[Show abstract][Hide abstract] ABSTRACT: Malaria 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.
Two 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.
In 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.
This 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.
[Show abstract][Hide abstract] ABSTRACT: In 2004, Sierra Leone adopted artesunate plus amodiaquine as first-line antimalarial treatment. We evaluated the efficacy of this combination in Kailahun, where a previous study had shown 70.2% efficacy of amodiaquine in monotherapy.
Method and outcome classification of the study complied with WHO guidelines. Children 6-59 months with uncomplicated malaria were followed-up for 28 days. PCR genotyping was used to distinguish recrudescence from reinfection. Reinfections were reclassified as cured.
Of 172 children who were referred to the study clinic, 126 satisfied inclusion criteria and were enrolled. No early treatment failures were reported. The day 14, efficacy was 98.2% (95% CI: 93.8-99.8). Of 65 recurrent parasitaemias analysed by PCR, 17 were recrudescences. The PCR-adjusted day 28 efficacy was 84.5% (95% CI: 76.4-90.7). All true failures occurred in the last 8 days of follow-up. Of 110 children who completed the 28-day follow-up, 54 (49.1%) experienced a novel infection.
The efficacy of this combination was disappointing. The high reinfection rate suggested little prophylactic effect. In Kailahun a more efficacious combination might be necessary in the future. The efficacy of AS + AQ needs to be monitored in Kailahun and in the other regions of Sierra Leone.
Tropical Medicine & International Health 08/2006; 11(7):1017-21. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report two 28-day in-vivo antimalarial efficacy studies carried out in the urban centres of Bongor and Koumra, southern Chad. We assess chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) to treat Plasmodium falciparum uncomplicated malaria. Methods and outcome classification complied with latest WHO guidelines. Out of the 301 and 318 children aged 6-59 months included in Bongor and Koumra, respectively, 246 (81.7%) and 257 (80.8%) were eligible for analysis. In Bongor and Koumra, the 28-day PCR-adjusted failure rates for CQ were 23.7% (95% CI 14.7-34.8%) and 32.9% (95% CI 22.1-45.1%), respectively, and those for SP were 16.3% (95% CI 9.4-25.5%) and 4.3% (95% CI 1.2-10.5%). AQ failure rates were 6.4% (95% CI 2.1-14.3%) and 2.2% (95% CI 0.3-7.6%). The current use of CQ in Bongor and Koumra is questionable, and a more efficacious treatment is needed. Considering the reduced efficacy of SP in Bongor, AQ seems to be the best option for the time being. Following WHO recommendations that prioritize the use of artemisinin-based combinations, artesunate plus amodiaquine could be a potential first-line treatment. Nevertheless, the efficacy of this combination should be evaluated and the change carefully prepared, implemented and monitored.
Transactions of the Royal Society of Tropical Medicine and Hygiene 06/2006; 100(5):419-26. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa.
C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001).
Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination.
[Show abstract][Hide abstract] ABSTRACT: Mass violence against civilians in the west of Sudan has resulted in the displacement of more than 1.5 million people (25% of the population of the Darfur region). Most of these people are camped in 142 settlements. There has been increasing international concern about the health status of the displaced population.
To perform rapid epidemiological assessments of mortality and nutritional status at 3 sites in South Darfur for relief efforts.
In August and September 2004, mortality surveys were conducted among 137,000 internally displaced persons (IDPs) in 3 sites in South Darfur (Kass [n = 900 households], Kalma [n = 893 households], and Muhajiria [n = 900 households]). A nutritional survey was performed concomitantly among children aged 6 to 59 months using weight for height as an index of acute malnutrition (Kass [n = 894], Kalma [n = 888], and Muhajiria [n = 896]). A questionnaire detailing access to food and basic services was administered to a subset of households (n = 210 in each site).
Crude and under 5-year mortality rates and nutritional status of IDPs in Kass, Kalma, and Muhajiria, South Darfur.
Crude mortality rates, expressed as deaths per 10,000 per day, were 3.2 (95% confidence interval [CI], 2.2-4.1) in Kass, 2.0 (95% CI, 1.3-2.7) in Kalma, and 2.3 (95% CI, 1.2-3.4) in Muhajiria. Under 5-year mortality rates were 5.9 (95% CI, 3.8-8.0) in Kass, 3.5 (95% CI, 1.5-5.7) in Kalma, and 1.0 (95% CI, 0.03-1.9) in Muhajiria. During the period of displacement covered by our survey in Muhajiria, violence was reported to be responsible for 72% of deaths, mainly among young men. Diarrheal disease was reported to cause between 25% and 47% of deaths in camp residents and mainly affected the youngest and oldest age groups. Acute malnutrition was common, affecting 14.1% of the target population in Kass, 23.6% in Kalma, and 10.7% in Muhajiria.
This study provides epidemiological evidence of the high rates of mortality and malnutrition among the displaced population in South Darfur and reinforces the need to mount appropriate and timely humanitarian responses.
JAMA The Journal of the American Medical Association 04/2005; 293(12):1490-4. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria.
We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis.
38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of 303) and 98.0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved.
Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.
The Lancet 01/2005; 365(9469):1467-73. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: (95% confidence interval (CI), 2.2-4.1) in Kass, 2.0 (95% CI, 1.3-2.7) in Kalma, and 2.3 (95% CI, 1.2-3.4) in Muhajiria. Under 5-year mortality rates were 5.9 (95% CI, 3.8-8.0) in Kass, 3.5 (95% CI, 1.5-5.7) in Kalma, and 1.0 (95% CI, 0.03-1.9) in Muhajiria. During the period of displacement covered by our survey in Muhajiria, vio- lence was reported to be responsible for 72% of deaths, mainly among young men. Diarrheal disease was reported to cause between 25% and 47% of deaths in camp residents and mainly affected the youngest and oldest age groups. Acute malnutrition was common, affecting 14.1% of the target population in Kass, 23.6% in Kalma, and 10.7% in Muhajiria. Conclusion This study provides epidemiological evidence of the high rates of mor- tality and malnutrition among the displaced population in South Darfur and reinforces the need to mount appropriate and timely humanitarian responses.