Clozapine-induced pneumonitis mimicking an atypical pneumonia.

Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever. Clozapine-induced fever often occurs in the first 2 weeks of treatment and settle after a few days. We report a case of a woman in her mid-30s who developed fever and infective symptoms suggestive of an atypical pneumonia while on clozapine titration. She was on clozapine for 16 days before developing high-grade fever, dry cough, diarrhoea, headache and photophobia with a very high CRP. We performed an extensive infection workup that returned negative results except for bilateral upper lobe ground glass changes of the lungs on CT. Despite antibiotic therapy, which would cover an atypical pneumonia, her CRP remained elevated and her fever persisted. Focus was directed to clozapine-induced pneumonitis as the cause for her symptoms. Her antibiotics were ceased, and clozapine was downtitrated. With the adjustment of her clozapine dose, her fevers and associated symptoms resolved, and CRP downtrended. Her fevers did not return when clozapine was uptitrated in the community subsequently. Clozapine-induced fever or other immune-allergic reactions should be systematically considered when patients develop fever during the initiation phase of clozapine therapy. Ruling out infective causes is desirable prior to attributing fevers to clozapine especially when they are accompanied by infective symptoms and high inflammatory markers. Careful downtitration of clozapine should be considered rather than abrupt cessation in managing clozapine-induced fevers and subsequent slow uptitration could be considered.

Blood culture-negative infective endocarditis: are we looking hard enough?

INTRODUCTION: Infective endocarditis is a common cardiac condition, with significant mortality. Blood culture-negative endocarditis is an important subgroup of endocarditis that holds significant morbidity and mortality. METHOD: We performed an updated review of the literature. We searched the databases of Web of Science, MEDLINE, EMBAS and Scopus for the latest clinical guidelines and literature on blood culture negative endocarditis to provide a narrative synthesis of the literature. RESULTS: There is significant heterogeneity in causes and complications of culture-negative infective endocarditis, due to an insensitivity in available clinical diagnostic pathways. Despite significant advances in diagnostic tools, the diagnostic criterion for infective endocarditis (the modified Duke's criterion) remains insensitive to the detection of culture-negative infective endocarditis. CONCLUSION: The natural history of BCNE and our diagnostic resources are changing. It is time our criterion did too. Remembering, BCNE holds significant morbidity and mortality-the absence of organism of culture should not reassure, rather concern clinicians. Every effort should be made to accurately identify organisms.

A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection.

It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as 'post-COVID syndrome'. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illnesses following acute SARS-CoV-2 infection. We searched the scientific literature using MedLine, SCOPUS, Europe PubMed Central and medRxiv from December 2019 to July 2023. Two reviewers independently identified 45 eligible articles, which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. The study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptoms of any nature and duration was 10.8% compared with 4.9% in healthy controls. For seven studies at low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1%, with a median follow-up time of 18 weeks. We also identified a higher risk for future illnesses such as irritable bowel syndrome, dyspepsia, hepatic and biliary disease, liver disease and autoimmune-mediated illnesses such as inflammatory bowel disease and coeliac disease in historically SARS-CoV-2-exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal illness, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.

High-throughput barcoding method for the genetic surveillance of insecticide resistance and species identification in Anopheles gambiae complex malaria vectors.

Surveillance of malaria vector species and the monitoring of insecticide resistance are essential to inform malaria control strategies and support the reduction of infections and disease. Genetic barcoding of mosquitoes is a useful tool to assist the high-throughput surveillance of insecticide resistance, discriminate between sibling species and to detect the presence of Plasmodium infections. In this study, we combined multiplex PCR, custom designed dual indexing, and Illumina next generation sequencing for high throughput single nucleotide polymorphism (SNP)-profiling of four species from the Anopheles (An.) gambiae complex (An. gambiae sensu stricto, An. coluzzii, An. arabiensis and An. melas). By amplifying and sequencing only 14 genetic fragments (500 bp each), we were able to simultaneously detect Plasmodium infection; insecticide resistance-conferring SNPs in ace1, gste2, vgsc and rdl genes; the partial sequences of nuclear ribosomal internal transcribed spacers (ITS1 and ITS2) and intergenic spacers (IGS), Short INterspersed Elements (SINE), as well as mitochondrial genes (cox1 and nd4) for species identification and genetic diversity. Using this amplicon sequencing approach with the four selected An. gambiae complex species, we identified a total of 15 non-synonymous mutations in the insecticide target genes, including previously described mutations associated with resistance and two new mutations (F1525L in vgsc and D148E in gste2). Overall, we present a reliable and cost-effective high-throughput panel for surveillance of An. gambiae complex mosquitoes in malaria endemic regions.

The seroprevalence of SARS-CoV-2 during the first wave in Europe 2020: A systematic review.

BACKGROUND: A year following the onset of the COVID-19 pandemic, new infections and deaths continue to increase in Europe. Serological studies, through providing evidence of past infection, can aid understanding of the population dynamics of SARS-CoV-2 infection. OBJECTIVES: This systematic review of SARS-CoV-2 seroprevalence studies in Europe was undertaken to inform public health strategies including vaccination, that aim to accelerate population immunity. METHODS: We searched the databases Web of Science, MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews and grey literature sources for studies reporting seroprevalence of SARS-CoV-2 antibodies in Europe published between 01/12/2019-30/09/20. We provide a narrative synthesis of included studies. Studies were categorized into subgroups including healthcare workers (HCWs), community, outbreaks, pregnancy and children/school. Due to heterogeneity in other subgroups, we only performed a random effects meta-analysis of the seroprevalence amongst HCWs stratified by their country. RESULTS: 115 studies were included spanning 17 European countries, that estimated the seroprevalence of SARS-CoV-2 from samples obtained between November 2019 -August 2020. A total of 54/115 studies included HCWs with a reported seroprevalence among HCWs ranging from 0.7% to 45.3%, which did not differ significantly by country. In community studies significant heterogeneity was reported in the seroprevalence between different age groups and the majority of studies reported there was no significant difference by gender. CONCLUSION: This review demonstrates a wide heterogeneity in reported seroprevalence of SARS-CoV-2 antibodies between populations. Continued evaluation of seroprevalence is required to understand the impact of public health measures and inform interventions including vaccination programmes.

Investigation of SARS-CoV-2 faecal shedding in the community: a prospective household cohort study (COVID-LIV) in the UK.

BACKGROUND: SARS-CoV-2 is frequently shed in the stool of patients hospitalised with COVID-19. The extent of faecal shedding of SARS-CoV-2 among individuals in the community, and its potential to contribute to spread of disease, is unknown. METHODS: In this prospective, observational cohort study among households in Liverpool, UK, participants underwent weekly nasal/throat swabbing to detect SARS-CoV-2 virus, over a 12-week period from enrolment starting July 2020. Participants that tested positive for SARS-CoV-2 were asked to provide a stool sample three and 14 days later. In addition, in October and November 2020, during a period of high community transmission, stool sampling was undertaken to determine the prevalence of SARS-CoV-2 faecal shedding among all study participants. SARS-CoV-2 RNA was detected using Real-Time PCR. RESULTS: A total of 434 participants from 176 households were enrolled. Eighteen participants (4.2%: 95% confidence interval [CI] 2.5-6.5%) tested positive for SARS-CoV-2 virus on nasal/throat swabs and of these, 3/17 (18%: 95% CI 4-43%) had SARS-CoV-2 detected in stool. Two of three participants demonstrated ongoing faecal shedding of SARS-CoV-2, without gastrointestinal symptoms, after testing negative for SARS-CoV-2 in respiratory samples. Among 165/434 participants without SARS-CoV-2 infection and who took part in the prevalence study, none had SARS-CoV-2 in stool. There was no demonstrable household transmission of SARS-CoV-2 among households containing a participant with faecal shedding. CONCLUSIONS: Faecal shedding of SARS-CoV-2 occurred among community participants with confirmed SARS-CoV-2 infection. However, during a period of high community transmission, faecal shedding of SARS-CoV-2 was not detected among participants without SARS-CoV-2 infection. It is unlikely that the faecal-oral route plays a significant role in household and community transmission of SARS-CoV-2.

Prospective observational study of SARS-CoV-2 infection, transmission and immunity in a cohort of households in Liverpool City Region, UK (COVID-LIV): a study protocol.

INTRODUCTION: The emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time. METHODS AND ANALYSIS: Households in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively. ETHICS AND DISSEMINATION: The study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity.