A global resurgence of pertussis has been observed beginning in the 1990s and the early 21st century. This study demonstrates a re-emergence of pertussis in Brazil, especially since 2012. In the US, since 1993, the incidence of pertussis has increased, reaching over 25,000 cases per year in 2004 and 2005, 48,277 cases in 2012, and approximately 28,000 cases per year in 2013 and 2014 , with some localized outbreaks [2, 16, 17]. In Europe, most countries recorded an increase in the number of cases, especially the Netherlands, UK, Denmark and Norway. Between 2003 and 2007, the overall average annual incidence was 4.1/100,000, rising to 4.9/100,000 in 2009 [18–20]. In some countries, such as the Netherlands, abrupt increases occurred . Data from this study suggest that epidemic levels were reached in Brazil in 2011, increased in 2012, and reached another peak in 2014. However, these values are still below those observed in other countries, such as in Europe, possibly because of underreporting.
In any epidemiological surveillance system, there is concern about underreporting. It has been demonstrated through capture-recapture methods that pertussis is significantly underreported; in the US, it is likely that the actual number of cases is 5–6 times than the reported number. This failure to report cases may be even greater for teenagers and adults because the symptoms are usually mild and may go unnoticed [22–24]. Thus, the actual state of the disease in Brazil may be even more alarming.
Cyclic epidemic peaks of pertussis are observed in many countries. The interval between these peaks varies from one study to another, suggesting that they occur every 2–5 years [2, 6, 18, 25, 26]. Brazilian data show increases in the years 1997, 1998, 2004 and 2005. This study shows increasing incidence from 2011 to 2014; in 2014, it reached the highest number of cases in 30 years .
This study shows that pertussis has a clear seasonal pattern in Brazil, with an increase in the number of cases between late spring and summer (in the Southern Hemisphere), specifically in the months of November, December, January and February and especially in South and Southeast regions. Similarly, it has been reported that in the Northern Hemisphere, pertussis occurs most frequently in summer and autumn . Interestingly, in Brazil, other acute respiratory tract infections are more common between the autumn and spring and peak in the winter . These differences in seasonal patterns may be useful for identifying and diagnosing pertussis.
The age distribution of pertussis cases vary between the distinct regions of the world and from one period to another. During an epidemic in the US, the incidence was higher among children under 6 months of age; during the second epidemic, the incidence increased considerably for children aged 14–16 years [2, 17]. Similar variations in age distribution have been reported in Europe [20, 29].
In the present study, we found that 1/3 of the confirmed cases occurred in infants aged 0 to 2 months, an age at which they have not received any dose of a pertussis vaccine. A little over half the cases occurred in children under the age of seven months, i.e., while they were in the process of immunization. During the period of increased incidence (2012–2014), the proportion of confirmed cases in not fully immunized subjects decreased, while an increase in the proportion of cases in older children and adolescents was observed.
Regarding the diagnostic criteria used, most cases were confirmed by clinical and epidemiological criteria, and laboratory confirmation was obtained in a little more than one-third of cases. This is a low proportion; however, it can be explained by the difficulties of obtaining a nasopharyngeal swab in most hospitals and health centres. Nevertheless, laboratory tests are important for confirming pertussis because clinical diagnosis can be difficult [30–32]. In the US, the significant increase in the number of cases may be associated with the introduction of more accurate techniques, such as PCR [16, 33]. In Mexico, there was a substantial increase in pertussis confirmations when PCR testing was implemented . Interestingly, in Italy, the case definition is based on clinical criteria, and laboratory confirmation is not routine . In Spain, the proportion of laboratory confirmation has gradually increased, reaching 69 % . In the US, each confirmed case is linked to a positive laboratory test or is epidemiologically associated with a case confirmed by culture or PCR . Unfortunately, the culture of nasopharyngeal secretions of B. pertussis, despite high specificity, presents low sensitivity, and its applicability is subject to logistic limitations. The state of São Paulo, which has used the PCR technique since 2009, had the highest rate of laboratory confirmation of the country. In general, the Southern and Southeastern regions had the highest laboratory confirmation rates in Brazil. Efforts to improve pertussis laboratory diagnosis capacity in Brazil should be undertaken, health professionals involved in patient care in health services should be engaged, and laboratory infrastructure within the Unified Health System should be improved.
The pertussis complications are more prevalent in children under one year of age. In this study, pneumonia was the most commonly observed complication, especially in infants under 3 months of age. In California in 2010, 18.8 % of patients with pertussis had pneumonia. In Russia, the most frequent complications were encephalopathy, followed by bronchitis and pneumonia [17, 36]. A study in the state of Paraná in Brazil also showed that pneumonia was the complication most often associated with death . The overall pertussis case fatality rate in Brazil is higher than that of other countries. In Canada between 1991 and 1997, there was a fatality rate of 0.9 %, less than half the rate observed in Brazil between 2007 and 2014 [37, 38]. Additionally, the absolute number of deaths from pertussis in Brazil is higher than those observed in other countries. In England between 2001 and 2011, there were 48 deaths, the same number of deaths reported in a 6-month period during the epidemic years of the disease in Brazil . In the US in 2013, there were only 13 deaths from pertussis, with a case fatality rate of 0.02 % .
A global resurgence of pertussis has been noticed, especially in developed countries. Major hypotheses to explain it include a lower immunogenicity of aP compared with wP vaccines, which would lead to the early weaning of vaccine-induced immunity, the circulation of B. pertussis among adolescents and adults and, from these groups, the infection of infants who are not fully immunized. This phenomenon may also be associated with vaccines’ selective pressure on circulating strains, which could cause them to block the antibodies produced by immunization .
However, in Brazil, aP vaccines have never been introduced universally and are available only in private vaccination clinics. The proportion of Brazilian children and adults who have been immunized with aP vaccines is not known. Vaccines containing the aP component are available in the NIP only to pregnant women and children who have developed serious side effects after the use of wP vaccines. Thus, the increase in the incidence of pertussis observed in recent years in Brazil should have other possible explanations.
This study reveals that most cases of pertussis reported in Brazil from 2007 to 2014 occurred in subjects older than 6 months of age, with almost 13 % of these cases recorded in fully immunized infants and children aged 7 months to 4 years. Almost 1/3 of these cases were laboratory confirmed. These data point to the possibility of some degree of vaccine escape in the context of the DTwP-Hib-HBV vaccine. We observed that among the reported cases, the proportion of confirmed cases was significantly lower among fully vaccinated children, demonstrating the protective effect of the vaccines, although our study did not aim to evaluate the effectiveness of the vaccines currently being used in Brazil. Nevertheless, the difference in vaccination rates among the confirmed and unconfirmed cases was lower during the period of June 2012 through December 2014 compared with the period of January 2007 through May 2012. This may point to a lower performance of DTwP-Hib-HBV compared with the DTwP-Hib.
Interestingly, the increase in the incidence of pertussis in Brazil coincides with the introduction of the DTwP-Hib-HBV to the NIP in 2012, although an initial increase in the incidence was already evident in 2011, before the DTwP-Hib was replaced. It is also worth noting that during this period, there was a relative reduction in vaccine coverage, which increased the number of states that did not reach 95 % coverage. In the present study, we found that 2 % of the confirmed cases occurred in incompletely vaccinated infants older than 6 months of age. During the pre-epidemic period there was a trend for states with lower vaccination coverage present the highest rates of incidence of pertussis. This pattern was not observed in the 2012–2014 period.
In 2013, Brazil introduced the DaPT for pregnant women as a measure to contain the resurgence of pertussis. Brazil’s main challenges in facing pertussis resurgence will be to offer the highest quality medical attention to reduce mortality, to improve the infrastructure for laboratory diagnoses, and to maintain high vaccination coverage. Additional studies to assess the effectiveness of the current vaccination schedule, including basic research on the genetics and evolution of circulating B. pertussis strains, are also needed.