Pharmacovigilance of suspected or confirmed therapeutic ineffectiveness of artemisinin-based combination therapy: extent, associated factors, challenges and solutions to reporting.

BACKGROUND: Therapeutic ineffectiveness of artemisinin-based combination therapy (ACT) increases the risk of malaria-related morbidity and mortality, and raises healthcare costs. Yet, little has been done to promote the pharmacovigilance (PV) of ACT ineffectiveness in sub-Saharan Africa, particularly in Uganda. This study aimed to determine the extent and associated factors of the past 6 months reporting of suspected or confirmed ACT therapeutic ineffectiveness by healthcare professionals (HCPs), and difficulties and potential solutions to the PV of ACT therapeutic ineffectiveness. METHODS: Survey of 685 HCPs conducted using a self-administered questionnaire from June to July 2018 in a nationally representative sample of public and private health facilities in Uganda. HCPs disclosed if they had spontaneously reported ACT therapeutic ineffectiveness to appropriate authorities in the previous 6 months. Multivariable logistic regression models were used to identify determinants of past 6-months, HCP-reported ACT therapeutic ineffectiveness. RESULTS: One in five (20%, 137/685; 95% CI 17-23%) HCPs reported ACT therapeutic ineffectiveness to an appropriate authority in the previous 6 months. HCPs commonly reported ACT therapeutic ineffectiveness to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever submitted a written report of ACT therapeutic ineffectiveness to Uganda's National Pharmacovigilance Centre. Common difficulties of reporting ACT therapeutic ineffectiveness were: unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT therapeutic ineffectiveness in the past 6 months were: hospital-status (vs other; OR = 2.4, 95% CI 1.41-4.21), HCPs aged under 25 years (OR = 2.2, 95% CI 1.29-3.76), suspicion of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.3, 95% CI 1.29-3.92), receipt of patient-complaint(s) of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.9, 95% CI 1.62-5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI 0.28-0.93) and western (vs central; OR = 0.4, 95% CI 0.17-0.77) parts of Uganda. CONCLUSION: One in five HCPs reported ACT therapeutic ineffectiveness, mostly verbally to supervisors. The existing adverse drug reaction (ADR)-reporting infrastructure could be leveraged to promote the PV of ACT therapeutic ineffectiveness.

Healthcare professionals' perspective can guide post-marketing surveillance of artemisinin-based combination therapy in Uganda.

BACKGROUND: Efficient testing to identify poor quality artemisinin-based combination therapy (ACT) is important to optimize efforts to control and eliminate malaria. Healthcare professionals interact with both ACT and malaria patients they treat and hence could observe, first-hand, suspect poor quality artemisinin-based combinations linked to poor malaria treatment outcomes and the factors associated with inappropriate use or treatment failure. METHODS: A cross-sectional study of 685 HCP perspectives about the efficacy of ACT between June and July 2018 at selected health facilities in Uganda. Medicine samples were obtained from the seven regions of Uganda and tested for quality using the Germany Pharma Health Fund™ minilabs. RESULTS: The average age of the 685 respondents was 30 (SD = 7.4) years. There was an almost equal distribution between male and female respondents (51:49), respectively. Seventy percent (n = 480) were diploma holders and the nurses contributed to half (49%, n = 334) of the study population. Sixty-one percent of the HCPs reported having ever encountered ACT failures while treating uncomplicated malaria. Nineteen percent of HCPs thought that dihydroartemisinin/piperaquine gave the most satisfactory patient treatment outcomes, while 80% HCPs thought that artemether/lumefantrine gave the least satisfactory patient treatment outcomes, possibly due to dosing schedule and pill burden. Healthcare professionals from the Central region (OR = 3.0, CI 0.3-1.0; P = 0.0001), Eastern region (OR = 5.4, CI 2.9-9.8; P = 0.0001) and Northern region (OR = 5.3, CI 2.9-9.9; P = 0.0001) had a higher chance of encountering ACT failure in 4 weeks prior to the survey as compared to those from the western region. Healthcare professionals from private health facilities also had higher chances of encountering ACT failures in past 4 weeks as compared to those from public health facilities (OR = 2.7, CI 1.7-3.9; P = 0.0001). All 192 samples passed the quality screening tests. The random sample of 10% of all samples randomly obtained by the laboratory staff also passed the chemical content analysis and dissolution tests. CONCLUSION: ACT medicines are widely available over-the-counter to the public and it is very difficult to report and monitor a decrease in efficacy or treatment failure. The perspectives of HCPs on treatment failure or lack of efficacy may potentially guide optimization efforts of sampling methodologies for the quality survey of ACT medicines.