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

Background: 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. Methods: 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). Results: 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. Conclusion: 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.

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Breath can discriminate tuberculosis from other lower respiratory illness in children

Scientific Reports ◽

10.1038/s41598-021-80970-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Carly A. Bobak ◽

Lili Kang ◽

Lesley Workman ◽

Lindy Bateman ◽

Mohammad S. Khan ◽

...

Keyword(s):

Machine Learning ◽

Lower Respiratory Tract ◽

Cross Validation ◽

Pediatric Patients ◽

Respiratory Illness ◽

Health Crisis ◽

Machine Learning Model ◽

Childhood Tb ◽

Pediatric Tb ◽

Pediatric Tuberculosis

AbstractPediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose symptoms improved while treated for TB. While more work is necessary to validate the utility of using patient breath to diagnose pediatric TB, it shows promise as a triage instrument or paired as part of an aggregate diagnostic scheme.

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Developing National Genotype-Independent Indicators for Recent Mycobacterium Tuberculosis Transmission Using Pediatric Cases—United States, 2011-2017

Public Health Reports ◽

10.1177/0033354920985215 ◽

2021 ◽

pp. 003335492098521

Author(s):

Alexia V. Harrist ◽

Clinton J. McDaniel ◽

Jonathan M. Wortham ◽

Sandy P. Althomsons

Keyword(s):

United States ◽

Mycobacterium Tuberculosis ◽

Statistical Model ◽

Moving Average ◽

The United States ◽

Tuberculosis Transmission ◽

Average Proportion ◽

Pediatric Tb ◽

Case Rate ◽

Pediatric Tuberculosis

Introduction Pediatric tuberculosis (TB) cases are sentinel events for Mycobacterium tuberculosis transmission in communities because children, by definition, must have been infected relatively recently. However, these events are not consistently identified by genotype-dependent surveillance alerting methods because many pediatric TB cases are not culture-positive, a prerequisite for genotyping. Methods We developed 3 potential indicators of ongoing TB transmission based on identifying counties in the United States with relatively high pediatric (aged <15 years) TB incidence: (1) a case proportion indicator: an above-average proportion of pediatric TB cases among all TB cases; (2) a case rate indicator: an above-average pediatric TB case rate; and (3) a statistical model indicator: a statistical model based on a significant increase in pediatric TB cases from the previous 8-quarter moving average. Results Of the 249 US counties reporting ≥2 pediatric TB cases during 2009-2017, 240 and 249 counties were identified by the case proportion and case rate indicators, respectively. The statistical model indicator identified 40 counties with a significant increase in the number of pediatric TB cases. We compared results from the 3 indicators with an independently generated list of 91 likely transmission events involving ≥2 pediatric cases (ie, known TB outbreaks or case clusters with reported epidemiologic links). All counties with likely transmission events involving multiple pediatric cases were identified by ≥1 indicator; 23 were identified by all 3 indicators. Practice Implications This retrospective analysis demonstrates the feasibility of using routine TB surveillance data to identify counties where ongoing TB transmission might be occurring, even in the absence of available genotyping data.

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Dengue Fever in Italy: The “Eternal Return” of an Emerging Arboviral Disease

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed7010010 ◽

2022 ◽

Vol 7 (1) ◽

pp. 10

Author(s):

Matteo Riccò ◽

Simona Peruzzi ◽

Federica Balzarini ◽

Alessandro Zaniboni ◽

Silvia Ranzieri

Keyword(s):

Incidence Rate ◽

Central Italy ◽

Denv Infection ◽

Incidence Rates ◽

Annual Incidence ◽

Annual Reports ◽

Foreign Born ◽

Time Period ◽

Adjusted Incidence Rate ◽

Adjusted Incidence

Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010–2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187–0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314–0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015–2019 (risk ratio [RR] 1.808, 95% CI 1.594–2.051) and even during 2020–2021 (RR 1.771, 95% CI 1.238–2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036–1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165–1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338–1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555–3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

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Uncovering reasons for treatment initiation delays among children with TB in Lima, Peru

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.20.0079 ◽

2020 ◽

Vol 24 (12) ◽

pp. 1254-1260

Author(s):

J. Coit ◽

M. Wong ◽

J. T. Galea ◽

M. Mendoza ◽

H. Marin ◽

...

Keyword(s):

Treatment Initiation ◽

Complex Interventions ◽

Diagnostic Tools ◽

Diagnostic Study ◽

Burden Of Care ◽

Structured Interviews ◽

Tb Treatment ◽

Pediatric Tb ◽

Field Workers ◽

Pediatric Tuberculosis

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0–14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7–117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

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Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.653898 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nathella Pavan Kumar ◽

Syed Hissar ◽

Kannan Thiruvengadam ◽

Velayuthum V. Banurekha ◽

N. Suresh ◽

...

Keyword(s):

Plasma Levels ◽

Validation Cohort ◽

Diagnostic Study ◽

Operating Characteristics ◽

Discovery Cohort ◽

Roc Curve Analysis ◽

Immune Biomarkers ◽

Cytokine Plasma ◽

Pediatric Tb ◽

Pediatric Tuberculosis

Pediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls (discovery cohort) and obtained a separate “validation” cohort of confirmed cases of pediatric TB and controls. Multiplex ELISA was performed to examine the plasma levels of cytokines. Discovery and validation cohorts revealed that baseline plasma levels of IFNγ, TNFα, IL-2, and IL-17A were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics (ROC) curve analysis revealed that IFNγ, IL-2, TNFα, and IL-17A (in the discovery cohort) and TNFα and IL-17A (in the validation cohort) could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 90%. In the discovery cohort, cytokines levels were significantly diminished following anti-tuberculosis treatment. In both the cohorts, combiROC models offered 100% sensitivity and 98% to 100% specificity for a three-cytokine signature of TNFα, IL-2, and IL-17A, which can distinguish confirmed or unconfirmed TB children from unlikely TB. Thus, a baseline cytokine signature of TNFα, IL-2, and IL-17A could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.

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Post Endoscopy Barrett’s Neoplasia (PEBN) After A Negative Index Endoscopy: A Systematic Review & Proposal For Definitions and Performance Measures in Endoscopy

Endoscopy ◽

10.1055/a-1729-8066 ◽

2022 ◽

Author(s):

Madhav Desai ◽

David A Lieberman ◽

Sachin Srinivasan ◽

Venkat Nutalapati ◽

Abhishek Challa ◽

...

Keyword(s):

Systematic Review ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Meta Analysis ◽

Incidence Rates ◽

High Rate ◽

Negative Index ◽

Inclusion Criteria ◽

Surveillance Interval ◽

And Performance

Background and aims: A high rate of neoplasia (high grade dysplasia; HGD and esophageal adenocarcinoma; EAC) has been reported in Barrett’s Esophagus at index endoscopy but precise rates of post endoscopy Barrett’s neoplasia (PEBN) are unknown. Methods: Systematic review and meta-analysis was performed examining electronic databases (inception to October 2021) for studies reporting PEBN. Consistent with definitions of Post Colonoscopy Colorectal Cancer as proposed by the World Endoscopy Organization, we defined neoplasia(HGD/EAC) detected at index endoscopy and/or within 6 months of a negative index endoscopy as “prevalent” neoplasia; those detected after 6 months of a negative index endoscopy and prior to next surveillance interval(i.e. 3 years) as PEBN or “interval” neoplasia, and those detected after 36 months of a negative index endoscopy as “incident” neoplasia. Pooled incidence rates and proportion relative to total neoplasia were analyzed. Results: 11 studies (n=59,795, age:62.3±3.3 years, 61%males) met inclusion criteria. The pooled incidence rates were: prevalent neoplasia 4.5% (95%confidence interval: 2.2-8.9) at baseline and additional 0.3%(0.1-0.7) within first 6 months, PEBN 0.52%(0.48-0.58) and incident neoplasia: 1.41%(0.93-2.14). At 3 years from index endoscopy, PEBN accounted for 3% while prevalent neoplasia accounted for 97% of total Barrett’s neoplasia. Conclusion: Neoplasia detected at or within 6 months of index endoscopy account for most of the Barrett’s neoplasia(>90%). Post-Endoscopy Barrett’s Neoplasia account for ~3% of cases and can be used for validation in future. This highlights the importance of a high-quality index endoscopy in Barrett’s Esophagus and the need to establish quality benchmarks to measure endoscopists’ performance.

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Pediatric glioma and medulloblastoma risk and population demographics: a Poisson regression analysis

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa089 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Ivo S Muskens ◽

Qianxi Feng ◽

Stephen S Francis ◽

Kyle M Walsh ◽

Roberta Mckean-Cowdin ◽

...

Keyword(s):

Poisson Regression ◽

Incidence Rates ◽

Seer Database ◽

Foreign Born ◽

Calendar Time ◽

Related Factors ◽

Annual Percent Change ◽

Pediatric Glioma ◽

Race Ethnicity ◽

Hispanic White

Abstract Background The incidence of pediatric brain tumors varies by race and ethnicity, but these relationships may be confounded by socioeconomic status (SES). In this study, the Surveillance, Epidemiology, and End Results Program (SEER) database was evaluated for associations between race/ethnicity and pediatric glioma and medulloblastoma risk with adjustment for SES. Methods Pediatric glioma and medulloblastoma cases from the SEER database (years: 2000–2016) were included. Differences in incidence rates by ethnicity, sex, age, and SES-related factors were evaluated by calculation of age-adjusted incidence rates (AAIRs) and annual percent change (APC). SES-related factors (percentage without less than high school graduation, median household income, and percentage foreign-born) were derived from the census at the county-level (year: 2000). Multivariable Poisson regression models with adjustment for selected covariates were constructed to evaluate risk factors. Results The highest AAIRs of pediatric glioma were observed among non-Hispanic Whites (AAIR: 2.91 per 100 000, 95%-CI: 2.84–2.99). An increasing incidence of pediatric glioma by calendar time was observed among non-Hispanic Whites and non-Hispanic Blacks (APC: 0.97%, 95%-CI: 0.28–1.68 and APC: 1.59%, 95%-CI: 0.03–3.18, respectively). Hispanic and non-Hispanic Black race/ethnicity was associated with lower risk when compared with non-Hispanic White (incidence rate ratios [IRRs]: 0.66, 95%-CI: 0.63–0.70; and 0.69, 95%-CI: 0.65–0.74, respectively). For medulloblastoma, the highest AAIR was observed for non-Hispanic Whites with a positive APC (1.52%, 95%-CI: 0.15–2.91). Hispanics and non-Hispanic Blacks had statistically significant lower IRRs compared with non-Hispanic Whites (IRRs: 0.83, 95%-CI: 0.73–0.94; and 0.72, 95%-CI: 0.59–0.87, respectively). Conclusion Non-Hispanic White race/ethnicity was associated with higher pediatric glioma and medulloblastoma IRRs in models with adjustments for SES.

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Immunobiology of Pediatric Tuberculosis: Lessons Learned and Implications for an Improved TB-Vaccine

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0037-1607233 ◽

2017 ◽

Vol 13 (02) ◽

pp. 113-121 ◽

Cited By ~ 1

Author(s):

Mardi Boer ◽

Deborah Lewinsohn ◽

Christina Lancioni

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Mycobacterial Infection ◽

Lessons Learned ◽

Bacillus Calmette Guerin ◽

Partial Protection ◽

Young Infants ◽

Pediatric Tb ◽

Pediatric Tuberculosis ◽

Disseminated Disease

AbstractChildren, especially neonates and young infants, are uniquely vulnerable to tuberculosis (TB) and frequently present with primary progressive pulmonary or disseminated disease. There is an urgent need to understand the unique immunobiology of Mycobacterium tuberculosis (Mtb) in young infants and to identify protective infant immune responses. The existing vaccine against TB, Mycobacterium bovis bacillus Calmette–Guérin (M. bovis BCG), provides a partial protection against TB disease and disseminated forms of TB in infants; however, it is unknown how this partial protection is mediated. To end pediatric TB morbidity and mortality, a fully efficacious next-generation TB-vaccine is needed. Here, we focus on our current understanding of TB immunobiology as it pertains to young infants, and we evaluate what BCG-vaccination, as well as recently trialed novel TB-vaccines, has taught us about the immunobiology of mycobacterial infection in this population.

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Assessment of Late Thromboembolic Complications Post–Fontan Procedure in Relation to Different Antithrombotic Regimens: 30-Years’ Follow-up Experience

Annals of Pharmacotherapy ◽

10.1177/1060028019829860 ◽

2019 ◽

Vol 53 (8) ◽

pp. 786-793

Author(s):

Abdulrazaq S. Al-Jazairi ◽

Hana A. Al Alshaykh ◽

Giovanni Di Salvo ◽

Edward B. De Vol ◽

Zohair Y. Alhalees

Keyword(s):

Incidence Rate ◽

Rate Ratio ◽

Fontan Procedure ◽

Incidence Rates ◽

Drug Selection ◽

Thromboembolic Complications ◽

Inclusion Criteria ◽

Duration Of Therapy ◽

The Difference

Background: The current CHEST guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboembolic complications (TECs) prophylaxis in patients who undergo Fontan procedure, without specification on drug selection or duration of therapy. Objective: To investigate the incidence rate of late TECs, occurring after 1-year post–Fontan procedure and to assess the difference in rate of late TECs between warfarin and aspirin. Methods: A retrospective cohort study included patients who had Fontan procedures between 1985-2010 at our institution. Patients were stratified according to the antithrombotic regimen—warfarin, aspirin, or no therapy—at the time of TECs. Results: We screened 499 patients who underwent Fontan procedures; 431 procedures met the inclusion criteria. Over a median follow-up of 13.6 years (IQR= 8.7), freedom from late TECs at 5, 10, 15, and 20 years was 97.54%, 96.90%, 90.78%, and 88.07%, respectively. There was no difference in late TEC incidence rates per 1000 patient-years between warfarin and aspirin: 7.82 and 5.83 events, respectively; rate ratio= 1.34 (95% CI= 0.68-2.60). Warfarin was associated with a higher major bleeding incidence rate per 1000 patient-years: 3.70 versus 2.91 events with aspirin; rate ratio= 1.27 (95% CI= 0.49 to 3.29). Conclusion and Relevance: The incidence rate of late clinical TECs post–Fontan procedure in our population is low. Warfarin was not superior to aspirin for prevention of late TECs. Yet warfarin was associated with a higher rate of bleeding. This finding suggests a simpler antithrombotic regimen for prevention of TEC after 1-year post-Fontan procedure.

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Incidence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210963 ◽

2017 ◽

Vol 76 (9) ◽

pp. 1591-1597 ◽

Cited By ~ 24

Author(s):

Alexander Egeberg ◽

Lars Erik Kristensen ◽

Jacob P Thyssen ◽

Gunnar Hilmar Gislason ◽

Alice B Gottlieb ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Certolizumab Pegol ◽

National Level ◽

Temporal Trends ◽

Linkage Study ◽

Incidence Rates ◽

Biologic Agents ◽

Clear Trend ◽

Number Of Patients ◽

Gender And Age

ObjectivesTo examine the incidence and temporal trends of psoriatic arthritis (PsA) in the general population in Denmark.MethodsUsing nationwide registry data, we estimated the number of patients with incident PsA within each 1-year period between 1997 and 2011 and calculated the rate of PsA cases within gender and age subgroups. Incidence rates were presented per 100 000 person-years.ResultsThere was a female predominance ranging from 50.3% (1998) to 59.2% (2010), and the mean age at time of diagnosis was 47–50 years. We identified a total of 12 719 patients with PsA (prevalence=0.22%), including 9034 patients where the PsA diagnosis was made by a rheumatologist (prevalence=0.16%). Incidence rates of PsA (per 100 000 person-years) increased from 7.3 in 1997 to a peak incidence of 27.3 in 2010. Incidence rates were highest for women and patients aged 50–59 years, respectively. The use of systemic non-biologic agents, that is, methotrexate, leflunomide, ciclosporin or sulfasalazine increased over the 15-year study course and were used in 66.3% of all patients. Biologic agents (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab or ustekinumab) were used in 17.7% of patients with PsA.ConclusionsWe found a clear trend of rising PsA incidence on a national level. While the cause remains unclear, our findings might be explained by increased attention by patients and physicians.

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