Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal.

BACKGROUND: Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking. METHODS: In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing. RESULTS: A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P<0.001). A total of 132 serious adverse events (61 in the TCV group and 71 in the MenA vaccine group) occurred in the first 6 months, and 1 event (pyrexia) was identified as being vaccine-related; the participant remained unaware of the trial-group assignment. Similar rates of adverse events were noted in the two trial groups; fever developed in 5.0% of participants in the TCV group and 5.4% in the MenA vaccine group in the first week after vaccination. In the immunogenicity subgroup, seroconversion (a Vi IgG level that at least quadrupled 28 days after vaccination) was 99% in the TCV group (677 of 683 participants) and 2% in the MenA vaccine group (8 of 380 participants). CONCLUSIONS: A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age. (Funded by the Bill and Melinda Gates Foundation; Current Controlled Trials number, ISRCTN43385161.).

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.

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.

Comparing the physical performance of liquid barrier films.

BACKGROUND: Barrier films have been used for many years to protect skin from the damaging effects of excessive moisture and mechanical injury. The performance characteristics important for these protective effects are mainly product durability and its ability to reduce the force of adhesive removal. Additionally, the moisture vapor transmission rate through the film needs to be high enough that maceration is prevented. The current study was undertaken to investigate various physical performance characteristics of six commercially available barrier films. MATERIALS AND METHODS: Several bench tests were used to simulate performance features of the barriers on skin including barrier durability, breathability (moisture vapor permeability), and the effect on adhesive dressing force of removal. RESULTS: Results indicated that barrier films did not perform equivalently. However, Cavilon™ No Sting Barrier Film (NSB) was shown to have significantly greater durability in the barrier integrity test than all other barriers tested and was tied for highest breathability and highest reduction in peel force from steel. No other tested barrier film performed as consistently across the different tests. CONCLUSION: These results may provide mechanistic understanding of how barriers such as NSB may clinically assist with the prevention of adhesive- and moisture-related skin damage.

Effect of sub-toxic exposure to Malathion on glucose uptake and insulin signaling in L6 myoblast derived myotubes.

Biochemical basis of Malathion exposure-induced diabetes mellitus is not known. Hence, effects of its sub-toxic exposure on redox sensitive kinases (RSKs), insulin signaling and insulin-induced glucose uptake were assessed in rat muscle cell line. In this in vitro study, rat myoblast (L6) cells were differentiated to myotubes and were exposed to sub-toxic concentrations (10 mg/l and 20 mg/l) of Malathion for 18 hours. Total antioxidant level and insulin-stimulated glucose uptake by myotubes were assayed. Activation of JNK, NFκB, p38MAPK and insulin signaling from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were assessed in myotubes after Malathion exposure by western blot and was compared with those in controls. Paraoxonase (PON) activity was measured in cell lysate using p-nitrophenyl acetate as substrate. PON1 and PON2 expression in myotubes were assessed by PCR. The glucose uptake and total antioxidant level in L6-derived myotubes after sub-toxic exposure to Malathion were decreased in a dose-dependent manner. Phosphorylation levels of RSKs (JNK, p38MAPK and IκBα component of NFκB) were increased and that of IRS-1 and Akt on insulin stimulation was decreased following Malathion exposure as compared to those in controls. PON1 and PON2 genes were expressed in myotubes with and without Malathion exposure. Significant PON activity was present in cell lysate. We conclude that sub-toxic Malathion exposure induces oxidative stress in muscle cells activating RSKs that impairs insulin signaling and thereby insulin-stimulated glucose uptake in muscle cells. This probably explains the biochemical basis of Malathion-induced insulin resistance state and diabetes mellitus.

Assessing the Impact of a Vi-polysaccharide Conjugate Vaccine in Preventing Typhoid Infections Among Nepalese Children: A Protocol for a Phase III, Randomized Control Trial.

BACKGROUND: Enteric fever is estimated to affect 11-20 million people worldwide each year. Morbidity and mortality from enteric fever primarily occur in lower-income countries, with children under 5 years of age experiencing a significant portion of the burden. Over the last few decades, the control of enteric fever has focused primarily on improved water and sanitation, with the available vaccines unsuitable for children and primarily used by travelers. A new typhoid conjugate vaccine (Vi-TCV), prequalified by the World Health Organization (WHO) and highly immunogenic in children under 5, has the potential to reduce the typhoid burden in endemic countries. METHODS: This study is a double-blinded, randomized, controlled trial with a 2-year follow-up to assess the protective impact of the Vi-TCV vaccine, compared with a control vaccine, in children from 9 months to 16 years of age. The primary outcome of interest is the reduction in the number of culture-confirmed typhoid cases attributable to Vi-TCV. Approximately 20 000 children living in the Lalitpur district, within the Kathmandu valley, will be enrolled in the study and followed to measure both safety and efficacy data, which will include adverse events, hospitalizations, antibiotic use, and fever frequency. RESULTS: Both the intervention and control vaccines are WHO prequalified vaccines, which provide a health benefit to all participants. Children have been chosen to participate because they bear a substantial burden of both typhoid morbidity and mortality in this population. The results of this study will be disseminated through a series of published articles. The findings will also be made available to the participants and the broader community, as well as local stakeholders, within Nepal. CONCLUSIONS: This is the first large-scale, individually randomized, controlled trial of Vi-TCV in children in an endemic setting, and will provide new data on Vi-TCV field efficacy. With Vi-TCV introduction being considered in high-burden countries, this study will support important policy decisions. CLINICAL TRIALS REGISTRATION: The trial is registered on the ISRCTN registry (for details, see https://doi.org/10.1186/ISRCTN43385161; registry number: ISRCTN 43385161).

Logistics of Implementing a Large-scale Typhoid Vaccine Trial in Kathmandu, Nepal.

Typhoid fever is estimated to affect over 20 million people per year worldwide, with infants, children, and adolescents in south-central and southeast Asia experiencing the greatest burden of disease. The Typhoid Vaccine Acceleration Consortium (TyVAC) aims to support the introduction of typhoid conjugate vaccines into Gavi-eligible countries in an effort to reduce morbidity and mortality from typhoid. TyVAC-Nepal is a large-scale, participant- and observer-blind, individually randomized, controlled trial evaluating the efficacy of a newly developed typhoid conjugate vaccine in an urban setting in Nepal. In order to effectively deliver the trial, a number of key elements required meticulous planning. Public engagement strategies were considered early, and involved the implementation of a tiered approach. Approximately 300 staff were employed and trained in order to achieve the mass vaccination of 20 000 children aged 9 months to ≤16 years old over a 4-month period. There were 19 vaccination clinics established across the Lalitpur metropolitan city in the Kathmandu valley. Participants will be followed for 2 years post-vaccination to measure the rate reduction of blood culture-confirmed typhoid fever in the vaccination arm as compared to the control arm. The experience of conducting this large-scale vaccine trial suggests that comprehensive planning, continuous monitoring, and an ability to adapt plans in response to feedback are key.

Serotype-Specific Correlates of Protection for Pneumococcal Carriage: An Analysis of Immunity in 19 Countries.

Background: Pneumococcal conjugate vaccines (PCVs) provide direct protection against disease in those vaccinated, and interrupt transmission through the prevention of nasopharyngeal (NP) carriage. Methods: We analyzed immunogenicity data from 5224 infants who received PCV in prime-boost schedules. We defined any increase in antibody between the 1-month postpriming visit and the booster dose as an indication of NP carriage ("seroincidence"). We calculated antibody concentrations using receiver operating characteristic curves, and used generalized additive models to compute their protective efficacy against seroincidence. To support seroincidence as a marker of carriage, we compared seroincidence in a randomized immunogenicity trial in Nepal with the serotype-specific prevalence of carriage in the same community. Results: In Nepalese infants, seroincidence of carriage closely correlated with serotype-specific carriage prevalence in the community. In the larger data set, antibody concentrations associated with seroincidence were lowest for serotypes 6B and 23F (0.50 µg/mL and 0.63 µg/mL, respectively), and highest for serotypes 19F and 14 (2.54 µg/mL and 2.48 µg/mL, respectively). The protective efficacy of antibody at these levels was 62% and 74% for serotypes 6B and 23F, and 87% and 84% for serotypes 19F and 14. Protective correlates were on average 2.15 times higher in low/lower middle-income countries than in high/upper middle-income countries (geometric mean ratio, 2.15 [95% confidence interval, 1.46-3.17]; P = .0024). Conclusions: Antibody concentrations associated with protection vary between serotypes. Higher antibody concentrations are required for protection in low-income countries. These findings are important for global vaccination policy, to interrupt transmission by protecting against carriage.

Work-health needs of high-altitude mountain guides (Sherpas) in Nepal - a pilot study.

Much of the research in high-altitude medicine has been concerned with non-indigenous travellers; no study has examined the work-related health issues of high altitude mountain guides (Sherpas) in Nepal. This pilot study was performed to investigate the work-related health issues of people working as Sherpas by evaluating their perceptions of their general health and its relation to work. An occupational and general health questionnaire was tailored for the Sherpas following a focus group with five Sherpa workers. 131 Sherpas participated in this study. Respiratory (60%) and musculoskeletal symptoms (55%) were reported significantly more frequently than other health problems (p < .05). 33 Sherpas reported work accident experiences (25%) and 27 (21%) reported eye conditions. This pilot study identified respiratory and musculoskeletal problems as well as accidents as the main work-related health issues of high altitude climbing Sherpas. Another important finding was the high prevalence of reported eye conditions (21%). Better occupational health and safety arrangements including routine recording of accidents or work-related health problems would give better insight into the health needs of Sherpas.

Development of a PICU in Nepal: the experience of the first year.

OBJECTIVE: Analysis of hospitalization data can help elucidate the pattern of morbidity and mortality in any given area. Little data exist on critically ill children admitted to hospitals in the resource-limited nation of Nepal. We sought to characterize the profile, management, and mortality of children admitted to one PICU. DESIGN: Retrospective analysis. SETTING: A newly established PICU in Nepal. PATIENTS: All patients between the ages of 0 to 16 years admitted to the PICU from July 2009 to July 2010. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: In 12 months, 126 children were admitted to the PICU including 43% female patients. Sixty-three percent were under 5 years. Twenty-nine percent came from tertiary care hospitals and 38% from rural areas outside Kathmandu. Only 18% were transported by ambulance. Median distance travelled to be admitted was 30 km (interquartile range, 10-193). Highest number of admissions were in spring (40%) followed by summer (25%). Almost half were admitted for shock (45%), particularly septic shock (30%). The second commonest reason for admission was neurologic etiologies (15%). Neonatal admissions were also significant (19%). Mortality was 26% and was significantly associated with septic shock (p < 0.01), mechanical ventilation (p < 0.01), and multiple organ dysfunction (< 0.05). Almost one third of patients required mechanical ventilation; median duration was 4 days (interquartile range, 2-8). Mean length of stay in the hospital was 6.2 days (± 5.3) and median 4 (interquartile range, 2.5-9.0). Median Pediatric Risk of Mortality II score for nonsurvivors was 12 (interquartile range, 7-21), and median Pediatric Index of Mortality II for nonsurvivors was 10 (interquartile range, 3-32). CONCLUSIONS: Within a short time of opening, the PICU has been seeing significant numbers of critically ill children. Despite adverse conditions and limited resources, survival of 75% is similar to many units in developing nations. Sepsis was the most common reason for PICU admission and mortality.

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.

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.

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.

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.

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).

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.

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.

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.

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.