Molecular incidence and clearance of Plasmodium falciparum infection

Abstract

Background: Although the epidemiology of malaria has been based primarily on microscopy and rapid diagnostic tests, molecular methods are necessary to understand the complexity of natural infection in regions where transmission is intense and simultaneous infection with multiple parasite genotypes is common such as sub-Saharan Africa.

Methods: To compare microscopic and molecular estimates of the incidence and clearance of Plasmodium falciparum infection, we followed 80 children monthly for 1 year in the village of Bancoumana in Mali.

Results and discussion: Similar seasonal patterns were observed with both methods (rainy season peak, dry season nadir), although molecular methods detected more infections than microscopy (571 vs 331 in 906 specimens), more new infections (311 vs 104 during 829 person-months) and spontaneous clearance events (317 vs 116) and found higher incidence (0.38 vs 0.13 new genotypes/person/month, p < 0.001) and spontaneous clearance rates (0.38 vs 0.14 genotypes cleared/person/month, p < 0.001). These differences were greatest for persistently-infected subjects in whom neither new infections nor the clearance of old infections could be detected by microscopy (0.71 new infections and 0.73 cleared infections per month using molecular methods vs 0.000 by microscopy, p < 0.001).

Conclusions: Molecular methods provide information about genetic diversity, the intensity of transmission and spontaneous clearance in the absence of drug treatment that cannot be obtained by microscopy. They will be necessary to evaluate the efficacy of vaccines, drugs and other control strategies for diseases such as malaria in which simultaneous infection with more than one organism (genotype) is common.

Fig. 1

Number of infections per person (prevalence of P. falciparum infection). Data provided compare slide-based estimates of the number of infections per person (filled squares) with molecular estimates of the number of infections per person (filled circles) for the 80 subjects in the pilot cohort

Fig. 2

Incidence of P. falciparum infection. a Slide-negative subjects. Data compare slide-based estimates of incidence (filled squares) with molecular estimates of incidence (filled circles) for the subset of subjects who were slide-negative at the beginning of each monthly observation period. b All subjects in the cohort. Data compare slide-based estimates of incidence (filled squares) with molecular estimates of incidence (filled circles) for all subjects in the cohort

Fig. 3

Spontaneous clearance of P. falciparum infection. a Slide-positive subjects. Data compare slide-based estimates of clearance (inverted triangles) with molecular estimates of clearance (triangles) for subjects who were slide-positive at the beginning of each monthly observation period. b All subjects in the cohort. Data compare slide-based estimates of clearance for all subjects (inverted triangles) with molecular estimates of clearance (triangles) for all the subjects in the pilot cohort

Fig. 4

Incidence and clearance of P. falciparum infection in persistently-infected subjects. Data compare molecular estimates of incidence (filled circles) and molecular estimates of clearance (filled triangles) with microscopic estimates of incidence and clearance for subjects who were slide-positive at the beginning and the end of each monthly observation period (diamonds)