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Manish P Shrestha,1 Mark Borgstrom,2 Eugene Abraham Trowers3 1Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA; 2Research Computing Group of University Information Technology Services, University of Arizona, Tucson, AZ, USA; 3Division of Gastroenterology, University of Arizona College of Medicine, Tucson, AZ, USA Background and aims: Initial clinical management decision in patients with acute gastrointestinal bleeding (GIB) is often based on identifying high- and low-risk patients. Little is known about the role of lactate measurement in the triage of patients with acute GIB. We intended to assess if lactate on presentation is predictive of need for intervention in patients with acute GIB. Patients and methods: We performed a single-center, retrospective, cross-sectional study including patients ≥18 years old presenting to emergency with acute GIB between January 2014 and December 2014. Intensive care unit (ICU) admission, inpatient endoscopy (upper endoscopy and/or colonoscopy), and packed red blood cell (PRBC) transfusion were assessed as outcomes. Analyses included univariate and multivariate logistic regression analyses. Results: Of 1,237 patients with acute GIB, 468 (37.8%) had venous lactate on presentation. Of these patients, 165 (35.2%) had an elevated lactate level (>2.0 mmol/L). Patients with an elevated lactate level were more likely to be admitted to ICU than patients with a normal lactate level (adjusted odds ratio [AOR] 2.96, 95% confidence interval [CI] 1.74–5.01; p

Lekhjung Thapa,1 Suman Bhattarai,1 Milan P Shrestha,1 Rajesh Panth,2 Dinesh Nath Gongal,3 Upendra Prasad Devkota,31Department of Neurology, 2Department of Pathology, 3Department of Neurosurgery, National Institute of Neurological and Allied Sciences, Kathmandu, Nepal Abstract: Neuroacanthocytosis is a group of rare disorders. We report a 36-year-old right-handed female who presented with gradually progressive abnormal facial movements, generalized weakness, and lower-lip biting starting 4 years ago. On examination, she had lower-lip ulcer, orofacial dyskinesias, and peripheral neuropathy. Her peripheral blood smears showed acanthocytosis and magnetic resonance imaging revealed atrophied head of caudate nuclei and putaminal hyperintensities on T2-weighted and fluid attenuated inversion recovery images. Work-up for autoimmune and metabolic causes was negative. She was diagnosed with chorea-acanthocytosis, an entity under neuroacanthocytosis syndrome and the patient was offered symptomatic treatment. Keywords: acanthocytes, lip-biting, neuroacanthocytosis, orofacial dyskinesia, movement disorder

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Clostridioides difficile infection (CDI) is an important cause of inflammatory bowel disease (IBD) exacerbation and is associated with increased risk of hospitalization, colectomy, and mortality. Previous analysis have reported an increasing rate of CDI and associated mortality in IBD patients. We examined the trends in CDI-associated outcomes in hospitalized patients with Crohn's disease (CD) and ulcerative colitis (UC) over the last decade., Materials and Methods: We used data from the National Inpatient Sample to identify patients hospitalized with both CDI and IBD from 2006 to 2014. Outcomes included in-hospital mortality, partial/total colectomy, hospital length of stay, and charges. Analysis included univariate and multivariate regression analysis., Results: Between 2006 and 2014, CDI-related hospitalizations increased in both CD (1.6% to 3.2%; P<0.001) and UC (4.9% to 8.6%; P<0.001). CDI-associated mortality in CD and UC patients decreased from 2.4% to 1.2% (P<0.001) and 11.3% to 9.7% (P<0.001), respectively. CDI-associated colectomy rate increased from 4.3% to 8.8% (P<0.001) in UC but decreased from 4.5% to 2.8% (P<0.001) in CD. In multivariable analysis, compared with 2006, there was a nonsignificant decrease in mortality in 2014 in both CD [adjusted odds ratio (AOR) 0.56, 95% confidence interval (CI) 0.25-1.24] and UC (AOR 0.81, 95% CI 0.61-1.07), but a significant increase in colectomy in 2014 only in UC (AOR 2.12, 95% CI 1.46-3.06)., Conclusions: CDI rates have increased in CD and UC over the last decade. Although there has been a significant increase in colectomies in UC, CDI-associated mortality in CD and UC has not increased over this time., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Hepatitis E (HE) during pregnancy can be fatal; there are no prospective risk estimates for HE and its complications during pregnancy. We followed 2,404 pregnant women for HE and pregnancy outcomes from 1996 to 1998. Subjects from Nepal were enrolled at an antenatal clinic with pregnancy of ≤ 24 weeks. Most women (65.1%) were anti-HE virus negative. There were 16 cases of HE (6.7 per 1,000); three mothers died (18.8%) having had intrauterine fetal death (IUFD). Thirteen mothers survived: five preterm and seven full-term deliveries, one IUFD. HE among seronegative women was the sole cause of maternal death and increased the risk of IUFD (relative risk [RR]: 10.6; 95% confidence interval [CI]: 4.29-26.3) and preterm delivery (RR: 17.1, 95% CI 7.56-38.5). HE vaccination of females in at-risk regions before or as they attain reproductive age would reduce their risk for preterm delivery, IUFD, and maternal death.

Background: Nepal adopted the Multisectoral Action Plan for the Prevention and Control of Non-Communicable Diseases (MSAP) in 2014. Implementation of the plan has been challenging, with limited participation from non-health sectors., Objectives: The overall aim of the study was to gain the perspectives of key stakeholders involved in the Nepal MSAP on the barriers and facilitators to its implementation, through the participation of relevant sectors in the plan., Methods: We held face-to-face semi-structured interviews with 12 stakeholders working in sectors involved in the MSAP. These sectors included the Office of the Prime Minister and Council of Ministries; Ministry of Health and Population (MOHP); Ministry of Education, Science and Technology; Ministry of Forest and Environment; academia; and professional organizations. Thematic analysis of transcripts was used to identify themes on awareness of NCDs, awareness of the MSAP, and barriers and facilitators to participation in the MSAP., Results: Participants recognised NCDs as a growing and major burden in Nepal. However, a number of participants were not familiar with the MSAP, identifying a lack of leadership and poor dissemination. Political and systemic transformation, since the adoption of the MSAP, was seen as a key barrier to implementation. International commitments to develop multisectoral action made by the Government of Nepal were identified as drivers. The recent establishment of a separate section for NCDs and Mental Health within the Department of Health Services of MOHP and the promotion of a Health in All Policies (HiAP) approach in recent national documents, were both considered to support implementation., Conclusions: The establishment of permanent multisectoral or multistakeholder mechanisms has been challenging despite strong political calls for their development. Moving beyond 2020, multisectoral action plans should engage with stakeholders from federal, provincial and local governments in order to develop costed action plans with specific roles and responsibilities for each sector.

Background: The COVID-19 pandemic response is affecting maternal and neonatal health services all over the world. We aimed to assess the number of institutional births, their outcomes (institutional stillbirth and neonatal mortality rate), and quality of intrapartum care before and during the national COVID-19 lockdown in Nepal., Methods: In this prospective observational study, we collected participant-level data for pregnant women enrolled in the SUSTAIN and REFINE studies between Jan 1 and May 30, 2020, from nine hospitals in Nepal. This period included 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. Women were eligible for inclusion if they had a gestational age of 22 weeks or more, a fetal heart sound at time of admission, and consented to inclusion. Women who had multiple births and their babies were excluded. We collected information on demographic and obstetric characteristics via extraction from case notes and health worker performance via direct observation by independent clinical researchers. We used regression analyses to assess changes in the number of institutional births, quality of care, and mortality before lockdown versus during lockdown., Findings: Of 22 907 eligible women, 21 763 women were enrolled and 20 354 gave birth, and health worker performance was recorded for 10 543 births. From the beginning to the end of the study period, the mean weekly number of births decreased from 1261·1 births (SE 66·1) before lockdown to 651·4 births (49·9) during lockdown-a reduction of 52·4%. The institutional stillbirth rate increased from 14 per 1000 total births before lockdown to 21 per 1000 total births during lockdown (p=0·0002), and institutional neonatal mortality increased from 13 per 1000 livebirths to 40 per 1000 livebirths (p=0·0022). In terms of quality of care, intrapartum fetal heart rate monitoring decreased by 13·4% (-15·4 to -11·3; p<0·0001), and breastfeeding within 1 h of birth decreased by 3·5% (-4·6 to -2·6; p=0·0032). The immediate newborn care practice of placing the baby skin-to-skin with their mother increased by 13·2% (12·1 to 14·5; p<0·0001), and health workers' hand hygiene practices during childbirth increased by 12·9% (11·8 to 13·9) during lockdown (p<0·0001)., Interpretation: Institutional childbirth reduced by more than half during lockdown, with increases in institutional stillbirth rate and neonatal mortality, and decreases in quality of care. Some behaviours improved, notably hand hygiene and keeping the baby skin-to-skin with their mother. An urgent need exists to protect access to high quality intrapartum care and prevent excess deaths for the most vulnerable health system users during this pandemic period., Funding: Grand Challenges Canada., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Nepal has made considerable progress on improving child survival during the Millennium Development Goal period, however, further progress will require accelerated reduction in neonatal mortality. Neonatal survival is one of the priorities for Sustainable Development Goals 2030. This paper examines the trends, equity gaps and factors associated with neonatal mortality between 2001 and 2016 to assess the likelihood of Every Newborn Action Plan (ENAP) target being reached in Nepal by 2030., Methods: This study used data from the 2001, 2006, 2011 and 2016 Nepal Demographic and Health Surveys. We examined neonatal mortality rate (NMR) across the socioeconomic strata and the annual rate of reduction (ARR) between 2001 and 2016. We assessed association of socio-demographic, maternal, obstetric and neonatal factors associated with neonatal mortality. Based on the ARR among the wealth quintile between 2001 and 2016, we made projection of NMR to achieve the ENAP target. Using the Lorenz curve, we calculated the inequity distribution among the wealth quintiles between 2001 and 2016., Results: In NDHS of 2001, 2006, 2011 and 2016, a total of 8400, 8600, 13,485 and 13,089 women were interviewed respectively. There were significant disparities between wealth quintiles that widened over the 15 years. The ARR for NMR declined with an average of 4.0% between 2001 and 2016. Multivariate analysis of the 2016 data showed that women who had not been vaccinated against tetanus had the highest risk of neonatal mortality (adjusted odds ratio [AOR] 3.38; 95% confidence interval [CI] 1.20-9.55), followed by women who had no education (AOR 1.87; 95% CI 1.62-2.16). Further factors significantly associated with neonatal mortality were the mother giving birth before the age of 20 (AOR 1.76; CI 95% 1.17-2.59), household air pollution (AOR 1.37; CI 95% 1.59-1.62), belonging to a poorest quintile (AOR 1.37; CI 95% 1.21-1.54), residing in a rural area (AOR 1.28; CI 95% 1.13-1.44), and having no toilet at home (AOR 1.21; CI 95% 1.06-1.40). If the trend of neonatal mortality rate of 2016 continues, it is projected that the poorest family will reach the ENAP target in 2067., Conclusions: Although neonatal mortality is declining in Nepal, if the current trend continues it will take another 50 years for families in the poorest group to attain the 2030 ENAP target. There are different factors associated with neonatal mortality, reducing the disparities for maternal and neonatal care will reduce mortality among the poorest families.

Background: Obesity and inflammatory bowel disease (IBD) are associated with increased risk of Clostridium difficile infection (CDI). The effect of obesity on IBD course and development of complications is poorly understood. We performed this study to examine the effect of obesity on CDI-related morbidity and mortality in hospitalized patients with IBD., Methods: We used data from the National Inpatient Sample across five study years (2010-2014) to identify patients ≥ 18 years hospitalized with both CDI and IBD. We compared the outcomes of in-hospital mortality, partial or total colectomy, hospital length of stay, and hospital charges between obese and non-obese IBD-CDI patients. Analysis included univariate and multivariate linear and logistic regression analyses., Results: Of 304,298 hospitalized patients with IBD, 13,517 (4.4%) patients had CDI. Of these, 996 (7.4%) patients were obese. Obese IBD-CDI patients had a higher risk of colectomy (adjusted odds ratio, AOR 1.60, 95% CI 1.30-1.96; p < 0.001), longer hospital length of stay (difference 0.8 days, 95% CI 0.02-1.58; p = 0.04), and higher hospital charges (difference $11,051, 95% CI 1939-20,163; p = 0.02) than non-obese IBD-CDI patients, but no significant difference in mortality was found between the two groups., Conclusions: Obesity is associated with a 60% increase in the risk of colectomy, longer hospital stay, and higher charges in IBD patients hospitalized with CDI. Further epidemiological and clinical studies are needed to confirm these findings.

The incidence rate of ulcerative colitis (UC) in older patients is rising. Diagnosis of UC may be difficult in older patients as several common gastrointestinal disorders can mimic UC in these patients. Compared with younger adults, left-sided colitis is more common in older-onset UC, while rectal bleeding, abdominal pain, and extraintestinal manifestations are less common. The disease course of older-onset UC may be similar to that of adult-onset UC. The management of UC in older patients includes medical and surgical options. A majority of older UC patients are treated with 5-aminosalicylates. The underuse of immunosuppressants or biologics may lead to poor disease control, higher use of corticosteroids, and worse clinical outcomes in older UC patients. Serious infections and malignancy are the most concerning complications of immune-modifying agents or biologics in the elderly. Timely surgical referral of older UC patients with poor disease control is of utmost importance as elective colectomy may be associated with improved survival in these patients.

Background: Clostridium difficile infection has emerged as a major public health problem in the United States over the last 2 decades. We examined the trends in the C. difficile-associated fatality rate, hospital length of stay, and hospital charges over the last decade., Methods: We used data from the National Inpatient Sample to identify patients with a principal diagnosis of C. difficile infection from 2004 to 2014. Outcomes included in-hospital fatality rate, hospital length of stay, and hospital charges. For each outcome, trends were also stratified by age categories because the risk of infection and associated mortality increases with age., Results: Clostridium difficile infection discharges increased from 19.9 per 100,000 persons in 2004 to 33.8 per 100,000 persons in 2014. Clostridium difficile-associated fatality decreased from 3.6% in 2004 to 1.6% in 2014 (P < .001). Among patients aged 45-64 years, fatality decreased from 1.2% in 2004 to 0.7% in 2014 (P < .001). Among patients aged 65-84 years, fatality decreased from 4.3% in 2004 to 2.0% in 2014 (P < .001). Among patients aged ≥85 years, fatality decreased from 6.9% in 2004 to 3.6% in 2014 (P < .001). The mean length of hospital stay decreased from 6.9 days in 2004 to 5.8 days in 2014 (P < .001). The mean hospital charges increased from 2004 ($24,535) to 2014 ($35,898) (P < .001)., Conclusion: In-hospital fatality associated with C. difficile infection in the United States has decreased more than 2-fold in the last decade, despite increasing infection rates., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although digital rectal examination is an established part of physical examinations in patients with acute gastrointestinal bleeding, clinicians are reluctant to perform a rectal examination. We intended to assess whether rectal examination affects the clinical management decision in these patients., Methods: We performed a single-center, retrospective, cross-sectional study using data from electronic health records of patients aged ≥18 years presenting to the emergency department with acute gastrointestinal bleeding. Hospital admissions, intensive care unit admissions, gastroenterology consultation, initiation of medical therapy (proton pump inhibitor or octreotide), and inpatient endoscopy (upper endoscopy or colonoscopy) were assessed as outcomes. Univariate and multivariate logistic regression analyses were performed., Results: Of 1237 patients with acute gastrointestinal bleeding, 549 (44.4%) did not have a rectal examination. Patients who had a rectal examination were less likely to be admitted than patients who did not have a rectal examination (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.30-0.79; P = .004). Patients who had a rectal examination were less likely to be started on medical therapy (AOR, 0.64; 95% CI, 0.41-0.98; P = .04) and to have endoscopy (AOR, 0.64; 95% CI, 0.44-0.94; P = .02) than patients who did not have a rectal examination., Conclusions: Rectal examination in patients with acute gastrointestinal bleeding can assist clinicians with clinical management decision and reduce admissions, endoscopies, and medical therapy in these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Goals: We intended to identify the factors associated with missed appointments at a gastroenterology (GI) clinic in an academic setting., Background: Missed clinic appointments reduce clinic efficiency, waste resources, and increase costs. Limited data exist on subspecialty clinic attendance., Study: We performed a case-control study using data from the electronic health record of patients scheduled for an appointment at the adult GI clinic at the Banner University Medical Center between March and October of 2014. Patients who missed their appointment during the study period served as cases. Controls were randomly selected from patients who completed their appointment during the study period. Analysis included univariate and multivariate logistic regression analysis., Results: Of 2331 scheduled clinic appointments, 195 (8.4%) were missed appointments. Longer waiting time from referral to scheduled appointment was significantly associated with missed appointment (AOR=1.014; 95% CI, 1.01-1.02; P<0.001). Patients with primary care providers (PCPs) were less likely to miss their appointment than those without PCPs (AOR=0.35; 95% CI, 0.18-0.66; P=0.001). Among patient demographic characteristics, ethnicity and marital status were associated with missed appointment., Conclusions: Wait time, ethnicity, marital status, and PCP status were associated with missed GI clinic appointments. Further investigations are needed to assess the effects of intervention strategies directed at reducing appointment wait time and increasing PCP-based care.

The increasing number of older patients (age ≥60 years) with inflammatory bowel disease (IBD) highlights the importance of healthcare maintenance in this vulnerable population. Older IBD patients are more susceptible and have higher rates of many disease- and treatment-related adverse effects. Compared to younger IBD patients, older patients are at increased risk for infection, malignancy, bone disease, eye disease, malnutrition and thrombotic complications. Preventive strategies in the elderly differ from those in younger adults and are imperative. Changes to the immune system with aging can decrease the efficacy of vaccinations. Cancer screening guidelines in older IBD patients have to account for unique considerations, such as life expectancy, functional performance status, multimorbidity, financial status, and patient desires. Additionally, providers need to be vigilant in screening for osteoporosis, ocular disease, depression, and adverse events arising from polypharmacy., Competing Interests: Conflict of Interest: Joannie Ruel: speaker and consultant for AbbVie, Janssen, Takeda, Shire, Ferring

Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virus-host relationship.

Bartonellae were detected in a total of 152 (23.7%) of 642 tissues from 108 (48.4%) of 223 small mammals trapped in several urban areas of Nepal. Based on rpoB and gltA sequence analyses, genotypes belonging to seven known Bartonella species and five genotypes not belonging to previously known species were identified in these animals.

The geographic distribution of leptospirosis is widespread but no national surveillance program exists in Nepal to establish the incidence of leptospirosis or the disease burden. This study reports the incidence of symptomatic leptospirosis in military personnel participating in an efficacy study of a hepatitis E virus vaccine in Nepal. Among the 1566 study volunteers who completed follow-up, we evaluated 271 illnesses over 2.2 years for the presence of leptospira IgM antibodies by ELISA. Positive ELISA results were confirmed by the microscopic agglutination test. The annual incidence of disease was between 3.5 and 6.1 cases/1000. The prevalence of confirmed leptospirosis was 9% among hepatitis cases and 8% among febrile cases. The most reactive serovars were Bratislava, Autumnalis, Icterohaemorrhagiae, and Sejroe. Leptospirosis should be considered in the differential diagnosis of febrile illnesses and icteric syndromes in Nepal. Additional studies are needed to establish the broader distribution and the spectrum of disease in Nepal.

A cohort of 62 Nepalese adults with acute hepatitis E was identified and total Ig as well as IgM levels to hepatitis E virus (HEV) capsid protein were determined using the Walter Reed Army Institute of Research (WRAIR) immunoassay. An antibody profile was constructed from serial serum specimens collected up to 14 months following the onset of illness. The decline in total Ig was rapid for the first 3 months. There followed a slow, sustained decline, but antibodies remained above the seropositive level of 20 WRAIR units. The decline of IgM was steeper than total Ig for the first 3 months, but IgM remained detectable after 14 months in 25% of cases. Study data contribute to an understanding of the pathophysiology of human hepatitis E and set an antibody response pattern to be targeted as a part of HEV vaccine development.

A nutritional survey was carried out among residents (39 males and 46 females) of Dzong village in the northern area of the Gandaki region of Nepal. The results were compared with our previous findings. The mean body mass index value was under 21 for both sexes, but the mean percentage of body fat of females (17-19 years old, 25.8 +/- 9.4%; 20-29 years old, 31.0 +/- 8.4%) was higher than that of males (17-19 years old, 12.0 +/- 1.0%; 50-59 years old, 24.4 +/- 7.6%). Most serum nutritional markers for both sexes were generally at normal levels although the iron levels were lower and packed red cell volume levels were higher than normal. As determined by results of the 24-hr dietary recall survey, the main food groups consumed by both sexes were cereals, potatoes, pulses, meats and vegetables. The mean daily intake of nutrients was similar for both sexes, with a few exceptions. The relatively high serum TG levels of the subjects may have been due to the high consumption of carbohydrate-laden cereals. The amounts of food consumed were not adequate, resulting in a latent and chronic deficiency of nutrients, especially calcium and iron. These results suggest that improvements in the nutritional status of this group of people are necessary.

Objective: The food consumption and serum nutritional status of people living in the Kathmandu valley, Nepal, were examined to obtain actual data for comparison with our previous findings., Methods: A dietary survey of 45 males and 60 females was carried out in March 1997 by the 24-hr dietary recall method and nutrient intake was calculated from food tables of India and Japan. Fasting venous blood samples were obtained and serum biochemical parameters were measured using clinical kits., Results: The mean body mass index values was at about the same level in both sexes, although the mean percentage body fat of females was higher than that of males, and vice versa for packed red cell volume. The main foods consumed by both sexes, were rice, potatoes, meats, milk & dairy products and vegetables, with a difference in the amounts consumed. Females did not drink alcoholic beverages. The mean daily intakes of energy, protein, lipids, iron and vitamin B group for the males were higher than those for the females, while those of vitamins A and C for the males were lower than those for the females. The mean values of serum biochemical parameters for both sexes were generally at the normal levels, but those of ALT and TG were at the higher end of the normal range. Differences of correlation between food groups and between serum parameters were observed depending on the sex, however, no clear relationship between food and nutrient intake and serum biochemical parameters were observed., Conclusions: The present food intake study revealed that the amounts of food consumption for both sexes, especially for the females, were mostly insufficient although the serum parameters were at the normal levels. The energy intake of both sexes was lower than that of estimated requirements and those in Terai region. The relatively high serum TG level of the subjects may be due to the consumption of large amounts of cereals containing much carbohydrate. Our findings suggested a marked influence on food consumption by food price and income in spite of the easier food availability in the city, and also lack of knowledge about nutrients and health, thus there is need for improvement of the nutritional status of this group of people.

Objective: The present study examined the levels of serum α-Tocopherol (Toc), retinol (Ret), cholesterol (Chol) and triglycerides (TG), and their correlations in the sera of people in Nepal., Methods: The survey was conducted on the general populace in the agricultural Terai region in southern Nepal. The study population consisted of 93 males and 83 females aged 10-68 years. Serum Toc and Ret were measured by high-performance liquid chromatography., Results: No significant differences were observed between the genders for the average of total Chol (T-Chol) (140 and 145 mg/100 ml, respectively), HDL-C (45 and 47 mg/100 ml), LDL-C (94 and 97 mg/100 ml), and TG (106 and 110 mg/100 ml), and the ratio of LDL/HDL (2.16). The levels of mean Toc (4.32 and 4.27 μg/ml) were about the same for both genders, while the mean Ret levels were significantly higher for males (624 ng/ml) than for females (535 ng/ml) (p<0.001). A direct relationship was found between the levels of Toc and Ret (r=0.46, p<0.001 and r=0.28, p<0.05 for males and females, respectively). Serum levels of Toc and Ret were positively related to the levels of Chol (r=0.48 and r=0.58, p<0.001 for males and r=0.49, p<0.01 and r-0.28, p<0.05 for females, respectively). The ratio of Toc/TG normalized to serum TG was directly correlated to the ratio of Ret/TG (r=0.79 for males, and r=0.72 for females, p<0.001, respectively) and the ratios of Toc/TG and Ret/TG were negatively related to the LDL/HDL levels (r=-0.49 and r=-0.43, for males, and r=-0.46 and r=-0.57 for females, p<0.001, respectively)., Conclusion: The levels of Toc and Ret were low in the sera of people living in the southern rural Terai region in Nepal, and it was found that lower levels of Toc and Ret normalized to TG increased the ratio of LDL/HDL. These results suggest that greater intake of foods rich in Toc and Ret should be encouraged to reduce the erisk of coronary heart disease.

Background: Rheumatic heart disease remains a major public health problem in developing countries with its very high prevalence. Rheumatic and congenital heart disease are significant causes of morbidity and mortality among Nepalese schoolchildren. The aim of our study was to determine the prevalence of rheumatic and congenital heart disease among schoolchildren of the Kathmandu valley in Nepal., Methods and Results: The study included 9420 students, of whom 4466 were male and 4954 were female, with ages ranging from 5 to 18 years. A clinical survey was conducted by the examining team in selected schools, and involved answering standard questionnaires. A total of 83 children were suspected of having heart disease. Out of these 83 children, 23 were confirmed to have heart disease; 11 had rheumatic heart disease, and 12 congenital heart disease, giving a prevalence of 1.2/1000 and 1.3/1000, respectively. The commonest cardiac lesions were mitral regurgitation in the rheumatic heart disease group, and atrial septal defect in the congenital heart disease group. A higher prevalence of congenital heart disease was detected in females., Conclusions: The prevalence of rheumatic heart disease and congenital heart disease among schoolchildren of Kathmandu is 1.2/1000 and 1.3/1000, respectively, with mitral regurgitation and atrial septal defect being the commonest lesions.

Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GTP), lactate dehydrogenase (LDH), urea nitrogen (BUN), uric acid (UA) and creatinine (CRE) levels were examined in 183 people (98 males and 85 females aged 10 to 68 years) living in Terai region in Nepal. The mean values of serum components examined did not differ by sex in the age group of 10-14 years. The mean values of serum AST, ALT and gamma-GTP levels differed significantly between the sexes (P<0.01). The all physical measurements and serum parameters observed correlated well in males, but a few of them correlated in females. The AST-ALT, AST-gamma-GTP, ALT-CRE and BUN-CRE correlated well in both sexes. The UA correlated with ALT and gamma-GTP, CRE with gamma-GTP, LDH and UA in males, while only AST-LDH and gamma-GTP-BUN correlated in females. The levels of most of the serum components examined in this study were within normal ranges for Japanese and others. However, it seemed to be necessary to improve their living conditions as these serum components are related to hepatic or renal function and the infectious diseases.

About 47% of Nepal's total population is living in Terai region and 90% of them are relying on groundwater as their major source of drinking water. About 200,000 shallow tubewells have been installed by different agencies in 20 Terai districts, serving 11 million people. Recently, arsenic contamination of groundwater has been recognized as a public health problem in Nepal. This has sensitized government, national and international nongovernment organizations working on water quality sector to carry out water quality assessment for arsenic in the affected communities. So far, 15,000 tubewells has been tested where 23% samples exceeded World Health Organization guideline value of 10 microg/L and 5% exceeded "Nepal Interim Arsenic Guideline" of 50 microg/L. It is estimated that around 0.5 million people in Terai are living at risk of arsenic poisoning (>50 microg/L). Some recent studies have reported the prevalence of dermatosis related to arsenicosis from 1.3 to 5.1% and the accumulation of arsenic in biological samples like hair and nail much higher than the acceptable level. Though some steps are being taken by government and private organizations to combat the problem, it has not been able to cover all the affected communities. Nepal still needs more research work on arsenic occurrence and effects and mitigation programs simultaneously.

Hepatitis E virus (HEV) is an important cause of enterically transmitted hepatitis in developing countries. Sporadic autochthonous cases of hepatitis E have been reported recently in the United States and other industrialized countries. The source of HEV infection in these cases is unknown; zoonotic transmission has been suggested. Antibodies to HEV have been detected in many animals in areas where HEV is endemic and in domestic swine and rats in the United States. There is evidence supporting HEV transmission between swine and humans. Nevertheless, HEV has not been detected in wild rodents. We tested murid rodents and house shrews trapped in Nepal's Kathmandu Valley, where hepatitis E is hyperendemic, for HEV infection. The most commonly trapped species was Rattus rattus brunneusculus. Serum samples from 675 animals were tested for immunoglobulin G against HEV by enzyme-linked immunosorbent assay; 78 (12%) were positive, indicating acute or past infection. Antibody prevalence was higher among R. rattus brunneusculus and Bandicota bengalensis than in Suncus murinus. Forty-four specimens from 78 antibody-positive animals had sufficient residual volume for detection of HEV RNA (viremia) by reverse transcription-PCR. PCR amplification detected four animals (9%; three were R. rattus brunneusculus and one was B. bengalensis) with viremia. Phylogenetic analysis of the four genome sequences (405 bp in the capsid gene) recovered showed that they were identical, most closely related to two human isolates from Nepal (95 and 96% nucleotide homology, respectively), and distinct from HEV sequences isolated elsewhere. These data prove that certain peridomestic rodents acquire HEV in the wild and suggest that cross-species transmission occurs, with rodents serving as a virus reservoir for humans.

Diagnosis of acute hepatitis E by detection of hepatitis E virus (HEV)-specific immunoglobulin M (IgM) is an established procedure. We investigated whether quantitation of HEV IgM and its ratio to HEV total Ig furnished more information than conventional IgM tests that are interpreted as positive or negative. A previously described indirect immunoassay for total Ig against a baculovirus-expressed HEV capsid protein was modified to quantitate HEV-specific IgM in Walter Reed (WR) antibody units by using a reference antiserum and the four-parameter logistic model. A receiver-operating characteristics curve derived from 197 true-positive specimens and 449 true-negative specimens identified 30 WR units/ml as an optimum cut point. The median HEV IgM level in 36 patients with acute hepatitis E fell from 3,000 to 100 WR units/ml over 6 months, suggesting that 100 WR units/ml would be a more appropriate cut point for distinguishing recent from remote IgM responses. Among three hepatitis E case series, determination of the HEV IgM-to-total-Ig ratio in acute-phase serum revealed that most patients had high ratios consistent with primary infections whereas a few had low ratios, suggesting that they had sustained reinfections that elicited anamnestic antibody responses. The diagnostic utility of the new IgM test was similar to that of a commercially available test that uses different HEV antigens. In conclusion, we found that HEV IgM can be detected specifically in >95% of acute hepatitis E cases defined by detection of the virus genome in serum and that quantitation of HEV IgM and its ratio to total Ig provides insight into infection timing and prior immunity.

Objective: This study examined the levels of serum protein fractionation, immunoglobulin (Ig) and antistreptolysin O (ASO) of people (91 males and 84 females aged 10-68 years) living in the Terai region of southern Nepal, as there has previously been no information available about them., Methods: Blood samples were collected early in the morning after overnight fasting. Serum protein fractionation was carried out by cellulose-acetate electrophoresis. IgG, IgA, IgM and ASO were measured by immuno-turbidimetry with clinical kits., Results: The mean proportion of albumin (Alb) was rather low due to increased globulin (Glb). The Alb level of males was significantly higher than that of females, while the male γ-Glb level was significantly lower than that of females. The mean values of IgG, IgM and ASO for males were lower than those values for females, although the difference was significant only for the IgM value. The mean values of IgM for female age groups of 30-39 years or less were significantly higher than those for the corresponding male age groups. Age correlated positively with IgA, and negatively with ASO in both sexes. γ-Glb and IgG correlated significantly with TP, AlB, α(1)-Glb and IgA in both sexes. ASO correlated with β-Glb and IgA in males, and with γ-Glb and IgG in females., Conclusions: The fact that the level of γ-Glb, a major component of serum globulin, was high suggested exposure to a highly bacterial and viral environment. These results point to the need to prevent infectious diseases as well as improve their nutritional status, especially for children and young adults.

We developed a quantitative enzyme immunoassay (EIA) for antibody to hepatitis E virus (HEV) by using truncated HEV capsid protein expressed in the baculovirus system to improve seroepidemiology, to contribute to hepatitis E diagnosis, and to enable vaccine evaluations. Five antigen lots were characterized; we used a reference antiserum to standardize antigen potency. We defined Walter Reed antibody units (WR U) with a reference antiserum by using the four-parameter logistic model, established other reference pools as assay standards, and determined the conversion factor: 1 WR U/ml = 0.125 World Health Organization unit (WHO U) per ml. The EIA performed consistently; median intra- and inter-test coefficients of variation were 9 and 12%, respectively. The accurate minimum detection limit with serum diluted 1:1,000 was 5.6 WR U/ml; the test could detect reliably a fourfold antibody change. In six people followed from health to onset of hepatitis E, the geometric mean antibody level rose from 7.1 WR U/ml to 1,924.6 WR U/ml. We used the presence of 56- and 180-kDa bands by Western blotting as a confirmatory test and to define true-negative and -positive serum specimens. A receiver-operating characteristics plot identified 30 WR U/ml as an optimum cut-point (sensitivity, 86%; specificity, 89%). The EIA detected antibody more sensitively than a commercially available test. The EIA was transferred to another laboratory, where four operators matched reference laboratory results for a panel of unknowns. Quantitation of antibody to HEV and confirmation of its specificity by Western blotting make HEV serology more meaningful.

The Kathmandu Basin in Nepal contains up to 550 m of Pliocene-Quaternary fluvio-lacustrine sediments which have formed a dual aquifer system. The unconfined sand and gravel aquifer is separated by a clay aquitard, up to 200 m thick, from the deeper, confined aquifer, comprised of Pliocene sand and gravel beds, intercalated with clay, peat, and lignite. The confined aquifer currently provides an important water supply to the central urban area but there are increasing concerns about its sustainability due to overexploitation. A limited number of determinations of the radioisotope 36Cl have been made on bore waters in the basin, allowing us to postulate on the age of ground water in the deeper, confined aquifer. Ground water evolution scenarios based on radioisotope decay, gradual dissolution of formational salts as the ground waters move downgradient, and flow velocity estimations produce comparable ground water ages for the deep waters, ranging from 200,000 to 400,000 years. From these ages, we deduce a mean ground water flow velocity of only 45 mm/year from recharge in the northeast to the main extraction region 15 km to the southwest. We thus estimate current recharge at about 5 to 15 mm/year, contributing 40,000 to 1.2 million m3/year to the ground water system. Current ground water extraction is estimated to be 20 times this amount. The low specific discharge confirms that the resource is being mined, and, based on current projections, reserves will be used up within 100 years.

Military global influenza surveillance began in 1976 as an Air Force program. In 1997, the Department of Defense (DoD) Global Emerging Infections Surveillance and Response System expanded the program to include all services. Also included were local residents in areas where DoD overseas research activities operated. This new, worldwide DoD surveillance infrastructure provides valuable information and can respond quickly to outbreaks. This was demonstrated during the current influenza season when a suspected outbreak was reported in Panama. In less than 3 weeks, specimens were collected, transported, and cultured, and isolates were subtyped and sent to the Centers for Disease Control and Prevention for further studies. This influenza surveillance initiative combines viral isolation, antigenic characterization, and molecular sequencing with clinical and public health management of information. The information obtained is shared with the Centers for Disease Control and Prevention and the World Health Organization and has contributed to important decisions in influenza vaccine composition.

The physical status and serum mineral concentrations for people aged 10 to 68 years living in an agricultural southern region of Nepal were determined. Systolic (SBP) and diastolic blood pressure (DBP) for both sexes in the 10-14 year age group were low (p<0.05. vs the other age groups) and those for the over 50-year-olds tended to be higher than the other age groups. The mean values of total proteins (TP) (8.6 ± 0.5 g/dl for males and 8.7 ± 0.6 g/dl for females) were high due to an increase of globulin (3.9 ± 0.4 g/dl for males and 4.1 ± 0.5 g/dl for females). More than three-fourths of the subjects of both sexes showed calcium (Ca) levels of 9.0-11.2 mg/dl and about 65% of them showed potassium (K) levels of 4.8-5.4 mEq/1. A significant positive correlation between DBP and serum K was observed (p<0.05). Serum inorganic phosphorus (IP) correlated with age (p<0.001) and body mass index (BMI) (p<0.001). The serum Ca levels correlated with TP (r=0.31, p<0.001), albumin (Alb) (r=0.50, p<0.001), IP (r=0.31, p<0.001), K (r=0.32, p<0.001) and chlorine (Cl)(r=-0.37, p<0.001). Cl was associated with TP (r=-0.21, p<0.05), Alb (r=-0.36, p<0.001) and IP (r=-0.21, p<0.05). These results suggested that Ca intake for the subjects seemed to be insufficient although their serum Ca level was within normal.

Hepatitis E disease is responsible for substantial morbidity in Nepal. A socioeconomic analysis was performed to describe the costs and the effects of hepatitis E disease (HE) on health status in a Nepalese population living in the Kathmandu Valley. A modified health status index was used to quantify healthy days lost associated with HE. One hundred thirty-four individuals recently recovered from HE were interviewed in June 1998. The median age was 22 years and 60% were female. Study participants were sick and bedridden for a median of 22 and 10 days, respectively. The median healthy days lost per individual was 35 (768,000 total per region). The median cost of illness per individual, including direct and indirect, was $37 ($1,238,676 total per region). The percentage of yearly income lost for wage earners totaled 19.4%. Hepatitis E disease is associated with significant costs and loss of healthy days in Nepal. Further research is warranted to understand and limit this common disease.