Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

Community-acquired Staphylococcus aureus bacteraemia among people who inject drugs: a national cohort study in England, 2017-2020.

BACKGROUND: People who inject drugs (PWID) are at increased risk of community-acquired Staphylococcus aureus bacteraemia (CA-SAB), but little is known about clinical outcomes of CA-SAB in PWID compared with the wider population of patients with CA-SAB. METHODS: Three national datasets were linked to provide clinical and mortality data on patients hospitalised with CA-SAB in England between 1 January 2017 and 31 December 2020. PWID were identified using the ICD-10 code for "mental health and behavioural disorder due to opioid use" (F11). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for associations of PWID with 30-day all-cause mortality and 90-day hospital readmission. RESULTS: In 10,045 cases of CA-SAB, 1,612 (16.0%) were PWID. Overall, 796 (7.9%) patients died within 30 days of CA-SAB admission and 1,189 (11.8%) patients were readmitted to hospital within 90 days of CA-SAB. In those without infective endocarditis there was strong evidence of lower odds of mortality among PWID compared with non-PWID (aOR: 0.47, 95% confidence interval, CI: 0.33-0.68, p < 0.001) whereas there was no association in CA-SAB case fatality with endocarditis (aOR 1.40, CI 0.87-2.25, p = 0.163). PWID were less likely to be re-admitted within 90 days of CA-SAB (aOR 0.79, CI 0.65-0.95, p = 0.011). CONCLUSIONS: In this large cohort study of patients with CA-SAB in England, PWID had lower odds of death in the absence of endocarditis and lower odds of re-admission within 90 days compared to non-PWID patients. This study highlights the over-representation of PWID among patients with CA-SAB nationally.

The immune status of migrant populations in Europe and implications for vaccine-preventable disease control: a systematic review and meta-analysis.

BACKGROUND: Ensuring vaccination coverage reaches established herd immunity thresholds (HIT) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPD) and outbreaks, yet it is not clear to what extent they are an under-immunised group. METHODS: We did a systematic review and meta-analysis to synthesise peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella, and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (January 1st 2000 to June 10th 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666). FINDINGS: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% CI: 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%), and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%), and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies. INTERPRETATION: Migrants in Europe are an under-immunised group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents, and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses, and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life-course in under-immunised groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity.

Retrospective testing for mpox virus in routine STI screens from men who have sex with men in England, August-October 2022.

OBJECTIVES: A global outbreak of mpox (monkeypox) has been ongoing since 2022, with most cases in the UK detected in gay, bisexual and other men who have sex with men (GBMSM). Asymptomatic and pauci-symptomatic mpox infection has been reported outside of the UK. We aimed to investigate whether mpox could be detected in specimens from GBMSM in England who were attending sexual health services (SHSs) for asymptomatic sexually transmitted infection screening. METHODS: Anonymised, residual clinical specimens from GBMSM undertaking routine asymptomatic screening for gonorrhoea (Neisseria gonorrhoeae (NG)) and chlamydia (Chlamydia trachomatis (CT)) infection were tested for the presence of mpox virus. Specimens were collected between 1 August and 7 October 2022 from three SHSs in high-mpox incidence areas in England. Testing was performed using a dual-clade, mpox virus-specific real-time PCR. RESULTS: During the collection period, 2927 clinical specimens (951 pharyngeal swabs, 1022 urine specimens and 954 rectal swabs) were obtained from 1159 GBMSM. Mpox virus was detected in four specimens from two participants who attended the same SHS at different times (the first during the week 8-12 of August, the second during the week 19-23 of September). One participant was positive in the urine specimen only, while the other tested positive at all three sites. CONCLUSIONS: A very low prevalence (2 of 1159, 0.17%) of mpox infection was detected in GBMSM attending SHS in England for asymptomatic NG/CT screening, suggesting that undetected infection in this population was unlikely to be a main driver of transmission. Confirmed mpox cases in the UK declined from over 1100 per month in June and July to 764 cumulatively during the collection period. These data give reassurance that the observed reduction in cases during the collection period was not due to undetected infection or changes in presentation among SHS attendees. Currently, there is insufficient evidence to support routine testing of asymptomatic GBMSM for mpox infection in England.

Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis up to October 2021 to inform public health control measures.

BackgroundPublic health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base.AimTo estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis.MethodsWe searched Ovid MEDLINE (1946-), EMBASE (1974-) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions.ResultsOf 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3-9 were 6.9% (95% CI: 2.7-16.8%), 5.4% (95% CI: 2.1-13.3%) and 2.6% (95% CI: 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5-16.1%) and 1.6% (95% CI: 0.04-42.9%), respectively. Overall, for 9.1% (95% CI: 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias.ConclusionsOur review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals.

Is Panton-Valentine leucocidin (PVL) toxin associated with poor clinical outcomes in patients with community-acquired Staphylococcus aureus bacteraemia?

Introduction. Panton-Valentine leucocidin (PVL) toxin is a potential determinant of virulence associated with S. aureus infection.Gap Statement. The contribution of PVL to S. aureus pathogenicity remains unclear.Aim. To compare clinical outcomes in hospitalized patients with PVL-positive and PVL-negative community-acquired (CA) S. aureus bacteraemia.Methods. Three national datasets were combined to provide clinical and mortality data for patients with CA S. aureus blood culture isolates sent to the UK reference laboratory for PVL testing, August 2018 to August 2021. Multivariable logistic regression models were built for the effect of PVL positivity on 30 day all-cause mortality and 90 day readmission.Results. In 2191 cases of CA S. aureus bacteraemia, there was no association between PVL and mortality (adjusted odds ratio, aOR: 0·90, 95 % confidence interval, CI: 0·50-1·35, P=0·602) and no difference in median LOS (14 versus 15 days, P=0.169). PVL-positive cases had lower odds of readmission (aOR 0·74, CI 0·55-0.98, P=0·038). There was no evidence that MRSA status modified this effect (P=0·207).Conclusions. In patients with CA S. aureus bacteraemia PVL toxin detection was not associated with worse outcomes.

Screening for Chronic Infectious Diseases by Serology in Those Presenting with Malaria in London, United Kingdom.

The United Kingdom's cases of malaria infection are primarily acquired in sub-Saharan Africa, with the majority of infections presenting in London.1 When patients go to a hospital with malaria, there is a screening opportunity for other geographically associated chronic infections. We identified patients who were diagnosed with malaria after presenting to our emergency department in London over a 2-year period, to assess whether there may be clinical benefit in screening for chronic viral (hepatitis B, hepatitis C, HIV) or parasitic (schistosomiasis, strongyloidiasis) infection in this cohort. Over this period, 131 patients were diagnosed with malaria. Crude seropositivity rates for HIV, hepatitis B, and strongyloidiasis were higher than expected compared with local population estimates, 7 and 28 times higher for HIV and hepatitis B, respectively. Those patients with previously unidentified cases were offered appropriate treatment. These findings support the potential clinical and public health benefits of screening for other infectious diseases in the context of a malaria diagnosis.

Acute myopericarditis caused by Salmonella enterica serovar Enteritidis: a case report.

BACKGROUND: Acute myopericarditis can be caused by a myriad of infectious and non-infectious aetiologies, however, it is often considered to be due to self-limiting viral infection. Salmonella spp. myopericarditis is rare and the few cases in the literature suggest significant associated morbidity and mortality. CASE SUMMARY: A 44-year-old man presented with fever, dyspnoea, and chest pain. He was found to have a large pericardial effusion with clinical signs of tamponade and sepsis. Therapeutic pericardiocentesis was performed and ceftriaxone and levofloxacin were administered. Fully sensitive Salmonella enterica serovar Enteritidis (S. Enteritidis) was isolated in his pericardial fluid and he made a full recovery after a 4-week course of ciprofloxacin. A new diagnosis of type 2 diabetes mellitus was made on admission. A follow-up cardiac magnetic resonance (CMR) scan was suggestive of myocarditis which was unexpected given a normal Troponin T level on presentation. DISCUSSION: We report a rare case of S. Enteritidis myopericarditis. Our case is notable as the patient was immunocompetent apart from newly diagnosed diabetes. This case highlights the value of CMR imaging in assessing for myocarditis and ventricular function.

Extraspinal articular tuberculosis: An 11-year retrospective study of demographic features and clinical outcomes in East London.

OBJECTIVES: To describe demographic features, clinical outcomes and diagnostic delay amongst patients with extra-spinal articular tuberculosis (TB) in a low-incidence setting. METHODS: Cases of TB treated at our institution between 2004 and 2014 were identified via the London TB register (LTBR). Demographic features of extra-spinal articular TB cases were compared to controls with TB at all other sites. For articular cases (excluding individuals <16 years or with spinal TB without peripheral joint involvement) clinical data were retrospectively collected. RESULTS: 6,146 TB patients were identified over the study period; 146 (2.4%) cases had extra-spinal articular infection. There was no difference in median age between extra-spinal articular TB cases and controls with TB at other sites (31 vs 32 years, p = 0.57). Articular cases were more likely to be male (70.6% vs 59.5%, p = 0.007), Bangladeshi (28.7% vs 18.0%) or Pakistani (24.0% vs 16.1%) and were less likely to be Black-African (9.5% vs 19.8%) (p < 0.001). 93 cases were included in the case series; 85 (88.5%) were migrants and 83 (89.2%) were South Asian. Knee and elbow joints were affected in 22 (23.7%) and 18 (19.4%) cases respectively. The median durations of pre-healthcare and healthcare associated delay were 16 and 6 weeks respectively. Where mycobacterial culture was performed, 57/75 (76%) were positive for Mycobacterium tuberculosis. 86 (92.5%) cases received standard quadruple therapy for a median of 6 months (IQR 6-9). Recurrence of TB infection occurred in 4 (4.3%) cases and there were no TB related deaths. Seven (7.6%) cases required surgical intervention. CONCLUSIONS: Extra-spinal articular TB more commonly affected men and people of South Asian ethnicity. Significant diagnostic delays were identified, including avoidable healthcare-associated delays.

Breast tuberculosis in East London: A 13-year retrospective observational study.

SETTING: Breast tuberculosis (TB) is rare in Western Europe, and its diagnosis may be delayed through lack of awareness of presenting features. Our institution serves a large East London population with a high incidence of TB. OBJECTIVE: To characterize presenting features and avoidable diagnostic delay in breast TB patients. DESIGN: We conducted a 13-year retrospective study of breast TB patients treated at our institution including demographic, clinical, microbiology, and pathology data. RESULTS: Forty-seven cases were included; 44 (94%) were female, with a median age of 33 years (IQR 28.5-39.5). The main presenting feature was a breast lump in 41 cases (87%); which were predominantly solitary unilateral lesions (25, 61%) and frequently located in the upper outer quadrant (28, 68%). Where performed, Mycobacterium tuberculosis was cultured in 15/36 (42%) cases. Granulomata were present on biopsy or aspirate in 21 (47%) and 17 (36%) cases, respectively. The median duration between symptom onset and treatment was 20 weeks (IQR 15-30). Forty-six (98%) completed treatment successfully and one relapsed. CONCLUSION: A high index of suspicion for TB is required for individuals presenting with breast symptoms from countries where TB is endemic. Development of standardized pathways may improve detection and management of breast TB may reduce diagnostic delay.

Is Strongyloides seropositivity associated with diabetes mellitus? A retrospective case-control study in an East London NHS Trust.

BACKGROUND: The association between diabetes and Strongyloides stercoralis remains controversial. We conducted a case-control study examining the association between diabetes and Strongyloides seropositivity in a large UK centre. METHODS: Between January 2013 and October 2016, cases and controls were identified by positive and negative Strongyloides serology, respectively. Demographic, clinical and microbiological data were retrospectively collected. Multivariate logistic regression analysis was performed. RESULTS: Over the study period, 532 samples were serologically tested for Strongyloides. After exclusion of duplicates and cases with missing data, 100 (22.3%; 95% CI 18.5-26.4%) out of 449 tested positive. Of seropositive cases, the mean age was 57 years (SD 16), 71 (71%) were male, 94 (94%) were migrants and 92 (92%) had eosinophilia.Univariate logistic regression analysis demonstrated a significant association between Strongyloides seropositivity and age (OR 1.04, 95% CI 1.02-1.05), male sex (OR 2.22, 95% CI 1.37-3.59), migration (OR 5.36, 95% CI 2.27-12.67), eosinophilia (OR 4.36, 95% CI 2.04-9.33) and diabetes (OR 3.52, 95% CI 2.19-5.66). In multivariate analysis, there remained a significant association between diabetes and Strongyloides seropositivity (OR 1.81, 95% CI 1.04-3.16). CONCLUSIONS: We demonstrated a high rate of Strongyloides seropositivity in our East London cohort and a significant association with diabetes.

Shigellosis and toxic megacolon secondary to Shigella flexneri serotype 3a: The challenges of laboratory diagnosis.

We present a rare case of Shigella flexneri bacteraemia and toxic megacolon, and discuss the challenges of conventional laboratory techniques versus molecular PCR platforms in differentiating between Shigella species and Escherichia coli.