Background 

The World Health Organization recommends uncomplicated P. falciparum malaria is treated using Artemisinin-based Combination Therapy (ACT). This review aims to assist the decision making of malaria control programmes by providing an overview of the relative benefits and harms of the available options. Objectives To compare the effects of ACTs with other available ACT and non-ACT combinations for treating uncomplicated P. falciparum malaria. 

Search strategy 

We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) to March 2009. 

Selection criteria 

Randomized head to head trials of ACTs in uncomplicated P. falciparum malaria. This review is limited to: dihydroartemisinin-piperaquine; artesunate plus mefloquine; artemether-lumefantrine (six doses); artesunate plus amodiaquine; artesunate plus sulfadoxine-pyrimethamine and amodiaquine plus sulfadoxine-pyrimethamine. 

Data collection and analysis 

Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on P. vivax, gametocytes, haemoglobin, and adverse events.

Main results 

Fifty studiesmet the inclusion criteria. All five ACTs achieved PCR adjusted failure rates of <10%, in line with WHO recommendations, at most study sites. Dihydroartemisinin-piperaquine performed well compared to the ACTs in current use (PCR adjusted treatment failure versus artesunate plus mefloquine in Asia; RR 0.39, 95% CI 0.19 to 0.79; three trials, 1062 participants; versus artemether-lumefantrine in Africa; RR 0.39, 95% CI 0.24 to 0.64; three trials, 1136 participants). ACTs were superior to amodiaquine plus sulfadoxine-pyrimethamine in East Africa (PCR adjusted treatment failure versus artemether-lumefantrine; RR 0.12, 95% CI 0.06 to 0.24; two trials, 618 participants; versus AS+AQ; RR 0.44, 95% CI 0.22 to 0.89; three trials, 1515 participants). Dihydroartemisinin-piperaquine (RR 0.32, 95% CI 0.24 to 0.43; four trials, 1442 participants) and artesunate plus mefloquine (RR 0.30, 95% CI 0.21 to 0.41; four trials, 1003 participants) were more effective than artemether-lumefantrine at reducing the incidence of P. vivax over 42 days follow up. 

Authors' conclusions 

Dihydroartemisinin-piperaquine is another effective first-line treatment for P. falciparum malaria. The performance of the non-ACT (amodiaquine plus sulfadoxine-pyrimethamine) falls below WHO recommendations for first-line therapy in parts of Africa. In areas where primaquine is not being used for radical cure of P. vivax, ACTs with long half-lives may provide some benefit.

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Artemisinin-based combination therapy for treating uncomplicated malaria.

BACKGROUND

Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution.

METHODS AND FINDINGS

We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations.

CONCLUSIONS

Resistant dhps has emerged independently in multiple sites in Africa during the past 10-20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.

/pdf/multiple-origins-and-regional-dispersal-of-resistant-dhps-in-1gwcav61l1.pdf

Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

Recent research indicates a high recall in Google Scholar searches for systematic reviews. These reports raised high expectations of Google Scholar as a unified and easy to use search interface. However, studies on the coverage of Google Scholar rarely used the search interface in a realistic approach but instead merely checked for the existence of gold standard references. In addition, the severe limitations of the Google Search interface must be taken into consideration when comparing with professional literature retrieval tools. The objectives of this work are to measure the relative recall and precision of searches with Google Scholar under conditions which are derived from structured search procedures conventional in scientific literature retrieval; and to provide an overview of current advantages and disadvantages of the Google Scholar search interface in scientific literature retrieval. General and MEDLINE-specific search strategies were retrieved from 14 Cochrane systematic reviews. Cochrane systematic review search strategies were translated to Google Scholar search expression as good as possible under consideration of the original search semantics. The references of the included studies from the Cochrane reviews were checked for their inclusion in the result sets of the Google Scholar searches. Relative recall and precision were calculated. We investigated Cochrane reviews with a number of included references between 11 and 70 with a total of 396 references. The Google Scholar searches resulted in sets between 4,320 and 67,800 and a total of 291,190 hits. The relative recall of the Google Scholar searches had a minimum of 76.2% and a maximum of 100% (7 searches). The precision of the Google Scholar searches had a minimum of 0.05% and a maximum of 0.92%. The overall relative recall for all searches was 92.9%, the overall precision was 0.13%. The reported relative recall must be interpreted with care. It is a quality indicator of Google Scholar confined to an experimental setting which is unavailable in systematic retrieval due to the severe limitations of the Google Scholar search interface. Currently, Google Scholar does not provide necessary elements for systematic scientific literature retrieval such as tools for incremental query optimization, export of a large number of references, a visual search builder or a history function. Google Scholar is not ready as a professional searching tool for tasks where structured retrieval methodology is necessary.

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Google Scholar as replacement for systematic literature searches: good relative recall and precision are not enough

Molecular approaches to diversity of populations of apicomplexan parasites

Background: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. Methods: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints.

/pdf/efficacy-of-artesunate-amodiaquine-for-treating-dql27korvg.pdf

Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis

In the last five years, countries have been faced with changing their malaria treatment policy to an artemisinin-based combination therapy (ACT), many with no national data on which to base their decision. This is particularly true for a number of West African countries, including Guinea, where these studies were performed. Two studies were conducted in 2004/2005 in programmes supported by Medecins Sans Frontieres, when chloroquine was still national policy, but artesunate (AS)/sulphadoxine-pyrimethamine (SP) had been used in refugee camps for two years. In Dabola (central Guinea), 220 children aged 6–59 months with falciparum malaria were randomized to receive either AS/amodiaquine (AQ) or AS/SP. In vivo efficacy was assessed following the 2003 World Health Organization guidelines. In a refugee camp in Laine (south of Guinea), where an in vivo study was not feasible due to the unstable context, a molecular genotyping study in 160 patients assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 436, 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulphadoxine, respectively. In Dabola, after 28 days of follow-up, Polymerase Chain Reaction (PCR)-adjusted failure rates were 1.0% (95%CI 0–5.3) for AS/AQ and 1.0% (95%CI 0–5.5) for AS/SP. In the refugee camp in Laine, the molecular genotyping study found three dhfr mutations in 85.6% (95%CI 79.2–90.7) patients and quintuple dhfr/dhps mutations in 9.6% (95%CI 5.2–15.9). Both AS/AQ and AS/SP are highly efficacious in Dabola, whereas there is molecular evidence of established SP resistance in Laine. This supports the choice of the national programme of Guinea to adopt AS/AQ as first line antimalarial treatment. The results highlight the difficulties faced by control programmes, which have gone through the upheaval of implementing ACTs, but cannot predict how long their therapeutic life will be, especially in countries which have chosen drugs also available as monotherapies.

/pdf/efficacy-of-antimalarial-treatment-in-guinea-in-vivo-study-49z73jh13y.pdf

Efficacy of antimalarial treatment in Guinea: in vivo study of two artemisinin combination therapies in Dabola and molecular markers of resistance to sulphadoxine-pyrimethamine in N'Zérékoré

Léonie Coulibaly

Papers

Efficacy of antimalarial treatment in Guinea: in vivo study of two artemisinin combination therapies in Dabola and molecular markers of resistance to sulphadoxine-pyrimethamine in N'Zérékoré