ZIKA VIRUS (21): AMERICAS, RESEARCH, OBSERVATIONS

Posted on 09TH OCT 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

North America
---
USA (Cameron county, Texas)

South America
---
Brazil (Parana state)

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

[2] Ocular lesions
[3] Rapid diagnostic test
[4] Blood screening test
[5] Hearing loss
[6] Guillain-Barré syndrome severity

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[1] Cases in various countries
Americas cumulative case numbers
As of 5 Oct 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 / 523 / 0 / 1
USA / 0 / 225 / 5255 / 0 / 98

Latin America:
Mexico / 0 / 10 097 / 15 / 0 / 20

Central American Isthmus:
Belize / 2005 / 355 / 0 / 0 / 0
Costa Rica / 7554 / 1956 / 32 / 0 / 6
El Salvador / 11 688 / 51 / 0 / 0 / 4
Guatemala / 3822 / 1000 / 0 / 0 / 140
Honduras / 32 385 / 308 / 0 / 0 / 8
Nicaragua / 0 / 2065 / 3 / 0 / 2
Panama / 5646 / 1177 / 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 / 40 588 / 137 / 5 / 47
Saint Barthélemy / 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 / 7772 / 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 / 2553 / 786 / 4 / 0 / 14
Colombia / 98 532 / 9925 / 0 / 0 / 248
Ecuador / 3753 / 3058 / 15 / 0 / 7
Peru / 6509 / 1517 / 22 / 0 / 0
Venezuela / 60 097 / 2413 / 0 / 0 / 0

[Brazil and] Southern Cone:
Brazil / 231 725 / 137 288 / 0 / 11 / 2952
Argentina / 539 / 276 / 40 / 0 / 2
Chile / 0 / 0 / 34 / 0 / 0
Paraguay / 668 / 18 / 0 / 0 / 2
Uruguay / 0 / 0 / 1 / 0 / 0

Totals, Americas / 581 262 / 221 520 / 6227 / 20 / 3689

[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 (Cameron county, Texas). 5 Oct 2017. (susp) 1 locally acquired case.
http://www.krgv.com/story/36533700/cameron-co-health-officials-confirm-f...

South America
---
Brazil (Parana state). 27 Sep 2017. (conf) 30 cases.
https://g1.globo.com/pr/parana/noticia/parana-registra-56-casos-suspeito... [in Portuguese]

Imported cases with little or no possibility of ongoing mosquito transmission
---
USA
- Case numbers states. Zika virus disease in the United States, 1 Jan-4 Oct 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 27 / 3
Colorado 5 / 0
Connecticut 0 / 0
Delaware 0 / 0
District of Columbia 1 / 0
Florida 54 / 3
Georgia 1 / 0
Hawaii 2 / 0
Idaho 0 / 0
Illinois 6 / 0
Indiana 2 / 0
Iowa 1 / 0
Kansas 2 / 0
Kentucky 2 / 0
Louisiana 1 / 0
Maine 1 / 0
Maryland 10 / 0
Massachusetts 9 / 0
Michigan 7 / 0
Minnesota 6 / 0
Mississippi 2 / 0
Missouri 1 / 0
Montana 0 / 0
Nebraska 1 / 0
Nevada 1 / 0
New Hampshire 0 / 0
New Jersey 7 / 0
New Mexico 0 / 0
New York 54 / 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 29 / 1
Utah 4 / 0
Vermont 3 / 0
Virginia 6 / 0
Washington 8 / 0
West Virginia 1 / 1
Wisconsin 4 / 0
Wyoming 2 / 0
Totals 288 / 10

- Territories and Commonwealth with local transmission:
Symptomatic / Blood donors
American Samoa 52 / 0
Puerto Rico 476 / 6
US Virgin Islands 41 / 0
Total 569 / 6

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

--
Communicated by:
ProMED-mail

******
[2] Ocular lesions
Date: Thu 21 Sep 2017
Source: JAMA Ophthalmology journal [edited]
http://jamanetwork.com/journals/jamaophthalmology/fullarticle/2654136

ref: Fernandez MP, Parra Saad E, Ospina Martinez M, et al. Ocular histopathologic features of congenital Zika syndrome. JAMA Ophthalmol. 2017; doi: 10.1001/jamaophthalmol.2017.3595. [Epub ahead of print]
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Key points
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Question: What are the ocular histopathologic features of fetuses with congenital Zika syndrome?
Findings: In this case series of 4 eyes from 4 fetuses with congenital Zika syndrome, expression of the Zika virus antigen was identified within the iris, neural retina, choroid, and optic nerve. Histopathologic examination revealed a pupillary membrane, an immature anterior chamber angle, lack of differentiation of the nuclear layers of the neural retina, a thin photoreceptor layer, loss of pigment and thinning of the retinal pigment epithelium, a perivascular inflammatory infiltrate within the choroid, and choroidal thinning.
Meaning: Detection of Zika virus antigens within different ocular tissues in the context of congenital Zika syndrome suggests that the histopathologic findings may be associated with Zika virus infection.
Abstract
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Importance: Congenital Zika syndrome (CZS) is known to be associated with severe malformations in newborns. Although microcephaly is the hallmark of this disease, the ocular findings are important given the severe visual impairment that has been observed in these patients. Regardless of the increased number of CZS cases reported, to date, no studies have described the ocular histopathologic findings of this entity.
Objectives: To evaluate the presence of Zika virus (ZIKV) antigens and describe the associated ocular histopathologic features of 4 cases of CZS.
Design, setting, and participants: In this observational case series performed from 19 Jun 2015, through 30 Apr 2017, ocular tissue samples from 4 deceased fetuses with a diagnosis of CZS from the National Institute of Health in Colombia were sent to the Florida Lions Ocular Pathology Laboratory for evaluation.
Main outcomes and measures: The microscopic features of each specimen were described, and immunostaining was performed using a ZIKV NS2B protein antibody.
Results: Ocular tissue samples from the 4 deceased fetuses (2 female, 2 male) ranging from 21.5 to 29 weeks' gestation with a diagnosis of CZS were studied. The 4 eyes manifested with pupillary membranes, immature anterior chamber angles, loss of pigment and thinning of the retinal pigment epithelium, choroidal thinning, undifferentiated nuclear layers of the retina, and a perivascular inflammatory infiltrate within the choroid. The optic nerve, present in 2 of the eyes, demonstrated atrophy. Expression of ZIKV antigen was present in the iris in cases 1, 3, and 4; the neural retina and choroid in case 1; and in the optic nerve in case 4.
Conclusions and relevance: Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were consistently present. These findings may be attributed to ZIKV infection and warrant further study.

--
Communicated by:
ProMED-mail

[This report provides additional detail on the ocular lesions caused by fetal Zika virus infection. - Mod.TY]

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[3] Rapid diagnostic test
Date: Wed 27 Sep 2017
Source: Science Translational Medicine journal [edited]
http://stm.sciencemag.org/content/9/409/eaan1589

ref: Bosch I, de Puig H, Hiley M, et al. Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum. Sci Transl Med. 2017; 9(409). pii: eaan1589. doi: 10.1126/scitranslmed.aan1589.
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Distinguishing dengue from Zika
------------------------------
More than mere summer pests, mosquitoes can transmit viruses, such as dengue and Zika. Diagnosing infections of these related flaviviruses can be difficult because of cross-reactivity in diagnostic tests. Bosch et al. developed monoclonal antibodies to detect viral nonstructural 1 (NS1) protein antigens specific to dengue and Zika. Incorporating the antibodies into an immunochromatography format yielded a rapid diagnostic assay that produces a visual readout in the presence of NS1. The assay identified the 4 dengue serotypes and Zika viral infections without cross-reaction when testing human serum samples from endemic areas in Central and South America and India. This approach could be useful for developing rapid diagnostics for other emerging pathogens.

Abstract
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The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the 4 DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1-4 tests and the pan-DENV test, which detects all 4 dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction-positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall
and
Roland Hübner
Superior Health Council
Brussels
Belgium

[Sensitive, specific, and technically simple tests are needed to differentiate dengue and Zika virus infections. The report above indicates that they have developed a test that meets those criteria. It will be interesting to see how long it takes for follow up ground truthing and deployment in the field. - Mod.TY]

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[4] Blood screening test
Date: Thu 5 Oct 2017
Source: FDA News Release [edited]
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm579313.htm

FDA approves 1st test for screening Zika virus in blood donations
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The US Food and Drug Administration today [5 Oct 2017] approved the cobas Zika test, a qualitative nucleic acid test for the detection of Zika virus RNA in individual plasma specimens obtained from volunteer donors of whole blood and blood components, and from living organ donors. It is intended for use by blood collection establishments to detect Zika virus in blood donations, not for the individual diagnosis of Zika virus infection.

"Today's action represents the 1st approval of a Zika virus detection test for use with screening the nation's blood supply, "said Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research. "Screening blood donations for the Zika virus is critical to preventing infected donations from entering the US blood supply. Today's approval is the result of a commitment by the manufacturer to work rapidly and collaboratively with the FDA and the blood collection industry to respond to a public health crisis and ensure the safety of blood in the US and its territories."

In August 2016, the FDA issued a final guidance document recommending that all states and territories screen individual units of whole blood and blood components with an investigational blood screening test available under an investigational new drug (IND) application, or a licensed (approved) test when available.

Before today, several blood collection establishments used the cobas Zika test under IND in order to follow the recommendations in the FDA's 2016 guidance document. The data collected from this testing, and from additional studies performed by the manufacturer, demonstrated that the cobas Zika test is an effective test to screen blood donors for Zika virus infection. The test's clinical specificity was evaluated by testing individual samples from blood donations at 5 external laboratory sites, resulting in clinical specificity of more than 99 percent.

The Zika virus is transmitted primarily by mosquitos (_Aedes aegypti_), but it can also be spread through blood transfusion and sexual contact.

The cobas Zika test is intended for use on the fully automated cobas 6800 and cobas 8800 systems. The cobas Zika test, cobas 6800, and cobas 8800 systems are manufactured by Roche Molecular Systems, Inc.

--
Communicated by:
ProMED-mail

[It is good to now have a standard test for screening blood and blood components for the presence of Zika virus. Although _Aedes aegypti_ is the major transmitter of the virus, infection from blood transfusion occurs often enough to warrant a reliable screening test to eliminate this risk. - Mod.TY]

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[5] Hearing loss
Date: Thu 5 Oct 2017
Source: JAMA Otolaryngology-Head & Neck Surgery journal [edited]
https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/265...

ref: Mittal R, Fifer RC, Liu XZ. Possible association between hearing loss and Zika virus infections. JAMA Otolaryngol Head Neck Surg. 2017 Oct 5. doi: 10.1001/jamaoto.2017.1798. [Epub ahead of print]
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[Abstract]
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Among the many etiologies of hearing loss (HL), viral infection of the auditory system is also implicated as the underlying causative factor. Emerging new viral infections, including Zika virus (ZIKV), have been associated with HL in both infants and adults, warranting studies to elucidate the underlying molecular mechanisms that lead to hearing impairment. Early reports of infants with congenital ZIKV syndrome (CZS) estimated a rate of 6-9 percent HL, comparable to some of the other viral causes of congenital HL, although prevalence needs to be further studied. In one retrospective study, the complete auditory function evaluation in a series of 70 children with microcephaly and laboratory evidence of congenital ZIKV infection revealed that 4 (6 percent) infants had sensorineural HL (SNHL). Click auditory brainstem response (ABR) was performed as a newborn screening test, and frequency-specific ABR was conducted one month later to confirm SNHL. Another study of 104 neonates with microcephaly and presumed congenital ZIKV infection in Brazil reported 9 percent HL by otoacoustic emission (OAE) testing. However, ZIKV testing was not performed because it was not available at the time of the study and incomplete testing for TORCHES (toxoplasmosis, rubella, cytomegalovirus [CMV], herpes, human immunodeficiency virus, and syphilis) was performed. Nevertheless, both reports may be underestimating the incidence of HL because only infants with microcephaly were included. Studies of other congenital infections, such as CMV, have revealed that 8 percent of infants with CMV who have normal imaging results have HL and up to 25 percent of infants with CMV eventually have HL. Further studies are warranted to determine whether and when infants with ZIKV infection without neurological manifestations develop HL.

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Communicated by:
ProMED-mail

[It would be desirable for infants with or without microcephaly born to Zika virus infected mothers to have their hearing tested. - Mod.TY]

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[6] Guillain-Barré syndrome severity
Date: Fri 6 Oct 2017
Source: MedPage Today [edited]
https://www.medpagetoday.com/meetingcoverage/idweek/68373

Researchers in Puerto Rico said they found no difference in disability rates at 6 months in patients with Guillain-Barré syndrome (GBS) linked to Zika virus compared to those with GBS alone, suggesting that GBS's course is the same whether it stems from Zika or other causes.

But the GBS/Zika cases showed more signs of virus-related features such as cranial neuropathy, according to Emilio Dirlikov, PhD, a CDC epidemic intelligence service officer.

"Our analysis suggests that Zika virus infection does not trigger a more severe form of GBS," Dirlikov told MedPage Today at the annual IDWeek conference [4-8 Oct 2017], sponsored jointly by the Infectious Diseases Society of American (IDSA), the Pediatric Infectious Diseases Society (PIDS), the Society for Healthcare Epidemiology of America (SHEA), and the HIV Medicine Association (HIVMA).

Researchers have previously linked infection with the Zika virus to subsequent GBS cases, although the risk of GBS is thought to be small.

For the new study, Dirlikov and colleagues tracked 71 Puerto Rican cases of GBS with evidence of Zika and 36 of GBS alone. The GBS patients with Zika were more likely to be female (52 percent versus 28 percent, P=0.017), but researchers didn't find statistically significant differences between the groups in terms of age or days of hospitalization.

"We were surprised that Puerto Rico GBS patients with and without evidence of Zika virus infection were clinically similar," Dirlikov said. "For example, there was no difference in terms of the time from antecedent illness to onset of neurologic illness, contrary to other reports that only examined this time step among GBS patients with evidence of Zika virus infection."

In terms of antecedent illness, rash was much more common in GBS/Zika patients (51 percent versus 8 percent, P less than 0.001). Joint pain and rhinorrhea were also more common (p=0.032, 0.004, respectively).

As for neurological symptoms, facial weakness (62 percent versus 28 percent, p less than 0.001) and dysphagia (54 percent versus 25 percent, P=0.005) were much more common in GBS/Zika patients. Shortness of breath and facial paresthesia were also significantly more common.

Previous reports have also indicated higher rates of cranial neuropathy, Dirlikov said. These findings suggest that "that the cranial nerves may be targeted by either virus or antibody," he said.

GBS/Zika patients were also more likely to require intensive care (66 percent versus 44 percent, P=0.031) and mechanical ventilation (31 percent versus 11 percent, P=0.024).

"There was no difference in the disability at clinical nadir, in-hospital mortality rates, and disability measured by 3 different metrics at 6 months post-neurologic illness onset," Dirlikov said.

At 6 months, the remaining patients (n=27 for GBS alone, n=60 for GBS/Zika) showed no difference in disability, although the GBS/Zika patients had more tearing/eye dryness, drinking difficulties, and reported pain.

Clinical virologist David Smith, MBBS, of the University of Western Australia, who was not involved with the research, cautioned that the study "identified cases based on hospital coding, which can be inaccurate, and they didn't directly assess or classify the patients. Other studies have used stricter criteria for diagnosis and follow up assessment."

Consequently, he said it remains possible that Zika virus could worsen GBS, although the study "does strengthen some of the previous findings" about GBS/Zika.

In a separate study [at the IDWeek conference], researchers led by Lina Villa of the Universidad Nacional de Colombia prospectively analyzed 20 GBS/Zika patients (75 percent male, median age 45) at hospitals in Valledupar, Colombia, and also found a course similar to what is seen in non-Zika GBS [see https://goo.gl/Bby4Yt].

At a median follow-up time of 193 days, 80 percent of 15 remaining patients had functional independence in regard to basic functions; 40 percent had paresis in 4 limbs, 27 percent had difficulty walking, and 27 percent had hyporeflexia or areflexia.

"When compared to GBS secondary to conventional triggers, the outcomes seem to not vary much. It is reassuring to know that even though we are dealing with a new threatening pandemic, the long-term outcomes seem to be fairly equal to GBS in general," neurologist Ivan Rocha Ferreira DaSilva, MD, PhD, of Rush University in Chicago, told MedPage Today.

DaSilva, who was not part of the study, praised it but added: "My biggest concern is how testing for Zika infection was done, as only serologies were performed. Cross reactivity among Zika and dengue is frequent, even more in a country with endemic presence of both viruses."

[Byline: Randy Dotinga]

--
Communicated by:
ProMED-mail

[It is reassuring to learn that Zika virus infection does not exacerbate the long-term consequences in GBS patients. - Mod.TY]

See Also

Zika virus (20): Americas, Asia, research, observations 20170925.5339356
Zika virus (19): Americas, research, observations 20170917.5322171
Zika virus (18): Americas, research, observations 20170908.5303860
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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