Risk factors for Plasmodium falciparum gametocyte positivity in a longitudinal cohort

Abstract

Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.

Fig 1. Map of Dielmo village.

The village is located at 13°45’N, 16°25’W and is composed of two hamlets showing the houses within the gametocyte hotspots (hotspot 1—blue, 1996–2003, Relative Risk (RR) 1.95, log likelihood ratio (LLR) 14.35 P = 0.0012; cluster 2—green, 1995–2002, RR 1.77, LLR 12.7 P = 0.0053) identified by SaTScan Also shown (large open red circle), area of the P. falciparum clinical episode hotspot identified by SaTScan; 1995–2003, RR 1.42, LLR 11.01 P = 0.026.

Fig 2. Gametocyte prevalence rate per year-trimester.

Shown are means and 95% binomial confidence intervals.

Fig 3. The proportion of P. falciparum positive bloodslides that are gametocyte positive.

This is according to time since last antimalarial drug treatment for each of the drug treatment regimens and separating the Chloroquine drug period into hotspot vs. non hotspot. Also shown are 95% binomial confidence intervals. Open: ≤ 30 days; Grey 30–60 days; Diagonal 61–90 days; Speckled 91–360 days.