Chapter 3Infectious Diseases Related To Travel
Influenza (Seasonal, Zoonotic, & Pandemic)
Margaret McCarron, David K. Shay
Influenza in humans is caused by infection with influenza viruses; these viruses can be divided into 3 types: A, B, and C. Only types A and B cause widespread illness in humans. Influenza A viruses are further classified into subtypes on the basis of 2 surface proteins: hemagglutinin (H) and neuraminidase (N). Both influenza A and B viruses undergo continual minor antigenic change (antigenic drift), but influenza B viruses evolve more slowly and are not divided into subtypes. Only influenza A viruses demonstrate major changes (antigenic shift), in which at least the H or the H and N are replaced and a new influenza A virus with pandemic potential can result. New influenza A viruses that may emerge and spread among humans may be the result of an animal-origin influenza virus that jumps from animals to humans or the result of an influenza virus that has a new constellation of genes derived through reassortment of 2 different influenza A viruses. Influenza A (H1N1), A (H3N2), and influenza B viruses circulate globally among humans.
In April 2009, a novel A (H1N1) virus of swine origin was detected in North America. This virus is a reassortant virus, containing a combination of influenza virus gene segments not previously seen in either animal or human influenza viruses. The virus gene segments were most closely related to genes from contemporary influenza viruses circulating in North American pigs and Eurasian pigs. Contemporary North American lineage swine influenza viruses are triple reassortant viruses containing genes from human, swine, and avian influenza virus lineages, and Eurasian lineage swine influenza viruses are most closely related to Eurasian avian lineage viruses. Thus, multiple reassortant events and transmissions between animal species and humans predated the emergence of this new pandemic strain. The spread of this new virus, which was later called 2009 pandemic influenza A (H1N1) virus, resulted in a worldwide influenza pandemic.
MODE OF TRANSMISSION
Traditionally, influenza viruses have been thought to spread from person to person, primarily through large-particle respiratory droplet transmission (such as when an infected person coughs or sneezes near a susceptible person). Transmission via large-particle droplets requires close contact between the source and the recipient, because droplets generally travel only short distances (approximately ≤6 ft) through the air, but then settle out of the air. Indirect contact transmission via hand transfer of influenza virus from virus-contaminated surfaces or objects to mucosal surfaces of the face (nose, mouth) may also occur. Airborne transmission via small-particle aerosols in the vicinity of the infectious person may also occur; however, the relative contribution of the different modes of influenza transmission is unclear. All respiratory secretions and bodily fluids, including diarrheal stools, of patients with influenza should be considered infectious; however, the predominant source of infection is respiratory secretions. Viable influenza virus is rarely detected in blood or stool of infected patients. Most healthy adults who are ill with influenza may shed virus and be infectious to others from the day before symptom onset to 5–7 days after symptom onset; children, severely immunocompromised people, and more severely ill people, including those who are hospitalized, may shed influenza virus for ≥10 days after the onset of symptoms.
Infection with seasonal influenza viruses is common. In temperate climates, most cases occur during the winter months. The influenza season in the Northern Hemisphere may begin as early as October and can extend until May, and the influenza season in the Southern Hemisphere may begin in April and last through September. In tropical and subtropical areas, infection with influenza virus may occur throughout the year.
CDC estimates that from 1976 through 2006, annual seasonal influenza-associated deaths in the United States ranged from a low of approximately 3,000 people to a high of approximately 49,000 people; about 90% of these deaths occur among people aged ≥65 years. Influenza virus infections can cause disease in all age groups. Infection rates are highest among infants and children, while rates of severe illness (including death) are highest among people aged ≥65 and people of any age who have underlying medical conditions that place them at increased risk for complications. Children aged <2 years have rates of influenza-related hospitalization that are as high as those in the elderly.
Influenza A viruses circulate in many different animal populations. The primary reservoirs for influenza A viruses of all subtypes are wild birds. Influenza viruses found in birds are typically referred to as avian influenza viruses. Influenza A viruses are also endemic in pigs globally and in horses in many countries. Other animal species may also become infected with influenza A viruses, including domestic poultry and marine mammals. During the 2009 pandemic, infections of domesticated cat and dogs, ferrets, turkeys, a cheetah, and other animals were also reported.
Human infections with animal-origin viruses are uncommon, but they occur. Before the 2009 H1N1 pandemic, occasional swine influenza infections among humans were reported in the United States and elsewhere. In addition, more than 500 human infections with highly pathogenic avian influenza A H5N1 (HPAI-H5N1) have been reported globally since 2003. Human infections with HPAI-H5N1 are particularly concerning because of the high case-fatality ratio of approximately 60% and because this virus is widespread among poultry in some countries in Asia and the Middle East. Thus far, however, the spread of HPAI-H5N1 viruses from one ill person to another has been reported rarely and has thus far been limited, inefficient, and unsustained. Human infections with other avian influenza viruses have also included avian H7N7, H7N2, and H9N2. No sustained transmission of these other avian influenza viruses has been documented, but these viruses, along with H5N1, still have the potential to result in a pandemic.
A global pandemic was declared by the World Health Organization after 30,000 confirmed cases of 2009 pandemic influenza A (H1N1) virus had been reported from 74 countries. The virus spread from North America to the rest of the world. Severe illness resulting from infection with this virus was associated with risk factors such as chronic medical conditions, immunosuppression, pregnancy, young age, morbid obesity, and being a member of an indigenous population. However, in contrast to the epidemiology of seasonal influenza, CDC estimates that almost 90% of deaths from this virus occurred among people aged <65 years. The 2009 pandemic influenza A (H1N1) virus continues to circulate and was included as a component of the 2010–11 seasonal influenza vaccine.
Uncomplicated influenza illness is characterized by the abrupt onset of constitutional and respiratory signs and symptoms (such as fever, myalgia, headache, malaise, nonproductive cough, sore throat, vomiting, and rhinitis), typically occurring 1–4 days after exposure. However, many people will not have fever. Among children, nausea, vomiting, and diarrhea also can occur with influenza illness. Influenza illness typically resolves within 1 week for most people, although cough and malaise can persist for >2 weeks. A list of people who are at high risk of developing complications of influenza can be found on the CDC website at www.cdc.gov/flu/about/disease/high_risk.htm.
Respiratory illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone. The predictive value of clinical definitions can vary, depending on the degree of circulation of other respiratory pathogens and the background level of influenza activity. Among studies conducted with children and adults, the positive predictive value of clinical signs and symptoms for laboratory-confirmed influenza virus infection has ranged from 30% to 88%. Laboratory testing can aid in diagnosis. Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, immunofluorescence assays, and RT-PCR. Sensitivity and specificity of any test for influenza might vary by the laboratory that performs the test, the type of test used, and the type of specimen tested. Among respiratory specimens for viral isolation or rapid detection, nasopharyngeal specimens are typically more effective than throat swab specimens.
Most patients with clinical illness consistent with uncomplicated influenza who reside in an area where influenza viruses are circulating do not require diagnostic influenza testing for clinical management. Patients who should be considered for influenza diagnostic testing include:
- Hospitalized patients with suspected influenza
- Patients for whom a diagnosis of influenza will inform decisions regarding clinical care, infection control, or management of close contacts
- Patients who died of an acute illness in which influenza was suspected
When a decision is made to use antiviral treatment for influenza, treatment should be initiated as soon as possible, without waiting for influenza test results, since antiviral treatment is most effective when administered as early as possible in the course of illness. The sensitivities of rapid influenza diagnostic tests and immunofluorescence assays are lower than those of RT-PCR tests and viral culture. Thus, a negative rapid test or immunofluorescence test result does not rule out influenza virus infection, and clinicians should not rely on a negative test to make decisions about treatment. CDC’s current information on influenza diagnosis can be found on the CDC website (www.cdc.gov/flu/professionals/diagnosis).
Influenza-specific antiviral drugs are adjuncts to the influenza vaccine. Empiric antiviral treatment is recommended, as early as possible, for any patient with confirmed or suspected influenza who has severe, complicated, or progressive illness, is hospitalized, or is at higher risk for influenza complications.
When indicated, antiviral treatment should be started as soon as possible after illness onset. While the most benefit is seen when antiviral treatment is started within 48 hours of illness onset, antiviral treatment may still be beneficial when started 3–4 days after illness onset, especially in people at high risk for influenza complications.
CDC recommends 2 neuraminidase inhibitors: oseltamivir and zanamivir. CDC makes revisions to antiviral recommendations periodically, in response to new data on antiviral resistance patterns among circulating strains and risk factors for influenza complications. For up-to-date antiviral recommendations, visit www.cdc.gov/flu/antivirals. People at increased risk for complications of influenza should discuss antiviral treatment and chemoprophylaxis issues with their physician before travel, if traveling to areas where influenza virus is circulating.
The effectiveness of antivirals for treating H5N1 virus infections has not been fully studied, although evidence from countries where H5N1 has caused most human cases indicates that early treatment has been associated with lower risk of death. For more information about influenza antiviral drugs, see the Avian Influenza A Virus Infections of Humans webpage at www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm.
PREVENTIVE MEASURES FOR TRAVELERS
Indications for Use
Annual vaccination of all people aged ≥6 months is recommended by CDC and the Advisory Committee on Immunization Practices (ACIP) as the most effective way to prevent influenza and its complications. Vaccination of pregnant women and household contacts of children aged <6 months can also reduce the risk of influenza in these children who are too young to receive influenza vaccination.
Travelers who want to reduce their risk of influenza should receive influenza vaccination ≥2 weeks before departure. Travelers who are part of large tourist groups may be exposed to influenza at any time of year through exposure to travelers from areas of the world where influenza viruses are circulating; data from cruise ships have shown that, as with other close contact environments, these settings can facilitate the transmission of influenza from person to person or through contact with contaminated environmental surfaces.
Two types of influenza vaccines are available for use in the United States: trivalent inactivated vaccine (TIV), administered by intramuscular injection, and trivalent live, attenuated influenza vaccine (LAIV), administered by nasal spray. LAIV is approved for use only in healthy people aged 2–49 years who are not pregnant.
In the United States, universal annual influenza vaccination is recommended by the ACIP for all US residents aged ≥6 months. Annual recommendations are published by CDC, including information about the season’s vaccine composition, dosage and administration, and recommendations for specific populations. Current recommendations are available on the CDC website at www.cdc.gov/flu/professionals/acip/index.htm.
Vaccine Safety and Adverse Reactions
The most frequent side effects of vaccination with TIV are soreness and redness at the vaccination site that last up to 2 days. These local reactions generally are mild and rarely interfere with the ability to conduct usual daily activities. Fever, malaise, myalgia, and other systemic symptoms can occur uncommonly after vaccination and may more often affect people who have had no previous exposure to the influenza virus antigens in the vaccine (such as young children). These reactions can begin 6–12 hours after vaccination and can persist for 1–2 days. A high-dose TIV is an option for people aged ≥65 years. More information on influenza vaccine safety can be accessed on the CDC website (www.cdc.gov/mmwr/pdf/rr/rr5908.pdf).
The most frequent side effects reported in healthy adults include runny nose or nasal congestion (28%–78%), headache (16%–44%), and sore throat (15%–27%). Some children and adolescents have reported runny nose, headache, fever, vomiting, myalgia, and wheezing. These symptoms, particularly fever, are associated more often with the first dose and are self-limited.
LAIV may result in an increase in asthma or reactive airway disease in children aged <5 years. LAIV should not be administered to any children aged <2 years or to children aged 2–4 years who have a history of wheezing in the past year or who had a diagnosis of asthma. People aged 5–49 years who have conditions that increase the risk of severe influenza, including pregnancy, should receive TIV and not LAIV.
Precautions and Contraindications
Immediate reactions (such as hives, angioedema, allergic asthma, and systemic anaphylaxis) rarely occur after influenza vaccination. These reactions probably result from hypersensitivity to some vaccine component; most reactions likely are caused by residual egg protein and occur among people who have severe egg allergy. People who have developed hives, have had swelling of the lips or tongue, or have experienced acute respiratory distress or collapse after eating eggs should consult a physician for appropriate evaluation to determine if vaccine should be administered. People who have documented IgE-mediated hypersensitivity to eggs, including those who have had occupational asthma or other allergic responses due to exposure to egg protein, may also be at increased risk for reactions from influenza vaccine, and a similar consultation should be advised. Protocols have been published for safely administering influenza vaccine to people with egg allergies. There is some evidence of local hypersensitivity reactions to vaccines containing the preservative thimerosal, which is used as the preservative in multidose vials of inactivated influenza vaccine.
Personal Protection Measures
Measures that may help prevent influenza infection and other infections during travel include washing hands often with soap and water (where soap and water are not available, using an alcohol-based hand cleaner); avoiding touching one’s eyes, nose, and mouth; avoiding close contact with sick people; avoiding contact with others while sick; and covering coughs and sneezes with a tissue, then disposing of the tissue.
- Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI. Adamantane resistance among influenza A viruses isolated early during the 2005–2006 influenza season in the United States. JAMA. 2006 Feb 22;295(8):891–4.
- CDC. Estimates of deaths associated with seasonal influenza—United States, 1976–2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057–62.
- CDC. Role of laboratory diagnosis of influenza. Atlanta: CDC; 2010 [cited 2010 Aug]. Available from: http://www.cdc.gov/flu/professionals/diagnosis/labrole.htm.
- Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Jun 18;360(25):2605–15.
- Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1–60.
- Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, Singleton JA, et al. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm Rep. 2010 Aug 6;59(RR-8):1–62.
- Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N Engl J Med. 2009 Nov 12;361(20):1935–44.
- World Health Organization. Influenza A (H1N1) virus resistance to oseltamivir—2008 influenza season, Southern Hemisphere. Geneva: World Health Organization; 2008 [updated 2008 Jul 18; cited 2010 Oct 19]. Available from: http://www.paho.org/common/Display.asp?Lang=E&RecID=11596.
- World Health Organization. New influenza A (H1N1) virus: global epidemiological situation, June 2009. Wkly Epidemiol Rec. 2009 Jun 19;84(25):249–57.
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