Active Pharmacovigilance for Primaquine Radical Cure of Plasmodium vivax Malaria in Odisha, India

View More View Less
  • 1 National Institute of Malaria Research, Dwarka, New Delhi, India;
  • | 2 National Vector Borne Disease Control Programme (NVBDCP), Odisha, India;
  • | 3 Medicines for Malaria Venture, Geneva, Switzerland

Plasmodium vivax malaria elimination requires radical cure with chloroquine/primaquine. However, primaquine causes hemolysis in glucose-6-phosphate dehydrogenase-deficient (G6PDd) individuals. Between February 2016 and July 2017 in Odisha State, India, a prospective, observational, active pharmacovigilance study assessed the hematologic safety of directly observed 25 mg/kg chloroquine over 3 days plus primaquine 0.25 mg/kg/day for 14 days in 100 P. vivax patients (≥ 1 year old) with hemoglobin (Hb) ≥ 7 g/dL. Pretreatment G6PDd screening was not done, but patients were advised on hemolysis signs and symptoms using a visual aid. For evaluable patients, the mean absolute change in Hb between day 0 and day 7 was −0.62 g/dL (95% confidence interval [CI]: −0.93, −0.31) for males (N = 53) versus −0.24 g/dL (95%CI: −0.59, 0.10) for females (N = 45; P = 0.034). Hemoglobin declines ≥ 3 g/dL occurred in 5/99 (5.1%) patients (three males, two females); none had concurrent clinical symptoms of hemolysis. Based on G6PD qualitative testing after study completion, three had a G6PD-normal phenotype, one female was confirmed by genotyping as G6PDd heterozygous, and one male had an unknown phenotype. A G6PDd prevalence survey was conducted between August 2017 and March 2018 in the same region using qualitative G6PD testing, confirmed by genotyping. G6PDd prevalence was 12.0% (14/117) in tribal versus 3.1% (16/509) in nontribal populations, with G6PD Orissa identified in 29/30 (96.7%) of G6PDd samples. Following chloroquine/primaquine, notable Hb declines were observed in this population that were not recognized by patients based on clinical signs and symptoms.

Author Notes

Address correspondence to Anupkumar R. Anvikar, National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110077, India. E-mail: anvikar@gmail.com

Financial support: This study was funded by Medicines for Malaria Venture.

Disclosure: A. R. A., N. V., S. S, N. A., and C. P. Y. are employees of the National Institute of Malaria Research. M. M. P., S. P., and P. S. are employees of the National Vector Borne Disease Control Programe, Odisha. S. D. is an employee of Medicines for Malaria Venture; P. G. D was an employee of Medicines for Malaria Venture at the time of the study and now serves as a consultant.

Authors’ addresses: Anupkumar R. Anvikar, Supriya Sharma, Naseem Ahmed, Chander P. Yadav, and Neena Valecha, Epidemiology and Clinical Research, National Institute of Malaria Research, New Delhi, India, E-mails: anvikar@gmail.com, supsmicro@gmail.com, nks.nimr@gmail.com, cpyadav123@gmail.com, and neenavalecha@gmail.com. Prajyoti Sahu, Madan M. Pradhan, and Sreya Pradhan, National Vector Borne Disease Control Programme, NVBDCP, Odisha, Rourkela, India, E-mails: sahuprajyoti999@gmail.com, drmmpradhan@gmail.com, and sreya16@gmail.com. Stephan Duparc and Penny G. Daumerie, Medical R&D, Medicines for Malaria Venture, Geneva, Switzerland, E-mails: duparcs@mmv.org and grewalp-consultant@mmv.org.

Save