Abstract
BackgroundArtemisinin-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.MethodsFrom 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.ResultsPlasmodium 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.ConclusionsIn 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.
Highlights
Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes
Through their combined impacts upon both the short-term infectiousness of treated individuals, and perhaps more importantly [6], upon the long-term duration of infection and infectiousness, ACT might reduce the reservoir of parasites in the human population that eventually infects mosquitoes
Whilst it is disappointing that no obvious reduction of human infectiousness was evident after introduction of ACT for malaria case management in this first large-area trial in a region of intense transmission, perhaps this is not entirely surprising
Summary
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. While nongametocyctocidal drugs will cure otherwise lengthy infections and reduce the period of infectiousness to mosquitoes, gametocytes will remain in the cured individual for some time, allowing for transmission In principle, through their combined impacts upon both the short-term infectiousness of treated individuals, and perhaps more importantly [6], upon the long-term duration of infection and infectiousness, ACT might reduce the reservoir of parasites in the human population that eventually infects mosquitoes. This implies that ACT may effectively reduce human-to-mosquito and mosquitoto-human transmission under normal conditions of programmatic use, as has been suggested in individually randomized, controlled trials evaluating the infectiousness of patients receiving ACT [9,10,11]
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