Browsing by Author "Mabuza, Aaron"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Open Access
    Absence of kelch13 artemisinin resistance markers but strong selection for lumefantrine-tolerance molecular markers following 18 years of artemisinin-based combination therapy use in Mpumalanga Province, South Africa (2001–2018)
    (2019-08-22) Raman, Jaishree; Kagoro, Frank M; Mabuza, Aaron; Malatje, Gillian; Reid, Anthony; Frean, John; Barnes, Karen I
    Abstract Background The ability of Plasmodium falciparum parasites to develop resistance to widely used anti-malarials threatens malaria control and elimination efforts. Regular drug efficacy monitoring is essential for ensuring effective treatment policies. In low transmission settings where therapeutic efficacy studies are often not feasible, routine surveillance for molecular markers associated with anti-malarial resistance provides an alternative for the early detection of emerging resistance. Such a longitudinal survey of changes in the prevalence of selected molecular markers of resistance was conducted in the malaria-endemic regions of Mpumalanga Province, South Africa, where malaria elimination at a district-level is being pursued. Methods Molecular analyses to determine the prevalence of alleles associated with resistance to lumefantrine (mdr86N, crt76K and mdr1 copy number variation) and sulfadoxine–pyrimethamine (dhfr triple, dhps double, SP quintuple) were conducted between 2001 and 2018, while artemisinin resistance markers (kelch13 mutations) were assessed only in 2018. Results Parasite DNA was successfully amplified from 1667/2393 (70%) of malaria-positive rapid diagnostic tests routinely collected at primary health care facilities. No artemisinin resistance-associated kelch13 mutations nor amplification of the mdr1 gene copy number associated with lumefantrine resistance were observed. However, prevalence of both the mdr86N and crt76K alleles increased markedly over the study period, with all isolates collected in 2018 carrying these markers. SP quintuple mutation prevalence increased steadily from 14% in 2001 to 96% in 2018. Mixed alleles at any of the codons assessed were rare by 2018. Conclusion No kelch13 mutations confirmed or suspected to be associated with artemisinin resistance were identified in 2018. Although parasites carrying the mdr86N and crt76K alleles associated with reduced lumefantrine susceptibility were strongly selected for over the study period, nearing fixation by 2018, the marker for lumefantrine resistance, namely increased mdr1 copy number, was not observed in this study. The increase in mdr86N and crt76K allele prevalence together with intense regional artemether–lumefantrine drug pressure, raises concern regarding the sustained artemether–lumefantrine efficacy. Regular, rigorous anti-malarial resistance marker surveillance across all three South African malaria-endemic provinces to inform case management is recommended.
  • Thumbnail Image
    Item
    Open Access
    Exploring the seasonality of reported treated malaria cases in Mpumalanga, South Africa
    (Public Library of Science, 2013) Silal, Sheetal Prakash; Barnes, Karen I; Kok, Gerdalize; Mabuza, Aaron; Little, Francesca
    South Africa, having met the World Health Organisation's pre-elimination criteria, has set a goal to achieve malaria elimination by 2018. Mpumalanga, one of three provinces where malaria transmission still occurs, has a malaria season subject to unstable transmission that is prone to sporadic outbreaks. As South Africa prepares to intensify efforts towards malaria elimination, there is a need to understand patterns in malaria transmission so that efforts may be targeted appropriately. This paper describes the seasonality of transmission by exploring the relationship between malaria cases and three potential drivers: rainfall, geography (physical location) and the source of infection (local/imported). Seasonal decomposition of the time series by Locally estimated scatterplot smoothing is applied to the case data for the geographical and source of infection sub-groups. The relationship between cases and rainfall is assessed using a cross-correlation analysis. The malaria season was found to have a short period of no/low level of reported cases and a triple peak in reported cases between September and May; the three peaks occurring in October, January and May. The seasonal pattern of locally-sourced infection mimics the triple-peak characteristic of the total series while imported infections contribute mostly to the second and third peak of the season (Christmas and Easter respectively). Geographically, Bushbuckridge municipality, which exhibits a different pattern of cases, contributed mostly to the first and second peaks in cases while Maputo province (Mozambique) experienced a similar pattern in transmission to the imported cases. Though rainfall lagged at 4 weeks was significantly correlated with malaria cases, this effect was dampened due to the growing proportion of imported cases since 2006. These findings may be useful as they enhance the understanding of the current incidence pattern and may inform mathematical models that enable one to predict the impact changes in these drivers will have on malaria transmission.
  • Thumbnail Image
    Item
    Open Access
    Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa: an open-label, randomized controlled trial
    (2019-06-24) Raman, Jaishree; Allen, Elizabeth; Workman, Lesley; Mabuza, Aaron; Swanepoel, Hendrik; Malatje, Gillian; Frean, John; Wiesner, Lubbe; Barnes, Karen I
    Abstract Background 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 WHO-recommended SLD primaquine without G6PD testing to advance malaria elimination in South African districts with low-intensity residual transmission. Trial registration Pan African Clinical Trial Registry, PACTR201611001859416. Registered 11 November 2016, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1859
  • Thumbnail Image
    Item
    Open Access
    Therapeutic efficacy of sulfadoxine-pyrimethamine for plasmodium falciparum malaria
    (2005) Mabuza, Aaron; Govere, John; La Grange, Kobus; Mngomezulu, Nicros; Allen, Elizabeth; Zitha, Alpheus; Mbokazi, Frans; Durrheim, David; Barnes, Karen
    Objectives. To assess the therapeutic efficacy of sulfadoxinepyrimethamine (SP) after 5 years of use as first-line treatment of uncomplicated Plasmodium falciparum malaria, and thus guide the selection of artemisinin-based combination therapy in Mpumalanga, South Africa. Design. An open-label, in vivo therapeutic efficacy study of patients with uncomplicated P. falciparum malaria treated with a single oral dose of SP, with response to treatment monitored clinically and parasitologically on days 1, 2, 3, 7, 14, 21, 28 and 42. Setting. Mangweni and Naas public health care clinics, Tonga district in rural Mpumalanga. Subjects, outcome measures and results. Of 152 patients recruited sequentially, 149 (98%) were successfully followed up for 42 days. One hundred and thirty-four patients (90%) demonstrated adequate clinical and parasitological response. Of the 15 patients (10%) who failed treatment, 2 (1.3%) had an early treatment failure, and polymerase chain reaction confirmed recrudescent infection in all 13 patients (8.7%) who had late parasitological (N = 11) or clinical (N = 2) failure. Gametocyte carriage was prevalent following SP treatment (84/152) and this has increased significantly since implementation in 1998 (relative risk 2.77 (confidence interval 1.65 - 4.66); p = 0.00004). Conclusion. Asexual P. falciparum parasites in Mpumalanga remain sensitive to SP, with no significant difference between the baseline cure rate (94.5%) at introduction in 1998, and the present 90% cure rate (p = 0.14). However, since gametocyte carriage has increased significantly we recommend that SP be combined with artesunate in Mpumalanga to reduce gametocyte carriage and thus decrease malaria transmission and potentially delay antimalarial resistance. S Afr Med J 2005; 95: 346-349.