Modelling the effect of changes in vaccine effectiveness and transmission contact rates on pertussis epidemiology

Abstract

The incidence of the highly infectious respiratory disease named pertussis or whooping cough has been increasing for the past two decades in different countries, as in much of the highly vaccinated world. A decrease in vaccine effectiveness over time, especially when acellular vaccines were used for primary doses and boosters, and pathogen adaptation to the immunity conferred by vaccines have been proposed as possible causes of the resurgence. The contributions of these factors are not expected to be the same in different communities, and this could lead to different epidemiological trends. In fact, differences in the magnitude and dynamics of pertussis outbreaks as well as in the distribution of notified cases by age have been reported in various regions. Using an age-structured mathematical model designed by us, we evaluated how the changes in some of the parameters that could be related to the above proposed causes of disease resurgence - vaccine effectiveness and effective transmission rates - may impact on pertussis transmission. When a linear decrease in vaccine effectiveness (VE) was assayed, a sustained increase in pertussis incidence was detected mainly in infants and children. On the other hand, when changes in effective transmission rates (βij) were made, a dynamic effect evidenced by the presence of large peaks followed by deep valleys was detected. In this case, greater incidence in adolescents than in children was observed. These different trends in the disease dynamics due to modifications in VE or βij were verified in 18 possible scenarios that represent different epidemiological situations. Interestingly we found that both incidence trends produced by the model and their age distribution resemble the profiles obtained from data reported in several regions. The implications of these correlations are discussed.

Waning Tdap Effectiveness in Adolescents

“…Mathematical models have found that pertussis transmission is affected by both variations in VE and pertussis transmission rates. 30 Additional modeling may be helpful in further determining factors important for future interventions on a population basis.…”

Old Disease and New Challenges: Major Obstacles of Current Strategies in the Prevention of Pertussis

“…Decreases in vaccine effectiveness over time, especially with acellular vaccines, have been proposed as a possible cause of the resurgence. This fact has been addressed by researchers and confirmed by various observational studies during the disease epidemics ( 2 , 26 - 28 ). Augmented T-helper-2 responses instead of T-helper-1 have also been suggested as an explanation for the waning antibody responses with these types of vaccines ( 29 ).…”

“…Genes encoding pertactin (Prn) and the tracheal colonization factor have been suggested to be responsible for changing the ability of colonization. Strains containing Prn2 and Prn3 have a higher potency for colonization versus those that have Prn1, and a higher colonization rate leads to increased transmissibility ( 2 ). Some researchers have also proposed that pathogen adaptation (increasing strain fitness) correlates with accelerated waning of immunity by decreasing the period in which pertussis vaccines are effective ( 34 ).…”

“…To better understand the epidemiology of pertussis, physicians must be familiar with basic epidemiologic concepts such as vaccine effectiveness (VE) and efficacy, effective transmission (or contact) rates, pathogen adaptation, pathogen fitness, and selection pressure. Because discussion of these concepts is beyond the scope of this review, readers should refer to the available resources that can be found elsewhere for additional background information as required ( 1 , 2 ).…”

Modelos estocásticos para epidemias recurrentes

“…Simulamos variaciones temporales en distintos parámetros del modelo, como la eficacia y el contacto efectivo, que pueden asociarse a las posibles causas de la reemergencia, y correlacionamos los resultados obtenidos en estas simulaciones con datos epidemiológicos de distintos estados de EEUU. Estos estudios fueron publicados en la revista Epidemics [133]. Por otro lado hemos evaluado la incidencia de la enfermedad al contemplar los retrasos en la vacunación en las primeras tres dosis DTP utilizando datos de registros públicos.…”