Pyrazinamide is important in tuberculosis treatment, as it is bactericidal to semidormant mycobacteria not killed by other antituberculosis drugs. Pyrazinamide is also one of the cornerstone drugs retained in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, due to technical difficulties, routine drug susceptibility testing of Mycobacterium tuberculosis for pyrazinamide is, in many laboratories, not performed. The objective of our study was to generate information on pyrazinamide susceptibility among South African MDR and susceptible M. tuberculosis isolates from pulmonary tuberculosis patients. Seventy-one MDR and 59 fully susceptible M. tuberculosis isolates collected during the national surveillance study (

Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Background During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in healthcare workers (HCW) due to overburdened healthcare systems. However, whether infected HCW acquire protective immunity against SARS-CoV-2 is unclear. Here, we characterized SARS-CoV-2-specific antibody responses in Norwegian HCW in a prospective cohort study. Methods We enrolled 607 HCW pre- and post-the first COVID-19-pandemic wave. Exposure history, COVID-19-like symptoms and serum samples were collected. SARS-CoV-2-specific antibodies were characterized by spike-protein IgG/IgM/IgA enzyme-linked immunosorbent and live-virus neutralization assays. Results Spike-specific IgG, IgM, and IgA antibodies increased after the first pandemic wave in HCW with COVID-19-patient exposure, but not in HCW without patient exposure. Thirty-two HCW (5.3%) had spike-specific antibodies (11 seroconverted with ≥4-fold increase, 21 were seropositive at baseline). Neutralizing antibodies were found in 11 HCW that seroconverted, of whom 4 (36.4%) were asymptomatic. Ninety-seven HCW were tested by reverse-transcriptase-polymerase chain reaction (RT-PCR) during follow-up, 8 were positive (7 seroconverted and 1 had undetectable antibodies). Conclusions We found increases in SARS-CoV-2-neutralizing antibodies in infected HCW, especially after COVID-19-patient exposure. Our data show a low number of SARS-CoV-2-seropositive HCW in a low prevalence setting, however, the proportion of seropositivity was higher than RT-PCR positivity, highlighting the importance of antibody testing.

This study provides the first molecular characterization of isoniazid- and rifampicin-resistant M. tuberculosis isolates from Myanmar and gives information on the molecular basis for rifampicin and isoniazid drug resistance in M. tuberculosis. The study generates useful information for the development of potential rapid molecular drug susceptibility tests.

We have developed a rapid colorimetric method for testing the susceptibility of M. tuberculosis to isoniazid (INH) and rifampin (RIF) based on incorporation of nitrate in broth cultures containing growth supplements. The performance of this colorimetric nitrate reductase-based antibiotic susceptibility (CONRAS) test was compared with that of the radiometric BACTEC 460TB system in determining the susceptibilities of 74 M. tuberculosis strains to INH and RIF. By using the BACTEC 460TB system as the "gold standard," the sensitivity (i.e., the ability to detect true drug resistance) and specificity (i.e., the ability to detect true drug susceptibility) of the CONRAS test were 100 and 95% for INH and 94 and 100% for RIF, respectively. The repeatability of the CONRAS test was excellent (for INH, kappa ‫؍‬ 1 and P < 0.001; for RIF, kappa ‫؍‬ 0.88 and P < 0.001). For the majority of strains, results were obtained within 5 days. The CONRAS test is rapid, accurate, and inexpensive and is an adequate alternative, particularly for resource-poor countries.The resurgence of tuberculosis (TB) worldwide has been accompanied by an increase in the incidence of drug-resistant TB and, more importantly, also in that of multidrug-resistant (MDR) TB (strains resistant to at least isoniazid [INH] and rifampin [RIF], the two most important first-line drugs). The spread of MDR strains of Mycobacterium tuberculosis has become a major public health problem (24). Current TB diagnostic tests are expensive (automated liquid-based culture systems and molecular methods) or slow (culture on solid media and biochemical tests). Standard methods for antibiotic susceptibility testing (AST) of M. tuberculosis such as the proportion method and the absoluteconcentration method depend on culture on solid media and are also time-consuming. The BACTEC 460TB system (Becton Dickinson, Sparks, Md.) using liquid media is faster but involves radioactive substrates and expensive technology (17). The radiometric BACTEC 460TB system is being replaced by the BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 (Becton Dickinson) and MB/Bact (bioMérieux, Inc., Durham, N.C.) automated liquid-based systems for detection and AST. The turnaround times for the latter systems are comparable to that for the radiometric BACTEC 460TB system, but reagents for automated systems are expensive. The manual BACTEC MGIT system is nonautomated and thus does not require additional instrumentation (22). Several studies have validated the performance of this system for AST (19,22). Molecular methods for AST have also been described (14) but need substantial investments in equipment and quality control.A number of low-cost colorimetric AST assays, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (3, 13), the Alamar blue assay (15), and an assay based on microscopic detection of cord-like growth by M. tuberculosis (4), have been described. However, these tests have limitations; mycobacteria other than M. tuberculosis can produce cord factor (10), an...

Purpose To review the incidence, aetiology and outcomes of endophthalmitis during a 20‐year period in a Norwegian university hospital. Methods Single‐centre retrospective review. Medical records of all patients admitted to Stavanger University Hospital with suspected endophthalmitis between January 1999 and December 2018 were reviewed. Results We identified 84 eyes of 81 patients. Postoperative endophthalmitis (PE) was seen in 64 eyes (76%), endogenous endophthalmitis in thirteen eyes (15%), trauma in four eyes (5%) and three eyes (4%) had keratitis‐associated endophthalmitis. Administration of intravitreal injections (IVI) was the most common cause (30%), followed by cataract surgery (CS) (21%). Of 40238 IVI, 23 PE cases were identified (incidence, 0.057%; 95% confidence interval [CI] 0.036–0.086%). Of 39697 CS, 12 PE cases were identified (incidence, 0.030%; 95%CI 0.016–0.053%). After introduction of intracameral cefuroxime PE incidence after CS decreased from 0.10% in 1999–2003 to 0.015% in 2004–2018 (p = 0.003). Eighty‐four per cent of organisms were Gram‐positive. Coagulase‐negative staphylococci accounted for 54% of culture‐proven cases, and 89% of post‐IVI culture‐proven cases. Thirty eyes (36%) either regained their previous vision or lost ≤1 Early Treatment Diabetic Retinopathy Study line. One third of endophthalmitis cases had a favourable visual outcome of logMAR 0.2 or better. Conclusion PE after IVI occurred in 1 in 1750 procedures, and was the most common cause of PE. The incidence of PE after CS has decreased >sixfold since 2003, to 1 in 6700 surgeries. A high proportion of low‐virulence bacterial species may have contributed to the favourable visual outcome.

An enzyme-linked immunosorbent assay (ELISA)-based investigation of anti-lipoarabinomannan (LAM) antibody levels in the sera of patients with acid-fast bacilli (AFB)-positive pulmonary tuberculosis (PTB), AFB-negative PTB and non-TB respiratory tract symptoms was conducted. The anti-LAM results were further evaluated using urine LAM detection and a clinical diagnostic score (DS) system as references. Using sputum AFB as a reference, positive anti-LAM was found in 66.9% of 139 AFB-positive PTB, 34.4% of 61 AFB-negative PTB and 23.5% of 800 non-TB patients and in 8% of 50 healthy individuals. The positive and negative predictive values were 48.7% and 87.4%, respectively. Using the DS as a reference, the sensitivity and specificity were 50.5% and 78.3%, respectively, whereas 45.8% of urine LAM positives and 77.9% of urine LAM negatives were correctly identified by the anti-LAM ELISA. In TB endemic areas a negative anti-LAM could be of practical value, particularly when other indicators of PTB are negative. Using any of these methods as a reference, a positive anti-LAM would mislead in about one-quarter of cases. Had all the 3 methods been combined and at least 2 positive tests sufficed, 90.6% of AFB-positive PTB, 52.5% of AFB-negative PTB and 94.9% of non-TB patients would have been correctly diagnosed. Apart from the possible impact of HIV, the low accuracy of the current assay could be due to intravascular formation of LAM-anti-LAM complexes, latent TB or environmental mycobacterial infections.

The CONRAS tests were rapid, cheap and easy to perform and interpret. Both tests should be evaluated on extended strain batteries in multicentre studies before they can be considered for use in susceptibility testing of M. tuberculosis to pyrazinamide in resource-limited settings.