Developing and sustaining high-quality care for children with cancer: the WHO Global Initiative for Childhood Cancer / Desarrollo y mantenimiento de una atención de alta calidad para pacientes pediátricos con cáncer: la Iniciativa Mundial de la OMS contra el Cáncer Infantil / Desenvolvimento e manutenção de atenção de alta qualidade para crianças com câncer: a Iniciativa Global para o Câncer Infantil da OMS

[ABSTRACT]. Cancer is a major public health concern, impacting nearly 20 million people each year, and it is responsible for 1 in 6 deaths worldwide. The burden of cancer is increasing rapidly, straining health systems that are unable to prevent and manage the disease. Childhood cancer constitutes a significant and relevant public health challenge; it was the ninth leading cause of childhood disease globally, according to findings by the Global Burden of Disease 2017 study. Almost 80% of all children diagnosed with cancer live in low- and middle-income countries where treatment is often unavailable or unaffordable. As a result, only about 15–45% of these children survive compared with more than 80% in high-income countries. This represents a great health inequity. Delivering on the mandate provided by World Health Assembly resolution 70.12, WHO together with St. Jude Children’s Research Hospital and other global partners launched the Global Initiative for Childhood Cancer at the United Nations General Assembly during the third High-level Meeting on the prevention and control of noncommunicable diseases in September 2018. The Initiative aims to increase global survival for children with cancer to at least 60% by 2030, while reducing suffering for all children with cancer. Five years after launching the Initiative, more than 70 countries across the World Health Organization’s 6 regions have advanced to different phases of action through implementation of the Initiative’s CureAll framework for action. Many successful approaches to implementing the CureAll pillars and enablers have demonstrated that improving care for children with cancer in low- and middle-income countries is possible as long as there is strong political will, multisectoral commitments and strategic investment.

[RESUMEN]. El cáncer es un importante problema de salud pública: afecta a cerca de 20 millones de personas cada año y es responsable de 1 de cada 6 muertes a nivel mundial. La carga del cáncer está aumentando rápidamente, lo que somete a una gran presión a los sistemas de salud que no pueden prevenir y manejar la enfermedad. El cáncer infantil constituye un importante problema de salud pública y tiene gran relevancia: fue la novena causa de enfermedad infantil a nivel mundial, según los hallazgos del estudio sobre la carga mundial de enfermedad correspondiente al 2017. Casi el 80% de todos los casos de cáncer infantil se registran en países de ingresos bajos o medianos, donde el tratamiento a menudo resulta inasequible o no está disponible. Por este motivo, solo sobreviven entre el 15% y el 45% de estos pacientes pediátricos, frente a más del 80% en los países de ingresos altos. Esto constituye una gran inequidad en materia de salud. En cumplimiento del mandato establecido en la resolución WHA70.12 de la Asamblea Mundial de la Salud, la Organización Mundial de la Salud (OMS) —junto con el hospital pediátrico de investigación St. Jude y otros asociados mundiales— puso en marcha la Iniciativa Mundial contra el Cáncer Infantil ante la Asamblea General de las Naciones Unidas, en ocasión de la tercera reunión de alto nivel sobre la prevención y el control de las enfermedades no transmisibles, celebrada en septiembre del 2018. Esta iniciativa tiene como objetivo incrementar la tasa de supervivencia mundial de los pacientes pediátricos con cáncer hasta por lo menos el 60% para el 2030 y, simultáneamente, reducir el sufrimiento de toda la población infantil con cáncer. Transcurridos cinco años de la puesta en marcha de la iniciativa, más de 70 países de las seis regiones de la OMS han logrado avanzar a distintas fases de actuación mediante la aplicación del marco de acción de la iniciativa denominado CureAll. Ha habido muchos enfoques que han dado buenos resultados para la consecución de los pilares y los elementos facilitadores de CureAll y que han demostrado que es posible mejorar la atención de la población infantil con cáncer en los países de ingresos bajos y medianos, siempre que haya una férrea voluntad política, compromisos multisectoriales e inversiones estratégicas.

[RESUMO]. O câncer é um importante problema de saúde pública que afeta cerca de 20 milhões de pessoas a cada ano e é responsável por uma em cada seis mortes em todo o mundo. A carga do câncer está aumentando rapidamente, sobrecarregando os sistemas de saúde, que não conseguem prevenir e controlar a doença. O câncer infantil constitui um desafio significativo e relevante para a saúde pública: essa foi a nona principal causa de doenças infantis em todo o mundo, de acordo com os resultados do estudo Global Burden of Disease 2017. Quase 80% de todas as crianças diagnosticadas com câncer vivem em países de baixa e média renda, onde o tratamento geralmente não está disponível ou é inacessível. Como resultado, apenas cerca de 15% a 45% dessas crianças sobrevivem, em comparação com mais de 80% nos países de alta renda. Isso representa uma grande falta de equidade em saúde. Cumprindo o estabelecido pela Resolução 70.12 da Assembleia Mundial da Saúde, a Organização Mundial da Saúde (OMS), juntamente com o Saint Jude Children's Research Hospital e outros parceiros mundiais, lançou a Iniciativa Global para o Câncer Infantil na Assembleia Geral das Nações Unidas, durante a terceira Reunião de Alto Nível sobre prevenção e controle de doenças não transmissíveis, em setembro de 2018. A Iniciativa tem como objetivo aumentar a sobrevida global de crianças com câncer para pelo menos 60% até 2030 e, ao mesmo tempo, reduzir o sofrimento de todas as crianças com câncer. Cinco anos após o lançamento da Iniciativa, mais de 70 países das seis regiões da OMS avançaram para diferentes fases de ação por meio da implementação da estrutura CureAll da Iniciativa. O sucesso de muitas abordagens para implementação dos pilares e facilitadores da CureAll demonstraram que é possível melhorar o atendimento a crianças com câncer em países de baixa e média renda, desde que haja forte vontade política, compromissos multissetoriais e investimento estratégico.

Developing and sustaining high-quality care for children with cancer: the WHO Global Initiative for Childhood Cancer.

Cancer is a major public health concern, impacting nearly 20 million people each year, and it is responsible for 1 in 6 deaths worldwide. The burden of cancer is increasing rapidly, straining health systems that are unable to prevent and manage the disease. Childhood cancer constitutes a significant and relevant public health challenge; it was the ninth leading cause of childhood disease globally, according to findings by the Global Burden of Disease 2017 study. Almost 80% of all children diagnosed with cancer live in low- and middle-income countries where treatment is often unavailable or unaffordable. As a result, only about 15-45% of these children survive compared with more than 80% in high-income countries. This represents a great health inequity. Delivering on the mandate provided by World Health Assembly resolution 70.12, WHO together with St. Jude Children's Research Hospital and other global partners launched the Global Initiative for Childhood Cancer at the United Nations General Assembly during the third High-level Meeting on the prevention and control of noncommunicable diseases in September 2018. The Initiative aims to increase global survival for children with cancer to at least 60% by 2030, while reducing suffering for all children with cancer. Five years after launching the Initiative, more than 70 countries across the World Health Organization's 6 regions have advanced to different phases of action through implementation of the Initiative's CureAll framework for action. Many successful approaches to implementing the CureAll pillars and enablers have demonstrated that improving care for children with cancer in low- and middle-income countries is possible as long as there is strong political will, multisectoral commitments and strategic investment.

El cáncer es un importante problema de salud pública: afecta a cerca de 20 millones de personas cada año y es responsable de 1 de cada 6 muertes a nivel mundial. La carga del cáncer está aumentando rápidamente, lo que somete a una gran presión a los sistemas de salud que no pueden prevenir y manejar la enfermedad. El cáncer infantil constituye un importante problema de salud pública y tiene gran relevancia: fue la novena causa de enfermedad infantil a nivel mundial, según los hallazgos del estudio sobre la carga mundial de enfermedad correspondiente al 2017. Casi el 80% de todos los casos de cáncer infantil se registran en países de ingresos bajos o medianos, donde el tratamiento a menudo resulta inasequible o no está disponible. Por este motivo, solo sobreviven entre el 15% y el 45% de estos pacientes pediátricos, frente a más del 80% en los países de ingresos altos. Esto constituye una gran inequidad en materia de salud.En cumplimiento del mandato establecido en la resolución WHA70.12 de la Asamblea Mundial de la Salud, la Organización Mundial de la Salud (OMS) ­junto con el hospital pediátrico de investigación St. Jude y otros asociados mundiales­ puso en marcha la Iniciativa Mundial contra el Cáncer Infantil ante la Asamblea General de las Naciones Unidas, en ocasión de la tercera reunión de alto nivel sobre la prevención y el control de las enfermedades no transmisibles, celebrada en septiembre del 2018. Esta iniciativa tiene como objetivo incrementar la tasa de supervivencia mundial de los pacientes pediátricos con cáncer hasta por lo menos el 60% para el 2030 y, simultáneamente, reducir el sufrimiento de toda la población infantil con cáncer. Transcurridos cinco años de la puesta en marcha de la iniciativa, más de 70 países de las seis regiones de la OMS han logrado avanzar a distintas fases de actuación mediante la aplicación del marco de acción de la iniciativa denominado CureAll. Ha habido muchos enfoques que han dado buenos resultados para la consecución de los pilares y los elementos facilitadores de CureAll y que han demostrado que es posible mejorar la atención de la población infantil con cáncer en los países de ingresos bajos y medianos, siempre que haya una férrea voluntad política, compromisos multisectoriales e inversiones estratégicas.

O câncer é um importante problema de saúde pública que afeta cerca de 20 milhões de pessoas a cada ano e é responsável por uma em cada seis mortes em todo o mundo. A carga do câncer está aumentando rapidamente, sobrecarregando os sistemas de saúde, que não conseguem prevenir e controlar a doença. O câncer infantil constitui um desafio significativo e relevante para a saúde pública: essa foi a nona principal causa de doenças infantis em todo o mundo, de acordo com os resultados do estudo Global Burden of Disease 2017. Quase 80% de todas as crianças diagnosticadas com câncer vivem em países de baixa e média renda, onde o tratamento geralmente não está disponível ou é inacessível. Como resultado, apenas cerca de 15% a 45% dessas crianças sobrevivem, em comparação com mais de 80% nos países de alta renda. Isso representa uma grande falta de equidade em saúde.Cumprindo o estabelecido pela Resolução 70.12 da Assembleia Mundial da Saúde, a Organização Mundial da Saúde (OMS), juntamente com o Saint Jude Children's Research Hospital e outros parceiros mundiais, lançou a Iniciativa Global para o Câncer Infantil na Assembleia Geral das Nações Unidas, durante a terceira Reunião de Alto Nível sobre prevenção e controle de doenças não transmissíveis, em setembro de 2018. A Iniciativa tem como objetivo aumentar a sobrevida global de crianças com câncer para pelo menos 60% até 2030 e, ao mesmo tempo, reduzir o sofrimento de todas as crianças com câncer. Cinco anos após o lançamento da Iniciativa, mais de 70 países das seis regiões da OMS avançaram para diferentes fases de ação por meio da implementação da estrutura CureAll da Iniciativa. O sucesso de muitas abordagens para implementação dos pilares e facilitadores da CureAll demonstraram que é possível melhorar o atendimento a crianças com câncer em países de baixa e média renda, desde que haja forte vontade política, compromissos multissetoriais e investimento estratégico.

A cross-sectional study evaluating the prevalence and predictors of malnutrition among children and adolescents visiting an urban academic hospital in Nepal.

OBJECTIVE: To examine the prevalence of malnutrition among children and adolescents visiting Kanti Children's Hospital (KCH) and identify predictors associated with malnutrition. Results will guide the development of a newly established nutrition programme at KCH. DESIGN: This cross-sectional pilot study recruited children and adolescents over a 1-month period. Nutritional anthropometrics (height, weight and mid-upper arm circumference (MUAC)) and socio-demographic questionnaires were administered. Clinical data were abstracted from the medical chart. SETTING: KCH in Kathmandu, Nepal. PARTICIPANTS: 370 children and adolescents. RESULTS: Most participants were male (65·1 %); mean age was 3·9 years (±3·4 years). The prevalence of stunting was 25·9 %, wasting was 17·3 % and 24·0 % when classified by BMI-for-age Z-score or MUAC, respectively. Two percent of participants were overweight. Notably, 32·1 % of children ≥5 years were classified with wasting based on MUAC-for-age Z-score, which is higher than that observed in children <5 (20·2 %). Food insecurity was reported among 58·2 % of children with stunting and 34·0 % with wasting. Chronic medical conditions predicted stunting and wasting. The lowest level of wealth predicted stunting, while ethnicity predicted wasting. Ethnicity and education level predicted food insecurity. CONCLUSIONS: We found that the prevalence of stunting and wasting at KCH are higher than previously published studies in Nepal. Malnutrition persists beyond 5 years, and we identified several predictors of malnutrition. Increased provision of and access to clinical nutrition programmes is an essential need for KCH. Twinning programs that provide local clinicians with increased opportunities for education and mentorship of local staff remains a pressing need in Nepal.

Conducting a phase III clinical trial in children during the COVID- 19 pandemic: Experience and lessons learnt from a clinical research facility of Nepal.

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.

Developing and sustaining high-quality care for children with cancer: the WHO Global Initiative for Childhood Cancer / Desarrollo y mantenimiento de una atención de alta calidad para pacientes pediátricos con cáncer: la Iniciativa Mundial de la OMS contra el Cáncer Infantil / Desenvolvimento e manutenção de atenção de alta qualidade para crianças com câncer: a Iniciativa Global para o Câncer Infantil da OMS

ABSTRACT Cancer is a major public health concern, impacting nearly 20 million people each year, and it is responsible for 1 in 6 deaths worldwide. The burden of cancer is increasing rapidly, straining health systems that are unable to prevent and manage the disease. Childhood cancer constitutes a significant and relevant public health challenge; it was the ninth leading cause of childhood disease globally, according to findings by the Global Burden of Disease 2017 study. Almost 80% of all children diagnosed with cancer live in low- and middle-income countries where treatment is often unavailable or unaffordable. As a result, only about 15-45% of these children survive compared with more than 80% in high-income countries. This represents a great health inequity. Delivering on the mandate provided by World Health Assembly resolution 70.12, WHO together with St. Jude Children's Research Hospital and other global partners launched the Global Initiative for Childhood Cancer at the United Nations General Assembly during the third High-level Meeting on the prevention and control of noncommunicable diseases in September 2018. The Initiative aims to increase global survival for children with cancer to at least 60% by 2030, while reducing suffering for all children with cancer. Five years after launching the Initiative, more than 70 countries across the World Health Organization's 6 regions have advanced to different phases of action through implementation of the Initiative's CureAll framework for action. Many successful approaches to implementing the CureAll pillars and enablers have demonstrated that improving care for children with cancer in low- and middle-income countries is possible as long as there is strong political will, multisectoral commitments and strategic investment.

RESUMEN El cáncer es un importante problema de salud pública: afecta a cerca de 20 millones de personas cada año y es responsable de 1 de cada 6 muertes a nivel mundial. La carga del cáncer está aumentando rápidamente, lo que somete a una gran presión a los sistemas de salud que no pueden prevenir y manejar la enfermedad. El cáncer infantil constituye un importante problema de salud pública y tiene gran relevancia: fue la novena causa de enfermedad infantil a nivel mundial, según los hallazgos del estudio sobre la carga mundial de enfermedad correspondiente al 2017. Casi el 80% de todos los casos de cáncer infantil se registran en países de ingresos bajos o medianos, donde el tratamiento a menudo resulta inasequible o no está disponible. Por este motivo, solo sobreviven entre el 15% y el 45% de estos pacientes pediátricos, frente a más del 80% en los países de ingresos altos. Esto constituye una gran inequidad en materia de salud. En cumplimiento del mandato establecido en la resolución WHA70.12 de la Asamblea Mundial de la Salud, la Organización Mundial de la Salud (OMS) —junto con el hospital pediátrico de investigación St. Jude y otros asociados mundiales— puso en marcha la Iniciativa Mundial contra el Cáncer Infantil ante la Asamblea General de las Naciones Unidas, en ocasión de la tercera reunión de alto nivel sobre la prevención y el control de las enfermedades no transmisibles, celebrada en septiembre del 2018. Esta iniciativa tiene como objetivo incrementar la tasa de supervivencia mundial de los pacientes pediátricos con cáncer hasta por lo menos el 60% para el 2030 y, simultáneamente, reducir el sufrimiento de toda la población infantil con cáncer. Transcurridos cinco años de la puesta en marcha de la iniciativa, más de 70 países de las seis regiones de la OMS han logrado avanzar a distintas fases de actuación mediante la aplicación del marco de acción de la iniciativa denominado CureAll. Ha habido muchos enfoques que han dado buenos resultados para la consecución de los pilares y los elementos facilitadores de CureAll y que han demostrado que es posible mejorar la atención de la población infantil con cáncer en los países de ingresos bajos y medianos, siempre que haya una férrea voluntad política, compromisos multisectoriales e inversiones estratégicas.

RESUMO O câncer é um importante problema de saúde pública que afeta cerca de 20 milhões de pessoas a cada ano e é responsável por uma em cada seis mortes em todo o mundo. A carga do câncer está aumentando rapidamente, sobrecarregando os sistemas de saúde, que não conseguem prevenir e controlar a doença. O câncer infantil constitui um desafio significativo e relevante para a saúde pública: essa foi a nona principal causa de doenças infantis em todo o mundo, de acordo com os resultados do estudo Global Burden of Disease 2017. Quase 80% de todas as crianças diagnosticadas com câncer vivem em países de baixa e média renda, onde o tratamento geralmente não está disponível ou é inacessível. Como resultado, apenas cerca de 15% a 45% dessas crianças sobrevivem, em comparação com mais de 80% nos países de alta renda. Isso representa uma grande falta de equidade em saúde. Cumprindo o estabelecido pela Resolução 70.12 da Assembleia Mundial da Saúde, a Organização Mundial da Saúde (OMS), juntamente com o Saint Jude Children's Research Hospital e outros parceiros mundiais, lançou a Iniciativa Global para o Câncer Infantil na Assembleia Geral das Nações Unidas, durante a terceira Reunião de Alto Nível sobre prevenção e controle de doenças não transmissíveis, em setembro de 2018. A Iniciativa tem como objetivo aumentar a sobrevida global de crianças com câncer para pelo menos 60% até 2030 e, ao mesmo tempo, reduzir o sofrimento de todas as crianças com câncer. Cinco anos após o lançamento da Iniciativa, mais de 70 países das seis regiões da OMS avançaram para diferentes fases de ação por meio da implementação da estrutura CureAll da Iniciativa. O sucesso de muitas abordagens para implementação dos pilares e facilitadores da CureAll demonstraram que é possível melhorar o atendimento a crianças com câncer em países de baixa e média renda, desde que haja forte vontade política, compromissos multissetoriais e investimento estratégico.

Immune non-interference and safety study of Vi-DT typhoid conjugate vaccine with a measles, mumps and rubella containing vaccine in 9-15 months old Nepalese infants.

BACKGROUND: Typhoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9-15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine. METHODS: This was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9-15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination. RESULTS: Using the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were -2.73% (-8.85, 3.38), -3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the -10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events . CONCLUSIONS: Results indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid.

Factors affecting willingness to participate in vaccine clinical trials in an underdeveloped country: perspective from Nepal.

Due to the inherent complex nature of clinical trials, individual's willingness to participate and hence, enrollment in a clinical trial maybe challenging. When it comes to vaccine clinical trial in children, informed consent needs to be secured from the parents or legally acceptable representatives (LARs). Some of the factors which contribute to hesitancy in taking part in clinical trials are based on the level of education, living standards, part of the world they live, associated burden of disease, fear of different procedures in clinical trial, side effects, limited understanding, limited time, and mistrust with Investigational product. This study included 201 parents/LARs, who approached Kanti Children Hospital site in Kathmandu with the interest to get their children enrolled in a vaccine clinical trial with objectives of describing the reasons for agreeing or disagreeing to participate in the vaccine clinical trial, factors affecting decision making, and finding the major concerns of parents/LARs. The acceptance for the study vaccine was 136 (67.7%) whereas denial was 65 (32.3%). This study showed that age, education level, family structure, advice from family and friends, and medical guidance play important roles in willingness of parents to get their child enrolled in the trial. If a proper counseling is done, fear of blood sampling is not a big factor which is contrary to the belief among clinical researchers. Safety of vaccine, frequency of injections, and cost of vaccine were the main concerns of the parents, which need to be addressed extensively while planning for any clinical trial in children.

Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

BACKGROUND: Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country. METHODS: We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to <2 years, 2 years to <18 years, and 18 years to 45 years), into one of four groups (A-D). Participants in groups A-C received a single dose (25 µg; 0·5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 µg; 0·5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A-C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and (2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97·5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A-C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of -10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99·17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0·67 and 1·50, which is the predefined equivalence margin recommended by WHO. The co-primary immunogenicity endpoints were assessed in all randomised participants who had received their assigned vaccine and had completed at least one post-baseline immunogenicity assessment. Safety was descriptively summarised by group and age strata, and was assessed in all participants who had received one dose of the investigational vaccine. The trial is registered with ClinicalTrials.gov, NCT03933098. FINDINGS: Between Nov 20, 2019, and March 10, 2020, 1854 individuals were screened, of whom 1800 were enrolled and randomly assigned to groups A-D (450 participants in each group). 1786 (99·2%; 443 in group A, 450 in group B, 447 in group C, and 446 in group D) were included in the immunogenicity assessments at 4 weeks post vaccination, and all 1800 participants were included in the safety analysis. In the immunogenicity analysis, the anti-Vi-IgG seroconversion rate in all age strata was 99·33% (97·5% CI 98·61 to 99·68; 1331 of 1340 participants) in Vi-DT vaccine groups A-C and 98·88% (97·10 to 99·57; 441 of 446) in Vi-TT vaccine group D. The difference in seroconversion rates between Vi-DT vaccine groups A-C combined versus Vi-TT group D was 0·47% (97·5% CI -0·68 to 1·61), indicating non-inferiority of the Vi-DT vaccine. Anti-Vi-IgG GMT ratios at 4 weeks post-vaccination were 1·02 (99·17% CI 0·85 to 1·22) for lot 1 versus lot 2, 1·02 (0·85 to 1·23) for lot 1 versus lot 3, and 1·01 (0·84 to 1·21) for lot 2 versus lot 3, indicating lot-to-lot equivalence according to the predefined, WHO-recommended equivalence margin. The proportion of participants reporting adverse events was similar between Vi-DT vaccine groups A-C and Vi-TT vaccine group D; 260 (19·3%) of 1350 participants in Vi-DT vaccine groups A-C and 115 (25·6%) of 450 in Vi-TT vaccine group D reported solicited adverse events within 7 days after vaccination, and 208 (15·4%) in Vi-DT vaccine groups A-C and 76 (16·9%) in Vi-TT vaccine group D reported unsolicited adverse events within 4 weeks after vaccination. Seven serious adverse events (four [0·3%] participants in Vi-DT vaccine groups A-C and three [0·7%] in Vi-TT vaccine group D), including one death in the Vi-TT vaccine group, were reported during the 24-week follow-up period, none of which were considered related to the investigational product. INTERPRETATION: When administered as a single dose, the Vi-DT test vaccine was safe, immunogenic, and non-inferior to the Vi-TT vaccine at 4 weeks post vaccination. Equivalent immunogenicity of the three lots of Vi-DT vaccine was also shown, supporting the manufacturing process of this vaccine. Once prequalified by WHO, this vaccine could be an option for purchase by UN agencies. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATION: For the Nepali translation of the abstract see Supplementary Materials section.

Practice among Healthcare Workers Regarding the Use of Respiratory Protective Equipment during COVID-19 Pandemic in a Tertiary Care Center: A Descriptive Cross-sectional Study.

INTRODUCTION: Healthcare workers are always at the risk of exposure to different diseases like respiratory illness including COVID-19. Using appropriate face mask or respiratory protective equipment correctly can prevent transmission of diseases from and to healthcare workers while caring for patients. The study aimed to find out the practice regarding use of face masks during the COVID-19 pandemic in a tertiary care center. METHODS: A descriptive cross-sectional study was conducted at a tertiary care hospital during June-July 2020 after receiving ethical approval from the review committee regarding practice of use of face masks. Convenience sampling method was used and a sample size of 162 was taken. Descriptive statistical analysis was done. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Among 162 participants, 123 (75.9%) knew the correct way of using the masks (72.5-79.3 at 95% Confidence Interval). CONCLUSIONS: In this study regarding practice of use of face masks, most of the healthcare workers knew the correct way of using masks and practised hygiene before and after using masks.

Challenges and opportunities in setting up a phase III vaccine clinical trial in resource limited settings: Experience from Nepal.

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants' to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity. The initial site selection, set up and preparatory activities for the clinical trial are crucial to minimizing the risks to both participants and to successful completion during the subsequent study execution.In this paper, we describe the experience and lessons learned of building clinical trial site capacity in terms of infrastructure and human resource development for a Phase III vaccine clinical trial. We believe that sharing the experience of setting up a clinical trial in a resource-limited country will enable other entities contemplating clinical research in these countries, to prepare and plan ahead, to minimize the impact of barriers, and to contribute to bringing more studies to the countries where people live with the burden of vaccine-preventable, poverty-associated diseases.

Ewing's Sarcoma of Rib in a Four Year Old: A Case Report.

Although rare, the Ewing's sarcoma family of tumors represents the second most common primary bone malignancy that typically occurs in adolescents and young adults aged 10-25 years, presenting with localized pain and swelling of a long bone. We report a case of Ewing's sarcoma of rib in a four years old child that presented with acute onset of fever, cough, shortness of breath and was initially treated as pneumonia. Although the patient did not belong to typical demography and the symptoms were suggestive of infective pathology, careful scrutiny of the radiographic findings led to further investigations and diagnosis of Ewing's sarcoma of rib after correlating computerized tomography scan findings with immunohistochemistry reports.

Clinico-Laboratory Profile, Complications and Therapeutic Outcome of Scrub Typhus in Children.

BACKGROUND: Scrub typhus, an important cause of undifferentiated fever, is grossly neglected and often misdiagnosed in low and middle income countries like Nepal. The main aim of this study was to describe the clinico-laboratory profile, drug used in treatment, predictor of PICU admission and therapeutic outcome of serologically confirmed scrub typhus among Nepalese children. METHODS: A prospective observational study was carried out in children aged up to 14 years with serologically (IgM ELISA) diagnosed Scrub typhus, admitted in a tertiary care hospital of central Nepal between Jan 2019 to Dec 2019. RESULTS: All 100 children with scrub typhus presented with fever. Other symptoms and sign were cough (29%), abdominal distension (22%) hepatomegaly (45%), splenomegaly (28%), crepitation (10%) and eschar (6%). Similarly, thrombocytopenia (72%), and increased liver enzymes SGPT (51%) and SGOT (62%) were found. Co-infection with dengue (5%) brucella (5%) and UTI (5%) were seen. Thirty six percent has some form of complication. Fifty eight percent of children were treated with azithromycin and 25% treated with doxycycline. The mean length of hospital stay was 6.68 ±2.97 days with a mean duration of defervescence being 30.07 ± 26.65 hours. The increased risk of PICU admission was found in those children with crepitation in chest (OR: 15.17, 95% CI: 3.4-66.8) during presentation and those children not getting azithromycin as treatment (OR: 3.8, 95% CI: 1.2-11.7) Conclusions: Scrub typhus should be considered as a differential diagnosis in any community acquired acute undifferentiated febrile illness regardless of the presence of an eschar. Sepsis, meningitis and pneumonia are important complications. Child having crepitation on presentation has an increased chance admission in critical care unit. The child receiving azithromycin has less chance to land in PICU.

Effect of the 2015 earthquake on pediatric inpatient pattern at a tertiary care hospital in Nepal.

BACKGROUND: Earthquakes impact child health in many ways. Diseases occurring immediately following an earthquake have been studied in field based hospitals but studies on the inpatient disease pattern among children without trauma in a permanent hospital setup is lacking. METHODS: We examined the diagnoses of all children without trauma, admitted to Kanti Children's Hospital, Kathmandu for fifteen-week duration (from 4th week to end of the 18th week) following the 7.8 magnitude Nepal earthquake on 25th April 2015. The admitted children were grouped based on direct effect of earthquake on their family (house damaged or family member injured or dead) and on whether their place of residence was located in an earthquake affected district. Most common diagnoses were identified and their distribution between the aforementioned groups analyzed to examine differences, if any, in disease occurrence or presentation. The fifteen weeks study duration was divided into three parts of five weeks each, to study trends in illness presentation. Variables were compared among various groups using appropriate statistical tests (p < 0.05). RESULTS: A total of 1057 patients were admitted. The proportion of patients requiring admission for pneumonia, acute gastroenteritis and acute or poststreptococcal glomerulonephritis (AGN/PSGN) was significantly higher among children belonging to earthquake affected districts. Proportion of patients with any infective condition was also significantly higher in this group. Acute gastroenteritis and any infective condition were significantly higher among children from substantially affected families. The proportion of AGN/PSGN among admitted patients increased in successive time categories among patients from affected districts and from substantially affected families. Urinary Tract Infection, bronchiolitis, tuberculosis, pleural effusion, protein energy malnutrition/failure to thrive, nephrotic syndrome, meningitis/meningoencephalitis, epilepsy or seizure disorders, leukemia/malignancies, enteric fever, infective hepatitis and congenital heart disease were not significantly different among children from affected and not affected districts or between substantially affected and not affected families. Patients from substantially affected families were admitted to semi-intensive care ward or ICU in significantly higher proportions (12.6% vs 7.8%, p = 0.014). CONCLUSION: Children seeking care for certain diseases were more likely to be from earthquake affected families and districts. Those from affected families required critical care more often.

Retrospective study of the clinical profile and prognostic indicators in patients of alcoholic liver disease admitted to a tertiary care teaching hospital in Western Nepal.

BACKGROUND/AIM: Alcohol is the most common substance abused in Nepal. Liver disease caused by alcohol abuse, including its end stage, cirrhosis, is a major health care problem, which is difficult to treat. OBJECTIVES: To study the demographic profile, laboratory parameters, complications and their prognostic implications among patients of alcoholic liver disease (ALD). MATERIALS AND METHODS: Records of all patients of ALD admitted from January1 , 2005 to December 31 , 2006 were studied and followed up to December 31, 2007. A total of 181 patients were analyzed. Their clinical profile and laboratory parameters were noted and analyzed using SPSS-10.0 software. RESULTS: Among the 181 patients, 80.7% were male, 30.9% were army/ex-army and 65.2% were documented smokers. The mean age of presentation was 52.08 years. Jaundice (57.5%) was the most common presentation followed by hepatomegaly (51.4%). Hypoalbuminemia (50.3) followed by ascites (48.1) were common complications. Death occurred in 19.1% of the patients, the most common cause being hepatic encephalopathy (72.2%) followed by variceal bleeding and hepatorenal syndrome. Jaundice, ascites and hepatic encephalopathy at presentation and female sex were significantly associated with increased mortality along with discriminant score > 32, aspartate aminotransferase (AST): Alanine aminotranferase (ALT) > or = 2, ultrasonography (USG)-proven cirrhosis, rise in prothrombin time > or =5 s, total bilirubin > or = 4 mg/dL and ESR > or =34. CONCLUSION: ALD was predominantly seen among the productive age group with a high morbidity and mortality. Jaundice, ascites, hepatic encephalopathy at presentation and female sex are poor prognostic indicators along with discriminant score > 32, AST:ALT > or = 2, USG-proven cirrhosis, coagulopathy, hyperbilirubenemia and high ESR.

Surgical site infection and antibiotics use pattern in a tertiary care hospital in Nepal.

OBJECTIVE: To obtain information on surgical site infection (SSI) and the regimens used for surgical prophylaxis. METHODS: The study was carried out at Manipal Teaching Hospital, Pokhara, Nepal from 1st January to 30th June 2004. Inpatients and outpatients undergoing surgical procedures in General Surgery department were included. Data was collected on a specially designed proforma. Demographic details, details of SSI, results of culture/sensitivity testing and antibiotics used for prophylaxis were noted. Associations of SSI with different variables were studied. RESULTS: A total of 507 patients were included. SSI was noted in 37 patients (7.3%), of which 21 (56.8%) were superficial SSI. Total duration of antibiotic use, type of anaesthesia and post-operative fever showed significant statistical association with SSI. Organisms were isolated in 12 out of 37 SSI cases (32.4%). E. coli was the most organism isolated. Combination of ampicillin and cloxacillin was the most commonly used antibiotic regimen (138 patients) followed by combination of ampicillin, cloxacillin and metronidazole (26 patients). CONCLUSIONS: The incidence of SSI was higher compared to developed countries. Surveillance systems for SSI and hospital guidelines for antibiotic prophylaxis are required.