Cases Of Tuberculosis Disease Research Articles

Simulation age-specific tuberculosis model for the Cape Town metropole

Tuberculosis (TB) continues to present an insurmountable health burden in the Western Cape Province of South Africa. TB dynamics in adults is different from that in children, with the former determining the latter. Because the dynamics of TB are largely dependent on age, planning for interventions requires reasonable and realistic projections of the incidence across ages. It is thus important to model the dynamics of TB using mathematical models as predictive tools. We considered a TB compartmental model that is age dependent and whose parameters are set as functions of age. The model was fitted to the TB incidence data from the Cape Town metropole. The effective contact rate, a function of both age and time, was changed to fit the model to the notification rates of active TB disease cases. Our simulations illustrate that age structure plays an important role in the dynamics of TB. Projections on the future of the epidemic were made for each age group. The projected results show that TB incidence is likely to increase in the lower age groups of the population. It is clearly evident that even very simple models when applied to limited data can actually give valuable insights. Our results show that the age groups who have the highest incidence rates of active TB disease have the highest contribution in the transmission of TB. Furthermore, interventions should be targeted in the age group 25–34 years.

Migration and tuberculosis in the UK: targeting screening for latent infection to those at greatest risk of disease

Active tuberculosis (TB) in the UK predominantly affects the non-UK born, but is generally not manifest at the time of UK entry. Strategies to detect latent TB infection (LTBI) in...

Comparison of the tuberculin skin test and Quanti-FERON-TB Gold In-Tube (QFT-G) test for the diagnosis of latent tuberculosis infection in dialysis patients

Dialysis patients are more likely than the general population to develop active tuberculosis (TB). In these patients, the availability of a highly sensitive and specific test to diagnose latent TB will ensure earlier treatment and decreased progression to active disease. In the current study, the Quanti-FERON-TB Gold In-Tube (QFT-G) test was compared with the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) among 200 hemodialysis patients and 15 confirmed TB disease cases in a tertiary care center in Saudi Arabia. Among the LTBI cases, 26 (13%) were TST positive, and 65 (32.5%) were positive by the QTF-G test, with an overall agreement between the 2 tests of 75.5% (k=0.34) being observed. Among the confirmed tuberculosis disease cases, none were positive by TST, and 10 (66.7%) were positive by the QTF-G test, resulting in an overall agreement of 33.3% (k=0). A comparison between the TST and the QTF-G test was performed based on the sensitivity, specificity, and area under the curve (AUC) obtained for the tests. The QTF-G test was more sensitive and less specific than the TST in predicting the confirmed TB disease cases. When we tested the correspondence of the AUC values between the 2 diagnostic modalities, the obtained p-value was 0.0003. In conclusion, the AUCs of the examined diagnostic modalities are significantly different in predicting LTBI and tuberculosis.

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

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.

TNF-α/IL-2 ratio discriminates latent from active tuberculosis in immunocompetent children: a pilot study

Distinguishing latent tuberculosis (LTB) from tuberculosis (TB) disease may be challenging in children. Here, we analyzed cytokine profiles that can distinguish the two infection stages in a nonendemic country (France). Immunocompetent children with LTB (n = 6) or TB disease (n = 8) (median age: 6.2 and 5.7 years, respectively) were analyzed. Four young uninfected children were included as controls. A Luminex assay evaluated cytokine responses to Mycobacterium tuberculosis antigens. Poor interleukin-4 (IL-4) and IL-10 responses precluded analysis of these cytokines. Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-2, and T-helper type 1 (Th1) cytokines and IL-5, IL-13, T-helper type 2 (Th2) cytokines were simultaneously induced by antigens in 14/14 infected but 0/4 uninfected children. Th1 cytokine levels were similar in LTB and TB disease: IFN-γ: 12,254 and 10,495 pg/ml; IL-2: 2,097 and 1,869 pg/ml; and TNF-α: 1,020 and 2,875 pg/ml, respectively. Th2 cytokine levels were similar and even higher in LTB than in TB disease: IL-5: 23 and 10 pg/ml; IL-13: 284 and 109 pg/ml, respectively. Positive correlation of cytokine levels, whether Th1 or Th2, was observed. Higher (P = 0.008) TNF-α/IL-2 ratios distinguished 6/8 active TB disease cases from 6/6 LTB cases. TNF-α/IL-2 ratio may discriminate TB disease from LTB in immunocompetent children. Larger studies in TB endemic settings must verify these results.

Contage tuberculeux néonatal en maternité : dépistage et évolution d’une cohorte de nourrissons exposés

Few data are available on the impact of a tuberculosis exposure on newborns in a maternity ward. To describe the screening and clinical course of infants exposed during the neonatal period to a caregiver with bacillary tuberculosis. Infants exposed during the postnatal period in a maternity unit in Paris, from March to August 2005, to a caregiver with bacillary tuberculosis were included in a standardized screening protocol. The screening performed at baseline (M0) and at 3 months (M3) included a clinical evaluation, a tuberculin skin test (TST), and a chest X-ray. A preventive treatment for tuberculosis with isoniazid and rifampicin for 3 months was systematically proposed. At M0, 182 of the 217 infants (84%) with significant exposure were evaluated. Data were available for 172 infants. The median age at M0 was 4.9 months (IQR=3.8-6.2). At M0, 4 of 172 infants (2.3%) had latent TB infection. Between M0 and M3, 19 infants (11%) were lost to follow-up and 1 on 153 developed a latent TB infection. No cases of tuberculosis disease were diagnosed. The treatment was administered properly in 83% of cases and side effects were observed in 11% of infants without any serious adverse event. Four infants received no treatment and 11 stopped their treatment prematurely. In the absence of neonatal massive exposure, although low (2.9%), the risk of latent TB infection requires close monitoring of the infants exposed. However, in the context of a mild exposure in the maternity unit, surveillance without systematic initiation of TB preventive treatment could be discussed.

Tuberculosis, bacillus Calmette–Guérin vaccination, and allergic disease: Findings from the International Study of Asthma and Allergies in Childhood Phase Two

Some have suggested a protective effect of tuberculosis (TB) infection on allergic disease risk, but few studies have examined the association between the two. We therefore investigated whether TB disease and bacillus Calmette-Guérin (BCG) vaccination in early life protect against allergic disease. Information on allergic disease symptoms, past TB disease, and BCG vaccination as well as potential confounding factors was gathered by parental questionnaire from a randomly selected subset of 23,901 8- to 12-yr-old schoolchildren in 20 centers in both developed and developing countries. Children were also physically examined for flexural eczema and underwent skin prick testing. Pooled odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) across study centers were calculated, using random effects meta-analysis models. There were 245 (1.0%) reported cases of TB disease, and 66.3% (15,857) of all children received the BCG vaccine. Asthma, hay fever, and flexural eczema symptoms in the past year as well as flexural eczema on skin examination were all positively linked to a history of TB (adjusted pooled OR 'wheeze in the past year' = 2.27, 95% CI 1.52-3.41; adjusted pooled OR 'hay fever symptoms in the past year' = 2.23, 1.22-4.09; adjusted pooled OR 'flexural eczema symptoms in the past year' = 3.21, 2.01-5.12; adjusted pooled OR 'flexural eczema on skin examination' = 4.04, 1.71-9.56). Even higher risk estimates were seen for severe asthma and eczema symptoms [adjusted OR = 4.02 (2.17-7.47) and adjusted OR = 6.31 (2.19-18.17), respectively]. There was no significant association between past TB and skin prick test positivity (adjusted pooled OR = 1.32, 0.87-2.02). BCG vaccination during the first year of life was also not associated with any of the allergy outcomes. We found a uniform positive association between TB and all allergic disease outcomes, including eczema on skin examination. As this was a cross-sectional study, it is unclear whether this positive association is attributable to a causal relationship, and further longitudinal studies are required.

Decay Kinetics of an Interferon Gamma Release Assay with Anti-Tuberculosis Therapy in Newly Diagnosed Tuberculosis Cases

BackgroundQualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy.MethodsNewly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models.ResultsA total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found.ConclusionsTB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy.

Tuberculosis investigations associated with air travel: U. S. Centers for Disease Control and Prevention, January 2007–June 2008

Contact investigations conducted in the United States of persons with tuberculosis (TB) who traveled by air while infectious have increased. However, data about transmission risks of Mycobacterium tuberculosis on aircraft are limited. We analyzed data on index TB cases and passenger contacts from contact investigations initiated by the U.S. Centers for Disease Control and Prevention from January 2007 through June 2008. Contact investigations for 131 index cases met study inclusion criteria, including 4550 passenger contacts. U.S. health departments reported TB screening test results for 758 (22%) of assigned contacts; 182 (24%) had positive results. Of the 142 passenger contacts with positive TB test results with information about risk factors for prior TB infection, 130 (92%) had at least one risk factor and 12 (8%) had no risk factors. Positive TB test results were significantly associated with risk factors for prior TB infection (OR 23; p<0.001). No cases of TB disease among passenger contacts were reported. The risks of M. tuberculosis transmission during air travel remain difficult to quantify. Definitive assessment of transmission risks during flights and determination of the effectiveness of contact-tracing efforts will require comprehensive cohort studies.

Interferon-Gamma Release Assay Improves the Diagnosis of Tuberculosis in Children

Interferon-gamma release assays (IGRAs) have been recently developed for the diagnosis of tuberculosis (TB) infection. The aim of the present study was to evaluate the performance of an enzyme-linked immunosorbent assay (ELISA)-based IGRA for detecting TB in children. A prospective study in 336 children at risk for TB infection was carried out. All children were tested with tuberculin skin test (TST) and a commercial ELISA-based IGRA [QuantiFERON-TB Gold In-Tube (Cellestis)]. TST were positive in 58 of 336 (17.3%) and IGRA in 60 of 336 (17.9%) children. Two (0.6%) IGRA results were indeterminate. The overall agreement between the 2 tests was intermediate (86.2%, kappa= 0.533). IGRA was positive in 15 of 16 (93.8%) children with active pulmonary TB. The discordant pattern IGRA-/TST+ was significantly associated with Bacille Calmette-Guérin (BCG) vaccination. Among IGRA+ children (excluding cases of TB disease), TST- were significantly younger than TST+ children. The good agreement between positive IGRA and active TB disease suggests a good sensitivity of IGRA. Discrepancies between IGRA and TST can be a result of higher specificity of IGRA that is not influenced by previous BCG vaccination. IGRA may be more sensitive in children younger than 48 months.

Lessons Learned from Two School Tuberculosis Investigations

We describe the results from tuberculosis (TB) contact investigations of two high-school students. Following the development of active TB in two foreign-born students, contact investigations were performed to detect contacts with active TB disease or latent TB infection (LTBI). The two students developed pulmonary TB within 2 years of immigrating to the United States. Among household contacts, no case of active TB was identified; however, LTBI was identified in 7 of 20 persons screened (35%). Of the 104 high-risk school contacts identified, no cases of active TB disease were found, but 7 (9.3%) were diagnosed with LTBI. An additional 683 low-risk contacts were screened and 9 (1.5%) were positive. Schools and Public Health departments needs to be prepared for outbreak investigations and should screen only persons with a high risk of exposure to the index case with active TB in an attempt to identify secondary infections. Those persons with a low risk of exposure should not be screened.

Tuberculosis Among Foreign-Born Persons in the United States

Foreign-born persons accounted for 57% of all tuberculosis (TB) cases in the United States in 2006. Current TB control strategies have not sufficiently addressed the high levels of TB disease and latent TB infection in this population. To determine the risk of TB disease and drug-resistant TB among foreign-born populations and the potential impact of adding TB culture to overseas screening procedures for foreign-born persons entering the United States. Descriptive epidemiologic analysis of foreign-born persons in the United States diagnosed with TB from 2001 through 2006. TB case rates, stratified by time since US entry, country of origin, and age at US entry; anti-TB drug-resistance patterns; and characteristics of TB cases diagnosed within 3 months of US entry. A total of 46,970 cases of TB disease were reported among foreign-born persons in the United States from 2001 through 2006, of which 12,928 (28%) were among recent entrants (within 2 years of US entry). Among the foreign-born population overall, TB case rates declined with increasing time since US entry, but remained higher than among US-born persons--even more than 20 years after arrival. In total, 53% of TB cases among foreign-born persons occurred among the 22% of the foreign-born population born in sub-Saharan Africa and Southeast Asia. Isoniazid resistance was as high as 20% among recent entrants from Vietnam and 18% for recent entrants from Peru. On average, 250 individuals per year were diagnosed with smear-negative, culture-positive TB disease within 3 months of US entry; 46% of these were from the Philippines or Vietnam. The relative yield of finding and treating latent TB infection is particularly high among individuals from most countries of sub-Saharan Africa and Southeast Asia.

Surveillance of air-travel-related tuberculosis incidents, England and Wales: 2007-2008

The potential spread of tuberculosis (TB) from infectious passengers during air travel has recently received increasing attention in the media and from public health authorities. We reviewed all air travel-related tuberculosis incidents reported to the Health Protection Agency Centre for Infections between January 2007 and February 2008 in England and Wales and investigated the effectiveness of contact investigation. Incidents involving air travel were defined according to the World Health Organization's guidelines on TB and Air Travel. We collected data on the index case, the incident and the outcome of contact investigation where available. We identified 24 incidents involving 39 flights. The median flight duration was 8.9 hours (inter-quartile range (IQR) 8 to 11.7). Most flights (36) were from or to a high burden country and 19 of the 24 incidents reported had a smear-positive index case. Two index cases had multidrug-resistant tuberculosis. In 17 incidents, no further investigation could be undertaken due to the lack of passenger information. In the remaining seven incidents, the quality of contact information obtained was variable. No further cases of TB infection or disease were identified. This study suggests that the process of investigating passenger contacts of a TB infected individual travelling by air is complicated and usually unsuccessful without dedicated resources and availability of high-quality contact information from airlines. Further research into the effectiveness of contact investigation in this setting is needed.

Exposure to Pulmonary Tuberculosis in a Neonatal Intensive Care Unit: Unique Aspects of Contact Investigation and Management of Hospitalized Neonates

We describe the investigation of a tuberculosis (TB) exposure in which a neonatal intensive care unit (NICU) respiratory therapist was the index patient, as well as the rationale by which exposed infants were managed and possible explanations for the lack of transmission to these patients. Description of an exposure investigation. Academic, level IV NICU of a tertiary care children's hospital. Contacts of a respiratory therapist with pulmonary TB disease, including household members, healthcare coworkers, and infant patients. In addition to 5 household contacts, 248 healthcare coworkers and 180 infant patients were identified as possibly exposed during the 24 days that the index patient worked between December 3, 2004, and January 30, 2005. Tuberculin skin tests (TSTs) were performed for 233 of the 235 contacts with the greatest degree of exposure (household and coworker contacts) who had a previously documented negative TST result or whose TST status was unknown prior to the investigation. No cases of latent tuberculosis infection or TB disease were identified. Because of characteristics of the index case, the exposure duration and setting, the infants' small lung volumes, and lack of evidence of transmission to higher-risk contacts, infants were not clinically evaluated or empirically treated for TB disease. Surveillance for subsequent illness was carried out by primary healthcare providers and parents. No TB disease or unexplained illness in these infants was reported in the 20 months following the exposure. After limited hospital exposure to a healthcare worker with pulmonary TB disease who is not highly contagious, neonates can be safely managed without specific evaluation for TB disease or empirical treatment.

A community outbreak of tuberculosis in Southern Austria: lessons learned for a targeted use of molecular epidemiological methods and tuberculin skin testing

A cluster of 10 cases of tuberculosis disease (one of them extrapulmonary) occurred from July 2001 until November 2003 in a health district in Southern Austria. Eight patients were culture confirmed and shared an identical strain. One of these eight cases was identified as outbreak-related by molecular strain typing only. Due to public pressure, a further 600 persons received chest X-ray and clinical examinations. Apart from one case which could be excluded from the outbreak because of a different strain pattern, no outbreak-related case of active tuberculosis was detected by this non-targeted procedure. Tuberculin skin testing, not part of the Austrian routine protocol of contact investigation in adults, was initiated after diagnosis of case 8. Forty-nine latently infected contacts were detected. Population-based genotyping of all isolates, prioritization of contact investigations and early use of targeted tuberculin skin testing are critical for effective tuberculosis control in low-incidence countries.

Tuberculosis and Homelessness in the United States, 1994-2003

Tuberculosis (TB) rates among US homeless persons cannot be calculated because they are not included in the US Census. However, homelessness is often associated with TB. To describe homeless persons with TB and to compare risk factors and disease characteristics between homeless and nonhomeless persons with TB. Cross-sectional analysis of all verified TB cases reported into the National TB Surveillance System from the 50 states and the District of Columbia from 1994 through 2003. Number and proportion of TB cases associated with homelessness, demographic characteristics, risk factors, disease characteristics, treatment, and outcomes. Of 185,870 cases of TB disease reported between 1994 and 2003, 11,369 were among persons classified as homeless during the 12 months before diagnosis. The annual proportion of cases associated with homelessness was stable (6.1%-6.7%). Regional differences occurred with a higher proportion of TB cases associated with homelessness in western and some southern states. Most homeless persons with TB were male (87%) and aged 30 to 59 years. Black individuals represented the highest proportion of TB cases among the homeless and nonhomeless. The proportion of homeless persons with TB who were born outside the United States (18%) was lower than that for nonhomeless persons with TB (44%). At the time of TB diagnosis, 9% of homeless persons were incarcerated, usually in a local jail; 3% of nonhomeless persons with TB were incarcerated. Compared with nonhomeless persons, homeless persons with TB had a higher prevalence of substance use (54% alcohol abuse, 29.5% noninjected drug use, and 14% injected drug use), and 34% of those tested had coinfection with human immunodeficiency virus. Compared with nonhomeless persons, TB disease in homeless persons was more likely to be infectious but not more likely to be drug resistant. Health departments managed 81% of TB cases in homeless persons. Directly observed therapy, used for 86% of homeless patients, was associated with timely completion of therapy. A similar proportion in both groups (9%) died from any cause during therapy. Individual TB risk factors often overlap with risk factors for homelessness, and the social contexts in which TB occurs are often complex and important to consider in planning TB treatment. Nevertheless, given good case management, homeless persons with TB can achieve excellent treatment outcomes.

Simit Epidemiological Multicentric Study on Hospitalized Immigrants in Italy During 2002

The aim of this article is to retrospectively evaluate the patient characteristics and the most common infectious diseases in immigrant patients hospitalized in 46 Italian infectious disease clinics during 2002. The main Italian infectious disease clinics were invited to fill in a questionnaire that regarded the number and type of hospital admissions, the country of origin, and demographic features (age, sex, and resident state) of immigrants. A total of 46 clinics including 2255 patients participated in the study. Most patients were men (63%) with an age between 16 and 40 years (63.4%) covered by the National Health Service (71%) and coming from Africa (44.3%). The main infectious diseases observed were: 378 (16.76%) cases of HIV infection, 303 (13.43%) cases of tuberculosis diseases, 282 (12.5%) cases of various forms of viral hepatitis, 177 (7.84%) cases of respiratory diseases, and 196 (8.69%) gastrointestinal diseases. Tropical diseases found were 134 (5.94%) including 95 cases of malaria (70.9%). In conclusion, a broad range of diseases was noted in immigrants which were directly correlated with conditions of poverty. Only a few tropical diseases were diagnosed and therefore the immigrant should not be considered as an infectious disease carrier.

Tuberculosis Associated With Blocking Agents Against Tumor Necrosis Factor-Alpha—California, 2002-2003

The Food and Drug Administration (FDA) has determined that tuberculosis (TB) disease is a potential adverse reaction from treatment with the tumor necrosis factor-alpha (TNF-alpha) antagonists infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira); the three products are labeled accordingly. These products work by blocking TNF-alpha, an inflammatory cytokine, and are approved for treating rheumatoid arthritis and other selected autoimmune diseases. TNF-alpha is associated with the immunology and pathophysiology of certain infectious diseases, notably TB; blocking TNF-alphacan allow TB disease to emerge from latent Mycobacterium tuberculosis infection. In 2002, a California county health department reported three cases of TB disease occurring in association with infliximab therapy. This report summarizes those cases and nine subsequently reported cases and provides interim recommendations for TB prevention and management in recipients of these blocking agents. Health-care providers should take steps to prevent TB in immunocompromised patients and remain vigilant for TB as a cause of unexplained febrile illness.

Investigations à conduire autour d’un cas de tuberculose-maladie ou de tuberculose-infection récente

The objectives of the investigation are double. Not only must the sick patients be identified and treated to stop the transmission chain since they could be sources of infection, but recently infected patients must also be identified and offered treatment for tuberculosis-infection if necessary. The goal of this step is to prevent their infection from evolving rapidly to tuberculosis-disease. Moreover, in a community, it is necessary to evaluate the risk of transmission and to identify the possible factors favoring this transmission in order to set up preventive measures. When a case of tuberculosis-disease or infection is diagnosed, the risk of BK transmission and individual risk factors of the people living close to the detected patient must be assessed. When a case of recent tuberculosis-infection is diagnosed the source patient must be looked for.