ZIKA VIRUS (18): AMERICAS, RESEARCH, OBSERVATIONS

Posted on 09TH SEP 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 (Cuernavaca, Morelos state)
Panama (San Miguelito district, Panama province)

South America
---
Brazil (Sergipe state)
Peru (La Libertad region)

Imported cases with little or no possibility of ongoing mosquito transmission
USA:
- Case numbers mainland
- Texas (Brownsville)
- Territories and Commonwealth

[2] Zika and Guillain-Barré Syndrome
[3] Vaccine withdrawal
[4] Antivirus drug
[5] Retinal maldevelopment

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[1] Cases in various countries
Americas cumulative case numbers
As of 7 Sep 2017
http://www.paho.org/hq/index.php?option=com_content&view=article&id=1239...
Country / Locally acquired: suspected / Confirmed /Imported / Deaths / Conf. Congenital Syndrome
North America:
Bermuda / 0 / 0 / 6 / 0 / 0
Canada / 0 / 0 / 507 / 0 / 1
USA / 0 / 224 / 5168 / 0 / 95

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

Central American Isthmus:
Belize / 1854 / 308 / 0 / 0 / 0
Costa Rica / 7290 / 1920 / 32 / 0 / 6
El Salvador / 11 649 / 51 / 0 / 0 / 4
Guatemala / 3741 / 983 / 0 / 0 / 140
Honduras / 32 385 / 308 / 0 / 0 / 8
Nicaragua / 0 / 2060 / 3 / 0 / 2
Panama / 4802 / 1095 / 42 / 0 / 13

Latin Caribbean:
Cuba / 0 / 187/ 58 / 0 / 0
Dominican Republic / 4919 / 335 / 0 / 0 / 85
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 / 40 576 / 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 / 3
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) / 1165 / 1024 / 2 / 0 / 0

Andean Area:
Bolivia / 2535 / 785 / 4 / 0 / 14
Colombia / 98 587 / 9802 / 0 / 0 / 243
Ecuador / 3753 / 3058 / 15 / 0 / 7
Peru / 6434 / 1515 / 22 / 0 / 0
Venezuela / 60 081 / 2413 / 0 / 0 / 0

[Brazil and] Southern Cone:
Brazil / 231 725 / 137 288 / 0 / 11 / 2869
Argentina / 539 / 276 / 40 / 0 / 2
Chile / 0 / 0 / 34 / 0 / 0
Paraguay / 661 / 16 / 0 / 0 / 2
Uruguay / 0 / 0 / 1 / 0 / 0

Totals, Americas / 579 700 / 220 693 / 6124 / 20 / 3593

[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 and Central America
---
Mexico (Cuernavaca, Morelos state). 25 Jul 2017. (registered) 53 cases of whom 19 pregnant.
https://www.elsoldecuernavaca.com.mx/local/suman-102-casos-de-dengue-y-5... [in Spanish]

Panama (San Miguelito district, Panama province). 31 Jul 2017. (reported) 23 cases.
http://www.telemetro.com/nacionales/Contabilizan-dengue-chikungunya-San-... [in Spanish]

South America
---
Brazil (Sergipe state). 31 Aug 2017. (reported) cases of suspected Zika virus infection-related microcephalic cases in 2015, 181 cases; in 2016, 93 cases; thus far in 2017, 2 cases under investigation.
http://www.infonet.com.br/noticias/saude/ler.asp?id=204383 [in Portuguese]

Peru (La Libertad region). 10 Aug 2017. (reported) 18 cases.
http://peru21.pe/actualidad/dengue-reportan-quinta-muerte-este-mal-liber... [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-6 Sep 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 25 / 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 2 / 0
Louisiana 1 / 0
Maine 1 / 0
Maryland 9 / 0
Massachusetts 8 / 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 44 / 1
North Carolina 5 / 0
North Dakota 0 / 0
Ohio 3 / 0
Oklahoma 1 / 0
Oregon 4 / 0
Pennsylvania 5 / 1
Rhode Island 3 / 0
South Carolina 2 / 0
South Dakota 0 / 0
Tennessee 0 / 0
Texas 22 / 1
Utah 3 / 0
Vermont 3 / 0
Virginia 5 / 0
Washington 6 / 0
West Virginia 1 / 1
Wisconsin 3 / 0
Wyoming 2 / 0
Totals 231 / 9

- Brownsville, Texas. 31 Aug 2017. (reported) Brownsville is no longer a yellow (cautionary) zone for Zika, according to the Centers for Disease Control and Prevention. The designation was lifted in collaboration with the Texas Department of State Health Services.
http://www.brownsvilleherald.com/news/local/article_aa082f32-8ebf-11e7-b...

- Territories and Commonwealth with local transmission:
Territory Symptomatic cases / Viremic blood donors
American Samoa 39 / 0
Puerto Rico 474 / 3
US Virgin Islands 41 / 0
Total 554 / 3

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

--
Communicated by:
ProMED-mail

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[2] Zika and Guillain-Barré syndrome
Date: Wed 30 Aug 2017
Source: PLoS Neglected Tropical Diseases journal [edited]
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005869

Ref: Styczynski AR, Malta JMAS, Krow-Lucal ER, et al. Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil. PLoS Negl Trop Dis. 2017; 11(8): e0005869
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Abstract
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In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April-July 2015 among those 12 years of age and older was 5.6 cases/100 000 population/year and increased markedly with increasing age to 14.7 among those 60 years of age and older. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83 percent) compared to controls (21 percent) reported an antecedent illness (OR 18.1, CI 6.9-47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

Author summary
--------------
Shortly following the introduction of Zika virus (ZIKV), a type of flavivirus transmitted by mosquitoes, into Brazil in early 2015, the Brazil Ministry of Health began receiving increased reports of a paralyzing condition known as Guillain-Barré syndrome (GBS). The areas with the greatest number of GBS cases appeared to correlate geographically and temporally with the areas reporting the highest rate of ZIKV infections. This association had been previously observed during a ZIKV outbreak in French Polynesia, however, this had not been systematically examined in a case-control investigation for the ZIKV outbreak in South America. In this investigation, the authors found that the occurrence of GBS in the affected population was nearly 4 times higher than would be expected, and the risk for GBS was particularly elevated among older adults. GBS was associated with ZIKV-like symptoms and with a combination of ZIKV-like symptoms plus laboratory evidence of a recent flavivirus infection. Taken together, these findings provide strong support for and greater understanding of the link between ZIKV and GBS.

--
Communicated by:
ProMED-mail

[Although it is difficult to prove causality, the report above shows a strong GBS-Zika virus infection association through their case-control study. Many other previous reports have provided anecdotal associations with Zika virus infection, but the report above provides a more formal study. - Mod.TY]

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[3] Vaccine withdrawal
Date: Sat 2 Sep 2017
Source: STAT [edited]
https://www.statnews.com/2017/09/02/sanofi-zika-vaccine/

Vaccine giant Sanofi Pasteur has quietly pulled the plug on its Zika vaccine project, a move that underscores how difficult it may be at this stage to develop a vaccine against the virus.

The company announced the move in a statement posted on its website at 3 pm [Fri 1 Sep 2017], pointing to a decision by a federal funding body to scale back spending on Zika-related research. Sanofi said BARDA -- the Biomedical Advanced Research and Development Authority, an arm of the Department of Health and Human Services -- informed the company in mid-August that it was reducing its financial assistance for Sanofi's Zika vaccine project.

"Consequently, Sanofi does not intend to continue development of, or seek a license from, the Walter Reed Army Institute of Research for the Zika vaccine candidate at this time," the company stated.

While a number of experimental Zika vaccines are at various stages in clinical testing, Sanofi was the only major pharmaceutical company working on a vaccine for the virus with a near-term market goal.

A spokeswoman said [Sat 2 Sep 2017] that Jon Heinrichs -- the Sanofi executive who was spearheading the Zika project -- was not available for an interview. Neither was BARDA director Rick Bright, though he commented briefly by email about the agency's shift in funding plans.
"Zika remains a public health threat, and BARDA plans to continue working with industry partners including Sanofi on developing Zika vaccines and diagnostics to make them available commercially as quickly as possible," Bright told STAT. "The specific activities of development projects often change based on a variety of technical and epidemiological factors."

Commercial concerns
-------------------
Sanofi was the target of a lot of negative press earlier this year [2017] when a number of federal and state lawmakers raised concerns about Sanofi's contract with Walter Reed, where federal government scientists designed the vaccine. They complained that a vaccine that had been created with taxpayer funding might be priced out of the reach of Americans. Those statements led to a bruising and public back-and-forth about the company's pricing intentions.

With Zika out of the headlines and infections in the Americas seemingly at very low levels, the company's decision to stop work on the project is not surprising. The financial prospects for a Zika vaccine are unclear at this point.

There were loud calls for a vaccine to protect against the virus in the winter of 2016. That's when it became apparent that Zika was responsible for a huge surge in cases of microcephaly in Brazil. The condition, which can be caused by a number of exposures during pregnancy, results in the underdevelopment of the head of a baby, and sometimes the brain as well. Zika's impact on microcephaly falls on a spectrum. Some children develop normally, but others have developmental delays and other health issues. Many of the microcephaly cases in Brazil were at the severe end of the spectrum and the early photographs of those babies were haunting.

US officials fast-tracked Zika vaccine development, making bold promises that a vaccine might be available within 2 years. Though Congress was slow to fund then-President Obama's Zika emergency response request, a number of candidate vaccines began human clinical trials before the end of 2016. Given that laboratories hadn't been working on Zika vaccines previously, that speed was extraordinary.

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Communicated by:
ProMED-mail Rapporteur Mary Marshall

[Developing and testing a vaccine in 2 years would be a remarkable feat. There has been an active debate about production, distribution and sale of the Sanofi vaccine. As noted above, the vaccine was developed by the Walter Reed Army Institute of Research, with production and sales by Sanofi Pasteur. The issue related to this, and any other vaccine, is if it will be affordable in countries with the populations most at risk. This type of private/federal relationship raises the question about who can and should set prices. - Mod.TY]

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[4] Antivirus drug
Date: Thu 10 Aug 2017
Source: International Journal of Antimicrobial Agents journal [edited]
http://www.ijaaonline.com/article/S0924-8579(17)30308-4/fulltext

Ref: de Carvalho OV, Félix DM, de Mendonça LR, et al. The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication. Int J Antimicrob Agents. 2017. pii: S0924-8579(17)30308-4. doi: 10.1016/j.ijantimicag.2017.08.016
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Highlights
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- For the 1st time, 6MMPr was identified as a potential antiviral drug against ZIKV;
- All assays used the epidemic ZIKV strain circulating in Brazil;
- Antiviral activity was tested in both epithelial and human neuronal cells;
- 6MMPr was much less toxic to neuronal cells compared to epithelial cells;
- 6MMPr decreased ZIKV production in both cells by more than 99 percent.

Abstract
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Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of the disease caused by the virus. The ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here, we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analog derived from the prodrug azathioprine (AZA), against the epidemic ZIKV strain circulating in Brazil. In all the assays, an epithelial (Vero) and an human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and the effective concentrations of 6MMPr against ZIKV. The levels of ZIKV RNA, viral infectious titer and the percentage of infected cells at the presence or absence of 6MMPr was used to determine the antiviral efficacy. We show that 6MMPr decreased ZIKV production by more than 99 percent in both cell lines in a dose- and time-dependent way. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared to Vero cells, presenting a 50 percent cytotoxic concentration (CC50) of 460.3 µM and 291 µM, respectively. The selectivity index of 6MMPr for Vero and SH-SY5Y cells was 11.9 and 22.7, respectively, highlighting the safety profile of the drug to neuronal cells. Taken together, our results identify, for the 1st time, the thiopurine nucleoside analog 6MMPr as promising antiviral candidate against ZIKV that warrants further in vivo evaluation.

--
Communicated by:
ProMED-mail

[This finding is promising and warrants further research. The authors are correct that further evaluation in animal models is essential to test for innocuity and potency. - Mod.TY]

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[5] Retinal maldevelopment
Date: Thu 7 Sep 2017
Source: JAMA Ophthalmology journal [edited]
http://jamanetwork.com/journals/jamaophthalmology/fullarticle/2652891

Ref: Aleman TS, Ventura CV, Cavalcanti MM, et al. Quantitative assessment of microstructural changes of the retina in infants with congenital Zika syndrome.

Key points
Question: What are the microstructural changes of the retina in congenital Zika syndrome?
Findings: In this case series of 8 patients with congenital Zika syndrome and 8 individuals with cobalamin C deficiency, retinal regions without chorioretinal atrophy demonstrated ganglion cell layer loss on spectral-domain optical coherence tomography that was disproportionately more severe than coexisting changes in the photoreceptor and inner nuclear layers.
Meaning: Consistent with a murine model of congenital Zika syndrome, this study provides in vivo evidence of depletion of a specific neuronal population (ganglion cells) in this condition, which may constitute the primary event that ultimately leads to foveal maldevelopment and central chorioretinal atrophy.
Abstract
Importance: A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS).
Objective: To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment.
Design, Setting, and Participants: This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from 1 Jan-17 Mar 2016, for patients with CZS and from 4 May 2015-23 Apr 2016, for patients with cblC deficiency.
Main outcomes and measures: The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles.
Results: Included in the analysis were 8 infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years). All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (less than 30 percent of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer. The inner nuclear layer was normal or had borderline thinning. The central retinal degeneration was similar to that of cblC deficiency.
Conclusions and relevance: Congenital Zika syndrome showed a central retinal degeneration with severe GCL loss, borderline inner nuclear layer thinning, and less prominent photoreceptor loss. The findings provide the 1st, to date, in vivo evidence in humans for possible retinal maldevelopment with a predilection for retinal GCL loss in CZS, consistent with a murine model of the disease and suggestive of in utero depletion of this neuronal population as a consequence of Zika virus infection.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[This study provides a more detailed description of retinal maldevelopment resulting from Zika virus infection of infants. Clinicians examining infants who have been Zika virus infected or possibly exposed to the virus in utero should look for these changes. - Mod.TY]

See Also

Zika virus (17): Americas, research, observations 20170830.5283102
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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