Clinical Significance, Species Distribution, and Temporal Trends of Nontuberculous Mycobacteria, Denmark, 1991-2022.

Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991-2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method. The incidence of pulmonary NTM increased throughout the study period, in contrast to earlier findings. Mycobacterium malmoense, M. kansasii, M. szulgai, and M. avium complex were the most clinically significant species based on microbiologic findings; M. avium dominated in incidence. This study shows the need for surveillance for an emerging infection that is not notifiable in most countries, provides evidence to support clinical decision-making, and highlights the importance of not considering NTM as a single entity.

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: A nationwide register-based cohort study from 1991 through 2021.

BACKGROUND: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. METHOD: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. RESULTS: 433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3-4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9-1.2), possible disease 1.0 (95%CI 0.8-1.2), and isolation 1.7 (95%CI 1.4-1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR] = 2.1, 95%CI 1.9-2.3, p < 0.001), possible disease (IRR = 2.4, 95%CI 2.0-3.0, p < 0.001), and isolation (IRR = 4.6, 95%CI 3.9-5.4, p < 0.001) compared to Danish-born, but not of definite disease (IRR = 1.1, 95%CI 0.9-1.3, p = 0.562). IRs of migrants with positive NTM cultures did not increase over time (-0.8 %/year, p = 0.133). CONCLUSIONS: Migrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for Mycobacterium tuberculosis. Microbiologically classified definite NTM disease is not substantially more common among migrants.

Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis.

Introduction: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC. Methods: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-É£, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC. Results: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-É£, ZYM-IFN-É£, ZYM-TNF-α, ZYM-IL-1ß, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-É£, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity. Discussion: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.

The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention.

BACKGROUND: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. OBJECTIVE: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. MAIN FINDINGS: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a "proof of concept" for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.

Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark.

OBJECTIVES: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level. DESIGN: This was a nationwide register-based cohort study. SETTING: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System. PARTICIPANTS: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study. RESULTS: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care. CONCLUSION: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

Drug-resistant tuberculosis is a global cause of concern.

The number of patients with drug-resistant tuberculosis (DR-TB) is increasing worldwide. This review summarises the global epidemiology of DR-TB and current treatment challenges. Luckily, novel regimens comprising bedaquiline, pretomanid, linezolid, and moxifloxacin have seemingly mitigated the global threat posed by DR-TB. However, emerging resistance against bedaquiline and pretomanid, among other factors, persists as ongoing concerns in the global fight against DR-TB. While the new regimens are groundbreaking, the sustained development of novel drugs targeting the most resistant forms of tuberculosis is of utmost importance for future efforts against DR-TB.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017-2022.

In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).

Infectious purpura fulminans associated with pneumococcal septicaemia in a patient with unacknowledged functional asplenia.

Purpura fulminans (PF) is a life-threatening complication of septic shock that can occur due to disseminated infections with Streptococcus pneumoniae The spleen is an important organ in the immunisation process against encapsulated bacteria. Patients with asplenia, either functional or anatomical, are therefore at increased risk of developing serious infections and complications, such as PF, if infected with such bacteria.This case report presents a woman in her late 40s with unacknowledged functional asplenia who was admitted to the hospital with signs of an acute disseminated infection causing septic shock, signs of disseminated intravascular coagulation and infectious PF. A few days after admission, the blood cultures showed growth of S. pneumoniae With early sepsis treatment, the patient survived although with some complications. Clinical presentation, investigations, differential diagnosis, treatment and outcome are presented. Treatment and early recognition of PF are presented and discussed. Relevant recognition and preventative treatment strategies for patients with asplenia are also reviewed and discussed.This case demonstrates the importance of early recognition and treatment of PF in septic patients and the importance of preventive treatment strategies for patients with asplenia to avoid serious infections and complications.

Screening for latent tuberculosis in migrants-status quo and future challenges.

OBJECTIVES: To review the evidence that migrants from tuberculosis (TB) high-incidence countries migrating to TB low-incidence countries significantly contribute to active TB cases in the counties of destination, primarily through reactivation of latent TB. METHODS: This is a narrative review. The different screening programs in the countries of destination are reviewed either based on screening and preventive treatment of latent TB pre or more commonly - post arrival. RESULTS: Screening can be performed using interferon-gamma release assays (IGRA) or tuberculin skin tests (TST). Preventive treatment of latent TB is using either monotherapy with isoniazid, or in combination with rifampicin or rifapentine. We discuss the ethical issues of preventive treatment in asymptomatic individuals and how these are addressed in different screening programs. CONCLUSION: Screening migrants from TB high endemic countries to TB low endemic countries is beneficial. There is a lack of standardization and agreement on screening protocols, follow up and treatment.

The association between common mental disorders and tuberculosis: a case-control study from Guinea-Bissau.

OBJECTIVE: The aim of the study was to explore the association between tuberculosis (TB) and common mental disorders (CMD), in an area with high prevalence of TB. METHODS: We performed a case-control study of TB patients and unmatched healthy controls, from a demographic surveillance site in Guinea-Bissau. Screening for CMD was performed once for controls and at inclusion and follow-up for TB patients. Kessler 10 (K-10) and a brief version of Hopkins Symptom Checklist 25 (SCL-8d) were used as screening instruments. RESULTS: 571 controls were interviewed and 416 interviews were performed for 215 TB cases. Estimated CMD prevalence at the time of diagnosis of TB was 33.6 % (SCL-8d) and 46.2 % (K-10), compared with 6.8 % (SCL-8d) and 6.7 % (K-10) among controls; adjusted OR 7.18 (95 % CI 4.07 to 12.67) and 14.52 (95 % CI 8.15 to 25.84), respectively. No significant difference in CMD prevalence rates was observed between TB patients, after 6 months of treatment, and controls. CONCLUSION: Psychological distress and common mental disorders were more prevalent among TB patients at the time of diagnosis compared with the background population, but after completion of TB treatment no increased prevalence of psychological distress was found.