Ventriculostomy-associated infection (VAI) in patients with acute brain injury-a retrospective study.

BACKGROUND: Ventriculostomy-associated infection (VAI) is common after external ventricular drains (EVD) insertion but is difficult to diagnose in patients with acute brain injury. Previously, we proposed a set of criteria for ruling out VAI in traumatic brain injury. This study aimed to validate these criteria. For exploratory purposes, we sought to develop and validate a score for VAI risk assessment in patients with different types of severe acute brain injury. METHODS: This retrospective cohort study included adults with acute brain injury who received an EVD and in whom CSF samples were taken over a period of 57 months. As standard non-coated bolt-connected EVDs were used. The predictive performance of biomarkers was analyzed as defined previously. A multivariable regression model was performed with five variables. RESULTS: A total of 683 patients with acute brain injury underwent EVD placement and had 1272 CSF samples; 92 (13.5%) patients were categorized as culture-positive VAI, 130 (19%) as culture-negative VAI, and 461 (67.5%) as no VAI. A low CSF WBC/RBC ratio (< 0.037), high CSF/plasma glucose ratio (> 0.6), and low CSF protein (< 0.5g/L) showed a positive predictive value of 0.09 (95%CI, 0.05-0.13). In the multivariable logistic regression model, days to sample (OR 1.09; 95%CI, 1.03-1.16) and CSF WBC/RBC ratio (OR 34.86; 95%CI, 3.94-683.15) were found to predict VAI. CONCLUSION: In patients with acute brain injury and an EVD, our proposed combined cut-off for ruling out VAI performed satisfactorily. Days to sample and CSF WBC/RBC ratio were found independent predictors for VAI in the multivariable logistic regression model.

Global treatment outcomes of extensively drug-resistant tuberculosis in adults: A systematic review and meta-analysis.

INTRODUCTION: Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes. METHODS: We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961. RESULTS: Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5). CONCLUSION: Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.

Mortality, risk factors, and causes of death among people with tuberculosis in Denmark, 1990-2018.

OBJECTIVES: This study aimed to analyze mortality, risk factors, and causes of death among people with tuberculosis (TB). METHODS: This is a population-based cohort study with patients with TB ≥18 years notified from 1990 to 2018 in Denmark, compared with sex- and age-matched controls. Mortality was assessed in Kaplan-Meier models and risk factors for death were estimated in Cox proportional hazards models. RESULTS: Overall mortality was twofold higher among people with TB compared with controls up to 15 years after TB diagnosis (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 2.06-2.29, P <0.0001). Danes with TB were three times more likely to die than migrants (adjusted HR: 3.13, 95% CI: 2.84-3.45, P <0.0001). Risk factors for death included living alone, being unemployed, having low income, and comorbidities such as mental illness with substance abuse, lung diseases, hepatitis, and HIV. TB was the most common cause of death (21%), followed by chronic obstructive pulmonary disease (7%), lung cancer (6%), alcoholic liver disease (5%), and mental illness with substance abuse (4%). CONCLUSION: People with TB had substantially inferior survival up to 15 years after TB diagnosis, in particular, socially disadvantaged Danes with TB with specific comorbidities. This may reflect unmet needs for enhanced treatment of other medical/social conditions during TB treatment.

Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report.

Tuberculosis (TB) presents a serious health problem with approximately a quarter of the world's population infected with Mycobacterium tuberculosis (M. tuberculosis) in an asymptomatic latent state of which 5-10% develops active TB at some point in their lives. The antimicrobial protein cathelicidin has broad antimicrobial activity towards viruses and bacteria including M. tuberculosis. Vitamin D increases the expression of cathelicidin in many cell types including macrophages, and it has been suggested that the vitamin D-mediated antimicrobial activity against M. tuberculosis is dependent on the induction of cathelicidin. However, unraveling the immunoregulatory effects of vitamin D in humans is hampered by the lack of suitable experimental models. We have previously described a family in which members suffer from hereditary vitamin D-resistant rickets (HVDRR). The family carry a mutation in the DNA-binding domain of the vitamin D receptor (VDR). This mutation leads to a non-functional VDR, meaning that vitamin D cannot exert its effect in family members homozygous for the mutation. Studies of HVDRR patients open unique possibilities to gain insight in the immunoregulatory roles of vitamin D in humans. Here we describe the impaired ability of macrophages to produce cathelicidin in a HVDRR patient, who in her adolescence suffered from extrapulmonary TB. The present case is a rare experiment of nature, which illustrates the importance of vitamin D in the pathophysiology of combating M. tuberculosis.

Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review.

OBJECTIVES: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. METHODS: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated. RESULTS: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%). CONCLUSION: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.

Social determinants of tuberculosis: a nationwide case-control study, Denmark, 1990-2018.

BACKGROUND: The global vision is a world free of tuberculosis (TB). Even in resource-rich TB low-incidence settings, we need more focus on the role of social risk factors to end the TB epidemic. METHODS: Nationwide, retrospective register-based, case-control study from 1990 to 2018, including all TB patients in Denmark ≥18 years old (n = 9581) matched 1:3 on sex and age with population controls. TB risk factors were assessed in logistic regression models and estimated by odds ratio (OR). RESULTS: All TB patients had considerably lower socio-economic status compared with controls (P < 0.0001). Among ethnic Danes, TB was mostly found among males, persons between 35 and 65 years, those living alone, those with low educational level, persons on social welfare benefits and those with low income. Conversely, for migrants, being younger, sex and living alone were less important, whereas having children was protective. In an adjusted multivariable regression model among Danes, key risk factors for TB were being on disability pension (OR = 2.7) and cash benefits (OR = 4.7). For migrants, fewer social risk factors increased TB risk, although low income and cash benefits did (OR = 3.1). CONCLUSION: Even today in a resourceful setting, socio-economic status drives disparities in health. In our study, multifactorial social deprivation was highly associated with TB. Especially household structure, education, employment and income were important risk factors that should be addressed in the future to accelerate TB control and end the TB epidemic.

Pregnancy and post-partum tuberculosis; a nationwide register-based case-control study, Denmark, 1990 to 2018.

BackgroundPregnancy increases the risk of tuberculosis (TB), however, data on TB epidemiology in pregnant women are limited.AimTo guide possible interventions, we analysed risk factors for TB in pregnant and post-partum women.MethodsWe conducted a nationwide retrospective register-based case-control study from January 1990 to December 2018 in Denmark. Cases were women diagnosed with TB during their pregnancy or in the post-partum period. We selected two control groups: pregnant or post-partum women without TB, and non-pregnant women with TB. Differences were assessed by chi-squared or Fisher's exact test. Risk factors for TB were identified through logistic regression and estimated by odds ratio (OR).ResultsWe identified 392 cases, including 286 pregnant and 106 post-partum women. Most were migrants (n = 366; 93%) with a shorter median time spent in Denmark (2.74 years; interquartile range (IQR): 1.52-4.64) than non-pregnant TB controls (3.98 years; IQR: 1.43-8.51). Cases less likely had a Charlson comorbidity index ≥ 2compared with non-pregnant TB controls (p < 0.0001), and had no increased risk of severe disease (p = 0.847). Migrants from other World Health Organization regions than Europe, especially Africa (OR: 187; 95%CI: 125-281) had persistently higher odds of TB.ConclusionsIn Denmark, the risk of TB in pregnant and post-partum women is increased in migrant women who have stayed in the country a median time of approximately 3 years. We recommend increased focus on TB risk during pregnancy and suggest evaluating targeted TB screening of selected at-risk pregnant women to promote early case finding and prevent TB among mothers and their newborn children.

Disseminated Mycobacterium avium complex infection in a woman with anti-interferon-γ autoantibodies.

Defects in the interleukin-12/interferon-gamma (IFN-γ) pathway and anti-IFN-γ antibodies have been associated with severe nontuberculous mycobacteria (NTM) infections. Consequently, disseminated NTM infections should prompt investigations for immunodeficiency. Herein, we report a case of a treatment refractory and ultimately disseminated and fatal Mycobacterium avium complex infection in a 71-year-old woman of Thai origin. Simultaneously, she had recurrent Salmonella kentucky cultured from stool samples and chronic perianal HSV-2 lesions. Late in the course of disease, anti-IFN-γ autoantibodies were demonstrated. Clinical studies investigating immunomodulating therapy and treatment among patients with anti-IFN-γ autoantibodies are lacking and, in this case, treatment seemed of a more palliative nature.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

CT and MR neuroimaging findings in patients with Lyme neuroborreliosis: A national prospective cohort study.

BACKGROUND: We aimed to describe the use and findings of cranial computerized tomography (CT-head), spine and brain magnetic resonance imaging (MRI-spine/MRI-brain) in Lyme neuroborreliose (LNB). METHODS: Patients with LNB were identified using a nationwide, population-based prospective cohort of all adults treated for neuroinfections at departments of infectious diseases in Denmark from 2015 to 2019. Multivariate logistic regression analyses assessed associations between clinical characteristics and MRI-findings consistent with LNB. RESULTS: We included 368 patients (272 definite LNB and 96 probable LNB), 280 scans were performed in 198 patients. Neuroimaging was associated with older age (59 vs. 57, p = 0.03), suspicion of other diseases (77% vs. 37%, p < 0.0001), no history of tick bites (58% vs. 43%, p = 0.01), physical/cognitive deficits prior to admission (15% vs 5%, p = 0.006), peripheral palsy (10% vs. 2%, p = 0.0008), encephalitis (8% vs. 1%, p = 0.0007) and cognitive impairment (8% vs. 2%, p = 0.03) compared with those without neuroimaging. Normal or incidental findings were common (93/98 CT-head and 154/182 MRI). 1/98 CT-head, 19/131 MRI-brain and 6/51 MRI-spine had findings consistent with LNB. Symptoms ≥45 days was associated with MRI-findings consistent with LNB (adjusted odds ratio (aOR) 4.2, 95%confidence interval 1.2-14.4, p = 0.02). CONCLUSION: In this Danish cohort including 368 LNB-patients, use of neuroimaging was common and often performed in older comorbid patients without previous tick-bite intended to investigate alternative diagnoses. The results were in general without pathology and neuroimaging cannot exclude LNB or replace lumbar puncture. MRI is of value when investigating alternative neurological diseases and may support suspicion of LNB in cases with meningeal/leptomeningeal/neural enhancement.

Tuberculosis among Patients Undergoing Solid Organ Transplantation or Dialysis in a Low-Endemic Country, 2004-2017.

BACKGROUND: The risk of active TB among solid organ transplant (SOT) recipients and patients initiating chronic dialysis in a country with low incidence of TB is not well elucidated. METHODS: Patients aged >18 years who were transplanted with a solid organ or initiated chronic dialysis at Copenhagen University Hospital in the period 2004-2017 were followed from date of transplantation or initiation of dialysis. Data on demographics and outcomes were obtained from nationwide registries. RESULTS: We included 1,989 SOT recipients and 1,305 patients initiating chronic dialysis, who were followed for a total of 9,785 and 4,196 person-years (PY), respectively. Only a minority of patients had been screened for latent TB prior to SOT or initiation of dialysis. The incidence rates (IRs)/100,000 PY of TB among patients from medium/high TB endemic areas were 358 (95% CI 115-1,110) and 1,266 (95% CI 681-2354) for SOT and dialysis patients, respectively, whereas IRs among patients of Danish origin were 11 (95% CI 2-81) and 31 (95% CI 4-218). CONCLUSION: The incidence of TB among immunosuppressed immigrants from medium/high TB endemic countries was very high, while the risk of TB among patients from low-endemic countries was minimal.

Mycobacterium arosiense, an unexpected cause of osteomyelitis in a patient with sarcoidosis: a case report.

BACKGROUND: Nontuberculous mycobacteria belonging to the Mycobacterium avium complex are recognized as opportunistic pathogens to humans. Mycobacterium arosiense is one of the novel members of the Mycobacterium avium complex. The organism has only rarely been reported in human clinical cases and may be routinely misidentified. CASE PRESENTATION: An adult male with a history of a discus prolapse and sarcoidosis presented with high fever and a strong back pain with projection to the extremities. A Magnetic Resonance Imaging scan of columna revealed a tumor suspect process at thoracic vertebrae 11/12 with changes at the second lumbar vertebra, which was partly removed by laminectomy. Biopsy smears revealed acid-fast bacilli and turned out to be Mycobacterium tuberculosis complex PCR negative. The routine line probe assay INNO-LiPa v2 (INNOGENETICS NV, Gent), which differentiates 16 mycobacterial species indicated the presence of a not readily identifiable NTM species. Whereas, the GenoType Mycobacterium CM v2.0 (HAIN Lifescience GmbH) that routinely differentiates 14 clinically relevant mycobacteria revealed a Mycobacterium intracellulare species. However, additional diagnostic sequencing of the 16S rRNA gene confirmed the presence of a Mycobacterium arosiense species. CONCLUSIONS: This is the second unusual case of osteomyelitis with clinical significance ever to be reported, caused by Mycobacterium arosiense and complicated by an underlying sarcoidosis. Mycobacterium arosiense has rarely been reported clinically and the first description of the species was identified as the cause of osteomyelitis in a child with a hereditary partial interferon gamma deficiency. Symptoms attributed to sarcoidosis waned on Mycobacterium arosiense treatment and it is inconclusive whether the patient ever suffered from sarcoidosis. Mycobacterium arosiense was misidentified by the GenoType as Mycobacterium intracellulare and implicates that the diagnosis requires supplemental sequencing of the 16S rRNA gene.

Set-up and validation of mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) analysis of Mycobacterium tuberculosis using BioNumerics software.

The objective was to describe and validate a new and alternative software procedure for 24-locus mycobacterial interspersed repetitive unit-variable number-tandem repeat (MIRU-VNTR) typing of Mycobacterium tuberculosis (Mtb) based on the multipurpose BioNumerics software. DNA from randomly selected isolates of Mtb from two European laboratories, including external control samples for MIRU-VNTR typing, were analysed. Samples were genotyped using the commercial 24-locus VNTR typing kit from GenoScreen. The PCR amplified fragments were separated by capillary electrophoresis. For the subsequent analyses, the currently used software GeneMapper was compared with BioNumerics. The endpoint was the level of concordance when comparing genotyping results obtained from BioNumerics with results obtained from GeneMapper and the ECDC proficiency study reference results. Also, the number of necessary manual standard size corrections and allele assignments in the two different software methods were compared. In total, 272 DNA samples, including the ECDC proficiency panel, were analysed. For all samples, there were 100% concordance of results. For a randomly selected set of 96 samples the numbers of manual corrections needed for size standards were 199 with GeneMapper versus zero for BioNumerics. The numbers of manual corrections for allele assignments were 122 with GeneMapper versus 16 with BioNumerics. In conclusion, we have validated the multipurpose software BioNumerics for standard 24-locus MIRU-VNTR typing and the software shows promising benefits in terms of simplification and minimization of hand-on time.

Prevalence and significance of Mycoplasma genitalium in women living with HIV in Denmark.

OBJECTIVE: Mycoplasma genitalium (M. genitalium) is a sexually transmitted pathogen associated with urethritis, cervicitis, and pelvic inflammatory disease. Previous studies have shown a strong association between M. genitalium and HIV infection, therefore screening and treatment for M. genitalium has been suggested as part of HIV prevention strategies. The objective of this study was to determine the prevalence of M. genitalium in women living with HIV (WLWH) in Denmark, and to compare the result with data on symptoms from the lower abdomen, sexual habits and immune status. 234 women, recruited from Danish HIV centres as part of a larger observational study on aspects of living with HIV as a woman (the SHADE study), were included. RESULTS: We tested cervical samples for M. genitalium by specific PCR. We found three samples positive (1.3%). The women were between 30 and 50 years old, all were of Asian origin, sexually active, and on antiretroviral treatment with supressed HIV RNA and CD4 count >350 cells/µL. None reported symptoms from the lower abdomen. The prevalence of M. genitalium infection in WLWH in Denmark is low, thus systematic screening for M. genitalium in this group does not seem relevant.

Erythema nodosum and the risk of tuberculosis in a high incidence setting.

OBJECTIVE: This study estimates the erythema nodosum (EN) incidence in a tuberculosis (TB) endemic setting and evaluates the likelihood of a subsequent TB diagnosis among individuals with Mycobacterium tuberculosis infection (MTI) with or without EN. DESIGN: We estimated EN incidence rates (IRs) in East Greenland in 2010-2011 and conducted a cohort study following all individuals who tested positive for MTI from 1 January 2010 until 31 December 2012. A personal identifier allowed individual follow-up in the mandatory TB register. MTI was defined by a positive interferon-gamma release assay. TB incidence rate ratios (IRRs) among participants with or without EN were estimated with the Cox proportional hazard model. RESULTS: We identified 38 EN cases corresponding to an IR of 500/100,000 inhabitants/year. All cases were among individuals with MTI. The EN IR was 11.79 (95% CI 5.73-24.27) times higher for BCG-unvaccinated compared with BCG-vaccinated individuals. The TB IRR was 25 (95% CI 11-60) within 1 month of EN compared to individuals without EN. CONCLUSION: This study documents a high EN incidence in a TB endemic region. EN occurred only in individuals with MTI, and predominantly among BCG-unvaccinated individuals. EN was significantly associated with a TB diagnosis within 1 month of diagnosis.

Tuberculosis screening in patients with HIV: use of audit and feedback to improve quality of care in Ghana.

BACKGROUND: Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice is scarce. OBJECTIVES: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. DESIGN: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations' guidelines for symptom-based tuberculosis screening among PLHIV. RESULTS: Twenty-one healthcare providers registered a total of 2,666 consultations; 1,368 consultations before and 1,298 consultations after the feedback intervention. Tuberculosis suspicion rate during consultation increased from 12.6 to 20.9% after feedback (odds ratio, OR 1.83; 95% confidence interval, CI: 1.09-3.09). Before feedback, sputum smear microscopy was requested for 58.7% of patients with suspected tuberculosis, for 47.2% of patients with cough ≥2 weeks, and for 27.5% of patients with a positive World Health Organization (WHO) symptom screen (any of current cough, fever, weight loss or night sweats). After feedback, patients with a positive WHO symptom screen were more likely to be suspected of tuberculosis (OR 2.21; 95% CI: 1.19-4.09) and referred for microscopy (OR 2.71; 95% CI: 1.25-5.86). CONCLUSIONS: A simple prospective audit tool identified flaws in clinical practices for tuberculosis screening of PLHIV. There was no systematic identification of people with suspected active tuberculosis. We found low initial tuberculosis suspicion rate compounded by low referral rates of relevant patients for sputum smear microscopy. Adherence to recommended standards and guidelines for tuberculosis screening improved after performance feedback.

Tuberculosis and non-tuberculous mycobacteria among HIV-infected individuals in Ghana.

OBJECTIVES: To assess the prevalence and clinical importance of previously unrecognised tuberculosis (TB) and isolation of non-tuberculous mycobacteria (NTM) among HIV-infected individuals in a teaching hospital in Ghana. METHODS: Intensified mycobacterial case finding was conducted among HIV-positive individuals before initiation of antiretroviral therapy (ART). Data were collected on socio-demographic characteristics, medical history and TB-related signs and symptoms, and participants were followed for six months to determine treatment and vital status. Two sputum samples were obtained and examined for mycobacteria with smear microscopy, culture and Xpert MTB/RIF assay. NTM species were identified with the GenoType Mycobacterium CM/AS or sequence analysis of 16S rRNA gene. RESULTS: Of 473 participants, 60 (12.7%) had confirmed pulmonary TB, and 38 (8.0%) had positive cultures for NTM. Mycobacterium avium complex was identified in 9/38 (23.7%) of NTM isolates. Participants with NTM isolated were more likely to have CD4 cell count< 100 cells/µL (aOR 2.37; 95% CI: 1.10-5.14), BMI<18.5kg/m(2) (aOR 2.51; 95% CI: 1.15-5.51) and fever ≥2 weeks (aOR 2.76; 95% CI: 1.27-6.03) at baseline than participants with no mycobacteria. By six months, 76 (16.1%) participants had died; 20 (33.3%) with confirmed TB and 9 (23.7%) with NTM-positive culture. Mortality at six months was independently associated with TB diagnosis at enrolment (aHR 1.97; 95% CI 1.09-3.59), but not with NTM isolation after controlling for age, sex, CD4 cell count, BMI, prolonged fever and ART initiation. CONCLUSIONS: Intensified mycobacterial screening of HIV-infected individuals revealed a high burden of unrecognised pulmonary TB before ART initiation, which increased risk of death within six months. NTM were frequently isolated and associated with signs of poor clinical status but not with increased mortality.

Occupational Tuberculosis in Denmark through 21 Years Analysed by Nationwide Genotyping.

Tuberculosis (TB) is a well-known occupational hazard. Based on more than two decades (1992-2012) of centralized nationwide genotyping of all Mycobacterium tuberculosis culture-positive TB patients in Denmark, we compared M. tuberculosis genotypes from all cases notified as presumed occupational (N = 130) with M. tuberculosis genotypes from all TB cases present in the country (N = 7,127). From 1992 through 2006, the IS6110 Restriction Fragment Length Polymorphism (RFLP) method was used for genotyping, whereas from 2005 to present, the 24-locus-based Mycobacterial Interspersed Repetitive Unit-Variable Number of Tandem Repeat (MIRU-VNTR) was used. An occupational TB case was classified as clustered if the genotype was 100% identical to at least one other genotype. Subsequently, based on genotype, time period, smear positivity, geography, susceptibility pattern, and any reported epidemiological links between the occupational cases and any potential source cases, the occupational case was categorized as confirmed, likely, possible or unlikely occupationally infected. Among the 130 notified presumed occupational cases, 12 (9.2%) could be classified as confirmed and 46 (35.4%) as unlikely, accounting for nearly half of all cases (44.6%). The remaining 72 cases (55.4%) were categorized as possible. Within this group, 15 cases (11.5%) were assessed to be likely occupational. Our study shows that genotyping can serve as an important tool for disentangle occupational TB in high-income low incidence settings, but still needs to be combined with good epidemiological linkage information.