Chapter 3Infectious Diseases Related To Travel
Adena Greenbaum, 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, however, commonly cause illness in humans. Influenza A(H1N1), A(H3N2), and influenza B viruses currently circulate globally among humans. In the spring of 2009, a new influenza A(H1N1) virus with a combination of genes not previously detected was identified. This virus, now called influenza A(H1N1)pdm09, resulted in an influenza pandemic in 2009–2010. Travelers aided the rapid global spread of this virus, which continues to circulate worldwide and behave as a seasonal human influenza A virus. The predominant types and subtypes in circulation can vary from year to year and can differ between geographic areas and time of year. Information on current circulating virus strains in various regions can be found via CDC (www.cdc.gov/flu/weekly/fluactivitysurv.htm) or the World Health Organization (www.who.int/influenza).
Influenza viruses 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 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 through hand transfer of influenza virus from virus-contaminated surfaces to mucosal surfaces of the face (such as the nose or mouth) may also occur. However, the relative contribution of the different modes of transmission to the spread of influenza viruses is unclear.
Most healthy 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. Generally, people are most contagious in the 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 diarrheal stool or blood.
Influenza season varies geographically and by climate. In temperate climates, influenza activity generally occurs during the winter months. The influenza season in the Northern Hemisphere may begin as early as October and can extend until May. The influenza season in the Southern Hemisphere may begin in April and last through September. In tropical and subtropical areas, influenza may occur throughout the year, but most countries will have defined seasonal peaks.
Influenza virus infections can cause disease in all age groups. Infection rates are highest in children, and rates of severe illness and death are 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-related 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; about 90% of these deaths occurred among people aged ≥65 years.
While influenza B viruses circulate among humans, influenza A viruses circulate among many animal populations. The primary reservoir for influenza A viruses is wild birds, especially waterfowl. Influenza A viruses found in birds are typically referred to as avian influenza viruses. Swine influenza A viruses circulate widely among pigs worldwide. Influenza A viruses can also be found in other animal species such as domestic poultry, cats, dogs, horses, and bats.
Human infections with animal-origin influenza A viruses are uncommon, but they do occur. From 2005 through early 2012, 36 human influenza illnesses caused by swine-origin influenza A virus were reported in the United States (called “variant” influenza virus infections). A large increase in cases of an influenza A(H3N2) variant virus that contains the M gene from the influenza A(H1N1)pdm09 virus was identified starting in July 2012. As of September 2012, over 300 confirmed cases have been identified in the United States. Most occurred after direct or indirect contact with an infected animal, and though limited person-to-person transmission has occurred, no sustained community spread of H3N2v has been detected as of September 2012. The severity of illness has been similar to that seen with seasonal influenza.
Although avian influenza A viruses do not commonly infect humans, sporadic cases of human infection with these viruses have been reported. From 2003 through mid-2012, >600 human cases of illness from infection with highly pathogenic avian influenza (HPAI) virus (H5N1) have been reported globally, with approximately 60% mortality. Most human infections with HPAI H5N1 virus have occurred after direct or close contact with sick or dead infected poultry. HPAI H5N1 virus 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. From 2003 through mid-2012, 87% of all recognized human cases have occurred in these countries. Rare instances of limited, nonsustained human-to-human transmission of HPAI H5N1 virus have been reported. Human infections with other avian influenza A viruses, although rare, have been reported, including H7N2, H7N3, H7N7, and H9N2 viruses.
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 elderly people. 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, or 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 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 diagnostic tests, 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 influenza testing for clinical management. For individual patients, tests are most useful when they are likely to help with diagnosis and treatment decisions. 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, especially those with high-risk conditions
- 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 rapid influenza diagnostic tests is substantially lower than for RT-PCR or viral culture. Therefore, a negative rapid test result does not rule out influenza virus infection, and clinicians should not rely on a negative rapid test to make decisions about treatment.
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 complications (see www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm). Antiviral treatment can also be considered for any previously healthy patient not at high risk of complications, with confirmed or suspected influenza, 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 neuraminidase inhibitors are available for antiviral treatment and chemoprophylaxis of influenza: oral oseltamivir (Tamiflu) and inhaled zanamivir (Relenza). Both are active against influenza A and B viruses. Oseltamivir is approved for treatment and 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 3-05). Two other medications, amantadine and rimantadine, which belong to the adamantane class of antivirals, are active only against influenza A but not influenza B viruses and are not recommended for treatment or chemoprophylaxis because of widespread viral resistance among circulating influenza A 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.
The effectiveness of antivirals for treating HPAI H5N1 virus infections has not been fully studied, although limited observational evidence suggests that early treatment has been associated with lower risk of death. CDC recommends treatment with oseltamivir for human infection with avian or swine influenza A viruses.
Indications for Use
Annual influenza vaccination for those aged ≥6 months is the most effective way to prevent influenza and its complications.
Two types of influenza vaccines are available for use in the United States: trivalent inactivated vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). TIV 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. For adults aged ≥65 years, a high-dose TIV is also available, containing higher levels of antigen. LAIV, administered by nasal spray, is approved for use only in healthy people aged 2–49 years who are not pregnant. Within indicated groups for each vaccine, there is no preference for TIV, high-dose TIV, or LAIV. In February 2012, the Food and Drug Administration approved the first quadrivalent LAIV (approved for ages 2–49 years), which is administered by nasal spray.
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. Vaccination of pregnant women and household contacts of children aged <6 months can reduce the risk of influenza in children who are too young to receive influenza vaccine. Travelers, especially those who are part of large tourist groups, may be exposed to influenza at any time of year through exposure to others from areas of the world where influenza viruses are circulating. To maximize the protective benefit, travelers being vaccinated against influenza should receive their vaccine ≥2 weeks before departure if vaccine is available. In order to optimize the immune response, children aged 6 months through 8 years being vaccinated for the first time are recommended to receive 2 doses of influenza vaccine administered a minimum of 4 weeks apart.
Vaccine Safety and Adverse Reactions
The most frequent side effects of vaccination with intramuscular and intradermal TIV in adults are soreness and redness at the vaccination site. These local reactions are slightly more common with intradermal vaccine and high-dose TIV. 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 those 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 has demonstrated a similar increase in GBS. Currently, the estimated risk for vaccine-related GBS is low, approximately 1 additional case per 1 million vaccinated.
The most frequent side effects of trivalent and quadrivalent 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 to children aged 2–4 years who have a history of wheezing in the past year or who have 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 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. People who have developed only hives from egg exposure may receive the influenza vaccine. CDC recommends they receive TIV, administered by a provider familiar with egg allergies, and are observed after vaccine administration. Those who have had a severe reaction to eggs, including angioedema, acute respiratory distress, or required epinephrine after egg exposure, should consult a physician experienced in allergic reactions for evaluation to determine if vaccine should be administered. Influenza vaccine is contraindicated in those who have had a previous severe allergic reaction to influenza vaccine, regardless of which vaccine component was responsible for the reaction.
Personal Protection Measures
Measures that may help prevent influenza virus infection and other infections during travel include avoiding contact with others while sick; avoiding close contact with sick people; washing hands often with soap and water (where soap and water are not available, using an alcohol-based hand sanitizer containing ≥60% alcohol); avoiding touching one’s eyes, nose, and mouth; and covering coughs and sneezes with a tissue, then disposing of the tissue. In countries where HPAI H5N1 virus outbreaks are occurring among poultry, travelers should avoid markets and farms where live poultry are sold or raised, avoid contact with dead poultry, and not drink chicken blood or eat undercooked chicken.
CDC website: www.cdc.gov/flu
Table 3-05. Recommended dosage and schedule of influenza antiviral medications1 for treatment2 and chemoprophylaxis3
|AGE GROUP (Y)|
Treatment, influenza A and B
10 mg4 bid
10 mg4 qd
10 mg4 bid
10 mg4 qd
10 mg4 bid
10 mg4 qd
Treatment,6 influenza A and B
Dose varies by child’s weight6
Dose varies by child’s weight7
Dose varies by child’s weight6
Dose varies by child’s weight7
Dose varies by child’s weight;6 >40 kg, give adult dose
Dose varies by child’s weight;7 >40 kg, give adult dose
75 mg bid
75 mg qd
Abbreviations: NA, not approved.
1Zanamivir is approved to treat people aged ≥7 years and approved for chemoprophylaxis of people aged ≥5 years. Zanamivir is not recommended for people with underlying airway disease. Oseltamivir is approved for treatment or chemoprophylaxis of people aged ≥1 year. No antiviral medications are approved for treatment or chemoprophylaxis of influenza among children aged <1 year. This information is based on data published by the Food and Drug Administration, available at www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm100228.htm.
2Recommended duration for antiviral treatment is 5 days. Longer treatment courses can be considered for patients who remain severely ill after 5 days of treatment.
3Recommended duration for prophylaxis is 10 days when administered after a household exposure and 7 days after the most recent known exposure in other situations. For control of outbreaks in long-term care facilities and hospitals, CDC recommends antiviral chemoprophylaxis for a minimum of 2 weeks and up to 1 week after the most recent known case was identified.
410 mg Zanamivir is 2 inhalations.
5See Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza, Recommendations of the Advisory Committee on Immunization Practices (ACIP) for information about use of oseltamivir for infants aged <1 year. A reduction in the dose of oseltamivir is recommended for people with creatinine clearance <30 mL/min.
6The treatment dosing recommendation for oseltamivir for children aged ≥1 year who weigh ≤15 kg is 30 mg bid. For children who weigh >15 kg but ≤23 kg, the dose is 45 mg bid. For children who weigh >23 kg but ≤40 kg, the dose is 60 mg bid. For children who weigh >40 kg, the dose is 75 mg bid.
7The chemoprophylaxis dosing recommendation for oseltamivir for children aged ≥1 year who weigh ≤15 kg is 30 mg qd. For children who weigh >15 kg but ≤23 kg, the dose is 45 mg qd. For children who weigh >23 kg but ≤40 kg, the dose is 60 mg qd. For children who weigh >40 kg, the dose is 75 mg qd.
- Block SL, Yi T, Sheldon E, Dubovsky F, Falloon J. A randomized, double-blind noninferiority study of quadrivalent live attenuated influenza vaccine in adults. Vaccine. 2011 Nov 21;29(50):9391–7.
- 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. Influenza antiviral medications: summary for clinicians. Atlanta: CDC; 2011 [cited 2012 Sep 20]. Available from: http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm.
- CDC. Influenza symptoms and the role of laboratory diagnostics. Atlanta: CDC; 2011 [cited 2012 Sep 20]. Available from: http://www.cdc.gov/flu/professionals/diagnosis/labrolesprocedures.htm.
- CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011 Aug 26;60(33):1128–32.
- 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, 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.
- McGeer A, Green KA, Plevneshi A, Shigayeva A, Siddiqi N, Raboud J, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007 Dec 15;45(12):1568–75.
- 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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