Patterns of cerebral tissue oxygen tension and cytoplasmic redox state in bacterial meningitis.

BACKGROUND: Compromised cerebral energy metabolism is common in patients with bacterial meningitis. In this study, simultaneous measurements of cerebral oxygen tension and lactate/pyruvate ratio were compared to explore whether disturbed energy metabolism was usually caused by insufficient tissue oxygenation or compromised oxidative metabolism of pyruvate indicating mitochondrial dysfunction. SUBJECT AND METHODS: Ten consecutive patients with severe streptococcus meningitis were included in this prospective cohort study. Intracranial pressure, brain tissue oxygen tension (PbtO2 ), and energy metabolism (intracerebral microdialysis) were continuously monitored in nine patients. A cerebral lactate/pyruvate (LP) ratio <30 was considered indicating normal oxidative metabolism, LP ratio >30 simultaneously with pyruvate below lower normal level (70 µmol/L) was interpreted as biochemical indication of ischemia, and LP ratio >30 simultaneously with a normal or increased level of pyruvate was interpreted as mitochondrial dysfunction. The biochemical variables were compared with PbtO2 simultaneously monitored within the same cerebral region. RESULTS: In two cases, the LP ratio was normal during the whole study period and the simultaneously monitored PbtO2 was 18 ± 6 mm Hg. In six cases, interpreted as mitochondrial dysfunction, the simultaneously monitored PbtO2 was 20 ± 6 mm Hg and without correlation with the LP ratio. In one patient, exhibiting a pattern interpreted as ischemia, PbtO2 decreased below 10 mm Hg and a correlation between LP and PbtO2 was observed. CONCLUSION: This study demonstrated that compromised cerebral energy metabolism, evidenced by increased LP ratio, was common in patients with severe bacterial meningitis while not related to insufficient tissue oxygenation.

Urine lipoarabinomannan point-of-care testing in patients affected by pulmonary nontuberculous mycobacteria--experiences from the Danish Cystic Fibrosis cohort study.

BACKGROUND: The urine lipoarabinomannan (LAM) strip test has been suggested as a new point-of-care test for active tuberculosis (TB) among human immunodeficiency virus (HIV) infected individuals. It has been questioned if infections with nontuberculous mycobacteria (NTM) affect assay specificity. We set forth to investigate if the test detects LAM in urine from a Danish cystic fibrosis (CF) population characterized by a high NTM prevalence and negligible TB exposure. METHOD: Patients followed at the Copenhagen CF Center were comprehensively screened for pulmonary NTM infection between May 2012 and December 2013. Urine samples were tested for LAM using the 2013 Determine™ TB LAM Ag strip test. RESULTS: Three-hundred and six patients had a total of 3,322 respiratory samples cultured for NTM and 198 had urine collected (65%). A total of 23/198 (12%) had active pulmonary NTM infection. None had active TB. The TB-LAM test had an overall positive rate of 2.5% applying a grade 2 cut-point as positivity threshold, increasing to 10.6% (21/198) if a grade 1 cut-point was applied. Among patients with NTM infection 2/23 (8.7%) had a positive LAM test result at the grade 2 cut-point and 9/23 (39.1%) at the grade 1 cut -point. Test specificity for NTM diagnosis was 98.3% and 93.1 for grade 2 and 1 cut-point respectively. CONCLUSIONS: This is the first study to assess urine LAM detection in patients with confirmed NTM infection. The study demonstrated low cross-reactivity due to NTM infection when using the recommended grade 2 cut-point as positivity threshold. This is reassuring in regards to interpretation of the LAM test for TB diagnosis in a TB prevalent setting. The test was not found suitable for NTM detection among patients with CF.

Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania.

BACKGROUND: There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages. METHODS: Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients' level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M. tuberculosis lineage of the infectious agent for each patient. RESULTS: The most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST's out of 248 isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the 'modern' (TbD1-) Euro-American lineage induced higher levels of α1-acid glycoprotein (ß = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (ß = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (ß = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern') isolates induced higher levels of CRP (ß = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (ß = 0.9, P = 0.03; 95% CI[0.09-1.70]). CONCLUSION: The low diversity of genotypes may be explained by an evolutionary advantage of the most common lineages over other lineages combined with optimal conditions for transmission, such as overcrowding and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by 'modern' lineage isolates compared to 'ancient' lineages may suggest increased virulence among 'modern' lineage isolates.

Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia.

BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months). RESULTS: Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS: Our data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART. However, the documented occurrence of transmitted resistance and accumulation of acquired HIVDR mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations.

BCG protects against tuberculosis irrespective of HIV status: a matched case-control study in Mwanza, Tanzania.

While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced risk of TB (OR 0.3, 95% CI 0.2 to 0.7, p=0.005), irrespective of HIV status (interaction, p=0.623). BCG vaccination considerably reduced the risk of TB, both among individuals with and without HIV infection.

Sex, smoking, and socioeconomic status are associated with body composition among tuberculosis patients in a deuterium dilution cross-sectional study in Mwanza, Tanzania.

Underweight is common among tuberculosis (TB) patients. However, there is little information on determinants of body composition at TB treatment initiation in high-TB-burdened countries. This study aimed to determine factors associated with body composition at commencement of TB treatment in Mwanza, Tanzania. A cross-sectional study was conducted from 2007 to 2008 among newly diagnosed TB patients. Fat and fat-free mass were determined using a deuterium dilution technique and fat and fat-free mass indices were computed. Correlates were assessed using multiple regression analysis. A total of 201 pulmonary TB patients were recruited; of these, 37.8% (76) were female, 51.7% (104) were HIV infected, 65.3% (126) had sputum-positive TB, and 24.4% (49) were current smokers. In multiple regressions analysis, males had a 2.2-kg/m(2) [(95% CI = 1.6, 2.9); P < 0.0001] lower fat mass index but 1.5 kg/m(2) [(95% CI = 0.9, 2.0); P < 0.0001] higher fat-free mass index compared with females. Sputum-positive TB was associated with a lower fat mass index among HIV-uninfected patients [-1.4 kg (95% CI = -2.5, -0.4); P = 0.006] but not among HIV-infected patients (P-interaction = 0.09). Current smokers had a 0.7-kg/m(2) [(95% CI = 0.02, 1.5); P = 0.045] lower fat mass index, but smoking did not affect fat-free mass. High socioeconomic status (SES) was associated with higher fat as well as fat-free mass. HIV infection, cluster of differentiation 4 count, and antiretroviral therapy were not correlates. Sex, smoking, and SES were associated with body composition of TB patients at treatment commencement. Prospective studies are needed to determine the role of these factors on weight gain, functional recovery, and survival during and after treatment.

Diabetes is a strong predictor of mortality during tuberculosis treatment: a prospective cohort study among tuberculosis patients from Mwanza, Tanzania.

OBJECTIVE: Strong evidence suggests diabetes may be associated with tuberculosis (TB) and could influence TB treatment outcomes. We assessed the role of diabetes on sputum culture conversion and mortality among patients undergoing TB treatment. METHODS: A total of 1250 Tanzanian TB patients were followed prospectively during TB treatment with sputum culture after 2 and 5 months. Survival status was assessed at least 1 year after initiation of treatment. At baseline, all participants underwent testing for diabetes and HIV, and the serum concentration of the acute phase reactant alpha-1 glycoprotein (AGP) was determined. RESULTS: There were no differences between participants with and without diabetes regarding the proportion of positive cultures at 2 (3.8% vs. 5.8%) and 5 (1.3% vs. 0.9%) months (P > 0.46). However, among patients with a positive TB culture, relatively more patients with diabetes died before the 5-month follow-up. Within the initial 100 days of TB treatment, diabetes was associated with a fivefold increased risk of mortality (RR 5.09, 95% CI 2.36; 11.02, P < 0.001) among HIV uninfected, and a twofold increase among HIV co-infected patient (RR 2.33 95% CI 1.20; 4.53, P = 0.012), while diabetes was not associated with long-term mortality. Further adjustment with AGP did not change the estimates. CONCLUSION: Diabetes considerably increases risk of early mortality during TB treatment. The effect may not be explained by increased severity of TB, but could be due to impaired TB treatment response. Research is needed to clarify the mechanism and to assess whether glycaemic control improves survival.

The role of diabetes on the clinical manifestations of pulmonary tuberculosis.

OBJECTIVE: Diabetes is associated with pulmonary tuberculosis (TB), possibly due to impaired immunity, and diabetes may exacerbate the clinical manifestations of TB. Our aim was to assess the role of diabetes in the clinical manifestations of TB. METHODS: We studied 1250 patients with pulmonary TB in an urban population in a cross-sectional study in Tanzania. All participants were tested for diabetes and HIV co-infection, and TB culture intensity was assessed. Levels of white blood cells, haemoglobin, acute phase reactants, CD4 count and HIV viral load were measured, and a qualitative morbidity questionnaire was used to identify the prevalence of disease-related symptoms. RESULTS: Tuberculosis patients with diabetes had a higher neutrophil count (B 0.5 × 10(9) cells/l, 95% CI 0.2; 0.9, P = 0.001) than non-diabetic TB patients. Serum C-reactive protein (B 18.8 mg/l, CI 95% 8.2; 29.4, P = 0.001) and alpha-1-acid glycoprotein (B 0.2 g/l, CI 95% 0.03; 0.3, P = 0.02) were similarly higher in patients with diabetes. Diabetes did not affect culture intensity or HIV status, but self-reported fever was three times higher among participants with diabetes than in those without diabetes (OR 2.9, CI 95% 1.5; 5.7, P = 0.002). CONCLUSION: Diabetes is associated with small changes in the manifestations of TB, but may have little clinical significance.

CD4 lymphocyte dynamics in Tanzanian pulmonary tuberculosis patients with and without HIV co-infection.

BACKGROUND: The interaction of HIV and tuberculosis (TB) on CD4 levels over time is complex and has been divergently reported. METHODS: CD4 counts were assessed from time of diagnosis till the end of TB treatment in a cohort of pulmonary TB patients with and without HIV co-infection and compared with cross-sectional data on age- and sex-matched non-TB controls from the same area. RESULTS: Of 1,605 study participants, 1,250 were PTB patients and 355 were non-TB controls. At baseline, HIV was associated with 246 (95% CI: 203; 279) cells per µL lower CD4 counts. All PTB patients had 100 cells per µL lower CD4 counts than the healthy controls. The CD4 levels were largely unchanged during a five-month of TB treatment. HIV infected patients not receiving ART at any time and those already on ART at baseline had no increase in CD4 counts after 5 months of TB treatment, whereas those prescribed ART between baseline and 2 months, and between 2 and 5 months increased by 69 (22;117) and 110 (52; 168) CD4 cells per µL after 5 months. CONCLUSIONS: The increase in circulating CD4 levels observed in PTB in patients is acquired after 2 months of treatment irrespective of HIV status. Initiation of ART is the strongest factor correlated with CD4 increase during TB treatment. TRIAL REGISTRATION NUMBER: Clinical trials.gov: NCT00311298.

Negative effect of smoking on the performance of the QuantiFERON TB gold in tube test.

BACKGROUND: False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. METHODS: Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. RESULTS: Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). CONCLUSIONS: Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status.

Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection predisposes to tuberculosis (TB). We described incidence, risk factors and prognosis of TB in HIV-1 infected patients during pre (1995-1996), early (1997-1999), and late Highly Active Antiretroviral Therapy (HAART) (2000-2007) periods. METHODS: We included patients from a population-based, multicenter, nationwide cohort. We calculated incidence rates (IRs) and mortality rates (MRs). Cox's regression analysis was used to estimate risk factors for TB infection with HAART initiation included as time updated variable. Kaplan-Meier was used to estimate mortality after TB. RESULTS: Among 2,668 patients identified, 120 patients developed TB during the follow-up period. The overall IR was 8.2 cases of TB/1,000 person-years of follow-up (PYR). IRs decreased during the pre-, early and late-HAART periods (37.1/1000 PYR, 12.9/1000 PYR and 6.5/1000 PYR respectively). African and Asian origin, low CD4 cell count and heterosexual and injection drug user route of HIV transmission were risk factors for TB and start of HAART reduced the risk substantially. The overall MR in TB patients was 34.4 deaths per 1,000 PYR (95% Confidence Interval: 22.0-54.0) and was highest in the first two years after the diagnosis of TB. CONCLUSIONS: Incidence of TB still associated with conventional risk factors as country of birth, low CD4 count and route of HIV infection while HAART reduces the risk substantially. The mortality in this patient population is high in the first two years after TB diagnosis.

BCG vaccination status may predict sputum conversion in patients with pulmonary tuberculosis: a new consideration for an old vaccine?

BACKGROUND: Failure to convert (persistent sputum and/or culture positivity) while on antituberculosis (anti-TB) treatment at the end of the second month of anti-TB therapy has been reported to be a predictor of treatment failure. Factors that could be associated with persistent bacillary positivity at the end of the second month after initiation of anti-TB treatment were assessed. METHODS: A prospective cohort study was conducted in 754 patients with sputum culture positive pulmonary TB in Mwanza, Tanzania. Information on social demographic characteristics, anthropometric measurements, BCG scar status, HIV status, CD4+ count, white blood cell count, haemoglobin and sputum culture status was obtained. RESULTS: Factors associated with sputum culture non-conversion at the end of the second month of anti-TB treatment were initial acid-fast bacilli (AFB) culture grading of 3+ (OR 5.70, 95% CI 1.34 to 24.31, p=0.02) and absence of a BCG scar (OR 3.35, 95% CI 1.48 to 7.58, p=0.004). CONCLUSION: Patients with pulmonary TB with no BCG scar and high initial AFB sputum intensity are at risk of remaining sputum culture positive at the end of the second month of anti-TB treatment. These findings reflect a beneficial role for BCG vaccination on sputum conversion which should also be examined in large studies in other areas. The finding of a beneficial role for BCG vaccination on the treatment of pulmonary TB is important for TB control and vaccination programmes.

Infrequent detection of Pneumocystis jirovecii by PCR in oral wash specimens from TB patients with or without HIV and healthy contacts in Tanzania.

BACKGROUND: In tuberculosis (TB) endemic parts of the world, patients with pulmonary symptoms are managed as "smear-negative TB patients" if they do not improve on a two-week presumptive, broad-spectrum course of antibiotic treatment even if they are TB microscopy smear negative. These patients are frequently HIV positive and have a higher mortality than smear-positive TB patients. Lack of access to diagnose Pneumocystis jirovecii pneumonia might be a contributing reason. We therefore assessed the prevalence of P. jirovecii by PCR in oral wash specimens among TB patients and healthy individuals in an HIV- and TB-endemic area of sub-Saharan Africa. METHODS: A prospective study of 384 patients initiating treatment for sputum smear-positive and smear-negative TB and 100 healthy household contacts and neighbourhood controls. DNA from oral wash specimens was examined by PCR for P. jirovecii. All patients delivered sputum for TB microscopy and culture. Healthy contacts and community controls were clinically assessed and all study subjects were HIV tested and had CD4 cell counts determined. Clinical status and mortality was assessed after a follow-up period of 5 months. RESULTS: 384 patients and 100 controls were included, 53% and 8% HIV positive respectively. A total number of 65 patients and controls (13.6%) were at definitive risk for PCP based on CD4 counts <200 cells per mm3 and no specific PCP prophylaxis. Only a single patient (0.3% of the patients) was PCR positive for P. jirovecii. None of the healthy household contacts or neighbourhood controls had PCR-detectable P. jirovecii DNA in their oral wash specimens regardless of HIV-status. CONCLUSIONS: The prevalence of P. jirovecii as detected by PCR on oral wash specimens was very low among TB patients with or without HIV and healthy individuals in Tanzania. Colonisation by P. jirovecii was not detected among healthy controls. The present findings may encourage diagnostic use of this non-invasive method.

Diabetes prevalence by HbA1c and oral glucose tolerance test among HIV-infected and uninfected Tanzanian adults.

BACKGROUND: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania. METHODS: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes. RESULTS: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/µL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT. CONCLUSIONS: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.

A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs.

INTRODUCTION: Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK). OBJECTIVES: The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature. METHODS: Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250). RESULTS: Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration (Cmax) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration-time curve and/or Cmax for at least one FLD. CONCLUSIONS: HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.

Mycobacterium marinum infections in Denmark from 2004 to 2017: A retrospective study of incidence, patient characteristics, treatment regimens and outcome.

Mycobacterium marinum (M. marinum) is a slowly growing nontuberculous mycobacterium. The incidence of M. marinum infections in Denmark is unknown. We conducted a retrospective nationwide study including all culture confirmed cases of M. marinum from 2004 to 2017 in Denmark. All available medical records were reviewed. Demographics, clinical characteristics, and treatment regiments were analyzed. Fifty-five patients were identified, 40 (72.7%) were men with a median age of 50 years. Aquatic exposure was reported by 48 (90.6%) of the patients. Site of infection was upper extremities in 49 (92.5%) patients and 49 (92.5%) had superficial infection. The median time from symptom presentation to diagnosis was 194 days. All patients received antibiotics. Median time of treatment duration among all patients was 112 days. Treatment outcome was classified as improved in 40 (75%), improved with sequela in 4 (7.6%) patients and only 3 patients (3.8%) were classified as failed. Infection with M. marinum is rare and there is a long delay from symptom manifestation to diagnosis. The infection is predominantly related to aquatic exposure. M. marinum should be a differential diagnose in patients with slow-developing cutaneous elements and relevant exposure. Treatment outcomes are overall good and severe sequela are rare.

The prevalence of latent Mycobacterium tuberculosis infection based on an interferon-γ release assay: a cross-sectional survey among urban adults in Mwanza, Tanzania.

INTRODUCTION: One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. METHODS: The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. RESULTS: 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10(B) 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test. CONCLUSION: LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies.

Anti-tuberculosis drug resistance pattern among pulmonary tuberculosis patients with or without HIV infection in Mwanza, Tanzania.

Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control, particularly multi-drug resistance TB (MDR-TB). The objective of this study was to determine the prevalence of primary and acquired anti-TB drug resistance among newly diagnosed pulmonary TB (PTB) and relapse cases. Sputa were collected from newly diagnosed and relapse PTB patients. Drug susceptibility tests (DST) were performed on sputum culture positive isolates of Mycobacterium tuberculosis using resistance ratio method on four first-line anti-TB drugs: rifampicin, isoniazid, ethambutol and streptomycin. Demographic and anthropometric information was collected and HIV status was determined. Of the 523 culture positive isolates, DST results were available for 503 (96%), 455 were new and 48 were relapse cases. Resistance to at least one of the four drugs was observed in 7.8% (39/503) of the isolates, 7.3% (33/455) were new and 12.5% (6/48) were from relapse cases. Mono resistance to isoniazid was higher in both among new 45.5% (15/33) and relapse 50.0% (3/6) cases. Resistance to rifampicin and streptomycin alone was equal 4/33 (12.1%) and only among new cases. Resistance to ethambutol alone was only one among new cases. Overall MDR-TB prevalence was 2.4% (12/503), nine were new and three were relapse cases. MDR-TB was 17.9% (7/39) for rifampicin and isoniazid. Prevalence of HIV was 43.3% and was similar among new and relapse cases and not risk factor for drug resistance. Majority of PTB patients (52%) had BMI below 18 kg/m2. Those with BMI greater than 18 kg/m2 were more likely to develop drug resistance than those with BMI below 18 kg/m2 (P=0.004). With the resurgence of TB and the high prevalence of HIV among TB patients, prevalence of drug resistance is still low both among new and relapses cases. Despite the current low drug resistance, there is a need for continuous monitoring of the resistance.

How dormant is Mycobacterium tuberculosis during latency? A study integrating genomics and molecular epidemiology.

Mycobacterium tuberculosis may survive for decades in the human body in a state termed latent tuberculosis infection (LTBI). We investigated the occurrence during LTBI of insertion/deletion events in a selected set of mononucleotide simple sequence repeats, DNA sequence changes in four M. tuberculosis genes, and large sequence variations in 4750 M. tuberculosis open reading frames. We studied 13 paired M. tuberculosis clinical isolates, with each pair representing a reactivation of LTBI more than three decades after primary infection. Absence of sequence variations between paired isolates in nearly all investigated loci suggests a low likelihood of bacterial replication during LTBI.