https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)66417-3.pdf

Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial

Purpose of review Artemisinin-based combination treatments have been the mainstay of treatment for falciparum malaria in Southeast Asia for more than 10 years and are now increasingly recommended as first-line treatment throughout the rest of the world. Recent findings A large multicentre randomised trial conducted in East Asia has shown a 35% reduction in mortality from severe malaria following treatment with parenteral artesunate compared with quinine. There is increasing evidence that artemisinin-based combination treatments are safe and rapidly effective. Artemether–lumefantrine (six doses) has been shown to be very effective in large trials reported from Uganda and Tanzania. A once daily three-dose treatment of dihydroartemisinin piperaquine, a newer fixed combination, was a highly efficacious and well tolerated treatment for multi-drug resistant falciparum malaria in Southeast Asia. Summary Early diagnosis and treatment of uncomplicated malaria with effective drugs remains a priority as part of a comprehensive malaria control strategy. Artemisinin-based combination treatments have consistently been shown to be highly effective and safe. The challenge is to make them accessible in tropical countries.

Artemisinin-based combinations.

Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana.

In this study, we aimed to describe the evolution of three cholera epidemics that occurred in Lusaka, Zambia, between 2003 and 2006 and to analyse the association between the increase in number of cases and climatic factors. A Poisson autoregressive model controlling for seasonality and trend was built to estimate the association between the increase in the weekly number of cases and weekly means of daily maximum temperature and rainfall. All epidemics showed a seasonal trend coinciding with the rainy season (November to March). A 1 degrees C rise in temperature 6 weeks before the onset of the outbreak explained 5.2% [relative risk (RR) 1.05, 95% CI 1.04-1.06] of the increase in the number of cholera cases (2003-2006). In addition, a 50 mm increase in rainfall 3 weeks before explained an increase of 2.5% (RR 1.02, 95% CI 1.01-1.04). The attributable risks were 4.9% for temperature and 2.4% for rainfall. If 6 weeks prior to the beginning of the rainy season an increase in temperature is observed followed by an increase in rainfall 3 weeks later, both exceeding expected levels, an increase in the number of cases of cholera within the following 3 weeks could be expected. Our explicative model could contribute to developing a warning signal to reduce the impact of a presumed cholera epidemic.

Influence of temperature and rainfall on the evolution of cholera epidemics in Lusaka, Zambia, 2003-2006: analysis of a time series.

Background: Severe side effects following ivermectin treatment of onchocerciasis in areas of coendemicity with loaisis have been an impediment for the work of the African Programme for Onchocerciasis Control (APOC) in forested regions of several countries. Doxycycline has been shown to be effective in the treatment of onchocerciasis and has the added advantages of killing adult Onchocerca volvulus but neither adult Loa loa nor their microfilariae. This drug therefore offers great potential for the treatment of onchocerciasis in areas of co-endemicity with loiasis. The limitation of use of this drug is the duration of treatment that may pose a potential problem with therapeutic coverage and compliance with treatment. To benefit from the advantages that doxycycline offers in the treatment of onchocerciasis, it will be necessary to establish an effective distribution system that can access remote communities. This study assessed the feasibility of a large-scale distribution of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis using a community-directed approach. Methods: The study was carried out in 5 health areas co-endemic for Onchocerca volvulus and Loa loa which had no prior experience of the Community Directed Treatment with Ivermectin (CDTI). The community-directed delivery process was introduced using a cascade mechanism from the central health system that passed through the regional health delegation, health district and the health areas. Community health implementers (CHIs) were trained to deliver doxycycline to community members and, under the supervision of the health system, to monitor and document drug intake and side effects.

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Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon.

In the Maheba Refugee Settlement, in the clinics supported by Medecins Sans Frontieres, all children aged up to 5 years with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulfadoxine/pyrimethamine (SP) and artesunate (AS). We compared the treatment's efficacy and effectiveness. Patients were randomized in order to receive the treatment supervised (efficacy) or unsupervised (effectiveness). Therapeutic response was determined after 28 days of follow up. The difference between recrudescence and re-infection was ascertained by polymerase chain reaction (PCR). We also assessed genetic markers associated to SP resistance (dhfr and dhps). Eighty-five patients received treatment under supervision and 84 received it unsupervised. On day 28, and after PCR adjustment, efficacy was found to be 83.5% (95% CI: 74.1-90.5), and effectiveness 63.4% (95% CI: 52.6-73.3) (P < 0.01). Point mutations on dhfr (108) and dhps (437) were found for 92.0% and 44.2% respectively of the PCR samples analysed. The significant difference in therapeutic response after supervised and unsupervised treatment intake can only be explained by insufficient patient adherence. When implementing new malaria treatment policies, serious investment in ensuring patient adherence is essential to ascertain the effectiveness of the new treatment schedules.

Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3-day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia.

Philippe Eldin de Pecoulas

Papers

Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3-day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia.