Oral Fluid Testing for Pertussis, England and Wales, June 2007–August 2009 - Volume 20, Number 6—June 2014 - Emerging Infectious Disease journal - CDC

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Oral Fluid Testing for Pertussis, England and Wales, June 2007–August 2009 - Volume 20, Number 6—June 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 6—June 2014

Research

Oral Fluid Testing for Pertussis, England and Wales, June 2007–August 2009

Article Contents

• Methods
• Results
• Discussion
• Acknowledgment
• References
• Figure1
• Figure 2
• Figure 3
• Table 1
• Table 2
• Suggested Citation

Helen Campbell , Gayatri Amirthalingam, Norman K. Fry, David Litt, Timothy G. Harrison, Karen Wagner, Natasha S. Crowcroft, and Elizabeth Miller

Author affiliations: Public Health England, Colindale, London, UK (H. Campbell, G. Amirthalingam, N.K. Fry, D. Litt, T.G. Harrison, K. Wagner, E. Miller); Public Health Ontario, Toronto, Ontario, Canada (N.S. Crowcroft)

Suggested citation for this article

Abstract

Existing pertussis surveillance systems tend to underidentify less severe cases among older children and adults. For routine follow-up of notified, nonconfirmed, clinically diagnosed pertussis cases, use of an oral fluid test was pilot tested in England and Wales during June 2007–August 2009. During that period, 1,852 cases of pertussis were confirmed by established laboratory methods and another 591 by oral fluid testing only. Although introduction of serologic testing in 2002 led to the greatest increase in ascertainment of pertussis, oral fluid testing increased laboratory ascertainment by 32% overall; maximal increase (124%) occurred among children 5–9 years of age. Patients whose pertussis was confirmed by oral fluid testing were least likely to be hospitalized, suggesting that milder community cases were being confirmed by this method. Oral fluid testing is an easily administered, noninvasive surveillance tool that could further our understanding of pertussis epidemiology and thereby contribute to decisions on vaccination strategies.

Existing surveillance systems for pertussis are incomplete and tend to be biased toward identifying severe cases in infants (1,2), as reflected by extremely high reported incidence for this age group (3–5). Underascertainment of cases in older patients is well recognized because of a combination of factors, including reduced likelihood that patients with milder symptoms will seek health care, underdiagnosis for patients who do seek health care, and underreporting (6–9). Although these persons usually experience milder disease, often without classic signs and symptoms, some become substantially ill (9) and can still infect vulnerable infants. Additional test methods that provide adequate sensitivity and specificity and that are acceptable to health professionals and patients could therefore improve ascertainment of pertussis and provide data that are more representative of disease within the population.

Since the early 1960s, Bordetella pertussis has been isolated from the nasopharynx by use of conventional microbiological techniques. However, culture requires that a specimen be collected early in the illness and might lack sensitivity because the organism is delicate and any delay in processing specimens can reduce the probability of isolation (10). Isolation of the organism is more difficult if the patient has been vaccinated, if the patient has received antimicrobial drugs, and if too much time has gone by since onset of cough. PCR testing for the presence of B. pertussis DNA in nasopharyngeal samples is more sensitive than culture because the organism does not need to be viable (11). PCR sensitivity, however, decreases substantially with increasing patient age and duration of symptoms (12). Serologic testing has been established as a diagnostic method complementary to PCR, and recommendations by European Union reference laboratories for such assays have been described (13). Serologic testing is used in at least 20 European countries (14) (including the United Kingdom since 2002), Japan, and Australia to diagnose infection in patients who have been coughing for at least 2 weeks, when culture and PCR are less likely to yield positive results (10) as has been demonstrated in certain studies (15). Serologic testing has been used predominantly for older children and adults who tend to seek care later (5).

The Health Protection Agency (HPA; which became Public Health England on April 1, 2013) Respiratory and Systemic Infection Laboratory (which became the Respiratory and Vaccine Preventable Reference Unit on April 1, 2013) developed an ELISA to detect IgG against pertussis toxin in oral fluid (16). This test was intended to act as a surrogate for the serum antibody assay. Oral fluid sampling is appealing because collection is straightforward; it is noninvasive (oral fluid is collected from around the gum line by using an absorbent swab) and can be collected by the patient or parent/guardian in the home and mailed to the laboratory for testing. The oral fluid assay detects seropositivity with a sensitivity of 79.7% (95% CI 68.3%–88.4%) and a specificity of 96.6% (95% CI 91.5%–99.1%) (16). Thus, oral fluid titers of >70 arbitrary units have a positive predictive value of 76.2%–93.2% for pertussis among children with chronic cough when used as a surrogate for the serum ELISA, assuming disease prevalence of 12%–37% (which includes the lower and upper limits of disease prevalence shown by other studies) (17).

Similar oral fluid antibody tests have been developed by HPA as surrogates for serologic testing for measles, mumps, and rubella (18,19). Oral fluid testing of patients after their formal notification of clinically diagnosed measles, mumps, and rubella has been conducted in England and Wales since 1994; this test has been acceptable and is used to augment routine serologic diagnosis for these diseases (18). After completion of a successful small-scale study in 2 areas of England (20), it was decided to conduct a national pilot test for the use of oral fluid testing for pertussis as a similar surveillance tool to obtain laboratory confirmation of pertussis cases statutorily notified on the basis of clinical diagnosis. Oral fluid testing was chosen because of the ease of sample collection and the predicted increased patient compliance with use of a noninvasive testing method. All laboratory-confirmed cases of pertussis are coordinated on a national basis, and each is followed up by asking the Health Protection Units (HPUs) or patients’ general practitioners to complete a detailed surveillance questionnaire.

The aim of this national oral fluid surveillance was to improve case ascertainment and representativeness, increase rates of confirmation of notified cases, and provide more detailed information on notified cases of pertussis (if confirmed) via the surveillance questionnaire. Such improvements would strengthen the evidence base for vaccination policy decision making. We compared the effects of oral fluid testing as a notification follow-up service over the 27 months that it was available with effects during a comparable 27 months before its availability.

Acknowledgment

We thank the staff of the former Respiratory and Systemic Infection Laboratory (now Respiratory and Vaccine Preventable Bacteria Reference Unit), particularly John Duncan and Lalita Vaghji, for generating the serologic testing, oral fluid testing, PCR, and culture-confirmation results. We also thank Nick Andrews for generating the positive predictive values, and we thank all health professionals who contributed through their participation in the oral fluid pilot testing and enhanced surveillance of pertussis.

References

1. Van Buynder PG, Owen D, Vurdien JE, Andrews NJ, Matthews RC, Miller E. Bordetella pertussis surveillance in England and Wales: 1995–7. Epidemiol Infect.1999;123:403–11 . DOIPubMed
2. Clarkson JA, Fine PE. The efficiency of measles and pertussis notification in England and Wales. Int J Epidemiol. 1985;14:153–68 . DOIPubMed
3. Centers for Disease Control and Prevention. 2013 provisional pertussis surveillance report. Provisional 2013 reports of notifiable diseases. 2013:62 [cited 2013 Sep 3].http://www.cdc.gov/pertussis/downloads/pertussis-surveillance-report.pdf 
4. Public Health Agency of Canada. Pertussis [cited 2012 Jul 23].http://www.phac-aspc.gc.ca/im/vpd-mev/pertussis-eng.php
5. Campbell H, Amirthalingam G, Andrews N, Fry NK, George RC, Harrison TG, Accelerating control of pertussis in England and Wales. Emerg Infect Dis. 2012;18:38–47. DOIPubMed
6. Miller E, Fleming DM, Ashworth LA, Mabbett DA, Vurdien JE, Elliott TS. Serological evidence of pertussis in patients presenting with cough in general practice in Birmingham. [Erratum in: Commun Dis Public Health 2000;3:221.]. Commun Dis Public Health. 2000;3:132–4 .PubMed
7. Nardone A, Pebody RG, Maple PAC, Andrews N, Gay NJ, Miller E. Sero-epidemiology ofBordetella pertussis in England and Wales. Vaccine. 2004;22:1314–9 . DOIPubMed
8. Harnden A, Grant C, Harrison T, Perera R, Brueggemann AB, Mayon-White R, Whooping cough in school age children with persistent cough: prospective cohort study in primary care. BMJ. 2006;333:174–7 . DOIPubMed
9. Rothstein E, Edwards K. Health burden of pertussis in adolescents and adults. Pediatr Infect Dis J. 2005;24(Suppl):S44–7 . DOIPubMed
10. Hallander HO. Microbiological and serological diagnosis of pertussis. Clin Infect Dis.1999;28(Suppl 2):S99–106 . DOIPubMed
11. Fry NK, Duncan J, Wagner K, Tzivra O, Doshi N, Litt DJ, Role of PCR in the diagnosis of pertussis infection in infants: 5 years’ experience of provision of a same-day real-time PCR service in England and Wales from 2002 to 2007. J Med Microbiol. 2009;58:1023–9. DOIPubMed
12. van der Zee A, Agterberg C, Peeters M, Mooi F, Schellekens J. A clinical validation ofBordetella pertussis and Bordetella parapertussis polymerase chain reaction: comparison with culture and serology using samples from patients with suspected whooping cough from a highly immunized population. J Infect Dis. 1996;174:89–96. DOIPubMed
13. Guiso N, Berbers G, Fry NK, He Q, Riffelmann M, Wirsing von König CH. EU Pertstrain Group. What to do and what not to do in serological diagnosis of pertussis: recommendations from EU reference laboratories. Eur J Clin Microbiol Infect Dis.2011;30:307–12. Epub 2010 Nov 11. DOIPubMed
14. He Q, Barkoff AM, Mertsola J, Glismann S, Bacci S. European Bordetella expert group (EU Pertstrain); European Surveillance Network for Vaccine-Preventable Diseases (EUVAC.NET). High heterogeneity in methods used for the laboratory confirmation of pertussis diagnosis among European countries, 2010: integration of epidemiological and laboratory surveillance must include standardisation of methodologies and quality assurance. Euro Surveill. 2012;17:20239 .PubMed
15. Crowcroft NS, Booy R, Harrison T, Spicer L, Britto J, Mok Q, Severe and unrecognised: pertussis in UK infant. Arch Dis Child. 2003;88:802–6. DOIPubMed
16. Litt DJ, Samuel D, Duncan J, Harnden A, George RC, Harrison TG. Detection of anti-pertussis toxin IgG in oral fluids for use in diagnosis and surveillance of Bordetella pertussis infection in children and young adults. J Med Microbiol. 2006;55:1223–8. DOIPubMed
17. Fry NK, Litt DJ, Duncan J, Vaghji L, Warrener L, Samuel D, Modelling anti-pertussis toxin IgG antibody decay following primary and preschool vaccination with an acellular pertussis vaccine in UK subjects using a modified oral fluid assay. J Med Microbiol.2013;62:1281–9. Epub 2013 May 30. DOIPubMed
18. Manikkavasagan G, Bukasa A, Brown KE, Cohen BJ, Ramsay ME. Oral fluid testing during 10 years of rubella elimination, England and Wales. Emerg Infect Dis. 2010;16:1532–8. DOIPubMed
19. Brown DW, Ramsay ME, Richards AF, Miller E. Salivary diagnosis of measles: a study of notified cases in the United Kingdom, 1991–3. BMJ. 1994;308:1015–7. DOIPubMed
20. Crowcroft NS, Fry NK, Litt DJ, Harrison TG, George RC, Abid M, Whooping cough—better methods of diagnosis are now available. BMJ Rapid Responses 2007 [cited 2007 June 21].http://www.bmj.com/rapid-response/2011/11/01/whooping-cough-%E2%80%93-better-methods-diagnosis-are-now-available
21. Public Health Laboratory Service. Whooping cough: enhanced laboratory surveillance of pertussis, England and Wales 2002. CDR Weekly 2003;13:7–9.
22. de Melker HE, Versteegh FG, Conyn-Van Spaendonck MA, Elvers LH, Berbers GA, van Der Zee A, Specificity and sensitivity of high levels of immunoglobulin G antibodies against pertussis toxin in a single serum sample for diagnosis of infection with Bordetella pertussis. J Clin Microbiol. 2000;38:800–6 .PubMed
23. Health Protection Agency. Laboratory-confirmed cases of pertussis reported to the enhanced pertussis surveillance programme in 2011. Health Protection Report 2012; 6 [cited 2013 Sep 3].http://www.hpa.org.uk/hpr/archives/2012/hpr0812.pdf 
24. Amirthalingam G. Strategies to control pertussis in infants. Arch Dis Child. 2013 May 22. [Epub ahead of print]http://adc.bmj.com/content/98/7/552.full.pdf+html?sid=0a6a8493-4c2b-4b58-9fc0-112e37264597
25. UK Department of Health. Pregnant women to be offered whooping cough vaccination, [cited 2012 Sep 28].http://www.dh.gov.uk/health/2012/09/whooping-cough/
26. Centers for Disease Control and Prevention. Pertussis epidemic—Washington, 2012.MMWR Morb Mortal Wkly Rep. 2012;61:517–22.PubMed
27. Campbell P, McIntyre P, Quinn H, Hueston L, Gilbert GL, McVernon J. Increased population prevalence of low pertussis toxin antibody levels in young children preceding a record pertussis epidemic in Australia. PLoS ONE. 2012;7:e3587. Epub 2012 Apr 27. DOIPubMed
28. Government of New Brunswick. Update/whooping cough outbreak. News release [cited 2012 Mar 26].http://www2.gnb.ca/content/gnb/en/news/news_release.2012.03.0255.html
29. Health and Safety Watch Inc. Update: according to Vancouver Coastal Health, pertussis activity declined significantly in the fall of 2012 [cited 2013 Jan 16].http://www.healthandsafetywatch.com/HSWEvents.aspx?EventID=c2e8c6d3-b2d9-4b52-b594-fed31c386bbd
30. Ramsay MEB, Farrington CP, Miller E. Age-specific efficacy of pertussis vaccine during epidemic and non-epidemic periods. Epidemiol Infect. 1993;111:41–8. DOIPubMed
31. Philipson K, Goodyear-Smith F, Grant CC, Chong A, Turner N, Stewart J. When is acute persistent cough in school-age children and adults whooping cough? A prospective case series study. Br J Gen Pract. 2013;63:573–9. DOIPubMed
32. Public Health England. Laboratory-confirmed cases of pertussis reported to the enhanced pertussis surveillance programme during October to December 2012. Health Protection Report Vol. 7, Nos. 14–17: 5, 12, 19 and 26 April 2013 [cited 2013 Sep 9].http://www.hpa.org.uk/hpr/archives/2013/hpr14-1713.pdf 
33. Misegades LK, Winter K, Harriman K, Talarico J, Messonnier NE, Clark TA, Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine dose, California, 2010. JAMA. 2012;308:2126–32. DOIPubMed
34. Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak. Clin Infect Dis.2012;54:1730–5. DOIPubMed
35. Gabutti G, Rota MC. Pertussis: a review of disease epidemiology worldwide and in Italy.Int J Environ Res Public Health. 2012;9:4626–38 . DOIPubMed

Figures

• Figure1. Distribution of notified cases of pertussis and pertussis samples submitted to the Health Protection Agency (HPA; became Public Health England on April 1, 2013) Respiratory and Systemic Infection Laboratory (RSIL;...
• Figure 2. Rates of pertussis notification and laboratory confirmation (nocases/100,000 population), by test method, England and Wales, 1998–2009When >1 test method was used, culture takes precedence over PCR, which takes precedence...
• Figure 3. Proportion of cases hospitalized by age group and test method, England and Wales, June 2007–August 2009When >1 test method was used, culture takes precedence over PCR, which takes precedence...

Tables

• Table 1. Distribution of samples received by RSIL for pertussis testing, England and Wales, June 2007–August 2009
• Table 2. Total and proportion of confirmed pertussis cases, England and Wales, June 2007–August 2009

Suggested citation for this article: Campbell H, Amirthalingam G, Fry NK, Litt D, Harrison TG, Wagner K, et al. Oral fluid testing for pertussis, England and Wales, June 2007–August 2009. Emerg Infect Dis [Internet]. 2014 Jun [date cited]. http://dx.doi.org/10.3201/eid2006.131069

DOI: 10.3201/eid2006.131069