Nepali oral microbiomes reflect a gradient of lifestyles from traditional to industrialized.

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remains less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called 'vanishing microbiomes' potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations. RESULTS: Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the United States within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain source. CONCLUSION: Our findings demonstrate that by controlling for geography, we can isolate an important role for lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes.

Climate change and infectious disease surveillance in Nepal: qualitative study exploring social, cultural, political and institutional factors influencing disease surveillance.

BACKGROUND: To explore the impacts of contextual issues encompassing social, cultural, political and institutional elements, on the operation of public health surveillance systems in Nepal concerning the monitoring of infectious diseases in the face of a changing climate. METHODS: Semi-structured interviews (n = 16) were conducted amongst key informants from the Department of Health Services, Health Information Management System, Department of Hydrology and Meteorology, World Health Organization, and experts working on infectious disease and climate change in Nepal, and data were analysed using thematic analysis technique. RESULTS: Analysis explicates how climate change is constructed as a contingent risk for infectious diseases transmission and public health systems, and treated less seriously than other 'salient' public health risks, having implications for how resources are allocated. Further, analysis suggests a weak alliance among different stakeholders, particularly policy makers and evidence generators, resulting in the continuation of traditional practices of infectious diseases surveillance without consideration of the impacts of climate change. CONCLUSIONS: We argue that along with strengthening systemic issues (epidemiological capacity, data quality and inter-sectoral collaboration), it is necessary to build a stronger political commitment to urgently address the influence of climate change as a present and exponential risk factor in the spread of infectious disease in Nepal.

Bacteriological Profile of Surgical Site Infection Following Gastrointestinal Surgery and Their Antibiogram.

BACKGROUND: Surgical site infection is one of the common complication following abdominal surgery. It causes great morbidity and mortality, further increasing prevalence of multidrug resistant bacteria have made its management very challenging. The current study aims to identify causative agent responsible for surgical site infection and their antibiotic resistance patterns. METHODS: This study was conducted among patients developing surgical site infection following gastrointestinal surgery in Tribhuvan university teaching hospital over a period of one year. The samples were collected and processed according to standard methods. The bacterial pathogens with their antimicrobial susceptibility were determined and resistant pattern like methicillin resistant Staphylococcus aureus and extended spectrum beta lactamase were further detected. RESULTS: A total of 832 patients had under gone gastrointestinal surgery during the study period. Among them, 162 cases (19.5%) developed surgical site infection and 125 cases showed growth in culture. A total of 160 aerobic bacteria were isolated; Escherichia coli (29.9%) was the commonest organism with 40.8% being extended spectrum beta lactamase producer and 47.4% of Staphylococcus aureus were methicillin resistant. About 75.9% (85/112) of gram negative bacteria and 60.4% (29/48) gram positive bacteria were multi drug resistant. CONCLUSIONS: The burden of multi drug resistant bacteria causing surgical site infection is high which needs to be addressed timely. Good surveillance of bacterial antibiogram and rational antimicrobial use is necessary to reduce emergence and spread of resistant bacteria.

Prevalence and determinants of hypertension in underrepresented indigenous populations of Nepal.

Indigenous populations residing in low- and middle-income countries (LMICs) are highly underrepresented in medicine and public health research. Specifically, data on non-communicable diseases (NCDs) from indigenous populations remains scarce. Despite the increasing burden of NCDs in the Himalayan region, their prevalence in many indigenous populations remains understudied. The nationally representative public health surveys often do not include the indigenous communities, especially those that reside in rural areas or exist in small numbers. This observational cross-sectional survey study aimed to assess the prevalence of three NCD risk factors namely obesity, hypertension, and tachycardia and identify dietary and lifestyle variables associated with them across underrepresented indigenous populations of Nepal. A total of 311 individuals (53.3% women, 46.7% men) with mean age 43±15 years from 12 indigenous Nepali communities residing in rural (47.9%) or semi-urban (52.1%) areas volunteered to participate in this study. Univariate tests and multivariable logistic regressions were used to analyze the survey data. The mean systolic and diastolic blood pressures were 121.3±19.5 mmHg and 81.3±11.8 mmHg respectively. Overall, the prevalence of obesity and tachycardia was low (0.64% and 3.22%, respectively) but hypertension was prevalent at 23.8%. Hypertension was not significantly different across populations, but it was associated with age, BMI, and tobacco use, and collectively, these variables explained 13.9% variation in hypertension prevalence. Although we were unable to detect direct associations between individual determinants of hypertension identified in non-indigenous Nepalis, such as education levels, alcohol consumption, and smoking in this study, having one or more determinants increased the odds of hypertension in the indigenous participants. Furthermore, ~14% of the hypertensive individuals had none of the universally identified hypertension risk factors. The lack of association between previously identified risk factors for hypertension in these individuals indicates that the additional determinants of hypertension remain to be identified in indigenous Nepali populations.

Biofilm Formation by Pathogens Causing Ventilator-Associated Pneumonia at Intensive Care Units in a Tertiary Care Hospital: An Armor for Refuge.

BACKGROUND: Emerging threat of drug resistance among pathogens causing ventilator-associated pneumonia (VAP) has resulted in higher hospital costs, longer hospital stays, and increased hospital mortality. Biofilms in the endotracheal tube of ventilated patients act as protective shield from host immunity. They induce chronic and recurrent infections that defy common antibiotics. This study intended to determine the biofilm produced by pathogens causing VAP and their relation with drug resistance. METHODS: Bronchoalveolar lavage and deep tracheal aspirates (n = 70) were obtained from the patients mechanically ventilated for more than 48 hours in the intensive care units of Tribhuvan University Teaching Hospital, Kathmandu, and processed according to the protocol of the American Society for Microbiology (ASM). Antibiotic susceptibility testing was done following Clinical and Laboratory Standards Institute (CLSI) 2017 guidelines. Biofilm formation was determined using the microtiter plate method described by Christensen and modified by Stepanovoic et al. RESULTS: Significant microbial growth was seen in 78.6% of the total samples with 52.7% monomicrobial, 45.5% polymicrobial, and 1.8% fungal infection. Among the 71 isolates obtained, bulk was gram-negative (n = 64, 90.1%). Pseudomonas aeruginosa (31.0%) was the predominant isolate followed by Acinetobacter calcoaceticus baumannii complex (16.9%), Klebsiella pneumoniae (16.9%), Citrobacter freundii (15.5%), Staphylococcus aureus (7.0%), Escherichia coli (5.6%), Citrobacter koseri (2.8%), Enterococcus faecalis (1.4%), Burkholderia cepacia complex (1.4%), and Candida albicans (1.4%). Of the total isolates, 56.3% were biofilm producers. Multidrug-resistant (MDR) organisms, extended-spectrum ß-lactamase (ESBL), and metallo-ß-lactamase (MBL) producers were preeminent among the biofilm producers. The highest producer of biofilm was P. aeruginosa (19.7%). Among gram-negative biofilm producers, 42.2% were MDR, 21.9% were ESBL producers, and 7.8% were MBL producers. CONCLUSION: Gram-negative nonfermenter bacteria account for the bulk of nosocomial pneumonia. MDR, ESBL, and MBL production was preponderant among the biofilm producers. The rampant spread of drug resistance among biofilm producers is summoning novel interventions to combat multidrug resistance.

Carbapenem Resistance in Non-Fermentative Gram-Negative Bacilli Isolated from Intensive Care Unit Patients of a Referral Hospital.

BACKGROUND: Non-fermentative Gram-negative bacilli or non-fermenters are opportunistic pathogens associated with serious infections in intensive care unit patients. Although carbapenems were considered as a backbone of treatment for life-threatening infections, these bacteria are increasingly acquiring resistance to carbapenems. Carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are prioritized as critical pathogens by the World Health Organization. The objective of the study was to document the status of carbapenem-resistant and carbapenemase-producing non-fermenters isolated from intensive care unit patients. METHODS: This study was conducted at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The clinical specimens collected from intensive care unit patients were processed for isolation and identification of non-fermenters and antibiotic susceptibility profile of bacterial isolates was determined. The multidrug-resistant isolates were identified and carbapenemase enzyme was detected in the carbapenem-resistant isolates. RESULTS: A total of 157 non-fermenters were isolated from 1063 samples which included Acinetobacter species (n=85), Pseudomonas aeruginosa (n=55), Burkholderia cepacia complex (n=15), and Stenotrophomonas maltophilia (n=2). Carbapenem resistance was reported in 85.9%, 72.7%, and 33.3% of Acinetobacter species, Pseudomonas aeruginosa, and Burkholderia cepacia complex, respectively. Among total non-fermenters, 91.1% isolates were multidrug-resistant and 60.8% carbapenem-resistant isolates were carbapenemase producers. The carbapenem-resistant isolates demonstrated an extremely high degree of resistance than carbapenem-susceptible isolates towards other antimicrobial classes. CONCLUSIONS: This study reported high rates of carbapenem-resistant, carbapenemase-producing, and multidrug-resistant non-fermenters isolates. Therefore, preventing the spread of these superbugs among the critically ill patients in intensive care units should be a major initiative in hospitals.

Scrub Typhus and Molecular Characterization of Orientia tsutsugamushi from Central Nepal.

Scrub typhus is a vector-borne, acute febrile illness caused by Orientia tsutsugamushi. Scrub typhus continues to be an important but neglected tropical disease in Nepal. Information on this pathogen in Nepal is limited to serological surveys with little information available on molecular methods to detect O. tsutsugamushi. Limited information exists on the genetic diversity of this pathogen. A total of 282 blood samples were obtained from patients with suspected scrub typhus from central Nepal and 84 (30%) were positive for O. tsutsugamushi by 16S rRNA qPCR. Positive samples were further subjected to 56 kDa and 47 kDa molecular typing and molecularly compared to other O. tsutsugamushi strains. Phylogenetic analysis revealed that Nepalese O. tsutsugamushi strains largely cluster together and cluster away from other O. tsutsugamushi strains from Asia and elsewhere. One exception was the sample of Nepal_1, with its partial 56 kDa sequence clustering more closely with non-Nepalese O. tsutsugamushi 56 kDa sequences, potentially indicating that homologous recombination may influence the genetic diversity of strains in this region. Knowledge on the circulating strains in Nepal is important to the development of diagnostic tests and vaccines to support public health measures to control scrub typhus in this country.

Bacteria on Medical Professionals' White Coats in a University Hospital.

The transient contamination of medical professional's attires including white coats is one of the major vehicles for the horizontal transmission of microorganisms in the hospital environment. This study was carried out to determine the degree of contamination by bacterial agents on the white coats in a tertiary care hospital in Nepal. Sterilized uniforms with fabric patches of 10 cm × 15 cm size attached to the right and left pockets were distributed to 12 nurses of six different wards of a teaching hospital at the beginning of their work shift. Worn coats were collected at the end of the shifts and the patches were subjected for total bacterial count and identification of selected bacterial pathogens, as prioritized by the World Health Organization (WHO). Fifty percent of the sampled swatches were found to be contaminated by pathogenic bacteria. The average colony growth per square inch of the patch was 524 and 857 during first and second workdays, respectively, indicating an increase of 63.6% in colony counts. The pathogens detected on patches were Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter sp. Additional bacteria identified included Bacillus sp., Micrococcus sp., and coagulase-negative staphylococci (CoNS). The nurses working in the maternity department had their white coats highly contaminated with bacteria. On the other hand, the least bacterial contamination was recorded from the nurses of the surgery ward. One S. aureus isolate from the maternity ward was resistant to methicillin. This study showed that pathogens belonging to the WHO list of critical priority and high priority have been isolated from white coats of nurses, thus posing the risk of transmission to patients. White coats must be worn, maintained, and washed properly to reduce bacterial contamination load and to prevent cross-contamination of potential superbugs. The practice of wearing white coats outside the healthcare zone should be strictly discouraged.

Non-linear effect of temperature variation on childhood rotavirus infection: A time series study from Kathmandu, Nepal.

INTRODUCTION: This study aimed to investigate the effects of temperature variability on rotavirus infections among children under 5 years of age in Kathmandu, Nepal. Findings may inform infection control planning, especially in relation to the role of environmental factors in the transmission of rotavirus infection. METHODS: Generalized linear Poisson regression equations with distributed lag non-linear model were fitted to estimate the effect of temperature (maximum, mean and minimum) variation on weekly counts of rotavirus infections among children under 5 years of age living in Kathmandu, Nepal, over the study period (2013 to 2016). Seasonality and long-term effects were adjusted in the model using Fourier terms up to the seventh harmonic and a time function, respectively. We further adjusted the model for the confounding effects of rainfall and relative humidity. RESULTS: During the study period, a total of 733 cases of rotavirus infection were recorded, with a mean of 3 cases per week. We detected an inverse non-linear association between rotavirus infection and average weekly mean temperature, with increased risk (RR: 1.52; 95% CI: 1.08-2.15) at the lower quantile (10th percentile) and decreased risk (RR: 0.64; 95% CI: 0.43-0.95) at the higher quantile (75th percentile). Similarly, we detected an increased risk [(RR: 1.93; 95% CI: 1.40-2.65) and (RR: 1.42; 95% CI: 1.04-1.95)] of rotavirus infection for both maximum and minimum temperature at their lower quantile (10th percentile). We estimated that 344 (47.01%) cases of rotavirus diarrhoea among the children under 5 years of age were attributable to minimum temperature. The significant effect of temperature on rotavirus infection was not observed beyond lag zero week. CONCLUSION: An inverse non-linear association was estimated between rotavirus incidence and all three indices of temperature, indicating a higher risk of infection during the cooler times of the year, and suggesting that transmission of rotavirus in Kathmandu, Nepal may be influenced by temperature.

Emergence of multidrug-resistant non-fermentative gram negative bacterial infection in hospitalized patients in a tertiary care center of Nepal.

OBJECTIVE: This study was designed for the characterization and establishment of antibiotic susceptibility profiles of non-fermentative gram negative bacteria isolated from hospitalized patients in a tertiary care hospital of Nepal. RESULTS: A total of 402 non-fermentative gram negative bacteria was isolated in 1486 culture-positive cases from 6216 different clinical samples obtained from hospitalized patients. Among total non-fermentative gram negative bacterial isolates, the highest number was recovered from specimens collected from lower respiratory tract infections (n = 173, 43.0%) of hospitalized patients followed by pus/swab samples (n = 99, 24.6%) and urinary tract infections (n = 49, 12.2%). The most common non-fermentative gram negative bacteria identified were Acinetobacter baumannii (n = 177, 44.0%), Pseudomonas aeruginosa (n = 161, 40.1%) and Burkholderia cepacia complex (n = 33, 8.2%). These bacterial isolates exhibited a higher rate of insusceptibility to beta-lactam antibiotics, fluoroquinolones, and aminoglycosides. On the other hand, all the isolates of P. aeruginosa and A. baumannii were completely susceptible to colistin sulfate and polymyxin B. Among total isolates, 78.1% (n = 314) were multidrug-resistant with a high rate of multidrug-resistant among A. baumannii (91.0%).

Burden of Multidrug-Resistant Acinetobacter baumannii Infection in Hospitalized Patients in a Tertiary Care Hospital of Nepal.

INTRODUCTION: Acinetobacter baumannii has emerged as a significant multidrug-resistant (MDR) nosocomial pathogen worldwide and is responsible for various healthcare-associated infections. The MDR strains have been reported increasingly during the last decades in hospitalized patients. They have developed resistance to most of the available antibiotics and are known to produce various acquired ß-lactamases. The ß-lactamase producing strains have a potential for rapid dissemination in hospital settings, as it is often plasmid-mediated. The Infectious Diseases Society of America (ISDA) stated A. baumannii as one of the "red alert" pathogens that greatly threatens the utility of our current antibacterial armamentarium. The study attempted to investigate the spectrum and antimicrobial resistance among MDR A. baumannii and their potential implications in hospitalized patients in a tertiary care hospital of Nepal. METHODS: This study was conducted at Tribhuvan University Teaching Hospital (TUTH), Nepal from January 2017 to December 2017. A total of 177 A. baumannii isolated from hospitalized patients were included in the study. The AST was performed by disc diffusion method. The MDR strains were identified by the criteria of Magiorakos et al, ESBL production by CLSI guidelines, and AmpC ß-lactamase production by the AmpC disc test. MBL and KPC production were detected as per the method of Tsakris et al. RESULTS: Out of 177 A. baumannii, 91.0% were MDR isolates. Among the MDR isolates, the majority were isolated from respiratory tract specimens and were isolated from ICU patients. Most of the MDR isolates were resistant to all first-line antibiotics and all were completely sensitive to only polymyxin B and colistin sulfate. MBL (67.7%) was the common ß-lactamase production among MDR isolates. CONCLUSION: Acinetobacter baumannii can cause a vast variety of infections in hospitalized patients. The highly resistant MDR strains are common in tertiary care hospitals. This bacteria lead to high morbidity and mortality as we are left with the only option of treating them by potentially toxic antibiotics like colistin sulfate and polymyxin B. Detection of drug resistance and rational use of antibiotics play a crucial role in the fight against this MDR pathogen.

Carriage of Extended-Spectrum-ß-Lactamase- and AmpC-ß-Lactamase-Producing Enterobacteriaceae (ESBL-PE) in Healthy Community and Outpatient Department (OPD) Patients in Nepal.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)- and AmpC-ß-lactamase (ESBL)- and AmpC-Enterobacteriaceae have recently emerged as a public threat in the treatment of nosocomial as well as community-acquired infections. Very little information is currently available about its existence in Nepal. We, therefore, aim to determine the prevalence of ESBL and AmpC-ß-lactamase (ESBL)- and AmpC-Enterobacteriaceae have recently emerged as a public threat in the treatment of nosocomial as well as community-acquired infections. Very little information is currently available about its existence in Nepal. We, therefore, aim to determine the prevalence of ESBL and AmpC. METHODS: During a 6-month period (November 2014-April 2015), a total of 190 stool specimens from 190 participants were obtained from different population. Of the total 260 fecal isolates, 152 from outpatient department (OPD) and 108 from healthy volunteer were collected. Stool specimens were cultured and enterobacterial isolates were subjected to antimicrobial susceptibility tests according to the standard microbiologic guidelines. ESBL was screened using ceftazidime (CAZ, 30 µg) and cefotaxime (CTX, 30 µg) and cefotaxime (CTX, 30 ß-lactamase (ESBL)- and AmpC. RESULTS: The prevalence of ESBL, AmpC-ß-lactamase (ESBL)- and AmpC-ß-lactamase (ESBL)- and AmpC-Enterobacteriaceae have recently emerged as a public threat in the treatment of nosocomial as well as community-acquired infections. Very little information is currently available about its existence in Nepal. We, therefore, aim to determine the prevalence of ESBL and AmpC-E. coli was 70.2% followed by K. pneumoniae (12.7%), and among AmpC-ß-lactamase (ESBL)- and AmpC-E. coli was 70.2% followed by E. coli was 70.2% followed by K. pneumoniae (12.7%), and among AmpC-K. pneumoniae (12.7%), and among AmpC-C. freundii 2/7 (28.57%) were detected highest among AmpC-ß-lactamase (ESBL)- and AmpC. CONCLUSION: Our study revealed a high prevalence of ESBL- and AmpC-ß-lactamase-producing enteric pathogen in Nepalese OPD and healthy population. The significant increase of these isolates and increased rate of drug resistance indicates a serious threat that stress the need to implement the surveillance system and a proper control measure so as to limit the spread of ESBL-producing Enterobacteriaceae (ESBL-PE) in both OPD as well as in community. Therefore, healthcare providers need to be aware that ESBL- and AmpC-ß-lactamase-producing strains are not only circulating in hospital environments but also in the community and should be dealt with accordingly.ß-lactamase (ESBL)- and AmpC-Enterobacteriaceae have recently emerged as a public threat in the treatment of nosocomial as well as community-acquired infections. Very little information is currently available about its existence in Nepal. We, therefore, aim to determine the prevalence of ESBL and AmpC-ß-lactamase (ESBL)- and AmpC.

Diagnostic evaluation of IgM ELISA and IgM Immunofluorescence assay for the diagnosis of Acute Scrub Typhus in central Nepal.

BACKGROUND: Scrub typhus is an acute febrile illness caused by the obligate intracellular bacterium, Orientia tsutsugamushi. Immunochromatography (ICT) and IgM ELISA are two of the routinely employed antibody based assays for diagnosis of Scrub typhus fever in Nepal, although the recommended gold standard diagnostic test is IgM Immunofluorescence assay (IFA). This study evaluated InBios Scrub Typhus Detect™ Immunoglobulin M (IgM) ELISA and IgM Immunofluorescence assays in single serum sample at the time of admission. METHOD: Study participants (1585 suspected cases), were enrolled based on acute febrile illness with suspected scrub typhus cases in central Nepal. Blood sample was collected from the suspected patients of scrub typhus, presenting with acute febrile illness. IgM antibody to Orientia tsusugamushi was detected by using Scrub Typhus Detect™ Kit and an in-house IgM IFA. The IFA assay was performed with the Gilliam, Karp, Kato strains and O. chuto antigens following the ARRL protocol. RESULT: Statistical analysis of IgM ELISA results when compared to reference test, IgM IFA results demonstrated the following characteristics, sensitivity 84.0% (95%CI: 79.73-87.68%), specificity 94.82% (95% CI: 93.43-95.99%), positive likelihood ratio 16.21% (95% CI: 12.71-20.67%), negative likelihood ratio 0.17% (95% CI: 0.13-0.21%), disease prevalence 22.08% (95% CI: 20.06 -24.21%), positive predictive value 82.12% (95% CI: 78.28-85.42%) and negative predictive value 95.44% (95% CI: 94.27-96.38%) respectively. CONCLUSION: Although IgM IFA is considered the gold standard test for the diagnosis of scrub typhus cases, it is relatively expensive, requires trained personal and a microscope with fluorescence filters. Scrub typhus IgM ELISA may be the best alternative test and possible viable option for resource limited endemic countries like Nepal.

Climate change and infectious disease research in Nepal: Are the available prerequisites supportive enough to researchers?

Although Nepal has been identified as a country highly vulnerable to adverse health and socioeconomic impacts arising from climate change, extant research on climate sensitive infectious diseases has yet to develop the evidence base to adequately address these threats. In this opinion paper we identify and characterise basic requirements that are hindering the progress of climate change and infectious disease research in Nepal. Our opinion is that immediate attention should be given to strengthening Nepal's public health surveillance system, promoting inter-sectoral collaboration, improving public health capacity, and enhancing community engagement in disease surveillance. Moreover, we advocate for greater technical support of public health researchers, and data sharing among data custodians and epidemiologists/researchers, to generate salient evidence to guide relevant public health policy formulation aimed at addressing the impacts of climate change on human health in Nepal. International studies on climate variability and infectious diseases have clearly demonstrated that climate sensitive diseases, namely vector-borne and food/water-borne diseases, are sensitive to climate variation and climate change. This research has driven the development and implementation of climate-based early warning systems for preventing potential outbreaks of climate-sensitive infectious diseases across many European and African countries. Similarly, we postulate that Nepal would greatly benefit from a climate-based early warning system, which would assist in identification or prediction of conditions suitable for disease emergence and facilitate a timely response to reduce mortality and morbidity during epidemics.

Assessing the effect of climate factors on childhood diarrhoea burden in Kathmandu, Nepal.

INTRODUCTION: This study was undertaken to assess the effect of climate variability on diarrhoeal disease burden among children under 5 years of age living in Kathmandu, Nepal. The researchers sought to predict future risk of childhood diarrhoea under different climate change scenarios to advance the evidence base available to public health decision-makers, and the Nepalese infection control division, in planning for climate impacts. METHODS: A time series study was conducted using the monthly case count of diarrhoeal disease (2003-2013) among children under 5 years of age living in Kathmandu, Nepal. A quasi Poisson generalised linear equation with distributed lag linear model was fitted to estimate the lagged effect of monthly maximum temperature and rainfall on childhood diarrhoea. The environmental framework of comparative risk assessment was used to assess the environmental burden of diarrhoea within this population. RESULTS: A total of 219,774 cases of diarrhoeal disease were recorded during the study period with a median value of 1286 cases per month. The results of a regression model revealed that the monthly count of diarrhoea cases increased by 8.1% (RR: 1.081; 95% CI: 1.02-1.14) per 1 °C increase in maximum temperature above the monthly average recorded within that month. Similarly, rainfall was found to have significant effect on the monthly diarrhoea count, with a 0.9% (RR; 1.009; 95% CI: 1.004-1.015) increase in cases for every 10 mm increase in rainfall above the monthly cumulative value recorded within that month. It was estimated that 7.5% (95% CI: 2.2%-12.5%) of the current burden of diarrhoea among children under 5 years of age could be attributed to climatic factors (maximum temperature), and projected that 1357 (UI: 410-2274) additional cases of childhood diarrhoea could be climate attributable by the year 2050 under low-risk scenario (0.9 °C increase in maximum temperature). CONCLUSION: It is estimated that there exists a significant association (p < 0.05) between childhood diarrhoea and an increase in maximum temperature and rainfall in Kathmandu, Nepal. The findings of this study may inform the conceptualization and design of early warning systems for the prediction and control of childhood diarrhoea, based upon the observed pattern of climate change in Kathmandu.

Melioidosis: misdiagnosed in Nepal.

BACKGROUND: Melioidosis is a life-threatening infectious disease that is caused by gram negative bacteria Burkholderia pseudomallei. This bacteria occurs as an environmental saprophyte typically in endemic regions of south-east Asia and northern Australia. Therefore, patients with melioidosis are at high risk of being misdiagnosed and/or under-diagnosed in South Asia. CASE PRESENTATION: Here, we report two cases of melioidosis from Nepal. Both of them were diabetic male who presented themselves with fever, multiple abscesses and developed sepsis. They were treated with multiple antimicrobial agents including antitubercular drugs before being correctly diagnosed as melioidosis. Consistent with this, both patients were farmer by occupation and also reported travelling to Malaysia in the past. The diagnosis was made consequent to the isolation of B. pseudomallei from pus samples. Accordingly, they were managed with intravenous meropenem followed by oral doxycycline and cotrimoxazole. CONCLUSION: The case reports raise serious concern over the existing unawareness of melioidosis in Nepal. Both of the cases were left undiagnosed for a long time. Therefore, clinicians need to keep a high index of suspicion while encountering similar cases. Especially diabetic-farmers who present with fever and sepsis and do not respond to antibiotics easily may turn out to be yet another case of melioidosis. Ascertaining the travel history and occupational history is of utmost significance. In addition, the microbiologist should be trained to correctly identify B. pseudomallei as it is often confused for other Burkholderia species. The organism responds only to specific antibiotics; therefore, correct and timely diagnosis becomes crucial for better outcomes.

Epidemiology, Risk Factors and Seasonal Variation of Scrub Typhus Fever in Central Nepal.

Orientia. tsutsugamushi, a zoonotic bacterial infection common in the region known as the tsutsugamushi triangle. This study aims to determine the seroprevalence, seasonal variation, and risk factors of scrub typhus among the acute febrile illness patients attending different hospitals of central Nepal. Blood samples were collected from hospitalized patients of acute febrile illness suspected of scrub typhus infection attending different hospitals of central Nepal from April 2017 to March 2018. The IgM antibody to Orientia tsutsugamushi was detected by using the Scrub Typhus Detect™ Kit. Among the total cases (1585), 358 (22.58%) were positive for IgM Antibodies. Multivariate analysis identified several risks factors to be significantly associated with the scrub typhus infection, including gender (female) (odds ratio [OR] = 1.976, p ≤ 0.001, confidence interval [CI] = 1.417⁻2.756), rural residential location (odds ratio [OR] = 0.431, p = 0.001, confidence interval [CI] = 0.260⁻0.715), house near grassland (odds ratio [OR] = 3.288, p ≤ 0.001, confidence interval [CI] = 1.935⁻5.587), and working in the field (odds ratio [OR] = 9.764, p = 0.004, confidence interval [CI] = 2.059⁻46.315). The study findings indicate scrub typhus infection to be a significant health problem in Nepal. The proper diagnosis of infection cases, timely institution of therapy, public awareness, and vector control are important measures to be taken for the prevention and management of scrub typhus.

Gut microbiome transition across a lifestyle gradient in Himalaya.

The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle. Whether shifts away from the foraging lifestyle that characterize much of humanity's past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying levels of agricultural dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across lifestyles. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of determining how large-scale gut microbiome reconfiguration impacts human biology.

Correction to: Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal.

Following publication of the original article [1], a typesetting mistake is reported. The captions of Figure 2 and Figure 3 were interchanged. The incorrect and correct combination of the figures and captions are given in this Correction and the original article has been updated.

Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal.

BACKGROUND: Pulmonary nocardiosis is an opportunistic infection in an immunocompromised patient; however, often neglected in the immunocompetent patient from the diagnosis considerations. CASE PRESENTATIONS: We describe a case of pulmonary nocardiosis masquerading renascence of tuberculosis, in a 51-years-Nepali farmer. After a 6 month of presumed successful antitubercular therapy; the patient develops the clinical presentations and radiological features showing similarities with that of tuberculosis and malignancy. MTB complex was not detected with Xpert MTB/RIF assay and cytological examinations were negative for the malignant cells, however. The Ziehl-Neelsen staining of the broncho-alveolar-lavage revealed acid-fast, thin branching filamentous organisms suggestive Nocardia spp. Further, identifications and susceptibility pattern against recommended antibiotics were assessed as per the CLSI guidelines. The case was then, subsequently, diagnosed as pulmonary nocardiosis. Trimethoprim-sulfamethoxazole was prescribed for 12 months. The patient underwent progressive changes and no relapse was noted in a periodic follow-up. CONCLUSIONS: This case underscores that pulmonary nocardiosis requires diagnostic considerations, regardless of a patient's immunologic status and other mimicking infections.