RJ, AR, DM, and MP conceived and designed the study. RJ and MP collected, analyzed, and interpreted the data. RJ and MP drafted the manuscript. RJ, AR, DM, and MP performed critical revision of the manuscript.
The authors have declared that no competing interests exist.
The risk of transmission of
We conducted a systematic review to summarize the evidence on the incidence and prevalence of latent TB infection (LTBI) and disease among HCWs in LMICs, and to evaluate the impact of various preventive strategies that have been attempted. To identify relevant studies, we searched electronic databases and journals, and contacted experts in the field. We identified 42 articles, consisting of 51 studies, and extracted data on incidence, prevalence, and risk factors for LTBI and disease among HCWs. The prevalence of LTBI among HCWs was, on average, 54% (range 33% to 79%). Estimates of the annual risk of LTBI ranged from 0.5% to 14.3%, and the annual incidence of TB disease in HCWs ranged from 69 to 5,780 per 100,000. The attributable risk for TB disease in HCWs, compared to the risk in the general population, ranged from 25 to 5,361 per 100,000 per year. A higher risk of acquiring TB disease was associated with certain work locations (inpatient TB facility, laboratory, internal medicine, and emergency facilities) and occupational categories (radiology technicians, patient attendants, nurses, ward attendants, paramedics, and clinical officers).
In summary, our review demonstrates that TB is a significant occupational problem among HCWs in LMICs. Available evidence reinforces the need to design and implement simple, effective, and affordable TB infection-control programs in health-care facilities in these countries.
A systematic review demonstrates that tuberculosis is an important occupational problem among health care workers in low and middle-income countries.
One third of the world's population is infected with
But what about low- and middle-income countries (LMICs) where more than 90% of the world's cases of TB occur? Here, there is little money available to implement even low-cost strategies to reduce TB transmission in health-care facilities—so how important an occupational disease is TB in HCWs in these countries? In this study, the researchers have systematically reviewed published papers to find out the incidence and prevalence (how many people in a population have a specific disease) of active TB and latent TB infections (LTBIs) in HCWs in LMICs. They have also investigated whether any of the preventative strategies used in high-income countries have been shown to reduce the TB burden in HCWs in poorer countries.
To identify studies on TB transmission to HCWs in LMICs, the researchers searched electronic databases and journals, and also contacted experts on TB transmission. They then extracted and analyzed the relevant data on TB incidence, prevalence, risk factors, and control measures. Averaged-out over the 51 identified studies, 54% of HCWs had LTBI. In most of the studies, increasing age and duration of employment in health-care facilities, indicating a longer cumulative exposure to infection, was associated with a higher prevalence of LTBI. The same trend was seen in a subgroup of medical and nursing students. After accounting for the incidence of TB in the relevant general population, the excess incidence of TB in the different studies that was attributable to being a HCW ranged from 25 to 5,361 cases per 100, 000 people per year. In addition, a higher risk of acquiring TB was associated with working in specific locations (for example, inpatient TB facilities or diagnostic laboratories) and with specific occupations, including nurses and radiology attendants; most of the health-care facilities examined in the published studies had no specific TB infection-control programs in place.
As with all systematic reviews, the accuracy of these findings may be limited by some aspects of the original studies, such as how the incidence of LTBI was measured. In addition, the possibility that the researchers missed some relevant published studies, or that only studies where there was a high incidence of TB in HCWs were published, may also affect the findings of this study. Nevertheless, they suggest that TB is an important occupational disease in HCWs in LMICs and that the HCWs most at risk of TB are those exposed to the most patients with TB. Reduction of that risk should be a high priority because occupational TB leads to the loss of essential, skilled HCWs. Unfortunately, there are few data available to indicate how this should be done. Thus, the researchers conclude, well-designed field studies are urgently needed to evaluate whether the TB-control measures that have reduced TB transmission to HCWs in high-income countries will work and be affordable in LMICs.
Please access these Web sites via the online version of this summary at
• US National Institute of Allergy and Infectious Diseases
• US Centers for Disease Control and Prevention
• MedlinePlus
• NHS Direct Online, from the UK National Health Service,
• US National Institute for Occupational Health and Safety,
• American Lung Association
The risk of transmission of
The situation is very different in low- and middle-income countries (LMICs), which account for more than 90% of the global TB burden [
We conducted a systematic review to summarize the evidence on the incidence and prevalence of latent TB infection (LTBI) and TB disease among HCWs in LMICs. We specifically addressed the following questions: (1) What is the prevalence of LTBI and what are the risk factors for LTBI in HCWs? (2) What is the incidence of LTBI in HCWs and what risk factors are associated with higher incidence rates? (3) What is the incidence of TB disease in HCWs and how does it compare with the incidence in the population? (4) Are certain occupations, or some work locations within a health-care facility, at higher risk of TB than others? (5) How effective are various strategies in reducing the incidence of LTBI and/or disease among HCWs in LMICs?
We searched the following electronic databases for primary studies: PubMed (
Our search strategy aimed to identify all the available published studies in the English language that reported data on the incidence and prevalence of LTBI and TB disease in HCWs. Although non-English studies were excluded, we extracted data from studies that had English abstracts, and these limited data are included in
Two reviewers (RJ and MP) independently extracted data from a subset of eligible studies. The inter-rater agreement on TB outcomes (such as LTBI incidence and prevalence, and TB disease incidence, etc.) was 100% in this pilot study. Subsequently, data from the full set of included studies were extracted by one reviewer (RJ). Data extracted included: country, survey year, type of health-care facility, number of TB patients managed in the facility, infection-control practices (such as personal protection, administrative measures, engineering controls, etc.) in the facility at the time of the study, prevalence and incidence of LTBI, prevalence and incidence of TB disease, risk factors for LTBI or TB disease, infection-control interventions (personal, administrative, and engineering controls), and evaluations of their effectiveness, delays in diagnosis at the facility, and demographic and other relevant details about HCWs included in the studies. We used the following definitions to standardize the data-extraction process.
Health-care facility: All facilities where patients seek health care, including hospitals, clinics, dispensaries, health centers, and imaging and laboratory facilities. We did not include prisons, nursing homes, correctional facilities, and other congregate settings.
HCW: Any individual who works in a health-care setting including, but not restricted to, physicians, nurses, allied health personnel (nursing assistants, operation theater technicians, etc.), health educators, social workers, midwives, community health workers based in hospitals, laboratory personnel, pharmacists, radiographers, volunteers, orderlies, and health-facility administrators.
LTBI: A positive tuberculin skin test (TST) done by any standard method using 1TU (tuberculin unit) or 2TU of purified protein derivative of tuberculin (PPD) RT23 or 5TU of PPD-S, with induration size ≥ 10 mm on a single test [
Tuberculin conversion: Defined as a newly positive TST after a documented negative-baseline TST (at any time after a negative two-step baseline, or more than 1 y after a negative single TST). An increase of 10 mm over the baseline was defined as conversion [
TB disease: Included all forms of pulmonary, as well as extra-pulmonary, TB where a definitive (microbiologically confirmed), or presumptive (based on clinical, imaging, or pathology criteria) diagnosis was made. The definition included self-reported past treatment for TB disease.
Income category definitions: The countries were grouped according to 2004 gross national income per capita criteria as suggested by the World Bank, which classifies LMICs as those with per capita income value of less than US$10,066 [
Infection-control interventions were defined as any personal protection (including, but not limited to, respirators), administrative measures (including, but not limited to, early diagnosis and isolation policy, reducing time for which TB patients would be hospitalized, and reducing waiting times for infectious patients in outpatient and radiology facilities), and environmental controls (including, but not limited to, negative-pressure isolation rooms, HEPA filters, etc.)
Data on the estimated incidence of all forms of TB disease in the general population were obtained from the World Health Organization's (WHO) global TB database [
Studies were heterogeneous in many respects, including baseline TB incidence in the population, institutional TB case loads, types of tests used to detect TB, job descriptions and classifications of HCWs, and preventive measures used at health-care facilities. Hence we analyzed the studies in prespecified subgroups. Studies of medical or nursing students were analyzed separately, as their risk of exposure may be different from other HCWs. Studies on TB disease were analyzed separately from studies on LTBI.
The incidence rates of LTBI and TB disease among HCWs, and corresponding estimates in the general population, were used to determine the excess risk among HCWs attributable to nosocomial exposure. We calculated the risk estimates for the incidence of TB disease in HCWs for various occupations and work locations, with incidence of TB disease in the general population as a reference. Data were analyzed using Stata (Version 9) and Meta-DiSc (Version 1.2) software.
In meta-analyses, heterogeneity refers to a substantial degree of variability in study results. Such heterogeneity can be due to differences in methodological quality, study design, sampling variability, and study populations across studies. In the presence of significant heterogeneity, pooled or summary estimates from meta-analyses are difficult to interpret. We addressed heterogeneity using subgroup (stratified) analyses. Because the studies estimating the prevalence of LTBI had comparable methodologies, we generated pooled (summary) estimates by using a fixed-effects model, where studies were weighed by the overall sample size, and we corrected for over-dispersion to allow for heterogeneity that was due to between-study variability.
Of the 1,901 unique citations identified in the literature search, 42 articles describing the results of 51 studies met our eligibility criteria (
As seen in
The circles and the lines represent the point estimates and 95% CIs, respectively. The size of the circle indicates the study size, and the diamond indicates the pooled estimate (weighted average) and its 95% CI. The heterogeneity chi-square statistics are 142.6 (
Prevalence of LTBI in Medical or Nursing Students as Determined by TST Surveys in LMICs
As shown in
Prevalence of LTBI in All HCWs as Determined by TST Surveys
Extended.
Several studies reported a prevalence of LTBI in nurses, a subgroup with a high level of patient contact, and thus potential exposure to TB cases. As seen in
Prevalence of LTBI in Nurses
In six out of the seven studies covered in
Incidence of LTBI or Tuberculin Conversion in HCWs
Results of studies that estimated the incidence of TB disease are shown in
Incidence of TB Disease (All Forms) in HCWs
Studies that reported rates of TB disease by work location and occupational categories are shown in
Occupational Risk Factors for TB Disease in HCWs
Most authors reported that no specific TB infection-control programs were being used in the health-care facilities where the studies were carried out. Only three studies [
As seen in
Impact of Multiple Administrative, Personal, and Engineering Control Measures on Nosocomial Transmission of TB
The introduction of multiple administrative, personal, and engineering controls in a single hospital in Thailand [
In another study from Brazil [
In a case-control study by Jelip et al. [
Our systematic review of 51 studies demonstrates that the prevalence (range 33% to 79%) and incidence (range 0.5% to 14.3% per year) of LTBI, and the attributable risk of TB disease due to nosocomial exposure (from 25 to 5,361 per 100,000 per year), were high among HCWs in LMICs. The attributable risk was higher in health-care facilities that had more TB patients per HCW. Certain work locations (inpatient TB facility, laboratory, general medicine, and emergency facilities) and occupational categories (radiology technicians, patient attendants, nurses, ward attendants, paramedics, and clinical officers) were associated with a higher risk of TB disease. Finally, there is little published evidence on the effects of infection-control measures in LMIC.
In a recent review of TB among HCWs in high-income settings, the prevalence of LTBI ranged from 5% to 55%, in different occupations [
In such low-income countries, more years of clinical training and greater exposure to TB patients are important risk factors for acquiring new TB infection.
Our systematic review had several strengths. We used a comprehensive search strategy using multiple sources and databases to retrieve relevant studies. Two reviewers (RJ and MP) independently selected and extracted data from the included studies. Subgroup analyses were done to minimize heterogeneity across studies. Data were pooled only when studies were reasonably consistent in their methods. However, our review had certain limitations. First, despite the comprehensive literature search, a few eligible studies were missed, because we included only English-language studies. Our literature search had identified ten non-English articles [
In addition to the limitations of the review, the primary studies included within its scope had several limitations. These limitations are discussed separately for each of the four main outcomes in our review: (1) the prevalence of LTBI; (2) the incidence of LTBI; (3) the incidence of TB disease; and (4) the impact of infection-control measures.
Studies that reported LTBI prevalence among HCWs had several limitations. The first limitation pertains to the use of the TST. The prevalence of occupational LTBI could have been over-estimated because it was based on TST. The TST detects lifetime cumulative occupational plus nonoccupational exposure to
The practice, timing, and frequency of BCG vaccination vary widely across countries, which complicates the analyses as BCG can be an important cause of false-positive TST. The results of TST are also influenced by the type of test material (PPD), technique of reading, and definition of a positive test. Although all studies used the definition of 10 mm or more induration after 48–72 h for TST to be positive, the PPD used varied, which could reduce comparability of studies. These limitations may affect the prevalence of LTBI, but should not affect the analysis of risk factors associated with LTBI.
Recently, interferon-gamma release assays (IGRAs) have become available for the diagnosis of LTBI. In contrast to the TST, IGRAs use antigens that are significantly more specific than PPD. Thus, IGRAs are highly specific and are therefore less likely to be affected by previous BCG vaccination and NTM exposure [
Another major limitation of prevalence studies is the lack of concurrent data on LTBI prevalence in the population. Thus, it is not easy to determine whether HCWs had a significantly higher LTBI prevalence than the community. However, despite this limitation, our review shows that the prevalence of LTBI was lower among young medical or nursing students newly entering the health-care profession, but increased with each year of training (an index of cumulative exposure). Similarly, the prevalence of LTBI among other HCWs increased with duration of employment, again reflecting cumulative exposure. HCWs whose occupation involves closer patient contact (such as nurses) also had higher LTBI prevalence. These results indirectly suggest that nosocomial TB contributes to the burden of LTBI among HCWs.
Almost all studies that estimated the incidence of new TB infections used serial tuberculin skin testing. In addition to the known limitations of TST, serial TST has additional problems such as boosting, choice between a single-step or a two-step baseline protocol, and the definitions used for conversion. Most studies followed the two-step testing protocol so as not to overestimate true LTBI incidence due to boosting. Only one study used an IGRA for estimating the rate of new TB infection [
Despite the above limitations, the results suggest that HCWs have a higher risk of TB infection than the estimates of risk in the general population. The high attributable risk estimates for LTBI incidence provide the most convincing evidence for nosocomial transmission of TB in health-care settings. In these studies, more years of clinical training and greater exposure to TB patients were risk factors for new infection, and this provides additional support for nosocomial transmission.
The incidence of TB disease in HCWs was generally higher than the estimated TB rates in the general population. However, several methodological problems may affect the interpretation of these studies. HCWs may be more likely to seek medical care, and hence case-detection rates may be higher than in the general population. Our review included probable and self-reported TB cases, which also could have inflated the incidence of TB disease among HCWs. On the other hand, HCWs are less likely to develop TB because HCWs have a higher average socio-economic status, and are younger and healthier, than the general population in LMIC (i.e., healthy-worker effect) [
Despite the above limitations, most studies reported higher estimates of TB disease among HCWs than in the general population, and this is suggestive of nosocomial transmission. The high rates of TB disease among young HCWs are particularly worrisome. Some of this may be explained by coinfection with HIV—particularly in countries with a very high prevalence of HIV, such as in Sub-Saharan Africa. Few studies reported the prevalence of HIV infection among HCWs,and thus the impact of HIV on TB disease among HCWs could not be addressed.
Molecular studies involving DNA fingerprinting could provide confirmatory evidence of nosocomial transmission, as they have in high-income countries [
Only three studies [
In summary, there is consistent epidemiologic evidence that TB is an important occupational disease in HCWs. There is clear evidence of heavy exposure, with little or no infection-control measures in place. Thus, it is not surprising that there is consistent evidence of excess prevalence and incidence of TB infection, as well as a higher incidence of TB disease among HCWs than in the general populations in the same LMICs. Although estimates vary widely, infection and disease are roughly correlated with indicators of exposure—including more years of work, or clinical training, and work that has been identified as high risk among HCWs in high-income countries. Finally, there is evidence, albeit limited and weak, that the incidence of infection drops after the implementation of infection-control measures. This epidemiological evidence implies that a substantial proportion of LTBI and TB disease in the HCWs in LMICs is the result of nosocomial TB transmission.
Our review presents fairly strong evidence that nosocomial TB is an important occupational problem among HCWs in LMICs, and reduction of that risk should be a priority. Currently available evidence is limited, but it suggests that relatively simple interventions, such as early diagnosis of TB, segregation of infectious TB patients, or education and training of HCWs, might be effective. Additional low-cost measures could include engineering controls such as exhaust ventilation, improved natural ventilation, or sunlight [
There are several important reasons as to why nosocomial transmission of TB should be addressed in LMICs. First, occupational TB can lead to the loss of skilled workers, and this can adversely impact health-care services in the long run. Second, transmission of TB can have serious, and even fatal, consequences for patients and HCWs. This is particularly true with MDR-TB strains, and in patient populations with high HIV seroprevalence. Hospitals have been shown to be important focal points of MDR-TB transmission, with explosive outbreaks, and associated with high mortality. Third, implementation of effective TB infection control can promote awareness of TB, and the adoption of improved practices for the diagnosis and treatment of TB, particularly in the private health sector. Low-cost administrative interventions are feasible and, if implemented, should require minimal resources. Given the evidence summarized in this review, national TB-control programs and public health agencies in LMICs must begin to address nosocomial TB transmission as an integral part of their TB-control efforts. HCWs are essential in the fight against TB, and their health needs to be protected as well as that of patients with TB. With the recent emergence of extensively drug-resistant tuberculosis (XDR-TB), the need to implement infection-control measures has been reemphasized by global agencies such as the WHO and the Stop TB Partnership [
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confidence interval
health-care worker
interferon-gamma release assay
incidence rate ratio
low- and middle-income country
latent TB infection
multidrug-resistant tuberculosis
non-tuberculous mycobacteria
odds ratio
purified protein derivative of tuberculin
tuberculosis
tuberculin skin test
tuberculin unit
World Health Organization
extensively drug-resistant tuberculosis