Abstract
While significant advances have been made in the prevention and treatment of malaria in recent years, these successes continue to fall short of the World Health Organization (WHO) goals for malaria control and elimination. For elimination strategies to be effective, limited disease transmission, achieved through rapid reduction in the infectious parasite reservoir and decreased gametocyte carriage, will be critical. Artemisinin-based combination therapy (ACT) forms the cornerstone of WHO-recommended treatment for uncomplicated Plasmodium falciparum malaria, and in combination with other effective interventions will undoubtedly play a vital role in elimination programmes. The gametocytocidal properties of artemisinins are a bonus attribute; there is epidemiological evidence of reductions in malaria incidence and transmission in African regions since the introduction of these agents. Many studies and analyses have specifically investigated the effects of the ACT, artemether-lumefantrine (AL) on gametocyte carriage. In this systematic review of 62 articles published between 1998 and January 2014, the effects of AL on gametocyte carriage and malaria transmission are compared with other artemisinin-based anti-malarials and non-ACT. The impact of AL treatment of asymptomatic carriers on population gametocyte carriage, and the potential future role of AL in malaria elimination initiatives are also considered. Despite the inherent difficulties in comparing data from a range of different studies that also utilized different diagnostic approaches to assess baseline gametocyte counts, the gametocytocidal effect of AL was proportionately consistent across the studies reviewed, suggesting that AL will continue to play a vital role in the treatment of malaria and contribute to clearing the path towards malaria elimination. However, the specific place of AL is the subject of much ongoing research and will undoubtedly be dependent on different demographic and geographical scenarios. Utilizing ACT, such as AL, within malaria elimination strategies is also associated with a number of other challenges, such as balancing potential increased use of ACT (e g, treatment of asymptomatic carriers and home-based treatment) with rational use and avoidance of drug resistance development.
Highlights
From malaria control to elimination Between 2000 and 2012 estimated malaria mortality rates across all age groups dropped by 42% and 49% globally and in Africa, respectively, and deaths decreased by 51% in Africa in children < five years of age [1]
Information extracted from each article included study type and year, geographic location, study population, intervention evaluated, gametocyte diagnostic method, sampling schedule for gametocyte data, key data regarding gametocyte carriage and malaria transmission, and key conclusions regarding effects of AL
Superior gametocyte clearance rates and reduced infectiousness to mosquitoes has been demonstrated with AL when compared with DP in studies of >2,000 children and adults, and when compared with other Artemisinin-based combination therapy (ACT) in studies involving >18,000 children and adults. These findings suggest that AL is a logical ACT option for use in future malaria elimination programmes, possibly combined with a further gametocytocidal agent, such as primaquine [21], or in combination with preventative measures such as vector control (e g, Insecticide-treated net (ITN) and long-lasting insecticide-treated nets) and potentially future malaria transmission-blocking vaccines
Summary
From malaria control to elimination Between 2000 and 2012 estimated malaria mortality rates across all age groups dropped by 42% and 49% globally and in Africa, respectively, and deaths decreased by 51% in Africa in children < five years of age [1]. The rate of decline in estimated malaria mortality slowed between 2011 and 2012. This is reported; the number of delivered treatment courses has increased from 76 million in 2006 to 331 million in 2012 [1]. Despite all of the above measures, during 2012 there were an estimated 207 million cases of malaria, resulting in approximately 627,000 malaria deaths. While significant advances have been made in managing malaria in recent years, these successes continue to fall short of WHO goals for malaria control and elimination (i e, to reduce global malaria deaths to near zero by end of 2015; to reduce global malaria cases by 75% by end of 2015; and to eliminate malaria by end of 2015 in ten new countries since 2008, including in the WHO European Region) [1]
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