Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2024 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2019.

Dengue Types 1 and 3 Identified in Travelers Returning from Kathmandu, Nepal, during the October 2022 Outbreak Are Related to Strains Recently Identified in India.

Phylogenetic analysis of dengue serotypes 1 and 3, which were diagnosed in travelers and Nepalese infected in Kathmandu during the October 2022 outbreak, revealed that both serotypes were clustered closest to the sequences sampled in India. This suggests both serotypes may have originated in India.

Weather variables as important clinical predictors of bacterial diarrhoea among international travellers.

BACKGROUND: Clinicians and travellers often have limited tools to differentiate bacterial from non-bacterial causes of travellers' diarrhoea (TD). Development of a clinical prediction rule assessing the aetiology of TD may help identify episodes of bacterial diarrhoea and limit inappropriate antibiotic use. We aimed to identify predictors of bacterial diarrhoea among clinical, demographic and weather variables, as well as to develop and cross-validate a parsimonious predictive model. METHODS: We collected de-identified clinical data from 457 international travellers with acute diarrhoea presenting to two healthcare centres in Nepal and Thailand. We used conventional microbiologic and multiplex molecular methods to identify diarrheal aetiology from stool samples. We used random forest and logistic regression to determine predictors of bacterial diarrhoea. RESULTS: We identified 195 cases of bacterial aetiology, 63 viral, 125 mixed pathogens, 6 protozoal/parasite and 68 cases without a detected pathogen. Random forest regression indicated that the strongest predictors of bacterial over viral or non-detected aetiologies were average location-specific environmental temperature and red blood cell on stool microscopy. In 5-fold cross-validation, the parsimonious model with the highest discriminative performance had an area under the receiver operator curve of 0.73 using 3 variables with calibration intercept -0.01 (standard deviation, SD 0.31) and slope 0.95 (SD 0.36). CONCLUSIONS: We identified environmental temperature, a location-specific parameter, as an important predictor of bacterial TD, among traditional patient-specific parameters predictive of aetiology. Future work includes further validation and the development of a clinical decision-support tool to inform appropriate use of antibiotics in TD.

Health problems in travellers to Nepal visiting CIWEC clinic in Kathmandu - A GeoSentinel analysis.

BACKGROUND: Nepal has always been a popular international travel destination. There is limited published data, however, on the spectrum of illnesses acquired by travellers to Nepal. METHODS: GeoSentinel is a global data collection network of travel and tropical medicine providers that monitors travel-related morbidity. Records for ill travellers with at least one confirmed or probable diagnosis, were extracted from the GeoSentinel database for the CIWEC Clinic Kathmandu site from January 1, 2009 to December 31, 2017. RESULTS: A total of 24,271 records were included. The median age was 30 years (range: 0-91); 54% were female. The top 3 system-based diagnoses in travellers were: gastrointestinal (32%), pulmonary (16%), and dermatologic (9%). Altitude illness comprised 9% of all diagnoses. There were 278 vaccine-preventable diseases, most frequently influenza A (41%) and typhoid fever (19%; S. typhi 52 and S. paratyphi 62). Of 64 vector-borne illnesses, dengue was the most frequent (64%), followed by imported malaria (14%). There was a single traveller with Japanese encephalitis. Six deaths were reported. CONCLUSIONS: Travellers to Nepal face a wide spectrum of illnesses, particularly diarrhoea, respiratory disease, and altitude illness. Pre-travel consultations for travellers to Nepal should focus on prevention and treatment of diarrhoea and altitude illness, along with appropriate immunizations and travel advice.

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.

Travel-related hepatitis E: a two-decade GeoSentinel analysis.

BACKGROUND: Hepatitis E virus (HEV) is widely distributed worldwide and is endemic in developing countries. Travel-related HEV infection has been reported at national levels, but global data are missing. Moreover, the global availability of HEV diagnostic testing has not been explored so far. The aim of this study is to describe the epidemiology of HEV infections in returning travellers and availability of HEV diagnostic testing in the GeoSentinel surveillance network. METHODS: This was a multicentre retrospective cross-sectional study. All confirmed and probable HEV travel-related infections reported in the GeoSentinel Network between 1999 and 2018 were evaluated. GeoSentinel sites were asked to complete a survey in 2018 to assess the availability and accessibility of HEV diagnostic procedures (i.e. serology and molecular tests) throughout the study period. RESULTS: Overall, 165 travel-related HEV infections were reported, mainly since 2010 (60%) and in tourists (50%). Travellers were exposed to hepatitis E in 27 countries; most travellers (62%) were exposed to HEV in South Asia. One patient was pregnant at the time of HEV infection and 14 had a concomitant gastrointestinal infection. No deaths were reported. In the 51% of patients with information available, there was no pre-travel consultation. Among 44 GeoSentinel sites that responded to the survey, 73% have access to HEV serology at a local level, while 55% could perform (at a local or central level) molecular diagnostics. CONCLUSION: Reported access to HEV diagnostic testing is suboptimal among sites that responded to the survey; this could negatively affect diagnosing HEV. Pre-travel consultations before travel to South Asia and other low-income and high-prevalence areas with a focus on food and water precautions could be helpful in preventing hepatitis E infection. Improved HEV diagnostic capacity should be implemented to prevent and correctly diagnose travel-related HEV infection.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2019 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2014.

Traveler's diarrhea in Nepal-changes in etiology and antimicrobial resistance.

BACKGROUND: We conducted a comprehensive investigation to update our knowledge of traveler's diarrhea (TD) etiology and antimicrobial resistance (AMR) in Nepal. METHODS: A case-control study of TD etiology was conducted at the CIWEC Clinic Travel Medicine Center in Kathmandu from 2012 to 2014. Stool samples were tested by microscopy, culture and molecular techniques for identification of bacterial, viral and parasitic enteric pathogens, and AMR. We analysed patient demographic data, pre-treatment information and clinical outcomes. RESULTS: We enrolled 433 TD cases and 209 non-diarrhea controls. At least one of enteric pathogens was identified among 82% of cases and 44% of controls (P < 0.001). Multiple pathogens were observed among 35% of cases and 10% of controls. The most common pathogens significantly identified among cases in comparison with controls were Campylobacter (20%), norovirus (17%), enterotoxigenic E. coli (ETEC) (12%), rotavirus (9%) and Shigella (8%) (P < 0.001). We noted Campylobacter, Shigella and ETEC resistance to azithromycin at 8, 39 and 22% and to ciprofloxacin at 97, 78 and 23%, respectively. CONCLUSION: Among travellers to Nepal with TD, viral pathogens were commonly found and norovirus was the second most common pathogen after campylobacter. We noted increased AMR to fluoroquinolones (FQs) and azithromycin (AZM). There is heightened concern for AZM treatment failures, though this continues to remain the drug of choice for TD treatment in our setting where FQs should not be used.

Determination of azithromycin heteroresistant Campylobacter jejuni in traveler's diarrhea.

Campylobacter is the most common cause of traveler's diarrhea (TD) and human bacterial gastroenteritis. A heteroresistant Campylobacter jejuni (C. jejuni) isolate, identified by microbiological methods and characterized with molecular techniques, was obtained from a traveler in Nepal suffering TD. The presence of atypical colonies within the clear zone of inhibition was the first evidence of an atypical phenotype, leading to additional characterization of this heteroresistant strain. Antimicrobial susceptibility testing (AST) and population analysis profiling (PAP) demonstrated heteroresistance to azithromycin (AZM), a first-line antibiotic treatment for Campylobacter infections. Molecular analysis indicated a point mutation occurred on the 23S rRNA gene at the A2075G transitions, and the number of mutated gene copies was proportional to AZM resistance. Heteroresistant C. jejuni subpopulations from acute TD are likely underestimated, which may lead to treatment failures, as was the case for this patient. The presence of a heteroresistant strain in a high antibiotic environment may select for additional drug resistance and enable distribution into hospital and local communities.

Health Problems while Working as a Volunteer or Humanitarian Aid Worker in Post-Earthquake Nepal.

INTRODUCTION: Volunteers and humanitarian aid workers working in disaster struck areas of the world are a vulnerable group of travelers. Nepal saw an influx of these humanitarian aid workers following earthquakes in April and May 2015. This study was undertaken to find out the pre-travel preparation and to estimate the risk of disease while the volunteers were deployed in Nepal. METHODS: This was a descriptive cross-sectional study conducted at CIWEC Hospital located in Kathmandu. A questionnaire was given to all volunteers and aid workers who arrived at the hospital for evaluation of health related problems and agreed to be part of the study. RESULTS: Ninety-five volunteers were enrolled in the study. Among these, 65 (68%) were female and 30 (32%) were male. The immunizations received before travel were Hepatitis A 82 (86%), Hepatitis B 82 (86%), Typhoid 70 (73%), Rabies 38 (40%), Japanese Encephalitis 34 (36%), Influenza within last one year 23 (24%), measles 48 (51%), Cholera 34 (36%),Tetanus within 10 years 71 (75%) and Varicella 38 (40%). Forty-four (45%) of travelers carried medication for treatment of Traveler's Diarrhea (TD) which included Ciprofloxacin, Azithromycin, Loperamide and others like Metronidazole and Charcoal. The common illnesses encountered were gastrointestinal, skin problems , injury and musculoskeletal problems, respiratory problems, genitourinary problems, cardiovascular, psychological problems, syncope, and miscellaneous. CONCLUSIONS: Traveler's Diarrhea and dermatological problems were the most common health related problems. Volunteers were not properly prepared for self-treatment and pre-travel preparation was sub-optimal. Important pre travel health advice will decrease the incidence of health problems in this group.

Perforation Peritonitis at High Altitude.

Trekkers going to high altitude can suffer from several ailments both during and after their treks. Gastro-intestinal symptoms including nausea, vomiting, and abdominal pain are common in high altitude areas of Nepal due to acute mountain sickness or due to a gastro-intestinal illness. Occasionally, complications of common conditions manifest at high altitude and delay in diagnosis could be catastrophic for the patient presenting with these symptoms. We present two rare cases of duodenal and gastric perforations in trekkers who were evacuated from the Everest trekking region. Both of them had to undergo emergency laparotomy and repair of the perforation using modified Graham's patch in the first case and distal gastrectomy that included the perforated site, followed by two-layer end-to-side gastrojejunostomy and two-layer side-to-side jejunostomy in the second case. Perforation peritonitis at high-altitude, though rare, can be life threatening. Timely evacuation from high altitude, proper diagnosis and prompt treatment are essential for taking care of such patients. Keywords: duodenal ulcer; Everest; hypoxia; mountaineering; trekking.

Case Report of Frostbite with Delay in Evacuation: Field Use of Iloprost Might Have Improved the Outcome.

Frostbite is a common injury in high altitude medicine. Intravenous vasodilators have a proven efficacy and, recently, have been proposed as a safe outpatient treatment. Nevertheless, the lack of availability and consequently delayed application of this treatment option can result in poor clinical outcomes for patients. We present the case of a 60-year-old Chilean man with severe frostbite injuries suffered while climbing Mount Everest. The patient was initially given field treatment to the extent permitted by conditions and consensus guidelines. Unfortunately, advanced management was delayed, with iloprost administered 75 hours after the initial injury. The patient also underwent 5 days of hyperbaric and analgesic/antibiotic therapies. An early bone scan predicted a poor clinical outcome, and five of the patient's fingers, between both hands, were incompletely amputated. We present this case to exemplify the importance of advanced in-field management of frostbite injuries.

Extended-spectrum ß-lactamase prevalence and virulence factor characterization of enterotoxigenic Escherichia coli responsible for acute diarrhea in Nepal from 2001 to 2016.

Background: Multidrug-resistant (MDR) Gram-negative bacterial species are an increasingly dangerous public health threat, and are now endemic in many areas of South Asia. However, there are a lack of comprehensive data from many countries in this region determining historic and current MDR prevalence. Enterotoxigenic Escherichia coli (ETEC) is a leading cause of both acute infant diarrhea and traveler's diarrhea in Nepal. The MDR prevalence and associated resistance mechanisms of ETEC isolates responsible for enteric infections in Nepal are largely unknown. Methods: A total of 265 ETEC isolates were obtained from acute diarrheal samples (263/265) or patient control samples (2/265) at traveler's clinics or regional hospitals in Nepal from 2001 to 2016. Isolates were screened for antibiotic resistance, to include extended spectrum beta-lactamase (ESBL) production, via the Microscan Automated Microbiology System. ETEC virulence factors, specifically enterotoxins and colonization factors (CFs), were detected using multiplex PCR, and prevalence in the total isolate population was compared to ESBL-positive isolates. ESBL-positive isolates were assessed using multiplex PCR for genetic markers potentially responsible for observed resistance. Results: A total of 118/265 (44.5%) ETEC isolates demonstrated resistance to ≥2 antibiotics. ESBL-positive phenotypes were detected in 40/265 isolates, with isolates from 2008, 2013, 2014, and 2016 demonstrating ESBL prevalence rates of 1.5, 34.5, 31.2, and 35.0% respectively. No difference was observed in overall enterotoxin characterization between the total ETEC and ESBL-positive populations. The CFs CS2 (13.6%), CS3 (25.3%), CS6 (30.2%), and CS21 (62.6%) were the most prevalent in the total ETEC population. The ESBL-positive ETEC isolates exhibited a higher association trend with the CFs CS2 (37.5%), CS3 (35%), CS6 (42.5%), and CS21 (67.5%). The primary ESBL gene identified was blaCTX-M-15 (80%), followed by blaSHV-12 (20%) and blaCTX-M-14 (2.5%). The beta-lactamase genes blaTEM-1 (40%) and blaCMY-2 (2.5%) were also identified. It was determined that 42.5% of the ESBL-positive isolates carried multiple resistance genes. Conclusion: Over 30% of ETEC isolates collected post-2013 and evaluated in this study demonstrated ESBL resistance. Persistent surveillance and characterization of enteric ETEC isolates are vital for tracking the community presence of MDR bacterial species in order to recommend effective treatment strategies and help mitigate the spread of resistant pathogens.

Case Report: Severe Frostbite in Extreme Altitude Climbers-The Kathmandu Iloprost Experience.

Severe frostbite occurs frequently at extreme altitude in the Himalayas, often resulting in amputations. Recent advances in treatment of frostbite injuries with either intravenous or intra-arterial tissue plasminogen activator, or with iloprost, have improved outcomes in frostbite injuries, but only if the patient has access to these within 24 to 48 h postinjury, and ideally even sooner. Frostbitten Himalayan climbers are seldom able to reach medical care in this time frame. We wished to see if delayed iloprost use (up to 72 h) would help reduce tissue loss in grade 3 to 4 frostbite. In a series of 5 consecutive climbers with severe frostbite in whom we used iloprost, 4 of whom received treatment between 48 and 72 h from injury, 2 had excellent results with minimal tissue loss, and 2 had good results with tissue loss less than expected. The 1 patient with a poor outcome likely experienced a freeze-thaw-refreeze injury. This small series suggests that iloprost can be beneficial for severe frostbite, even after the standard 48-h window and perhaps for up to 72 h.

Incidence of Campylobacter concisus and C. ureolyticus in traveler's diarrhea cases and asymptomatic controls in Nepal and Thailand.

BACKGROUND: Campylobacter concisus and C. ureolyticus have emerged in recent years as being associated with acute and prolonged gastroenteritis and implicated in the development of inflammatory bowel diseases. However, there are limited data on the prevalence of these microorganisms in Southeast Asia. In this study, 214 pathogen-negative stool samples after laboratory examination for common enteric pathogens to include C. jejuni and C. coli by culture from two case-control traveler's diarrhea (TD) studies conducted in Thailand (cases = 26; controls = 30) and Nepal (cases = 83; controls = 75) respectively were assayed by PCR for the detection of Campylobacter 16S rRNA and two specific heat shock protein genes specific for C. concisus (cpn60) and C. ureolyticus (Hsp60) respectively. RESULTS: Campylobacter 16S rRNA was detected in 28.5% (61/214) of the pathogen-negative TD stool samples (CIWEC Travel Medicine Clinic, Kathmandu, Nepal: cases = 36, control = 14; Bamrungrad International Hospital, Bangkok, Thailand: cases = 9, controls = 2). C. consisus was identified significantly more often in TD cases in Nepal (28.9%; 24/83) as compared to controls (4%; 3/75) (OR = 9.76; 95% CI 2.80-34.02; P = 0.0003) while C. consisus was detected in only two cases (2/26; 7.7%) and none of the controls stool samples from Thailand. C. ureolyticus was detected in four cases (4.8%; 4/83) and four controls (5.3%; 4/75) and in one case (3.8%; 1/26) and one control (3.1%; 1/30) from Nepal and Thailand respectively. C. jejuni and C. coli were isolated in 18.3 and 3.4% of the cases and in 4.0 and 1.4% of the controls in stool samples from both Thailand and Nepal respectively while C. concisus nor C. ureolyticus were not tested for in these samples. CONCLUSION: These findings suggest that C. concisus potentially is a pathogen associated with TD in Nepal. To our knowledge, this is the first report of C. concisus and C. ureolyticus detected from traveler's diarrhea cases from travelers to Nepal and Thailand.