RESUMO
Selection of resistant malaria strains occurs when parasites are exposed to inadequate antimalarial drug concentrations. The proportion of uncomplicated falciparum malaria patients at risk of being sub-optimally dosed with the current World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs) is unknown. This study aims to estimate this proportion and the excess number of treatment failures (recrudescences) associated with sub-optimal dosing in Sub-Saharan Africa. Sub-populations at risk of sub-optimal dosing include wasted children <5 years of age, patients with hyperparasitaemia, pregnant women, people living with HIV, and overweight adults. Country-level data on population structure were extracted from openly accessible data sources. Pooled adjusted Hazard Ratios for PCR-confirmed recrudescence were estimated for each risk group from published meta-analyses using fixed-effect meta-analysis. In 2020, of the estimated 153.1 million uncomplicated P. falciparum malaria patients in Africa, the largest risk groups were the hyperparasitaemic patients (13.2 million, 8.6% of uncomplicated malaria cases) and overweight adults (10.3 million, 6.7% of uncomplicated cases). The estimated excess total number of treatment failures ranged from 0.338 million for a 98% baseline ACT efficacy to 1.352 million for a 92% baseline ACT efficacy. Our study shows that an estimated nearly 1 in 4 people with uncomplicated confirmed P. falciparum malaria in Africa are at risk of receiving a sub-optimal antimalarial drug dosing. This increases the risk of antimalarial drug resistance and poses a serious threat to malaria control and elimination efforts. Changes in antimalarial dosing or treatment duration of current antimalarials may be needed and new antimalarials development should ensure sufficient drug concentration levels in these sub-populations that carry a high malaria burden.
RESUMO
OBJECTIVES: The objectives of the study were to describe outcomes of children with uncomplicated severe acute malnutrition (SAM) attending community-based management of acute malnutrition (CMAM) treatment centres in Accra Metropolitan Area (AMA) and explore factors associated with non-adherence to clinic visits and defaulting from the treatment programme. DESIGN: A retrospective cohort study analysing routinely collected data on children with uncomplicated SAM enrolled into CMAM in 2017 was conducted. SETTING: Study was conducted at seven sites comprising Princess Marie Louise Children's Hospital, three sub-metropolitan health facilities and three community centres, located in five sub-metropolitan areas in AMA. PARTICIPANTS: Children with uncomplicated SAM aged 6-59 months, enrolled from community-level facilities (pure uncomplicated SAM, PUSAM) or transferred after completing inpatient care (post-stabilisation uncomplicated SAM, PSSAM), participated in the study. RESULTS: Out of 174 cases studied (105 PUSAM, sixty-nine PSSAM), 56·3 % defaulted, 34·5 % recovered and 8·6 % were not cured by 16 weeks. No deaths were recorded. Mid-upper arm circumference (MUAC) increased by 2·2 (95 % CI 1·8, 2·5) mm/week with full compliance and 0·9 (95 % CI 0·6, 1·2) mm/week with more than two missed visits. In breast-feeding children, MUAC increased at a slower rate than in other children by 1·3 (95 % CI 1·0, 1·5) mm/week. Independent predictors of subsequent missed visits were diarrhoea and fever, while children with MUAC < 110 mm on enrolment were at increased risk of defaulting. CONCLUSION: A high default rate and a long time to recovery are challenges for CMAM in AMA. Efforts must be made to improve adherence to treatment to improve outcomes.
