Predictions of the emergence of vaccine-resistant hepatitis B in The Gambia using a mathematical model

Abstract

SUMMARYVaccine escape variants of hepatitis B virus (HBV) have been identified world-wide. A mathematical model of HBV transmission is used to investigate the potential pattern of emergence of such variants. Attention is focused on The Gambia as a country with high quality epidemiological data, universal infant immunization and in which escape mutants after childhood infections have been observed. We predict that a variant cannot become dominant for at least 20 years from the start of vaccination, even when using a vaccine which affords no cross protection. The dominant factor responsible for this long time scale is the low rate of infectious contacts between infected and susceptible individuals (we estimate the basic reproduction number of hepatitis B in The Gambia to be 1n7). A variant strain that achieves high prevalence will also take many years to control, and it is questionable whether emergence will be identifiable by sero-surveillance until of high prevalence. The sensitivity of the model predictions to epidemiological and demographic factors is explored.

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

“…Variants in the dominant population, defined as variants replacing the wild-type strain in the major viral population, may be acquired at the onset of HBV infection. This concept is supported by the results of previous studies, which have shown that the replacement of the wild-type strain with a variant may take Ͼ50 years (64)(65)(66). Some immune escape variants were identified in the dominant population, which indicates that these variants are relatively stable in the absence of the wild-type strain.…”

Occult hepatitis B virus infection in a North American community-based population

“…Previous studies have suggested that such variants are more common in patients with long-standing or more advanced HBV infections, but others have not confirmed these findings [15][16][17][18][19]. That S-variants were significantly more common in the older age groups of Groups 1 and 2 subjects would be in keeping with the former findings.…”

Seroepidemiology of hepatitis B virus in Addis Ababa, Ethiopia: transmission patterns and vaccine control

“…However, the level of HBV prevalence identified from our study would remain consistent with values of R 0 <3. In addition, an analysis based on a fully age-structured mathematical model of HBV transmission in The Gambia [15] gave an estimate of R 0 y2 for this high endemicity country.…”

“…Such data help in the development of appropriate control measures, for example, estimating the optimal age for vaccine delivery, the level of vaccine coverage required for elimination, and possible high-risk target groups [10,11]. They support predictive mathematical models by which to explore the merits of different control options [11][12][13], to assess cost-effectiveness of intervention programmes [14], and to predict the risk of evolution of escape mutants [15].…”