Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children.

BACKGROUND: Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa. METHODS: We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up. RESULTS: The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination. CONCLUSIONS: Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture-confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.).

Antibiotic Use and Stewardship Indicators in the First- and Second-Level Hospitals in Zambia: Findings and Implications for the Future.

Introduction: There are increasing concerns with growing rates of antimicrobial resistance (AMR) across Africa, including in Zambia, enhanced by inappropriate utilization of antibiotics across the sectors. There is a need in hospitals to document current prescribing patterns via point prevalence surveys (PPS) alongside recognized indicators to improve future use. The findings can subsequently be used to develop and instigate appropriate antimicrobial stewardship programs (ASPs) to improve the quality of future antimicrobial prescribing across Zambia. This includes encouraging the prescribing of 'Access' over 'Watch' and 'Reserve' antibiotics where pertinent. Methods: A PPS was undertaken using the WHO methodology among 10 first- and second-level public hospitals across the 10 provinces of Zambia. A sampling process was used to select the hospitals. Results: The prevalence of antibiotic use among the in-patients was 307/520 (59.0%), with a high rate of empiric prescribing of ceftriaxone at 36.1% of all antibiotics prescribed (193/534). The reason for antibiotic use was recorded in only 15.7% of occasions and directed treatment prescribed in only 3.0% of occasions. Compliance with the national standard treatment guidelines (STGs) was also low at only 27.0% of occasions. Conclusion: High empiric prescribing, limited documentation of the rationale behind antibiotic prescribing, high use of 'Watch' antibiotics, and limited compliance to STGs among surveyed hospitals requires the urgent instigation of ASPs across Zambia to improve future prescribing.

Practical Pharmacist-Led Interventions to Improve Antimicrobial Stewardship in Ghana, Tanzania, Uganda and Zambia.

The World Health Organisation (WHO) and others have identified, as a priority, the need to improve antimicrobial stewardship (AMS) interventions as part of the effort to tackle antimicrobial resistance (AMR). An international health partnership model, the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme, was established between selected countries in Africa (Ghana, Tanzania, Zambia and Uganda) and the UK to support AMS. This was funded by UK aid under the Fleming Fund and managed by the Commonwealth Pharmacists Association (CPA) and Tropical Health and Education Trust (THET). The primary aims were to develop local AMS teams and generate antimicrobial consumption surveillance data, quality improvement initiatives, infection prevention and control (IPC) and education/training to reduce AMR. Education and training were key components in achieving this, with pharmacists taking a lead role in developing and leading AMS interventions. Pharmacist-led interventions in Ghana improved access to national antimicrobial prescribing guidelines via the CwPAMS mobile app and improved compliance with policy from 18% to 70% initially for patients with pneumonia in one outpatient clinic. Capacity development on AMS and IPC were achieved in both Tanzania and Zambia, and a train-the-trainer model on the local production of alcohol hand rub in Uganda and Zambia. The model of pharmacy health partnerships has been identified as a model with great potential to be used in other low and middle income countries (LMICs) to support tackling AMR.

Antibiotic Prescribing Patterns in Ghana, Uganda, Zambia and Tanzania Hospitals: Results from the Global Point Prevalence Survey (G-PPS) on Antimicrobial Use and Stewardship Interventions Implemented.

Antimicrobial resistance (AMR) remains an important global public health issue with antimicrobial misuse and overuse being one of the main drivers. The Global Point Prevalence Survey (G-PPS) of Antimicrobial Consumption and Resistance assesses the prevalence and the quality of antimicrobial prescriptions across hospitals globally. G-PPS was carried out at 17 hospitals across Ghana, Uganda, Zambia and Tanzania. The overall prevalence of antimicrobial use was 50% (30-57%), with most antibiotics prescribed belonging to the WHO 'Access' and 'Watch' categories. No 'Reserve' category of antibiotics was prescribed across the study sites while antimicrobials belonging to the 'Not Recommended' group were prescribed infrequently. Antimicrobials were most often prescribed for prophylaxis for obstetric or gynaecological surgery, making up between 12 and 18% of total prescriptions across all countries. The most prescribed therapeutic subgroup of antimicrobials was 'Antibacterials for systemic use'. As a result of the programme, PPS data are now readily available for the first time in the hospitals, strengthening the global commitment to improved antimicrobial surveillance. Antimicrobial stewardship interventions developed included the formation of AMS committees, the provision of training and the preparation of new AMS guidelines. Other common interventions included the presentation of findings to clinicians for increased awareness, and the promotion of a multi-disciplinary approach to successful AMS programmes. Repeat PPS would be necessary to continually monitor the impact of interventions implemented. Broader participation is also encouraged to strengthen the evidence base.