The pertussis enigma: reconciling epidemiology, immunology and evolution

Abstract

Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980-2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies.

Keywords: infection-derived immunity; pertussis; pertussis epidemiology; pertussis resurgence; pertussis vaccines; vaccine-derived immunity.

Figure 1.

Annual incidence data in 20 countries that switched to aP vaccines for primary immunization. We extracted 1980–2012 yearly case counts and pertussis vaccine coverage estimates from the WHO database (http://www.who.int/immunization/monitoring_surveillance/data/en/). For definiteness, we restricted our analysis to countries with more than 80% complete case count and more than 5 million inhabitants. Before analysis, incidence data were log₁₀-transformed and a 5-year moving average was applied to remove the known 2–5 year cycles [21]. To detect long-term trends in pertussis reports, we proceeded in two steps. First, a series of segmented regression models with 0–3 breakpoints and time segments longer than 5 years were applied for each country [3,20]; of these, the most parsimonious model was selected according to the Bayesian information criterion. Second, to account for autocorrelation, we used generalized least-squares on each time segment identified in the first step, assuming the residuals autocorrelation structure followed an autoregressive process of order 1. For each country, the time segments were then classified according to their slope, as increasing (significantly positive slope), decreasing (significantly negative slope) or not significant. For each country, we represent the annual incidence (black solid lines), the fitted values from segmented regression, coloured according to the trend (red lines: significantly increasing; grey lines: no significant trend; blue lines: significantly decreasing), and the date of switch to aP vaccination (black vertical dotted lines). Coloured blue areas indicate the vaccine coverage for the third dose of DTaP vaccine. From left to right and top to bottom, countries are ranked by decreasing value of the last slope.

Figure 2.

Epidemiological evidence of herd immunity induced by aP vaccines: decrease of cases in infants. (a) Yearly incidence (per 100 000) in infants less than 1 year old after the 1996 introduction of aP in Sweden (data redrawn from table 3 in [34]). (b) Mean yearly number of cases before (years 1992–1994) and after (overall period 1996–2011 or outbreak years) introduction of aP in Sweden, stratified by month of age in the first year of life. (c) Yearly cases per doctor in infants less than 1 year old after the 1981 introduction of aP in Japan (adapted from fig. 3 in [35]). (d) Yearly incidence (per 100 000) in infants less than 1 year old in Italy (adapted from fig. 5 in [36]).