Immigration from areas of high incidence is thought to have fueled the resurgence of tuberculosis (TB) in areas of low incidence. To reduce the risk of disease in low-incidence areas, the main countermeasure has been the screening of immigrants on arrival. This measure is based on the assumption of a prompt decline in the incidence of TB in immigrants during their first few years of residence in a country with low overall incidence. We have documented that this assumption is not true for 619 Somali immigrants reported in Denmark as having TB. The annual incidence of TB declined only gradually during the first 7 years of residence, from an initial 2,000 per 100,000 to 700 per 100,000. The decline was described by an exponential function with a half-time of 5.7 (95% confidence interval 4.0 to 9.7) years. This finding seriously challenges the adequacy of the customary practice of screening solely on arrival.

As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.

Infliximab is a humanized antibody against tumor necrosis factor alpha (TNF-alpha) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-alpha in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-alpha in patients with tuberculosis.

Does immigration from a high-prevalence area contribute to an increased risk of tuberculosis in a low-incidence country? The tuberculosis incidence in Somalia is among the highest ever registered. Due to civil war and starvation, nearly half of all Somalis have been forced from their homes, causing significant migration to low-incidence countries. In Denmark, two-thirds of all tuberculosis patients are immigrants, half from Somalia. To determine the magnitude of Mycobacterium tuberculosis transmission between Somalis and Danes, we analyzed DNA fingerprint patterns of isolates collected in Denmark from 1992 to 1999, comprising >97% of all culture-positive patients (n = 3,320). Of these, 763 were Somalian immigrants, 55.2% of whom shared identical DNA fingerprint patterns; 74.9% of these were most likely infected before their arrival in Denmark, 23.3% were most likely infected in Denmark by other Somalis, and 1.8% were most likely infected by Danes. In the same period, only 0.9% of all Danish tuberculosis patients were most likely infected by Somalis. The Somalian immigrants in Denmark could be distributed into 35 different clusters with possible active transmission, of which 18 were retrieved among Somalis in the Netherlands. This indicated the existence of some internationally predominant Somalian strains causing clustering less likely to represent recent transmission. In conclusion, M. tuberculosis transmission among Somalis in Denmark is limited, and transmission between Somalis and Danes is nearly nonexistent. The higher transmission rates between nationalities found in the Netherlands do not apply to the situation in Denmark and not necessarily elsewhere, since many different factors may influence the magnitude of active transmission.

The whole-genome fingerprinting technique, fluorescent amplified-fragment length polymorphism (FAFLP) analysis, was applied to Mycobacterium tuberculosis. Sixty-five clinical isolates were analyzed to determine the value of FAFLP as a stand-alone genotyping technique and to compare it with the well-established IS6110 typing system. The genome sequence of M. tuberculosis strain H37Rv (S. T. Cole et al., Nature 393:537-544, 1998) was used to model computer-generated informative primer combination(s), and the precision and reproducibility of FAFLP were evaluated by comparing the results of in vitro and computer-generated experiments. Multiplex FAFLP was used to increase resolving power in a predictable and systematic fashion. FAFLP analysis was broadly congruent with IS6110 typing for those strains with multiple IS6110 copies. It was also able to resolve an epidemiologically unlinked group of strains with only one copy of IS6110; up to 10% of clinical isolates may fall into this category. For certain epidemiological investigations, it was concluded that a combination of FAFLP and IS6110 typing would give higher resolution than would either alone. FAFLP data were digital, precise, reproducible, and suitable for rapid electronic dissemination, manipulation, interlaboratory comparison, and storage in national or international epidemiological databases. Because FAFLP samples and analyzes base substitution across the genome as a whole, FAFLP could generate new information about the microevolution of the M. tuberculosis complex.

To estimate the risk and prevalence of Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB) incidence, prevalence, and mortality, including disease attributable to human immunodeficiency virus (HIV), for 212 countries in 1997.

The present study is based on notified cases of tuberculosis (TB) in the National tbc. register 1972-1996. A decline in Tb incidence was seen from 1972 and until the mid-1980's. Subsequently the trend has reversed due to an increasing number of TB cases in foreigners. In 1996, 60% of all cases of TB in Denmark were found in foreigners reflecting the rising number of refugees and their families arriving in Denmark from highly endemic areas, mainly Somalia. Among native Danes the TB incidence fell from 14 per 100,000 in 1972 to 4 per 100,000 in the 1980's and stabilized at this very low level. The unchanged incidence in Danes covers a falling incidence in the older and a rising incidence in the younger and middle-aged adult population, mainly in the capital. Approximately half of the cases occur in high-risk groups. The TB-epidemic is close to elimination in the indigenous Danish population, but the disease is maintained at a low level probably due to increased patient and doctor delay and resulting microepidemics primarily in high-risk populations.

Abstract Background To investigate the diagnostic value of the interferon-γ release assay (IGRA) for detecting tuberculosis (TB) infection in patients with Behçet’s disease (BD). Methods We retrospective analyzed the data collected from 173 BD patients hospitalized between 2010 and 2015. Ninety-nine healthy volunteers were enrolled as a control group. IGRA was performed using T-SPOT.TB. The diagnosis of active TB (ATB) was based on clinical, radiological, microbiological, histopathological information and the response to anti-TB therapy. Latent TB (LTB) infection was defined as asymptomatic patients with positive T-SPOT.TB. Results TB infection was documented in 59 BD patients (34.1%). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of T-SPOT.TB for the diagnosis of ATB were 88.9%, 74.8%, 29.1%, 98.3%, 3.53 and 0.15, respectively. The receiver-operating-characteristic curve demonstrated that spot-forming cells (SFCs) of 70/106 PBMC was the optimal cutoff for diagnosing ATB, with an area under the curve of 0.891. Furthermore, the median SFCs in ATB group was significantly higher than those in LTB infection (466/106 PBMC vs. 68/106 PBMC, p = 0.007) or previous TB infection (466/106 PBMC vs. 96/106 PBMC, p = 0.018). A significant discrepancy between T-SPOT.TB and tuberculin skin test was noted (kappa coefficient = 0.391, p = 0.002). Conclusions T-SPOT.TB, an IGRA, may assist in the diagnosis of ATB in BD patients, and the higher SFCs suggest ATB in BD patients.…

Jackson Mukonzo, Eleni Akillu, Vincent Marconi, Raymond F. Schinazi

Gardner Toren K, Spitters C, Pecha M, et al.

AbstractBackgroundIn the United States, tuberculosis (TB) incidence rates are highest among adults 65 years of age and older. We performed this study to evaluate outcomes of older patients undergoing treatment for TB disease, including the frequency of adverse events related to TB treatment.MethodsThis study evaluated adult patients who were diagnosed with pulmonary TB from 2009 to 2014 in King County, Washington. Patient characteristics, manifestation of TB, and treatment outcomes in different age groups were compared. Frequency and type of adverse events that resulted in treatment interruption were evaluated and patients aged ≥65 years were compared to selected younger patients.ResultsThere were 403 patients who met the study criteria, among whom 111 were age ≥ 65. Older patients were significantly less likely to have cavitation on chest radiographs. Patients age ≥65 were less likely to complete TB treatment (76.6% vs. 94.9%, p-value

Verrall A, Schneider M, Alisjahbana B, et al.

AbstractIntroductionA proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed ‘early clearance’.MethodsIndonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post-recruitment. Blood cell populations and ex-vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive.ResultsAmong 1347 case contacts, 317 were early clearers and 116 converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae.ConclusionsEarly clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.

Hong H, Dowdy , Dooley K, et al.

AbstractBackgroundIndividuals treated for drug-resistant tuberculosis (DR-TB) with aminoglycosides (AGs) in resource-limited settings often experience permanent hearing loss, yet there is no practical method to identify those at higher risk. We sought to develop a clinical prediction model of AG-induced hearing loss among patients initiating DR-TB treatment in South Africa.MethodsUsing nested, prospective data from a cohort of 379 South African adults being treated for confirmed DR-TB with AG-based regimens we developed the prediction model using multiple logistic regression. Predictors were collected from clinical, audiological, and laboratory evaluations conducted at the initiation of DR-TB treatment. The outcome of AG-induced hearing loss was identified from audiometric and clinical evaluation by a worsened hearing threshold compared to baseline during the 6-month intensive phase.Results63% of participants (n=238) developed any level of hearing loss. The model predicting hearing loss at frequencies from 250 to 8,000Hz included: weekly AG dose, HIV status with CD4 count, age, serum albumin, BMI, and pre-existing hearing loss. This model demonstrated reasonable discrimination (AUC=0.71) and calibration (χ2[8]=6.10, p=.636). Using a cutoff of 80% predicted probability of hearing loss, the positive predictive value of this model was 83% and negative predictive value was 40%. Model discrimination was similar for ultrahigh-frequency hearing loss (frequencies higher than 9,000Hz; AUC=0.81) but weaker for clinically determined hearing loss (AUC=0.60).ConclusionsThis model may identify patients with DR-TB who are at the highest risk of developing AG-induced ototoxicity and may help prioritize patients for AG-sparing regimens in clinical settings where access is limited.

Abstract Background Drug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco. Methods It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco. Results In our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients’ age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327–14.292]). Conclusion Treatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.…

Vlad Nikolayevskyy, Stefan Niemann, Richard Anthony, Dick van Soolingen, Elisa Tagliani, Csaba Ködmön, Marieke J. van der Werf, Daniela Maria Cirillo

Tuberculosis (TB) remains a serious public health threat worldwide. Theoretically ultimate resolution of whole genome sequencing (WGS) for Mycobacterium tuberculosis complex (MTBC) strain classification makes this technology very attractive for epidemiological investigations.

Devan Jaganath, Eric Wobudeya, Moorine Penninah Sekadde, Betty Nsangi, Heather Haq, Adithya Cattamanchi

by Devan Jaganath, Eric Wobudeya, Moorine Penninah Sekadde, Betty Nsangi, Heather Haq, Adithya Cattamanchi Background Seasonality in tuberculosis (TB) has been described, especially in children. However, few studies have assessed seasonality of TB in the equatorial region, and none in children. Objectives To assess for seasonality of childhood TB cases in Kampala, Uganda, and determine the role of temperature, rainfall patterns, and influenza cases on TB diagnoses. Methods We retrospectively analyzed demographic and clinical data of children (under 15 years) diagnosed with TB at a pediatric TB clinic in Kampala, Uganda from 2010 to 2015. We performed decomposition analysis of the monthly case time series to assess seasonality. We compared monthly mean plots and performed Poisson regression to assess any association between TB diagnoses and temperature, rainfall, and influenza. Results Of the 713 childhood TB cases diagnosed at the clinic, 609 (85%) were clinically diagnosed and 492 (69%) were pulmonary cases. There were minimal monthly variations in TB cases, with a trough in December and peaks in July and October, but there was no significant seasonality. Temperature variations did not show a clear pattern with TB diagnoses. Rainfall alternated with TB diagnoses in the first half of the year, but then overlapped in the second half and was significantly associated with TB diagnoses. Influenza cases were significantly related to TB diagnoses with (β = 0.05, 95% CI 0.01 to 0.09, p = 0.01) or without (β = 0.06, 95% CI 0.01 to 0.1, p = 0.01) rainfall, and had particular overlap with pulmonary TB cases. Conclusions Seasonal variations in childhood TB diagnoses were non-significant. Temperature did not have a clear pattern with TB diagnoses, but rainfall and influenza cases correlated with the primarily clinically diagnosed childhood TB cases.…

Alex J. Goodell, Priya B. Shete, Rick Vreman, Devon McCabe, Travis C. Porco, Pennan M. Barry, Jennifer Flood, Suzanne M. Marks, Andrew Hill, Adithya Cattamanchi, James G. Kahn

by Alex J. Goodell, Priya B. Shete, Rick Vreman, Devon McCabe, Travis C. Porco, Pennan M. Barry, Jennifer Flood, Suzanne M. Marks, Andrew Hill, Adithya Cattamanchi, James G. Kahn Rationale As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (…

Berube, B. J., Russell, D., Castro, L., Choi, S.-r., Narayanasamy, P., Parish, T.

Mycobacterium tuberculosis is the leading cause of morbidity and mortality by infectious disease worldwide. The incredible disease burden combined with the long course of drug treatment and increasing incidence of antimicrobial resistance among M. tuberculosis isolates necessitates a need for both novel drugs and drug targets to treat this deadly pathogen. Recent work has produced several promising clinical candidates targeting components of the electron-transport chain (ETC) of M. tuberculosis, highlighting this pathway's potential as a viable drug target. Menaquinone is an essential component of the M. tuberculosis ETC, as it functions to shuttle electrons through the ETC to produce the electrochemical gradient required for ATP production for the cell. We show inhibitors of MenA, a component of the menaquinone biosynthetic pathway, are highly active against M. tuberculosis. MenA inhibitors are bactericidal against M. tuberculosis under both replicating and non-replicating conditions, with ten-fold higher bactericidal activity against nutrient-starved bacteria compared to replicating cultures. MenA inhibitors have enhanced activity in combination with bedaquiline, clofazimine, and inhibitors of QcrB, a component of the cytochrome bc1 oxidase. Together these data support MenA as a viable target for drug treatment against M. tuberculosis. MenA inhibitors not only kill M. tuberculosis under a variety of physiological states, but also enhanced activity in combination with ETC inhibitors in various stages of the clinical trial pipeline.…

Loiseau, C., Brites, D., Moser, I., Coll, F., Pourcel, C., Robbe-Austerman, S., Escuyer, V., Musser, K. A., Peacock, S. J., Feuerriegel, S., Kohl, T. A., Niemann, S., Gagneux, S., Köser, C. U.

Using 894 phylogenetically diverse genomes of the Mycobacterium tuberculosis complex (MTBC), we simulated in silico the ability of the Hain Lifescience GenoType MTBC to differentiate the causative agents of tuberculosis. We propose a revised interpretation of this assay to reflect its strengths (e.g. it can distinguish some strains of M. canettii and variants of M. bovis that are not intrinsically resistant to pyrazinamide) and limitations (e.g. M. orygis cannot be differentiated from M. africanum).…

Ranjan, R., Srivastava, A., Bharti, R., Roy, T., Verma, S., Ray, L., Misra, A.

We compared pharmacokinetics and efficacy of a combination of D-cycloserine (DCS) and ethionamide (ETO) via oral and inhalation routes in mice. The plasma t1/2 of oral ETO at human-equivalent dose reduced from 4.63±0.61 h. to 1.64±0.40 h when DCS was co-administered. AUC(0-t) reduced to one-third. Inhalation overcame the interaction. Inhalation, but not oral doses reduced lung CFU/g of Mycobacterium tuberculosis H37Rv from 6 to 3 log10 in four weeks, indicating bactericidal activity.…

Hoft, S. G., Sallin, M. A., Kauffman, K. D., Sakai, S., Ganusov, V. V., Barber, D. L.

The specific chemokine receptors utilized by Th1 cells to migrate into the lung during Mycobacterium tuberculosis infection is unknown. We previously showed in mice that CXCR3+ Th1 cells enter the lung parenchyma and suppress Mtb growth, while CX3CR1+KLRG1+ Th1 cells accumulate in lung vasculature and are non-protective. Here we quantify the contributions of these chemokine receptors to the migration and entry rate of Th1 cells into Mtb-infected lungs using competitive adoptive transfer migration assays and mathematical modeling. We find that in 8.6 hours half of Mtb-specific CD4 T cells migrate from the blood to the lung parenchyma. CXCR3 deficiency decreases the average rate of Th1 cell entry into the lung parenchyma by half, while CX3CR1 deficiency doubles it. KLRG1 blockade has no effect on Th1 cell lung migration. CCR2 and CXCR5, and to a lesser degree CCR5 and CXCR6, also promote entry of Th1 cells into the lungs of infected mice. Moreover, blockade of G protein coupled receptors with pertussis toxin treatment prior to transfer only partially inhibited T cell migration into the lungs. Thus, the fraction of Th1 cell input into the lungs during Mtb infection that is regulated by chemokine receptors likely reflects the cumulative effects of multiple chemokine receptors that mostly promote but can also inhibit entry into the parenchyma.…

Ugarte-Gil C, Alisjahbana B, Ronacher K, et al.

AbstractBackgroundDiabetes mellitus (DM) increases the risk of active tuberculosis (TB) and worsens TB outcomes, putting TB control in jeopardy especially in TB endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania and South Africa.MethodsAge-adjusted DM prevalence was estimated using laboratory glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) in TB patients. Detailed and standardized socio-demographic, anthropometric and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multi-level mixed effect regression models with robust standard errors.ResultsOf 2185 TB patients (median 36.6 years, 61.2% male, 3.8% HIV-infected), 12.5% (267/2128) had DM, 1/3 of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB-DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB-DM patients were older with higher Body Mass Index (BMI) (p-value

Abstract Background Tuberculosis (TB) is a major public health problem and it is among the top 10 causes of death worldwide. One of the challenges against attaining an effective TB control program is delay in seeking health care to diagnosis and treatment of TB patients. The aim of this study was to assess health care-seeking delay among pulmonary TB patients. Methods An institutional based cross-sectional study was conducted among new pulmonary tuberculosis (PTB) patients > 15 years of age who were enrolled in the intensive phase TB treatment from November 1, 2015 – January 30, 2016. Data were collected by an interviewer administered technique using a structured questionnaire. Health care seeking delay was categorized by using a median cutoff point of > 30 days as a prolonged health care seeking delay. Logistic regression analyses were employed to determine factors independently associated with the delays in health care seeking. Results A total of 422 PTB patients were included in this study. The median age of respondents was 37 years (interquartile range (IQR) =35–44). The median time of health care seeking delay was 30 days (IQR) = 21-60). Respondents occupation, knowledge about pulmonary tuberculosis, health facility visited first, seeking treatment from traditional or religious healers before visiting health facilities, reason for not seeking treatment early from health facilities, and reason for first consultation were found to be significantly associated with health care seeking delay. Conclusion The study showed the magnitude of health care seeking delay among pulmonary tuberculosis patient was very long and the factors associated with health care seeking delay were: occupation, knowledge status, health facility visited first and seeking treatment from religious or traditional healer before health facilities. To overcome delay of health care seeking among tuberculosis patients, efforts should required availing tuberculosis diagnostic and treatment services at the primary health care level.…

Sophie Henrard, Véronique Corbière, Liliane Schandené, Martine Ducarme, Anne Van Praet, Emmanuelle Petit, Mahavir Singh, Camille Locht, Violette Dirix, Françoise Mascart

by Sophie Henrard, Véronique Corbière, Liliane Schandené, Martine Ducarme, Anne Van Praet, Emmanuelle Petit, Mahavir Singh, Camille Locht, Violette Dirix, Françoise Mascart Background Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed. Methods and findings We investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%. Conclusions The analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.…

Abstract Background Rapid detection of rifampicin resistance is essential for early management and prevention of transmission of multidrug-resistant tuberculosis (MDR-TB). We studied the prevalence of rifampicin resistance of Mycobacterium tuberculosis (MTB) among presumptive TB patients in Addis Ababa, Ethiopia. Methods A retrospective cross sectional study was conducted in three referral hospitals and the regional laboratory in Addis Ababa city from March 2015 to October 2017. Data was collected by data-extraction sheet from registration books. It was analyzed using SPSS version 20. Statistically significant association was taken with P 

Giovanni Battista Migliori, The members of the International Study Group on new anti-tuberculosis drugs and adverse events monitoring

Tsang C, Shah N, Armstrong L, et al.

AbstractBackgroundIn 2016, the World Health Organization (WHO) recommended a shorter (9–12 month) multidrug-resistant tuberculosis (MDR-TB) treatment regimen (as compared to the conventional 18–24 month regimen) for patients without extrapulmonary TB, pregnancy, previous second-line TB medication exposure, or drug resistance to pyrazinamide, ethambutol, kanamycin, moxifloxacin, ethionamide, or clofazimine. The recommendation was based on successful clinical trials conducted in Asia and Africa, but studies, using mainly European data, have shown few patients in higher resource settings would meet WHO eligibility criteria.MethodsWe assessed eligibility for the shorter regimen among U.S. MDR-TB cases that had full drug susceptibility testing (DST) results and were reported during 2011–2016 to the U.S. National TB Surveillance System. We estimated costs by applying the eligibility criteria for the shorter regimen, and proportional inpatient/outpatient costs from a previous population-based study to all MDR-TB patients reported to NTSS.ResultsOf 586 reported MDR cases, 10% (59) were eligible for the shorter regimen. Of 527 ineligible patients, 386 had full DST, of which 246 were resistant to ethambutol and 217 resistant to pyrazinamide. Compared with conventional MDR-TB treatment, implementing the shorter regimen would reduce the U.S. annual societal MDR-TB cost burden by 4%, but the cost burden for eligible individuals would be reduced by 37–46%.ConclusionsRelying on full DST use, our analysis found a minority of U.S. MDR-TB patients would be eligible for the shorter regimen. Cost reductions would be minimal for society, but large for eligible individuals.

Jennifer L. Guthrie, Alex Marchand-Austin, Kirby Cronin, Karen Lam, Daria Pyskir, Clare Kong, Danielle Jorgensen, Mabel Rodrigues, David Roth, Patrick Tang, Victoria J. Cook, James Johnston, Frances B. Jamieson, Jennifer L. Gardy

by Jennifer L. Guthrie, Alex Marchand-Austin, Kirby Cronin, Karen Lam, Daria Pyskir, Clare Kong, Danielle Jorgensen, Mabel Rodrigues, David Roth, Patrick Tang, Victoria J. Cook, James Johnston, Frances B. Jamieson, Jennifer L. Gardy Objectives Compare the molecular epidemiology of tuberculosis (TB) between two large Canadian provinces–Ontario and British Columbia (BC)–to identify genotypic clusters within and across both provinces, allowing for an improved understanding of genotype data and providing context to more accurately identify clusters representing local transmission. Design We compared 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping for 3,314 Ontario and 1,602 BC clinical Mycobacterium tuberculosis isolates collected from 2008 through 2014. Laboratory data for each isolate was linked to case-level records to obtain clinical and demographic data. Results The demographic characteristics of persons with TB varied between provinces, most notably in the proportion of persons born outside Canada, which was reflected in the large number of unique genotypes (n = 3,461). The proportion of clustered isolates was significantly higher in BC. Substantial clustering amongst non-Lineage 4 TB strains was observed within and across the provinces. Only two large clusters (≥10 cases/cluster) representing within province transmission had interprovincial genotype matches. Conclusion We recommend expanding analysis of shared genotypes to include neighbouring jurisdictions, and implementing whole genome sequencing to improve identification of TB transmission, recognize outbreaks, and monitor changing trends in TB epidemiology.…