Serological evidence of pertussis in patients presenting cough

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					original reports

                   Serological evidence of pertussis in patients
                   presenting with cough in general practice in
                   E Miller, DM Fleming, LAE Ashworth, DA Mabbett, JE Vurdien, TSJ Elliott

                   Summary: Three hundred and fifty-six patients in a large suburban practice                          Key words:
                   (registered population 10 400), were diagnosed clinically with acute laryngitis/             Bordetella pertussis
                   tracheitis or whooping cough (acute spasmodic cough of three weeks duration)                              cough
                   between March 1996 and November 1997. Forty out of 145 who provided specimens                  pertussis vaccine
                                                                                                               primary health care
                   for serological testing had evidence of recent infection with Bordetella pertussis.
                   During the study a further 18 patients (mostly younger patients who presented
                                                                                                                  whooping cough
                   early) had a diagnosis of pertussis confirmed by culture. Fifty-eight cases of
                   pertussis in this population and time period was equivalent to an annual incidence
                   of 330 per 100 000, whereas statutory notifications of pertussis in England and
                   Wales suggested an incidence of less than 4 per 100 000 in the same period.
                   Whooping cough remains an important cause of respiratory illness in all age groups.
                   These results are a reminder for general practitioners to be alert to the diagnosis
                   and a prompt to reconsider national vaccination policy.

                   Commun Dis Public Health 2000; 3: 132-4.

                   Introduction                                               supplemented by statutory notifications of clinically
                   The high coverage achieved with whole cell                 diagnosed cases from general practitioners and
                   diphtheria/tetanus/pertussis (wDTP) vaccine in the         paediatricians, and data from general practitioners
                   United Kingdom (UK) in recent years has resulted in        who report to the Weekly Returns Service of the Royal
                   a marked decline in the incidence of whooping cough        College of General Practitioners 2. All data sources
                   in all age groups 1 . In consequence, immunised            are inevitably biased towards diagnosing cases in
                   children now have less opportunity for boosting            young, unvaccinated children who present with
                   immunity through exposure to the disease. Currently        clinically typical disease and in whom culture
                   no booster doses of pertussis vaccine are given in the     positivity rates are highest. It is more difficult to
                   UK after completion of the primary course at 4             diagnose pertussis in older people and in those who
                   months of age, but this policy may need to be revised      have already been vaccinated since the clinical
                   since there is less opportunity for natural boosting.      features are often atypical and the diagnosis is
                      Surveillance of the incidence of pertussis in the       usually not considered until late in the illness when
                   UK relies on laboratory reports of Bordetella pertussis,   there is little chance of isolating B. pertussis.
                                                                                 Increased clinical suspicion of infection and more
                                                                              sensitive laboratory diagnostic methods are needed
                   E Miller, LAE Ashworth, JE Vurdien                         to assess the true extent of pertussis in older people
                   PHLS Communicable Disease Surveillance Centre              and those who have been vaccinated. Serological
                   DM Fleming                                                 methods using antigen-specific enzyme linked
                   Birmingham Research Unit of the Royal College of General   immunoassays (ELISAs) have been used extensively
                                                                              in recent trials of acellular pertussis vaccine to
                   DA Mabbett
                                                                              increase the sensitivity of the laboratory diagnostic
                   Northfield Health Centre, Birmingham
                                                                              methods in vaccinated children 3,4 . The results of
                   T J Elliot
                   Queen Elizabeth Hospital, Birmingham                       serological investigation for evidence of recent
                                                                              pertussis infection in patients presenting with
                   Address for correspondence:
                   Dr Douglas Fleming                                         spasmodic or prolonged cough in one general
                   RCGP Birmingham Research Unit                              practice surgery in England are reported here.
                   Lordswood House
                   54 Lordswood Road
                   Birmingham B17 9DB
                   tel: 0121 426 1125                                         The study was carried out in a surgery with 10 400
                   fax: 0121 428 2084                                         registered patients (2400 aged 0-14 years) in
                   email:                       Birmingham between March 1996 and November

  132              VOL 3 NO 2 JUNE 2000                                            COMMUNICABLE DISEASE AND PUBLIC HEALTH
                                                                                                                                   original reports
1997. The study included patients who presented                (6%) reported whooping and 42 (29%) vomiting.
clinically with acute tracheitis or spasmodic cough                Twenty-eight pernasal swabs were cultured for
that persisted for more than three weeks and who               B. pertussis, four of which were positive. The patients
consented to serological investigation for pertussis.          thus investigated were generally younger than the
Histories of vaccination against pertussis were                group studied serologically and presented earlier in
obtained from practice records. A blood sample was             the course of the illness.
taken at presentation and tested for IgG and IgA                   Serological evidence of recent pertussis infection
antibodies to pertussis toxin (PT) and agglutinogens           was found in 28% (40/145) patients with acute
2 and 3 (Aggs) by ELISA at the Centre for Applied              trachicitis or whooping cough studied serologically
Microbiology and Research5. Antibody levels in the             (mean age 31 years; range 5-78); 17 had a documented
study patients were compared with those in 323 age             history of full pertussis immunisation (table). One
matched controls. Control sera were residues from              of the cases negative on serology, whose only blood
specimens submitted to 16 public health laboratories           sample was taken only two weeks after onset,
in England and Wales in 1996 for other serological             provided a swab that yielded B. pertussis.
investigations 6 . Serum specimens from patients                   Among the 356 patients were 211 (mainly children)
investigated for suspected pertussis would not have            who were not investigated serologically. About half
been included as these laboratories do not offer               provided a pernasal swab, 17 of which grew
serological diagnosis of pertussis. The criteria for           B. pertussis; 15 of the 17 cases were fully immunised
the diagnosis of pertussis based on a single specimen          (age range 9 months - 15 years). Thus, during the 20
were either at least two antibodies with levels ≥2             months of the study, 58 patients were identified with
standard deviations (SD), or at least one antibody with        serological and/or bacteriological evidence of
a level ≥3 SD, above the mean of the age matched               pertussis, 32 (55%) of whom were known to be fully
controls. Only IgG antibodies to Aggs showed a                 vaccinated. The use of serology increased the
significant age related trend, thus requiring an age-          number of confirmed cases from 21 to 58. The 58
dependent threshold.                                           confirmed cases in a population of 10 400 per year
    The results of investigating pernasal swabs taken          roughly equates to 330 cases per 100 000 per year.
as routine clinical practice for culture of B. pertussis
in the same period were also studied.                          Discussion
    The study was approved by the South Birmingham             Stringent serological criteria were used to diagnose
Local Research Ethics Committee on the assumption              pertussis, requiring antibody levels to specific
that patients from whom serum specimens were                   pertussis antigens which, using normality
requested were given a written explanation of the              assumptions for log titres, are exceeded by less than
experimental nature of the test.                               1% of a control population. The presence of
                                                               compatible symptoms in the 40 patients who met
Results                                                        these criteria supported the serological diagnosis.
Three hundred and fifty-six patients (153 males and            Inappropriately early sampling for evaluating
203 females) presented with symptoms leading to a              pertussis using a single titre estimation, or
clinical diagnosis of acute tracheitis (75%) or                excessively stringent serological criteria, may have
whooping cough (25%). Of these, 145 mostly older               led to an underestimate of the true proportion of
patients (57 males and 88 females, mean age 38 years;          patients presenting with pertussis.
range 5-92) provided serum specimens, which were                  The discrepancy between the true incidence of
requested because their cough had a paroxysmal                 pertussis and official notifications is well recognised,
character and had lasted more than three weeks or              but the extent of the difference disclosed by this
was accompanied by whooping or vomiting. Blood                 study of confirmed cases, particularly in older people
samples were taken at a median of four weeks after             in whom the diagnosis may not commonly be
the onset of cough (range 1-26 weeks). Eight patients          considered by clinicians, is greater than we had

TABLE Consultations for acute tracheitis/pertussis and results in patients serologically tested for pertussis: March 1996
– November 1997

                                                                                  Patients serologically investigated
                                   Total consultations for
                                    tracheitis/pertussis                  total                              fully vacinated

       Age group (years)             n      annual rate/1000        n             Pos. (%)              n               Pos. (%)

       0-4                           76            37               –              –                     –               –
       5-14                         120            22              29             13   (45)             18               9 (50)
       15-44                         82             6              58             16   (28)             16               8 (50)
       45-64                         48             8              35              6   (17)              –               –
       65+                           30             7              23              5   (22)              –
       Total                        356            12             145             40 (28)               34              17 (50)

COMMUNICABLE DISEASE AND PUBLIC HEALTH                                                                   VOL 3 NO 2 JUNE 2000       133
original reports

                   expected. In the two years 1995 and 1996 (when more             population in the under 15 year age group did not
                   notifications were made than in recent years) there             exceed 90%, an observed proportion of 82% of
                   were 4256 statutory notifications of pertussis in               confirmed cases in vaccinated children suggests a
                   England and Wales, equivalent to an annual                      vaccine efficacy of less than 50%10.
                   incidence of about 4/100 000. In this study the annual             Further studies using enhanced laboratory
                   incidence of confirmed pertussis was around 330/                diagnostic methods combined with increased clinical
                   100 000. Our results accord with studies in Australia7,         awareness are needed to define the true burden of
                   the United States 8, and Germany 9, which have shown            morbidity attributable to whooping cough and to
                   that adult pertussis is under-recognised and may be             make rational decisions about the need for booster
                   important in maintaining endemic transmission in                immunisation in the UK.
                   vaccinated populations. All doctors, especially
                   general practitioners, need to be more alert to the             References
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