Details of clinical diagnosis
(extract from doctorate thesis)
This study has revolved around a clinical diagnosis of whooping cough, a disease with a broad spectrum of severity and a belief that about 25% of infections sufficient to provide immunity are asymptomatic or subclinical.1,2 But what is the basis for clinical diagnosis, which in practice undoubtedly causes great difficulty and confusion? There is, as might be expected, no universally accepted clinical definition, although there is general acceptance that it causes two to three weeks of paroxysmal coughing, sometimes with vomiting, whooping or apnea. A large number do not whoop at all. A whoop is an inspiratory stridor after a paroxysm and therefore its presence will depend on a variety of factors unrelated to the disease, such as age, inspiratory flow rate and individual variation in laryngeal anatomy. It is also well known that infants may have apnea without even coughing in "whooping cough". So a "whoop" is not a very useful symptom for diagnosis, and in some circumstances neither is a cough.
There is a clinical definition used by the WHO which is undoubtedly useful for standardizing epidemiological data but is unlikely to be better than astute local and clinical knowledge when making a clinical diagnosis. A definition that requires three weeks of paroxysmal coughing, whooping and apnea will be more specific but less sensitive than one that requires only two weeks of paroxysmal coughing, not least because the concept of a paroxysm is itself subjective. Fortunately, in everyday practice "possible whooping cough" or "probable whooping cough" is sufficient to ensure adequate care.
The gold standard for laboratory diagnosis is a positive culture, but in opportunistic studies often fewer than half are confirmed this way,3,4 although a recent prospective vaccine efficacy study that identified cases at an early stage isolated the organism in more than three quarters.5 Polymerase chain reaction techniques can detect four times the number confirmed by culture,6 but even that relies on the presence of retrievable Bordetella DNA in the nasopharynx, a condition that may have ceased to exist by the time the diagnosis is suspected, and serological diagnosis is not generally available for routine use. Until there is a test available that renders clinical diagnosis unnecessary, it will remain important. Improving it will be difficult unless there is already a poorly known feature of the disease whose recognition would help with diagnosis. Some infections are presumed to be asymptomatic so clinical diagnosis will always be lacking in sensitivity but it might be made more specific than the current "best buy" of three weeks of paroxysmal coughing if there were such a "new" symptom. I think there may be.
From the very start of my experience with whooping cough I believed it was not difficult to make a clinical diagnosis. I did not at that time in 1977 have any special knowledge of the disease, but the two health visitors I worked with, and my senior partners and I had little trouble deciding who had it and who did not. Once one had heard the cough and an articulate and observant parent's description of it there was little doubt. If we did not hear the cough and the parents were articulate and observant we could be almost as sure. If the parents were neither of these things and the child did not cough, verbal clues would trigger a suspicion which would prompt some probing questions. Parents used words such as "Choking" or "He cannot get his breath"; or "He's never had a cough like it before"; or "We are up several times in the night"; or "I have to go to him"; or "It only happens when he runs about", or "He coughs 'till he's sick". That is not to say there were no dubious cases, there were plenty, but most could be confirmed or refuted by the existence of a link with a source of infection. Usually some child in close contact would have definite whooping cough and the interval between onsets would be consistent with the incubation period. The most difficult cases to diagnose were those at the start of an outbreak when there was no known link between suspected cases. I found linkage to be one of the strongest pieces of supporting evidence for whooping cough, and others agree.7
I could never quite understand why some people found whooping cough easier to suspect and diagnose than others, but now, after nearly 20 years I think I may have an idea why. Health professionals are unlikely to hear the patient cough as paroxysms are infrequent, and there are usually no physical signs. Much therefore depends on the description, or rather the struggle for a description. Pattern recognition is a process quickly developed when dealing with recurring situations such as medical consultations, as easily as it is developed in everyday activities such as driving. Doctors by and large do not solve common diagnostic problems by systematically analysing all the available data, they do it by matching the available data with previous experiences and then mentally or physically testing for a mismatch. Further relevant questions will usually resolve remaining doubts. I believe that whooping cough diagnosis becomes more sensitive by recognizing the pattern of phrases used by parents to describe the unique phenomenon of whooping cough that most of them do not have the vocabulary for. What is this characteristic that is so difficult to describe? I used to believe it was just the paroxysm (few people know that word), but now I don't. It is a paradox that causes the difficulty, the paradoxical contrast between the choking attacks of coughing and the unique distinguishing feature of whooping cough, the long coughless periods between paroxysms.
The unique thing about whooping cough is that you don't cough! Well, at least not for a long time, often many hours, and an eternity compared with what might be expected having heard a paroxysm. It is the discomfort caused by the irreconcilability of these two phenomena which produces the verbal contortions of description which is the pattern recognizable to those who know. When you suspect it you can say to the parent. "Do you mean that for a week or more he/she has been getting choking attacks of coughing where he/she goes red in the face and looks as if he/she is going to be sick and then doesn't cough again for hours on end until the next choking cough comes?" And they say "Yes, that is exactly it". Then you have it.
I cannot prove this is applicable only to whooping cough as the argument is circular; what I am calling whooping cough is what this description applies to. Until there is a certain way of confirming whether or not only Bordetella pertussis causes this syndrome the question will remain open, but it would be interesting to test a case definition that took account of this non coughing aspect against other definitions. I must also add a caveat. Many cases of whooping cough develop a presumed secondary infection with sputum production which causes an element of "normal" coughing also, but I think that almost all would have significant "coughing absences" for a substantial part of the illness. Paroxysmal coughing is also caused by Bronchiolitis and asthma but they do not pass the "almost exclusively paroxysmal" test, they have an "ordinary" cough as well. All are more clearly distinguished with hindsight, which is plentiful commodity in a long term general practice population study such as this.
I have condensed these ideas into a definition that I regard as the best compromise between sensitivity and specificity to capture the greatest number of recognizable true cases of pertussis infection as follows. "A paroxysmal coughing illness for a minimum of three weeks, at least one week of which is characterized by a total absence of coughing apart from paroxysms."
For the sake of completeness it needs to be pointed out that several studied have confirmed that evidence of Bordetella pertussis infection can be found in roughly 6% of teenagers with a prolonged cough. Quite how this fits into what we understand of the epidemiology of "whooping cough" is unclear so far.
1. Christie AB. Whooping cough. In: Infectious diseases: epidemiology and practice. Edinburgh: Churchill Livingstone, 1980:726-58.
2. Gordon JE, Hood RI. Whooping cough and its epidemiological anomalies. Am J Med Sci 1951;333‑361.
3. Grob PR, Crowder MJ, Robbins JF. Effect of vaccination on severity and dissemination of whooping cough. Br Med J 1981;282:1925‑8.
4. Report from the Swansea Research Unit of the Royal College of General Practitioners. Effect of low pertussis vaccination uptake on a large community. Br Med J 1981;282:23‑6.
5. Greco D, Salmaso S, Mastrantonio P, Giuliano M, Tozzi A et al. A controlled trial of two acellular vaccines and one whole‑cell vaccine against pertussis. N Engl J Med 1996;334:341‑8.
6. Schläpfer G, Cherry JD, Heininger U, Uberall M, Schmitt-Grohé S, et al. Polymerase chain reaction identification of Bordetella pertussis infections in vaccinees and family members in a pertussis vaccine efficacy trial in Germany. Pediatr Infect Dis J 1995;14:209‑14.
7. Thomas MG, Lambert HP. From whom do children catch pertussis? Br Med J 1987;295:751‑2.