Limits...
A review of the effects of artemether-lumefantrine on gametocyte carriage and disease transmission.

Makanga M - Malar. J. (2014)

Bottom Line: 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.Many studies and analyses have specifically investigated the effects of the ACT, artemether-lumefantrine (AL) on gametocyte carriage.

View Article: PubMed Central - HTML - PubMed

Affiliation: European & Developing Countries Clinical Trials Partnership (EDCTP), PO Box 19070, Tygerberg, Cape Town, South Africa. makanga@edctp.org.

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.

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Reduction in gametocyte carriage with artemether-lumefantrine in adults and children with uncomplicated Plasmodium falciparum malaria [[30]]. Giemsa-stained thick blood smears were examined for gametocytes. AL: artemether-lumefantrine; mITT: modified intention-to-treat.
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Figure 3: Reduction in gametocyte carriage with artemether-lumefantrine in adults and children with uncomplicated Plasmodium falciparum malaria [[30]]. Giemsa-stained thick blood smears were examined for gametocytes. AL: artemether-lumefantrine; mITT: modified intention-to-treat.

Mentions: Rapid clearance of gametocytes has been demonstrated following treatment with AL in several geographic regions in adults and children. In one of the earliest studies to report the gametocytocidal properties of AL [70], the median time to gametocyte clearance following treatment with AL was 72 hours (three days). The largest dataset evaluating AL therapy to date is provided by a pooled analysis of seven studies conducted over the period 1996 to 2007 involving 1,332 children and 647 adults [30]. Six of the studies were conducted in malaria-endemic areas (four in Thailand and two in Africa) [70,73-77], and the other in non-immune adult travellers in Europe and non-endemic regions of Colombia [54]. Treatment with AL was associated with a rapid reduction in (microscopically determined) gametocyte carriage (from 5.1% of children with gametocytes at baseline to 0.9% after day 7, and from 9.7% of adults at baseline to 4.2% after day 7) (Figure 3) [30].


A review of the effects of artemether-lumefantrine on gametocyte carriage and disease transmission.

Makanga M - Malar. J. (2014)

Reduction in gametocyte carriage with artemether-lumefantrine in adults and children with uncomplicated Plasmodium falciparum malaria [[30]]. Giemsa-stained thick blood smears were examined for gametocytes. AL: artemether-lumefantrine; mITT: modified intention-to-treat.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4126813&req=5

Figure 3: Reduction in gametocyte carriage with artemether-lumefantrine in adults and children with uncomplicated Plasmodium falciparum malaria [[30]]. Giemsa-stained thick blood smears were examined for gametocytes. AL: artemether-lumefantrine; mITT: modified intention-to-treat.
Mentions: Rapid clearance of gametocytes has been demonstrated following treatment with AL in several geographic regions in adults and children. In one of the earliest studies to report the gametocytocidal properties of AL [70], the median time to gametocyte clearance following treatment with AL was 72 hours (three days). The largest dataset evaluating AL therapy to date is provided by a pooled analysis of seven studies conducted over the period 1996 to 2007 involving 1,332 children and 647 adults [30]. Six of the studies were conducted in malaria-endemic areas (four in Thailand and two in Africa) [70,73-77], and the other in non-immune adult travellers in Europe and non-endemic regions of Colombia [54]. Treatment with AL was associated with a rapid reduction in (microscopically determined) gametocyte carriage (from 5.1% of children with gametocytes at baseline to 0.9% after day 7, and from 9.7% of adults at baseline to 4.2% after day 7) (Figure 3) [30].

Bottom Line: 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.Many studies and analyses have specifically investigated the effects of the ACT, artemether-lumefantrine (AL) on gametocyte carriage.

View Article: PubMed Central - HTML - PubMed

Affiliation: European & Developing Countries Clinical Trials Partnership (EDCTP), PO Box 19070, Tygerberg, Cape Town, South Africa. makanga@edctp.org.

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.

Show MeSH
Related in: MedlinePlus