Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study.

BACKGROUND: Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population.

METHODS: We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test.

FINDINGS: There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17,858 person-months of follow-up. The incidence density of malaria attacks averaged 5·45 (95% CI 4·90-6·05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0·41 (0·29-0·55) between August, 2008, and August, 2010, but increased back to 4·57 (3·54-5·82) between September and December, 2010--ie, 27-30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0·0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0·0009).

INTERPRETATION: Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented.

FUNDING: Institut de Recherche pour le Développement and the Pasteur Institute of Dakar.