Hepatitis E in Bentiu: analysis of data from the first reactive mass vaccination campaign

Methodology

Vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination 

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.

Methodology

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.

Résults

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).

Conclusion

These results reveal moderate to high efficacy in preventing hepatitis E with only the first two doses. This is a significant finding in epidemic contexts, where logistical constraints make it difficult to comply with the three-dose schedule. This result paves the way for the use of a two-dose regimen, better suited to emergency situations where health infrastructures are limited."

Methodology 

Emulated target trial

Results:

Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9).

Conclusion 

In comparing the groups, the researchers found no significant increase in the risk of vaccine-related fetal loss. This provides evidence of the vaccine's safety for a large number of vaccinated pregnant women. 

Prior to this study, the only available information came from a small number of women inadvertently vaccinated during trials in China.

Impact 

These results contributed to new recommendations by the WHO's Strategic Advisory Group of Experts (SAGE). In March 2024, the SAGE recommended priority vaccination of women of childbearing age in regions where hepatitis E is endemic (1). The group also validated the option of a two-dose vaccine schedule (at 0 and 1 month) as an acceptable alternative to the three-dose schedule, particularly in fragile or conflict-affected areas. In addition, the International Coordinating Group on Vaccine Provision (ICG) approved the establishment of the first global stockpile of hepatitis E vaccine. 

(1) https://www.who.int/publications/i/item/WER-9922-285-306

Methodology

Latent class model to estimate test performance and accelerated failure time models to estimate time from jaundice onset to a negative test for PCR and ELISA.

Results

Among 893 suspected cases, test sensitivity declined with time from jaundice onset. Within 30 days of jaundice onset, PCR sensitivity was 73% (95% Credible Interval (CrI) 27, 90), compared to 86% for RDT (95% CrI: 74, 93), and 95% for ELISA (95% CrI: 91, 98). Specificity was high across tests: PCR at 98% (95% CrI: 98, 99), RDT at 95% (95% CrI: 93, 96), and ELISA at 95% (95% CrI: 93, 96). Median time from jaundice onset to negative test was 19 days (95% CI: 17, 21) for PCR and 113 days (95% CI: 87, 163) for ELISA.

Conclusion 

The Assure IgM RDT showed higher sensitivity for identifying hepatitis E than PCR and similar specificity to IgM ELISA, supporting its use in surveillance. Care seeking delays can greatly influence the interpretation of diagnostic tests.