Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model.

OBJECTIVES: Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS: The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS: As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of  ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION: INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER: Not applicable as this is a retrospective study.

Seroprevalence and Shifting Endemicities of Hepatitis A Virus Infection in Two Different Geographical Areas in the Philippines.

INTRODUCTION: Infection with hepatitis A virus (HAV) is often asymptomatic in young children, but most adolescents and adults will have symptoms ranging from nausea and tiredness to acute liver failure and even death. The risk of severe disease is higher in older adults and people with pre-existing liver disease. Immunization is recommended in regions with low HAV endemicity levels, i.e., where people get infected later in life. In the Philippines, recent epidemiologic data on HAV infection are lacking. The objective of this study was to assess age-specific seroprevalence and evaluate risk factors associated with HAV seropositivity. METHODS: People from two geographic areas (urban and rural) were recruited/enrolled and stratified by age group. HAV-specific immunoglobulin G (IgG) antibodies were measured with a chemiluminescent microparticle immunoassay. Sociodemographic parameters, hepatitis medical history, disease knowledge, hygiene measures and sanitation were assessed via a purpose-made questionnaire. Age at midpoint of population immunity (AMPI) was estimated using Kaplan-Meier curves. Logistic regression analyses were carried out to determine factors that were statistically significantly associated (p < 0.05) with HAV seropositivity. RESULTS: Overall, 1242 participants were included in the analysis; 250/602 (41.5%) participants from urban regions and 283/640 (44.2%) participants from rural regions tested positive for HAV IgG antibodies. AMPI was 35 and 37 years for the rural and urban region, respectively. Higher education was associated with lower HAV seropositivity prevalence ratios, while not living in the same region for the last 5 years, regularly consuming street food and lack of handwashing after defecation were associated with a higher likelihood of HAV seropositivity. CONCLUSION: Results suggest that HAV endemicity is low in the Philippines. Factors associated with HAV seropositivity were traveling, consuming street food and lack of basic hygienic gestures. Immunization might be an option to protect vulnerable populations against severe hepatitis A disease.

Hepatitis A virus (HAV) is transmitted via the fecal-oral route through consumption of contaminated food or water or by close contact with an infected person. In children, HAV is usually of no concern, but in adults and people with existing liver disease, HAV infection can lead to severe symptoms and even death. In areas where most people get hepatitis during childhood (high endemicity), vaccination is not required, since people acquire life-long immunity after infection. In regions with low and intermediate HAV endemicity, people may remain at risk of infection later in life and vaccination could be considered to prevent severe HAV disease and its associated complications. In the Philippines, the current endemicity level is unknown. The goal of this study was to determine the endemicity level in the Philippines and to determine risk factors for HAV infection. We measured the proportion of people (by age group) who had previously been infected with HAV. Results showed that by age of 5 years < 20% of the study population was infected by HAV. By the age of 37 years in the urban population and 35 years in the rural population, 50% of people tested positive for HAV antibodies, indicating previous infection. This means that the Philippines has low HAV endemicity. Risk factors for HAV seropositivity were traveling, regularly eating street food and not washing hands after defecation. Vaccination against HAV might be of benefit in the Philippines, especially early in life to prevent most severe outcomes in adulthood.

Global outbreaks of foodborne hepatitis A: Systematic review and meta-analysis.

Hepatitis A Virus (HAV) is a significant threat in terms of food safety. A systematic literature search with the research question "What are the clinical outcomes of foodborne Hepatitis A virus infections?" was conducted. The pooled estimate of the outcomes-mortality, hospitalization, and severity rates, along with a 95% confidence interval (CI), was estimated. After screening, 33 studies were included for the data extraction and meta-analysis. The pooled prevalence of hospitalization among the HAV-positive patients was estimated to be 32% (95% CI 21-44), with high heterogeneity (I2 = 98%, p < 0.01). Australia had the highest hospitalization rate, with 82%, followed by Europe (42%). The hospitalization rate showed a significantly increasing trend (beta = 0.015, p=0.002) over the period. The pooled prevalence of mortality among the HAV-positive patients was estimated to be <1%, with low heterogeneity (I2 = 5%, p = 0.39). A wide range of food products were linked with the HAV outbreaks.

Expression and Purification of His-Tagged Variants of Human Hepatitis A Virus 3C Protease.

BACKGROUND: Protease 3C (3Cpro) is the only protease encoded in the human hepatitis A virus genome and is considered a potential target for antiviral drugs due to its critical role in the viral life cycle. Additionally, 3Cpro has been identified as a potent inducer of ferroptosis, a newly described type of cell death. Therefore, studying the molecular mechanism of 3Cpro functioning can provide new insights into viral-host interaction and the biological role of ferroptosis. However, such studies require a reliable technique for producing the functionally active recombinant enzyme. OBJECTIVE: Here, we expressed different modified forms of 3Cpro with a hexahistidine tag on the N- or C-terminus to investigate the applicability of Immobilized Metal Ion Affinity Chromatography (IMAC) for producing 3Cpro. METHODS: We expressed the proteins in Escherichia coli and purified them using IMAC, followed by gel permeation chromatography. The enzymatic activity of the produced proteins was assayed using a specific chromogenic substrate. RESULTS: Our findings showed that the introduction and position of the hexahistidine tag did not affect the activity of the enzyme. However, the yield of the target protein was highest for the variant with seven C-terminal residues replaced by a hexahistidine sequence. CONCLUSION: We demonstrated the applicability of our approach for producing recombinant, enzymatically active 3Cpro.

Gender differences in hepatitis A seropositivity rates according to the Republic of Korea's vaccination policy.

Objectives: This study aimed to investigate differences in the anti-hepatitis A (HAV) antibody seropositivity rate by age and gender. Methods: We collected information on anti-HAV immunoglobulin G and immunoglobulin M status from samples submitted for HAV antibody testing in 2012-2022. A total of 1,333,615 cases were included in the analysis. Results: By age, the seropositivity rate was represented by a U-shaped curve, such that the rate was low for the group aged 20 to 39 years and higher in those who were younger or older. Over time, the curve shifted rightward, and the seropositivity rate declined gradually in the group aged 35 to 39 years and older. A gender-based difference in antibody seropositivity rate was especially noticeable in the group aged 20 to 29 years. This difference between genders widened in the participants' early 20s-when men in the Republic of Korea enlist in the military-and the divergence continued subsequently for older individuals. Conclusion: These results indicate a higher risk of severe infection among older individuals and a gender-based difference in seroprevalence. Therefore, it is necessary to implement policies to promote vaccination in adults.

CO-INFECTION OF DENGUE AND HEPATITIS A VIRUSES: A RARE CASE REPORT.

Dengue fever and hepatitis A are endemic infections caused by viruses that mostly affect developing countries (Volchkova et al., 2016). Co-infection is rare, and represents a diagnostic challenge due to their overlapping symptoms (Yakoob et al., 2009). The febrile syndrome accompanied by abdominal pain and vomiting are the common clinical manifestations of both pathologies. However, confirmation of diagnosis depends on laboratory tests ( Khetarpal and Khanna, 2016; Abutaleb and Kottilil, 2020). We report a case of a young female with dengue and hepatitis A co-infection.

Hepatitis A Virus Infection in Cynomolgus Monkeys Confounds the Safety Evaluation of a Drug Candidate.

In a 3-month toxicity study in cynomolgus monkeys at a European contract laboratory, animals were infected with HAV, initially resulting in hepatic injury being incorrectly attributed to the test compound. Elevated serum ALT/AST/GLDH (5- to 10-fold) were noted in individual animals from all groups including controls, with no apparent dose, exposure, or time-related relationship. Liver histopathology revealed minimal to slight inflammatory cell accumulation in periportal zones of most animals, and minimal to slight hepatocyte degeneration/necrosis in 10/42 animals from all groups. As these findings were more pronounced in 6 drug-treated animals, including 2/6 in the low dose group, the draft report concluded: "treatment-related hepatotoxicity at all dose levels precluded determination of a NOAEL." However, the unusual pattern of hepatotoxicity suggested a factor other than drug exposure might have caused the hepatic effects. Therefore, snap-frozen liver samples were tested for hepatitis viruses using a PCR method. Tests for hepatitis B, C, and E virus were negative; however, 20/42 samples were positive for hepatitis A virus (HAV). Infection was strongly associated with increased serum ALT/GLDH, and/or hepatocyte degeneration/necrosis. Re-evaluation of the study in light of these data concluded that the hepatic injury was not drug-related. A subsequent 6-month toxicology study in HAV-vaccinated cynomolgus monkeys confirmed the absence of hepatotoxicity. Identification of HAV infection supported progression of the drug candidate into later clinical trials. Although rarely investigated, subclinical HAV infection has occasionally been reported in laboratory primates, including those used for toxicology studies and it may be more prevalent than the literature indicates.

Interleukin-2 enhancer binding factor 2 negatively regulates the replication of duck hepatitis A virus type 1 by disrupting the RNA-dependent RNA polymerase activity of 3D polymerase.

The interaction between viral components and cellular proteins plays a crucial role in viral replication. In a previous study, we showed that the 3'-untranslated region (3'-UTR) is an essential element for the replication of duck hepatitis A virus type 1 (DHAV-1). However, the underlying mechanism is still unclear. To gain a deeper understanding of this mechanism, we used an RNA pull-down and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay to identify new host factors that interact with the 3'-UTR. We selected interleukin-2 enhancer binding factor 2 (ILF2) for further analysis. We showed that ILF2 interacts specifically with both the 3'-UTR and the 3D polymerase (3Dpol) of DHAV-1 through in vitro RNA pull-down and co-immunoprecipitation assays, respectively. We showed that ILF2 negatively regulates viral replication in duck embryo fibroblasts (DEFs), and that its overexpression in DEFs markedly suppresses DHAV-1 replication. Conversely, ILF2 silencing resulted in a significant increase in viral replication. In addition, the RNA-dependent RNA polymerase (RdRP) activity of 3Dpol facilitated viral replication by enhancing viral RNA translation efficiency, whereas ILF2 disrupted the role of RdRP in viral RNA translation efficiency to suppress DHAV-1 replication. At last, DHAV-1 replication markedly suppressed the expression of ILF2 in DEFs, duck embryo hepatocytes, and different tissues of 1 day-old ducklings. A negative correlation was observed between ILF2 expression and the viral load in primary cells and different organs of young ducklings, suggesting that ILF2 may affect the viral load both in vitro and in vivo.

A retrospective analysis on seroprevalence of acute viral hepatitis observed among dengue patients attending a tertiary care centre in central India.

PURPOSE: The present study was conducted retrospectively to assess the frequency of acute viral hepatitis among the clinically suspected dengue cases presented at our tertiary care centre during 2021. METHODS: To determine the presence of acute viral hepatitis; Hepatitis A virus (HAV) and Hepatitis E virus (HEV) infections, 104 specimens were selected from the dengue-suspected clinical specimens received during 2021 on the basis of acute viral hepatitis symptoms. Following this, serological diagnosis was performed on those samples using anti-HAV IgM and anti-HEV IgM ELISA kits. RESULTS: Based on sero-positivity for IgM antibodies, 3 (5.3%) dengue virus (DENV) seropositive samples were positive for both HAV and HEV, while among DENV seronegative cases, 11 (22.91%) samples were positive for HEV and 1 (2.08%) sample was positive for HAV, pointing towards misdiagnosis due to overlapping symptoms. Additionally, co-infection of HAV & HEV in 1 sample was also observed in this study. CONCLUSIONS: This study revealed the presence of acute hepatitis infections among the dengue cases during monsoon and post-monsoon season. Overlapping of the clinical manifestations of these diseases can create misdiagnosis incidences raising risk for underreporting of the true cases of acute viral hepatitis infection. Dengue-suspected patients with selected symptoms during the monsoon and post-monsoon season should additionally be screened for acute hepatitis infections, as suggested in this study.

Concurrent Outbreaks of Hepatitis A, Invasive Meningococcal Disease, and Mpox, Florida, USA, 2021-2022.

In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March--June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups.

Assessing Immunity to Hepatitis A and Hepatitis B Among Individuals in Custody Living With HIV.

Screening upon entry into prison for hepatitis A virus (HAV) and hepatitis B virus (HBV) provides an ideal public health opportunity to offer vaccination to individuals who are nonimmune. We conducted a retrospective review of HAV and HBV immunity among adults living with HIV in the Illinois Department of Corrections between January 1, 2019, and December 31, 2019. The primary objective was to assess rates of HAV and/or HBV immunity in individuals with HIV. In total, 436 people were included in the study. Of 425 patients who had data for HAV vaccination, 335 were immune. Of 421 patients who had data for HBV vaccination, 272 were immune. Of the 149 patients who were nonimmune to HBV, 22 had active HBV and 6 had an equivocal HBV surface antibody and negative HBV surface antigen. In total, 212 (52%) were immune to both HAV and HBV, and 31 (8%) had no immunity to either HAV or HBV. These data demonstrate an important opportunity to discuss and provide vaccination while in custody.

Complete heart block associated with hepatitis A infection in a female child with fatal outcome.

Hepatitis A virus (HAV) infection can cause extra-hepatic manifestations like myocarditis. An 8-year-old female with HAV infection presented with fever, abdominal pain, vomiting, and icterus. She developed viral myocarditis with complete AV dissociation on ECG and was treated with a temporary pacemaker, but her condition worsened, and she died. Hepatitis A viral infection can be associated with viral myocarditis and complete heart block that can lead to cardiogenic shock and death eventually.

Epidemiology of Viral Hepatitis in the Indigenous Populations of the Arctic Zone of the Republic of Sakha (Yakutia).

The indigenous populations of the Arctic regions of Russia experience the lowest coverage of health-related services. We assessed the prevalence of hepatitis A, B, C, D and E viruses (HAV, HBV, HCV, HDV and HEV) among 367 healthy adult Native people of the Arctic zone of Yakutia. The HAV seroprevalence was above and increased with age. The anti-HEV IgM and IgG antibody detection rates were 4.1% and 2.5%, respectively. The average HBsAg detection rate was 4.6%, with no positive cases identified in participants aged under 30 years, confirming the effectiveness of the newborn vaccination program that began in 1998. Anti-HDV antibodies were detected in 29.4% of HBsAg-positive cases. The anti-HCV and HCV RNA detection rates peaked in the age cohort of 50-59 years (10.8% and 3.9%). No statistically significant gender differences in the prevalence of different viral hepatitis were observed. The time-scaled phylogenetic analysis demonstrated that all HBV genotype A and D strains isolated in this study were autochthonous and had an estimated most common recent ancestor (MCRA) age of around the 11th to 14th century. Unlike HBV, the HCV strains of subtypes 1b, 2a and 2k/1b were introduced from other regions of Russia in the 1980s and 1990s. The HCV 1b sequence analysis revealed a series of transmission events. In conclusion, these data emphasize the urgent need for expanded viral hepatitis screening and care programs in the indigenous populations of the Arctic zone of Yakutia.

Decreasing parvovirus B19 and hepatitis A nucleic acid test positivity rates in Canadian plasma donors following the initiation of COVID-19 restriction in March 2020.

BACKGROUND AND OBJECTIVES: In Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre-COVID-19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post-COVID-19 restriction era. MATERIALS AND METHODS: Pooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing. RESULTS: Between 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre-pandemic period (1 January 2015-31 March 2020; B19V tested n = 2,412,701, B19V NAT-positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT-positive n = 26 [0.001%]); (2) a two-year mixed-impact period (1 April 2020-31 March 2022; B19V tested n = 968,250, B19V NAT-positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT-positive n = 2 [0.0002%]); and (3) a pandemic-impact period (1 April 2022-31 March, 2023; B19V tested n = 597,668, B19V NAT-positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT-positive n = 1 [0.0002%]). CONCLUSION: The percentage of B19V- and HAV-positive donations was significantly reduced from the pre-pandemic period to the pandemic-impact period.

Off-Label Yellow Fever and Hepatitis A Vaccination in Traveling Children.

There are few data on yellow fever (YF) and hepatitis A (HA) off-label vaccination. Given the rising trend of travel to endemic countries, there is a growing necessity to broaden vaccination coverage among the pediatric population. For this reason, we aim to assess the adverse effects associated with off-label vaccination, with the ultimate purpose of expanding the vaccine spectrum. We analyzed ambispectively ninety-four children under 12 months of age who received YF or HA off-label vaccines. The YF vaccine was administered to children aged 6-9 months and those allergic to eggs (with a prior negative prick test and no history of anaphylaxis), while the HA vaccine was given to children aged 6-12 months. Overall, 71 (75%) were vaccinated against YF, and 57 (60%) against HA; 34 against both. All of them fulfilled off-label vaccination criteria. No immediate adverse effects (AEs) were reported. Mild common AEs (diarrhea, fever, or malaise) were experienced by 10.8% of patients within 10 days after vaccination. The rate of AEs associated with off-label vaccination for HA and YF is low, suggesting that the vaccines could be considered safe.

Biochemical analysis of the host factor activity of ZCCHC14 in hepatitis A virus replication.

Relatively little is known of the mechanisms underlying hepatitis A virus (HAV) genome replication. Unlike other well-studied picornaviruses, HAV RNA replication requires the zinc finger protein ZCCHC14 and non-canonical TENT4 poly(A) polymerases with which it forms a complex. The ZCCHC14-TENT4 complex binds to a stem-loop located within the internal ribosome entry site (IRES) in the 5' untranslated RNA (5'UTR) and is essential for viral RNA synthesis, but the underlying mechanism is unknown. Here, we describe how different ZCCHC14 domains contribute to its RNA-binding, TENT4-binding, and HAV host factor activities. We show that the RNA-binding activity of ZCCHC14 requires both a sterile alpha motif (SAM) and a downstream unstructured domain (D4) and that ZCCHC14 contains two TENT4-binding sites: one at the N-terminus and the other around D4. Both RNA-binding and TENT4-binding are required for HAV host factor activity of ZCCHC14. We also demonstrate that the location of the ZCCHC14-binding site within the 5'UTR is critical for its function. Our study provides a novel insight into the function of ZCCHC14 and helps elucidate the mechanism of the ZCCHC14-TENT4 complex in HAV replication.IMPORTANCEThe zinc finger protein ZCCHC14 is an essential host factor for both hepatitis A virus (HAV) and hepatitis B virus (HBV). It recruits the non-canonical TENT4 poly(A) polymerases to viral RNAs and most likely also a subset of cellular mRNAs. Little is known about the details of these interactions. We show here the functional domains of ZCCHC14 that are involved in binding to HAV RNA and interactions with TENT4 and describe previously unrecognized peptide sequences that are critical for the HAV host factor activity of ZCCHC14. Our study advances the understanding of the ZCCHC14-TENT4 complex and how it functions in regulating viral and cellular RNAs.

The Association between Message Framing and Intention to Vaccinate Predictive of Hepatitis A Vaccine Uptake.

As ongoing, sporadic outbreaks of hepatitis A virus (HAV) infections present public health challenges, it is critical to understand public perceptions about HAV, especially regarding vaccination. This study examines whether message framing changes the intention to vaccinate against HAV and self-reported vaccine behavior. Using a randomized controlled trial (N = 472) in February 2019 via Amazon Mechanical Turk, participants were randomized to one of four HAV vaccination message groups or a no-message control group. The message groups varied in their emphasis on the nature of outcomes (gain versus loss) and for whom (individual versus collective). The message frames were compared by intention to vaccinate, differences in message characteristics, and behavioral determinants. There was no difference in intention to vaccinate between gain- versus loss-framed messages (MD = 0.1, 95% CI = -0.1, 0.3) and individual- versus collective-framed messages (MD = 0.1, 95% CI = -0.1, 0.3). The intention to vaccinate against HAV in the no-message control group was very similar to that in the message groups. However, gain-framed messages were rated more positively in valence than loss-framed messages (MD = -0.5, 95% CI = -0.7, -0.3), which may be helpful for cultivating a positive public perception of HAV vaccination. The study also highlights the importance of comparing message frames to a no-message control in designing health communication messaging promoting HAV vaccination.

The Burden of Hepatitis A Outbreaks in the United States: Health Outcomes, Economic Costs, and Management Strategies.

BACKGROUND: Hepatitis A (HepA) vaccines are recommended for United States (US) adults at risk of HepA. Ongoing US HepA outbreaks since 2016 have primarily spread person-to-person, especially among at-risk groups. We investigated the health outcomes, economic burden, and outbreak management considerations associated with HepA outbreaks from 2016 onwards. METHODS: A systematic literature review was conducted to assess HepA outbreak-associated health outcomes, healthcare resource utilization (HCRU), and economic burden. A targeted literature review evaluated HepA outbreak management considerations. RESULTS: Across 33 studies reporting on HepA outbreak-associated health outcomes/HCRU, frequently reported HepA-related morbidities included acute liver failure/injury (n=6 studies/33 studies) and liver transplantation (n=5/33); reported case fatality rates ranged from 0-10.8%. Hospitalization rates reported in studies investigating person-to-person outbreaks ranged from 41.6-84.8%. Ten studies reported on outbreak-associated economic burden, with a national study reporting an average cost of over $16,000 per hospitalization. Thirty-four studies reported on outbreak management; challenges included difficulty reaching at-risk groups and vaccination distrust. Successes included targeted interventions and increasing public awareness. CONCLUSIONS: This review indicates a considerable clinical and economic burden of ongoing US HepA outbreaks. Targeted prevention strategies and increased public awareness and vaccination coverage are needed to reduce HepA burden and prevent future outbreaks.

Modelling the Cost-Effectiveness of Hepatitis A in South Africa.

The World Health Organization (WHO) recommends the consideration of introducing routine hepatitis A vaccination into national immunization schedules for children ≥ 1 years old in countries with intermediate HAV endemicity. Recent data suggest that South Africa is transitioning from high to intermediate HAV endemicity, thus it is important to consider the impact and cost of potential routine hepatitis A vaccination strategies in the country. An age-structured compartmental model of hepatitis A transmission was calibrated with available data from South Africa, incorporating direct costs of hepatitis A treatment and vaccination. We used the calibrated model to evaluate the impact and costs of several childhood hepatitis A vaccination scenarios from 2023 to 2030. We assessed how each scenario impacted the burden of hepatitis A (symptomatic hepatitis A cases and mortality) as well as calculated the incremental cost per DALY averted as compared to the South African cost-effectiveness threshold. All costs and outcomes were discounted at 5%. For the modelled scenarios, the median estimated cost of the different vaccination strategies ranged from USD 1.71 billion to USD 2.85 billion over the period of 2023 to 2030, with the cost increasing for each successive scenario and approximately 39-52% of costs being due to vaccination. Scenario 1, which represented the administration of one dose of the hepatitis A vaccine in children < 2 years old, requires approximately 5.3 million vaccine doses over 2023-2030 and is projected to avert a total of 136,042 symptomatic cases [IQR: 88,842-221,483] and 31,106 [IQR: 22,975-36,742] deaths due to hepatitis A over the period of 2023 to 2030. The model projects that Scenario 1 would avert 8741 DALYs over the period of 2023 to 2030; however, it is not cost-effective against the South African cost-effectiveness threshold with an ICER per DALY averted of USD 21,006. While Scenario 3 and 4 included the administration of more vaccine doses and averted more symptomatic cases of hepatitis A, these scenarios were absolutely dominated owing to the population being infected before vaccination through the mass campaigns at older ages. The model was highly sensitive to variation of access to liver transplant in South Africa. When increasing the access to liver transplant to 100% for the baseline and Scenario 1, the ICER for Scenario 1 becomes cost-effective against the CET (ICER = USD 2425). Given these findings, we recommend further research is conducted to understand the access to liver transplants in South Africa and better estimate the cost of liver transplant care for hepatitis A patients. The modelling presented in this paper has been used to develop a user-friendly application for vaccine policy makers to further interrogate the model outcomes and consider the costs and benefits of introducing routine hepatitis A vaccination in South Africa.

The Effectiveness of National Expanded Program on Immunization With Hepatitis A Vaccines in the Chinese Mainland: Interrupted Time-Series Analysis.

BACKGROUND: The high prevalence of hepatitis A delivered a blow to public health decades ago. The World Health Organization (WHO) set a goal to eliminate viral hepatitis including hepatitis A by 2030. In 2008, hepatitis A vaccines were integrated into the Expanded Program on Immunization (EPI) in China to alleviate the burden of hepatitis A, although the effectiveness of the EPI has not been well investigated. OBJECTIVE: We aimed to evaluate the intervention effect at both provincial and national levels on the incidence of hepatitis A in the Chinese mainland from 2005 to 2019. METHODS: Based on the monthly reported number of hepatitis A cases from 2005 to 2019 in each provincial-level administrative division, we adopted generalized additive models with an interrupted time-series design to estimate province-specific effects of the EPI on the incidence of hepatitis A among the target population (children aged 2-9 years) from 2005 to 2019. We then pooled province-specific effect estimates using random-effects meta-analyses. We also assessed the effect among the nontarget population and the whole population. RESULTS: A total of 98,275 hepatitis A cases among children aged 2-9 years were reported in the Chinese mainland from 2005 to 2019, with an average annual incidence of 5.33 cases per 100,000 persons. Nationally, the EPI decreased the hepatitis A incidence by 80.77% (excess risk [ER] -80.77%, 95% CI -85.86% to -72.92%) during the study period, guarding an annual average of 28.52 (95% empirical CI [eCI] 27.37-29.00) cases per 100,000 persons among the target children against hepatitis A. Western China saw a more significant effect of the EPI on the decrease in the incidence of hepatitis A among the target children. A greater number of target children were protected from onset in Northwest and Southwest China, with an excess incidence rate of -129.72 (95% eCI -135.67 to -117.86) and -66.61 (95% eCI -67.63 to -64.22) cases per 100,000 persons on average, respectively. Intervention effects among nontarget (ER -32.88%, 95% CI -39.76% to -25.21%) and whole populations (ER -31.97%, 95% CI -39.61% to -23.37%) were relatively small. CONCLUSIONS: The EPI has presented a lasting positive effect on the containment of hepatitis A in the target population in China. The EPI's effect on the target children also provided a degree of indirect protection for unvaccinated individuals. The continuous surveillance of hepatitis A and the maintenance of mass vaccination should shore up the accomplishment in the decline of hepatitis A incidence to ultimately achieve the goal set by the WHO.