We have analyzed the dynamics and periodicity patterns of pertussis incidence in Chile by making use of almost 60 years of data along a unique latitudinal gradient in Chile. In fact, to the best of our knowledge, this is the first large-scale comparative analysis based on a latitudinal gradient of pertussis incidence. The same comparative approach has been applied to understand the global patterns of pertussis dynamics across different countries [3, 11]. One interesting component of our analysis is the relatively homogeneity of the epidemiological data originating from a consistent source of information and methodology. However, we are aware that despite having a single source of information (Chilean Ministry of Health), the great temporal and spatial extent of the data are sources of error and bias in aspects of notification, diagnostic tools and vaccination coverage.
Our findings underscore transient dynamic changes observed in time and space across an extensive latitudinal gradient. Specifically, three different dynamic behaviors can be distinguished at the national and regional scales namely high frequency dynamics, 4–5 year cycles and a resurgent pattern occurring during the last 20 years. During the pre-vaccination period (1932–1955) pertussis dynamics showed a weak cyclic behavior with a 2–3 years period, as predicted by theory the increase in birth rates observed among 1955–1965 produced a decrease in the inter-epidemic periods [18, 19] due to the increase of the susceptible pool. This dynamic change occurred despite the onset of vaccination in 1955. However, the first vaccination period in Chile (1955–1974) was characterized by a low coverage rate of two doses of a DP whole cell vaccine . Not surprisingly, during this period the reduction in mean incidence rates was weak and pertussis dynamics seems to be driven by birth rates. The most important change in the variance occurred at the beginning of the 1970s, which is the result of a dramatic and synchronized reduction in the mean incidence across the country. During this period there were changes in the type of pertussis vaccine, the corresponding coverage levels and demographic characteristics in Chile. For example, in 1974, the vaccination program was initiated with three doses of the DTwP type vaccine and a vaccination program at national level that increased coverage . A previous study based on eight countries with long epidemiological records showed that vaccination increased the periodicity of pertussis outbreaks [3, 11], which supports the idea that immunization plays an important role in decreasing transmission . Nevertheless, Chile experienced important reductions in birth rates during this period; birth rates peaked in 1960 and declined by almost 40 % during the first half of the 1970s. Therefore, it is difficult to assess the effect of the relative contribution of immunization and demographic factors on the dramatic change in mean incidence rates and triggering 4-year periodic cycles.
The differences in pertussis dynamics observed along the regions appear to reflect the large climatic, social and demographic differences of the country and potentially also the vaccination coverage differences (data not available). For example, central Chile (regions IV–VIII) comprises about 70 % of the total population including the largest cities (Santiago, Viña del Mar, Valparaiso and Concepcion). These regions exhibited very similar dynamics; the strong 4-years cycles observed during the period 1974–1995 are associated with an important reduction in transmission rates caused by the increase in vaccination coverage, the addition of a third dose  and the decrease in birth rates. On the other hand, the extreme northern and southern regions characterized by lower population sizes and lower birth rates showed cyclic dynamics. The theory of infectious diseases predicts that outbreak periodicity is mainly driven by birth rates and vaccine coverage [18, 19, 22]. Consequently, outbreak periodicity appears to be driven by the susceptible recruitment dynamics (birth rates and vaccination coverage). Nevertheless, other studies have emphasized the role of waning immunity as the main driver of susceptible recruitment dynamics and outbreak periodicity in pertussis [23, 24]. In Chile, during the first period of vaccination (1955–1974) the periodicity of the outbreaks appears to be clearly influenced by demography (birth and infant mortality rates). In particular, the regions characterized by low birth rates exhibited longer periodic patterns, which is in line with theoretical results  and the observed patterns [3, 11]. However, the interaction between the different factors generating the dynamics of pertussis is still not clearly understood. For example, the immunization program in Chile increased the periodicity of the outbreaks in those regions characterized by high population size, while decreased the periodicity, especially in southern regions with low population sizes. This result is intriguing and poses some interesting questions about the complex dynamics of this infectious disease. The 3–to 4-year periodicity trend in pertussis dynamics has been observed in countries with very different vaccination levels and socio-demographic conditions , suggesting that other factors are operating beyond the role of susceptible recruitment and vaccination coverage , such as, population density, urbanization and the degree of biases in the notification of the disease. In fact, we found that in northern and southern Chile the periodicity of pertussis decreased following vaccination efforts. These particular regions were characterized by low population size and low birth rates, but because we have no information about vaccination rates among regions the causal factors are only speculative. Importantly, despite the existence of major demographic and social differences between regions, no effects were observed in the magnitude of the incidence rates associated with these factors.
During the last decade the resurgence of pertussis has been the subject of considerable attention, especially in countries with a long history of vaccination [5, 8, 25–29]. In general, the resurgence has been characterized by an increase in the mean age of infection [8, 11, 25–29]. Our analysis determined that the increase of pertussis incidence in Chile started around twenty years ago and displays differences with other countries. For example, in Canada, Sweden and USA, pertussis resurgence was driven by an increase in the number of preteens and teens [8, 25–27]. In Chile, the corresponding increase is in infants (<1 year old) and adults (20–44 and >45). The introduction of the DTPw vaccine in 1974 caused a dramatic reduction in incidence in the age-group 1–9, but the effects were less marked on the infants. This shift toward infants was also reported in Sweden , but the resurgent era in USA and Canada was characterized by about half of the cases reported in children > 10 year old [4, 8, 25, 26]. Different plausible hypotheses have been proposed for explaining this resurgent pattern and age distribution shift in highly immunized populations; evolution of Bordetella pertussis , improvements in the recognition of the disease in adolescents and adults [26, 27], waning of vaccine-induced immunity [8, 25–29], and the role of contact networks in highly immunized countries . Moreover, the study by Rohani et al.  suggested that the social contact network can be the key piece for understanding the epidemiology of B. pertussis. The number of daily contacts among the different age classes could be an important factor for determining the epidemiology of B. pertussis [7, 31]. On the other hand, the increase of pertussis incidence was closely related with the regional geographic structure of Chile. Northern regions did not show any evidence of increases during the last 20 years, which is in contrast to the observed pattern in central and southern regions of Chile. In fact, the most important increases in pertussis were observed in the southern regions (VIII, X and XI).