Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study

Abstract

BackgroundHome-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home.MethodsAn open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961.ResultsA total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046).ConclusionsProvision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

Community Health Workers and Stand-Alone or Integrated Case Management of Malaria: A Systematic Literature Review

“…All except one of the studies reporting this indicator involved pre-packaged antimalarial drugs (co-blistered or co-formulated) 45. Although direct data on user adherence to the correct dose was not generally reported, four studies investigated polymerase chain reaction–adjusted cure rates of a sub-sample of patients treated with ACT by a CHW, all of which were > 90% 40,47. This finding supports the notion that pre-packaged ACTs can be administered effectively by CHWs and adhered to by the users of these services.…”

Plasmodium falciparum Drug Resistance Phenotype as Assessed by Patient Antimalarial Drug Levels and Its Association With pfmdr1 Polymorphisms

“…Full details of these studies have been reported previously and are summarized in brief in Table 1 [9, 10]. …”

Dried Blood Spot Analysis to Assess Medication Adherence and to Inform Personalization of Treatment

“…or no parasites reappearance (median 217 ng/ml). [57]. The PCR assessed cure rate by day 42 of treatment was 93% [57] but elsewhere it has been noted that these adherence levels are only maintained where the patients are involved in specific tests [54].…”

“…The robustness and cost effectiveness of the DBS approach supported the evaluation of field samples in Tanzania for malaria patients treated with Artemether and Lumifantrine [57,58]. DBS samples were stable for 4 months at 22°C.…”

“…[57]. The PCR assessed cure rate by day 42 of treatment was 93% [57] but elsewhere it has been noted that these adherence levels are only maintained where the patients are involved in specific tests [54]. The malaria parasites become drug resistant and changes in first line treatment is required [60].…”