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Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren

Michael T Bretscher1*, Supargiyono Supargiyono2, Mahardika A Wijayanti2, Dian Nugraheni2, Anis N Widyastuti2, Neil F Lobo3, William A Hawley4, Jackie Cook5 and Chris J Drakeley1

Author Affiliations

1 Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, UK

2 Center for Tropical Medicine Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia

3 Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA

4 UNICEF, Jakarta, Indonesia

5 Department of Medicine Solna Malaria Research Unit, Karolinska Institutet, Stockholm, Sweden

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Malaria Journal 2013, 12:21  doi:10.1186/1475-2875-12-21

Published: 17 January 2013

Abstract

Background

As malaria transmission intensity approaches zero, measuring it becomes progressively more difficult and inefficient because parasite-positive individuals are hard to detect. This situation may arise shortly before achieving local elimination, or during surveillance post-elimination to prevent reintroduction. Antibody responses against the parasite last longer than the infections themselves. This “footprint” of infection may thus be used for assessing transmission intensity. A statistical approach is presented for measuring the seroconversion rate (SCR), a correlate of the force of infection, from individual-level longitudinal data on antibody titres in an area of low Plasmodium falciparum transmission.

Methods

Blood samples were collected from 160 Indonesian schoolchildren every month for six months. Titres of antibodies against AMA-1 and MSP-119 antigens of P. falciparum were measured using ELISA. The distribution of antibody titres among seronegative and -positive individuals, respectively, was estimated by comparing the titres from the study data (a mixture of both seropositive and -negative individuals) with titres from a (unexposed) negative control group of Indonesian individuals. Two Markov-Chain models for the transition of individuals between serological states were fitted to individual anti-PfAMA-1 or anti-PfMSP-1 titre time series using Bayesian Markov-Chain-Monte-Carlo (MCMC). This yielded estimates of SCR as well as of the duration of seropositivity.

Results

A posterior median SCR of 0.02 (Pf AMA-1) and 0.09 (PfMSP-1) person-1 year-1 was estimated, with credible intervals ranging from 1E-4 to 0.2 person-1 year-1. This level of transmission intensity is at the lower range of what can reliably be measured with the present study size. A Bayesian test for seroconversion of an individual between two observations is presented and used to identify the subjects who have most likely experienced an infection. Furthermore, the theoretical limits of measuring transmission intensity, and how these depend on duration and size of a study as well as on transmission intensity itself, is illustrated.

Conclusions

This analysis shows that it is possible to measure SCR's from individual-level longitudinal data on antibody titres. In addition, individual seroconversion events can be identified, which can be useful in assessing interruption of transmission. Analyses of further serological datasets using the present method are required to improve and validate it. This includes measurement of the duration of antibody responses, how it depends on host age or cumulative exposure, or on the particular antigen used.

Keywords:
Malaria; Plasmodium falciparum; Serology; Epidemiology; Cohort study; Force of infection; Measuring transmission intensity; Antibodies; Elimination; Longitudinal data