2018年8月2日

エボラ(58)-コンゴ(民) ザイール確定
麻疹(48) PAHO、ベネズエラ、ブラジル、米国、英国、ウクライナ
ジカウイルス(08)
  米国、メキシコ、グアテマラ、ホンジュラス、コスタリカ
  プエルトリコ、ブラジル、コロンビア、ポルトガル アンゴラから、台湾

エボラ(58)-コンゴ(民) ザイール株確定
PRO/AH/EDR> Ebola update (58): Congo DR (NK) outbreak, Ebola Zaire confirmed
Archive Number: 20180802.5944088
[1] 最新情報: Ebola Zaire confirmed
情報源 Ministry of Health press release 2018年8月2日
保健相は 2日、保健省の専門家および WHO, UNICEF, the World Bank, and MONUSCO 等の関係者らとともに Beni and Mangina, North Kivu province を訪れ、現地の状況およびニーズの調査を行った ... the mobile laboratory が設置され、2日から稼働している。10回目となる今回の流行の発生の中心地とみられる Mangina は、Beni からおよそ 30km、the neighboring health area of Makeke, in Ituri province からは 400mに位置する ... the Mangina Reference Health Center (CSR) には複数の患者 some active cases が隔離入院している ... 7月31日に the INRB で行われた the 6 samples のうち、 4 件の検体で Ebola virus serotype Zaire 陽性が確認された。
[Mod.LK 注- ... アクセスが困難かつ危険とみられる North Kivu, DRC において、ontact tracing and ring vaccination は可能なのだろうか]
[2] エボラ: 新たなアウトブレイク
情報源 Reuters 2018年8月1日
北西部における 33人が死亡したアウトブレイクの終息が宣言されてから、わずか数日後のコンゴ民主共和国の東部で 4人がエボラ検査で陽性と確認されたと、1日保健省が明らかにした。southwest of the city of Beni から約 30km、ウガンダ国境からは 100kmに位置する、人口が密集する町 in and around Mangina において、出血熱によりすでに 20人が死亡したと発表されたが、死亡した時期は明らかにされていない ... around Beni  では、2014年以降およそ 1000人の市民が武装勢力や政府軍兵士により殺害されており、the wider region of North Kivu は 100万人を超える難民を抱えている。[Mod.LK 注-ウイルス学に関するブログ Virology Down Under のサイトには、内戦 the DRC conflict にが多数の性暴力の被害者、食料不安、難民を生んでいると記載] ... この地域は、隣国のルワンダとウガンダとの間の商取引が盛んであり、ウイルスが国境を越えて拡大するリスクが懸念されている ... 保健省は、2018年4月に 2500km以上離れた北西部で発生した最近のアウトブレイクとの関連を示す証拠はないとしている。ウイルス名の由来となっている北部のエボラ川付近のおける 1976年の発見以来、アフリカ中央部にある同国で発生した 10回目のアウトブレイクであり、他のどの国と比べても 2倍以上の回数となっている ...  the Merck vaccine は the Zaire strain of Ebola に対するワクチンであり、今回のアウトブレイクのウイルス株は特定されておらず、the WHO も "presumptive Ebola." と述べるにとどまっている。ワクチンの使用の可能性についても言及を避けた。しかしワクチンの使用の有無に関わらず、過去のアウトブレイクへの対策において重要なことは、積極的な患者の拾い上げと素早い対応であることが示されている ...
[Mod.LK 注-20180801.5941427 においても、この地域で活動することの危険性が議論されており、”Travel into and out of the village of Mangina has been blocked” [Washington Post]。また、発生地域の近くに有名な野生動物公園 2 of Africa's best-known wildlife parks, Virunga and Rwenzori がある。今回のアウトブレイクが起きている North Kivu province はルワンダおよびウガンダに接している。また、近年 Beni は激しい戦闘が行われている場所で、2014年から 2016年の間に 800人以上が殺害されているが、その多くが machete(サトウキビ刈り取り用のなた)によるものである。
The Bikoro outbreak は、実験的ワクチン an experimental vaccine provided by Merck that targeted the Ebola Zaire strain の使用により終息した ... エボラウイルスには 6種類のウイルス species of ebolavirus があり、Ebola outbreaks in the DRC の多くが Ebola Zaire によるものであったが、2007年にウガンダ西部で発生した大規模アウトブレイク (1) と、2012年の the DRC in 2012 (2), in Orientale Province in the NE は、Bundibugyo ebolavirus (BEBOV) が原因ウイルスであった ... 2500km も離れていることから、9回目のアウトブレイクからの感染拡大の可能性は低い。the Merck vaccine rVSV-ZEBOV は、the anti-viral ZMapp と同じく against Zaire Ebola virus として開発されていることから、このアウトブレイクも Ebola Zaire によるものであることを願う。 rVSV-ZEBOV が、どの程度の他のエボラウイルス株への交差感染防御作用 cross-protection レベルを有するかは不明である ... "rVSV-ZEBOV の単回接種により、相当な交差感染防御 significant cross-protection (75 percent survival) が認められたことから、この monovalent rVSV-based vaccines ワクチンによる、新興株ウイルス newly emerging species への効果が期待される" (www.ScienceTranslationalMedicine.org. 9 Dec 2015; 7(317): 24)]
[3] 準備態勢
情報源 WHO 2018年8月1日
FORTHより
コンゴ民主共和国政府は本日、予備的な検査の結果、北東部の北キブ(Kivu)州においてエボラウイルス病の集団発生が示されたと発表した ... 保健省は、キンシャサの国立医生物学研究所(Institut National de Recherche BiomedicaleINRB))において検査された6つの検体のうち4つがエボラウイルス陽性と診断されたとWHOに伝え、さらに検査は継続されている ... 症例の大半はベニ(Beni)市から30kmのマンギナ(Mangina)保健区域にで発生した ... 北キブ州には、100万人以上の避難民が生活しており、ルワンダとウガンダとの国境では、貿易活動のために多くの人々が国境を越えて移動している ...
[4] 対応
情報源 Actualite.cd [machine trans.] 2018年8月2日
保健省の専門家らが 2日、Beni (North Kivu) 市から 30 km の the locality of Mangina で報告された the outbreak of Ebola に対応するため、同市に到着した ... 今回 the 10th Ebola outbreak reported in the DRC となる。保健省によると、the health wing of Mangina located in the health zone of Mabalako, Beni territory, in the province of North Kivu において、すでに 20人の死亡が報告されている。
[Mod.LK 注-This report states that the United Nations Mission for the Stabilization of the Democratic Republic of Congo (MONUSCO) will provide logistical support and security ... MONUSCO and the United Nations Development Assistance Framework (UNDAF) for the period 2013-2017 developed jointly with the DRC government ...]
関連項目
Ebola update (57): Congo DR (NK): 20180801.5941427

麻疹(48) PAHO、ベネズエラ、ブラジル、米国、英国、ウクライナ
PRO/EDR> Measles update (48): Americas, Europe
Archive Number: 20180802.5943952
[1] 南北アメリカ: increase in cases, update, PAHO
Measles in the Americas: New epidemiological update
情報源 PAHO/WHO [in Spanish] [in English] 2018年7月26日
7月20日に発表された、汎米保健機関の最新の疫学報告 the latest epidemiological update from the Pan American Health Organization (PAHO) によると、今年、地域内の 11カ国から合計 2472例の確定された麻疹感染 confirmed cases of measles が報告されている: ベネズエラ (1613 cases)、ブラジル (677), followed by 米国 (91), コロンビア (40), カナダ(19), エクアドル(17), アルゼンチン(5), メキシコ(5), ペルー(3), アンティグア・バーブーダ (1) and グアテマラ(1)。前回の 6月8日の時点では、1685例が報告されていた。ベネズエラとブラジル両国で、92% 以上の患者が報告されている ...
Measles in indigenous communities
原文参照願います。
[2] ベネズエラ (Tachira)
First case of measles in Tachira, Venezuela
情報源 El Pitazo [machine trans.] 2018年7月29日
生後 11ヶ月の乳児が、ベネズエラ人の両親とともに首都カラカス [Caracas] がやってきた。麻疹症状が現れている時期に国境に向かった。地域の疫学担当者によると、この症例が the region (Tachira state) で確定診断された唯一の麻疹感染例である。the Andean entity において診断が確定された。同じく、the area of Palo Gordo, Cardenas municipality でも麻疹感染が疑われる例があったが、検査で水痘であることが判明した。
[3] ブラジル
情報源 Naaju 2018年7月25日
ワクチンの接種率の低下(2014年 100% → 2017年 85 %、貧しい Para 州では 2017 年 68.45 %) がアウトブレイクの要因、the state of Roraima ではベネズエラからの移民による輸入感染、Amazonas and Roraima において 660 confirmed cases of measles が確認されたほか、the confirmed ones in Rio Grande do Sul (8), Rio de Janeiro (7), Sao Paulo (1) and Rondonia (1) と報告、など(長文、原文参照願います)。
[4] 米国 (Michigan)
情報源 Up Matters 2018年8月2日
ミシガン州保健当局 MDHHS [Michigan Department of Health and Human Services] が 2 additional cases of measles in Michigan for 2018 を確認し、2018年の 7月までの時点で、州内で確認された患者は合計 4例となった。昨年は 1年間で 2例のみだった。今回感染が確認された residents of Oakland and Washtenaw counties は、以前の 2例に関連していたが、4例とも海外での暴露によるものだった ...
[5] 英国 (Yorkshire)
情報源 Hull Live 2018年8月1日
Yorkshire において 70例を超える麻疹感染が確認されており、Hull parents に対し、自身と子供のワクチン接種を確認するよう呼びかけられている。1月以降、英国各地で 757 cases -- including 73 in Yorkshire and the Humber -- が報告されている ... イタリア、フランス、ギリシャのほか、ルーマニア、ウクライナ、セルビア、ロシア、アルバニアで、多数の麻疹が報告されている ...
[6] ウクライナ
情報源 Ukrinform 2018年8月1日
ウクライナ国内で先週、合計 822人が麻疹に感染したが、前週比では 6.8 % 減少したと、公衆衛生当局 the Public Health Center of the Health Ministry が報告した。 " ... 352 adults and 470 children. ...," と報告されている。年初以来 27 502 人: 11 142 adults and 16 360 children が麻疹に感染し、13 people -- 9 children and 4 adults -- が合併症で死亡している。

ジカウイルス(08)
  米国、メキシコ、グアテマラ、ホンジュラス、コスタリカ
  プエルトリコ、ブラジル、コロンビア、ポルトガル アンゴラから、台湾
PRO/AH/EDR> Zika virus (08): Americas, Europe, Africa, Asia, research, observations
Archive Number: 20180802.5943825
[1] Cases in various countries
Americas cumulative case numbers
As of 4 Jan 2018 [A list of 2018 cases is not available but 2017 cases by country]
- 米国 (Alabama). 5 Jun 2018. (conf.) アラバマ州の Mobile, Alabama で 20年ぶりに、ネッタイシマカ _Aedes aegypti_ が確認された。
- メキシコ (Jalisco state). 1 Aug 2018. (conf.) 27 cases: Affected municipalities: Tomatlan 10 cases, Puerto Vallarta 11 cases and San Sebastian del Oeste 6 cases.
- グアテマラ (Quetzaltenango department). 18 Jul 2018. [in Spanish](Conf.) 278 cases.
- ホンジュラス 17 May 2018. [in Spanish](conf.) 28 cases; Guillain-Barre syndrome 22 cases [not stated if all had been infected by Zika virus]
[A 13 Jul 2018 report  [in Spanish] では、2 pregnant women infected by Zika virus are under observation. と伝えられていた]
- コスタリカ 27 Jun 2018. (probable) up to week 23, 218 cases, (conf.) 865 cases.
[An earlier report [in Spanish]indicated that there are 4 cases of microcephaly]
Mexico(メキシコ)and Central America retrospective. 24 May 2018. (published) 61 Zika virus genomes の解析により、2014年後半のホンジュラス経由でブラジルからの導入など、multiple independent ZIKV introductions to Central America and Mexico があったことが確認されており、2年ごとの感染伝播ピーク発生 biannual peaks of ZIKV transmission in the region の説明にもなっている
- プエルトリコ 27 Jul 2018. (published) the study confirmed infectious virus in semen from 8 of 97 patients for up to 38 days after initial detection when virus loads are higher than 1.4x10 ^6 GCE/mL.
[This study illustrates that the presence of detectable genomic fragments in semen, in one instance for over 180 days after the appearance of symptoms, does not necessarily imply that infectious virus is present. ]
- ブラジル
 National. 10 Jul 2018.[in Portuguese] (conf.) 1674 cases; Southeast Brazil most  National. 9 Jun 2018.  [in Portuguese](susp.) as of 21 Apr 2018, 2985 cases.
 Births. 29 May 2018. (Published) 出産数減少 119 095 fewer births than expected
 Genetically modified mosquitoes. 24 May 2018. (announced)
- コロンビア 6 Jun 2018. [in Spanish] (conf.) 194 cases; Congenital infections 3 cases, one of whom had microcephaly.
-ポルトガル、アンゴラから 25 Jul 2018. (conf.) 1st report that shows the circulation of the Asian lineage in Angola and the 1st report of a congenital Zika syndrome in continental Africa.
Trans R Soc Trop Med Hyg. 2018 Jul 25. doi: 10.1093/trstmh/try074
- ウガンダ
 Case count. 5 Jul 2018. (published) 384件の血液検体のうち、5件が positive for ZIKV IgM だった ...
 WHO advisory. 13 Jul 2018. (reported) The World Health Organization (WHO) has issued guidelines advising pregnant women against travelling to Uganda as a classified Zika-Infected country, with a potential of causing birth defects to unborn babies.
- 台湾、フィリピンから 29 Jul 2018. (conf.) 1st case, woman ex Cebu, Philippines.
- タイ 9 Sep 2018. (published on line ahead of print) 3人の妊婦の the Asian lineage ウイルス感染が確認され、妊娠 9週で感染した妊婦は胎児の小頭症が認められたが、weeks 20 and 24 で感染した妊婦の胎児には認められなかった。これまでにアジアで報告された、小頭症を伴うジカウイルス感染例は 3例のみ (2 Thailand, 1 Vietnam).
Imported cases with little or no possibility of ongoing mosquito transmission 
[2] Infants, children and adolescents
Date: Tue 29 May 2018
Source: AMA Pediatr. Published online doi:10.1001/jamapediatrics.2018.0870 [edited]
https://jamanetwork.com/journals/jamapediatrics/article-abstract/2681638?resultClick=1


Jennifer S. Read, MD, Brenda Torres-Velasquez, PhD, Olga Lorenzi, MS1; et al. Symptomatic Zika Virus Infection in Infants, Children, and Adolescents Living in Puerto Rico.

Key Points
Question: What are the clinical manifestations and viral loads of symptomatic infants, children, and adolescents infected with Zika virus?
Findings: In this cohort of 351 infants, children, and adolescents with Zika virus infection in Puerto Rico, most had fever, an often pruritic maculopapular rash, facial or neck erythema, and conjunctival hyperemia; presented for evaluation at fewer than 3 days after the onset of symptoms; and were discharged without hospitalization. Median viral loads obtained from the serum specimens differed significantly according to the number of days after the onset of symptoms.
Meaning: Symptomatic infants, children, and adolescents infected with Zika virus generally have a mild, often nonspecific illness not requiring hospitalization; and, although not significantly different according to age, sex, or disposition, Zika virus viral loads decreased with an increasing number of days since the onset of illness.

Abstract
Importance: Little information is available regarding Zika virus (ZIKV) infection in children.
Objective: To describe patients younger than 18 years who were infected with ZIKV and were enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS).

Design, Setting, and Participants: Children infected with ZIKV with 7 or fewer days of fever or emancipated minors aged 14 - 17 years with a generalized maculopapular rash, arthritis or arthralgia, or nonpurulent conjunctivitis were eligible for enrollment on or before 31 Dec 2016, in Puerto Rico. Patients were evaluated using ZIKV polymerase chain reaction testing at 7 or fewer days after the onset of symptoms. Available ZIKV polymerase chain reaction-positive specimens were evaluated to determine viral loads.

Exposures: Confirmed polymerase chain reaction-positive ZIKV infection.

Main Outcomes and Measures: Clinical characteristics and viral loads of symptomatic children with confirmed ZIKV infection.
Results: Of 7191 children enrolled in SEDSS on or before 31 Dec 2016, only those with confirmed ZIKV infection (351 participants) were included in this study. Participants who had confirmed ZIKV infection included 25 infants (7.1 percent), 69 children (19.7 percent) aged 1 to 4 years, 95 (27.1 percent) aged 5 to 9 years, and 162 (46.1 percent) aged 10 to 17 years. Among these, 260 patients (74.1 percent) presented for evaluation of ZIKV infection at fewer than 3 days after the onset of symptoms, 340 (96.9 percent) were discharged to home after evaluation, and 349 (99.4 percent) had fever, 280 (79.8 percent) had a rash, 243 (69.2 percent) had facial or neck erythema, 234 (66.7 percent) had fatigue, 223 (63.5 percent) had headache, 212 (60.4 percent) had chills, 206 (58.7 percent) had pruritus, and 204 (58.1 percent) had conjunctival hyperemia. Of 480 specimens collected (317 serum and 163 urine specimens) from 349 children, the median number of days after the onset of symptoms was lower for children who had serum specimens (1 day [interquartile range (IQR), 1-2 days]) than for children who had urine specimens (2 [1-3] days) (P < .001). Of 131 children who had both serum and urine specimens collected on the same day, the median viral load was higher in serum than in urine (median [IQR], 23 098 [8784-88 242] copies/mL for serum vs 9966 [2815-52 774] copies/mL for urine; P = .02). When a single serum sample from each of 317 patients was analyzed, there were no statistically significant differences in median viral loads according to age, sex, or disposition. However, the median serum viral load varied significantly according to the number of days after the onset of symptoms (0 days, 106 778 [IQR, 9772-1 571 718] copies/mL; 1 day, 46 299 [10 663-255 030] copies/mL; 2 days, 20 678 [8763-42 458] copies/mL; and ≥3 days, 15 901 [5135-49 248] copies/mL; P = .001).

Conclusions and Relevance: This study represents the largest study to date of ZIKV infection in the pediatric population. Most children infected with ZIKV had fever, rash, and conjunctival hyperemia. The children usually presented for evaluation at fewer than 3 days after the onset of symptoms. Viral loads for ZIKV were higher in serum vs urine specimens. Median viral loads in serum specimens differed significantly according to the number of days after the onset of symptoms.

--
Communicated by:
Roland Hübner
Superior Health Council
Brussels
Belgium
<roland.hubner@sante.belgique.be>

[The above report provides a useful overview of the clinical picture and virus presence in the population of children studied. This study was not designed to quantify the proportion of Zika virus infected children who had inapparent or subclinical infections, to determine if they comprised the majority of infections as is the case with adults. Perhaps future prospective studies might address this question. - Mod.TY]

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[3] Subsequent developmental problems
Date: Fri 1 Jun 2018
Source: Arch Dis Child Vol 0 (0) http://dx.doi.org/10.1136/archdischild-2018-314782 [edited]
http://adc.bmj.com/content/early/2018/06/01/archdischild-2018-314782


Taissa Ferreira Cardoso, Rosana Silva dos Santos, Raquel Miranda Correa, Juliana Vieira Campos, Ricardo de Bastos Silva, Christine Castinheiras Tobias,Arnaldo, Prata-Barbosa et al. Congenital Zika infection: neurology can occur without microcephaly.

[Introduction]
The fetal repercussions of Zika virus (ZIKV) infection during pregnancy is of interest for maternal and child health. Studies on the psychomotor and neurodevelopment of children exposed in utero to arboviruses, especially non-microcephalic children, are lacking. At a maternity university hospital in Brazil, we started following the development of children without microcephaly, born to mothers infected with ZIKV during pregnancy, searching for early warning signs of abnormalities.

[Conclusions]
These findings suggest that ZIKV infection in pregnancy can lead to neurodevelopmental abnormalities, even in children without microcephaly. One previous study of intrauterine ZIKV exposure has reported the development of children with normal head circumference at birth. The authors reported postnatal development of microcephaly in 11 of 13 infants and all had reduced brain volume on neuroimaging. The clinical findings were similar to ours, since all children had some degree of hypertonia, and some had dysphagia, irritability, a diagnosis of epilepsy, dystonia and spastic hemiparesis In congenital Zika syndrome, irritability is reported as one of the most frequent symptoms, and we found it present in about half of the patients. These findings, even in children without microcephaly, were compatible with those observed in children with cerebral palsy, and prognosis may be compromised. Therapeutic actions should begin early to reduce possible sequelae.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[This study provides additional evidence that children without microcephaly a t birth born to Zika virus infected mothers may develop significant postnatal abnormalities. Clinicians who have patients who had been infected with Zika virus while pregnant and gave birth to infants without microcephaly should monitor the development of those infants over time. Zika virus Readers interested in the details of the findings in the above study can find the report at the above URL.

An additional study supports effects of neonatal Zika virus infection that persist into adulthood. The results showed that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities. (http://stm.sciencemag.org/content/10/444/eaar2749).

Interestingly, a 2 Jul 2018 published study reported that 26 percent of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection (https://www.nature.com/articles/s41591-018-0088-50).

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall. - Mod.TY

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[4] Peripheral nerve damage
Date: August 2018 [ahead of print]
Source: Emerg Infect Dis. 2018 Aug. https://doi.org/10.3201/eid2408.180057 DOI: 10.3201/eid2408.180057 [edited]
https://wwwnc.cdc.gov/eid/article/24/8/18-0057_article#suggestedcitation


Rajapakse NS, Ellsworth K, Liesman RM, Ho ML, Henry N, Theel ES, et al. Unilateral phrenic nerve palsy in infants with congenital Zika syndrome.

Abstract
Since the 1st identification of neonatal microcephaly cases associated with congenital Zika virus infection in Brazil in 2015, a distinctive constellation of clinical features of congenital Zika syndrome has been described. Fetal brain disruption sequence is hypothesized to underlie the devastating effects of the virus on the central nervous system. However, little is known about the effects of congenital Zika virus infection on the peripheral nervous system. We describe a series of 4 cases of right unilateral diaphragmatic paralysis in infants with congenital Zika syndrome suggesting peripheral nervous system involvement and Zika virus as a unique congenital infectious cause of this finding. All the patients described also had arthrogryposis (including talipes equinovarus) and died from complications related to progressive respiratory failure.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[This report indicates that peripheral nerve damage can occur in congenital Zika virus infections. There is no indication of how frequently this occurs. Perhaps similar cases will be reported from other groups in Brazil that attended many neonates with congenital Zika virus infections. - Mod.TY]

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[5] Blockage of vertical transmission
Date: Tue 5 Jun 2018
Source: Nature Scientific Reports 8 [edited]
https://www.nature.com/articles/s41598-018-19526-4


Pinar Mesci, Angela Macia, Spencer M. Moore, Sergey A. Shiryaev, Antonella Pinto, Chun-Teng Huang, et al., Blocking Zika virus vertical transmission.

Abstract
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the 1st time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[In these experiments, Sofosbuvir (SOF) looks promising indeed for blockage of Zika virus infection of the fetus. Assuming that SOF has no adverse effects on the developing human fetus and that the cost of administration is low enough to be affordable for women living under marginal conditions where Zika transmission is high, SOF could provide prophylactic protection avoid the risk of teratogenic effects with their serious adverse health, social and economic impacts. - Mod.TY]

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[6] Zika in HIV positive pregnant women
Date: Fri 6 Jul 2018
Source: .PLoS ONE 13(7): e0200168. https://doi.org/10.1371/journal.pone.0200168 [edited]
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200168


Joao EC, Ferreira OdC Jr, Gouvea MI, Teixeira MdLB, Tanuri A, Higa LM, et al. Pregnant women co-infected with HIV and Zika: Outcomes and birth defects in infants according to maternal symptomatology.

Abstract

Background
In Brazil, the 1st reported case of ZIKV infection was in May 2015. Additionally, dengue (DENV) is endemic and there has been a recent outbreak of chikungunya (CHIKV). Since the clinical manifestations of different arboviral infections (AI) can be similar, definitive diagnosis requires laboratory testing.

Objectives
To determine the prevalence of ZIKV, DENV, and CHIKV infections in a Brazilian cohort of HIV-infected pregnant women, to assess clinical/immunological characteristics and pregnancy outcomes of women with evidence of recent AI.

Study design
Laboratory diagnosis of ZIKV, DENV and CHIKV infections utilized serological assays, RT-PCR and PRNT. The tests were performed at the 1st visit, 34-36 weeks of gestation and at any time if a woman had symptoms suggestive of AI. Mann-Whitney tests were used for comparison of medians, Chi-square or Fisher's to compare proportions; p< 0.05 was considered statistically significant. Poisson regression was used to analyze risk factors for central nervous system (CNS) malformations in the infant according to maternal symptomatology.

Results
Of 219 HIV-infected pregnant women enrolled, 92 percent were DENV IgG+; 47(22 percent) had laboratory evidence of recent AI. Of these, 34 (72 percent) were ZIKV+, 9 (19 percent) CHIKV+, and 2 (4 percent) DENV+. Symptoms consistent with AI were observed in 23 (10 percent) women, of whom 10 (43 percent) were ZIKV+, 8 (35 percent) CHIKV+. No CNS abnormalities were observed among infants of DENV+ or CHIKV+ women; 4 infants with CNS abnormalities were born to ZIKV+ women (3 symptomatic). Infants born to ZIKV+ women had a higher risk of CNS malformations if the mother was symptomatic (RR = 7.20), albeit not statistically significant (p = 0.066).

Conclusions
Among HIV-infected pregnant women with laboratory evidence of a recent AI, 72 percent were ZIKV-infected. In this cohort, CNS malformations occurred among infants born to both symptomatic and asymptomatic pregnant women with Zika infection.

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ProMED-mail
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[The authors point out in their discussion that despite the relatively large population of women enrolled in the study, there were relatively few infants born with CNS abnormalities, thus limiting their analyses of pregnancy outcomes according to arboviral infection and maternal symptomatology.

In another study of Zika virus infection in HIV infected patients, ZIKV-confirmed and suspected patients reported similar signs and symptoms. Pruritic rash was the most common symptom, followed by myalgia, nonpurulent conjunctivitis, arthralgia, prostration, and headache. In the short-term follow-up [median 67.5 days CD4 cell count and HIV viral load did not change significantly post ZIKV infection. There were no hospitalizations, complications, or deaths. In conclusion, among HIV-infected patients with suspected arboviral disease, 42.6 percent were ZIKV-infected. CD4 cell counts and HIV viral load were not different post ZIKV infection (https://www.ncbi.nlm.nih.gov/pubmed/29912006). Greg Folkers is thanked for sending in this report. - Mod.TY]

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[7] Placenta infection
Date: Mon 16 Jul 2018
Source: bio Rx iv doi: https://doi.org/10.1101/370528 [edited]
https://www.biorxiv.org/content/early/2018/07/16/370528


Lucia Noronha, Camila Zanluca, Marion Burger, Andreia A Suzukawa, Marina Azevedo, Patricia Rebutini, et al. Zika Virus Infection At Different Pregnancy Stages: Anatomopathological Findings, Target Cells And Viral Persistence In Placental Tissues.
Abstract

Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barre syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects remain unknown. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the 1st, 2nd or 3rd trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the 3rd trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these 3rd-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Of women infected during pregnancy, 33 percent delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

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Communicated by:
ProMED-mail
<promed@promedmail.org>

[Placental tissue analysis may be a useful and practical diagnostic tool, especially in cases of fetal abnormality. The occurrence of fetal abnormalities in 33 percent of the 24 women infected by Zika virus during pregnancy seems high, but might be a reflection of a small study population. - Mod.TY]

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[8] Pooled testing of blood
Date: Fri 6 Jul 2018
Source: US Food and Drug Administration [edited]
https://www.fda.gov/NewsEvents/Newsroom/FDAInBrief/ucm612702.htm?utm_campaign=07062018_FIB_FDA%20announces%20revised%20Zika%20testing%20guidance%20for%20blood%20donations&utm_medium=email&utm_source=Eloqua


Today [Fri 6 Jul 2018] the FDA announced the availability of a revised final guidance: "Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components." This revised guidance replaces the August 2016 guidance, which recommended universal nucleic acid testing for Zika virus of individual units of blood donated in the U.S. states and territories. The revised guidance explains that, in order to comply with applicable testing regulations, blood establishments must continue to test all donated whole blood and blood components for Zika virus using a nucleic acid test. The revised guidance explains the basis for the FDA's determination that pooled testing of donations using a screening test licensed for such use by the FDA is a sufficient method for complying with these regulations and effectively reducing the risk of Zika Virus transmission, unless there is an increased risk of local mosquito-borne transmission of Zika virus in a specific geographic area that would trigger individual donation testing in that location. Alternatively, blood establishments may use an FDA-approved pathogen-reduction device for plasma and certain platelet products.

The change comes after careful consideration of all available scientific evidence, including consultation with other public health agencies, and following the recommendations of the December 2017 meeting of the Blood Products Advisory Committee. The agency is confident that today's recommendations will continue to ensure the safety of the U.S. blood supply by reducing the risk of transmission of Zika virus, while reducing the burden of testing for blood establishments.

Zika virus is transmitted primarily by the _Aedes_ mosquito, but it can also be spread by other routes, including by blood and sexual contact. Many people infected with the virus never develop symptoms, however when symptoms do occur they may include fever, arthralgia (joint pain), maculopapular rash (red area with small bumps), and conjunctivitis (red, irritated eyes). Zika virus can also be associated with Guillain-Barre syndrome and severe neurological complications. Zika virus infection during pregnancy can cause serious birth defects and is associated with other adverse pregnancy outcomes.

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Communicated by:
ProMED-mail Rapporteur Mary Marshall

[Testing individual units of whole blood and blood products was extremely expensive. Given the low prevalence of Zika virus in blood and in these products pooling makes good sense and does not compromise safety. - Mod.TY]

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[9] Host specificity
Date: Mon 18 Jun 2018
Source: PNAS 201803406; published ahead of print June 18, 2018. https://doi.org/10.1073/pnas.1803406115 [edited]
http://www.pnas.org/content/early/2018/06/14/1803406115


Qiang Ding, Jenna M. Gaska, Florian Douam, Lei Wei, David Kim, Metodi Balev, Brigitte Heller, and Alexander Ploss. Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease.

Significance
To shed light on the host range of Zika virus (ZIKV), we surveyed the virus' ability to infect cells of evolutionarily diverse species. ZIKV replicates efficiently in human, great ape, Old and New World monkey, but not rodent cells. These observations correlated with ZIKV's ability to blunt the cGAS/STING signaling pathway in all primate cells tested but not in mice. We demonstrate that an enzyme shared by many flaviviruses (NS2B3) is responsible for functionally inactivating this antiviral defense. Our results highlight the importance of the cGAS/STING pathway in shaping the host range of ZIKV, which in turn may guide the development of murine models with inheritable susceptibility to ZIKV and other flaviviruses.

Abstract
The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human--but not murine--cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells. Indeed, human, but not mouse, STING is subject to cleavage by proteases encoded by ZIKV, dengue virus, West Nile virus, and Japanese encephalitis virus, but not that of yellow fever virus. The protease cleavage site, located between positions 78/79 of human STING, is only partially conserved in nonhuman primates and rodents, rendering these orthologs resistant to degradation. Genetic disruption of STING increases the susceptibility of mouse--but not human--cells to ZIKV. Accordingly, expression of only mouse, not human, STING in murine STING knockout cells rescues the ZIKV suppression phenotype. STING-deficient mice, however, did not exhibit increased susceptibility, suggesting that other redundant antiviral pathways control ZIKV infection in vivo. Collectively, our data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. Furthermore, our results explain--at least in part--the decreased permissivity of rodent cells to ZIKV, which could aid in the development of mice model with inheritable susceptibility to ZIKV and other flaviviruses.

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Communicated by:
ProMED-mail
<promed@promedmail.org>

[The question of species susceptibility arises when the possibility of Zika virus non-human animal reservoirs is considered. There is great vertebrate biodiversity of the tropical countries in which Zika virus has been found. How many of the vertebrate animals are susceptible to Zika virus infection is an open question when considering the natural history of this virus. The ability of Zika virus to evade cGAS/STING-dependent signaling may provide some clues about species susceptibility, and permit consideration of the wide variety of rodents, for example, and not just laboratory _Mus domesticus _ that might be of potential importance in maintenance of this virus in nature. - Mod.TY]

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[10] Illness in USA Veterans
Date: Thu 24 May 2018
Source: PLoS Neglected Tropical Diseases https://doi.org/10.1371/journal.pntd.0006416 [edited]
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006416


Patricia L. Schirmer, Aaron Wendelboe, Cynthia A. Lucero-Obusan, A. Ryono Mark A. Winters, Gina Oda, et al. Zika virus infection in the Veterans Health Administration (VHA), 2015-2016

Abstract

Background
Zika virus (ZIKV) is an important flavivirus infection. Although ZIKV infection is rarely fatal, risk for severe disease in adults is not well described. Our objective was to describe the spectrum of illness in U.S. Veterans with ZIKV infection.

Methodology
Case series study including patients with laboratory-confirmed or presumed positive ZIKV infection in all Veterans Health Administration (VHA) medical centers. Adjusted odds ratios of clinical variables associated with hospitalization and neurologic complications was performed.

Principal findings
Of 1538 patients tested between January 2015-October 2016 and observed through March 2017, 736 (48 percent) were RT-PCR or confirmed IgM positive; 655 (89 percent) were male, and 683 (93 percent) from VA Caribbean Healthcare System (VACHCS). Of these, 94 (13 percent) were hospitalized, 91 (12 percent) in the VACHCS; 19 (3 percent) died after ZIKV infection. Hospitalization was associated with increased Charlson co-morbidity index (adjusted odds ratio [OR] 1.2; 95 percent confidence interval [CI], 1.1-1.3), underlying connective tissue disease (OR, 29.5; CI, 3.6-244.7), congestive heart failure (OR, 6; CI, 2-18.5), dementia (OR, 3.6; CI, 1.1-11.2), neurologic symptom presentation (OR, 3.9; CI, 1.7-9.2), leukocytosis (OR, 11.8; CI, 4.5-31), thrombocytopenia (OR, 7.8; CI, 3.3-18.6), acute kidney injury (OR, 28.9; CI, 5.8-145.1), or using glucocorticoids within 30 days of testing (OR, 13.3; CI 1.3-133). Patients presenting with rash were less likely to be hospitalized (OR, 0.29; CI, 0.13-0.66). Risk for neurologic complications increased with hospitalization (OR, 5.9; CI 2.9-12.2), cerebrovascular disease (OR 4.9; CI 1.7-14.4), and dementia (OR 2.8; CI 1.2-6.6).

Conclusion
Older Veterans with multiple comorbidities or presenting with neurologic symptoms were at increased risk for hospitalization and neurological complications after ZIKV infection.

Author summary
Zika virus (ZIKV) infection has become an important flavivirus infection that affected over a half of a million people in the Western Hemisphere by the end of 2016. Here we show risk factors for hospitalizations and neurologic complications in a US Veteran population. Over 700 Veterans with confirmed or presumed positive ZIKV were included. Our study showed that older Veterans with multiple comorbidities and those presenting with neurologic symptoms were more likely to be hospitalized, while if a patient presented with a rash they were less likely to be hospitalized. Neurologic complications were more likely in those hospitalized or those with a prior history of a cerebrovascular disease or dementia. Better understanding of those patients most at risk for severe disease can help providers when evaluating and treating patients with ZIKV infection.

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Communicated by:
ProMED-mail Rapporteur Mary Marshall

[This report provides useful information for clinicians who attend elderly patients with Zika virus infections, especially those with comorbidities. Studies like the one above often depend in part on serological diagnosis of Zika virus infections. Differentiating Zika and Dengue virus infections serologically can be difficult because of antigenic cross-reactivity. A recent study found that urea wash in a Zika virus nonstructural protein 1 IgG ELISA distinguishes secondary dengue virus infection from Zika virus infection with previous dengue (sensitivity 87.5 percent, specificity 93.8 percent). This test will aid serodiagnosis, serosurveillance, and monitoring of Zika complications in dengue-endemic regions (https://wwwnc.cdc.gov/eid/article/24/7/17-1170_article). Roland Hübner is thanked for sending in this report. - Mod.TY]

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[11] Acute GBS more severe
Date: Mon 21 May 2018 [on line ahead of print]
Source: JAMA Neurol. May 21, 2018. doi:10.1001/jamaneurol.2018.1058 [edited]
https://jamanetwork.com/journals/jamaneurology/article-abstract/2680895


Emilio Dirlikov, PhD1,2; Chelsea G. Major, MPH3,4; Nicole A. Medina, MPH3; et al. Clinical Features of Guillain-Barré Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

Abstract

Importance: The pathophysiologic mechanisms of Guillain-Barre syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features.

Objective: To identify specific clinical features of GBS associated with ZIKV infection.

Design, Setting, and Participants: During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barre syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated.

Main Outcomes and Measures: Acute and long-term clinical characteristics of GBS associated with ZIKV infection.
Results: Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3 percent) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0 percent] vs 10 [27.8 percent]; P < .001), dysphagia (38 [53.5 percent] vs 9 [25.0 percent]; P = .005), shortness of breath (33 [46.5 percent] vs 9 [25.0 percent]; P = .03), facial paresthesia (13 [18.3 percent] vs 1 [2.8 percent]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2 percent] vs 23 [71.9 prcent]; P = .008), admission to the intensive care unit (47 [66.2 percent] vs 16 [44.4 percent]; P = .03), and required mechanical ventilation (22 [31.0 percent] vs 4 [11.1 percent]; P = .02). Patients with GBS and evidence of ZIKV infection 6 months after neurologic illness onset more frequently reported having excessive or inadequate tearing (30 [53.6 percent] vs 6 [26.1 percent]; P = .03), difficulty drinking from a cup (10 [17.9 percent] vs 0; P = .03), and self-reported substantial pain (15 [27.3 percent] vs 1 [4.3 percent]; P = .03).

Conclusions and Relevance.
In this study, GBS associated with ZIKV infection was found to have higher morbidity during the acute phase and more frequent cranial neuropathy during acute neuropathy and 6 months afterward. Results indicate GBS pathophysiologic mechanisms that may be more common after ZIKV infection.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[The authors conclude that Zika virus-infected GBS patients had higher morbidity during acute-phase neuropathy and manifested more frequent acute and residual cranial neuropathy. - Mod.TY]

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[12] Vertical transmission in _Aedes aegypti_
Date: Mon 16 Jul 2018
Source: PLoS Negl Trop Dis 12(7): e0006594. https://doi.org/10.1371/journal.pntd.0006594 [edited]
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006594


Costa CFd, Silva AVd, Nascimento VAd, Souza VCd, Monteiro DCdS, Terrazas WCM, et al. (2018) Evidence of vertical transmission of Zika virus in field-collected eggs of Aedes aegypti in the Brazilian Amazon.

Abstract

Background
Arboviruses are viruses transmitted to humans and other animals by the bite of hematophagous arthropods. Infections caused by chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and the deadlier yellow fever virus (YFV) are current public health problems in several countries, mainly those located in tropical and subtropical regions. One of the main prevention strategies continues to be vector control, with the elimination of breeding sites and surveillance of infested areas. The use of ovitraps for _Aedes_ mosquitos monitoring has already demonstrated promising results, and maybe be also useful for arboviral surveillance.

Methods
This work aimed to detect natural vertical transmission of arboviruses in _Aedes aegypti_ and _Aedes albopictus_. Mosquito egg collection was carried out using ovitraps in Itacoatiara, a mid-size city in Amazonas state, Brazil. Collected eggs were allowed to hatch and larvae were tested for CHIKV, DENV, and ZIKV RNA by RT-qPCR.

Results
A total of 2057 specimens (1793 _Ae. aegypti_ and 264 _Ae. albopictus_), in 154 larvae pools were processed. Results showed one positive pool for CHIKV and one positive pool for ZIKV. The active ZIKV infection was further confirmed by the detection of the negative-strand viral RNA and nucleotide sequencing which confirmed the Asian genotype. The Infection Rate per 1000 mosquitoes tested was assessed by Maximum Likelihood Estimation (MLE) with 0.45 and 0.44 for CHIKV and ZIKV, respectively, and by Minimum Infection Rate (MIR) with 0.45 for both viruses.

Conclusion
To our knowledge, this is the 1st detection of ZIKV in natural vertical transmission in the _Ae. aegypti_, a fact that may contribute to ZIKV maintenance in nature during epidemics periods. Furthermore, our results highlight that the use of ovitraps and the molecular detection of arbovirus may contribute to health surveillance, directing the efforts to more efficient transmission blockade.

Author summary
The control of the vast majority of arbovirus infections relies on entomological measures to reduce mosquito infestation. Therefore, this study analyzed the use of ovitraps for arboviral surveillance in a mid-size city of the Amazonas state, Brazil. We found one larva pool infected with chikungunya virus, before the 1st human case confirmed in this municipality. Another pool was infected with Zika virus, demonstrating the 1st evidence that vertical transmission occurs in naturally infected _Aedes aegypti_ mosquito populations.

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Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The detection of transovarial transmission (TOT) is of epidemiological significance. Should TOT be efficient, the virus might be sustained in _Aedes aegypti_ populations without requiring human infectious blood meals and making control of the virus difficult. Further field and laboratory studies are needed.

Detection of Zika virus in mosquitoes has been laborious and costly. A recent published report stated that for the 1st time near-infrared spectroscopy (NIRS) is a rapid, reagent-free, and cost-effective tool that can be used to noninvasively detect ZIKV in heads and thoraces of intact Aedes aegypti_ mosquitoes with prediction accuracies of 94.2 - 99.3 percent relative to quantitative reverse transcription polymerase chain reaction (RT-qPCR). NIRS involves simply shining a beam of light on a mosquito to collect a diagnostic spectrum. It is estimated in this study that NIRS is 18 times faster and 110 times cheaper than RT-qPCR. It will be interesting to learn if this technique is technically uncomplicated enough to be established in tropical laboratories that need it most. https://outlook.office.com/owa/?realm=wisc.edu&path=/mail/inbox/rp. Roland Hübner is thanked for sending in this report. - Mod.TY]

[The incidence of Zika virus infections in the Americas this year (2018) is considerably reduced from the outbreak of 2016-2017. However, the virus is still present and vector populations are still abundant. It is important to continue aggressive surveillance of cases and implementation of the novel mosquito vector control measures that have recently been shown to be effective. Studies are needed to explore the role of wild animals, especially nonhuman primates, as possible reservoirs in the tropical countries in the Americas. - Mod.TY]