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Abstract Background In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated P. falciparum malaria since 2004. Methods Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively. Results Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7%) presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events. Conclusions AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with P. vivax possibly from relapse or new infection was observed. Trial Registration NCT01052584

Background Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. Methods and findings Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. Conclusions Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. Trial registration ClinicalTrials.gov NCT01680406, Author(s): Tesfay Abreha 1, Jimee Hwang 2,3, Kamala Thriemer 4,*, Yehualashet Tadesse 1, Samuel Girma 1, Zenebe Melaku 1, Ashenafi Assef 5, Moges Kassa 5, Mark D. Chatfield 4, Keren [...]

Background The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y ('under five') and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar. Methods and Findings Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28-1.08), and for 2006, 0.03 (0.00-0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1-4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period. Conclusions Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions., Introduction The increased malaria-related morbidity and mortality, especially in children under the age of 5 y ('under five'), due to emerging resistance of Plasmodium falciparum to conventional antimalarial drugs calls [...]

Malaria is a major cause of death among children in many parts of the world, even though simple and effective treatments exist. This study examines care-seeking patterns and barriers to appropriate treatment for Zambian children with fever or convulsions, two key symptoms of malaria. The study focuses on community perceptions of and response to febrile illness, using illness narratives as the primary data collection vehicle. The 154 detailed narratives indicate that mothers recognize fever and treat promptly, and consider chloroquine in conjunction with anti-pyretics to be the appropriate treatment. Synchronic and diachronic analyses show that most treatment begins at home, although the majority of cases are also seen in the formal health system. However, whether treated at home or taken to the health center, most children do not receive appropriate care in this case, a 3-day course of chloroquine because of problems of access and lack of understanding of the importance of giving the full dose. Further, those children who continue to have fever despite receiving chloroquine seldom receive the recommended second-line treatment with sulfadoxine-pyrimethamine. Most children with symptoms of convulsions are taken to the health center, but are more likely than children with simple malaria to receive traditional treatments as well. Keywords: Health-seeking behavior; Malaria; Fever; Zambia; Treatment-seeking; Resort to care

The number of school-associated deaths appears to be higher than originally estimated. Researchers used newspaper clipping services and online newspaper databases to identify 105 deaths of elementary and secondary school students that occurred at 101 schools in 25 states between July, 1992 and June, 1994. Additional data were provided by local police, medical examiners and school officials. Twenty of the deaths (19%) were suicides. Forty-three percent occurred during an activity sponsored by the school. However, only 29% occurred inside the school building, indicating that metal detectors and security cameras may have little effect on reducing student violence. Sixty percent of the deaths occurred in urban schools and 77% involved firearms. Most of the firearms used were handguns and many were automatic or semiautomatic. One-third of the incidents involved personal disputes and 31% were gang-related. Most of the victims were younger than 20, 83% were male and almost half were non-Hispanic blacks. Twenty-one percent had a criminal background., Objectives. - To conduct the first nationwide investigation of violent deaths associated with schools in the United States, to quantify the risk of school-associated violent death, and to identify epidemiologic features of these deaths. Design. - Descriptive case series. Setting. - United States, July 1, 1992, through June 30, 1994. Methods. - School-associated violent deaths were identified by study collaborators and through 2 online news databases. Police reports, medical examiners&apos; records, and interviews with police and school officials provided detailed information about each case. Results. - In a 2-year period, 105 school-associated violent deaths were identified. The estimated incidence of school-associated violent death was 0.09 per 100 000 student-years. Students in secondary schools, students of minority racial and ethnic backgrounds, and students in urban school districts had higher levels of risk. The deaths occurred in communities of all sizes in 25 different states. Homicide was the predominant cause of death (n=85 [80.90%]), and firearms were responsible for a majority (n=81 [77.1%]) of the deaths. Most victims were students (n=76 [72.4%]). Both victims and offenders tended to be young (median ages, 16 and 17 years, respectively) and male (82.90% and 95.60%, respectively). Approximately equal numbers of deaths occurred inside school buildings (n=31 [29.5%]), outdoors but on school property (n=37 [35.2%]), and at off-campus locations while the victim was in transit to or from school (n=37 [35.21%]). Equal numbers of deaths occurred during classes or other school activities (n=46 [43.80%]) and before or after official school activities (n=46 [43.8%]). Conclusions. - School-associated violent deaths were more common than previously estimated. The epidemiologic features of these deaths were similar to those of homicides and suicides that occur elsewhere. A comprehensive approach that addresses violent injury and death among young people at school and elsewhere in the community is suggested.

Background Global gains toward malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. Methods Twenty clusters were randomly assigned to 3 rounds of MTaT per year for 2 years or control (standard of care for testing and treatment at public health facilities along with government-sponsored mass long-lasting insecticidal net [LLIN] distributions). During rounds, community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after 3 rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year, adjusted for age, reported LLIN use, enhanced vegetative index, and socioeconomic status. Results Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage across the 3 annual rounds ranged between 75.0% and 77.5% in year 1, and between 81.9% and 94.3% in year 2. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (95% confidence interval [CI],.79–1.08) and 0.92 (95% CI,.76–1.10) after year 1 and year 2, respectively. Conclusions MTaT performed 3 times per year over 2 years did not reduce malaria parasite prevalence in this high-transmission area. Clinical Trials Registration NCT02987270. [ABSTRACT FROM AUTHOR]