Prenatal and Perinatal Risk Factors for Autism at National Children’s Hospital

Background: Autism, or autism spectrum disorder, refers to a broad conditions characterized by challenges with social skills, repetitive behaviors, speech and nonverbal communication. Objectives: To determine the demographic profile of patients diagnosed with ASD, determine the significant prenatal and perinatal risk factors associated with ASD. Results: A total of 116 subjects were included in the study with 58 cases and 58 controls. They belong to the age ranging from 4 to 16 years old. Every case had a confirmed diagnosis of autism at NCH. There was a significant association noted between neonatal jaundice, nulliparity (OR=2.38; 95% CI, 0.85-6.8) and family history of autism (OR=5.30; 95% CI, 1.29-25.1) with ASD. Exposure to x-ray, medical problems, medicine intake and maternal complications during pregnancy were not significantly associated with ASD with OR 0.74; 95% CI, (0.12-4.15), OR 1.00; 95% CI (0.38-2.61), OR1.49; 95% CI, (0.63-3.53), and OR 1.27; 95% CI, (0.28-6.05), respectively. Conclusion: The current study indicates that the only significant predictor of ASD is a family history of autism. However, neonatal jaundice, maternal age of >40 years old, smoking during pregnancy and nulliparity showed a trend towards being risk factors for ASD. None of the other prenatal and perinatal characteristics significantly predicts ASD

Management of Acute Abdomen: Acute Appendicitis

Background: Traditionally, appendectomy has been the treatment of choice for acute appendicitis but many times diagnosis can be difficult. Clinicians are looking through different ways to come to the correct diagnosis to decrease negative appendectomy. The aim of this study was to determine relation between clinical pattern, laboratory and ultrasonography findings with histopathological report of appendectomy specimen and to evaluate the Alvarado scoring regarding its usefulness in the early diagnosis in our set up. Methods: Prospective cross-sectional study was carried out in Gandaki Medical College Teaching Hospital and Fewa City Hospital from Jan 1, 2016 to Dec 31, 2018 on consecutively admitted patients with clinical diagnosis of acute appendicitis with study variables as demography, Alvarado score, radiological/laboratory investigations, surgical management, histopathology, and clinical outcome. Results: Among 1021 patients (48.8% men, 51.2% women), patients with Alvarado score offive and more (967, 88.8%) had abdominal USG and some (134) with score of 5-6 (13.12%) had CT scan. On the basis which 818patients (151 patients with score 5-6 and 667 with score 7 to 10) underwent emergency appendectomy; 705 (86.19%) by open and 113 (13.81%) by laparoscopic technique. Appendicitis was suggestive per-operatively in 76.2% of patients with Alvarado score of 5-6 and 97.4% of patients with the score of 7-10. Histo-pathologically diagnosis was correct in 752 (91.9%), 91.2% in open appendectomy and 96.5% in laparoscopic appendectomy cases. Only two patients had infective complication and no mortality. Conclusion: Alvarado scoring in patients presenting with acute abdominal pain is reliable predicting tool for acute appendicitis

Persistence of Immunity Following 2-Dose Priming with a 10-Valent Pneumococcal Conjugate Vaccine at 6 and 10 Weeks or 6 and 14 Weeks of Age in Nepalese Toddlers

BACKGROUND: The pneumococcal conjugate vaccine has had a substantial impact on invasive pneumococcal disease. Previously, we compared immunity following vaccination with the 10-valent pneumococcal conjugate vaccine (PCV10) administered at 2 slightly different schedules: at 6 and 10 weeks of age, and at 6 and 14 weeks of age, both followed by a 9-month booster. In this study, we followed up those participants to evaluate the medium-term persistence of serotype-specific pneumococcal immunity at 2-3 years of age. METHOD: Children from the previous studies were contacted and after taking informed consent from their parents, blood samples and nasopharyngeal swabs were collected. Serotype-specific IgG antibody concentrations were determined by enzyme-linked immunosorbent assay, for the 10 vaccine serotypes, at a WHO pneumococcal serology reference laboratory. FINDINGS: Two hundred twenty out of the 287 children who completed the primary study returned at 2-3 years of age to provide a blood sample and nasopharyngeal swab. The nasopharyngeal carriage rate of PCV10 serotypes in the 6 + 14 group was higher than the 6 + 10 group (13.4% vs. 1.9%). Nevertheless, the proportion of toddlers with serum pneumococcal serotype-specific IgG greater than or equal to 0.35 µg/mL was comparable for all PCV10 serotypes between the 6 + 10 week and 6 + 14 week groups. Similarly, the geometric mean concentrations of serum pneumococcal serotype-specific IgG levels were similar in the 2 groups for all serotypes, except for serotype 19F which was 32% lower in the 6 + 10 group than the 6 + 14 group. CONCLUSION: Immunization with PCV10 at 6 + 10 weeks or 6 + 14 weeks, with a booster at 9 months in each case, results in similar persistence of serotype-specific antibody at 2-3 years of age. Thus, protection from pneumococcal disease is expected to be similar when either schedule is used

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Childhood invasive bacterial disease in Kathmandu, Nepal (2005-2013)

Background: Invasive bacterial disease (IBD; including pneumonia, meningitis, sepsis) is a major cause of morbidity and mortality in children in low-income countries. Methods: We analyzed data from a surveillance study of suspected community-acquired IBD in children Results: Enhanced surveillance of IBD was undertaken during 2005–2006 and 2010–2013. During enhanced surveillance, a total of 7956 children were recruited of whom 7754 had blood or CSF culture results available for analysis, and 342 (4%) had a pathogen isolated. From 2007 to 2009, all 376 positive culture results were available, with 259 pathogens isolated (and 117 contaminants). Salmonella enterica serovar Typhi was the most prevalent pathogen isolated (167 cases, 28% of pathogens), followed by Streptococcus pneumoniae (98 cases, 16% pathogens). Approximately, 73% and 78% of pneumococcal serotypes were contained in 10-valent and 13-valent PCV, respectively. Most cases of invasive pneumococcal disease (IPD) were among children ≥5 years of age from 2008 onward. Antigen and PCR testing of CSF for pneumococci, Haemophilus influenzae type b and meningococci increased the number of these pathogens identified from 33 (culture) to 68 (culture/antigen/PCR testing). Conclusions: S. enterica serovar Typhi and S. pneumoniae accounted for 44% of pathogens isolated. Most pneumococcal isolates were of serotypes contained in PCVs. Antigen and PCR testing of CSF improves sensitivity for IBD pathogens.</p

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study

Background In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. Methods We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0–8 weeks, 6–23 months, and 24–59 months were recruited from Kathmandu, and healthy children aged 6–23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014–15), adjusted for calendar month, age, and sex. Findings Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6–23 months, 761 aged 24–59 months, and 2110 aged 0–8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07–0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16–4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6–23 months (aPR 0·25 [95% CI 0·19–0·33]) but not in those aged 24–59 months (aPR 0·59 [0·29–1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18–0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6–23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. Interpretation The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. Funding Gavi, the Vaccine Alliance and the World Health Organization

Persistence of immunity following 2-dose priming with a 10-valent pneumococcal conjugate vaccine at 6 and 10 weeks or 6 and 14 weeks of age in Nepalese toddlers

Background: The pneumococcal conjugate vaccine has had a substantial impact on invasive pneumococcal disease. Previously, we compared immunity following vaccination with the 10-valent pneumococcal conjugate vaccine (PCV10) administered at 2 slightly different schedules: at 6 and 10 weeks of age, and at 6 and 14 weeks of age, both followed by a 9-month booster. In this study, we followed up those participants to evaluate the medium-term persistence of serotype-specific pneumococcal immunity at 2-3 years of age. Method: Children from the previous studies were contacted and after taking informed consent from their parents, blood samples and nasopharyngeal swabs were collected. Serotype-specific IgG antibody concentrations were determined by enzyme-linked immunosorbent assay, for the 10 vaccine serotypes, at a WHO pneumococcal serology reference laboratory. Findings: Two hundred twenty of the 287 children who completed the primary study returned at 2–3 years of age to provide a blood sample and nasopharyngeal swab. The nasopharyngeal carriage rate of PCV10 serotypes in the 6 + 14 group was higher than the 6 + 10 group (13.4% vs. 1.9%). Nevertheless, the proportion of toddlers with serum pneumococcal serotype-specific IgG greater than or equal to 0.35 µg/mL was comparable for all PCV10 serotypes between the 6 + 10 week and 6 + 14 week groups. Similarly, the geometric mean concentrations of serum pneumococcal serotype-specific IgG levels were similar in the 2 groups for all serotypes, except for serotype 19F which was 32% lower in the 6 + 10 group than the 6 + 14 group. Conclusion: Immunization with PCV10 at 6 + 10 weeks or 6 + 14 weeks, with a booster at 9 months in each case, results in similar persistence of serotype-specific antibody at 2-3 years of age. Thus, protection from pneumococcal disease is expected to be similar when either schedule is used