title: Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren.
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-1(19) 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.
authors: Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, UK. michael.bretscher@lshtm.ac.uk
authors: Michael T
authors: MT
authors: Bretscher
authors: Supargiyono
authors: S
authors: Supargiyono
authors: Mahardika A
authors: MA
authors: Wijayanti
authors: Dian
authors: D
authors: Nugraheni
authors: Anis N
authors: AN
authors: Widyastuti
authors: Neil F
authors: NF
authors: Lobo
authors: William A
authors: WA
authors: Hawley
authors: Jackie
authors: J
authors: Cook
authors: Chris J
authors: CJ
authors: Drakeley
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015994:Incidence; D007214:Indonesia / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000635:transmission*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D016036:Seroepidemiologic Studies
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium