Nora Fritschi

University Children’s Hospital Basel

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Nicole Ritz

University Children’s Hospital Basel

Marc Tebruegge

University College London

Tamara Diesch

University Children’s Hospital Basel

Cornelia Filippi

University of Basel

Andreas Filippi

University of Basel

Jürg Hammer

University Children’s Hospital Basel

Ulrich Heininger

University Children’s Hospital Basel

Charlotte Rinderknecht

University of Basel

Nina Vaezipour

Swiss Tropical and Public Health Institute

Urs Simmen

Federal Statistical Office

Cooperative Institutions

University of Basel

University Children’s Hospital Basel

Johns Hopkins University

Royal Children's Hospital

University of Melbourne

Charité - Universitätsmedizin Berlin

University College London

Instituto de Salud Carlos III

Murdoch Children's Research Institute

Freie Universität Berlin

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Associations between salivary cytokines and oral health, age, and sex in healthy children

Research Square (Research Square) (2022)

Charlotte Rinderknecht Cornelia Filippi Nicole Ritz Nora Fritschi Urs Simmen

Abstract Human saliva is a complex fluid containing proteins such as salivary cytokines, which can be used for diagnostic purposes, particularly among the pediatric population. This study aimed to assess the concentrations of salivary cytokines in healthy children and adolescents and determine their associations with age, sex, and oral and dental findings. Healthy children and adolescents aged 4–18 years were enrolled in this cross-sectional study. The concentrations of the following salivary cytokines were measured by Luminex technology: IFN-γ, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IP-10, TNF-α, and VEGF-A. Additionally, oral and dental parameters were recorded using a standardized protocol. A total of 128 participants (mean age, 10.7 years; males, 50.8%) were enrolled. The levels of 1β, IL-6, IL-8, and IL-10 were significantly higher in those with gingivitis. Increased salivary flow rates were negatively correlated with IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, and VEGF-A concentrations. The findings of this study showed that the concentrations of most of the salivary cytokines were positively correlated with age and the presence of oral pathologies (such as gingivitis and caries) and negatively correlated with salivary flow rate.

Proinflammatory cytokine

10.21203/rs.3.rs-1771732/v1

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Pediatric Tuberculosis Disease during Years of High Refugee Arrivals: A 6-Year National Prospective Surveillance Study

Respiration (2021)

Nora Fritschi Axel J. Schmidt Jürg Hammer Nicole Ritz

In Europe, surveillance and monitoring of pediatric tuberculosis (TB) remains important, particularly in the light of migration in recent years. The aim of the study was to evaluate incidence rates of childhood TB and detailed diagnostic pathways and treatment.Data were collected through the Swiss Pediatric Surveillance Unit (SPSU) from December 2013 to November 2019. Monthly -notifications are obtained from the 33 pediatric hospitals in the SPSU, and a detailed questionnaire was sent out upon notification. Inclusion criteria were children and adolescents aged up to 15 years with culture- or molecular-confirmed TB disease or for whom a treatment with ≥3 antimycobacterial drugs had been initiated. Data were compared with age-matched notification data from the Swiss Federal Office of Public Health (FOPH).Of the 172 cases notified to SPSU, a detailed questionnaire was returned for 161 (93%) children, of which 139 met the inclusion criteria. Reasons for exclusion were age >15 years, double reporting, and not fulfilling the criteria for TB disease. During the same time period, 172 pediatric TB cases were reported to the FOPH, resulting in an incidence of 2.1 per 100,000, ranging from 1.4 to 2.8 per year, without a clear trend over time. In the 64 (46.0%) foreign-born children, incidence rates were higher and peaked in 2016, with 13.7 per 100,000 (p = 0.018). The median interval between arrival in Switzerland and TB diagnosis was 5 (IQR 1-21) months, and 80% were diagnosed within 24 months of arrival. In 58% of the cases, TB disease was confirmed by culture or molecular assays. Age >10 years, presence of fever, or weight loss were independent factors associated with confirmed TB.The annual pediatric TB incidence rate only varied among foreign-born children and was highest in 2016 when refugee influx peaked in Europe. Importantly, most foreign-born children with TB were diagnosed within 2 years after arrival in Switzerland. Thus, the early period after arrival in Switzerland is associated with a higher risk of TB disease in children, and this should be considered for screening guidance in refugees.

Public health surveillance

10.1159/000517029

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Monocyte, Lymphocyte and Neutrophil Ratios – Easy-to-Use Biomarkers for the Diagnosis of Pediatric Tuberculosis

The Pediatric Infectious Disease Journal (2023)

Mirjam Kissling Nora Fritschi Philipp Baumann Michael Buettcher Jan Bonhoeffer

Background: The neutrophil-to-lymphocyte-ratio (NLR), neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) and monocyte-to-lymphocyte-ratio (MLR) may have diagnostic potential for tuberculosis (TB). Methods: Data of two prospective multicenter studies in Switzerland were used, which included children <18 years with TB exposure, infection or disease or with febrile non-TB lower-respiratory-tract infection (nTB-LRTI). Results: Of the 389 children included 25 (6.4%) had TB disease, 12 (3.1%) TB infection, 28 (7.2%) were healthy TB exposed and 324 (83.3%) nTB-LRTI. Median (IQR) NLR was highest with 2.0 (1.2, 2.2) in children with TB disease compared to TB exposed [0.8 (0.6, 1.3); P = 0.002] and nTB-LRTI [0.3 (0.1, 1.0); P < 0.001]. Median (IQR) NMLR was highest with 1.4 (1.2, 1.7) in children with TB disease compared to healthy exposed [0.7 (0.6, 1.1); P = 0.003] and children with nTB-LRTI [0.2 (0.1, 0.6); P < 0.001). Receiver operating characteristic curves to detect TB disease compared to nTB-LRTI for NLR and NMLR had an area under the curve of 0.82 and 0.86, the sensitivity of 88% and 88%, and specificity of 71% and 76%, respectively. Conclusion: NLR and NMLR are promising, easy-to-obtain diagnostic biomarkers to differentiate children with TB disease from other lower respiratory tract infections. These results require validation in a larger study and in settings with high and low TB endemicity.

Monocyte

10.1097/inf.0000000000003901

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Comparative analysis of salivary cytokine profiles in newly diagnosed pediatric patients with cancer and healthy children

Scientific Reports (2025)

Alessandro M. Paganini Nora Fritschi Cornelia Filippi Nicole Ritz Urs Simmen

Salivary cytokines have the potential to serve as biomarkers for evaluating cancer progression and treatment response in specific cancer types. This study explored salivary cytokine profiles in pediatric cancer patients and healthy controls, examining changes during chemotherapy. We conducted a prospective study involving newly diagnosed cancer patients and healthy controls under 19 years old. Saliva samples were collected at diagnosis, and three and six months post-diagnosis for cancer patients, while healthy controls provided samples at a single time point. Cytokine levels were analyzed using Luminex technology. Our study included 19 cancer patients (10 with leukemia, 5 with lymphoma, and 4 with solid tumors) and 128 healthy controls aged 4 to 18 years. At diagnosis, patients with leukemia and solid tumors showed elevated levels of interferon-γ, interleukin (IL)-1α, IL-1β, IL-4, IL-5, IL-8, IL-10, and tumor necrosis factor. After three months, IL-6, IL-10, and inducible protein-10 levels significantly increased, while IL-1α, IL-1β, and IL-8 rose by six months. These findings indicate that salivary cytokines are elevated at diagnosis and during initial treatment phases in pediatric cancer patients, highlighting saliva's potential as a noninvasive medium for early detection of systemic diseases in children.

Pediatric cancer

10.1038/s41598-025-87608-1

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Diagnosis of tuberculosis infection in children with a novel skin test and the traditional tuberculin skin test: An observational study

PLoS ONE (2024)

Nora Fritschi Tatyana Gureva Platon Eliseev Charlotte Jackson Edith B. Milanzi

Background A novel skin test–called Diaskintest (DT)—containing specific M . tuberculosis antigens is in clinical use in the Russian Federation (RF). This test may improve diagnosis of tuberculosis (TB) infection. The use and performance of the DT was described and compared to the tuberculin skin test (TST). Methods Data on children <18 years referred to a TB reference centre (Jan/2018- Dec/2019) with ≥1 DT and TST result available were analysed. An immune correlate of TB infection was defined as a positive TST (≥10 mm induration) or a positive DT (any induration). Results Of 2710 included cases, the median age was 9.0 (IQR 5.7–13.1) years and 97.5% were BCG immunised. Overall, 1976 (79.9%) were TB uninfected, 724 (26.7%) had an immune correlate of TB infection and 10 (0.4%) TB disease. Reasons for referral were: positive or increasing skin test results in routine screening (992, 36.6%), screening before admission to a health care institution (501, 18.5%) and TB contact (457, 16.9%). DT was positive in 11.7% (308/2625) and TST in 63.1% (467/740) (Kappa 0.08, 95% CI:0.013–0.14). A positive DT was associated with older age (OR 1.16 (95% CI: 1.13–1.19) per year). Among TB contacts DT positivity was associated with contagiousness: highest proportion of positivity of 12.0% was observed when the index case was smear positive. Conclusion In a setting with universal BCG vaccination and regular screening with TST, DT was used to rule out TB infection as TST was commonly positive. We found an association of DT positivity and contagiousness of the index case in children contacts. These observations may suggest improved specificity and sensitivity of DT compared to TST.

Skin test

Tuberculosis diagnosis

10.1371/journal.pone.0293272

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Cytokines in saliva as biomarkers of oral and systemic oncological or infectious diseases: A systematic review

Cytokine (2021)

Tamara Diesch Cornelia Filippi Nora Fritschi Andreas Filippi Nicole Ritz

Recent evidence suggests that salivary cytokines provide information about both oral conditions and systemic diseases. This review summarizes evidence for the use of salivary cytokines as biomarkers for oral and systemic diseases. We included studies in adults and children with a focus on the latter, due to the importance of non-invasive diagnostic methods in the paediatric age group. A systematic review was performed using Medline and Web of Science covering the period of January 1996 to December 2019 according to the preferred reporting items for systematic reviews. Thirty-four studies were included in the final analysis, for a total of 2407 patients and healthy controls. Pro-inflammatory cytokines including interleukin (IL)-1β, IL-2, IL-6 and tumor necrosis factor (TNF)-α were associated with the severity of oral mucosal tissue damage in patients with cancer, and IL-1β may be an early marker of graft-versus-host disease. Salivary interferon-γ levels were correlated with oral complications and the presence of the underlying disease in HIV-infected individuals, and salivary cytokine patterns may be useful for diagnosing tuberculosis. In summary, current data illustrate that salivary cytokines are associated with oral inflammation, making them potential biomarkers for disease diagnosis and treatment efficacy. Because of the simplicity of saliva collection, this method may be useful in pediatric studies and in resource-limited settings.

10.1016/j.cyto.2021.155506

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Subclinical Tuberculosis in Children: Diagnostic Strategies for Identification Reported in a 6-year National Prospective Surveillance Study

Clinical Infectious Diseases (2021)

Nora Fritschi Ante Wind Jürg Hammer Nicole Ritz

Subclinical tuberculosis (TB) is well recognized and defined as a disease state with absent or nonrecognized symptoms. The study identifies factors associated with subclinical TB and diagnostic strategies in a low-burden, high-resource country.Data were collected between December 2013 and November 2019 through the Swiss Pediatric Surveillance Unit (SPSU). Children with culture/molecular confirmed TB, or who were treated with ≥3 antimycobacterial drugs, were included.A total of 138 (80%) children with TB disease were included in the final analysis, of which 43 (31%) were subclinical. The median age of children with subclinical compared to symptomatic TB was 3.7 (interquartile range [IQR] 2.2-7) and 9.7 (IQR 2.7-14.3) years, respectively (P = .003). The cause of investigation for TB was recorded in 31/43 (72.1%) of children with subclinical TB and included contact exposure in 25 (80.6%) of children. In children with subclinical TB, diagnosis was made by a combination of the following abnormal/confirming results: culture/molecular + immunodiagnostic + chest radiography in 12 (27.9%) cases, immunodiagnostic + chest radiography in 19 (44.2%) cases, culture/molecular + chest radiography in 2 (4.7%) cases, culture + immunodiagnostic in 1 (2.3%) case, chest radiography only in 8 (18.6%) cases, and immunodiagnostic only in 1 (2.3%) case.A notable proportion of children with TB had subclinical disease. This highlights the importance of non-symptom-based TB case finding in exposed children and refugees from high-TB-prevalence settings. TB screening in these asymptomatic children should therefore include a combination of immunodiagnostic testing and imaging followed by culture and molecular testing.

Subclinical infection

Interquartile range

10.1093/cid/ciab708

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Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects

Paediatric Respiratory Reviews (2020)

Nora Fritschi Nigel Curtis Nicole Ritz

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

BCG vaccine

10.1016/j.prrv.2020.08.004

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Pertussis vaccination campaign among health care workers and validity of recall of previous adverse events following immunization

Vaccine (2025)

Nora Fritschi Ulrich Heininger

Pertussis vaccine

10.1016/j.vaccine.2025.126850

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Beitrag der kommunalen und kantonalen Raumplanung zur Steuerung des Wohnraumangebots: Empirische Untersuchung von drei Fallbeispielen

Zenodo (CERN European Organization for Nuclear Research) (2020)

Nora Fritschi

10.5281/zenodo.4298501

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