In China, 90% reported pertussis cases were infants or young children who suffered from classical “whooping cough” symptoms. Studies suggested that only 40-50% of pertussis cases had a classical clinical manifestation of a paroxysmal cough , often leading to a misdiagnosis as a general respiratory infection and a failure to investigate for pertussis. Since the methods for laboratory confirmation of B.pertussis were not routinely used in China, many of pertussis cases without classical paroxysmal cough symptom among vaccinated children, adolescents and adults failed to be notified and were possibly considered as common respiratory infections. The misdiagnoses clearly contributed to the reported low incidence under the 1 per 100,000 since 1990s in China. In Guangdong, the number of reported pertussis cases ranged from 18 to 115 cases in each year during the period of 2004–2011, and only one death was reported in 2005. There were only 18 and 22 cases notified in 2010 and 2009. Therefore this cross sectional study was aimed to investigate seroprevalence of pertussis in all age groups in a region of China.
Threshold employed in this study were based on combination of mean value of anti-PT IgG of studied population, China pertussis vaccine programs, instruction of ELISA kit and previous studies of EU. Mean concentration of anti-PT IgG in subgroups of subjects was relatively low fluctuating between 10 IU/mL and 20 IU/mL. This result was similar to our recent study carried out in Shandong province, eastern part of China . In China, no booster dose was used in adolescents and/or adults. The levels of anti-PT IgG antibodies observed in China might be lower than that of European countries and US in which boosters for adolescents and young adults were introduced [22, 23]. Regarding the performance of available commercial ELISA kits for diagnosis of pertussis, a recent German study showed that only kits using PT as a coating antigen gave overall good sensitivities and specificities compared to their in-house ELISA , suggesting that our results obtained by using the commercial ELISA kits are true. Therefore, considering the high specificity of anti-PT IgG, one cut-off was set at 30 IU/mL rather than a higher cut-off with lower sensitivity, which was used to indicate a probable recent contact with B.pertussis, if no booster has been received within the previous one year. Various cutoff values for anti-PT IgG with recent contact to B. pertussis antigens have been proposed by various countries [19, 24–26]. In this study, we also applied the diagnostic algorithm described by Riffelmann that anti-PT IgG ≥100 IU/mL as diagnostic of recent or active infection with B.pertussis.
In order to avoid the possible influence of antibodies derived from vaccinations, we mainly estimated the incidence rates among individuals older than 7 years age based on high anti-PT IgG titer in serum sample. It is known that the vaccine-induced antibodies began to wane 3 to 5 years after the last dose of vaccination, and immunity to pertussis vaccine diminished to 0%-20% over a 10-year interval [27, 28]. Primary pertussis vaccination in China has been targeted routinely only at the infant age group with a fourth dose injected at 18–24 months, and no further booster doses were used in this country. High level of anti-PT IgG antibodies in subjects older than 7 years age are most likely due to contact of B.pertussis. Therefore, information about the sero-prevalence of high levels of anti-PT antibodies in combination with the post-infection antibody decline rate allows us to study B.pertussis infections in > 7 years age groups irrespective of clinical manifestation and reporting symptom.
Our results clearly showed that despite a high vaccination coverage (>98%) in Guangdong province, pertussis is common in the communities, particularly in the adolescents and adults. The estimated incidence rate of recent infection was found that 9.39% (or 9395 per 100,000) of the population older than 7 years of age had experienced contact with B. pertussis in the year before sampling, which was found to be ten thousand times higher compared to that based on the notifications in 2010 (0.176/100,000). Many countries have observed pertussis is under-reported and under-diagnosed , for example, the estimated incidence rates of infection is more than 600-times higher than the notified cases numbers in Netherland . We have to realize that raised anti-PT IgG antibodies could reflect exposure/infection rather than clinical disease. Due to absence of clinical symptom, many adults cases with higher anti-PT IgG were considered as atypical or asymptomatic infection. The high proportion of study subjects with atypical or asymptomatic infection clearly contributed to the high estimated incidence rate of infection observed in this study. It remains to be shown if the pathogen of B. pertussis could be transmitted by subjects with asymptomatic or atypical infections.
Previous studies suggest that the amount of under-reporting in pertussis varies among different age groups, and the under reporting was higher for older children, adolescents, and adults than for younger children [30, 31]. Our results were in consistent with the earlier findings. In this study, the higher incidences were observed in adolescents and adults older than 40 years of age. Due to more crowding students in schools, high rate of person to person transmission in this age group can occur and therefore the incidence rate of recent infection was highest. In addition, our data also revealed the relative higher sero-positive among population living in county than in city. According to the reported vaccination coverage rate in Guangdong province, the lower access to health facilities didn’t seem to produce lower immunization coverage. One explanation might be that due to the low number of hospitals or department of diseases control and prevention and lack of awareness to pertussis, subjects with pertussis could not be diagnosed or could not have access to treatment and control strategy. This may have resulted in disease transmission.
The concentrations of anti-PT antibodies induced by vaccination or by infection couldn’t be differentiated by laboratory technique, eg, ELISA, but in this study, a distinctively increased level of anti-PT IgG was not noted after fresh vaccination among 0–2 years group. In China, children receive four doses of pertussis vaccines before two years of age. Therefore, higher level of anti-PT antibodies in age group 0–2 compared to other age groups would have been expected. In this present study, however, we did not observe such a difference. One explanation might be that homemade DTwP or DTaP vaccines from various manufactuers differ considerably in their immunogenicity. According to the Chinese Pharmacopoeia, DTaP are mainly composed of PT and FHA in pertussis ingrendients, but the proportion and content of two antigens were not described in instruction. It was indicated in other study that apart from high anti-PT antibody titers as correlate of protection, high titer of anti-FHA Antibody can also provide some protection against pertussis . This could be one explanation. In this study we didn’t measure anti-FHA Abs among children who received homemade DTP vaccines. However we believed that the increasing immunization coverage in China should contribute to the decreasing trend in pertussis cases reported. Unfortunately we do not have efficacy data from the vaccine trials in China. Another explanation might be the low number of studied subjects included in the age group.
We had to realize that the serological cut-off value for estimating the incidence was consulted to the data of present study on asymptomatic population and previous studies of EU. We have not validated its power for diagnosing pertussis patients who were confirmed by other methods such as PCR or culture. A prospective cohort study on pertussis infection in hospitalization is being planned in China CDC in which all three laboratory methods PCR, culture and serology ELISA will be used. Since China is a big country with 1.3 billion populations and this study was only carried out in one province, a multi-center studies should be conducted to further understand the burden of pertussis in this country.