ZIKA VIRUS (01): AMERICAS, ASIA, AFRICA, RESEARCH
Posted on 17TH JAN 2017
tagged Zika Virus
In this update:
 PAHO/WHO epidemiological update
 Cases in various countries:
Americas cumulative case numbers
- Florida (Miami-Dade county)
- Texas (Travis county)
- Rhode Island
Mexico and Central America
Costa Rica (national)
St Lucia (national)
Turks and Caicos (national)
Martinique blood donors, 2016
- Microcephaly, national
- Eye involvement
Viet Nam (national)
Malaysia (Petaling Jaya, Selangor)
Imported cases with no possibility of ongoing mosquito transmission
- Case numbers mainland
- New York City, New York
- Territories and Commonwealth
 Brazil: fetal infections, Brazil
 USA: birth defects
 Prolonged viremia
 Virus protein and neurological defects
 Virus molecular evolution
 Antibody-dependent enhancement
 False positive test
 Mosquito vectors
 Severe thrombocytopenia
 PAHO/WHO epidemiological update
Date: Thu 12 Jan 2017
Source: PAHO/WHO Zika - epidemiological update [edited]
Zika virus - incidence and trends
Since epidemiological week (EW) 44 of 2016 [29 Oct-4 Nov 2016], no additional countries or territories of the Americas have confirmed autochthonous, vectorborne transmission of Zika virus disease. To date, 48 countries and territories in the Americas (1) have confirmed autochthonous, vectorborne transmission of Zika virus disease since 2015 (figure 1). In addition, 5 countries in the Americas have reported sexually transmitted Zika cases (2).
Figure 1. [available at the source URL above] Countries and territories in the Americas with confirmed autochthonous (vectorborne) Zika virus cases, 2015-2017
(1) Anguilla; Antigua and Barbuda; Argentina; Aruba; the Bahamas; Barbados; Belize; Bolivia (Plurinational State of); Bonaire, Sint Eustatius, and Saba; Brazil; the British Virgin Islands; Cayman Islands; Colombia; Costa Rica; Cuba; Curaçao; Dominica; the Dominican Republic; Ecuador; El Salvador; French Guiana; Grenada; Guadeloupe; Guatemala; Guyana; Haiti; Honduras; Jamaica; Martinique; Mexico; Montserrat; Nicaragua; Panama; Paraguay; Peru; Puerto Rico; Saint Barthélemy; Saint Kitts and Nevis; Saint Lucia; Saint Martin; Saint Vincent and the Grenadines; Sint Maarten; Suriname; Trinidad and Tobago; Turks and Caicos Islands; the United States of America; the United States Virgin Islands; and Venezuela (Bolivarian Republic of).
(2) Argentina, Canada, Chile, Peru, and the USA.
Highlighted below is a summary of the epidemiological situation by sub-regions of the Americas.
In the United States, since 30 Dec 2016, the US Centers for Disease Control and Prevention (CDC) has not reported new locally-acquired cases of Zika virus disease.
In Panama, a growing trend of suspected and confirmed cases continued to be observed between EW 30 to EW 49. In the other countries of the sub region, the number of cases continues a downward trend.
In the countries and territories in the Caribbean, the downward trend in the number of Zika cases continues.
In Peru, between EW 40 and 50 of 2016 [1 Oct-16 Dec 2016], an increase in the number of suspected and confirmed cases was observed, particularly in the 4 districts of the city of Iquitos.
All the other countries and territories in South America continue to report decreasing numbers of Zika cases.
Congenital syndrome associated with Zika virus infection
To date, 22 countries and territories in the Americas have reported confirmed cases of congenital syndrome associated with Zika virus infection. Since December of 2016, no additional countries or territories have reported confirmed cases of congenital syndrome associated with Zika virus infection for the 1st time. In the last 2 weeks, Brazil, Colombia, and the United States of America updated their number of cases of congenital syndrome associated with Zika virus infection.
As of 1 Sep 2016, the table with the number of confirmed cases of congenital syndrome is published on a weekly basis on the PAHO/WHO website and is available on the Zika Cumulative Cases website [http://www.paho.org/hq/index.php?option=com_content&view=article&id=1239....
Guillain-Barré syndrome (GBS) and other neurological disorders
Since December 2016, no additional countries or territories have reported cases of Guillain-Barré syndrome (GBS) associated with Zika virus infection.
Following is a list of countries and territories in the Americas reporting increased cases of Guillain-Barré syndrome (GBS) and/or laboratory confirmation of Zika virus in at least one GBS case.
Table 1. Countries and territories in the Americas with GBS in the context of Zika virus circulation.
Increase in GBS with Zika virus lab confirmation in at least one case of GBS:
Zika virus infection laboratory confirmation in at least one case of GBS:
Increase in GBS with no Zika virus lab confirmation in any of the cases:
Saint Vincent and the Grenadines
ProMED-mail rapporteur Marianne Hopp
[It will be interesting to see if the case numbers begin to increase in South America with the onset of warmer, summer weather. - Mod.TY]
 Cases in various countries
Americas cumulative case numbers
As of 12 Jan 2017
Country / Locally acquired: suspected / confirmed / Imported / Deaths / Conf. Congenital Syndrome
Bermuda / 0 / 0 / 5 / 0 / 0
Canada / 0 / 0 / 439 / 0 / 1
USA / 0 / 217 / 46449 / 0 / 41
Mexico / 0 / 7575 / 15 / 0 / 0
Central American Isthmus:
Belize / 756 / 68 / 0 / 0 / 0
Costa Rica / 5737 / 1649 / 32 / 0 / 2
El Salvador / 11 434 / 51 / 0 / 0 / 4
Guatemala / 3343 / 788 / 0 / 0 / 15
Honduras / 31 936 / 298 / 0 / 0 / 2
Nicaragua / 0 / 2053 / 3 / 0 / 2
Panama / 2663 / 676 / 42 / 0 / 5
Cuba / 0 / 3 / 30 / 0 / 0
Dominican Republic / 4908 / 322 / 0 / 0 / 22
French Guiana / 9700 / 483 / 10 / 0 / 16
Guadeloupe / 30 845 / 379 / 0 / 0 / 6
Haiti / 2955 / 5 / 0 / 0 / 1
Martinique / 36 680 / 12 / 0 / 0 / 18
Puerto Rico / 0 / 36 375 / 1 / 5 / 10
Saint Barthélemy / 975 / 61 / 0 / 0 / 0
Saint Martin / 3115 / 200 / 0 / 0 / 0
Anguilla / 28 / 16 / 1 / 0 / 0
Antigua and Barbuda / 465 / 14 / 2 / 0 / 0
Aruba / 676 / 28 / 7 / 0 / 0
Bahamas / 0 / 22 / 3 / 0 / 0
Barbados / 699 / 46 / 0 / 0 / 0
Bonaire, St Eustatius, and Saba / 0 / 85 / 0 / 0 / 0
Caymans / 211 / 30 / 10 / 0 / 0
Curacao / 0 / 820 / 0 / 0 / 0
Dominica / 1150 / 79 / 0 / 0 / 0
Grenada / 316 / 111 / 0 / 0 / 1
Guyana / 0 / 37 / 0 / 0 / 0
Jamaica / 7052 / 186 / 0 / 0 / 0
Montserrat / 2 / 5 / 0 / 0 / 0
Saint Kits and Nevis / 549 / 33 / 0 / 0 / 0
Saint Lucia / 822 / 50 / 0 / 0 / 0
Saint Vincent and the Grenadines / 508 / 83 / 0 / 0 / 0
Sint Maarten / 367 / 143 / 0 / 0 / 0
Suriname / 2760 / 723 / 0 / 4 / 2
Trinidad and Tobago / 0 / 643 / 1 / 0 / 1
Turks and Caicos / 179 / 17 / 3 / 0 / 0
Virgin Islands (UK) / 74 / 52 / 0 / 0 / 0
Virgin Islands (USA) / 1034 / 917 / 0 / 0 / 0
Bolivia / 741 / 156 / 4 / 0 / 14
Colombia / 96 860 / 9799 / 0 / 0 / 77
Ecuador / 2680 / 875 / 15 / 0 / 0
Peru / 1767 / 389 / 21 / 0 / 0
Venezuela / 59 235 / 2380 / 0 / 0 / 0
[Brazil and] Southern Cone:
Brazil / 214 193 / 128 266 / 0 / 9 / 2366
Argentina / 1821 / 26 / 29 / 0 / 1
Chile / 0 / 0 / 33 / 0 / 0
Paraguay / 555 / 14 / 0 / 0 / 2
Uruguay / 0 / 0 / 1 / 0 / 0
Totals, Americas / 539 791 / 197 271 / 5356 / 18 / 2609
[Maps showing the location of the affected islands and countries in the Americas mentioned above and below
can be accessed at
North America at http://healthmap.org/promed/p/106;
Central America http://healthmap.org/promed/p/39455;
Caribbean http://www.mapsofworld.com/caribbean-islands/, and
South America at http://healthmap.org/promed/p/6186. - Mod.TY]
- National. 6 Jan 2017. 2 more babies have been born in the United States with Zika-related birth defects, raising the total to 36, the Centers for Disease Control and Prevention (CDC) said yesterday [5 Jan 2016] in an update. The number of Zika-related pregnancy losses remained at 5; of 1292 women who were included in the US Zika Pregnancy Registry as of 27 Dec 2016, 875 pregnancies have been completed with or without birth defects.
[A 13 Jan 2017 study in the USA reported a study reporting that out of 442 cases, 271 pregnant were asymptomatic, 167 had symptoms related to Zika, and symptoms were missing in 4 cases. 26 fetuses or infants (6 percent) had birth defects, 22 had a brain anomaly, while 4 had other malformations. Among the 22 cases, where the brain was affected, 14 had microcephaly and other brain abnormalities together, 4 had only microcephaly, while 4 had only other brain malformations. Among the 4 cases, where brain abnormalities were not detected, 2 had encephalocele (a protrusion of the brain), 1 had eye and 1 had hearing anomalies. The risk of abnormalities was the same in both symptomatic and asymptomatic cases (6 per cent). In cases where pregnant women were only exposed in the first trimester, 11 per cent had birth defects, while in cases where exposure took place in multiple trimesters including the 1st trimester, 7 per cent of the fetuses or infants presented with birth defects. However, exposure in only the 2nd trimester did not result in birth defects (https://www.medicalnewsbulletin.com/birth-defects-zika-related-pregnanci...)]
- Florida (Miami-Dade county). 12 Jan 2017. (confirmed [conf]) 1 new locally acquired case in Miami-Dade County, bringing the total of locally acquired cases to 257.
- Georgia. 11 Jan 2017. (conf) A Zika-related birth defect has been documented in Georgia, public health officials reported.
- Texas (Travis county). 7 Jan 2017. (conf) Health officials say a child born in Travis County with microcephaly has a Zika virus infection.
[A 22 Dec 2016 reports the occurrence of the 6th locally acquired case in Texas, in Cameron county (http://www.krgv.com/story/34117108/cameron-co-health-officials-confirm-s...)
On 14 Dec 2016, CDC issued guidance related to Zika for people living in or traveling to Brownsville, Cameron County, Texas (https://www.cdc.gov/zika/intheus/texas-update.html). - Mod.TY]
- Rhode Island. 21 Dec 2016. (conf) 1st infant born with the virus in state, had no defects, mother traveled to a Zika prevalent area while pregnant.
Mexico and Central America
Mexico (national). 17 Dec 2016. (reported) 347 cases.
http://sipse.com/novedades/cancun-zika-microcefalia-chikungunya-gestacio... [in Spanish]
Costa Rica (national). 2 Jan 2017. (conf) in 2016, 1581 cases. Cantons most affected: Orotina 159 cases for each 10 000 residents, Nandayure, Liberia, Santa Cruz, Nicoya and Abangares each ranked within the top 20 cantons.
Honduras (national). 30 Dec 2016. (reported) 623 pregnant women under surveillance, 127 cases of microencephaly of which 13 recently; Guillain-Barré syndrome 164 cases.
St Lucia (national). 16 Dec 2016. (reported) 50 pregnant women have tested positive for Zika virus infections and are bing monitored due to concerns about microcephaly.
Turks and Caicos (national). 6 Jan 2017. (conf) 24 cases, of which 8 are new cases, 7 on Grand Turk.
Martinique blood donors, 2016. 12 Jan 2017. (conf.) between 19 Jan-10 Jun 2016, 4129 consecutive blood donations were tested (mean age, 41.9 years; sex ratio [M/F], 0.88). Positive individual nucleic acid testing detection occurred in 76 blood donations (1.8 per cent), with the most intense detection rate (3 per cent) during weeks 17-20 (mean age, 41.8 years; sex ratio, 1.2). Inquiry consisted of a telephone call at day 7 post-donation to identify symptoms compatible with ZIKV infection. When the donor declared no sign, a new call was 14 days after donation. This information was obtained from 75 viremic donors: 34 (45.3 per cent) remained asymptomatic, and 41 (54.7 per cent) reported symptoms (1-6 days post-donation).
Bolivia (national). 20 Dec 2016. (conf) 2 new cases of microcephaly, bringing the total to 13, of these, 12 in Santa Cruz and 1 in Chuquisaca.
http://www.eldeber.com.bo/santacruz/Confirman-otros-dos-casos-de-microce... [in Spanish]
- Microcephaly, national. 12 Jan 2017. Microcephaly (conf) 2289 cases, with 3144 other suspected cases pending confirmation.
- Eye involvement. 11 Jan 2017. (reported) 2 cases of blindness in babies born Greater São Paulo -- one in Guarulhos and another in the capital -- because of the Zika virus infections in utero.
Colombia (national). 31 Dec 2016. (reported) week 32 of 2015-week 52 of 2016 [9 Aug 2015-31 Dec 2016], (suspected [susp]) 3578 cases, (susp clinically) 93 262 cases, (conf laboratory) 9799 cases.
[AC Jaramillo MD is thanked for sending in this bulletin. - Mod.TY]
[A good summary of Zika virus infections in Asia 1952-2016 is available at http://www.ijidonline.com/article/S1201-9712(16)31640-X/fulltext. - Mod.TY]
Philippines (national). 28 Dec 2016. (conf) 52 cases, 4 of whom are pregnant (1 of them already gave birth to a normal baby).
Viet Nam (national). 15 Jan 2017. (conf) since the 1st cases were detected, 212 cases. Most affected locality: Ho Chi Minh city 186 cases with 12 pregnant. From December 2016 to early January 2017, 4 cases of Zika infections in Vinh Thanh commune, Nhon Trach district, 1 case in Ben Tri province.
[Maps of Viet Nam can be accessed at http://www.onlineasiatravel.com/images/vn/vietnam-map.png and http://healthmap.org/promed/p/152. - Mod.TY]
Singapore (national). 27 Dec 2016. (conf) no new cases since 11 Dec 2016. Zika virus infected pregnant women 17 as of 21 Dec 2016, 3 have given birth to babies without microcephaly, all babies to be monitored until age 3 for development progress.
[Maps of Singapore can be accessed at http://sunsite.nus.edu.sg/SEAlinks/maps/singapore.gif and http://healthmap.org/promed/p/150. - Mod.TY]
Malaysia (Petaling Jaya, Selangor). 18 Dec 2016. (conf) 8th case in a 67 year old man from Petaling Jaya, Selangor.
[Maps of Malaysia can be accessed at http://www.ezilon.com/maps/images/asia/political-map-of-Malaysian.gif and http://healthmap.org/promed/p/2293. - Mod.TY]
Angola (national). 9 Jan 2017. (conf). 2 cases, one a French tourist, another local Luanda resident.
[Maps of Angola can be accessed at http://www.un.org/Depts/Cartographic/map/profile/angola.pdf and http://healthmap.org/promed/p/165. - Mod.TY]
Imported cases with no possibility of ongoing mosquito transmission (except USA Florida and Texas)
Canada. 5 Jan 2017. (conf.) As of 13 Dec 2016, 421 cases of whom 20 pregnant with 2 Zika-related abnormalities in fetuses and newborns; 3 cases sexually transmitted.
[A HealthMap/ProMED-mail map of Canada can be accessed at http://healthmap.org/promed/p/12. - Mod.TY]
Israel. 22 Dec 2016. (conf) 20 cases in recent months, all imported.
[A HealthMap/ProMED-mail map of Israel can be accessed at http://healthmap.org/promed/p/90. - Mod.TY]
South Korea. 6 Jan 2017. (conf) 17 cases of which 13 ex South East Asia, 4 ex Latin America.
[A HealthMap/ProMED-mail map of South Korea can be accessed at http://healthmap.org/promed/p/195. - Mod.TY]
- Case numbers mainland. Zika virus disease in the United States, 2015-2016 as of 11 Jan 2017
State / no. imported cases / no. locally acquired cases
Alabama / 30 / 0
Arizona / 52 / 0
Arkansas / 15 / 0
California / 393 / 0
Colorado / 49 / 0
Connecticut / 58 / 0
Delaware / 17 / 0
District of Columbia / 31
Florida / 833 / 210
Georgia / 106 / 0
Hawaii / 16 / 0
Idaho / 4 / 0
Illinois / 90 / 0
Indiana / 50 / 0
Iowa / 21 / 0
Kansas / 19 / 0
Kentucky / 31 / 0
Louisiana / 35 / 0
Maine / 13 / 0
Maryland / 129 / 0
Massachusetts / 117 / 0
Michigan / 65 / 0
Minnesota / 64 / 0
Mississippi / 23 / 0
Missouri / 35 / 0
Montana / 7 / 0
Nebraska / 13 / 0
Nevada / 19 / 0
New Hampshire / 12 / 0
New Jersey / 173 / 0
New Mexico / 9 / 0
New York / 997 / 0
North Carolina / 86 / 0
North Dakota / 2 / 0
Ohio / 82 / 0
Oklahoma / 29 / 0
Oregon / 42 / 0
Pennsylvania / 167 / 0
Rhode Island / 50 / 0
South Carolina / 54 / 0
South Dakota / 2 / 0
Tennessee / 59 / 0
Texas / 290 / 6
Utah / 20 / 0
Vermont / 11 / 0
Virginia / 107 / 0
Washington / 62 / 0
West Virginia / 11 / 0
Wisconsin / 48 / 0
Wyoming / 2
Total / 4650 / 216
- New York City, New York. 7 Dec 2016. (conf) The city has 4 new cases of congenital Zika virus syndrome.
- Territories and Commonwealth:
American Samoa: 1 imported, 114 locally acquired
Puerto Rico: 132 imported, 34 249 locally acquired
US Virgin Islands: 2 imported, 917 locally acquired
Total locally acquired 35 280
[A map of the USA showing the states and territories mentioned above can be accessed at http://www.mapsofworld.com/usa/]
Superior Health Council
 Brazil: fetal infections
Date: Tue 13 Dec 2016
Source: Stat [edited]
The toll that Zika virus takes on pregnancies appears to be even higher than was previously estimated, with a newly updated study from Brazil suggesting that 42 per cent of infants infected in the womb may have significant birth defects. When the authors factored in stillbirths and miscarriages suffered by women who had been infected with Zika, 46 per cent of pregnancies were affected. Microcephaly (a condition in which babies are born with smaller than normal heads) was seen in only about 3 per cent of babies in the study.
"Microcephaly is just the tip of the iceberg. It's definitely not where the focus should be," said Dr Karin Nielsen-Saines, the paper's senior author. "For every case of microcephaly you're probably going to have 10 cases of other problems that haven't been recognized." Nielsen-Saines is a professor in the division of pediatric infectious diseases at the University of California, Los Angeles. Her co-authors are from Brazil and the US.
The group reported adverse outcomes (pregnancy losses or birth defects) in 55 per cent of pregnancies in which infection occurred in the 1st trimester, 52 per cent of pregnancies in which infection occurred in the 2nd trimester, and 29 per cent in which infection occurred in the 3rd trimester.
Nielsen-Saines told STAT on [Tue 13 Dec 2016] that she'd been surprised by the 29 per cent figure and is more surprised still by the updated estimates. But on the issue of the danger the virus poses to developing fetuses, she is now clear. "I actually don't think there's anything more harmful to a fetus than Zika [virus]," she said. "It's probably the most teratogenic virus that exists." The March study and the update are published in the New England Journal of Medicine.
An unrelated study, from scientists at the Centers for Disease Control and Prevention, may shed some light on why Zika is so harmful to developing brains. That study, published in the journal Emerging Infectious Diseases, found levels of virus in the brains of infected infants (who died after birth) were 1000 times higher than in viral levels in women's placentas.
"Our findings show that Zika virus can continue to replicate in infants' brains even after birth, and that the virus can persist in placentas for months; much longer than we expected," said Julu Bhatnagar, head of the molecular pathology team at CDC's Infectious Diseases Pathology Branch and the study's lead author. "We don't know how long the virus can persist, but its persistence could have implications for babies born with microcephaly and for apparently healthy infants whose mothers had Zika [virus infections] during their pregnancies."
Women who developed a fever and a rash were enrolled in the study and tested to see if they had Zika [virus]. The study, which is ongoing, follows both women who tested positive for the virus and women who didn't. The latter group is used as a comparator.
Several scientists not involved in the study noted that the effect it recorded might be artificially high, because all women who had Zika [virus] had a symptomatic infection. It's known that most people who contract Zika [virus] don't have symptoms, and women with those milder infections may not give birth to babies with birth defects at the same rate, suggested Dave O'Connor, a professor of pathology and laboratory medicine at the University of Wisconsin-Madison who has been studying Zika in non-human primates. "Asymptomatic infections certainly carry risk too, but symptomatic infections may have disproportionately high risk. This is still speculative, but an important caveat on their results," O'Connor said in an email.
It is known that women who have asymptomatic Zika infections do sometimes give birth to babies with microcephaly. Scientists from Colombia and the Centers for Disease Control and Prevention reported on 4 such cases in June .
In the Brazilian study, researchers reported on 125 pregnant women who were infected with Zika [virus] and had given birth or lost their pregnancy between 1 Jan and 31 Jul . They compared them to 61 women who were not infected with Zika [virus] during their pregnancies. Cases of microcephaly were actually rare in the study; 4 babies born to Zika-infected mothers had microcephaly, but 2 of those babies were small and their heads were proportionate to their bodies. There would have been at least 1 more case. But a woman whose ultrasound showed a profoundly affected fetus dropped out of the study; Nielsen-Saines said multiple attempts to find her failed.
The range of other birth defects was substantial, including seizure activity, visual and hearing impairment, spasticity, contracted limbs, and difficulty swallowing and feeding. All these are signs of brain damage, Nielson-Saines said, adding she expects with time that more developmental problems will become apparent. "The newborns may appear to be normal, but they may not be normal at 6 months, and there's a whole gradient of problems," she said. The researchers plan to track these babies for 2 years, if their mothers will allow it. Nielsen-Saines admitted some mothers are reluctant to bring the babies back for medical assessment. "They don't want to know."
While infection early in pregnancy appeared to carry the highest risk, infection as late as 39 weeks was associated with problems in some cases. This is unlike rubella (another virus infamous for causing birth defects) where the danger period for infection is in the first 20 weeks of pregnancy, the authors noted. Note: paper said 16 [weeks] but she said 20 and multiple websites say 20.
The women who were not infected with Zika also had an unusually high percentage of problems; 11.5 per cent. But 42 per cent of them were infected during their pregnancy with chikungunya, another virus that has also been associated with pregnancy losses (stillbirths and miscarriages).
Two of the leaders of the Zika response team at the Centers for Disease Control and Prevention said the findings suggest the Zika virus will have a large effect where it spreads. "The scope of the ZIKV outbreak in the Americas suggests that ZIKV infections will have a profound impact on the cohort of infants delivered in the 9 months after the outbreak peak in each country," Margaret Honein and Dr Denise Jamieson wrote in an editorial published by the journal.
[Zika virus infections of mothers and their fetuses continue to provide unpleasant surprises. Those surprises may continue as the status of apparently normal but infected neonates is studied prospectively over 2 or more years. The adverse social and economic consequences of Zika virus infected newborns and their families are certain to be significant.
Readers interested in seeing the original 13 Dec 2016 New England Journal of Medicine can find it at http://www.nejm.org/doi/full/10.1056/NEJMoa1602412 and the 13 Dec 2016 Emerging Infectious Diseases at https://wwwnc.cdc.gov/eid/article/23/3/16-1499_article#suggestedcitation.
A 3 Jan 2017 review of more than 100 studies in various reporting sources found sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS (Guillain-Barré Syndrome) http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.10.... - Mod.TY]
 USA: birth defects
Date: Tue 13 Dec 2016
Source: JAMA [edited]
Honein MA, Dawson AL, Petersen EE, et al. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA. 2017;317(1):59-68. doi: 10.1001/jama.2016.19006, PMID: 27960197.
Question: What proportion of fetuses and infants of women in the United States with laboratory evidence of possible Zika virus infection during pregnancy have birth defects?
Findings: Based on preliminary data from the US Zika Pregnancy Registry, among 442 completed pregnancies, 6 per cent overall had a fetus or infant with evidence of a Zika virus-related birth defect, primarily microcephaly with brain abnormalities, whereas among women with possible Zika virus infection during the first trimester, 11 per cent had a fetus or infant with a birth defect.
Meaning: These findings support the importance of screening pregnant women for Zika virus exposure.
Importance: Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births.
Objective: To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms.
Design, setting, and participants: Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from 15 Jan to 22 Sep 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments.
Exposures: Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample.
Main outcomes and measures: Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences.
Results: Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6 per cent; 95 per cent confidence interval [CI] 4-8 per cent) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6 per cent; CI 4-9 per cent) pregnant asymptomatic women and 10 of 167 (6 per cent; CI 3-11 per cent) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4 per cent of completed pregnancies. Birth defects were reported in 9 of 85 (11 per cent; CI 6-19 per cent) completed pregnancies with maternal symptoms or exposure exclusively in the 1st trimester (or 1st trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the 2nd or 3rd trimesters.
Conclusions and relevance: Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6 per cent of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with 1st-trimester Zika infection, 11 per cent of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.
 Prolonged viremia
Date: Thu 29 Dec 2016
Source: N Engl J Med [edited]
Suy A, Sulleiro E, Rodó C, et al. Prolonged Zika virus viremia during pregnancy. N Engl J Med. 2016;375(26):2611-2613. doi: 10.1056/NEJMc1607580, PMID: 27959695.
We describe a case of Zika virus (ZIKV) infection during pregnancy in a Colombian woman. She was infected in December 2015 while she was visiting her home country. At 9 weeks' gestation, she had a self-limited maculopapular, nonconfluent rash for 3 days that affected her trunk, arms, and legs; she had no fever or other concurrent symptoms. She was screened for ZIKV and other flaviviruses.
A reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay (RealStar Zika Virus RT-PCR Kit 1.0, Altona Diagnostics) of a serum sample was positive for ZIKV, and testing remained positive for 89 days (or 107 days after the onset of symptoms, until 29 weeks' gestation), in 6 consecutive blood samples. Testing for ZIKV in the urine, vagina, and endocervix was negative. No fetal brain abnormalities were observed on scans obtained at 12 and 15 weeks' gestation. Neurosonography performed at 20, 24, and 29 weeks' gestation revealed bilateral mild ventriculomegaly and a shortened corpus callosum. The posterior fossa was normal. The brain parenchyma had calcifications and severe atrophy. Similar findings were seen on magnetic resonance imaging (MRI). No other anomalies were found in the fetus or the placenta. An RT-PCR assay of the amniotic fluid was positive for ZIKV, and screening was negative for dengue virus, chikungunya virus, cytomegalovirus, varicella-zoster virus, parvovirus B19, _Toxoplasma gondii_, and sexually transmitted infectious agents (_Chlamydia trachomatis_, _Neisseria gonorrhoeae_, _Mycoplasma hominis_, _Ureaplasma parvum_, _M. genitalium_, _U. urealiticum_, and _Trichomonas vaginalis_). The ZIKV viral load in the amniotic fluid was higher than that in the maternal serum (cycle threshold values, 28 vs. 35; RT-PCR cycle threshold values were used as an indirect marker of viral load). Results of targeted genetic testing of the amniotic fluid by means of microarray-based comparative genomic hybridization (SurePrint G3 Unrestricted CGH ISCA v2 Microarray Kit, 8x60K, Agilent Technologies) were normal.
The baby was delivered at 37 weeks' gestation because of suspected growth restriction. At this time, RT-PCR assays of the maternal serum, urine, amniotic fluid, placenta, membranes, and umbilical cord were negative for ZIKV. RT-PCR assays of the neonatal serum, urine, and cerebrospinal fluid were also negative. Postnatal ultrasonography and MRI studies confirmed the presence of microcephaly with a thinned corpus callosum and brain atrophy with parenchymal calcifications. (Table 1.shows the evolution of laboratory and ultrasonographic findings in the mother and the baby.) [see in the URL].
ZIKV has been documented to be detectable in maternal blood by means of molecular techniques during the acute phase of the infection (the first 5 days after the onset of clinical symptoms). Driggers et al. (2 Jun 2016 issue) detected ZIKV RNA in maternal serum 8 weeks after the onset of clinical symptoms. They suggested that persistent viremia may occur as a consequence of viral replication in the fetus or placenta. In our case, certain findings would support this hypothesis. 1st, the viral load in the amniotic fluid was higher than that in the maternal serum. 2nd, the viral load in the maternal serum remained stable (cycle threshold value, approximately 35) for 14 weeks and then became negative, instead of decreasing progressively, as would be expected. 3rd, neutralizing antibodies and ZIKV RNA were present in the maternal serum. In addition, RT-PCR assays of the maternal urine were negative, while testing of the maternal serum was positive. According to previous studies, ZIKV RNA would be detectable in urine longer than in serum, so an RT-PCR assay of the maternal urine would be expected to be positive in the presence of maternal viremia. For all these reasons, we would hypothesize that the persistent viremia that was detected in the mother could be the result of viral replication in the fetus or placenta, which thus acts as a reservoir.
We presume that the RT-PCR testing of neonatal samples was negative because the clinical infection occurred during prenatal life; hence, it is possible that ZIKV antibodies developed in the baby's immune system before birth. In summary, persistent ZIKV RNA in maternal serum could be a sign of fetal infection, and thus the fetus may play a role in persistent maternal viremia.
[This report provides some further insight into the maternal-fetal-placenta dynamics of Zika virus infection. A maternal viremia of 89 days is remarkable. - Mod.TY]
 Virus protein and neurological defects
Date: Thu 1 Dec 2016
Source: PNAS [edited]
Li G, Poulsen M, Fenyvuesvolgyi C, et al. Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast. Proc Natl Acad Sci U S A. 2017. pii: 201619735. doi: 10.1073/pnas.1619735114, PMID: 28049830.
The Zika virus (ZIKV) causes various neurologic defects including microcephaly and the Guillain-Barré syndrome. However, little is known about how ZIKV causes those diseases or which viral protein(s) is responsible for the observed cytopathic effects involved in restricted neuronal cellular growth, dysregulation of the cell cycle, and induction of cell hypertrophy or cell death. A genome-wide analysis of ZIKV proteins and peptides was conducted using fission yeast as a surrogate host. Seven ZIKV proteins conferred various cytopathic effects in which NS4A-induced cellular hypertrophy and growth restriction were mediated through the target of rapamycin (TOR) cellular stress-response pathway. These findings provide a foundation for identifying viral pathogenicity factors associated with the ZIKV diseases.
The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. We used fission yeast for the rapid, global functional analysis of the ZIKV genome. All 14 proteins or small peptides were produced under an inducible promoter, and we measured the intracellular localization and the specific effects on ZIKV-associated cytopathic activities of each protein. The subcellular localization of each ZIKV protein was in overall agreement with its predicted protein structure. Five structural and 2 nonstructural ZIKV proteins showed various levels of cytopathic effects. The expression of these ZIKV proteins restricted cell proliferation, induced hypertrophy, or triggered cellular oxidative stress leading to cell death. The expression of premembrane protein (prM) resulted in cell-cycle G1 accumulation, whereas membrane-anchored capsid (anaC), membrane protein (M), envelope protein (E), and nonstructural protein 4A (NS4A) caused cell-cycle G2/M accumulation. A mechanistic study revealed that NS4A-induced cellular hypertrophy and growth restriction were mediated specifically through the target of rapamycin (TOR) cellular stress pathway involving Tor1 and type 2A phosphatase activator Tip41. These findings should provide a reference for future research on the prevention and treatment of ZIKV diseases.
[A 10 Jan 2017 report in MBio (http://mbio.asm.org/content/8/1/e02150-16) identified that the p38-Mnk1 cascade regulating phosphorylation of eIF4E is a target of DENV infection and plays an important role in virus production. "Our results define several molecular interfaces by which flaviviruses, which include Zika virus, hijack host cell translation and interfere with stress responses to optimize the production of new virus particles. Unlike other RNA viruses, these flaviviruses concomitantly suppress host cell stress responses, thereby uncoupling translation suppression from stress granule formation." This suppression likely contributes to pathogenesis. Roland Hübner is thanked for sending in this report. - Mod.TY]
 Virus molecular evolution
Date: Mon 12 Dec 2016
Source: Cladistics [edited]
Schneider AB, Malone RW, Guo JT, et al. Molecular evolution of Zika virus as it crossed the Pacific to the Americas. Cladistics 2017;33(1):1-20, DOI: 10.1111/cla.12178.
Zika virus was previously considered to cause only a benign infection in humans. Studies of recent outbreaks of Zika virus in the Pacific, South America, Mexico and the Caribbean have associated the virus with severe neuropathology. Viral evolution may be one factor contributing to an apparent change in Zika disease as it spread from South East Asia across the Pacific to the Americas. To address this possibility, we have employed computational tools to compare the phylogeny, geography, immunology and RNA structure of Zika virus isolates from Africa, Asia, the Pacific and the Americas. In doing so, we compare and contrast methods and results for tree search and rooting of Zika virus phylogenies. In some phylogenetic analyses we find support for the hypothesis that there is a deep common ancestor between African and Asian clades (the "Asia/Africa" hypothesis). In other phylogenetic analyses, we find that Asian lineages are descendent from African lineages (the "out of Africa" hypothesis). In addition, we identify and evaluate key mutations in viral envelope protein coding and untranslated terminal RNA regions. We find stepwise mutations that have altered both immunological motif sets and regulatory sequence elements. Both of these sets of changes distinguish viruses found in Africa from those in the emergent Asia-Pacific-Americas lineage. These findings support the working hypothesis that mutations acquired by Zika virus in the Pacific and Americas contribute to changes in pathology. These results can inform experiments required to elucidate the role of viral genetic evolution in changes in neuropathology, including microcephaly and other neurological and skeletomuscular issues in infants, and Guillain-Barré syndrome in adults.
Superior Health Council
[Interviews with the authors and scientists working in this area are quoted in the 13 Dec 2016 issue of the Medical Express (http://medicalxpress.com/news/2016-12-mutations-trans-pacific-key-zika-s...). The analysis provides the most complete study of the virus's history to date and reveals specific genetic changes that occurred as the virus crossed the Pacific Ocean on its way to the Americas. An analysis of the genes involved also suggests new hypotheses to explain the virus's association with microcephaly and GBS.
"We looked at the viral changes that correspond to the 1st reports of microcephaly and we saw the origins of these changes in the Pacific lineages," Janies noted. "There are mutations that occurred in the part of the viral genome that codes the viral envelope protein and the ends of the viral genome that are called untranslated regions. We focused on the envelope protein because that's the part responsible for the entry of the virus to host's cells. We studied the untranslated regions since they mediate the types of tissues the virus attacks and viral replication."
Both sets of mutations suggested potential relationships to the virus's new association with neurological and developmental problems in adults and infants.
"Members of our team found that Zika has recently started making its envelope proteins with features, called epitopes, that are similar to human proteins, which could cause a human host immune response to the virus to be diluted," Janies said. "The theory underlying this idea is called epitope mimicry. The similarity is advantageous to the virus because it confuses the host's immune system and blunts the immune reaction to the virus."
However, the researchers suspect that the human proteins being mimicked may be significant for reasons besides providing immune system "cover" for the attacking virus.
An important element of the envelope protein mutation, Janies points out, is not only in the mimicry itself, but also, in the specific genes being mimicked: "Our team members found that 2 of the human proteins that Zika is mimicking are involved in the signaling that goes on when the sensory organs are being formed in the fetus. These genes are called 'Neuron Navigator Protein 2' and 'Human Neurogenic Differentiation Factor 4'," he said. "Because these are the proteins are being mimicked, a hypothesis is that the developmental pathways that rely on the proteins may be being disrupted by the immune system," Janies said.
The other mutations, on the untranslated regions, suggest other possible effects that might change where Zika virus infects in the body.
"Although epitope mimicry hypothesis helps clarify the protein-immune interaction, the mutations in the untranslated regions may explain the types of tissues Zika attacks" UNC Charlotte Bioinformatics and Genomics graduate student Adriano de Bernardi Schneider said. "The presence of specific binding regions on untranslated regions of the Zika viral genome, called "Musashi Binding Elements" provides bases for the study of changes in tissue preference of the virus."
In this part of the study, the authors evaluated the changes in the virus' Musashi Binding Elements and found that they increased the efficiency of the Zika virus that is circulating in the Americas in hijacking human cells. Musashi is a family of RNA-binding proteins in the host cells that control gene expression and the development of stem cells. The finding that Zika has mutated to be better at binding to human Musashi proteins, leads to the hypothesis that Zika is adapting to be more efficient at attacking human cells. Moreover, the role of Musashi proteins in stem cells provides another possible target for the study of developmental defects in the fetus associated with Zika infection in pregnancy. - Mod.TY]
 Antibody-dependent enhancement
Date: Fri 16 Dec 2016
Source: Clinical & Translational Immunology [edited]
Paul LM, Carlin ER, Jenkins MM, et al. Dengue virus antibodies enhance Zika virus infection. Clin Transl Immunology. 2016;5(12):e117. doi: 10.1038/cti.2016.72, PMID: 28090318
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.
Superior Health Council
[This report again raises questions about DENV vaccines resulting in ADE for Zika virus infections, and vice versa. With a tetravalent dengue vaccine now in use in several countries, one hopes that prospective monitoring for ADE in Zika virus infections is being carried out. - Mod.TY]
 False positive test
Date: Wed 28 Dec 2016
Source: Infection Control and Clinical Quality [edited]
The Food and Drug Administration issued a safety alert on [23 Dec 2016] warning physicians who care for pregnant women to not make healthcare decisions for their patients based on test results from a commercial Zika test.
The alert was issued after the regulatory agency received reports from the Laboratory Corporation of America of the ZIKV Detect IgM Capture ELISA assay (manufactured by InBios International) producing false positives. The FDA has not yet determined if the false positives are attributable to the Zika test or potential missteps on the part of the testing facility.
In August , the FDA authorized commercial use of the test. Since the approval, several commercial laboratories have moved their serological testing away from the CDC's assay to the new commercial assay. After that transition, LabCorp began identifying higher rates of false positives than expected.
The FDA now recommends results of the commercial test be considered presumptive and that these results need to be confirmed by the CDC or another qualified laboratory. The regulatory agency is also urging providers to communicate the test's presumptive status to their patients.
[byline: Brian Zimmerman]
[It is important that the doubt about the reliability of this test has emerged relatively quickly from both the FDA and the manufacturer. False positives pose a difficult problem for pregnant women, given the concern about teratogenic effects for the developing fetuses. False positives could lead to the parents deciding to terminate the pregnancy when there is no risk of their fetuses becoming infected by the virus.
Interestingly, a 15 Dec 2016 report in Eurosurveillance indicated the development of a serological test providing high specificity and low cross-reactivity. This NS1-based ELISA has the potential to aid in counseling patients, pregnant women and travellers after returning from ZIKV-endemic areas (http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=22670). This report was sent in by Roland Hübner.
In a 28 Dec 2016 paper, researchers in China reported on the isolation of 2 antibodies that can neutralize the Zika virus without cross-reactivity to dengue viruses. Their results, published in Science Translational Medicine, demonstrate the therapeutic potential of monoclonal antibodies against Zika and provide a structure-based rationale for the design of future specific antivirals. These monoclonal antibodies cold be useful for development of specific diagnostic tests. (http://www.asianscientist.com/2016/12/in-the-lab/zika-neutralizing-antib...). - Mod.TY]
 Mosquito vectors
Date: Thu 12 Jan 2017
Source: Euro Surveillance [edited]
Heitmann A, Jansen S, Lühken R, et al. Experimental transmission of Zika virus by mosquitoes from central Europe. Euro Surveill. 2017;22(2):pii=30437. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.2.30437.
Mosquitoes collected in Germany in 2016, including _Culex pipiens pipiens_ biotype _pipiens_, _Culex torrentium_ and _Aedes albopictus_, as well as _Culex pipiens pipiens_ biotype _molestus_ (in colony since 2011) were experimentally infected with Zika virus (ZIKV) at 18 C [approx. 64 F] or 27 C [approx. 80 F]. None of the _Culex_ taxa showed vector competence for ZIKV. In contrast, _Aedes albopictus_ were susceptible for ZIKV but only at 27 C [approx. 80 F], with transmission rates similar to an _Aedes aegypti_ laboratory colony tested in parallel.
Superior Health Council
[Several previous studies agree with _Culex_ spp as refractory or inefficient vector mosquitoes. These studies stand in contrast to a study in China that indicated that _Culex quinquefasciatus_ were susceptible to the virus and transmitted it efficiently. It is difficult to explain the discrepancy, and indicates that additional experiments with _Culex_ spp. from various geographically different populations are needed before final conclusions can be reached.
In December 2016, The USA National Science and Technology Council Committee issued a report from their Science Task Force on Science and Technology for Zika Vector Control (http://bit.ly/2j6rpyP). This report addresses control of _Aedes_ vector mosquitoes that transmit not only Zika virus, but dengue, chikungunya and yellow fever viruses as well. Interested ProMED readers may wish to read this report. - Mod.TY]
 Severe thrombocytopenia
Date: 15 Apr 2017 [Epub ahead of print]
Source: CDC, Emerging Infectious Diseases [edited]
Boyer Chammard TH, Schepers K, Breurec S, et al. Severe thrombocytopenia after Zika virus infection, Guadeloupe, 2016. Emerg Infect Dis. 2017;23(4). doi: 10.3201/eid2304.161967, PMID: 27997330.
Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia.
[Zika virus infections provide another surprise. In cases of severe thrombocytopenia, one usually thinks of severe dengue virus infections and DHF. Clinicians treating individuals infected by Zika virus should be aware that rare cases of thrombocytopenia may occur. - Mod.TY]
A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/promed/p/6075.]
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