Infectious Diseases

Glenn W. Mitchell

Gregory J. Martin

Diseased Nature oftentimes breaks forth in strange eruptions.

—King Henry IV. Part I. Act iii. Sc. 1. William Shakespeare (1564-1616)

HISTORICAL PERSPECTIVE

Travel has been a significant vector for infectious diseases since the beginning of time. The spread of the Black Death in the 14th and 15th centuries is a vivid example of the problems of travel when a highly contagious disease is introduced into a nonimmune population (1). People traveled to avoid the plague as it entered their towns, but they were already incubating the disease and only spreading it further. Slow transportation by foot, horse, and carriage kept the plague from exhausting its pool of new victims for many years. The introduction of smallpox, chicken pox, and measles into the New World by Pizzaro and other explorers decimated the indigenous peoples of the Americas and facilitated the cultural dominance of Europeans there. In return, it appears that new world explorers returned to Europe with syphilis, which subsequently became a scourge throughout Europe in the 16th and 17th centuries. Until the late 19th century, lack of understanding of disease transmission led to care for the sick with essentially no effective protective measures for either health care workers or families.

However, acceptance of the “germ theory” and recognition of the need for infection control did not eliminate disease spread because transportation advances continued to increase the ability for infections to be transmitted rapidly across great distances. The influenza pandemic of 1918 provides a good illustration of the role of improving travel modes, as coal- and oil-fired ships provided a faster and more convenient way for persons who were ill to continually expose others to novel diseases; the deploying American troops probably brought influenza with them to Europe from their training camps. Cholera is another disease whose history of increasingly rapid worldwide spread is based on improvements in the speed of travel, thereby permitting infectious passengers and crew to arrive in distant ports and establish novel foci of infection. Outbreaks of cholera in South and Central America during the 1980s illuminated the fact that aircraft are also effective vectors for this disease (2).

Air travel has become a well-recognized and highly visible risk for transmission of infectious agents. The outbreak of Ebola virus in Kitwit, Uganda, in 1978 demonstrated that persons who are ill might well be flown in commercial aircraft without knowledge of risks by the rest of the passengers. Fortunately, more recent studies have demonstrated that direct contact with body fluids is usually necessary for any significant risk for transmission of this disease. The outbreak and threat of worldwide spread of severe acute respiratory syndrome (SARS) in 2002 to 2003 resulted in quarantines and restrictions on air travel, and focused worldwide attention on the impact of air travel on the rapid spread of potentially serious disease across continents. Most recently, commercial aircraft passengers with active tuberculosis (TB), including one case with an extensively drug resistant (XDR) TB strain, have led to intensive discussions in the press and more in-depth investigations of potential problems with spread of infectious diseases inside sealed passenger aircraft cabins (see subsequent text).

Recognition of outbreaks of highly pathogenic avian influenza (HPAI) in birds in many areas of the world and associated human cases has appropriately raised concern for rapid transmission of pandemic influenza through air travel. Unlike TB, which generally requires prolonged, close contact, influenza can be relatively quickly and efficiently transmitted. If HPAI becomes adapted to human-to-human transmission, rapid identification and quarantine of infected patients and their contacts will be needed. In 2005, President of the United States, Bush announced at the United Nations the formation of the International Partnership on Avian and
Pandemic Influenza (IPAPI), which includes management of potentially infected air travelers. The U.S. Department of Health and Human Services has developed a national Pandemic Influenza Plan with specific guidelines for travelassociated influenza in a supplement (3).

This chapter will concentrate on diseases of interest to the medical practitioner considering the possible diagnoses for a patient’s illness when the condition is associated with a recent history of air travel.

SIGNIFICANT INFECTIOUS DISEASES

Potentially, nearly any infectious agent could be transmitted during air travel. An exhaustive list of potential infectious diseases that could be associated with air travel is too lengthy to compile here. However, a broad sample of significant diseases with their associated common signs and symptoms as well as their relevant characteristics is relevant to the practice of aerospace medicine. For example, travelers may present at varying times after their journey and knowledge of the various incubation periods and geographic locations for common diseases is invaluable. In the interest of brevity, the parasitic diseases and the purely sexually transmitted diseases are not described in this table. These categories of infectious disease do not overlap significantly with those likely to be intentionally spread nor are they commonly spread aboard aircraft. Diseases transmitted in aircraft can be divided as follows:

1. Directly transmitted among passengers. These are mainly respiratory illnesses, and, to a lesser extent, some diarrheal pathogens that can be transmitted in lavatories or through hand-to-hand contact. Viral respiratory pathogens are probably the most commonly transmitted diseases in aircraft. Acute respiratory infections, although exceptionally common, are typically mild. The experience with SARS, and potentially pandemic influenza, demonstrates that very serious respiratory infections may be transmitted in aircraft. These are listed in Table 19-1.

2. Food and waterborne illnesses that are acquired from items served to passengers while on board. These risks are little different from those seen in restaurants and can also be associated with passenger-to-passenger transmission through fomites and are included in Table 19-1.

3. Vector-borne illnesses that are potentially acquired by passengers who are exposed to mosquitoes, sand flies, fleas, or animals that may be intentionally or accidentally on board the aircraft. With the exception of malaria and dengue, transmission of these illnesses aboard aircraft is exceedingly rare; however, the vectors may be transmitted to a nonendemic site and establish the infection in local insects or animals. These potential threats are listed in Table 19-2.

4. Intentionally released agents of bioterrorism such as anthrax, plague, smallpox, and others that could be surreptitiously released in aircraft and with incubation periods would not be detected until the passengers are dispersed throughout the receiving country. Most of the more likely threat agents are listed in Table 19-3.

Table 19-4 gives their common presenting signs and symptoms. More detailed descriptions of each disease can be found in standard medical references (4,5). Control measures, including isolation and personal protection, as well as currently recommended antibiotics should be used appropriately for each disease.

Approximately 50% of travelers to developing countries develop some illness during or after travel and approximately 8% seek medical attention (6). In a country the size of Australia, where 2,000,000 citizens travel overseas each year, this results in approximately 15,000 medical visits. Of course, gastrointestinal infections are most frequent, but various respiratory, cutaneous, and sexually transmitted diseases are also common. The most common life-threatening diagnoses are malaria, dengue, typhoid, amebiasis, and hepatitis. The diagnoses taking the longest time, on average, to manifest are TB, leprosy, and parasitic diseases such as Chagas disease, filariasis, and paragonimiasis. In fact, some do not manifest for months to years after travel. However, more than 90% of these infections (unless the traveler was resident for long periods in developing countries) will become manifest within 6 months of the exposure. Be aware that health problems in immigrants from the developing world often present in the opposite manner, with most infections appearing after 6 months in the new location.

PREVENTIVE ASPECTS OF TRAVEL MEDICINE

The best methods of prevention require education of the traveler and include common sense measures such as careful food selection (“cook it, peel it, boil it, or forget it”), hand washing, avoidance of contact with bodily fluids and lesions, mosquito netting and repellent use, and avoidance of heavily infested areas. Immunization remains the cornerstone of primary prevention of infectious disease. Travelers completing recommended pretravel immunization, such as hepatitis (A and B), yellow fever, rabies, tetanus, polio, measles, mumps, rubella, and varicella, are afforded highly effective protection against these common illnesses. However, other vaccines only reduce—but do not eliminate—the risk of illness, for example, typhoid, meningococcal, and cholera vaccines. Prophylactic medications are the mainstay against several diseases without available vaccines. Diseases with probably effective oral prophylaxis regimens other than vaccines include influenza, plague, leptospirosis, meningococcal meningitis (postexposure), and some types of traveler’s diarrhea. Malaria prophylaxis is complicated by regional variation in the presence of multidrug-resistant strains, and the latest recommendation for a region should be researched on websites of the Centers for Disease Control and Prevention (CDC), and the World Health Organization (WHO), or obtained by consultation with a travel medicine specialist before traveling to malarious areas of the world.

Travelers often take medications including antibiotics, purchased either prior to or while traveling, that profoundly alter the course of a disease and potentially mask common symptoms and signs and/or alter diagnostic tests. Toxic reactions may occur to readily available medicines obtained in unregulated areas, as well as drug fever or other reaction to many formulations. For example, sulfa-based drugs, used for prevention of altitude illness (acetazolamide), malaria treatment (sulfadoxine-pyramethamine), or diarrhea (trimethoprim sulfamethoxazole), may not only cause drug fever or rash but also potentially serious bone marrow suppression. The form and packaging of the tablet, capsule, or suspension obtained may not be readily identifiable using national drug formulary references.

TABLE 19-1

Infectious Agents Potentially Transmitted Among Passengers in Aircraft
Disease	Major Vector(s)	Person-to-person Spread	Infectivity	Incubation Period	Illness Duration	Untreated Lethality	Vaccine/Antisera Available?	Effective Antibiotics?	Common Geographic Location(s)
Respiratory Transmission
Influenza	Aerosol droplets; fluids	High	High	1-3 d	2-7 d	Low (except for very young and old)	Yes, but organism mutates easily	Antivirals	Worldwide, sometimes in pandemics
Melioidosis (Pseudomonas pseudomallei)	Aerosol	Rarely	High: 10-100 organisms	2 d-yr	4-20 d	Variable	No	Yes	Southeast Asia, Central and South America, and Caribbean
Plague (pneumonic Yersinia pestis)	Fleas (rats); aerosol	Moderately high	High: 100-500 organisms	2-3 d	1-7 d (usually 2-4 pneumonic)	Very high (˜100%)	Yes, but questionably effective for aerosol	Yes	Worldwide
Psittacosis (Chlamydia psittaci)	Aerosol (birds)	Very rarely	Moderate	4-15 d	Weeks to months	Very low	No	Yes	Worldwide
Q fever (Coxiella burnetti)	Food; aerosol (infected biologicals)	Very rarely	High: 1-10 organisms	10-40 d	2-14 d	Low	Yes	Yes	Worldwide
Smallpox	Contact with infected materials; aerosol	High	High: 10-100 organisms	7-17 d (usually 12)	4 wk (usually 1-2)	High	Yes	Experimental antivirals	Nowhere
Tuberculosis (Mycobacterium tuberculosis)	Aerosol (dust and droplets); milk	Yes	Moderate	4-12 wk for IPPD^a conversion	Years	Moderate if active disease	Yes (BCG^b is partially effective)	Yes, but lengthy course of multiple drugs	Worldwide
Blood or Body Fluid Transmission
Congo-Crimean hemorrhagic fever	Ticks; body fluids; aerosol	Moderate	High	3-12 d	Days to weeks	High (˜50%)	Experimental; antisera in Bulgaria	Yes	Europe, Africa, Central Asia, Middle East
Ebola virus	Body fluids; aerosol	Moderate	High	7-9 d	2-21 d	Very high (50%-90%)	No	No	Africa
Lassa virus	Body fluids; aerosol	Moderate	High	10-14 d	1-4 wk	Low to moderate (1% overall)	No; antisera experimental	Antivirals	Africa
Rift Valley fever	Mosquitoes; infected biologicals; aerosol	Low	High	2-5 d	Days to weeks	Low	Yes	No	Africa
Food and Fomite Transmission
Botulism (Clostridium botulinum)	Food, water; aerosol	No	LD₅₀ = 0.001 μm/kg for Type A	1-5 d	24-72 hr or longer	High	Yes	No	Worldwide
Clostridium perfringens	Food, water; aerosol	No	High	8-12 hr	24 hr	Low	No	No	Worldwide
Hepatitis A	Food; fecal	Yes	High	15-50 d (usually 4 wk)	1-2 wk	Very low	Yes	No	Worldwide
Salmonellosis (Salmonella sp)	Food; fecal	Yes	High	6-72 hr (usually 12-36)	1-3 d	Very low (except in very young and old)	No	Yes	Worldwide
Shigellosis (Shigella sp)	Food; fecal	Yes	High	12-96 hr	4-7 d	Low (except very young and old)	No	Yes	Worldwide
Staphylococcal enterotoxin B	Foods/aerosol	No	LD₅₀ = 0.03 μm/person incapacitating	1-12 hr	Hours to a week	Low: <1%	No, but under development	No	Worldwide
Typhoid fever (Salmonella typhi)	Food, water; fecal/urine	Rarely	Moderate	7-21 d	Weeks	Moderate (10%)	Yes	Yes	Worldwide
^aIPPD, intradermal purified protein derivative. ^bBCG, Bacille Calmette-Guérin.

TABLE 19-2

Characteristics of Vector-Borne Infections Potentially Transmitted in Aircraft
Disease	Major Vector(s)	Person-to-person Spread	Infectivity	Incubation Period	Illness Duration	Untreated Lethality	Vaccine/Antisera Available?	Effective Antibiotics?	Common Geographic Location(s)
Babesiosis (Babesia sp)	Ticks	No (transfusable)	High	1 wk-12 mo	Days to months	Low (except if asplenic)	No	Yes	North America, Europe
Bartonellosis (Bartonella bacilliformis)	Sand flies	No (transfusable)	High	16-22 d (up to 4 mo)	Days to weeks	High/moderate (10%-90%)	No	No	Peru, Ecuador, and Colombia (600-2800 m ASL)
Dengue fever	Mosquitoes; aerosol	No	High	3-14 d (usually 5-7)	Days to weeks	Low	Experimental	No	Tropics
Viral encephalities
Eastern equine encephalitis	Mosquitoes; aerosol	No	High: 10-100 organisms	5-10 d	1-3 wk	High	Yes	No	Americas
Russian spring-summer encephalitis	Milk; mosquitoes; aerosol	No	High: 10-100 organisms	8-14 d	Days to months	Moderate	Yes	No	Asia
Venezuelan equine encephalitis	Mosquitoes; aerosol	Low	High: 10-100 organisms	2-6 d	Days to weeks	Low	Yes	No	Americas
Western equine encephalitis	Aerosol	No	High: 10-100 organisms	1-20 d	1-3 wk	Low	Yes	No	Americas
Hanta pulmonary syndrome	Aerosol	No	Assumed moderate	3 d-2 mo (usually 2-4 wk)	9-17 d	High (40%-50%)	No	No	Southwest United States
Hemorrhagic fevers
Chikungunya	Aerosol	No	High	2-6 d	2 wk	Very low	Experimental	No	Southeast Asia, India
Korean (Hantaan)	Body fluids; aerosol	No	High	4-42 d	Days to weeks	Moderate	Experimental	No	Asia
Lassa	Body fluids; aerosol	Moderate	High	10-14 d	1-4 wk	Low to moderate (1% overall)	No; antisera experimental	Antivirals	Africa
Omsk	Water; aerosol	Rarely	High	3-7 d	7-10 d	Low	Experimental	No	Western Siberia
Leishmaniasis, cutaneous (Leishmania and Viannia sp)	Sand flies	Rarely	Assumed low	1 wk-mo	Months-1 yr	Low	No	Yes	South and Central America, Asia, Central Africa, Dominican Republic, Mediterranean basin
Leishmaniasis, visceral (Leishmania and Viannia sp)	Sand flies	Rarely	Assumed low	10 d-2 yr (usually 2-6 mo)	Can be prolonged	High	No	Yes	South and Central America, Asia, Central Africa, Dominican Republic, Mediterranean basin
Lyme disease (Borrelia burgdorferi)	Ticks	No (transfusable)	Low	3-32 d (first stage may be asymptomatic)	Weeks to years	Low	No	Yes	North America, Europe, Asia
Malaria (Plasmodium sp)	Mosquitoes	No (transfusable)	Low	7-30 d (depends on type and may be delayed)	Attacks: days; recurrences: years	Falciparum high; others low	No	Yes	Localized, but worldwide (see CDC^a website)
Relapsing fevers (Borrelia sp)	Ticks and lice	No	Low	5-15 d (usually 8)	1-10 relapses of 2-9 d of fever with 2-4 d between bouts	Low/moderate (10%)	No	Yes	Localized, but worldwide
Rift Valley fever	Mosquitoes; infected biologicals; aerosol	Low	High	2-5 d	Days to weeks	Low	Yes	No	Africa
Rocky mountain spotted fever (Rickettsia rickettsii)	Ticks	No	High	3-14 d	2-3 wk	High (25%)	No	Yes	The United States (April-September)
Tularemia (Francisella tularensis)	Mosquitoes, ticks, deerflies; infected biologicals; aerosol	No	High: 10-50 organisms	1-14 d (usually 3-5)	>2 wk	Moderate (10%)	Yes	Yes	North America, Asia, and Europe
Typhus (epidemic)	Lice	No	High	6-16 d	Weeks to months	High	No	Yes	Colder areas; especially during war or famine
Typhus (scrub)	Mites	No	High	4-15 d	6-21 d (usually 10-12)	Usually low; but some strains are 60%	No	Yes	Central, eastern and Southeast Asia, and South Pacific
Yellow fever	Mosquitoes; aerosol	No	High	3-6 d	1-2 wk	High, if jaundiced (50%), rest are moderate	Yes	No	Africa, South and Central America
^aCDC, Centers for Disease Control and Prevention.

TABLE 19-3

Characteristics of Bioterrorist Agents Potentially Released in Aircraft
Disease	Major Vector(s)	Person-to-person Spread	Infectivity	Incubation Period	Illness Duration	Untreated Lethality	Vaccine/Antisera Available?	Effective Antibiotics?	Common Geographic Location(s)
Anthrax	Deliberate or accidental aerosol	No	Moderate: 8,000-50,000 spores	1-6 d	3-5 d	High (pulmonary)	Aerosol 200 LD₅₀ efficacy in monkeys; antisera experimental	Yes, but only effective early	Worldwide
Brucellosis	Deliberate aerosol or in food supply (raw milk)	No	High: 10-100 organisms	5-60 d (usually 1-2 mo)	Weeks to years	Low <5%	No	Yes, but limited effectiveness	Worldwide
Venezuelan equine encephalitis	Mosquitoes; aerosol	Low	High: 10-100 organisms	2-6 d	Days to weeks	Low	Yes	No	Americas
Congo-Crimean	Ticks; body fluids; aerosol	Moderate	High	3-12 d	Days to weeks	High (˜50%)	Experimental; antisera in Bulgaria	Yes	Europe, Africa, Central Asia, Middle East
Ebola	Body fluids; aerosol	Moderate	High	7-9 d	2-21 d	Very high (50%-90%)	No	No	Africa
Korean (Hantaan)	Body fluids; aerosol	No	High	4-42 d	Days to weeks	Moderate	Experimental	No	Asia
Plague (pneumonic)	Fleas (rats); aerosol	High	High: 100-500 organisms	2-3 d	1-7 d (usually 2-4 pneumonic)	Very high (˜100%)	Yes, but questionably effective for aerosol	Yes	Worldwide
Q fever	Food; aerosol (infected biologicals)	Rarely	High: 1-10 organisms	10-40 d	2-14 d	Low	Yes	Yes	Worldwide
Smallpox	Contact with infected materials; aerosol	High	High: 10-100 organisms	7-17 d (usually 12)	4 wk (usually 1-2)	High	Yes	No	Nowhere
Toxins
Botulism	Food, water; aerosol	No	LD₅₀ = 0.001 μm/kg for Type A	1-5 d	24-72 hr or longer	High	Yes	No	Worldwide
Clostridium perfringens	Food, water; aerosol	No	High	8-12 hr	24 hr	Low	No	No	Worldwide
Staphylococcal enterotoxin B	Foods/aerosol	No	LD₅₀ = 0.03 μm/person incapacitating	1-12 hr	Hours to a week	Low: <1%	No, but under development	No	Worldwide
Tuberculosis	Aerosol (dust and droplets); milk	Yes	Moderate	4-12 wk for IPPD^a conversion	Years	Moderate if activated	Yes (BCG^b)	Yes, but lengthy course of multiple drugs	Worldwide
Tularemia	Mosquitoes, ticks, deerflies; infected biologicals; aerosol	No	High: 10-50 organisms	1-14 d (usually 3-5)	>2 wk	Moderate (10%)	Yes	Yes	North America, Asia, and Europe
Typhoid fever	Food, water; fecal/urine	Rarely	Moderate	7-21 d	Weeks	Moderate (10%)	Yes	Yes	Worldwide
Typhus (epidemic)	Lice	No	High	6-16 d	Weeks to months	High	No	Yes	Colder areas; especially during war or famine
Typhus (scrub)	Mites	No	High	4-15 d	6-21 d (usually 10-12)	Usually low; but some strains are 60%	No	Yes	Central, eastern and Southeast Asia, and South Pacific
Yellow fever	Mosquitoes; aerosol	No	High	3-6 d	1-2 wk	High, if jaundiced (50%), rest are moderate	Yes	No	Africa, South and Central America
^aIPPD, intradermal purified protein derivative. ^bBCG, Bacille Calmette-Guérin.