Describing Elephants: An Update on the Immunopathology of Multisystem Inflammatory Syndrome in Children.

First described in 2020, multi-system inflammatory syndrome in children (MIS-C) is an, initially life-threatening, disease characterised by severe inflammation and following exposure to SARS-CoV-2. The immunopathology of MIS-C involves a hyperinflammation characterised by a cytokine storm and activation of both the innate and adaptive immune system, eventually leading to multi-organ failure. Several etiological theories are described in literature. Firstly, it is suggested that the gut plays an important role in the translocation of microbial products to the systemic circulation. Additionally, the production of autoantibodies that develop after the initial infection with SARS-CoV-2 might lead to many of its broad clinical symptoms. Finally, the superantigen theory where non-specific binding of the SARS-CoV-2 spike glycoprotein to the T-cell receptor leads to a subsequent activation of T cells, generating a powerful immune response. Despite the sudden outbreak of MIS-C and alarming messages, as of 2024, cases have declined drastically and subsequently show a less severe clinical spectrum. However, subacute cases not meeting current diagnostic criteria might be overlooked even though they represent a valuable research population. In the future, research should focus on adjusting these criteria to better understand the broad pathophysiology of MIS-C, aiding early detection, therapy, and prediction.

Coverage and determinants of COVID-19 child vaccination in Munich, Germany in October 2022-January 2023: Results of the COVIP-Virenwächter study.

COVID-19 vaccination reduces the risk of severe disease, in children as well as adults. We studied COVID-19 vaccination coverage among children, parental COVID-19 vaccination intent for their children and determinants of vaccination among children to inform communication strategies. We invited parents of children aged 6 months-11 years in Munich, Germany, to an anonymous online survey between 13.10.2022 and 15.01.2023. Parents reported COVID-19 vaccination status and, for unvaccinated children, vaccination intent per child. We determined vaccination coverage (≥ 1 dose) and parental intent, and subsequently used logistic regression to identify determinants of vaccination, including the 5C psychological antecedents of vaccination (confidence, complacency, constraints, calculation, collective responsibility). In total, 339 parents reported on 591 children. Vaccination coverage was 7% (6/86) amongst 6-months-4-year-olds and 59% (295/498) amongst 5-11-year-olds. For unvaccinated 6-months-4-year-olds, 31% of parents reported high, 13% medium, 56% low vaccination intent; for 5-11-year-olds 8% reported high, 20% medium, 71% low intent. Positive determinants of vaccination were older child age, child belonging to a clinically vulnerable group, as well as parental COVID-19 vaccination, higher education level, country of birth Germany, and high level of trust in official guidelines; a negative determinant was previous vaccination refusal. For 5-11-year-olds, additional positive determinants were higher confidence and lower complacency.    Conclusion: While a substantial proportion of 5-11-year-olds were vaccinated against COVID-19, coverage was low among 6-months-4-year-olds. Parental vaccination intent for unvaccinated children was low. Vaccination communication should take into account parental socio-demographic characteristics and specifically address individual risks and benefits of child vaccination. What is Known: • COVID-19 vaccination lowers severe disease risk in all ages. • Germany recommends vaccination for 5-11-years-olds since December 2021 and for 6 months-4 year-olds since November 2022. What is New: • In Munich, vaccine uptake was high in 5-11-year-olds but parental intent for not yet vaccinated children was low; the opposite was the case for 6-months-4-year-olds; vaccination determinants were eligibility, parental education, birth country and general vaccination hesitancy; psychological antecedents were confidence and complacency. • Tailored interventions should address guidelines, health literacy, cultural sensitivity, and boost confidence in vaccines and institutions while raising awareness of COVID-19 risks for children.

Epidemiology of common infectious diseases before and during the COVID-19 pandemic in Bavaria, Germany, 2016 to 2021: an analysis of routine surveillance data.

BackgroundUnprecedented non-pharmaceutical interventions to control the COVID-19 pandemic also had an effect on other infectious diseases.AimWe aimed to determine their impact on transmission and diagnosis of notifiable diseases other than COVID-19 in Bavaria, Germany, in 2020 and 2021.MethodsWe compared weekly cases of 15 notifiable infectious diseases recorded in Bavaria between 1 January 2016 and 31 December 2021 in time series analyses, median age and time-to-diagnosis using Wilcoxon rank sum test and hospitalisation rates using univariable logistic regression during three time periods: pre-pandemic (weeks 1 2016-9 2020), pandemic years 1 (weeks 10-52 2020) and 2 (2021).ResultsWeekly case numbers decreased in pandemic year 1 for all diseases assessed except influenza, Lyme disease and tick-borne encephalitis; markedly for norovirus gastroenteritis (IRR = 0.15; 95% CI: 0.12-0.20) and pertussis (IRR = 0.22; 95% CI: 0.18-0.26). In pandemic year 2, influenza (IRR = 0.04; 95% CI: 0.02-0.09) and pertussis (IRR = 0.11; 95% CI: 0.09-0.14) decreased markedly, but also chickenpox, dengue fever, Haemophilus influenzae invasive infection, hepatitis C, legionellosis, noro- and rotavirus gastroenteritis and salmonellosis. For enterohaemorrhagic Escherichia coli infections, median age decreased in pandemic years 1 and 2 (4 years, interquartile range (IQR): 1-32 and 3 years, IQR: 1-18 vs 11 years, IQR: 2-42); hospitalisation proportions increased in pandemic year 1 (OR = 1.60; 95% CI: 1.08-2.34).ConclusionReductions for various infectious diseases and changes in case characteristics in 2020 and 2021 indicate reduced transmission of notifiable diseases other than COVID-19 due to interventions and under-detection.

Smad7 in intestinal CD4+ T cells determines autoimmunity in a spontaneous model of multiple sclerosis.

Environmental triggers acting at the intestinal barrier are thought to contribute to the initiation of autoimmune disorders. The transforming growth factor beta inhibitor Smad7 determines the phenotype of CD4+ T cells. We hypothesized that Smad7 in intestinal CD4+ T cells controls initiation of opticospinal encephalomyelitis (OSE), a murine model of multiple sclerosis (MS), depending on the presence of gut microbiota. Smad7 was overexpressed or deleted in OSE CD4+ T cells to determine the effect on clinical progression, T cell differentiation, and T cell migration from the intestine to the central nervous system (CNS). Smad7 overexpression worsened the clinical course of OSE and increased CNS inflammation and demyelination. It favored expansion of intestinal CD4+ T cells toward an inflammatory phenotype and migration of intestinal CD4+ T cells to the CNS. Intestinal biopsies from MS patients revealed decreased transforming growth factor beta signaling with a shift toward inflammatory T cell subtypes. Smad7 in intestinal T cells might represent a valuable therapeutic target for MS to achieve immunologic tolerance in the intestine and suppress CNS inflammation.

Tuberculosis contact investigation following the stone-in-the-pond principle in the Netherlands - Did adjusted guidelines improve efficiency?

BackgroundIn low tuberculosis (TB) incidence countries, contact investigation (CI) requires not missing contacts with TB infection or disease without unnecessarily evaluating non-infected contacts.AimWe assessed whether updated guidelines for the stone-in-the-pond principle and their promotion improved CI practices.MethodsThis retrospective study used surveillance data to compare CI outcomes before (2011-2013) and after (2014-2016) the guideline update and promotion. Using negative binomial regression and logistic regression models, we compared the number of contacts invited for CI per index patient, the number of CI scaled-up according to the stone-in-the-pond principle, the TB and latent TB infection (LTBI) testing coverage, and yield.ResultsPre and post update, 1,703 and 1,489 index patients were reported, 27,187 and 21,056 contacts were eligible for CI, 86% and 89% were tested for TB, and 0.70% and 0.73% were identified with active TB, respectively. Post update, the number of casual contacts invited per index patient decreased statistically significantly (RR = 0.88; 95% CI: 0.79-0.98), TB testing coverage increased (OR = 1.4; 95% CI: 1.2-1.7), and TB yield increased (OR = 2.0; 95% CI: 1.0-3.9). The total LTBI yield increased from 8.8% to 9.8%, with statistically significant increases for casual (OR = 1.2; 95% CI: 1.0-1.5) and community contacts (OR = 2.0; 95% CI: 1.6-3.2). The proportion of CIs appropriately scaled-up to community contacts increased statistically significantly (RR = 1.8; 95% CI: 1.3-2.6).ConclusionThis study shows that promoting evidence-based CI guidelines strengthen the efficiency of CIs without jeopardising effectiveness. These findings support CI is an effective TB elimination intervention.

Patient support during treatment for active tuberculosis and for latent tuberculosis infection: Policies and practices in European low-incidence countries.

AIM: To provide an overview of the policies and practices of patient support during treatment for active tuberculosis and for latent tuberculosis infection in European countries with a low incidence of tuberculosis and to identify potential best practices. BACKGROUND: Policies, practices and its' evaluations from similar settings may aid in the development of evidence-based patient support guidelines. DESIGN: Descriptive study. METHODS: In June 2016, a survey was conducted among the 24 European low tuberculosis incidence countries (<20 patients per 100,000 population). RESULTS: Nineteen of the 24 countries approached responded. Most countries (18/19) gave some form of tuberculosis patient support including various treatment supervision options and treatment adherence interventions such as health education, psycho-emotional and socio-economic support. Patient support for persons on treatment for latent tuberculosis infection was less widely (9/19) implemented. Patient support guidelines were available in 13 countries, but none of the interventions included had been quantitatively evaluated for their effects on treatment adherence. Potential best practices included appointing a tuberculosis coordinator in charge of organizing patient support; putting a treatment plan meeting with patients, providers and stakeholders in place; supplying direct enablers for marginalized patients; organizing cultural-sensitive community support; and dispensing pill cases. A lack of resources impeded the provision of patient support, especially for home-based treatment supervision. CONCLUSION: We summarized policies and practices of tuberculosis and latent tuberculosis infection patient support in low tuberculosis incidence European countries. Given the lack of quantitative evaluations, more research is needed to verify the effectiveness of identified potential best practices.

Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice.

Current therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical features of MS including relapsing-remitting episodes and secondary-progressive disability. To address the contribution of recurrent inflammatory events and ageing as factors that amplify progressive neurological disease, we examined EAE in 8- to 12-week-old and 12-month-old ABH mice. Compared with the relapsing-remitting (RREAE) and secondary progressive (SPEAE) EAE observed in young mice, old mice developed progressive disease from onset (PEAE) associated with pronounced axonal damage and increased numbers of CD3(+) T cells and microglia/macrophages, but not B cells. Whereas the clinical neurological features of PEAE and SPEAE were comparable, the pathology was distinct. SPEAE was associated with significantly reduced perivascular infiltrates and T-cell numbers in the central nervous system (CNS) compared with PEAE and the acute phase of RREAE. In contrast to perivascular infiltrates that declined during progression from RREAE into SPEAE, the numbers of microglia clusters remained constant. Similar to what is observed during MS, the microglia clusters emerging during EAE were associated with axonal damage and oligodendrocytes expressing heat-shock protein B5, but not lymphocytes. Taken together, our data reveal that the course of EAE is dependent on the age of the mice. Younger mice show a relapsing-remitting phase followed by progressive disease, whereas old mice immediately show progression. This indicates that recurrent episodes of inflammation in the CNS, as well as age, contribute to progressive neurological disease.

Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions.

Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction. Neonatal ventral hippocampal lesions (NVHL) have previously been demonstrated to produce post-adolescent-onset, pharmacological, neurobiological and cognitive-deficit features of schizophrenia. Here, we show that NVHLs increase adult nicotine self-administration, potentiating acquisition-intake, total nicotine consumed and drug seeking. Behavioral sensitization to nicotine in adolescence prior to self-administration is not accentuated by NVHLs in contrast to increased nicotine self-administration and behavioral sensitization documented in adult NVHL rats, suggesting periadolescent neurodevelopmental onset of nicotine addiction vulnerability in the NVHL model. Delivering a nicotine regimen approximating the exposure used in the sensitization and self-administration experiments (i.e. as a treatment) to adult rats did not specifically reverse NVHL-induced cortical-hippocampal-dependent cognitive deficits and actually worsened cognitive efficiency after nicotine treatment stopped, generating deficits that resemble those due to NVHLs. These findings represent the first prospective evidence demonstrating a causal link between disease processes in schizophrenia and nicotine addiction. Developmental cortical-temporal limbic dysfunction in mental illness may thus amplify nicotine's reinforcing effects and addiction risk and severity, even while producing cognitive deficits that are not specifically or substantially reversible with nicotine.

Acetaminophen overdose: analysis of 2018 US nationwide emergency database.

INTRODUCTION: Recognized risk factors for acetaminophen overdose include alcohol, opioids, and mood disorders. The aim of this study is to assess additional risk factors for acetaminophen overdose evaluated in the emergency department (ED). METHODS: A retrospective study was performed using the 2018 US Nationwide Emergency Department Sample (NEDS). All adult ED visits for acetaminophen overdose were included in the study group and those without it were taken as control. STATA, 16.1 was used to perform multivariable logistic regression analysis and adjusted odds ratios (ORadj) were reported. RESULTS: We identified 27,792 ED visits for acetaminophen overdose. Relative to non-acetaminophen ED visits, this group was younger (median age 32 vs 47 years; p < 0.0001), more often female (66.1% vs 57.0%; p < 0.0001), had higher ED charges ($3,506 vs $2,714; p < 0.0001), higher proportion of alcohol-related disorders (15.8% vs 3.5%; p < 0.0001), anxiety disorders (30.2% vs 8.3%; p < 0.0001), cannabis use (8.7% vs 1.4%; p < 0.0001), hematology/oncology diagnoses (13.3% vs 10.9%; p < 0.0001), mood disorders (52.4% vs 7.9%; p < 0.0001), opioid-related disorders (4.1% vs 1.0%; p < 0.0001), and suicide attempt/ideation (12.2% vs 1.1%; p < 0.0001). Multivariable analysis showed alcohol-related disorders (ORadj 2.67), anxiety disorders (ORadj 1.24), cannabis (ORadj 1.63), females (ORadj 1.45), Income Q3 (ORadj 1.09), hematology/oncology diagnoses (ORadj 1.40), mood disorders (ORadj 10.07), opioid-related disorders (ORadj 1.20), and suicide attempt/ideation (ORadj 1.68) were associated with acetaminophen overdose. CONCLUSION: In addition to previously recognized risks, our study demonstrated that cannabis use and hematologic/oncologic comorbidities were more common among acetaminophen-overdose ED visits. These new findings are concerning because of rapid legalization of cannabis and the increasing incidence of cancer worldwide. Additional investigation into these risks should be a priority for clinicians, policymakers, and researchers.

Rapid Market Screening to assess lead concentrations in consumer products across 25 low- and middle-income countries.

Lead exposure can have serious consequences for health and development. The neurological and behavioral effects of lead are considered irreversible. Young children are particularly vulnerable to lead poisoning. In 2020, Pure Earth and UNICEF estimated that one in three children had elevated blood lead levels above 5 µg/dL. The sources of lead exposure vary around the world and can range from household products, such as spices or foodware, to environmental pollution from nearby industries. The aim of this study was to analyze common products from markets in low- and middle-income countries (LMICs) for their lead content to determine whether they are plausible sources of exposure. In 25 LMICs, the research teams systematically collected consumer products (metal foodware, ceramics, cosmetics, paints, toys, spices and other foods). The items were analyzed on site for detectable lead above 2 ppm using an X-ray fluorescence analyzer. For quality control purposes, a subset of the samples was analyzed in the USA using inductively coupled plasma mass spectrometry. The lead concentrations of the individual product types were compared with established regulatory thresholds. Out of 5007 analyzed products, threshold values (TV) were surpassed in 51% for metal foodware (TV 100 ppm), 45% for ceramics (TV 100 ppm), and 41% for paints (TV 90 ppm). Sources of exposure in LMICs can be diverse, and consumers in LMICs lack adequate protection from preventable sources of lead exposure. Rapid Market Screening is an innovative, simple, and useful tool to identify risky products that could be sources of lead exposure.

The effects of the COVID-19 pandemic on PICU admissions for severe asthma exacerbations: A single-center experience.

BACKGROUND: The incidence of severe asthma exacerbations (SAE) requiring a pediatric intensive care unit (PICU) admission during the coronavirus disease 2019 (COVID-19) pandemic (and its association with public restrictions) is largely unknown. We examined the trend of SAE requiring PICU admission before, during, and after COVID-19 restrictions in Amsterdam, the Netherlands, and its relationship with features such as environmental triggers and changes in COVID-19 restriction measures. METHODS: In this single-center, retrospective cohort study, all PICU admissions of children aged ≥2 years for severe asthma at the Amsterdam UMC between 2018 and 2022 were included. The concentrations of ambient fine particulate matter (PM2.5 ) and pollen were obtained from official monitoring stations. RESULTS: Between January 2018 and December 2022, 228 children were admitted to the PICU of the Amsterdam UMC for SAE. While we observed a decrease in admissions during periods of more stringent restriction, there was an increase in the PICU admission rate for SAE in some periods following the lifting of restrictions. In particular, following the COVID-19 restrictions in 2021, we observed a peak incidence of admissions from August to November, which was higher than any other peak during the indicated years. No association with air pollution or pollen was observed. CONCLUSION: We hypothesize that an increase in clinically diagnosed viral infections after lockdown periods was the reason for the altered incidence of SAE at the PICU in late 2021, rather than air pollution and pollen concentrations.

Pediatric Toxicology: An Updated Review.

Pediatricians should be familiar with principles of medical toxicology given that intentional and unintentional ingestions are commonly encountered in different medical settings. Most exploratory ingestions are well tolerated and do not cause significant health effects, but a few noteworthy exceptions can lead to serious illness and death. This article reviews common medications and household products likely to cause significant toxicity in pediatric patients, even in small, exploratory ingestions. Increasing cannabis exposures among children and adolescents are also reviewed. Additionally, indications for gastric decontamination with activated charcoal are reviewed. Finally, poisoning prevention strategies are reviewed. [Pediatr Ann. 2023;52(4):e139-e145.].

The influence of disparities on intensive care outcomes in children with respiratory diseases: A systematic review.

CONTEXT: The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. OBJECTIVE: The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants and PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children's respiratory diseases at the PICU. METHODS: A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. RESULTS: Eight thousand seven hundred fourty-six references were reviewed, and 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. CONCLUSION: Disparities in socioeconomic (such as a low-income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children's respiratory diseases and can negatively influence the outcomes of these children admitted and treated at the PICU.

Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015-2020.

INTRODUCTION: Fomepizole inhibits formation of toxic acetaminophen (APAP) metabolites and may prevent or reverse mitochondrial toxicity. Given these mechanisms, it may be beneficial in patients with severe APAP toxicity. Current patterns of use for this indication are not well-studied. METHODS: This is a secondary analysis of patients enrolled in the Toxicology Investigators Consortium (ToxIC) database from January 2015 to July 2020. We queried cases in which APAP was listed as an ingested agent and fomepizole was also administered. We excluded cases in which APAP was not the primary agent, N-acetylcysteine (NAC) was not administered, or fomepizole was explicitly administered for another indication. Additionally, we sent a survey to each ToxIC site that administered fomepizole for APAP toxicity to better understand when, why, and how they were using it for this indication. RESULTS: Twenty-five cases of fomepizole administration following an APAP ingestion met our inclusion criteria. There were one to four cases per year between 2015 and 2019 and eight cases in 2020. Seventeen of 25 (68%) cases were for a known acute ingestion. Eighteen of 25 (72%) patients developed hepatotoxicity (AST or ALT > 1000 IU/L) and 10 of 25 (40%) developed coagulopathy (PT > 15s). This was an ill patient population, with 18 of 25 (72%) developing metabolic acidosis (pH <7.20), 12 of 25 (48%) were intubated, 9 of 25 (36%) receiving vasopressors, and 6 of 25 (24%) receiving continuous renal replacement therapy. Overall, mortality was 24%. CONCLUSION: The use of fomepizole is increasing in frequency in a small subset of critically ill and acutely APAP-poisoned patients.

Severe acute asthma at the pediatric intensive care unit: can we link the clinical phenotypes to immunological endotypes?

INTRODUCTION: The clinical phenotype of severe acute asthma at the pediatric intensive care unit (PICU) is highly heterogeneous. However, current treatment is still based on a 'one-size-fits-all approach'. AREAS COVERED: We aim to give a comprehensive description of the clinical characteristics of pediatric patients with severe acute asthma admitted to the PICU and available immunological biomarkers, providing the first steps toward precision medicine for this patient population. A literature search was performed using PubMed for relevant studies on severe acute (pediatric) asthma. EXPERT OPINION: Omics technologies should be used to investigate the relationship between cellular molecules and pathways, and their clinical phenotypes. Inflammatory phenotypes might guide bedside decisions regarding the use of corticosteroids, neutrophil modifiers and/or type of beta-agonist. A next step toward precision medicine should be inclusion of these patients in clinical trials on biologics.

Temperature-Dependent Low-Frequency Modes in the Active Site of Bovine Carbonic Anhydrase II Probed by 2D-IR Spectroscopy.

Enzyme catalysis achieves tremendous rate accelerations. Enzyme reaction centers provide a constraint geometry that preferentially binds an activated form of the substrate and thus lowers the energy barrier. However, this transition state picture neglects the flexibility of proteins and its role in enzymatic catalysis. Especially for proton transfer reactions, it has been suggested that motions of the protein modulate the donor-acceptor distance and prepare a tunneling-ready state. We report the detection of frequency fluctuations of an azide anion (N3-) bound in the active site of the protein carbonic anhydrase II, where a low-frequency mode of the protein has been proposed to facilitate proton transfer over two water molecules during the catalyzed reaction. 2D-IR spectroscopy resolves an underdamped low-frequency mode at about 1 THz (30 cm-1). We find its frequency to be viscosity- and temperature-dependent and to decrease by 6 cm-1 between 230 and 320 K, reporting the softening of the mode's potential.

Collaborative tuberculosis/HIV activities in the European Region.

INTRODUCTION: An estimated 12% of tuberculosis (TB) patients are co-infected with HIV in the World Health Organization European Region (the Region). Reducing morbidity and mortality from HIV-associated TB requires strong collaboration between TB and HIV services at all levels with integrated people-centred models of care. METHODS: We collected information on the current models of integration of TB and HIV services in the Region via a comprehensive survey among the TB and HIV National Focal Points, and identified challenges and opportunities. RESULTS: 47 out of 55 (85%) countries responded. HIV testing in all TB patients and screening for active TB in all people living with HIV (PLHIV) was recommended in 40 (85%) and 34 (72%) countries, respectively. 30 (64%) countries recommended latent TB infection (LTBI) screening in all PLHIV, while 13 (28%) had a selective approach and four (9%) did not recommend LTBI screening. In most countries, testing for HIV and screening for active TB and LTBI was done by the specialist treating the patient, i.e. TB patients were tested for HIV by a TB specialist in 42 (89%) countries and PLHIV were screened for active TB by an HIV specialist in 34 (72%) countries. CONCLUSIONS: TB and HIV care are well integrated in policies of especially high TB and high HIV burden countries; however, implementation needs to be improved. Continuous monitoring of TB and HIV services integration enables assessing the quality of TB/HIV care and to identify where further improvements are needed.

Antimicrobial Resistance in Isolates from Cattle with Bovine Respiratory Disease in Bavaria, Germany.

Patterns of antimicrobial resistance (AMR) regarding Pasteurella multocida (n = 345), Mannheimia haemolytica (n = 273), Truperella pyogenes (n = 119), and Bibersteinia trehalosi (n = 17) isolated from calves, cattle and dairy cows with putative bovine respiratory disease syndrome were determined. The aim of this study was to investigate temporal trends in AMR and the influence of epidemiological parameters for the geographic origin in Bavaria, Germany, between July 2015 and June 2020. Spectinomycin was the only antimicrobial agent with a significant decrease regarding not susceptible isolates within the study period (P. multocida 88.89% to 67.82%, M. haemolytica 90.24% to 68.00%). Regarding P. multocida, significant increasing rates of not susceptible isolates were found for the antimicrobials tulathromycin (5.56% to 26.44%) and tetracycline (18.52% to 57.47%). The proportions of multidrug-resistant (MDR) P. multocida isolates (n = 48) increased significantly from 3.70% to 22.90%. The proportions of MDR M. haemolytica and P. multocida isolates (n = 62) were significantly higher in fattening farms (14.92%) compared to dairy farms (3.29%) and also significantly higher on farms with more than 300 animals (19.49%) compared to farms with 100 animals or less (6.92%). The data underline the importance of the epidemiological farm characteristics, here farm type and herd size regarding the investigation of AMR.