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Rapid Responses: Rapid Responses published:
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Validation of negative smear
- Paul McWhinney (12 September 2008)
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Worries with Lesson of the Week
- Ed Cooper (14 September 2008)
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Facilitators of disease progression and transmission in Mycobacterium tuberculosis infection
- Shantini Paranjothy, Eisenhut M, Lilley M, Bracebridge S, Abubakar I, Mulla R, Lack K, Chalkley D, Howard J, Thomas S, McEvoy M. (19 September 2008)
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Paul McWhinney, Consultant Physician Bradford Royal Infirmary, BD16 1LQ
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Although it is an important lesson that smear negative TB may be infectious, there may be other reasons why there was extensive transmission. The chest x-ray is markedly abnormal and it would be surprising to find this much disease associated with a negative smear. Clearly, the right decision regarding wider screening was made, presumably prompted by the chest x-ray and evidence of infection in close contacts. Thus it does raise the possibility that the smear results were false negatives, whether due to poor specimens, or a laboratory problem. A finding such as this should stimulate an extensive review of the clinicians and laboratories methodology. Although a poor surrogate, what was the time to positive culture? For the article to carry any weight I would have hoped that details of the technique used for the smear, the validation of the laboratory and general experience of the laboratory would be described. What was done to ensure that the smear result was accurate? Competing interests: None declared |
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Ed Cooper, Retired paediatrician London N4
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This report has made me uneasy. It raises questions on the ethics of reporting in such a public forum as the BMJ website and on what exactly the family gave permission to report (see Editorial, Jane Smith, 10 September, BMJ 2008;337:a1572 and comment, 11 September, Fiona Godlee, BMJ 2008;337:a1633 and the current correspondence these are giving rise to). But it cannot be ignored, because it is "Lesson of the Week" and I find that the lesson is potentially quite misleading. There is a glaring omission in the report: there is no mention of retroviral status. We are not told whether a test for HIV was done, and if it was, whether it was positive or negative. If it was not done, we are not told why not. Clinically, there can be no doubt that HIV testing is indicated in this child; but there are many sensitive questions of parental agreement, confidentiality, stigma, exposure to accusations of national/ethnic stereotyping, the school community's anxietes, autonomy and public health to consider. For the drawing of lessons from this case and school outbreak it is important to recognise that the clinical and x-ray features of this child are highly uncharacteristic of primary tuberculosis, the form of childhood infection expected before the pandemic of HIV infection, but highly typical of tuberculosis in HIV-infected children. These are, in effect, those of secondary TB and the index child is, in effect, from the point of view of infectiousness, not a child but an adult. The first sentence of the report begins: "Patients with pulmonary tuberculosis and either a positive sputum smear or cavitating pulmonary lesions have been considered to be infectious ..." Note the either-or. I think the reported child does have cavitating pulmonary lesions and so fulfills the criteria, irrespective of smear positivity. I say this because (1) the x-ray would be typical of cavitating pulmonary TB in an adult, (2) when a child produces sputum this is a clinical sign of cavitation within the lungs. Sputum must be copious for it to be coughed or expectorated rather than swallowed by a child. This clinical pearl of wisdom is routinely used by paediatricians in diagnosing bronchiectasis. There is real danger of the lesson from this "Lesson of the Week" being taken as "Contrary to previous teaching, children with pulmonary TB are infectious". No; children with primary TB are not significantly infectious, never have been and still aren't. However, children with cavitating, adult-type TB are as infectious as adults with cavitating, adult-type TB. Unfortunately, we see more of the latter from countries with high prevalence of HIV infection, and the pattern is highly characteristic in individual children who are also infected with the retrovirus. Competing interests: I have no other knowledge of the case reported nor have I had any contact with any of the authors. I respond purely as an on-line reader of the paper. |
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Shantini Paranjothy, Walport Clinical Lecturer in Public Health Medicine Department of Primary Care and Public Health, School of Medicine, Cardiff University, CF14 4YS, Eisenhut M, Lilley M, Bracebridge S, Abubakar I, Mulla R, Lack K, Chalkley D, Howard J, Thomas S, McEvoy M.
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We would like to thank Drs McWhinney and Cooper for their interest in our report. In response to Dr. McWhinney's comments we confirm that the three smear negative sputum samples were concentrated by centrifugation, phenol auramine stained and read by staff with specific training and many years of experience in a tuberculosis laboratory; a process which is subject to regular external quality assessment. In response to Dr. Coopers comments we confirm that the child was HIV negative and that the parents had given written consent to use of all data pertaining to the child’s condition for research and publication, and that the BMJ's policy for obtaining consent was followed. We agree that the radiological appearance of the child's chest x-ray was uncharacteristic of primary tuberculosis. The radiological appearance was however not typical of tuberculosis in an HIV infected child. According to previous studies, radiological appearances of pulmonary tuberculosis in HIV infection are characterised by features of dissemination and miliary patterns. In contrast, cavitating disease is significantly underrepresented in patients with HIV infection (1,2). The x -ray in our child was reported by a consultant radiologist who did not find features of cavitation. There is no published evidence to support the claim that pulmonary cavitation in tuberculosis is associated with more copious sputum. Apart from cavitation, the radiological features associated with more infective sputum include consolidation and bronchial lesions (3). Our patient had radiological evidence of bronchogenic spread to the right lower lobe supporting bronchial involvement. Children with primary tuberculosis can be highly infectious if there is rapid progression of primary tuberculosis which can lead to cavitation even in infancy and such cases have been reported from the time before the advent of HIV infection (4,5,6). Factors other than HIV related to such a progression may be vitamin D deficiency common in the dark skinned population living in the United Kingdom (7). Transmission of tuberculosis from smear negative cases is not a new finding, and there have been previous reports (8). The key message in our paper was about the need to raise awareness that sputum smear results alone are insufficient as an indicator of infectivity when considering whether or not to screen wider contacts. Longstanding exposure to a coughing tuberculous patient with extensive pulmonary lesions should be included in the criteria for contact screening. References: 1. Swaminathan S, Narendran C, Menon PA et al. Impact of HIV infection on radiographic features in patients with pulmonary tuberculosis. Indian J Chest Dis Allied Sci 2007; 49: 133-136. 2. Kayantao D, Maiga I, Bougoudogo F et al. Radiographic and bacteriologic data on pulmonary tuberculosis in Bamako as a function of HIV status. Rev Pneumol clin 2001; 57: 423-6. 3. Ors F, Deniz O, Bozlar U et al. High-resolution CT findings in patients with pulmonary tuberculosis: correlation with the degree of smear positivity. J Thorac Imaging 2007; 22: 154-9. 4. Extensive transmission of mycobacterium tuberculosis from a child. N Engl J Med 1999:341:1491-5. 5. Aderele WI. Radiological patterns of pulmonary tuberculosis in Nigerian children. Tubercle 1980; 61:157-63. 6. Cunningham DG, McGraw TT, Griffin AJ, O'Keefe JP. Neonatal tuberculosis with pulmonary cavitation. Tubercle 1982; 63:217-9. 7. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol 2008;37:113-9. 8. Behr MA, Warren SA, Salamon H, Hopewell PC, Poce de Leon A, Daley CL, et al. Transmission of Mycobacterium tuberculosis from patients smear- negative for acid-fast bacilli. Lancet 1999;353:444-9. Competing interests: None declared |
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