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Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

Bernadette J Huho128, Gerard F Killeen13, Heather M Ferguson14, Adriana Tami56, Christian Lengeler28, J Derek Charlwood3, Aniset Kihonda1, Japhet Kihonda1, S Patrick Kachur17*, Thomas A Smith28 and Salim MK Abdulla1

Author Affiliations

1 Ifakara Health Institute, Dar-es-Salaam, Tanzania

2 Swiss Tropical and Public Health Institute, Basel, Switzerland

3 Liverpool School of Tropical Medicine, Liverpool, UK

4 Division of Infection and Immunity, University of Glasgow, G12 8TA, Glasgow, UK

5 Department of Medical Microbiology, University Medical Center Groningen, Groningen, The Netherlands

6 Royal Tropical Institute, Biomedical Research, Amsterdam, The Netherlands

7 Malaria Branch, US Centers for Disease Control and Prevention, Atlanta, USA

8 University of Basel, Petersplatz 1, Basel CH-4003, Switzerland

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Malaria Journal 2012, 11:118  doi:10.1186/1475-2875-11-118

Published: 18 April 2012

Abstract

Background

Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect vector mosquitoes. However, this has never been verified at a population level in a setting with intense transmission, where chronically infectious asymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected.

Methods

From 2001 to 2004, malaria vector densities were monitored using light traps in three Tanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates. Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxine-pyrimethamine (SP) monotherapy was used for treatment of uncomplicated malaria in the contiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, the standard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003. The effects of this change in case management on malaria parasite infection in the vectors were analysed.

Results

Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites per person per year at both sites over the whole period. The introduction of AS + SP in Rufiji was associated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p < 0.001), but had no consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). The estimated infectiousness of the human population in Rufiji was very low prior to the change in drug policy. Emergence rates and parous rates of the vectors varied substantially throughout the study period, which affected estimates of infectiousness. The latter consequently cannot be explained by the change in drug policy.

Conclusions

In high perennial transmission settings, only a small proportion of infections in humans are symptomatic or treated, so case management with ACT may have little impact on overall infectiousness of the human population. Variations in infection levels in vectors largely depend on the age distribution of the mosquito population. Benefits of ACT in suppressing transmission are more likely to be evident where transmission is already low or effective vector control is widely implemented.

Keywords:
Malaria; Artemisinin-based combination therapy; Transmission reduction; Malaria