ZIKA VIRUS (16): AMERICAS, RESEARCH, OBSERVATIONS

Posted on 30TH AUG 2017
tagged Zika Virus, Americas

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

Cases in various countries not mentioned above or more recent case numbers.

Mexico
- Coahuila state

Caribbean
---
Sint Maarten ex Saba

South America
---
Bolivia (Santa Cruz department)

Imported cases with little or no possibility of ongoing mosquito transmission
USA
- Case numbers mainland
- Territories and Commonwealth

[2] Ribavirin inhibits Zika virus
[3] Zika virus skewed immunosuppression
[4] Virus alters mosquito genes
[5] Virus effects on sperm, body fluids
[6] Vaccine update

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[1] Cases in various countries
Americas cumulative case numbers
As of 24 Aug 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 / 507 / 0 / 1
USA / 0 / 224 / 5150 / 0 / 93

Latin America:
Mexico / 0 / 9378 / 15 / 0 / 15

Central American Isthmus:
Belize / 1832 / 290 / 0 / 0 / 0
Costa Rica / 7100 / 1887 / 32 / 0 / 6
El Salvador / 11 628 / 51 / 0 / 0 / 4
Guatemala / 3741 / 983 / 0 / 0 / 140
Honduras / 32 130 / 302 / 0 / 0 / 4
Nicaragua / 0 / 2060 / 3 / 0 / 2
Panama / 4802 / 1035 / 42 / 0 / 13

Latin Caribbean:
Cuba / 0 / 187 / 58 / 0 / 0
Dominican Republic / 4913 / 345 / 0 / 0 / 93
French Guiana / 10 500 / 483 / 10 / 0 / 1
Guadeloupe / 30 845 / 382 / 0 / 0 / 5
Haiti / 2955 / 5 / 0 / 0 / 1
Martinique / 36 680 / 21 / 0 / 0 / 5
Puerto Rico / 0 / 40 569 / 137 / 5 / 47
Saint Barthelemy / 1005 / 61 / 0 / 0 / 0
Saint Martin / 3283 / 200 / 0 / 0 / 1

Non-Latin Caribbean:
Anguilla / 31 / 23 / 1 / 0 / 0
Antigua and Barbuda / 540 / 25 / 2 / 0 / 0
Aruba / 1208 / 703 / 7 / 0 / 0
Bahamas / 531 / 25 / 3 / 0 / 0
Barbados / 715 / 150 / 0 / 0 / 1
Bonaire, St Eustatius and Saba / 235 / 437 / 0 / 0 / 0
Caymans / 237 / 30 / 11 / 0 / 0
Curacao / 4476 / 2049 / 0 / 0 / 0
Dominica / 1154 / 79 / 0 / 0 / 0
Grenada / 335 / 118 / 0 / 0 / 2
Guyana / 0 / 37 / 0 / 0 / 0
Jamaica / 7650 / 203 / 0 / 0 / 0
Montserrat / 18 / 5 / 0 / 0 / 0
Saint Kits and Nevis / 554 / 33 / 0 / 0 / 0
Saint Lucia / 822 / 50 / 0 / 0 / 0
Saint Vincent and the Grenadines / 508 / 83 / 0 / 0 / 0
Sint Maarten / 253 / 149 / 0 / 0 / 0
Suriname / 2768 / 724 / 0 / 4 / 4
Trinidad and Tobago / 0 / 718 / 1 / 0 / 17
Turks and Caicos / 203 / 25 / 3 / 0 / 0
Virgin Islands (UK) / 74 / 53 / 0 / 0 / 0
Virgin Islands (USA) / 1158 / 1024 / 2 / 0 / 0

Andean Area:
Bolivia / 2525 / 785 / 4 / 0 / 14
Colombia / 98 515 / 9802 / 0 / 0 / 187
Ecuador / 3753 / 3058 / 15 / 0 / 7
Peru / 6391 / 1502 / 22 / 0 / 0
Venezuela / 59 965 / 2413 / 0 / 0 / 0

[Brazil and] Southern Cone:
Brazil / 220 717 / 136 846 / 0 / 11 / 2869
Argentina / 869 / 138 / 40 / 0 / 2
Chile / 0 / 0 / 34 / 0 / 0
Paraguay / 662 / 16 / 0 / 0 / 2
Uruguay / 0 / 0 / 1 / 0 / 0

Totals, Americas / 568 181 / 219 766 / 6106 / 20 / 3539

[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]

Cases in various countries not mentioned above or more recent case numbers.
Mexico
---
Mexico (Coahuila state). 24 Aug 2017. (conf.) 4 new cases, 2 of whom pregnant.
http://laprensademonclova.com/portal/2017/08/24/detectan-4-casos-de-zika... [in Spanish]

Caribbean
---
Sint Maarten ex Saba. 21 Aug 2017. (conf.) 1 case of microcephaly. The mother was unaware that she had been infected.
https://www.thedailyherald.sx/islands/68711-country-sees-first-case-of-s...

South America
---
Bolivia (Santa Cruz department). 17 Aug 2017 (registered) 145 cases of whom 40 are pregnant. Microcephaly 1 case.
http://elmundo.com.bo/web2/index.php/noticias/index?id=confirman-que-beb... [in Spanish]

Imported cases with little or no possibility of ongoing mosquito transmission
---
USA
- Case numbers mainland. Zika virus disease in the United States, 1 Jan 2017-23 Aug 2017
http://www.cdc.gov/zika/geo/united-states.html
State / Symptomatic cases / Viremic blood donors
Alabama 3 / 0
Alaska 1 / 0
Arizona 1 / 0
Arkansas 0 / 0
California 22 / 2
Colorado 4 / 0
Connecticut 0 / 0
Delaware 0 / 0
District of Columbia 0 / 0
Florida 31 / 3
Georgia 2 / 0
Hawaii 1 / 0
Idaho 0 / 0
Illinois 3 / 0
Indiana 1 / 0
Iowa 1 / 0
Kansas 2 / 0
Kentucky 1 / 0
Louisiana 1 / 0
Maine 1 / 0
Maryland 8 / 0
Massachusetts 7 / 0
Michigan 7 / 0
Minnesota 5 / 0
Mississippi 2 / 0
Missouri 1 / 0
Montana 0 / 0
Nebraska 1 / 0
Nevada 1 / 0
New Hampshire 0 / 0
New Jersey 6 / 0
New Mexico 0 / 0
New York 43 / 1
North Carolina 5 / 0
North Dakota 0 / 0
Ohio 3 / 0
Oklahoma 1 / 0
Oregon 3 / 0
Pennsylvania 4 / 1
Rhode Island 3 / 0
South Carolina 2 / 0
South Dakota 0 / 0
Tennessee 0 / 0
Texas 18 / 1
Utah 3 / 0
Vermont 3 / 0
Virginia 5 / 0
Washington 3 / 0
West Virginia 1 / 1
Wisconsin 3 / 0
Wyoming 2 / 0
Totals 215 / 9

- Territories and Commonwealth with local transmission:
Symptomatic / Blood donors
American Samoa 39 / 0
Puerto Rico 475 / 3
US Virgin Islands 41 / 0
Total 555 / 3

[A map of the USA showing the states and territories mentioned above can be accessed at http://www.mapsofworld.com/usa/. - Mod.TY]

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ProMED-mail

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[2] Ribavirin inhibits Zika virus
Date: 14 Aug 2017
Source: Antiviral Research journal [edited]
http://www.sciencedirect.com/science/article/pii/S0166354217301973

ref: Kamiyama N, Soma R, Hidano S, et al. Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice. Antiviral Res. 2017; 146: 1-11. doi: 10.1016/j.antiviral.2017.08.007
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Highlights
- Ribavirin inhibits ZIKV replication in mammalian cells.
- Ribavirin prevents ZIKV-induced apoptosis and cell death.
- Ribavirin administration abrogates viremia in ZIKV-infected STAT1-deficient mice.
- Leading to a prolonged survival.
Abstract
Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-beta (IFN-beta), on ZIKV replication. In mammalian cells, we observed an inhibitory effect of ribavirin on ZIKV replication and ZIKV-induced cell death without cytotoxic effect. Furthermore, we found that STAT1-deficient mice, which lack type I IFN signaling, were highly sensitive to ZIKV infection and exhibited lethal outcome. Ribavirin abrogated viremia in ZIKV-infected STAT-1-deficient mice. These data suggest that the inhibition of viral RNA-dependent RNA polymerases may be effective for treatment of ZIKV infection. Our data provide a new insight into the mechanisms for inhibition of ZIKV replication and prevention of Zika fever.

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Communicated by:
ProMED-mail

[It will be interesting to see if these encouraging results showing inhibition of Zika virus replication can be replicated in non-human primates. The challenge for use of drugs to inhibit Zika virus infection in humans is that most (around 80 percent) Zika virus infections are asymptomatic or have very mild symptoms. These individuals will probably not seek medical treatment, even though their fetuses are at risk of infection with teratogenic effects. - Mod.TY]

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[3] Zika virus skewed immunosuppression
Date: Mon 21 Aug 2017
Source: Nature Microbiology journal [edited]
http://www.nature.com/articles/s41564-017-0016-3

ref: Foo SS, Chen W, Chan Y, et al. Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy. Nat Microbiol. 2017. doi: 10.1038/s41564-017-0016-3
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Abstract
Blood CD14+ monocytes are frontline immunomodulators categorized into classical, intermediate or non-classical subsets, and subsequently differentiated into M1 pro- or M2 anti-inflammatory macrophages on stimulation. Although the Zika virus (ZIKV) rapidly establishes viraemia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses. Using human blood infection, we identified CD14+ monocytes as the primary target for African- or Asian-lineage ZIKV infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by the African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by the Asian-lineage ZIKV infection. Importantly, infection of the blood of pregnant women revealed an enhanced susceptibility to ZIKV infection. Specifically, Asian-lineage ZIKV infection of pregnant women's blood led to an exacerbated M2-skewed immunosuppression of non-classical monocytes in conjunction with a global suppression of type I interferon-signaling pathway and an aberrant expression of host genes associated with pregnancy complications. Also, 30 ZIKV+ sera from symptomatic pregnant patients showed elevated levels of M2-skewed immunosuppressive cytokines and pregnancy-complication-associated fibronectin-1. This study demonstrates the differential immunomodulatory responses of blood monocytes, particularly during pregnancy, on infection with different lineages of ZIKV.

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Communicated by:
ProMED-mail from HealthMap Alerts

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[4] Virus alters mosquito genes
Date: Tue 22 Aug 2017
Source: bioRxiv journal [edited]
http://www.biorxiv.org/content/early/2017/08/22/179416

ref: Etebari K, Hegde S, Saldana MA, et al. Global transcriptome analysis of _Aedes aegypti_ mosquitoes in response to Zika virus infection. bioRxiv 179416; doi:10.1101/179416
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Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito _Aedes aegypti_ that also vectors dengue virus, however little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole _Ae. aegypti_ mosquitoes in response to ZIKV infection at 2, 7, and 14 days post-infection using RNA-Seq. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the 3 time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic process, cellular process and proteolysis. In addition, 486 long intergenic non-coding RNAs were identified altered upon ZIKV infection. Further, we found correlational changes of a number of potential mRNA target genes with that of altered host microRNAs. The outcomes provide a basic understanding of _Ae. aegypti_ responses to ZIKV and helps to determine host factors involved in replication or mosquito host anti-viral response against the virus.

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Communicated by:
ProMED-mail

[Mosquito vector competence depends on the relationship of virus and the mosquito, and the defenses that the mosquito can mobilize against the virus infection. Studies, such as the one above, can document the changes that occur when the virus infects the mosquito, and if differences in relative vector efficiency of different geographic strains of this mosquito might be related to alternations in mosquito genes when infected. It would be interesting to know if these gene changes affect fitness, and especially longevity of infected mosquitoes. - Mod.TY]

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[5] Virus effects on sperm, body fluids
Date: Mon 21 Aug 2017
Source: The Lancet Infectious Diseases journal [edited]
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30444-9/abstract

ref: Joguet G, Mansuy JM, Matusali G, et al. Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. Lancet Infect Dis. 2017. pii: S1473-3099(17)30444-9. doi: 10.1016/S1473-3099(17)30444-9
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Summary
Background
Evidence of human sexual transmission during Zika virus emergence is a matter of concern, particularly in procreation, but to date, kinetics of seminal shedding and the effects of infection on human reproductive function have not been described. To investigate the effects of Zika virus infection on semen and clearance of Zika virus from semen and body fluids, we aimed to study a cohort of Zika virus-infected men.

Methods
This prospective observational study recruited men presenting with acute Zika virus infection at Pointe-Ã -Pitre University Hospital in Guadeloupe, French Caribbean, where a Zika virus outbreak occurred between April and November, 2016. Blood, urine, and semen were collected at days 7, 11, 20, 30, 60, 90, and 120 after symptom onset, and semen characteristics, such as total sperm count, sperm motility, vitality, and morphology, and reproductive hormone concentrations, such as testosterone, inhibin, follicle-stimulating hormone, and luteinising hormone, were assessed. At days 7, 11, and 20, semen was processed to isolate motile spermatozoa. Zika virus RNA was detected by RT-PCR using whole blood, serum, urine, seminal plasma, semen cells, and motile spermatozoa fractions. Zika virus was isolated from different sperm fractions on Vero E6 cultures.

Findings
15 male volunteers (mean age 35 years [SD 5; range 25-44) with acute Zika virus infection and positive Zika virus RNA detection in blood or urine were enrolled. Total sperm count was decreased from median 119 Ã-- 10^6 spermatozoa (IQR [interquartile range] 22-234) at day 7, to 45.2 Ã-- 10^6 (16.5-89.6) at day 30, and 70 Ã-- 10^6 (28.5-81.4) at day 60, respectively, after Zika virus infection. Inhibin values increased from 93.5 pg/mL (IQR 55-162) at day 7 to 150 pg/mL (78-209) at day 120 when total sperm count recovered. In motile spermatozoa obtained after density gradient separation, Zika virus RNA was found in 3 of 14 patients at day 7, 4 of 15 at day 11, and 4 of 15 at day 20, and replication-competent virus was found in the tested patient. Seminal shedding kinetics seemed heterogeneous among patients. Whole blood was the fluid most frequently positive for Zika virus RNA (62 of 92 samples) and 3 patients remained positive at day 120.

Interpretation
Semen alterations early after acute Zika virus infection might affect fertility and could be explained by virus effects on the testis and epididymis. Frequency of shedding and high viral load in semen, together with the presence of replicative virus in a motile spermatozoa fraction, can lead to Zika virus transmission during sexual contact and assisted reproduction procedures. Whole blood seems to be the best specimen for Zika virus RNA detection, diagnosis, and follow-up.

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Communicated by:
ProMED-mail Rapporteur Mary Marshall

[In a new study that included 12 men in French Guiana who had Zika virus, 4 never had any detectable Zika in their semen, 1 excreted Zika virus in his semen for at least 3 days, and 7 had Zika virus in semen for at least 1 month. The maximum duration of detectable Zika in semen in the study was 45 days (http://tinyurl.com/y9nhtgtk). This report was provided by Roland Hübner. - Mod.TY]

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[6] Vaccine update
Date: 22/29 Aug 2017
Source: Journal of the American Medical Association, JAMA [edited]
http://jamanetwork.com/journals/jama/fullarticle/2649168

ref: Lyon J. Vaccines protect fetus from Zika. JAMA. 2017; 318(8): 689. doi:10.1001/jama.2017.11200
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Researchers funded in part by the National Institutes of Health have recently demonstrated that 2 experimental vaccines can restrict transmission of Zika virus from pregnant mice to their fetuses, thereby shielding offspring from congenital damage or death.

Multiple candidate Zika vaccines have been shown protective against infection with the virus in animal studies, with several now in human trials, but none were tested in the context of pregnancy, according to the authors of the study published in Cell [http://www.cell.com/cell/fulltext/S0092-8674(17)30759-6]. The 2 vaccine candidates investigated in the new study are the 1st to demonstrate efficacy in preventing vertical transmission of the virus and related fetal death in an animal model. Although the vaccines were administered to female mice prior to pregnancy, the result is considered an important step toward developing a vaccine that could be safely given to pregnant women.

One of the 2 candidates is a modified messenger RNA (mRNA) vaccine encoding Zika genes, developed by the biotechnology company Moderna. It is already in safety trials in women who are not pregnant. The other is a live-attenuated Zika strain developed by researchers at the University of Texas Medical Branch (UTMB).

The testing was carried out by scientists from the National Institute of Allergy and Infectious Diseases, Washington University School of Medicine, and UTMB. The researchers 1st vaccinated the mice with 1 of the vaccines or a placebo. After mating, the animals were challenged with the virus 6 days into pregnancy. A week later, more than 50 percent of placentas and fetuses from mice administered the mRNA vaccine had virtually no Zika RNA. The remainder had "substantially lower" levels relative to placebo.
The live vaccine provided broader protection: 78 percent of placentas and 83 percent of fetuses had Zika RNA at or below the level of detection, while the placebo group exhibited significantly higher levels of placental and fetal Zika RNA. Mice vaccinated with either vaccine had significantly higher rates of fetal viability; whereas 100 percent of fetuses from mice vaccinated with the mRNA vaccine were born, none survived to term in the placebo group.

A working group funded by the Wellcome Trust recently approved ethical guidelines for testing such vaccines in pregnant women, normally excluded from drug trials.

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Communicated by:
ProMED-mail

[It is reassuring to learn that at least 2 vaccines are now entering clinical trials in women. Although anti-Zika virus drugs are under development, preventing infection through vaccination seems to be the most effective measure to prevent fetal infection and adverse effects of the virus infection in adults. - Mod.TY]

See Also
Zika virus (16): Americas, Asia, research, observations 20170819.5261363
Zika virus (15): Americas, research, observations 20170701.5144254
Zika virus (14): Americas, Asia, research, observations 20170623.5127418
Zika virus (13): Americas, research, observations 20170617.5112404
Zika virus (12): Americas, Asia, research, observations 5099103
Zika virus (11): Americas, research, observations 20170604.5083731
Zika virus (10): Americas, Asia, Middle East, research 20170529.5069572
Zika virus (09): Americas, Asia, Europe, research, observations 20170517.5043638
Zika virus (08): Americas, Asia, research, observations 20170501.5005629
Zika virus (07): Americas, PAHO/WHO 20170429.5003908
Zika virus (06): Americas, Pacific, Asia, Africa, research 20170416.4974439
Zika virus (05): Americas, Pacific, Asia, research, observations 20170326.4927523
Zika virus (04): Americas, Asia Europe, research, observations 20170320.4912123
Zika virus (03): Americas, research 20170309.4888510
Zika virus (02): Americas, Asia, Africa, Pacific, research, observations 20170217.4846633
Zika virus (01): Americas, Asia, Africa, research 20170117.4772206
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