Efficacy and safety of pyronaridine-artesunate versus artemether-lumefantrine in the treatment of acute uncomplicated malaria in children in South-West Nigeria: an open-labelled randomized controlled trial.

BACKGROUND: In Nigeria, declining responsiveness to artemether-lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine-artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared. METHODS: In an open-labelled, randomized, controlled clinical trial, 172 children aged 3-144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation. RESULTS: 165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise. CONCLUSION: PA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria. RETROSPECTIVE TRIAL REGISTRATION: Clinicaltrials.gov: NCT05192265.

Non-Malaria Causes of Fever among under-5 Children with Negative Results for Malaria Rapid Diagnostic Test in South-Western Nigeria.

BACKGROUND: Although the global malaria burden is decreasing, there are still concerns about overdiagnosis of malaria and the danger of misdiagnosis of non-malaria causes of fever. Clinicians continue to face the challenge of differentiating between these causes despite the introduction of malaria rapid diagnostic tests (mRDTs). AIM: To determine the prevalence and causes of non-malaria-caused fever in children in South-Western Nigeria. METHODS: Secondary analysis of data obtained to evaluate the effect of restricting antimalarial treatment to positive mRDT children in rural and urban areas of southwest Nigeria. Clinical examinations, laboratory tests for malaria parasites (including thick blood film and mRDT) and bacterial identification were performed on children aged 3-59 months (n = 511). The non-malaria group comprised febrile children who had both negative mRDT and microscopy results, while the malaria group included those who were positive for either mRDT or microscopy. We compared the causes of fever among children with non-malaria fever and those with malaria. RESULTS: The prevalence of non-malaria fever and bacteria-malaria co-infection was 37.2% and 2.0%, respectively. Non-malarial pathogens identified were viral (54.7%) and bacterial (32.1%) infections. The bacterial infections included bacteriaemia (2.7%), urinary tract infections (21.6%), skin infections (11.6%) and otitis media (2.6%). The leading bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae. CONCLUSION: The high prevalence and wide range of non-malarial infections reinforces the need for point-of-care tests to identify bacterial and viral infections to optimize the treatment of febrile illnesses in malaria-endemic areas.

Surveillance of Pretreatment Drug Resistance Among HIV-Infected Children in Ibadan, Nigeria.

There are about 2.1 million children infected with HIV globally and about 120,000 deaths annually. Nigeria has one of the highest rates of pediatric HIV infection globally. Pretreatment HIV drug resistance data inform the choice of first- and second-line antiretroviral therapy (ART) regimens. This study investigated the prevalence of HIV drug-resistant strains among ART-naive children in Ibadan, Nigeria. A total of 20 children aged <15 years were enrolled. Demographic, clinical, and laboratory data were documented. Total nucleic acid was extracted from blood samples after which amplification of HIV-1 pol gene was done using polymerase chain reaction. Amplified gene was sequenced using big dye sequencing method. The sequenced HIV-1 pol gene was typed and analyzed for identification of mutations indicative of drug resistance across the different classes of ART. HIV-1 RNA pol gene was successfully amplified in 12/20 (60%) children. All were identified as HIV-1 and the subtypes were G and CRF 02AG, recombinant of 02_AG/G and recombinant of 02_AG/A1. Drug-resistant mutations (DRMs) were identified in 4/12 (33%). Three out of the four mutations were identified as non-nucleoside reverse transcriptase inhibitors DRM (K103N), whereas the fourth had nucleoside reverse transcriptase inhibitors DRM (M184V). Results from this preliminary study show that drug resistance among ART-naive children is a problem in Ibadan. Pretreatment drug resistance testing is desirable in children before initiation of ART to guide effective treatment.