Difficulties in distinguishing silicosis and pulmonary tuberculosis in silica-exposed gold miners: A report of four cases.

Silicosis and tuberculosis (TB) are both global health concerns, with high prevalence among miners from the South African gold mines. Although knowledge has accumulated about these two conditions as distinct diseases since the early 20th century, and despite progress in technology with multiple diagnostic tools and treatment options available for TB, the challenge of distinguishing and therefore efficiently managing these two conditions in this population remains as current as it was 100 years ago. To illustrate the diagnostic and health service problems of distinguishing TB and silicosis clinically and radiologically in former gold miners from the South African mines living in resource-poor areas, we discuss four cases reviewed for this report by a panel of experts. For each case, occupational history, past and current medical history, physical examination, radiological and laboratory findings are described. Common themes are: (1) poor agreement between radiological and clinical presentation; (2) poor agreement between radiology findings and detection of active TB on sputum Xpert MTB/RIF testing; and (3) difficulty in distinguishing the clinical and radiological presentations of silicosis and tuberculosis. Possible consequences at the population level are undertreatment or overtreatment of TB, and underdiagnosis or overdiagnosis of silicosis. There is a need for training of practitioners who are screening or attending to former gold miners in the clinical and radiological features of combined disease, using a curated database of miners' chest X-ray images. Investment in protocols for management of both acute and chronic silicotuberculosis in ex-miners is needed, as is clinical, epidemiologic, and operations research.

The association between silica exposure, silicosis and tuberculosis: a systematic review and meta-analysis.

BACKGROUND: 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, 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. METHODS: We 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. RESULTS: Nine 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. CONCLUSIONS: The 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.

Predictors of silicosis and variation in prevalence across mines among employed gold miners in South Africa.

BACKGROUND: The stated intention to eliminate silicosis from the South African goldmining industry as well as current programmes to find and compensate ex-miners with silicosis require an understanding of variation in silicosis prevalence across the industry. We aimed to identify the predictors of radiological silicosis in a large sample of working miners across gold mines in South Africa. METHODS: Routine surveillance chest radiographs were collected from 15 goldmine "clusters" in a baseline survey undertaken in preparation for a separate tuberculosis isoniazid prophylaxis trial. All images were read for silicosis by a health professional experienced in using the International Labour Organisation (ILO) classification. Profusion thresholds of > 1/0 and > 1/1 were used. Demographic and occupational information was obtained by questionnaire. Predictors of silicosis were examined in a multivariable logistic regression model, including age, gender, racial ascription, country of origin, years since starting mine employment, mine shaft, skill category, underground work status and tuberculosis. RESULTS: The crude silicosis prevalence at ILO > 1/1 was 3.8% [95% confidence interval (CI) 3.5-4.1%]. The range across mine shafts was 0.8-6.9%. After adjustment for covariates, the interquartile range across shafts was reduced from 2.4 to 1.2%. Black miners [adjusted odds ratio (aOR) 2.8; 95% CI 1.1-7.2] and miners in full-time underground work (aOR 2.1; 95% CI 1.3-3.4) had substantially elevated odds of silicosis, while workers from Mozambique had lower odds (aOR 0.54; 95% CI 0.38-0.77). Silicosis odds rose sharply with both age and years since starting in the industry (p for linear trend < 0.005), with 95.5% of affected miners having > 15 years since first exposure and 2.2% < 10 years. CONCLUSIONS: In surveillance of silicosis in working gold miners time since first exposure remains a powerful predictor. Age appears to be an independent predictor, while the detection of radiological silicosis in short-service miners requires attention. Public risk reporting by mines should include factors bearing on silicosis prevalence, specifically dust concentrations, with independent verification. Studies of silicosis and tuberculosis in ex-miners are needed, supported by an accessible electronic database of the relevant medical and dust exposure records of all gold miners.

Predictors of discordant latent tuberculosis infection test results amongst South African health care workers.

BACKGROUND: The tuberculin skin test (TST) and interferon-gamma-release-assays (IGRAs) are utilized in screening programmes for presumed latent tuberculosis infection (LTBI) in health care workers (HCWs). However, inter-test comparison yields high rates of discordance, which is poorly understood. The aim of the study was therefore to identify factors associated with discordance amongst HCWs in a TB and HIV endemic setting. METHODS: 505 HCWs were screened for LTBI in South Africa using the TST and two IGRA assays (QuantiFERON-TB-Gold-In-Tube (QFT-GIT) and TSPOT.TB). Factors associated with discordance were analyzed using a multinomial logistic regression model. RESULTS: TST-IGRA discordance was negatively associated with longer duration of employment for both TSPOT.TB (OR = 0.92; 95% confidence interval (CI) 0.85-0.99) and QFT-GIT (OR = 0.90; 95% CI 0.84-0.96). Marked test discordance occurred in HIV-infected individuals who were more likely to have TSPOT.TB + ve / TST-ve discordance (OR 4.44; 95% CI 1.14-17.27) or TSPOT.TB + ve / QFT-GIT-ve test discordance (OR 5.72; 95% CI 1.95-16.78). Those engaged in home care were less likely to have QFT-GIT + ve/TSPOT.TB -ve / discordance (OR 0.32; 95% CI 0.10-0.95). CONCLUSION: The marked TST-IGRA and IGRA-IGRA discordance in HIV-infected individuals suggest greater sensitivity of TSPOT.TB in immunocompromised persons or potential greater reactivity of TSPOT.TB in this population.

Precarious transition: a mortality study of South African ex-miners.

BACKGROUND: Despite their burden of a triple epidemic of silicosis, tuberculosis and HIV infection, little is known about the mortality experience of miners from the South African mining industry once they leave employment. Such information is important because of the size and dispersion of this population across a number of countries and the progressive nature of these diseases. METHODS: This study included 306,297 South African miners who left the industry during 2001-2013. The study aimed to calculate crude and standardised mortality rates, identify secular trends in mortality and model demographic and occupational risk factors for mortality. RESULTS: Crude mortality rates peaked in the first year after exit (32.8/1000 person-years), decreasing with each year from exit. Overall mortality was 20% higher than in the general population. Adjusted annual mortality halved over the 12 year period. Mortality predictors were being a black miner [adjusted hazard ratio (aHR) 3.30; 95% confidence interval (CI) 3.15-3.46]; underground work (aHR 1.33; 95% CI 1.28-1.39); and gold aHR 1.15 (95% CI 1.12-1.19) or multiple commodity employment (aHR 1.15; 95% CI 1.11-1.19). CONCLUSIONS: This is the first long-term mortality assessment in the large ex-miner population from the South African mining industry. Mortality patterns follow that of the national HIV-tuberculosis epidemic and antiretroviral treatment availability. However, ex-miners have further elevated mortality and a very high mortality risk in the year after leaving the workforce. Coordinated action between the mining industry, governments and non-governmental organisations is needed to reduce the impact of this precarious transition.

Effectiveness of control measures to prevent occupational tuberculosis infection in health care workers: a systematic review.

BACKGROUND: A number of guideline documents have been published over the past decades on preventing occupational transmission of tuberculosis (TB) infection in health care workers (HCWs). However, direct evidence for the effectiveness of these controls is limited particularly in low-and middle-income (LMIC) countries. Thus, we sought to evaluate whether recommended administrative, environmental and personal protective measures are effective in preventing tuberculin skin test conversion among HCWs, and whether there has been recent research appropriate to LMIC needs. METHODS: Using inclusion criteria that included tuberculin skin test (TST) conversion as the outcome and longitudinal study design, we searched a number of electronic databases, complemented by hand-searching of reference lists and contacting experts. Reviewers independently selected studies, extracted data and assessed study quality using recommended criteria and overall evidence quality using GRADE criteria. RESULTS: Ten before-after studies were found, including two from upper middle income countries. All reported a decline in TST conversion frequency after the intervention. Among five studies that provided rates, the size of the decline varied, ranging from 35 to 100%. Since all were observational studies assessed as having high or unclear risk of bias on at least some criteria, the overall quality of evidence was rated as low using GRADE criteria. CONCLUSION: We found consistent but low quality of evidence for the effectiveness of combined control measures in reducing TB infection transmission in HCWs in both high-income and upper-middle income country settings. However, research is needed in low-income high TB burden, including non-hospital, settings, and on contextual factors determining implementation of recommended control measures. Explicit attention to the reporting of methodological quality is recommended. TRIAL REGISTRATION: This systematic review was registered with PROSPERO in 2014 and its registration number is CRD42014009087 .

Subradiological silicosis.

The purpose of this commentary is to bring the neglected phenomenon of subradiological silicosis and its implications to the attention of readers. We define subradiological silicosis as silicosis detectable on pathological examination of lung tissue but not visible radiologically. For extent of the phenomenon, we draw on a study using a large South African autopsy database of deceased miners and chest radiographs taken in life. At an International Labour Organization threshold of >1/0 only 43% of all pathologically detected cases were detected on chest radiograph, and only 62% of those classified on pathology as "moderate or marked" silicosis. Subradiological silicosis has a number of implications for research and practice: for dose-response studies of silicosis; for studies of the relationship between silica and conditions such as tuberculosis, lung cancer, and autoimmune disease, including the mechanistic role of fibrogenesis; for prognostication in silica exposed workers; and for workers' compensation criteria.

Comparison of digital and film chest radiography for detection and medical surveillance of silicosis in a setting with a high burden of tuberculosis.

BACKGROUND: Continuing use of analog film and digital chest radiography for screening and surveillance for pneumoconiosis and tuberculosis in lower and middle income countries raises questions of equivalence of disease detection. This study compared analog to digital images for intra-rater agreement across formats and prevalence of changes related to silicosis and tuberculosis among South African gold miners using the International Labour Organization classification system. METHODS: Miners with diverse radiological presentations of silicosis and tuberculosis were recruited. Digital and film chest images on each subject were classified by four expert readers. RESULTS: Readings of film and soft copy digital images showed no significant differences in prevalence of tuberculosis or silicosis, and intra-rater agreement across formats was fair to good. Hard copy images yielded higher prevalences. CONCLUSION: Film and digital soft copy images show consistent prevalence of findings, and generally fair to good intra-rater agreement for findings related to silicosis and tuberculosis.

Public health implications of changing patterns of recruitment into the South African mining industry, 1973-2012: a database analysis.

BACKGROUND: The triple epidemic of silicosis, tuberculosis and HIV infection among migrant miners from South Africa and neighbouring countries who have worked in the South African mining industry is currently the target of regional and international control efforts. These initiatives are hampered by a lack of information on this population. METHODS: This study analysed the major South African mining recruitment database for the period 1973 to 2012 by calendar intervals and demographic and occupational characteristics. Changes in area of recruitment were mapped using a geographic information system. RESULTS: The database contained over 10 million contracts, reducible to 1.64 million individuals. Major trends relevant to health projection were a decline in gold mining employment, the major source of silicosis; increasing recruitment of female miners; and shifts in recruitment from foreign to South African miners, from the Eastern to the Northwestern parts of South Africa, and from company employees to contractors. CONCLUSIONS: These changes portend further externalisation of the burden of mining lung disease to home communities, as miners, particularly from the gold sector, leave the industry. The implications for health, surveillance and health services of the growing number of miners hired as contractors need further research, as does the health experience of female miners. Overall, the information in this report can be used for projection of disease burden and direction of compensation, screening and treatment services for the ex-miner population throughout Southern Africa.

Do children with cystic fibrosis receiving outreach care have poorer clinical outcomes than those treated at a specialist cystic fibrosis centre?

INTRODUCTION: Although cystic fibrosis (CF) centre care is generally considered ideal, children living in regional Australia receive outreach care supported by the academic CF centres. METHODS: This is a retrospective database review of children with CF treated at the Royal Children's Hospital in Melbourne and its outreach clinics in Albury (Victoria), and Tasmania. The aim was to compare the outcomes of children with CF managed at an academic centre with that of outreach care, using lung function, nutritional status and Pseudomonas aeruginosa colonisation. Three models of care, namely CF centre care, Shared care and predominantly Local care, were compared, based on the level of involvement of CF centre multidisciplinary team. In our analyses, we controlled for potential confounders, such as socio-economic status and the degree of remoteness, to determine its effect on the outcome measures. RESULTS: There was no difference in lung function, i.e. forced expiratory volume in 1 s (FEV1 ), the prevalence of Pseudomonas aeruginosa colonisation or nutritional status (body mass index (BMI)) between those receiving CF centre care and various modes of outreach care. Neither socio-economic status, measured by the Socio-Economic Index for Area (SEIFA) for disadvantage, nor distance from an urban centre (Australian Standard for Geographical Classification (ASGC)) were associated with lung function and nutritional outcome measures. There was however an association between increased Pseudomonas aeruginosa colonisation and poorer socio-economic status. CONCLUSION: Outcomes in children with CF in regional and remote areas receiving outreach care supported by an academic CF centre were no different from children receiving CF centre care.

Incidence of occupational latent tuberculosis infection in South African healthcare workers.

The test-specific incidence of latent tuberculosis infection (LTBI) in healthcare workers from sub-Saharan Africa is unknown. 505 healthcare workers from South Africa were screened at baseline, and after 12 months, with a questionnaire, the tuberculin skin test (TST), and two T-cell assays (T-SPOT.TB and QuantiFERON-TB Gold-In-Tube). Test-specific conversion rates were calculated. The prevalence of presumed LTBI at baseline was 84, 69 and 62% using the TST, QuantiFERON-TB Gold-In-Tube and T-SPOT.TB, respectively. The annual test-specific conversion rate, depending on the cut-off point used, was as follows: TST 38%; QuantiFERON-TB Gold-In-Tube 13-22%; and T-SPOT.TB 18-22%. Annual reversion rates were 4, 7 and 16%, respectively. The annual TST conversion rate was significantly higher than that derived from published local community-based data (IRR 3.53, 95% CI 1.81-6.88). Factors associated with conversion (any test) included healthcare sector of employment, counselling of tuberculosis patients, and a baseline positive TST (for T-SPOT.TB). The annual rate of tuberculosis infection in South African healthcare workers was very high, irrespective of the testing method used, and may be explained by occupational exposure, as the rate was considerably higher than non-healthcare workers from the same community. Collectively, these data support the need for implementation of tuberculosis-specific infection control measures in Africa.

Trends in silicosis prevalence and the healthy worker effect among gold miners in South Africa: a prevalence study with follow up of employment status.

BACKGROUND: Given the intimate association between silicosis and tuberculosis, understanding the epidemiology of the South African gold mining industry silicosis epidemic is essential to current initiatives to control both silicosis and tuberculosis in this population, one of the most heavily affected globally. The study's objectives were to compare the prevalence of silicosis among working black gold miners in South Africa during 2004-2009 to that of previous studies, including autopsy series, and to analyse the influence of silicosis and/or tuberculosis on exiting employment. METHODS: Routine chest radiographs from a cohort of gold miners were read for silicosis by an experienced reader (I), and a subset re-read by a B-trained reader (II). Two methods of presenting the readings were used. Additionally, with baseline status of silicosis and previous or active tuberculosis as predictors, survival analysis examined the probability of exiting the workforce for any reason during 2006-2011. RESULTS: Reader I read 11 557 chest radiographs and reader II re-read 841. Overall, silicosis prevalence (ILO ≥ 1/0: 5.7 and 6.2% depending on reader method) was similar to the age adjusted prevalence found in a large study in 1984 (5.0%). When comparison was restricted to a single mine shaft previously studied in 2000, a decline in prevalence (ILO ≥ 1/1) was suggested for one of the reading methods (duration adjusted 20.5% vs. 13.0% in the current study). These findings are discordant with a long-term rising autopsy prevalence of silicosis over this period. Overall, relative to miners with neither disease, the adjusted hazard ratio for exiting employment during the follow-up period was 1.54 for baseline silicosis [95% confidence interval (CI) 1.17, 2.04], 1.71 for tuberculosis (95% CI 1.51, 1.94) and 1.53 for combined disease (95% CI 1.20, 1.96). CONCLUSIONS: This study found, a) there was no significant decline in overall silicosis prevalence among working black miners in the South African gold mining industry between 1984 and 2004-2009, and b) a possible decline at one mine shaft more recently. In the absence of evidence of declining respirable silica concentrations between the 1980s and 2000s, the trends found are plausibly due to a healthy worker survivor effect, which may be accelerating.

Complicated silicotuberculosis in a South African gold miner: A case report.

We present a case of complicated silicotuberculosis in a former gold miner with a sufficiently heavy silica dust exposure to cause International Labor Organization grade 2/2 silicosis after a cumulative exposure duration of 11 years. We describe a cascade of complications-active pulmonary tuberculosis despite recent isoniazid prophylactic therapy, non-tuberculous mycobacterial disease, chronic airways obstruction, and spontaneous pneumothorax-and the difficulties, which arose, in diagnosis and management of such combined disease. We highlight three implications of such cases: the need to understand the interaction of silicosis and tuberculosis in this setting, the importance of maintaining continuity of care in the management of these conditions in miners and former miners, and control of silica dust exposure as a primary form of prevention of tuberculosis.

Analysing the socioeconomic determinants of hypertension in South Africa: a structural equation modelling approach.

BACKGROUND: Epidemiological research has long observed a varying prevalence of hypertension across socioeconomic strata. However, patterns of association and underlying causal mechanisms are poorly understood in sub-Saharan Africa. Using education and income as indicators, we investigated the extent to which socioeconomic status is linked to blood pressure in the first wave of the National Income Dynamics Study--a South African longitudinal study of more than 15,000 adults--and whether bio-behavioural risk factors mediate the association. METHODS: In a cross-sectional analysis, structural equation modelling was employed to estimate the effect of socioeconomic status on systolic and diastolic blood pressure and to assess the role of a set of bio-behavioural risk factors in explaining the observed relationships. RESULTS: After adjustment for age, race and antihypertensive treatment, higher education and income were independently associated with higher diastolic blood pressure in men. In women higher education predicted lower values of both diastolic and systolic blood pressure while higher income predicted lower systolic blood pressure. In both genders, body mass index was a strong mediator of an adverse indirect effect of socioeconomic status on blood pressure. Together with physical exercise, alcohol use, smoking and resting heart rate, body mass index therefore contributed substantially to mediation of the observed relationships in men. By contrast, in women unmeasured factors played a greater role. CONCLUSION: In countries undergoing epidemiological transition, effects of socioeconomic status on blood pressure may vary by gender. In women, factors other than those listed above may have substantial role in mediating the association and merit investigation.

Airborne infection prevention and control implementation: A positive deviant organisational case study of tuberculosis and COVID-19 at a South African rural district hospital.

There are many examples of poor TB infection prevention and control (IPC) implementation in the academic literature, describing a high-risk environment for nosocomial spread of airborne diseases to patients and health workers. We developed a positive deviant organisational case study drawing on Weick's theory of organisational sensemaking. We focused on a district hospital in the rural Eastern Cape, South Africa and used four primary care clinics as comparator sites. We interviewed 18 health workers to understand TB IPC implementation over time. We included follow-up interviews on interactions between TB and COVID-19 IPC. We found that TB IPC implementation at the district hospital was strengthened by continually adapting strategies based on synergistic interventions (e.g. TB triage and staff health services), changes in what value health workers attached to TB IPC and establishing organisational TB IPC norms. The COVID-19 pandemic severely tested organisational resilience and COVID-19 IPC measures competed instead of acted synergistically with TB. Yet there is the opportunity for applying COVID-19 IPC organisational narratives to TB IPC to support its use. Based on this positive deviant case we recommend viewing TB IPC implementation as a social process where health workers contribute to how evidence is interpreted and applied.

Problem drinking as a risk factor for tuberculosis: a propensity score matched analysis of a national survey.

BACKGROUND: Epidemiological and other evidence strongly supports the hypothesis that problem drinking is causally related to the incidence of active tuberculosis and the worsening of the disease course. The presence of a large number of potential confounders, however, complicates the assessment of the actual size of this causal effect, leaving room for a substantial amount of bias. This study aims to contribute to the understanding of the role of confounding in the observed association between problem drinking and tuberculosis, assessing the effect of the adjustment for a relatively large number of potential confounders on the estimated prevalence odds ratio of tuberculosis among problem drinkers vs. moderate drinkers/abstainers in a cross-sectional, nationally representative sample of the South African adult population. METHODS: A propensity score approach was used to match each problem drinker in the sample with a subset of moderate drinkers/abstainers with similar characteristics in respect to a set of potential confounders. The prevalence odds ratio of tuberculosis between the matched groups was then calculated using conditional logistic regression. Sensitivity analyses were conducted to assess the robustness of the results in respect to misspecification of the model. RESULTS: The prevalence odds ratio of tuberculosis between problem drinkers and moderate drinkers/abstainers was 1.97 (95% CI: 1.40 to 2.77), and the result was robust with respect to the matching procedure as well as to incorrect adjustment for potential mediators and to the possible presence of unmeasured confounders. Sub-population analysis did not provide noteworthy evidence for the presence of interaction between problem drinking and the observed confounders. CONCLUSION: In a cross-sectional national survey of the adult population of a middle income country with high tuberculosis burden, problem drinking was associated with a two fold increase in the odds of past TB diagnosis after controlling for a large number of socio-economic and biological confounders. Within the limitations of a cross-sectional study design with self-reported tuberculosis status, these results adds to previous evidence of a causal link between problem drinking and tuberculosis, and suggest that the observed higher prevalence of tuberculosis among problem drinkers commonly found in population studies cannot be attributed to the confounding effect of the uneven distribution of other risk factors.