Estimating the annual dengue force of infection from the age of reporting primary infections across urban centres in endemic countries.

BACKGROUND: Stratifying dengue risk within endemic countries is crucial for allocating limited control interventions. Current methods of monitoring dengue transmission intensity rely on potentially inaccurate incidence estimates. We investigated whether incidence or alternate metrics obtained from standard, or laboratory, surveillance operations represent accurate surrogate indicators of the burden of dengue and can be used to monitor the force of infection (FOI) across urban centres. METHODS: Among those who reported and resided in 13 cities across the Philippines, we collected epidemiological data from all dengue case reports between 2014 and 2017 (N 80,043) and additional laboratory data from a cross-section of sampled case reports (N 11,906) between 2014 and 2018. At the city level, we estimated the aggregated annual FOI from age-accumulated IgG among the non-dengue reporting population using catalytic modelling. We compared city-aggregated FOI estimates to aggregated incidence and the mean age of clinically and laboratory diagnosed dengue cases using Pearson's Correlation coefficient and generated predicted FOI estimates using regression modelling. RESULTS: We observed spatial heterogeneity in the dengue average annual FOI across sampled cities, ranging from 0.054 [0.036-0.081] to 0.249 [0.223-0.279]. Compared to FOI estimates, the mean age of primary dengue infections had the strongest association (ρ -0.848, p value<0.001) followed by the mean age of those reporting with warning signs (ρ -0.642, p value 0.018). Using regression modelling, we estimated the predicted annual dengue FOI across urban centres from the age of those reporting with primary infections and revealed prominent spatio-temporal heterogeneity in transmission intensity. CONCLUSIONS: We show the mean age of those reporting with their first dengue infection or those reporting with warning signs of dengue represent superior indicators of the dengue FOI compared to crude incidence across urban centres. Our work provides a framework for national dengue surveillance to routinely monitor transmission and target control interventions to populations most in need.

Automated verbal autopsy: from research to routine use in civil registration and vital statistics systems.

BACKGROUND: The majority of low- and middle-income countries (LMICs) do not have adequate civil registration and vital statistics (CRVS) systems to properly support health policy formulation. Verbal autopsy (VA), long used in research, can provide useful information on the cause of death (COD) in populations where physicians are not available to complete medical certificates of COD. Here, we report on the application of the SmartVA tool for the collection and analysis of data in several countries as part of routine CRVS activities. METHODS: Data from VA interviews conducted in 4 of 12 countries supported by the Bloomberg Philanthropies Data for Health (D4H) Initiative, and at different stages of health statistical development, were analysed and assessed for plausibility: Myanmar, Papua New Guinea (PNG), Bangladesh and the Philippines. Analyses by age- and cause-specific mortality fractions were compared to the Global Burden of Disease (GBD) study data by country. VA interviews were analysed using SmartVA-Analyze-automated software that was designed for use in CRVS systems. The method in the Philippines differed from the other sites in that the VA output was used as a decision support tool for health officers. RESULTS: Country strategies for VA implementation are described in detail. Comparisons between VA data and country GBD estimates by age and cause revealed generally similar patterns and distributions. The main discrepancy was higher infectious disease mortality and lower non-communicable disease mortality at the PNG VA sites, compared to the GBD country models, which critical appraisal suggests may highlight real differences rather than implausible VA results. CONCLUSION: Automated VA is the only feasible method for generating COD data for many populations. The results of implementation in four countries, reported here under the D4H Initiative, confirm that these methods are acceptable for wide-scale implementation and can produce reliable COD information on community deaths for which little was previously known.

A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines.

BACKGROUND: In dengue-endemic countries, targeting limited control interventions to populations at risk of severe disease could enable increased efficiency. Individuals who have had their first (primary) dengue infection are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Currently, there is no reliable algorithm for determining primary and post-primary (infection with more than one flavivirus) status from a single serum sample. In this study, we developed and validated an immune status algorithm using single acute serum samples from reporting patients and investigated dengue immuno-epidemiological patterns across the Philippines. METHODS: During 2015/2016, a cross-sectional sample of 10,137 dengue case reports provided serum for molecular (anti-DENV PCR) and serological (anti-DENV IgM/G capture ELISA) assay. Using mixture modelling, we re-assessed IgM/G seroprevalence and estimated functional, disease day-specific, IgG:IgM ratios that categorised the reporting population as negative, historical, primary and post-primary for dengue. We validated our algorithm against WHO gold standard criteria and investigated cross-reactivity with Zika by assaying a random subset for anti-ZIKV IgM and IgG. Lastly, using our algorithm, we explored immuno-epidemiological patterns of dengue across the Philippines. RESULTS: Our modelled IgM and IgG seroprevalence thresholds were lower than kit-provided thresholds. Individuals anti-DENV PCR+ or IgM+ were classified as active dengue infections (83.1%, 6998/8425). IgG- and IgG+ active dengue infections on disease days 1 and 2 were categorised as primary and post-primary, respectively, while those on disease days 3 to 5 with IgG:IgM ratios below and above 0.45 were classified as primary and post-primary, respectively. A significant proportion of post-primary dengue infections had elevated anti-ZIKV IgG inferring previous Zika exposure. Our algorithm achieved 90.5% serological agreement with WHO standard practice. Post-primary dengue infections were more likely to be older and present with severe symptoms. Finally, we identified a spatio-temporal cluster of primary dengue case reporting in northern Luzon during 2016. CONCLUSIONS: Our dengue immune status algorithm can equip surveillance operations with the means to target dengue control efforts. The algorithm accurately identified primary dengue infections who are at risk of future severe disease.

Epidemiology of Japanese encephalitis in the Philippines prior to routine immunization.

BACKGROUND: Findings were published in 2015 that highlighted the endemicity of Japanese Encephalitis (JE) in the Philippines. The policymakers responded by conducting an immunization campaign and strengthening the surveillance system. Using data on the revitalized surveillance system, the epidemiology of JE in the country was updated. METHODS: Electronic databases were searched, and conference proceedings related to JE in the Philippines were identified until 31 December 2018. Surveillance data from 01 January 2014 to 31 December 2017 were used. The 2015 population census was used to estimate the national and regional incidence for children aged <15 years. RESULTS: Four studies reported the seroprevalence of JE in the Philippines, which showed increasing seroprevalence with increasing age. Seroprevalence rates were from 0% for infants (aged <1 year) to 65.7% in adolescents (12-18 years) before the immunization campaign. Among five studies on the clinical profile of JE, case fatality ranged from 0 to 21.1% and neurologic sequelae ranged from 5.2 to 81.8% of diagnosed cases. In the surveillance data, JE cases peaked annually from July to October, coinciding with the wet season. The national incidence was estimated at a minimum of 0.7 JE cases/100,000 among children aged <15 years, but higher rates were seen in the northern regions of the country. CONCLUSION: Improved surveillance affirmed the burden of JE in the Philippines. A subnational immunization campaign in April 2019 was conducted in the northern regions of the country. This paper highlights the importance of including the JE vaccine in the immunization program and sustained high-quality surveillance to monitor its impact on JE control.

Serological Evidence of Widespread Zika Transmission across the Philippines.

Zika virus (ZIKV) exposure across flavivirus-endemic countries, including the Philippines, remains largely unknown despite sporadic case reporting and environmental suitability for transmission. Using laboratory surveillance data from 2016, 997 serum samples were randomly selected from suspected dengue (DENV) case reports across the Philippines and assayed for serological markers of short-term (IgM) and long-term (IgG) ZIKV exposure. Using mixture models, we re-evaluated ZIKV IgM/G seroprevalence thresholds and used catalytic models to quantify the force of infection (attack rate, AR) from age-accumulated ZIKV exposure. While we observed extensive ZIKV/DENV IgG cross-reactivity, not all individuals with active DENV presented with elevated ZIKV IgG, and a proportion of dengue-negative cases (DENV IgG-) were ZIKV IgG-positive (14.3%, 9/63). We identified evidence of long-term, yet not short-term, ZIKV exposure across Philippine regions (ZIKV IgG+: 31.5%, 314/997) which was geographically uncorrelated with DENV exposure. In contrast to the DENV AR (12.7% (95%CI: 9.1-17.4%)), the ZIKV AR was lower (5.7% (95%CI: 3-11%)) across the country. Our results provide evidence of widespread ZIKV exposure across the Philippines and suggest the need for studies to identify ZIKV infection risk factors over time to better prepare for potential future outbreaks.

Management of the dead in Tacloban City after Typhoon Haiyan.

INTRODUCTION: The post-disaster management of the dead involves a series of steps including on-site identification, transfer, storage and examination of bodies and delivery to families for burial. Two weeks after Typhoon Haiyan, a team from the Department of Health (DOH) was tasked with identifying the dead in Tacloban City. METHODS: A suitable site for the collection of bodies was identified and an algorithm and standard data collection form developed. The retrieval of bodies was coordinated with the Bureau of Fire Protection personnel. Upon receipt of a body, two team members conducted a systematic external examination. Findings were documented, photos were taken and each body was assigned a unique number. RESULTS: The DOH team examined 128 bodies. Of these, the majority (86%) were complete bodies; 95% were decomposed and two were skeletonized. Two thirds (66%) were adults, sex was identifiable for 92%, and the male to female ratio was 1:1.4. The majority of adults were females. Only 11% were presumptively identified from documents in clothing; 89% remained unidentified. CONCLUSION: From the limited setting of this study, we describe the process of rapid body processing post-Haiyan. We prioritized rapid processing over more technically complicated means of identification, including DNA testing. Our protocol showed a dignified and efficient way of identifying corpses. As local and regional laboratory capacity increases in the Philippines, the collection of DNA specimens may become part of the identification algorithm.