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Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2018-08-01
End Date 2021-08-31
Project Code TMA2016CDF1555
Status Active

Title

Single low-dose primaquine efficacy and safety for treatment of uncomplicated Plasmodium falciparum malaria based on cytochrome P450 2D6 activity in Bagamoyo district, Tanzania.

Objectives

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.

Host Organisation

Institution Country
Tropical Pesticides Research Institute (TPRI) Tanzania, United Republic of

Study Design

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.

Sites

Yombo Primary health facility, Bagamoyo district.

Phd Study

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

Students Supervised

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

Results & Outcomes

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).

Publications

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

Current Organisation

Tropical Pesticides Research Institute

Current Job Title

Research Scientist

Students Supervised

Type Name Title University Start Date End Date
MSc Dominick Msolo Mr University of Dar es Salaam 2019 2021

Education

Institution Degree Year
Muhimbili University of Health and Allied Sciences, Tanzania, United Republic of PhD

Areas Of Specialisation

Malaria

Publications

Authors:
Billy Ngasala , author
Doreen D. Mutemi , author
Richard O. Mwaiswelo , author
Date:
2019-10-02
Journal:
The American Journal of Tropical Medicine and Hygiene
Content:
Identifiers:
DOI: 10.4269/ajtmh.19-0394
Part of ISSN: 0002-9637
Authors:
Billy Ngasala , author
Hamza Juma , author
Richard O. Mwaiswelo , author
Date:
2020-01-01
Journal:
International Journal of Infectious Diseases
Content:
Identifiers:
Authors:
Richard Mwaiswelo , author
Billy Ngasala , author
Irina Jovel , author
Berit Aydin-Schmidt , author
Roland Gosling , author
Zul Premji , author
Bruno Mmbando , author
Anders Björkman , author
Andreas Mårtensson , author
Date:
2016-08-01
Journal:
Malaria Journal
Content:
Identifiers:
Authors:
Billy Ngasala , author
Ferdinand Matata , author
Richard Mwaiswelo , author
Bruno P. Mmbando , author
Date:
2019-11-06
Journal:
The American Journal of Tropical Medicine and Hygiene
Content:
Identifiers:
DOI: 10.4269/ajtmh.19-0362
Part of ISSN: 0002-9637
Authors:
Richard Mwaiswelo , author
Billy Ngasala , author
Irina Jovel , author
Weiping Xu , author
Erik Larsson , author
Maja Malmberg , author
Jose Pedro Gil , author
Zul Premji , author
Bruno P. Mmbando , author
Andreas Mårtensson , author
Date:
2019-05-01
Journal:
The American Journal of Tropical Medicine and Hygiene
Content:
Identifiers:
DOI: 10.4269/ajtmh.18-0729
Part of ISSN: 0002-9637
Authors:
Richard Mwaiswelo , author
Maja Malmberg , author
Bruno P. Mmbando , author
J. Pedro Gil , author
Zul Premji , author
Andreas Mårtensson , author
Weiping Xu , author
Irina Jovel , author
Anders Björkman , author
Billy Ngasala , author
Date:
2017-08-02
Journal:
The American Journal of Tropical Medicine and Hygiene
Content:
Identifiers:
DOI: 10.4269/ajtmh.16-0780
Part of ISSN: 0002-9637
Authors:
Richard O. Mwaiswelo , author
Hamis Kabuga , author
Eliningaya J. Kweka , author
Vito Baraka , author
Date:
2022-02-25
Journal:
Tropical Medicine and Health
Content:
Identifiers:
Authors:
Kasia Stepniewska , author
Georgina S Humphreys , author
Bronner P Gonçalves , author
Elaine Craig , author
Roly Gosling , author
Philippe J Guerin , author
Ric N Price , author
Karen I Barnes , author
Jaishree Raman , author
Menno R Smit , author
Umberto D’Alessandro , author
Will J R Stone , author
Anders Bjorkman , author
Aaron M Samuels , author
Maria I Arroyo-Arroyo , author
Guido J H Bastiaens , author
Joelle M Brown , author
Alassane Dicko , author
Badria B El-Sayed , author
Salah-Eldin G Elzaki , author
Alice C Eziefula , author
Simon Kariuki , author
Titus K Kwambai , author
Amanda E Maestre , author
Andreas Martensson , author
Dominic Mosha , author
Richard O Mwaiswelo , author
Billy E Ngasala , author
Joseph Okebe , author
Michelle E Roh , author
Patrick Sawa , author
Alfred B Tiono , author
Ingrid Chen , author
Chris J Drakeley , author
Teun Bousema , author
Date:
2020-08-11
Journal:
The Journal of Infectious Diseases
Content:
Identifiers:
DOI: 10.1093/infdis/jiaa498
Part of ISSN: 0022-1899
Authors:
Richard Mwaiswelo , author
Billy E. Ngasala , author
Irina Jovel , author
Roland Gosling , author
Zul Premji , author
Eugenie Poirot , author
Bruno P. Mmbando , author
Anders Björkman , author
Andreas Mårtensson , author
Date:
2016-06-10
Journal:
Malaria Journal
Content:
Identifiers:
Authors:
Richard O. Mwaiswelo , author
Luzia Helena Carvalho , editor
Bruno P. Mmbando , author
Frank Chacky , author
Fabrizio Molteni , author
Ally Mohamed , author
Samwel Lazaro , author
Sylvia F. Mkalla , author
Bushukatale Samuel , author
Billy Ngasala , author
Date:
2021-12-02
Journal:
PLOS ONE
Content:
Identifiers:
Authors:
Richard Mwaiswelo , author
Bill Ngasala , author
Date:
2020-04-01
Journal:
Malaria Journal
Content:
Identifiers:
Authors:
Bruno P. Mmbando , author
Richard O. Mwaiswelo , author
Frank Chacky , author
Fabrizio Molteni , author
Ally Mohamed , author
Samwel Lazaro , author
Billy Ngasala , author
Hoh Boon-Peng , editor
Date:
2022-04-01
Journal:
PLOS ONE
Content:
Identifiers:
Authors:
Richard Owden Mwaiswelo , author
Billy Ngasala , author
Dominick Msolo , author
Eliningaya Kweka , author
Bruno P. Mmbando , author
Andreas Mårtensson , author
Date:
2022-12-01
Journal:
Malaria Journal
Content:
Identifiers:

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