Efficacy and feasibility of SMS m-Health for the detection of adverse events following immunisation (AEFIs) in resource-limited setting-The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised control trial.

INTRODUCTION: The mHealth active participant centred (MAPC) adverse events following immunisation (AEFI) surveillance is a promising area for early AEFI detection resulting in risk minimisation. Passive (spontaneous) AEFI surveillance is the backbone for vaccine pharmacovigilance, but has inherent drawbacks of under reporting, and requires strengthening with active surveillance methods. AIM: The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised controlled trial (RCT) sought to evaluate the efficacy and feasibility of AEFI detection using a short message service (SMS) and computer assisted telephone interview (CATI) approach. METHOD: A multicentre Zm-STARSS RCT enrolled consented adult vaccinees or parents or guardians of children receiving vaccines, including COVID-19 vaccines, at study vaccination clinics. At enrolment study participants were randomised to either SMS-CATI group or control group. SMS prompts were sent on days 0-2 and 14 post-vaccination to SMS-CATI group to ascertain if a medically attendance or attention due to an Adverse event following immunisation (AEFI) had occurred. However, no SMSs were sent to the control group. SMS-CATI group who responded "Yes" to SMS prompts were interviewed by research healthcare workers (RHCWs) who completed a CATI to determine if an AEFI had occurred whilst an AEFI in control group was determined from passive AEFI reporting channels. The primary study outcome was the AEFI detection rate in the SMS-CATI group compared to the control group. RESULTS: A total of 4560 participants were enrolled after signed informed consent, all were encouraged to report AEFIs and randomised automatically on 1:1 basis into two arms SMS CATI intervention group (n = 2280) and a control passive AEFI surveillance group (n = 2280) on day 0. A total of 704 (31 %) participants responded to the SMS prompts, with 75 % (528/704) indicating "No" and 25 % (176/704) reporting "Yes" to seeking medical attention or attendance post-immunisation. 69 % (121/176) completed a CATI survey but in only 36 % (44/121) was the AEFI confirmed. There were no AEFIs reported in control group participants. The detection rate of a AEFI associated with medically attendance or attention using the SMS-CATI methodology was 2 % (44/2280) on an intention to treat cohort. CONCLUSION: Despite the low SMS response and CATI completion rate, we demonstrated that Zm-STARSS SMS system improves AEFI detection compared to passive AEFI surveillance. We recommend that this and similar approaches are explored further using cost-effective multi-channel digital approaches for holistic pharmacovigilance to improve AEFI detection in Low Middle-Income Countries (LMICs) for all vaccines.

Enhanced surveillance for adverse events following immunization during the 2019 typhoid conjugate vaccine campaign in Harare, Zimbabwe.

BACKGROUND: During February 25-March 4, 2019, Zimbabwe's Ministry of Health and Child Care conducted an emergency campaign using 342,000 doses of typhoid conjugate vaccine (TCV) targeting individuals 6 months-15 years of age in eight high-risk suburbs of Harare and up to 45 years of age in one suburb of Harare. The campaign represented the first use of TCV in Africa outside of clinical trials. METHODS: Three methods were used to capture adverse events during the campaign and for 42 days following the last dose administered: (1) active surveillance in two Harare hospitals, (2) national passive surveillance, and (3) a post-campaign coverage survey. RESULTS: Thirty-nine adverse events were identified during active surveillance, including 19 seizure cases (16 were febrile), 16 hypersensitivity cases, 1 thrombocytopenia case, 1 anaphylaxis case, and two cases with two conditions. Only 21 (54%) of 39 patients were hospitalized and 38 recovered without sequelae. Attack rates per 100,000 TCV doses administered were highest for seizures (6.27) and hypersensitivity (5.02). Only 6 adverse events were reported through passive surveillance by facilities other than the two active surveillance hospitals. A total of 177 (10%) of 1,817 vaccinees surveyed reported experiencing an adverse event during the post-campaign coverage survey, of which 25 (14%) sought care. CONCLUSIONS: In line with previous evaluations of TCV, enhanced adverse event monitoring during an emergency campaign supports the safety of TCV. The majority of reported events were minor or resulted in recovery without long-term sequelae. Attack rates for seizures and hypersensitivity were low compared with previous active surveillance studies conducted in Kenya and Burkina Faso. Strengthening adverse event monitoring in Zimbabwe and establishing background rates of conditions of interest in the general population may improve future safety monitoring during new vaccine introductions.

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

INTRODUCTION: Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. OBJECTIVES: To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). METHODS: We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. RESULTS: A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). CONCLUSION: Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for psychosis. There is a need to carefully manage TB/HIV co-infected patients, due to the higher risk of adverse drug reactions which may lead to poor treatment adherence and outcomes.

Experiences and Lessons From Implementing Cohort Event Monitoring Programmes for Antimalarials in Four African Countries: Results of a Questionnaire-Based Survey.

INTRODUCTION: Cohort event monitoring (CEM) is an intensive method of post-marketing surveillance for medicines safety. The method is based on prescription event monitoring, which began in the 1970s, and has since been adapted by WHO for monitoring the safety of medicines used in Public Health Programmes. CEM aims to capture all adverse events that occur in a defined group of patients after starting treatment with a specific medicine during the course of routine clinical practice. OBJECTIVE: The aims of this study were to describe the experiences of National Pharmacovigilance Centres (NCs) that have used CEM to monitor artemisinin-based combination therapy (ACT) for uncomplicated malaria in the African setting, to raise awareness of some of the challenges encountered during implementation and to highlight aspects of the method that require further consideration. METHOD: A questionnaire-based survey was conducted to capture the experiences of NCs that have implemented CEM for active post-marketing surveillance of antimalarial medicines in sub-Saharan Africa. Six NCs were identified as having implemented CEM programmes and were invited to participate in the survey; five NCs indicated willingness to participate and were sent the questionnaire to complete. RESULTS: Four NCs responded to the survey-Ghana, Kenya, Nigeria and Zimbabwe-providing information on the implementation of a total of six CEM programmes. Their experiences indicate that CEM has helped to build pharmacovigilance capacity within the participating NCs and at the monitoring sites, and that healthcare providers (HCPs) are generally willing to participate in implementing the CEM method. All of the programmes took longer than expected to complete: contributing factors included a prolonged enrolment period and unexpectedly slow data entry. All of the programmes exceeded their budget by 11.1-63.2 %. Data management was identified as a challenge for all participating NCs. CONCLUSIONS: The reported experiences of four NCs that have undertaken CEM studies on ACTs indicate that CEM has helped to build pharmacovigilance capacity within NCs and monitoring sites and that HCPs are willing to participate in CEM programmes; however, the method was found to be labour intensive and data management was identified as a challenge. Reducing the workload associated with CEM, particularly in relation to data management, and integrating the method into the routine work of HCPs and NCs should be considered for future implementation.