Modeling the hepatitis A epidemiological transition in Brazil and Mexico

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Latin America; clean water; hepatitis A; mathematical model; seroprevalence; urbanization.

Figure 1.

Urbanization, access to safe drinking water and seroprevalence of anti-HAV antibodies. (A) Percentage of the total population in urban areas over time in Brazil; (B) Percentage with access to safe drinking water over time in Brazil; (C) Percentage of HAV-seropositive by age (synthesized seroprevalence curves by setting) in Brazil. (D) Percentage of the total population in urban areas over time in Mexico; (E) Percentage with access to safe drinking water over time in Mexico; (F) Percentage of HAV-seropositive by age (synthesized seroprevalence curves by setting) in Mexico. For A and D black curves: by 5 calendar years. For B-C-E-F, green: rural setting; blue: urban setting; dashed lines: observed data; continuous lines: adjusted data (taking into account stricter definitions of access to clean drinking water and assuming the actual access never declines).

Figure 2.

Transmission level vs access to safe drinking water and transmission level over time. (A) Transmission level vs percentage with access to safe drinking water in Brazil; (B) Derived transmission level over time in Brazil; (C) Transmission level vs percentage with access to safe drinking water in Mexico; (D) Derived transmission level over time in Mexico. Green: rural setting; blue: urban setting.

Figure 3.

Model-projected anti-HAV IgG seropositive in the different settings. Model-projected anti-HAV IgG seropositive in rural setting (A), urban setting (B) and at country level (C) in Brazil and rural setting (D), urban setting (E) and at country level (F) in Mexico every 25 calendar years between 1950 and 2050. Black: 1950; blue: 1975; green: 2000; magenta: 2025; red: 2050. Blue stars in rural and urban settings: years of the seroprevalence surveys (Table S1); at country level: 2010 as reference year.

Figure 4.

Projected HAV epidemiological outcomes over time from 1950 to 2050. (A) Projected first age at which at least 50% of the population is anti-HAV seropositive (AMPI) in Brazil; (B) Projected mean age of symptomatic HAV-infection in Brazil; (C) Projected annual incidence rate of all HAV-infections (per 100,000) in Brazil; (D) Projected annual incidence rate of symptomatic HAV-infections (per 100,000) in Brazil. (E) Projected first age at which at least 50% of the population is anti-HAV seropositive (AMPI) in Mexico; (F) Projected mean age of symptomatic HAV-infection in Mexico; (G) Projected annual incidence rate of all HAV-infections (per 100,000) in Mexico; (H) Projected annual incidence rate of symptomatic HAV-infections (per 100,000) in Mexico. Green: rural setting; blue: urban setting; black: country level.

Figure 5.

Projected percentage of population susceptible to HAV infection. Projected percentage of population (all age groups) susceptible to HAV infection from 1950 to 2050, in Brazil (A) and in Mexico (B). Green: rural setting; blue: urban setting.