Tuberculosis Exposure Research Articles

Analysis of Clinical Characteristics and Risk Factors for Drug Resistance in Newly-Treated Patients with Pulmonary Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease.

ObjectiveTo analyze the clinical characteristics and risk factors of drug resistance of newly-treated chronic obstructive pulmonary disease (COPD) complicated pulmonary tuberculosis (PTB).MethodsA total of 489 newly-treated PTB patients admitted to Beijing Geriatric hospital were retrospectively enrolled in this study. Of these, 138 patients with COPD were allocated to the study group, and the remaining 351 patients without COPD were allocated to the control group. The baseline information, clinical characteristics of PTB and drug resistance of Mycobacterium tuberculosis were compared between the two groups. Logistic regression was used to explore the correlation between drug resistance and COPD complications.ResultsPatients complicated with COPD had a higher proportion of respiratory failure, cough, fever and night sweats, chest short breath, and emaciation between the study group and the control group (P<0.05). In terms of medical history, patients complicated with COPD also had a higher proportion of childhood TB history, cough, tuberculosis exposure rate, dust exposure rate, and malnutrition (P<0.05). There were significantly more patients with pulmonary cavities and a delayed diagnosis of TB in the study group than in the control group (P<0.05). The single drug resistance rates of isoniazid, ethambutol, rifampicin, pyrazinamide, and rifapentine, and drug resistance with any two or more drugs in the study group were significantly higher than those in the control group (P<0.05). Multivariate Logistic regression analysis showed that smoking, extrapulmonary tuberculosis, tuberculosis exposure history, malnutrition, pulmonary cavity, and delayed TB diagnosis were risk factors for drug resistance in newly-treated COPD complicated PTB patients.ConclusionThe symptoms of COPD complicated PTB were more serious. Smoking history, extrapulmonary tuberculosis, tuberculosis exposure history, malnutrition, pulmonary cavity, and delayed diagnosis of tuberculosis were risk factors for TB resistance in these patients.

Correlation between tuberculosis-specific interferon-γ release assay and intrathoracic calcification: A cross-sectional study.

BackgroundAlthough persistent tuberculosis (TB) infection is known to cause calcification in the lungs, the relationship between intrathoracic calcification and the results of the interferon-γ release assay (IGRA) has not been fully elucidated. This study aimed to assess the association between intrathoracic calcification and IGRA results.MethodsWe retrospectively included consecutive patients who concurrently underwent chest X-ray, chest computed tomography (CT), and an IGRA. Patients with a current diagnosis of active TB or treatment history of active TB or latent tuberculosis infection (LTBI) were excluded. The association between calcification according to the chest X-ray or CT and IGRA results were analyzed using binomial logistic regression.ResultsThis study included 574 patients, and 38 (7%) patients had a positive IGRA result. Patients with a positive result were significantly older and had a higher proportion of comorbidities, and history of tuberculosis exposure compared to those with a negative result. Calcification of the lung field and mediastinal lymph nodes according to chest CT was more frequently observed in patients with a positive IGRA result, whereas no significant difference was observed concerning the proportion of lung field calcification on chest X-ray between patients with positive and negative IGRA results. In multivariate analysis, calcification of mediastinal lymph nodes alone (adjusted odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.76–8.26) and the combination of lung field and mediastinal lymph node calcification (adjusted OR = 4.12, 95% CI = 1.51–11.76) on chest CT was independently associated with positive IGRA results.ConclusionsThe finding of mediastinal lymph node calcification, with or without lung field calcification, on chest CT was associated with positive IGRA results independent of TB exposure history. Previous TB infection including eliminated TB infection and LTBI can be suspected when calcified lymph nodes in are observed the mediastinum on chest CT.

Pilot study to identify missed opportunities for prevention of childhood tuberculosis

Tuberculosis (TB) in exposed children can be prevented with timely contact tracing and preventive treatment. This study aimed to identify potential barriers and delays in the prevention of childhood TB in a low-incidence country by assessing the management of children subsequently diagnosed with TB. A pilot retrospective cohort study included children (< 15 years) treated for TB between 2009 and 2016 at a tertiary care hospital in Berlin, Germany. Clinical data on cases and source cases, information on time points of the diagnostic work up, and preventive measures were collected and analyzed. Forty-eight children (median age 3 years [range 0.25–14]) were included; 36 had been identified through contact tracing, the majority (26; 72.2%) being < 5 years. TB source cases were mostly family members, often with advanced disease. Thirty children (83.3%) did not receive prophylactic or preventive treatment, as TB was already prevalent when first presented. Three cases developed TB despite preventive or prophylactic treatment; in three cases (all < 5 years), recommendations had not been followed. Once TB was diagnosed in source cases, referral, assessment, TB diagnosis, and treatment were initiated in most children in a timely manner with a median duration of 18 days (interquartile range 6–60, range 0–252) between diagnosis of source case and child contact (information available for 35/36; 97.2%). In some cases, notable delays in follow-up occurred.Conclusion: Prompt diagnosis of adult source cases appears to be the most important challenge for childhood TB prevention. However, improvement is also needed in the management of exposed children.What is Known:• Following infection with Mycobacterium tuberculosis, young children have a high risk of progression to active and severe forms of tuberculosis (TB).• The risk of infection and disease progression can be minimized by prompt identification of TB-exposed individuals and initiation of prophylactic or preventive treatment.What is New:• We could show that there are avoidable time lags in diagnosis in a relevant proportion of children with known TB exposure.• Delayed diagnosis of adult source cases, losses in follow-up examinations, and delay in referral to a specialized TB clinic of TB-exposed children, especially among foreign-born children, appear to be the main issue in this German pediatric study cohort.

Tuberculosis Exposure from a Healthcare Worker to Patients in a Neonatal Intensive Care Unit (NICU).

The nosocomial spread of Mycobacterium tuberculosis from a healthcare worker with infectious pulmonary tuberculosis disease to patients remains a risk in the healthcare environment, including neonatal intensive care units. In this paper, we outlined a protocol for neonates exposed to tuberculosis in a neonatal intensive care unit that includes skin testing, chest X-ray imaging, and prophylactic isoniazid. Neonatal patients were followed up with tuberculosis skin testing at both three months corrected age and two months postexposure. To our knowledge, this is the first Canadian study to illustrate a protocol following tuberculosis exposure in a neonatal intensive care unit for exposed neonates.

Detection of M. tuberculosis in the environment as a tool for identifying high-risk locations for tuberculosis transmission

Tuberculosis (TB) remains a leading cause of infectious mortality globally, yet most cases cannot be epidemiologically linked even with extensive contact investigations and whole genome sequencing. Consequently, there remain major gaps in our understanding of where and when M. tuberculosis (Mtb) exposures occur. We aimed to investigate whether Mtb can be detected in environments where TB patients were recently present, which could serve as a tool for characterizing exposure risk. We collected 389 environment surface (ES) swabs from two high TB burden prisons in Brazil, sampling 41 (n = 340) cells occupied by individuals with active TB and 7 (n = 49) cells from individuals without TB. In a subset of pooled swabs (n = 6) and a swab from a cigarette lighter from the cell with active TB patients, we enriched Mtb DNA using RNA-bait hybrid capture assays and performed whole genome sequencing. In prison cells, Mtb DNA was detected in 55/340 (16 %) of ES swabs from cells occupied by active TB patients and none (0/49) from cells in which no active TB patients were present. Mtb was detected in 13/16 (81 %) prison cells occupied by the individuals with high/medium sputum Xpert Mtb load and 8/25 (32 %) with low/very low sputum Mtb load (p = 0.003). Seven hybrid capture samples had a median genomic coverage of 140×. rpoB mutations conferring high-level rifampin resistance were detected in 3/7 ES swabs. Mtb was frequently detectable in environments recently occupied by individuals with active TB. This approach could be applied in congregate environments to identify and characterize high-risk settings for Mtb exposure.

Novel HLA associations with outcomes of Mycobacterium tuberculosis exposure and sarcoidosis in individuals of African ancestry using nearest-neighbor feature selection.

Tuberculosis and sarcoidosis are inflammatory diseases characterized by granulomas that may occur in any organ but are often found in the lung. The panoply of classical human leukocyte antigen (HLA) alleles associated with occurrence and/or severity of both diseases varies considerably across studies. This heterogeneity of results, due to variation in factors like ancestry and disease subphenotype, as well as the use of simple modeling strategies to elucidate likely complex relationships, has made conclusions about underlying commonalities difficult. Here we perform HLA association analyses in individuals of African ancestry, using a greater resolution to include subphenotypes of disease and employing more comprehensive analytical techniques. Using a novel application of nearest-neighbor feature selection to score allelic importance, we investigated HLA allele association with Mycobacterium tuberculosis exposure outcomes in the first analysis of both latent Mycobacterium tuberculosis infection and active disease compared with those who, despite long-term exposure to active index cases, have neither positive diagnostic tests nor display clinical symptoms. We also compared persistent to resolved sarcoidosis. This led to the identification of novel HLA associations and evidence of main effects and interaction effects. We found strikingly similar main effects and interaction effects at HLA-DRB1, -DQB1, and -DPB1 in those resistant to tuberculosis (either latent or active) and persistent sarcoidosis.

Toddler With Fever and Limp.

Toddler With Fever and Limp.

Contribution of Reinfection to Annual Rate of Tuberculosis Infection (ARI) and Incidence of Tuberculosis Disease.

Modeling studies have concluded that 60-80% of tuberculosis (TB) infections result from reinfection of previously infected persons. The annual rate of infection (ARI), a standard measure of the risk of TB infection in a community, may not accurately reflect the true risk of infection among previously infected persons. We constructed a model of infection and reinfection with Mycobacterium tuberculosis to explore the predictive accuracy of ARI and its effect on disease incidence. We created a deterministic simulation of the progression from TB infection to disease and simulated the prevalence of TB infection at the beginning and end of a theoretical year of infection. We considered 10 disease prevalence scenarios ranging from 100/100 000 to 1000/100 000 in simulations where TB exposure probability was homogeneous across the whole simulated population or heterogeneously stratified into high-risk and low-risk groups. ARI values, rates of progression from infection to disease, and the effect of multiple reinfections were obtained from published studies. With homogeneous exposure risk, observed ARI values produced expected numbers of infections. However, when heterogeneous risk was introduced, observed ARI was seen to underestimate true ARI by 25-58%. Of the cases of TB disease that occurred, 36% were among previously infected persons when prevalence was 100/100 000, increasing to 79% of cases when prevalence was 1000/100 000. Measured ARI underestimates true ARI as a result of heterogeneous population mixing. The true force of infection in a community may be greater than previously appreciated. Hyperendemic communities likely contribute disproportionally to the global TB disease burden.

Reproducibility of a protocol for standardized reading of chest X-rays of children household contact of patients with tuberculosis

BackgroundThe interpretation of the chest radiograph may vary because it depends on the reader and due to the non-specificity of findings in tuberculosis (TB). We aim to assess the reproducibility of a standardized chest radiograph reading protocol in contacts of patients with pulmonary TB under the 5 years of age.MethodsDescriptive, cross-sectional study with children under the age of five, household contacts of patients with confirmed pulmonary TB from Medellín, Bello and Itagüí (Colombia) between Jan-01–2015 and May-31–2016. Standardized reading protocol: two radiologists, blinded independent reading, use of template (Dr. Andronikou design) in case of disagreement a third reading was performed. Kappa coefficient for intra and inter observer agreement, and prevalence ratio were estimated of sociodemographic characteristics, TB exposure and interpretation of chest X-ray.ResultsFrom 278 children, standardized reading found 255 (91.7%) normal X-rays, 10 (3.6%) consistent with TB, and 13 (4.7%) other alterations. Global agreement was 91.3% (Kappa = 0.51). Inter-observer agreement between readers 1–2 was 90.0% (Kappa = 0.59) and 1–3 93.2% (Kappa = 0.59). Intra-observer agreement for reader 1 was 95.5% (Kappa = 0.86), 2 84.0% (Kappa = 0.51), and 3 94.7% (Kappa = 0.68). Greater inter-observer disagreement was between readers 1–2 for soft tissue density suggestive of adenopathy (4.6%), airspace opacification (1.17%) and pleural effusion (0.58%); between readers 1–3 for soft tissue density suggestive of adenopathy (4.2%), opacification of airspace (2.5%) and cavities (0.8%).ConclusionsChest radiographs are an affordable tool that contributes to the diagnosis of TB, so having a standardized reading protocol showed good agreement and improves the reproducibility of radiograph interpretation.

Paediatric progressive primary tuberculosis

A previously healthy 13-year-old Japanese girl with a BCG vaccination history and no tuberculosis (TB) exposure history presented to the hospital with mild dyspnea for 1 month and fever for 5 days. Computed tomography showed consolidation with a pleural effusion, obstructed left main bronchus with an air bronchogram, and traction bronchiectasis of the left upper lobe (Fig. 1A, B). No improvement was observed with ampicillin. Computed tomography on day 23 showed a new granular shadow in the right upper lobe (Fig. 1C). Despite a negative interferon-gamma release assay (IGRA) result, the sputum on day 55 was positive for acid-fast bacilli on a ZiehlNeelsen stain and Mycobacterium tuberculosis on polymerase chain reaction. A fourdrug antituberculous regimen was initiated and she recovered rapidly. TB exposure history, positive tuberculin skin test or IGRA, and typical imaging findings are the triad for primary TB diagnosis (Perez-Velez and Marais, 2012; Lewinsohn et al., 2017; Ahmed et al., 2020). In pediatric primary TB, consolidation may be present and can be misdiagnosed as bacterial pneumonia; however, massive consolidation is rare (GriffithRichards et al., 2007). Primary pulmonary TB should be considered in children with lung consolidation that is unresponsive to antibiotics, despite negative IGRA and TB exposure history.

CHARACTERIZING TUBERCULOSIS PROGRESSION IN WILD MEERKATS (SURICATA SURICATTA) FROM FECAL SAMPLES AND CLINICAL SIGNS.

Tuberculosis (TB) is an increasing threat to wildlife, yet tracking its spread is challenging because infections often appear to be asymptomatic, and diagnostic tools such as blood tests can be invasive and resource intensive. Our understanding of TB biology in wildlife is therefore limited to a small number of well-studied species. Testing of fecal samples using PCR is a noninvasive method that has been used to detect Mycobacterium bovis shedding amongst badgers, yet its utility more broadly for TB monitoring in wildlife is unclear. We combined observation data of clinical signs with PCR testing of 388 fecal samples to characterize longitudinal dynamics of TB progression in 66 wild meerkats (Suricata suricatta) socially exposed to Mycobacterium suricattae between 2000 and 2018. Our specific objectives were 1) to test whether meerkat fecal samples can be used to monitor TB; 2) to characterize TB progression between three infection states (PCR-negative exposed, PCR-positive asymptomatic, and PCR positive with clinical signs); and 3) estimate individual heterogeneity in TB susceptibility, defined here as the time between TB exposure and detection, and survival after TB detection. We found that the TB detection probability once meerkats developed clinical signs was 13% (95% confidence interval 3-46%). Nevertheless, with an adapted test protocol of 10 PCR replicates per sample we detected hidden TB infections in 59% of meerkats before the onset of clinical signs. Meerkats became PCR positive approximately 14 mo after initial exposure, developed clinical signs approximately 1 yr after becoming PCR positive, and died within 5 mo of developing clinical signs. Individual variation in disease progression was high, with meerkats developing clinical signs from immediately after exposure to 3.4 yr later. Overall, our study generates novel insights into wildlife TB progression, and may help guide adapted management strategies for TB-susceptible wildlife populations.

High Prevalence of Tuberculosis Infection and Disease in Child Household Contacts of Adults With Rifampin-resistant Tuberculosis.

Household contact (HHC) investigation is an important strategy to identify individuals with tuberculosis (TB) exposure, infection and disease, including those who may benefit from tuberculosis preventive therapy (TPT). Data in children exposed to rifampin-resistant TB are limited. In preparation for and to inform the feasibility of an interventional trial, HHC of adults with pulmonary rifampin-resistant TB from high TB-burden countries were evaluated in a cross-sectional study. Using interferon-gamma release assay and study-specific and 2015 international consensus definitions of intrathoracic TB in children, we evaluated the prevalence and predictors of TB infection and disease in child (<15 years) HHCs. Of 303 child HHCs, median age (range) 7 years (0-14), 57% [95% confidence interval (CI): 50%-64%] had a positive interferon-gamma release assay result (TB infected). TB infection was associated with the index case smoking (P = 0.034), being the parent or sleeping in the same room (P = 0.002) and the child HHC being age ≥5 years and having attended school (P = 0.013). Four had study-defined confirmed TB and 9 had probable TB, a prevalence of 4.3% (95% CI: 2.6%-7.1%). Using the international consensus definitions, 4 had confirmed TB and 49 had unconfirmed TB, a prevalence of 17.2% (95% CI: 12.9%-22.4%). Twenty (7%) children had received TPT. The prevalence of TB infection and disease was high in child HHC exposed to rifampin-resistant TB. Few children had routinely received TPT. High-quality evidence is needed to inform strong recommendations for and access to TPT in children exposed to TB resistant to rifampin.

N95 masks worn to protect against COVID-19 prevented tuberculosis exposure in healthcare workers

Since the start of the COVID-19 pandemic, the healthcare workers in our institution have been equipped with N95 masks when performing aerosol-generating procedures, as these are associated with an increased risk of infection. We present a case in which using an N95 mask prevented tuberculosis (TB) exposure among healthcare workers administering prehospital care in rapid response vehicles. Even after the resolution of the COVID-19 pandemic in the future, wearing N95 masks among healthcare workers is recommended to protect against pathogens, including TB, when performing aerosol-producing procedures or prehospital activities for patients suspected of having respiratory diseases.

Association between TAP gene polymorphisms and tuberculosis susceptibility in a Han Chinese population in Guangdong

Tuberculosis (TB) is an important public health problem. Studies indicated that TAP plays a key role in the presentation and transport of antigenic peptides during anti-M.tb infection. Given the important biological role of the TAP gene involved in anti-M.tb infection, a family-based case–control study including 133 tuberculosis patients, 107 healthy household contacts, and 173 healthy controls was conducted to assess the association between TAP gene polymorphisms and TB susceptibility. The basic information of subjects and their blood samples were collected. Four SNPs including rs1135216, rs1057141, rs241447, and rs3819721 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). Our results suggested that BMI, residence, bedroom crowding, indoor humidity, fitness activities, history of smoking, and TB exposure history were associated with the occurrence of tuberculosis (P < 0.05). A significant association was observed between the TAP1 rs1135216 CT/CC genotype and increased TB risk, and the ORs were 2.56 (95% CI 1.31–4.99) and 6.73 (95% CI 1.33–34.02), respectively. TAP2 rs3819721 GG genotype carriers also showed an increased risk of TB when compared TB patients to healthy household contacts. Haplotype analysis revealed that the haplotype CT at rs1057141 and rs1135216 (OR = 11.34, 95% CI 1.49–86.56; OR = 7.45, 95% CI 1.43–38.76), as well as TA at rs241447 and rs3819721 (OR = 2.20, 95% CI 1.07–4.56) had a significantly increased risk of TB. The genetic risk scores (GRS) analysis of the four loci indicated that the risk of tuberculosis increased with increasing GRS scores in TB vs HHC (Ptrend = 0.010) and in TB vs HC (Ptrend = 0.001). In conclusion, our findings suggested that the SNPs of rs1135216 and rs3819721 were associated with TB susceptibility among the tuberculosis-prone families in the Chinese Han population and the risk of developing tuberculosis increases with the number of risk alleles, which could help identify high-risk groups in time and take scientific preventive measures. Further cohort studies with large samples are needed to validate the role of TAP gene variants on TB susceptibility.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00438-022-01885-3.

Esophageal tuberculosis induced dysphagia: a case report

BackgroundPatients can present for a wide variety of etiologies for dysphagia, and it is important to consider less common causes once common etiologies have been ruled out. Extrapulmonary Mycobacterium tuberculosis (TB) presentations are rare to see in the western populations due to relative lack of TB exposure and overall less immunocompromised populations, but should be considered for at-risk patients. Gastrointestinal (GI) TB is rare, and the GI tract is considered only the sixth most frequent site of extrapulmonary TB (EPTB).Case presentationThis is a case report of a 35-year-old Ethiopian male presenting with dysphagia and retrosternal odynophagia who was found to have infiltration of mediastinal lymphadenopathy into the esophageal wall secondary to TB. This patient underwent an upper endoscopy, which revealed a linear 2 cm full thickness mucosal defect in the middle esophagus concerning for an infiltrative process with full thickness tear. Computed tomography (CT) of the chest demonstrated a subcarinal soft tissue mass that was inseparable from the esophagus. He was referred to thoracic surgery and underwent an exploratory mediastinal dissection. A mediastinoscopy scope was inserted and the mediastinal dissection was made until the subcarinal nodes were identified and removed. Biopsy results showed necrotizing and non-necrotizing granulomas, and acid-fast bacilli (AFB) culture from the surgically removed lymph node showed Mycobacterium TB complex growth. He had no known TB exposures and did not have any TB risk factors. He then followed up in infectious disease clinic and was managed with anti-tuberculosis treatment (ATT) with complete resolution of symptoms.ConclusionsOur patient was ultimately found to have esophageal TB secondary to mediastinal invasion into the esophageal wall from lymphadenopathy associated with TB. This is an extremely rare presentation in western populations due to diminished exposure rates and overall less immunocompromised populations compared to impoverished countries with increased TB exposure and human immunodeficiency virus (HIV) infection rates. Although TB is not as commonly seen in western populations, it should be considered on the differential for any atypical presentations of GI diseases for patients with clinical or geographic risk factors.

Prevalence of latent tuberculosis infection among pre-clinical and clinical medical students using QuantiFERON-TB gold plus and tuberculin skin test at a teaching hospital in Thailand: A cross-sectional study

BackgroundHealthcare workers are considered to be at a higher risk of acquiring tuberculosis (TB) infection than the general population. Clinical medical students are part of the healthcare team and clinical practice are done during their clinical rotation. They could be exposed to similar occupational risks as the healthcare workers. Most students who become infected have latent tuberculosis infection (LTBI) and may not exhibit any clinical symptoms. Some students with LTBI can progress to TB disease during clinical rotations in the hospitals. Therefore, screening for LTBI in this population represents hospital aspect of public health strategy and infection control in medical school in high TB burden countries. ObjectiveWe aimed to determine the prevalence of LTBI among fourth-year medical students and sixth-year medical students by using QuantiFERON-TB Gold Plus (QFT-Plus) and Tuberculin Skin Test (TST). MethodsA cross-sectional study of fourth-year medical students (n = 73) and sixth-year medical students (n = 85) was conducted at the School of Medicine, Chulalongkorn University, Bangkok, Thailand. The medical students (n = 158) who met the eligibility criteria were recruited into the study. LTBI was detected by using QFT-Plus and some of the participants had a tuberculin skin test (TST). The TST was interpreted after 48–72 h. The participants who tested positive by QFT-Plus were considered to have LTBI. Demographic information and data on occupational TB exposure were collected via a questionnaire. A multivariate logistic regression was used to test for associations between independent variables and results of the QFT-Plus. ResultsA total of 158 participants were included in this study. The overall prevalence of LTBI was 6.3% (n = 10) as determined by QFT-Plus. The LTBI prevalence was higher in the sixth-year medical students (9.4%) compared to the fourth-year medical students (2.7%). Higher risk of LTBI was associated with sixth-year medical students (odds ratio, 3.69 [95%CI, 0.75–17.96]), but this was not significant. Moreover, history of occupational TB exposure without PPE yielded an odds ratio of 2.98 [95%CI, 0.68–13.12] but it was not statistically significant due to the small sample size. One hundred thirty-nine (88%) participants were BCG vaccinated as per the national vaccination requirements. No abnormal chest X-rays were found for any of the positive participants. Of the 158 participants, 41 (25.9%) of them had TST. Of the 41 participants, 6 (14.6%) tested positive at a cut-off of ≥ 10 mm for TST, which was concordant with QFT-Plus results. The agreement between the two tests was 0.57 using kappa coefficients. ConclusionThe screening of TB infection in new healthcare workers (HCWs), especially medical students, is essential to reduce future nosocomial TB incidences in the hospitals. This study showed that there was a high prevalence of LTBI among sixth-year medical students compared to fourth-year medical students. Our results suggest that tendency of higher LTBI prevalence might be associated with advanced clinical years, thus tailored public health education strategy and infection control in tertiary care hospitals for new healthcare workers in TB endemic countries may prevent nosocomial TB disease from developing in the future. Therefore, active surveillance should be done for all new HCWs, and TB preventive therapy should be administered to recent converters.

Transmission Of Tuberculosis Among illicit drug use Linkages (TOTAL): A cross-sectional observational study protocol using respondent driven sampling.

People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis (Mtb) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602. Date of Registration: 5 November 2019.

Congenital tuberculosis presenting with erythema nodosum: a case report

Erythema nodosum is an entity with a relatively low incidence of 1 to 5 per 100,000 live births. The condition is relatively uncommon in prepubertal children and exceptionally rare before 2 years of age. In the paediatric age group, both sexes are equally affected. Although uncommon in children, it remains the most frequent form of panniculitis in paediatrics for which the diagnosis is almost always clinical. The most common cause in children is streptococcal pharyngitis.The association of erythema nodosum with tuberculosis is well known in endemic areas and must always be excluded. All children with erythema nodosum should be stratified by risk for tuberculosis exposure. Congenital tuberculosis is an unusual and severe clinical presentation of tuberculosis infection. It is rare, even where tuberculosis is endemic. Timely administration of standard antitubercular treatment results in a good outcome. We report a two-month-old male infant who presented with fever, lethargy, dyspnea, and refusal to feed and whose mother was diagnosed as probable multidrug-resistant tuberculosis. Our patient emphasizes the importance of maternal history, typical skin lesions, and histopathological study in order to approach a definitive diagnosis and institute timely administration of antitubercular drugs.

Mycobacterium Species on the Cutaneous Microbiome of Very Preterm Neonates.

The neonatal skin microbiome consists of all the genomes and genetic products of microorganisms harboring on an infant's skin. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. This study was conducted to understand the neonatal skin microbiome of very preterm neonates (under 32 weeks) admitted to the Neonatal Intensive Care Unit(NICU) at a tertiary healthcare setting before and after kangaroo mother care (KMC), using next-generation sequencing (NGS). Skin swabs were collected on two different occasions and analyzed using the NGS technique after amplification via polymerase chain reaction. The results showed relative abundance for Mycobacterium tuberculosis in 83.33% and 66.67% (p = 0.29) and Mycobacteroides abscessus in 100% and 93.33% (p = 0.30) of the very preterm neonates on the skin microbiome before and after KMC, respectively as an incidental finding. The mere presence of these bacilli as commensals or as potential pathogens is alarming due to the risk of early exposure and incidence of tuberculosis from birth. These findings, in our view, are the first findings to be established in such a setting.

Diagnostic and public health investigation of Mycobacterium tuberculosis infection in a dog in Ontario, Canada

A 4-y-old, female mixed-breed dog was presented to the Ontario Veterinary College for further evaluation of multiple pulmonary and hepatic masses, intrathoracic lymphadenitis, and recent development of a pyogranulomatous pleural effusion. Along with other comprehensive tests, a thoracic lymph node biopsy was performed, and Mycobacterium tuberculosis complex infection was confirmed by real-time PCR. The dog’s condition declined post-operatively, and euthanasia was elected. Postmortem examination confirmed severe granulomatous pneumonia, hepatitis, intrathoracic and intraabdominal lymphadenitis, omentitis, and nephritis. Line-probe assays performed on samples collected postmortem confirmed the species as M. tuberculosis. 24-loci MIRU-VNTR genotyping, spoligotyping, and whole-genome sequencing revealed relations to known human isolates, but no epidemiologic link to these cases was investigated. Given the concern for potential human exposure during this animal’s disease course, a public health investigation was initiated; 45 individuals were tested for M. tuberculosis exposure, and no subsequent human infections related to this animal were identified. Our case highlights the need for more readily available, minimally invasive testing for the diagnosis of canine mycobacteriosis, and highlights the ability of canid species to act as potential contributors to the epidemiology of M. tuberculosis infections.