1,533 research outputs found

    Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy!

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    Artemisinin-based combination therapies (ACTs) are the best anti-malarial drugs available now. Artemisinin enhances efficacy and has the potential of lowering the rate at which resistance emerges and spreads. Under low transmission intensity, ACTs have an additional public health benefit of reducing the overall malaria transmission and studies are urgently needed to investigate modalities of attaining similar benefits under high transmission. Despite being recommended by WHO since 2001, overall deployment of ACT has been slow. Limiting factors are high cost, limited knowledge and public awareness on the concept of combination therapy (CT) and ACT in particular, limited knowledge on safety of ACTs in pregnancy, operational issue such as inappropriate drug use, lack of suitable drug formulations, lack of post-marketing surveillance (PMS) systems, and the imbalance between demand and supply. Through concerted efforts of multilateral organizations, the local scientific community with involvement of policy-makers progress has been on several fonts leading to improved ACT uptake rates in the last 2 years. Of 43 countries that had adopted ACT by February 2005, 18 (42%) adopted the policy in 2004. Preference to co-formulated Coartem has led to a surge in its demand with consequent shortage. Alternative ways for increased production of ACTs are urgently needed otherwise most policies will remain adopted on paper. Despite limitations, opportunities are opening up for effective malaria control. Insecticides, insecticide-treated nets (ITNs) and ACTs are proven efficacious controls available that should be accessed by many. Substantial funding is now available for biomedical malaria research and for policy implementation. While the Global Fund is the financial engine behind the scaling up of ACT uptake, delays in cash flow after grant approval has led to many countries adopting ACT in 2004 but only few (nine) implementing it. Clear policies on granted funds and minimal politics within funding agencies might improve the situation. Increased interest in drug development together with the public and private sector partnership have led to new anti-malarials, some less expensive and therefore affordable by poor malaria endemic countries. Dihydroartemisinin-piperaquine (Artekin) has a cost advantage over other ACTs (USD 1 for an adult treatment) making it a potential best candidate for deployment in Africa. Part of available funds should be invested into capacity building and strengthening (personnel, resources and infrastructure) of institutions in malaria endemic countries. This will create enabling environment and a critical mass of scientists and public health experts to spearhead ACT policy implementation. Active involvement of scientists from malaria endemic countries in recent International Scientific Forums like the Malaria in Pregnancy Working Group and the Consortium on ACT Implementation is the best way forward to emulate

    A possible role for proguanil-dapsone against SP-resistant P.falciparum?

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    A two-armed trial was conducted in July 2000 in 4 villages near Muheza, Tanga Region, in Tanzania, asymptomatic children with P.falciparum parasitaemia > 200/ul (Mutabingwa et al. 2001 Trans Roy Soc Trop Med Hyg 95: 433-438). In one of the arms 188 children were treated with sulfadoxine-pyrimethamine and only 14.3% showed parasite clearance at day 7 (16.1% at day 14). The SP batch used was checked for good quality and the low clearance rate is indicative of one of the worst levels of SP resistance yet recorded in Africa. SP resistance in this area has increased from about 20% in 1995 (Trigg et all 1997 Acta Trop 63: 1865-189) to 45% in 1998/9 (Mutabingwa et al 2001 Lancet 358: 1218-1233) and is now 86

    The contribution of microscopy to targeting antimalarial treatment in a low transmission area of Tanzania.

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    BACKGROUND: There is a need for improved targeting of antimalarial treatment if artemisinin combination therapy is to be successfully introduced in Africa. This study aimed to explore why malaria slides are requested and how their results guide treatment decisions in an area of low transmission of P. falciparum. METHODS: Outpatients attending a district hospital in a highland area of Tanzania were studied over a 3-week period. Clinical and social data were collected from patients who had been prescribed an antimalarial or sent for a malaria slide. Hospital slides were re-read later by research methods. RESULTS: Of 1,273 consultations 132(10%) were treated presumptively for malaria and 214(17%) were sent for a malaria slide; only 13(6%) of these were reported positive for P. falciparum but 96(48%) of the 201 slide-negative cases were treated for malaria anyway. In a logistic regression model, adults (OR 3.86, P < 0.01), a history of fever (OR1.72, P = 0.03) and a longer travel time to the clinic (OR 1.77 per hour travelled, P < 0.01) independently predicted the request for a malaria slide. Only a history of a cough predicted (negatively) the prescription of an antimalarial with a negative slide result (OR 0.44, P < 0.01). The sensitivity and specificity of hospital slide results were 50% and 96% respectively. CONCLUSION: Progress in targeting of antimalarials in low malaria transmission settings is likely to depend on consistent use of malaria microscopy and on the willingness of health workers to be guided by negative slide results. Further studies are needed to identify how this can be achieved

    Malaria in 2002.

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    The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used

    Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria.

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    The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum

    The impact of endemic and epidemic malaria on the risk of stillbirth in two areas of Tanzania with different malaria transmission patterns.

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    BACKGROUND: The impact of malaria on the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable component. METHODS: A retrospective analysis was completed of stillbirth differences between primigravidae and multigravidae in relation to malaria cases and transmission patterns for two different areas of Tanzania with a focus on the effects of the El Niño southern climatic oscillation (ENSO). One area, Kagera, experiences outbreaks of malaria, and the other area, Morogoro, is holoendemic. Delivery and malaria data were collected over a six year period from records of the two district hospitals in these locations. RESULTS: There was a significantly higher prevalence of low birthweight in primigravidae compared to multigravidae for both data sets. Low birthweight and stillbirth prevalence (17.5% and 4.8%) were significantly higher in Kilosa compared to Ndolage (11.9% and 2.4%). There was a significant difference in stillbirth prevalence between Ndolage and Kilosa between malaria seasons (2.4% and 5.6% respectively, p < 0.001) and during malaria seasons (1.9% and 5.9% respectively, p < 0.001). During ENSO there was no difference (4.1% and 4.9%, respectively). There was a significant difference in low birthweight prevalence between Ndolage and Kilosa between malaria seasons (14.4% and 23.0% respectively, p < 0.001) and in relation to malaria seasons (13.9% and 25.2% respectively, p < 0.001). During ENSO there was no difference (22.2% and 19.8%, respectively). Increased low birthweight risk occurred approximately five months following peak malaria prevalence, but stillbirth risk increased at the time of malaria peaks. CONCLUSION: Malaria exposure during pregnancy has a delayed effect on birthweight outcomes, but a more acute effect on stillbirth risk

    Impact of El Niño and malaria on birthweight in two areas of Tanzania with different malaria transmission patterns.

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    BACKGROUND: Malaria infection increases low birthweight especially in primigravidae. Malaria epidemics occur when weather conditions favour this vector borne disease. Forecasting using the El Niño Southern Oscillation (ENSO) may assist in anticipating epidemics and reducing the impact of a disease which is an important cause of low birthweight. The aim of the present study was to determine the impact of the malaria epidemic in East Africa during 1997-1998 on birthweights in two different areas of Tanzania and to explore ESNO's potential for forecasting low birthweight risk in pregnant women. METHOD: A retrospective analysis of birthweight differences between primigravidae and multigravidae in relation to malaria cases and rainfall for two different areas of Tanzania: Kagera, which experiences severe outbreaks of malaria, and Morogoro which is holoendemic. Birthweight and parity data and malaria admissions were collected over a 10-year period from two district hospitals in these locations. RESULTS: The risk of delivering a low birthweight baby in the first pregnancy increases approximately 5 months following a malaria epidemic. An epidemic of marked reduced birthweight in primigravidae compared with multigravidae occurred, related to the ENSO of 1997-1998. In Kagera this birthweight difference and the risk of low birthweight were significantly lower compared with Morogoro, except after the ENSO when the two areas had similar differences. No significant interaction was noted between secundigravidae and any of the risk periods. The results indicate that the pressure of malaria is much greater on pregnant women, especially primigravidae, living in the Morogoro location. CONCLUSIONS: Surveillance of birthweight differences between primigravidae and multigravidae is a useful indicator of malaria exposure

    Case management of malaria in pregnancy.

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    In all malarious areas, infection by any of the main human plasmodial species during pregnancy is detrimental to the mother and the fetus. These potentially fatal infections must be prevented, but when they develop they require prompt diagnosis and treatment. Current tools to detect malaria parasites in pregnant women are often not used and remain too insensitive to detect a low parasitaemia. The kinetics, safety, and efficacy of available antimalarial drugs are poorly documented because pregnant women are systematically excluded from clinical trials. A considerable effort, involving clinical trials, is urgently required to improve the diagnosis and case management of malaria during pregnancy if the morbidity and mortality of maternal malaria is to be reduced

    Putting the genie back in the bottle? Availability and presentation of oral artemisinin compounds at retail pharmacies in urban Dar-es-Salaam.

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    BACKGROUND\ud \ud Recently global health advocates have called for the introduction of artemisinin-containing antimalarial combination therapies to help curb the impact of drug-resistant malaria in Africa. Retail trade in artemisinin monotherapies could undermine efforts to restrict this class of medicines to more theoretically sound combination treatments.\ud \ud METHODS\ud \ud This paper describes a systematic search for artemisinin-containing products at a random sample of licensed pharmacies in Dar-es-Salaam, Tanzania in July 2005.\ud \ud RESULTS\ud \ud Nineteen different artemisinin-containing oral pharmaceutical products, including one co-formulated product, one co-packaged product, and 17 monotherapies were identified. All but one of the products were legally registered and samples of each product were obtained without a prescription. Packaging and labeling of the products seldom included local language or illustrated instructions for low-literate clients. Packaging and inserts compared reasonably well with standards recommended by the national regulatory authority with some important exceptions. Dosing instructions were inconsistent, and most recommended inadequate doses based on international standards. None of the monotherapy products mentioned potential benefits of combining the treatment with another antimalarial drug.\ud \ud CONCLUSION\ud \ud The findings confirm the widespread availability of artemisinin monotherapies that led the World Health Organization to call for the voluntary withdrawal of these drugs in malaria-endemic countries. As the global public health community gathers resources to deploy artemisinin-containing combination therapies in Africa, planners should be mindful that these drugs will coexist with artemisinin monotherapies in an already well-established market place. In particular, regulatory authorities should be incorporated urgently into the process of planning for rational deployment of artemisinin-containing antimalarial combination therapies

    Malaria in pregnancy and the endemicity spectrum: what can we learn?

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    The increased susceptibility of pregnant women to malaria infection has long been recognized, but the magnitude of the disease burden in this particular group, together with the pathophysiology of maternal malaria and the specific difficulties in treatment, have only recently been the focus of research. Most research on maternal malaria has derived from sub-Saharan Africa where transmission is high, whereas most of the studies on the treatment of malaria and the effect of non-falciparum species has been conducted in low-transmission areas of Asia. In this paper, we attempt to improve our understanding of the disease and its mechanisms from observed differences and similarities between contrasting areas of transmission, and to identify priorities for future research
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