Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa : an open-label, randomized controlled trial

dc.contributor.authorRaman, Jaishree
dc.contributor.authorAllen, Elizabeth
dc.contributor.authorWorkman, Lesley
dc.contributor.authorMabuza, Aaron
dc.contributor.authorSwanepoel, Hendrik
dc.contributor.authorMalatje, Gillian
dc.contributor.authorFrean, John
dc.contributor.authorWiesner, Lubbe
dc.contributor.authorBarnes, Karen I.
dc.date.accessioned2020-08-05T12:09:15Z
dc.date.available2020-08-05T12:09:15Z
dc.date.issued2019-06
dc.description.abstractBACKGROUND: To reduce onward falciparum malaria transmission, the World Health Organization recommends adding single low-dose (SLD) primaquine to artemisinin-based combination treatment in low transmission areas. However, uptake of this recommendation has been relatively slow given concerns about whether individual risks justify potential community benefit. This study was undertaken to generate comprehensive local data on the risk–benefit profile of SLD primaquine deployment in a pre-elimination area in South Africa. METHODS: This randomized, controlled open-label trial investigated adding a single low primaquine dose on day 3 to standard artemether–lumefantrine treatment for uncomplicated falciparum malaria. Efficacy, safety and tolerability of artemether–lumefantrine and primaquine treatment were assessed on days 3, 7, 14, 28 and 42. Lumefantrine concentrations were assayed from dried blood spot samples collected on day 7. RESULTS: Of 217 patients screened, 166 were enrolled with 140 randomized on day 3, 70 to each study arm (primaquine and no primaquine). No gametocytes were detected by either microscopy or PCR in any of the follow-up samples collected after randomization on day 3, precluding assessment of primaquine efficacy. Prevalence of the CYP2D6*4, CYP2D6*10 and CYP2D6*17 mutant alleles was low with allelic frequencies of 0.02, 0.11 and 0.16, respectively; none had the CYP2D6*4/*4 variant associated with null activity. Among 172 RDT-positive patients G6PD-genotyped, 24 (14%) carried the G6PD deficient (A−) variant. Median haemoglobin concentrations were similar between treatment arms throughout follow-up. A third of participants had a haemoglobin drop > 2 g/dL; this was not associated with primaquine treatment but may be associated with G6PD genotype [52.9% (9/17) with A− genotype vs. 31% (36/116) with other genotypes (p = 0.075)]. Day 7 lumefantrine concentrations and the number and nature of adverse events were similar between study arms; only one serious adverse event occurred (renal impairment in the no primaquine arm). The artemether–lumefantrine PCR-corrected adequate clinical and parasitological response rate was 100%, with only one re-infection found among the 128 patients who completed 42-day follow-up. CONCLUSIONS: Safety, tolerability, CYP2D6 and G6PD variant data from this study support the deployment of the WHOrecommended SLD primaquine without G6PD testing to advance malaria elimination in South African districts with low-intensity residual transmission.en_ZA
dc.description.departmentUP Centre for Sustainable Malaria Control (UP CSMC)en_ZA
dc.description.librarianpm2020en_ZA
dc.description.sponsorshipSouth African Medical Research Council Collaborating Centre; UCT; South African Medical Research Council SIR; NICD; UP Institute for Sustainable Malaria Control; MRC Collaborating Centre for Malaria Research, at UPen_ZA
dc.description.urihttps://malariajournal.biomedcentral.comen_ZA
dc.identifier.citationRaman, J., Allen, E., Workman, L. et al. 2019, 'Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa : an open-label, randomized controlled trial', Malaria Journal, vol.18, art. a209, pp. 1-13.en_ZA
dc.identifier.other10.1186/s12936-019-2841-8
dc.identifier.urihttp://hdl.handle.net/2263/75584
dc.language.isoenen_ZA
dc.publisherBioMed Central (BMC)en_ZA
dc.rights© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.en_ZA
dc.subjectPrimaquineen_ZA
dc.subjectArtemether–lumefantrineen_ZA
dc.subjectEfficacyen_ZA
dc.subjectSafetyen_ZA
dc.subjectTolerabilityen_ZA
dc.subjectGametocyte carriageen_ZA
dc.subjectSouth Africa (SA)en_ZA
dc.subjectSingle low-dose (SLD)en_ZA
dc.titleSafety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa : an open-label, randomized controlled trialen_ZA
dc.typeArticleen_ZA

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