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.

Valerie ACM. Koeken, Ayesha J. Verrall, Mihai G. Netea, Philip C. Hill, Reinout van Crevel

Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This ‘early clearance’ of Mycobacterium tuberculosis is associated with a history of bacillus Calmette-Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed ‘trained immunity’, we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis.

Barbara Reis-Santos, Priya Shete, Adelmo Bertolde, Carolina M. Sales, Mauro N. Sanchez, Denise Arakaki-Sanchez, Kleydson B. Andrade, M. Gabriela M. Gomes, Delia Boccia, Christian Lienhardt, Ethel L. Maciel

by Barbara Reis-Santos, Priya Shete, Adelmo Bertolde, Carolina M. Sales, Mauro N. Sanchez, Denise Arakaki-Sanchez, Kleydson B. Andrade, M. Gabriela M. Gomes, Delia Boccia, Christian Lienhardt, Ethel L. Maciel Introduction Tuberculosis incidence is disproportionately high among people in poverty. Cash transfer programs have become an important strategy in Brazil fight inequalities as part of comprehensive poverty alleviation policies. This study was aimed at assessing the effect of being a beneficiary of a governmental cash transfer program on tuberculosis (TB) treatment cure rates. Methods We conducted a longitudinal database study including people ≥18 years old with confirmed incident TB in Brazil in 2015. We treated missing data with multiple imputation. Poisson regression models with robust variance were carried out to assess the effect of TB determinants on cure rates. The average effect of being beneficiary of cash transfer was estimated by propensity-score matching. Results In 2015, 25,084 women and men diagnosed as new tuberculosis case, of whom 1,714 (6.8%) were beneficiaries of a national cash transfer. Among the total population with pulmonary tuberculosis several determinants were associated with cure rates. However, among the cash transfer group, this association was vanished in males, blacks, region of residence, and people not deprived of their freedom and who smoke tobacco. The average treatment effect of cash transfers on TB cure rates, based on propensity score matching, found that being beneficiary of cash transfer improved TB cure rates by 8% [Coefficient 0.08 (95% confidence interval 0.06–0.11) in subjects with pulmonary TB]. Conclusion Our study suggests that, in Brazil, the effect of cash transfer on the outcome of TB treatment may be achieved by the indirect effect of other determinants. Also, these results suggest the direct effect of being beneficiary of cash transfer on improving TB cure rates.…

Basra Esmail Doulla, Stephen Bertel Squire, Eleanor MacPherson, Esther Stanslaus Ngadaya, Beatrice Kemilembe Mutayoba, Ivor Langley

by Basra Esmail Doulla, Stephen Bertel Squire, Eleanor MacPherson, Esther Stanslaus Ngadaya, Beatrice Kemilembe Mutayoba, Ivor Langley Background Routine surveillance is required to monitor the performance of tuberculosis diagnostic programme and is essential for the rapid detection of drug resistance. The main objective of this study was to explore the effectiveness and stakeholder perception of the current routine surveillance system for previously treated tuberculosis cases in Tanzania with a view to identify interventions to improve and accelerate positive patient outcomes. Methods A study using quantitative and qualitative methods of data collection including in-depth interviews and focus group discussions with health care service providers was conducted in four regions. Quantitative data were extracted from the routine databases to assess performance. Results Quantitative findings from 2011 to 2013 showed 2,750 specimens from previously treated TB cases were received at the reference laboratory. The number increased year on year, but even in the most recent year was only 61% of that expected. The median and interquartile range of turnaround time in days from specimen reception to results reported for smear microscopy, culture and drug susceptibility testing were 1(1, 1), 61(43, 71) and 129(72, 170) respectively. Contaminated specimens were reported in 3.6% of cases. The qualitative analysis showed the system of sending specimens using postal services was seen to be efficient by participants. However, there were many challenges and significant delays in specimens reaching the reference laboratory associated with lack of funds to transfer specimens, weak form completion, inadequate training and poor supervision. These all adversely affected the implementation of the routine surveillance system. Conclusions Many issues limit the effectiveness of the routine surveillance system in Tanzania. Priority areas for strengthening are; specimen transportation, supervision and availability of commodities. A pilot study of a revised routine surveillance system that takes into account the observations from this study alongside improved access to drug susceptibility testing using Xpert MTB/RIF should be considered.…

Eskild Petersen, Martin Rao, Giuseppe Ippolito, Gina Gualano, Jeremiah Chakaya, David A.J. Moore, Katherine Gaskell, Joanna Nederby Öhd, Maria-Pia Hergens, Sriram Krishnamoorthy, Cesar Ugarte-Gil, Daniela E. Kirwan, Isobella Honeyborne, Timothy D. McHugh, Claudio U. Köser, Katharina Kranzer, Simon Tiberi, Giovanni Battista Migliori, Qiang Mao, Yahong Yang, Simoni Pimenta de Oliveira, Rosilene Fressatti Cardoso, Anne Detjen, Ben Marais, David de Gijsel, C. Fordham von Reyn, Lara Goscé, Ibrahim Abubakar, Mark

Tuberculosis today remains the world’s number one cause of death from an infectious disease (WHO, 2018a). According to data from the World Health Organization Global Tuberculosis Report (WHO Report, 2018a), global efforts to control tuberculosis are not on target to achieve the goals of the WHO Strategy to end the global tuberculosis epidemic by 2030 (WHO, 2015). In 2017, an estimated 10 million people (5·8 million men, 3·2 million women, and 1 million children) developed tuberculosis and 4 million people with tuberculosis remained undiagnosed and untreated.

Cesar Ugarte-Gil, Rodrigo M. Carrillo-Larco, Daniela E. Kirwan

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.

Mario Alberto Flores-Valdez

Here, I describe the most recent findings of what host immune factors seem to be involved in successfully controlling M. tuberculosis infection in humans, leading to Latent TB Infection (LTBI) and how such potential biomarkers could be incorporated in preclinical and clinical trials of new vaccine candidates, especially those aimed against LTBI.I consider that there is not that much information as to produce a review, but that considering the clinical trials of over a dozen new vaccine candidates against TB, it could be a timely piece of work for the community evaluating these candidates or developing new ones.

Hezekiah K. Adesokan, Elizabeth M. Streicher, Paul D. van Helden, Rob M. Warren, Simeon I. B. Cadmus

by Hezekiah K. Adesokan, Elizabeth M. Streicher, Paul D. van Helden, Rob M. Warren, Simeon I. B. Cadmus Molecular typing techniques are useful in understanding tuberculosis epidemiology; yet, they have been under-utilised at the human-animal interface in Nigeria. Sixty-four Mycobacterium tuberculosis complex (MTBC) isolates including 42 M. tuberculosis, 13 M. bovis and nine M. africanum obtained from livestock workers (LW, n = 47) and their cattle (n = 17) in three geographical zones of Nigeria were genotyped to identify and evaluate the genetic diversity of the circulating MTBC using spoligotyping. Distribution into clades of M. tuberculosis revealed; 45.3% Uganda I- [SIT46- cattle: 1; LW: 28], 14.1% Latin American Mediterranean- [SIT61, cattle: 1; LW: 8], and 1.6% T- [SIT53—LW: 1]. The M. bovis strains were 6.3% SB0944 [cattle: 4] and 1.6% each of SB0300, SB1026, SB1027 and SB1439 [cattle: 4]. Seventeen MTBC isolates [cattle: 7; LW: 10] yielded 14 new spoligotype patterns including three M. tuberculosis strains (three isolates), five M. bovis strains (five isolates) and six M. africanum strains (nine isolates), two of which belonged to MAF1. Only few families namely, the not previously described Uganda I-, LAM and SB0944 are predominant among the LW and cattle, with other types in lower prevalences. The strain population structure indicates an intriguing diversity and possible zoonotic linkage with consequences for TB control in the country. The need to employ newer molecular techniques such as Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats and whole genome sequence to decipher circulating MTBC strains in Nigeria is advocated.

Abstract Background In spite of an alarmingly high tuberculosis (TB) burden amongst the Saharia tribe of central India, there is hardly any study to investigate the impact of DOTS implementation on the magnitude of tuberculosis disease and the changes over time. This article present the findings of TB prevalence surveys conducted amongst this indigenous population in two different time periods to know the change in the prevalence of TB. Methods A cross sectional survey was conducted among Saharia population in Shivpuri district, Madhya Pradesh during February 2013 to May 2013 and resurvey during March 2015 to July 2015. All individuals (≥15 years) were examined for chest symptoms suggestive of TB. Sputum samples were collected from all presumptive TB cases and were confirmed by laboratory examination by Ziehl-Neelsen smear microscopy and solid media culture methods. All detected cases were referred to health facility for anti-tuberculosis treatment as per RNTCP guidelines. Results There was significant reduction (trend Chi square 19.97; OR = 1.521; p = 0.000) in the prevalence of TB at the endline (1995 per 100,000) as compared to baseline (3003 per 100,000). The reduction was significant among males as compared to females (OR 1.55; p = 0.000) and in the age group of 25–34 years (OR 2.0; p = 0.007) and 45–54 years (OR 4.39; p = 0.003). There was significant reduction in the prevalence in both smear (OR 1.29; p = 0.02) and culture positive (OR 1.57; p = 0.000) TB at the endline survey. Conclusion The study findings highlight a reduction in the prevalence of TB among Saharia tribal population. Further studies are needed to identify the factors associated with reduction in prevalence among this population and also further surveys to monitor the prevalence trend over a period.…

Xu, J., Wang, B., Fu, L., Zhu, H., Guo, S., Huang, H., Yin, D., Zhang, Y., Lu, Y.

The riminophenazine agent clofazimine (CFZ) is repurposed as an important component of the new short-course multidrug-resistant tuberculosis regimen and significantly shortens first-line regimen for drug-susceptible tuberculosis in mice. However, CFZ use is hampered by its unwelcome skin discoloration in patients. A new riminophenazine analog TBI-166 was selected as a potential next-generation antituberculosis riminophenazine following an extensive medicinal chemistry effort. Here, we evaluated the activity of TBI-166 against Mycobacterium tuberculosis and its potential to accumulate and discolor skin. In vitro activity of TBI-166 against both drug-sensitive and drug-resistant M. tuberculosis is more potent than that of CFZ. Spontaneous mutants resistant to TBI-166 were found at a frequency of 2.3x10-7 in wild strains of M. tuberculosis. TBI-166 demonstrates at least equivalent activity compared to CFZ against intracellular M. tuberculosis and in low-dose aerosol infection models of acute and chronic murine tuberculosis. Most importantly, TBI-166 causes less skin discoloration than CFZ despite its higher tissue accumulation. The efficacy of TBI-166, along with its decreased skin pigmentation, warrants further study and potential clinical use.…

Milyausha Yunusbaeva, Liliya Borodina, Pavel Alekseev, Rostislav Davydov, Ural Yunusbaev, Raul Sharipov, Fanil Bilalov, Bayazit Yunusbayev

Baharak Afshar, Jacqueline Carless, Anita Roche, Sooria Balasegaram, Charlotte Anderson

by Baharak Afshar, Jacqueline Carless, Anita Roche, Sooria Balasegaram, Charlotte Anderson Recurrence of TB in an individual can occur due to relapse of the same strain or reinfection by a different strain. The contribution of reinfection and relapse to TB incidence, and the factors associated with each are unknown. We aimed to quantify and describe cases attributable to relapse or reinfection, and identify associated risk factors in order to reduce recurrence. We categorised recurrent TB cases from notifications in London (2002–2015) as relapse or reinfection using molecular (MIRU VNTR strain type) and epidemiological information (hierarchical approach using time since notification, site of disease and method of case finding). Factors associated with each outcome were determined using logistic regression in Stata Version 13.1 (2009–2015 only). Of 43,465 TB cases, 1.4% (618) were classified as relapse and 3.8% (1,637) as reinfection. The proportion with relapse decreased from 2002 (2.3%) to 2015 (1.3%), while the proportion of reinfection remained around 4%. Relapse was more common among recent migrants (11 years, OR = 1.67, p =…

Collins Timire, Charles Sandy, Ajay MV Kumar, Mkhokheli Ngwenya, Barbara Murwira, Kudakwashe C Takarinda, Anthony D Harries

S. C. Ring, D. C. Purfield, M. Good, P. Breslin, E. Ryan, A. Blom, R. D. Evans, M. L. Doherty, D. G. Bradley, D. P. Berry

by S. C. Ring, D. C. Purfield, M. Good, P. Breslin, E. Ryan, A. Blom, R. D. Evans, M. L. Doherty, D. G. Bradley, D. P. Berry Bovine tuberculosis (bTB) is an infectious disease of cattle generally caused by Mycobacterium bovis, a bacterium that can elicit disease humans. Since the 1950s, the objective of the national bTB eradication program in Republic of Ireland was the biological extinction of bTB; that purpose has yet to be achieved. Objectives of the present study were to develop the statistical methodology and variance components to undertake routine genetic evaluations for resistance to bTB; also of interest was the detection of regions of the bovine genome putatively associated with bTB infection in dairy and beef breeds. The novelty of the present study, in terms of research on bTB infection, was the use of beef breeds in the genome-wide association and the utilization of imputed whole genome sequence data. Phenotypic bTB data on 781,270 animals together with imputed whole genome sequence data on 7,346 of these animals’ sires were available. Linear mixed models were used to quantify variance components for bTB and EBVs were validated. Within-breed and multi-breed genome-wide associations were undertaken using a single-SNP regression approach. The estimated genetic standard deviation (0.09), heritability (0.12), and repeatability (0.30) substantiate that genetic selection help to eradicate bTB. The multi-breed genome-wide association analysis identified 38 SNPs and 64 QTL regions associated with bTB infection; two QTL regions (both on BTA23) identified in the multi-breed analysis overlapped with the within-breed analyses of Charolais, Limousin, and Holstein-Friesian. Results from the association analysis, coupled with previous studies, suggest bTB is controlled by an infinitely large number of loci, each having a small effect. The methodology and results from the present study will be used to develop national genetic evaluations for bTB in the Republic of Ireland. In addition, results can also be used to help uncover the biological architecture underlying resistance to bTB infection in cattle.

Bocar Baya, Chad J. Achenbach, Bourahima Kone, Yacouba Toloba, Djeneba K. Dabitao, Bassirou Diarra, Drissa Goita, Seydou Diabaté, Mamoudou Maiga, Dianguina Soumare, Khadidia Ouattara, Tenin Kanoute, Gaoussou Berthe, Youssouf M. Kamia, Yeya dit Sadio Sarro, Moumine Sanogo, Antieme C.G. Togo, Bindongo P.P. Dembele, Nadie Coulibaly, Amadou Kone, Maxwell Akanbi, Michael Belson, Sounkalo Dao, Susan Orsega, Sophia Siddiqui, Seydou Doumbia, Robert L. Murphy, Souleymane Diallo

Thomas Schön, Erika Matuschek, Sagal Mohamed, Mrudula Utukuri, Scott Heysell, Jan-Willem Alffenaar, Soyoun Shin, Elena Martinez, Vitali Sintchenko, Florian P. Maurer, Peter M. Keller, Gunnar Kahlmeter, Claudio U. Köser

Lachmandas E, Eckold C, Böhme J, et al.

AbstractBackgroundMetformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis.MethodsWe investigated in-vitro and in-vivo effects of metformin in humans. ResultsMetformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in-vitro cellular metabolism whilst inhibiting the mammalian target of rapamycin (mTOR) targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation, and increased phagocytosis. Metformin administered to healthy human volunteers led to significant down-regulation of genes involved in oxidative phosphorylation, mTOR signaling and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species (ROS) production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to non-classical monocytes. At a functional level, metformin lowered ex vivo production of TNF-α, IFN-γ and IL-1β but increased phagocytosis and ROS production. ConclusionMetformin has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcription involved in innate host responses to M. tuberculosis.

D. P. Holland et al.

Abstract Background Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI). Methods In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay. Results Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1β in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15nil) and negatively with that of TB antigen-stimulated IL-32 (IL-32TB) in QFT-GIT supernatants. Although the IL-15nil and IL-15TB levels were higher in LTBI subjects than patients with active TB, the IL-32nil and IL-32TB levels were higher in the latter patients. A combination of the IL-15nil and IL-32TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964. Conclusions Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.…

Bulabula A, Nelson J, Musafiri E, et al.

AbstractBackgroundMultidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program.Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death.ResultsOf 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71).ConclusionsFavorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

Wendi D. Roe, Baukje Lenting, Anna Kokosinska, Stuart Hunter, Padraig J. Duignan, Brett Gartrell, Lynn Rogers, Desmond M. Collins, Geoffrey W. de Lisle, Kristene Gedye, Marian Price-Carter

by Wendi D. Roe, Baukje Lenting, Anna Kokosinska, Stuart Hunter, Padraig J. Duignan, Brett Gartrell, Lynn Rogers, Desmond M. Collins, Geoffrey W. de Lisle, Kristene Gedye, Marian Price-Carter Mycobacterium pinnipedii causes tuberculosis in a number of pinniped species, and transmission to cattle and humans has been reported. The aims of this study were to: characterize the pathology and prevalence of tuberculosis in New Zealand marine mammals; use molecular diagnostic methods to confirm and type the causal agent; and to explore relationships between type and host characteristics. Tuberculosis was diagnosed in 30 pinnipeds and one cetacean. Most affected pinnipeds had involvement of the pulmonary system, supporting inhalation as the most common route of infection, although ingestion was a possible route in the cetacean. PCR for the RD2 gene confirmed M. pinnipedii as the causal agent in 23/31 (74%) cases (22 using DNA from cultured organisms, and one using DNA from formalin-fixed paraffin-embedded (FFPE) tissue), including the first published report in a cetacean. RD2 PCR results were compared for 22 cases where both cultured organisms and FFPE tissues were available, with successful identification of M. pinnipedii in 7/22 (31.8%). In cases with moderate to large numbers of acid-fast bacilli, RD2 PCR on FFPE tissue provided a rapid, inexpensive method for confirming M. pinnipedii infection without the need for culture. VNTR typing distinguished New Zealand M. pinnipedii isolates from M. pinnipedii isolated from Australian pinnipeds and from common types of M. bovis in New Zealand. Most (16/18) M. pinnipedii isolates from New Zealand sea lions were one of two common VNTR types whereas the cetacean isolate was a type detected previously in New Zealand cattle.