In recognition of the fact that the signs and symptoms of pertussis differ by age, we have tailored criteria for pertussis diagnosis in 3 different age cohorts (0–3 months, 4 months–9 years, and ≥10 years). These criteria are presented in Figure . In Figure , clinical case definitions of pertussis for surveillance purposes are presented.
Figure 1. Algorithm for the diagnosis of pertussis. Abbreviations: IgG, immunoglobin G; PCR, polymerase chain reaction; PT, pertussis toxin; RSV, respiratory syncytial virus; WBC, white blood cell. aIn resource-limited areas where PCR is not available, samples (more ...)
Clinical case definition of pertussis for surveillance purposes.
These case definitions are intended to: (1) be more specific and/or more sensitive than existing case definitions of pertussis (which were developed more than 40 years ago and were primarily designed either for surveillance purposes or for vaccine efficacy studies), (2) be applicable to both resource-rich and resource-poor settings, (3) encourage the increased use of laboratory confirmation, and (4) increase the sensitivity and specificity of pertussis reporting.
If a patient meets 1 or more of the criteria for pertussis diagnosis, the physician should treat the patient and report the case to the appropriate health agencies. General comments on the clinical presentation of pertussis and its laboratory diagnosis are presented in Tables and , respectively.
General Comments on Clinical Presentation of Pertussis
General Comments on Laboratory Diagnostics of Pertussis
There are a number of strong indicators of pertussis that differ by age group. In young infants, the occurrence of coryza and cough in an afebrile child is usually not alarming. When these young infants are seen by physicians, they are thought to have a viral respiratory infection, and the parents are reassured. However, over the next day or two, the parents recognize the worsening of symptoms, but more often than not, the physicians do not (based on author experience in California in 2010 [J. D. C.]). The key indicators of pertussis in these young infant cases are the afebrile nature of the illness combined with a cough that is increasing in frequency and severity and a coryza that remains watery. Therefore, the presence of this triad would be expected to have high sensitivity and good specificity. The addition of apnea, seizures, cyanosis, emesis, or pneumonia would result in both high sensitivity and specificity. In these young infant cases, an elevated white blood cell count (≥20 000 cells/µL) with absolute lymphocytosis is virtually diagnostic.
In older children (4 months to 9 years), the presence of a worsening paroxysmal, nonproductive cough of ≥7 days’ duration in an afebrile child with coryza that has not become purulent also would indicate high sensitivity and good specificity for pertussis. As noted with current case definitions, the addition of whoop, apnea, and posttussive emesis will each increase specificity. In those persons ≥10 years of age, the same triad listed above for those 4 months to 9 years would also result in high sensitivity with good specificity. In addition, the notation of sweating episodes between paroxysms will significantly increase specificity. In dealing with adult patients, it is important to ask specific questions about productive cough. Adults will often say that the cough is productive, but on further questioning, it is apparent that they actually do not produce purulent sputum.
The case definitions of pertussis delineated here should first be tested in clinical trials to determine their utility to the average clinician and then be compared with existing case definitions to determine whether they confer increased sensitivity and/or specificity. Although retrospective analyses are subject to bias, such analyses could be performed first in a “proof-of-principle” approach. If the new case definitions appear promising, a prospective study should be conducted to evaluate the proposed diagnostic criteria in the 3 different age categories (0–3 months, 4 months to 9 years, ≥10 years).
The protocol we propose would involve the prospective evaluation of all persons in a defined population with cough illnesses of ≥7 days’ duration stratified into the 3 different age categories. The study populations should include geographic regions with different vaccine usage patterns (acellular, whole-cell, or both). Protocols could be adopted from the Adult Pertussis Trial (APERT) and the vaccine efficacy trial in Erlangen, Germany [12
]. In both of these studies, investigators contacted participants every 2 weeks, and all subjects with cough illness of ≥7 days that was not improving were evaluated. Intensive education programs will be necessary to prevent observer bias [36
]. Studies should be of such duration that they cover the cyclical epidemiologic patterns of pertussis and include populations of sufficient size to allow statistical analysis.
The development and utilization of 3 age-related definitions for pertussis can be expected to increase both the sensitivity and specificity in its diagnosis, which will result in the recognition of pertussis in all age groups, potentially leading to better control of pertussis.