Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.

Decline in pneumococcal vaccine serotype carriage, multiple-serotype carriage, and carriage density in Nepalese children after PCV10 introduction: A pre-post comparison study.

BACKGROUND: Carriage studies are an efficient means for assessing pneumococcal conjugate vaccine effect in settings where pneumococcal disease surveillance programmes are not well established. In this study the effect of 10-valent pneumococcal conjugate vaccine (PCV10) introduction on pneumococcal carriage and density among Nepalese children using a bacterial microarray and qPCR was examined. METHODS: PCV10 was introduced into the Nepalese infant immunisation schedule in August 2015. Nasopharyngeal swabs were collected from healthy Nepalese children in Kathmandu between April 2014 and December 2021. Samples were plated on blood agar, incubated overnight, and DNA extracted from plate sweeps. Pneumococcal serotyping was done using the Senti-SPv1.5 microarray (BUGS Bioscience, UK). DNA was extracted from swab media and qPCR performed for pneumococcal autolysin (lytA). RESULTS: A significant decline in prevalence of PCV10 serotypes was observed when comparing pre-PCV10 with post-PCV10 collection periods (36.5 %, 454/1244 vs 10.3 %, 243/2353, p < 0.0001). Multiple-serotype carriage was also observed to significantly decline when comparing pre-PCV10 with post-PCV10 periods (31.4 %, 390/1244 vs 22.2 %, 522/2353, p < 0.0001). Additionally, a significant decline in median pneumococcal density was observed when comparing pre-PCV10 with post-PCV10 periods (3.3 vs 3.25 log10 GE/ml, p = 0.0196). CONCLUSIONS: PCV10 introduction was associated with reduced, prevalence of all PCV10 serotypes, multiple serotype carriage, and pneumococcal carriage density.

Immune responses to typhoid conjugate vaccine in a two dose schedule among Nepalese children <2 years of age.

BACKGROUND: Previously, the Vi-typhoid conjugate vaccine (Vi-TT) was found to be highly efficacious in Nepalese children under 16 years of age. We assessed the immunogenicity of Vi-TT at 9 and 12 months of age and response to a booster dose at 15 months of age. METHODS: Infants were recruited at Patan Hospital, Kathmandu and received an initial dose of Vi-TT at 9 or 12 months of age with a booster dose at 15 months of age. Blood was taken at four timepoints, and antibody titres were measured using a commercial ELISA kit. The primary study outcome was seroconversion (4-fold rise in antibody titre) of IgG one month after both the doses. FINDINGS: Fifty children were recruited to each study group.Some visits were disrupted by the COVID19 pandemic and occurred out of protocol windows.Both the study groups attained 100 % IgG seroconversion after the initial dose. IgG seroconversion in the 9-month group was significantly higher than in the 12-month group (68.42 % vs 25.8 %, p < 0.001). Among individuals who attended visits per protocol, IgG seroconversion after the first dose occurred in 100 % of individuals (n = 27/27 in 9-month and n = 32/32 in 12-month group). However, seroconversion rates after the second dose were 80 % in the 9-month and 0 % in the shorter dose-interval 12-month group (p < 0.001) (n = 16/20 and n = 0/8, respectively). INTERPRETATION: Vi-TT is highly immunogenic at both 9 and 12 months of age. Stronger response to a booster in the 9-month group is likely due to the longer interval between doses.

Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) - a protocol for two parallel, open-label, randomised controlled trials.

BACKGROUND: Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines. METHODS: The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety. DISCUSSION: These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood. TRIAL REGISTRATIONS: ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).

COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case-control study with SARS-CoV-2 genetic sequencing.

INTRODUCTION: Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants. METHODS AND ANALYSIS: This is a hospital-based, prospective test-negative case-control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.

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.

Risk Factors Associated with Diabetic Ketoacidosis at the Onset of Type 1 Diabetes Mellitus.

BACKGROUND: There are various factors which increase the risk of diabetic ketoacidosis at the onset of type 1 diabetes mellitus. There have not been any such studies in our setting. This study was done to find the prevalence and risk factors associated with the development of diabetic ketoacidosis at onset of type 1 diabetes mellitus. METHODS: Children and young adults with type 1 diabetes mellitus being treated at Patan hospital were approached and after obtaining an informed consent, all the patient information on various risk factors for diabetic ketoacidosis were collected in a pre-developed proforma. Data was entered in Microsoft Excel and analysis was done using statistical package for the social sciences-16. Ethical approval was taken from Institutional Review Committee- Patan Academy of Health Sciences. RESULTS: Out of 99 patients with type 1 diabetes enrolled in the study, 52.5% presented in diabetic ketoacidosis at the onset. The duration of symptoms was significantly less in patient presenting with diabetic ketoacidosis than without diabetic ketoacidosis (6.45±7.57 vs 9.13±10.12, p=0.04). There was no significant difference in the mean age, mean glycosylated hemoglobin, mean body mass index, gender, parents' literacy and medical consultations prior to diagnosis. CONCLUSIONS: More than half of the patients with type 1 diabetes presented in diabetic ketoacidosis. The shorter duration of symptoms prior to presentation was the only significant factor leading to presentation as diabetic ketoacidosis.

Effect of childhood vaccination and antibiotic use on pneumococcal populations and genome-wide associations with disease among children in Nepal: an observational study.

BACKGROUND: Pneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences. METHODS: Whole-genome sequencing was performed on pneumococcal isolates collected between January, 2005, and May, 2018, in Kathmandu, Nepal, which included programmatic ten-valent pneumococcal conjugate vaccine (PCV10) introduction in 2015. Isolates were from three distinct cohorts: nasopharyngeal swabs of healthy community-based children, nasopharyngeal swabs of children admitted to hospital with pneumonia, and sterile-site cultures from children admitted to hospital. Across these cohorts we examined serotype distribution, antibiotic resistance, strain distribution, and regions of recombination to determine genes that were undergoing diversifying selection. Genome-wide association studies comparing pneumonia and sterile-site isolates with healthy carriage were used to determine novel variants associated with disease. FINDINGS: After programmatic introduction of PCV10, there was a decline in vaccine covered serotypes; however, strains that had expressed these serotypes continued to exist in the post-PCV population. We identified GPSC9 to be a strain of concern due to its high prevalence in disease, multidrug resistance, and ability to switch to an unencapsulated phenotype via insertion of virulence factor pspC into the cps locus. Antibiotic resistance loci to co-trimoxazole were found to be prevalent (pre-PCV10 78% vs post-PCV10 81%; p=0·27) and increasingly prevalent to penicillin (pre-PCV10 15% vs post-PCV10 32%; p<0·0001). Regions with multiple recombinations were identified spanning the surface protein virulence factors pspA and pspC and antibiotic targets pbpX, folA, folC, folE, and folP. Furthermore, we identified variants in lacE2 to be strongly associated with isolates from children with pneumonia and PRIP to be strongly associated with isolates from sterile sites. INTERPRETATION: Our work highlights the effect of pneumococcal conjugate vaccines, antibiotics, and host-pathogen interaction in pneumococcal variation, and the pathogen's capability of adapting to these factors at both population-wide and strain-specific levels. Ongoing surveillance of disease-associated strains and further investigation of lacE2 and PRIP as serotype-independent targets for therapeutic interventions is required. FUNDING: Gavi, The Vaccine Alliance; WHO; Bill & Melinda Gates Foundation; Wellcome Sanger Institute; and US Centers for Disease Control and Prevention.

Does Inclusion of Mental Agility Test in Admission Exam Help Better Student Selection in the Health Professions Education Programs?

Academic ability test has been used predominantly in student selection of medical and allied health profession education programs in Nepal. But the use of academic performance as the single selection criterion puts the students from low socioeconomic background at greater disadvantage despite equal suitability due to the lack of adequate guidance and support during their schooling. To address this limitation, use of aptitude test i.e. both the general cognitive and non-cognitive ability tests that measures fluid intelligence and personality traits respectively has been practiced. The measurement of non-cognitive traits has been found to predict the clinical examination score. In Nepal, for the first time, Patan Academy of Health Sciences implemented the assessment of aptitude test (both cognitive and non-cognitive ability test) for the student selection in the undergraduate medical program. Since the inception, Medical Education Commission in Nepal embraced Mental Agility Test, a component of an aptitude test, along with the academic ability test for the nationwide common entrance test in all the undergraduate Health Professions Education Programs. This indeed is an innovative approach in student selection, but in the context of Nepal whether the use of these tools is appropriate in the entrance exam requires psychometric evaluation and further validation through graduates' performance after their enrolment. Keywords: Health professions education; mental agility test; student selection.

COVID-19 fosters social accountability in medical education.

The COVID-19 pandemic has highlighted embedded inequities and fragmentation in our health systems. Traditionally, structural issues with health professional education perpetuate these. COVID-19 has highlighted inequities, but may also be a disruptor, allowing positive responses and system redesign. Examples from health professional schools in high and low- and middle-income countries illustrate pro-equity interventions of current relevance. We recommend that health professional schools and planners consider educational redesign to produce a health workforce well equipped to respond to pandemics and meet future need.

Public engagement during a typhoid conjugate vaccine trial in Lalitpur, Nepal- experience, challenges and lessons learnt.

Typhoid is a public health problem in Nepal. To generate evidence on the impact of Typhoid Conjugate Vaccine (TCV), a phase 3, double-blind, randomized controlled trial was conducted in Lalitpur, Nepal. 20,000 children aged between 9 months and ≤16 years were vaccinated with a new TCV, or control vaccine. Participants were actively followed for safety and efficacy over 2 years through passive surveillance (PS) clinics. Several challenges were encountered during vaccination and PS stemming from misinformation, misconception, and fear around clinical trials in the community. Public engagement (PE) activities were conducted across various tiers moving from decision makers in the first tier; to elected local representatives in the second tier; ending with interaction in community with parents/guardians of the targeted population. Prior and during vaccination, engagement was conducted to inform about the study and discuss the importance of vaccination. Post-vaccination, engagement was conducted to inform about PS clinics, alleviate study concerns and share study updates. Direct and continuous interaction with community stakeholders, including parents/guardians of the targeted population contributed to build trust around the study and community willingness to be involved. It helped to raise awareness, drive away misconceptions, and allowed adaptation according to feedback from community members.

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 <15 years of age in Kathmandu, Nepal, from 2005 to 2013 before introduction of pneumococcal conjugate vaccines (PCV). We detailed the serotype-specific distribution of invasive pneumococcal disease (IPD) and incorporated antigen and PCR testing of cerebrospinal fluid (CSF) from children with meningitis. 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.

Dental Caries among Adult Population of a Municipality: A Descriptive Cross-sectional Study.

Introduction: Oral disease as a public health problem poses a serious burden globally. The most common oral disease affecting adults is dental caries followed by periodontal disease leading to tooth loss. Early detection of dental caries can help reduce the severity and prevent further complications. This study aimed to ind out the prevalence of dental caries among adult population of a municipality. Methods: This descriptive cross-sectional study was conducted among adults attending ive different dental camps in a municipality from 1 April 2022 to 2 June 2022. Ethical approval was obtained from Institutional Review Committee (Reference number: 060-078/079). Convenience sampling method was used. The prevalence of dental caries was determined by dentition status adopted from basic oral health surveys recommended by World Health Organization. Point estimate and 95% Conidence Interval were calculated. Results: Among 239 adults, 138 (57.74%) (51.48-64, 95% Conidence Interval) had dental caries. Conclusions: The prevalence of dental caries among adults in the municipality was lower than in similar studies done in similar settings. Keywords: cross-sectional study; dental decay; prevalence.

Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial.

BACKGROUND: Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children. Here we report the final results after 2 years of follow-up. METHODS: We did a participant-masked and observer-masked individually randomised trial in Lalitpur, Nepal, in which 20 019 children aged 9 months to younger than 16 years were randomly assigned in a 1:1 ratio to receive a single dose of TCV (Typbar TCV, Bharat Biotech International, India) or capsular group A meningococcal conjugate vaccine (MenA). Participants were followed up until April 9, 2020. The primary outcome was blood culture-confirmed typhoid fever. Cases were captured via passive surveillance and active telephone surveillance followed by medical record review. The trial is registered at ISRCTN registry, ISRCTN43385161 and is ongoing. FINDINGS: From Nov 20, 2017, to April 9, 2018, of 20 119 children screened, 20 019 participants were randomly assigned to receive TCV or MenA vaccine. There were 75 cases of blood culture-confirmed typhoid fever included in the analysis (13 in the TCV group and 62 in the MenA group) over the 2-year period. The protective efficacy of TCV against blood culture-confirmed typhoid fever at 2 years was 79·0% (95% CI 61·9-88·5; p<0·0001). The incidence of typhoid fever was 72 (95% CI 38-123) cases per 100 000 person-years in the TCV group and 342 (95% CI 262-438) cases per 100 000 person-years in the MenA group. Adverse events occurring within the first 7 days post-vaccination were reported previously. INTERPRETATION: The final results of this randomised, controlled trial are in keeping with the results of our published interim analysis. There is no evidence of waning protection over a 2-year period. These findings add further support for the WHO recommendations on control of enteric fever. FUNDING: Bill & Melinda Gates Foundation.

Impact of Vaccination on Haemophilus influenzae Type b Carriage in Healthy Children Less Than 5 Years of Age in an Urban Population in Nepal.

BACKGROUND: Reduction in detection of asymptomatic carriage of Haemophilus influenzae type b (Hib) can be used to assess vaccine impact. In Nepal, routine vaccination against Hib in children at 6, 10, and 14 weeks of age was introduced in 2009. Before vaccine introduction, Hib carriage was estimated at 5.0% among children aged <13 years in Nepal, with higher rates among children under 5. Large-scale evaluation of Hib carriage in children has not been investigated since the introduction of the pentavalent diphtheria-tetanus-pertussis/Hib/hepatitis B (DTP-Hib-HepB) vaccine in Nepal. METHODS: A total of 666 oropharyngeal swabs were collected between August and December 2018 from healthy children between 6 months and 5 years of age attending the vaccination clinic at Patan Hospital, Kathmandu, Nepal. Of these 666 swabs, 528 (79.3%) were tested for Hib by culture. Demographic and vaccination data were collected. RESULTS: Among 528 swabs tested for Hib, 100% came from fully vaccinated children. No swabs were positive for Hib (95% confidence interval, .0-.7). The absence of Hib in 2018 suggests vaccine-induced protection against Hib carriage 9 years after vaccine introduction. CONCLUSIONS: Following 3 doses of pentavalent DTP-Hib-HepB vaccine, Hib carriage in children under the age of 5 years in Nepal is no longer common. Ongoing high coverage with Hib vaccine in early childhood is expected to maintain protection against Hib disease in Nepal.

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.

Diagnostic Accuracy of Serum Cystatin C for Early Recognition of Nephropathy in Type 2 Diabetes Mellitus.

OBJECTIVES: Diabetic nephropathy is one of the major complications that develop over time in type 2 diabetes mellitus (T2DM). This prospective study was conducted to assess the diagnostic accuracy of serum cystatin C in detecting diabetic nephropathy at earlier stages. MATERIALS AND METHODS: This study was undertaken on 50 cases of T2DM and 50 healthy subjects as controls. Demographic and anthropometric data and blood and urine samples were collected. The concentration of serum cystatin C (index test) and traditional markers of diabetic nephropathy, serum creatinine, and urinary microalbumin (the reference standard) were estimated. Similarly, blood glucose, glycated haemoglobin (HbA1c), triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and urinary creatine were measured. RESULTS: The mean ± SD serum cystatin C was significantly higher in T2DM as compared to control (1.07 ± 0.38 and 0.86 ± 0.12 mg/dl, respectively, p < 0.001). The mean ± SD bodyweight, BMI, W : H ratio, pulse, SBP, and DBP were 66.4 ± 12.6 kg, 26.2 ± 5.6 kg/m2, 1.03 ± 0.09, 78 ± 7, 125 ± 16 mm of Hg, and 77 ± 9 mm of Hg, respectively, in cases. A significant difference in HDL cholesterol (p=0.018) and serum cystatin C (p < 0.001) was observed among different grades of nephropathy. Cystatin C had a significant positive correlation with age (r = 0.323, p=0.022), duration of T2DM (r = 0.326, p=0.021), and UACR (r = 0.528, p < 0.001) and a significant negative correlation with eGFR CKD-EPI cystatin C (r = -0.925, p < 0.001). The area under ROC curve for serum cystatin C (0.611, 95% CI: 0.450-0.772) was greater than for serum creatinine (0.429, 95% CI: 0.265-0.593) though nonsignificant. CONCLUSION: Serum cystatin C concentration increases with the progression of nephropathy and duration of diabetes in Nepalese T2DM patients suggesting cystatin C as a potential marker of renal impairment in T2DM patients.

Competency Based Post Graduate Residency Program at Patan Academy of Health Sciences, Nepal.

Competency-based medical education has evolved as an alternative approach in the residency training program. It shows potential to align educational programs with health system priorities through defining the competencies of graduating doctors. Designing and implementing Competency Based Post Graduate (CBPG) training in a resource-limited setting, where most of the trainings are still run in a conventional approach, is a big challenge. Patan Academy of Health Sciences, School of Medicine has taken the competency-based approach in the postgraduate residency training. Defining core competencies and connecting those to teaching methodology and assessment system are important initial steps in implementing the competency-based approach. The institution has implemented Entrustable Professional Activity (EPA), which is a unit of professional practice and helps to measure the trainees' achievements in the form of milestones. This paper describes the process of piloting and implementing the CBPG program at this school. The school launched the CBPG training in 2018 and so far, three batches of residents have been enrolled in nine different subjects/disciplines. The first batch of trainee, having the PAHS Core competencies and the pre-defined discipline-specific EPAs certified, will be completing their training soon. The program is time and resource consuming. Continuous faculty development, commitment, supportive leadership and faculty readiness to adapt to newer approaches are the key to the program's successful implementation. Keywords: Competency based medical education; Nepal; patan academy of health sciences; post graduate training; residency program.