title: An assessment of the supply, programmatic use, and regulatory issues of single low-dose primaquine as a Plasmodium falciparum gametocytocide for sub-Saharan Africa.
abstract: BACKGROUND
  Global ambitions to eliminate malaria are intensifying, underscoring a critical need for transmission blocking tools. In 2012, the WHO recommended the use of 0.25 mg/kg of single low-dose (SLD) primaquine to stop Plasmodium falciparum transmission. To ensure the availability of SLD primaquine to countries in need of this tool, more information on the supply, programmatic, and regulatory barriers to the rollout of SLD primaquine is required.
  
  
  METHODS
  Challenges to the rollout of SLD primaquine in sub-Saharan Africa were established through semi-structured qualitative interviews with three primaquine manufacturers, 43 key informants from Ethiopia, Senegal, Swaziland, Zambia, and Tanzania, and 16 malaria research experts.
  
  
  RESULTS
  Sanofi and Remedica are the only two sources of SRA-approved primaquine suitable for procurement by international donors. Neither manufacturer produces primaquine tablet strengths suitable for the transmission blocking indication. In-country key informants revealed that the WHO weight-based recommendation to use SLD primaquine is challenging to implement in actual field settings. Malaria programmes expressed safety concerns of SLD primaquine use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as well as potential interactions between primaquine and co-morbidities, and drug-drug interactions with HIV and/or tuberculosis treatments. Regulatory processes are a major barrier to the rollout of SLD primaquine, requiring multiple steps at both the country and global level. Despite these barriers, demand for SLD primaquine is growing, and malaria researchers are interested in primaquine deployment through mass screen and treat and/or mass drug administration campaigns.
  
  
  CONCLUSIONS
  Demand for primaquine as a transmission blocking agent is growing rapidly yet multiple barriers to SLD primaquine use exist. Research is needed to define the therapeutic dose range, which will guide dosing regimens in the field, inform the development of new, lower strength primaquine tablets and/or formulation(s), and allay programmatic safety concerns in individuals with G6PD deficiency. Potential interactions between primaquine and co-morbidities and treatments should be explored. To minimize regulatory delays, countries need to prepare for product registration at an early stage, WHO prequalification for suitable primaquine tablet strengths and/or new formulations should be sought, and in the meanwhile only Stringent Regulatory Authority (SRA)-approved primaquine should be used.
authors.affiliation: Global Health Sciences, University of California, San Francisco, 550 16th Street, 3rd Floor, San Francisco, CA, 94158, USA. Ingrid.Chen@ucsf.edu.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Chen
authors.affiliation: Global Health Sciences, University of California, San Francisco, 550 16th Street, 3rd Floor, San Francisco, CA, 94158, USA. Eugenie.Poirot@ucsf.edu.
authors.forename: Eugenie
authors.initials: E
authors.lastname: Poirot
authors.affiliation: Clinton Health Access Initiative, Boston, MA, USA. mark.h.newman@gmail.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Newman
authors.affiliation: Clinton Health Access Initiative, Boston, MA, USA. dkandula@clintonhealthaccess.org.
authors.forename: Deepika
authors.initials: D
authors.lastname: Kandula
authors.affiliation: Clinton Health Access Initiative, Boston, MA, USA. rshah@clintonhealthaccess.org.
authors.forename: Renee
authors.initials: R
authors.lastname: Shah
authors.affiliation: Global Health Sciences, University of California, San Francisco, 550 16th Street, 3rd Floor, San Francisco, CA, 94158, USA. jhwang@cdc.gov.|Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USA. jhwang@cdc.gov.
authors.forename: Jimee
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Clinton Health Access Initiative, Boston, MA, USA. jcohen@clintonhealthaccess.org.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Global Health Sciences, University of California, San Francisco, 550 16th Street, 3rd Floor, San Francisco, CA, 94158, USA. Roly.Gosling@ucsf.edu.
authors.forename: Roly
authors.initials: R
authors.lastname: Gosling
authors.affiliation: Clinton Health Access Initiative, Boston, MA, USA. lrooney@clintonHealthAccess.org.
authors.forename: Luke
authors.initials: L
authors.lastname: Rooney
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000962:Antimalarials / Q000600:supply & distribution / Q000627:therapeutic use*; D004347:Drug Interactions; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology / Q000209:etiology; D007722:Health Knowledge, Attitudes, Practice; D006291:Health Policy / Q000331:legislation & jurisprudence*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects; D011319:Primaquine / Q000600:supply & distribution / Q000627:therapeutic use*; D011795:Surveys and Questionnaires
chemical_list: D000962:Antimalarials; D011319:Primaquine