Outcomes after Chemotherapy with WHO Category II Regimen in a Population with High Prevalence of Drug Resistant Tuberculosis

Standard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB). A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74%) became culture negative, while 43 (18%) remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance

Management of latent Mycobacterium tuberculosis infection:WHO guidelines for low tuberculosis burden countries

ABSTRACT Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing an

Prevalence, risk factors and social context of active pulmonary tuberculosis among prison inmates in Tajikistan.

SETTING: Tuberculosis (TB) is highly prevalent in prisons of the former Soviet Union. OBJECTIVE: To understand the behavioral, demographic and biological factors placing inmates in Tajikistan at risk for active TB. DESIGN: We administered a behavioral and demographic survey to 1317 inmates in two prison facilities in Sughd province, Tajikistan along with radiographic screening for pulmonary TB. Suspected cases were confirmed bacteriologically. Inmates undergoing TB treatment were also surveyed. In-depth interviews were conducted with former prisoners to elicit relevant social and behavioral characteristics. RESULTS: We identified 59 cases of active pulmonary TB (prevalence 4.5%). Factors independently associated with increased prevalence of active TB were: HIV-infection by self-report (PR 7.88; 95%CI 3.40-18.28), history of previous TB (PR 10.21; 95%CI 6.27-16.63) and infrequent supplemental nutrition beyond scheduled meals (PR 3.00; 95%CI 1.67-5.62). Access to supplemental nutrition was associated with frequency of visits from friends and family and ability to rely on other inmates for help. CONCLUSION: In prison facilities of Tajikistan, HIV-infection, injection drug use and low access to supplemental nutrition were associated with prevalent cases of active pulmonary TB. Policies that reduce HIV transmission among injection drug users and improve the nutritional status of socially isolated inmates may alleviate the TB burden in Tajikistan's prisons

Demographic characteristics of inmates and risk factors for active pulmonary TB.

<p>Demographic characteristics of inmates and risk factors for active TB in univariate and multivariate analysis. Prevalence ratios (PR) and 95% confidence intervals (95%CI) were weighted using random effects modeling. Adjusted prevalence ratios (aPR) and their respective 95% confidence intervals (95%CI) were derived from multivariate regression analysis. * p<0.05.</p

Prevalence of HIV (registered cases per 100,000 population) and WHO notification rates for TB (cases per 100,000 person-years) in the republic of Tajikistan from 1998–2008 [1][41].

<p>Prevalence of HIV (registered cases per 100,000 population) and WHO notification rates for TB (cases per 100,000 person-years) in the republic of Tajikistan from 1998–2008 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086046#pone.0086046-World1" target="_blank">[1]</a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086046#pone.0086046-Republican1" target="_blank">[41]</a>.</p

Social characteristics of inmates surveyed and prevalence of risk behaviors among respondents.

<p>IQR = interquartile range.</p

Social context and nutrition.

<p>Frequency of supplemental nutrition is correlated with both A) number of visits from friends and family, and B) number of other inmates respondents felt they could rely on for help if necessary, representing social networks outside of and within the prison facilities.</p

Clinical and microbiological characteristics of prevalent TB cases.

<p>Radiographic findings were defined as any features determined to be suspicious for TB after reading of MMR films by two independent radiologists. In this table, presence of symptoms refers to report by respondents of having any of the following symptoms at the time of the survey: “cough,” “sputum with or without blood,” “weight loss in the last three months,” “loss of appetite,” “chest pain,” “night sweats,” “generalized weakness or fatigue,” “shortness of breath.”</p

Screening and Rapid Molecular Diagnosis of Tuberculosis in Prisons in Russia and Eastern Europe: A Cost-Effectiveness Analysis

<div><h3>Background</h3><p>Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission.</p> <h3>Methods and Findings</h3><p>We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics.</p> <h3>Conclusions</h3><p>In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time.</p> <p> <em>Please see later in the article for the Editors' Summary</em></p> </div

Socio-demographic and clinical characteristics of patients at enrolment.

<p>* Body mass index is calculated as the weight in kilograms divided by the square of the height in meters.</p><p>° Delay: time in days between admission to Colony 33 and the start of treatment.</p><p>§ t-test; # Chi square test.</p