Conference Material > Abstract
Nesbitt RC
Epicentre Scientific Day Paris 2023. 2023 June 8
BACKGROUND
Hepatitis E causes high mortality among pregnant women with case fatality risks of 10-25%, and adverse fetal outcomes. Hecolin® is a safe and efficacious vaccine against Hepatitis E, but there is an evidence gap on its safety in pregnant women. In 2015 the WHO recommended its use in response to outbreaks, including vaccinating pregnant women. The first mass reactive vaccination campaign against Hepatitis E was conducted in Bentiu including pregnant women and achieved high administrative vaccination coverage. We aimed to document pregnancy outcomes in a cohort of vaccinated and non-vaccinated pregnant women.
METHODS
An exhaustive pregnancy census was conducted after the second vaccination round from 16 May to 30 June 2022 to recruit women who were pregnant between 1 January 2022 and the interview date. Women were recontacted a minimum of 28 days after expected delivery to assess pregnancy outcome. Categorization of the cohort according to timing of potential vaccine exposure in pregnancy and regression models to evaluate the association between at least one dose in pregnancy and pregnancy outcomes is ongoing.
RESULTS
Of 20,674 women of childbearing age who consented for interview, 3,458 (16.7%) reported being pregnant since 1 January 2022. Women were a mean of 25.5 years old, had a median of 2 previous pregnancies (0-11), and 21 (0.6%) reported experiencing jaundice during their current pregnancy. Overall, 2723 (78.7%) women received at least one dose of Hecolin®. Access to delivery care was high, with 90% of women delivering in a health facility; 357 (10.3%) women reported a complication during delivery and 16 (0.5%) reported a caesarean section. According to interview, 3233 (93.5%) women had a livebirth, and 225 (6.9%) had a pregnancy loss, including 57 (1.6%) reported stillbirths, translating to a stillbirth rate of 17.6/1000 pregnancies, compared to the national estimate of 25.8/1000 pregnancies.
CONCLUSION
It was feasible to implement an observational study on the safety of vaccination in pregnancy alongside the first deployment of Hecolin® in a humanitarian emergency setting. Access to delivery care is reflected in the lower than national average rate of stillbirth in the camp. Results are expected to narrow the evidence gap on the safety of this vaccine in pregnancy.
KEY MESSAGE
A cohort study on the safety of vaccination in pregnancy was implemented alongside the first deployment of Hecolin® in a humanitarian emergency setting. Preliminary results show overall high coverage with at least one dose and access to delivery care among women in the cohort
This abstract is not to be quoted for publication.
Hepatitis E causes high mortality among pregnant women with case fatality risks of 10-25%, and adverse fetal outcomes. Hecolin® is a safe and efficacious vaccine against Hepatitis E, but there is an evidence gap on its safety in pregnant women. In 2015 the WHO recommended its use in response to outbreaks, including vaccinating pregnant women. The first mass reactive vaccination campaign against Hepatitis E was conducted in Bentiu including pregnant women and achieved high administrative vaccination coverage. We aimed to document pregnancy outcomes in a cohort of vaccinated and non-vaccinated pregnant women.
METHODS
An exhaustive pregnancy census was conducted after the second vaccination round from 16 May to 30 June 2022 to recruit women who were pregnant between 1 January 2022 and the interview date. Women were recontacted a minimum of 28 days after expected delivery to assess pregnancy outcome. Categorization of the cohort according to timing of potential vaccine exposure in pregnancy and regression models to evaluate the association between at least one dose in pregnancy and pregnancy outcomes is ongoing.
RESULTS
Of 20,674 women of childbearing age who consented for interview, 3,458 (16.7%) reported being pregnant since 1 January 2022. Women were a mean of 25.5 years old, had a median of 2 previous pregnancies (0-11), and 21 (0.6%) reported experiencing jaundice during their current pregnancy. Overall, 2723 (78.7%) women received at least one dose of Hecolin®. Access to delivery care was high, with 90% of women delivering in a health facility; 357 (10.3%) women reported a complication during delivery and 16 (0.5%) reported a caesarean section. According to interview, 3233 (93.5%) women had a livebirth, and 225 (6.9%) had a pregnancy loss, including 57 (1.6%) reported stillbirths, translating to a stillbirth rate of 17.6/1000 pregnancies, compared to the national estimate of 25.8/1000 pregnancies.
CONCLUSION
It was feasible to implement an observational study on the safety of vaccination in pregnancy alongside the first deployment of Hecolin® in a humanitarian emergency setting. Access to delivery care is reflected in the lower than national average rate of stillbirth in the camp. Results are expected to narrow the evidence gap on the safety of this vaccine in pregnancy.
KEY MESSAGE
A cohort study on the safety of vaccination in pregnancy was implemented alongside the first deployment of Hecolin® in a humanitarian emergency setting. Preliminary results show overall high coverage with at least one dose and access to delivery care among women in the cohort
This abstract is not to be quoted for publication.
Journal Article > ReviewFull Text
Lancet Gastroenterol Hepatol. 2019 February 1; Volume 4 (Issue 2); 135-184.; DOI:10.1016/S2468-1253(18)30270-X
Cooke GS, Andrieux-Meyer I, Applegate TL, Atun R, Burry J, et al.
Lancet Gastroenterol Hepatol. 2019 February 1; Volume 4 (Issue 2); 135-184.; DOI:10.1016/S2468-1253(18)30270-X
Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.
Journal Article > LetterFull Text
Emerg Infect Dis. 2023 February 1; Volume 29 (Issue 2); DOI:10.3201/eid2902.221495
Azman AS, Gignoux E, Nesbitt R, Rumunu J, Aggarwal R, et al.
Emerg Infect Dis. 2023 February 1; Volume 29 (Issue 2); DOI:10.3201/eid2902.221495
Journal Article > LetterFull Text
Emerg Infect Dis. 2008 April 1; Volume 14 (Issue 4); 681-683.; DOI:10.3201/eid1404.070833
Escribà JM, Nakoune E, Recio C, Massamba PM, Matsika-Claquin MD, et al.
Emerg Infect Dis. 2008 April 1; Volume 14 (Issue 4); 681-683.; DOI:10.3201/eid1404.070833
Conference Material > Abstract
Nesbitt RC
Epicentre Scientific Day Paris 2022. 2022 June 1
BACKGROUND
Hepatitis E (HEV) is likely the most common cause of acute viral hepatitis and jaundice worldwide. The virus causes high mortality among pregnant women with case fatality risks of 10-25%, and adverse fetal outcomes. A safe and efficacious 3- dose recombinant vaccine (Hecolin®) has been licensed in China since 2011 and considered for use during outbreaks by the WHO since 2015. South Sudan has reported confirmed Hepatitis E cases for over a decade, with protracted outbreaks occurring in camps of displaced people. Bentiu IDP camp in Unity States hosts over 100,000 people displaced from conflict and flooding. A large outbreak of hepatitis E occurred in 2015, and despite numerous interventions, cases and deaths continue. In response, the MoH and MSF planned the first mass reactive vaccination campaign of the Hecolin® vaccine.
METHODS
The first round of vaccination started on 22 March 2022 and second round on 19 April 2022. The target population was 26,686 individuals aged 16-40 years residing in Bentiu IDP camp. Operational research alongside the vaccination campaign, including clinical surveillance at MSF Bentiu hospital, a case-control study, and a pregnancy cohort, is ongoing to document feasibility, safety and two-dose vaccine effectiveness.
RESULTS
Using a combination of fixed and mobile sites, 49,903 doses were administered during the two rounds of vaccination. Based on administrative population counts, coverage in the first round was 91% and second round was 95%. Clinical surveillance documented 288 suspect hepatitis E cases and 2 deaths from 21 March – 15 May, 2022. Among them, 61.5% of cases and both deaths were children less than 16 years, ineligible for vaccination. HEV IgM RDT positivity overall was 41.6%; 74.6% of RDT confirmed cases had elevated ALT (≥2.5-times ULN) and 29.7% of suspect cases testing negative.
CONCLUSION
The deployment of Hecolin® in a humanitarian emergency setting achieved high administrative vaccination coverage. This experience and the anticipated research results could allow for broader use of the vaccine in the fight against epidemics caused by hepatitis E virus.
KEY MESSAGE
The first mass reactive vaccination campaign against Hepatitis E was conducted in Bentiu IDP camp, South Sudan with high administrative vaccination coverage. Most cases in Bentiu are ineligible for vaccination due to age limitations of the vaccine.
This abstract is not to be quoted for publication.
Hepatitis E (HEV) is likely the most common cause of acute viral hepatitis and jaundice worldwide. The virus causes high mortality among pregnant women with case fatality risks of 10-25%, and adverse fetal outcomes. A safe and efficacious 3- dose recombinant vaccine (Hecolin®) has been licensed in China since 2011 and considered for use during outbreaks by the WHO since 2015. South Sudan has reported confirmed Hepatitis E cases for over a decade, with protracted outbreaks occurring in camps of displaced people. Bentiu IDP camp in Unity States hosts over 100,000 people displaced from conflict and flooding. A large outbreak of hepatitis E occurred in 2015, and despite numerous interventions, cases and deaths continue. In response, the MoH and MSF planned the first mass reactive vaccination campaign of the Hecolin® vaccine.
METHODS
The first round of vaccination started on 22 March 2022 and second round on 19 April 2022. The target population was 26,686 individuals aged 16-40 years residing in Bentiu IDP camp. Operational research alongside the vaccination campaign, including clinical surveillance at MSF Bentiu hospital, a case-control study, and a pregnancy cohort, is ongoing to document feasibility, safety and two-dose vaccine effectiveness.
RESULTS
Using a combination of fixed and mobile sites, 49,903 doses were administered during the two rounds of vaccination. Based on administrative population counts, coverage in the first round was 91% and second round was 95%. Clinical surveillance documented 288 suspect hepatitis E cases and 2 deaths from 21 March – 15 May, 2022. Among them, 61.5% of cases and both deaths were children less than 16 years, ineligible for vaccination. HEV IgM RDT positivity overall was 41.6%; 74.6% of RDT confirmed cases had elevated ALT (≥2.5-times ULN) and 29.7% of suspect cases testing negative.
CONCLUSION
The deployment of Hecolin® in a humanitarian emergency setting achieved high administrative vaccination coverage. This experience and the anticipated research results could allow for broader use of the vaccine in the fight against epidemics caused by hepatitis E virus.
KEY MESSAGE
The first mass reactive vaccination campaign against Hepatitis E was conducted in Bentiu IDP camp, South Sudan with high administrative vaccination coverage. Most cases in Bentiu are ineligible for vaccination due to age limitations of the vaccine.
This abstract is not to be quoted for publication.
Journal Article > ResearchFull Text
J Med Virol. 2005 December 1; Volume 77 (Issue 4); DOI:10.1002/jmv.20487
Nicand E, Armstrong GL, Enouf V, Guthmann JP, Guerin JP, et al.
J Med Virol. 2005 December 1; Volume 77 (Issue 4); DOI:10.1002/jmv.20487
The within-outbreak diversity of hepatitis E virus (HEV) was studied during the outbreak of hepatitis E that occurred in Sudan in 2004. Specimens were collected from internally displaced persons living in a Sudanese refugee camp and two camps implanted in Chad. A comparison of the sequences in the ORF2 region of 23 Sudanese isolates and five HEV samples from the two Chadian camps displayed a high similarity (>99.7%) to strains belonging to Genotype 1. But four isolates collected in one of the Chadian camps were close to Genotype 2. Circulation of divergent strains argues for possible multiple sources of infection.
Conference Material > Abstract
Aumuller J
Epicentre Scientific Day 2024. 2024 May 23
BACKGROUND
In September 2023, the South Sudan Ministry of Health declared an outbreak of hepatitis E virus in Fangak County, Jonglei State. From April to November 2023, MSF identified 169 hepatitis E cases, among them 45% pregnant women. Cases reported at the hospital were severe and the case fatality ratio (CFR) was high with 18 deaths, 53% were women of reproductive age and 42% were pregnant women. In response, MSF together with the Ministry of Health conducted the 2nd ever reactive vaccination campaign with the Hecolin vaccine. The 1st to target exclusively women of reproductive age.
METHODS
This is a descriptive, cross-sectional cluster survey with a two-stage cluster sampling design. The two strata selected were the Old Fangak and Mareang/Toch Payams.
To complement the vaccination coverage estimates, understand perception of the vaccine, and the acceptance of the strategy to vaccinate only women of reproductive age, qualitative methods were utilized following the second round of vaccination.
RESULTS
High coverage was observed of at least one dose of hepatitis E vaccine, according to recall or card, among vaccine eligible women: 94% [95% CI 92-95] in Old Fangak and Mareang /Toch Payams. Coverage of two doses was lower, with estimated coverage of 77% [95% CI 74-80%] according to recall or card. Vaccination coverage was similar in both strata, even in hard-to-reach areas.
While community members reported high acceptance of vaccine, many were critical of the vaccine strategy targeting women aged 16 to 45. This was perceived to conflict with the observed cases of Hepatitis E among the population and physical reproductive age, exclude other vulnerable groups, and not consider community priorities or decision-making structures.
CONCLUSION
The vaccination campaign reached high coverage despite challenging field conditions, and low acceptance of the strategy.
In September 2023, the South Sudan Ministry of Health declared an outbreak of hepatitis E virus in Fangak County, Jonglei State. From April to November 2023, MSF identified 169 hepatitis E cases, among them 45% pregnant women. Cases reported at the hospital were severe and the case fatality ratio (CFR) was high with 18 deaths, 53% were women of reproductive age and 42% were pregnant women. In response, MSF together with the Ministry of Health conducted the 2nd ever reactive vaccination campaign with the Hecolin vaccine. The 1st to target exclusively women of reproductive age.
METHODS
This is a descriptive, cross-sectional cluster survey with a two-stage cluster sampling design. The two strata selected were the Old Fangak and Mareang/Toch Payams.
To complement the vaccination coverage estimates, understand perception of the vaccine, and the acceptance of the strategy to vaccinate only women of reproductive age, qualitative methods were utilized following the second round of vaccination.
RESULTS
High coverage was observed of at least one dose of hepatitis E vaccine, according to recall or card, among vaccine eligible women: 94% [95% CI 92-95] in Old Fangak and Mareang /Toch Payams. Coverage of two doses was lower, with estimated coverage of 77% [95% CI 74-80%] according to recall or card. Vaccination coverage was similar in both strata, even in hard-to-reach areas.
While community members reported high acceptance of vaccine, many were critical of the vaccine strategy targeting women aged 16 to 45. This was perceived to conflict with the observed cases of Hepatitis E among the population and physical reproductive age, exclude other vulnerable groups, and not consider community priorities or decision-making structures.
CONCLUSION
The vaccination campaign reached high coverage despite challenging field conditions, and low acceptance of the strategy.
Conference Material > Abstract
Gignoux EM
Epicentre Scientific Day 2024. 2024 May 23
BACKGROUND
Hepatitis E was first identified in the 1990s, but major epidemics date back to the 1950s. There is no specific treatment, and it can be fatal especially for pregnant women, causing spontaneous abortion and stillbirths. In 2011, the first vaccine was made available, and in 2015, the WHO recommended its use during epidemics, including for pregnant women. However, several major epidemics occurred without vaccine use. The first mass reactive vaccination took place in 2022 at the Bentiu camp in South Sudan, alongside operational research.
METHODS
We assessed vaccination feasibility and acceptance through coverage surveys and conducted focus group discussions on acceptance. We monitored adverse events following immunization (AEFI) for pharmacovigilance. To assess safety in pregnancy, we monitored the pregnancy outcomes of all women identified as pregnant during the vaccination campaign through a census. Despite the significant efficacy shown in a phase 3 clinical trial after three doses, we aimed to evaluate the vaccine's efficacy in South Sudan during an epidemic after administering two doses through a case-control study.
RESULTS
Coverage of at least one dose of the Hecolin vaccine after three rounds was estimated at 86% (95% CI: 84-88), with no cases of severe AEFI. Focus groups revealed strong concern about hepatitis E and high confidence and demand for the vaccine. An emulated target trial showed a relative risk of foetal loss between vaccinated and unvaccinated pregnant women at 1.1 (95% CI: 0.7-1.8). Vaccine effectiveness after two doses was estimated at 88.3% (95% CI: 53.8-97.6) using a test-negative design.
CONCLUSION
We found high vaccine coverage, good acceptance, and demand from the population. There was no evidence of increased risk of foetal loss among vaccinated pregnant women. Despite the small number of cases, the reduced dose regimen appeared effective in reducing disease risk in this highly exposed population.
KEY MESSAGE
Studies from the first mass reactive vaccination against hepatitis E demonstrated high coverage and acceptance, no safety issues among pregnant women, and good effectiveness after two doses.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2024 January 22; Volume 18 (Issue 1); e0011661.; DOI:10.1371/journal.pntd.0011661
Nesbitt RC, Asilaza VK, Gignoux EM, Koyuncu A, Gitahi P, et al.
PLoS Negl Trop Dis. 2024 January 22; Volume 18 (Issue 1); e0011661.; DOI:10.1371/journal.pntd.0011661
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.
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.
Conference Material > Video (talk)
Gignoux EM
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/LJs5Xz