Identifying Areas at Greatest Risk for Recent Zika Virus Importation — New York City, 2016

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Introduction: The New York City Department of Health and Mental Hygiene sought to detect and minimize the risk of local, mosquito-borne Zika virus (ZIKV) transmission. We modeled areas at greatest risk for recent ZIKV importation, in the context of spatially biased ZIKV case ascertainment and no data on the local spatial distribution of persons arriving from ZIKV-affected countries.

Methods: For each of 14 weeks during June-September 2016, we used logistic regression to model the census tract-level presence of any ZIKV cases in the prior month, using eight covariates from static sociodemographic census data and the latest surveillance data, restricting to census tracts with any ZIKV testing in the prior month. To assess whether the model discriminated better than random between census tracts with and without recent cases, we compared the area under the receiver operating characteristic (ROC) curve for each week’s fitted model versus an intercept-only model applied to cross-validated data. For weeks where the ROC contrast test was significant at P < 0.05, we output and mapped the model-predicted individual probabilities for all census tracts, including those with no recent testing.

Results: The ROC contrast test was significant for 8 of 14 weekly analyses. No covariates were consistently associated with the presence of recent cases. Modeled risk areas fluctuated across these 8 weeks, with Spearman correlation coefficients ranging from 0.30 to 0.93, all P < 0.0001. Areas in the Bronx and upper Manhattan were in the highest risk decile as of late June, while as of late August, the greatest risk shifted to eastern Brooklyn.

Conclusion: We used observable characteristics of areas with recent, known travel-associated ZIKV cases to identify similar areas with no observed cases that might also be at-risk each week. Findings were used to target public education and Aedes spp. mosquito surveillance and control. These methods are applicable to other conditions for which biased case ascertainment is suspected and knowledge of how cases are geographically distributed is important for targeting public health activities.

A Possible Link Between Pyriproxyfen and Microcephaly

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The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus’s role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented—it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about molecular mechanisms and toxicological evidence, we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further.

Isolation of Zika Virus Imported from Tonga into Australia

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Introduction: The globally emergent Zika virus (ZIKV) is a threat to Australia, given the number of imported cases from epidemic regions and the presence of competent mosquito vectors. We report the isolation of ZIKV from a female traveler who recently returned from Tonga to Brisbane, Queensland, Australia in 2016.

Methods: A specific TaqMan real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) assay was used to detect ZIKV in serum and urine samples. Conventional cell culture techniques and suckling mice were employed in an attempt to isolate ZIKV from serum and urine.

Results: A ZIKV isolate (TS17-2016) was recovered from the serum sample after one passage in suckling mouse brains and harvested 11 days post inoculation. Phylogenetic analysis of complete envelope (E) gene sequences demonstrated TS17-2016 shared 99.9% nucleotide identity with other contemporary sequences from Tonga 2016, Brazil 2015 and French Polynesia 2013 within the Asian lineage.

Discussion: This is the first known report of successful isolation of ZIKV from a human clinical sample in Australia and the first from a traveler from Tonga. This study highlights the potential difficulties in isolating ZIKV from acute clinical samples using conventional cell culture techniques, particularly in non-endemic countries like Australia where access to samples of sufficient viral load is limited. The successful isolation of TS17-2016 will be essential for continued investigations of ZIKV transmission and pathogenicity and will enable the advancement of new preventative control measures extremely relevant to the Australian and Pacific region.

Utility of a Dengue-Derived Monoclonal Antibody to Enhance Zika Infection In Vitro

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Introduction: Zika virus (ZIKV) has emerged in dengue (DENV) endemic areas, where these two related flaviviruses continue to co-circulate. DENV is a complex of four serotypes and infections can progress to severe disease. It is thought that this is mediated by antibody dependent enhancement (ADE) whereby antibodies from a primary DENV infection are incapable of neutralizing heterologous DENV infections with another serotype. ADE has been demonstrated among other members of the Flavivirus group.

Methods: We utilize an in vitro ADE assay developed for DENV to determine whether ZIKV is enhanced by a commonly available DENV serotype 2-derived monoclonal antibody (4G2).

Results: We show that ZIKV infection in vitro is enhanced in the presence of the 4G2 mAb.

Discussion: Our results demonstrate that ADE between ZIKV and DENV is possible and that the 4G2 antibody is a useful tool for the effects of pre-existing anti-DENV antibodies during ZIKV infections.

FLIRT-ing with Zika: A Web Application to Predict the Movement of Infected Travelers Validated Against the Current Zika Virus Epidemic

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Introduction: Beginning in 2015, Zika virus rapidly spread throughout the Americas and has been linked to neurological and autoimmune diseases in adults and babies. Developing accurate tools to anticipate Zika spread is one of the first steps to mitigate further spread of the disease. When combined, air traffic data and network simulations can be used to create tools to predict where infectious disease may spread to and aid in the prevention of infectious diseases. Specific goals were to: 1) predict where travelers infected with the Zika Virus would arrive in the U.S.; and, 2) analyze and validate the open access web application’s (i.e., FLIRT) predictions using data collected after the prediction was made.

Method: FLIRT was built to predict the flow and likely destinations of infected travelers through the air travel network. FLIRT uses a database of flight schedules from over 800 airlines, and can display direct flight traffic and perform passenger simulations between selected airports. FLIRT was used to analyze flights departing from five selected airports in locations where sustained Zika Virus transmission was occurring. FLIRT’s predictions were validated against Zika cases arriving in the U.S. from selected airports during the selected time periods.  Kendall’s τ and Generalized Linear Models were computed for all permutations of FLIRT and case data to test the accuracy of FLIRT’s predictions.

Results: FLIRT was found to be predictive of the final destinations of infected travelers in the U.S. from areas with ongoing transmission of Zika in the Americas from 01 February 2016 – 01 to April 2016, and 11 January 2016 to 11 March 2016 time periods. MIA-FLL, JFK-EWR-LGA, and IAH were top ranked at-risk metro areas, and Florida, Texas and New York were top ranked states at-risk for the future time period analyzed (11 March 2016 – 11 June 2016). For the 11 January 2016 to 11 March 2016 time period, the region-aggregated model indicated 7.24 (95% CI 6.85 – 7.62) imported Zika cases per 100,000 passengers, and the state-aggregated model suggested 11.33 (95% CI 10.80 – 11.90) imported Zika cases per 100,000 passengers.

Discussion: The results from 01 February 2016 to 01 April 2016 and 11 January 2016 to 11 March 2016 time periods support that modeling air travel and passenger movement can be a powerful tool in predicting where infectious diseases will spread next. As FLIRT was shown to significantly predict distribution of Zika Virus cases in the past, there should be heightened biosurveillance and educational campaigns to medical service providers and the general public in these states, especially in the large metropolitan areas.  

Genetically Modified (GM) Mosquito Use to Reduce Mosquito-Transmitted Disease in the US: A Community Opinion Survey

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Introduction: Mosquito-borne infectious diseases such as dengue, chikungunya, and now Zika, pose a public health threat to the US, particularly Florida, the Gulf Coast states, and Hawaii. Recent autochthonous transmission of dengue and chikungunya in Florida, the recent dengue outbreak in Hawaii, and the potential for future local spread of Zika in the US, has led to the consideration of novel approaches to mosquito management. One such novel approach, the release of sterile genetically modified mosquitoes, has been proposed as a possible intervention, and a trial release of GM mosquitoes is being considered in one Florida community. However, this proposal has been controversial. The objective of this research was to increase understanding of community knowledge, attitudes, and beliefs regarding mosquito control and GM mosquitoes.  

Methods: An 18-question self-administered survey was mailed to all households in the identified Key West, Florida neighborhood where a GM mosquito trial has been proposed. This survey was fielded between July 20, 2015 and November 1, 2015. The main outcome variable was opposition to the use of GM mosquitoes. Measures included demographic information and opinions on mosquitoes, mosquito control, and vector-borne diseases.  

Results: A majority of survey respondents did not support use of GM mosquitoes as a mosquito control method.

Discussion: Reasons for opposition included general fears about possible harmful impacts of this intervention, specific worries about human and animal health impacts from the GM mosquitoes, and environmental concerns about potential negative effects on the ecosystem. Residents were more likely to oppose GM mosquito use if they had a low perception of the potential risks posed by diseases like dengue and chikungunya, if they were female, and if they were less concerned about the need to control mosquitoes in general. These findings suggest a need for new approaches to risk communication, including educational efforts surrounding mosquito control and reciprocal dialogue between residents and public health officials.

Zika Virus, Elevation, and Transmission Risk

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Introduction: Zika virus has appeared in the Americas in the form of a major outbreak, and is now known to cause birth defects when pregnant women are infected. As a result, the Centers for Disease Control and Prevention issued travel guidelines, in the form of an elevational risk definition: destinations below 2000m are considered as at-risk.

Methods: We explored the distribution of known Zika virus vector mosquito species in relation to climatic conditions, elevation, latitude, and air traffic connections to the United States.

Results: In view of the tropical and subtropical nature of the mosquito species that are the primary Zika virus vectors, we point out that climate varies rather dramatically with respect to elevation and latitude, such that a single elevational criterion will be a poor predictor of potential for transmission.

Discussion: We suggest an initial adjustment would consider latitude in addition to elevation; a more definitive, quantitative analysis of risk would consider variables of ecology, climate, human condition, and connectivity of areas.

Clinical and Epidemiological Characterization of Laboratory-Confirmed Autochthonous Cases of Zika Virus Disease in Mexico

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Introduction: Since 2014, autochthonous circulation of Zika virus (ZIKV) in the Americas was detected (Easter Island, Chile). In May 2015, Brazil confirmed autochthonous ­­transmission and in October of that year Colombia reported their first  cases. Now more than 52 countries have reported cases, including Mexico. To deal with this contingency in Mexico, several surveillance systems, in addition to systems for vector-borne diseases were strengthened with the participation of all health institutions. Also, the Ministry of Health defined an Action Plan against ZIKV for the whole country.

Methods: We analyzed 93 autochthonous cases of ZIKV disease identified by Epidemiological Surveillance System for Zika Virus in Mexico. All autochthonous cases confirmed by laboratory since November 25, 2015 to February 19, 2016 were included. A description of clinical and epidemiological characteristics of 93 cases of ZIKV disease are presenting and, we describe the Action Plan against this public health emergency. 

Results: The distribution of cases by sex was 61 men and 32 women; mean age was 35 years old (S.D. 15, range 6-90). The main clinical features in the 93 cases were fever (96.6%), rash (93.3%), non-purulent conjunctivitis (88.8%), headache (85.4%), and myalgia (84.3%). No deaths were reported.

Conclusion: The ZIKV epidemic poses new challenges to public health systems. The information provided for basic, clinical, and epidemiological research, in addition to the data derived from epidemiological surveillance is essential. However, there are still many unanswered questions regarding mechanisms of transmission, complications, and impact of this virus.

Unintended Pregnancies in Brazil – A Challenge for the Recommendation to Delay Pregnancy Due to Zika

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Figure 2.

Because of the potential link between the ongoing Zika virus outbreak and a surge in the number of cases of congenital microcephaly, officials in Latin America have recommended that women postpone pregnancy until this association is firmly established or the outbreak subsides. However, in all these countries a large proportion of babies are still born out of unplanned pregnancies. Teenage girls are particularly at high risk, as they often lack access to preventive contraception methods, or the knowledge to use them appropriately. To gauge the magnitude of the barriers preventing the implementation of such a recommendation in Brazil, the country so far most affected by the Zika epidemic, we evaluated pregnancy rates in teenage girls, and their spatial heterogeneity in the country, in recent years (2012-2014). Nearly 20% of children born in Brazil today (~560,000 live births) are by teenage mothers. Birth incidence is far higher in the tropical and poorer northern states. However, in absolute terms most births occur in the populous southeastern states, matching to a large extent the geographic distribution of dengue (an indicator of suitable climatic and sociodemographic conditions for the circulation of Aedes mosquitoes). These findings indicate that recommendation to delay pregnancy will leave over half a million pregnant adolescents in Brazil vulnerable to infection every year if not accompanied by effective education and real access to prevention.