Tuberculosis Exposure Research Articles

Isoniazid preventive therapy in HIV-infected and -uninfected children (0 - 14 years)

Isoniazid preventive therapy (IPT) prevents tuberculosis (TB) in immunocompetent children <5 years of age after exposure to an infectious TB source case. Routine IPT has been advocated in all HIV-infected children without TB, but has been controversial. Antiretroviral therapy markedly reduces the risk for TB in HIV-infected children, especially when started early in infancy. In HIV-infected children, as in HIV- uninfected children, we recommend post-exposure IPT after each TB exposure episode; but in HIV-infected children, this should be given irrespective of age or antiretroviral therapy. However, evidence for routine IPT without known exposure to TB in HIV-infected children is not convincing and is therefore not recommended.

Evaluation of immunological parameters in purified protein derivative positive tuberculin workers.

According to the occupationally risk of infection in staff workers who have direct contact with mycobacterium species, we investigated their immunological parameters and compared with healthy purified protein derivative (PPD) negative volunteers. Materials and Methods : We investigated 20 PPD positive volunteers working at Tuberculin Unit of Razi Vaccine and Serum Research Institute and PPD negative healthy controls with no exposure or history of active tuberculosis. The percentages of circulating lymphocyte subpopulations were detected by flowcytometry. IL-4 and IFN-γ production levels were measured by ELISA in supernatants of PPD-stimulated peripheral blood mononuclear cells (PBMCs) culture. Results : Tuberculin workers showed an increase in IFN-γ level and significant decrease of CD4+ T cells percentage and CD4/CD8 ratio compared to PPD negative normal individuals. However the IL-4 production and percentage of other lymphocyte population has been unchanged. These observations suggest that the immunological parameters of tuberculin workers with PPD positive reaction, who are occupationally exposed to mycobacterium antigens, could be changed. Future studies will be directed towards cytokine networking and regulatory lymphocytes, which will help us validate the significant data presented in this study.

Prevalence of latent tuberculosis infection and its risk factors in schoolchildren and adolescents in Shanghai, China

As tuberculosis (TB) infection in childhood contributes to the pool of individuals with latent tuberculosis infection (LTBI) from which future tuberculosis cases arise, this study aimed to determine the prevalence and risk factors associated with LTBI in schoolchildren and adolescents from Shanghai, China. In this cross-sectional study, we administered T-SPOT.TB and TB infection risk factor questionnaire to children and adolescents aged between 10 and 18 years in 2010 in Shanghai. LTBI cases were defined by positive T-SPOT.TB test results and X-ray confirmation. A total of 1106 schoolchildren and adolescents were enrolled, of which 46.1% were male, and 91.8% were vaccinated with Bacille Calmette Guerin (BCG). Overall, 52 (4.7%) children had a positive T-SPOT.TB result, with significant increase in age distribution. However, none of the participants demonstrated TB-related abnormality on X-ray examination. Multivariate analysis showed that LTBI was associated with no BCG vaccination (odds ratio: 2.40; 95% confidence interval: 1.182-5.335) and a history of TB exposure (odds ratio: 6.89; 95% confidence interval: 3.095-15.35). For 46 children and adolescents with history of TB exposure, contact hours per week of TB cases were significantly associated with risk of LTBI. Prevalence of LTBI in schoolchildren and adolescents in Shanghai is relatively low compared with other high epidemic areas of TB. A higher risk of LTBI was observed among children with no BCG vaccination and those with a history of TB exposure, which suggests that the prevalence of LTBI among schoolchildren could be further reduced by strengthening BCG vaccination under the national immunization programme and enhancing contact investigation of active TB patients.

MDR TB Transmission, Singapore

MDR TB Transmission, Singapore

PredictingMycobacterium tuberculosisin patients with community-acquired pneumonia

The 22 risk factors suggested by the Centers for Disease Control and Prevention (CDC) to predict patients at risk for Mycobacterium tuberculosis have not been evaluated in hospitalised patients with community-acquired pneumonia (CAP). We evaluated which of the CDC risk factors best predict M. tuberculosis in these patients. To our knowledge, this is the first time a score has been developed assessing these risk factors. This was a secondary analysis of 6976 patients hospitalised with CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort Study. Using Poisson regression, we selected the subset of risk factors that best predicted the presence of CAP due to M. tuberculosis. This subset was compared to the CDC risk factors using receiver operating characteristic (ROC) curve analysis. Five risk factors were found to best predict CAP due to M. tuberculosis: night sweats, haemoptysis, weight loss, M. tuberculosis exposure and upper lobe infiltrate. The area under the ROC curve for all CDC risk factors was 71% and 89% for the subset of five risk factors. The CDC-suggested risk factors are poor at predicting the presence of M. tuberculosis in hospitalised patients with CAP. With a subset of five risk factors identified in this study, we developed a new score, which will improve our capacity to isolate patients at risk of CAP due to M. tuberculosis at the time of hospitalisation.

Expatriates: Special Considerations in Pretravel Preparation

Expatriates comprise a diverse set of travelers who face unique medical, psychiatric, and non-health-related risks as a result of increased exposure to host country environment and associated lifestyle. Expatriates have an increased risk of developing malaria, gastrointestinal disorders, latent tuberculosis, vaccine-preventable infections, and psychological disorders, when compared with other travelers, yet the majority of existing pretravel guidelines have been designed to suit the needs of nonexpatriates. Although greater interest in expatriate health issues has led to improved characterization of illness in this population, expatriate-specific risk mitigation strategies—including modifications to chemoprophylaxis recommendations, limiting tuberculosis exposure, and prevention of occupational or sexual blood-borne virus transmission—are poorly described. Occupations and destinations affect travel-related disease risk and should inform the pretravel consultation.

AB0363 Rate of tuberculin skin test or interferon gamma release assay conversion during anti-tumor necrosis factor therapy in rheumatic patients

BackgroundDespite negative baseline testing for tuberculosis (TB) with traditional (tuberculin skin test/TST, chest X-ray/CXR) or newer (interferon-gamma release assays/IGRAs) screening methods, a small number of patients receiving anti-tumor necrosis factor...

Usefulness of Sputum Tests at Admission to Prevent Tuberculosis Exposure from Retrospective Cohort Study of 1,527 Elderly Pneumonias in Japan

Japanese population is aging rapidly with the rate of people over 65 years being 23.3% in 2012. Also, it has been reported by Japanese tuberculosis (TB) Statistics that the elderly over 70 years old accounts for 53.8% of all TB patients in 2011. Consequently, TB in the elderly is getting to be our problem. The elderly with TB have little respiratory symptoms and cavity formations on the chest X-ray, resulting in the difficulty to diagnose TB. In case of TB being diagnosed after hospitalization, we have to consider and practice TB infection control which includes finding exposed persons who are more likely to be infected and planning how to follow them up.

Tuberculosis exposure among evacuees at a shelter after earthquake, Japan, 2011.

Tuberculosis was diagnosed in a person who had stayed in a shelter after the 2011 Great East Japan Earthquake. A contact investigation showed that the prevalence of latent tuberculosis infection among other evacuees at the shelter was 20%. Our report underscores the importance of tuberculosis prevention and control after natural disasters.

Expression of TNF-Alpha-Dependent Apoptosis-Related Genes in the Peripheral Blood of Malagasy Subjects with Tuberculosis

The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective “protective immunity” against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis.Newly diagnosed tuberculosis patients (n = 23), their close household contacts (n = 80), and community controls (n = 46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up.Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes.These data suggest tuberculosis may be associated with decreased T-cell survival (perhaps due to apoptosis) while inhibition of apoptosis in monocytes could lead to a relative increase in these cells: a situation predicted to favour Mtb.

How frequently do tuberculosis screening tests convert in inflammatory bowel disease patients on anti-tumour necrosis factor-alpha? A pilot study

Tuberculosis reactivation can lead to severe complications in patients treated with anti-tumour necrosis factor-alpha. To assess the usefulness of repeat tuberculosis screening tests in inflammatory bowel disease patients on stable anti-TNF therapy. Cross-sectional study, in patients on prolonged anti-TNF treatment (≥ 12 months) and basal negative screening for latent tuberculosis. Quantiferon(®)-TB Gold In-tube test was performed and then, tuberculin skin test was administered. 74 patients were included, median duration of anti-TNF treatment was 30 months (IQR 19-54); 47 patients on infliximab and 27 on adalimumab; no patient was on glucocorticoids. Previous BCG vaccination was present in 5 cases. After anti-TNF was started, 4 patients suffered from potential tuberculosis exposure and two cases travelled to endemic areas. The cumulative incidence of tuberculin skin test conversion was 2.7% (95% CI 0.3-9.4%, 2/74), and the incidence rate of tuberculin skin test conversion was 0.83% (95% CI 0.1-2.9%) per patient-year of treatment with anti-TNF drugs. All Quantiferon tests but one (a patient with an indeterminate result and a negative tuberculin skin test) were negative. The incidence rate of conversion of tuberculosis screening tests among patients on anti-TNF treatment seems to be low and these conversions were diagnosed based on a positive tuberculin skin test and were discordant with Quantiferon testing.

Detecting Tuberculosis Infection in HIV-infected Children

Accurate identification of Mycobacterium tuberculosis infection in young and HIV-infected children could guide delivery of preventive therapy, improve resource utilization and help prevent tuberculosis. We assessed the performance of the tuberculin skin test (TST) and interferon-γ release assays (IGRAs) for identifying M. tuberculosis infection in South African children presenting for outpatient care. Tuberculosis contact was quantified using a standardized measure of M. tuberculosis exposure. Logistic regression assessed the association among test positivity, age, nutritional and HIV status, while controlling for M. tuberculosis exposure, bacille Calmette-Guérin vaccination and prior tuberculosis treatment. Among 250 (130 HIV infected) children (age 0.25-14.6 years, median 39 months), the proportion positive for each test varied: 34% (TST), 21% (T-SPOT.TB) and 25% (QuantiFERON-TB Gold In-Tube). IGRAs were more likely to be positive in HIV-uninfected compared with HIV-infected children; TST positivity did not differ between these groups. Agreement between tests was good-to-excellent in HIV-uninfected children and poor-to-good in HIV-infected children. In adjusted models, TST and T-SPOT.TB were positively associated with age; this effect varied by HIV status. The QuantiFERON-TB Gold In-Tube was negatively associated with chronic malnutrition; this effect varied by HIV status. Because 93% of children had received bacille Calmette-Guérin, we could not assess the contribution of bacille Calmette-Guérin to false-positive TST results. Our findings indicate that the TST and IGRAs perform similarly for the detection of M. tuberculosis infection in well-nourished HIV-uninfected children, but test performance is differentially affected by chronic malnutrition, HIV infection and age. Similar to TST interpretation, clinicians and researchers should interpret IGRAs in children with caution taking age, nutritional and HIV status into consideration.

Infections in Children Treated With Biological Agents

Infections in Children Treated With Biological Agents

Twice-weekly therapy for children with tuberculosis infection or exposure

Children's tuberculosis clinic, Houston, TX, United States. To determine the safety, adherence and efficacy of intermittent directly observed preventive therapy (DOPT). Retrospective cohort of children receiving intermittent DOPT for exposure to tuberculosis (TB) or latent TB infection (LTBI) seen from 1989 to 2011 at one clinic. A total of 1383 children were treated for either TB exposure for 2-3 months (n = 935, 68%) or LTBI for 9 months (n = 448, 32%) with isoniazid 20-30 mg/kg/dose or rifampin 10-15 mg/kg/dose biweekly. All children with exposure and 411 (92%) with LTBI were identified via contact investigations. Twelve (1.3%) children with exposure experienced adverse effects (5 abdominal pain, 4 vomiting, 3 rash); 8 had transaminases evaluated and only 1 had elevated levels. Thirty (6.7%) children with LTBI experienced adverse effects (16 abdominal pain, 6 rash, 3 vomiting, 3 headache and 2 abdominal pain/vomiting); 19 had transaminases obtained and 2 had elevated transaminases. All transaminases normalized after the discontinuation of medication. Over 99% of exposed and 95.8% of infected children completed treatment. One child, who had sickle cell anemia, was treated for LTBI and later developed TB disease. When compared to rates of disease progression by age, the efficacy of intermittent DOPT was 98%. Intermittent DOPT in childhood TB is safe, effective and offers high adherence rates.

Incidence of tuberculosis infection among healthcare workers: Risk factors and 20-year evolution

To determine the incidence of latent tuberculosis infection (LTBI), and risk factors for tuberculosis skin test (TST) conversion among Healthcare workers (HCWs) during a 20-year follow-up period. Prospective cohort analysis. Surveillance was conducted from January 1, 1988, to December 31, 2007. 600-bed tertiary referral hospital in Barcelona, Spain. HCWs in risk for occupational tuberculosis (TB) exposure, with negative baseline TST, direct contact with patients and/or biological samples and at least one follow-up visit with TST. TST is performed in HCWs with no previous history of TB or no previous positive TST. When TST is negative this test is performed once a year in high-risk workers, or at least every 2 years according to the hospital's guidelines. In all cases an interview questionnaire to gather information on possible risk factors was performed. The study included 614 HCWs, 27% worked in areas of risk for TB exposure. Annual incidence rate had decreased from 46.8 per 100 person-years in 1990 to 1.08 per 100 person-years in 2007. Cumulative incidence was higher in HCWs who work in high-risk areas (p=0.004) and in time periods from 1990 to 1995, and from 1996 to 2001 (p<0.0001). Cox regression model showed a hazard ratio of 1.55 (CI 95%; 1.05-2.27) in high-risk workers, adjusted by gender, age and professional status. Incidence of LTBI among HCWs is high, although it decreased throughout the follow-up period. It is crucial to maintain surveillance programs in HCWs.

Diagnosis, treatment and prevention of tuberculosis in children

In Australia, tuberculosis notification rates have plateaued at a low level and disease is highly concentrated in immigrant communities where children may be affected. Many clinicians regard tuberculosis as an adult disease, hence it is rarely considered in the differential diagnosis of sick children. This paper provides a brief overview of the natural history of the disease in children to demonstrate the importance of taking a careful tuberculosis exposure history. It also provides guidance regarding the diagnosis, treatment and prevention of tuberculosis in children. The management of paediatric cases is not difficult if important differences with adult disease are carefully considered; these differences are discussed in detail.

Pediatric and Adolescent Tuberculosis in the United States, 2008–2010

We examined heterogeneity among children and adolescents diagnosed with tuberculosis (TB) in the United States, and we investigated potential international TB exposure risk. We analyzed demographic and clinical characteristics by origin of birth for persons <18 years with verified case of incident TB disease reported to National TB Surveillance System from 2008 to 2010. We describe newly available data on parent or guardian countries of origin and history of having lived internationally for pediatric patients with TB (<15 years of age). Of 2660 children and adolescents diagnosed with TB during 2008-2010, 822 (31%) were foreign-born; Mexico was the most frequently reported country of foreign birth. Over half (52%) of foreign-born patients diagnosed with TB were adolescents aged 13 to 17 years who had lived in the United States on average >3 years before TB diagnosis. Foreign-born pediatric patients with foreign-born parents were older (mean, 7.8 years) than foreign-born patients with US-born parents (4.2 years) or US-born patients (3.6 years). Among US-born pediatric patients, 66% had at least 1 foreign-born parent, which is >3 times the proportion in the general population. Only 25% of pediatric patients with TB diagnosed in the United States had no known international connection through family or residence history. Three-quarters of pediatric patients with TB in the United States have potential TB exposures through foreign-born parents or residence outside the United States. Missed opportunities to prevent TB disease may occur if clinicians fail to assess all potential TB exposures during routine clinic visits.

Pleural effusion arising from a rare pancreatic neoplasm

To the Editors: Pleural effusions are common entities and may complicate a number of disease processes. We present the case of a large pleural effusion associated with a rare pancreatic neoplasm. The patient, a 67-yr-old female, was referred for respiratory opinion by the Breast Cancer Service at St Vincent’s University Hospital (Dublin, Ireland). She had a background of invasive ductal carcinoma of the right breast 4 yrs previously for which she had undergone a wide local excision and was taking hormonal therapy. Other past medical history included a diagnosis of seropositive rheumatoid arthritis requiring only analgesic therapy. She had known tuberculosis (TB) exposure in childhood and was a nonsmoker. She drank alcohol only on occasion. She had initially noticed that she was sinking to the left side while swimming over the previous month. This was followed by progressive dyspnoea on exertion, left-sided chest pain and nocturnal non-productive cough. She denied haemoptysis or weight loss and was systemically well. Physical examination identified stony-dull percussion and reduced breath sounds over the mid-lower left lung. She was comfortable at rest with oxygen saturations of 96% on room air. There was no clubbing or lymphadenopathy. A chest radiograph confirmed a large left-sided pleural effusion (fig. 1a). Pleural …

Effects of manganese on routine semen quality parameters: results from a population-based study in China

BackgroundManganese (Mn) is an essential element in humans but its effect on semen quality is unclear. This study therefore aimed to assess the effects of Mn on semen quality in healthy men with no occupational exposure to Mn.MethodsSemen samples were obtained from healthy Chinese men 20–59 years old who were recruited from six provinces in China. Individuals with urogenital tract diseases, tuberculosis, or occupational exposure to heavy metals were excluded. A questionnaire survey was conducted, and the external genitalia, semen quality, and serum Mn levels were examined.ResultsA total of 1,179 volunteers were enrolled in this study. The median serum Mn concentration was 8.2 μg/L (25th percentile (P25)=3.7 μg/L, P75=16.2μg/L). After adjusted area (six provinces), abstinence interval, season, registered residence, age of subjects, education level, income, smoking, and drinking, the risk of teratospermia was increased at serum Mn concentrations >19.40 μg/L (P80) group, with an adjusted odds ratio of 2.27 (95% confidence interval: 1.18–4.37).ConclusionHigh serum Mn levels appeared to have harmful effects on sperm morphology and motility among healthy men with no occupational exposure to Mn.

Conversion rates of an interferon-γ release assay and the tuberculin skin test in the serial monitoring of healthcare workers

Regular monitoring of latent tuberculosis (TB) infection in healthcare workers (HCWs) is recommended, but the view about the effective method and performance of serial monitoring is controversial. The aim of this study was to determine differences in conversion rates according to TB exposure risk using the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT), and to evaluate the reproducibility and within-subject variability of the QFT-GIT in South Korea. Fifty-three HCWs were grouped according to their risk for TB exposure: group 1, high risk (n = 21); group 2, low risk (n = 32). Baseline and follow-up TSTs and QFT-GITs were performed from June 2009 to July 2011. Enzyme-linked immunosorbent assays (ELISAs) were repeated for the second QFT-GIT and a third QFT-GIT was performed after 8 weeks when discordant results of the second TST and QFT-GIT or a conversion or reversion were observed. No difference in the QFT-GIT conversion rate was evident between the two groups (15.4 vs. 6.5 %, p = 0.57), and no TST conversion was observed. The rate of QFT-GIT positivity was higher in the high-risk group (first QFT-GIT: 38.1 vs. 3.1 %, p = 0.002; second QFT-GIT: 33.3 vs. 9.4 %, p = 0.039). The re-test reproducibility of QFT-GIT results was high (100 %), and the within-subject results of repetitive QFT-GITs were variable. Stricter prevention strategies remain necessary in HCWs at high risk of TB exposure, and serial interferon-γ release assays (IGRAs) should be interpreted with caution in HCWs.