Risk of TB infection among HCWs in the era of HIV and MDR-TB Madhukar Pai, MD, PhD Assistant Professor of Epidemiology McGill University Montreal
TB exposure: a fact of life for health care workers in developing countries
Joshi et al. PLoS Med 2006
Review questions In HCWs in low and middle income countries : What is the prevalence of TB infection in HCWs and what are the risk factors for LTBI? What is the incidence of TB infection in HCWs and what are the risk factors for tuberculin conversion? What is the incidence of TB disease in HCWs and how does it compare with the incidence in the community? Are some work locations or certain occupations within a health care facility at higher risk of TB disease than others? What is the impact of various TBIC strategies on reducing the incidence of TB disease or TB infection?
Definitions: Outcomes Latent TB infection (LTBI): Positive TST, by any standard method using 1TU or 2TU of RT-23 or 5TU of PPD-S, with induration size 10mm on a single test. Tuberculin conversion: Defined as a newly positive TST after a documented negative baseline TST (at any time after a negative twostep baseline, or more than one year after a negative single TST). An increase of 10 mm over the baseline was defined as conversion. Tuberculosis disease (TB disease): Includes all forms of pulmonary as well as extra-pulmonary tuberculosis where a definitive (acid fast bacilli demonstrated), or presumptive (based on clinical, imaging or pathology criteria) diagnosis was made. The definition includes self-reported past treatment for TB disease.
Definitions: Low-middle income country (LMIC) The countries were grouped according to 2004 gross national income per capita criteria as suggested by the World Bank. This criteria classifies LMICs as those with per capita income value of less than $ 10,000
Methods Search (- 2005) PubMed, BIOSIS, Embase, and Web of Science Hand-searched the indices of the IJTLD, Tuberculosis, and Tubercle & Lung Disease Contacted experts to identify additional studies Study selection and data abstraction Two reviewers screened all citations. Selected for English language articles on the topic.
Data extraction Country, year of study Type of healthcare facility Demographic, occupational details about the HCWs Number of TB patients managed in the facility Infection control practices in the facility at the time of the study Prevalence and incidence of TB infection Incidence of TB disease Risk factors for TB infection or disease Data on infection control interventions and their effectiveness Personal Administrative Engineering controls Delays in diagnosis at the facility
Data synthesis Pre-specified subgroups TB infection (LTBI) Medical or nursing students All other health care workers TB disease Excess rates among HCWs, attributable to nosocomial exposure calculated with respect to the rates in the general population of that country or region were calculated. We calculated the risk estimates for incidence of TB disease in HCWs for different occupations and work locations, with incidence of TB disease in general population as a reference. There was considerable heterogenity in the estimates. The studies estimating prevalence of TB infection had similar and comparable methodologies, so we obtained their pooled estimates. No other estimates were pooled. Data analyzed using Stata (version 9), and Meta-DiSc (version 1.2).
Prevalence of TB infection (LTBI)
Risk of TB infection Mid-incidence countries: Medical Students in Brazil Silva et.al. IJTLD 2000; 4:420-426 % of Reaction 20 15 10 5 Engineering Students Medical Students 0 Early 0-2 Intermediate 3-4 Years of training Senior 5-6 Average ARI: Preclinical 0.2% Clinical 2.9% Incidence of TB in Brazil: 75/100 000
Prevalence of TB infection among nurses
Risk factors for LTBI Male sex Presence of BCG scar Risk Factor Senior year of training in medical school Age medical students 23 years + vs. 18 years Age (for every year increase) More than 1 year in employment (Ref <1year) More than 10 years in profession (Ref <1year) High vs Low TB incidence facility in hospital Participation in autopsies Range of estimates (after multivariate analysis) 1.9 (1.0-3.5) 1 to 2.9 (1.1-7.6) 2 4.2 (1.9-9.3) 3 1.02 to 1.04 (1.02-1.07) 4-6 1.5 (1.2-1.7) 6 1.9(1.6-2.2) 6 1.5 (1.0-2.2) 7 to 2.3 (1.2-4.3) 8 3.20 (1.08-9.45) 3 3.4 (1.8-6.2) 9 9.3 (2.1-40.5) 5 1 Silva 2000, 2 Teixeira 2005, 3 Pai 2005, 4 Kayanja 2005, 5 Garcia 2001, 6 Roth 2005, 7 Alonso 2001, 8 Do 1999, 9 Kassim 2000
Incidence of TB infection (tuberculin conversion)
Risk of TB infection high-incidence countries: Nursing Students in Zimbabwe Corbett et.al. CID 2007
Risk factors for tuberculin conversion Risk Factor Range of estimates (after multivariate analysis) Senior year of training in medical school 4.77 (1.01-22.46) 1 BCG vaccination after baseline TST 2.9 (1.1-7.6) 2 Nursing occupation 1.7 (1.1-2.7) 2 Recent TB exposure 1.6 (1.0-2.6) 2 1 Silva 2002, 2 Roth 2005,
Incidence of TB disease in HCWs All rates are per 100,000 HCWs
Relative risk of TB disease by work location Realtive risk of TB disease by work location Relative risk estimates 100 90 80 70 60 50 40 30 20 10 0 99 (42.5, 135.5) 29.5 (0.7, 166.7) 16.2(12.8, 20.7) 14.6(8.0, 25.6) 78.6 (42.5, 135.3) 36.6 (9.9. 95.5) 18.9 (8.4, 37.2) 16 (9.6,26.6) 3.9 (2.0, 7.3) 31.9 (10.2, 76.8) 26.6 (12.1, 52.8) 11.6 (0.3, 65.2) 7.3 (2.8, 16.1) 4.2 (3.2, 5.5) 0 1 2 3 4 5 6 Work location Inpatient TB facility (TB ward) Laboratory facility (General lab) Inpatient general medicine facility Emergency facility /ICU Outpatient Medicine/TB facility Combined inpatient and outpatient TB facility 1 2 3 4 5 6 10.9 (8.6, 14.0) Figures represent point estimates and confidence intervals. TB disease in HCWs by work location compared with general population TB disease incidence in the area where health care facility was located
Relative risk of TB disease by work location Realtive risk of TB disease by work location Relative risk estimates 10 8 6 4 2 0 8.8 (1.8, 26.3) 7.8 (3.0, 16.5) 2 (0.7,4.7) 2.9 (0.08, 16.3) 0.6 (0.06, 3.7) 2.8 (0.7, 7.6) 6 7 8 9 10 Work location Surgical facility Obstetrics and Gynecology Administrative facility Operation theater 7 8 9 10 1.5 (0.2, 5.6) Figures represent point estimates and confidence intervals. TB disease in HCWs by work location compared with general population TB disease incidence in the area where health care facility was located
Relative risk of TB disease by occupation Relatiev risk 35 30 25 20 15 10 5 0 32.1 18.9 9.5 3.4 3.1 2.3 1.1 1.5 Relative risk of TB disease by occupation 28.8 25.9 14.3 3.9 3.5 24.33 17.1 11.9 12.5 6.7 10.4 7 6.1 2.9 2.6 1.9 2.3 2.6 2 0.4 0 1 2 3 4 5 6 7 Occupational category 1 2 3 4 5 6 7 Nurses Allied staff Orderlies Doctors Laboratory staff Security/Drivers Administrative 9.1 1.9 1.3 Figures represent point estimates. TB disease in HCWs by work location compared with general population TB disease incidence in the area where health care facility was located
Effect of TBIC strategies
High vs. low income countries Epidemiological measure Estimates from lowmiddle income countries Estimates from high income countries Prevalence of TB infection Incidence of TB infection (ARTI) Incidence of TB disease in HCWs per 100,000 per year Median 63% (33% to 79%) Median 5.3% (0.5% to 14.3%) 69 to 5780 Median 24% (4% to 46%) Median 1% (0.2% to 12%) 2 to 25
Summary of findings Risk of TB infection and disease is high among HCWs in low-mid income countries Much higher than general population Particularly high in certain jobs and locations Limited evidence on which TBIC interventions work in low-mid income countries
Will new tools help us revise the epidemiology of nosocomial TB? Molecular epidemiology IFN-γ assays (IGRAs)
IGRAs for screening of healthcare workers QuantiFERON had a much higher conversion rate than TST, and TST increases were associated with massive increases in interferon-g Pai M et al. Am J Respir Crit Care Med 2006
IGRAs for screening of healthcare workers Figure 1: TST versus ELISPOT conversion rates ELISPOT TST 19.3 27.6 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 Rate (conversions per 100 person-years) ELISPOT had a higher conversion rate than TST, and TST increases were associated with increases in T-cell responses Corbett et al. IUATLD Conference, Paris, 2006
Pai et al. PLoS Med 2007
Thank you (Merci!)