•Group B Streptococcus (GBS) and Escherichia coli remain the most common causes of meningitis in neonates and young infants•GBS screening and intrapartum antibiotic prophylaxis were effective in ...preventing early-onset GBS meningitis•Antibiotic-resistant Escherichia coli in neonatal meningitis is an increasing concern
Meningitis in neonates and young infants leads to significant morbidity and mortality worldwide. This study aimed to investigate pathogens, antibiotic resistance and secular change of incidence in Hong Kong.
A retrospective search was performed on meningitis in neonates and infants aged <3 months in three Hong Kong public hospitals from 2004 to 2019. Medical charts were reviewed, with focus on the identification and antibiotic resistance of the pathogens.
A total of 200 cases of meningitis were identified (67% were bacterial). Group B Streptococcus (GBS) and Escherichia coli (E. coli) were the commonest bacterial pathogens. The annual rates of early-onset GBS meningitis decreased after the implementation of universal GBS screening and intrapartum antibiotic prophylaxis (IAP) in 2012, while that of late-onset GBS meningitis remained similar. A significant portion of E. coli isolates were resistant to ampicillin and/or gentamicin.
GBS and E. coli were the most common bacteria for meningitis in this age group. The annual rate of bacterial meningitis in Hong Kong has declined in recent years, which has been attributed to the decline in early-onset GBS meningitis due to universal GBS screening and IAP. Antimicrobial-resistant bacterial strains that cause meningitis require further clinical and public health attention.
Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of ...acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination.
This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed.
Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval CI, 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated.
There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.
Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in fully vaccinated individuals. However, incompletely ...vaccinated children may develop Omicron‐related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro‐COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron‐related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1–13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9‐month follow‐up. SARS‐CoV‐2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike‐and‐wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron‐related neurological manifestations had significantly higher blood levels of IL‐6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL‐6 (p = 0.002) than children with non‐COVID‐19‐related febrile illnesses. Higher CSF‐to‐blood ratios of IL‐8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL‐6 and IL‐8 were associated with higher blood tau level. The role of CSF:blood ratio of IL‐6, IL‐8, and CHI3L1 as prognostic markers for neuro–COVID should be further evaluated.
Aim: Rotavirus and norovirus gastro‐enteritis (GE) are common in children. Complications, except severe dehydration, are rare. Rotavirus was known to cause seizures and even GE encephalopathy, but ...these complications are less described in norovirus infection. The objective of this study is to compare the demographic features, clinical manifestations including the incidence of afebrile seizure, and the outcomes in children with rotavirus and norovirus infections.
Methods: This is a retrospective review of children between age 1 month and 6 years admitted to the paediatric department of a regional hospital in Hong Kong with rotavirus and norovirus infections over a period of 3 years from 1 June 2006 to 31 May 2009. Their demographic data, clinical features, laboratory results and outcomes were compared and analysed.
Results: Two hundred and thirty‐two children with rotavirus and 173 children with norovirus GE were admitted within the study period. Afebrile seizure commonly occurred in norovirus infection (8.67% vs. 1.29%, P < 0.001). Children with rotavirus infection had higher temperature and more diarrhoea episodes, while more blood‐stained stool was noted in the norovirus group. Rotavirus‐infected patients stayed longer in hospital. All of them had full recovery without any complication. Among the 18 patients who developed afebrile convulsions, 17 of them had neuroimaging performed, which was normal. Fourteen of them had electroencephalogram (EEG) performed, demonstrating normal or non‐specific findings. None of them developed subsequent seizure attack after the GE episode.
Conclusions: Norovirus is more commonly associated with benign convulsion in GE than rotavirus. We need to identify the presence of virus, in particular norovirus, in children with GE and afebrile generalised tonic–clonic seizure. Further neuro‐investigations may not be necessary once the aetiology is established. Prognosis is excellent in this group of children and prophylactic anticonvulsant is not needed.
As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 ...infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p=0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin (p = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age.
Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths.
To compare the clinical ...characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020.
This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021.
Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections.
Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals 50.0%) and third wave (94 of 265 individuals 35.5%) than in the first wave (1 of 14 individuals 7.1%) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals 71.4%; second wave: 22 individuals 18.5%; third wave: 98 individuals 37.0%; P < .001) or cough (first wave: 6 individuals 42.9%; second wave: 15 individuals 12.7%; third wave: 52 individuals 19.6%; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post-COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals 90.0%) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts.
This cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small.
Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in
. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients ...confirmed with biallelic
mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation
(NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.
The implication of gastrointestinal infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its transmission remains to be fully understood. We studied 4 paediatric ...patients with several weeks of faecal excretion of SARS-CoV-2 RNA who had only mild symptoms. International consensus on isolation practices is urgently needed.
Background and Aims
Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV ...integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear.
Approach and Results
We adopted a targeted sequencing strategy to survey HBV integrations in human HBV‐associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients’ HCCs. Furthermore, we performed array‐based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis‐activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere‐forming ability in HCC cells.
Conclusions
Our results reveal a cis‐activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV‐integrated HCCs may achieve TERT activation in hepatocarcinogenesis.
The lack of representative nasopharyngeal carcinoma (NPC) models has seriously hampered research on EBV carcinogenesis and preclinical studies in NPC. Here we report the successful growth of five NPC ...patient-derived xenografts (PDXs) from fifty-eight attempts of transplantation of NPC specimens into NOD/SCID mice. The take rates for primary and recurrent NPC are 4.9% and 17.6%, respectively. Successful establishment of a new EBV-positive NPC cell line, NPC43, is achieved directly from patient NPC tissues by including Rho-associated coiled-coil containing kinases inhibitor (Y-27632) in culture medium. Spontaneous lytic reactivation of EBV can be observed in NPC43 upon withdrawal of Y-27632. Whole-exome sequencing (WES) reveals a close similarity in mutational profiles of these NPC PDXs with their corresponding patient NPC. Whole-genome sequencing (WGS) further delineates the genomic landscape and sequences of EBV genomes in these newly established NPC models, which supports their potential use in future studies of NPC.
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