BackgroundThe Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications’ therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces.MethodsEnrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance.ResultsOf 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91–100%, 95% confidence interval) in Zaire and 97% (93–100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97–100%) in Benguela and 93% (88–99%) in Zaire. The corrected efficacy of DP was 100% (96–100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure.ConclusionsAL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2290-9) contains supplementary material, which is available to authorized users.

BackgroundRecent anti-malarial resistance monitoring in Angola has shown efficacy of artemether–lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013.MethodsDuring January–June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate–amodiaquine (ASAQ), or dihydroartemisinin–piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1).ResultsA total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91–100) for AL in Benguela, 99.9% (95–100) for ASAQ in Benguela, 88.1% (81–95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96–100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility.ConclusionsNo evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1712-4) contains supplementary material, which is available to authorized users.

BackgroundMalaria accounts for the largest portion of healthcare demand in Angola. A pillar of malaria control in Angola is the appropriate management of malaria illness, including testing of suspect cases with rapid diagnostic tests (RDTs) and treatment of confirmed cases with artemisinin-based combination therapy (ACT). Periodic systematic evaluations of malaria case management are recommended to measure health facility readiness and adherence to national case management guidelines.MethodsCross-sectional health facility surveys were performed in low-transmission Huambo and high-transmission Uíge Provinces in early 2016. In each province, 45 health facilities were randomly selected from among all public health facilities stratified by level of care. Survey teams performed inventories of malaria commodities and conducted exit interviews and re-examinations, including RDT testing, of a random selection of all patients completing outpatient consultations. Key health facility readiness and case management indicators were calculated adjusting for the cluster sampling design and utilization.ResultsAvailability of RDTs or microscopy on the day of the survey was 71% (54–83) in Huambo and 85% (67–94) in Uíge. At least one unit dose pack of one formulation of an ACT (usually artemether–lumefantrine) was available in 83% (66–92) of health facilities in Huambo and 79% (61–90) of health facilities in Uíge. Testing rates of suspect malaria cases in Huambo were 30% (23–38) versus 69% (53–81) in Uíge. Overall, 28% (13–49) of patients with uncomplicated malaria, as determined during the re-examination, were appropriately treated with an ACT with the correct dose in Huambo, compared to 60% (42–75) in Uíge. Incorrect case management of suspect malaria cases was associated with lack of healthcare worker training in Huambo and ACT stock-outs in Uíge.ConclusionsThe results reveal important differences between provinces. Despite similar availability of testing and ACT, testing and treatment rates were lower in Huambo compared to Uíge. A majority of true malaria cases seeking care in health facilities in Huambo were not appropriately treated with anti-malarials, highlighting the importance of continued training and supervision of healthcare workers in malaria case management, particularly in areas with decreased malaria transmission.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1843-7) contains supplementary material, which is available to authorized users.

Background: Biennial therapeutic efficacy monitoring is a crucial activity for ensuring efficacy of currently used artemisinin-based combination therapy in Angola. Methods: Children with acute uncomplicated P. falciparum infection in sentinel sites in Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate amodiaquine (ASAQ) and followed for 28 days to assess clinical and parasitological response. Molecular correction was performed using seven microsatellite markers. Samples from treatment failures were genotyped for the pfk13, pfcrt, and pfmdr1 genes. Results: Day 3 clearance rates were ≥95% in all arms. Uncorrected Day-28 Kaplan-Meier efficacy estimates ranged from 84.2 to 90.1% for the AL arms, and 84.7 to 100% for the ASAQ arms. Corrected Day-28 estimates were 87.6% (95% Confidence interval [CI]: 81–95%) for the AL arm in Lunda Sul, 92.2% (95%CI: 87-98%) for AL in Zaire, 95.6% (95%CI: 91-100%) for ASAQ in Zaire, 98.4% (95%CI: 96-100%) for AL in Benguela, and 100% for ASAQ in Benguela and Lunda Sul. All 103 analyzed samples had wildtype pfk13 sequences. The 76T pfcrt allele was found in most (92%, 11/12) ASAQ late failure samples but only 16% (4/25) of AL failure samples. The N86 pfmdr1 allele was found in 97% (34/35) of treatment failures. Conclusion: AL efficacy in Lunda Sul was below the 90% World Health Organization threshold, the third time in four rounds that this threshold was crossed for an AL arm in Angola. In contrast, observed ASAQ efficacy has not been below 95% to date in Angola, including this latest round.

We conducted a health facility-based survey of patients with fever during malaria transmission season to determine the proportion with laboratory-confirmed malaria in Luanda, Angola. We enrolled 864 patients at 30 facilities; each underwent a blood film for malaria and a questionnaire. Only 3.6% had a positive blood film. When stratified by distance of the facility to city center (< 15 km and > or = 15 km), the proportions were 1.5% (9/615) and 8.8% (22/249), respectively (P < 0.0001). Of patients traveling outside Luanda in the preceding 3 months, 6.8% (6/88) had malaria, compared with 3.2% (26/776) not traveling (P = 0.13). Children < 5 years of age were less likely to have malaria (2.4%; 12/510) than children ages 5-14 (8.7%; 9/104) and adults (4.0%; 10/250) (P = 0.03). The prevalence of laboratory-confirmed malaria in febrile patients in Luanda is very low, but increases with distance from the urban center. Prevention and treatment should be focused in surrounding rural areas.