Ratios from full blood count as markers for TB diagnosis, treatment, prognosis: a systematic review.

BACKGROUND: The monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte (NLR) ratio are calculated from routine full blood counts. The aim of this study was to systematically review MLR and NLR as biomarkers for diagnosis, treatment response monitoring and prognostic biomarker for TB infection or disease.METHODS: A systematic literature search was conducted in Medline, Embase and the Cochrane Library on 12 January 2022. The following search terms were used: tuberculosis AND (monocyte OR neutrophils), AND lymphocytes AND (diagnostic OR prognostic OR treatment).RESULTS: A total of 2,314 studies were identified, of which 41, covering 11,952 individuals, were included in the final analysis. Studies enrolled a median of 154 individuals (IQR 108-301). Increased MLR and NLR were associated with TB disease when compared to healthy controls and individuals with TB infection. MLR was shown to be prognostic for progression to TB disease and to decrease in response to TB treatment. The cut-offs determined in the studies were highly variable for MLR and NLR, making it impractical to conduct a meta-analysis of sensitivity and specificity.CONCLUSION: Higher MLR and NLR are associated with TB disease and could be used as easy-to-obtain, low-cost additional diagnostic biomarkers. Further studies investigating these biomarkers are needed.

[Care of infectious diseases in underage refugees exemplified by Ukraine]. / Infektiologische Versorgung minderjähriger Flüchtlinge am Beispiel der Ukraine: Vorgehen in Deutschland gemäß der S1-Leitlinine (AWMF-Register Nr. 048-017).

Background: By early June 2022, around 300,000 children and adolescents from Ukraine were registered in the German central registry for foreigners.The updated recommendations for action should provide the foundations for an evidence-based and targeted care for the diagnosis and prevention of infectious diseases in underage refugees and asylum seekers, exemplified by Ukraine. Objective: The recommendations for action are intended to support medical personnel in the care of minor refugees in order to1) ensure early recognition and completion of an incomplete vaccination status,2) diagnose and treat common infectious diseases,3) ensure early recognition and treatment of infectious diseases that are rare in the German healthcare system. Material and methods: The recommendations for action were drafted as level 1 (S1) guidelines coordinated by the Association of the Scientific Medical Societies in Germany (AWMF) and were adapted to the situation of refugees from Ukraine.The recommendations were compiled by a representative expert panel appointed by the participating professional societies in an informal consensus and finally officially adopted by the board of directors of all societies concerned. Results: Recommendations are given for the extent of the medical evaluation of minor refugees, including the medical history and physical examination, adapted to the situation of refugees from Ukraine. A blood count and screening for tuberculosis, hepatitis B and C as well as human immunodeficiency virus (HIV) infections are recommended for all minor refugees.For a rapid completion of the vaccination status, an age-related and indications-related prioritization of individual vaccinations will be undertaken. Conclusion: In view of the continuing high numbers of refugees not only from Ukraine, a further professionalization of medical health care is necessary. For this purpose, the necessary structural and personnel framework conditions need to be accomplished.

Asylum-Seeking Children with Medical Complexity and Rare Diseases in a Tertiary Hospital in Switzerland.

The aim of this study was to assess the characteristics of asylum-seeking children with medical complexity visiting a tertiary care hospital in Switzerland, detailing their underlying medical conditions and management. Asylum-seeking patients with frequent visits between January 2016 and December 2017 were identified using administrative and electronic health records. Of 462 patients, 19 (4%) fulfilled the inclusion criteria with 811 (45%) visits. The age of the 19 patients ranged from 0 to 16.7 years (median of 7 years) with two main age groups identified: < 2 years and > 12 years. Nine (47%) patients originated from Syria. A total of 34/811(4%) visits were hospital admissions, 66/811 (8%) emergency department visits and 320/811(39%) outpatient department visits. In children < 2 years genetic diseases (5/8; 63%) and nutritional problems (6/8; 75%) were most common; in adolescents, orthopedic diseases (4/8; 50%) and mental health problems (4/8; 50%). Asylum-seeking children with medical complexity represent a small but important group of patients requiring frequent medical consultations. The high proportion of young patients with genetic diseases and severe nutritional problems suggests that new strategies are required in the management of this specific group of asylum-seeking children. This could be achieved by improved co-ordination between hospital and non-hospital care exploring options for integrated care.

Cost-effectiveness of tuberculosis screening for migrant children in a low-incidence country.

Detection of latent tuberculous infection (LTBI) is important to prevent progression to active tuberculosis (TB), particularly in migrant children. We evaluated the cost-effectiveness of TB screening in migrant children in a low-incidence country. Retrospective analysis of a school-based TB screening programme in Switzerland. Migrant children were screened using the tuberculin skin test (TST). TST was considered positive if induration was 10 mm in non-bacille Calmette-Guérin (BCG) vaccinated children, and 15 mm in BCG-vaccinated children. Screening and treatment costs were extracted from hospital records. Cost impact was analysed as the difference between the cost of treatment for active TB and screening plus LTBI treatment. Cost per disability-adjusted life-years (DALY) was assessed based on Global Burden of Disease disability weight estimates. Of 1462 children screened, 1120 (77%; mean age 10.9 years; 46% female) underwent a TST. TST induration of 10 mm was documented in 78 (6.9%), and TST induration of 15 mm in 19 (1.6%). Twenty-one were TST-positive, and 17 children were diagnosed with LTBI; none had active TB. The highest rates of TST induration 10 mm were found in migrant children from Africa (16.6%) and Turkey (15.4%). Screening for LTBI was cost-effective if LTBI prevalence was 14%, with a progression rate of 5%; in case of lower LTBI prevalence, LTBI screening is cost-effective if progression rates to active TB are higher. School-based TB screening programmes targeting migrant children are cost-effective if populations with a relatively increased LTBI prevalence and/or high progression rates are included. .

Cytokine kinetic profiles in children with acute lower respiratory tract infection: a post hoc descriptive analysis from a randomized control trial.

OBJECTIVES: Standard inflammatory markers and chest radiography lack the ability to discriminate bacterial from non-bacterial lower respiratory tract infection (LRTI). Cytokine profiles may serve as biomarkers for LRTI, but their applicability to identify aetiology, severity of disease and need for antibiotic prescription in children remains poorly defined. Objectives were to determine the cytokine kinetic profiles over 5 days in paediatric patients with LRTI, to investigate the relationship between cytokine patterns, and clinical and laboratory variables. METHODS: We included patients aged 1 month to 18 years, with febrile LRTI and three consecutive cytokines measurements on days 1, 3 and 5 of a randomized controlled trial (ProPAED study). We evaluated differences in cytokine concentrations between days and associations with clinical and laboratory variables. RESULTS: A total of 181 patients (median age 4.1 years) were included; 72/181 (40%) received antibiotics. Serum concentrations of interferon (IFN)-γ, interleukin (IL)-1ra, IL-6, IL-10, IFN-γ-inducible protein (IP)-10 and tumor necrosis factor-α were elevated on day 1 and decreased subsequently, with the greatest decline between day 1 and 3 (by -8 to >-94%). Procalcitonin (PCT) and C-reactive protein (CRP) values showed a protracted decrease with the most prominent reduction in concentrations between days 3 and 5. Significantly elevated IL-6 concentrations were associated with hospital admission, antibiotic treatment, and prolonged antibiotic treatment. Bacteraemic LRTI patients had higher concentrations of IL-1ra (p <0.0055) and IL-6 (p <0.0055) on day 1. CONCLUSIONS: We observed an earlier decrease of elevated cytokines compared to PCT or CRP. Both pro- and anti-inflammatory cytokines may serve as markers for severity of LRTI.

[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

Sulfate-reducing bacteria slow intestinal transit in a bismuth-reversible fashion in mice.

BACKGROUND: Hydrogen sulfide (H2 S) serves as a mammalian cell-derived gaseous neurotransmitter. The intestines are exposed to a second source of this gas by sulfate-reducing bacteria (SRB). Bismuth subsalicylate binds H2 S rendering it insoluble. The aim of this study was to test the hypothesis that SRB may slow intestinal transit in a bismuth-reversible fashion. METHODS: Eighty mice were randomized to five groups consisting of Live SRB, Killed SRB, SRB+Bismuth, Bismuth, and Saline. Desulfovibrio vulgaris, a common strain of SRB, was administered by gavage at the dose of 1.0 × 109 cells along with rhodamine, a fluorescent dye. Intestinal transit was measured 50 minutes after gavage by euthanizing the animals, removing the small intestine between the pyloric sphincter and the ileocecal valve and visualizing the distribution of rhodamine across the intestine using an imaging system (IVIS, Perkin-Elmer). Intestinal transit (n=50) was compared using geometric center (1=minimal movement, 100=maximal movement). H2 S concentration (n=30) was also measured when small intestinal luminal content was allowed to generate this gas. KEY RESULTS: The Live SRB group had slower intestinal transit as represented by a geometric center score of 40.2 ± 5.7 when compared to Saline: 73.6 ± 5.7, Killed SRB: 77.9 ± 6.9, SRB+Bismuth: 81.0 ± 2.0, and Bismuth: 73.3 ± 4.2 (P<.0001). Correspondingly, the Live SRB group had the highest luminal H2 S concentration of 4181.0 ± 968.0 ppb compared to 0 ± 0 ppb for the SRB+Bismuth group (P<.0001). CONCLUSIONS & INFERENCES: Live SRB slow intestinal transit in a bismuth-reversible fashion in mice. Our results demonstrate that intestinal transit is slowed by SRB and this effect could be abolished by H2 S-binding bismuth.

European shortage of purified protein derivative and its impact on tuberculosis screening practices.

SETTING: In June 2014, we became aware that shortages of purified protein derivative (PPD), the test substance used for the tuberculin skin test (TST), had occurred in several European health care institutions providing care for children with tuberculosis (TB). OBJECTIVE: To establish the extent of the shortage, a survey was performed. DESIGN: Survey conducted over a 1-month period (June-July 2014) among members of the Paediatric Tuberculosis Network European Trials Group (ptbnet). RESULTS: Thirty-five physicians from 23 European countries contributed data. The most commonly used PPD product was RT23 (Statens Serum Institut; n = 22, 63%). Twenty-one (60%) participants reported that their institution was experiencing a PPD shortage. The majority (n = 17, 81%) of those reporting a shortage were using RT23. Thirteen (37%) participants reported changes in screening practices resulting from the shortage, including sourcing PPD from alternative manufacturers, restricting remaining supplies to patients at greatest risk or replacing TST by an interferon-gamma release assay. CONCLUSIONS: The data show that a PPD shortage occurred in 2014, affecting multiple European countries. The shortage resulted in changes in TB screening capabilities and practices, potentially compromising both patient care as well as public health efforts. Appropriate actions to prevent future PPD shortages should be explored urgently by public health agencies and key stakeholders.

Absence of interferon-gamma release assay conversion following tuberculin skin testing.

BACKGROUND: The tuberculin skin test (TST) has been the established screening method for tuberculosis (TB) for over a century. Interferon-gamma release assays (IGRAs) using Mycobacterium tuberculosis-specific antigens are increasingly used as diagnostic tests for TB. Tuberculin comprises multiple antigens, including the antigens used in the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. Exposure to these antigens by means of a TST may prime an immune response that leads to a false-positive result in a subsequent IGRA, limiting the validity of IGRAs in patients in whom these tests are performed sequentially. The current data on the influence of prior TST on IGRAs show inconsistent results. METHODS: Sixteen non-bacille Calmette-Guérin immunised medical students with no history of TB exposure and minimal risk of exposure to TB during the study period were tested simultaneously with a TST and QFT-GIT. The QFT-GIT assay was repeated 6 and 10 weeks later. RESULTS: At baseline, all TST and QFT-GIT results were negative and remained negative 6 and 10 weeks after the TST. CONCLUSION: These data show that negative QFT-GIT results are reproducible and suggest that a TST does not result in conversion of subsequent QFT-GIT assays in the absence of concomitant TB exposure. Therefore, a positive QFT-GIT should not be attributed to boosting induced by a previous TST.

Tuberculous dactylitis--an easily missed diagnosis.

The prevalence of tuberculosis (TB) continues to rise worldwide. Current migration patterns and increased travel to high-prevalence TB countries will result in more frequent presentations of less common forms of TB. Tuberculous dactylitis, a form of tuberculous osteomyelitis, is well recognised in countries with a high prevalence of TB. We provide a systematic review of all published cases of tuberculous dactylitis in children and adolescents and describe a case to illustrate the typical features of the disease. Our review revealed 37 cases of tuberculous dactylitis in children and adolescents, all reported in the last 17 years. Children less than 10 years of age are most frequently affected and the hand is the most commonly affected site. Concurrent pulmonary TB is present in a fifth of cases and systemic symptoms are usually absent. Positive TST and IGRA support the presumptive diagnosis, but cannot be used as rule-out tests. The definitive diagnosis relies on the detection M. tuberculosis by PCR or culture. Treatment should comprise of a standard three to four drug anti-tuberculous regimen. The optimal treatment duration remains unknown. Surgery has a limited role in the treatment in general but may play a supportive role, and curettage of the cavity has been recommended for avascular lesions.

Evolution of Sézary syndrome in the course of hairy cell leukemia.

A patient with a history of "leukemia" for 19 yr and documented hairy cell (HC) leukemia for 10 yr developed mycosis fungoides and the Sézary syndrome. The manifestations of both diseases were diagnostic on clinical and pathologic grounds. Ultrastructural, immunohistochemical, and surface marker techniques proved the HC to have phenotypic characteristics of the T-helper subset of lymphocytes to which the Sézary cells (SC) also belonged. Both types of cells contained tartrate-resistant acid phosphatase. HC did not infiltrate the skin. SC did not contain ribosome lamellar complexes. Because of otherwise overlapping morphology and the apparent replacement of HC by SC, it is likely that the Sézary cells constituted a genetic variant of the original neoplastic clone represented by the hairy cells. Since the biologic and therapeutic implications of such clonal evolution may be important, subtle phenotypic changes should be looked for repeatedly in patients with these diseases.