Latent tuberculosis infection and non-infectious co-morbidities: Diabetes mellitus type 2, chronic kidney disease and rheumatoid arthritis.

The prevalence of non-communicable diseases is increasing worldwide, which coincides with the persistence of infectious diseases including tuberculosis. These can synergistically affect individual and population health. Three non-communicable diseases that are relevant because of their associated morbidity, mortality and disability are type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis. There is some evidence that patients with these conditions are at increased risk of acquiring latent tuberculosis infection (LTBI) and of this progressing to active disease. Unfortunately, evidence on accurate testing and effective prophylactic treatment in these populations is lacking. This review discusses current evidence and recommendations for management of LTBI in these patients

Is there an association between cutaneous leishmaniasis and skin cancer? A systematic review

Background: Cutaneous leishmaniasis is a prevalent communicable disease in low- and middle-income countries, where non-communicable diseases like skin cancer are on the rise. However, the study of multi-morbidity or co-morbidity between communicable and non-communicable diseases is limited, and even null for some tropical or neglected diseases. Nevertheless, looking at these conditions together instead of as isolated entities in places where these illnesses exist, could show new prevention and treatment paths. We aimed to summarize and critically appraise the epidemiological evidence on the association between cutaneous leishmaniasis and skin cancer. Methods: Following the PRISMA guidelines, we conducted a systematic review using five search engines (Embase, Medline, Global Health, Scopus and Web of Science). We sought observational studies in which the outcome was skin cancer whilst the exposure was cutaneous leishmaniasis; these conditions should have had laboratory or pathology confirmation. Results: No epidemiological investigations have studied the association between cutaneous leishmaniasis and skin cancer. Most of the evidence about the association of interest is still based on case reports and other clinical observations rather than strong epidemiological observational studies. Conclusions: Research is much needed to verify the repeatedly clinical observation that cutaneous leishmaniasis may be a risk factor for skin cancer. This evidence could inform and guide early diagnosis or prevention of skin cancer in survivors of cutaneous leishmaniasis or where cutaneous leishmaniasis is still highly prevalent. Registration: PROSPERO ID CRD42018111230; registered on 16/10/18

Microscopic Observation Drug Susceptibility Assay for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance.

In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic algorithms for extrapulmonary TB

Type 2 diabetes mellitus and antibiotic-resistant infections: A Systematic Review and meta-analysis

Background: Type 2 diabetes mellitus (T2DM) has been associated with infectious diseases; however, whether T2DM is associated with bacterial-resistant infections has not been thoroughly studied. We ascertained whether people with T2DM were more likely to experience resistant infections in comparison to T2DM-free individuals. Methods: Systematic review and random-effects meta-analysis. The search was conducted in Medline, Embase, and Global Health. We selected observational studies in which the outcome was resistant infections (any site), and the exposure was T2DM. We studied adult subjects who could have been selected from population-or hospital-based studies. I-squared was the metric of heterogeneity. We used the Newcastle-Ottawa risk of bias scale. Results: The search retrieved 3,370 reports, 97 were studied in detail and 61 (449,247 subjects) were selected. Studies were mostly cross-sectional or case-control; several infection sites were studied, but mostly urinary tract and respiratory infections. The random-effects meta-analysis revealed that people with T2DM were two-fold more likely to have urinary tract (OR= 2.42; 95% CI: 1.83-3.20; I-squared 19.1%) or respiratory (OR= 2.35; 95% CI: 1.49-3.69; I-squared 58.1%) resistant infections. Although evidence for other infection sites was heterogeneous, they consistently suggested that T2DM was 66associated with resistant infections. Conclusions: Compelling evidence suggests that people with T2DM are more likely to experience antibiotic-resistant urinary tract and respiratory infections. The evidence for other infection sites was less conclusive but pointed to the same overall conclusion. These results could guide empirical treatment for patients with T2DM and infections

Accuracy of diabetes screening methods used for people with tuberculosis, Indonesia, Peru, Romania, South Africa

Objective To evaluate the performance of diagnostic tools for diabetes mellitus, including laboratory methods and clinical risk scores, in newly-diagnosed pulmonary tuberculosis patients from four middle-income countries. Methods In a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen initial random plasma glucose was ≥ 6.1 mmol/L. Findings The overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6–14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75–0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81–0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru. Conclusion Random plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemia, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation

Impact of Reversion of Mycobacterium tuberculosis Immunoreactivity Tests on the Estimated Annual Risk of Infection

A key metric in tuberculosis epidemiology is the annual risk of infection (ARI), which is usually derived from tuberculin skin test (TST) and interferon-gamma release assay (IGRA) prevalence surveys in children. Deriving the ARI assumes that immunoreactivity is persistent over time; however, reversion of immunoreactivity has long been documented. Here we use a deterministic, compartmental model of Mycobacterium tuberculosis (Mtb) infection to explore the impact of reversion on ARI estimation using age-specific reversion probabilities for TST and IGRA. Using empirical data of TST reversion (22.2%/year for 0-19yo), the true ARI is 2-5 times higher than estimated from immunoreactivity studies in 8-12 year-olds. Applying empirical reversion probabilities for IGRA (9.9%/year for 12-18yo) showed a 1.5-2-fold underestimation. ARIs are increasingly underestimated in older populations, due to the cumulative impact of reversion on population reactivity over time. Declines in annual risk did not largely affect the results. Ignoring reversion leads to a stark underestimation of the true ARI in populations and our interpretation of Mtb transmission intensity. Future surveys should adjust for reversion probabilities and its cumulative effect with increasing age to provide a more accurate reflection of the burden and dynamics of Mtb infection

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

Diabetes is associated with genotypically drug-resistant tuberculosis.

Diabetes is associated with failure of tuberculosis (TB) treatment, but it is unclear whether this is related to genotypic drug resistance of the infecting mycobacteria. We used whole genome sequencing (WGS) to examine 1365 known drug resistance mutations in 896 Mycobacterium tuberculosis isolates from TB patients that were screened for diabetes using HbA1c testing as part of the TANDEM project [1]. Ethical approval was received from the London School of Hygiene and Tropical Medicine and institutional review boards in Indonesia and Peru. In Peru we selected all available M. tuberculosis isolates from TANDEM patients (44 with and 445 without diabetes), and in Indonesia we selected all available isolates from diabetic patients (n=115) plus a subset of isolates from non-diabetic patients (n=292) from the same clinics, during the same time period, frequency-matched by age. We used TB Profiler version 0.3.8 [2] to determine M. tuberculosis lineage and drug resistance. A phylogeny was constructed using PhyML version 3.0 [3], and the minimum pairwise distance for isolates was calculated separately for patients with and without diabetes, stratified by country. We examined if diabetes was associated with genotypic drug resistance against individual drugs or with MDR-TB for the two countries separately and combined, with multilevel multivariable logistic regression, taking into account the country of origin and adjusting for age, gender, HIV-infection, previous TB treatment, and M. tuberculosis lineag

Simplifying Consent for HIV Testing Is Associated with an Increase in HIV Testing and Case Detection in Highest Risk Groups, San Francisco January 2003–June 2007

Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis.Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH) medical care system were included in the analysis. The monthly HIV testing rate per 1000 had patient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language.By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17-6.60, p<0.001) over the number predicted if the policy change had not occurred (representing a 44% increase). The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3-11.5) to 14.9 (CI, 10.6-19.2, p<0.001), representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change.The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change

Modeling the Impact of Tuberculosis Control Strategies in Highly Endemic Overcrowded Prisons

International audienceBACKGROUND: Tuberculosis (TB) in prisons is a major health problem in countries of high and intermediate TB endemicity such as Brazil. For operational reasons, TB control strategies in prisons cannot be compared through population based intervention studies. METHODOLOGY/PRINCIPAL FINDINGS: A mathematical model is proposed to simulate the TB dynamics in prison and evaluate the potential impact on active TB prevalence of several intervention strategies. The TB dynamics with the ongoing program was simulated over a 10 year period in a Rio de Janeiro prison (TB prevalence 4.6 %). Then, a simulation of the DOTS strategy reaching the objective of 70 % of bacteriologically-positive cases detected and 85 % of detected cases cured was performed; this strategy reduced only to 2.8% the average predicted TB prevalence after 5 years. Adding TB detection at entry point to DOTS strategy had no major effect on the predicted active TB prevalence. But, adding further a yearly X-ray mass screening of inmates reduced the predicted active TB prevalence below 1%. Furthermore, according to this model, after applying this strategy during 2 years (three annual screenings), the TB burden would be reduced and the active TB prevalence could be kept at a low level by associating X-ray screening at entry point and DOTS. CONCLUSIONS/SIGNIFICANCE: We have shown that X-ray mass screenings should be considered to control TB in highly endemic prison. Prisons with different levels of TB prevalence could be examined thanks to this model which provides a rational tool for public health deciders