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The World Health Organization (WHO) recommends parasitological testing of all suspected malaria cases using malaria rapid diagnostic tests (mRDTs) or microscopy prior to treatment. Some governments have extended this responsibility to community health workers (CHWs) to reduce malaria morbidity and mortality through prompt and appropriate treatment. This is an update of a Cochrane Review first published in 2013.To evaluate community-based management strategies for treating malaria or fever that incorporate both a definitive diagnosis with an mRDT and appropriate antimalarial treatment.We searched CENTRAL, MEDLINE, Embase, five other databases, and three trials registers up to 14 September 2021.We included individually randomized trials and cluster-randomized controlled trials (cRCTs), controlled before-after studies, and controlled interrupted time series studies in people living in malaria-endemic areas, comparing programmes that train CHWs and drug shop vendors to perform mRDTs and provide appropriate treatment versus similar programmes that do not use mRDTs, and versus routine health facility care.We used standard Cochrane methods. For each dichotomous outcome, we extracted the number of participants with the event and the total number of participants in each group, unless studies presented results at a population level only. Primary outcomes were all-cause mortality, hospitalizations, and number of people receiving an antimalarial within 24 hours. Secondary outcomes were malaria-specific mortality, severe malaria, outcomes related to antimalarial treatments, antibiotic prescribing to people with a negative microscopy or polymerase chain reaction (PCR) result, parasitaemia, anaemia, and all adverse events.We included eight studies from several African countries, Afghanistan, and Myanmar. Staff included CHWs and drug shop vendors. Community use of malaria rapid diagnostic tests compared to clinical diagnosis Compared to clinical diagnosis, mRDT diagnosis results in reduced prescribing of antimalarials to people who are found to be malaria parasite-negative by microscopy or PCR testing (71 fewer per 100 people, 95% confidence interval (CI) 79 to 51 fewer; risk ratio (RR) 0.17, 95% CI 0.07 to 0.40; 3 cRCTs, 7877 participants; moderate-certainty evidence). This reduction may be greater among CHWs compared to drug shop vendors. People diagnosed by mRDT are more likely to receive appropriate treatment; that is, an antimalarial if they are microscopy- or PCR-positive and no antimalarial if they are microscopy- or PCR-negative (RR 3.04, 95% CI 2.46 to 3.74, 3 cRCTs, 9332 participants; high-certainty evidence). Three studies found that a small percentage of people with a negative mRDT result (as read by the CHW or drug shop vendors at the time of treatment) were nevertheless given an antimalarial: 38/1368 (2.8%), 44/724 (6.1%) and 124/950 (13.1%). Conversely, in two studies, a few mRDT-positive people did not receive an antimalarial (0.5% and 0.3%), and one small cross-over study found that 6/57 (10.5%) people classified as non-malaria in the clinical diagnosis arm received an antimalarial. Use of mRDTs probably increases antibiotic use compared to clinical diagnosis (13 more per 100 people, 95% CI 3 to 29 more; RR 2.02, 95% CI 1.21 to 3.37; 2 cRCTs, 5179 participants; moderate-certainty evidence). We were unable to demonstrate any effect on mortality. Community use of malaria rapid diagnostic tests compared to health facility care Results were insufficient to reach any conclusion.Use of mRDTs by CHWs and drug shop vendors compared to clinical diagnosis reduces prescribing of antimalarials to people without malaria. Deaths were uncommon in both groups. Antibiotic prescribing was higher in those with a negative mRDT than in those with a negative clinical diagnosis.

Background Accurate measurement of anti-malarial drug concentrations in therapeutic efficacy studies is essential to distinguish between inadequate drug exposure and anti-malarial drug resistance, and to inform optimal anti-malarial dosing in key target population groups. Methods A sensitive and selective LC–MS/MS method was developed and validated for the simultaneous determination of amodiaquine and its active metabolite, desethylamodiaquine, and used to describe their pharmacokinetic parameters in Ghanaian patients with uncomplicated falciparum malaria treated with the fixed-dose combination, artesunate-amodiaquine. Results The day-28 genotype-adjusted adequate clinical and parasitological response rate in 308 patients studied was > 97% by both intention-to-treat and per-protocol analysis. After excluding 64 patients with quantifiable amodiaquine concentrations pre-treatment and 17 with too few quantifiable concentrations, the pharmacokinetic analysis included 227 patients (9 infants, 127 aged 1–4 years, 91 aged ≥ 5 years). Increased median day-3 amodiaquine concentrations were associated with a lower risk of treatment failure [HR 0.87 (95% CI 0.78–0.98), p = 0.021]. Amodiaquine exposure (median AUC0-∞) was significantly higher in infants (4201 ng h/mL) and children aged 1–5 years (1994 ng h/mL) compared to older children and adults (875 ng h/mL, p = 0.001), even though infants received a lower mg/kg amodiaquine dose (median 25.3 versus 33.8 mg/kg in older patients). Desethylamodiaquine AUC0-∞ was not significantly associated with age. No significant safety concerns were identified. Conclusions Efficacy of artesunate-amodiaquine at currently recommended dosage regimens was high across all age groups. Reassuringly, amodiaquine and desethylamodiaquine exposure was not reduced in underweight-for-age young children or those with high parasitaemia, two of the most vulnerable target populations. A larger pharmacokinetic study with close monitoring of safety, including full blood counts and liver function tests, is needed to confirm the higher amodiaquine exposure in infants, understand any safety implications and assess whether dose optimization in this vulnerable, understudied population is needed.