CitationSupervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial., 365 (9469 Articles IntroductionWith an estimated 500 million individuals affected every year, malaria is a leading cause of morbidity and mortality in sub-Saharan Africa along with HIV/AIDS. 1Of the 1 million deaths caused by malaria worldwide, about 90% occur in African children, a situation compounded by the emergence of drug resistance. 2In Uganda, which had a population of 24·7 million in 2003, an estimated 9·8 million individuals are infected with malaria every year (John Bosco Rwakimari, Ugandan Ministry of Health, Uganda, personal communication; http://www.health.go.ug). To tackle malaria-related mortality and morbidity, the Ugandan Ministry of Health (MoH) is concentrating on early diagnosis and effective treatment of the disease. In the 1970s and the 1980s, high malaria awareness in the population and easy access to cheap and effective antimalarials such as chloroquine and sulfadoxinepyrimethamine ensured the disease was reasonably well controlled. However, resistance to these drugs is now widespread in Uganda and in other parts of east Africa, with adverse consequences for malaria control. 3-7The MoH-recommended first-line antimalarial drug in Uganda is chloroquine combined with sulfadoxinepyrimethamine, 6 though introduction of artemisininbased combination treatments (ACTs) is planned for 2005.8 Day-28 cure rates of 52%, 9 65%, 7 and 77% 10 have been reported for this combination in different parts of Uganda. ACTs are judged effective in Africa, where they improve cure rates and reduce gametocyte carriage compared with presently used monotherapies.11,12 To combat drug-resistant malaria in Africa, WHO advocates the adoption of ACTs as first-line treatment.2 The use of the non-ACT combination of amodiaquine and sulfadoxine-pyrimethamine is considered by some as an interim measure while waiting for ACTs to become widely available. Day-28 efficacy rates of this combination were 84% and 90% in two studies in Uganda. 7,9 Artemether-lumefantrine (Coartem, Novartis Pharma, Basel, Switzerland) is the only fixed-dose formulation ACT on the WHO essential drug list. However, the combination is not registered for use in pregnant women, and was not registered for children under 10 kg in weight when we did our trial. Results of studies [13][14][15] from southeast Asia show that the six-dose regimen of artemether-lumefantrine has cure rates of more than 96%, is well tolerated, and has a good safety profile when Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial Patrice Piola, Carole Fogg, Francis Bajunirwe, Samuel Biraro, Francesco Grandesso, Eugene Ruzagira, Joseph Babigumira, Isaac Kigozi, James Kiguli, Juliet Kyomuhendo, Laurent Ferradini, Walter Taylor, Francesco Checchi, Jean-Paul Guthmann S...

Médecins Sans Frontières.

BackgroundThe performance of different malaria rapid diagnostic tests (RDT) may be influenced by transmission intensity and by the length of time each test requires to become negative after treatment and patient’s recovery.MethodsResults of three RDTs (two HRP2 and one pLDH antigen-based tests) were compared to blood smear microscopy (the gold standard method) in children under 5 years of age living in a high versus low malaria intensity setting in southwestern Uganda. In each setting, 212 children, who tested positive by at least one RDT and by microscopy, were treated with artemether-lumefantrine. RDTs and microscopy were then repeated at fixed intervals to estimate each test’s time to negativity after treatment and patient recovery.ResultsIn the two settings, sensitivities ranged from 98.4 to 99.2 % for the HRP2 tests and 94.7 to 96.1 % for the pLDH test. Specificities were 98.9 and 98.8 % for the HRP2 tests and 99.7 % for the pLDH test in the low-transmission setting and 79.7, 80.7 and 93.9 %, respectively, in the high-transmission setting. Median time to become negative was 35–42 or more days for the HRP2 tests and 2 days for the pLDH test.ConclusionsHigh transmission contexts and a long time to become negative resulted in considerably reduced specificities for the HRP2 tests. Choice of RDT for low- versus high-transmission settings should balance risks and benefits of over-treatment versus missing malaria cases. Trial registration: Registry number at ClinicalTrial.gov: NCT01325974Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1529-6) contains supplementary material, which is available to authorized users.

BackgroundMalaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.MethodsTwo cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed.ResultsIn 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors.ConclusionsThis study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4–6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5–95.3) sensitivity and 100% (95% CI: 94.4–100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2–93.6) for culture performed on site and 72.2% (95% CI: 54.8–85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7–100) and 100% (95% CI: 94.5–100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited.

From September through December 2005, an outbreak of hemorrhagic fever occurred in South Kordofan, Sudan. Initial laboratory test results identified IgM antibodies against yellow fever (YF) virus in patient samples, and a YF outbreak was declared on 14 November. To control the outbreak, a YF mass vaccination campaign was conducted and vector control implemented in parts of South Kordofan. Surveillance data were obtained from the Sudan Federal Ministry of Health. Clinical information and serum samples were obtained from a subset of patients with illness during the outbreak. Nomads, health personnel and village chiefs were interviewed about the outbreak. Mosquitoes were collected in 11 villages and towns in North and South Kordofan. From 10 September to 9 December 2005 a total of 605 cases of outbreak-related illness were reported, of which 45% were in nomads. Twenty-nine percent of 177 patients seen at clinics in Julud and Abu Jubaiyah had illness consistent with YF. Five of 18 unvaccinated persons with recent illness and 4 of 16 unvaccinated asymptomatic persons had IgM antibodies to YF virus. IgM antibodies to chikungunya virus were detected in five (27%) ill persons and three (19%) asymptomatic persons. These results indicate that both chikungunya and YF occurred during the outbreak.

Background: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data.

Two community-based density case-control studies were performed to assess risk factors for cholera transmission during inter-peak periods of the ongoing epidemic in two Haitian urban settings, Gonaives and Carrefour. The strongest associations were: close contact with cholera patients (sharing latrines, visiting cholera patients, helping someone with diarrhoea), eating food from street vendors and washing dishes with untreated water. Protective factors were: drinking chlorinated water, receiving prevention messages via television, church or training sessions, and high household socioeconomic level. These findings suggest that, in addition to contaminated water, factors related to direct and indirect inter-human contact play an important role in cholera transmission during inter-peak periods. In order to reduce cholera transmission in Haiti intensive preventive measures such as hygiene promotion and awareness campaigns should be implemented during inter-peak lulls, when prevention activities are typically scaled back.