Title
Prediction and prevention of tuberculosis in contacts – Authors' reply
Date Issued
01 December 2017
Access level
open access
Resource Type
letter
Author(s)
Saunders M.J.
Wingfield T.
Innovación por la Salud y Desarrollo
Publisher(s)
Lancet Publishing Group
Start page
1238
End page
1239
Volume
17
Issue
12
Language
English
OCDE Knowledge area
Salud pública, Salud ambiental
Scopus EID
2-s2.0-85034602082
PubMed ID
Source
The Lancet Infectious Diseases
ISSN of the container
14733099
Source funding
Research and Development
Sponsor(s)
Matthew J Saunders a b c matthew.saunders@ifhad.org Tom Wingfield a b c d e f Marco A Tovar a b Matthew R Baldwin b c g Sumona Datta a c Carlton A Evans a b c a Section of Infectious Diseases and Immunity, and Wellcome Trust Imperial College Centre for Global Health Research, Imperial College London, London W12 0NN, UK Section of Infectious Diseases and Immunity and Wellcome Trust Imperial College Centre for Global Health Research Imperial College London London W12 0NN UK b Innovation for Health and Development (IFHAD), Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Innovation for Health and Development (IFHAD) Laboratory of Research and Development Universidad Peruana Cayetano Heredia Lima Peru c Innovación por la Salud y Desarrollo (IPSYD), Asociación Benéfica PRISMA, Lima, Peru Innovación por la Salud y Desarrollo (IPSYD) Asociación Benéfica PRISMA Lima Peru d The Institute for Infection and Global Health, University of Liverpool, Liverpool, UK The Institute for Infection and Global Health University of Liverpool Liverpool UK e Tropical and Infectious Diseases Unit, Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool, UK Tropical and Infectious Diseases Unit Royal Liverpool and Broadgreen University Hospitals Trust Liverpool UK f Department of Social Medicine, Karolinska Institutet, Stockholm, Sweden Department of Social Medicine Karolinska Institutet Stockholm Sweden g College of Physicians and Surgeons, Columbia University, New York, NY, USA College of Physicians and Surgeons Columbia University New York NY USA We thank Sandra Arend and Jonathan Uzorka for their interest in our study. They argue that because our risk score predicts tuberculosis independently of the contact tuberculin skin test (TST) results and index case smear grade, it is likely that subsequent re-exposure to tuberculosis was an important risk factor. Therefore, they debate the justification for our calculation of numbers needed to treat (NNT) with preventive therapy at the time of known exposure to prevent each tuberculosis case. Although we agree that re-exposure might have been an important, unmeasured risk factor in our population, the highest rate of tuberculosis among contacts was in the first year after known exposure, and nearly all the cases occurred during the first 3 years. Furthermore, prolonged exposure to the index case was an important risk factor. Taken together, these findings suggest that the known exposure was by far the most important factor in determining tuberculosis risk. 1 However, we appreciate the potential importance of subsequent re-exposure and therefore calculated the NNT to prevent each tuberculosis case within 5 as well as 10 years. Importantly, we calculated NNT principally to illustrate practical differences between risk groups. Because the cutoffs used to define risk groups were arbitrary and our risk score is a continuous variable, these NNTs inherently change depending on how a high-risk contact is defined. Because addition of TST results to our predictive model did not substantially improve its power, Arend and Uzorka suggest that our results disagree with several studies that report an association between a positive TST and development of tuberculosis among contacts. As we described in our study report, 1 having a positive TST compared with a negative TST was associated with double the tuberculosis risk in our cohort (adjusted hazard ratio 1·8, p=0·02). Our finding that adding TST results to a composite risk score including nine other factors did not improve prediction might at first appear surprising, but is consistent with the known limitations of TST and the high prevalence of positivity in our cohort. Indeed, our results are very similar to those described in a systematic review. 2 Our study included only index cases with laboratory-confirmed tuberculosis, the great majority of whom had smear-positive tuberculosis, so we could not meaningfully compare index cases who had smear-positive tuberculosis with those who had smear-negative tuberculosis. Although we agree with the evidence cited by Arend and Uzorka, the association between crude smear grade and infectiousness might not be that straightforward when considering risk of disease among contacts, because infectiousness is influenced by a variety of other factors, including the capacity to generate aerosolised Mycobacterium tuberculosis through coughing, the quantity of viable mycobacteria in sputum, the quality of the sputum sample, the length of exposure, and the contact's own health. 3–5 We also thank Nidhi Tejan and colleagues for their enthusiastic response to our study. Tejan and colleagues make the point that non-inclusion of pathogen-related factors, frequently determined by genomics, might lead to varying predictability in different regions. We agree with the authors and encourage use, validation, and most importantly adaptation of our score across other settings to characterise this phenomenon and explore how other environmental, behavioural, and cultural factors might affect implementation. However, routinely incorporating factors that require expensive and cumbersome tests would substantially reduce the usability of our score in resource-limited settings. Ending the tuberculosis epidemic calls for the expansion of contact investigation and preventive treatment. 6 Our study incorporates important results into a practical tool that could be used to benefit and prioritise people who currently receive little or no attention from tuberculosis programmes in resource-limited settings. We believe that this approach should be combined with interventions addressing the social determinants of tuberculosis, which are the true drivers of the global tuberculosis epidemic. 7,8
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