Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data

Abstract

Background: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings.

Methods: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia.

Findings: The median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity.

Interpretation: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission.

Funding: Wellcome Trust.

Figure 1

Estimated proportion of Plasmodium falciparum infections in populations detected within health systems (P[Detect]) compared with the corresponding prevalence of infection in the community (A) All age groups. (B) Individuals older than 5 years of age. (C) Children aged 5 years and younger, with the significant interaction in non-African and African populations shown in the separate panels. The average fitted linear mixed model trend is shown by the red line and corresponding 95% CI band is shaded in grey. Each dot represents a paired community and health facility cluster, with their size representing the sample size of the community survey as small (<50 people), medium (50–100 people), or large (>150 people). The 95% credible intervals around each metric are shown by the horizontal and vertical grey lines around each cluster.

Figure 2

Estimated proportion of Plasmodium falciparum infections in populations detected within health systems (P[Detect]) in 12 communities sampled at 13 monthly intervals over 2 years in The Gambia (A) The annual variation within each study village (A to M) is shown as a boxplot, with low transmission villages represented in orange and high transmission villages in blue. (B) The locally estimated scatterplot smoothing (LOESS) trends for all villages combined with the different colours representing the 12 individual villages. (C) The LOESS trends for villages stratified according to high transmission intensity (blue line) or low transmission intensity (orange line). The 95% CIs from the LOESS estimate are shown as the shaded grey area. The 95% credible intervals around P(Detect) are shown by the vertical grey lines around each, with the point size representing the estimated community prevalence for that sample month. The dashed vertical red line identifies the period where a mass drug administration of dihydroartemisinin–piperaquine was deployed in all study villages.

Figure 3

Estimated proportion of Plasmodium vivax infections detected in health facilities compared with the corresponding prevalence of infection in the community (A) All age groups. (B) Individuals older than 5 years of age. The average fitted linear mixed model trend is shown by the red line and corresponding 95% CI band is shaded in grey. Each dot represents a paired community and health facility cluster, with their size representing the sample size of the community survey as small (<50 people), medium (50–100 people), or large (>150 people). The 95% credible intervals around each metric are shown by the horizontal and vertical grey lines around each cluster.