Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (ß 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. FUNDING: None.

Molecular epidemiology of fluoroquinolone-resistant ST131 Escherichia coli producing CTX-M extended-spectrum beta-lactamases in nursing homes in Belfast, UK.

OBJECTIVES: Between January 2004 and May 2006 Escherichia coli producing extended-spectrum ß-lactamases (ESBLs) were isolated from the faeces of 118/294 residents from 16 nursing homes in Belfast. Of these, 58 isolates belonged to UK strain A, a variant of the international ST131 clone. Here we investigated the remaining 60 ESBL producers. METHODS: MICs were determined and interpreted using BSAC methodology. Isolates were characterized by phylogenetic typing, real-time PCR and PFGE. Plasmids were rep typed by PCR and their similarity to IncI1 reference plasmid pEK204 was investigated by restriction fragment length polymorphism analysis. The molecular environments surrounding bla(CTX-M) were determined by DNA sequencing and PCR. RESULTS: Fifty-nine of 60 isolates belonged to the B2, ST131 lineage; of these 28 belonged to the previously defined UK strain C, while the other 31 were clustered into five groups by PFGE. Forty-nine isolates harboured bla(CTX-M-3) on plasmids of five different rep types (I1, FIA, FIA-FIB, N and Y) and 11 harboured bla(CTX-M-15) on F-type plasmids (FIA and FIA-FIB). All CTX-M-3 ESBL producers and three with CTX-M-15 ESBL had an intact copy of ISEcp1 immediately upstream of bla(CTX-M); the remaining eight with CTX-M-15 ESBL had a truncated ISEcp1. CONCLUSIONS: Gut colonization among nursing home residents in Belfast with ciprofloxacin-resistant E. coli producing ESBLs almost entirely involves clonal spread of ST131 variants, with similar genetic environments for bla(CTX-M-3) or bla(CTX-M-15) as in pEK204 and pEK499. Such diversity indicates dissemination of both plasmids and ESBL genes among a single commonly multiresistant clone.

Nursing homes as a reservoir of extended-spectrum beta-lactamase (ESBL)-producing ciprofloxacin-resistant Escherichia coli.

BACKGROUND: To assess the prevalence and risk factors for faecal carriage of fluoroquinolone-resistant, extended-spectrum beta-lactamase (ESBL)-producing, Escherichia coli (MDR E. coli) among residents in nursing homes in Northern Ireland. METHODS: Between January 2004 and May 2006, retrospective histories of hospital admissions, antimicrobial treatment and co-morbidities were collected. Faecal samples were cultured for MDR E. coli. These isolates and their ESBL genes were typed by a reference laboratory. RESULTS: Of the 294 patients included in the study, faecal samples from 119 (40.5%) grew MDR E. coli. The proportion of carriers in the different homes ranged from 0% to 75%. Epidemic strain A belonging to the ST131, O25:H4 lineage with the CTX-M-15 enzyme accounted for 58 (49%) of all isolates; its proportion varied from 0% to 100% among homes. Fifty-one percent of carriers had no history of recent hospital admission and only 13.5% had a known history of ESBL E. coli colonization or infection. In a multivariate logistic regression model, days of fluoroquinolone use [odds ratio (OR) = 1.33, 95% confidence interval (CI) 1.04-1.69, P = 0.02] and a history of urinary tract infection (OR = 2.56, 95% CI 1.37-4.78, P = 0.003) were the only variables independently associated with the risk of carrying MDR E. coli. CONCLUSIONS: The high level of faecal carriage of MDR E. coli in nursing home residents demonstrates their importance as a reservoir population. Public health measures to combat spread of these organisms should address the needs of this group.

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow - results from a community based survey and laboratory surveillance.

BACKGROUND: South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. METHODS: A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. RESULTS: In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. CONCLUSIONS: South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.

The association between alcohol use and hepatitis C status among injecting drug users in Glasgow.

BACKGROUND: We investigated the association between actual and self-reported hepatitis C virus (HCV) status and alcohol consumption among injecting drug users (IDUs) to determine whether IDUs who self-report as HCV infected comply with UK guidelines on safe drinking and to determine risk factors for drinking. METHODS: We conducted a repeat cross-sectional survey of IDUs accessing harm reduction services in Glasgow in 2005 and 2007. We measured self-reported weekly alcohol consumption, excess drinking (defined as exceeding the UK Royal College of Physician's guidelines for safe drinking of 14 units/week for women and 21 units/week for men) and HCV antibodies (anonymously in oral fluid). RESULTS: Among IDUs who tested HCV antibody positive, 65% drank alcohol and 29% drank to excess, compared to 61% (p=0.3) and 18% (p<0.001) of those who tested negative, respectively. IDUs who self-reported as HCV positive were less likely to drink but as likely to drink to excess as self-reported negatives or those with HCV status unknown, both among all IDUs and those who tested HCV antibody positive. Among the antibody positives, excess drinking was associated with incarceration (aOR=2.56; 95% CI: 1.28-5.12), homelessness within six months of interview (aOR=3.60; 95% CI: 2.00-6.48) and homelessness more than six months before interview (aOR=1.93; 95% CI: 1.06-3.53). CONCLUSIONS: IDUs who believe they are HCV infected are more likely to abstain from alcohol, but those who drink continue to do so to excess. IDUs diagnosed with HCV need greater support to reduce their alcohol consumption.

Effect of Aubergiene (Solanum melongena) on Serum and Hepatic Cholesterol and Triglycerides in rats

A beringela (Solanum melongena) tem sido apontada como possuidora da capacidade de reduzir o colesterol sérico. O chá do vegetal vem senso utilizado com este propósito, devido ao interesse na descoberta de formas alternativas para o controle da hipercolesterolemia. No presente trabalho testou-se o efeito do chá de beringela no níveis séricos e hepáticos de colesterol e triglicerídeos em ratos adultos. Ratos Fisher foram divididos em tres grupos: o primeiro recebeu dieta normolipídica ad libitum e água para beber, funcionando como controle; os outros dois receberam dieta hipercolesterolêmica com 30 por cento de óleo vegetal e 1 por cento de colesterol, sendo dada a um destes grupos água para beber, enquanto que o outro recebeu apenas chá de beringela. Após 28 dias os animais foram sacrificados e dosaram-se os níveis de colesterol e triglicerídeos séricos e hepáticos. Os resultados obtidos indicam que, nas condiçöes experimentais utilizadas, o chá de beringela eleva o colesterol sérico, reduz o hepático e tem pouco ou nenhum efeito sobre os triglicerídeos, tanto séricos quanto hepáticos