Tuberculosis Incidence Countries Research Articles

P2.045 Serial Testing with an Interferon-Gamma Release Assay in HIV-1-Infected Individuals

BackgroundThe clinical utility of serial screening for tuberculosis (TB) by interferon-gamma release assays has not been established in HIV-1-infected individuals.MethodsIn this prospective study HIV-1-infected subjects underwent repeated QuantiFERON-TB Gold In-Tube...

Biomarkers of Tuberculosis: A Research Roadmap

Tuberculosis (TB) continues to represent a major public health problem worldwide. Prompt and accurate diagnosis and effective treatment are fundamental to reducing morbidity and mortality and curtailing spread of infection. Furthermore, tackling the large reservoir of latent infection is the cornerstone to TB control in many high income low TB incidence countries. However, our existing toolkit for prevention, diagnosis and treatment remains outdated and inadequate. Here, we discuss the key targets for biomarker research and discovery in TB and recent developments in the field. We focus on host biomarkers, in particular: correlates of vaccine efficacy and sterilizing immunity; biomarkers of latent TB infection, including diagnosis, risk of progression to active TB and response to treatment; and markers of active TB, including diagnosis, response to treatment and risk of relapse. Recent scientific and technological advances have contributed to significant recent progression in biomarker discovery. Although there are clear remaining paucities, continued efforts within scientific, translational and clinical studies are likely to yield a number of clinically useful biomarkers of TB in the foreseeable future.

THU0204 The Positive Effect of Stringent Criteria for Purified Protein Derivation (PPD) Skin Test on Patients Treated with Certolizumab Pegol

BackgroundTreatment with biologics is associated with increased risk of tuberculosis (TB).1,2 Before starting an anti-TNF, patients (pts) should undergo screening for latent TB, including Purified Protein Derivation (PPD) skin test....

FRI0164 Local tuberculosis incidence affects the rate of positive conversion in the quantiferon®-tb gold test among patients receiving infliximab or ct-p13 therapy

BackgroundTreatment with an anti-TNF agent can increase the risk of tuberculosis (TB) by reactivation of latent tuberculosis infection (LTBI) or new infection.ObjectivesTo identify the risk of positive conversion in the...

Tuberkuloza - 60 godina sistematske primene vakcine Bacille Calmette Guerin u Srbiji

Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines in the world and is currently given to children at birth or soon after birth in over 100 countries, including Serbia, to minimize the risk of developing serious forms of tuberculosis (TB). Despite different data about its efficacy, it is evident that BCG protects infants from disseminated and meningeal TB (there is a decreasing trend of such cases over the past six decades in Serbia) and TB - related death. Serbia is an intermediate-to-low TB incidence country in socio-economic transition. Its current epidemiologic situation when it comes to TB shows a slightly decreasing overall trend of TB, a constant decreasing time trend of childhood TB as well as a dramatically increasing trend of TB in the elderly. Some forms of extra - pulmonary TB are on the increase as well. At the beginning of the 21st century, BCG is a useful resource for individual protection in particular situations where the spread of TB infection and disease and the limited application of preventive measures cannot provide an objective control of TB.

Evaluation of Immigrant Tuberculosis Screening in Industrialized Countries

In industrialized countries, tuberculosis (TB) cases are concentrated among immigrants and driven by reactivation of imported latent TB infection (LTBI). We examined mechanisms used to screen immigrants for TB and LTBI by sending an anonymous, 18-point questionnaire to 31 member countries of the Organisation for Economic Co-operation and Development. Twenty-nine (93.5%) of 31 responded; 25 (86.2%) screened immigrants for active TB. Fewer countries (16/29, 55.2%) screened for LTBI. Marked variations were observed in targeted populations for age (range <5 years of age to all age groups) and TB incidence in countries of origin of immigrants (>20 cases/100,000 population to >500 cases/100,000). LTBI screening was conducted in 11/16 countries by using the tuberculin skin test. Six countries used interferon-γ release assays, primarily to confirm positive tuberculin skin test results. Industrialized countries performed LTBI screening infrequently and policies varied widely. There is an urgent need to define the cost-effectiveness of LTBI screening strategies for immigrants.

Diagnosis and Management of Tuberculosis in Transplant Donors: A Donor-Derived Infections Consensus Conference Report

Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.

Treatment of Latent Tuberculosis Infection in HIV: Shorter or Longer?

Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another-both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.

Risk of tuberculosis among people with diabetes mellitus: an Australian nationwide cohort study

ObjectivePrevious studies that have found an increased risk for tuberculosis (TB) in people with diabetes mellitus (DM) have been conducted in segments of the population and have not adjusted for...

Risk of Tuberculosis in Dialysis Patients: A Nationwide Cohort Study

BackgroundThe ability to identify individuals at increased risk of developing tuberculosis (TB) has important implications for public health policy and patient care. We conducted a general population historical cohort study in all Australian States and Territories to establish the risk of TB arising in people on chronic hemo- or peritoneal dialysis.Methodology/Principal FindingsCases of TB disease in patients receiving chronic dialysis were identified by record linkage using the Australia & New Zealand Dialysis and Transplant Registry (ANZDATA) and State and Territory TB notification databases 2001 to 2006. Main outcome measure was the relative risk of TB in people on dialysis, adjusted for TB incidence in country of birth, sex, age and indigenous status. A total of 6,276 cases of active TB were reported among 19,855,283 people living in Australia between 2001 and 2006. Among 14,506 patients on dialysis, 37 had a notification for TB disease after commencing dialysis, of whom 28 were culture positive. The incidence of TB was 66.8/100,000/year (95% CI 47.7 to 93.2) among people on dialysis and 5.7/100,000/year (95% CI 5.5 to 5.8) in the general population. The adjusted relative risk (aRR) of TB in people on dialysis was 7.8 (95% CI 3.3 to 18.7), and the aRR of culture positive TB was 8.6 (95% CI 3.9 to 19.3).Conclusions/SignificancePatients on dialysis are at increased risk of TB. The final decision to screen for, and to treat, LTBI in individual dialysis patients will be influenced by a cumulative assessment of the risk of reactivation of TB and by assessment of risk factors for adverse effects of treatment.

New approaches in the diagnosis and treatment of latent tuberculosis infection.

With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence.

Tuberculosis contact investigation in low prevalence countries: a European consensus

Contact investigation to identify individuals with tuberculosis and latent infection with Mycobacterium tuberculosis is an important component of tuberculosis control in low tuberculosis incidence countries. This document provides evidence-based and best-practice policy recommendations for contact tracing among high- and medium-priority contacts in a variety of settings. It provides a basis for national guidelines on contact investigation and tuberculosis outbreak management, and should support countries and tuberculosis control managers in evaluating and revising national policies. A review of existing guidelines, a literature search, several meetings and consultation with experts were used to formulate and grade recommendations for action during contact investigation. Available tests to identify individuals with latent infection with M. tuberculosis are designed to identify immune response against mycobacterial antigens and have variable predictive value for the likelihood to develop active tuberculosis in different populations. Contact investigation should therefore be limited to situations with a clear likelihood of transmission or to those with a higher probability of developing active tuberculosis, for instance, young children and immunocompromised persons. A risk assessment-based approach is recommended, where the need to screen contacts is prioritised on the basis of the infectiousness of the index case, intensity of exposure and susceptibility of contacts.

Mining and Risk of Tuberculosis in Sub-Saharan Africa

We estimated the relationship between mining and tuberculosis (TB) among countries in sub-Saharan Africa. We used multivariate regression to estimate the contribution of mining activity to TB incidence, prevalence, and mortality, as well as rates of TB among people living with HIV, with control for economic, health system, and population confounders. Mining production was associated with higher population TB incidence rates (adjusted b = 0.093; 95% confidence interval [CI] = 0.067, 0.120; with an increase of mining production of 1 SD corresponding to about 33% higher TB incidence or 760,000 more incident cases), after adjustment for economic and population controls. Similar results were observed for TB prevalence and mortality, as well as with alternative measures of mining activity. Independent of HIV, there were significant associations between mining production and TB incidence in countries with high HIV prevalence (≥ 4% antenatal HIV prevalence; HIV-adjusted B = 0.066; 95% CI = 0.050, 0.082) and between log gold mining production and TB incidence in all studied countries (HIV-adjusted B = 0.053; 95% CI = 0.032, 0.073). Mining is a significant determinant of countrywide variation in TB among sub-Saharan African nations. Comprehensive TB control strategies should explicitly address the role of mining activity and environments in the epidemic.

Latent tuberculosis in a newborn: diagnostic challenges

In countries where the incidence of tuberculosis is low, perinatal tuberculosis is seldom diagnosed. With increasing numbers of human immunodeficiency virus-infected people and increasing immigrant population from high tuberculosis incidence countries, one might expect perinatal tuberculosis to become more frequent. Early recognition of newborns at risk for perinatal tuberculosis infection is of utmost importance to prevent disease by chemoprophylaxis. We describe a case of latent perinatal tuberculosis infection in a newborn infected from a mother with extrapulmonary primary tuberculosis. Tuberculin skin test was negative, and latent tuberculosis infection was eventually diagnosed by specific immunological tests. We discuss the difficulties in diagnosis of recent tuberculosis infection in neonates and infants, and the risk factors for vertical transmission of tuberculosis, which need to be taken into account in considering the need for chemoprophylaxis in the newborn. Although perinatal TB infection is a rare condition and diagnosis is difficult due to poor diagnostic testing in pregnancy and newborns, a high index of suspicion is needed to limit the diagnostic delay and to avoid progression to perinatal TB disease.

Survey of tuberculosis incidents in hospital healthcare workers, England and Wales, 2005

Tuberculosis (TB) incidence has increased in England and Wales since 1987, with much of the increase in migrants from high TB incidence countries. The National Health Service increasingly depends on healthcare workers (HCWs) trained abroad, often from areas of high TB incidence. A retrospective survey of TB incidents in hospital-based HCWs was carried out to describe their frequency, distribution and characteristics. Reports of HCWs with TB in hospitals were identified among routine surveillance of TB incidents. Additional data on these and reports of further incidents fitting the study definition were obtained by contacting local and regional Health Protection Units. At least 105 incidents of TB in hospital-based HCWs occurred in England and Wales in 2005. Most involved HCWs from high incidence countries, and most cases had pre-employment occupational health screening. We found no evidence of onward transmission within hospitals. Pre-employment screening for active disease may not be enough to prevent the occurrence of these incidents. A high index of suspicion among HCWs with TB symptoms is needed. Detection of latent infection with interferon gamma release assays, and the use of preventive treatment, should be evaluated.

Tuberculosis in blood and marrow transplant recipients.

Although one third of the world's population is infected with tuberculosis (TB), TB in blood and marrow transplant (BMT) recipients is relatively less well studied, as the incidence of TB is relatively low in developed countries with BMT units. Since the report of the first two cases in 1983, 52 cases of TB complicating BMT have been reported in the English literature from BMT centers in ten different countries. Not unexpectedly, the two largest series were reported from areas with a high incidence of TB in the general population, with about 45 cases per 10(5) inhabitants per year in Spain and about 100 cases per 10(5) inhabitants per year in Hong Kong respectively. The overall frequency of occurrence of TB in BMT recipients was 0.4% (52 cases among 13 881 BMT recipients), with a male:female ratio of 11:9 and median age of 33 (range 7-57). The incidence of TB in the general population is a major predictor of a higher frequency of occurrence in BMT recipients. Moreover, allogeneic transplantation, graft-versus-host disease, and total body irradiation were found to be risk factors associated with TB. Among the 48 cases in whom the time of manifestation were reported, only one case manifested during the neutropenic period (day 11). On the other hand, 11 cases (23%) manifest after engraftment but before day 100, and 36 (75%) manifest after day 100. The most important aspect towards making the diagnosis is a high index of suspicion, as TB occurred in relatively low frequencies especially in developed countries, and the clinical patterns usually mimic other more common infectious and non-infectious complications after BMT. As the incidence of drug resistant TB is increasing, we prefer to treat our patients for at least one year (as compared with six months in immunocompetent hosts) with four drugs in the first six months and two or three drugs for another six months. In those patients who could not tolerate oral medication, we used an intravenous regimen of rifampicin, ciprofloxacin, and amikacin until oral therapy could be instituted. The absence of relapse after termination of treatment in our patients suggested that secondary prophylaxis would not be necessary as long as immune function has been restored. With the rising incidence of TB in countries that previously enjoyed a very low prevalence of TB, attributed to the growing population of HIV-infected subjects with TB, and the changing patterns of population migration, it is important to bear a high index of suspicion of Mycobacterium tuberculosis as a pathogen in BMT recipients.

What use is a clinical case definition for AIDS in Africa?

The article proposes that the clinical case definition for Acquired Immunodeficiency Syndrome in Africa is an unworkable concept, with the wrong definition, incorrect validation, improper use, and consequently is a poor surveillance tool. The definition was proposed by the World Health Organization in 1986 to satisfy the use in countries with limited diagnostic resources, and resources for serological testing. Critical review until now of this procedure was lacking. Currently serological testing is available and of high quality. It does not seem justifiable to continue using a provisional surveillance definition. Abandoning this classification procedure may also lead to the focus on problems other than opportunistic infections and AIDs. Clinical surveillance is important, but as well morbidity and mortality need monitoring. It is argued that the definition is an unworkable concept because patients with underlying immunosuppression disorders such as AIDs can not be easily distinguished from chronic disease patients; i.e., pulmonary tuberculosis, renal failure, uncontrolled diabetes, or diarrhea with weight loss. Clinical accuracy is insufficient. It is the wrong definition because pulmonary tuberculosis with a persistent cough cannot be distinguished for those HIV positive and those not. There is inconsistency in the WHO clinical definition and the Centers for Disease Control definitions of AIDs. The incidence of tuberculosis in countries with unmodified clinical case definitions may contribute to an inflated number of AIDs cases. The wrong standards were used to validate the WHO definition in evaluative studies. The reference sensitivity ranges indicate that the definition is insensitive to identifying seropositive patients. Also, the HIV status of patients does not equate with AIDs. Although designed for surveillance, the clinical case definition is used by doctors for individual patient management. Labeling a patient as having AIDs, when he is HIV negative, leads to negative consequences. Researchers compare African AIDs data with North American data with imprecise and noncomparable definitions. As a surveillance tool in countries with a fragmentary or without a vital registration system, it is an inaccurate tool. Alternatives to obtaining data about the spread and impact of HIV are cluster sampling, hospital surveillance of selected populations, anonymous testing of pregnant women or patients in sexually transmitted disease clinics. In Nairobi, a necropsy survey found that 16% had AIDs but 38% were HIV positive.