Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia

Abstract

Background: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear.

Methods: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria.

Results: Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season.

Conclusion: Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.

Keywords: Asymptomatic; Clinical malaria; Plasmodium falciparum; Seasonal transmission.

Fig. 1

Study site and design. A Map of The Gambia with the study site (4 villages) circled. Made with Natural Earth. B Presentation of the two cohorts and the 2-year sampling period in the four villages. The bar charts show the cumulative number of fingerprick samples per timepoint for each village. The green colour represents the low malaria transmission season and the red colour represents the high transmission malaria season in The Gambia. The colours in the bars indicate village of residence (P = blue, N = light blue, K = light grey, J = grey)

Fig. 2

Plasmodium detection by different diagnostic tools. A Proportion of P. falciparum detected with different diagnostic methods. B Venn diagram of Plasmodium positivity by varATS, 18S rRNA qPCR and/or microscopy. C Correlation in parasitaemia between diagnostic tools. Error bars in A correspond to 95% confidence interval for estimated prevalence. Spearman rank correlation (C) is presented as the best fit line and the coefficient (r), as well as the p-value (p), are shown for each correlation pair between parasitaemia. LM light microscopy, qPCR quantitative polymerase chain reaction, rRNA ribosomal ribonucleic acid, ATS acidic terminal segment

Fig. 3

Trend analysis for P. falciparum infection prevalence (A) and parasitaemia (B) by age groups in the second cohort (2016). In A, error bars represent 95% confidence intervals for prevalence. Box in B plots representing interquartile ranges (25th, median and 75th percentile, whisker percentile (1st and 99th)). B Parasite density by varATS was not available for October in the < 5 year group

Fig. 4

Asymptomatic P. falciparum carriage at the end of dry season and during the subsequent transmission season. Being carrier in the dry season increases the risk of both P. falciparum infection (A) and malaria symptoms in the following transmission season (B). Time to infection and/or onset of clinical malaria were grouped into a 1-month interval