RESUMO
Since the 2007 Zika epidemic in the Micronesian state of Yap, it has been apparent that not all people infected with Zika virus (ZIKV) experience symptoms. However, the proportion of infections that result in symptoms remains unclear. Existing estimates have varied in their interpretation of symptoms due to other causes and the case definition used, and they have assumed perfect test sensitivity and specificity. Using a Bayesian model and data from ZIKV serosurveys in Yap (2007), French Polynesia (2013-2014), and Puerto Rico (2016), we found that assuming perfect sensitivity and specificity generally led to lower estimates of the symptomatic proportion. Incorporating reasonable assumptions for assay sensitivity and specificity, we estimated that 27% (95% credible interval (CrI): 15, 37) (Yap), 44% (95% CrI: 26, 66) (French Polynesia), and 50% (95% CrI: 34, 92) (Puerto Rico) of infections were symptomatic, with variation due to differences in study populations, study designs, and case definitions. The proportion of ZIKV infections causing symptoms is critical for surveillance system design and impact assessment. Here, we accounted for key uncertainties in existing seroprevalence data and found that estimates for the symptomatic proportion ranged from 27% to 50%, suggesting that while the majority of infections are asymptomatic or mildly symptomatic, symptomatic infections might be more common than previously estimated.
Assuntos
Infecção por Zika virus/epidemiologia , Infecção por Zika virus/fisiopatologia , Teorema de Bayes , Humanos , Micronésia/epidemiologia , Polinésia/epidemiologia , Porto Rico/epidemiologia , Sensibilidade e Especificidade , Estudos SoroepidemiológicosRESUMO
French Polynesia and the French Territories of the Americas (FTAs) have experienced outbreaks of Zika virus (ZIKV) infection. These territories used similar sentinel syndromic surveillance to follow the epidemics. However, the surveillance system only takes into account consulting patients diagnosed with ZIKV disease, while non-consulting cases, as well as asymptomatic cases, are not taken into account. In the French territories under study, the ratio of consulting to non-consulting patients was found to likely be as low as 1/3 to 1/4, and rough estimates of the ZIKV asymptomatic infections indicated a lower rate than previously reported (i.e., not more than half).
Assuntos
Infecção por Zika virus/epidemiologia , Surtos de Doenças , França/epidemiologia , França/etnologia , Guadalupe/epidemiologia , Humanos , Martinica/epidemiologia , Polinésia/epidemiologia , Vigilância de Evento Sentinela , Zika virus , Infecção por Zika virus/etnologiaRESUMO
The spread of Zika virus in the Americas has been associated with a surge in Guillain-Barré syndrome (GBS) cases. Given the severity of GBS, territories affected by Zika virus need to plan health-care resources to manage GBS patients. To inform such planning in Martinique, we analyzed Zika virus surveillance and GBS data from Martinique in real time with a modeling framework that captured dynamics of the Zika virus epidemic, the risk of GBS in Zika virus-infected persons, and the clinical management of GBS cases. We compared our estimates with those from the 2013-2014 Zika virus epidemic in French Polynesia. We were able to predict just a few weeks into the epidemic that, due to lower transmission potential and lower probability of developing GBS following infection in Martinique, the total number of GBS cases in Martinique would be substantially lower than suggested by simple extrapolations from French Polynesia. We correctly predicted that 8 intensive-care beds and 7 ventilators would be sufficient to treat GBS cases. This study showcased the contribution of modeling to inform local health-care planning during an outbreak. Timely studies that estimate the proportion of infected persons that seek care are needed to improve the predictive power of such approaches.
Assuntos
Surtos de Doenças , Síndrome de Guillain-Barré/epidemiologia , Planejamento em Saúde/organização & administração , Infecção por Zika virus/epidemiologia , Síndrome de Guillain-Barré/etiologia , Planejamento em Saúde/métodos , Humanos , Martinica/epidemiologia , Avaliação das Necessidades , Polinésia/epidemiologia , Infecção por Zika virus/complicaçõesRESUMO
Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barré syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections.
Assuntos
Anticorpos Neutralizantes/imunologia , Reações Cruzadas/imunologia , Vírus da Dengue/imunologia , Epitopos/química , Vacinas Virais/química , Zika virus/imunologia , Anticorpos Monoclonais/imunologia , Complexo Antígeno-Anticorpo/química , Complexo Antígeno-Anticorpo/imunologia , Brasil , Cristalografia por Raios X , Dengue/imunologia , Vacinas contra Dengue/química , Vacinas contra Dengue/imunologia , Vírus da Dengue/química , Epitopos/imunologia , Humanos , Modelos Moleculares , Filogenia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Zika virus/química , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controleRESUMO
Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern, with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed substantial cross-reaction to ZIKV and was able to drive antibody-dependent enhancement (ADE) of ZIKV infection. Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.