We also analyzed the datausing the Bonferroni adjustment, a conventional method ofcorrecting for multiple comparisons.
In the prospective cohort study, time to event was measured
from the date of the index visit (i.e., the ﬁrst instance of anabnormal cytology result) to the date of the visit at which
cytological transition to CIN3 was ﬁrst detected. Women
whose lesions did not progress to CIN3 were censored at theirlast recorded return visit dates. The cumulative probability of
progression to CIN3 was estimated using the Kaplan–Meiermethod and compared with a log–rank test, and the Cox
regression model was used for statistical adjustments. Patientage, CIN grade, at the time of entry, HPV risk category(HPV16 ⁄ 18 ⁄ 31 ⁄ 33 ⁄ 35 ⁄ 45 ⁄ 52 ⁄ 58, other carcinogenic types, or
carcinogenic HPV negative), smoking status, parity, OC use,
number of lifetime sexual partners, and age at ﬁrst sexualintercourse were included in the multivariate model for adjustments. As the results did not differ among the 10 hospitals, thestudy sites were not included in the multivariate models.
All analyses were carried out using the STATA 9 (StataCorp
LP, College Station, TX, USA) statistics package. Two-sided
P-values were calculated throughout and considered to be signiﬁcant at <0.05.
Results
Cross-sectional analysis. The distribution of HLA-DRB1 andHLA-DQB1 alleles in 1253 Japanese women with normal
cytology or cervical diseases is shown in Table 1. To examine
the step at which HLA class II alleles may contribute to cervical carcinogenesis, the HLA data were compared among fourgroups: NL (n = 341), CIN1 (n = 505), CIN2 ⁄ 3 (n = 96), andICC (n = 311).
We could not ﬁnd any association between HLA class II
alleles and development of CIN1, because HLA class II allele
frequencies were very similar between women with NL and
CIN1 (Table 1). DRB1*0901 frequency was signiﬁcantly
decreased among women with CIN2 or worse (CIN2+) compared with women with NL or CIN1 (<CIN2) (15.0% vs.
26.2%; P = 0.0003; Pc = 0.007). In addition, DRB1*1302 frequency was also signiﬁcantly lower among women with
CIN2 + (5.9% vs. 11.2%, P = 0.0003, Pc = 0.007). Although
the number of women with CIN2 ⁄ 3 was small (n = 96),
DRB1*0901 frequency was signiﬁcantly decreased in womenwith ICC compared with women with CIN2 ⁄ 3 (14.5% vs.
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.

―２７８―

Original Article
HLA class II alleles and risk of cervical cancer in Japan

www.wileyonlinelibrary.com/journal/cas

Table 1. Correlation between human leukocyte antigen class II carrier frequencies and cervical diseases in Japanese women (n = 1253) at thecommencement of the study
NL

DRB1*
0101
0401
0403
0405
0406
0407
0410
0701
0802
0803
0901
1001
1101
1201
1202
1301
1302
1401
1403
1405
1406
1501
1502
1602
DQB1*
0202
03
0301
0302
03032
0401
0402
0501
0502
05031
0601
0602
0603
0604

CIN2 ⁄ 3

CIN1

Relative risk of CIN2 orworse†ICC

n = 341%n = 505%n = 96%n = 311%

OR (95% CI)

P-value

30
9
25
91
17
5
16
4
28
45
90
3
18
22
9
2
40
33
12
11
10
46
76
5

9
3
7
27
5
1
5
1
8
13
26
1
5
6
3
1
12
10
4
3
3
13
22
1

57
5
27
107
25
6
32
3
44
92
136
10
26
22
13
5
60
36
18
18
16
84
115
7

11
1
5
21
5
1
6
1
9
18
27
2
5
4
3
1
12
7
4
4
3
17
23
1

8
3
8
18
4
0
4
2
9
16
27
1
6
4
1
3
5
9
4
7
3
18
25
2

8
3
8
19
4
0
4
2
9
17
28
1
6
4
1
3
5
9
4
7
3
19
26
2

33
12
18
68
10
1
18
5
24
48
45
5
14
17
4
1
18
22
10
14
11
48
91
1

11
4
6
22
3
0
6
2
8
15
14
2
5
5
1
0
6
7
3
5
4
15
29
0

0.98 (0.66–1.45)
2.27 (1.09–4.76)
1.04 (0.64–1.69)
0.87 (0.66–1.17)
0.68 (0.37–1.26)
0.19 (0.02–1.45)
0.95 (0.57–1.60)
2.10 (0.73–6.02)
0.95 (0.62–1.49)
0.97 (0.70–1.33)
0.59 (0.44–0.79)
0.96 (0.36–2.54)
0.94 (0.54–1.62)
0.99 (0.58–1.69)
0.47 (0.18–1.24)
1.19 (0.35–4.09)
0.44 (0.28–0.71)
0.92 (0.60–1.44)
0.97 (0.51–1.85)
1.52 (0.86–2.72)
1.12 (0.58–2.18)
1.07 (0.77–1.47)
1.37 (1.04–1.79)
0.52 (0.14–1.84)

0.91
0.03
0.87
0.37
0.21
0.12
0.85
0.17
0.81
0.83
0.0003§
0.93
0.83
0.98
0.15
0.75
0.0003§
0.74
0.92
0.15
0.73
0.70
0.02
0.41

2
203
77
60
96
89
29
33
24
26
110
42
2
39

1
60
23
18
28
26
9
10
7
8
32
12
1
11

2
282
94
86
138
105
55
66
24
41
189
80
5
59

0
56
19
17
27
21
11
13
5
8
37
16
1
12

1
58
21
15
31
18
10
9
6
8
40
17
3
5

1
60
22
16
32
19
10
9
6
8
42
18
3
5

3
176
56
50
86
66
29
37
14
29
134
46
1
16

1
57
18
16
28
21
9
12
5
9
43
15
0
5

2.09 (0.51–8.40)
1.01 (0.79–1.28)
0.92 (0.68–1.24)
0.91 (0.66–1.25)
1.06 (0.81–1.37)
0.87 (0.65–1.17)
0.96 (0.64–1.43)
0.96 (0.66–1.39)
0.86 (0.52–1.47)
1.16 (0.76–1.77)
1.37 (1.07–1.74)
1.09 (0.78–1.51)
1.19 (0.35–4.09)
0.41 (0.26–0.68)

0.28
0.96
0.59
0.57
0.69
0.35
0.85
0.84
0.58
0.48
0.01
0.62
0.78
0.0001§

Correction for
multiple comparison
Corrected P-value‡

0.72

0.007

0.007

0.48

0.24

0.001

†

Relative risks of cervical intraepithelial neoplasia grade 2 ⁄ 3 (CIN2 ⁄ 3) ⁄ invasive cervical cancer (ICC) were analyzed in comparison with <CIN2(normal cytology or CIN1, n = 846). ‡P-values were calculated by Bonferroni adjustment to correct for multiple comparison. §Bold letters indicate
statistical signiﬁcance. CI, conﬁdence interval; NL, normal cytology; OR, odds ratio.

28.1%; P = 0.003). DRB1*1302 frequency was similar
between women with ICC and CIN2 ⁄ 3 (5.8% vs. 5.2%;
P = 0.99).
DQB1*0604 frequency was also signiﬁcantly decreased
among women with CIN2+ compared to those with <CIN2(5.2% vs. 11.6%; P = 0.0001; Pc = 0.001).
In the cross-sectional analysis, we could not detect any signiﬁcant associations between other HLA class II alleles anddevelopment of CIN2 + (Table 1). The DRB1*0401,
DRB1*1502, and DQB1*0601 allele frequencies were signiﬁcantly associated with an increased risk of CIN2 + (P = 0.03,
P = 0.02, and P = 0.01, respectively), but these associations
lost signiﬁcance after correction for multiple comparison.

Although DRB1*1501 and DQB1*03 alleles have been suggested as relevant to an increased risk of cervical cancer inprevious HLA studies,(7) the frequencies of these alleles weresimilar between women with <CIN2 and CIN2 + (P = 0.99
and P = 0.95, respectively). Another analysis comparing HLA
allele frequencies between women with and without ICC did
not change the ﬁndings (data not shown).
Prospective analysis. The clinical outcomes of 454 womenwith LSIL cytology were monitored by cytologic and colposcopic testing at intervals of 3–4 months. Table 2 shows thecharacteristics of the study subjects included in the prospective
analysis. At baseline, 407 women had biopsy-proven CIN1 and47 had biopsy results of CIN2. The mean age of the study sub-© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.

Cancer Sci | October 2015 | vol. 106 | no. 10 | 1450

―２７９―

Original Article
Matsumoto et al.

www.wileyonlinelibrary.com/journal/cas
Table 2. Characteristics of Japanese women with low-grade
squamous intraepithelial lesion cytology (n = 454) included inprospective analysis
All study
subjects(n = 454),n (%)

DRB1*1302 status
Positive(n = 47),n (%)

Negative(n = 407),n (%)

P-value

Age, years
18–29
30–39
40+

86 (18.9)
217 (47.8)
151 (33.3)

7 (14.9)
18 (38.3)
22 (46.8)

79 (19.4)
199 (48.9)
129 (31.7)

0.13

Histology at entry
CIN grade 1
CIN grade 2389 (85.7)
65 (14.3)

44 (94)3 (6)345 (85)
62 (15)0.10

201 (44.3)

19 (40.4)

182 (44.7)

0.49

110 (24.2)
67 (14.8)

17 (36.2)
4 (8.5)93 (22.9)
63 (15.5)

32 (7.0)38 (8.4)

5 (10.6)
2 (4.2)27 (6.6)
36 (8.8)151 (33.3)
243 (53.5)
60 (13.2)

15 (31.9)
28 (59.6)
4 (8.5)136 (30.4)
215 (52.8)
56 (13.8)

0.50

Use of oral contraceptives
Yes
39 (8.6)
No378 (90.6)
Unknown
37 (8.1)

3 (6.7)42 (93.3)
4 (8.5)36 (8.8)336 (82.6)
33 (8.1)

0.49

Smoking
Never smokers
Smokers
Current smokers
Former smokers
Unknown

209 (46.0)
210 (46.3)
151 (33.3)
59 (13.0)
35 (7.8)

15 (31.9)30 (63.8)
24 (51.1)
6 (12.8)
2 (4.3)185 (45.5)
189 (46.4)
136 (33.4)
53 (14.2)
33 (8.1)

0.89

Number of lifetime sexual partners
1
68 (15.0)
2–3
115 (25.3)
4235 (51.8)
Unknown
36 (7.9)

6 (12.8)
13 (27.7)
26 (55.3)
2 (4.3)62 (15.2)
102 (25.1)
209 (51.4)
34 (8.4)

0.84

Age at ﬁrst sexual intercourse, years≤20
150 (33.0)
21–23
176 (38.8)≥24
93 (20.5)
Unknown
35 (7.7)

16 (34.0)
17 (36.2)
12 (25.5)
2 (4.3)134 (32.9)
159 (39.1)
81 (19.9)
33 (8.1)

0.72

HPV genotypes
HPV16, 18, 31, 33,
35, 45, 52, 58
HPV39, 51, 56, 59, 68
Low-risk types
or negative
Undetermined
Multiple infection
Parity0
1–2
3+

CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.

jects was 35.9 years (range, 19–54 years). In the current study,
we updated the previous cohort data and extended the meanfollow-up period from 39.0 months (range, 6.8–84.9 months)
to 62.7 months (range, 6.8–155.9 months). By updating thedata, the number of women diagnosed as progressing to CIN3
over the period of follow-up increased from 39 to 61.
Unlike the cross-sectional analysis results, DRB1*0901 was
not associated with progression to CIN3 in the prospective
Cancer Sci | October 2015 | vol. 106 | no. 10 | 1451

analysis (P = 0.88; Fig. 1a). Adjustment for age, CIN grade at
the time of entry, HPV risk category, parity, smoking status,
OC use, number of lifetime sexual partners, and age at ﬁrst
sexual intercourse did not change this ﬁnding (P = 0.71;
Table 3).
The risk of progression to CIN3 was signiﬁcantly reduced
among DRB1*1302-positive women (P = 0.03, log–rank test;
Fig. 1b), which was consistent with the cross-sectional analysis
results. This protective effect of DRB1*1302 against progression to CIN3 remained statistically signiﬁcant, even after
adjustment for possible risk factors of cervical cancer (adjusted
P = 0.04; Table 3). Distributions of baseline characteristics
among the DRB1*1302-positive and DRB1*1302-negative
women are presented in Table 2. Because of the poor reproducibility of cervical histologic interpretations,(13,14) some
CIN3 lesions may have been classiﬁed incorrectly as CIN2 atbaseline. Therefore, we also analyzed the follow-up data for
CIN1 and CIN2 separately. In women with CIN1 histology(n = 407), the cumulative risk of CIN3 diagnosed within
10 years was lower among DRB1*1302-positive women (3.5%
vs. 17.6%; P = 0.09). In women with CIN2 histology(n = 47), progression to CIN3 did not occur in DRB1*1302positive women (cumulative probability of histological CIN3
diagnosis within 10 years, 0.0% vs. 48.9%; P = 0.28).
Although these associations did not reach statistical signiﬁcance due to limitations imposed by the small sample size,
similar patterns were observed in separate analyses for CIN1
and CIN2.
We analyzed the protective effect of DRB1*1302 allele inrelation to HPV type-speciﬁc risk category. Among
DRB1*1302-positive women, only one case positive for
HPV33 progressed to CIN3. Therefore, in women positive for
HPV16, 18, 31, 33, 35, 45, 52, or 58, the cumulative risk of
CIN3 diagnosed within 10 years was 5.9% for those who were
DRB1*1302-positive and 39.6% for those who were
DRB1*1302-negative (P = 0.04, log–rank test). In women positive for HPV39, 51, 56, 59, or 68, the CIN3 risk within
10 years was 0.0% for those who were DRB1*1302-positive
and 9.6% for those who were DRB1*1302-negative (P = 0.29,
log–rank test). In women negative for high-risk HPVs, theCIN3 risk was 0.0% for DRB1*1302-positives and 1.9% for
DRB1*1302-negatives (P = 0.78).
The DQB1*0604 allele was closely linked to the
DRB1*1302 allele, indicating a strong correlation (r2 = 0.96).
As the DRB1*1302 and DQB1*0604 alleles were in linkage
disequilibrium, similar ﬁndings were observed for the
DRB1*1302 and DQB1*0604 alleles (Table 3). Therefore,
only DRB1*1302 data are shown in Fig. 1.
We could not ﬁnd any signiﬁcant association between other
HLA class II alleles and progression to CIN3. Data are only
shown on two representative HLA class II alleles (DRB1*1501
and DQB1*03) that have been reported to be a risk factor for
cervical cancer in previous HLA studies.(7) In the present
study, these alleles did not affect the risk of progression to
CIN3 within the next 10 years (Fig. 1c,d). Adjustment for possible cervical cancer risk factors did not change these ﬁndings(Table 3).
Discussion

By using cross-sectional and prospective study designs, we
indicated the protective effect of the DRB1*1302 allele against
progression to cervical cancer and precancer. The consistent
results obtained by two different analyses appear to provide© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.

―２８０―Original Article
HLA class II alleles and risk of cervical cancer in Japan

www.wileyonlinelibrary.com/journal/cas

(a)

(c)

(b)

(d)

Fig. 1. Cumulative risks of cervical intraepithelial neoplasia grade 3 within 10 years in relation to human leukocyte antigen class II polymorphisms. A Kaplan–Meier plot was used to estimate the cumulative 10-year probabilities of progression to cervical intraepithelial neoplasia grade
3 among women with low-grade squamous intraepithelial lesion cytology for selected human leukocyte antigen class II alleles: DRB1*0901 (a),DRB1*1302 (b), DRB1*1501 (c), and DQB1*03 alleles (d). P-values were calculated using the log–rank test.

stronger evidence for the protective effect of the DRB1*1302
allele. In addition, negative associations between the DRB1*13
alleles and cervical cancer have been consistently reported incase–control studies.(7) In a small prospective study of French
women with CIN1 (n = 86), a relationship between the
DRB1*13 alleles and cytological regression was observed.(15)
These observations also support the protective effect of the
DRB1*13 alleles. However, some studies have reported a protective effect of DRB1*1301,(16,17) and other studies have suggested that DRB1*1302 decreases the risk of cervicalcancer.(18,19) In the present study, we conﬁrmed only the protective effect of the DRB1*1302 allele because the
DRB1*1301 allele is rarely detected in Japanese populations.
Cervical cancer arises by way of several carcinogenic steps:
HPV acquisition, HPV persistence (development of low-grade
cervical precursor lesion), progression of a persisting infection
to cervical precancer, and invasion through the basement membrane of the epithelium.(3,20) In multistage cervical carcinogenesis, however, the step at which DRB1*13 alleles exert theirprotective effect is not fully understood. Two prospective studies of HPV infections have shown that DRB1*13 alleles do
not play a protective role against the acquisition and persistence of viral infections.(21,22) This is consistent with our ﬁnding that the DRB1*1302 frequency was similar between
women with NL (12%) and CIN1 (11%). In the present study,

the DRB1*1302 frequency signiﬁcantly decreased to 5.2% for
CIN2 ⁄ 3 and 5.8% for ICC. In the prospective analysis of
women with cytological LSIL and histological CIN1 ⁄ 2, thecumulative probability of CIN3 diagnosed within the next
10 years was signiﬁcantly low among DRB1*1302-positive
women. These observations suggest that the DRB1*1302 allele
may act protectively against progression from CIN1 to CIN2
⁄ 3. Several studies have reported the poor reproducibility of
CIN grading, even among well-trained observers.(13,14) In particular, CIN2 is an equivocal diagnosis of precancer (a heterologous borderline category between CIN1 and CIN3).(3)Therefore, it may be difﬁcult to strictly determine whether the
DRB1*1302 allele protects against progression from CIN1 to
CIN2, or from CIN2 to CIN3. The protective effect of the
DRB1*1302 allele against progression to cervical precancer
suggests that DRB1*13 alleles could contribute to theimmunological recognition of viral antigens such as the E7
protein, which is increasingly expressed during progression tocervical precancer.(23,24) However, very little is known about
the binding of DRB1*13 molecules to HPV-related antigens.
As the DRB1*1302 and DQB1*0604 alleles were in linkage
disequilibrium, very similar ﬁndings were observed for the
DRB1*1302 and DQB1*0604 alleles in both cross-sectional
and prospective analyses. Although the protective effect of
DRB1*13 alleles is the most consistent HLA ﬁnding in© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.

Cancer Sci | October 2015 | vol. 106 | no. 10 | 1452

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Original Article
Matsumoto et al.

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Table 3. Effect of selected human leukocyte antigen (HLA) class II alleles on progression to cervical intraepithelial neoplasia grade 3 inJapanese women with low-grade squamous intraepithelial lesion (n=454)
HLA class
II allelesnPersonmonths

EventsAdjusted analysis†

10-year progression
rate (95% CI)

Log–rank test
P-value

Hazard ratio (95% CI)

P-value

DRB1*0901
Positive
Negative

118
336

7274.920 715.1

15
43

22.5 (11.9–38.6)
21.4 (15.2–29.4)

0.88

1.15 (0.53–2.33)
1.00

0.71

DRB1*1302
Positive
Negative47
407

2916.725 073.3

157

3.2 (0.5–20.8)
23.7 (17.6–31.5)

0.03

0.13 (0.02–0.94)
1.00

0.04

DRB1*1501
Positive
Negative82372

5163.522 826.5

1345

21.3 (12.3–35.5)
21.8 (15.5–30.1)

0.43

1.12 (0.56–2.425
1.00

0.76

DQB1*03
Positive
Negative244
210

14 438.9
13 551.1

32
26

23.5 (15.3–35.0)
19.8 (13.1–29.2)

0.62

1.26 (0.72–2.20)
1.00

0.41

DQB1*0604
Positive
Negative

46408

2879.625 110.4

157

3.2 (0.5–20.8)
23.7 (17.6–31.4)

0.03

0.13 (0.02–0.95)
1.00

0.04

†
Cox regression model was used for statistical adjustments. Patient age, histological grade at the time of entry, human papillomavirus (HPV) risk
category (HPV16 ⁄ 18 ⁄ 31 ⁄ 33 ⁄ 35 ⁄ 45 ⁄ 52 ⁄ 58, other carcinogenic types, or carcinogenic HPV negative), smoking status, parity, use of oral contraceptives, number of lifetime sexual partners, and age at ﬁrst sexual intercourse were included in the multivariate model for adjustments. CI, conﬁdence interval.

published reports, the question is still open as to whether
DRB1*1302 alone, DQB1*0604 alone, or both are associatedwith reduced risk of cervical diseases, or whether other MHC
complex genes in linkage disequilibrium with these alleles are
more important. To evaluate the independent effect of the
DRB1*1302 and DQB1*0604 alleles, larger studies will be
required.
The cross-sectional analysis suggested that the DRB1*0901
allele may act protectively against cervical cancer pathogenesis. A meta-analysis also reported the protective effect of
DRB1*0901 against invasive cervical squamous cell carcinoma
in Caucasian populations.(25) Interestingly, this allele was not
associated with progression to CIN3 in the prospective analysis, suggesting that the DRB1*0901 allele could exert a protective effect on progression from CIN2 ⁄ 3 to ICC. The
DRB1*0901 allele frequency was signiﬁcantly lower in womenwith ICC than in those with CIN2 ⁄ 3. Alternatively or additionally, the discrepancy may be explained by the HPV type-speciﬁc effect of the DRB1*0901 allele. When the analysis was
conﬁned to HPV16-positive women with LSIL cytology, thecumulative probability of progression to CIN3 was lower
among
DRB1*0901-positive
women
compared
with
DRB1*0901-negative women (data not shown), but this effectwas not statistically signiﬁcant (P = 0.12) due to limitations
imposed by the small sample size.
We could not ﬁnd any signiﬁcant association between
DRB1*1501 or DQB1*03 and risk of developing CIN2 ⁄ 3 or
ICC. Effects of the DRB1*1501 and DQB1*03 alleles havenot been found in prospective cohort studies so far,(15,21,22)
and the results from case–control studies have not been
entirely consistent.(7,16–19,25–27) Although several groups havesuggested a signiﬁcant association of DRB1*1501 or
DQB1*0602 (or the corresponding haplotype DRB1*1501DQB1*0602) with HPV16-positive cervical cancer,(17,26,27) an

increased risk of progression to CIN3 was not observed for
either the DRB1*1501 or DQB1*0602 allele, even among
HPV16-positive women in the present study (data not shown).
The inconsistent results regarding the DRB1*1501 andDQB1*0602 alleles may be explained by two studies suggesting that cancer risks associated with these alleles may vary
according to HPV16 E6 variations.(27,28)
One may speculate that HLA class II DRB1*13 testing,alone or in combination with genotype-speciﬁc HPV testing,for women with low-grade cervical abnormalities might beuseful for identifying populations at decreased risk of diseaseprogression. Interestingly, the protective effect of the
DRB1*1302 allele appears to be non-speciﬁc to the HPV
genotype. However, HLA class II testing may not be recommended in clinical practice because only 10–20% of womenamong various ethnic populations have the DRB1*13 alleles.(7)In addition, DRB1*13 does not prevent all cervical cancer;
some women with cervical cancer are positive for DRB1*13.
The present study had several limitations. First, possible
misclassiﬁcation of CIN lesions may have affected the results.
Recently, p16INK4a immunohistochemistry has been shown toincrease the sensitivity and speciﬁcity of CIN2–3 detection in
cervical biopsies.(29) Although two pathologists reviewed all
histological specimens, the histological diagnosis of cervical
specimens was obtained by H&E examination alone. Second,
the present study may have missed several HLA associations
with cervical diseases due to limitations imposed by the small
sample size. Although this is the ﬁrst large-scale study on
HLA association with cervical cancer in Japan, larger studies
will be required to further evaluate the risk of cervical cancer
and precancer in relation to HLA polymorphism. Finally, thepresent study did not clarify the mechanism by which the
DRB1*1302 allele protects against cervical precancer. To
address this, immunological studies on the binding ofCancer Sci | October 2015 | vol. 106 | no. 10 | 1453

© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.

―２８２―

Original Article
HLA class II alleles and risk of cervical cancer in Japan

www.wileyonlinelibrary.com/journal/cas

DRB1*13 molecules to HPV-related antigens will be required.
Analyses of other genes in the MHC complex found in linkage
disequilibrium with the DRB1*13 alleles may also give insightto this protective effect.
In conclusion, our results conﬁrmed the protective effects of
DRB1*1302 through two different types of analysis in a single
study. Our data also suggested that the DRB1*1302 allele may
function protectively against progression from CIN1 to CIN2
⁄ 3. However, the mechanism underlying the protective effectof DRB1*1302 allele is not fully understood. To enhance ourbiological understanding of this effect, identiﬁcation of speciﬁcviral epitopes presented by the DRB1*1302 allele will beneeded.
Acknowledgments
The authors thank Dr. Tadahito Kanda (Center for Pathogen Genomics,
National Institute of Infectious Diseases, Tokyo, Japan) for his comments on the study design, Dr. Tomoyuki Kitagawa (Department of
Pathology, Cancer Institute Hospital, Japanese Foundation of Cancer
Research, Tokyo, Japan) for his histological review, Mr. Masafumi

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Disclosure Statement
The authors have no conﬂict of interest.

Abbreviations
CIN1–3
HLA
ICC
HPV
LSIL
NL
OC
Pc

cervical intraepithelial neoplasia grade 1–3
human leukocyte antigen
invasive cervical cancer
human papillomavirus
low-grade squamous intraepithelial lesion
normal cytology
oral contraceptive
P corrected by the Bonferroni method

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value of cervical cancer screening compared to HPV DNA. Gynecol Oncol
2011; 120: 89–93.
25 Yang YC, Chang TY, Lee YJ et al. HLA-DRB1 alleles and cervical squamous cell carcinoma: experimental study and meta-analysis. Hum Immunol
2006; 67: 331–40.
26 Apple RJ, Erlich HA, Klitz W et al. HLA DR-DQ associations with cervicalcarcinoma show papillomavirus-type speciﬁcity. Nat Genet 1994; 6: 157–62.
27 Cuzick J, Terry G, Ho L et al. Association between high-risk HPV types,
HLA DRB1* and DQB1* alleles and cervical cancer in British women. Br J
Cancer 2000; 82: 1348–55.
28 Matsumoto K, Yasugi T, Nakagawa S et al. Human papillomavirus type 16
E6 variants and HLA class II alleles among Japanese women with cervicalcancer. Int J Cancer 2003; 106: 919–22.
29 Darragh TM, Colgan TJ, Cox JT et al. Members of LAST Project WorkGroups. The lower anogenital squamous terminology standardization Projectfor HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society
for Colposcopy and Cervical Pathology. Arch Pathol Lab Med 2012; 136:
1266–97.

© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd
on behalf of Japanese Cancer Association.

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Cancer Sci | October 2015 | vol. 106 | no. 10 | 1454

Seiki et al. BMC Cancer (2015) 15:230
DOI 10.1186/s12885-015-1141-0

RESEARCH ARTICLE

Open Access

HPV-16 impairs the subcellular distribution andlevels of expression of protein phosphatase 1γ in
cervical malignancy
Takayuki Seiki1, Kazunori Nagasaka1*, Christian Kranjec2, Kei Kawana1, Daichi Maeda3, Hiroe Nakamura1,
Ayumi Taguchi1, Yoko Matsumoto1, Takahide Arimoto1, Osamu Wada-Hiraike1, Katsutoshi Oda1,
Shunsuke Nakagawa4, Tetsu Yano5, Masashi Fukayama3, Lawrence Banks2, Yutaka Osuga1 and Tomoyuki Fujii1

Abstract
Background: The high risk Human Papillomavirus (HPV) E6 oncoproteins play an essential role in the developmentof cervical malignancy. Important cellular targets of E6 include p53 and the PDZ domain containing substrates suchas hScrib and Dlg. We recently showed that hScrib activity was mediated in part through recruitment of protein
phosphatase 1γ (PP1γ).
Methods: Expression patterns of hScrib and PP1γ were assessed by immunohistochemistry of HPV-16 positive
cervical intraepithelial neoplasm (CIN), classified as CIN1 (n = 4), CIN2 (n = 8), CIN3 (n = 8), cervical carcinoma tissues(n = 11), and HPV-negative cervical tissues (n = 8), as well as by subfractionation assay of the HPV-16 positive cervicalcancer cell lines, CaSki and SiHa. To explore the effects of the HPV-16 oncoproteins, we have performed siRNAknockdown of E6/E7 expression, and monitored the effects on the expression patterns of hScrib and PP1γ.
Results: We show that PP1γ levels in HPV-16 positive tumour cells are reduced in an E6/E7 dependent manner.
Residual PP1γ in these cells is found mostly in the cytoplasm as opposed to the nucleus where it is predominantly
found in normal cells. We have found a striking concordance with redistribution in the pattern of expression (9/11;
81.8%) and loss of PP1γ expression in HPV-16 positive cervical tumours (2/11; 18.2%). Furthermore, this loss of PP1γ
expression and redistribution in the pattern of expression occurs progressively as the lesions develop (8/8; 100%).
Conclusion: Together, these results suggest that PP1γ may be a novel target of the HPV-16 oncoproteins andindicate that it might be a potential novel biomarker for HPV-16 induced malignancy.
Keywords: Cervical cancer, Immunohistochemistry, hScrib, Protein phosphatase 1, Proteasome degradation, Human
papillomavirus 16

Background
Human Papillomaviruses (HPVs) are the aetiologicalagents of cervical cancer [1]. This is caused by infection
with the high risk subset of HPV types, of which HPV16 is the most important, being responsible for over 60%
of global cervical cancer cases [2]. Cancer-causing HPVs
encode two oncoproteins, E6 and E7, whose continued expression and activity is essential for maintaining the malignant phenotype, many years after the initial immortalising* Correspondence: nagasakak-tky@umin.ac.jp
1
Department of Obstetrics and Gynecology, Faculty of Medicine, The
University of Tokyo, Tokyo 113-8655, Japan
Full list of author information is available at the end of the article

events [3,4]. Both viral oncoproteins function by perturbing the normal activity of a variety of different cellular
control mechanisms. HPV E7 promotes cell cycle progression, in part through its association with members of thepocket protein family of tumour suppressors [5], whilst
HPV E6 counteracts the pro-apoptotic effects of E7
through targeting the p53 tumour suppressor [6]. In bothcases, the viral oncoproteins make efficient use of the cellular ubiquitin-proteasome machinery, with E7 targeting
pRb through the cullin 2 ubiquitin ligase complex [7],whilst E6 uses the E6AP ubiquitin ligase to target p53 [8].
The effects of E6 and E7 are therefore cooperative, andthis is reflected both in tissue culture systems, where they

© 2015 Seiki et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.

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cooperate in the immortalisation of primary keratinocytes[9-11], and in animal models of tumourigenesis, where
they cooperate in the induction of tumours in the skinand cervix [12,13].
Whilst targeting the pRb and p53 pathways is obviously very important for cervical tumourigenesis, it isalso clear that E6 and E7 have a large number of otheractivities, many of which are also important for tumour
development. In the case of high risk HPV E6 oncoproteins, an intriguing class of targets that appear to be important for HPV E6 induced malignancy are the PDZ(PSD/Dlg/ZO) domain containing substrates [14,15].
These are bound by E6 via a short stretch of amino acids
within the extreme carboxy terminal region of the E6
oncoprotein. Most importantly, this PDZ binding motif(PBM) is only found in the high risk HPV E6 oncoproteins and is absent from the benign HPV E6 proteins[16,17]. Through this PBM, E6 can interact with a large
number of cellular PDZ domain containing proteins,
many of which are subject to E6-induced proteasomal
degradation and E6-induced redistribution [16,18-21].
One of the most important of these targets is the cellulartumour suppressor hScrib. In Drosophila Scrib was originally identified as a potential tumour suppressor [22],and more recent studies in mammalian tissues also indicate tumour suppressive potential for hScrib. Loss of
Scrib cooperates with c-Myc in the development of
mammary carcinogenesis and Scrib also downregulates
ERK signaling, with hScrib deregulation correlating withpoor cancer prognosis [23-27]. In cervical tumourigenesis, hScrib patterns of expression are also perturbed aslesions develop, with hScrib being completely absent inmany late stage tumours [28]. We recently found that
hScrib could interact with PP1γ [29] a protein phosphatase that plays a critical role in controlling chromatinorganization and also has an important role in the DNA
damage response pathway [30,31] This suggested that
PP1γ expression patterns in cervical tumourigenesis
might likewise be perturbed. Therefore we initiated aseries of studies to investigate the pattern of PP1γ expression in HPV16 positive cervical tumours and derived
cell lines. We show that PP1γ is indeed subject to a
striking alteration in both its levels of expression and localisation, both as lesions develop, and in the tumour
derived cell lines. However this altered pattern of expression is independent of hScrib, is due directly to E6/
E7 expression, and highlights PP1γ as potential novel
biomarker of HPV induced neoplasia.

Methods
Cell lines and culture

HPV positive cervical cancer cell lines, CaSki, SiHa and
HeLa plus HPV negative C33A (cervical cancer derived)and HaCaT (human keratinocytes) cells were cultured in

Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum at 37°C in a humidified incubator with 5% CO2 [32]. The effect ofproteasome inhibitor was determined 24 hours posttransfection after 3 hours of treatment with 10 μM
MG132 (Calbiochem).
For plasmid transfection, 293 cells were transfectedusing TransIT-293 transfection reagent (Mirus Bio) and
HaCaT cells were transfected using Lipofectamine 2000
(Invitrogen), according to the manufacturer’s instructions, with pcDNA-HPV-16 E6. A plasmid expressing βgalactosidase was included in each transfection and
pcDNA was used to equalize the input DNA.
Antibodies

The following commercial antibodies were used at thedilution indicated: anti-hScrib goat polyclonal antibody(Santa Cruz WB 1:1000, IHC 1:100), anti-PP1γ goatpolyclonal antibody (Santa Cruz WB 1:1000), anti-PP1
Gamma/PPP1CC Antibody LS-B4960 IHC-plus (tm)rabbit polyclonal antibody (Lifespan bioscience, Inc. IHC
1:200), anti-PP1γ sheep polyclonal antibody (Abcam,
WB 1:1000), anti-actin monoclonal antibody (Sigma,
WB 1:5000), mouse monoclonal anti-p53 (DO-1) (Santa
Cruz WB 1:500), anti-p84 mouse monoclonal antibody(Abcam, WB 1:1000), anti-E-Cadherin rabbit polyclonal
antibody (Santa Cruz WB 1:500), anti-α-tubulin mousemonoclonal antibody (Abcam, WB 1:1000), mouse monoclonal anti-vimentin antibody (Santa Cruz WB 1:500).
siRNA transfection

The HPV-positive cervical cancer cells were seeded on
6 cm dishes and transfected using Lipofectamine 2000
(Invitrogen) with control siRNA against Luciferase (siLuc),or siRNA against HPV-16 and 18 E6 sequences (Dharmacon) described previously by Kranjec C et al., 2011.
72 hours post-transfection cells were harvested and total
cell extracts or cell fractionated extracts were then analysed by western blotting. Alexa 568 labeled negative control siRNA (Qiagen) was used to measure transfection
efficiency. The transfection efficiency was determined to
be over 70% for each cell line.
Subcellular fractionation assays

Differential extraction of the cells to obtain cytoplasmic,
membrane, cytoskeleton, and nuclear fractions was performed using the Calbiochem Proteo Extract Fractionation Kit according to the manufacturer’s instructions.
To inhibit phosphatase activity during the preparation ofcell lysates, phosphatase inhibitors (1 mM Na3VO4,
1 mM β-Glycerophosphate, 2.5 mM Sodium Pyrophosphate, 1 mM Sodium Fluoride) were also included.

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Page 3 of 9Western blotting

Total cellular extracts were prepared by directly lysing
cells from dishes in SDS lysis buffer. Alternatively cells
were lysed in either E1A buffer (25 mM HEPES pH 7.0,
0.1% NP-40, 150 mM NaCl, plus protease inhibitor
cocktail; Calbiochem) or RIPA buffer (50 mM Tris HCl
pH 7.4, 1% NP-40, 150 mM NaCl, 1 mM EDTA, plus
protease inhibitor cocktail; Calbiochem). For western
blotting, 0.45 μm nitrocellulose membrane (Schleicher

A

and Schuell) was used and membranes were blocked
for 1 hour at 37°C in 10% milk/PBS followed by incubation with the appropriate primary antibody diluted in
10% milk/0.5% Tween 20 for 1 hour. After several
washings with PBS 0.5% Tween 20, HRP-conjugatedsecondary antibodies (DAKO) in 10% milk/0.5% Tween
20 were incubated for 1 hour. Blots were developed using
Amersham ECL reagents according to the manufacturer's
instructions.

hScribPP1

hScribPP1

hScribPP1

HPV (-)

HPV16 SCC
patternApattern
B

B

HPV negative normal
cervixPP1

HPV 16 type positive SCC
cervical cancer
PP1

Figure 1 Immunohistochemical analysis of the expression and localisation of hScrib and PP1γ in advanced squamous cervical carcinomas.
(A) Paraffin embedded excised tissues were immunostained with anti-hScrib or anti-PP1γ as indicated, and counterstained with haematoxylin. For theantibodies, immunostaining was performed according to standard techniques using an autostainer (BenchMark XT; Ventana Medical Systems, Inc.,
Tucson, AZ, USA). Representative experiments for a section of cervical epitheliums from normal cervix and advanced squamous cervical carcinomas(×200 original magnification). (B) High resolution microscopic images (scale bars: 20 μm) for a section of cervical epitheliums from normal cervix andHPV-16 positive advanced squamous cervical carcinomas.

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Immunohistochemistry

All tissue samples were fixed in formalin and embedded
in paraffin (obtained from patients under Institutional
Review Board approval through the University of Tokyo
Hospital). For all antibodies, immunostaining was performed according to standard techniques using an autostainer (BenchMark XT; Ventana Medical Systems, Inc.,
Tucson, AZ, USA). Immunoreactivity was interpreted
based on the negative control, which was incubatedwithout the primary antibody. Detection of hScrib expression was evaluated based on the existence of basolateral membrane staining as described previously [28].
For PP1γ, the expression was evaluated by nuclear staining. The immunostaining patterns of each sample were
evaluated independently and blindly by pathologists specializing in gynaecological pathology, and cytology.
PCR-based HPV DNA testing

DNA was extracted from cervical smear samples by using
the QIAGEN® DNeasy® Blood & Tissue Kits. PCR-based
HPV DNA testing was performed using the PGMYCHUV assay. Briefly, standard PCR was conducted using
the PGMY09/11 L1 consensus primer sets and HLA-dQ
primer sets. Reverse blotting hybridization was subsequently performed as described previously [33].

Results
Distribution patterns of hScrib and PP1γ in HPV-16
positive cervical intraepithelial neoplasm (CIN) andcervical carcinoma tissues

Previous studies had highlighted hScrib as a potential
biomarker for HPV-16 induced malignancy [19,28,34].
We reasoned that if PP1γ was also regulated directly by
hScrib, this should be similarly affected in HPV-16 induced malignancy. In order to investigate this we performed IHC analysis of hScrib and PP1γ expression in
HPV-16 positive cervical tumours and control cervix.
The results obtained are shown in Figure 1 and Table 1.
In normal tissue hScrib is found primarily at cell-celljunctions, with high levels of expression as the cells
begin to differentiate. However, hScrib distribution is altered significantly in all the HPV-16 positive tumours,with significant redistribution in the pattern of expression in 5/11 tumours and a complete loss of expressionin 6/11 tumours. These results are largely in agreementwith previous studies [28,35]. In the case of PP1γ, thisdisplays a largely nuclear pattern of expression and thisis present throughout the differentiating epithelium inthe normal cervical tissue. In contrast, in the cervical tumours there is a complete loss of expression of PP1γ in
2/11 cases, with a striking redistribution in the patternof expression in the remaining 9 samples, where there
was a shift from a nuclear localisation to a cytoplasmic
pattern of expression.

Table 1 Immunostaining patterns for hScrib and PP1γ inclinical samples of human uterine cervix
hScribNormal16-positive

Membrane

80

Cytoplasm

05

Nuclear00

No expression

0

6

Total

8

11

PP1y
HPV negative

16-positive

Membrane00

Cytoplasm

09

Nuclear

80

No expression

0

2

Total

8

11

We were then interested in investigating whether perturbation in the pattern of PP1γ expression was an earlyor late event during HPV-induced neoplastic progression. To do this we repeated the PP1γ IHC analysis on
lesions exhibiting different grades of CIN. The lesions
were classified as CIN1 (n = 4), CIN2 (n = 8), CIN3 (n = 8).
As shown in Figure 2, there is a marked loss in nuclear
PP1γ expression, which is already apparent in CIN2, andthis is more evident in the CIN3 lesion, where there arealso much lower levels of PP1γ expression. Interestingly,
PP1γ positive cells were distributed only in the lower thirdof the epithelial layer in CIN1 cases (4/4) and 8/8 of patients with CIN3 had PP1γ positive cells distributed in
the lower, middle, and upper third of the epithelium(Figure 2B). In the case of hScrib, there is a similar perturbation in the pattern of expression as the lesions develop, but similar to what has been reported previously,
there is a tendency in some lower grade lesions to findhighly overexpressed hScrib in regions of the epithelium.
These results indicate that hScrib and PP1γ, whilstboth being perturbed during the progression to malignancy, are altered in a manner that is not interdependent, suggesting that PP1γ might be an independent
marker for cervical tumour development. Indeed, thepattern and expression levels of PP1γ declined with analmost linear relationship from normal tissue, throughincreasing grades of CIN lesion, to invasive cancer.
Analysis of PP1γ expression in HPV-16-positive cells

In order to determine whether perturbation of PP1γ expression was a direct result of HPV-16 oncoproteinfunction, we proceeded to examine the pattern of PP1γ
expression in cell lines derived from HPV-16 positive
cervical tumours. To do this we analysed the pattern ofPP1γ expression in HPV-16 positive CaSki and SiHa

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Seiki et al. BMC Cancer (2015) 15:230

A

Page 5 of 9

hScribhScribNormalHPV16 positive CIN2-3
CIN2

CIN3

PP1

PP1
NormalHPV16 positive CIN2-3
CIN3

B

CIN2

CIN3

CIN1

Figure 2 Immunohistochemical analysis of the expression and localisation of hScrib and PP1γ in various stages of cervical intraepithelial
neoplasms. (A) Paraffin embedded excised tissues were immunostained with anti-hScrib or anti-PP1γ as indicated, and counterstained withhaematoxylin. For the antibodies, immunostaining was performed according to standard techniques using an autostainer (BenchMark XT; Ventana
Medical Systems, Inc., Tucson, AZ, USA). Representative experiments for a section of cervical epitheliums from normal cervix (left) and cervicalintraepithelial neoplasms (CIN) grade 2 and 3 (right) (×200 original magnification). (B) High resolution microscopic images (scale bars: 20 μm) for asection of cervical epithelia from CIN grade 1 and 3.

cells, and compared this with HPV negative HaCaT cells.
To determine whether any alterations might be HPVspecific, we also transfected the cells with siRNA E6/E7
and siLuc as a control. After 72 hours the cells were harvested and cells fractionated into cytosolic, membrane,
nuclear and cytoskeletal pools, such that the pattern ofPP1γ subcellular distribution could be monitored. The
pattern of PP1γ expression was then ascertained bywestern blotting and the results obtained are shown in
Figure 3. PP1γ is found predominantly within the nucleus in HaCaT cells (Figure 3A), whilst in the HPV-16

positive cells it is found weakly re-localised both in nuclear and cytoplasmic locations. However when E6/E7
expression is ablated there is a dramatic redistribution
in the pattern of PP1γ expression, with much higher
levels being found within the nuclear fraction of the cells(Figure 3B). In contrast, we found no difference in PP1γtranscript levels after siRNA E6/E7 treatment in HPV-16
positive cells (data not shown).
These results suggest that loss of nuclear PP1γ expression in HPV positive tumour cells is a direct result of
the expression of the HPV E6/E7 oncoproteins.

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A

F1

F2

F4

F3

F1: cytosol
F2: membrane&organ
F3: nucleus
F4: cytoskeleton

HaCaT hScrib
PP1
alfa-tubulin
E-Cadherin
p84
VimentinBsi luciferase

CaSki

F1

F2

F3

siE6/E7
F4

F1

F2

F3

F4

hScrib
PP1
F1: cytosol
F2: membrane&organ
F3: nucleus
F4: cytoskeleton

p53
E-Cadherin
alfa-tubulin
p84
Vimentinsi luciferase

SiHa

F1

F2

F3

siE6/E7
F4

F1

F2

F3

F4

hScrib
PP1
F1: cytosol
F2: membrane&organ
F3: nucleus
F4: cytoskeleton

E-Cadherin
alfa-tubulin
p84
Vimentin

Figure 3 PP1γ is mislocalised in HPV-16 positive tumour cells. (A) HaCaT cells, and (B) siE6/E7or siluciferase control transfected CaSki and
SiHa cells were fractioned into cytoplasmic (F1), membrane (F2), nuclear (F3), and cytoskeleton (F4) pools and hScrib and PP1γ were detected bywestern blotting. α-tubulin was a loading control for the cytoplasmic fraction, E-Cadherin was a loading control for the membrane fraction, p84
was a loading control for the nuclear fraction, and Vimentin was a loading control for the cytoskeleton fraction.

PP1γ is subject to degradation in HPV-16 positive cells

Interestingly, the fractionation studies indicate thatwhilst there is a significant increase in nuclear PP1γ in
the absence of E6/E7, there is not a significant loss ofcytoplasmic PP1γ, suggesting that some of the loss of
nuclear expression may be due to proteasome mediateddegradation. Therefore we were first interested in determining whether E6/E7 expression could affect the total
levels of PP1γ expression. To do this we analysed thelevels of PP1γ expression in total cell extracts from

CaSki and SiHa cells previously transfected with siRNA
E6/E7 or siLuc as a control. After 72 hours the cells
were extracted and the levels of PP1γ expression monitored by western blotting. The results in Figure 4A showthat loss of E6/E7 expression induces a marked increasein the total levels of PP1γ expression in HPV-16 positive
cells, in a manner similar to that seen for restoration of
p53 levels, which served as a positive control for efficient
ablation of E6/E7 expression. We also monitored the efficiency of E6/E7 knockdown by RT-PCR and found that

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A

SiHa

CaSKi
Si: si luciferase siE6/E7

Si: si luciferase siE6/E7

hScrib
PP1
p53
Actin

B
pcDNA

16E6
4μg

16E6
8μg

C

16E6
10μg

16E6
5μg

pcDNA

hScribhScrib

Lac Z

PP1

PP1

D

HaCaT
-

+

SiHa
-

+

CaSki
-

HeLa

C33A
+

-

+

-

+

MG132

PP1

p53

Actin
Figure 4 PP1γ levels are downregulated in HPV16 positive cells by HPV E6/E7 oncogenes. (A) HPV-16 positive CaSki and SiHa cells weretransfected with siRNAE6/E7 or siLuc as control. Total cell extracts were then made after 72 hours, and hScrib, PP1γ, p53 and Actin were detectedby western blotting. (B) 293 cells were transfected with 4, 8, 10 μg of HPV-16 E6 expression plasmid, and hScrib and PP1γ were analysed byWestern blotting. The middle panel shows the LacZ transfection efficiency and loading control. (C) HaCaT cells were transfected with 5 μg of
HPV-16 E6 expression plasmid, and hScrib and PP1γ were analysed by Western blotting. Tubulin was detected as control. (D) CaSki, SiHa, HeLa,
C33A and HaCaT cells were incubated in the presence of either 10 μM MG132 or solvent before harvesting and analysed by western blotting.
Actin was used as a loading control.

E6/E7 transcripts were reduced by around 60% following
siRNA transfection (data not shown). In contrast to thechange in PP1γ protein levels, we found no difference inPP1γ transcript levels after siRNA E6/E7 treatment in
HPV-16 positive cells. Furthermore, to determine whether
the cell type or E6 expression contributed to the alterations in PP1γ expression levels, we compared the abilityof E6 to direct the degradation of PP1γ in 293 and HaCaT
cells. First 293 cells were transfected with increasing

amounts of HPV-16 E6, as indicated in Figure 4B.
Then, we performed the same analysis using HaCaT
cells (Figure 4C). The results demonstrated that overexpression of HPV-16 E6 results in a decrease in the levelof PP1γ expression. In order to determine whether theloss of PP1γ expression was proteasome-mediated HPVpositive SiHa, CaSki and HeLa cells, and HPV-negative
C33A and HaCaT cells were grown in the presence of theproteasome inhibitor, MG132 for 3 hours, after which the―２９０―Seiki et al. BMC Cancer (2015) 15:230

Page 8 of 9cells were harvested and the levels of PP1γ expression
ascertained by western blotting. As can be seen from
Figure 4D, there are minimal changes in the levels of PP1γ
expression following proteasome inhibition, regardless ofthe presence or absence of HPV DNA sequences, whilst
there is efficient rescue of p53 following proteasome inhibition in HPV positive cells. These results indicate thatthe effects of E6 upon PP1γ patterns of expression are
most likely proteasome independent.

Discussion
PP1 is a major serine/threonine protein phosphatase,normally regulating the phosphorylation status of a large
number of important cellular regulatory proteins [36-39].
Important activities include the regulation of chromosome
structure during mitosis and also following DNA damage,through de-phosphorylation of histones [30,40], and thecontrol of centrosome disjunction through antagonism of
Nek2A kinase activity [41].
In this study we have identified PP1γ as a potential new
biomarker of HPV-16 induced malignancy. Using HPV-16
positive cervical tumour derived cell lines, IHC analysis of
HPV-16 positive cervical tumours and CIN lesions, we
present compelling evidence that PP1γ expression patterns are perturbed as a result of infection with HPV-16.
We originally considered that the PP1γ/hScrib complex might be a general target for HPV-16 E6, based on
our previous studies showing complex formation between hScrib and PP1γ. However, analysis of the expression patterns of PP1γ and hScrib in cervical tissues
indicate that this is not the case. Most importantly however, this highlights PP1γ as an independent target of
the HPV-16 oncoproteins. In the normal cervix, PP1γ isexpressed throughout the differentiating cervical epithelium, with a predominantly nuclear pattern of expression, which is consistent with previous studies [42]. To
our surprise, we found that in all the HPV-16 positive
cervical tumours analysed, this nuclear localisation ofPP1γ was undetectable. Low levels of PP1γ can still befound within the cytoplasm of many cells within the majority of the cervical tumours that we analysed, althoughin 2/11 cases all PP1γ expression appeared to be lost.
Similarly, perturbation in the pattern of PP1γ expression
is apparent in CIN2 lesions, and this becomes moremarked as the lesions progress to CIN3, suggesting that
perturbation in the pattern of PP1γ expression is anearly event in the development of cervical malignancy.
In order to understand whether these effects on PP1γ
expression patterns were a direct consequence of E6/E7
activity, we then focused our attention on cells derived
from HPV-16 positive cervical tumours. Again we foundstriking parallels with the IHC data, with very little PP1γ
expression in the nucleus of HPV-16 positive CaSki or
SiHa cells. In contrast, readily detectable nuclear PP1γ

was observed in HaCaT cells. Most strikingly, siRNA ablation of E6/E7 expression resulted in a dramatic rescueof PP1γ expression within the nucleus of the HPV-16
positive cells, which appeared very similar to the effects
seen upon the pattern of p53 expression. In contrast to
p53 however, the alteration in the levels and pattern ofPP1γ expression by E6 does not appear to involve theproteasome in cells derived from cervical tumours. Obviously further studies will be required to elucidate theprecise mechanisms by which HPV-16 targets PP1γ.

Conclusions
Currently we have no information as to whether theHPV-16 E6/E7 oncoproteins can modulate any of these
phosphorylation events in a PP1γ dependent manner, it
is nonetheless intriguing that all of these pathways are
perturbed to some extent in cells containing the HPV-16
oncoproteins. Future studies will investigate these aspects further, but it is tempting to speculate that targeting of the nuclear forms of PP1γ might contributedirectly towards the generation of genome instability,
chromatin remodeling and tumour progression. The cellular redistribution of PP1γ seems to have an importantrole in the development of centrosome abnormalities
and chromosomal instability at early stages of cervicalcarcinogenesis. Taken together this study highlights thepotential value of PP1γ as a novel biomarker for HPVinduced cervical neoplasia.
Competing interests
All the authors declare no competing interests.
Authors' contributions
TS performed the experiments and wrote the manuscript. KN (corresponding
author) and LB supervised the experiments and wrote the manuscript. TS,
KN, CK, KK, DM, HK-N, AT, YM, TA, OH-W, KO, SN, TY, MF, LB, YO, and TF
contributed reagents, materials, experimental techniques, and data analysis.
KN, DM, MF contributed pathological evaluation. All authors read andapproved the final manuscript.
Acknowledgement
The authors are grateful to Kei Sakuma (Department of Pathology, Graduate
School of Medicine, The University of Tokyo) for technical support on the
preparation of IHC staining. Additionally, we thank Michihiro Tanikawa, Yuichiro
Miyamoto, Kenbun Sone, Yuriko Uehara, Yuji Ikeda, Aki Miyasaka, Takahiro Koso,
Tomoko Kashiyama, Tomohiko Fukuda, Kanako Inaba, Satoko Kojima, andKensuke Tomio for their support and assistance. We also gratefully
acknowledge the particular assistance of all members in Lawrence Banks's lab,and valuable comments on the manuscript from Miranda Thomas and David
Pim. This work was supported by a Grant-in-Aid for Scientific Research (K.N.)
from the Ministry of Education, Science and Culture, Japan, and in part by aresearch grant from the Associazione Italiana per la Ricerca sul Cancro (L.B).
Author details
1
Department of Obstetrics and Gynecology, Faculty of Medicine, The
University of Tokyo, Tokyo 113-8655, Japan. 2International Centre for Genetic
Engineering and Biotechnology, Area Science Park, Padriciano-99, I-34012
Trieste, Italy. 3Department of Pathology, Graduate School of Medicine, The
University of Tokyo, Tokyo 113-8655, Japan. 4Department of Obstetrics andGynecology, Graduate School of Medicine, Teikyo University, Tokyo 173-8605,
Japan. 5Department of Obstetrics and Gynecology, National Center for Global
Health and Medicine, Tokyo 162-8655, Japan.

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Received: 31 May 2014 Accepted: 27 February 2015

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