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.
BackgroundThe World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs.ObjectivesTo evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013.Selection criteriaRandomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria.Data collection and analysisTwo 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 gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach.Main resultsWe included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women.DHA-P versus artemether-lumefantrineIn Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower with DHA-P (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials, 5417 participants, high quality evidence). DHA-P has a longer prophylactic effect on new infections which may last for up to 63 days (PCR-unadjusted treatment failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high quality evidence).In Asia and Oceania, no differences have been shown at day 28 (four trials, 1143 participants, moderate quality evidence), or day 63 (one trial, 323 participants, low quality evidence).Compared to artemether-lumefantrine, no difference was seen in prolonged QTc (low quality evidence), and no cardiac arrhythmias were reported. The frequency of other adverse events is probably similar with both combinations (moderate quality evidence).DHA-P versus artesunate plus mefloquineIn Asia, over 28 days follow-up, DHA-P is as effective as artesunate plus mefloquine at preventing further parasitaemia (PCR-unadjusted treatment failure: eight trials, 3487 participants, high quality evidence). Once adjusted by PCR to exclude new infections, treatment ...
BackgroundResearch in 2007 showed that World Health Organization (WHO) recommendations were largely based on expert opinion, rarely used systematic evidence-based methods, and did not follow the organization's own “Guidelines for Guidelines”. In response, the WHO established a “Guidelines Review Committee” (GRC) to implement and oversee internationally recognized standards. We examined the impact of these changes on WHO guideline documents and explored senior staff's perceptions of the new procedures.Methods and FindingsWe used the AGREE II guideline appraisal tool to appraise ten GRC-approved guidelines from nine WHO departments, and ten pre-GRC guidelines matched by department and topic. We interviewed 20 senior staff across 16 departments and analyzed the transcripts using the framework approach. Average AGREE II scores for GRC-approved guidelines were higher across all six AGREE domains compared with pre-GRC guidelines. The biggest changes were noted for “Rigour of Development” (up 37.6%, from 30.7% to 68.3%) and “Editorial Independence” (up 52.7%, from 20.9% to 73.6%). Four main themes emerged from the interviews: (1) high standards were widely recognized as essential for WHO credibility, particularly with regard to conflicts of interest; (2) views were mixed on whether WHO needed a single quality assurance mechanism, with some departments purposefully bypassing the procedures; (3) staff expressed some uncertainties in applying the GRADE approach, with departmental staff concentrating on technicalities while the GRC remained concerned the underlying principles were not fully institutionalized; (4) the capacity to implement the new standards varied widely, with many departments looking to an overstretched GRC for technical support.ConclusionsSince 2007, WHO guideline development methods have become more systematic and transparent. However, some departments are bypassing the procedures, and as yet neither the GRC, nor the quality assurance standards they have set, are fully embedded within the organization.
BackgroundThe translation of research into policy and practice is enhanced by policymakers who can recognise and articulate their information needs and researchers that understand the policymakers’ environment. As researchers, we sought to understand the policymaking process and how research evidence may contribute in South Africa and Cameroon.MethodsWe conducted qualitative in-depth interviews in South Africa and focus group discussions in Cameroon with purposively sampled subnational (provincial and regional) government health programme managers. Audio recorded interviews were transcribed, thematically coded and analysed.ResultsParticipants in both countries described the complex, often lengthy nature of policymaking processes, which often include back-and-forth consultations with many diverse stakeholder groups. These processes may be influenced by political structures, relationships between national and subnational levels, funding and international stakeholder agendas. Research is not a main driver of policy, but rather current contextual realities, costs, logistics and people (clinicians, NGOs, funders) influence the policy, and research plays a part. Research evidence is frequently perceived as unavailable, inaccessible, ill-timed or not applicable. The reliability of research on the internet was questioned. Evidence-informed health decision-making (EIDM) is regarded as necessary in South Africa but is less well understood in Cameroon. Insufficient time and capacity were hindrances to EIDM in both countries. Good relationships between researchers and policymakers may facilitate EIDM. Researchers should have a good understanding of the policymaking environment if they want to influence it. Greater interaction between policymakers and researchers is perceived as beneficial when formulating research and policy questions as it raises researchers’ awareness of implementation challenges and enables the design of tailored and focused strategies to respond to policymakers’ needs.ConclusionsPolicymaking is complicated, lengthy and mostly done at national level. Provinces/regions are tasked with implementation, with more room for adaptation in South Africa than in Cameroon. Research evidence plays a role in policy but does not drive it and is seen as mostly unavailable. Researchers need a thorough understanding of the policy process and environment, how the health system operates, as well as the priorities of policymakers. This can inform effective dialogue between researchers and policymakers, and contribute to enhancing use of research evidence in decision-making.Electronic supplementary materialThe online version of this article (doi:10.1186/s13012-015-0315-0) contains supplementary material, which is available to authorized users.
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