Modeling the hepatitis A epidemiological transition in Brazil and Mexico.
ABSTRACT: Many low- to middle-income countries have completed or are in the process of transitioning from high or intermediate to low endemicity for hepatitis A virus (HAV). Because the risk of severe hepatitis A disease increases with age at infection, decreased incidence that leaves older children and adults susceptible to HAV infection may actually increase the population-level burden of disease from HAV. Mathematical models can be helpful for projecting future epidemiological profiles for HAV.An age-specific deterministic, dynamic compartmental transmission model with stratification by setting (rural versus urban) was calibrated with country-specific data on demography, urbanization, and seroprevalence of anti-HAV antibodies. HAV transmission was modeled as a function of setting-specific access to safe water. The model was then used to project various HAV-related epidemiological outcomes in Brazil and in Mexico from 1950 to 2050.The projected epidemiological outcomes were qualitatively similar in the 2 countries. The age at the midpoint of population immunity (AMPI) increased considerably and the mean age of symptomatic HAV cases shifted from childhood to early adulthood. The projected overall incidence rate of HAV infections decreased by about two thirds as safe water access improved. However, the incidence rate of symptomatic HAV infections remained roughly the same over the projection period. The incidence rates of HAV infections (all and symptomatic alone) were projected to become similar in rural and urban settings in the next decades.This model featuring population age structure, urbanization and access to safe water as key contributors to the epidemiological transition for HAV was previously validated with data from Thailand and fits equally well with data from Latin American countries. Assuming no introduction of a vaccination program over the projection period, both Brazil and Mexico were projected to experience a continued decrease in HAV incidence rates without any substantial decrease in the incidence rates of symptomatic HAV infections.
Project description:There are indications of a shift in the pattern of hepatitis A (HAV) in Mexico from high to intermediate endemicity, progressively increasing the mean age of infection and the proportion of cases which are symptomatic. This study estimated the potential impact of universal infant HAV vaccination in Mexico with two doses of Havrix™ at 12 and 18 mo of age on all HAV infections and symptomatic HAV infections. We developed a dynamic transmission model that accounts for changes in demography and HAV epidemiology. It was calibrated using Mexican age-specific seroprevalence and symptomatic HAV incidence data. With 70% first-dose coverage and 85% second-dose coverage, the calibrated model projected that HAV vaccination would reduce the incidence of all HAV infections (symptomatic and asymptomatic) after the first 25 y of vaccination by 71-76% (minimum and maximum for different transmission scenarios). The projected reduction in cumulative incidence of symptomatic HAV infections over the first 25 y of vaccination was 45-51%. With 90% first-dose coverage and 85% second-dose coverage, the projected reduction in incidence of all HAV infections was 85-93%, and the projected reduction in the cumulative incidence of symptomatic HAV infections was 61-67%, over a 25-y time frame. Sensitivity analyses indicated that second-dose coverage is important under the conservative base-case assumptions made about the duration of vaccine protection. The model indicated that universal infant HAV vaccination could substantially reduce the burden of HAV disease in Mexico.
Project description:BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV) infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists. MATERIALS AND METHODS: We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period. DISCUSSION: Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1) infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50) infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively), largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation. CONCLUSION: The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.
Project description:BACKGROUND: In populations in which the incidence of hepatitis A virus (HAV) infection has declined due to socio-economic improvements, better sanitation and hygiene, and vaccination, birth cohorts who have long-term immunity through exposure early in life are now being replaced by non-immune cohorts, meaning that more cases in the elderly may occur in future. Our goal was to qualitatively investigate the interaction of this cohort effect and demographic change (population ageing) on the estimated disease burden of HAV infection in the Netherlands. METHODS: We used dynamic MSIR (maternal immunity-susceptible-infectious-recovered) transmission and demographic models to simulate annual HAV incidence over the period 2000-2030, and estimated disease burden using the disability-adjusted life years (DALY) measure and a pre-defined disease progression model. Five scenarios representing different force of infection situations were simulated. RESULTS: The overall disease burden was projected to decrease over the simulation period in the baseline scenario (310 DALYs in 2000 compared with 67 in 2030). This decreasing trend was absent for the 55+ years age group; 23.5% of all new infections were predicted to occur in the 55+ group in 2030, compared with 5.5% in the 55+ group in 2000. CONCLUSIONS: In the absence of further public health interventions and under the assumption of a continued steady decline in the force of infection, the HAV disease burden in the Netherlands is predicted to decrease over the coming decades, but with proportionally more of the burden occurring within the increasingly larger segment of the population represented by elderly persons who are no longer naturally immune.
Project description:Although a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti-HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015-2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti-HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV-IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole-genome sequencing and phylogenetic analyses revealed local HAV-IIA evolutionary events in Central Africa, indicating the circulation of HAV-IIA strains of a region-specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV-IIA possibly acquired the 5'-untranslated region (5'-UTR) of the rare subgenotype HAV-IIB in recent years, suggesting the present existence of HAV-IIB in Central Africa. These findings indicate a currently stable HAV-IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.
Project description:The resurgence of pertussis in some countries that maintain high vaccination coverage has drawn attention to gaps in our understanding of the epidemiological effects of pertussis vaccines. In particular, major questions surround the nature, degree and durability of vaccine protection. To address these questions, we used mechanistic transmission models to examine regional time series incidence data from Italy in the period immediately following the introduction of acellular pertussis (aP) vaccine. Our results concur with recent animal-challenge experiments wherein infections in aP-vaccinated individuals proved as transmissible as those in naive individuals but much less symptomatic. On the other hand, the data provide evidence for vaccine-driven reduction in susceptibility, which we quantify via a synthetic measure of vaccine impact. As to the precise nature of vaccine failure, the data do not allow us to distinguish between leakiness and waning of vaccine immunity, or some combination of these. Across the range of well-supported models, the nature and duration of vaccine protection, the age profile of incidence and the range of projected epidemiological futures differ substantially, underscoring the importance of the remaining unknowns. We identify key data gaps: sources of data that can supply the information needed to eliminate these remaining uncertainties.
Project description:BACKGROUND:Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. OBJECTIVE:To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. METHODS:This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. RESULTS:The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001). During the study period, the reported incidence rate in individuals aged ?19 years declined to the historically lowest record in 2014. Compared with individuals aged ?19 years, those aged ?20 years showed the highest incidence rate (P< 0.001). Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases. CONCLUSIONS:Childhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ?19 years. Those aged ?20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.
Project description:The Coronary Heart Disease (CHD) Policy Model-China, a national scale cardiovascular disease computer simulation model, was used to project future impact of urbanization.Populations and cardiovascular disease incidence rates were stratified into four submodels: North-Urban, South-Urban, North-Rural, and South-Rural. 2010 was the base year, and high and low urbanization rate scenarios were used to project 2030 populations.Rural-to-urban migration, population growth, and aging were projected to more than double cardiovascular disease events in urban areas and increase events by 27.0-45.6% in rural areas. Urbanization is estimated to raise age-standardized coronary heart disease incidence by 73-81 per 100,000 and stroke incidence only slightly.Rural-to-urban migration will likely be a major demographic driver of the cardiovascular disease epidemic in China.
Project description:Viral hepatitis is a considerable public health burden affecting millions of people throughout the world. The incidence of viral hepatitis varies greatly depending upon geographic locations, age and gender. Exploring the etiological spectrum and clinic-epidemiological profile of acute viral hepatitis (AVH) becomes essential for strategizing the preventive measures to control the diseases. An epidemiological data depicting AVH situation and its etiologies is missing from central India. With the aim of fulfilling this lacuna, the present analysis was done on samples tested over a period of 2 years from July 2015 to June 2017. Of the 1901 hepatitis cases, 597 individuals (31.4%) were positive for AVH infection and HEV was the predominant cause followed by HBV, HAV and HCV. Co-infections of hepatitis viruses were detected in 42 cases. Co-infection of HEV with HBV was the commonest pattern. Male preponderance was observed among AVH positive cases and the age group of 26-45 years was the most susceptible to the viral hepatitis infections, except hepatitis A, which was the most frequent among children. Two hundred patients (33.45%) required hospitalization and 51 deaths were attributed to AVH infections. The analysis for the first time reports intricacies and viral etiologies of AVH in central India. Regular diagnosis of AVH etiology and monitoring of cases will help in patient management and assist disease control programs to take policy decisions.
Project description:Vaccination for hepatitis A virus (HAV) has been implemented as one of the national vaccination programs despite the epidemiological transition of HAV in the Republic of Korea. While the national HAV vaccination program is largely associated with the shift of socioeconomic trend in the country, concerns have been raised on the effectiveness of the HAV immunization. The objective of this study was to examine the epidemiological trend of HAV and assess the effectiveness of the nationwide HAV vaccination policy based on a nationally representative sample of the Korean population collected in 2015.We analyzed anti-HAV of 5,856 respondents aged ?10 years collected from Korean National Health and Nutrition Examination Survey (KNHANES) data in 2015. We estimated age-adjusted anti-HAV prevalence by sociodemographic and other characteristics. We evaluated the factors associated with anti-HAV positivity among each age group (10-19, 20-29, 30-45 and over 45 years old).The prevalence of anti-HAV among adults aged ?10 years was 72.5% (95% confidence interval, CI, 73.7-71.4) in 2015. The lowest age-specific prevalence was among adults aged 20-29 years with 11.9% (95% CI 9.3-15.1%). The prevalence of anti-HAV among those aged 10-14 and 15-19 years was 59.7% (95% CI 52.7-66.4) and 24.0% (95% CI 19.5-29.3), respectively. The prevalence of anti-HAV among adults aged between 30 and 44 years rapidly increased from below 20% to above 90%. The prevalence of anti-HAV among adults aged ?45 years was 97.8% (95% CI 96.0-97.6). Factors significantly associated with anti-HAV positivity among those aged 10-19 years old were young age, higher house income and high influenza vaccination rate. Compared to the respondents aged 10-19 years (those who were subject to the national childhood vaccine recommendation), those aged 20-29 years (those who were not subject to the recommendation) had low adjusted odds ratio (OR, 0.52 95% CI 0.34-.81 P-value = 0.004) for anti-HAV positivity.The age-adjusted anti-HAV prevalence showed a U-shaped association, implying the high dependence of anti-HAV prevalence on age and the epidemiological shift. The inclusion of the hepatitis A vaccine into the national immunization recommendation was effective shown by the increase of immunity in the general population. However, the vaccination rate was low in the low-income group. Young adults aged 20-39 years may benefit from inclusion in the HAV vaccination program due to the significantly low vaccination rate.
Project description:To assess the current hepatitis A virus (HAV) endemicity in the Autonomous Province of Vojvodina, Serbia, we examined the seroprevalence and susceptibility profiles of the general population. A serum bank of 3466 residual samples, collected in 2015-16 as per the specifications of the European Sero-Epidemiology Network 2 project (ESEN2), was tested for anti-HAV antibodies with an enzyme immunoassay. Relationships between anti-HAV positivity and demographic features of respondents were examined by univariable and multivariable analyses. Present-day HAV seroprevalence was compared with that obtained in 1978-79. Surveillance data for hepatitis A recorded between 2008 and 2017 were also analyzed. Age was the only demographic variable found to be independently associated with a HAV seropositive status. Seropositivity (17% overall vs. 79% in 1978-79) increased with age to a maximum of 90% in the elderly ?60 years. Only 5% of subjects <30 years were seropositive, unlike the 44% of seropositives ?30 years. The estimated age at midpoint of population immunity (AMPI) increased markedly from 14 years in the late 70s to 55 years in 2015-16. Meanwhile, disease incidence decreased noticeably in recent years (from 11 in 2008 to 2 per 100,000 population in 2017). In the ongoing pre-vaccine era, natural infection provides immunity for merely a third (31%) and two thirds (57%) of people in their 40s and 50s, respectively. Hence, the majority of people ?40 years (94%) and middle-aged adults 40-49 years (69%) are susceptible to HAV. Older susceptible individuals, particularly those ?50 years (24%), are prone to severe symptoms. Taken together, these changes reflect the epidemiological transition of Vojvodina and Serbia from high to very low HAV endemicity, thereby supporting the current national policy of immunization of only high-risk groups.