Advancing new diagnostic tests for latent tuberculosis infection due to multidrug-resistant strains of Mycobacterium tuberculosis - End of the road?

An estimated 1.8 billion people worldwide have a latent tuberculosis infection (LTBI), with wide variations in LTBI rates across countries. LTBI can be due to infection with either drug-sensitive or drug-resistant Mycobacterium tuberculosis (Mtb) strains. Accurate data on the prevalence of LTBI due to multidrug-resistant (MDR) Mtb strains are unavailable, since the strains cannot be isolated for resistance testing. There are no 'gold standard' tests for accurately diagnosing LTBI. Only three tests are currently available and approved by the World Health Organization (WHO) for the diagnosis of LTBI: the now outdated tuberculin skin test (TST), developed a century year ago, and the two interferon-gamma release assays (IGRAs) developed and rolled out over the past decade, the QuantiFERON (Qiagen, Germany) and T-SPOT.TB (Oxford Immunotec, United Kingdom) tests. These latter tests are not ideal due to issues of sensitivity, specificity, inability to distinguish infection with MDR-Mtb strains, and high costs. Achieving the WHO End TB Strategy target of an 80% reduction in global TB incidence by 2030 will require a major reduction in the number of persons with LTBI progressing to active TB disease. Critical to this will be the development of new diagnostic tests that are better than currently available LTBI tests at predicting who is at risk of progression to active TB disease. The diagnostic product development portfolio for LTBI appears to have reached the end of the road. Every attempt to make optimal use of currently available IGRAs using WHO LTBI guidelines for LTBI testing and treatment must be made to achieve WHO End TB strategy targets

Factors associated with default from treatment among tuberculosis patients in nairobi province, Kenya: A case control study

<p>Abstract</p> <p>Background</p> <p>Successful treatment of tuberculosis (TB) involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi.</p> <p>Methods</p> <p>A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945) defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied.</p> <p>Results</p> <p>Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned treatment within first and second months (intensive phase) of treatment respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7% (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0), alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16-4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1.56; 95% CI 1.25-1.94) and male gender (OR 1.43; 95% CI 1.15-1.78) were independently associated with default.</p> <p>Conclusion</p> <p>The rate of defaulting was highest during initial two months, the intensive phase of treatment. Multiple factors were attributed by defaulting patients as cause for abandoning treatment whereas several were independently associated with default. Enhanced patient pre-treatment counseling and education about TB is recommended.</p

Clinical standards for the assessment, management, and rehabilitation of post-TB lung disease

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic

Cost-Effectiveness Analysis of Diagnostic Options for Pneumocystis Pneumonia (PCP)

Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented.We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90$189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68$109 per life-year gained) compared with several molecular diagnostic options.For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone

Pneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression

Objective: Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings. Design Systematic review and meta-regression. METHODS: Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies). RESULTS: The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10 3/ ml. CONCLUSIONS: There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii , ubiquitous in all settings, then becomes a greater relative threat