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As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naive phenotypes and diverse TCRαß repertoires. Our study demonstrates the generation of SARS-CoV-2-specific T cell memory with common TCRαß motifs in unvaccinated seroconverted children after their first virus encounter.
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COVID-19 , SARS-CoV-2 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Epítopos de Linfocito T , Humanos , Memoria Inmunológica , Receptores de Antígenos de Linfocitos T , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Glicoproteína de la Espiga del CoronavirusRESUMEN
Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Huésped Inmunocomprometido , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , SARS-CoV-2/inmunología , COVID-19/inmunología , Quimioterapia Combinada , Anticuerpos Neutralizantes/uso terapéuticoRESUMEN
Coronavirus disease 2019 (COVID-19) in immunocompromised patients can lead to severe and prolonged illness. Data are limited with regard to management of COVID-19 in this setting, particularly in persistent or recrudescent infection. The authors conducted an online survey among infectious diseases doctors to determine current approaches to treatment across Australasia. There was marked variability in responses relating to the diagnostic modalities and use of antiviral agents in patients with immunocompromise, highlighting the need for high-quality studies to guide treatment decisions in this group.
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COVID-19 , Humanos , Antivirales/uso terapéutico , Huésped Inmunocomprometido , Encuestas y Cuestionarios , Australasia/epidemiologíaRESUMEN
PURPOSE OF REVIEW: This review provides an update on recent findings about the clinical and microbiological characteristics of Staphylococcus lugdunensis . RECENT FINDINGS: European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) differ in their methodology and breakpoints for the detection of penicillin and oxacillin resistance in S. lugdunensis . The EUCAST method for beta-lactamase detection recommends a 1-unit penicillin disk and has demonstrated superior performance compared to the 10-unit penicillin disk recommended by CLSI. A similar outcome has been previously reported in Staphylococcus aureus. In addition, there is emerging oxacillin resistance in some geographical areas. Of particular concern is that oxacillin resistance in mecA positive isolates may not be reliably detected by current cefoxitin breakpoints. SUMMARY: Coagulase negative staphylococci are now recognised as a heterogenous group of organisms that do not microbiologically or clinically behave the same way. The spectrum of clinical disease is species dependent and is particularly true for S. lugdunensis , which causes an array of clinical infections like that of S. aureus. Further studies are needed to assess the performance of phenotypic tests to detect resistance, to ensure that appropriate antimicrobial therapy is delivered to patients.
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Infecciones Estafilocócicas , Staphylococcus lugdunensis , Humanos , Staphylococcus aureus , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas , Oxacilina , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVE: To compare the concordance and acceptability of saliva testing with standard-of-care oropharyngeal and bilateral deep nasal swab testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in children and in general practice. DESIGN: Prospective multicentre diagnostic validation study. SETTING: Royal Children's Hospital, and two general practices (cohealth, West Melbourne; Cirqit Health, Altona North) in Melbourne, July-October 2020. PARTICIPANTS: 1050 people who provided paired saliva and oropharyngeal-nasal swabs for SARS-CoV-2 testing. MAIN OUTCOME MEASURES: Numbers of cases in which SARS-CoV-2 was detected in either specimen type by real-time polymerase chain reaction; concordance of results for paired specimens; positive percent agreement (PPA) for virus detection, by specimen type. RESULTS: SARS-CoV-2 was detected in 54 of 1050 people with assessable specimens (5%), including 19 cases (35%) in which both specimens were positive. The overall PPA was 72% (95% CI, 58-84%) for saliva and 63% (95% CI, 49-76%) for oropharyngeal-nasal swabs. For the 35 positive specimens from people aged 10 years or more, PPA was 86% (95% CI, 70-95%) for saliva and 63% (95% CI, 45-79%) for oropharyngeal-nasal swabs. Adding saliva testing to standard-of-care oropharyngeal-nasal swab testing increased overall case detection by 59% (95% CI, 29-95%). Providing saliva was preferred to an oropharyngeal-nasal swab by most participants (75%), including 141 of 153 children under 10 years of age (92%). CONCLUSION: In children over 10 years of age and adults, saliva testing alone may be suitable for SARS-CoV-2 detection, while for children under 10, saliva testing may be suitable as an adjunct to oropharyngeal-nasal swab testing for increasing case detection.
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Prueba de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/aislamiento & purificación , Manejo de Especímenes/métodos , Adolescente , Adulto , Factores de Edad , Anciano , COVID-19/virología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Orofaringe/virología , Estudios Prospectivos , ARN Viral/aislamiento & purificación , SARS-CoV-2/genética , Saliva/virología , Adulto JovenRESUMEN
We report four cases of invasive pulmonary aspergillus co-infection in patients with coronavirus disease 2019 (COVID-19) infection and acute respiratory distress syndrome requiring intensive care unit (ICU) admission. Aspergillus fumigatus and Aspergillus terreus were isolated, with early infection onset following ICU admission. Clinicians should be aware of invasive pulmonary aspergillosis in ICU patients with COVID-19 infection, particularly those receiving dexamethasone. We propose screening of these high-risk patients with twice-weekly fungal culture from tracheal aspirate and, if feasible, Aspergillus polymerase chain reaction. Diagnosis is challenging and antifungal treatment should be considered in critically ill patients who have new or worsening pulmonary changes on chest imaging and mycological evidence of infection.
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COVID-19 , Aspergilosis Pulmonar Invasiva , Enfermedad Crítica , Humanos , Unidades de Cuidados Intensivos , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Aspergilosis Pulmonar Invasiva/epidemiología , SARS-CoV-2RESUMEN
BACKGROUND: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation. METHODS: Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT). RESULTS: Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%-60.4%) to 67.9% (95% CI, 59.4%-75.6%), and specificities from 95.6% (95% CI, 89.2%-98.8%) to 100.0% (95% CI, 96.1%-100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%-75.6%), increasing to 93.8% (95% CI, 85.0%-98.3%) for samples >14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%-68.4%), rising to 91.2% (95% CI, 81.8%-96.7%) for samples >14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%-97.5%). CONCLUSIONS: Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.
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Infecciones por Coronavirus/sangre , Neumonía Viral/sangre , Algoritmos , Anticuerpos Antivirales/sangre , Australia/epidemiología , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Pruebas de Neutralización/métodos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , SARS-CoV-2 , Pruebas Serológicas/métodos , Pruebas Serológicas/normasRESUMEN
OBJECTIVES: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate. SETTING: SARS-CoV-2 was isolated from a 58-year-old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID-19 (the illness caused by SARS-CoV-2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS-CoV-2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS-CoV-2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS-CoV-2 genomes. Within 24 hours of isolation, the first Australian SARS-CoV-2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.
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Betacoronavirus/genética , Infecciones por Coronavirus/genética , Difusión de la Información/métodos , Aislamiento de Pacientes/métodos , Neumonía Viral/genética , Australia , COVID-19 , Infecciones por Coronavirus/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , SARS-CoV-2 , Secuenciación Completa del GenomaRESUMEN
OBJECTIVES: To design and evaluate 3D-printed nasal swabs for collection of samples for SARS-CoV-2 testing. DESIGN: An iterative design process was employed. Laboratory evaluation included in vitro assessment of mock nasopharyngeal samples spiked with two different concentrations of gamma-irradiated SARS-CoV-2. A prospective clinical study compared SARS-CoV-2 and human cellular material recovery by 3D-printed swabs and standard nasopharyngeal swabs. SETTING, PARTICIPANTS: Royal Melbourne Hospital, May 2020. Participants in the clinical evaluation were 50 hospital staff members attending a COVID-19 screening clinic and two inpatients with laboratory-confirmed COVID-19. INTERVENTION: In the clinical evaluation, a flocked nasopharyngeal swab sample was collected with the Copan ESwab and a mid-nasal sample from the other nostril was collected with the 3D-printed swab. RESULTS: In the laboratory evaluation, qualitative agreement with regard to SARS-CoV-2 detection in mock samples collected with 3D-printed swabs and two standard swabs was complete. In the clinical evaluation, qualitative agreement with regard to RNase P detection (a surrogate measure of adequate collection of human cellular material) in samples collected from 50 hospital staff members with standard and 3D-printed swabs was complete. Qualitative agreement with regard to SARS-CoV-2 detection in three pairs of 3D-printed mid-nasal and standard swab samples from two inpatients with laboratory-confirmed SARS-CoV-2 was also complete. CONCLUSIONS: Using 3D-printed swabs to collect nasal samples for SARS-CoV-2 testing is feasible, acceptable to patients and health carers, and convenient.
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Técnicas de Laboratorio Clínico/instrumentación , Infecciones por Coronavirus/diagnóstico , Técnicas de Diagnóstico del Sistema Respiratorio/instrumentación , Aceptación de la Atención de Salud/estadística & datos numéricos , Neumonía Viral/diagnóstico , Impresión Tridimensional , Adulto , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Pandemias , SARS-CoV-2Asunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , Vacunas contra la COVID-19 , COVID-19/prevención & control , SARS-CoV-2 , Linfocitos T , Inhibidores del Factor de Necrosis Tumoral , Anticuerpos Antivirales , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , VacunaciónRESUMEN
In Victoria, Australia, invasive meningococcal disease caused by Neisseria meningitidis serogroup W increased from 4% of all cases in 2013 to 30% in 2015. This increase resulted largely from strains similar to those in the serogroup W sequence type 11 clonal complex, previously described in the United Kingdom and South America.
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Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/microbiología , Neisseria meningitidis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Infecciones Meningocócicas/fisiopatología , Persona de Mediana Edad , Neisseria meningitidis/clasificación , Serotipificación , Victoria , Adulto JovenAsunto(s)
COVID-19/transmisión , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/estadística & datos numéricos , Enfermedades Profesionales/epidemiología , Personal de Hospital , Adulto , Australia/epidemiología , COVID-19/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Femenino , Departamentos de Hospitales , Hospitales Universitarios , Humanos , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Masculino , Enfermedades Profesionales/prevención & control , SARS-CoV-2Asunto(s)
Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Neumonía Viral/diagnóstico , Saliva/virología , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , SARS-CoV-2 , Sensibilidad y EspecificidadAsunto(s)
Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Betacoronavirus , Investigación Biomédica/tendencias , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/epidemiología , Predicción , Humanos , Pandemias , Neumonía Viral/epidemiología , Pruebas en el Punto de Atención , SARS-CoV-2RESUMEN
OBJECTIVES: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance. METHODS: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context. RESULTS: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs. CONCLUSION: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Isoniazida/farmacología , Isoniazida/uso terapéutico , Victoria/epidemiología , Filogenia , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Secuenciación Completa del Genoma , Mutación , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
BACKGROUND AND OBJECTIVES: Ongoing symptoms of COVID-19 can persist for weeks or months after the initial COVID-19 infection. The aim of this study was to identify persistent symptoms (fatigue, cognition, quality of life, anxiety, depression and physical measures) in unvaccinated community-managed patients following COVID-19 infection. METHOD: This was a prospective nested observational study of health and wellbeing measures determined seven and 13 months after COVID-19 infection, alongside physical abilities after 18 months. RESULTS: Data analyses were completed on 62 participants (60% female, median age 35 years). Severe fatigue was noted in 47% of participants at seven months and this had not improved significantly by 13 months (45%). Quality of life and mental health scores were significantly worse in individuals with severe fatigue. One-quarter of participants demonstrated mild cognitive impairment at seven months. After 18 months, walking and lung function were normal, but grip strength was reduced in 26% of participants. DISCUSSION: A significant proportion of unvaccinated COVID-19 patients had not returned to pre-illness levels of health and function after one year; screening functional ability and mental wellbeing is warranted in unvaccinated people with COVID-19.
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COVID-19 , Calidad de Vida , Humanos , COVID-19/complicaciones , COVID-19/fisiopatología , Femenino , Masculino , Estudios Prospectivos , Adulto , Calidad de Vida/psicología , SARS-CoV-2 , Fatiga/etiología , Fatiga/fisiopatología , Ansiedad/etiología , Ansiedad/psicología , Depresión/etiología , Depresión/psicología , Depresión/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Persona de Mediana EdadRESUMEN
Objective: Clostridioides difficile infection (CDI) is the commonest cause of healthcare-associated diarrhea and undergoes standardized surveillance and mandatory reporting in most Australian states and territories. Historically attributed to nosocomial spread, local and international whole genome sequencing (WGS) data suggest varied sources of acquisition. This study describes C. difficile genotypes isolated at a tertiary center in Melbourne, Australia, their likely source of acquisition, and common risk factors. Design: Retrospective observational study. Setting: The Royal Melbourne Hospital (RMH), a 570-bed tertiary center in Victoria, Australia. Methods: Short-read whole genome sequencing was performed on 75 out of 137 C. difficile isolates obtained from 1/5/2021 to 28/2/2022 and compared to previous data from 8/11/2015 to 1/11/2016. Existing data from infection control surveillance and electronic medical records were used for epidemiological and risk factor analysis. Results: Eighty-five (62.1%) of the 137 cases were defined as healthcare-associated from epidemiological data. On genome sequencing, 33 different multi-locus sequence type (MLST) subtypes were identified, with changes in population structure compared to the 2015-16 period. Risk factors for CDI were present in 130 (94.9%) cases, including 108 (78.8%) on antibiotics, 86 (62.8%) on acid suppression therapy, and 25 (18.2) on chemotherapy. Conclusion: In both study periods, most C. difficile isolates were not closely related, suggesting varied sources of acquisition and that spread of C. difficile within the hospital was unlikely. Current infection control precautions may therefore warrant review. Underlying risk factors for CDI were common and may contribute to the proportion of healthcare-associated infections in the absence of proven hospital transmission.
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Objectives: Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti-Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel of commercial monoclonal anti-IgG1 clones for capacity to universally recognise two dominant IgG1 haplotypes (G1m-1,3 and G1m1,17). Methods: Four commercial monoclonal anti-human IgG1 clones were assessed via ELISAs and multiplex bead-based assays for their ability to bind G1m-1,3 and G1m1,17 IgG1 variants. Detection antibodies were validated against monoclonal IgG1 allotype standards and tested for capacity to recognise antigen-specific plasma IgG1 from G1m-1,3 and G1m1,17 homozygous and heterozygous SARS-CoV-2 BNT162b2 vaccinated (n = 28) and COVID-19 convalescent (n = 44) individuals. An Fc-specific pan-IgG detection antibody corroborated differences between hinge- and Fc-specific anti-IgG1 responses. Results: Hinge-specific anti-IgG1 clone 4E3 preferentially bound G1m1,17 compared to G1m-1,3 IgG1. Consequently, SARS-CoV-2 Spike-specific IgG1 levels detected in G1m1,17/G1m1,17 BNT162b2 vaccinees appeared 9- to 17-fold higher than in G1m-1,3/G1m-1,3 vaccinees. Fc-specific IgG1 and pan-IgG detection antibodies equivalently bound G1m-1,3 and G1m1,17 IgG1 variants, and detected comparable Spike-specific IgG1 levels between haplotypes. IgG1 responses against other human coronaviruses and influenza were similarly poorly detected by 4E3 anti-IgG1 in G1m-1,3/G1m-1,3 subjects. Conclusion: Anti-IgG1 clone 4E3 confounds assessment of antibody responses in clinical cohorts owing to bias towards detection of G1m1,17 IgG1 variants. Validation of anti-Ig clones should include evaluation of binding to relevant antibody variants, particularly as the role of immunogenetics upon humoral immunity is increasingly explored in diverse populations.
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In addition to its motor functions, the cerebellum is involved in emotional regulation, anxiety and affect. We found that suppressing the firing of cerebellar Purkinje cells (PCs) rapidly excites forebrain areas that contribute to such functions (including the amygdala, basal forebrain and septum), but that the classic cerebellar outputs, the deep cerebellar nuclei, do not directly project there. We show that PCs directly inhibit parabrachial nuclei (PBN) neurons that project to numerous forebrain regions. Suppressing the PC-PBN pathway influences many regions in the forebrain and is aversive. Molecular profiling shows that PCs directly inhibit numerous types of PBN neurons that control diverse behaviors that are not involved in motor control. Therefore, the PC-PBN pathway allows the cerebellum to directly regulate activity in the forebrain, and may be an important substrate for cerebellar disorders arising from damage to the posterior vermis.