In 2021 in response to an outbreak of hepatitis E in Bentiu internally displaced persons camp the South Sudanese Ministry of Health with support from Médecins Sans Frontières implemented the first-ever mass reactive vaccination campaign with HEV239 (Hecolin; Innovax, Xiamen, China). We conducted qualitative research to assess knowledge, attitudes, and practices related to hepatitis E and the hepatitis E vaccine. We conducted 8 focus group discussions (FGDs) with community leaders, the general population of vaccine-eligible adults, vaccine-eligible pregnant women (vaccinated and non-vaccinated), and healthcare workers. FGDs were separate by gender and were audio recorded, transcribed, and translated to English. Two coders used inductive thematic analysis to organize emergent themes. Data were collected in November 2022. Most participants had experiences with hepatitis E (e.g., infected themselves or knowing someone that had been infected) and viewed hepatitis E as a dangerous disease. Participants believed children, pregnant women, and older persons were the highest risk groups and frequently made requests for additional hepatitis E vaccination campaigns and expanded eligibility criteria for vaccination. Knowledge of the negative impacts of hepatitis E and trusted relationships with the organizations offering the vaccine were key facilitators of vaccine acceptance. The primary barriers to vaccination were practical issues related to being away from the camp during the campaign or not knowing about the campaign, but participants shared that some in the community were unvaccinated due to fears about injections, social pressure, misinformation, and concerns about why some groups were eligible for vaccination and not others (e.g., young children). Personal experiences with hepatitis E illness, perceived severity of illness, and confidence in organizations recommending the vaccine were drivers of high demand for hepatitis E vaccines in the first-ever use of the vaccine in an outbreak setting. Addressing practical issues related to population mobility can improve coverage in future campaigns.

BACKGROUND

Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.

METHODS

In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points.

RESULTS

A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.

CONCLUSIONS

A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.

BACKGROUND

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis, particularly in Asia and Africa, where HEV genotypes 1 and 2 are prevalent. Although a recombinant vaccine, Hecolin, is available, it has not been used to control outbreaks. The licensed three-dose regimen might pose challenges for it to be an impactful outbreak control tool. Our study aimed to estimate the effectiveness of two doses of Hecolin in the context of the first-ever reactive use of the vaccine.

METHODS

We conducted a case-control study during an HEV outbreak in the Bentiu internally displaced persons camp, South Sudan. Patients with acute jaundice syndrome (suspected cases) seeking care at the Médecins Sans Frontières hospital were screened for study eligibility. Eligible participants were those that had been eligible for vaccination (ie, living in the camp and aged 16-40 years). Confirmed cases were defined as individuals who tested positive for hepatitis E by RT-PCR or anti-HEV IgM ELISA. Each case was matched to six controls by age, sex, pregnancy status, and residence. Self-reported vaccination status was verified through vaccination cards. The primary analysis was two-dose vaccine effectiveness, which we estimated with a matched case-control design using conditional logistic regression models. In secondary analyses we estimated vaccine effectiveness using a test-negative design and the screening method. We used test-negative cases and their matched controls as a bias indicator analysis to help quantify potential health seeking behaviour biases.

FINDINGS

Between May 10 and Dec 30, 2022, we identified 859 patients with suspected hepatitis E. Of these, 201 met the eligibility criteria and 21 cases had laboratory confirmed hepatitis E. Among the confirmed cases, 10 (48%) were unvaccinated compared with 33 (27%) of 121 matched controls. In the primary analysis we estimated an unadjusted two-dose vaccine effectiveness of 67·8% (95% CI -28·6 to 91·9), and a two-dose vaccine effectiveness of 84·0% (-208·5 to 99·2) after adjustment for potential confounders. The bias indicator analysis suggested that test-negative cases might have been more likely to have been vaccinated than their matched community controls due to different health-care seeking behaviours, potentially meaning underestimation of effectiveness estimates. The test-negative design, which uses facility-matched controls, led to an adjusted two-dose effectiveness of 89·4% (56·4 to 98·0).

INTERPRETATION

Despite the small sample size, our estimates provide evidence of effectiveness of a two-dose regimen against HEV genotype 1 during a protracted outbreak, supporting its use in similar contexts.

BACKGROUND

In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger.

METHODS

In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign. Independently sampled carriage surveys were done among 2268 households 6 months before and after vaccination, collecting nasopharyngeal swabs from healthy children for culture and serotyping; those with contraindication to nasopharyngeal swabbing were excluded. The primary outcome was nasopharyngeal carriage of vaccine-serotype pneumococcus. We tested whether vaccine-type carriage was reduced in full-dose versus control clusters; and whether fractional doses were non-inferior to full-doses (lower bound 95% CI more than -7·5%), using generalised estimating equations to analyse cluster summaries at baseline and follow-up, controlling for covariates to estimate risk differences and their 95% CIs. The study is registered with ClinicalTrials.gov (NCT05175014) and the Pan-African Clinical Trials Registry (PACTR20211257448484).

FINDINGS

Surveys were done between Dec 22, 2021, and March 18, 2022, and between Dec 12, 2022, and March 9, 2023. The vaccination campaign ran from June 15 to Aug 2, 2022. Participants' characteristics were consistent across surveys and groups. Pre-vaccination, vaccine-type carriage was 15·6% (149 of 955 participants) in the full-dose group, 17·9% (170 of 948) in the fractional-dose group, and 18·8% (60 of 320) in the control group. Post-vaccination, vaccine-type carriage was 4·6% (44 of 967) in the full-dose group, 8·0% (77 of 962) in the fractional-dose group, and 16·5% (53 of 321) in the control group. The primary analysis showed a risk difference of -16·2% (95% CI -28·6 to -3·0) between the full-dose group and control group (p=0·002 for superiority), and -3·8% (-6·1 to -1·6) between the full-dose group and fractional-dose group, meeting the non-inferiority criteria. No adverse events were judged to be related to vaccination.

INTERPRETATION

Multi-age cohort campaigns had a marked effect on vaccine-type carriage and fractional-dose campaigns met non-inferiority criteria. Such campaigns should be considered in low-coverage settings, including humanitarian emergencies, to accelerate population protection.

BACKGROUND

Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

METHODS

We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON IFN-γ release assay [IGRA] and tuberculin skin test [TST]), and tuberculosis incidence. Cohort studies were included only for countries with a mandatory neonatal BCG vaccination policy. Exclusion criteria were previous or current tuberculosis disease, HIV infection, tuberculosis preventive treatment usage, and for household contacts, a positive baseline IGRA or TST test and young children aged 0–2 years; for randomised controlled trials, TST results within 2 years after random assignation were excluded. We contacted the investigators of the identified studies to provide IPD. We compared the protective efficacy of the BCG vaccine against M tuberculosis infection with that against tuberculosis disease using mixed-effects, multivariable proportional hazards modelling, by study type, M tuberculosis infection test (IGRA and TST), cutoff for defining test positivity, age, sex, and latitude.

FINDINGS

We identified 79 studies eligible for full screening and of these, IPD datasets from 14 studies were included in our analysis: 11 household contact studies (29 147 participants), two adolescent cohort studies (11 368 participants), and one randomised controlled trial (2963 participants). Among 28 188 participants we found no protection by the BCG vaccine against TST conversion regardless of cutoff in any type of study. Among 1491 household contacts, but not among 5644 adolescents, the BCG vaccine protected against QuantiFERON conversion at the primary cutoff of 0·7 IU/mL or more with the adjusted hazard ratio (0·65, 95% CI 0·51–0·82) being consistent with that for protection against disease (0·68, 0·18–2·59). Protection against QuantiFERON conversion at cutoff of 0·35 IU/mL or more (0·64, 0·51–0·81) was similar.

INTERPRETATION

Protection from the BCG vaccination against M tuberculosis infection, measured as QuantiFERON conversion, is inconsistent across different groups. Among groups with recent household exposure, QuantiFERON conversion is consistent with protection against disease and could be evaluated as a proxy for disease in tuberculosis vaccine trials. We found that TST lacks value for prevention in phase 2b proof-of-concept trials.

INTRODUCTION

Migrant populations (asylum seekers, permit holders, refugees, and undocumented migrants) living in South Africa face various individual, social, and physical circumstances that underpin their decisions, motivation, and ability to receive the COVID-19 vaccine. We conducted a qualitative study to explore the experiences and perceptions of migrant populations in South Africa on COVID-19 vaccines to inform recommendations for improved COVID-19 immunization.

METHODS

We conducted an Interpretative Phenomenological Analysis (IPA) with 20 asylum seekers, permit holders, refugees, and undocumented migrants living in South Africa. We applied a maximum variation purposive sampling approach to capture all three categories of migrants in South Africa. Semi-structured interviews were conducted and recorded electronically with consent and permission from the study participants. The recordings were transcribed and analyzed thematically following the IPA using Atlas.ti version 9.

RESULTS

Four major reflective themes emanated from the data analysis. (1) While some migrants perceived being excluded from the South African national immunization program at the level of advertisement and felt discriminated against at the immunization centers, others felt included in the program at all levels. (2) Skepticism, myths, and conspiracy theories around the origin of SARS-CoV-2 and the COVID-19 vaccine are pervasive among migrant populations in South Africa. (3) There is a continuum of COVID-19 vaccine acceptance/hesitancy ranging from being vaccinated through waiting for the chance to be vaccinated to refusal. (4) Accepting the vaccine or being hesitant follows the beliefs of the participant, knowledge of the vaccine’s benefits, and lessons learned from others already vaccinated.

CONCLUSION

COVID-19 vaccine inclusiveness, awareness, and uptake should be enhanced through migrant-aware policies and actions such as community mobilization, healthcare professional training, and mass media campaigns.

BACKGROUND

Zaire Ebolavirus disease (EVD) outbreaks can be controlled using rVSV-ZEBOV vaccination and other public health measures. People in high-risk areas may have pre-existing antibodies from asymptomatic Ebolavirus exposure that might affect response to rVSV-ZEBOV. Therefore, we assessed the impact pre-existing immunity had on post-vaccination IgG titre, virus neutralisation, and reactogenicity following vaccination.

METHODS

In this prospective cohort study, 2115 consenting close contacts (“proches”) of EVD survivors were recruited. Proches were vaccinated with rVSV-ZEBOV and followed up for 28 days for safety and immunogenicity. Anti-GP IgG titre at baseline and day 28 was assessed by ELISA. Samples from a representative subset were evaluated using live virus neutralisation.

RESULTS

Ten percent were seropositive at baseline. At day 28, IgG in baseline seronegative (GMT 0.106 IU/ml, 95% CI: 0.100 to 0.113) and seropositive (GMT 0.237 IU/ml, 0.210 to 0.267) participants significantly increased from baseline (both p < 0.0001). There was strong correlation between antibody titres and virus neutralisation in day 28 samples (Spearman’s rho 0.75). Vaccinees with baseline IgG antibodies against Zaire Ebolavirus had similar safety profiles to those without detectable antibodies (63.6% vs 66.1% adults experienced any adverse event; 49.1% vs 60.9% in children), with almost all adverse events graded as mild. No serious adverse events were attributed to vaccination. No EVD survivors tested positive for Ebolavirus by RT-PCR.

CONCLUSIONS

These data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection whose state does not blunt rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required.

BACKGROUND

Little is known about attitudes towards COVID-19 vaccination in sub-Saharan Africa, where immunisation coverage is the lowest in the world.

AIM

The study aimed to identify factors associated with COVID-19 vaccine hesitancy and uptake in Cameroon, and assess changes in these factors over a period of time.

SETTING

The study was conducted in the ten regions of Cameroon.

METHODS

The authors conducted a two-phase cross-sectional survey in the 10 regions of Cameroon, from July 2021 to August 2021 (Phase one) and from August 2022 to September 2022 (Phase two). We analysed reasons for vaccine hesitancy descriptively and used logistic regression to assess factors associated with hesitancy.

RESULTS

Overall, we enrolled 12 109 participants: 6567 (54.23%) in Phase one and 5542 (45.77%) in Phase two. Of these, 8009 (66.14%) were not interested in receiving the COVID-19 vaccine (n = 4176 in Phase one, n = 3833 in Phase two). The refusal rate increased significantly in the northern region from 27.00% in Phase 1 to 60.00% in Phase two. The leading contributor to COVID-19 vaccine hesitancy was fear that the vaccine was dangerous, which was significantly associated (95% confidence interval [CI], p < 0.05%) with vaccine refusal in both phases. Overall, 32.90% of participants (n = 2578) perceived the COVID-19 vaccine to be dangerous. Advanced age, male gender, Muslim religion and low level of education were associated with vaccine acceptance. Participants reported that healthcare workers were the most trusted source of information about the COVID-19 vaccine by 5005 (42.84%) participants.

CONCLUSION

Despite the investment of the Ministry of Health and its partners in community engagement, focussing on communication about the vaccine efficacy, tolerance and potential adverse events, fear of the vaccine remains high, likely leading to vaccine hesitancy in Cameroon between 2021 and 2022.

CONTRIBUTION

The study highlight regional variations in COVID-19 vaccine acceptance in Cameroon, with factors age, gender, religion and education influencing willingness to vaccine. Trust in health workers was high, indicating that, tailored, community-led vaccination strategies are key for improving vaccine uptake, not only for COVID-19 but also for future epidemics.

BACKGROUND

In 2019–2020, preventative Oral Cholera Vaccine campaigns were conducted in 24/32 non-contiguous health areas of Goma, DR Congo. In August 2022, we measured coverage and factors potentially influencing success of the delivery strategy.

METHODS

We used random geo-sampled stratified cluster survey to estimate OCV coverage and assess population movement, diarrhea history, and reasons for non-vaccination.

RESULTS

603 households were visited. Coverage with at least one dose was 46.4 % (95 %CI: 41.8–51.0), and 50.1 % (95 %CI: 45.4–54.8) in areas targeted by vaccination compared to 26.3 % (95 %CI: 19.2–34.9) in non-targeted areas. Additionally, 7.0 % of participants reported moving from outside Goma since 2019, and 5.4 % reported history of severe diarrhea. Absence and unawareness were the main reasons for non-vaccination.

CONCLUSION

Results suggest that targeting non-contiguous urban areas had a coverage-diluting effect. Targeting entire geographically contiguous areas, adapted distribution, and regular catch-up campaigns are operational recommendations to reach higher coverages arising from the study.

BACKRGOUND

The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature.

METHODS

We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018-20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times.

FINDINGS

1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70-92).

INTERPRETATION

This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo.