The relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% – 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% – 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens.

BackgroundMortality statistics form a crucial component of national Health Management Information Systems (HMIS). However, there are limitations in the availability and quality of mortality data at national level in Viet Nam. This study assessed the completeness of recorded deaths and the reliability of recorded causes of death (COD) in the A6 death registers in the national routine HMIS in Viet Nam.Methodology and findings1477 identified deaths in 2014 were reviewed in two provinces. A capture-recapture method was applied to assess the completeness of the A6 death registers. 1365 household verbal autopsy (VA) interviews were successfully conducted, and these were reviewed by physicians who assigned multiple and underlying cause of death (UCOD). These UCODs from VA were then compared with the CODs recorded in the A6 death registers, using kappa scores to assess the reliability of the A6 death register diagnoses. The overall completeness of the A6 death registers in the two provinces was 89.3% (95%CI: 87.8–90.8). No COD recorded in the A6 death registers demonstrated good reliability. There is very low reliability in recording of cardiovascular deaths (kappa for stroke = 0.47 and kappa for ischaemic heart diseases = 0.42) and diabetes (kappa = 0.33). The reporting of deaths due to road traffic accidents, HIV and some cancers are at a moderate level of reliability with kappa scores ranging between 0.57–0.69 (p<0.01). VA methods identify more specific COD than the A6 death registers, and also allow identification of multiple CODs.ConclusionsThe study results suggest that data completeness in HMIS A6 death registers in the study sample of communes was relatively high (nearly 90%), but triangulation with death records from other sources would improve the completeness of this system. Further, there is an urgent need to enhance the reliability of COD recorded in the A6 death registers, for which VA methods could be effective. Focussed consultation among stakeholders is needed to develop a suitable mechanism and process for integrating VA methods into the national routine HMIS A6 death registers in Viet Nam.

BackgroundArbovirus infections are a serious concern in tropical countries due to their high levels of transmission and morbidity. With the outbreaks of chikungunya (CHIKV) in surrounding regions in recent years and the fact that the environment in Vietnam is suitable for the vectors of CHIKV, the possibility of transmission of CHIKV in Vietnam is of great interest. However, information about CHIKV activity in Vietnam remains limited.MethodologyIn order to address this question, we performed a systematic review of CHIKV in Vietnam and a CHIKV seroprevalence survey. The seroprevalence survey tested for CHIKV IgG in population serum samples from individuals of all ages in 2015 from four locations in Vietnam.Principal findingsThe four locations were An Giang province (n = 137), Ho Chi Minh City (n = 136), Dak Lak province (n = 137), and Hue City (n = 136). The findings give us evidence of some CHIKV activity: 73/546 of overall samples were seropositive (13.4%). The age-adjusted seroprevalences were 12.30% (6.58–18.02), 13.42% (7.16–19.68), 7.97% (3.56–12.38), and 3.72% (1.75–5.69) in An Giang province, Ho Chi Minh City, Dak Lak province, and Hue City respectively. However, the age-stratified seroprevalence suggests that the last transmission ended around 30 years ago, consistent with results from the systematic review. We see no evidence for on-going transmission in three of the locations, though with some evidence of recent exposure in Dak Lak, most likely due to transmission in neighbouring countries. Before the 1980s, when transmission was occurring, we estimate on average 2–4% of the population were infected each year in HCMC and An Giang and Hue (though transmision ended earlier in Hue). We estimate lower transmission in Dak Lak, with around 1% of the population infected each year.ConclusionIn conclusion, we find evidence of past CHIKV transmission in central and southern Vietnam, but no evidence of recent sustained transmission. When transmission of CHIKV did occur, it appeared to be widespread and affect a geographically diverse population. The estimated susceptibility of the population to chikungunya is continually increasing, therefore the possibility of future CHIKV transmission in Vietnam remains.

Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population's natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states -naiveté, recent infection, non-recent infection, childhood infection -depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.The distribution of antibodies in a human population is a fossil imprint of the population's past exposure to infectious disease. If individuals' antibody concentrations can be measured accurately, they can be used to infer both the size and timing of past epidemics. The two key post-epidemic processes that need to be measured to make this inference possible are the rate of antibody acquisition and the rate of antibody waning. The rate of antibody acquisition post-infection is rapid (weeks) for most viral pathogens, but more difficult to measure for more complex pathogens that present the immune system with a diverse set of antigens. The rate of antibody waning, however, is rarely measured even for viral pathogens. To correctly translate a population's antibody titer distribution to its epidemic history, accurate measures of both these rates are necessary. To validate that this reconstruction has been done correctly, a large cohort with long-term follow-up and precise antibody measurements would be required. Studies like these are difficult to run and difficult to find in the scientific literature -both in methodological