Mosquito borne
diseasesNational Center for Global Health and Medicine

Disease Control and Prevention Center
Satoshi KUTSUNA, M.D., Ph.D.
10/18/2017
The Workshop for the Infection Prevention and Control,
Antimicrobial Resistance Emerging Infectious Diseases, Antimicrobial Resistancedengue infections in a world per year

3.9millions
Nature. 2013 Apr 25;496(7446):504-7.

Mosquitoes run
the way far ahead ofhumansジカウイルスはどのように世界で広がったのかFirst human ZIKA cases in Brazil: 2015
First ZIKV detected from mosquitoes in Brazil ：March-Nov 2013

Endemic area(as ofofOctober
Chikungunya
fever
20, 2015)

Countries and territories where chikungunya cases have been reported**Does not include countries or territories where only imported cases have been documented. This map is updated weekly if
http://www.cdc.gov/chikungunya/pdfs/chikungunyaworldmap_10-20-2015.pdf
there are new countries or territories that reportlocal chikungunya virus transmission.

Rapid communications

Autochthonous dengue virus infection in Japan
imported into Germany, September 2013
J Schmidt-Chanasit (jonassi@gmx.de)1,2, P Emmerich1, D Tappe1, S Günther1, S Schmidt3, D Wolﬀ 3, K Hentschel 4 , D Sagebiel 4 ,I Schöneberg5, K Stark5, C Frank5
1. Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference
and Research, Hamburg, Germany
2. German Centre for Infection Research (DZIF), partner site Hamburg-Luebeck-Borstel, Hamburg, Germany
3. Public Health Authority Steglitz-Zehlendorf, Berlin, Germany
4. State Oﬃce of Health and Social Aﬀairs, Berlin, Germany
5. Robert Koch Institute, Department for Infectious Disease Epidemiology, Division of Gastrointestinal Infections, Zoonoses andTropical Infections, Berlin, Germany
Citation style for this article:
Schmidt-Chanasit J, Emmerich P, Tappe D, Günther S, Schmidt S, Wolﬀ D, Hentschel K, Sagebiel D, Schöneberg I, Stark K, Frank C. Autochthonous dengue virus
infection in Japan imported into Germany, September 2013. Euro Surveill. 2014;19(3):pii=20681. Available online: http://www.eurosurveillance.org/ViewArticle.
aspx?ArticleId=20681
Article submitted on 18 January 2014 / published on 23 January 2014

In September 2013, dengue virus (DENV) infection was
diagnosed in a German traveller returning from Japan.
DENV-specific IgM and IgG and DENV NS1 antigen weredetected in the patient’s blood, as were DENV serotype
2-specific antibodies. Public health authorities should
be aware that autochthonous transmission of thisemerging virus may occur in Japan. Our findings also
highlight the importance of taking a full travel history,
even from travellers not returning from tropical countries, to assess potential infection risks of patients.

Airport to Tokyo Narita International Airport and cameback the same way. The patient was vaccinated against
yellow fever in 2009, because she had travelled to
Kenya that year. In the beginning of 2012, she travelled
to Singapore. Among several other diseases, dengue
fever was suspected, because of the clinical picture.

1 year before the autochthonous outbreak in JapanThe first serum sample, collected seven days after
symptom onset, gave a positive result in DENV IgM
and IgG antibody tests (in-house indirect immunoflu-

T h e n e w e ng l a n d j o u r na l o f m e dic i n e

C or r e sp ondence

Autochthonous
Japanese
The new e ng l a n dEncephalitis
j o u r na l o f m e with
dic i n eYellow Fever
Coinfection in Africa
A Japanese Encephalitis Virus

To the Editor: Japanese encephalitis virus andyellow fever virus are mosquito-borne flaviviruses
that circulate in disjunct geographic areas withdifferent mosquito vectors. Japanese encephalitis
is endemic to most of Asia and the Western
Pacific, whereas yellow fever occurs in tropicalareas of Africa and South America.
100 Both viruses
lead to a wide spectrum of disease severities that
include asymptomatic infection and mild illness
100
with influenza-like symptoms. However, severe
yellow fever disease can be fatal in 20 to 60% ofcases,1 whereas symptomatic Japanese encephalitis virus can progress to severe encephalitis, withcase fatality rates of up to 30%. Survivors often
have long-term neuropsychological sequelae.2
In March 2016, during the yellow fever outbreak in 0.07
Angola, a 19-year-old man was admitted
to the Cunene Provincial Hospital with a 5-day
history of fever, headache, and jaundice. The
patient, who survived, worked in the capital city
BofYellow
FeveratVirus
Luandathe onset of disease and had not
traveled abroad. A blood sample was obtained,

able with the full text of this letter at NEJM.org).
JF915894/China/2009
The 100
yellow fever virus sequence was closely reHM596272/Malaysia/1952 Genotype V
100lated to both a sequence
from the 1971 yellow
KM677246/Singapore/1952
fever virus AY184212/Indonesia/1981
outbreak in Angola andthe recently
GenotypeIVreported yellow
fever
virus
sequence
detectedin
HQ223287/Indonesia/1978
100
Genotype IIa sample from AF217620/Australia/1995
a Chinese traveler returning from
100 4
Angola(Fig. 1B).AB981183/Japan/2013
100AB853904/Japan/2010
The likelihoodof sample contamination is91 KF667326/Taiwan/2012 Genotype I
small, since neither
the Institut Pasteur of Dakar,
96
KT229573/China/2010
Senegal, where theRNA extracted from the samJN711458/China/2009
ples67in Angola was delivered, nor the laboratory
JX072965/India/2010
at the Institut
Pasteur, Paris, where the libraries
KU363309/China/2013100
were constructed and sequenced, has ever had
JN604986/South/Korea/2006
any
material
containing Japanese encephalitis
100
96KC915016/China/2010
Genotype III
virus.68 In addition,
none
of
the
15 additional
KF667314/Taiwan/2010
97
RNA
samples from patients with yellow fever
JEV/Angola/2016/Cahama-C17
virus
who were treated at the same time pro100 KF667312/Taiwan/2007
58
vided KF667313_Taiwan_2008
sequence reads that corresponded to Japanese encephalitis virus. Leftover sera from theweek’sletters
N Engl Jthis
Med.
2017
Apr 13;376(15):1483-1485.

AY640589/Ghana/1927

Background of increasingmosquito-borne diseases

https://ecdc.europa.eu/en/publications-data/mosquito-borne-diseases-emerging-threat

vaccination

Bladder cancer

Pathogen “escape”
from vaccine-induced
immunity

Degenerative brain disorder

Serotype replacement
including capsularswitching in Streptoco
pneumoniae

International Tourist Arrivals Received (million)

International Travelers
Actual1800

Forecasts
1.8 bn

1600
1400
1200
1000
800

1.4 bnAfricaMiddle East
Americans
Asia and the Pacific

940 mmEurope

600
400
200
0
1950

1960

1970

1980

1990

2000

2010

2020

2030

Mandell 8th. 14. Emerging and Reemerging Infectious Disease Threatshttp://www.flightradar24.com/

Globalization of Japan
In 2015…
16 Millions from Japan to abroad.
20 Millions from foreign countries to Japan.

日本旅行業協会HPより

WARMING

http://www.climatecentral.org/news/what-warming-means-summers-pests-19295

月 中 旬 ～10

確認地
未確認地

⼋八峰
能代

存 在 しな
本荘

常 に多 く、

秋⽥田

酒⽥田

2010年年
宮古(2007)
⼤大槌(2011〜～)
花巻(2007〜～）
気仙沼

横⼿手

新庄
⼭山形

県 以 南 ）から

布 している こ

盛岡( 2009〜～)

2000年年

⽯石巻

会津若若松

仙台
⽩白河

また、幼 虫C 以上

地影 響 で分とが示 唆 さ軽井沢〜～1950年年⽇日光

100 Km東京

URBANIZATION

Kinds of mosquitos andinfectious diseases

Kinds of Mosquitos

Culex

Aedes

Anopheles

Dengue Fever
infectious diseases

Japanese Encephalitis Chikungunya Fever
West Nile Fever

Zika Virus Infection

Malaria
Filariasis

Yellow fever
Jong Travel and Tropical Medicine Manual, 4th ed.を参考に作成

Aedes aegypti
vector for DENV,• MainCHIKV, ZIKVin tropical• Distributedand subtropic regions• In Japan: not distributed

IASR Vol.28 p 219-221

Aedes albopictus
vector for DENV,• Second
CHIKV, ZIKVin Southeast Asia,• Distributed
East Asia
distributed in American• Now
continent, and part of Europe.

ヒトスジシマカの生態と東北地方における分布域の拡大 (IASR Vol. 32 p. 167-168: 2011年6月号)
国立感染症研究所

デング熱国内感染事例発生時の対応・対策の手引き2014

Dengue feverin Japanantigen (Platelia Dengue NS1 Antigen assay; Bio-Rad and 10) shared 100% homology with that of patient 2.
Laboratories, Marnes-la-Coquette, France). The remaining case (case 11) was confirmed positive for IgM and IgG Conclusions
against DENV by dengue IgM ELISA (Focus Diagnostics, Our results suggest that a single strain may have caused
Inc., Cypress, CA, USA) and dengue IgG ELISA (Vircell, most of the DENV cases in Tokyo. A similar outbreak ofGranada, Spain), respectively. The serotype of the DENV dengue fever had been reported in Ningbo, China (68 casJapan,
in the other 18 patients was confirmed to be serotype 1. Nu- es) (7), and in Hawaii, USA (122 cases)(8).including Tokyo. Ae. albopictus mosquitoes arealso expanding into the northern regions of the main iscleotide sequences were determined by using BigDye TerDENV is transmitted mainly throughthe bite of theland becauseof global
warming(10).
is one of thehistoryofhavingcontracted
denguefever
while
inTokyothe PhilSatoshi
Kutsuna,YasuyukiKato,minator version 3.1 (Applied Biosystems, Foster City, CA, Aedes aegypti mosquito, which is distributed
tropicalmost heavilyinpopulated
cities in the world, and Yoyogi
ofis thepatients
had traveled overseas
Meng
Ling Moi,
MasayukiUSA). Phylogenetic
analysisof theAkira
DENVKotaki,
envelope(E) and Ota,
subtropical ippines
regions.in
In2006.
Japan,Nonethedistributionof Ae.
Park
located at thecenter of the Shinjuku-Shibuya area
duringthe 3 months
beforeKohobtained
Shinohara,
TetsuroTokyo.
protein genome sequence
from serumfrom Kobayashi,patient aegypti mosquitoes
is limited,
and asinof
2013, thetheseoutbreakmos- of dengue virus
The population
density of Ae. albopictus mosquitoes
type
1 (DENV-1)
in Narita
Japan.
Yoshihirothat
Fujiya,2 (GenBank accessionKei
no. Yamamoto,LC006123) demonstrated
quitoes had been
foundonly at theInternationalTokyo
is higherareas15(11). It is
exposures
were
assessed
forinallsuburban
patients;
the E protein shared 100%
homology
with the sequence
Airport (9), which isPlaces
locatedof≈60
kmin fromthesite
ofthanthethatMomokoMawatari,
TastuyaofSato,
possible that high human and mosquito population densia DENV-1 strain fromthe first
patient in thisoutbreakin DENV outbreakpatientsin Tokyo.
contrast,
the distribution
hadInrecently
YoyogiandAllwere
bittenhad been
Junwa
Kunimatsu,
NozomiTakeshita,
tiesvisitedcontributed
to this Parkoutbreak.
19 patientsJapan (GenBank accession
no.Hayakawa,
LC002828). Shuzo
The sequenceof Ae. Albopictus
vectorof DENV,bymosquitoes,
mosquitoesanotherwhile
there;
theremaining
patients
had
KayokoKanagawa,
bittenby a mosquito
while in 4Tokyo,
mainlyin Yoyogi
Park,
where
most
of the160 patients
withMeijiautochthonous
from patient 2 sharedTomohiko
99.7% identitywith the sequenceof a extends from westernregions toCentral
northern
regionsofvisited Shinjuku
Park,
Meiji
Jingu
Shrine,Takasaki,
Norio Ohmagari

Autochthonous Dengue Fever,Tokyo, Japan, 2014

dengue cases had also been (12).
ingu Gaien, and Ueno
Park. All of these parks have been
After 70 years with no confirmed autochthonous cases of reported as affected
Figure 1. regions
Locationsin
ofthis outbreak (3) (Figure 1).
dengue fever in Japan, 19 cases were reported during Aupresumptive
exposureto
The day of exposurewasestimatedfor 9 patients for whomgust–September 2014. Dengue virus serotype 1 was dedengue virus mosquito vectors
the day of visitationand mosquito bites while in the parks
for 19 patients, Tokyo, Japan,
tected in 18 patients. Phylogenetic analysis of the envelope
Among these9 patients, the median
August 26–September
22, 2014.
protein genome sequence from 3 patients revealed 100% could be confirmed.
Numbers
in circles
indicatewas
6 (range
3–9) days. For the other 10
identity with the strain from the first patient (2014) in Japan. incubation period
numbersofcases
contracted
at determined because
patients, the incubation period was noteach location.
they had visited the parks over several days or because theylthough ≈200 imported cases of dengue fever have re- lived near these parks. The dates of symptom onset ranged
cently been reported in Japan (1), an autochthonous from August 12, 2014, through September 22, 2014; peakcase had not been confirmed there for 70 years (2). How- incidence occurred in the beginning of September.
ever, on August 26, 2014, an autochthonous case of dengue
Of the 19 patients, 16 were admitted to the National
fever in a patient with no history of overseas travel was Center for Global Health and Medicine and discharged
reported in Tokyo, and as of October 31, 2014, a total of without sequelae; the other 3 received outpatient treatment
160 autochthonous cases in Japan had been confirmed (3). and recovered. The patient with a history of dengue fever(patient 19 in the online Technical Appendix Table) exThe Cases
perienced fever lasting 7 days, pleural effusion, spontaneWe report 19 cases of confirmed autochthonous dengue ous petechiae, and thrombocytopenia (15 × 103 cells/μL on
fever treated at the National Center for Global Health day 8 after illness onset); dengue hemorrhagic fever wasand Medicine in Tokyo, Japan, during August 26– diagnosed for this patient by using the World Health OrgaSeptember 22, 2014 (Tables 1, 2; online Technical Ap- nization guidelines (4). On the day of illness onset for thispendix Table, http://wwwnc.cdc.gov/EID/article/21/3/14- patient, serum was positive for DENV nonstructural pro1662-Techapp1.pdf). Because the National Center for tein 1 (NS1) antigen and IgG but negative for DENV IgM.
Figure 2. Phylogenetic analysis of a dengue virus (DENV)
Global Health and Medicine is located close to the epi- These results demonstrated
that this DENV infection was
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 3, March 2015
sequence derived from a patient with confirmed autochthonous
center of this outbreak, 19 (12%) of the 160 cases of thisA

518

AutochRecently,
from Japan wa(13). Previous
have been spre
the park (13).
period during
activities wereattracted a hig
to the park.
Before th
nosed for a Ge
in 2013 (14). N
eler’s infection
ly bitten by motraveled to Tok
local DENV c
may have been
dengue outbrea
Because avive the winterthe outbreak oend as mosquit
anese governm
measures and ivent similar ou

This work was p
Emerging and R
the Ministry of H
shinkou-ippan-0
funders had no r
analysis, decisio

Dr. Kustuna is a
Health and Medi
marily research
References

1. Takasaki T. I
cases in Japa
org/10.2149/
2. Hotta S. Den
albopictus an
ics of Japane
1998;49:267

Reported cases of DF
in Japan
350
280
210
140
70
0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
http://www.niid.go.jp/niid/ja/all-surveillance/2085-idwr/ydata/4405-report-ja2012.html

Yoyogi Park
Located in Shibuya-ku.
Always crowded
Many Mosquitoes

New Big Problem

http://style.nikkei.com/article/DGXMZO05498640R00C16A8000000

Rapid communications

Identification of dengue type 2 virus in febrile travellers
returning from Burkina Faso to France, related to an
ongoing outbreak, October to November 2016
C Eldin ¹ , P Gautret ¹ , A Nougairede ² , M Sentis ¹ , L Ninove ² , N Saidani ¹ , M Million ¹ , P Brouqui ¹ , R Charrel ² , P Parola ¹
1. URMITE, Aix Marseille Université (UM63, CNRS 7278, IRD 198, INSERM 1095, IHU - Méditerranée Infection), Marseille, France
2. UMR ‘Emergence des Pathologies Virales’ (EPV: Aix-Marseille Univ - IRD 190 - Inserm 1207 - EHESP), Marseille, France
Correspondence: Carole Eldin (carole.eldin@gmail.com)
Citation style for this article:
Eldin C, Gautret P, Nougairede A, Sentis M, Ninove L, Saidani N, Million M, Brouqui P, Charrel R, Parola P. Identification of dengue type 2 virus in febrile travellers
returning from Burkina Faso to France, related to an ongoing outbreak, October to November 2016. Euro Surveill. 2016;21(50):pii=30425. DOI: http://dx.doi.
org/10.2807/1560-7917.ES.2016.21.50.30425
Article submitted on 03 December 2016 / accepted on 15 December 2016 / published on 15 December 2016

Dengue fever is rarely reported in travellers returning

viral RNA [4] and typed as dengue 2 viral RNA [5]. Bloodnew england
journal of medicineThe

established in 1812

january 8, 2015

vol. 372

no. 2

Efficacy of a Tetravalent Dengue Vaccine in Childrenin Latin America
Luis Villar, M.D., Gustavo Horacio Dayan, M.D., José Luis Arredondo-García, M.D., Doris Maribel Rivera, M.D.,
Rivaldo Cunha, M.D., Carmen Deseda, M.D., Humberto Reynales, M.D., Maria Selma Costa, M.D.,
Javier Osvaldo Morales-Ramírez, M.D., Gabriel Carrasquilla, M.D., Luis Carlos Rey, M.D., Reynaldo Dietze, M.D.,
Kleber Luz, M.D., Enrique Rivas, M.D., Maria Consuelo Miranda Montoya, M.D., Margarita Cortés Supelano, M.D.,
Betzana Zambrano, M.D., Edith Langevin, M.Sc., Mark Boaz, Ph.D., Nadia Tornieporth, M.D.,
Melanie Saville, M.B., B.S., and Fernando Noriega, M.D., for the CYD15 Study Group*

A BS T R AC T
Background

ArticlesIn light of the increasing rate of dengue
infections throughout the world despite
vector-control measures, several dengue vaccine candidates are in development.
Methods

In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin Americancountries where dengue is endemic, we randomly assigned healthy children between
the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant,live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and
12 under blinded conditions. The children were then followed for 25 months. The
primary outcome was vaccine efficacy against symptomatic, virologically confirmed
dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days
after the third injection.

The authors’ affiliations are listed in the
Appendix. Address reprint requests to
Dr. Dayan at Sanofi Pasteur, Discovery
Dr., Swiftwater, PA, 18370, or at gustavo.dayan@sanofipasteur.com.
* A complete list of investigators in the
CYD15 Study Group is provided in the
Supplementary Appendix, available at
NEJM.org.

Clinical eﬃcacy and safety of a novel tetravalent dengue
This article was published on November 3,
at NEJM.org.
vaccine in healthy2014,children
in Asia: a phase 3, randomised,observer-masked, placebo-controlled trial

Results

N Engl J Med 2015;372:113-23.
DOI: 10.1056/NEJMoa1411037

Copyright © 2014 Massachusetts Medical Society.

Maria Rosario Capeding, Ngoc Huu Tran, Sri Rezeki S Hadinegoro, Hussain Imam HJ Muhammad Ismail, Tawee Chotpitayasunondh,

A total of 20,869 healthy children received either vaccine or placebo. At baseline,
Mary Noreen Chua, Chan Quang Luong, Kusnandi Rusmil, Dewa Nyoman Wirawan, Revathy Nallusamy, Punnee Pitisuttithum, Usa Thisyakorn,
79.4% of an immunogenicity subgroup of 1944 children had seropositive status for
In-Kyu Yoon, Diane van der Vliet, Edith Langevin, Thelma Laot, Yanee Hutagalung, Carina Frago, Mark Boaz, T Anh Wartel, Nadia G Tornieporth,one or more dengue serotypes. In the per-protocol population, there were 176 VCD
Melanie Saville, Alain Bouckenooghe, and the CYD14 Study Group*
cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with5809 person-years at risk) in the control group, for a vaccine
efficacy of 60.8% (95%
SummaryChikungunya FeverChikungunya Virus

Spreading of CHIK fever

2010

2007
2005 to present2013 to present

1958 to present
2008 to present

1952 to present
Areas infested with A. aegypti
Areas infested with A. albopictus
Areas infested with A. aegypti
and A. albopictus
West African enzootic
ECSA enzootic
Asian urban
IOL urban

2005–20112014 to present

1952 to present

Figure 2. Origin, Spread, and Distribution of Chikungunya Virus and Its Vectors.
The map shows the African origins of enzootic chikungunya virus strains and the patterns of emergence and spread of the Asian lineage
N Engl J Med. 2015 Mar 26;372(13):1231-9.
and Indian Ocean lineage (IOL) of the virus during epidemics since the 1950s, based on phylogenetic studies.4, 5 The distributions of theReported cases of CHIK feverin JapanSouth Asia

Southeast Asia

Oceania

Latin America

Unknown

16

12

8

4

0

2006

2007

2008

2009

2010

2011

2012

2013

2014

Mosquito-borne diseases are spreading!

ZIKV infectionHOW ZIKA SPREADS

Other, less common ways, people get Zika:

During pregnancy
A pregnant woman
can pass Zika virus
to her fetus during
pregnancy. Zika cause
microcephaly, a severebirth defect that is asign of incomplete bra
development

Most people get Zika
from a mosquito bite

A mosquito bitesa person infectedwith Zika virus

The mosquito becomes infected

Through sex
Zika virus can besexually transmitted by
man to his partners
More members in thecommunity become infected
A mosquito will often live in a single
house during its lifetime

Through bloodtransfusion
There is a strong
possibility that
Zika virus can be
spread throughblood transfusions

More mosquitoes get
infected and spreadthe virus

The infected mosquito bitesa family member or neighborand infects them

Zika Virus•

Belongs to genus
Flaviviridae, which
includes DENV, West
Nile, and yellow fever
viruses•

Firstly isolated from thesentinel rhesus monkey
from the Zika Forest in
Uganda in 1947
Viruses 2015, 7(1), 219-238

How ZIKV spread?

http://ecdc.europa.eu/en/healthtopics/zika̲virus̲infection/zika-outbreak/pages/zika-countries-withtransmission.aspx
Regional Zika Epidemiological Update (Americas) - 7 July 2016

Nowadays cases reported in USA

ECDC. Zika transmission in South East Asia, as of 27 July 2017

東南アジアで流行している株は増殖能が低い？

ZIKV/Hu/S36/Chiba/2016

ZIKV/Hu/NIID123/2016

Paciﬁc clade

Southeast Asian clade

Hashimoto T, Kutsuna S, Tajima S, Nakayama, et al. Emerg Infect Dis. 2017 Jul

ZIKA in indonesia

The ﬁrst human cases in the world
were reported from Indonesia.
They were diagnosed by serology(Viruses were not isolated).

Am. J. Trop. Med. Hyg., 89(3), 2013, pp. 516–517
doi:10.4269/ajtmh.13-0029
Copyright © 2013 by The American Society of Tropical Medicine and Hygiene

Case Report: Zika Virus Infection Acquired During Brief Travel to Indonesia
Jason C. Kwong,* Julian D. Druce, and Karin Leder
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, Victoria, Australia;
Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia; Department of Epidemiology
and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

Abstract. Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or
missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever andrash. Further case identification is required to determine the evolving epidemiology of this disease.

+

+

+

+

A previously healthy 52-year-old Australian woman had
malaise and rash after a 9-day holiday to Jakarta, Indonesia.
On arrival in Australia, she initially reported some fatigue andnon-specific malaise, followed by a prominent headache. The
headache subsequently began to subside, but on day 4 of her
symptoms, a maculopapular rash developed that started onher trunk before spreading to her back and limbs, but not her
face. This rash was accompanied by generalized myalgia, someloose bowel movements, and an occasional dry cough. She did
not experience any significant sweats or rigors.
Examination on day 5 of her illness showed mild bilateral
conjunctivitis and a diffuse maculopapular rash, but no evidence of lymphadenopathy or tenosynovitis. Investigations at
this time showed a total leukocyte count of 3.6 109 cells /L(reference range = 4.0–11.0
109 cells/L), a hemoglobin
level of 137 g/L (reference range = 115–150 g/L), a hematocritof 39%, and platelet count of 230
109 cells/L (reference
range = 140–400
109 cells/L). Reactive lymphocytes were
present on a blood film. Baseline liver and renal function test
results were normal.
Dengue serologic analysis on day 5 of her illness showed
a positive result for IgG, a weakly positive result for IgM,
but a negative result for nonstructural protein 1 (NS1 antigen) by enzyme immunoassay. A generic flavivirus group
polymerase chain reaction (PCR) result was positive, andthe patient was provisionally given a diagnosis of dengue

tion of specific antibodies against Zika virus in serum or by
PCR detection of the virus.4–6 Detailed serologic testing of
the Yap Islands Zika virus outbreak in 2007 showed limited
cross-reactivity with IgM against other flaviviruses, including
dengue virus.7
To our knowledge, this is the first case of Zika virus infection reported in a returned traveler to Australia, althoughserologic evidence of Zika virus infection has been reported
in Java, Indonesia.8 The only other reported cases outsidevirus-endemic regions were in two U.S. scientists working in
Senegal who showed development of clinical infection after
returning to the United States, and one scientist subsequently
infected his wife, possibly through sexual transmission.9 However, it is likely that many cases are either undiagnosed(because of mild symptoms) or misdiagnosed, presumably mostcommonly as dengue fever, given their clinical similarities.
Cross-sectional surveys in Africa and Asia show higher seroprevalence of antibodies against Zika virus than is suggestedon the basis of the reported incidence of Zika infection.2
For returned travelers, accurate diagnosis and rapid differentiation from other possible travel-related illnesses is important in minimizing healthcare-associated morbidity. In ourpatient, although a provisional diagnosis of dengue fever was
made, the absence of thrombocytopenia and the negative
results for nonstructural protein 1 in the context of a positive
PCR result for flavivirus was believed to be unusual. To ourZIKV distribution

ECDC. Current ZIKA Transmission. Last updated on 7 November 2016

DENV distribution

WHO

CHIKV
distribution(as of October
20, 2015)

Countries and territories where chikungunya cases have been reported**Does not include countries or territories where only imported cases have been documented. This map is updated weekly if
http://www.cdc.gov/chikungunya/pdfs/chikungunyaworldmap_10-20-2015.pdf
there are new countries or territories that reportlocal chikungunya virus transmission.

Areas of distribution
are almost common
in these 3 diseases

We should also consider
ZIKV infection when we
consider DF or CHIK

Now ZIKV is spreading
to Southeast Asia, again

Imported cases of
ZIKV infection in Japan

First 3 cases diagnosed in
NCGM in 2013-2014

Rapid communications

Two cases of Zika fever imported from French Polynesia
to Japan, December 2013 to January 2014
S Kutsuna (sonare.since1192@gmail.com)1, Y Kato1, T Takasaki2, M L Moi2, A Kotaki2, H Uemura1, T Matono1, Y Fujiya1, M
Mawatari1, N Takeshita1, K Hayakawa1, S Kanagawa1, N Ohmagari1
1. National Center for Global health and Medicine, Disease Control and Prevention Center, Tokyo, Japan
2. Department of Virology 1, National Institute of Infectious Diseases, Shinjukuku, Tokyo, Japan
Journal of Travel Medicine, 2016, 1–3
doi: 10.1093/jtm/tav011
Citation style for this article:
Kutsuna S, Kato Y, Takasaki T, Moi ML, Kotaki A, Uemura H, Matono T, Fujiya Y, Mawatari M, Takeshita N, Hayakawa K, KanagawaBrief
S, Ohmagari
N. Two cases
communicationof Zika fever imported from French Polynesia to Japan, December 2013 to January 2014 . Euro Surveill. 2014;19(4):pii=20683. Available online: http://www.
eurosurveillance.org/ViewArticle.aspx?ArticleId=20683

Article submitted on 19 January 2014 / published on 30 January 2014

Brief communication

Zika fever imported from Thailand to Japan, andWe present two cases of imported Zika fever to Japan,
cases have been reported [3]. Symptoms of most ZIKV
diagnosed
by
PCR
in
the
urinesin travellers returning from French Polynesia, where
infection cases are mild and self-limited (mean dura-Do1an outbreak due
Zika virusMD(ZIKV)
is ongoingsinceMD1*, Tomohikotion of symptoms
is 3–6
No hospitalisations for
Kohto
Shinohara,, Satoshi
Kutsuna,
Takasaki,
MD2days).
,
week 41 of 2013.
This
reportraise awareness
acute
infection
been reported.
MakikoIkeda, PhD2, Akira
Kotaki,
PhD2have, Kei Yamamoto,
MD1,
Meng
Ling
Moi,serves
PhD2,to1among healthcare
professionals,
the differential, Momoko
Mawatari, MD1, Nozomi Takeshita, MD1,
Yoshihiro
Fujiya, MDthat
11diagnosis of febrilesubfebrilepatientsrash
1, Shuzowith
Kanagawa,
MDCase, Yasuyuki
Kato, MD1, andKayokoandHayakawa,
MD
1should includeZIKVOhmagari,
infection,MD
especiallyin patients
A previously healthy Japanese man in his mid-20s preNorioClinical Presentation
on ZIKV infection

dka
ka
es
an
ng
enth
us

ed
an
erdy
as
of
s-

REG F

3rd

CASE

Revised

Line
4-C
"
ARTIST: ts
H/T
H/T
22p3Zika Virus
Enon
Table 1. Clinical Characteristics of 31 PatientswithConfirmed
Combo
EMail

Disease on Yap Island during the Period from April through July 2007.

!   & '(#  $)$* '(#  ( Sign or Symptom
No. of Patients (%)
 (  '   % *

Macular or papular rash
Fever*

JOB: 36024

28 (90)ISSUE: 06-11-09

20 (65)Arthritis or arthralgia

20 (65)

Nonpurulent conjunctivitis

17 (55)

Myalgia

15 (48)Headache14 (45)Retro-orbital pain

12 (39)Edema

6 (19)

Vomiting

3 (10)* Cases of measured and subjective fever are included.
N Engl J Med 2009; 360:2536.

Symptomsn(%)

Exanthema

56 (98)Fever†

38 (67)

Days from symptom onset to
exanthema
Arthralgia

1 (0–2)33 (58)Itching

32 (56)

Headache38 (67)

Myalgia28 (49)Retro-orbital pain

23 (40)Conjunctivitis

22 (39)

Joint swelling

13 (23)
Emerg Infect Dis. 2016 Jul 15;22(6).

Diagnosis of ZIKV infection•

Detection of ZIKV by PCR••

blood or urine：ZIKV detected longer inurine than in blood

Antibody•

Cross reactivity is reported among other
Flavivirus(etc. DENV, YFV, JEV, …).
Am J Trop Med Hyg. 2014 Nov;91(5):1035-8.

More longer detection in saliva(45 days),and in semen(181 days)

Euro Surveill. 2016;21(32):pii=30316.

J Infect Chemother xxx (2016) 1e3

Contents lists available at ScienceDirect

Journal of Infection and Chemotherapy
journal homepage: http://www.elsevier.com/locate/jic

Case Report

A case of consecutive infection with Zika virus and Chikungunya virus
in Bora Bora, French Polynesia
Satoshi Kutsuna a, *, Yasuyuki Kato a, Eri Nakayama b, Satoshi Taniguchi b,
Tomohiko Takasaki b, Kei Yamamoto a, Nozomi Takeshita a, Kayoko Hayakawa a,
Shuzo Kanagawa a, Norio Ohmagari aabDisease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
Department of Virology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japana r t i c l e i n f o

a b s t r a c t

Article history:
Received 20 June 2016
Received in revised form
27 July 2016
Accepted 15 August 2016
Available online xxx

Chikungunya fever (CHIK) and Zika virus (ZIKV) infection have similar endemic areas and clinicalmanifestations. We report a case of CHIK at 1 year after a ZIKV infection in Bora Bora (French Polynesia),
which we diagnosed based on IgM to the CHIK virus and neutralizing antibodies to ZIKV.
© 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
Published by Elsevier Ltd. All rights reserved.

Keywords:
Chikungunya fever
Mosquito-borne diseases
Zika virus infection
Neutralizing antibody

Neutralizing Antibody is useful for the cases
which was infected more than 12 weeks ago.

1. Introduction

2. Case report

Dengue fever (DF), chikungunya fever (CHIK), and Zika virus(ZIKV) infection are mosquito-borne infections that are transmitted
by Aedes spp. mosquitoes [1e3]. However, their clinical diagnosis is
difﬁcult, as they have similar endemic areas and clinical manifestations. In addition, since January 2012, the Paciﬁc has experienced
a high burden of mosquito-borne disease, because of concurrent
epidemics of DF, CHIK, and ZIKV infection [4]. Furthermore, two

A previously healthy 40 year-old Japanese woman presented
with persistent arthralgia after living in Bora Bora for several years.
She had experienced a fever, myalgia, and arthralgia on January 12,2015, and had returned to Japan on January 19, 2015. She had no
medical history or allergies. Although her fever and myalgia
spontaneously subsided within one week, the bilateral arthralgia in
her wrists, elbows, shoulders, and knees persisted for one month.

Treatment
•

None

•

Only symptomatic treatment•

NSAIDs are not recommended for thepatients not distinguished from DF

Prognosis•

Almost mild.

•Rarely fatal cases reported, especially inelderly or patients with comorbidity.

Complication of
ZIKV infection•

Guillain-Barre syndrome•

meningoencephalitis•

myelitis•Congenital ZIKV infection(including microcephaly)
Epidemiological update: Complications potentially linked to the Zika virus outbreak,Brazil and French Polynesia. 27 Nov 2015

Articles

Guillain-Barré Syndrome outbreak associated with Zika virus
infection in French Polynesia: a case-control study
Van-Mai Cao-Lormeau*, Alexandre Blake*, Sandrine Mons, Stéphane Lastère, Claudine Roche, Jessica Vanhomwegen, Timothée Dub,
Laure Baudouin, Anita Teissier, Philippe Larre, Anne-Laure Vial, Christophe Decam, Valérie Choumet, Susan K Halstead, Hugh J Willison, Lucile Musset,
Jean-Claude Manuguerra, Philippe Despres, Emmanuel Fournier, Henri-Pierre Mallet, Didier Musso, Arnaud Fontanet*, Jean Neil*, Frédéric Ghawché*

Summary

Background Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreakever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting
a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus anddengue virus infection in developing Guillain-Barré syndrome.

Published Online
February 29, 2016
http://dx.doi.org/10.1016/
S0140-6736(16)00562-6
See Online/Comment
http://dx.doi.org/10.1016/
S0140-6736(16)00564-X

Methods In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre
Lancet. 2016 Feb 29. pii: S0140-6736(16)00562-6.
Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were *Contributed equally
age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness Unit of Emerging Infectious

CúcutaMedellin

T h e n e w e ng l a n d j o u r na l o f m e dic i n e

Cali

Original Article

Guillain–Barré Syndrome Associatedwith Zika Virus Infection in Colombia

No. of ZIKV Cases

B

Beatriz Parra, Ph.D., Jairo Lizarazo, M.D., Jorge A. Jiménez-Arango, M.D.,
Ph.D., Guillain–Barré
Guillermosyndrome
González-Manrique,
M.D., 60
7000 Andrés F. Zea-Vera, M.D.,ZIKV cases
cases
José Vargas, M.D., Jorge A. Angarita, M.D., Gonzalo Zuñiga, M.D.,
6000
Reydmar Lopez-Gonzalez, M.D., Cindy L. Beltran, M.D., Karen H. Rizcala, M.D.,50
5000 Maria T. Morales, M.D., Oscar Pacheco, M.D., Martha L. Ospina, M.D.,
40
Anupama Kumar, M.B., B.S., David R. Cornblath, M.D., Laura S. Muñoz, M.D.,
4000
Lyda Osorio, M.D., Ph.D., Paula Barreras, M.D., and Carlos A. Pardo, M.D. 30
3000
2000
1000

20

A BS T R AC T

0BACKGROUND
41 42 43 44 45 46 47 48 49 50 51 52

1

2

10

3

4

5

6

7

8

9

10 11 120

Zika virus (ZIKV) infection
has been linked to the Guillain–Barré
syndrome. From
2015
2016
November 2015 through March 2016, clustersof cases of the Guillain–Barré synWeek
drome were observed during the outbreak of ZIKV infection in Colombia. We characterized
the clinicalof cases of Syndrome
Guillain–Barré
syndrome in the context of
Figure 1.
Cases of ZIKVInfectionfeatures
and the Guillain–Barréin Colombia.
this ZIKV infection outbreak and investigated their relationship with ZIKV infection.

No. of Guillain–Barré Syndrome Cases

Neiva

From the Departm(B.P., A.F.Z.-V.), thenal Medicine, Hosp
Valle (A.F.Z.-V., G.Z
Salud Publica (L.O
Valle, Cali, Hospita

Cases of meningoencephalitis and myelitis
T h e n e w e ng l a n d j o u r na l o f m e dic i n e

C or r e sp ondence

Zika Virus Associated with Meningoencephalitis
To the Editor: Zika virus (ZIKV) is currently relationship between ZIKV infection
andReport
cerebralCase
spreading widely, while its clinical spectrum re- birth abnormalities1,2 is growing.3 An increased
mains a matter of investigation. Evidence of a incidence of some peripheral nervous syndromes
A

B

Acute myelitis due to Zika virus infection
Sylvie Mécharles, Cécile Herrmann, Pascale Poullain, Tuan-Huy Tran, Nathalie Deschamps, Grégory Mathon, Anne Landais, Sébastien Breurec,
Annie Lannuzel

In January, 2016, a 15-year-old girl with a history only of an

myelitis suggests that this virus might be neurotropic. In

Published Online

Microcephaly

Microcephaly•

Occipitofrontal circumference (OFC) morethan 2SD below the mean for age, sex, andgestation•

TORCH infections: Toxoplasmosis, Other(syphilis), Rubella, Cytomegalovirus (CMV) ,Herpes simplex virus (HSV). Previously known
as the causes of congenital anomaly including
microcephaly.
ECDC. Microcephaly in Brazil potentially linked to the Zika virus epidemic

Table 3. Countries and territories that have reported microcephaly and/or CNS
malformation cases potentially associated with Zika virus infection

Bolivia
BrazilCabo Verde
CanadaCosta Rica
Colombia
Dominican Republic
El Salvador
French Guiana
French Polynesia
GrenadaGuatemalaHaiti
Honduras
Marshall Islands
Martinique
PanamaParaguay
Puerto Rico
Slovenia

Number of microcephaly and/or CNS malformation
cases suggestive of congenital Zika virus infections or
potentially associated with a Zika virus infection
2
3
3
2079
9
1
1
4
54
5
10
4
6
10
8
1
7
15
1
1
1
6
12
5
8
2
9
3
10
1

Spain

2

SurinameThailandTrinidad and Tobago
Viet Nam
United States of America

2
2
1
1
11
28

Reporting country or
territory

Probable location of
infection
Bolivia
BrazilCabo Verde
Undetermined
Costa Rica
Colombia
Dominican Republic
El Salvador
French Guiana
French Polynesia
GrenadaGuatemalaHaiti
Honduras
Marshall Islands
Martinique
PanamaParaguay
Puerto Rico
BrazilColombia, Venezuela(Bolivarian Republic of)SurinameThailandTrinidad and Tobago
Viet Nam
Undetermined**The probable locations of three of the infections were Brazil (1 case), Haiti (1 case) and Mexico, Belize or Guatemala (1 case).

WHO. Zika situation report 3 Nov 2016

Clinical features of congenital Zika syndrome
FeatureDetails

Microcephaly▪
▪

Defined as occipitofrontal circumference <3rd percentile
Both proportionate and disproportionate microcephaly can occur

Other cranial dysmorphisms

▪
▪
▪
▪
▪
▪
▪
▪▪

Craniofacial disproportion
Overriding cranial sutures
Craniosynostosis
Cutis gyrata (redundant scalp)
Focal pigmentary mottling
Chorioretinal atrophy
Optic nerve abnormalities
Microphthalmia
Sensorineural hearing loss

Arthrogryposis▪
▪

Congenital contractures (arthrogryposis)
Unilateral or bilateral club footNeuromotor abnormalities

▪
▪
▪
▪

Hypertonia/spasticity
Hyperreflexia
Irritability
Dysphagia and feeding difficulties

Seizures▪

Focal or generalized

Small size for gestational age▪

Defined as birth weight <10th percentile for gestational age

Neuroimaging abnormalities▪

Intracranial calcifications (most commonly at the junction between the corticaland subcortical white matter)
Ventriculomegaly
Reduced brain volume
Delayed myelination
Simplified gyral patterns (eg, polymicrogyria, pachygyria)
Hypogenesis of the corpus callosum
Hypoplasia of the brainstem and cerebellum
Enlargement of the cisterna magna
Increased extra-axial fluid

Ocular abnormalities

Hearing loss

▪
▪
▪
▪
▪
▪
▪
▪

Ocular abnormalities
in CZS

JAMA Ophthalmol. 2016 Feb 9

Hearing loss in CZST h e n e w e ng l a n d j o u r na l o f m e dic i n e

Prolonged Shedding of Zika Virus
Associated with Congenital Infection

C or r e sp ondence

To the Editor: The presence of Zika virus (ZIKV) fants. We report a case of a newborn who had
infection has been associated with microcephaly continued viremia with ZIKV for at least 67 daysin multiple studies,1-3 although little is known after birth.
about ZIKV shedding in congenitally infected inOn January 2, 2016, a male child was born with

Prolonged Shedding of Zika Virus
Associated with Congenital Infection

A

Serum, urine, and saliva:

Serum and semen: ZIKV–To the Editor: The presence of Zika virus (ZIKV) fants.
report a case of a newborn
who hadZIKV+ onWe
qRT-PCR;
on qRT-PCR; IgG+
herpes (1-6)–, parvovirus
Serum: ZIKV+
infection has been associated with microcephaly
continued
viremia
with
ZIKV
for
at least 67 dayson qRT-PCR; IgM−
CSF: normal results B19– on PCR;
1-3
ZIKV sequenced
and IgG+ (low titer)in multiple
studies,although little isandknown
after
birth.
MotherFatherNewborn
VDRL–
Serum: ZIKV– on(accession no., KX443145)
ZIKV–
qRT-PCR;
IgM– child was Serum:
about ZIKV shedding in congenitallyNewborn
infected in- IgM+
On
2, 2016,
a
male
born
with
andJanuary
IgG+ (low titer)on qRT-PCR;
and IgG+deliveryA

Day Day0
1

Toxoplasma/rubella/CMV:
IgM– and IgG+
Symptoms of
Normal USG
Mother ZIKV infection
FatherApr. 28, 2015at 23 wk ofHIV−/VDRL−

gestationof infant

1st trimester
May–July

2nd trimester
Aug–Oct

Toxoplasma/rubella/CMV:
IgM– and IgG+

IgG+ (titer, >320)

2015

Day
4

Day
45

4
5
6
Day Day
0
1

17

Day
54

Day
59

Day
67

Day
216

2
Day
54

9
Day
59

2
Day
67

Serum, urine, and saliva:
Serum and sem
Symptoms of
ZIKV+ on qRT-PCR;
on qRT-PCR; Ig
ZIKV infection
herpes (1-6)–, parvovirus
Serum: ZIKV+
Toxoplasma/
CSF: normal results
Serum: ZIKV– on
at 26 wk of
B19– on PCR;
Serum: ZIKV– on qRT-PCR; Ig
rubella/ CSF: normal
with results
CMV–, EBV–,qRT-PCR;
gestationZIKV sequenced
Newborn
on qRT-PCR;
IgG+and IgG+ (low t
CMV: IgM– and and VDRL–
herpes (1-2)–, andIgM– and IgG+
Serum:ZIKV– onno., KX443145)
IgG+
toxoplasma– on (accession
PCR;
Se
qRT-PCR; IgM–
Normal USG
IgM+
and
IgG+
(low
titer)
serum:
toxoplasma–on
PCR
Newbornonand IgG+
Dec. 28, 2015
deliveryIgG+
3rd trimester
Nov–Jan2

3

Symptoms of
ZIKV infection January
Toxoplasma/2016
at 26 wk of

Day
4

26

Day
45

February
March
AugustCSF: normal results 2016 Serum: ZIKV– on 20162016

Association between Zika virus and microcephaly in French
Polynesia, 2013–15: a retrospective study
Simon Cauchemez, Marianne Besnard, Priscillia Bompard, Timothée Dub, Prisca Guillemette-Artur, Dominique Eyrolle-Guignot, Henrik Salje,
Maria D Van Kerkhove, Véronique Abadie, Catherine Garel, Arnaud Fontanet*, Henri-Pierre Mallet*

Summary

Number of microcephaly cases per 10 000

Background The emergence of Zika virus in the Americas has coincided with increased reports of babies born with
75 1, 2016, WHO declared the suspected link 200
microcephaly. On Feb
between Zika virus and microcephaly to be a Public
Health Emergency of International Concern. This association, however, has not been precisely quantified.

Overall attack rate (%)

Methods We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest
documented outbreak before that in the Americas. We used serological and surveillance data to estimate theprobability of infection
70 with Zika virus for each week of the epidemic
150 and searched medical records to identify allcases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in
pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk.
Findings The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62–70) of thegeneral population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven(88%) occurred in65
the 4-month period March 1 to July 10, 2014.100
The timing of these cases was best explained by aperiod of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases(95% CI 0–8) per 10 000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases(34–191) per 10 000 women infected in the first trimester. We could not rule out an increased risk of microcephaly
from infection in other trimesters, but models that excluded the first trimester were not supported by the data.

60

50Interpretation Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose
mothers are infected with Zika virus.
Funding Labex-IBEID, NIH-MIDAS, AXA Research fund, EU-PREDEMICS.

Introduction

55

Zika virus is an arthropod-borne virus in the genus ofFlavivirus.1 Since identification of Zika virus infection in
Brazil in May, 2015, the virus has spread throughout the0

Published Online
March 15, 2016
http://dx.doi.org/10.1016/
S0140-6736(16)00651-6
See Online/Comment
http://dx.doi.org/10.1016/
S0140-6736(16)00742-X*Senior authors

dur
assu
con
in t

Mathematical Modelling of
Infectious Diseases(S Cauchemez PhD, H Salje PhD),
Emerging Diseases
Epidemiology Unit (T Dub MPH,
Prof A Fontanet DrPh), andCentre for Global Health(M D Van Kerkhove PhD,Prof A Fontanet), Institut
Pasteur, Paris, France; Neonatal
Care Department(M Besnard MD), Medical
Imaging Department(P Guillemette-Artur MD), andGynecology-Obstetrics
Department(D Eyrolle-Guignot MD), French
Polynesia Hospital Centre,
Pirae, Tahiti, French Polynesia;
Bureau de Veille Sanitaire,
Direction de la Santé, Papeete,
Tahiti, French Polynesia(P Bompard MPH,
H-P Mallet MD); Department of
Epidemiology, Johns Hopkins

been associated. Cases have also been reported after
Zika virus
intrauterine infectionBaseline
with West Nile virus (anotherflavivirus)17 and chikungunya virus.18
infection in T1
On Feb 1, 2016, WHO declared the suspected link

pI (w

T
bas
stud
out

ZIKV infection as STD

First report of sexuallytransmitted ZIKV infection

DOI: 10.3201/eid1705.101939

Suggested citation for this article: Foy BD, Kobylinski KC, Foy JLC, Blitvich BJ, Travassos da
Rosa A, Haddow AD, et al. Probable non–vector-borne transmission of Zika virus, Colorado,USA. Emerg Infect Dis. 2011 May; [Epub ahead of print]

Probable Non–Vector-borne Transmissionof Zika Virus, Colorado, USA
Brian D. Foy, Kevin C. Kobylinski, Joy L. Chilson Foy, Bradley J. Blitvich,
Amelia Travassos da Rosa, Andrew D. Haddow, Robert S. Lanciotti, and Robert B. Tesh
Author affiliations: Colorado State University, Fort Collins, Colorado, USA (B.D. Foy, K.C. Kobylinski); Poudre Valley
Hospital, Fort Collins (J.L.C. Foy); Iowa State University, Ames, Iowa, USA (B.J. Blitvich); University of Texas Medical
Branch, Galveston, Texas, USA (A. Travassos da Rosa, A.D. Haddow, R.B. Tesh); and Centers for Disease Control
and Prevention, Fort Collins (R.S. Lanciotti)

Emerg Infect Dis. 2011 May; 17(5): 880–882.

Potential Sexual Transmission of Zika Virus
Didier Musso, Claudine Roche, Emilie Robin, Tuxuan Nhan, Anita Teissier, Van-Mai Cao-Lormeau

ZIKV detected in semenVHPHQ
62 FRQ¿UPHG
days after
onset
KHPDWRVSHUPLD
:H H[WUDFWHG 51$ XV-

In December 2013, during a Zika virus (ZIKV) outbreak in
French Polynesia, a patient in Tahiti sought treatment forhematospermia, and ZIKV was isolated from his semen.
ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility
that ZIKV could be transmitted sexually.

LQJWKH1XFOL6(16HDV\0$*V\VWHPELR0pULHX[0DUF\Emerg Infect Dis. 2015
Feb;21(2):359-61.
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UHYHUVH WUDQVFULSWLRQ 3&5 U573&5  DV GHVFULEHG XVLQJ
ika virus (ZIKV) is a mosquitoborne arbovirus in the  SULPHUVSUREH DPSOL¿FDWLRQ VHWV VSHFL¿F IRU =,.9 3).
family Flaviviridae, genus Flavivirus,WZDV¿UVWLVR- 7KH U573&5 UHVXOWV ZHUH SRVLWLYH IRU =,.9 LQ VHPHQ
lated in 1947 from a rhesus monkey in the Zika forest of DQG QHJDWLYH LQ EORRG DQG FRQ¿UPHG E\ VHTXHQFLQJ RI
Uganda (1). Sporadic human cases were reported from the the genomic position 858–1138 encompassing the prM/EVLQ$VLDDQG$IULFD7KH¿UVWUHSRUWHGODUJHRXWEUHDN protein coding regions of ZIKV. The generated sequence*HQ%DQNDFFHVVLRQQR.0 ZDVLGHQWLFDOWRWKRVH
occurred in 2007 on Yap Island, Federated States of Micronesia (2). The largest known ZIKV outbreak reported start- previously reported at the beginning of the ZIKV outbreak
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estimated 28,000 persons (11% of the population) sought from this second collection were not found to contain tracblood by both
direct days
and macroscopic
medical care for the illness (4). The
most common
symp- es
ZIKV
detected
inofsemen
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toms of Zika fever are rash, fever, arthralgia, and conjuncti- U573&5GHWHFWHG=,.951$LQWKHVHPHQDQGXULQHEXW
vitis. Most of the patients had mild disease, but severe neu- not in the blood sample.
:HTXDQWL¿HG=,.951$ORDGVXVLQJDQ51$V\Qrologic complications have been described in other patients
thetic transcript standard that covers the region targetedin French Polynesia (5).
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7
Euro Surveill.
2016;21(32):pii=30316.
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The StudyZ

MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):372-4.

C
Correspondence
Zika virus in the female
genital tract

virus infection (RealStar Zika Virus
Symptom
May 9, 20
RT-PCR Kit 1.0; Altona Diagnostics
GmbH, Hamburg, Germany), and theBlood+
The first human Zika virus infection patient tested positive for Zika virus inUrine–
was documentedSymptom
in Nigeria
in 1954, the blood sample and negative in the
Cervical mucus··
onset, Genital testing, Follow-up,
ZIKV detected inEndocervicalfemaleswab
genitalwith very few documented··
May 9, 2016 infections
May 12, 2016urinary
Maysample.
20, 2016
The– patient was monitoredtract
for oocyte
after
until the·· virus
swab
11 daysGenital
after
onset ··
Bloodthis initial report,+
because we follow
outbreakin 2007– on Yap Island ··in the cryopreservation,
Urine–+=positive for Zika virus. –=negativ
Agence de la Biomedecine
western
Pacific Ocean.
The infectionis the French
Cervical mucus··++
Female to MaleTable:transmission
RT-PCR Zika virus results(ABM)
usually
asymptomaticbut symptoms
Endocervicalswab ··+·· recommendations for infertile5
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canconsistmaculopapular
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Zika virus infection has been terminated and she agreed to continue results could occur.
Table: RT-PCRwith
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associatedadversewith the ABM recommendations of safe
Our findings raise theZIKV detected in vaginal secretions 14days after onset

Rapid communications

Sexual transmission of Zika virus in an entirely
asymptomatic couple returning from a Zika epidemicarea, France, April 2016
T Fréour 1 2 , S Mirallié 1 2 , B Hubert 3 , C Splingart 1 , P Barrière ¹ , M Maquart ⁴ , I Leparc-Goﬀart ⁴
1. Service de médecine de la reproduction, CHU de Nantes
2. These authors contributed equally as first authors
3. Santé publique France, French national public health agency, Regional unit (Cire) Pays de la Loire, Saint-Maurice, France
4. French Armed Forces Biomedical Research Institute, Marseille, France
Correspondence: Isabelle Leparc-Goﬀart (isabelle.leparcgoﬀart@gmail.com)
Citation style for this article:
Fréour T, Mirallié S, Hubert B, Splingart C, Barrière P, Maquart M, Leparc-Goﬀart I. Sexual transmission of Zika virus in an entirely asymptomatic couple returningfrom a Zika epidemic area, France, April 2016. Euro Surveill. 2016;21(23):pii=30254. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.23.30254
Article submitted on 30 May 2016/ accepted on 09 June 2016 / published on 09 June 2016

The current Zika virus outbreak and its potential
severe health consequences, especially congenital
fetal syndrome, have led to increased concern about
sexual transmission, especially in pregnant women
and women of reproductive age. Here we report acase of Zika virus sexual transmission, likely male-tofemale, in a totally asymptomatic couple.
Zika virus (ZIKV) is a mosquito-borne flavivirus transmitted by Aedes species [1,2]. It is also the first flavivirus known to be sexually transmittable between
symptomatic patients [3-6]. We here report a ZIKV sexual transmission in a couple returning from Martinique,whereby both partners were asymptomatic.

Description of cases

after sperm preparation on gradient were also to betested for ZIKV RNA by RT-PCR [8]. The couple was thus
informed that the IVF-D cycle would be delayed and an
appointment for the ZIKV RNA tests was scheduled 39
days after their return from the holiday (Figure).
Virological diagnosis was performed as previously
described [3]. The woman tested positive for ZIKV RNA
by RT-PCR in blood (i.e. serum) and urine samples. The
man tested negative for ZIKV RNA in blood, but positive in urine and seminal plasma. Sperm cell suspension was not tested for ZIKV, as he was azoospermic.
Serological analysis for the man indicated the presenceof anti-ZIKV IgM (absence of anti-dengue IGM) and antiflaviviruses IgG. At the time of the consultation andduring the following week, both partners reported having no clinical symptoms of ZIKV infection during andafter their stay in Martinique (i.e. no fever, cutaneous
manifestation, arthritis, nor myalgia).

2 reports sexually transmitted fromasymptomatic male to female

A couple wishing to have children was referred to ourAssisted Reproduction Treatment (ART) centre for invitro fertilisation with donor semen (IVF-D), as the malepartner had non-obstructive azoospermia. The couple
presented for a first consultation in early February 2016

As Ae. albopictus and Ae. aegypti are not establishedRisk assessment about
sexual transmission•

ZIKV sexual transmission is not rare•

Male to Female, Female to Male, Male to Male reported.

•

Unknown how long do they continue to be infectious•

ZIKV detected in saliva, however unknown whether it isinfectious or not•

Transmission could happen from completely
asymptomatic male to female

Interim Guidance for Preconception Counseling andPrevention of Sexual Transmission of Zika Virus for
Persons with Possible Zika Virus Exposure
male
For Pregnant Women and
Their Partners

Not
pregnant

femaleduring pregnant

conﬁrmed or
symptomatic

6 months

8 weeks

No symptoms

6 months

8 weeks

Live in Areas with
Active Zika Virus
Transmission

should be counseled

MMWR Morb Mortal Wkly Rep. 2016 Oct 7;65(39):1077-1081.

T h e n e w e ng l a n d j o u r na l o f m e dic i n e

C or r e sp ondence
T h e n e w e ng l a n d j o u r na l o f m e dic i n e

Evidence for Transmission of Zika Virus by Platelet Transfusion
Table 1. Resultsof Molecular
Testing isof Samples
Obtainedsive
from
the Platelet
Donor pretransfusion
and the Two Recipients.*
To theEditor: andZikaSerologic
virus (ZIKV)
a mosquitotherapy.
Routinesamples ob-borne virus that has important secondary means tained from the two patients were negative on
PCR assay for CHIKV,
SerologicDENV,
Testing and ZIKV, butmodes.1-3 The potential for transmission in trans- samples collected 6 days after platelet transfuZIKV (Ct)‡blood components
CHIKV
DENV
PRNT§
IgG¶ 1 andZIKV
POC∥
DENV-Capture
fused donatedhas beena sion IFA
in Patient
23 to
51 days after
platelet ELISA**
concernowing tothe detectionZIKV viremia
in Patientfor ZIKV IgG
PlasmaUrine
Plasma ofPlasma
ZIKV transfusion
ZIKV
DENV
IgM 2 were
IgGpositive IgM
in healthy blood donors.4
on PCR assay.
Donor
This report from Brazil describes two cases
Molecular sequencing and phylogenetic analyDay −3
Pos (23)of likelyZIKV transmissionNeg
by bloodNeg
transfusion sis of ZIKV RNA isolated from the donor and
one presymptomatic
infected Neg
person 1:1280
who from++the two
confirmed
identity
Day 11 from Neg
Pos (33)
Neg+/−patientsPos (143)
Pos (239)thePos(1.4) ofNeg (0.5)
Patient 1 donated platelets by apheresis on January 16, their ZIKV isolates, with nucleotide changes in the2016.Neg
The two leukodepleted
plateletunits were envelope
gene(codons 11 Pos
and(57)186) Neg
sharedonly Pos (5.0)
Day −4Neg
Neg−+++ Neg (7)(0.6)
irradiated with 25 Gy delivered by an IBL-437C by the donor and platelet recipients among availDay 6
Pos (33)
Neg
Neg+++++ Neg (9)Sus (32)
Neg (0.7)
Pos (4.9)
gamma irradiator (Cis Bio International) and able isolates from Brazil (GenBank accession
Day 31 were transfused
Neg
1:2560 numbers,++++++++ Sus (33)
Pos (335)KX173842,
Pos (2.3) and Pos (5.4)
in different patients on January
KX173840,
KX173841,
Patient 2 19 (day 0). On January 21, the donor called the KX173844) (Table S1 in the Supplementary ApbloodNeg
bank to report a cutaneousrash, retro- pendix). Against a backdrop of a high degree ofDay −1Neg
Neg
orbitalNeg
pain, and pain in Neg
both knees
Day 1
Neg that had conservation (>99% nucleotide identity) of ZIKV
begun on January 18. An investigation was initi- isolates in the Western Hemisphere,5 the possibilDay 23
Pos (36)
Neg
Neg
Neg
1:40
−
−
Neg (7)
Sus (20)
Neg (0.1)
Neg (0.3)
ated under the hospital’s clinical protocol for ity of a single spatiotemporal cluster of mosquitoDay 51 transfusion-associated
Neg/Pos††+++/− wasNeg further(4) Neg(17) Neg (0.2)
adverse events, with 1:20
the acquiredcases
underminedby theNeg (0.3)
Day 71 donorNeg(12) 200
Neg(5) away from Rioand both patients providing written in- fact that Patient Neg
2 livedkm
formed consent.
de Janeiro. Although neither patient was hospiDonor orthat include
Patient† of transmission
Molecular
Testingperinatal and sexualT h e n e w e ng l a n d j o u r na l o f m e dic i n e

C or r e sp ondence

Fatal Zika Virus Infection with Secondary Nonsexual
Transmission
To the Editor: Epidemic transmission of Zika
virus (ZIKV) has rapidly occurred in the Americas, with most cases limited to mild or asymptomatic disease.1,2 To date, nine deaths from ZIKV
infection that were unrelated to the Guillain–Barré
syndrome have been confirmed in adults.1 Here,
we report a rapidly progressive, fatal ZIKV infection acquired outside the United States and secondary local transmission in the absence ofknown risk factors for ZIKV infection.
Patient 1, a 73-year-old man who had emigrated to the United States from Mexico in 2003,
was admitted to a hospital in Salt Lake City withhypotension and abdominal pain. Radiation
therapy for stage IIB prostate cancer had been
completed 1 month earlier, and he was receiving

anemia, and marked thrombocytopenia. (Details
are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.)
Testing for malaria and blood cultures were negative. A presumptive diagnosis of dengue shock
syndrome was made. The patient’s clinical deterioration progressed, with progressive respiratory and renal failure, metabolic acidosis, andhepatitis. On day 4 of hospitalization, the patient died shortly after care was withdrawn.
Testing was negative for dengue virus (DENV)
on polymerase-chain-reaction (PCR) assay. Serologic analysis for DENV was consistent with remote infection, with a highly elevated IgG level
and an equivocal IgM level. Serum testing for
ZIKV on real-time PCR assay was positive, with

Mysterious case of ZIKV infection without obvious exposure
・No exposure of mosquitos in ZIKV endemic countries
・No sexual exposure with patients of ZIKV infection
・The case had provided care to the patient of ZIKV
infection(with high level viremia)

Take Home Message•

Mosquito-borne disease is global threat•

DENV, CHIKV, ZIKV spreading all over theworld, and spreading of ZIKV in Southeast
Asia•

Microcephaly caused by congenital ZIKV
infection is serious problem