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Background Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis. Case presentation A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient’s condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient’s hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus—IgM antibodies positive on rapid diagnostic test. The patient’s symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis. Conclusions Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case.

Background As the global burden of disease evolves, lower-resource countries like Nepal face a double burden of non-communicable and infectious disease. Rapid adaptation is required for Nepal’s health system to provide life-long, person-centred care while simultaneously improving quality of infectious disease services. Social determinants of health be key in addressing health disparities and could direct policy decisions to promote health and manage the disease burden. Thus, we explore the association of social determinants with the double burden of disease in Nepal. Methods This is a retrospective, ecological, cross-sectional analysis of infectious and non-communicable disease outcome data (2017 to 2019) and data on social determinants of health (2011 to 2013) for 753 municipalities in Nepal. Multinomial logistic regression was conducted to evaluate the associations between social determinants and disease burden. Results The ‘high-burden’ combined double burden (non-communicable and infectious disease) outcome was associated with more accessible municipalities, (adjOR3.94[95%CI2.94–5.28]), municipalities with higher proportions of vaccine coverage (adjOR12.49[95%CI3.05–51.09]) and malnutrition (adjOR9.19E103[95%CI19.68E42-8.72E164]), lower average number of people per household (adjOR0.32[95%CI0.22–0.47]) and lower indigenous population (adjOR0.20[95%CI0.06–0.65]) compared to the ‘low-burden’ category on multivariable analysis. ‘High-burden’ of non-communicable disease was associated with more accessible municipalities (adjOR1.93[95%CI1.45–2.57]), higher female proportion within the municipality (adjOR1.69E8[95%CI3227.74–8.82E12]), nutritional deficiency (adjOR1.39E17[95%CI11799.83–1.64E30]) and malnutrition (adjOR2.17E131[95%CI4.41E79-1.07E183]) and lower proportions of population under five years (adjOR1.05E-10[95%CI9.95E-18–0.001]), indigenous population (adjOR0.32[95%CI0.11–0.91]), average people per household (adjOR0.44[95%CI0.26–0.73]) and households with no piped water (adjOR0.21[95%CI0.09–0.49]), compared to the ‘low-burden’ category on adjusted analysis. ‘High burden’ of infectious disease was also associated with more accessible municipalities (adjOR4.29[95%CI3.05–6.05]), higher proportions of population under five years (adjOR3.78E9[95%CI9418.25–1.51E15]), vaccine coverage (adjOR25.42[95%CI7.85–82.29]) and malnutrition (adjOR4.29E41[95%CI12408.29–1.48E79]) and lower proportions of households using firewood as fuel (adjOR0.39[95%CI0.20–0.79]) (‘moderate-burden’ category only) compared to ‘low-burden’. Conclusions While this study produced imprecise estimates and cannot be interpreted for individual risk, more accessible municipalities were consistently associated with higher disease burden than remote areas. Female sex, lower average number per household, non-indigenous population and poor nutrition were also associated with higher burden of disease and offer targets to direct interventions to reduce the burden of infectious and non-communicable disease and manage the double burden of disease in Nepal.

Background Minimally Invasive Tissue Sampling (MITS) has been successfully used to establish the cause of death in low- and middle-income countries, mostly in stillbirths and neonates. The objective of this study was to determine the causes of death among adults using MITS in the Gandaki province of Nepal and to find out the contribution of MITS to identify the causes of death. Methods A multicentric hospital-based pilot study was conducted to enroll 100 cases of adult deaths. The specimens of cerebrospinal fluid, blood, brain, lungs, and liver tissue were collected utilizing MITS. These specimens underwent standard histopathological, serological, and microbiological analyses. The findings from MITS, and if available, clinical records and forensic autopsy findings were compiled and the cause of death panel identified the causes of death. The final cause of death allocated to each case was based on the WHO International Medical Certificate of Death. Results Among a total of 100 cases enrolled during the study period, infectious cause attributed to the immediate cause of death in 77 (77%), cardiovascular in 10 (10%), neurological in 8 (8%), malignancy in two (2%), and gastrointestinal and hepatobiliary cause in one (1%) case. The mean age of the cases was 50.8 ± 15.9 years and 76 (76%) were males. MITS established the cause of death in the causal chain of events in 81(81%) cases and identified the cause of death significantly more with infectious than non-infectious causes ( p  < 0.001). Conclusions MITS was useful in establishing the cause of death in the majority of adult deaths and the most common cause was infectious disease. Our findings suggest that MITS can be a valuable and alternative tool for mortality surveillance in low-resource settings, where complete diagnostic autopsies are less accepted or less prioritized.

Background Heterozygous histone H3.3K27M mutation is a primary oncogenic driver of Diffuse Midline Glioma (DMG). H3.3K27M inhibits the Polycomb Repressive Complex 2 (PRC2) methyltransferase activity, leading to global reduction and redistribution of the repressive H3 lysine 27 tri-methylation (H3K27me3). This epigenomic rewiring is thought to promote gliomagenesis, but the precise role of K27M in gene regulation and tumorigenesis remains incompletely understood. Results We established isogenic DMG patient-derived cell lines using CRISPR-Cas9 editing to create H3.3 wild-type (WT), H3.3K27M, and combinations with EZH2 and EZH1 co-deletion, thereby eliminating PRC2 function and H3K27me3. RNA-seq and ATAC-seq analysis revealed that K27M exerts a novel epigenetic effect independent of PRC2 inhibition. While PRC2 loss led to widespread gene induction including HOX gene clusters, and activation of biological pathways, K27M induced a balanced gene deregulation with an overall repressive effect on pathway activity. Genes uniquely affected by K27M, independent of PRC2 loss, showed concordant changes in chromatin accessibility, with upregulated genes becoming more accessible. Importantly, xenografts of H3.3K27M/EZH1/2 WT cells formed tumors, whereas /EZH1/2 knockout cells did not, demonstrating a PRC2-independent role of K27M in tumorigenesis. Conclusion Our findings reveal that the H3.3K27M mutation alters chromatin accessibility and uniquely deregulates gene expression independent of H3K27 methylation loss. These PRC2-independent functions of K27M contribute to changes in biological pathway activity and are necessary for tumor development, highlighting novel mechanisms of K27M-driven gliomagenesis. Graphical Abstract

ObjectivesStillbirth is one of the vital indicators of quality care. This study aimed to determine maternal-fetal characteristics and causes of stillbirth in Nepal.DesignSecondary analysis of single-centred registry-based surveillance data.SettingThe study was conducted at the Department of Obstetrics and Gynecology, Chitwan Medical College Teaching Hospital, a tertiary care hospital located in Bharatpur, Nepal.ParticipantsAll deliveries of intrauterine fetal death, at or beyond 22 weeks’ period of gestation and/or birth weight of 500 g or more, conducted between 16 July 2017 and 15 July 2019 were included in the study.Main outcome measuresThe primary outcome measure of this study was stillbirth, and the secondary outcome measures were maternal and fetal characteristics and cause of stillbirth.ResultsOut of 5282 institutional deliveries conducted over 2 years, 79 (1.5%) were stillbirths, which gives the stillbirth rate of 15 per 1000 births. Of them, the majority (75; 94.9%) were vaginal delivery and only four (5.1%) were caesarean section (p<0.0001). The proportion of the macerated type of stillbirth was more than that of the fresh type (58.2% vs 41.8%; p=0.13). Only half of the mothers who experienced stillbirth had received antenatal care. While the cause of fetal death was unknown in one-third of cases (31.6%; 25/79), among likely causes, the most common was maternal hypertension (29.1%), followed by intrauterine infection (8.9%) and fetal malpresentation (7.6%). Four out of 79 stillbirths (5%) had a birth defect.ConclusionHigh rate of stillbirths in Nepal could be due to the lack of quality antenatal care. The country’s health systems should be strengthened so that pregnancy-related risks such as maternal hypertension and infections are identified early on. Upgrading mothers’ hygiene and health awareness is equally crucial in reducing fetal deaths in low-resource settings.

Introduction COVID‐19 had caused nearly 12,000 deaths in Nepal by March 2023. In this study, we compare COVID‐19‐associated mortality in the first (September 15 to November 30, 2020) and second (April 15 to June 30, 2021) waves of the pandemic in Nepal and investigate the associated epidemiological factors. Methods We disaggregated the COVID‐19‐related deaths between the first and second waves of the pandemic using the national COVID‐19 database and evaluated the association of independent variables with the deaths in the first versus second waves. Results Out of 8133 deaths, 25% died in the first wave and 75% in the second. Overall, 33.5% of the deceased were female, and 52% of the deaths were in those 60 years or older. A vast majority (92%) of deaths occurred in hospitals. Geographically, the middle “Hill” region (58.3%) witnessed the most significant number of deaths. About two thirds (64%) had at least one comorbid condition. Multivariable logistic regression showed a difference in the reported deaths by province (state) and geography (ecological region) between the first and second waves. Those in the age groups “19–39 years” and “40–59 years” were more likely to die in the second wave than in the first wave compared to the younger age group. Conclusions Overall, deaths were concentrated among older age groups, males, in the Hill regions, in the western provinces, and those with comorbidities. Therefore, the country must focus on these areas to ensure an efficient and effective pandemic response in the future. The aim of this study was to compare COVID‐19‐associated mortality during the first and second waves. The number of deaths was higher among Hill region, the Bagmati province, the older age group, and those with comorbid conditions. There was significantly higher death in the second wave by geography, administrative region, and age group.

Minimal invasive tissue sampling (MITS) technique detected HIV infection and disseminated cryptococcosis in an adult female with sudden death. A proper autopsy is essential to diagnose the exact cause of death and MITS can suffice in natural deaths. Minimal invasive tissue sampling (MITS) technique detected HIV infection and disseminated cryptococcosis in an adult female with sudden death. A proper autopsy is essential to diagnose the exact cause of death, and MITS can suffice in natural deaths.

Globally, SARS-CoV-2 has caused significant public health burden, mainly in patients with underlying comorbidities including both communicable and noncommunicable diseases. Solid organ transplant recipients under immunesupressive medication are also amongst the high risk group. There is only sparse data on immunity against SARS-CoV-2 infection among renal transplant recipients. In this case report, we present the level of anti-SARS-CoV-2 antibody of three kidney transplant recipients after vaccination against COVID-19 virus. All three cases had received two doses of Oxford-AstraZeneca COVID-19 vaccine AZD1222 (ChAdOx1). Serological analysis showed protective level of circulating antibodies in the blood of all three cases. Although two out of three patients in the study acquired COVID-19 infection after immunization, they recovered with mild clinical course. Hence, we conclude that despite immune-suppressed status of transplant recipients, COVID-19 vaccination could protect them against severe illness.

Background Hepatitis B is a dreadful infectious disease and a major global health problem. Health-care workers including clinical students are more vulnerable to such infections and non-sterile occupational exposures as their daily activities are closely related to patient’s blood and body fluids. Methods A descriptive cross sectional study was conducted at B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal from July till October 2012. All medical, dental and nursing students were surveyed for their Hepatitis B vaccination status and only those students in clinical rotations were surveyed for the prevalence and pattern of Needle-stick and Sharps-related Injuries (NSSIs) using a pre-tested, semi-structured, self-administered questionnaire. Descriptive and inferential statistics was used to analyze the data. Results Majority (86.5%) of students were vaccinated against Hepatitis B of which 83.7% had completed full doses. Among non-vaccinated students, 43.2% reported the main reason for non-vaccination as lack of vaccination programs. Out of 210 respondents from clinical rotations, 90 students (42.8%) reported at least one injury. Among those injured, two students reported exposure to Human immunodeficiency virus (HIV) positive cases and four to Hepatitis B virus (HBV) positive cases. Most of the injuries (44%) occurred during Internal Medicine rotation and the most common sharp involved (56.3%) was Hypodermic needle. Most injuries (35.6%) occurred while manipulating needle into patients. Following exposure, only 11.4% took Post exposure prophylaxis and 19.54% went for a Post-exposure serology test. Conclusions Needle-stick and Sharps-related Injuries occur frequently among health care workers including trainee students keeping them at high risk for acquiring dreadful infections like HBV, HCV and HIV. They need to be protected from unwarranted hazards by adopting routine Hepatitis B vaccination programs and by reinforcing education regarding universal precautions.