Acellular pertussis vaccines (APV) are known to be of suboptimal efficacy against typical pertussis or whooping cough (defined by the World Health Organization as ≥21 days of cough with ≥1 typical sign such as paroxysms, whoop, or post-tussive vomiting) caused by Bordetella pertussis with point estimates in the range of 70% to 92% after a complete primary immunization series of 3 or 4 doses in the first 2 years of life.1 Like immunization, natural infection with B. pertussis also does not lead to persistent and reliable immunity against reinfection with the same organism and the time intervals between repeated episodes published in the literature range from 4 to 20 years.2 Similarly, whooping cough caused by Bordetella parapertussis followed by whooping cough caused by B. pertussis infection was reported in 4 unimmunized Swedish children in 1994.3 Approximately 40 years earlier, as part of a large Danish whooping cough surveillance study from 1950 to 1957, Lautrop4 identified 78 children and 1 adult with either simultaneous B. pertussis and B. parapertussis infections in “about one-third” of cases, B. pertussis infection that was followed by B. parapertussis infections in 4 children and in the remaining great majority of cases, B. parapertussis infection was followed by B. pertussis infection. In this Danish case series, apparently only a few of these children had a history of 3 immunizations at weekly intervals with an unspecified whole-cell pertussis component vaccine (WPV) at that time, however, no vaccine effectiveness analyses were performed. With regards to prevention of whooping cough caused by B. parapertussis infection, one WPV (manufactured by Lederle [Pearl River, NY], at that time) was less efficacious than the APV comparator (Lederle/Takeda 4 component) in a study performed by members of our group5: the point estimates for efficacy against typical (ie, WHO defined) whooping cough were 58% (95% confidence interval: 14–80) and 25% (−45 to 61), respectively. In an efficacy trial of different manufacturers’ WPV and APV vaccines, no evidence of efficacy against whooping cough caused by B. parapertussis infection was found.6
It should be noted that these were post hoc analyses as none of the trials was designed to assess vaccine efficacy against B. parapertussis infections.
We report on a boy with polymerase chain reaction-proven consecutive B. pertussis and B. parapertussis infections leading to typical whooping cough disease at the age of 2 years and 1 month and 5 years and 2 months, that is, 4 and 41 months, respectively, after the 4th dose of a complete primary pertussis immunization series. To our knowledge, this is the first such report in an age-appropriately immunized child in the era of APVs and it adds to the enigma of B. pertussis and B. parapertussis infections.
This 5-year-old boy presented to one of us (D.S.) with a history of 14 days of cough. Since he had a very similar cough disease 37 months before, which had been diagnosed by PCR as pertussis caused by B. pertussis infection, the child’s parents and the pediatrician suspected a reinfection. Therefore, a nasopharyngeal swab was obtained for PCR that was negative for B. pertussis but positive for B. parapertussis. He received clarithromycin orally and continued to cough for 6 weeks. No other family members developed a cough and the source of infection remained unclear. At the age of 2, 3, 5 and 21 months, the boy had received a series of 4 doses of acellular pertussis combination vaccine according to the recommended 3 + 1 schedule in Germany. The vaccine used was Infanrix hexa, manufactured and distributed in many European countries by GlaxoSmithKline (Rixensart, Belgium), which contains defined amounts of diphtheria and tetanus toxoid, 3 B. pertussis antigens (pertussis toxoid, filamentous hemagglutinin and pertactin), inactivated poliomyelitis virus types 1–3, Haemophilus influenzae type B polyribosyl ribitol phosphate and hepatitis B surface antigen.
In comparative cohort studies, signs and symptoms of cough illness caused by B. parapertussis infection are on average milder and of shorter duration when compared with those caused by B. pertussis infection.7,8 However, as demonstrated in our case, when confronted with an individual patient, illness caused by B. parapertussis infection is clinically indistinguishable from illness caused by B. pertussis. Importantly, B. pertussis infection or vaccination with a whole-cell pertussis vaccine does not protect against whooping cough caused by B. parapertussis and infection with B. parapertussis does not appear to induce protection against disease caused by B. pertussis.3,5,6,8 Moreover, there is lack of evidence for APV in use today to protect against B. parapertussis disease. Therefore, there is a need for application of specific diagnostic tests to discriminate between B. pertussis and B. parapertussis infections as part of pertussis surveillance accompanying immunization programs.
Physicians confronted with children with cough illness must consider the possibility of B. parapertussis infection irrespective of the patient’s immunization history and/or previously diagnosed whooping cough by B. pertussis infection. In the absence of a specific serologic test to confirm B. parapertussis infection, a reliable diagnosis relies on demonstration of the organism by culture or PCR.9
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