title: Development of a pharmacovigilance safety monitoring tool for the rollout of single low-dose primaquine and artemether-lumefantrine to treat Plasmodium falciparum infections in Swaziland: a pilot study.
abstract: Countries remain reluctant to adopt the 2012 World Health Organization recommendation for single low-dose (0.25 mg/kg) primaquine (SLD PQ) for Plasmodium falciparum transmission-blocking due to concerns over drug-related haemolysis risk, especially among glucose-6-phosphate dehydrogenase-deficient (G6PDd) people, without evidence demonstrating that it can be safely deployed in their settings. Pharmacovigilance methods provide a systematic way of collecting safety data and supporting the rollout of SLD PQ.
  
  
  
  The Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT), comprising: (1) a standardized form to support the surveillance of possible adverse events following SLD PQ treatment; (2) a patient information card to enhance awareness of known adverse drug reactions of SLD PQ use; and (3) a database compiling recorded information, was developed and piloted. Data on patient characteristics, malaria diagnosis and treatment are collected. Blood samples are taken to measure haemoglobin (Hb) and test for G6PD deficiency. Active follow-up includes a repeat Hb measurement and adverse event monitoring on or near day 7. A 13-month prospective pilot study in two hospital facilities in Swaziland alongside the introduction of SLD PQ generated preliminary evidence on the feasibility and acceptability of PROMPT.
  
  
  
  PROMPT was well received by nurses as a simple, pragmatic approach to active surveillance of SLD PQ safety data. Of the 102 patients enrolled and administered SLD PQ, none were G6PDd. 93 (91.2 %) returned on or near day 7 for follow-up. Four (4.6 %) patients had falls in Hb ≥25 % from baseline, none of whom presented with signs or symptoms of anaemia. No patient's Hb fell below 7 g/dL and none required a blood transfusion. Of the 11 (11 %) patients who reported an adverse event over the study period, three were considered serious and included two deaths and one hospitalization; none were causally related to SLD PQ. Four non-serious adverse events were considered definitely, probably, or possibly related to SLD PQ.
  
  
  
  Improved pharmacovigilance to monitor and promote the safety of the WHO recommendation is needed. The successful application of PROMPT demonstrates its potential as an important tool to rapidly generate locally acquired safety data and support pharmacovigilance in resource-limited settings.
authors.affiliation: Global Health Group, University of California San Francisco, San Francisco, CA, USA. Eugenie.Poirot@ucsf.edu.|Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. Eugenie.Poirot@ucsf.edu.
authors.forename: Eugenie
authors.identifier: 0000-0002-5021-8345
authors.initials: E
authors.lastname: Poirot
authors.affiliation: Clinton Health Access Initiative, Mbabane, Swaziland.
authors.forename: Adam
authors.initials: A
authors.lastname: Soble
authors.affiliation: Clinton Health Access Initiative, Mbabane, Swaziland.
authors.forename: Nyasatu
authors.initials: N
authors.lastname: Ntshalintshali
authors.affiliation: University of Namibia, Windhoek, Namibia.
authors.forename: Asen
authors.initials: A
authors.lastname: Mwandemele
authors.affiliation: National Malaria Control Programme, Manzini, Swaziland.
authors.forename: Nomcebo
authors.initials: N
authors.lastname: Mkhonta
authors.affiliation: National Malaria Control Programme, Manzini, Swaziland.
authors.forename: Calisile
authors.initials: C
authors.lastname: Malambe
authors.affiliation: National Malaria Control Programme, Manzini, Swaziland.
authors.forename: Sibonakaliso
authors.initials: S
authors.lastname: Vilakati
authors.affiliation: Clinton Health Access Initiative, Mbabane, Swaziland.
authors.forename: Sisi
authors.initials: S
authors.lastname: Pan
authors.affiliation: International Center for AIDS Care and Treatment Programs, Mbabane, Swaziland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Darteh
authors.affiliation: Swaziland Health Laboratory Services, Mbabane, Swaziland.
authors.forename: Gugu
authors.initials: G
authors.lastname: Maphalala
authors.affiliation: Global Health Group, University of California San Francisco, San Francisco, CA, USA.|Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Joelle
authors.initials: J
authors.lastname: Brown
authors.affiliation: Global Health Group, University of California San Francisco, San Francisco, CA, USA.|President's Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Jimee
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Pace
authors.affiliation: Departments of Pharmacy and Global Health, Schools of Pharmacy and Public Health, University of Washington, Seattle, USA.
authors.forename: Andy
authors.initials: A
authors.lastname: Stergachis
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.affiliation: National Malaria Control Programme, Manzini, Swaziland.
authors.forename: Simon
authors.initials: S
authors.lastname: Kunene
authors.affiliation: Global Health Group, University of California San Francisco, San Francisco, CA, USA.|Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Gosling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D013541:Eswatini; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D010865:Pilot Projects; D011319:Primaquine / Q000008:administration & dosage / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011319:Primaquine
keywords: Elimination; G6PD; Glucose-6-phosphate dehydrogenase deficiency; Malaria; Pharmacovigilance; Plasmodium falciparum; Primaquine; Safety