Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018.

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

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.

Impact of urbanization on morbidity of hepatitis A: a national panel study in China during 2005-2018.

BACKGROUND: The effect of urbanization on the morbidity of hepatitis A remains unclear. We aimed to estimate the association between various urbanization-related indices and hepatitis A morbidity in China. METHODS: Data on the annual morbidity of hepatitis A, urbanization-related measures (i.e., gross domestic product per capita, the number of hospitalization beds per 1000 persons, illiteracy rate, tap water coverage, motor vehicles per 100 persons, population density, and the proportion of arable land), and meteorological factors in 31 provincial-level administrative divisions of Chinese mainland during 2005-2018 were collected from the National Population and Health Science Data Sharing Platform, China Statistical Yearbooks, and the China Meteorological Data Sharing Service System, respectively. Generalized linear mixed models were applied to quantify the impacts of different urbanization-related indices on the morbidity of hepatitis A in China after adjusting for covariates. RESULTS: A total of 537,466 hepatitis A cases were reported in China during 2005-2018. The annual morbidity had a decline of 79.4% from 5.64 cases to 1.16 cases per 100,000 people. There were obvious spatial variations with higher morbidity in western China. Nationally, gross domestic product per capita and the number of hospitalization beds per 1000 persons increased from 14,040 to 64,644 CNY and from 2.45 to 6.03 during 2005-2018, respectively. The illiteracy rate decreased from 11.0 to 4.9%. Gross domestic product per capita [relative risk (RR) = 0.96, 95% confidence interval (CI): 0.92-0.99], and the number of hospitalization beds per 1000 persons (RR = 0.79, 95% CI: 0.75-0.83) were associated with the declined morbidity of hepatitis A. By contrast, the increased morbidity of hepatitis A was linked to the illiteracy rate (RR = 1.04, 95% CI: 1.02-1.06). Similar influential factors were detected for children and adults, with greater effects witnessed for children. CONCLUSIONS: People in the western region suffered the heaviest burden of hepatitis A in Chinese mainland. Nationally, there was a sharp decline in the morbidity of hepatitis A. The urbanization process was associated with the reduction of hepatitis A morbidity in China during 2005-2018.

[Cost-effectiveness of universal childhood vaccination against hepatitis A in Spain: a dynamic approach]. / Coste-efectividad de la vacunación universal infantil frente a la hepatitis A en España: un enfoque dinámico.

OBJECTIVE: To evaluate the cost-effectiveness of infant universal vaccination against hepatitis A in Spain. METHOD: Using a dynamic model and decision tree model, a cost-effectiveness analysis was performed to compare three vaccination strategies against hepatitis A: non-vaccination strategy versus universal childhood vaccination of hepatitis A with one or two doses. The perspective of the study was that of the National Health System (NHS) and a lifetime horizon was considered. Both costs and effects were discounted at 3% per year. Health outcomes were measured in terms of quality adjusted life years (QALY) and the cost-effectiveness measure used was the incremental cost-effectiveness ratio (ICER). In addition, deterministic sensitivity analysis by scenarios was performed. RESULTS: In the particular case of Spain, with low endemicity for hepatitis A, the difference in health outcomes between vaccination strategies (with 1 or 2 doses) and non-vaccination are practically non-existent, terms of QALY. In addition, the ICER obtained is high, exceeding the limits of willingness to pay from Spain (€22,000-25,000/QALY). The deterministic sensitivity analysis showed that the results are sensitive to the variations of the key parameters, although in no case the vaccination strategies are cost-effective. CONCLUSIONS: Universal infant vaccination strategy against hepatitis A would not be a cost-effective option from the NHS perspective in Spain.

Assessment of risk factors associated with outbreak of hepatitis A in Shakrial, Rawalpindi, Pakistan.

INTRODUCTION: Two patients with jaundice reported to the National Institute of Health (NIH), Islamabad from Shakrial, Rawalpindi in April 2017. An outbreak investigation team was formulated to assess the disease magnitude, risk factors and control measures. METHODOLOGY: A case-control study was conducted in 360 houses in May 2017. The case definition was: onset of acute jaundice with any symptom including fever, right upper-quadrant pain, loss of appetite, dark urine, nausea and vomiting among Shakrial residents from March 10 - May 19, 2017. Four age and gender matched controls were selected for each case. Blood samples were sent to the NIH for laboratory confirmation. Frequencies, attack rates (AR), odd ratios, and logistic regression were computed at 95% confidence interval and p < 0.05. RESULTS: A total of 25 cases (23 new) were identified with mean age 8 years and male to female ratio 1.5:1. Overall AR was 1.39% and the most severely affected age-group was 5-10 years (AR of 3.92%). Multivariate analysis revealed that raw vegetable consumption, lack of awareness and poor handwashing practices had significant association with disease spread. All blood samples were positive for hepatitis A, and no resident was previously vaccinated. Lack of awareness of disease spread among the community was the most probable reason for the outbreak. There were no new cases during follow up until May 30, 2017. CONCLUSIONS: Healthcare departments should implement public policies towards the management of hepatitis A in Pakistan. Health awareness sessions and vaccination for children ≤ 16 years age is recommended.

The Global Burden of Viral Food-borne Diseases: A Systematic Review.

BACKGROUND: The objectives of this paper were to determine the overall number of diseases, deaths, and Disability-Adjusted Life Years (DALYs) caused by viral foodborne diseases (FBDs). An extensive search scheme was performed using several search terms; disease burden, foodborne disease, and foodborne viruses. METHODS: The obtained results were subsequently screened based on title, abstract, and, finally, full text. Relevant evidence on human food-borne virus diseases (prevalence, morbidity, and mortality) was selected. Of all viral foodborne diseases, norovirus was the most predominant one. RESULTS: The incidence rates of norovirus foodborne diseases ranged from 11 to 2,643 cases in Asia and from 418 to 9,200,000 in the USA and Europe. Norovirus had a high burden of disease Disability-Adjusted Life Years (DALYs) compared with other foodborne diseases. North America was reported as a country with a high burden of disease (DALYs = 9900) and illness costs. DISCUSSION: High variability of prevalence and incidence were observed in different regions and countries. Food-borne viruses pose a considerable burden on poor health throughout the world. CONCLUSION: We suggest the addition of foodborne viruses to the global burden of disease, and relevant evidence can be used to improve public health.

Quantitative Risk Assessment of Hepatitis a Virus Infection Arising from the Consumption of Fermented Clams in South Korea.

This study estimated the risk of hepatitis A virus (HAV) foodborne illness outbreaks through the consumption of fermented clams in South Korea. HAV prevalence in fermented clams was obtained from the Ministry of Food and Drug Safety Report, 2019. Fermented clam samples (2 g) were inoculated with HAV and stored at -20-25 °C. Based on the HAV titer (determined using plaque assay) in fermented clams according to storage, the Baranyi predictive models provided by Combase were applied to describe the kinetic behavior of HAV in fermented clams. The initial estimated HAV contamination level was -3.7 Log PFU/g. The developed predictive models revealed that, when the temperature increased, the number of HAV plaques decreased. The Beta-Poisson model was chosen for determining the dose-response of HAV, and the simulation revealed that there was a 6.56 × 10-11/person/day chance of contracting HAV foodborne illness by eating fermented clams. However, when only regular consumers of fermented clams were assumed as the population, the probability of HAV foodborne illness increased to 8.11 × 10-8/person/day. These results suggest that, while there is a low likelihood of HAV foodborne illness from consuming fermented clams across the country, regular consumers should be aware of the possibility of foodborne illness.

Age Group-Specific Assessment of Changing Seroepidemiology of Hepatitis A Virus Infection in North India.

Introduction Routine immunization against hepatitis A virus (HAV) infection has not been warranted in India, but an epidemiological shift from hyperendemicity to intermediate endemicity has been detected in recent years. The present study was planned to gather the age group-specific seroprevalence data of hepatitis A IgG antibodies in various age groups and evaluate any early trends of seroepidemiological shift. Method This was a hospital-based cross-sectional study. The detection of IgG antibodies for hepatitis A was done using an HAV Ab kit (Dia.Pro, Milan, Italy) in sera of individuals from >1 to 80 years of age and consenting to participate. Data on sociodemographic factors and potentially predisposing factors of HAV was collected on a predesigned questionnaire. At the time of final analysis, patients were divided into three groups children one to <18 years, adults ≥18 to <60 years, and old ≥60 to 80 years for comparative analysis. Result A total of 1,250 patients were included in the final analysis (129 children, 928 adults, and 193 old). The male/female ratio of the study participants was 1.4:1. The majority (85%) of them came from rural and semi-urban areas. They generally had lower socioeconomic status (SES) with poor literacy rates. Most of the enrolled cases (n=800/1,250, 64%) reported the use of groundwater, and 58.7% (n=734/1,250) consume water without any purification. Of the study participants, 90.8% reported the use of toilets for defecation, and 96.7% of the cases use soap for handwashing after defecation. The majority of adult (90%) and old age (99%) participants were seropositive for anti-HAV IgG antibodies as compared to children (80%). No significant differences were observed in the seropositivity rates and the SES class of the study participants. Conclusion About 20% of children did not have anti-HAV IgG antibodies in the present study, indicating that they are not exposed to HAV. This could be because of their better living conditions such as the availability of safe drinking water and improved sanitation and hygiene. We support the current guidelines of the Indian Academy of Pediatrics (IAP), which recommends immunization for hepatitis A vaccination at 12 months of age. Adult vaccination is not needed in North India.

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks.

Background: Despite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks. Methods: A HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated. Findings: R0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination. Interpretation: Although highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks. Funding: NIHR.

National report on healthcare utilization and mortality in patients with hepatitis A infection in the United States.

OBJECTIVES: Predictors of negative outcomes related to hepatitis A virus (HAV) need to be studied at a national level. STUDY DESIGN AND METHODS: A retrospective analysis using the Nationwide Inpatient Sample (2002-2013) and Nationwide Readmission Database (2010-2014) was performed to evaluate the outcomes of hospitalized patients with HAV. The Nationwide Inpatient Sample and the Nationwide Readmission Database included a varying number of states during the studied time and reflect the range of implementation dates of the HAV vaccines. Multivariable analyses were fit to determine predictors of outcomes. RESULTS: A total of 13,514 patients were admitted with HAV during the studied time. Thirty-day and 90-day readmission rates were 11.4% and 15%, respectively. Predictors of readmission, longer length of stay, and mortality included patients aged >60 years ([odds ratio [OR]: 1.02; 95% confidence interval [CI]: 1.001-1.03], [OR: 1.15; CI: 1.07-1.24], [OR: 4.06; 95% CI: 1.47-11.16], respectively), Medicare insurance ([OR:3.63; 95% CI: 2.18-6.03], [OR: 1.26; 95% CI: 1.17-1.37], [OR: 2.67; 95% CI: 1.18-6.04], respectively), and cirrhosis ([OR: 1.83; 95% CI: 1.05-3.21], [OR: 1.33; 95% CI: 1.20-1.47], [OR: 2.83; 95% CI: 1.14-7.05], respectively). Predictors of higher cost of admission included patients aged >60 years (OR: 1.32, 95% CI: 1.19-1.46), Hispanic (OR: 1.14; 95% CI: 1.05-1.24), Medicare insurance (OR: 1.22; 95% CI: 1.10-1.35), Medicaid insurance (OR: 1.10; 95% CI: 1.02-1.20), and cirrhosis (OR: 1.28; 95% CI: 1.11-1.46). CONCLUSIONS: Patients at increased healthcare utilization and mortality should be prioritized for HAV vaccination.

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa.

BACKGROUND: While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. OBJECTIVES: To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. METHODS: We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. RESULTS: In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients [Formula: see text] 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. CONCLUSION: More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.

Economic evaluation of hepatitis A vaccines by income level of the country: A systematic review.

Background & objectives: Although several reviews of economic evaluation (EE) studies on hepatitis A virus (HAV) vaccine exist, there remains a need to corroborate such data from time to time. This study aimed to systematically review the literature for reports on EE of HAV vaccination by type of population, characteristics of intervention and income level of the country. Methods: PubMed and Scopus were searched to identify relevant studies from inception up to May 2021 using topic-specific key words in various combinaiton. Full EE studies comparing HAV vaccination to no vaccine or immunoglobulin were included. The risk of bias was assessed by using the ECOBIAS checklist. Results: Among the 1984 identified studies, 43 were found eligible. Of these, 27 were from high-income countries (HICs), 15 from middle-income countries (MICs), and one from low income country. Majority of the studies used Markov model and/or decision tree (n=26). Eight studies used a dynamic model. The discount rate, perspective and time horizon varied across the studies. Universal HAV vaccination without screening was cost-effective among children (14/16, 87.5%) and adolescents (1/5, 20%) but not in adults (0/4, 0%). Analysis by the level of income found that universal HAV vaccination among children without screening was cost-effective in 81.8 per cent of the studies conducted in MICs (9/11) as compared to 66.7 per cent in HICs (4/6). About one-third of the studies conducted among children found that screening and HAV vaccination were cost-effective compared to no vaccination. Interpretation & conclusions: The finding of this review suggest that universal vaccination of children without screening was likely to be cost-effective, especially in MICs. Nevertheless, it should be noted that the methodology varied across studies. Several aspects should also be considered in transferring the EE results across jurisdictions.

Eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH) / Efficacy, safety and usage recommendations of vaccines against hepatitis A in children exposed and infected by the immunodeficiency virus human (HIV)

ANTECEDENTES: La inmunización de niños infectados o expuestos al VIH representa una estrategia fundamental para reducir la morbilidad y mortalidad por enfermedades infecciosas prevenibles por vacunación, cuyo riesgo es marcadamente elevado en esta población debido al compromiso del sistema inmune. Sin embargo, una menor cantidad de niños con VIH logran inmunidad protectora y aquellos que lo hacen pueden experimentar una disminución mayor y más rápida de la inmunidad. La importancia de prevenir la infección por el virus de la hepatitis A (VHA) en el contexto de la coinfección con VIH radica en que la inmunosupresión asociada al VIH puede incrementar la duración, virulencia y patogenicidad del VHA, a su vez que la infección por VHA puede afectar el curso de la enfermedad por VIH. OBJETIVO: Describir la evidencia científica disponible en relación a la eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). OBJETIVO: Describir la evidencia científica disponible en relación a la eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). MÉTODO: Búsqueda electrónica de estudios publicados en español o inglés en PubMed, Cochrane Library, Web of Science y LILACS hasta el 27 de noviembre de 2021. Adicionalmente, se realizó una búsqueda en PubMed y repositorios de organismos elaboradores de Guías de Práctica Clínica. La selección de estudios fue desarrollada por un solo revisor. RESULTADOS: Se incluyeron diez estudios para la evaluación de la eficacia y seguridad y cuatro documentos para la evaluación de las recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). Seroprevalencia contra VHA al inicio del estudio: El porcentaje de participantes con presencia de anticuerpos contra VHA al inicio de estudio fue generalmente bajo (mediana: 12.2%; rango: 2.9% a 48.3%). Inmunogenicidad de las vacunas contra VHA: Tras una primera dosis de inmunización contra el VHA, la seroconversión se produjo en un 68.6% a 87.1% de participantes (mediana: 76.7%). Tras una segunda dosis, el porcentaje de seroconversión se ubicó en el rango de 84.5% a 100% (mediana: 98%). El porcentaje o recuento inicial de CD4 fue un importante predictor de la concentración de anticuerpos. Un único estudio evaluó el efecto de una tercera dosis de vacuna contra el VHA aplicada 18 meses después de la segunda dosis, obteniendo seropositividad de 97%, con un 76% con altos títulos de anticuerpos (≥ 250 mIU/mL). El título medio de anticuerpos fue mayor con tres dosis, comparado con dos dosis de vacuna (602 vs. 287 mUI / ml; p< 0,0001). Eventos adversos asociados a la vacunación: La vacunación contra el VHA en niños infectados o expuestos al VIH produjo eventos adversos leves y en su mayoría autolimitados. La carga viral media de VIH no varió en los niños con VIH vacunados. Duración de la protección después de la inmunización: Se evaluó la presencia de anticuerpos contra el VHA habiendo transcurrido 18 meses después de la aplicación de la segunda dosis de la vacuna. De 120 participantes, 108 (90%) tenían títulos de anticuerpos protectores persistentes, mientras que 12 (10%) no los tenían. Entre quienes no los tenían, dos participantes nunca presentaron respuesta protectora, nueve tuvieron títulos de anticuerpos de ≥ 20 a ≤ 250 mUI/mL tras la segunda dosis, y uno tuvo títulos de anticuerpos de 329 mUI/mL tras la segunda dosis. Los sujetos con bajas respuestas de anticuerpos después de dos dosis de la vacuna contra el VHA tuvieron menor probabilidad de mantener seropositividad 18 meses después que aquellos con altas respuestas de anticuerpos (p= 0.0003). Recomendaciones sobre la vacunación contra VHA en niños con VIH: El NIH de Estados Unidos, y el Ministerio de Salud y Protección Social de Colombia recomiendan dos dosis de vacunas contra VHA en niños con VIH a los 12 y 18 meses. El Ministerio de Salud Pública de Ecuador recomienda solo una dosis a los 12 meses. La Organización Mundial de la Salud recomienda la inmunización contra VHA con un esquema de dos dosis en grupos de riesgo de contraer hepatitis A e inmunodeprimidos. CONCLUSIONES: En los diferentes estudios, la seroprevalencia inicial de anticuerpos contra el virus de la hepatitis A (VHA) fue muy baja, con una mediana de 12.2%, lo cual indica una gran proporción de niños infectados o expuestos a VIH susceptibles a infección por VHA. La aplicación de una primera dosis de vacuna contra VHA produjo una mediana de seroconversión de 76.7%, mientras que una segunda dosis alcanzó una mediana de seroconversión del 98%. El estado inicial de linfocitos T CD4+ fue un importante predictor de la concentración de anticuerpos contra el VHA tras la inmunización. Un mayor recuento o porcentaje inicial de CD4 se asoció con mayor seroconversión, títulos de anticuerpos más altos y mayor probabilidad de mantener seropositividad 18 meses después de la segunda dosis. Resultados de un único estudio muestran que 18 meses después de la aplicación de la segunda dosis de la vacuna contra VHA, un 8.3% de niños dejaron de tener anticuerpos protectores contra el VHA. Resultados de un único estudio muestran que la aplicación de una tercera dosis de vacuna contra VHA 18 meses después de la segunda dosis no alteró el porcentaje personas con seroconversión, pero produjo mayores concentraciones de anticuerpos que quienes solo recibieron dos dosis. La vacunación contra el VHA en niños infectados o expuestos al VIH produjo eventos adversos leves y en su mayoría autolimitados. La carga viral media de VIH no varió en los niños con VIH vacunados. El NIH de Estados Unidos y el Ministerio de Salud y Protección Social de Colombia recomiendan dos dosis de vacunas contra VHA en niños con VIH a los 12 y 18 meses. El Ministerio de Salud Pública de Ecuador recomienda solo una dosis a los 12 meses. La Organización Mundial de la Salud recomienda la inmunización contra VHA con un esquema de dos dosis en grupos de riesgo de contraer hepatitis A e inmunodeprimidos.

Cost-effectiveness of routine catch-up hepatitis a vaccination in the United States: Dynamic transmission modeling study.

BACKGROUND: Despite routine vaccination of children against hepatitis A (HepA), a large segment of the United States population remains unvaccinated, imposing a risk of hepatitis A virus (HAV) to adolescents and adults. In July of 2020, the Advisory Committee on Immunization Practices recommended that all children and adolescents aged 2-18 years who have not previously received a HepA vaccine be vaccinated. We evaluated the public health impact and cost-effectiveness of this HepA catch-up vaccination strategy. METHODS: We used a dynamic transmission model to compare adding a HepA catch-up vaccination of persons age 2-18 years to a routine vaccination of children 12-23 months of age with routine vaccination only in the United States. The model included various health compartments: maternal antibodies, susceptible, exposed, asymptomatic infectious, symptomatic infectious (outpatient, hospitalized, liver transplant, post- liver transplant, death), recovered, and vaccinated with and without immunity. Using a 3% annual discount rate, we estimated the incremental cost per quality-adjusted life year (QALY) gained from a societal perspective over a 100-year time horizon. All costs were converted into 2020 US dollars. FINDINGS: Compared with the routine vaccination policy at 12-23 months of age over 100 years, the catch-up program for unvaccinated children and adolescents aged 2-18 years, prevented 70,072 additional symptomatic infections, 51,391 outpatient visits, 16,575 hospitalizations, and 413 deaths. The catch-up vaccination strategy was cost-saving when compared with the routine vaccination strategy. In scenario analysis allowing administering a second dose to partially vaccinated children, the cost-effectiveness of was not favorable at a higher vaccination coverage ($196,701/QALY at 5% and $476,241/QALY at 50%). INTERPRETATION: HepA catch-up vaccination in the United States is expected to reduce HepA morbidity and mortality and save cost. The catch-up program would be optimized when focusing on unvaccinated children and adolescents and maximizing their first dose coverage.

The global trends and regional differences in incidence and mortality of hepatitis A from 1990 to 2019 and implications for its prevention.

BACKGROUND AND PURPOSE: Despite decades of improved sanitation and hygiene measures and vaccine introduction, hepatitis A has been spread through numerous outbreaks globally. We used data from the Global Burden of Disease (GBD) study to quantify hepatitis A burden at the global, regional and national levels. METHODS: Annual incident cases, deaths, age-standardized incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of hepatitis A between 1990 and 2019 were derived from the GBD study 2019. Percentage changes of cases and deaths, and estimated annual percentage changes (EAPCs) of ASIRs and ASMRs were calculated to quantify their temporal trends. RESULTS: Global hepatitis A incident cases increased by 13.90% from 139.54 million in 1990 to 158.94 million in 2019. ASIR of hepatitis A remained stable (EAPC = 0.00, 95% CI -0.01 to 0.01), whereas ASMR decreased (EAPC = -4.63, 95% CI -4.94 to -4.32) between 1990 and 2019. ASIR increased in low (EAPC = 0.09, 95% CI 0.04 to 0.14) and low-middle (EAPC = 0.04, 95% CI 0.03 to 0.06) socio-demographic index (SDI) regions. For GBD regions, the most significant increases of ASIR were detected in high-income Asia Pacific (EAPC = 0.53, 95% CI 0.41 to 0.66), Oceania (EAPC = 0.31, 95% CI 0.25 to 0.36), and Australasia (EAPC = 0.28, 95% CI 0.13 to 0.44). EAPC of ASIR was positively associated with SDI value in countries and territories with SDI value ≥ 0.7 (ρ = -0.310, p < 0.001). CONCLUSION: There is an unfavorable trend that hepatitis A is still pending in hyperendemic regions and is emerging in low endemic regions. These highlight the need of targeted and specific strategies to eliminate hepatitis A, such as sanitation measures and a comprehensive plan for surveillance and vaccination against hepatitis A.

Preclinical safety assessment of a combined vaccine against Hepatitis a virus and enterovirus 71.

Since 2007, Hepatitis A (HAV) vaccination has been a part of the National Immunization Program of China. Recognizing enterovirus 71 (EV71) as the most important pathogen in severe hand, foot and mouth disease, an inactivated EV71 vaccine was successfully marketed in 2015. Based on the concept of one vaccine preventing two diseases and owing to similarities in vaccine preparation and the overlap of the eligible population, a combination of the inactivated HAV vaccine and inactivated EV71 vaccine is theoretically feasible and desirable. However, the optimal vaccinationschedule for this combination vaccine has yet to be optimized. Use of this combined vaccine would not only decrease the number of vaccinations, but also lower associated cost. This study aimed to investigate the toxicity and adverse reactions of the combined HAV-EV71 vaccine under Good Laboratory Practice conditions to provide a reference for clinical studies/applications in the future. CD®(Sprague Dawley) IGS rats were employed for single-dose toxicity testing using a high dose, and repeated-dose toxicity testing using high, as well as low doses. Animals that received only a single dose showed no obvious clinical symptoms nor abnormal body weight, and no significant gross pathological change at the experimental endpoint at necropsy. In the rats injected with three doses, phagocytosis of basophilic granules by macrophages was observed in the inguinal, mesenteric, and local lymph nodes, besides irritation at the administration site. At 56 days after the last dose, no significant histopathological change was observed in the lymph nodes, and local irritation gradually faded. Further, systematic allergy testing was performed in guinea pigs. After systemic sensitization and challenge with the HAV-EV71 vaccine, animals showed normal weight gain and no allergic reactions. This study, therefore, confirmed a good safety profile of the inactivated HAV and EV71 combined vaccine.

Prevalence of past hepatitis A infection among Crohn's patients and controls - An examination of the 'hygiene hypothesis', and the need for hepatitis A vaccination.

Our study aimed to determine the prevalence of prior exposure to hepatitis A virus in Crohn's disease patients, whose IgG antibody levels against hepatitis A virus were compared with age and sex-matched controls. All of the 41 cases with Crohn's disease and 43 controls included in the study tested positive for IgG anti-hepatitis A virus antibody, with titres (38.8 IU/ml, 22-63.9; median, IQR) similar to those in controls (40.7 IU/ml, 17.3-66.7; p = 0.75). Environmental sanitation remains poor in India, despite reasonable economic gains as reflected by universal exposure to hepatitis A virus infection. Vaccination against hepatitis A may not be important in patients attending inflammatory bowel disease clinic, owing to natural immunity provided by prior infection. The observed rise in inflammatory bowel disease incidence seems to be increasing despite persistently poor environmental hygiene.

Hepatitis A outbreak among MSM in Berlin due to low vaccination coverage: Epidemiology, management, and successful interventions.

OBJECTIVES: To describe the characteristics of a large hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) in Berlin and to assess the impact of measures implemented. METHODS: Cases of laboratory-confirmed, symptomatic HAV infection notified in Berlin, Germany between August 2016 and February 2018 were analysed using routine and enhanced surveillance data including genotyping results. Several studies involving different groups of participants were conducted to further investigate the outbreak, including surveys on knowledge and practices of HAV vaccination among physicians and vaccination coverage and determinants of vaccination status among MSM. The measures implemented were categorized by target group in a Gantt chart. To assess their impact, health insurance data on HAV vaccination uptake were analysed, comparing Berlin and other federal states. RESULTS: During the outbreak period, a total of 222 cases were reported (of which 91 were sequence-confirmed), with a peak in case numbers in January 2017. Physicians were aware of the existing vaccination recommendations, but vaccination coverage among 756 MSM was low, with 32.7% being completely vaccinated and 17.3% being incompletely vaccinated before 2017. HAV vaccination before 2017 was associated with being born in Germany (odds ratio 2.36) and HIV-positive (odds ratio 1.80). HAV monovalent vaccination uptake increased by 164% from 2016 to 2017 among males in Berlin, compared to 7% in other federal states. CONCLUSIONS: Multiple measures targeting the MSM community, physicians, and public health to increase HAV vaccination uptake were successfully implemented. To prevent future HAV outbreaks, we recommend monitoring vaccination coverage among MSM, promoting awareness of existing recommendations among physicians, and ensuring access for foreign-born and young MSM.

The potential of plant-made vaccines to fight picornavirus.

INTRODUCTION: Several Picornaviruses are pathogens that generate serious problems for human and animal health worldwide. Vaccination is an attractive approach to fight against picornaviruses. In this regard, the development of low-cost vaccines is a priority to ensure coverage; especially in developing and low-income countries. In this context, plant-made vaccines are a convenient technology since plant cells are low-cost bioreactors capable of producing complex antigens that preserve their antigenic determinants; moreover, they can serve as biocapsules to achieve oral delivery. AREAS COVERED: In the present review the advances in the development of plant-made vaccines against picornaviruses are summarized and placed in perspective. The main diseases that have been targeted using this approach include Poliovirus, Food and mouth disease virus, Hepatitis A virus, and Enterovirus 71. EXPERT OPINION: Several vaccine candidates against picornavirus have been characterized at the preclinical level; with many of them capable of inducing humoral and cellular responses that led to neutralization of pathogens when evaluated in vitro and test animal challenge assays. Plant-made vaccines are a promise to fight picornaviruses; especially in the developing world where limited resources hamper vaccination coverage. A critical analysis of the road ahead for this technology is provided.