Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/106708

Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels

Arnold, B.·van der Laan, M. J.·Hubbard, A. E.·Steel, C.·Kubofcik, J.·Hamlin, K. L.·Moss, D. M.·Nutman, T. B.·Priest, J. W.·Lammie, P. J.
View original source ↗Export metadata ↓

Abstract

BackgroundSerologicalantibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels in low transmission settings. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays.\n\nMethods/Principal FindingsWe developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearmans rho=0.75). Seroprevalence estimates recapitulated patterns observed in quantitative antibody levels, albeit with lower resolution.\n\nConclusions/SignificanceAge-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, and scales to surveillance activities that require high spatiotemporal resolution. The approach represents a new opportunity to conduct integrated serological surveillance for neglected tropical diseases, malaria, and other infectious diseases with well-defined antigen targets.\n\nAuthor SummaryGlobal elimination strategies for infectious diseases like neglected tropical diseases and malaria rely on accurate estimates of pathogen transmission to target and evaluate control programs. Circulating antibody levels can be a sensitive measure of recent pathogen exposure, but no broadly applicable method exists to measure changes in transmission directly from quantitative antibody levels. We developed a novel method that applies recent advances in machine learning and data science to flexibly fit age-dependent antibody curves. Shifts in age-dependent antibody curves provided remarkably consistent, sensitive measures of transmission changes when evaluated across many globally important pathogens (filarial worms, malaria, enteric infections). The methods generality and performance in diverse applications demonstrate its broad potential for integrated serological surveillance of infectious diseases.

Source connections

Explore related subjects

epidemiologyPreprint

Keep this discovery

BibTeXRIS

Arnold, B., van der Laan, M. J., Hubbard, A. E., Steel, C., Kubofcik, J., Hamlin, K. L., Moss, D. M., Nutman, T. B., Priest, J. W., Lammie, P. J.. 2017-02-07. Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels. https://doi.org/10.1101/106708

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2018

Translating surveillance data into incidence estimates

Monitoring a population for a disease requires the hosts to be sampled and tested for the pathogen. This results in sampling series from which to estimate the disease incidence, i.e. the proportion of hosts infected. Existing estimation methods assume that disease incidence is not changing between monitoring rounds, resulting in underestimation of the disease incidence. In this paper we develop an incidence estimation model accounting for epidemic growth with monitoring rounds sampling varying incidence. We also show how to accommodate the asymptomatic period characteristic to most diseases. For practical use, we produce an approximation of the model, which is subsequently shown accurate for relevant epidemic and sampling parameters. Both the approximation and the full model are applied to stochastic spatial simulations of epidemics. The results prove their consistency for a very wide range of situations.

epidemiology↗
bioRxiv2018

The Swiss Primary Ciliary Dyskinesia registry: objectives, methods and first results

Primary Ciliary Dyskinesia (PCD) is a rare hereditary, multi-organ disease caused by defects in ciliary structure and function. It results in a wide range of clinical manifestations, most commonly in the upper and lower airways. Central data collection in national and international registries is essential to studying the epidemiology of rare diseases and filling in gaps in knowledge of diseases such as PCD. For this reason, the Swiss Primary Ciliary Dyskinesia Registry (CH-PCD) was founded in 2013 as a collaborative project between epidemiologists and adult and paediatric pulmonologists.\n\nThe registry records patients of any age, suffering from PCD, who are treated and resident in Switzerland. It collects information from patients identified through physicians, diagnostic facilities, and patient organisations. The registry dataset contains data on diagnostic evaluations, lung function, microbiology and imaging, symptoms, treatments, and hospitalizations.\n\nBy May 2018, CH-PCD has contacted 566 physicians of different specialties and identified 134 patients with PCD. At present this number represents an overall 1 in 63,000 prevalence of people diagnosed with PCD in Switzerland. Prevalence differs by age and region; it is highest in children and adults younger than 30 years, and in Espace Mittelland. The median age of patients in the registry is 25 years (range 5-73), and 49 patients have a definite PCD diagnosis based on recent international guidelines. Data from CH-PCD are contributed to international collaborative studies and the registry facilitates patient identification for nested studies.\n\nCH-PCD has proven to be a valuable research tool that already has highlighted weaknesses in PCD clinical practice in Switzerland. Development of centralised diagnostic and management centres and adherence to international guidelines are needed to improve diagnosis and management--particularly for adult PCD patients.

epidemiology↗
bioRxiv2018

Perfect Counterfactuals for Epidemic Simulations

Simulation studies are often used to predict the expected impact of control measures in infectious disease outbreaks. Typically, two independent sets of simulations are conducted, one with the intervetnion, and one without, and epidemic sizes (or some related metric) are compared to estimate the effect of the intervention. Since it is possible that controlled epidemics are larger than uncontrolled ones if there is substantial stochastic variation between epidemics, uncertainty intervals from this approach can include a negative effect even for an effective intervention. To more precisely estimate the number of cases an intervention will prevent within a single epidemic, here we develop a single world approach to matching simulations of controlled epidemics to their exact uncontrolled counterfac-tual. Our method borrows concepts from percolation approaches prune out possible epidemic histories and create potential epidemic graph that can be realized to create perfectly matched controlled and uncontrolled epidemics. We present an implementation of this method for a common class of compartmental models, and its application in a simple SIR model. Results illustrate how, at the cost of some computation time, this method substantially narrows confidence intervals and avoids non-sensical inferences.

epidemiology↗