Safety monitoring experience of single-low dose primaquine co-administered with artemether–lumefantrine among providers and patients in routine healthcare practice: a qualitative study in Eastern Tanzania

Abstract

Background Primaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention of Plasmodium falciparum malaria transmission. Safety monitoring concerns and the lack of a universal validated and approved primaquine pharmacovigilance tool is a challenge for a national rollout in many countries. This study aimed to explore the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT). Methods This study was conducted in three dispensaries in the Coastal region of Eastern Tanzania. The study held six in-depth interviews with healthcare providers and six participatory focus group discussions with malaria patients (3) and parents/guardians of sick children (3). Participants were purposively sampled. Thematic analysis was conducted with the aid of NVivo qualitative analysis software. Results The respondents’ general acceptance and perceived effectiveness of the single-low dose primaquine and PROMPT was good. Screening procedure for treatment eligibility and explaining to patients about the possible adverse events was considered very useful for safety reasons. Crushing and dissolving of primaquine tablet to get the appropriate dose, particularly in children, was reported by all providers to be challenging. Transport costs and poor access to the health facility were the main reasons for a patient failing to return to the clinic for a scheduled follow-up visit. Treatment was perceived to be safe by both providers and patients and reported no case of a severe adverse event. Some providers were concerned with the haemoglobin drop observed on day 7. Conclusion Single-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers. Further validation of the tool by involving the National Malaria Control Programme is pivotal to addressing key challenges and facilitating primaquine adoption in the national policy.

The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on hemoglobin levels in Ethiopia: a longitudinal cohort study

“…A similar nding was documented in a previous study from Burkina Faso [25]. Hemolysis of parasitized red blood cells may be the main reason for this reduction in Hb levels at the beginning of malaria treatment, regardless of the patient's G6PD status [50][51][52]. After adjusting for age, parasite density, temperature, and sex, a decrease in Hb was observed in the G6PDd patients compared to the G6PDn patients; however, this difference was not signi cant (P = 0.110).…”

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

“…Evidence from this analysis is insufficient to capture rare events (< 1/1000) with the use of single-dose primaquine to interrupt transmission of P. falciparum malaria. Therefore, as with any new treatment policy deployment, post-marketing pharmacovigilance should be encouraged, for which existing tools are available [9,12,20]. This could help address these real-world evidence gaps, as well as identify any effects of inadvertent exposure to SLD primaquine during pregnancy (when primaquine is contraindicated).…”

“…8 Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. 9 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 10 Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.…”

“…This safety profile is especially important for non-curative drugs that are meant to benefit the community and not necessarily the dosed individual [7]. SLD primaquine deployment is further challenged by the need to crush and dissolve the primaquine table in water prior to administration in children according to a weight-based dosing schedule [8,9]. Malaria control programmes concluded it would be easier to administer primaquine in weight-or agebased bands, requiring the establishment of the therapeutic range of SLD primaquine as a P falciparum transmission-blocking agent, spanning the lowest efficacious dose to the highest tolerable dose around the 0.25 mg/kg target dose [8,10].…”

Responsive Sensory Evaluation to Develop Flexible Taste-Masked Paediatric Primaquine Tablets against Malaria for Low-Resource Settings

“…Overall, 95% of the panel rated the drug as “3 = strongly bitter”, and 5% as “3+ = very strong” [ 10 ]. In a field study in Tanzania, concerns about the bitter taste of dissolved PQ tablets led healthcare providers to administer the medicine on a spoon mixed with a sweet beverage, mainly soda and fruit punch, to help mask the poor taste [ 11 ]. All healthcare providers reported that crushing and dissolving tablets to administer the appropriate dose was challenging, and there were concerns that the need for sweet beverages presented unnecessary additional costs to patients [ 11 ].…”