Group	  2	  progress	  reportat	  General	  Meetingon	  7th	  Apr	  2017
Nancy	  ZyongweBona	  ChitahDoreen	  Sakala

Yabe

Tembo

MuzanduNosikuSipilanyambe
Munyinda

Today’s	  Group2	  Presentation	  Topicsl Group2	  overall	  progress	  (Nakata)l Exposure	  assessment	  team	  (Nakata)l Economic	  assessment	  team	  (Hiwatari,	  Narita)l Neurodevelopment	  (ND)/QOL	  analysis	  team	  (Fujita)

Group2	  overall	  progress	  (2017	  Jan~Mar)ØMeeting	  &	  Trip	  to	  Zambia	  (Feb~Mar 2017)-­‐ Exposure	  assess	  team	  (Nakayama,	  Yared,	  Andrew,	  Nakata)-­‐ QOL	  team	  (Fujita,	  Yoshida,	  Yamasaki)-­‐ Economic	  assess	   team	  (Hiwatari,	  Narita,	  Yamada)ØNew	  member,	  Dr.	  Peter	  Hangoma (Sch.	  of	  Public	  Health)	  joined	  in	  Economic	  teamØTeam	  structure	  was	  updated	  (next	  slide)ØBroad	  Survey	  in	  July~Aug 2017	  was	  designed	  and	  arranged	  ØMonitoring	  sheet	  (1st term.	  May	  2016~Jan	  2017)ØNakata	  will	  be	  transferred	  Zambia	  at	  end	  of	  AprØ Team	  structure	  was	  updated
Team	  Leader:	  	  John	  Yabe	  /	  Shouta Nakayama(B)	  Economic	  Assessment(A)	  Health	  Risk	  Assessment
Exposure	  Assessment
John	  Yabe	  (UNZA,	  Vet)	  Kaampwe Muzandu(UNZA,	  Vet)
Andrew	  Kataba (UNZA/HU)
Tembo Backsion (UNZA)

Shouta Nakayama	  (HU,	  Vet)
Yared Beyene (HU,	  Vet)
Haruya Toyomaki (HU,	  Vet)
Hokuto	   Nakata	  (HU,	  Vet)
Takeshi	  Kuritani (HU,	  Sci)

Neurodevelopment	   /	  QOL	  analysis
Nosiku Sipilanyambe Munyinda
Wakako Fujita	  (Wakayama	  Med)(UNZA,	  Medical)	  Takeshi	  Saito	  (HU,	  HS)Doreen	  Sakala (MOH)Harukazu Tohyama (HU,	  HS)Nancy	  Zyongwe (UNZA,	  Medical) Takahiko	  Yoshida
Sandra	  Shanungu (Arise	  Africa)(Asahikawa	  Med)
Shojiro Yamasaki	  (HU,	  HS)	  Natsumi Nagai	  (HU,	  HS)IQ	  analysis(Robert	  Serphell (UNZA,	  Special	  Education))
Beatrice	  Matafwali (UNZA,	  Special	  Education)
Gabliel Walubita (UNZA,	  Special	  Education)
Joe	  Kalima (UNZA,	  Special	  Education)

Bona	  Chitah(UNZA,	  Economics)	  Chrispin Mphuka(UNZA,	  Economics)
Peter	  Hangoma(UNZA,	  Public	  Health)

Masato	  Hiwatari(HU,	  Economics)
Daiju Narita(HU,	  Economics)
Daichi Yamada(HU,	  Economics)

Statistician	  from	  Medical	  School	   Mr.	  Munbi Chola• Sub-­‐group化してメンバーを確認• Sub-­‐groupに日本・ザンビアのリーダー配置（IQチームはザンビアのみ）Ø Broad	  Survey	  in	  July~Aug 2017	  was	  designed	  and	  arranged	  【2016年末までの決定事項（→2017年の進捗）】
1. ①２０１７年7~８月頃に、チーム２のサブグループが同時にKabweの広範囲を対象とした大規模調査（②汚染域のDeep  Surveyは後で）→日程の大枠は確定
2.  UNZA医学部のエコノミストPeter  Hangoma氏をメンバーに追加（医学・経済がある程度両方分かる方）→正式に参画
3.  12月末に、サブグループごとに、調査アウトライン（PROPOSAL）を作成し、日本・ザンビア側のTV会議→大枠は決定。詳細をザンビア側と検討中。
4.  2017年１月にSTATISTIANとディスカッションして、サンプルサイズ（N数）の決定→決定
5.  経済班の統計データ等をもとに、ランダムサンプリングの対象を決める。
→データは収集済み。対象選定中。

【Decision	  by	  end	  of	  2016	  (→Progress	  in	  2017	  so	  far)】1.	  ①Broad	  Survey	  in	  Whole	  Kabwe by	  (all)	  subgroup	  in	  Group2	  &	  ②Deep	  survey	  around	  mines	  (Hot	  spots)	  in	  the	  future.
→Approximate	  schedule	  for	  ① was	  decided.
2.	  Dr.	  Peter	  Hangoma (Health	  economist)	  will	  join	  in	  economic	  group.
→Officially	  joined.
3.	  Research	  (survey)	  protocol	  will	  be	  created	  and	  discussed	  between	  Z/J	  side.
→The	  outline	  was	  decided.	  Further	  details	  are	  still	  under	  discussion.
4.	  Sample	  number	  will	  be	  decided	  by	  Jan	  2017.
→Decided.
5.	  Sampling	  target	  will	  be	  decided	  according	  to	  economic	  statistical	  data.
→Still	  under	  discussion.

Ø Broad	  Survey	  in	  July~Aug 2017	  was	  designed	  and	  arranged	  (cont’d)6.	   「１回の調査のみなら１０００世帯」、「世銀などによる工事前後のデータ比較ができるなら５００世帯程度必要」→世銀工事に依存せず、①で1000世帯を対象とする。
7.	  Health	  assessの対象は、各世帯で「父or/and母、子供1~2人」で2000~4000名？
→父、母、子供2人（7歳以上と未満）として、計4000名を対象
8.	  父親の骨中の鉛濃度測定を行い、長期暴露の指標として経済アセスに用いる（骨中濃度測定が不可な場合は、BLLで代用）。
→X-­‐ray式骨中濃度測定器は見積もりなど依頼中。骨中濃度が測定できた場合でも、BLLも測定する。

【今後の予定】◆４月～７月に、３月のPre調査の問題点など修正◆7月～8月頃に第１回大規模調査◆１０月以降、調査データのまとめ、サンプルを用いた実験
データ収集・解析

6.	  If	  we	  do	  ① before/after	  the	  WB	  remediation,	  500	  households	  is	  enough	  for	  the	  economic	  assess.	  But	  if	  one	  time,	  1000	  households	  is	  needed.
→1000	  households	  will	  be	  target	  for	  ①.
7.	  Target	  for	  health	  assess	  is	  “father	  or/and	  mother,	  1~2	  child”	  in	  each	  household	  =	  2000~4000	  specimens?
→Father,	  mother,	  and	  two	  children	  (above/less	  than	  7	  years	  old)	  =	  4000	  specimens.
8.	  Bone	  Pb level	  in	  father	  can	  be	  a	  long-­‐time	  (life-­‐time)	  exposure/accumulation.
→ Purchase	  of	  X-­‐ray	  bone	  Pb analyzer	  is	  still	  on	  the	  way.	  Both	  BLL	  and	  bone	  level	  data	  should	  be	  gotten.
【Future	  Plan】◆ Further	  detail	  plan	  for	  ① will	  be	  discussed	  and	  finalized	  in	  Apr~Jul◆ ①Broad	  Survey	  in	  Jul~Aug◆ Lab	  experiment	  and	  data	  analysis	  after	  OctThe	  challenging	  in	  previous	  meeting
1000世帯の中でも、子供の人数や男女比が家庭ごとに異なる
Among	   1000	  households,	   child	  numbers	   &	  boys/girl ratio	  is	  different	   in	  each	  house.
Ex.	  House	   No.	  1	  (3	  Boys	  and	  1	  Girl)Age

5 3	   1	   0	  B (Boy)G (Girl)B B G B1 2 1 3
House	  No.	  998	  (2	  Boys)

House	  No.	  2	  (1	  Boy)
10B
1House	  No.	  999	  (1	  Boy	  and	  1	  Girl)

15 13 7 7

6 3 4 1B B G B1 2 1 3B B G B4 5 2 6House	  No.	  1000	  (8	  Boys)
18 17 12 9 7 6 3 1

6 4B B
1 2

House	  No.	  3	  (6	  Boys	  and	  2	  Girls)

B G
1 1

B B
1 2

仮に経済チームがランダムに1000世帯を選んだとして、その中から、どのように血液サンプリングの対象の子供をバランスよく選ぶのか？ After	  Economics	  team	  randomly	  selected	  1000	  household,	   how	  can	  we	  choose	  target	  children	   for	  blood	   collection?

B B
3 4B B
5 6

B B
7 8

Which child should
be targeted???

Today’s	  Group2	  Presentation	  Topicsl Group2	  overall	  progress	  (Nakata)l Exposure	  assessment	  team	  (Nakata)l Economic	  assessment	  team	  (Hiwatari,	  Narita)l Neurodevelopment	  (ND)/QOL	  analysis	  team	  (Fujita)Sample	  number,	  team	  arrangement,	  rough	  schedule• Assuming	   10~20	  min	  for	  1	  sample	  collection	  (from	   past	  experience	  in	  Oct	  2016	  pre-­‐sampling)• Average	  10	  households	   (40	  persons/samples)	   per	  day• 17th July	  ~	  21st July:	  Preparation	  and	  practice• 24th July	  ~	  30th Aug:	  Sample	  collection	  (N=4000)	   with	  28	  working	   days	  and	  5	  Saturdays	  (half	  day,	  optional)• Four	  teams	  (Each	  team	  has	  one	  Zambian,	   one	   Hokudai member,	   two	  nurses,	  and	  two	  lab	  technician)→（Yabe,	  Muzandu,	   Andrew,	   Zyambo）×（Nakayama,	  Yared,	  Toyomaki,	   Nakata）

40	  samples	  × 4	  teams	  × 30	  days	  =	  4800	  samples• Questionnaire (2 person)• Blood	   collection	  (2 person)• Blood	   Dispense	  and	  Centrifuge (1 person)• LeadCareII BLL	  measurement (1 person)• 8 Nurses	  &	  Lab	  Technicians	  (2	  and	  2	  in	  each	  team)	  based	  in	  Kabwe• Community	  Health	  Worker (CHW)	  in	  Kabwe← will	  arrange	  by	  Yabe,	  Muzandu,	  Nakata,	  Odagiri

Proposal	  (Exposure	  assessment	  sub-­‐team)Sampling	  Target• Blood with	  heparin	  (at	  health	  center)-­‐ 5	  mL	  for	  father,	  mother,	  and	  child	  above	  7	  years-­‐ 2.5	  mL	  for	  child	  less	  than	  7	  years• Urine (up	  to	  10	  mL)	  using	  plastic	  cup	  and	  15	  mL	  tube
• Feces (2~3	  g)	  using	  stool	  container
Plastic	  cup	  and	  15	  mL	  tube

Stool	  container	  with	  spoon	   cap	  • Breast	  Milk (1~3	  mL	  for	  early	  stage,	  5~10	  mL	  for	  later	  lactation	  stage	  )• Umbilical	  cord	  blood (5~10	  mL?,	  with	  Syringe)• Bone	  Pb (X-­‐ray,	  still	  under	  arrangement)

Proposal	  – blood	  sample
Father	  &	  Mother【Blood	  collection】

Each	  data	  is	  shared	  with	  other	   sub-­‐groups.
＊Father	  -­‐ with	  Economic	  (Bone	  Pb is	  more	  appropriate),	   ND,	  IQ	  team＊Mother	   -­‐ with	  QOL,	  ND,	  IQ	  team
＊Child	  -­‐ with	  ND,	  IQ	  teamTransfer:	  2	  mL×2	  tubes(in	  2	  mL	  tube)
5	  mL	  with	  heparin【Pb conc.	  &	  Isotope	  analysis】【BLL	  measurement	  】(with	  only	  50	  uL)Child	  above	  5	  years
Centrifuge(4000	  rpm,	  10	  min)Transfer5	  mL	  with	  heparin

1	  mL	  ofremaining	  blood

Plasma	  Transfer	  0.5	  mL	  × 1	  tube(in	  1.5	  mL	  tube)【Blood	  biochemistry】

Child	  less	  than	  5	  years

Transfer

2.5	  mL	  with	  heparinTransfer:	  2	  mL×1	  tubes(in	  2	  mL	  tube)【Pb conc.	  &	  Isotope	  analysis】【BLL	  measurement	  】(with	  only	  50	  uL)3	  of	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  will	  be	  purchased	  until	  August	  sampling	  Points	  to	  be	  discussed/decidedØ How	  to	  decide	  the	  target	  area/household	  (by	  economic	  assess	  team)Ø How	  to	  collect	  Paired	  Blood	  of	  mother	  and	  child	  and	  Milk,	  umbilical	  cord	  blood → Need to	  discuss	  with	  ND	  team	  (Nosiku-­‐san)Ø Where	  do	  we	  measure	  bone	  Pb?	  (at	  clinic	  in	  parallel	  with	  blood	  collection?)	  How	  many	  min	  per	  sample?
→	  Arrange	  by	  Yabe	  &	  Dr.	  Linda,	  	  3-­‐min	  for	  one	  measurement
Ø How	  is	  overall	  flow	  for	  sampling?	  How	  many	  types	  and	  what	  timing	  are	  questionnaires	  taken?
Ø How	  to	  call	  people	  to	  come	  to	  the	  clinic	  for	  blood	  collection?
→	  Invitation	  letter	  &	  Reminder	  by	  CHWØ Need	  to	  arrange	  transport	  for	  participant	  from	  their	  house	  to	  clinic	  for	  sampling?
Ø How	  to	  employ	  our	  own	  nurse	  &	  lab	  tech	  for	  the	  sampling?
→ Arrange	  by	  Yabe,	  Muzandu,	  Nakata,	  OdagiriØ Where	  collected	  samples	  will	  be	  stored	  in	  Kabwe?	  Freezer	  in	  Kabwe	  will	  be	  necessary.
→ Freezer	  will	  be	  installed	  in	  somewhere	  Kabwe?	  How	  often	  do	  we	  need	  to	  transfer	  the	  samples	  from	  the	  Kabwe freezer	  to	  UNZA?

Rough	  scheduleØSelection	  of	  target	  households	  (By	  Economics	  team,	  statistical	  excel	  data)ØDecide	  a	  schedule	  of	  sampling	  for	  each	  household	  &	  make	  “Schedule	  Table”
ØMake	  “Invitation	  letter”	  for	  each	  household	  with	  note	  of	  sampling	  dayØDeliver	  “Invitation	  letter”	  in	  advance	  by	  CHW
(Reminde the	  day	  before	  sampling)ØEmploy	  8	  Lab	  Techs	  &	  8	  Nurses	  &	  CHWØPrepare	  consumables	  &	  Test	  kits	  for	  LeadCare analyzer	  (BLL	  tests)

Future	  Arrangement

ØOverall	  matter	  →	  Nakayama	  &	  YabeØBone	  Pb XRF	  →	  Yabe	  &	  Dr.	  Linda
ØNurse,	  Lab	  Tech,	  CHW	  employment →	  Nakata,	  Yabe,	  Odagiri,	  MuzanduØPb isotope ratio	  →	  Nakata,	  Dr. Kuritani (from	  Faculty	  of	  Science),	  HaruyaØBiomarkers,	  etc →	  Yared,	  Andrew

Schedule	  Table
Note;
This	  table	  is	  just	  an	  Image.
Date
House	  hold	  number
TargetCode	  IDNameGroup	  number
Health	  Center

Date
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01

Health	  center
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa
Chowa

Household	   number
CHOWA_#1
#1
#1
#1
#2
#2
#2#3
#3
#3
#3
#3

CodeName

Team	  leader
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe
Yabe

Date
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01

Health	  center
KasandaKasandaKasandaKasandaKasandaKasandaKasandaKasandaKasandaKasandaKasandaKasandaHousehold	   number
Kasanda_#1
#1
#1
#1
#2
#2
#2
#3
#3
#3
#3
#3

CodeName

Team	  leader
NakataNakataNakataNakataNakataNakataNakataNakataNakataNakataNakata
NakataDate
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01
2017/Aug/01

Health	  center
Makululu
Makululu
Makululu
Makululu
Makululu
Makululu
Makululu
Makululu
Makululu
Makululu
Makululu
MakululuHousehold	   number
Makululu_#1
#1
#1
#1
#2
#2
#2
#3
#3
#3
#3
#3

CodeNameTeam	  leader
Yared
Yared
Yared
Yared
Yared
Yared
Yared
Yared
Yared
Yared
Yared
Yared

⼦子供１５０名を対象とした⾎血中鉛濃度度調査（２０１６年年１０〜～１１⽉月）
Blood  Pb in  150  children  (Oct  2016)

鉱床の近く(Makululu, Kasanda, Chowa)では、ほぼ100％の⼦子供が10 μg/dLを超える鉛濃度度を⽰示した。
⼀一⽅方、鉱床から離離れたエリア（Bwacha, Nakoli）では、上記エリアよりも濃度度が低いが、鉛に曝露露されていることが分かった。
→

⾎血中鉛濃度度Mappingが必要

データ非公開Human	  sampling	  in	  Jan-­‐Mar	  of	  2017
ØMothers	  and	  Infants	  at	  5	  clinics
ØBlood	  samples	  of	  mothers	  and	  infantsØBreastmilk	  samples
ØFecal	  samples	  of	  infantsBlood	  Lead	  Levels	  (BLLs)	  in	  Mothers	  and	  Infants
Mothers	  (N	  =	  426)

データ非公開Infants	  (N	  =	  417)

データ非公開l BLLs	  >	  45	  μg/dL in	  mothers	  and	  infants	  were	  found:	  this	  level	  should	  be	  treated	  with	  Chelation	  Therapyl BLLs	  	  >	  100	  μg/dL in	  infants	  were	  also	  found	  :	  this	  level	  can	  cause	  encephalopathy	  and	  deaths	  in	  children→ No clinical	  case	  has	  been	  reported	  in	  Kabwel BLLs	  in	  infants	  were	  significantly	  higher than	  those	  in	  mothers	  (p <	  0.01)

Blood	  Lead	  Levels	  (BLLs)	  in	  Mothers	  and	  Infants
Mothers	  (N	  =	  426)

Infants	  (N	  =	  417)

データ非公開l BLLs	  >	  45	  μg/dL in	  mothers	  and	  infants	  were	  found:	  this	  level	  should	  be	  treated	  with	  Chelation	  Therapyl BLLs	  	  >	  100	  μg/dL in	  infants	  were	  also	  found	  :	  this	  level	  can	  cause	  encephalopathy	  and	  deaths	  in	  children→ No clinical	  case	  has	  been	  reported	  in	  Kabwel BLLs	  in	  infants	  were	  significantly	  higher than	  those	  in	  mothers	  (p <	  0.01)l The	  first	  time	  to	  collect	  samples	  in	  Katondo→	  	  	  BLLs	  in	  Katondo were	  similar	  to	  Chowa

Correlation	  between	  BLLs	  of	  paired	  mothers	  and	  infants

データ非公開There	  was	  a	  significant	  positive	  correlation	  between	  BLLs	  of	  paired	  mothers	  and	  infants	  	  (p	  <	  0.01,	  ρ	  =	  0.6)

Accurate	  Pb isotope	  analysis	  using	  NEPTUNE	  plus

データ非公開Ø Different  isotope  ratios  from  low  and  high  polluted  areaØ Similar  isotope  ratios  in  soil  and  chicken  kidney  at  each  siteNew	  topics
ØGut	  microbiota	  with	  Group1(rat	  and	  human	  feces)

Philipp	   Engel	  et	  al.,	  2012

ØEpigenetic	  analysis	  National	  Institutes	  of	  Health	  -­‐http://commonfund.nih.gov/epigenomics/figure.aspx.