Tuberculin Skin Test Conversion Research Articles

Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil

BackgroundIn household contact investigations of tuberculosis (TB), a second tuberculin skin test (TST) obtained several weeks after a first negative result consistently identifies individuals that undergo TST conversion. It remains unclear whether this delay in M. tuberculosis infection is related to differences in the infectious exposure, TST boosting, partial host resistance, or some other factor.MethodsWe conducted a household contact study Vitória, Brazil. Between 2008 and 2013, we identified culture-positive pulmonary TB patients and evaluated their household contacts with both a TST and interferon gamma release assay (IGRA), and identified TST converters at 8–12 weeks post study enrollment. Contacts were classified as TST-positive (≥10 mm) at baseline, TST converters, or persistently TST-negative. We compared TST converters to TST-positive and to TST-negative contacts separately, using generalized estimating equations.ResultsWe enrolled 160 index patients and 838 contacts; 523 (62.4%) were TST+, 62 (7.4%) TST converters, and 253 (30.2%) TST−. TST converters were frequently IGRA− at 8–12 weeks. In adjusted analyses, characteristics distinguishing TST converters from TST+ contacts (no contact with another TB patient and residence ownership) were different than those differentiating them from TST− contacts (stronger cough in index patient and contact BCG scar).ConclusionsThe individual risk and timing of M. tuberculosis infection within households is variable and dependent on index patient, contact and environmental factors within the household, and the surrounding community. Our findings suggest a threshold effect in the risk of infection in humans.

Solid Organ Transplant-Transmitted Tuberculosis Linked to a Community Outbreak - California, 2015.

In the spring of 2015, a local health department (LHD) in county A notified the California Department of Public Health (CDPH) about three adults with close ties to one another and a congregate community site who had received diagnoses of tuberculosis (TB) disease within a 3-month period. Subsequent review revealed matching TB genotypes indicating that the cases were likely part of a chain of TB transmission. Only three TB cases in California in the preceding 2 years shared this same genotype. One of those three previous cases occurred in a lung-transplant recipient who had no identified epidemiologic links to the outbreak. CDPH, multiple LHDs, and CDC conducted an investigation and determined that the lung-transplant donor (patient 1) was epidemiologically linked to the three outbreak cases and had a tuberculin skin test (TST) conversion detected in 2012 upon reentry at a local jail. Three other solid organ recipients from this donor were identified; none had developed TB disease. This investigation suggests that review of organ donors' medical records from high-risk environments, such as jails, might reveal additional information about TB risk. The evaluation of TB in organ recipients could include genotyping analysis (1) and coordination among local, state, and national partners to evaluate the potential for donor-derived TB.

Negative latent tuberculosis at time of incarceration: identifying a very high-risk group for infection.

The main aim was to measure the incidence of latent tuberculosis infection (LTBI) and identify risk factors associated with infection. In addition, we determined the number needed to screen (NNS) to identify LTBI and active tuberculosis. We followed 129 prisoners for 2 years following a negative two-step tuberculin skin test (TST). The cumulative incidence of TST conversion over 2 years was 29·5% (38/129), among the new TST converters, nine developed active TB. Among persons with no evidence of LTBI, the NNS to identify a LTBI case was 3·4 and an active TB case was 14·3. The adjusted risk factors for LTBI conversion were incarceration in prison number 1, being formerly incarcerated, and overweight. In conclusion, prisoners have higher risk of LTBI acquisition compared with high-risk groups, such as HIV-infected individuals and children for whom LTBI testing should be performed according to World Health Organization guidance. The high conversion rate is associated with high incidence of active TB disease, and therefore we recommend mandatory LTBI screening at the time of prison entry. Individuals with a negative TST at the time of entry to prison are at high risk of acquiring infection, and should therefore be followed in order to detect convertors and offer LTBI treatment. This approach has a very low NNS for each identified case, and it can be utilized to decrease development of active TB disease and transmission.

Late boosting phenomenon in TST conversion among health care workers.

Available information is insufficient to guide determination of whether tuberculin skin test (TST) conversions of health care workers (HCWs) within 2 years of two-step testing are related to occupational exposures or to other causes, including late boosting. To describe the epidemiologic factors of TST conversion in HCWs, comparing early TST conversion (≤2 years after two-step testing) with late conversion to possibly distinguish late boosting phenomenon from occupational TST conversion. Retrospective analysis of a database of TSTs of HCWs from 1 January 1998, through 31 May 2014, in the United States Midwest. In total, 40142 HCWs had 197932 tests over the 16 years, with 123 conversions (conversion rate: 0.3%; 95% CI 0.3-0.4%). Among 61 HCWs with a negative two-step TST, 30 (49%) were found to have early TST conversion within 2 years; 31 (51%) had late conversion, with likely occupational exposure but no identifiable community risks. Persons with early conversion were more likely to be born outside the USA (89% versus 57%; P < 0.05), had a higher rate of prior bacille Calmette-Guérin (BCG) vaccination (89% versus 52%; P < 0.05) and had no identifiable risk factors for conversion (63% versus 58%; P < 0.05). Early conversions among HCWs after negative two-step TST are associated with various nonoccupational factors, including international birth and BCG vaccination history. Therefore, conversion is not a reliable indicator of recent tuberculosis contact in this population, and two-step TST is insufficient to discount a delayed boosting response for HCWs.

The Long-term Effect of Bacille Calmette-Guérin Vaccination on Tuberculin Skin Testing: A 55-Year Follow-Up Study

Bacille Calmette-Guérin (BCG) vaccination is known to cause false-positive tuberculin skin test (TST) results from cross-reactions with mycobacterial antigens. However, the duration of BCG vaccination influence on the TST is poorly characterized. The objective of this study was to assess the long-term effect of BCG vaccination on TST reactivity. Data on TST reactivity were prospectively collected during 1935 to 1947 as part of a clinical trial among Native Americans/Alaskan Natives and were retrospectively collected thereafter between 1948 and 1998. TST induration of≥ 10mm was defined as a positive reaction. Kaplan-Meier analysis and multivariate Cox regression were used to compare the time to TST conversion and reversion between the BCG and placebo groups. BCG vaccination after infancy was associated with an increased risk of TST reactivity in the first 15 years after vaccination (adjusted hazard ratio [HR], 2.33). This association remained during the interval 16 to 55 years after vaccination, although the effect was attenuated (adjusted HR, 1.26). Age at vaccination modestly impacted the effect of BCG on TST results in the first 15 years. Positive TST results among the BCG-vaccinated group were more likely to revert to negative results during the first 15 years but not in the latter period. This study provides evidence that BCG vaccination after infancy may influence TST results beyond the 10-year period conventionally accepted by the Centers for Disease Control and Prevention (CDC), extending up to 55 years after vaccination. This suggests that BCG vaccination should be taken into account when interpreting TST results regardless of the time elapsed since vaccination.

LATENT TUBERCULOSIS AMONG PROFESSIONALS FROM A REFERRAL HOSPITAL IN ONCOLOGY

Introduction: Tuberculosis (TB) is an ancient contagious disease, and continues to be the leading cause of morbidity and mortality among infectious contagious diseases. It can be considered an occupational infectious disease when it happens in health professionals. These professionals are directly exposed to TB and are considered to be a high risk population for latent tuberculosis infection (LTBI) and active TB. The primary aim of this study was to estimate the prevalence of LTBI among the clinical and administrative staff of an oncology referral hospital in Rio Grande do Sul. The secondary aim of this study was evaluate tuberculin skin test (TST) conversion rate and the risk factors for TST positivity in this population. Methods : A cross-sectional study was carried out in a retrospective cohort with data collected in March 2013 and March 2014. Data of professionals from different hospital units were included. Those with induration ≥ 10 mm were considered as reactors, and conversion rate was assessed by an increase ≥ 10 mm in induration in the second TST compared with the first one. Results: Among the 225 professionals evaluated in 2013, 135 (60%) were reactors and 90 (40%) were non-reactors. The mean age was 32.9 (± 9.55), 176 (78.22%) were female, and most of the reactors worked in the hospital for 4 years or less. Non-reactors in 2013 were recommended to repeat the test in 2014, and the conversion rate was 9.37%. There was no significant difference in prevalence among the different professional categories, and the assessed risk factors were not associated with ILTB. Conclusions: The prevalence of LTBI in the study population was high, reinforcing the need to implement effective control measures to prevent LTBI in the hospital where the study was conducted. Keywords: Latent tuberculosis; occupational risk; tuberculin test; vulnerable populations

Impact of mass-screening on tuberculosis incidence in a prospective cohort of Brazilian prisoners.

BackgroundGlobally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood.MethodsWe performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ≥10 mm and an induration increase of at least 6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models were performed to identify risk factors associated with active TB. To evaluate the impact of screening on subsequent risk of disease, we compared TB notifications over one year among individuals randomized to screening for active TB with those not randomized to screening.ResultsAmong 3,771 inmates recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %) were diagnosed with TB over the subsequent year. Cases identified through active screening were less likely to be smear­positive than passively detected cases (10.0 % vs 50.9 %; p < 0.01), suggesting early case detection. However, there was no reduction in subsequent disease among individuals actively screened versus those not screened (1.3 % vs 1.7 %; p = 0.88). Drug use during the year (AHR 3.22; 95 % CI 1.05–9.89) and knows somebody with TB were (AHR 2.86; 95 % CI 1.01–8.10) associated with active TB during one year of follow upConclusionsMass screening in twelve Brazilian prisons did not reduce risk of subsequent disease in twelve Brazilian prisons, likely due to an extremely high force of infection. New approaches are needed to control TB in this high-transmission setting.

Conductas frente al viraje de la prueba de Tuberculina en estudiantes de medicina de una universidad de Lima, Perú

The aim of this study was to determine the behaviors in response to tuberculin skin test (PPD) conversion and the reasons for starting or not starting treatment for latent tuberculosis infection (TILT) among medical students at a university in Lima, Peru. A total of 548 participants completed a questionnaire; of them, 6.7% tested positive on university admission and 11.1% were recent converters. A total of 55.7% did not start TILT and had no explanation. Of the recent converters, most students who did start TILT were >22 years old (p = 0.01) and correctly answered general knowledge questions (p = 0.04). It is important to note that the PPD conversion rate was higher than that reported in the literature and that most students did not follow the treatment prophylaxis because of a lack of information.

Annual risk of tuberculosis infection in rural China: a population-based prospective study.

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.

Chest Radiographic Patterns and the Transmission of Tuberculosis: Implications for Automated Systems.

BackgroundComputer-aided detection to identify and diagnose pulmonary tuberculosis is being explored. While both cavitation on chest radiograph and smear-positivity on microscopy are independent risk factors for the infectiousness of pulmonary tuberculosis it is unknown which radiographic pattern, were it detectable, would provide the greatest public health benefit; i.e. reduced transmission. Herein we provide that evidence.Objectives1) to determine whether pulmonary tuberculosis in a high income, low incidence country is more likely to present with “typical” adult-type pulmonary tuberculosis radiographic features and 2) to determine whether those with “typical” radiographic features are more likely than those without such features to transmit the organism and/or cause secondary cases.MethodsOver a three-year period beginning January 1, 2006 consecutive adults with smear-positive pulmonary tuberculosis in the Province of Alberta, Canada, were identified and their pre-treatment radiographs scored by three independent readers as “typical” (having an upper lung zone predominant infiltrate, with or without cavitation but no discernable adenopathy) or “atypical” (all others). Each patient’s pre-treatment bacillary burden was carefully documented and, during a 30-month transmission window, each patient’s transmission events were recorded. Mycobacteriology, radiology and transmission were compared in those with “typical” versus “atypical” radiographs.FindingsA total of 97 smear-positive pulmonary tuberculosis cases were identified, 69 (71.1%) with and 28 (28.9%) without “typical” chest radiographs. “Typical” cases were more likely to have high bacillary burdens and cavitation (Odds Ratios and 95% Confidence Intervals: 2.75 [1.04–7.31] and 9.10 [2.51–32.94], respectively). Typical cases were also responsible for most transmission events—78% of tuberculin skin test conversions (p<0.002) and 95% of secondary cases in reported close contacts (p<0.01); 94% of secondary cases in “unreported” contacts (p<0.02).ConclusionAs a group, smear-positive pulmonary tuberculosis patients with typical radiographic features constitute the greatest public health risk. This may have implications for automated detection systems.

The Use of Interferon Gamma Inducible Protein 10 as a Potential Biomarker in the Diagnosis of Latent Tuberculosis Infection in Uganda.

BackgroundIn the absence of a gold standard for the diagnosis of latent tuberculosis (TB) infection (LTBI), the current tests available for the diagnosis of LTBI are limited by their inability to differentiate between LTBI and active TB disease. We investigated IP-10 as a potential biomarker for LTBI among household contacts exposed to sputum positive active TB cases.MethodsActive TB cases and contacts were recruited into a cohort with six months’ follow-up. Contacts were tested for LTBI using QuantiFERON®-TB Gold In-Tube (QFN) assay and the tuberculin skin test (TST). Baseline supernatants from the QFN assay of 237 contacts and 102 active TB cases were analysed for Mycobacterium tuberculosis (MTB) specific and mitogen specific IP-10 responses.ResultsContacts with LTBI (QFN+TST+) had the highest MTB specific IP-10 responses at baseline, compared to uninfected contacts (QFN-TST-) p<0.0001; and active cases, p = 0.01. Using a cut-off of 8,239 pg/ml, MTB specific IP-10 was able to diagnose LTBI with a sensitivity of 87.1% (95% CI, 76.2–94.3) and specificity of 90.9% (95% CI, 81.3–96.6). MTB specific to mitogen specific IP-10 ratio was higher in HIV negative active TB cases, compared to HIV negative latently infected contacts, p = 0.0004. Concentrations of MTB specific IP-10 were higher in contacts with TST conversion (negative at baseline, positive at 6-months) than in those that were persistently TST negative, p = 0.001.ConclusionIP-10 performed well in differentiating contacts with either latent or active TB from those who were uninfected but was not able to differentiate LTBI from active disease except when MTB specific to mitogen specific ratios were used in HIV negative adults. In addition, IP-10 had the potential to diagnose ‘recent TB infection’ in persons classified as having LTBI using the TST. Such individuals with strong IP-10 responses would likely benefit from chemoprophylaxis.

Tuberculin skin test conversion and association with occupation and demographic characteristics in workers at San Ignacio University Hospital

Objectives To establish the prevalence of positivity and conversion rate of the tuberculin skin test in workers of our hospital, and to describe the related demographic and occupational characteristics. Materials and Methods An observational, descriptive study was conducted in a cohort of hospital workers who underwent the tuberculin skin test. The positivity of the test was defined as a result of greater than or equal to 10 mm, and conversion was defined as an increase of 6 or 10 mm with respect to the initial test. Results Prevalence of 23.7 % and incidence of conversion of 13.6 % for the major cut-off point of 10 mm, and 23 % for the lesser cut-off point of 6 mm, was found. The age of the subjects was related to the conversion, but there was no relation with occupation. Conclusions The probability of tuberculosis transmission in health-care workers is higher than in the general population. Promotion and prevention measures must be implemented to decrease the transmission and to increase awareness of tuberculosis related to occupational activities.

Nosocomial exposure to active pulmonary tuberculosis in a neonatal intensive care unit

Nosocomial transmission of tuberculosis (TB) in a neonatal intensive care unit (NICU) is a recognized risk. We investigated TB transmission to neonates and health care workers (HCWs) exposed to a nurse with active TB in a NICU. A NICU nurse in a tertiary referral hospital in Seoul, Korea, developed pulmonary TB. The investigation included 108 infants and 75 HCWs. Tuberculin skin test (TST) and chest radiograph were performed at baseline. Isoniazid prophylaxis was started in neonates. After 3 months of prophylaxis, infants underwent repeat TST and chest radiograph. HCWs underwent a second TST after 3 months. Baseline chest radiographs were negative in infants and HCWs. Four (3.7%) of 108 infants screened had a positive TST, including 2 conversions, and received isoniazid for 6-9 months. Among the 59 HCWs screened, 27 (45.8%) had an initial positive TST result, and 6 (10.2%) had a positive TST result at 3 months. Four of the 6 HCWs with TST conversions received isoniazid treatment for 9 months. In the 2-year period after exposure, none of the exposed infants or HCWs developed active TB. In this investigation, 4 (3.7%) of 108 infants exposed to a nurse with active TB developed latent TB infection. They were given isoniazid therapy without any adverse events and did not progress to TB disease in the 2 years after exposure.

Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands.

The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.

Prevalence of latent tuberculosis infection in patients with moderate to severe psoriasis taking biologic therapies in a dermatologic private practice in Miami, Florida.

The reactivation of a latent tuberculosis infection is one of the possible major events that may occur during biologic therapies for inflammatory chronic diseases such as psoriasis. Although its main screening test is regularly used in clinical practice, there are few studies about the prevalence of this silent mycobacterial infection and the rate of positive convertors during treatment. To assess the prevalence of latent tuberculosis infection (LTBI) in patients with moderate to severe psoriasis receiving biologic therapy by using tuberculin skin test as a screening method and to evaluate the rate of conversion of tuberculin skin test (TST) during the treatment with biologics. A total of 445 patients were included in our retrospective study, conducted from January 2006 to September 2012. Tuberculin skin test was performed in all patients prior to treatment and once a year during the follow-up. PPD was considered positive with an induration above 5 mm, following the recommendations of Centers for Disease Control and Prevention/ America Thoracic Society. Data analysis was obtained with SPSS 20.0. The prevalence of LTBI in our population before initiating the treatment was 4.5% by using TST screening method. During the treatment, 10 cases that were initially TST-negative became positive. Only one of the patients developed active tuberculosis infection. The other 9 TST-positive patients were detected during the regular annual screening, and no symptoms or findings on chest x-ray were seen. All the patients were treated with isoniazid (INH) for nine months, and biologic therapy was restarted after one month of treatment with INH without development of overt TB infection in any of them during the follow-up period of the study. The mean time to becoming TST positive from start date was 26.7 months (range from 8 months to 5 years). As the PPD was done annually, it is unknown exactly when the patients became TST positive. Prior to initiating treatment, 20 patients were found to be TST positive. All patients had clear chest x-rays and were treated with nine months of INH prior to initiating biologic therapy at least month later. The use of a screening tool for LTBI is mandatory in patients taking biologic therapies to avoid severe infectious complications. Periodic follow-up is also crucial as positive results may be seen after prolonged use of these agents.

Institutional Tuberculosis Transmission. Controlled Trial of Upper Room Ultraviolet Air Disinfection: A Basis for New Dosing Guidelines.

Transmission is driving the global tuberculosis epidemic, especially in congregate settings. Worldwide, natural ventilation is the most common means of air disinfection, but it is inherently unreliable and of limited use in cold climates. Upper room germicidal ultraviolet (UV) air disinfection with air mixing has been shown to be highly effective, but improved evidence-based dosing guidelines are needed. To test the efficacy of upper room germicidal air disinfection with air mixing to reduce tuberculosis transmission under real hospital conditions, and to define the application parameters responsible as a basis for proposed new dosing guidelines. Over an exposure period of 7 months, 90 guinea pigs breathed only untreated exhaust ward air, and another 90 guinea pigs breathed only air from the same six-bed tuberculosis ward on alternate days when upper room germicidal air disinfection was turned on throughout the ward. The tuberculin skin test conversion rates (>6 mm) of the two chambers were compared. The hazard ratio for guinea pigs in the control chamber converting their skin test to positive was 4.9 (95% confidence interval, 2.8-8.6), with an efficacy of approximately 80%. Upper room germicidal UV air disinfection with air mixing was highly effective in reducing tuberculosis transmission under hospital conditions. These data support using either a total fixture output (rather than electrical or UV lamp wattage) of 15-20 mW/m(3) total room volume, or an average whole-room UV irradiance (fluence rate) of 5-7 μW/cm(2), calculated by a lighting computer-assisted design program modified for UV use.

The dynamics of QuantiFERON-TB gold in-tube conversion and reversion in a cohort of South African adolescents.

Interferon-γ release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described. To assess QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting. Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow up. Half of the participants had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to 5 years. Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions (κ = 0.74), but poor for reversions (κ = 0.12). Among recent QFT converters, the magnitude of the QFT value was strongly inversely associated with risk of reversion (P < 0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters than in participants with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011). In this tuberculosis-endemic setting, annual risk of infection was extremely high, whereas QFT and TST conversion concordance was higher and QFT reversion rates were lower than reported in low-burden settings.

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.

Annual risk of tuberculous infection measured using serial skin testing, Orel Oblast, Russia, 1991-2005.

To compare trends in direct annual risk of tuberculous infection (ARTI) during 1991-2005 in relation to tuberculosis (TB) incidence and to indirect estimates of ARTI derived from the prevalence of tuberculin skin test (TST) positivity in schoolchildren in Orel Oblast, Russia. In 2005, we abstracted annual TST results and vaccination histories from a representative sample of schoolchildren in Orel Oblast, Russia, where bacille Calmette-Guerin (BCG) vaccination and annual TST of children are nearly universal. We calculated direct ARTI based on the percentage of children tested with TST conversions each year, excluding conversions following BCG vaccination. We analysed records from 13 206 children, with a median of 10 recorded TST results per child. The ARTI increased from 0.2% in 1991 to 1.6% in 2000, paralleling trends in TB incidence. Similar results were observed when the ARTI was estimated based on prevalence of infection among children aged 3-5 years using a 12 mm cut-off to define TST positivity. Results differed substantially when 10 or 15 mm cut-offs were used or when prevalence was determined among children aged 6-8 years. ARTI measured through TST conversion increased as TB incidence increased in Orel Oblast. ARTI measured through serial TSTs can thus provide an indicator of changing trends in TB incidence.

Broad adaptive immune responses to M. tuberculosis antigens precede TST conversion in tuberculosis exposed household contacts in a TB-endemic setting.

BackgroundThe identification of Mycobacterium-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN–γ release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN–γ may help to define markers of early Mtb infection.MethodsWe assessed the TST status of Mtb-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST+); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST−). We assessed their short- and long-term immune responses to PPD and ESAT–6/CFP–10 (EC) via IFN–γ ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages.ResultsAfter 1 and 6 days stimulation with EC, 12 cytokines (IFN–γ, IL–2, IP–10, TNF–α, IL–13, IL–17, IL–10, GMCSF, MIP–1β, MCP–3, IL–2RA and IL–1A) were not different in TSTC compared to TST+ suggesting that robust adaptive Mtb-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN–γ ELISPOT to EC in combination with TST results revealed that IP–10 and IL–17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection.ConclusionWe describe a detailed analysis of Mtb-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for ‘at-risk’ populations beyond TST and IGRA.