Zika Virus Seroprevalence, French Polynesia, 2014-2015 (original) (raw)
BMC public health, 2018
We evaluated whether outbreaks of Zika virus (ZIKV) infection, newborn microcephaly, and Guillain-Barré syndrome (GBS) in Latin America may be detected through current surveillance systems, and how cases detected through surveillance may increase health care burden. We estimated the sensitivity and specificity of surveillance case definitions using published data. We assumed a 10% ZIKV infection risk during a non-outbreak period and hypothetical increases in risk during an outbreak period. We used sensitivity and specificity estimates to correct for non-differential misclassification, and calculated a misclassification-corrected relative risk comparing both periods. To identify the smallest hypothetical increase in risk resulting in a detectable outbreak we compared the misclassification-corrected relative risk to the relative risk corresponding to the upper limit of the endemic channel (mean + 2 SD). We also estimated the proportion of false positive cases detected during the outbr...
Preconceptual Zika virus asymptomatic infection protects against secondary prenatal infection
PLoS pathogens, 2017
Pregnant women, and their fetal offspring, are uniquely susceptible to Zika virus and other microbial pathogens capable of congenital fetal infection. Unavoidable exposure to Zika virus in endemic areas underscores the need for identifying at-risk individuals, and protecting expecting mothers and their fetal offspring against prenatal infection. Here we show that primary Zika virus asymptomatic infection in mice confers protection against re-infection, and that these protective benefits are maintained during pregnancy. Zika virus recovery was sharply reduced in maternal tissues and amongst fetal concepti after prenatal challenge in mothers with resolved subclinical infection prior to pregnancy compared with mice undergoing primary prenatal infection. These benefits coincide with expanded accumulation of viral-specific antibodies in maternal serum and fetal tissues that protect against infection by the identical or heterologous Zika virus genotype strains. Thus, preconceptual infecti...
PLOS Neglected Tropical Diseases
Vector control is still our primary intervention for both prevention and mitigation of epidemics of many vector-borne diseases. Efficiently targeting control measures is important since control can involve substantial economic costs. Targeting is not always straightforward, as transmission of vector-borne diseases is affected by various types of host movement. Here we assess how taking daily commuting patterns into consideration can help improve vector control efforts. We examine three tropical urban centers (San Juan, Recife, and Jakarta) that have recently been exposed to Zika and/or dengue infections and consider whether the distribution of human populations and resulting commuting flows affects the optimal scale at which control interventions should be implemented. We developed a stochastic, spatial model and investigated four control scenarios. The scenarios differed in the spatial extent of their implementation and were: 1) a response at the level of an individual neighborhood; 2) a response targeted at a neighborhood in which infected humans were detected and the one with which it was most strongly connected by human movement; 3) a limited area-wide response where all neighborhoods within a certain radius of the focal area were included; and 4) a collective response where all participating neighborhoods implemented control. The relative effectiveness of the scenarios varied only slightly between different settings, with the number of infections averted over time increasing with the scale of implementation. This difference depended on the efficacy of control at the neighborhood level. At low levels of efficacy, the scenarios mirrored each other in infections averted. At high levels of efficacy, impact increased with the scale of the intervention. As a result, the choice between scenarios will not only be a function of the amount of effort decision-makers are willing to invest, but largely epend on the overall effectiveness of vector control approaches. PLOS Neglected Tropical Diseases | https://doi.Control and prevention of Aedes-transmitted viruses, such as dengue, chikungunya, or Zika relies heavily on vector control approaches. Given the effort and cost involved in implementation of vector control, targeting of control measures is highly desirable. However, it is unclear to what extent the effectiveness of highly focal and reactive control measures depends on the commuting and movement patterns of humans. To investigate this question, we developed a model and four control scenarios that ranged from highly focal to area-wide larval control. The distribution of humans and their commuting patterns were modelled after three major tropical urban centers, San Juan, Recife, and Jakarta. We show that as implementation is applied across a wider area, a greater number of infections is averted. Critically, this only occurs if the efficacy of control at the neighborhood level is sufficiently high. A consistent outcome across the three settings was that the focal strategy was most likely to provide the best outcome at lower levels of effort, and when the efficacy of control was low. These outcomes suggest that optimal control strategies will likely have to be tailored to individual settings by decision makers and would benefit from localized cost-effectiveness modelling studies.
PLOS Neglected Tropical Diseases
Background Aedes mosquitoes severely affect the health and wellbeing of human populations by transmitting infectious diseases. In French Polynesia, Aedes aegypti is the main vector of dengue, chikungunya and Zika, and Aedes polynesiensis the primary vector of Bancroftian filariasis and a secondary vector of arboviruses. Tools for assessing the risk of disease transmission or for measuring the efficacy of vector control programmes are scarce. A promising approach to quantify the human-vector contact relies on the detection and the quantification of antibodies directed against mosquito salivary proteins. Methodology/Principal findings An ELISA test was developed to detect and quantify the presence of immunoglobulin G (IgG) directed against proteins from salivary gland extracts (SGE) of Ae. aegypti and Ae. polynesiensis in human populations exposed to either species, through a cross-sectional study. In Tahiti and Moorea islands where Ae. aegypti and Ae. polynesiensis are present, the test revealed that 98% and 68% of individuals have developed IgG directed against Ae. aegypti and Ae. polynesiensis SGE, respectively. By comparison, ELISA tests conducted on a cohort of people from metropolitan France, not exposed to these Aedes mosquitoes, indicated that 97% of individuals had no IgG directed against SGE of either mosquito species. The analysis of additional cohorts representing different entomological Aedes contexts showed no ELISA IgG cross-reactivity between Ae. aegypti and Ae. polynesiensis SGE. Conclusions/Significance The IgG response to salivary gland extracts seems to be a valid and specific biomarker of human exposure to the bites of Ae. aegypti and Ae. polynesiensis. This new immuno
International Journal of Gynecology & Obstetrics
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BMC Infectious Diseases
Background The State of Ceará, in Northeastern Brazil, suffers from a triple burden of arboviruses (dengue, Zika and chikungunya). We measured the seroprevalence of chikungunya, dengue and Zika and its associated factors in the population of Juazeiro do Norte, Southern Ceará State, Brazil. Methods A cross-sectional study of analytical and spatial analysis was performed to estimate the seroprevalence of dengue, Zika and chikungunya, in the year 2018. Participants were tested for IgM and IgG against these three viruses. Those with IgM and/or IgG positive tests results were considered positive. Poisson regression was used to analyze the factors associated with positive cases, in the same way that the spatial analysis of positive cases was performed to verify whether the cases were grouped. Results Of the 404 participants, 25.0% (103/404) were positive for CHIKV, 92.0% (373/404) for flavivirus (dengue or Zika) and of these, 37.9% (153/404) samples were classified as probable dengue infe...
Zika virus outbreak in the Pacific: Vector competence of regional vectors
PLOS Neglected Tropical Diseases
Background In 2013, Zika virus (ZIKV) emerged in French Polynesia and spread through the Pacific region between 2013 and 2017. Several potential Aedes mosquitoes may have contributed to the ZIKV transmission including Aedes aegypti, the main arbovirus vector in the region, and Aedes polynesiensis, vector of lymphatic filariasis and secondary vector of dengue virus. The aim of this study was to analyze the ability of these two Pacific vectors to transmit ZIKV at a regional scale, through the evaluation and comparison of the vector competence of wild Ae. aegypti and Ae. polynesiensis populations from different Pacific islands for a ZIKV strain which circulated in this region during the 2013-2017 outbreak. Methodology/principal findings Field Ae. aegypti (three populations) and Ae. polynesiensis (two populations) from the Pacific region were collected for this study. Female mosquitoes were orally exposed to ZIKV (10 7 TCID50/mL) isolated in the region in 2014. At 6, 9, 14 and 21 days post-infection, mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination, transmission rates and transmission efficiency, respectively. According to our results, ZIKV infection rates were heterogeneous between the Ae. aegypti populations, but the dissemination rates were moderate and more homogenous between these populations. For Ae. polynesiensis, infection rates were less heterogeneous between the two populations tested. The transmission rate and efficiency results revealed a low vector competence for ZIKV of the different Aedes vector populations under study. Conclusion/significance Our results indicated a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other
Veterinary Sciences
Infectious diseases are changing due to the environment and altered interactions among hosts, reservoirs, vectors, and pathogens. This is particularly true for zoonotic diseases that infect humans, agricultural animals, and wildlife. Within the subset of zoonoses, vector-borne pathogens are changing more rapidly with climate change, and have a complex epidemiology, which may allow them to take advantage of a changing environment. Most mosquito-borne infectious diseases are transmitted by mosquitoes in three genera: Aedes, Anopheles, and Culex, and the expansion of these genera is well documented. There is an urgent need to study vector-borne diseases in response to climate change and to produce a generalizable approach capable of generating risk maps and forecasting outbreaks. Here, we provide a strategy for coupling climate and epidemiological models for zoonotic infectious diseases. We discuss the complexity and challenges of data and model fusion, baseline requirements for data, ...
Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sequenced ZIKV genomes from Colombian clinical diagnostic samples and infected Aedes aegypti samples across the temporal and geographic breadth of the epidemic. Phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, indicates at least two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We estimate the timing of each introduction to Colombia, finding that ZIKV was introduced and circulated cryptically for 5 to 7 months prior to ZIKV confirmation in September 2015. These findings underscore the utility of genomic epidemiological studies for understanding epidemiologic dynamics, especially when many infections are asymptomatic.
BMC Infectious Diseases
Background Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia. Methods We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes aegypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia. Results We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeographic reconstruction indicates two separate introductions of ZIKV to Col...
Glycosylation of Zika Virus is Important in Host–Virus Interaction and Pathogenic Potential
International Journal of Molecular Sciences
Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their func...
Transfusion
BACKGROUND: To date, several cases of transfusiontransmitted ZIKV infections have been confirmed. Multiple studies detected prolonged occurrence of ZIKV viral RNA in whole blood as compared to plasma samples indicating potential ZIKV interaction with hematopoietic cells. Also, infection of cells from the granulocyte/macrophage lineage has been demonstrated. Patients may develop severe thrombocytopenia, microcytic anemia, and a fatal course of disease occurred in a patient with sickle cell anemia suggesting additional interference of ZIKV with erythroid and megakaryocytic cells. Therefore, we analyzed whether ZIKV propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells.
eLife
Dengue is a major health burden, but it can be challenging to examine transmission and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence transmission and control in island settings. Our results suggested the 10–19 year-old age group had the highest risk of infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. A mathematical model jointly fitted to surveillance and serological data suggested that herd immunity and seasonally varying transmission could not explain observed dynamics. However, the model showed evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in c...
eLife
It has been commonly assumed that Zika virus (ZIKV) infection confers long-term protection against reinfection, preventing ZIKV from re-emerging in previously affected areas for several years. However, the long-term immune response to ZIKV following an outbreak remains poorly documented. We compared results from eight serological surveys before and after known ZIKV outbreaks in French Polynesia and Fiji, including cross-sectional and longitudinal studies. We found evidence of a decline in seroprevalence in both countries over a two-year period following first reported ZIKV transmission. This decline was concentrated in adults, while high seroprevalence persisted in children. In the Fiji cohort, there was also a significant decline in neutralizing antibody titres against ZIKV, but not against dengue viruses that circulated during the same period.
Proceedings of the National Academy of Sciences of the United States of America, 2018
In 2015, a Zika epidemic in Brazil began spreading throughout the Americas. Zika virus (ZIKV) entered Managua, Nicaragua, in January 2016 and caused an epidemic that peaked in July-September 2016. ZIKV seropositivity was estimated among participants of pediatric ( = 3,740) and household ( = 2,147) cohort studies, including an adult-only subset from the household cohort ( = 1,074), in Managua. Seropositivity was based on a highly sensitive and specific assay, the Zika NS1 blockade-of-binding ELISA, which can be used in dengue-endemic populations. Overall seropositivity for the pediatric (ages 2-14), household (ages 2-80), and adult (ages 15-80) cohorts was 36, 46, and 56%, respectively. Trend, risk factor, and contour mapping analyses demonstrated that ZIKV seroprevalence increased nonlinearly with age and that body surface area was statistically associated with increasing seroprevalence in children. ZIKV seropositivity was higher in females than in males across almost all ages, with...
Epidemic potential of Zika virus in Australia: implications for blood transfusion safety
Transfusion
BACKGROUND: Zika virus (ZIKV) is transfusiontransmissible. In Australia the primary vector, Aedes aegypti, is established in the northeast , such that local transmission is possible following importation of an index case, which has the potential to impact on blood transfusion safety and public health. We estimated the basic reproduction number (R 0) to model the epidemic potential of ZIKV in Australian locations, compared this with the ecologically similar dengue viruses (DENV), and examined possible implications for blood transfusion safety. STUDY DESIGN AND METHODS: Varying estimates of vector control efficiency and extrinsic incubation period, "best-case" and "worst-case" scenarios of monthly R 0 for ZIKV and DENV were modeled from 1996 to 2015 in 11 areas. We visualized the geographical distribution of blood donors in relation to areas with epidemic potential for ZIKV. RESULTS: Epidemic potential (R 0 > 1) existed for ZIKV and DENV throughout the study period in a number of locations in northern Australia (Cairns, Darwin, Rockhampton, Thursday Island, Townsville, and Brisbane) during the warmer months of the year. R 0 for DENV was greater than ZIKV and was broadly consistent with annual estimates in Cairns. Increased vector control efficiency markedly reduced the epidemic potential and shortened the season of local transmission. Australian locations that provide the greatest number of blood donors did not have epidemic potential for ZIKV. CONCLUSION: We estimate that areas of northeastern Australia could sustain local transmission of ZIKV. This early contribution to understanding the epidemic potential of ZIKV may assist in the assessment and management of threats to blood transfusion safety. A rboviruses are a potential threat to blood transfusion safety. Globally, arboviral transfusion-transmission (TT) has been reported for dengue viruses (DENV) 1,2 and West Nile virus (WNV). 3 In Australia, outbreaks of Ross River virus (RRV) and DENV threaten blood supply safety, and transfusion-transmitted RRV has been reported. 4 Most recently, Zika virus (ZIKV) has been shown to have potential for TT. Transmission of ZIKV through platelet transfusion has been reported in Brazil, 5,6 and a number of countries have detected ZIKV-positive blood donations. 7-12 ZIKV is primarily transmitted to humans through the bite of an infected female Aedes aegypti or Aedes albopictus mosquito, which are both also principal vectors of DENV and chikungunya virus. Nonvector transmission of ZIKV is also possible through sexual contact, 13 perinatally, 14,15 and via blood transfusion. 5,6 ZIKV infection is asymptomatic in up to 80% of cases [50%-80%], 16,17 and symptomatic infection is usually mild, self-limiting, and nonspecific, with low-grade fever, arthralgia, myalgia, headache, and conjunctivitis. 18 ZIKV is a cause of Guillain-Barré syndrome 19 and, when acquired during pregnancy, can cause miscarriage or neurological birth defects. 20 As there is currently no From the
BackgroundBetween January 2015 and August 2016, two epidemic waves of Zika virus (ZIKV) disease swept the Northeastern region of Brazil. As a result, two waves of Guillain-Barré Syndrome (GBS), were observed concurrently. The mandatory reporting of ZIKV disease began region-wide in February 2016, and it is believed that ZIKV cases were significantly under-reported before that. The changing reporting rate has made it difficult to estimate the ZIKV infection attack rate, and studies in the literature vary widely from 17% to > 50%. The same applies for other key epidemiological parameters. In contrast, the diagnosis and reporting of GBS cases were reasonably reliable given the severity and easy recognition of the diseases symptoms. In this paper, we aim to estimate the real number of ZIKV cases (i.e., the infection attack rate), and their dynamics in time, by scaling up from GBS surveillance data in NE Brazil.MethodologyA mathematical compartmental model is constructed that makes it...
Zika Virus–Associated Birth Defects, Costa Rica, 2016–2018
Emerging Infectious Diseases
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Pathogens
While the Zika virus (ZIKV) 2014–2017 pandemic has subsided, there remains active transmission. Apart from horizontal transmission to humans, the main vector Aedes aegypti can transmit the virus vertically from mother to offspring. Large variation in vertical transmission (VT) efficiency between studies indicates the influence of parameters, which remain to be characterized. To determine the roles of extrinsic incubation time and gonotrophic cycle, we deployed an experimental design that quantifies ZIKV in individual progeny and larvae. We observed an early infection of ovaries that exponentially progressed. We quantified VT rate, filial infection rate, and viral load per infected larvae at 10 days post oral infection (d.p.i.) on the second gonotrophic cycle and at 17 d.p.i. on the second and third gonotrophic cycle. As compared to previous reports that studied pooled samples, we detected a relatively high VT efficiency from 1.79% at 10 d.p.i. and second gonotrophic cycle to 66% at ...
PLOS Neglected Tropical Diseases
Background Since 2015, Zika virus (ZIKV) outbreaks have occurred in the Americas and the Pacific involving mosquito-borne and sexual transmission. ZIKV has also emerged as a risk to global blood transfusion safety. Aedes aegypti, a mosquito well established in north and some parts of central and southern Queensland, Australia, transmits ZIKV. Aedes albopictus, another potential ZIKV vector, is a threat to mainland Australia. Since these conditions create the potential for local transmission in Australia and a possible uncertainty in the effectiveness of blood donor risk-mitigation programs, we investigated the possible impact of mosquito-borne and sexual transmission of ZIKV in Australia on local blood transfusion safety. Methodology/Principal findings We estimated 'best-' and 'worst-' case scenarios of monthly reproduction number (R 0) for both transmission pathways of ZIKV from 1996-2015 in 11 urban or regional population centres, by varying epidemiological and entomological estimates. We then estimated the attack rate and subsequent number of infectious people to quantify the ZIKV transfusiontransmission risk using the European Up-Front Risk Assessment Tool. For all scenarios and with both vector species R 0 was lower than one for ZIKV transmission. However, a higher risk of a sustained outbreak was estimated for Cairns, Rockhampton, Thursday Island, and theoretically in Darwin during the warmest months of the year. The yearly estimation of the risk of transmitting ZIKV infection by blood transfusion remained low through the study period for all locations, with the highest potential risk estimated in Darwin. Conclusions/Significance Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from infectious disease outbreak regions to source plasma PLOS NEGLECTED TROPICAL DISEASES
Journal of Medical Entomology
First autochthonous Zika clinical case was reported in the Republic of Marshall Islands (RMI) on Majuro Atoll in February 2016. An entomological survey of mosquito larvae and adult populations was carried out in four areas of Majuro, the most populated atoll of RMI encompassing different habitats (forest, rural, or urban) including some with confirmed clinical Zika cases to evaluate which mosquito species could be involved in the Zika transmission. A total of 2,367 immature and adult mosquito specimens were collected and identified to the species level. In total, five mosquito species were detected, Aedes aegypti (Linnaeus), Aedes albopictus (Skuse), Aedes marshallensis (Stone and Bohart), Culex quinquefasciatus (Say), and Culex annulirostris (Skuse) (Diptera: Culicidae), a first record for RMI. The most abundant species was Ae. aegypti presumed to be the main vector of Zika virus followed by Ae. albopictus. Improved management of breeding containers through better public awareness and community engagement, mosquito surveillance and innovative mosquito control strategies using the sterile insect technique (SIT) and/or the incompatible insect technique (IIT) could help prevent outbreaks of arboviruses in the RMI.
PLOS ONE, 2020
In the last 40 years, Latin America countries, including Brazil, have suffered from the emergence and reemergence of arboviruses, first Dengue (DENV) and recently Zika (ZIKV) and Chikungunya (CHIKV). All three arboviruses are currently endemic in Brazil and have caused major outbreaks in recent years. Rio de Janeiro city, host of the last Summer Olympic Games and the Football World Cup, has been specially affected by them. A surveillance system based on symptomatic reports is in place in Rio, but the true number of affected individuals is unknown due to the great number of Zika, Dengue and Chikungunya asymptomatic cases. Seroprevalence studies are more suitable to evaluate the real number of cases in a given population. We performed a populational seroprevalence survey in Rio, with recruitment of a sample of volunteers of all ages and gender from July to October 2018, within randomly selected census tracts and household. A total of 2,120 volunteers were interviewed and tested with r...
Zika Virus in the Male Reproductive Tract
Viruses, 2018
Arthropod-borne viruses (arboviruses) are resurging across the globe. Zika virus (ZIKV) has caused significant concern in recent years because it can lead to congenital malformations in babies and Guillain-Barré syndrome in adults. Unlike other arboviruses, ZIKV can be sexually transmitted and may persist in the male reproductive tract. There is limited information regarding the impact of ZIKV on male reproductive health and fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is critical to developing effective vaccines and therapies. Mouse and macaque models have begun to unravel the pathogenesis of ZIKV infection in the male reproductive tract, with the testes and prostate gland implicated as potential reservoirs for persistent ZIKV infection. Here, we summarize current knowledge regarding the pathogenesis of ZIKV in the male reproductive tract, the development of animal models to study ZIKV infection at this site, and prospects for vaccines and therapeutics against persistent ZIKV infection.
What we know and what we don't know about perinatal Zika virus infection: a systematic review
Expert review of anti-infective therapy, 2018
Zika virus (ZIKV) infection has caused the most challenging worldwide infectious epidemic outbreak in recent months. ZIKV causes microcephaly and other congenital malformations. There is a need to perform updated systematic reviews on ZIKV infection periodically because this epidemic is bringing up new evidence with extraordinary speed. Areas covered: Evidence related to ZIKV infection in the gestational, perinatal, and early infant periods covering epidemiology, virology, pathogenesis, risk factors, time of infection during pregnancy, newborn symptoms, treatment, and vaccines. To this end, a search was performed using terms ['Zika'] AND ['Perinatal Infection'] OR ['Congenital Infection'] in the PubMed® international electronic database. Out of a total of 1,538 articles published until 30 November 2017, we finally assessed 106 articles articles that were relevant to the research areas included in this study. Expert commentary: ZIKV is a new teratogenic/neurot...
Viruses, 2018
The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infections. To determine the role of DENV preimmunity in ZIKV infection, we analyzed the T- and B-cell responses against ZIKV in donors with or without previous DENV infection. Using peripheral blood mononuclear cells (PBMCs) from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the nonstructural (NS) proteins NS1, NS3, and NS5. Analyses of the T- and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors in comparison with DENV-naïve donors. Strikin...
PLOS Neglected Tropical Diseases, 2020
Understanding the transition of epidemic to endemic dengue transmission remains a challenge in regions where serotypes co-circulate and there is extensive human mobility. French Polynesia, an isolated group of 117 islands of which 72 are inhabited, distributed among five geographically separated subdivisions, has recorded mono-serotype epidemics since 1944, with long inter-epidemic periods of circulation. Laboratory confirmed cases have been recorded since 1978, enabling exploration of dengue epidemiology under monotypic conditions in an isolated, spatially structured geographical location. A database was constructed of confirmed dengue cases, geolocated to island for a 35-year period. Statistical analyses of viral establishment, persistence and fade-out as well as synchrony among subdivisions were performed. Seven monotypic and one heterotypic dengue epidemic occurred, followed by low-level viral circulation with a recrudescent epidemic occurring on one occasion. Incidence was asynchronous among the subdivisions. Complete viral die-out occurred on several occasions with invasion of a new serotype. Competitive serotype replacement has been observed previously and seems to be characteristic of the South Pacific. Island population size had a strong impact on the establishment, persistence and fade-out of dengue cases and endemicity was estimated achievable only at a population size in excess of 175 000. Despite island remoteness and low population size, dengue cases were observed somewhere in French Polynesia almost constantly, in part due to the spatial structuration generating asynchrony among subdivisions. Long-term persistence of dengue virus in this group of island populations may be enabled by island hopping, although could equally be explained by a reservoir of sub-clinical infections on the most populated island, Tahiti.
Low seroprevalence of Zika virus infection among adults in Southern Taiwan
BMC Infectious Diseases, 2019
Background We recently conducted a serosurvey of newly arrived workers in Taiwan from four Southeast Asian countries which revealed that 1% of the migrant workers had laboratory-confirmed recent Zika virus (ZIKV) infection. Taiwan, where Aedes mosquitoes are prevalent, has a close relationship with Southeast Asian countries. Up to now, 21 imported cases of ZIKV infection have been reported in Taiwan, but there has been no confirmed indigenous case. The aim of this serosurvey was to assess whether there was unrecognized ZIKV infections in Taiwan. Methods A total of 212 serum samples collected in a cross-sectional seroepidemiologic study conducted during the end of the 2015 dengue epidemic in Tainan, Taiwan, were analyzed. Anti-ZIKV IgM and IgG were tested using commercial enzyme-linked immunosorbent assays (ELISAs). Plaque reduction neutralization tests (PRNTs) for ZIKV and four dengue virus (DENV) serotypes were performed for samples with positive anti-ZIKV antibodies. A confirmed c...
Inactivation of Zika virus in platelet components using amotosalen and ultraviolet A illumination
Transfusion, 2017
BACKGROUND: Concerned over the risk of Zika virus (ZIKV) transfusion transmission, public health agencies recommended the implementation of mitigation strategies for its prevention. Those strategies included the use of pathogen inactivation for the treatment of plasma and platelets. The efficacy of amotosalen/ ultraviolet A to inactivate ZIKV in plasma had been previously demonstrated, and the efficacy of inactivation in platelets with the same technology was assumed. These studies quantify ZIKV inactivation in platelet components using amotosalen/ultraviolet A. STUDY DESIGN AND METHODS: Platelet components were spiked with ZIKV, and ZIKV infectious titers and RNA loads were measured by cell culturebased assays and real-time polymerase chain reaction in spiked platelet components before and after photochemical treatment using amotosalen/ultraviolet A. RESULTS: The mean ZIKV infectivity titers and RNA loads in platelet components before inactivation were either 4.9 log 10 plaque forming units per milliliter, or 4.4 log 10 50% tissue culture infective dose per milliliter and 7.5 log 10 genome equivalents per milliliter, respectively. No infectivity was detected immediately after amotosalen/ultraviolet A treatment. No replicative virus remained after treatment, as demonstrated by multiple passages on Vero cell cultures; and ZIKV RNA was not detected from the first passage after inactivation. Additional experiments in this study demonstrated efficient inactivation to the limit of detection in platelets manufactured in 65% platelet additive solution, 35% plasma, or 100% plasma. CONCLUSION: As previously demonstrated for plasma, robust levels of ZIKV inactivation were achieved in platelet components. With inactivation of higher levels of ZIKV than those reported in asymptomatic, RNAreactive blood donors, the pathogen-inactivation system using amotosalen/ultraviolet A offers the potential to mitigate the risk of ZIKV transmission by plasma and platelet transfusion. Z ika virus (ZIKV) is a single-stranded RNA arbovirus that, like the West Nile (WNV), dengue (DENV), and yellow fever viruses, is a member of the Flaviviridae family. ZIKV was discovered in a sentinel primate in Africa in 1947. Until the 2007 outbreak in Yap, ZIKV had not been associated with large epidemics or severe disease outcomes. From 2007 to late 2016, it spread quickly, and active ZIKV transmission was reported in 76 countries, including most of the Latin America and Caribbean regions as well as parts of Asia, the Pacific, Africa, and the contiguous United States. 1 Most ZIKVinfected patients are asymptomatic or present with only mild symptoms. 2 However, with the emergence of ZIKV in French Polynesia in 2013 and in Latin America in 2015 came reports of serious neurologic complications in ABBREVIATIONS: CAD 5 compound adsorption device; CHIKV 5 chikungunya virus; DENV 5 dengue virus; PC(s) 5 platelet component(s); PI 5 pathogen inactivation/ reduction; TT 5 transfusion transmission; WNV 5 West Nile virus; ZIKV 5 Zika virus.
Immunological Memory to Zika Virus in a University Community in Colombia, South America
Anais da Academia Brasileira de Ciências, 2020
Zika virus appeared in South America in 2015, generating alarm worldwide as it causes microcephaly and autoimmunity. This study aims to determine the serological footprint of the incoming epidemic in a student community and to characterize the memory functional cell response during post convalescence. In a cross-sectional study, Zika-specific IgG using LIA immunoassay was found in 328 university students (CI=95%), while in the second phase, the functional cellular memory response for IFN-γ and IL-2 was quantified using post-stimulus ELISpot with inactivated virus, starting with individuals seropositive for Zika and control individuals (seropositive only for Dengue and seronegative for Zika-Dengue). Depending on the antigen used, memory humoral response (IgG) against Zika Virus was observed in >60% of the population; seropositivity for NS1 was 21.1% higher than E antigen with high intensity. The analysis of cell functionality in 22 individuals seropositive for Zika virus revealed either IFN-γ+ or IL-2+ cells in 86.3% of cases (Th1 profile), presenting multifunctionality in 50% (11 individuals), 64% of which presented> 6 SFC/10 4 PBMCs (>600 SFC/10 6 PBMC), reflecting memory circulating cells. A good agreement (Kappa= 0.754) was observed between the coexistence of both cellular and humoral responses but not in their intensity.
Stochastic Epidemic Models inference and diagnosis with Poisson Random Measure Data Augmentation
Mathematical biosciences, 2021
We present a new Bayesian inference method for compartmental models that takes into account the intrinsic stochasticity of the process. We show how to formulate a SIR-type Markov jump process as the solution of a stochastic differential equation with respect to a Poisson Random Measure (PRM), and how to simulate the process trajectory deterministically from a parameter value and a PRM realisation. This forms the basis of our Data Augmented MCMC, which consists of augmenting parameter space with the unobserved PRM value. The resulting simple Metropolis-Hastings sampler acts as an efficient simulation-based inference method, that can easily be transferred from model to model. Compared with a recent Data Augmentation method based on Gibbs sampling of individual infection histories, PRM-augmented MCMC scales much better with epidemic size and is far more flexible. It is also found to be competitive with Particle MCMC for moderate epidemics when using approximate simulations. PRM-augmented MCMC also yields a posteriori estimates of the PRM, that represent process stochasticity, and which can be used to validate the model. If the model is good, the posterior distribution should exhibit no pattern and be close to the PRM prior distribution. We illustrate this by fitting a non-seasonal model to some simulated seasonal case count data. Applied to the Zika epidemic of 2013 in French Polynesia, our approach shows that a simple SEIR model cannot correctly reproduce both the initial sharp increase in the number of cases as well as the final proportion of seropositive. PRM augmentation thus provides a coherent story for Stochastic Epidemic Model inference, where explicitly inferring process stochasticity helps with model validation.
Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil
Virus Genes, 2020
Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014–2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5–2 years after the 2015–2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7–66.7%), and decreased to 38.6% (56/144, CI 31.3–47.0%) 1.5–2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals tha...
Military Medicine, 2020
Introduction The emergence of Zika virus disease (ZVD) in areas of military operations provided a new opportunity for force health protection. ZVD infection had an estimated 4:1 asymptomatic-to-symptomatic ratio and can cause neurologic sequelae. Materials and Methods We provide a brief report of a field investigation utilizing laboratory-based surveillance and survey instruments to characterize ZVD risk among personnel deployed to the Dominican Republic in support of Operation NEW HORIZONS (NH). Additionally, we describe a cluster of 3 ZVD cases among 8 aircrew on a short mission to St. Croix (U.S. Virgin Islands). Results Following Operation NH, 6 of a total 189 deployed cohort members tested positive for ZVD by immunoglobulin M and confirmatory plaque reduction neutralization test (3.2%). Reverse transcription polymerase chain reaction testing in urine or serum was positive in 4 of those 6 cases. All 6 cases reported at least one symptom, with 5 reporting subjective fever and art...
Estimating incidence of infection from diverse data sources: Zika virus in Puerto Rico, 2016
PLOS Computational Biology, 2021
Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, as seen with the Zika virus (ZIKV) epidemic where large proportions of infection were asymptomatic. However, multiple imperfect indicators of infection provide an opportunity to estimate the underlying incidence of infection. We developed a modeling approach that integrates a generic Time-series Susceptible-Infected-Recovered epidemic model with assumptions about reporting biases in a Bayesian framework and applied it to the 2016 Zika epidemic in Puerto Rico using three indicators: suspected arboviral cases, suspected Zikaassociated Guillain-Barré Syndrome cases, and blood bank data. Using this combination of surveillance data, we estimated the peak of the epidemic occurred during the week of August 15, 2016 (the 33 rd week of year), and 120 to 140 (50% credible interval [CrI], 95% CrI: 97 to 170) weekly infections per 10,000 population occurred at the peak. By the end of 2016, we estimated that approximately 890,000 (95% CrI: 660,000 to 1,100,000) individuals were infected in 2016 (26%, 95% CrI: 19% to 33%, of the population infected). Utilizing multiple indicators offers the opportunity for real-time and retrospective situational awareness to support epidemic preparedness and response.
Estimating incidence of infection from diverse data sources: Zika virus in Puerto Rico, 2016
2020
Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, as seen with the Zika virus (ZIKV) epidemic where large proportions of infection were asymptomatic. However, multiple imperfect indicators of infection provide an opportunity to estimate the underlying incidence of infection. We developed a modeling approach that integrates a generic Time-series Susceptible-Infected-Recovered epidemic model with assumptions about reporting biases in a Bayesian framework and applied it to the 2016 Zika epidemic in Puerto Rico using three indicators: suspected arboviral cases, suspected Zika-associated Guillain-Barré Syndrome cases, and blood bank data. Using this combination of surveillance data, we estimated the peak of the epidemic occurred during the week of August 15, 2016 (the 33 rd week of year), and 120 to 140 (50% credible interval [CrI], 95% CrI: 97 to 170) weekly infections per 10,000 population occurred at the peak. By the end of 2016, we estimated that approximately 890,000 (95% CrI: 660,000 to 1,100,000) individuals were infected in 2016 (26%, 95% CrI: 19% to 33%, of the population infected). Utilizing multiple indicators offers the opportunity for realtime and retrospective situational awareness to support epidemic preparedness and response. region. The first confirmed locally acquired ZIKV casein Puerto Rico was reported on December 31, 2015 (2), followed by more than 36,000 confirmed cases in 2016 (3). While confirmed cases provided an indicator of transmission intensity, reported cases represented a small proportion of actual infections (4) in part because many ZIKV infections are asymptomatic or mild, and are not captured by surveillance systems (5-7). Furthermore, distinguishing symptomatic (i.e. disease) cases of ZIKV infections from other arboviral infections (e.g., dengue, chikungunya) was difficult due to their similar symptoms (e.g. fever, rash), and serological cross-reactivity with dengue viruses (DENV). Despite these challenges, estimating the underlying ZIKV infection incidence was critical to assess useful metrics (e.g., transmission intensity, the number of people previously infected, and the number still at risk) that for use under a CC0 license.
PLOS Neglected Tropical Diseases, 2019
Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high proteinsequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIIIinduced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIIIspecific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a