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