Chapter 3 Infectious Diseases Related to Travel
Scott Epperson, Joseph Bresee
Influenza is caused by infection of the respiratory tract with influenza viruses, which are classified into 3 types: A, B, and C. Only virus types A and B commonly cause illness in humans. Influenza A viruses are further classified into subtypes based on 2 surface proteins, hemagglutinin (H) and neuraminidase (N). Although 3 types and subtypes of influenza virus cocirculate in humans worldwide (influenza A(H1N1)pdm09, A (H3N2), and influenza B viruses), the distribution of these viruses can vary from year to year and between geographic areas and time of year. Information on circulating virus strains in various regions can be found via CDC (www.cdc.gov/flu/weekly/) or the World Health Organization (www.who.int/topics/influenza/en/). Avian and swine influenza viruses can occasionally infect and cause disease in humans, usually associated with close exposure to infected animal populations. Notably, avian influenza A (H5N1) and A (H7N9) have led to sporadic human cases in recent years, and swine-origin A (H3N2) variant viruses have been associated with disease in the United States.
Influenza viruses spread from person to person, primarily through 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 feet or less) through the air, before settling onto surfaces. Airborne transmission via small-particle aerosols in the vicinity of the infectious person may also occur. Indirect transmission can also occur when a person touches a virus-contaminated surface and then touches his or her face. However, the relative contribution of the different modes of transmission to the spread of influenza viruses is unclear.
Most adults who are ill with influenza shed the virus in the upper respiratory tract and are infectious from the day before symptom onset to approximately 5–7 days after symptom onset. Ninety-five percent of virus transmission occurs within 3 days after illness onset. Children and those who are immunocompromised or severely ill, including those who are hospitalized, may shed influenza virus for 10 days or more after the onset of symptoms. Seasonal influenza viruses have rarely been detected from nonrespiratory sources such as stool or blood.
Influenza circulation varies geographically. The risk for exposure to influenza during travel depends on the time of year and destination. In temperate regions, influenza typically circulates at higher levels during colder winter months: October to May in the Northern Hemisphere and April to September in the Southern Hemisphere. In tropical or subtropical regions, although influenza activity may peak during rainy or dry seasons, or even have 2 annual peaks, year-round circulation is commonly observed.
Influenza virus can cause disease in all age groups. Infection rates are typically highest in children, especially in school-aged children. Rates of severe illness and death are typically highest among people aged ≥65, children <2 years, and people of any age who have underlying medical conditions that place them at increased risk for complications of influenza. Children aged <2 years have rates of influenza-associated hospitalizations that are as high as those in the elderly, although with much lower death rates. CDC estimates that from 1976 through 2006, annual influenza-associated deaths in the United States ranged from a low of approximately 3,000 people to a high of approximately 49,000 people; approximately 90% of these deaths occurred among people aged ≥65 years.
Although influenza B viruses circulate only among humans, influenza A viruses circulate among many animal populations. The primary reservoir for influenza A viruses is wild waterfowl. Influenza A viruses can also be found in other animal species, such as poultry, cats, dogs, horses, sea lions, and bats.
Human infections with animal-origin influenza A viruses are uncommon, but they do occur. In the United States, human influenza illnesses caused by swine-origin influenza A viruses (called “variant” influenza virus infections) have been sporadically identified. In 2012, a large number of human illnesses caused by an influenza A(H3N2) variant virus were identified, and >300 confirmed cases were reported in the United States from July through September. A smaller outbreak of this virus was seen in the summer months of 2013 with 18 cases identified in 4 states. Most illnesses caused by the H3N2 variant have occurred after direct or indirect contact with an infected pig, often among exhibitors or visitors to agricultural fairs. Limited person-to-person transmission has occurred with this virus and the severity of illness has been similar to that seen with seasonal influenza.
Although avian influenza viruses do not commonly infect humans, disease resulting from these viruses has been reported. From 2003 through March 2014, 650 human illnesses caused by avian influenza A(H5N1) were reported globally, approximately 60% of which were fatal. Most disease from H5N1 has occurred after direct or close contact with sick or dead infected poultry. H5N1 is widespread among poultry in some countries in Asia and the Middle East and is considered to be endemic among poultry in 6 countries: Bangladesh, China, Egypt, India (West Bengal), Indonesia, and Vietnam (Map 3-07). Distribution of H5N1 avian influenza. From January 2013 through March 2014, 65% of human H5N1 cases have been from Cambodia, where it is not considered endemic among poultry. Instances of limited, nonsustained human-to-human transmission of H5N1 virus have been reported.
Avian influenza A(H7N9) virus emerged in China in 2013, and as of March 2014, has caused nearly 400 confirmed human illnesses. Most cases have been identified in mainland China, but several cases associated with exposure in mainland China and subsequent travel have been identified in Malaysia, Taiwan, and Hong Kong. Most of the people with illness due to H7N9 had exposure to infected poultry or contaminated environments, as the virus has been found in poultry and environmental samples collected in China. While a small proportion of human H7N9 illnesses has been mild, most patients have developed severe respiratory illness, and 32% have died.
Human infections with other avian influenza A viruses, including H7N7, H9N2, and H10N8 viruses, although rare, have been reported in recent years.
Uncomplicated influenza illness is characterized by the abrupt onset of signs and symptoms that include fever, muscle aches, headache, malaise, nonproductive cough, sore throat, vomiting, and rhinitis. Illness without fever can occur, especially in the elderly. Children are more likely than adults to also experience nausea, vomiting, or diarrhea when ill with influenza. Physical findings are predominantly localized to the respiratory tract and include nasal discharge, pharyngeal inflammation without exudates, and occasionally rales on chest auscultation. The incubation period is usually 1–4 days after exposure. Influenza illness typically resolves within 1 week for most previously healthy children and adults who do not receive antiviral medication, although cough and malaise can persist for >2 weeks, especially in the elderly. Complications of influenza virus infection include primary influenza viral pneumonia, secondary bacterial pneumonia, exacerbation of underlying medical conditions (such as pulmonary and cardiac disease), encephalopathy, myocarditis, myositis, and coinfections with other viral or bacterial pathogens.
Influenza can be difficult to distinguish from respiratory illnesses caused by other pathogens on the basis of signs and symptoms alone. The positive predictive value of clinical signs and symptoms for influenzalike illness (fever with either cough or sore throat) for laboratory-confirmed influenza virus infection is 30%–88%, depending on the level of influenza activity.
Diagnostic tests available for influenza include viral culture, rapid influenza diagnostic tests (RIDTs), immunofluorescence assays, and RT-PCR. Most patients with clinical illness consistent with uncomplicated influenza in an area where influenza viruses are circulating do not require diagnostic testing for clinical management. Patients who should be considered for influenza diagnostic testing include the following:
- Hospitalized patients with suspected influenza
- Patients for whom a diagnosis of influenza will inform decisions regarding clinical care, especially those with medical conditions that place them at high risk of complications
- Patients for whom results of influenza testing would affect infection control or management of close contacts, including other patients, such as in institutional outbreaks or other settings (cruise ships or tour groups, for example)
The sensitivity of RIDTs varies but is substantially lower than for RT-PCR or viral culture. The sensitivity of RIDTs to detect animal-origin influenza viruses, including avian influenza viruses, can vary by test type and virus subtype. Therefore, a negative RIDT result does not rule out influenza virus infection, and health care providers should not rely on a negative RIDT result to make decisions about treatment.
Map 3-07. Distribution of H5N1 avian influenza
Early antiviral treatment can shorten the duration of fever and other symptoms and reduce the risk of complications from influenza. Antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who is hospitalized; has severe, complicated, or progressive illness; or is at a higher risk for influenza-associated complications (www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm). Antiviral treatment can also be considered for any previously healthy patient with confirmed or suspected influenza not at high risk of complications, if treatment can be initiated within 48 hours of illness onset.
Although antiviral therapy is ideally initiated within the first 48 hours of illness, for hospitalized patients, those with severe illness, or those at higher risk of complications, antiviral therapy may still be beneficial if started >48 hours after illness onset. Two influenza antiviral medications are available for the treatment and prophylaxis of influenza: oral oseltamivir (Tamiflu) and inhaled zanamivir (Relenza). Both are active against influenza A and B viruses. Oseltamivir is approved for treatment in children aged ≥14 days and for chemoprophylaxis of patients aged ≥1 year. Zanamivir is approved for treatment in those aged ≥7 years and for chemoprophylaxis in those aged ≥5 years (Table 3-5). Two other medications, amantadine and rimantadine, are not recommended for treatment or chemoprophylaxis of influenza because of widespread viral resistance among circulating influenza A viruses. Amantadine and rimantadine are not active against influenza B viruses.
People at increased risk for complications of influenza should discuss antiviral treatment and chemoprophylaxis with their health care provider before travel if traveling to areas where influenza activity is occurring. CDC recommends treatment with oseltamivir or zanamivir for human infection with avian or swine influenza viruses.
Table 3-05. Recommended dosage and duration of influenza antiviral medications for treatment and prophylaxis
Treatment (5 days)
If child is <1 year old1:
If child is <3 months old1: use of oseltamivir for chemo-
75 mg twice daily
75 mg once daily
Treatment (5 days)
10 mg (2 5-mg inhalations) twice daily (FDA approved and recommended for use in children ≥7 years)
10 mg (2 5-mg inhalations) twice daily (FDA approved and recommended for use in children ≥5 years)
10 mg (2 5-mg inhalations) twice daily
10 mg (2 5-mg inhalations) twice daily
1Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza with twice-daily dosing in people aged ≥14 days and for chemoprophylaxis with once-daily dosing in people aged ≥1 year. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants <14 days old, and for chemoprophylaxis in infants 3 months to 1 year of age, is recommended by CDC and the American Academy of Pediatrics.
2This is the FDA-approved oral oseltamivir treatment dose for infants aged ≥14 days and <1 year old and provides oseltamivir exposure in children similar to that achieved by the approved dose of 75 mg orally twice daily for adults, as shown in 2 studies of oseltamivir pharmacokinetics in children. The American Academy of Pediatrics has recommended an oseltamivir treatment dose of 3.5 mg/kg orally twice daily for infants aged 9–11 months for the 2013–2014 season. It is unknown whether this higher dose will improve efficacy or prevent the development of antiviral resistance. However, there is no evidence that the 3.5-mg/kg dose is harmful or causes more adverse events to infants in this age group.
3Current weight-based dosing recommendations are not appropriate for premature infants. Premature infants might have slower clearance of oral oseltamivir because of immature renal function, and doses recommended for full-term infants might lead to very high drug concentrations in this age group. CDC recommends dosing as also recommended by the American Academy of Pediatrics: 1.0 mg/kg/dose, orally, twice daily, for those <38 weeks postmenstrual age; 1.5 mg/kg/dose, orally, twice daily, for those 38–40 weeks postmenstrual age; 3.0 mg/kg/dose, orally, twice daily, for those >40 weeks postmenstrual age.
4Inhaled zanamivir is approved to treat acute uncomplicated influenza with twice-daily dosing in people aged ≥7 years and for chemoprophylaxis with once-daily dosing in people aged ≥5 years.
Indications for Use
Annual seasonal influenza vaccination is recommended for those aged ≥6 months and is the most effective way to prevent influenza and its complications. In the United States, annual influenza vaccination is recommended by the Advisory Committee on Immunization Practices for all US residents aged ≥6 months who do not have contraindications.
Many influenza vaccine products are available for use in the United States (www.cdc.gov/flu/protect/vaccine/vaccines.htm) and can be grouped into categories: inactivated influenza vaccine (IIV), live attenuated influenza vaccine (LAIV), and recombinant influenza vaccine (RIV). IIV can be administered by intramuscular or intradermal injection and is available for people ≥6 months of age. Specific age indications vary by manufacturer and product; label instructions should be followed. LAIV, administered by nasal spray, is approved for use only in healthy people aged 2–49 years who are not pregnant. RIV is indicated for people aged 18–49 years. Within indicated groups, there is no preference for any particular vaccine.
Any traveler, including people at high risk for complications of influenza, who did not receive influenza vaccine during the preceding fall or winter and wants to reduce the risk for influenza infection should consider influenza vaccination ≥2 weeks before departure if they plan to travel to the tropics, with organized tourist groups at any time of year, or to the Southern Hemisphere from April through September.
No information is available about the benefits of revaccinating people before summer travel who already were vaccinated during the preceding fall, and revaccination is not recommended. People at higher risk for influenza complications should consult with their health care provider to discuss the risk for influenza or other travel-related diseases before embarking on travel during the summer.
Seasonal influenza vaccines are not expected to provide protection against human infection with animal-origin influenza viruses, including avian influenza viruses H5N1 and A H7N9.
Vaccine Safety and Adverse Reactions
Inactivated influenza vaccine (IIV)
The most frequent side effects of vaccination with intramuscular and intradermal IIV in adults are soreness and redness at the vaccination site. These local reactions are slightly more common with vaccine administered intradermally and with high-dose IIV. They generally are mild and rarely interfere with the ability to conduct usual activities. Fever, malaise, myalgia, and other systemic symptoms sometimes occur after vaccination; these may be more frequent in people with no previous exposure to the influenza virus antigens in the vaccine (such as young children) and are generally short-lived.
Guillain-Barré syndrome (GBS) was associated with the 1976 swine influenza vaccine, with an increased risk of 1 additional case of GBS per 100,000 people vaccinated. None of the studies of influenza vaccines other than the 1976 influenza vaccine have demonstrated a similar increase in GBS. Currently, the estimated risk for vaccine-related GBS is low, approximately 1 additional case per 1 million people vaccinated.
Live attenuated influenza vaccine (LAIV)
The most frequent side effects of LAIV reported in healthy adults include minor upper respiratory symptoms, runny nose, and sore throat, which are generally well tolerated. Some children and adolescents have reported fever, vomiting, myalgia, and wheezing. These symptoms, particularly fever, are more often associated with the first administered LAIV dose and are self-limited.
LAIV should not be administered to any child aged <2 years or adult aged ≥50 years. Children aged 2–4 years who have a history of wheezing in the past year or who have a diagnosis of asthma should not receive LAIV. Children and adults aged 2–49 years who have conditions that increase the risk of severe influenza, including pregnancy, should receive IIV or RIV and not LAIV.
Recombinant influenza vaccine (RIV)
The first RIV was licensed in the United States in January 2013. Postmarketing safety data have not yet accumulated; however, prelicensure safety data indicate that the most common reactions were headache, fatigue, and myalgia. Safety and effectiveness of RIV have not been established in pregnant women, nursing mothers, children, or adults ≥50 years of age.
Precautions and Contraindications
Influenza vaccine is contraindicated in people who have had a previous severe allergic reaction to influenza vaccine, regardless of which vaccine component was responsible for the reaction. Immediate hypersensitivity reactions (such as hives, angioedema, allergic asthma, and systemic anaphylaxis) rarely occur after influenza vaccination. These reactions likely result from hypersensitivity to vaccine components, one of which is residual egg protein. Vaccine options are available for people with a history of egg allergy who have experienced only hives after exposure to egg, people with a history of severe reaction to egg, and people with no known history of egg allergy but who are suspected of being egg-allergic; these are outlined at www.cdc.gov/flu/professionals/vaccination/vax-summary.htm#egg-allergy.
Personal Protection Measures
Measures that may help prevent influenza virus infection and other infections during travel include avoiding close contact with sick people, washing hands often with soap and water (where soap and a safe source of water are not available, use of an alcohol-based hand sanitizer containing ≥60% alcohol is recommended), and avoiding touching one’s eyes, nose, and mouth. If you are ill, you can help prevent the spread of illness to others by covering your nose and mouth when coughing and sneezing and avoiding close contact with others.
The best way to prevent infection with animal-origin influenza viruses, including H5N1 and H7N9, is to follow standard travel safety precautions: follow good hand hygiene and food safety practices and avoid contact with sources of exposure. Most human infections with avian influenza viruses have occurred after direct or close contact with infected poultry. In countries where avian influenza virus outbreaks are occurring, travelers or those living abroad should avoid markets and farms where live animals are sold or raised, avoid contact with sick or dead animals, not eat undercooked or raw animal products (including eggs), and not eat or drink foods or beverages that contain animal blood.
CDC website: www.cdc.gov/flu
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- Page created: July 10, 2015
- Page last updated: July 10, 2015
- Page last reviewed: July 10, 2015
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