Despite numerous clinical studies demonstrating high cure rates and gametocytocidal effect of artemisinin derivatives
[9, 10, 40, 41], there is no evidence that this translates into any measurable impact on malaria transmission intensity at the population level in these Tanzanian sites. Although, the potential to reduce malaria transmission is widely cited, some mathematical models predict only a modest incremental impact of the routine use of ACT over non-gametocytocidal drugs in high transmission settings
. This observational study of the impact of routine delivery of ACT via health facilities provides some empirical support for this. Although, the parasitological study found a significant reduction in asexual parasitaemia prevalence following ACT introduction, this reduction was very modest (five percentage-points) and was not reflected in a measurable reduction of gametocytaemia prevalence in the human population
 . In the present study, the most direct indicator of human-to-mosquito transmission, namely oocyst prevalence, was substantially higher after ACT introduction. It is unclear what caused this increase, particularly since the sporozoite prevalence did not increase at the same time (Table
2), only factors, in particular weather patterns (Figure
4) changed considerably between the two periods. Because environmental conditions and availability of mosquitoes for analysis varied erratically throughout the study period, it is not possible to formally separate inter-annual and seasonal variation from effects of the policy change, but the overall conclusion is that any ACT-related reductions in human-to-mosquito or mosquito-to-human transmission in the mosquito population were small.
Overall, these two large-scale, complementary studies of malaria parasite prevalence in both humans and mosquitoes did not detect any epidemiologically meaningful suppression of human population infectiousness following ACT introduction. However, mosquito population dynamics in Rufiji were clearly profoundly affected by variations in rainfall during the study period. Rainfall affects both the emergence rates of vectors, and probably (via effects on humidity) the survival of adult mosquitoes. This does not directly affect the infectiousness of the human population to mosquitoes, but has profound effects on malaria transmission as measured either by the EIR or the oocyst prevalence. The large variations in emergence rates and survival of mosquitoes very likely account for most of the variation in oocyst prevalence, though this cannot explain why infectiousness was so low during the first half of the study (prior to ACT) in Rufiji, or why the oocyst prevalence increased after ACT introduction, while sporozoite prevalence did not. Far fewer mosquitoes were examined for oocysts than sporozoites, and sampling variation thus contributes more to the oocyst data.
The increase in oocyst prevalence thus seems very unlikely to be related to the change in drug policy. Nor is it likely that any substantive change in coverage of bed nets could have contributed to the observed difference in oocyst rates because net ownership and use remained relatively low and stable in Rufiji District until late 2005. There were no major changes in availability of nets in Kilombero-Ulanga during the study period
Although an efficacious ACT with known gametocytocidal properties was deployed and achieved reasonable population level coverage with an estimated 0.6 to 2.2 AS + SP treatments per person per year, the majority of persons receiving treatment with ACT were symptomatic children. Thus, the asymptomatic, chronically infected, semi-immune older children and adults who likely constituted the bulk of the reservoir of gametocytes
 were relatively untouched by the introduction of ACT for case management. There have even been suggestions of higher infectivity of gametocytes in asymptomatic carriers in comparison to symptomatic cases due to the large quantity of gametocytes in the former group
. In areas where the initial level of malaria transmission is relatively low, the ratio of symptomatic to asymptomatic infections is higher, and larger proportionate reductions in transmission may be likely following introduction of ACT
[6, 39, 43]. Conversely, in areas of high transmission such as investigated here, ACT may have little impact on prevalence, human population infectiousness and consequent mosquito-to-human transmission because a greater proportion of infections are only mildly symptomatic. Furthermore, even in settings such as these where artemisinins are combined with complementary partner drugs, such as SP which have long-lasting prophylactic effects
, ACT use may have little impact on overall transmission where it occurs at high intensities simply because individuals often become re-infected within weeks of treatment
ACT might only have a substantial effect on the infectious reservoir if most of the infections are actually being treated with this drug class. The delivery of ACT through public sector outlets in Rufiji rose steadily from 2003 to 2005 with a total of 450,000 doses being deployed for distribution to all registered health facilities by that time
, corresponding to a mean consumption rate of 2.22 doses per person per year. Adherence among recipients has been estimated at 75%
, which implies that this drug was delivered reasonably effectively. The proportion of care-seeking visits made to the health facilities that were fever-related rose from 31.8% in 2001 to 54.7% in 2004
, perhaps due to improved community perceptions, availability and affordability. Recent calls for accurately targeting ACT only to those with patent parasitaemia
 may, paradoxically, further undercut the potential for case management alone to contribute to transmission reduction in highly endemic settings.
While much emphasis has been placed upon the importance of the gametocytocidal properties of ACT, their most important contribution to lowering human population infectiousness is to terminate otherwise long-lasting infections with asexual stages, which intermittently but persistently generate gametocytes and can infect mosquitoes for over a year
. This is comparable to the effect of non-gametocytocidal blood schizonticides. Similarly, the impact of curative drugs upon onward transmission is probably primarily determined by the length of time successfully treated patients remain uninfected and consequently non-infectious, rather than whether that drug kills the relatively short-lived gametocytes already present at the time of administration. Therefore, while an effective cure may reduce human population infectiousness in an area with little transmission, in parts of Africa where it is common to become re-infected within weeks or even days, even regular treatment of symptomatic infections
[48, 49] will likely have only a modest effect upon the proportion of people’s lives spent infected and, therefore, on the mean infection prevalence as described