Therapeutic response to four artemisinin-based combination therapies in Angola, 2021

Publisher Copyright: Copyright © 2024 Dimbu et al.Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola.publishersversionpublishe

Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017

Background The 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. Methods Enrollment 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. Results Of 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. Conclusions AL, 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

Evaluation of the meningitis surveillance system in Luanda Province, Angola, March 2017

Introduction: Meningitis due to Neisseria meningitidis is a priority public health disease given its high epidemic potential and associated mortality. Angola is not one of the countries in the African meningitis belt and frequent outbreaks are uncommon. This might affect the preparedness and capacity of the surveillance system to promptly detect and effectively respond, should a meningitis outbreak occur. From 2014 to 2015, there was an increase in the number of meningitis cases identified in Angola, partly due to heightened disease surveillance. We evaluated the meningitis surveillance system to establish if the surveillance system was meeting its set objectives and made recommendations for improvement. Methods: A cross-sectional study was conducted among health workers in Luanda province in March 2017. Using a pretest structured questionnaire, we obtained information on the participants’ demographic characteristics, work experience, training and their knowledge about the meningitis surveillance system. Participants’ knowledge was graded poor (&lt;50%), reasonable (50 – 69%), good (70 – 90%) and excellent (&gt; 90%). We assessed the key system attributes using the updated CDC guidelines for evaluating public health surveillance systems. Results: Of the 52 operators interviewed, 51.9% were (27/52) nurses, 61.5% (32/52) had &gt;5years work experience and 85.6% (45/52) had not been trained in public health surveillance in the last 5 years. Doctors and nurses had knowledge score of &lt;20%, disease specific focal points and the program coordinator scored 85.7% and 100% respectively. Overall scores for the system’s attributes were as follows; simplicity-(33.3%), data quality-69.2 % and timeliness 33.3%. There was no evidence to suggest that data from the surveillance system was analysed at the source. Conclusion: Knowledge of surveillance system among doctors and nurses was very poor. Overall, the system was complex, with poor data quality, not timely and of low utility. We recommend periodic training of health workers, simplifying operation of the system, compliance with reporting timelines and regular data analysis and use for action at the sourc

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Additional file 2. Microsatellite marker results, Angola therapeutic efficacy monitoring, 2017

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Additional file 4. Day 7 lumefantrine levels in patients treated with artemether-lumefantrine, by treatment outcome, Zaire, Angola

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Additional file 1. Consort flow diagrams for follow-up outcomes in all six study arms, 2017