Vaccination coverage and adverse events following a reactive vaccination campaign against hepatitis E in Bentiu displaced persons camp, South Sudan.

INTRODUCTION: Hepatitis E (HEV) genotypes 1 and 2 are the common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 31% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16-40 years old, including pregnant women. METHODS: We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp. RESULTS: We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84-88%), 73% (95% CI 70-75%) with two or more doses and 58% (95% CI 55-61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue. CONCLUSIONS: We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response.

Effectiveness of case-area targeted interventions including vaccination on the control of epidemic cholera: protocol for a prospective observational study.

INTRODUCTION: Cholera outbreaks in fragile settings are prone to rapid expansion. Case-area targeted interventions (CATIs) have been proposed as a rapid and efficient response strategy to halt or substantially reduce the size of small outbreaks. CATI aims to deliver synergistic interventions (eg, water, sanitation, and hygiene interventions, vaccination, and antibiotic chemoprophylaxis) to households in a 100-250 m 'ring' around primary outbreak cases. METHODS AND ANALYSIS: We report on a protocol for a prospective observational study of the effectiveness of CATI. Médecins Sans Frontières (MSF) plans to implement CATI in the Democratic Republic of the Congo (DRC), Cameroon, Niger and Zimbabwe. This study will run in parallel to each implementation. The primary outcome is the cumulative incidence of cholera in each CATI ring. CATI will be triggered immediately on notification of a case in a new area. As with most real-world interventions, there will be delays to response as the strategy is rolled out. We will compare the cumulative incidence among rings as a function of response delay, as a proxy for performance. Cross-sectional household surveys will measure population-based coverage. Cohort studies will measure effects on reducing incidence among household contacts and changes in antimicrobial resistance. ETHICS AND DISSEMINATION: The ethics review boards of MSF and the London School of Hygiene and Tropical Medicine have approved a generic protocol. The DRC and Niger-specific versions have been approved by the respective national ethics review boards. Approvals are in process for Cameroon and Zimbabwe. The study findings will be disseminated to the networks of national cholera control actors and the Global Task Force for Cholera Control using meetings and policy briefs, to the scientific community using journal articles, and to communities via community meetings.

A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain.

BACKGROUND: In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in "Controlled Temperature Chain" (CTC; up to 40 °C for <30 days before administration), compared to standard cold chain (SCC; 2-8 °C). Prior to the study, stability parameters of TT-CTC were shown to meet international requirements. METHODS: A cluster randomized, non-inferiority trial was conducted in Moïssala district, Chad, December 2012-March 2013. Thirty-four included clusters were randomized to CTC or SCC. Women aged 14-49 years, eligible for TT vaccination and with a history of ≤1 TT dose, received two TT doses 4 weeks apart. Participants were blinded to allocation strategy. Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TTSCC-TTCTC) <5% and ratio of GMCs (TTSCC/TTCTC) <1.5. Adverse events were monitored at health centers and at next contact with participants. RESULTS: A total of 2128 women (CTC=1068; SCC=1060) were recruited. Primary intention to vaccinate analysis included 1830 participants; 272 of these were included in the seroconversion analysis. Seroconversion was reached by >95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded. CONCLUSIONS: This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained.