Background In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used.Methods and FindingsIn 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8–82.5) for AL and 90.8% (95% CI 83.6–94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1–95.1) for AL and to 97.2% (91.6–99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml.ConclusionsIn the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections.Trial RegistrationClinicalTrials.gov NCT01052584

BackgroundIn 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.MethodsBetween 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.ResultsOf 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.ConclusionsAL 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 RegistrationNCT01052584

BackgroundAccurate early diagnosis and prompt treatment is one of the key strategies to control and prevent malaria in Ethiopia where both Plasmodium falciparum and Plasmodium vivax are sympatric and require different treatment regimens. Microscopy is the standard for malaria diagnosis at the health centres and hospitals whereas rapid diagnostic tests are used at community-level health posts. The current study was designed to assess malaria microscopy capacity of health facilities in Oromia Regional State and Dire Dawa Administrative City, Ethiopia.MethodsA descriptive cross-sectional study was conducted from February to April 2011 in 122 health facilities, where health professionals were interviewed using a pre-tested, standardized assessment tool and facilities’ laboratory practices were assessed by direct observation.ResultsOf the 122 assessed facilities, 104 (85%) were health centres and 18 (15%) were hospitals. Out of 94 health facilities reportedly performing blood films, only 34 (36%) used both thin and thick smears for malaria diagnosis. The quality of stained slides was graded in 66 health facilities as excellent, good and poor quality in 11(17%), 31 (47%) and 24 (36%) respectively. Quality assurance guidelines and malaria microscopy standard operating procedures were found in only 13 (11%) facilities and 12 (10%) had involved in external quality assessment activities, and 32 (26%) had supportive supervision within six months of the survey. Only seven (6%) facilities reported at least one staff’s participation in malaria microscopy refresher training during the previous 12 months. Although most facilities, 96 (79%), had binocular microscopes, only eight (7%) had the necessary reagents and supplies to perform malaria microscopy. Treatment guidelines for malaria were available in only 38 (31%) of the surveyed facilities. Febrile patients with negative malaria laboratory test results were managed with artemether-lumefantrine or chloroquine in 51% (53/104) of assessed health facilities.ConclusionsThe current study indicated that most of the health facilities had basic infrastructure and equipment to perform malaria laboratory diagnosis but with significant gaps in continuous laboratory supplies and reagents, and lack of training and supportive supervision. Overcoming these gaps will be critical to ensure that malaria laboratory diagnosis is of high-quality for better patient management.

Summaryobjectives and methods Quality laboratory services are a requisite to guide rational case management of malaria. Using a pre-tested, standardized assessment tool, we assessed laboratory diagnostic capacity in 69 primary, secondary and tertiary health facilities as well as specialized laboratories in five administrative zones in Oromia Regional State, Ethiopia, during February and March 2009.results There was marked variability in laboratory diagnostic capacity among the facilities assessed.Of 69 facilities surveyed, 53 provided both comprehensive malaria laboratory diagnosis and outpatient treatment services, five provided malaria microscopy services (referring elsewhere for treatment), and 11 primary care health posts provided rapid diagnostic testing and outpatient malaria treatment. The facilities' median catchment population was 39 562 and 3581 people for secondary ⁄ tertiary and primary health facilities, respectively. Depending on facility type, facilities provided services 24 h a day, had inpatient capacity, and access to water and electricity. Facilities were staffed by general practitioners, health officers, nurses or health extension workers. Of the 58 facilities providing laboratory services, 24% of the 159 laboratory staff had received malaria microscopy training in the year prior to this survey, and 72% of the facilities had at least one functional electric binocular microscope. Facilities had variable levels of equipment, materials and biosafety procedures necessary for laboratory diagnosis of malaria. The mean monthly number of malaria blood films processed at secondary ⁄ tertiary facilities was 225, with a mean monthly 56 confirmed parasitologically. In primary facilities, the mean monthly number of clinical malaria cases seen was 75, of which 57 were tested by rapid diagnostic test (RDTs). None of the surveyed laboratory facilities had formal quality assurance ⁄ quality control protocols for either microscopy or RDTs.conclusions This is the first published report on malaria diagnostic capacity in Ethiopia. While our assessment indicated that malaria laboratory diagnosis was available in most facilities surveyed, we observed significant gaps in laboratory services which could significantly impact quality and accessibility of malaria diagnosis, including laboratory infrastructure, equipment, laboratory supplies and human resources.

ObjectiveTo evaluate the importance of external quality assessment program on malaria microscopic diagnosis.ResultsA total of 3148 slides were collected in 4 consecutive external quality assessment rounds and blindly rechecked at Amhara Public Health Institute. The average agreement between health facility and APHI slide readers was 96.6%. The percent agreement for parasite detection and species identification for P. falciparum became improved in four consecutive EQA rounds from 93.88 to 99.24% and 92.67 to 97.35% respectively. The rates of false positive and false negative were also dramatically decreased in each round from 10.5 to 0.79% and 2.14 to 0.74% respectively. Therefore, we recommend that malaria EQA program should maintain and expand in all malaria diagnostic health facilities in the region to provide accurate and reliable malaria microscopic service.