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InfectionsatHighAltitude

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OxfordJournals

Medicine&Health

ClinicalInfectiousDiseases

Volume33,Issue11

Pp.18871891.

ClinicalInfectiousDiseases
cid.oxfordjournals.org
ClinInfectDis.(2001)33(11):18871891.doi:10.1086/324163

InfectionsatHighAltitude
Charles D. Ericsson, Section Editor, Robert Steffen, Section Editor, Buddha Basnyat1,2,
Thomas A. Cumbo3, and Robert Edelman4,5
+

Author Affiliations

Reprints or correspondence: Dr. Buddha Basnyat, Nepal International Clinic, Laldurbar, GPO
Box 3596, Kathmandu, Nepal (NIC@naxal.wlink.com.np).

Abstract
Every year, thousands of outdoor trekkers worldwide visit high-altitude
(>2500 m) destinations. Although high-altitude areas per se do not

harbor any specific agents, it is important to know the pathogens


encountered in the mountains to be better able to help the ill sojourner at
high altitude. These are the same pathogens prevalent in the surrounding
lowlands, but various factors such as immunomodulation, hypoxia,
physiological adaptation, and harsh environmental stressors at high
altitude may enhance susceptibility to these pathogens. Against this
background, various gastrointestinal, respiratory, dermatological,

neurological, and other infections encountered at high altitude are


discussed. Because there are few published data on infections at high
altitude, this review is largely anecdotal and based on personal
experience.

In this review, we identify and discuss infections commonly encountered at


high altitude. Because there are few published data on infections at
altitude, this review is more anecdotal in nature and largely based on our
personal experience. Although 2 of us (B.B. and T.A.C.) have medical
experience in most popular mountain ranges, most of our time is spent in
the Himalayas, and we emphasize the Himalayas in this report. This review
is designed to serve as a guide for the counselors of people considering
mountain travel, for health professionals treating infections in the field,
and for those examining patients on return to base camp or to their home
country.
Background
High-altitude areas, defined here as >2500 m, do not harbor specific
infectious agents per se. Pathogens encountered in the mountains (table
1) are also seen in the surrounding lowlands. High mountain ranges are
distributed in diverse ecosystems, cover approximately one-fifth of the
Earth's surface, are home to >300 million people, and are visited annually
by tens of millions of persons who reside in lower elevations [1]. Many
ranges in developing countries attract travelers from developed countries
who have had no previous exposure to the area's indigenous pathogens.
The traveler to high altitudes typically treks or climbs through several
ecosystems en route, from tropical jungle or desert at the base of the
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climb to alpine and tundra zones at higher elevations.

Table 1

Infectious risks at high altitude.


Theoretically, the dramatic physiological changes that occur during
acclimatization [2] may modify innate defense mechanisms against

microbial infection, but there are few data that systematically examine

such interactions. High-altitude environments pose stressors in the form


of increased ultraviolet radiation, hypobaria, hypoxemia, hazardous
weather conditions, inability to maintain adequate personal hygiene,

cramped living arrangements, and isolation from adequate medical care.

Theoretically, insect vectors and microbial pathogens themselves may be


affected by such environmental stressors, but except for the paucity of
vector mosquitoes at higher altitudes, nothing is known about these
possible interactions either.

At high altitude, T lymphocyte function is mildly reduced, and defense


against bacterial infection may be compromised, although resistance to
viral infection is not affected and response to immunization is maintained
[3]. Recent studies have shown changes in the immune system secondary
to the production of immunomodulating compounds after exposure to
increased concentrations of ultraviolet light [4]. Studies of granulocyte
function during physical exercise at high altitude describe rapid reversal of
granulocytosis after initial extravasation, and decreased production of
superoxide anions [5]. In addition, hypoxia per se may induce systemic
increases in inflammatory markers [6] and influence disease at high
altitude.
GastrointestinalInfections
Enteric infections are the leading cause of illness in travelers regardless of
altitude [7]. Ten percent of all helicopter evacuations from the Nepal
Himalayas are secondary to complications arising from diarrheal diseases
[8]. Local inhabitants develop abdominal pain and diarrhea, but the
etiology may differ from that experienced by the foreign traveler or
resident [9]. Spread is usually via the fecal-oral route, with flies facilitating
transmission of organisms, such as Shigella, at lower elevations. At higher
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elevations, decreased prevalence of flies (the result of cold weather) and


hypoxic stress may decrease risk of transmission. A recent study in the
Himalayas found that 14% of a cohort of foreign outdoor trekkers
developed gastroenteritis [10]. This incidence of gastrointestinal

symptoms is half that seen at lower altitudes. Nevertheless, risk factors do


exist at altitude. Factors that promote the spread of enteric pathogens at
high altitude include cramped sleeping arrangements, poor hygiene, and
concurrent illness and medications such as ranitidine that increase the

gastric pH [11]. Many high-altitude areas are snowbound; others are more
or less desert communities, such as the Tibetan Plateau, northern
Pakistan, and Afghanistan. A relative lack of water and sewage

management facilities in such locales exacerbates the risk of diarrhea.


Specific causes can rarely be diagnosed in the field. No systematic surveys
have been conducted of the enteropathogens encountered at altitude. On
the basis of lowland data, enteropathogenic bacteria probably are the

most common cause of gastroenteritis in this cohort [12, 13]. In the Indian
subcontinent, the common causes of gastroenteritis are bacteria, Giardia,
and amoebas, in rank order [14]. Cyclospora cayetanensis appears on a
seasonal basis. Campylobacter species may cause a sizable number of
diarrhea cases. Guillain-Barr syndrome, often precipitated by

Campylobacter infection, has been confused with high-altitude cerebral


edema [15]. Typhoid fever deserves special emphasis. It is one of the most
common causes of fever in indigenous people living in the Indian

subcontinent [16]. Because headache and fatigue accompany typhoid,

patients have been mistakenly diagnosed as having altitude sickness and


flown to lower altitude (unpublished data). Visitors to the Himalayas and
the Andes should be immunized against Salmonella typhi.

Local residents of endemic areas are prone to parasitic worm infestations


with ascaris, Ancylostoma duodenale, Necator americanis (hookworm) [9],
or various kinds of tapeworms. Travelers to such areas rarely develop

these infections, but worm infections should be considered and a stool


screening examination conducted if they develop abdominal pain and

intermittent diarrhea while traveling or after return home. Gut cysticerci

can metastasize and present with end-organ symptoms. Cysticercosis of

the brain is a common cause of epilepsy in Nepal [17]. Hepatomegaly may


be seen with amoebic liver abscess, which is uncommon in tourists.
Tuberculosis of the abdomen is common in Nepalese natives, but not

tourists. It presents with fever, wasting, ascites, and intermittent diarrhea

[18]. Fluid intake should be encouraged, and attention should be paid to


potential electrolyte loss. Empiric treatment with a fluoroquinolone
effective against most bacterial pathogens and an antimotility drug would
be appropriate treatment for most cases of diarrhea and gastroenteritis in
the tourist at high altitude [19].
HepatitisAAndHepatitisE
Hepatitis A and E virus infections are common outside of developed
countries. Hepatitis E is one of the most common causes of jaundice in the
adult population of the Indian subcontinent [20]. Before the introduction
of the hepatitis A vaccine, many outdoor trekkers in the high Himalayas
were stricken with this disease and suffered miserably. Japanese tourists
to the Nepal Himalayas almost universally do not receive immunization
and have an increased risk of hepatitis A [21]. Prevention of hepatitis A is
achieved through hygienic practices and active immunization. Women of
childbearing age who wish to trek in the developing world should be
counseled about the high hepatitis E mortality rates of 20% that occur in
pregnant women. Efficacy trials of hepatitis E vaccine are ongoing in Nepal
[22].

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NeurologicalInfections
Rabies infection is a serious concern for those venturing into wild parts of
Latin America, Africa, and Asia. Those going to high altitudes are at an

increased risk because they cannot readily avoid rabid animals and cannot
be treated quickly after exposure. Clinical knowledge of rabies prevention
is paramount, and one should have a very low threshold for descent and

evacuation for rabies immunoglobulin and postexposure immunization in


the event of a dog or monkey bite in the mountains. Those considering
long wilderness trips should be strongly encouraged to receive rabies
immunization.

Japanese encephalitis (JE) is endemic in rural areas of Southeast Asia and

parts of the Indian subcontinent. Although recent reports have identified


JE as an emergent infection in the local population with no travel history
outside of Kathmandu [23], no tourists to high altitude have been

diagnosed, probably due to the rarity of the Culex mosquito vector at such
altitudes. In the Indian subcontinent, JE must be differentiated from

tuberculosis meningitis, bacterial meningitis, and typhoid encephalopathy,


all seen in the local population. Treatment is symptomatic. Prevention
involves mosquito avoidance and vaccination.
Tickborne encephalitis is endemic to central and eastern Europe, the
former Russian states, and sporadically throughout the eastern

Mediterranean. Because endemic areas include deciduous forest below the


altitude of 1200 m, tickborne encephalitis and perhaps its Ixodes tick

vector may be uncommon in sojourners to the Alps and Ural Mountains


unless the disease was acquired at a lower altitude.

Bacterial meningitis, although endemic in many developing country

settings such as the Indian subcontinent, is uncommon in the traveler to


high altitude. However, it remains important to consider bacterial

meningitis as a potential danger to the outdoor trekker in general


RespiratoryInfections
Respiratory problems are common at high altitude [10, 24, 25]. Symptoms
are exacerbated by hypoxic conditions, crowding into tents and huts,
smoky wood stoves, and cold, dry air [26]. Common manifestations

include sinusitis, pharyngitis, bronchitis, and pneumonia. Sore throat and


cough are common above 4000 m. Just like the ubiquitous Khumbu cough

in the Nepal Himalayas, bronchitis in Aconcagua climbers was seen in 13


of 19 climbers at 4300 m [27]. The cough can be purulent or dry, and it
can be severe enough to cause rib fractures. Nasal congestion may worsen
hypoxemia, especially at night when excessive oxygen desaturation is
common during episodes of periodic breathing. Respiratory infections may
predispose the outdoor trekker to acute mountain sickness [10, 24, 25]. In
fact, if acute altitude sickness develops after a respiratory infection,
further ascent up the mountain may need to be postponed because lifethreatening high-altitude cerebral edema or pulmonary edema may result.
The microbiological etiology, if any, of most respiratory illnesses remains
unknown. Nonspecific prevention of respiratory symptoms is important at
higher altitudes; such prevention includes keeping the head warm,
adequate hydration, use of nasal decongestants, and breathing through a
silk scarf to keep air humidified [28]. Even with purulent sputum
production, the role of antibiotics is not established [29]. The common
symptoms of cough, tachycardia, tachypnea, and shortness of breath are
shared by respiratory infections and by high-altitude pulmonary edema
[2]. We maintain a low threshold for treatment with decent should either
condition develop. However, antibiotics are often used. Before travel,
influenza vaccine should be considered, particularly for those not
immunized within the past year, who are visiting the tropics where
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influenza poses a year-round risk, who are part of a large travel group, or

who are visiting the Southern Hemisphere during April through September
[30].

In the local population of the developing world, the differential diagnosis

of cough must include pulmonary tuberculosis. An increased incidence of


chronic obstructive pulmonary disease and cor pulmonale occurs in the
mountain population of the Indian subcontinent. The high incidence is

thought to be secondary to chronic smoke inhalation in poorly ventilated,


smoke-filled dwellings [31].
DermatologicalInfections
Pyoderma, carbuncles, furuncles, and wound infections are among the

most common problems encountered among people sojourning to the

mountains [32]. Poor hygiene, prolonged exposure to moisture, trauma,

and frostbite are common in the mountain wilderness and predispose the
outdoor trekker to frequent and severe dermatological problems. In the
hypoxic high-altitude environment, wounds may heal slowly, despite

therapy with antibiotics. Superficial infections can be accompanied by

cellulitis and lymphangitis [33]. Descent to lower altitude may be the only
definitive treatment. Exposure to ultraviolet radiation and frigid weather
can reactivate herpes simplex infections. Scabies and lice are endemic. In
situations of trauma, burns, and surgical procedure at high altitude,

impaired immunity and poor hygiene associated with altitude may result in
a festering wound infection [28].
Local inhabitants commonly present with advanced cases of skin infections
that afflict visitors, but less severely. For example, septicemia and
osteomyelitis not uncommonly develop secondary to uncontrolled skin
infections in natives. Suppurative otitis media may predispose local
inhabitants to facial infection, bone infection, hearing loss, and

meningitis. Varicella is common in Nepalese children; visitors unsure of

their immune status should consider varicella immunization before travel.


InsectborneInfections
Malaria is a pervasive danger. Although Plasmodium species generally are
not transmitted at altitudes >2000 m [34], febrile illness from acute or

reactivated malarial infection acquired at lower elevations may manifest at

higher altitudes [35]. It may take weeks for Plasmodium falciparum and
months for P. vivax to manifest as a febrile illness after leaving the
lowlands for the mountains. Diagnosis is presumptive, and medical
evacuation from high altitude to a larger center is the norm. The
mainstays of malaria prevention when visiting endemic areas are mosquito
repellents and chemoprophylaxis.
Dengue fever, with Aedes aegypti mosquito vectors [36, 37], is endemic to
the tropics and subtropics, with transmission occurring between
approximately 25N and 25S latitude. Like malaria, travelers are infected
in the lowlands and become ill after reaching higher altitude. Diagnosis is
presumptive. Treatment is generally supportive and includes descent.
Prevention of mosquito bites should be stressed during pretravel
counseling. Dengue hemorrhagic fever occurs in natives at lower altitudes
and is rarely, if ever, seen in mountain travelers.
Typhus is probably an underdiagnosed cause of fever in mountain
travelers, although like most other infections at higher altitudes, the
prevalence is anecdotal. Typhus is caused by Rickettsia prowazekii, R.
typhi, R. tsutsugamushi vectored by lice, fleas, or mites, depending on
whether it is epidemic, endemic, or scrub typhus [38]. One individual
treated with ciprofloxacin for diarrhea and fever while outdoor trekking
did not improve and was subsequently diagnosed in Bangkok as having
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typhus; treatment with doxycycline resulted in rapid improvement


(unpublished data).

The Phlebotomus sandfly is the vector for bartonellosis, caused by


Bartonella bacilliformis, and occurs only in the Colombian, Ecuadorian, and
Peruvian Andes at 6002500 m. Diagnosis is made by the clinical

presentation in the presence of anemia and by visualization of the

pathogen via erythrocyte smears. Bartonella infections are treated with


tetracycline or chloramphenicol [39].
OtherInfections
Leptospirosis is commonly spread by direct contact of abraded skin with
contaminated water or soil. Mountain expeditions often require passage

through water at base camp, thus offering potential exposure. Treatment

involves therapy with doxycycline or ampicillin, depending on the severity


of infection [40]. Pain at the location of dental caries may occur, possibly

due to decreased atmospheric pressure with expansion of gas in the cavity


at high altitude.

Sexually transmitted diseases, yeast infections, and urinary tract infections


are common at sea level and at high altitude. Mountain sojourners who

have increased their frequency of sexual activity, who have acquired new
partners, who have started antibiotic therapy, or who are unable to
maintain usual levels of personal hygiene are prone to sexually

transmitted diseases. Gonorrhea, chlamydia, trichomonas, candidiasis,

genital herpes, and acute HIV infection may result, among other infections.
Urinary tract infections can be diagnosed in the field via urine dipstick, but
they are most often treated empirically. Descent is usually not necessary
unless severe pain and fever suggest pyelonephritis.
In essence, infections and infectious diseases at high altitude often

parallel those in adjacent lowland environments. Immunomodulation,

hypoxemia, hypobaria, physiological adaptation, harsh environmental

stressors, exposure to foreign agents, and reckless behavior can enhance


susceptibility to pathogens. The ultimate treatment may require descent.
Prevention is crucial; both counseling and immunization are essential
(table 2). Clearly, more research needs to be done on high-altitude
infections to better understand their pathogenic mechanisms and
epidemiology and to improve treatment and prevention.

Table 2

Infection and preventive measures at high altitude.


Received February 12, 2001.
Revision received August 14, 2001.
2001 by the Infectious Diseases Society of America

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2001 by the Infectious Diseases Society of America

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