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Human Vaccines & Immunotherapeutics 9:2, 322–324; February 2013; © 2013 Landes Bioscience

Case RepoRt

322 Human Vaccines & Immunotherapeutics Volume 9 Issue 2

*Correspondence to: Anandagiri Shankar; Email: giri.shankar@hpa.org.ukSubmitted: 08/29/12; Revised: 10/09/12; Accepted: 10/15/12http://dx.doi.org/10.4161/hv.22553

Introduction

Pertussis, commonly known as ‘whooping cough’ is an acute bacterial respiratory infection caused by Bordetella pertussis, a small, fastidious gram-negative aerobic coccobacillus with exclusive affinity for the mucosal layers of the human respira-tory tract. Bordetella pertussis is an exclusively human pathogen which can affect people of all ages. While adolescents and adults tend to display mild symptoms, infants and young children, particularly those who are not immunized, are the most vul-nerable group with the highest rates of complications and mor-tality. The majority of hospitalizations following pertussis have occurred in those under six months of age.1 Transmission of the organism is through airborne droplets of respiratory secretions and occurs as a result of close direct contact with an infected person.2 It is highly contagious, with up to 90% of susceptible household contacts developing the disease.2 The incubation period of pertussis is on average between 7–10 d (range 5–21 d), cases are infectious from six days after exposure to three weeks after the onset of typical paroxysms. Symptoms vary signifi-cantly depending on age but the usual clinical presentation is an initial catarrhal stage with a cough that becomes paroxysmal. Paroxysms of cough usually increase in frequency and severity as the illness progresses and persist for 2–6 weeks. These par-oxysms may end in vomiting, cyanosis and/or a characteristic

a 20 mo old male child, born at 31 weeks, presented to an out-of-hours General practitioner (Gp) with a 7 d history of cough and fever. there was history of post-tussive vomiting. on assessment a pernasal swab was cultured from which B. pertussis was isolated. this child had received a complete course of primary immunization. In the light of recent increase in pertussis cases in the United Kingdom we would like to use this case report to increase the awareness among clinicians to the possibility of a diagnosis of whooping cough even in children with completed primary immunization and particularly in preterm infants.

Bordetella pertussis infection in a child with completed primary immunization

A case reportananda Giri shankar,1,* alan Lee,2 Harish Reddy3 and Martin seymour4

1Consultant in communicable disease control; Norfolk, suffolk and Cambridgeshire; Health protection Unit; the Health protection agency; Norfolk, UK; 2General practitioner; Dryaton and st. Faiths’s Medical practice; Norwich, UK; 3Microbiologist; Norfolk and Norwich University Hospitals; Norwich, UK; 4specialty Registrar in public Health; Norfolk,

suffolk and Cambridgeshire; Health protection Unit; the Health protection agency; Norfolk, UK

Keywords: Bordetella pertussis, whooping cough, vaccine failure, vaccination, United Kingdom

Abbreviations: OOH, GP out of hours service; AP, acellular pertussis vaccines; WP, whole cell pertussis vaccine; CI, confidence interval; FHA, filamentous haemaglutinin; GP, General Practitioner; HPA, Health Protection Agency; PRN, Pertactin; FIM,

fimbiral agglutinogens 2 & 3; UK, United Kingdom

inspiratory “whoop.” Patients with pertussis are most infectious in the initial catarrhal stage and during the first three weeks after the onset of cough.2 Symptoms slowly improve in the con-valescent phase, which generally lasts 2–6 weeks but can persist for months. Serious complications include pneumonia, seizures, encephalitis and death. Vaccination is the only effective strat-egy for preventing pertussis transmission in the population, although protection afforded by vaccination or from past infec-tion is not lifelong.

The United Kingdom (UK) childhood immunization sched-ule consists of three primary infant doses of pertussis containing vaccine given at 2, 3 and 4 mo of age and a preschool booster dose between 3 y 4 mo and 5 y of age.3 This is given as a combination vaccine that contains DTaP, IPV and HiB. Along with this vac-cine, pneumococcal conjugate vaccine and vaccine against men-ingitis C are also given as appropriate for the age.3

In the UK there has been a marked increase in the number of laboratory confirmed pertussis cases in the last 18 mo. Over 2000 cases have been confirmed in 2012 alone. The bulk of the burden of infection is in young infants (< 3 mo) and adults (> 15 y).4

In light of the recent changing epidemiology of pertussis in the UK we thought that this case report would be timely to raise awareness among clinicians about considering pertussis as a diag-nosis in patients presenting with respiratory symptoms consistent

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Case RepoRt Case RepoRt

colonies on the selective blood agar were characteristic of B. per-tussis and were smooth, convex, pearly, glistening, gray-white and butyrous. Microscopically, the Gram stain of the colonies showed that it was Gram negative coccobacilli arranged singly and some in pairs, which is typical for B. pertussis. Oxidase test revealed a positive reaction (B. parapertussis gives a negative oxidase reac-tion). A slide agglutination test with B. pertussis polyvalent anti-serum gave a positive result. Based on these tests performed in the laboratory, a presumptive diagnosis of B. pertussis was made. The isolate was subsequently referred to the Respiratory and Systemic Infection Laboratory (HPA’s Pertussis reference laboratory) for confirmation.

Confirmation of Diagnosis

Further tests were performed on the isolate at the HPA’s Pertussis reference laboratory and was confirmed to be Bordatella pertussis Serotype 1, 3.

Outcomes

Confirmation from the microbiology laboratory, together with the clinical diagnosis led to the conclusion that the vaccination had failed or persistence of vaccine-induced protection was weak. The child was prescribed Azithromycin, 125 mg every 6 h for 7 d. The child was seen again by the GP two weeks later and was still coughing and had a wheeze. On this occasion Clarithromycin, 62.5 mg twice a day for 7 d was prescribed. Following this the child completely recovered and was given a booster vaccination. The child has not been seen by the GP for over a year now.

Discussion

This is a case of confirmed B. pertussis infection in a 20 mo old child, who was born preterm and had received a complete course of primary immunization against pertussis. Although the child was born preterm there were no known other underlying medical conditions.

Isolated cases of failure of primary immunization are not uncommon. The efficacy of primary 3 dose immunization for pertussis vaccine ranges from 85–90% in published literature.5 Multi-component whole cell (wP) vaccines were previously used in the UK but were replaced by acellular vaccines (aP) following concerns about the adverse side effects of whole cell pertussis (wP) vaccines which led to a fall off of uptake and subsequent resur-gence of pertussis cases in the 1970s and 80s.6 There remains some debate as to whether wP vaccines are more effective than multicomponent aP vaccines, but adverse events are known to be fewer with the aP vaccine.

Zhang et al.6 reported on the efficacy of different pertussis vac-cines for a Cochrane review. Reporting on 6 efficacy trials they concluded that multi-component (greater than 3) vaccines with an efficacy rate of 84–85% in preventing whooping cough and 71–78% in preventing mild pertussis disease were more success-ful than single component vaccines which ranged from 59–75% in preventing whooping cough, and 13–54% in preventing mild

with the infection and to particularly be aware that a primary course of vaccination, very rarely, does not protect individuals.

Patient Presentation

A 20 mo old male child presented to an out-of-hours General Practitioner (GP) with a 7 d history of cough and fever in May 2011. The child was immediately transferred to the Children’s Assessment Unit at the local university hospital. On examina-tion the child had a respiratory rate of 60 breaths per minute and a heart rate of 180 beats per minute; was febrile and had a cough and wheeze. A chest radiograph showed nothing abnor-mal. The child was given salbutamol (through nebulisation) which improved oxygen saturation from 93% to 99% and was discharged with a diagnosis of viral wheeze. Blood sample for routine investigations along with a pernasal swab was taken dur-ing this consultation.

The following day the child was seen by his regular GP and was found to be afebrile, well in himself and had a mild expira-tory wheeze. He was given steroids (prednisolone) for 3 d and a delayed prescription for amoxicillin. As the cough and wheeze still persisted the child’s parents ensured this course of antibiotics was completed. However the child remained unwell with cough and minimal wheeze even after this.

Past Medical History

This child had been born preterm at 31 weeks but had no devel-opmental delays or other complications. He was not breast fed and was on formula feeds from birth. Childhood immuniza-tions were given on schedule and were up to date. In particular the child had received 3 doses of pertussis containing vaccine (DTaP/IPV/HiB) at ages 2, 3 and 4 mo respectively as per the UK immunization schedule.3 The child had been away from UK when the family had traveled to India and stayed there for 2 mo. During the stay the child was reportedly unwell on and off with respiratory symptoms and had been admitted to a local hospi-tal where a diagnosis of bronchopneumonia was made This was treated with antibiotics and the child had recovered well.

Diagnosis

A pernasal swab was collected in the Children’s Assessment Unit of the local University Hospital which was received in the micro-biology laboratory on the same day. The sample was processed as per the standard operating procedure (SOP) of the labora-tory which is based upon the national SOP guidelines of Health Protection Agency.

The swab was inoculated on to a charcoal blood agar with cephelexin (Selcetive medium which supports growth of B. per-tussis and suppresses nasopharyngeal flora) and chocolate agar. The plates were then incubated aerobically at 35°C in a moist chamber containing 5–10% CO

2 and checked everyday for 7 d to

look for the presence of any growth. Following 7 d of incubation, there was a faint growth of bacterial colonies on the charcoal blood agar plate. There was no growth on the chocolate agar. The

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no difference in the immune response to pertussis vaccine as observed by Ab titer to PT, FHA and PRN between preterm and term infants.

The review conducted by Baxter et al.12 concluded that prema-ture infants given a 3 course of acellular pertussis vaccine (2, 3, 6 mo or 2, 4, 6 mo schedule) should respond equally to FHA and PRN but will have a reduced response to PT. They recommended considering extra vaccinations for preterm children as is currently the case in other countries including the USA which advises a 6 dose program at 2, 4, 6, 18 mo, preschool and school leaving for all children. These finding add to the wider debate over the wan-ing of immunity apparent in older teenage and young adults who received the aP vaccine and the discussion over the appropriate-ness of the current vaccine schedule in the UK. In conclusion this 20 mo old child developed pertussis infection despite hav-ing received a full course of primary immunization. Prematurity coupled with lowered immunity perhaps due to lack of breast feeding and weaker persistence of vaccine-induced immunity could have contributed to the susceptibility.

Recommendations

In the UK there has been a steep increase in the numbers of per-tussis cases and we recommend through this case report that cli-nicians should keep in mind a differential diagnosis of pertussis in cases presenting with respiratory symptoms consistent with the infection and be aware of the potential for impaired immunity and/or weaker persistence of vaccine-induced immunity among premature children who have received the pertussis vaccine, owing to the reported reduced response to the pertussis toxin component of the acellular vaccine. Further research is required to determine whether extra vaccinations for children should be considered.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

pertussis disease. In one of the studies included in this review Jefferson et al.7 reported the efficacy for aP vaccines as 67–70% for 1- or 2-component vaccines, 84% for 3-component vaccines, 80% for 4-component vaccines, and 84% for 5-component. Efficacy for wP ranged from 61% (RR 0.39, 95% CI: 0.27–0.57) to 89% (RR 0.11, 95% CI: 0.08 – 0.15).

In respect to doses received, a case control study of 184 sub-jects and 893 controls Bisgard et al.8 showed the unadjusted esti-mated vaccine efficacy for 1 or 2 pertussis doses was 83.6% (95% CI: 61.1–93.1%); for 3 doses was 95.6% (95% CI: 89.7–98.0%) and for ≥ 4 doses was 97.7% (95% CI: 94.7–99.0%) all com-pared with no doses of aP.8

The child in this case was born preterm at 31 weeks. Baxter9 asserts that preterm infants with gestational age of less than 32 weeks have impaired immune function which resolves at variable times after birth. The author refers to 2 studies showing a reduced response to the pertussis toxin (PT) component of the acellular vaccine, but no effect on the filamentous haemaglutinin (FHA), pertactin (PRN) and fimbrial agglutinogens 2 and 3 (FIM). Low levels of PT antibodies have been shown to be related to suscep-tibility to pertussis in children and young adults.10 Furthermore, premature infants have a lesser IgG anti-PT response and, while not specifically relevant to the current case, this is especially so in those treated with corticosteroids for respiratory distress. The child was also not breast fed and this could well have contributed to lowered immunity against natural infection as well as response to vaccination.

D’Angio11 also found that while larger premature infants mount immune responses to vaccines similar to those of full term infants, very premature infants (< 28–32 weeks’ gestation at birth) may have specific defects in vaccine responsiveness. The research concluded however that although there are minor dif-ferences in immunogenicity, the immune responses to pertussis (along with diphtheria, tetanus, and polio antigens) are similar enough between full-term and premature infants that clinical consequences are unlikely to result. Likewise Baxter et al.12 in a UK case series report from a special care baby unit also found

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