Serological Evidence of Japanese Encephalitis Virus Circulation in Asian Children From Dengue-Endemic Countries.

Background: Japanese encephalitis virus (JEV) is a zoonotic, mosquito-borne flavivirus, distributed across Asia. Infections are mostly mild or asymptomatic, but symptoms include neurological disorders, sequelae, and fatalities. Data to inform control strategies are limited due to incomplete case reporting. Methods: We used JEV serological data from a multicountry Asian dengue vaccine study in children aged 2-14 years to describe JEV endemicity, measuring antibodies by plaque reduction neutralization test (PRNT50). Results: A total 1479 unvaccinated subjects were included. A minimal estimate of pediatric JEV seroprevalence in dengue-naive individuals was 8.1% in Indonesia, 5.8% in Malaysia, 10.8% in the Philippines, and 30.7% in Vietnam, translating to annual infection risks varying from 0.8% (in Malaysia) to 5.2% (in Vietnam). JEV seroprevalence and annual infection estimates were much higher in children with history of dengue infection, indicating cross-neutralization within the JEV PRNT50 assay. Conclusions: These data confirm JEV transmission across predominantly urban areas and support a greater emphasis on JEV case finding, diagnosis, and prevention.

Improved tools and strategies for the prevention and control of arboviral diseases: A research-to-policy forum.

BACKGROUND: Research has been conducted on interventions to control dengue transmission and respond to outbreaks. A summary of the available evidence will help inform disease control policy decisions and research directions, both for dengue and, more broadly, for all Aedes-borne arboviral diseases. METHOD: A research-to-policy forum was convened by TDR, the Special Programme for Research and Training in Tropical Diseases, with researchers and representatives from ministries of health, in order to review research findings and discuss their implications for policy and research. RESULTS: The participants reviewed findings of research supported by TDR and others. Surveillance and early outbreak warning. Systematic reviews and country studies identify the critical characteristics that an alert system should have to document trends reliably and trigger timely responses (i.e., early enough to prevent the epidemic spread of the virus) to dengue outbreaks. A range of variables that, according to the literature, either indicate risk of forthcoming dengue transmission or predict dengue outbreaks were tested and some of them could be successfully applied in an Early Warning and Response System (EWARS). Entomological surveillance and vector management. A summary of the published literature shows that controlling Aedes vectors requires complex interventions and points to the need for more rigorous, standardised study designs, with disease reduction as the primary outcome to be measured. House screening and targeted vector interventions are promising vector management approaches. Sampling vector populations, both for surveillance purposes and evaluation of control activities, is usually conducted in an unsystematic way, limiting the potentials of entomological surveillance for outbreak prediction. Combining outbreak alert and improved approaches of vector management will help to overcome the present uncertainties about major risk groups or areas where outbreak response should be initiated and where resources for vector management should be allocated during the interepidemic period. CONCLUSIONS: The Forum concluded that the evidence collected can inform policy decisions, but also that important research gaps have yet to be filled.

Fetal Zika Virus Infection in Vietnam.

As of 13 July 2016, 13 countries have reported fetal Zika virus (ZIKV) infection. Here we report a case of fetal ZIKV infection that resulted from an infection originating in Vietnam.

A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

BACKGROUND: Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death. METHODOLOGY: Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients. PRINCIPAL FINDINGS: Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy. CONCLUSION: Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

Spatiotemporal dynamics of dengue epidemics, southern Vietnam.

An improved understanding of heterogeneities in dengue virus transmission might provide insights into biological and ecologic drivers and facilitate predictions of the magnitude, timing, and location of future dengue epidemics. To investigate dengue dynamics in urban Ho Chi Minh City and neighboring rural provinces in Vietnam, we analyzed a 10-year monthly time series of dengue surveillance data from southern Vietnam. The per capita incidence of dengue was lower in Ho Chi Minh City than in most rural provinces; annual epidemics occurred 1-3 months later in Ho Chi Minh City than elsewhere. The timing and the magnitude of annual epidemics were significantly more correlated in nearby districts than in remote districts, suggesting that local biological and ecologic drivers operate at a scale of 50-100 km. Dengue incidence during the dry season accounted for 63% of variability in epidemic magnitude. These findings can aid the targeting of vector-control interventions and the planning for dengue vaccine implementation.

Clinical and virological study of dengue cases and the members of their households: the multinational DENFRAME Project.

BACKGROUND: Dengue has emerged as the most important vector-borne viral disease in tropical areas. Evaluations of the burden and severity of dengue disease have been hindered by the frequent lack of laboratory confirmation and strong selection bias toward more severe cases. METHODOLOGY: A multinational, prospective clinical study was carried out in South-East Asia (SEA) and Latin America (LA), to ascertain the proportion of inapparent dengue infections in households of febrile dengue cases, and to compare clinical data and biological markers from subjects with various dengue disease patterns. Dengue infection was laboratory-confirmed during the acute phase, by virus isolation and detection of the genome. The four participating reference laboratories used standardized methods. PRINCIPAL FINDINGS: Among 215 febrile dengue subjects-114 in SEA and 101 in LA-28 (13.0%) were diagnosed with severe dengue (from SEA only) using the WHO definition. Household investigations were carried out for 177 febrile subjects. Among household members at the time of the first home visit, 39 acute dengue infections were detected of which 29 were inapparent. A further 62 dengue cases were classified at early convalescent phase. Therefore, 101 dengue infections were found among the 408 household members. Adding these together with the 177 Dengue Index Cases, the overall proportion of dengue infections among the study participants was estimated at 47.5% (278/585; 95% CI 43.5-51.6). Lymphocyte counts and detection of the NS1 antigen differed significantly between inapparent and symptomatic dengue subjects; among inapparent cases lymphocyte counts were normal and only 20% were positive for NS1 antigen. Primary dengue infection and a specific dengue virus serotype were not associated with symptomatic dengue infection. CONCLUSION: Household investigation demonstrated a high proportion of household members positive for dengue infection, including a number of inapparent cases, the frequency of which was higher in SEA than in LA.