Perspectives: The Role of the Traveler in Translocation of Disease
Since people began moving from one place to another, they have offered free passage to microorganisms on themselves, in their belongings, or on their conveyances. The consequences of such microbial hitchhiking have, at times, altered the course of history. Among the more notable examples are the great plagues that swept into Europe from Asia during the Middle Ages, the introduction of smallpox to the Americas by European explorers, and the reverse movement of syphilis into Europe in those same returning explorers.
Although the movement of pathogens by travelers is not a new phenomenon, today’s increasing pace and scale of global human movement have enhanced the opportunities and speed for disease spread. HIV infection, which generally takes years for symptoms to develop, spread to every corner of the world less than a decade after it was recognized in the early 1980s. In the 21st century, no place on earth is more than a day from any other location. Even diseases with short incubation periods have unprecedented opportunities for rapid spread through human movement. What follows are vivid examples of this phenomenon from the last several years that demonstrate how crucial travel has become to the spread of emerging diseases. They also remind us that all travelers, regardless of the purpose, duration, or distance of the journey, should take steps to prevent bringing more than luggage to and from their destinations.
MIDDLE EAST RESPIRATORY SYNDROME (MERS)
MERS was first identified in September 2012 by Dutch researchers who analyzed specimens from a Saudi Arabian patient who had died of severe pneumonia. The same month, a second case of this disease was diagnosed in a Qatari citizen with pneumonia. Thus after only 2 cases, it became clear that MERS could spread through international travelers. This phenomenon has since been seen repeatedly. Even though all known cases of MERS have been linked to exposure in countries on or near the Arabian Peninsula, through mid-2014 MERS has been diagnosed among travelers in other parts of the Middle East, Europe, North Africa, Asia, and North America (Map 1-01). Some of these travel-associated cases have resulted in limited person-to-person transmission.
MERS is caused by a newly recognized coronavirus; the earliest confirmed human cases occurred in a cluster of respiratory illnesses at a hospital in Zarga, Jordan, in April 2012. MERS represents the second coronavirus to cause a major global health concern in the last 10 years. In 2003, the severe acute respiratory syndrome (SARS) coronavirus produced a transcontinental outbreak that resulted in 8,098 illnesses with a case-fatality ratio of 9.5% before ending later that year. In one of the most astonishing examples of how travel can promote disease spread, the global dissemination of SARS occurred through just 10 guests of a Hong Kong hotel whose stay overlapped with that of a Chinese physician who was ill during his stay and quickly died of the disease. After their exposure but before illness onset, the 10 hotel guests boarded planes bound for different countries, igniting major chains of transmission at destinations as far away as Toronto, Canada.
SARS and MERS both may cause an acute respiratory illness characterized by severe pneumonia (although milder infections have been described), both have been transmitted in hospital settings (including to health care workers), and both have overlapping age distributions in adults with few infections found in children. However, MERS has proven to be more lethal. Among the first 837 laboratory-confirmed cases of MERS, a total of 291 (34.8%) have died from the illness.
Efforts are underway to understand the source and mode of transmission of MERS to humans. Serologic investigations have found the MERS coronavirus and similar coronaviruses are widely distributed in camels. Some people who later developed MERS had exposure to camels that had detectable MERS virus, which suggests that camels may play a role in spreading the virus or may even be an animal reservoir. Understanding risk factors for exposure is critical to developing preventive and therapeutic strategies, especially given that the Middle East is a hub for global travel, including tourism, a substantial foreign workforce, and the pilgrimage to Mecca and other religious events that bring millions of visitors to Saudi Arabia annually. Travel to areas affected by MERS offers major opportunities for ongoing international spread of this disease.
The last few years have been notable for a steady stream of newly recognized influenza A viruses causing human disease. This trend has implications for all international travelers. The most high-profile example is the 2009 variant of influenza A (H1N1) that produced the first flu pandemic of the 21st century. This virus initially appeared in early 2009 in central Mexico, where it caused a sizeable outbreak of respiratory disease. But it was not recognized as a new flu variant until it crossed over the US border in April 2009 and the first cases appeared in southern California. The virus proved to be easily transmissible, especially among children, affording rapid spread. After recognition, travelers with pandemic H1N1 who had visited Mexican tourist destinations were quickly detected elsewhere in the world, and an analysis of air traffic patterns found a strong correlation between the volume of air travel from Mexico and the likelihood that H1N1 was identified in a destination during the early stages of the pandemic. Through travelers, the virus quickly spread globally, and within only 2 months the outbreak was designated a pandemic by the World Health Organization. Although the pandemic has come and gone, the virus remains in circulation as the seasonal influenza A (H1N1) subtype and was the predominant influenza strain in the United States in 2013–2014.
Avian influenza A (H5N1) has also been a major global concern, although its epidemiologic features have been considerably different than the pandemic virus and less affected by travel. This virus first produced a limited-scale outbreak in Hong Kong in 1997, and then no human illness from H5N1 was seen for several years. The virus resurfaced in Vietnam and Thailand in 2003 and has been in continuous circulation in poultry and wild birds ever since. Since 2003, human disease has been relatively infrequent, with only 650 confirmed cases reported through the end of 2013. However, people in whom there is a recognized case of H5N1 infection almost always have severe pneumonia, and the disease has an overall case-fatality ratio of 59%. This figure is even more remarkable in light of the fact that most cases have been in children and young adults (median age 18 years). Most deaths from seasonal influenza occur in the elderly.
The virus has been found in birds in >60 countries encompassing parts of Asia, Europe, the Middle East, and Africa, and international movement in conveyances and animals has been documented and may explain some of its geographic spread. The 3 countries with the most human illnesses (Indonesia, Vietnam, and Egypt) account for 76% of all cases and are all major tourist destinations, although to date no tourism-associated illnesses have been identified in international visitors to these countries. This is because close contact with infected poultry is generally considered necessary for exposure; sustained human-to-human transmission has not been observed. In January 2014, the first H5N1 illness was documented in North America in a Canadian citizen who had traveled to Beijing for a 3-week visit and became ill with pneumonia and encephalitis on the way home. The patient, who died, had no known history of poultry exposure while in Beijing and the source of infection is unknown. This case demonstrates that H5N1 can be a risk for travelers, reinforcing the recommendation to avoid contact with live poultry in areas affected by this virus.
The third major influenza virus to recently emerge is avian influenza A (H7N9). This virus was first detected as a cause of human illness in March 2013 in eastern China, with cases seen in Shanghai and adjacent provinces. The number of identified cases rose sharply over the spring of 2013, then diminished until a second wave of infections occurred during the winter and spring of 2014. Through early April 2014 a total of 418 confirmed cases had been identified, with a 30% case-fatality ratio. People reported to have H7N9 infection have been considerably older (mean age of 55 years) than those reported to have H5N1.
Most avian influenza viruses that have been linked to human disease have also produced large-scale die-offs in poultry (they are highly pathogenic viruses). Therefore, poultry outbreaks allow the identification of locations where humans are at risk of exposure and infection. In contrast, H7N9 does not exhibit this characteristic, making it very difficult to know where and when it is circulating. To date, almost all cases have occurred in people in eastern and southern China, with illness often linked to exposure to live poultry in wet markets. Cases have been identified in Hong Kong and Taiwan among travelers to and from affected areas of mainland China. In addition, a Chinese traveler was diagnosed with the disease while on a visit to Malaysia.
Exotic mosquito-transmitted infections, particularly malaria and dengue fever, have long been major travel health concerns. Compounding the challenges of vectorborne diseases to travelers, a number of mosquito-transmitted viruses have recently expanded their geographic range through movement in infected mosquitoes, infected reservoir hosts such as birds, or infected people. The most notable contemporary example is the translocation of West Nile virus into the Western Hemisphere in 1999. Since an apparent single introduction into New York City, the virus has relentlessly spread throughout most of the Western Hemisphere and now produces disease annually throughout the mainland United States.
Chikungunya is a less well-known virus that, like West Nile virus before it, has recently become established in the Western Hemisphere. First identified in Tanzania in the 1950s, chikungunya causes fever accompanied by severe muscle and joint pain. Until the 21st century, chikungunya virus was largely confined to east Africa and Asia, where it produced small, localized outbreaks of disease. Beginning in 2005, it began to spread across the islands of the Indian Ocean to the Indian subcontinent, producing massive outbreaks involving hundreds of thousands of people in locations such as Réunion, Mauritius, and southern India. The transmission cycle of this virus includes only mosquitoes and humans, and infected travelers likely contribute to the movement of this virus. This was confirmed when the virus was introduced to Italy in 2007 through an infected traveler from India, resulting in 205 locally acquired cases in several adjacent towns near Ravenna on the Adriatic Coast. Local transmission of chikungunya also occurred in southeast France in 2010 but did not persist in either of the European locations. Chikungunya also spread eastward into other parts of Asia and even the western Pacific Islands, where locally acquired human disease has occurred.
Over the last few decades, cases of chikungunya have been occasionally diagnosed in the Western Hemisphere among travelers to or from affected areas (especially south Asia). But until late 2013, there was no evidence of local acquisition in the Western Hemisphere until disease suddenly appeared on the French side of the island of Saint Martin in the Caribbean, a major tourist destination, in people with no travel history. From what appears to be a single introduction, chikungunya has hopscotched across the islands of the Caribbean and even to the mainland of South and Central America, producing local outbreaks of disease. As of August 2014, locally acquired human illness has been detected in the Caribbean as far north as the Bahamas, and travel-associated cases have been detected elsewhere, including >600 in the United States (mainly Florida). Less than a year after its introduction, almost 600,000 confirmed and suspected cases of chikungunya have been reported from the Caribbean, with the largest number of cases in the Dominican Republic, Haiti, and on the French islands of Guadeloupe and Martinique. As of August 2014, 6 locally acquired cases of chikungunya have been reported in the United States, all in south Florida. These findings illustrate the potential for chikungunya to become established in some areas of the North American mainland.
CHOLERA IN THE CARIBBEAN
In October 2010, cholera unexpectedly appeared in Haiti for the first time in recorded history. The cholera outbreak struck 10 months after the devastating January 2010 Haiti earthquake, which killed an estimated 316,000 people. The Vibrio cholerae strain (toxigenic serogroup O1, serotype Ogawa, biotype El Tor) responsible for the outbreak did not genetically resemble the Latin American outbreak strain that appeared in the early 1990s or strains occasionally found along the coast of the Gulf of Mexico. Instead, it closely resembled strains that had been recently circulating in south Asia and Africa. Among the hypotheses to explain how the organism arrived in Haiti included the potential inadvertent introduction of cholera by Nepalese troops serving as part of the United Nations peacekeeping force housed upstream of the area where the first cases were recognized. Given Haiti’s widespread poverty, poor sanitation, and population displacement in the aftermath of the earthquake, cholera spread rapidly. In just weeks, thousands of cases were occurring throughout the country, and the outbreak has persisted with gradually decreasing intensity despite efforts to improve sanitary measures. As of August 2014, >700,000 cases of cholera, including almost 400,000 hospitalizations and 8,579 (1.2%) deaths, had been reported from Haiti, which has a population of only about 10 million people. Cholera has also spread to other countries in the region, in particular the Dominican Republic, which shares the island of Hispaniola with Haiti and saw its first cases in November 2010. Since then, more than 31,000 cases have been reported by the Dominican Republic. In 2012, cholera was recognized in Cuba, where >700 cases have been seen, and in the fall of 2013 it was reported in Mexico along the coastal Gulf of Mexico, where 187 cases were identified. Cholera has been detected in other countries in travelers to or from Haiti, including in the United States, but these other locations generally have good sanitation infrastructure and the risk of local spread is considered low.
CHILDHOOD VACCINE-PREVENTABLE DISEASES
Vaccination programs are considered among the most cost effective of public health interventions and have substantially reduced the global prevalence of childhood infectious diseases. In the United States, year-round indigenous measles and rubella transmission were declared eliminated in 2000 and 2004, respectively, and the incidence of diseases such as mumps and rubella is dramatically decreased compared with their incidence in the prevaccine era. The region of the Americas is certifying regional elimination of measles and rubella. Poliomyelitis is the second vaccine-preventable disease (after smallpox) targeted to be intentionally eradicated; in early 2014 India was certified as polio-free by the World Health Organization. However, most vaccine-preventable diseases are highly transmissible and can easily spread in unvaccinated travelers who become infected. The importance of travelers in the spread of vaccine-preventable diseases is evidenced by importations and associated outbreaks of measles in the United States every year and importations of wild poliovirus into Equatorial Guinea and Brazil.
Outside the Western Hemisphere, measles continues to circulate because of low vaccination coverage. In the United States, measles cases and outbreaks continue to be reported, despite measles being declared eliminated. Unvaccinated US residents traveling abroad, international visitors, and overseas adoptees have become infected while abroad and have brought the virus to the United States. These importations have ignited domestic outbreaks at the local level because of suboptimal levels of population immunity in some US communities, particularly in areas where parents elect not to vaccinate their children for religious, philosophical, or personal reasons. From 2001 through 2008, the reported median number of measles cases identified in the United States (56 cases per year) was low, but the number of cases has since risen sharply. In 2011, a total of 220 cases of measles were reported. Among these cases, 90% were linked to importation (the source for the remaining 10% could not be established). During 2014, the United States has had the highest number of reported measles cases since 1994; by August 22, 592 measles cases had been reported. In 2014, 99% of cases were associated with importation (the remainder had unknown source) from at least 18 countries. Among 49 instances of direct importation (the source case for an outbreak), 45 (92%) involved US residents returning from abroad (49% from the Philippines), while the other 5 (8%) were foreign visitors to the United States. The largest outbreak (378 cases) started when members of an Amish community were infected while visiting the Philippines (where a large outbreak of measles was occurring at the time), returned to Ohio, and introduced measles into Amish communities with low vaccination coverage.
In February 2014, an outbreak of measles occurred in Europe on a cruise ship sailing the western Mediterranean. A total of 27 cases (22 confirmed and 5 probable cases) of measles were identified, mostly among the crew. However, 4 passengers, including 2 infants, also contracted the disease. The virus strain responsible for the cruise ship outbreak is similar to measles viruses circulating in the Philippines.
In 1988, the World Health Assembly targeted poliomyelitis for eradication. Through the use of large-scale vaccination campaigns, by 2012 this goal appeared to be in sight, as only 223 cases of wild-type polio were reported from 5 countries, and the disease was endemic in only 3 countries (Afghanistan, Nigeria, and Pakistan). However, in 2013, the number of cases rose by 86% (to 414 cases), mostly in Pakistan. Polio was also identified in 5 countries in the Middle East and Africa, where it had not recently circulated. These countries include Syria and Somalia, locations marked by civil and humanitarian crises. The appearance of polio in these locations most likely represents importation through travel from an endemic country. In the early part of 2014, the number of identified cases had more than doubled (from 34 to 82) compared with the same period of 2013, and disease was identified in 2 additional countries (Iraq and Equatorial Guinea). As a result, on May 5, 2014, the World Health Organization declared polio to represent a public health emergency of international concern under the International Health Regulations and recommended that countries known to be exporting polio (Pakistan, Syria, and Cameroon) ensure departing residents and long-term visitors receive a dose of polio vaccine before travel and encouraged countries where the virus was present but there was no evidence of exportation to implement similar policies.
These examples highlight the diversity of opportunities for microbial movement afforded by travel, and the pivotal role travel has played in many of today’s major emerging disease threats. No amount of vigilance is likely to eliminate such opportunities, especially since microbes can be silent travelers. However, all travelers should be knowledgeable about the risks at their destinations and take precautions to prevent the spread of disease.
Map 1-01. Distribution of confirmed cases of Middle East Respiratory Syndrome by reporting country1
1Adapted from Figure 2 in: European Centre for Disease Prevention and Control. Epidemiological update: Middle East respiratory syndrome coronavirus (MERS-CoV). 5 Nov 2014 [cited 12 Nov 2014]. Available from: http://www.ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx....
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Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official recommendations contained in the book. The views and opinions expressed in this section are those of the author and do not necessarily represent the official position of CDC.
Stephen M. Ostroff