The global prevalence of latent tuberculosis: a systematic review and meta-analysis.

In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (LTBI), which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence.We conducted a systematic review and meta-analysis of LTBI estimates based on both IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model.Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI 19.7-30.0%) and 21.2% (95% CI 17.9-24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p<0.001).In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, we found that one-fourth of the world's population is infected. This is of relevance, as both tests, although imperfect, are used to identify individuals eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.

Delays in the Diagnosis and Treatment of Tuberculous Lymphadenitis in Low-Incidence Countries: A Systematic Review.

Early detection and treatment of tuberculosis (TB) is essential to achieve the goals appointed in the WHO End TB Strategy. Tuberculous lymphadenitis (TBLA) is the most common manifestation of extrapulmonary TB, but the diagnosis can be challenging in low-incidence countries due to sparse and inconsistent clinical features, resulting in delay. We aimed to summarize and discuss the current literature on patient delay, health care delay, and total delay (i.e., time to first health care contact, diagnosis, and treatment) in patients with TBLA in TB low-incidence countries. A systematic review using PubMed was conducted, searching for studies set in TB low-incidence countries (defined as <20 per 100,000 citizens) that reported on health care seeking behaviour, patient delay, health care delay, and/or total delay. Studies were categorized by type of delay and compared. We identified 11 heterogeneous studies with highly variable observations. Mean patient delay varied from 55 to 154 days (range, 14-1,461), mean health care delay from 44 to 94 days (range, 7-224) and median total delay from 77.5 to 122 days (range, 0-2,820). Evidently, more comprehensive insights into the diagnostic pathway and delay in TBLA patients are warranted.

[Tuberculosis among children and adolescents].

Diagnosing tuberculosis (TB) in children and adolescents pose a diagnostic challenge due to sparse symptoms and clinical signs. Children are at a much higher risk than adults of progression to severe disease. In this review, the presentation and management of childhood TB is described. TB in children indicates ongoing transmission and is an indicator of failing disease control in the community. Tests suited to predict progression are warranted, and targeting latent infection is essential to achieve TB elimination. We recommend a low threshold for referral of children suspected of active or latent TB.

Severe influenza in a paediatric patient with GATA2 deficiency and Emberger syndrome.

A 9-year-old girl was admitted to the paediatric intensive care unit with acute respiratory failure due to influenza. Nine months earlier, she presented with unexplained lymphoedema of the lower extremities and monocytopenia. She had a history of occasional finger warts and onychomycoses. During hospitalisation, the patient was diagnosed with Emberger syndrome caused by GATA2 deficiency. The admission was complicated by thromboses in the right hand, leading to amputation of multiple fingers. From then on, the patient has been in good recovery, the function of her right hand was improving and an allogeneic haematopoietic cell transplantation has now been successfully performed.

Recovery of Moderate Coronavirus Disease 2019 in a Liver Transplant Recipient on Continued Immunosuppression: A Case Report.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an enormous impact on the world. Owing to limited data available, it remains unclear to what extent liver transplant recipients should be considered at a higher risk of severe disease. We describe a moderate course of coronavirus disease 2019 (COVID-19) in a patient who underwent a liver transplant 2 years earlier because of Budd-Chiari syndrome. The patient presented with malaise, headache, dry cough, and fever for 4 days. Immunosuppressive therapy with tacrolimus and mycophenolate mofetil was continued throughout the course of infection. Oxygen therapy was given for a single night, and the patient gradually recovered with supportive care only. With this case report, we demonstrate that liver transplantation and immunosuppression is not necessarily associated with severe COVID-19 and emphasize that more information on this matter is urgently required. Withdrawal of immunosuppressive therapy could be associated with higher mortality.

Clinical features of tuberculous lymphadenitis in a low-incidence country.

BACKGROUND: Tuberculous lymphadenitis (TBLA) is the most common extrapulmonary manifestation of tuberculosis (TB) in Denmark. However, the clinical features of patients with TBLA have never been systematically studied in this setting. METHODS: Patients treated for TBLA in Central Region Denmark from 2007 to 2016 were identified using the national TB surveillance register and The Danish Hospital Patient Registry. Data of clinical characteristics and treatment were extracted from hospital records. RESULTS: Eighty-three TBLA patients were identified. The median age was 32 years (IQR 23-42); 71 (85.5%) were migrants; 58 (69.9%) presented with cervical lymphadenopathy; and 45 (54.2%) had one or more systemic TB symptom such as fever, chills, night sweats, fatigue, and weight loss. Sixty-five patients had no comorbidities (78.3%). HIV co-infection was seen in five (7.2%) of the 69 who were tested for HIV. Abscesses and/or draining sinuses were noted in 13 (15.7%) patients and 15 (18.1%) had concurrent pulmonary infection. The median time from first hospital contact to treatment initiation was 42 days (IQR 16-82) and admitted patients were hospitalised for a median of 7 days (IQR 3-13.5). For 24 patients (28.9%), lymph node material was not sent for mycobacterial culture and 52 (62.7%) had microbiologically confirmed TB. Treatment outcome was successful for 70 patients (84.3%). CONCLUSION: In Denmark, TBLA is mainly seen among young and previously healthy migrants presenting with cervical lymphadenopathy and sparse systemic symptoms. The diagnosis is often considerably delayed and not microbiologically verified, implying diagnostic difficulties. Treatment outcome needs to be improved.

Epidemiology of tuberculous lymphadenitis in Denmark: A nationwide register-based study.

BACKGROUND: Tuberculous lymphadenitis (TBLA) is the most common extrapulmonary manifestation of tuberculosis (TB), often claimed to be reactivation. We aimed to describe the epidemiology of TBLA in Denmark, as it has not previously been investigated specifically although extrapulmonary TB has been associated with an increased long-term mortality and delays in the diagnosis. METHODS: Register-based study of all patients notified with TBLA in Denmark from 2007 through 2016 utilizing six different nationwide registers. Patients were identified through the national TB surveillance register, and the diagnosis evaluated based on microbiology, pathology and/or clinical assessment. RESULTS: In total, 13.5% (n = 489) of all TB patients in Denmark had TBLA with annual proportions from 9.4 to 15.7%. Most patients were immigrants between 25-44 years. Incidence rates ranged from as high as 1,014/100,000 for Nepalese citizens to as a low as 0.06/100,000 for Danes. Danes had a significant higher median age and significant more risk factors and comorbidities, as well as an increased overall mortality, compared with immigrants (p<0.05). A significant and much higher proportion of unique MIRU-VNTR genotypes were seen among TBLA patients compared to other TB manifestations. CONCLUSION: In Denmark, TBLA is a common manifestation of TB, especially in young immigrants from high-incidence countries. In Danes, it is a rare disease manifestation and associated with higher morbidity and mortality. To our knowledge, this is the first study suggesting that TBLA is predominantly associated with reactivation of latent TB infection based on genotyping although this remains to be clarified.