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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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Related in: MedlinePlus

Time to disappearance of gametocytes in gametocyte-positive individuals (by quantitative real-time nucleic acid sequence-based amplification) at enrolment following treatment [[26]]. AL: artemether-lumefantrine (n = 32); DP: dihydroartemisinin-piperaquine (n = 35). (Sourced from Sawa et al. 2013, with permission [26]).
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Figure 4: Time to disappearance of gametocytes in gametocyte-positive individuals (by quantitative real-time nucleic acid sequence-based amplification) at enrolment following treatment [[26]]. AL: artemether-lumefantrine (n = 32); DP: dihydroartemisinin-piperaquine (n = 35). (Sourced from Sawa et al. 2013, with permission [26]).

Mentions: Further evidence of the importance of the gametocyte diagnostic method is provided by a randomized trial in 298 African children (aged six months to ten years) who were treated with AL or DP. A highly sensitive molecular assay was used to assess gametocyte carriage, and mosquito-feeding assays were used to determine infectiousness to mosquitoes [26]. The gametocytocidal effect of AL immediately after treatment was larger than that of DP. There was no difference between treatment arms in enrolment gametocyte prevalence (9.7% by microscopy and 71.3% by QT-NASBA). AL was associated with a significantly shorter mean duration of gametocyte carriage than DP (5.5 vs 15.3 days, respectively; p = 0.001). For individuals who were gametocyte-positive (by QT-NASBA) prior to treatment, the time to disappearance of gametocytes was significantly shorter for the AL group vs the DP group (HR 2.35) (Figure 4) [26]. In terms of gametocyte transmission to mosquitoes that fed on post-treatment blood samples, 1.9% (43/2293) became infected from AL-treated children and 3.5% (83/2371) were infected from the blood of DP-treated children (p = 0.06).


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

Makanga M - Malar. J. (2014)

Time to disappearance of gametocytes in gametocyte-positive individuals (by quantitative real-time nucleic acid sequence-based amplification) at enrolment following treatment [[26]]. AL: artemether-lumefantrine (n = 32); DP: dihydroartemisinin-piperaquine (n = 35). (Sourced from Sawa et al. 2013, with permission [26]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Time to disappearance of gametocytes in gametocyte-positive individuals (by quantitative real-time nucleic acid sequence-based amplification) at enrolment following treatment [[26]]. AL: artemether-lumefantrine (n = 32); DP: dihydroartemisinin-piperaquine (n = 35). (Sourced from Sawa et al. 2013, with permission [26]).
Mentions: Further evidence of the importance of the gametocyte diagnostic method is provided by a randomized trial in 298 African children (aged six months to ten years) who were treated with AL or DP. A highly sensitive molecular assay was used to assess gametocyte carriage, and mosquito-feeding assays were used to determine infectiousness to mosquitoes [26]. The gametocytocidal effect of AL immediately after treatment was larger than that of DP. There was no difference between treatment arms in enrolment gametocyte prevalence (9.7% by microscopy and 71.3% by QT-NASBA). AL was associated with a significantly shorter mean duration of gametocyte carriage than DP (5.5 vs 15.3 days, respectively; p = 0.001). For individuals who were gametocyte-positive (by QT-NASBA) prior to treatment, the time to disappearance of gametocytes was significantly shorter for the AL group vs the DP group (HR 2.35) (Figure 4) [26]. In terms of gametocyte transmission to mosquitoes that fed on post-treatment blood samples, 1.9% (43/2293) became infected from AL-treated children and 3.5% (83/2371) were infected from the blood of DP-treated children (p = 0.06).

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