Risk Of Mycobacterium Tuberculosis Infection Research Articles

Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants

Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-alpha2, TNF-alpha, CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.

Expert consensus on the treatment of chronic kidney disease with tuberculosis (2022 version)

China is a country with a high burden of chronic kidney disease(CKD) and tuberculosis. Patients with CKD are at increased risk of Mycobacterium tuberculosis infection, and the prevalence of CKD is also significantly higher in patients with tuberculosis. The coexistence of the two diseases brings great difficulties for clinical treatment. In this consensus, the general situation, clinical characteristics, metabolic characteristics of anti-tuberculous drugs, and the principles of protocol formulation of such patients were discussed and summarized. When making anti-tuberculosis regimen for patients with chronic renal failure, drugs that metabolized through liver, liver and kidney channels or metabolic pathways other than liver and kidney should be selected as far as possible. Drugs with significant renal toxicity and mainly metabolized by the kidney should be avoided. For CKD patients with mild decrease in GFR (60-89 ml·min-1·1.73 m-2), anti-tuberculosis regimen should be carried out according to the national standards and guidelines, without reducing the dose of anti-tuberculosis drugs. For CKD patients with significantly reduced GFR, mainly CKD3b, stages 4-5, and those receiving dialysis, the anti-tuberculosis regimen must be adjusted according to the GFR. For CKD patients with GFR less than 30 ml·min-1·1.73 m-2, this consensus also recommended anti-tuberculous regimen for initial, retreated and multi-drug-resistant tuberculosis patients. This consensus aimed to improve clinicians' understanding of CKD complicated with tuberculosis, standardize the clinical treatment, improve the curative effect, and reduce adverse reactions. Data from previous trials of CKD combined with TB treatment are still scarce. We look forward to further investigation and evidence-based medical research on CKD with tuberculosis in the future, and make positive efforts for the control of CKD and tuberculosis in China.

COVID-19 and Beyond: Exploring Public Health Benefits from Non-Specific Effects of BCG Vaccination.

Bacille Calmette–Guérin (BCG) vaccination, widely used throughout the world to protect against infant tuberculous meningitis and miliary tuberculosis (TB), can provide broad non-specific protection against infectious respiratory diseases in certain groups. Interest in BCG has seen a resurgence within the scientific community as the mechanisms for non-specific protection have begun to be elucidated. The impact of the COVID-19 pandemic on nearly every aspect of society has profoundly illustrated the pressure that respiratory infections can place on a national healthcare system, further renewing interest in BCG vaccination as a public health policy to reduce the burden of those illnesses. However, the United States does not recommend BCG vaccination due to its variable effectiveness against adult TB, the relatively low risk of Mycobacterium tuberculosis infection in most of the United States, and the vaccine’s interference with tuberculin skin test reactivity that complicates TB screening. In this review, we explore the broad immune training effects of BCG vaccination and literature on the effects of BCG vaccination on COVID-19 spread, disease severity, and mortality. We further discuss barriers to scheduled BCG vaccination in the United States and how those barriers could potentially be overcome.

Genetic Polymorphism of Tumor Necrosis Factor-Alpha, Interferon-Gamma and Interleukin-10 and Association With Risk of Mycobacterium Tuberculosis Infection.

Background. Mycobacterium tuberculosis has become the leading cause of morbidity and death in humans worldwide. Thus, genetic variability of the host plays a major role in human susceptibility to the pathogen, among others. Therefore, the objective of this finding was to assess the association of genetic polymorphisms of cytokines with tuberculosis infection.Method.A cross-sectional study was conducted between January and May 2018. Five ml of whole blood was collected and extracted the genomic DNA through simple salting out method. The patterns of genetic polymorphism were determined by amplification refractory method PCR using specific primers. Finally, the PCR run on electrophoresis of agarose gel and the band was visualized under UV light. A logistical regression model has been adapted to assess the association of genetic polymorphisms with tubercular infection. In order to determine the association between the explanatory and outcome variable, the odds ratio with 95% CI was calculated. P < 0.05 is a statistically significant value.Result.In present study, the frequency of TNF-α -308 G allele and GG genotype OR (95% CI)= 0.20 (0.11-0.37), and OR (95% CI)= 0.29 (0.18-0.46)), respectively) and IFN-γ +874 A allele and AA genotype OR (95% CI)= 3.80 (2.11-6.86) and (OR (95% CI)= 1.61(1.13-2.28), respectively) were significantly associated with tuberculosis incidence. In contrast, there is no significant correlation between IL-10 -1082 A and AA of allele and genotype, respectively in tuberculosis patients (p > 0.05) was evident.Conclusion.From our finding, the genetic variability of TNF-α -308 A and IFN-γ +874 alleles are the potent host genetic risk factors associated with tuberculosis infection.

The acquisition of Mycobacterium tuberculosis infection in village doctors in China: a prospective study.

BACKGROUND: Occupational exposure-related risk of Mycobacterium tuberculosis infection has been reported for village doctors in China. This prospective study aims to estimate the infection acquisition in this key population.METHODS: At baseline, all village doctors registered in Zhongmu County were tested by QuantiFERON®-TB Gold In-Tube (QFT) and QuantiFERON®-TB Gold Plus (QFT-Plus) in parallel. Those negatives for either of the tests were retested to identify conversions at the 2-year follow-up investigation.RESULTS: A total of 367 eligible participants completed the 2-year follow-up survey with frequency of conversion of 5.0% (18/361) for QFT and 6.1% (21/343) for QFT-Plus. The agreement of follow-up results between the tests was 93.2% with a κ coefficient of 0.43 (95%CI 0.20-0.65). Among QFT-Plus convertors, the difference between TB1 and TB2 tubes (TB2-TB1) was significantly increased as compared with baseline results (P = 0.039). Participants from the villages with occurrence of microbiologically confirmed pulmonary TB showed higher frequency of QFT conversions (11.0% vs. 3.2%, P = 0.011) and QFT-Plus conversions (12.3% vs. 4.4%, P = 0.027) than those from the villages without occurrence.CONCLUSION: Our results consistently suggest that capability on occupational protection and M. tuberculosis infection control should be improved in village doctors in China.

Metformin enhances anti-mycobacterial responses by educating CD8+ T-cell immunometabolic circuits

Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8+ T cells from Cxcr3−/− mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8+ T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection.

Essential Components of a Public Health Tuberculosis Prevention, Control, and Elimination Program: Recommendations of the Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association.

SummaryThis report provides an introduction and reference tool for tuberculosis (TB) controllers regarding the essential components of a public health program to prevent, control, and eliminate TB. The Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association recommendations in this report update those previously published (Advisory Council for the Elimination of Tuberculosis. Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep 1995;44[No. RR-11]). The report has been written collaboratively on the basis of experience and expert opinion on approaches to organizing programs engaged in diagnosis, treatment, prevention, and surveillance for TB at state and local levels.This report reemphasizes the importance of well-established priority strategies for TB prevention and control: identification of and completion of treatment for persons with active TB disease; finding and screening persons who have had contact with TB patients; and screening, testing, and treatment of other selected persons and populations at high risk for latent TB infection (LTBI) and subsequent active TB disease.Health departments are responsible for public safety and population health. To meet their responsibilities, TB control programs should institute or ensure completion of numerous responsibilities and activities described in this report: preparing and maintaining an overall plan and policy for TB control; maintaining a surveillance system; collecting and analyzing data; participating in program evaluation and research; prioritizing TB control efforts; ensuring access to recommended laboratory and radiology tests; identifying, managing, and treating contacts and other persons at high risk for Mycobacterium tuberculosis infection; managing persons who have TB disease or who are being evaluated for TB disease; providing TB training and education; and collaborating in the coordination of patient care and other TB control activities. Descriptions of CDC-funded resources, tests for evaluation of persons with TB or LTBI, and treatment regimens for LTBI are provided (Supplementary Appendices; https://stacks.cdc.gov/view/cdc/90289).

Case-control study to evaluate the role of smoking, alcohol abuse, intravenous drug abuse, tobacco use and biomass fuel exposure as risk factor in pulmonary tuberculosis

Background: An association between smoking and tuberculosis disease has been shown in various studies, it is less clear to what extent smoking increases the risk of Mycobacterium tuberculosis infection. Therefore the aim of this study is to evaluate the role of smoking, alcohol abuse, intravenous drug abuse, tobacco use and biomass fuel exposure as a risk factor for the development of pulmonary tuberculosis.Methods: This is a case control study and total 200 subjects will be included with 100 sputum smear positive pulmonary tuberculosis cases and 100 age and sex matched healthy subjects as controls. Data collected from both cases and controls using a proforma by enquiring smoking habits, alcohol abuse, intravenous drug abuse, biomass fuel exposure and documenting chest X-ray features.Results: The study showed significant association between tuberculosis and smoking as a risk factor with beedi smoking, early age of starting smoking, increased duration and quantity of smoking increases risk for tuberculosis. There was significant association between intravenous drug abuse, biomass fuel exposure and risk of tuberculosis. There was no significant association in the study between alcohol abuse, tobacco chewing and tuberculosis, but heavy drinking and tuberculosis showed significant association. The study also showed significant association of cavitary lesion with smoking.Conclusions: There is significant association between smoking, intravenous drug abuse, biomass fuel exposure and tuberculosis, since these risk factors impairs host immune defences that allows the development of active tuberculosis.

Disseminated tuberculosis in a pregnant immunocompetent healthcare worker

Health care workers (HCWs) have an increased risk of Mycobacterium Tuberculosis (TB) infection compared to general population. Pregnancy suppresses the Lymphocyte T-helper 1 (Th1) pro-inflammatory response. Frequent and consecutive pregnancies may also promote TB infection or reactivation of latent TB. But there is still no evidence of certain risk of severe disseminated infection. A 35-year-old pregnant woman, working as a laboratory officer, presented with fever, general weakness then acute respiratory failure. Miliary lung nodules were noted on chest X-ray. Under the impression of miliary tuberculosis, anti TB medication was administered. Likelihood of This diagnosis was due to her occupation, exposition to Mycobacterium Tuberculosis, clinical and radiologic findings. CT scan revealed cerebro-meningeal, pulmonary, splenic and ganglionary TB. The patient was treated successfully with ordinary anti TB combination regimen. Delivery and post partum was without complication. Cases of severe TB in an otherwise healthy pregnant woman are rare. This is an occupational disease to prevent.

Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil

BackgroundHost genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. MethodsWe examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. ResultsAmong 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI=1.15–12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR=24.84; 95%CI=2.26–272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). ConclusionsPolymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.

Polymorphisms in TLR4 and TNFA and Risk of Mycobacterium tuberculosis Infection and Development of Active Disease in Contacts of Tuberculosis Cases in Brazil: A Prospective Cohort Study.

The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood. We tested the single-nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as induration ≥5 mm after a negative TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models. Among the 526 contacts, 60 had TST conversion and 44 developed active TB during follow-up. Multivariable regression analysis demonstrated that male sex (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1-4.6), as well as SNPs in TLR4 genes (OR: 62.8, 95% CI: 7.5-525.3) and TNFA (OR: 4.2, 95% CI: 1.9-9.5) were independently associated with TST conversion. Moreover, a positive TST at baseline (OR: 4.7, 95% CI: 2.3-9.7) and SNPs in TLR4 (OR: 6.5, 95% CI: 1.1-36.7) and TNFA (OR: 12.4, 95% CI:5.1-30.1) were independently associated with incident TB. SNPs in TLR4 and TNFA predicted both TST conversion and active TB among contacts of TB cases in Brazil.

Le tabagisme et l’aide à l’arrêt du tabac des patients atteints de tuberculose

Tuberculosis and tobacco smoking are two major public health problems causing significant mortality worldwide. Tobacco smoke increases the risk of Mycobacterium tuberculosis infection, severe pulmonary or extrapulmonary TB, and death of TB. In emerging countries, quitting smoking is one way to control the TB epidemic. Compared with non-smokers, smokers with tuberculosis are less observant of anti-tuberculosis treatment. Smoking abstinence improves the course of their illness, the treatment compliance and facilitates the final cure justifying smoking cessation interventions. The involvement of all healthcare professionals in helping smokers stopping smoking is required.

Prevalence of tuberculosis infection among South African adolescents

Background: We aimed to measure changes in adolescent prevalence of latent tuberculosis (TB) infection (LTBI) over a 10-year period (2005-2015), in which TB disease incidence fell 34% from 1,038 – 682 per 100,000 per annum, in order to evaluate impact of effective TB control efforts on transmission to children. Methods & Materials: We compared baseline data from a TB cohort study (2005-2007) and a TB vaccine trial (2014-2015), which enrolled adolescents from the same 8 high schools near Cape Town, South Africa. LTBI was defined by positive QuantiFERON®-TB Gold In-Tube (QFT) test. Data were analysed by two-sample test of equality of proportions for survey data and logistic regression for survey data. Results: We analysed data from 6,848 adolescents with median age of 15.5 years (range 12.3 - 19.1). 4,880 (71%) adolescents were tested between 2005-2007 and 1,968 (29%) between 2014-2015. Prevalence of LTBI was 43.8% (95% Confidence Interval (CI) 28.4-59.1) vs 48.5% (CI: 41.1-55.8); and annual risk of Mycobacterium tuberculosis infection (ARTI) was 3.6% (CI: 2.1-5.5) vs 4.2% (CI: 3.4-5.2), in the period 2005-2007 vs 2014-2015, respectively. Marked heterogeneity in LTBI prevalence was observed at school level, ranging from 12-65%. LTBI prevalence increased on average by 13% between age 12-18 years in lower socio-economic quintile schools, in which average LTBI was 54% in 2005-2007 and 53% in 2014-2015, consistent with ongoing, but stable risk of TB transmission. By contrast, LTBI prevalence did not increase with age in highest socio-economic quintile schools, in which average LTBI prevalence increased from 20-38% over the same period, consistent with increased risk of transmission prior to school entry. Conclusion: Adolescent LTBI prevalence remained high over a decade, suggesting TB transmission to children was not yet impacted by effective TB control efforts that had reduced regional TB disease notification rate by more than one-third. Trends in school LTBI prevalence should be interpreted in the context of socio-economic and other TB risk factors that affect risk of transmission prior to school entry.

Particularités cliniques et radiologiques de la tuberculose pulmonaire chez le tabagique

Tobacco smoke alters lung defense mechanisms against infections and so increases the risk of mycobacterium tuberculosis infection. To determine the particular clinical features of tuberculosis in smokers and identify risk factors. We conducted a prospective, cross-sectional study over a period of nine months in Dakar, Senegal. The Chi-square test and multiple logistic regression were used to identify differences between smokers and non-smokers and to identify factors associated with clinical outcomes. We included 165 patients with active pulmonary tuberculosis (59 smokers versus 106 never-smokers). The average age of smokers was 43.8±12.7 versus 32.1±13.1 years (P<0.0001). Smokers were overwhelmingly male (98.3% versus 1.8%, P<0.0001). The average delay to consultation was longer among smokers (90 days [30-120] versus 60 days [30-90]; P<0.0001). In multivariate analysis, alcohol abuse, increasing age, male sex, and an unknown retroviral status were independent risk factors for pulmonary tuberculosis. Haemoptysis was observed more frequently in smokers (49.1% versus 31.1%, P=0.017). With regards to chest X-ray features, smokers presented with more advanced, bilateral and cavitating lung lesions. Diagnostic delay and haemoptysis are important characteristics of the pulmonary tuberculosis in tobacco smokers.

The Role of Powerlessness Among Health Care Workers in Tuberculosis Infection Control.

Due to their occupational exposure in health care settings, health care workers (HCW) have increased risk of Mycobacterium tuberculosis infection. They face challenges to remain up-to-date with evidence-based clinical practices and translate educational information into actions in infection control practices. Our purpose was to examine this "knowledge-action" gap about how HCWs understand their occupational M. tuberculosis risk and use recommended infection control measures in clinical practices in the Dominican Republic (DR). We conducted 10 focus groups with 40 physicians and nurses at two tertiary-level DR institutions. Using grounded theory methods, we developed a theoretical model to describe the decision-making process related to adherence to M. tuberculosis infection control measures in clinical practice. Findings highlight intrinsic and extrinsic factors that influenced the observed knowledge-action gap related to M. tuberculosis infection control practices in two DR health institutions.

A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa.

One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an “experiment of nature” design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection. Among these individuals, 244 tested were tuberculin skin test (TST) positive either at enrollment or during the >8 year follow up, while 225 were not. We identified a genome-wide significant association between a dominant model of rs877356 and binary TST status in the combined cohort (Odds ratio = 0.2671, p = 1.22x10-8). Association was replicated with similar significance when examining TST induration as a continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from IL9. Two-locus analyses of association of variants near rs877356 showed a haplotype comprised of rs877356 and an IL9 missense variant, rs2069885, had the most significant association (p = 1.59x10-12). We also replicated previously linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells and TH2 cells during inflammatory responses, providing a possible link between airway inflammation and protection from MTB infection. Our results indicate that studying uninfected, HIV-positive participants with extensive exposure increases the power to detect associations in complex infectious disease.

Challenges in the Estimation of the Annual Risk of Mycobacterium tuberculosis Infection in Children Aged Less Than 5 Years.

Accurate estimates of Mycobacterium tuberculosis infection in young children provide a critical indicator of ongoing community transmission of M. tuberculosis. Cross-reactions due to infection with environmental mycobacteria and/or bacille Calmette-Guérin (BCG) vaccination compromise the estimates derived from population-level tuberculin skin-test surveys using traditional cutoff methods. Newer statistical approaches are prone to failure of model convergence, especially in settings where the prevalence of M. tuberculosis infection is low and environmental sensitization is high. We conducted a tuberculin skin-test survey in 5,119 preschool children in the general population and among household contacts of tuberculosis cases in 2012–2014 in a district in northern Malawi where sensitization to environmental mycobacteria is common and almost all children are BCG-vaccinated. We compared different proposed methods of estimating M. tuberculosis prevalence, including a method described by Rust and Thomas more than 40 years ago. With the different methods, estimated prevalence in the general population was 0.7%–11.5% at ages <2 years and 0.8%–3.3% at ages 2–4 years. The Rust and Thomas method was the only method to give a lower estimate in the younger age group (0.7% vs 0.8%), suggesting that it was the only method that adjusted appropriately for the marked effect of BCG-attributable induration in the very young.

Mycobacterium tuberculosis infection among persons who inject drugs in San Diego, California

Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use. To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA. PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression. A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others. Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region.

What is the effect of antiretroviral treatment on the infectiousness of patients with smear-positive tuberculosis in rural Malawi?

BackgroundSeveral studies have found a lower risk of Mycobacterium tuberculosis infection among household contacts of HIV-positive patients with pulmonary tuberculosis than among patients with HIV-negative pulmonary tuberculosis, suggesting reduced transmission. Our hypothesis is that this association is reversed by antiretroviral therapy (ART). We examined the effect of ART on the prevalence of M tuberculosis infection among child contacts of adults with smear-positive tuberculosis. MethodsA cross-sectional household contact study of smear-positive tuberculosis index cases was conducted in Karonga, Malawi, between Jan 1, 2013, and Dec 31, 2014. Prevalence of tuberculin skin test (TST) positivity was compared between household contacts aged 11 years of index cases (HIV-negative, HIV-positive not on ART, and HIV-positive on ART [HIV status at diagnosis of tuberculosis]). A positive TST was defined as ≥10 mm induration. Data were analysed with a random-effects logistic regression model to account for clustering. FindingsThere were 376 child contacts (148 index cases), of whom 330 (88%) had a TST reading. The proportion of contacts of index cases with the highest mycobacillary burden, with smear-positivity as a proxy, was similar: HIV-negative (78%, 149/191) and HIV-positive index cases on ART (71%, 50/70), compared with HIV-positive index cases not on ART (57%, 39/69). The odds of a positive TST were 60% lower in contacts of HIV-positive patients not on ART (adjusted odds ratio 0·4, 95% CI 0·1–1·0; p=0·04) and 70% lower in contacts of HIV-positive patients on ART (0·3, 0·1–0·8; p=0·02) than in HIV-negative index cases, adjusted for degree of contact and age of index case. The reduction in odds of TST positivity among contacts of HIV-positive patients on ART remained after additionally adjusting for degree of smear-positivity. InterpretationContrary to expectation, we found a reduced prevalence of M tuberculosis infection among contacts of HIV-positive patients with tuberculosis on ART, after adjusting for degree of smear-positivity. This finding is suggestive of decreased transmission from these index cases. This reduction in transmission might be due to earlier diagnosis of tuberculosis in patients who are already engaged in care. FundingWellcome Trust.

High-resolution CT findings of pulmonaryMycobacterium tuberculosisinfection in renal transplant recipients

Renal transplantation recipients are at increased risk of Mycobacterium tuberculosis infection because of immunosuppression. The aim of this study was to assess high-resolution CT (HRCT) findings in renal transplantation recipients diagnosed with pulmonary tuberculosis (TB). We reviewed HRCT findings from patients diagnosed with pulmonary TB, established by M. tuberculosis detection in bronchoalveolar lavage, sputum or biopsy sample. Two observers independently reviewed HRCT images and reached consensus decisions on the presence and distribution of: (i) miliary nodules, (ii) cavitation and centrilobular tree-in-bud nodules, (iii) ground-glass attenuation and consolidation, (iv) mediastinal lymph node enlargement and (v) pleural effusion. The sample comprised 40 patients [26 males, 14 females; median age, 45 years (range, 12-69 years)]. The main HRCT pattern was miliary nodules (40%), followed by cavitation and centrilobular tree-in-bud nodules (22.5%), ground-glass attenuation and consolidation (15%), mediastinal lymph node enlargement (12.5%) and pleural effusion (10%). The distribution of findings in patients with miliary nodules was random. In patients with cavitation and centrilobular tree-in-bud nodules, 66.6% of abnormalities were found in the upper lobes. Pleural effusion was unilateral in 75% of cases. The overall mortality rate was 27.5%. This rate was 50% in patients with miliary nodules, and 72.6% of all deaths occurred in this group. Thus, mortality was increased significantly in patients with miliary nodules (p < 0.05). The main HRCT finding in renal transplantation recipients with pulmonary TB was miliary nodules, followed by cavitation and centrilobular tree-in-bud nodules. Miliary nodules were associated with a worse prognosis in these patients. We report the first series on HRCT findings of microbiologically confirmed pulmonary TB exclusively in renal transplantation recipients. The main HRCT finding was miliary nodules, and mortality was increased significantly in these patients.