Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study

Abstract

Background: In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes.

Methods: Two studies were run in parallel in Burkina Faso to evaluate the impact of systematic identification and treatment of asymptomatic carriers of P. falciparum, detected by rapid diagnostic test, on disease transmission and susceptibility to clinical malaria episodes. A clinical study assessed the incidence of symptomatic malaria episodes with a parasite density >5,000/μL after three screening and treatment campaigns ~1 month apart before the rainy season; and an entomological study determined the effect of these campaigns on malaria transmission as measured by entomological inoculation rate.

Results: The intervention arm had lower prevalence of asymptomatic carriers of asexual parasites and lower prevalence of gametocyte carriers during campaigns 2 and 3 as compared to the control arm. During the entire follow-up period, out of 13,767 at-risk subjects, 2,516 subjects (intervention arm 1,332; control arm 1,184) had symptomatic malaria. Kaplan-Meier analysis of the incidence of first symptomatic malaria episode with a parasite density >5,000/μL showed that, in the total population, the two treatment arms were similar until Week 11-12 after campaign 3, corresponding with the beginning of the malaria transmission season, after which the probability of being free of symptomatic malaria was lower in the intervention arm (logrank p < 0.0001). Similar trends were observed in infants and children <5 years and in individuals ≥5 years of age. In infants and children <5 years old who experienced symptomatic malaria episodes, the geometric mean P. falciparum density was lower in the intervention arm than the control arm. This trend was not seen in those individuals aged ≥5 years. Over the year, monthly variation in mosquito density and entomological inoculation rate was comparable in both arms, with September peaks in both indices.

Conclusion: Community screening and targeted treatment of asymptomatic carriers of P. falciparum had no effect on the dynamics of malaria transmission, but seemed to be associated with an increase in the treated community's susceptibility to symptomatic malaria episodes after the screening campaigns had finished. These results highlight the importance of further exploratory studies to better understand the dynamics of disease transmission in the context of malaria elimination.

Trial registration: ClinicalTrials.gov NCT01256658.

Figures

Figure 1

Single-center, controlled, parallel, cluster-randomized, 12-month prospective study. Reproduced from Tiono et al. 2013 [21].

Figure 2

Consort chart. Reproduced from Tiono et al. 2013 [21].

Figure 3

Kaplan-Meier plot of incidence of first SMRC5000 following screening campaign 3 – cluster level data.

Figure 4

Distribution of P. falciparum density during SMRC5000 in infants and children <5 years of age following screening campaign 3. I = intervention arm; C = control arm; numbers 1–3 indicate first, second and third episodes, and A any episode; n = number of subjects at each episode; central rectangles span the first quartile to the third quartile (IQR); the line inside each rectangle shows the median; the whiskers that extend from each box indicate the range of values that are outside of the intra-quartile range but close enough not to be considered outliers (a distance less than or equal to 1.5*IQR); ♦ = geometric mean.

Figure 5

Distribution of P. falciparum density during SMRC5000 in individuals ≥5 years of age following screening campaign 3. I = intervention arm; C = control arm; numbers 1–3 indicate first, second and third episodes, and A any episode; n = number of subjects at each episode; central rectangles span the first quartile to the third quartile (IQR); the line inside each rectangle shows the median; the whiskers that extend from each box indicate the range of values that are outside of the intra-quartile range but close enough not to be considered outliers (a distance less than or equal to 1.5*IQR); ♦ = geometric mean.

Figure 6

Mean P. falciparum gametocyte density at screening campaign 4.

Figure 7

Temporal variation of Anopheles density and entomological inoculation rate (EIR) by study arm.