Call | Career Development Fellowship (CDF) |
Programme | EDCTP2 |
Start Date | 2018-08-01 |
End Date | 2021-08-31 |
Project Code | TMA2016CDF1555 |
Status | Completed |
Single low-dose primaquine efficacy and safety for treatment of uncomplicated Plasmodium falciparum malaria based on cytochrome P450 2D6 activity in Bagamoyo district, Tanzania.
Broad Objective To compare the safety and efficacy of a 0.25 mg/kg single-dose PQ added to a standard artemether-lumefantrine regimen for clearance and transmission-blocking of P. falciparum gametocytes in patients with reduced/null compared to those with normal/increased CYP2D6 isoenzyme activities. Specific Objectives 1. To determine the prevalence of patients with reduced activities of CYP2D6 with the intention to treat malaria. 2. To determine the safety of 0.25 mg/kg single-dose PQ added to the first dose of artemether-lumefantrine in patients with reduced/null vs. normal/increased activities of CYP2D6. 3. To determine the prevalence of G6PD deficiency in patients with reduced/null vs. normal/increased activities of CYP2D6. 4. To determine the safety of 0.25 mg/kg single-dose PQ added to the first dose of artemether-lumefantrine in patients with G6PD deficiency and reduced/null vs. normal/increased activities of CYP2D6 5. To determine the efficacy of 0.25 mg/kg single-dose PQ added to the first dose of artemether-lumefantrine in the clearance of gametocytes in patients with reduced/null vs. normal/increased activities of CYP2D6. 6. To determine the efficacy of 0.25 mg/kg single-dose PQ added to the first dose of artemether-lumefantrine in blocking the transmission of P. falciparum gametocytes in patients with reduced/null vs. normal/increased activities of CYP2D6.
Institution | Country |
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Tropical Pesticides Research Institute (TPRI) | Tanzania, United Republic of |
Study Design There is no rapid diagnostic test that could be used to test and group participants based on their CYP2D6 status, therefore, this was a single-arm clinical trial to assess the safety and efficacy of a 0.25 mg/kg single-dose PQ added to standard artemether-lumefantrine treatment in individuals with CYP2D6 reduced or no activity compared to those with normal or increased activity for clearance and blocking transmission of P. falciparum gametocytes. Patients with microscopically confirmed uncomplicated P. falciparum mono-infection were enrolled in the study, treated with a standard artemether-lumefantrine regimen plus 0.25 mg/kg single-dose PQ, and then followed up until day 28 after treatment initiation for clinical and parasitological assessment. Only CYP2D6 alleles common in African Tanzanians were genotyped. Individuals with reduced CYP2D6 activity were defined as those with CYP2D6*17 and CYP*29 alleles, whereas those with no activity were those with CYP2D6*4 and CYP2D6*5, and normal individuals were those with CYP2D6*1, while those with CYP2D6*2 were defined as having increased activity [26,33]. However, a previous study indicated a very low prevalence of poor metabolizers, which probably wouldn't lead to a significant conclusion [33]. Therefore, poor metabolizers were combined with those with reduced CYP2D6 activity to form one group, the reduced CYP2D6 activity group.
Yombo Primary health facility, Bagamoyo district. |
Title | University | Start Date | End Date |
---|---|---|---|
Monitoring the efficacy and safety of artemether-lumefantrine alone or plus a single low-dose primaquine for the management of malaria in Bagamoyo district, Tanzania. | Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. | 2012-04-01 | 2016-12-15 |
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
MSc | Dominic Msolo | Efficacy of single low-dose of primaquine for treatment of uncomplicated Plasmodium falciparum malaria in Tanzania. | University of Dar es Salaam, Tanzania | 2018 | 2020 |
In total, 157 children (median age 6.4 (Interquartile range 4.0-8.2) years) were recruited, of whom 21.0% (33/157) and 12.7% (20/157) had reduced CYP2D6 and deficient G6PD activity, respectively. Day 3 mean absolute Hb concentration reduction was 1.50 g/dL (95% confidence interval [CI]: 1.10-1.90) and 1.51 g/dL (95%CI:1.31-1.71) in reduced and normal CYP2D6 patients, respectively (t=0.012, p=0.990). The day 3 mean absolute Hb concentration reduction in G6PD deficient, G6PD normal and heterozygous female was 1.82 g/dL (95%CI: 1.32-2.32), 1.48 g/dL (95%CI: 1.30-1.67) and 1.47 g/dL (95%CI: 0.76-2.18), respectively (F=0.838, p=0.435). Sixteen percent (16/98) of the patients each infected at least one mosquito on day 7, and of these, 10.0% (2/20) and 17.9% (14/78) had reduced and normal CYP2D6 enzyme activity, respectively (x2= 0.736, p=0.513).
Mwaiswelo, R.O., Ngasala, B., Msolo, D. et al. A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania. Malar J 21, 84 (2022). https://doi.org/10.1186/s12936-022-04100-1 |
Mwaiswelo, R.O., Mawala, W., Iversen, P.O. et al. Sickle cell disease and malaria: decreased exposure and asplenia can modulate the risk from Plasmodium falciparum. Malar J 19, 165 (2020). https://doi.org/10.1186/s12936-020-03212-w |
Mwaiswelo, R., Ngasala, B., Jovel, I. et al. Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial. Malar J 15, 435 (2016). https://doi.org/10.1186/s12936-016-1430-3 |
Mwaiswelo, R., Ngasala, B.E., Jovel, I. et al. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malar J 15, 316 (2016). https://doi.org/10.1186/s12936-016-1341-3 |
Tropical Pesticides Research Institute
Research Scientist
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
MSc | Dominick Msolo | Mr | University of Dar es Salaam | 2019 | 2021 |
Role | Committee/board | Start Date | End Date |
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Institution | Degree | Year |
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Muhimbili University of Health and Allied Sciences, Tanzania, United Republic of | PhD |
Malaria