The Burden of Malaria in the Democratic Republic of the Congo.

Despite evidence that older children and adolescents bear the highest burden of malaria, large malaria surveys focus on younger children. We used polymerase chain reaction data from the 2013-2014 Demographic and Health Survey in the Democratic Republic of Congo (including children aged <5 years and adults aged ≥15 years) and a longitudinal study in Kinshasa Province (participants aged 6 months to 98 years) to estimate malaria prevalence across age strata. We fit linear models and estimated prevalences for each age category; adolescents aged 10-14 years had the highest prevalence. We estimate approximately 26 million polymerase chain reaction-detectable infections nationally. Adolescents and older children should be included in surveillance studies.

Assessment of Efficacy and Safety of Arterolane Maleate-Piperaquine Phosphate Dispersible Tablets in Comparison With Artemether-Lumefantrine Dispersible Tablets in Pediatric Patients With Acute Uncomplicated Plasmodium falciparum Malaria: A Phase 3, Randomized, Multicenter Trial in India and Africa.

BACKGROUND: Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children. METHODS: This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days. RESULTS: The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar. CONCLUSIONS: The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients. CLINICAL TRIALS REGISTRATION: CTRI/2014/07/004764.

An operational comparative study of quinine and artesunate for the treatment of severe malaria in hospitals and health centres in the Democratic Republic of Congo: the MATIAS study.

BACKGROUND: The Democratic Republic of the Congo (DRC) has the highest number of severe malaria cases in the world. In early 2012, the National Malaria Control Programme (NMCP) changed the policy for treating severe malaria in children and adults from injectable quinine to injectable artesunate. To inform the scaling up of injectable artesunate nationwide, operational research is needed to identify constraints and challenges in the DRC's specific setting. METHODS: The implementation of injectable quinine treatment in 350 patients aged 2 months or older in eight health facilities from October 2012 to January 2013 and injectable artesunate in 399 patients in the same facilities from April to June 2013 was compared. Since this was an implementation study, concurrent randomized controls were not possible. Four key components were evaluated during each phase: 1) clinical assessment, 2) time and motion, 3) feasibility and acceptability, and 4) financial cost. RESULTS: The time to discharge was lower in the artesunate (median=2, 90% central range 1-9) compared to the quinine group (3 (1-9) days; p<0.001). Similarly, the interval between admission and the start of intravenous (IV) treatment (2 (0-15) compared to 3 (0-20) hours; p<0.001) and parasite clearance time (23 (11-49) compared to 24 (10-82) hours; p<0.001) were lower in the artesunate group. The overall staff pre-administration time (13 (6-38) compared to 20 (7-50) minutes; p<0.001) and the personnel time spent on patient management (9 (1-24) compared to 12 (3-52) minutes; p<0.001) were lower in the artesunate group. In hospitals and health centres, the mean (standard deviation, SD) total cost per patient treated for severe malaria with injectable artesunate was USD 51.94 (16.20) and 19.51 (9.58); and USD 60.35 (17.73) and 20.36 (6.80) with injectable quinine. CONCLUSIONS: This study demonstrates that injectable artesunate in the DRC is easier to use and it costs less than injectable quinine. These findings provide the basis for practical recommendations for rapid national deployment of injectable artesunate in the DRC.

Molecular malaria epidemiology: mapping and burden estimates for the Democratic Republic of the Congo, 2007.

BACKGROUND: Epidemiologic data on malaria are scant in many high-burden countries including the Democratic Republic of the Congo (DRC), which suffers the second-highest global burden of malaria. Malaria control efforts in regions with challenging infrastructure require reproducible and efficient surveillance. We employed new high-throughput molecular testing to characterize the state of malaria control in the DRC and estimate childhood mortality attributable to excess malaria transmission. METHODS AND FINDINGS: The Demographic and Health Survey was a cross-sectional, population-based cluster household survey of adults aged 15-59 years in 2007 employing structured questionnaires and dried blood spot collection. Parasitemia was detected by real-time PCR, and survey responses measured adoption of malaria control measures and under-5 health indices. The response rate was 99% at the household level, and 8,886 households were surveyed in 300 clusters; from 8,838 respondents molecular results were available. The overall prevalence of parasitemia was 33.5% (95% confidence interval [C.I.] 32-34.9); P. falciparum was the most prevalent species, either as monoinfection (90.4%; 95% C.I. 88.8-92.1) or combined with P. malariae (4.9%; 95% C.I. 3.7-5.9) or P. ovale (0.6%; 95% C.I. 0.1-0.9). Only 7.7% (95% CI 6.8-8.6) of households with children under 5 owned an insecticide-treated bednet (ITN), and only 6.8% (95% CI 6.1-7.5) of under-fives slept under an ITN the preceding night. The overall under-5 mortality rate was 147 deaths per 1,000 live births (95% C.I. 141-153) and between clusters was associated with increased P. falciparum prevalence; based on the population attributable fraction, 26,488 yearly under-5 deaths were attributable to excess malaria transmission. CONCLUSIONS: Adult P. falciparum prevalence is substantial in the DRC and is associated with under-5 mortality. Molecular testing offers a new, generalizable, and efficient approach to characterizing malaria endemicity in underserved countries.

High-throughput pooling and real-time PCR-based strategy for malaria detection.

Molecular assays can provide critical information for malaria diagnosis, speciation, and drug resistance, but their cost and resource requirements limit their application to clinical malaria studies. This study describes the application of a resource-conserving testing algorithm employing sample pooling for real-time PCR assays for malaria in a cohort of 182 pregnant women in Kinshasa. A total of 1,268 peripheral blood samples were collected during the study. Using a real-time PCR assay that detects all Plasmodium species, microscopy-positive samples were amplified individually; the microscopy-negative samples were amplified after pooling the genomic DNA (gDNA) of four samples prior to testing. Of 176 microscopy-positive samples, 74 were positive by the real-time PCR assay; the 1,092 microscopy-negative samples were initially amplified in 293 pools, and subsequently, 35 samples were real-time PCR positive (3%). With the real-time PCR result as the referent standard, microscopy was 67.9% sensitive (95% confidence interval [CI], 58.3% to 76.5%) and 91.2% specific (95% CI, 89.4% to 92.8%) for malaria. In total, we detected 109 parasitemias by real-time PCR and, by pooling samples, obviated over 50% of reactions and halved the cost of testing. Our study highlights both substantial discordance between malaria diagnostics and the utility and parsimony of employing a sample pooling strategy for molecular diagnostics in clinical and epidemiologic malaria studies.