Pathogens for Travelers’ Diarrhea in Nepal and Resistance Patterns

TROPICAL AND TRAVEL MEDICINE (LH CHEN, SECTION EDITOR)

Pathogens for Travelers’ Diarrhea in Nepal and ResistancePatterns

Holly Murphy & Prativa Pandey

Published online: 3 April 2012# Springer Science+Business Media, LLC 2012

Abstract At the top of the world, Nepal leads the world intravelers’ diarrhea. A review of the rates, pathogens andresistance patterns over 3 decades reveals a persistent prob-lem of increasing alarm. A look at root causes providesinsight into this oppressive, inconvenient offense to travel-ers to an otherwise mystical Himalayan paradise.

Keywords Travelers’ diarrhea . Nepal .Campylobacter .

ETEC . Shigella .Cyclospora . Antibiotic resistance .

Norovirus . Astrovirus

Introduction

A mountaineer trains and pays to summit Mt. Everest onlyto cancel the climb for diarrhea. A vacationer develops post-diarrheal Guillain-Barré Syndrome during a family holidayto Nepal spending the next year in intensive care and reha-bilitation. Thirty thousand Nepalese children die annually asa consequence of infectious diarrhea [1]. Amid a high-riskexposure to pathogens, the susceptible host is prey to infec-tious disease.

Diarrhea is the most common illness among travelers toNepal and travelers overall [2–4]. In a multicenter study ofgastrointestinal illness among international travelers, Nepal

had the highest reporting rate ratio among 28 countriesstudied [5]. In an exit poll of travelers at Kathmandu airport68 % of travelers experienced travelers’ diarrhea (TD) [2].Among long-term travelers to Nepal the risk of diarrheapersists at a monthly rate of 27 % over the first 2 years oftheir stay [6].

Diarrhea among travelers to Nepal is common, oppres-sive and, in some cases, persistent. Why does this tinynation at the top of the world lay claim to the highest TDrisk in the world? What can travelers do to avoid thistreacherous outcome?

Background on Travelers Diarrhea in Nepal

Historical TD in Nepal

In the mid-1980s, diarrhea accounted for 35 % of medicalvisits, approximately 2500 patient visits, by travelers resid-ing in Kathmandu [7]—a rate similar to that noted fortravelers to Mexico in the late 1950s [8]. Routine microbi-ologic methods available identified a pathogen nearly 50 %of the time. The three most common pathogens incriminatedwere enterotoxigenic Escherichia coli (ETEC), Shigella,and Campylobacter; nearly 30 % of patients were infectedwith multiple pathogens. Giardia and Cryptosporidiumwere significant contributors and rotavirus was prevalentin the winter. Nearly 3 decades later, little has changed.

In the ’80s drug resistance concerns were about co-trimoxazole (5 % of ETEC and 22 % of Shigella resistant)and tetracycline (22 % of ETEC and 52 % of Shigellaresistant). Co-trimoxazole use diminished as resistance rose,supplanted by the flouroquinolones (FQ). Interestingly, theebbing of co-trimoxazole, later found to be a treatment forCyclospora [9], coincided with the discovery of Cyclospora

H. Murphy (*) : P. PandeyCIWEC Clinic Travel Medicine Center,PO Box 12895, British-Indian Embassy Road, Lainchour,Kathmandu, Nepale-mail: [email protected]

P. Pandeye-mail: [email protected]

H. Murphy1133 Pomona Road,Ann Arbor, MI 48103, USA

Curr Infect Dis Rep (2012) 14:238–245DOI 10.1007/s11908-012-0253-9

in Nepal. What followed was a “Golden Age of FQ Use”with clinical success and minimal resistance in TD treat-ment. By the early ’90s Campylobacter resistance to bothciprofloxacin and azithromycin (AZM) was reported at sig-nificant levels in the region [10]. In Nepal, FQ resistanceescalated resulting in an upsurge in AZM use.

By 2001, Campylobacter replaced ETEC as the mostcommon TD pathogen in Nepal, similar to other parts ofSouth Asia. Resistance to the newer FQs: ciprofloxacin,levofloxacin had reached significant proportions with nearly80 % of Campylobacter showing reduced susceptibility toFQs and nalidixic acid (NA) resistance across the board.Nearly one-third of non-Campylobacter isolates expressedresistance to AZM.

Extrapolation of these data to the current time suggestincreased resistance to the two mainstays of therapy: AZMand the FQs. These data and clinical experience suggest thatTD treatment in Nepal is approaching an impasse. Thisunderscores the need for new drug strategies. More impor-tantly, improved sanitation, cleaner water and improvedhygiene by food handlers are imperative.

TD in Nepal vs. The Region and Other Travel Destinations

The Indian subcontinent region has consistently been foundto be high risk for TD [5, 11]. High attack rates for TD(54 %) are noted in India (Goa) and Africa (Mombasa)compared to 14 and 24 % respectively, for sites in SouthAmerica and the Caribbean [4].

Greenwood redefined the global map of TD with datafrom 6086 travelers presenting after travel with a gastro-intestinal illness to 30 GeoSentinel clinics on 6 continentswhere the highest risk region was South Asia [5]. Fromamong 28 individual countries Nepal had the highest report-ing rate ratio of diarrhea at 642.9 cases per 10 millionvisitors; followed closely by neighboring India [5].

History of CIWEC Clinic and Relation to TD Research

The Canadian International Water and Energy ConsultantsClinic (CIWEC) was founded in 1982 for the health needsof expatriates employed by a Canadian water project.Through a joint venture with the Armed Forces ResearchInstitute of Medical Science (AFRIMS) in Bangkok, TDresearch began in Nepal in 1986. This effective collabora-tion is largely responsible for TD data on Nepal. Researchby CIWEC lead to the discovery of a novel pathogen in1989, later identified as Cyclospora [12]. Collaboration withAFRIMS contributed to the epidemiology of and theplacebo-controlled trial of co-trimoxazole treatment ofCyclospora in Nepal [9, 13].

CIWEC remains a leading center for the investigation ofTD. In 2011, CIWEC treated over 8700 patients: 91 % were

travelers (49 % tourists and 42 % long term travelers). Thattranslates to over 2000 stool investigations and 2058 diag-noses of TD.

Summaries of “Classic” Papers on TD in Nepal

The greatest wealth of information on TD in Nepal isencompassed in three major studies conducted at CIWEC.In sum, there is an increased risk of TD from April to Juneand a bacterial source in nearly 80 % of cases [2, 7, 14••].Campylobacter has outpaced the other pathogens, but isfollowed closely by Shigella and ETEC (Table 1). The rateof isolation of Campylobacter has been relatively constantover the periods studied at 25 % [14••], 21 % [2] and 24 %of bacterial isolates [7]. However, the rate of detection ofETEC decreased significantly from 44 % in the 1988 studyto 18 % of bacterial isolates in 2001–03. This change isexplained, in part, by the increased use of FQ self-treatment.Cyclospora, discovered in the early 1990s, and norovirus—not studied earlier, emerged as relevant pathogens in thelatest investigation.

Narrowing the focus to expatriate persons living inNepal, Hoge demonstrated that long-term travelers appreci-ate only a slightly decreased risk compared to tourists. In asurvey of expatriates, an attack rate of approximately 50 %

Table 1 Comparison of Pathogen Detection for Travelers’ DiarrheaStudies from Nepal

Years of investigation: 2001–03 [14] 1992–93 [2] 1986–87 [7]

N0381 N0189 N0328

No (%) No (%) No (%)

Campylobacter 66 (17.3) 45 (23.8) 31 (9)

Enterotoxigenic E. Coli 47/318 (14.8) 49 (25.9) 79 (24)

Shigella 50 (13.1) 38 (20.1) 45 (14)

Salmonella (non-typhoidal)

14 (3.7) 6 (3.17) 10 (3)

Enteroinvasive E. Coli 3/318 (0.9) 5 (2.6) 7 (2)

Enteropathogenic E.Coli 37/318 (11.6) 33 (17.5) NI

Enterohemorrhagic E.Coli 0 (0) 1 (0.5) NI

Aeromonas 36 (9.4) 3 (1.6) NI

Plesiomonas 17 (4.5) 5 (2.6) NI

Yersinia Enterocolitica 3 (0.8) 0 (0) 4 (1)

Rotavirus 18/353 (5.1) 15 (7.9) 25 (8)

Norovirus 12/354 (3.4) NI NI

Entamoeba Histolytica 6/350 (1.7) 6 (3.2) 17 (5)

Cryptosporidium 5/372 (1.3) NI 15 (5)

Giardia 42/372 (11.3) 25 (13.2) 38 (12)

Cyclospora 31 (8.1) NI NI

Multiple pathogens 99 (26) 66 (17) 56 (17)

No pathogen detected 118 (31) 45 (23.8) 133 (43)

NI not investigated

Curr Infect Dis Rep (2012) 14:238–245 239

per month was noted during their first 2 years in Nepal [2].This approximates the rate among tourists during the “high”diarrhea season.

Shlim noted the incidence of TD among expatriate resi-dents living in Nepal at an astounding 3.2 per person peryear—a rate comparable to that for Nepalese children andexceeding the incidence of diarrheal disease among childrenunder 5 in developing countries [15]. In a cohort of expa-triates residing in Nepal for less than 2 years, stratified bycalendar quartile, there was no correlation between length ofstay in Nepal and decreased incidence of TD. ETEC lead thepathogen parade at 15 % of cases; Cyclospora (11 %) andGiardia (8 cases, 5 %) supplanted Campylobacter (4 %) andShigella (5 %). Rotavirus was detected at a significant level(8 % of 61 samples tested). Entamoeba histolytica andAeromonas were rare and helminths were not detected.

The annual incidence by pathogen was a staggering 42 %for ETEC, 32 % for Cyclospora, 16 % for Giardia, 16 % forShigella, 10 % for Campylobacter and 6 % for E. histoly-tica. Of note, when calculated by calendar quarter, theincidence of Cyclospora during the high-risk season (2ndquarter) was 8 %, exceeding that of ETEC during the sametime period. Notably, the risk of ETEC dropped off signif-icantly after the first 3 months of residence. It is not surpris-ing that though bacterial pathogens predominated, parasiticinfections were more prevalent among this population oflong-term travelers than among tourist populations. Thesedata emphasize the persistent risk of TD among expatriatesto Nepal and the high level of exposure to enteric pathogensin this setting.

Further evidence that a traveler to Nepal is likely toexperience an onslaught of enteric pathogens is theremarkable prevalence of pathogens in stools of asymp-tomatic controls. Hoge identified pathogens among thestools of healthy residents and tourists, 37 % and 52 %of the time, respectively [2]. Pandey et al. reported thata pathogen was isolated in the stool of 27 % of healthycontrols comprised of tourists and residents in a propor-tion of 2:1 [14••].

Avoiding TD in Nepal (Boil it, cook it, peel it…. Forget it!)

Simply put, diarrheal illness among travelers to Nepal is amanifestation of infectious disease in a susceptible host inthe milieu of high-risk exposure: a proxy of diarrheal dis-ease in Nepalese under 5’s. This perspective lessens thesurprise that among long-term travelers hygiene precautionsdo not prevent TD [2, 16]. Intake of items traditionallythought to be “risky” for infectious diarrhea—includingice, untreated water, raw vegetables, unpeeled fruit and fruitsalad was not associated with TD in a study conducted inNepal. Food items associated with an increased risk ofinfectious diarrhea included: foods requiring reheating (suchas lasagna, quiche, casserole, etc.) and yogurt drinks (localdrink of blended ice, yogurt and sometimes fruit called a“lassi”). Of note, eating at a restaurant at least once in theweek prior correlated with TD—suggesting that hygieneprecautions by the food handler may outweigh that of per-sonal precautions.

There is a point when a longer stay in Nepal is associatedwith a decreased risk of TD. Hoge demonstrated a linearrelationship between the odds of developing diarrhea andlength of stay in Nepal. The odds for diarrhea dropped offsomewhat after the first year, but remained significantthrough year 4, then dropped off significantly [2].

Resistance Patterns

Among Travelers

Antibiotic susceptibility for currently used TD drugs in Nepalhas been investigated in one study, conducted between 2001–2003 [14••] (Table 2). Though that data showed 80 % sensi-tivity overall to either ciprofloxacin or AZM—the two mostcommonly used antibiotics for TD currently, alarming trendsemerged. Among 277 bacterial isolates studied, reduced sus-ceptibility to NAwas noted among all pathogens with 78 %,47 %, and 40 % resistance for Campylobacter, Shigella and

Table 2 Antimicrobial Resis-tance Patterns of Bacterial Iso-lates from TD Cases, 2001–2003[14]

aIntermediate sensitivity by disk-diffusion method whereidentified

AM amoxicillin; AZM azithromy-cin; CIP ciprofloxacin; NAnalidixic acid; SXTtrimethoprim-sulfamethazole.

Number ofIsolates Tested

% Isolates Resistant or with Intermediatesusceptibility a

AM SXT NA CIP AZM

Campylobacter 72 15 68 78 78 0/0

Shigella 51 16 75 47 0 0/35

Enterotoxigenic E.coli 51 29 22 39 0 0/14

Enteropathogenic E.coli 38 42 34 36 5/5 16/24

Aeromonas 36 100 25 25 0/0 0/25

Plesiomonas 17 0/94 0 29 0/0 0/35

Salmonella (nontyphoidal) 13 23 23 31 0/0 0/27

240 Curr Infect Dis Rep (2012) 14:238–245

ETEC, respectively. Ciprofloxacin resistance was pri-marily a problem among Campylobacter with 71 %resistant and 7 % with intermediate sensitivity. ThoughAZM retained activity against Campylobacter, there wasreduced susceptibility to this drug for all other patho-gens studied.

These data are biased by inclusion of patients pretreatedwith a FQ (53 of 381 cases). Pathogens were isolated from12 of 53 FQ-exposed individuals. Among those patients 7 of7 Campylobacter isolates were resistant to ciprofloxacin,whereas Shigella (1), Salmonella (1) and ETEC (3) isolatesremained sensitive. This suggests that as of 2003 the FQsretained activity against several common pathogens. Thereare no published updates from Nepal but significant FQ-resistance across the board is expected based on recenttrends from the region regarding antibiotic resistance.

Antibiotic Resistance in the Region

Rates of FQ resistant Campylobacter in vitro have increasedin Thailand among US military personnel from 0 % in 1990to 84 % in 1995; exceeding 96 % in 1998 [17, 18]. FQresistance among Campylobacter isolates from internationaltravelers to India and locals exceed 70 % [19, 20].

Alarming news from Thailand noted the rise in AZMresistance among Campylobacter (15 %) and ETEC(15 %) already by 1998 [17]. This level of AZM resistanceamong Campylobacter has yet to be documented in Nepal,though there are no current surveillance projects underway.High minimum inhibitory concentrations for AZM amongSalmonella documented in Nepal and the region beg caution[21]. From our experience there is a significant rate ofclinical failure when AZM is used against Salmonella para-typhi with decreased susceptibility and a low but significantrate of clinical failures when AZM is used first-line for TD.

Resistance Patterns Among Locals

Due to limited laboratory facilities in both government andprivate sectors, there are limited data on antibiotic resistancefor Nepal. Increasing FQ resistance in Nepal is assumedconsidering the rate of ciprofloxacin availability and usefor the past 2 decades. A study of antimicrobial resistanceamong pathogens isolated from stool of local Nepaleseliving in the Kathmandu Valley conducted between 2002–2004 detected a significant rate of FQ-resistant Shigella[22]. Though the numbers are small, an alarming trend isnoted. In 2002, 42 % of Shigella isolates (5 of 12) showedresistance to NAwith 100 % susceptibility to ciprofloxacin.By 2004, one-quarter demonstrated resistance to ciproflox-acin (5 of 21); these isolates were all MDR and mostly S.dysentariae type-1 denoting a risk for outbreaks and highassociated mortality.

Beyond the capital in Eastern Nepal, FQ resistanceexceeded 80 % among Shigella dysenteriae among childrenunder 5 [23]. All isolates were also MDR. A linear trendover the 4-year period shows the rapid escalation ofciprofloxacin-resistance among Shigella dysenteriae type 1from 0 % to 80 %.

Diarrheal Outbreaks

Contaminated drinking water has been implicated as thecause of numerous diarrheal outbreaks in Nepal. In 1994an outbreak of Cyclospora among a detachment of Britishsoldiers and their families in western Nepal was linkedto a water supply [24]. Eleven of 12 (92 %) of indi-viduals in the camp were ill and Cyclosporawas identified in6 of 11 (75 %) cases. Though chlorine levels were withinacceptable limits, the filtration system was thought to beinadequate.

There have been numerous Vibrio cholera outbreaks inNepal. One epidemic resulted in nearly 92,000 cases and1800 deaths among the local population [25]. The pathogenwas located in at least 5 regions and was associated with thewater supply. Other seasonal outbreaks of V. cholera havebeen reported in subsequent years linked to unsafe water[26]. The most common serotypes have been V. cholerae 01Ogawa and Hikojima. To date, there are no reports oftravelers among cases during V. cholera outbreaks.Shigella shigae dysentery epidemics have been reportedamong Nepalese and foreigners living in Nepal—particular-ly refugees [27, 28].

Notable Pathogens

Cyclospora

A review of TD in Nepal would be incomplete without adetailed account of Cyclospora. In 1991 an unidentifiedorganism just larger than cryptosporidium, described as acyanobacterium-like body (CLB), was reported amongimmunocompetent travelers with prolonged diarrhea inNepal between the months of June and November, 1989[12]. Among the first 55 cases reported, 52 (95 %) werelong-term travelers. Fever was reported in 30 % ofpatients and average weight-loss was 3.6 kg +/− 3 kg(range 0–15). Upon further investigation in the first yearthat this illness was described, there were no cases seenbetween November 17, 1989 and May 16, 1990 whenanother 4 cases were detected. The diarrhea associatedwith CLB was described as prolonged, self-limited ill-ness characterized by fatigue, anorexia and weight loss.This early study characterized the seasonal nature of CLB


related diarrheal illness; rising just before the June monsoonduring the May heat and beginning to subside prior to the endof the monsoons in early Fall. In the subsequent 4 yearsanother 300 cases were documented at CIWEC among trav-elers [29] and the pathogenwas identified in water sources [9].A clinical trial showed that 7 days of co-trimoxazole waseffective treatment for Cyclospora in Nepal [9].

Two decades later, the seasonality is nearly identical tothat reported in 1989. Cyclospora persists at CIWEC withbetween 17 and 25 cases annually for the years 2010–2011[unpublished data]. Cyclospora among travelers peaks inthe early monsoons of June-July. The first case generallyoccurs in May and the last case of the season in November,overlapping with tourist peaks. Tourists represent nearly50 % of cases.

In a study of Nepalese children under 15 in eastern Nepal,Cyclospora represented 2 % of illness—clustering during therainy season [30]. In prior series, Cyclospora has beenisolated from up to 12 % of stools from Nepalesechildren [31, 32]. Though the natural reservoir forCyclospora cayatenensis remains unknown, the organismhas been isolated from stools of dogs, chicken and monkeysin Nepal [33].

ETEC Colonization Factor Antigens

In order to estimate the applicability of the new cholera Btoxin subunit vaccines in the context of Nepal, we isolatedcolonization factor antigens (CFAs) for ETEC strains.Among 50 ETEC strains from 47 TD cases, 13 (26 %)expressed heat labile toxin (LT), 17 (34 %) expressed heatstable toxin (ST) and 20 (40 %) expressed LT and ST enter-otoxins, respectively [14••]. CFAs were detected among 31/47 (66 %) ETEC strains. Among CFA-negative strains fromcases, 12 of 16 expressed LTor LT/ST, while 4 expressed STonly.

Considering 70 % of strains from cases expressed LTenterotoxins and 15 % of diarrheal cases were attributableto ETEC, the cholera B toxin subunit vaccines may prevent10 % of TD cases in this setting. Based on this limited data,we do not support vaccination with the currently availablecholera B toxin subunit vaccines for Nepal.

Astrovirus

Astroviruses are a recently identified viral cause of mammaland avian gastroenteritis [34, 35]. In a study of stool sam-ples from adult travelers in Nepal with gastroenteritis whohad no known enteric pathogen by standard microbiologicaltests, astrovirus was detected in 15 of 95 cases vs. none of95 healthy control samples [36]. Twelve of 15 astrovirusdetected were closely related to the first identified, and mostcommon, as t rov i rus (HAstV) l inked to human

gastroenteritis; 3 were novel astrovirus distantly linked tomink and ovine species [36].

Blastocystis hominis

A landmark study demonstrated a lack of pathogenicity ofBlastocystis hominis in TD among short and long-termtravelers to Nepal [37]. Though patients with diarrhea weremore likely to have >10 B. hominis organism per high-power (400x) field (hpf) than controls known pathogenswere also detected in the same stool samples. Amongdiarrheal cases without a pathogen identified there wasa low rate of B. hominis detection at >10 organism perhpf. B. hominis did not correlate with more severediarrhea.

Blastocystis sp. is commonly detected in stools ofpatients in Nepal with TD with and without pathogens.Subtyping has not been done in Nepal. In practice atCIWEC they are generally left untreated.

Illness Consequent to TD

Fortunately, long-term sequelae of TD occur in a minority ofcases. Some illnesses consequential to TD are worth men-tioning. Anecdotally at CIWEC, nearly 100 % of travelers toNepal experience loose stools during their time in Nepal thatgenerally resolves upon return to their home country.Considering estimates of between 5–10 % of acute TD casesresult in chronic disruption of the normal bowel pattern,including post-infectious irritable bowel syndrome(IBS), this entity is likely underreported for Nepal andis an area for research [38]. The majority of post-TDIBS is likely diagnosed upon return to the home countryso there is limited data from our “during travel”population.

Guillain-Barré Syndrome (GBS) is a notorious entity inNepal and there are numerous reports of post-CampylobacterGBS from the region among indigenous people [39–41].There is a single report of GBS after Campylobacter in atraveler to SE Asia [42] and 1 report of GBS attributed toSalmonella paratyphi A from a Nepali traveler to Quatar [43].GBS has been diagnosed at CIWEC at a rate of 0.25-1 casesannually, with 2 cases in 2010: one patient with fulminantdisease developed acute neuromuscular paralysis subsequentto TD resulting in medical evacuation. A second patientpresented after a trek and bus ride with foot drop after preced-ing TD. Antibody studies confirmed GBS in both cases andboth had favorable outcomes, though pathogens were notidentified in either case.

Reactive arthritis is seen occasionally at CIWEC as uve-itis and arthritis after TD. There is 1 report of a traveler toNepal developing reactive arthritis during TD; the patient


initially developed diarrheal symptoms while in India 6 daysprior [44]. No pathogen was identified.

A more common entity seen at CIWEC is altitude illness,with several hundred cases documented annually, particu-larly among rescues from the Everest Region. Diarrhealillness, as well as respiratory illness, is associated with anincreased risk of altitude illness in this region including highaltitude cerebral edema [45].

Root Causes of TD in Nepal

Sanitation

Safe drinking water and sewage disposal are essential ele-ments to reducing TD risk. In Nepal, water safety remains amajor public health challenge. Pathogen recovery from urbanwater supplies points to drinking water as a likely source ofhuman infection. Fecal E. coli with resistance plasmids havebeen recovered from ponds in Kathmandu [46]. In a 2003study of water in 3 cities in Nepal, Salmonella was recoveredin 14 % of 300 samples. The predominant species wasSalmonella typhimurium, though S. typhi, S. paratyphi Aand S. enteritidis were also common. The majority of isolateswere MDR, and some isolates of S. enteritidis wereceftriaxone-resistant [47].

Food Handler Hygiene

An investigation of hygiene at restaurants in Kathmandunoted numerous unhygienic practices [16]. Lapses in handwashing, refrigeration and food handling were noted.Window screens to disallow access to flies were inconsistent.The blenders that made lassis were not well cleaned betweenuses. More than a decade later, food safety codes for hoteliersare still lacking. Power outages, termed “load shedding,” areroutine, daily and significant. Over the last several years,during peak load shedding in winter and spring precedingthe monsoon, power outages reach 18 h per day. Many restau-rants do not have alternate power sources so food is routinelyfrozen and thawed and under refrigerated. Clearly, this cumu-lative negligence potentiates pathogen spread.

FQ use in Farming

The prevalence of FQ-resistance among Campylobacter hasbeen directly linked to the introduction of FQ use in poultryfarming in the United States [48]. In Australia, where FQ arenot used in poultry farming, Campylobacter isolates remainsusceptible to FQs [49]. In a recent study of raw poultryfrom 3 sites in the Kathmandu valley, antibiotic resistancewas alarming with nearly 100 % of Salmonella isolatesresistant to NA and all beta-lactams studied, 92 % resistant

to tetracycline and nearly 70 % of Salmonella were MDR[50]. Though surveillance is lacking, the numbers are notsurprising considering the 2 most common antibiotics usedin veterinary practice in Nepal are tetracycline and enroflox-acin [51].

Pharmacy and Treatment Practices

The extent of the spread of antibiotic-resistant bacteria inNepal is largely attributable to the wide availability of anti-biotics over-the-counter across the country and region.Pathogen-directed antimicrobial therapy is extremelylimited. Fellowship training programs for the specialty ofInfectious Diseases in Nepal or in the region are lacking[52]. Antibiotics are available over-the-counter and routinelyrecommended by self-run neighborhood pharmacists.Polypharmacy and over-prescribing of antibiotics is docu-mented in the region [53] though published reports fromNepal are sparse. A study in India noted 73 % of patientswere prescribed an antibiotic [54]. In this study, the averagenumber of drugs prescribed was 3, and only 2 of 312 patientsstudied were not prescribed a drug. FQ and cephalosporindrugs are used heavily. In a recent study from WesternNepal ciprofloxacin was the most used drug in an inpatientmedical ward at 6.83 defined daily dose/100 bed-days and42 % of ciprofloxacin use was prophylactic [55].

Drug Choice and Availability in Nepal

At CIWEC we employ either a FQ (ciprofloxacin or levo-floxacin) or AZM first-line for acute TD. We experience asmall but significant rate of clinical failure using this regi-men but rarely fail if a drug from the other class is employedconsecutively. The high rates of Campylobacter andShigella make the nonabsorbable antibiotic rifaximin lesssuitable for TD prevention and treatment for Nepal.Rifaximin is currently not available in Nepal.

Conclusions

As long as poverty abuts the natural beauty of the Nepallandscape and rich culture of the Nepalese people, diarrheawill vex travelers to this beloved tourist destination.Inconveniently, peak diarrheal risk times coincide with touristpeaks. Knowledge of the pathogens and resistance data isuseful for clinicians treating TD and prescribing antibioticsfor self-treatment. The traveler to Nepal should be informedabout the TD risk and armed with TD self-treatment includingboth a FQ and AZM. Large-scale efforts to improve sanitationand hygiene are crucial to address the problem of diarrhea forthe Nepalese and travelers to Nepal.


Disclosure No potential conflicts of interest relevant to this articlewere reported.

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Pathogens for Travelers’ Diarrhea in Nepal and Resistance Patterns