Abstract
BackgroundWhile the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, particularly of experience in the current era of less severe silicosis and treatable tuberculosis. We undertook a systematic review of the evidence for the association between (1) silicosis and pulmonary tuberculosis, and (2) silica exposure and pulmonary tuberculosis controlling for silicosis, and their respective exposure-response gradients.MethodsWe searched PUBMED and EMBASE, and selected studies according to a priori inclusion criteria. We extracted, summarised and pooled the results of published case-control and cohort studies of silica exposure and/or silicosis and incident active tuberculosis. Study quality was assessed on the Newcastle-Ottawa Scale. Where meta-analysis was possible, effect estimates were pooled using inverse-variance weighted random-effects models. Otherwise narrative and graphic synthesis was undertaken. Confidence regarding overall effect estimates was assessed using the GRADE schema.ResultsNine studies met the inclusion criteria. Meta-analysis of eight studies of silicosis and tuberculosis yielded a pooled relative risk of 4.01 (95% confidence interval (CI) 2.88, 5.58). Exposure-response gradients were strong with a low silicosis severity threshold for increased risk. Our GRADE assessment was high confidence in a strong association. Meta-analysis of five studies of silica exposure controlling for or excluding silicosis yielded a pooled relative risk of 1.92 (95% CI 1.36, 2.73). Exposure-response gradients were observable in individual studies but not finely stratified enough to infer an exposure threshold. Our GRADE assessment was low confidence in the estimated effect owing to inconsistency and use of proxies for silica exposure.ConclusionsThe evidence is robust for a strongly elevated risk of tuberculosis with radiological silicosis, with a low disease severity threshold. The effect estimate is more uncertain for silica exposure without radiological silicosis. Research is needed, particularly cohort studies measuring silica exposure in different settings, to characterise the effect more accurately as well as the silica exposure threshold that could be used to prevent excess tuberculosis risk.
Highlights
While the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, of experience in the current era of less severe silicosis and treatable tuberculosis
Systematic review and selection criteria We carried out a systematic review to assess the evidence from human controlled studies conducted from the 1970s onwards for the associations between silica, silicosis and tuberculosis in adults
Summary of evidence We have high confidence on the GRADE schema that further evidence would not change the conclusion that silicosis strongly increases the risk of tuberculosis, i.e. with a relative risk > 2.5 With regard to silica exposure controlling for radiological silicosis, the evidence suggests an elevated risk of tuberculosis with a exposureresponse gradient
Summary
While the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, of experience in the current era of less severe silicosis and treatable tuberculosis. Occupational silica exposure continues to occur in almost all countries and in many industries and occupations: construction, agriculture and mining being among the largest employers. In South Africa between 1973 and 2013 an estimated minimum 1.2 million workers passed through the gold mining industry with its high silica dust exposures [1, 2]. Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, most commonly affecting the lung. It may occur in the form of latent tuberculosis, a dormant state which may progress to active disease many years after the initial infection. All of the countries mentioned above are classified by the World Health Organization (WHO) as high burden tuberculosis countries [4]
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