ZIKA VIRUS (06): AMERICAS, PACIFIC, ASIA, AFRICA, RESEARCH

Posted on 16TH APR 2017
tagged Zika Virus, Worldwide

A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org

In this update:
[1] Cases in various countries:
Americas
Americas cumulative case numbers
North America
---
USA (San Diego, California)

Caribbean
---
Puerto Rico
USA Virgin Islands
Aruba

South America
---
Brazil:
- National
- Minas Gerais state
Peru (Ica region)
Paraguay

Asia
---
Singapore
Taiwan

Pacific
---
French Polynesia

Africa
---
Senegal and Nigeria

Other
---
USA CDC Alert

Imported cases with no possibility of ongoing mosquito transmission
---
South Korea
USA:
- Case numbers mainland
- Birth defects
- Territories and Commonwealth

[2] Geographic patterns
[3] Culex mosquito vectors
[4] Virus in semen, UK
[5] Virus in breast milk
[6] Vaccine
[7] Cardiovascular complications
[8] Zika virus and neurologic disease
[9] CRISPR diagnostic test
[10] QUASR diagnostic test
[11] Cost to countries

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Cases in various countries
Americas
---
Americas cumulative case numbers
As of 6 Apr 2017
http://www.paho.org/hq/index.php?option=com_content&view=article&id=1239...
Country / Locally acquired: suspected / Confirmed /Imported / Deaths / Confirmed congenital syndrome
North America:
Bermuda / 0 / 0 / 6 / 0 / 0
Canada / 0 / 0 / 486 / 0 / 1
USA / 0 / 223 / 4901 / 0 / 63

Latin America:
Mexico / 0 / 8199/ 15 / 0 / 5

Central American Isthmus:
Belize / 816 / 73 / 0 / 0 / 0
Costa Rica / 6247 / 1779 / 32 / 0 / 5
El Salvador / 11 464 / 51 / 0 / 0 / 4
Guatemala / 3598 / 921 / 0 / 0 / 59
Honduras / 32 130 / 302 / 0 / 0 / 2
Nicaragua / 0 / 2060 / 3 / 0 / 2
Panama / 4006 / 878 / 42 / 0 / 5

Latin Caribbean:
Cuba / 0 / 187/ 58 / 0 / 0
Dominican Republic / 4902 / 345 / 0 / 0 / 54
French Guiana / 10 320 / 483 / 10 / 0 / 17
Guadeloupe / 30 845 / 382 / 0 / 0 / 14
Haiti / 2955 / 5 / 0 / 0 / 1
Martinique / 36 680 / 21 / 0 / 0 / 22
Puerto Rico / 0 / 39 815 / 137 / 5 / 12
Saint Barthelemy / 990 / 61 / 0 / 0 / 0
Saint Martin / 3215 / 200 / 0 / 0 / 1

Non-Latin Caribbean:
Anguilla / 29 / 23 / 1 / 0 / 0
Antigua and Barbuda / 465 / 14 / 2 / 0 / 0
Aruba / 880 / 34 / 7 / 0 / 0
Bahamas / 0 / 25 / 3/ 0 / 0
Barbados / 699 / 46 / 0 / 0 / 0
Bonaire, St Eustatius and Saba / 0 / 343 / 0 / 0 / 0
Caymans / 217 / 31 / 10 / 0 / 0
Curacao / 2589 / 1259 / 0 / 0 / 0
Dominica / 1150 / 79 / 0 / 0 / 0
Grenada / 335 / 112 / 0 / 0 / 1
Guyana / 0 / 37 / 0 / 0 / 0
Jamaica / 7371 / 203 / 0 / 0 / 0
Montserrat / 18 / 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 / 247 / 147 / 0 / 0 / 0
Suriname / 2768 / 723 / 0 / 4 / 4
Trinidad and Tobago / 0 / 718 / 1 / 0 / 3
Turks and Caicos / 175 / 25 / 3 / 0 / 0
Virgin Islands (UK) / 74 / 52 / 0 / 0 / 0
Virgin Islands (USA) / 1074 / 1010 / 2 / 0 / 0

Andean Area:
Bolivia / 1767 / 585 / 4 / 0 / 14
Colombia / 97 735 / 9802 / 0 / 0 / 136
Ecuador / 2837 / 1100 / 15 / 0 / 0
Peru / 1954 / 921 / 22 / 0 / 0
Venezuela / 59 885 / 2413 / 0 / 0 / 0

[Brazil and] Southern Cone:
Brazil / 219 280 / 131 643 / 0 / 11 / 2542
Argentina / 2251 / 42 / 32 / 0 / 2
Chile / 0 / 0 / 34 / 0 / 0
Paraguay / 632 / 14 / 0 / 0 / 2
Uruguay / 0 / 0 / 1 / 0 / 0

Totals, Americas / 554 479 / 207 557 / 5827 / 20 / 2971

[Maps showing the location of the affected islands and countries in the Americas mentioned above and below can be accessed at
http://healthmap.org/promed/p/35574;
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]

North America
---
USA (San Diego, California). 28 Mar 2017. (confirmed [conf]) 1st case of microcephaly in the San Diego area; mother infected outside the USA in an area of Zika virus transmission.
http://fox5sandiego.com/2017/03/28/first-local-baby-born-with-zika-relat...

Caribbean
---
Puerto Rico. Apr 2017 [specific date not specified]. (conf) in 2017, over 1000 cases; brain damage at least 14 cases.
https://borgenproject.org/zika-infections-in-puerto-rico/

USA Virgin Islands. 12 Apr 2017. (conf) 8 new cases and 10 new presumed positives among pregnant women.
http://www.virginislandsdailynews.com/news/eight-new-confirmed-cases-of-...

[A 5 Apr 2017 report indicates that there are 1010 cases in the USA Virgin Islands. (http://www.virginislandsdailynews.com/news/confirmed-zika-cases-rise-in-...)

Aruba. 6 Apr 2017. (conf) 298 cases including 2 pregnant women.
https://www.tripadvisor.com/ShowTopic-g147247-i144-k10371081-Zika_in_the...

South America
---
Brazil:
- National. 4 Apr 2017. (registered) January - March 2017, (suspected [susp]) 3961 cases; at least 165 cases of microcephaly, (susp) 541 cases under investigation, 14 fetal or neonatal deaths, 16 spontaneous abortions; affected babies under surveillance 3165; states most affected: Bahía, Río de Janeiro, Sao Paulo
https://es-us.noticias.yahoo.com/brasil-registró-165-casos-microcefalia-zika-trimestre-2017-154400884.html [in Portuguese]

- Minas Gerais state. 4 Apr 2017. (susp) 509 cases, (conf) 128 cases in 30 municipalities.
http://hojeemdia.com.br/horizontes/minas-tem-mais-de-19-mil-casos-de-den... [in Portuguese]

Peru (Ica region). 5 Apr 2017. (conf) 33 cases
http://rpp.pe/peru/ica/confirman-33-casos-de-zika-en-la-region-ica-notic... [in Spanish]

Paraguay. 11 Apr 2017. (probable) 2 cases.
http://www.hoy.com.py/nacionales/reportan-casos-de-zika-dengue-chikungun... [in Spanish]

Asia
---
Singapore. 8 Apr 2017. (conf) A new Zika virus infection cluster of 2 cases has been confirmed at the Flower Road/Hendry Close area in Hougang, the 2nd such cluster found in a fortnight.
http://health.asiaone.com/health/health-news/new-zika-cluster-hougang

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]

Taiwan. 13 Apr 2017. (conf) 1 case ex Angola; 14 cases in 2016, all imported.
http://focustaiwan.tw/news/asoc/201704130019.aspx

[A HealthMap/ProMED-mail map of Taiwan can be accessed at http://healthmap.org/promed/p/193.]

Pacific
---
French Polynesia. April 2017 [ahead of print]. (conf) During 2013-2014, French Polynesia experienced an outbreak of Zika virus infection. Serosurveys conducted at the end of the outbreak and 18 months later showed lower than expected disease prevalence rates (49 per cent) and asymptomatic:symptomatic case ratios (1:1) in the general population but significantly different prevalence rates (66 per cent) and asymptomatic:symptomatic ratios (1:2) in schoolchildren.
https://wwwnc.cdc.gov/eid/article/23/4/16-1549_article

[The conventional concept is that 80 per cent of Zika virus infections are inapparent. In the French Polynesia outbreak, apparently, there was a greater proportion of symptomatic infections: 50 per cent in adults and 67 per cent in school children. It would be interesting to know asymptomatic:symptomatic case ratios in Brazil, Colombia or other countries with a substantial number of cases.

A HealthMap/ProMED-mail map showing the location of French Polynesia in the Pacific can be accessed at http://healthmap.org/promed/p/31048. - Mod.TY]

Africa
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Senegal and Nigeria. 13 Apr 2017. (reported) serological survey of blood samples collected from febrile patients from 1992 to 2016; of 387 samples tested, 24 were positive for Zika virus antibodies.
http://www.healio.com/infectious-disease/emerging-diseases/news/in-the-j...

[A map of Africa showing the locations of Senegal and Nigeria can be accessed at http://www.nationsonline.org/oneworld/map/africa-political-map.htm. - Mod.TY]

Other
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USA CDC alert. 29 Mar 2017. (reported) CDC has recently added 4 countries to its list of places with local transmission of Zika virus. These are Angola, Guinea-Bissau, Maldives and Solomon Islands.
http://www.health24.com/Medical/infectious-diseases/Mosquito-borne-disea...

Imported cases with no possibility of ongoing mosquito transmission (except USA Florida and Texas)

---
South Korea. 23 Mar 2017. (conf) 19 cases, 1 recent case imported from Bolivia.
http://www.koreaherald.com/view.php?ud=20170323000809

[A HealthMap/ProMED-mail map of South Korea can be accessed at http://healthmap.org/promed/p/195. - Mod.TY]

USA:
- Case numbers mainland. Zika virus disease in the United States, 2015-2017 as of 12 Apr 2017
http://www.cdc.gov/zika/geo/united-states.html
State / Symptomatic cases / Viremic blood donors
Alabama 40 / 0
Arizona 55 / 1
Arkansas 15 / 0
California 439 / 5
Colorado 58 / 0
Connecticut 58 / 0
Delaware 17 / 0
District of Columbia 40 / 0
Florida 1125 / 26
Georgia 110 / 0
Hawaii 16 / 0
Idaho 4 / 0
Illinois 108/ 0
Indiana 51 / 0
Iowa 27 / 1
Kansas 22 / 0
Kentucky 33 / 0
Louisiana 39 / 0
Maine 14 / 0
Maryland 134 / 0
Massachusetts 126 / 1
Michigan 72 / 0
Minnesota 64 / 0
Mississippi 25 / 0
Missouri 36 / 0
Montana 9 / 0
Nebraska 13 / 0
Nevada 22 / 1
New Hampshire 13 / 0
New Jersey 188 / 0
New Mexico 10 / 0
New York 1020 / 3
North Carolina 100 / 0
North Dakota 3 / 0
Ohio 85 / 0
Oklahoma 29 / 0
Oregon 48 / 0
Pennsylvania 178 / 0
Rhode Island 55 / 0
South Carolina 57 / 0
South Dakota 3 / 0
Tennessee 61 / 0
Texas 321 / 3
Utah 22 / 0
Vermont 13 / 0
Virginia 115 / 0
Washington 72 / 0
West Virginia 11 / 1
Wisconsin 56 / 0
Wyoming 2 / 0
Total 5243 / 42

- Birth defects. 4 Apr 2017. Lab tests confirmed Zika infection in 250 pregnant women. Of those, 24 completed their pregnancy with a fetus or baby that suffered birth defects linked to the virus, CDC said. The rate of birth defects found in confirmed Zika cases is more than 30 times higher than the rate of similar birth defects that occurred in the United States prior to the start of the Zika outbreak,
https://medlineplus.gov/news/fullstory_164446.html
[The CDC report on this topic is available at https://www.cdc.gov/mmwr/volumes/66/wr/mm6613e1.htm?s_cid=mm6613e1_e.

This report was provided by Kathryn Soderholm .]

- Territories and Commonwealth:
Symptomatic / Blood donors
American Samoa 132 / 0
Puerto Rico 35 397 / 325
US Virgin Islands 997 / 0
Total 36 526 / 325
[A map of the USA showing the states and territories mentioned above can be accessed at
http://www.mapsofworld.com/usa/.]

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ProMED-mail

and
Roland Hübner
Superior Health Council
Brussels
Belgium

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[2] Geographic patterns
Date: Tue 21 Mar 2017
Source: PeerJ 5:e3015; DOI 10.7717/peerj.3015 [edited]
https://peerj.com/articles/3015/

Ying-Hen Hsieh (2017), Temporal patterns and geographic heterogeneity of Zika virus (ZIKV) outbreaks in French Polynesia and Central America.

Abstract
Background.
Zika virus (ZIKV) transmission has been reported in 67 countries/territories in the Oceania region and the Americas since 2015, prompting the World Health Organization (WHO) to declare ZIKV as a Public Health Emergency of International Concern in February 2016, due to its strong association with medical complications such as microcephaly and Guillain-Barré syndrome (GBS). However, a substantial gap in knowledge still exists regarding differing temporal pattern and potential of transmission of ZIKV in different regions of the world.
Methods. We use a phenomenological model to ascertain the temporal patterns and transmission potential of ZIKV in various countries/territories, by fitting the model to Zika case data from Yap Island and French Polynesia in the Oceania region and 11 countries/territories with confirmed case data, namely, Colombia, Ecuador, French Guiana, Guadeloupe, Guatemala, Mexico, Nicaragua, Panama, Puerto Rico, Saint Martin, and Suriname, to pinpoint the waves of infections in each country/territory and to estimate the respective basic reproduction number R0.
Results. 6 of these time series datasets resulted in statistically significant model fit of at least one wave of reported cases, namely that of French Polynesia, Colombia, Puerto Rico, Guatemala, Suriname and Saint Martin. However, only Colombia and Guatemala exhibited 2 waves of cases while the others had only one wave. Temporal patterns of the 2nd wave in Colombia and the single wave in Suriname are very similar, with the respective turning points separated by merely a week. Moreover, the mean estimates of R0 for Colombia, Guatemala and Suriname, all land-based populations, range between 1.05 and 1.75, while the corresponding mean estimates for R0 of island populations in French Polynesia, Puerto Rico and Saint Martin are significantly lower with a range of 5.70-6.89. We also fit the Richards model to Zika case data from 6 main archipelagos in French Polynesia, suggesting the outbreak in all 6 island populations occurred during the same time, albeit with different peak time, with mean R0 range of 3.09-5.05.
Discussion. Using the same modeling methodology, in this study we found a significant difference between transmissibility (as quantified by R0) in island populations as opposed to land-based countries/territories, possibly suggesting an important role of geographic heterogeneity in the spread of vectorborne diseases and its future course, which requires further monitoring. Our result has potential implications for planning respective intervention and control policies targeted for island and land-based populations.

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[3] Culex mosquito vectors
Date: Sat 1 Oct 2016
Source: Vector-Borne and Zoonotic Diseases. October 2016, 16(10): 673-676. doi:10.1089/vbz.2016.2058 [edited]
http://online.liebertpub.com/doi/10.1089/vbz.2016.2058

Huang Yan-Jang S, Ayers Victoria B, Lyons Amy C, Unlu Isik, Alto Barry W, Cohnstaedt Lee W, et al. _Culex_ species mosquitoes and Zika virus.

Abstract
Recent reports of Zika virus (ZIKV) isolates from _Culex_ species mosquitoes have resulted in concern regarding a lack of knowledge on the number of competent vector species for ZIKV transmission in the new world. Although observations in the field have demonstrated that ZIKV isolation can be made from _Culex_ species mosquitoes, the detection of ZIKV in these mosquitoes is not proof of their involvement in a ZIKV transmission cycle. Detection may be due to recent feeding on a viremic vertebrate, and is not indicative of replication in the mosquito. In this study, susceptibility of recently colonized _Culex_ species mosquitoes was investigated. The results showed a high degree of refractoriness among members of _Culex pipiens_ complex to ZIKV even when exposed to high-titer bloodmeals. Our finding suggests that the likelihood of _Culex_ species mosquitoes serving as secondary vectors for ZIKV is very low, therefore vector control strategies for ZIKV should remain focused on _Aedes_ species mosquitoes. Our demonstration that _Culex quinquefasciatus_ from Vero Beach, FL, is refractory to infection with ZIKV is especially important and timely. Based on our data, we would conclude that the autochthonous cases of Zika in Florida are not due to transmission by _C. quinquefasciatus_, and so control efforts should focus on other species, logically _Aedes aegypti_ and _Aedes albopictus_.

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[Although this report was published in October 2016, it is worth including in this post because it reports another experiment indicating that _Culex quinqueasciatus_ is refractory to Zika virus infection. Only one report (http://www.nature.com/emi/journal/v5/n9/abs/emi2016102a.html) indicating that this mosquito species is an efficient vector has come to ProMED-mail: Zika virus (50): Americas, Asia, Europe, Pacific, research, observations 20160922.4506931.

_Aedes aegypti_ and _Ae. albopictus_ remain the recognized main Zika virus vector mosquitoes. A map of predicted Zika virus transmission hotspots, based on the prevalence of these 2 species can be accessed at (https://www.slu.edu/news/2017/march/predicted-zika-hot-spots.php). - Mod.TY]

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[4] Virus in semen, UK
Date: April 2017 [ahead of print]
Source: Emerg Infect Dis. 2017;23(4):611-615. https://dx.doi.org/10.3201/eid2304.16169 [edited]
https://wwwnc.cdc.gov/eid/article/23/4/16-1692_article

Atkinson B, Thorburn F, Petridou C, Bailey D, Hewson R, Simpson A, et al. Presence and persistence of Zika virus RNA in semen, United Kingdom, 2016.

Abstract
Zika virus RNA has been detected in semen collected several months after onset of symptoms of infection. Given the potential for sexual transmission of Zika virus and for serious fetal abnormalities resulting from infection during pregnancy, information regarding the persistence of Zika virus in semen is critical for advancing our understanding of potential risks. We tested serial semen samples from symptomatic male patients in the United Kingdom who had a diagnosis of imported Zika virus infection. Among the initial semen samples from 23 patients, Zika virus RNA was detected at high levels in 13 (57 per cent) and was not detected in 9 (39 per cent); detection was indeterminate in 1 sample (4 per cent). After symptomatic infection, a substantial proportion of men have detectable Zika virus RNA at high copy numbers in semen during early convalescence, suggesting high risk for sexual transmission. Viral RNA clearance times are not consistent and can be prolonged.

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[This report provides additional evidence of Zika virus in semen of convalescent men, with implications for the risk of transmission to sexual partners. - Mod.TY]

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[5] Virus in breast milk
Date: April 2017 [ahead of print, on line 7 Feb 2017]
Source: International Journal of Infectious Disease 57:70-72 DOI: http://dx.doi.org/10.1016/j.ijid.2017.01.042 [edited]
http://www.ijidonline.com/article/S1201-9712(17)30045-0/abstract

Marta G Cavalcanti, Mauro J Cabral-Castro, Jorge L S Gonçalves, Larissa S Santana, et al. Zika virus shedding in human milk during lactation: an unlikely source of infection?

Highlights

- Breastfeeding as a potential route of Zika virus (ZIKV) transmission needs to be proved.
- Breastfed children of ZIKV-infected mothers showed no ZIKV infection.
- The presence of replicative particles in milk is insufficient to infect breastfed children.
- Breastfeeding might be a less efficient route of ZIKV transmission.

Summary
Zika virus (ZIKV) transmission through non-mosquito-dependent routes has become increasingly important since reports of sexual transmission. Breastfeeding is a potential means of ZIKV transmission, but data on this remain limited. The cases of 4 mothers with laboratory-proven infections are reported. No disease evolved in 3 of the breastfed babies despite detectable maternal viremia and viruria, the presence of viral RNA shedding, and the isolation of infective particles in one milk sample. Fever and rash in one infant of a ZIKV-infected mother proved to be related to chikungunya virus infection. The results suggest that the presence of infective particles in breast milk may not be sufficient for the efficient perinatal transmission of ZIKV.

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[Although the number of mothers and their babies is small in the above study, the results -- only one in 4 -- suggest that the risks of Zika virus infection via breast milk are small. Another study on breast milk transmission describes 3 cases of ZIKV-infected breastfeeding mothers who were symptomatic within 3 days of delivery, and 2 cases with ZIKV-infected newborns. While ZIKV was detected in the breast milk of all 3 mothers, the data are not sufficient to conclude ZIKV transmission via breastfeeding. More evidence is needed to distinguish breastfeeding transmission from other perinatal transmission routes. (http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005528). - Mod.TY]

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[6] Vaccine
Date: Fri 31 Mar 2017
Source: National Institutes of Health News Release [edited]
https://www.nih.gov/news-events/news-releases/phase-2-zika-vaccine-trial...

Phase 2 Zika vaccine trial begins in US, Central and South America. Study will evaluate NIH's experimental DNA vaccine.
---------
Vaccinations have begun in a multi-site Phase 2/2b clinical trial testing an experimental DNA vaccine designed to protect against disease caused by Zika infection. The vaccine was developed by government scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). NIAID is leading the trial, which aims to enroll at least 2490 healthy participants in areas of confirmed or potential active mosquito-transmitted Zika infection, including the continental United States and Puerto Rico, Brazil, Peru, Costa Rica, Panama and Mexico. The 2-part trial, called VRC 705, further evaluates the vaccine's safety and ability to stimulate an immune response in participants, and assesses the optimal dose for administration. It also will attempt to determine if the vaccine can effectively prevent disease caused by Zika [virus] infection.

Most people with Zika infection have either no or only mild symptoms, such as fever, rash, joint pain and conjunctivitis (red eyes). However, when Zika infection occurs during pregnancy, the pregnant woman can pass the virus to her fetus, which can result in a range of fetal defects known collectively as congenital Zika syndrome. Currently there is no licensed vaccine to prevent disease caused by Zika infection, which is mainly transmitted via the bite of infected _Aedes aegypti_ mosquitoes but also can be transmitted sexually.

"We are pleased to have advanced rapidly one of NIAID's experimental Zika vaccines into this next stage of testing in volunteers. We expect this study will yield valuable insight into the vaccine's safety and ability to prevent disease caused by Zika infection," said NIAID director Anthony S Fauci, MD. "A safe and effective Zika vaccine is urgently needed to prevent the often-devastating birth defects that can result from Zika virus infection during pregnancy. Evidence also is accumulating that Zika can cause a variety of health problems in adults as well. This trial marks a significant milestone in our efforts to develop countermeasures for a pandemic in progress."

Scientists at NIAID's Vaccine Research Center (VRC) developed the NIAID Zika virus investigational DNA vaccine. It entered early-stage human testing in 2016 following extensive testing in animal models. Initial findings indicate the vaccine is safe and able to induce a neutralizing antibody response against Zika virus. The Phase 2/2b trial aims to gain more safety and immune response data and determine if this immune response protects against disease caused by natural Zika infection.

The Zika vaccine platform is based on a strategy VRC scientists used previously to develop a West Nile virus vaccine candidate. The Zika vaccine candidate being tested in this study contains a small circular piece of DNA called a plasmid into which scientists have inserted genes that encode 2 proteins found on the surface of the Zika virus. Once injected into muscle, the encoded proteins assemble into particles that mimic Zika virus and trigger the body's immune system to respond. The vaccine does not contain infectious material, so it cannot cause Zika infection.

The trial is being led by protocol co-chairs Julie E Ledgerwood, DO, chief of VRC's Clinical Trials Program, and Grace L Chen, MD, deputy chief of the same program.

The trial consists of 2 studies: part A and part B. Part A will build on ongoing Phase 1 trials to further evaluate the vaccine's safety and ability to stimulate an immune response, specifically in populations where Zika could be endemic. It will also help determine the optimal dose and injection sites for administration. Part A will enrol 90 healthy men and non-pregnant women aged 18-35 years at three sites in Houston, Miami and San Juan, Puerto Rico. All participants will receive the investigational vaccine intramuscularly at 3 separate clinic visits each 4 weeks apart. Participants will be randomly assigned to receive either a standard dose or a high dose of the investigational vaccine at all 3 visits, and will be followed for about 32 weeks total.

Part B of the trial will enroll at least 2400 healthy men and non-pregnant women aged 15-35 years. This part of the trial aims to determine if the vaccine can effectively protect against Zika-related disease when someone is naturally exposed to the virus. Sites will include the 3 locations from part A (Houston, Miami and San Juan) as well as 2 additional sites in San Juan, 2 sites in Costa Rica, and one site each in Peru, Brazil, Panama and Mexico. Additional sites might be added in the future. Participants will be randomly assigned to receive either the investigational vaccine or a placebo at 3 separate clinic visits each 4 weeks apart. The trial is double-blind, meaning neither the study investigators nor the participants will know who receives the investigational vaccine.

Part B participants will be followed for nearly 2 years, during which time they will undergo assessments for adverse events and symptoms of Zika infection. Trial participants in both parts will be counseled on how to protect against Zika infection. Investigators will compare the rates of confirmed cases of Zika in the placebo group and the vaccinated group to determine if the investigational vaccine protects against disease caused by Zika infection.

Each site will have a principal investigator responsible for ensuring daily review of safety data as they become available. A protocol safety review team that includes the protocol chairs and other medical officers at NIAID will review safety data reports weekly. The NIAID Intramural Data and Safety Monitoring Board will also review cumulative study data at least twice per year. The study is currently expected to be completed by 2019.

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[Two live attenuated Zika virus vaccines are advancing, with one research group reporting promising findings in mice and the other announcing that the 1st trial has been launched in humans (http://www.cidrap.umn.edu/news-perspective/2017/04/two-live-attenuated-z...). The findings in mice indicated complete protection after a single dose of vaccine (https://www.utmb.edu/newsroom/article11496.aspx, report submitted by Roland Hübner). This progress with different types of vaccines is very encouraging. It is important to inform the public about the 3 phases that determining vaccine safety and potency require so that there is public support for the costs of development and patience and understanding about the time it requires. - Mod.TY]

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[7] Cardiovascular complications
Date: 11 Apr 2017
Source: Healio Cardiology Today [edited]
http://www.healio.com/cardiology/arrhythmia-disorders/news/online/%7Bf87...

The Zika virus may be linked to CV complications, according to a case report presented at the American College of Cardiology Scientific Session. Since the majority of people with Zika virus infections present with mild or nonspecific symptoms, and symptoms of CV complications may not occur right away, we need to raise awareness about the possible association," Karina Gonzalez Carta, MD, a cardiologist and research fellow at the department of cardiovascular diseases at Mayo Clinic, said in a press release.

Carta and colleagues enrolled 9 patients (mean age, 47 years; 6 women) who exhibited CV symptoms in a prospective, observational, multicenter study from a Venezuelan outbreak. The 9 patients received clinical, ECG, laboratory, radiology, echocardiogram, Holter and cardiac MRI evaluations.

Arrhythmias occurred in 8 patients and included acute AF, paroxysmal and persistent AF, nonsustained atrial tachycardia and ventricular arrhythmias. In 6 patients, there were symptoms of HF (5 with reduced ejection fraction and one with preserved ejection fraction, preeclampsia and moderate to severe pericardial effusion).

According to the researchers, awareness of the association between Zika and CV complications is key, and studies are needed to define the incidence of Zika myocarditis systematically. In the release, Carta said patients should consult with their doctor when traveling to areas with known Zika virus.

"Our report provides clear evidence that there is a relationship between the Zika virus infection and [CV] complications," Carta said. "Based on these initial results, people need to be aware that if they travel to or live in a place with known Zika virus and develop rash, fever or conjunctivitis, and within a short timeframe also feel other symptoms such as fatigue, shortness of breath or their heart skipping beats, they should see their doctor."

[byline: Dave Quaile]

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[Although the number of patients with cardiovascular problems in this study was small, it does sound the alert for clinicians to be aware of these problems in patients convalescent from Zika virus infections. - Mod.TY]

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[8] Zika virus and neurologic disease
Date: Wed 29 Mar 2017 updated Thu 6 Apr 2017
Source: New England Journal of Medicine DOI: 10.1056/NEJMc1608612 [edited]
http://www.nejm.org/doi/full/10.1056/NEJMc1608612

Correspondence

Wanderson K de Oliveira, Eduardo H Carmo, Claudio M Henriques, et al. Zika virus infection and associated neurologic disorders in Brazil.

The number of suspected cases of ZIKV infection began to increase in the north east region of Brazil starting in March 2015 (week 9). Cases were subsequently reported in the other 4 regions, beginning in late 2015 and greatly expanding in 2016. Together with phylogenetic analysis of viral RNA sequences, these findings suggest that ZIKV was dispersed widely after a single introduction of infection in the north east region.

The spread of ZIKV in Brazil has been associated with an increase in the incidence of neurologic disorders, most visibly in cases reported as GBS [Guillain-Barré syndrome] and microcephaly. Weekly reports of cases from hospitals reveal that the incidence of GBS was markedly higher in the north east region in 2015 and 2016 and in other areas of Brazil in 2016 than in the years before the ZIKV epidemic (2010 to 2014) (figure 1B, and section 3 in the supplementary appendix [see original paper for figures]). The rise and fall of suspected cases of ZIKV infection and GBS were approximately synchronous in 2015, although a comparison of the 2 case series suggests that the incidence of ZIKV infection was underreported in the northeast region early in 2015 (figure 1B). In Pernambuco state, some of the cases of ZIKV infection were probably misclassified (mainly as dengue) in clinics in 2015, and such misclassification could have been widespread.

The incidence of microcephaly peaked in late November 2015 (week 47), an average of 23 weeks after the start of the epidemics of ZIKV infection and GBS (figure 1B). If there was a delay of 3 weeks between the exposure of patients to ZIKV and the development of GBS (that is, an incubation period plus a typical reporting delay), infections leading to microcephaly would have occurred on average 12 weeks after conception (that is, with about half the cases occurring during the 1st trimester and half later in pregnancy) (section 4 in the supplementary appendix).

In view of the apparent resurgence of ZIKV infection and GBS early in 2016, we anticipated a further increase in cases of microcephaly later in the year. But such a resurgence did not happen (figure 1B), for at least 3 possible reasons. The 1st possibility is that in 2016, infections that were attributed to ZIKV and that were linked to an increase in the incidence of GBS were caused by another arbovirus that is also transmitted by _Aedes aegypti_ mosquitoes, since by then there was herd immunity against ZIKV infection after widespread infection in 2015. Dengue virus has been identified throughout the Americas (section 5 in the supplementary appendix) but does not appear to be a major cause of GBS. Chikungunya virus was introduced into Brazil in 2014 and caused successively larger epidemics in the north east region in 2015 and 2016. Chikungunya [virus infection] is a cause of GBS as well, and some chikungunya [virus] infections were evidently misclassified as ZIKV infection in Pernambuco in 2016 (Brito C: personal communication). Chikungunya [virus infection] has not been identified as a cause of microcephaly.

A 2nd possibility is that ZIKV infection during pregnancy is a necessary but not a sufficient condition for the development of microcephaly in newborn infants -- in other words, the presence of some other unknown cofactor that is not essential for GBS is required. A 3rd possibility is that fear of the adverse consequences of ZIKV infection led to fewer conceptions or a greater number of pregnancy terminations in 2016. Routinely collected data are not yet complete enough to determine whether birth rates fell or abortion rates increased in 2016 (section 6 in the supplementary appendix). However, since any changes in the number of live births would be small, this hypothesis cannot be the principal reason why few cases of microcephaly were reported in the northeast region in 2016.

Among these hypotheses, the 1st seems to be the most plausible, that is, both ZIKV and chikungunya viruses are important causes of GBS, but among the arboviruses circulating in Brazil, only ZIKV causes microcephaly and other neurologic disorders after infection during pregnancy. However, the 3 possibilities are not mutually exclusive, and none can be ruled out with the present data. Further investigations are needed -- aided by more sensitive and specific diagnostic tools and the careful interpretation of surveillance data -- to clarify the causal links between arbovirus infections, GBS, and microcephaly in Brazil.

--
communicated by:
ProMED-mail rapporteur Mary Marshall

[This report illustrates the need for accurate diagnosis to differentiate between Zika, dengue and chikungunya virus infections, especially in the cases of pregnant women.

There is a January 2017 article providing a description with photographs of the phenotypic spectrum of congenital Zika syndrome (http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.38170/epdf) that was sent in by Roland Hübner. - Mod.TY]

******
[9] CRISPR diagnostic test
Date: Thu 13 Apr 2017
Source: Science eaam9321 DOI: 10.1126/science.aam9321 [edited]
http://science.sciencemag.org/content/early/2017/04/12/science.aam9321?v...

Jonathan S Gootenberg, Omar O Abudayyeh, Jeong Wook Lee, Patrick Essletzbichler. Nucleic acid detection with CRISPR-Cas13a/C2c2.

Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting CRISPR effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous RNAse activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity. We use this Cas13a-based molecular detection platform, termed SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing), to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify cell-free tumor DNA mutations. Furthermore, SHERLOCK reaction reagents can be lyophilized for cold-chain independence and long-term storage, and readily reconstituted on paper for field applications.

--
communicated by:
Roland Hübner
Superior Health Council
Brussels
Belgium

******
[10] QUASR Diagnostic test
Date: 20 Mar 2017
Source: Scientific Reports 7, Article no: 44778 doi:10.1038/srep44778 [edited]
https://www.nature.com/articles/srep44778

Aashish Priye, Sara W Bird, Yooli K Light, Cameron S Ball, Oscar A Negrete, Robert J Meagher. A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses.

Abstract
Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. Here we demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable "LAMP box" supplemented with a consumer class smartphone. The entire assembly can be powered by a 5 V USB source such as a USB power bank or solar panel. Our smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device's utility for widespread clinical deployment. Together, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most.

--
communicated by:
Roland Hübner
Superior Health Council
Brussels
Belgium

[Because the symptoms of early Zika, dengue and chikungunya virus infections are similar, a rapid, specific, sensitive and low-cost differential diagnostic test that can detect Zika virus infections is needed urgently. The need is especially important for pregnant women who become infected with Zika virus so that their pregnancies can be closely monitored due to the risk of teratogenic effects on their developing fetuses. - Mod.TY]

******
[11] Cost to countries
Date: Tue 10 Apr 2017
Source: Public Finance International [edited]
http://www.publicfinanceinternational.org/news/2017/04/zika-outbreak-cou...

The Zika epidemic could cost Latin America and the Caribbean USD 18 billion by 2018, an analysis by the United Nations Development Programme has found. Falling tourism revenues, strain on health systems and lost productivity are among the short- and long-term costs the epidemic could have, with the poorest countries in the region likely to be hit the hardest.

The UNDP's report, published last week, used 3 scenarios, based on different rates of infection, to gauge the impact Zika might have. It estimated the virus could cost the region between USD 7 billion in the best case scenario and USD 18 billion in the worst, from 2015, when the outbreak began, to 2018.

Jessica Faieta, UN assistant secretary-general and UNDP director for Latin America and the Caribbean, warned there would also be more intangible costs. "Aside from losses to GDP and to economies heavily dependent on tourism, and the stresses on health care systems, the long-term consequences of the Zika virus can undermine decades of social development, hard-earned health gains and slow down progress towards the Sustainable Development Goals," she said.

Zika is a mosquitoborne virus that can cause children to be born with a condition called microcephaly [and other teratogenic effects. - Mod.TY] if their mother is infected during pregnancy. Microcephaly is characterised by an abnormally small head size and incomplete brain development. Later in life, children with the disease can develop epilepsy, cerebral palsy, learning difficulties and hearing or vision problems. Since 2015, 2971 confirmed cases of microcephaly associated with Zika infection have been recorded, according to the World Health Organization.

The virus has also prompted a smaller increase in Guillain-Barré syndrome, which affects the nervous system and can lead to paralysis, lasting for weeks or several months.

While larger economies such as Brazil are expected to bear the greatest share of the absolute cost (between 14-26 per cent), the impact on the Caribbean will be 5 times that in South America and will be the most severe in the poorest countries, the UNDP said. In some cases, the total cost of Zika could exceed 2 per cent of countries' GDP (in Aruba and the US Virgin Islands), while it could exceed one per cent in some of the region's poorest nations, Haiti (1.13 per cent) and Belize (1.19 per cent).

Caribbean nations rely heavily on tourism, and more than 80 per cent of potential losses in the subregion would result from declining revenues brought by visitors from abroad. This could potentially cost USD 10.5 billion over 3 years, or 0.06 per cent of the Caribbean's GDP annually.

Other short-term costs include strain on health systems to do with diagnosis and care, especially for children born with microcephaly. In the long term, it is likely one of their parents will withdraw from the labour market in order to care for them, with substantial consequences for productivity. The UNDP estimated that, in the worst case scenario, the total direct and indirect lifetime cost of microcephaly cases caused by Zika could hit USD 29 billion.

[byline: Emma Rumney]

--
communicated by:
ProMED-mail

[The loss of GDP impacts the entire country's population, not just families with cases of Zika virus infection. The social and economic cohorts in those countries most affected by Zika virus infections are most likely those cohorts least able to cope with the resulting financial loss and social stress. Families with children that have suffered terotogenic effects from the infection can result in the need for lifetime care of those children that can continue for years or decades. - Mod.TY]

See Also

Zika virus (05): Americas, Pacific, Asia, research, observations 20170326.4927523
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Zika virus (01): Americas, Asia, Africa, research 20170117.4772206
2016
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Zika virus (45): worldwide, WHO, research, comment 20160904.4464015
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Zika virus (07): update 20160216.4023810
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Zika virus (06): overview 20160209.4007411
Zika virus (05): Americas, Asia, Pacific 20160203.3990632
Zika virus (04): WHO declares worldwide PHEIC 20160201.3985366
Zika virus (03): Americas, Asia 20160128.3974426
Zika virus - Americas (02) 20160111.3925377
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