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On This Page
Travel Notices in Effect
Safety and Security Abroad
Preparing for Your Trip to Belize
Other Diseases Found in Mexico and Central America
Staying Healthy During Your Trip
After You Return Home
Travel Notices in Effect
Update: Dengue, Tropical and Subtropical Regions Updated: September 19, 2007
Update: 2007 Measles and Mumps Outbreaks Updated: May 17, 2007
Safety and Security Abroad
Registration of Traveler Emergency Contact and Itinerary Information Updated: June 18, 2007
Transportation Security Administration
U.S. Department of State
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Preparing for Your Trip to Belize
Before visiting Belize, you may need to get the following vaccinations and medications for vaccinepreventable diseases and other diseases you might be at risk for at your destination: (Note: Your doctor
or health-care provider will determine what you will need, depending on factors such as your health and
immunization history, areas of the country you will be visiting, and planned activities.)
To have the most benefit, see a health-care provider at least 4–6 weeks before your trip to allow time for
your vaccines to take effect and to start taking medicine to prevent malaria, if you need it.
Even if you have less than 4 weeks before you leave, you should still see a health-care provider for needed
vaccines, anti-malaria drugs and other medications and information about how to protect yourself from
illness and injury while traveling.
CDC recommends that you see a health-care provider who specializes in Travel Medicine. Find a travel
medicine clinic near you. If you have a medical condition, you should also share your travel plans with any
doctors you are currently seeing for other medical reasons.
If your travel plans will take you to more than one country during a single trip, be sure to let your health-care
provider know so that you can receive the appropriate vaccinations and information for all of your
destinations. Long-term travelers, such as those who plan to work or study abroad, may also need additional
vaccinations as required by their employer or school.
Although yellow fever is not a disease risk in Belize, the government requires travelers arriving from
countries where yellow fever is present to present proof of yellow fever vaccination. If you will be
traveling to one of these countries where yellow fever is present before arriving in Belize, this requirement
must be taken into consideration.
Be sure your routine vaccinations are up-to-date. Check the links below to see which vaccinations
adults and children should get.
Routine vaccines, as they are often called, such as for influenza, chickenpox (or varicella), polio,
measles/mumps/rubella (MMR), and diphtheria/pertussis/tetanus (DPT) are given at all stages of life; see the
childhood and adolescent immunization schedule and routine adult immunization schedule.
Routine vaccines are recommended even if you do not travel. Although childhood diseases, such as measles,
rarely occur in the United States, they are still common in many parts of the world. A traveler who is not
vaccinated would be at risk for infection.
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Vaccine-Preventable Diseases
Vaccination or
Disease
Recommendations or Requirements for Vaccine-Preventable Diseases
Recommended if you are not up-to-date with routine shots such as, measles/mumps/rubella
(MMR) vaccine, diphtheria/pertussis/tetanus (DPT) vaccine, etc.
Recommended for all unvaccinated people traveling to or working in countries with an
Hepatitis A or
intermediate or high level of hepatitis A virus infection (see map) where exposure might
immune globulin occur through food or water. Cases of travel-related hepatitis A can also occur in travelers to
(IG)
developing countries with "standard" tourist itineraries, accommodations, and food
consumption behaviors.
Recommended for all unvaccinated persons traveling to or working in countries with
intermediate to high levels of endemic HBV transmission (see map) and who might be
Hepatitis B
exposed to blood or body fluids, have sexual contact with the local population, or be exposed
through medical treatment, such as for an accident, and for all adults requesting protection
from HBV infection.
Recommended for all unvaccinated people traveling to or working in Mexico and Central
Typhoid
America, especially if visiting smaller cities, villages, or rural areas and staying with friends
or relatives where exposure might occur through food or water.
Recommended for travelers spending a lot of time outdoors, especially in rural areas,
Rabies
involved in activities such as bicycling, camping, hiking, or work. Also, children are
considered at higher risk because they tend to play with animals and may not report bites.
Routine
Malaria
Drugs to Prevent Malaria (Antimalarial drugs)
If you will be visiting a malaria risk area in Belize, chloroquine is the recommended antimalarial drug.
Malaria risk area in Belize: All, except no risk in Belize City
A Special Note about Antimalarial Drugs
You should purchase your antimalarial drugs before travel. Drugs purchased overseas may not be
manufactured according to United States standards and may not be effective. They also may be dangerous,
contain counterfeit medications or contaminants, or be combinations of drugs that are not safe to use.
Halofantrine (marketed as Halfan) is widely used overseas to treat malaria. CDC recommends that you do
NOT use halofantrine because of serious heart-related side effects, including deaths. You should avoid using
antimalarial drugs that are not recommended unless you have been diagnosed with life-threatening malaria
and no other options are immediately available.
For detailed information about these antimalarial drugs, see Information for the Public: Prescription
Drugs for Malaria.
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More Information About Malaria
Malaria is always a serious disease and may be a deadly illness. Humans get malaria from the bite of a
mosquito infected with the parasite. Prevent this serious disease by seeing your health-care provider for a
prescription antimalarial drug and by protecting yourself against mosquito bites (see below).
Travelers to malaria risk-areas in Belize, including infants, children, and former residents of Belize,
should take one of the following antimalarial drugs listed above.
Symptoms
Malaria symptoms may include
fever
chills
sweats
headache
body aches
nausea and vomiting
fatigue
Malaria symptoms will occur at least 7 to 9 days after being bitten by an infected mosquito. Fever in the first
week of travel in a malaria-risk area is unlikely to be malaria; however, you should see a doctor right away if
you develop a fever during your trip.
Malaria may cause anemia and jaundice. Malaria infections with Plasmodium falciparum, if not promptly
treated, may cause kidney failure, coma, and death. Despite using the protective measures outlined above,
travelers may still develop malaria up to a year after returning from a malarious area. You should see a
doctor immediately if you develop a fever anytime during the year following your return and tell the
physician of your travel.
Items to Bring With You
Medicines you may need:
The prescription medicines you take every day. Make sure you have enough to last during your trip.
Keep them in their original prescription bottles and always in your carry-on luggage. Be sure to
follow security guidelines, if the medicines are liquids.
Antimalarial drugs, if traveling to a malaria-risk area in Belize and prescribed by your doctor.
Medicine for diarrhea, usually over-the-counter.
Note: Some drugs available by prescription in the US are illegal in other countries. Check the US
Department of State Consular Information Sheets for the country(s) you intend to visit or the embassy or
consulate for that country(s). If your medication is not allowed in the country you will be visiting, ask your
health-care provider to write a letter on office stationery stating the medication has been prescribed for you.
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Other items you may need:
Iodine tablets and portable water filters to purify water if bottled water is not available. See
Preventing Cryptosporidiosis: A Guide to Water Filters and Bottled Water and Safe Food and
Water for more detailed information.
Sunblock and sunglasses for protection from harmful effects of UV sun rays. See Skin Cancer
Questions and Answers for more information.
Antibacterial hand wipes or alcohol-based hand sanitizer containing at least 60% alcohol.
To prevent insect/mosquito bites, bring:
o Lightweight long-sleeved shirts, long pants, and a hat to wear outside, whenever possible.
o Flying-insect spray to help clear rooms of mosquitoes. The product should contain a pyrethroid
insecticide; these insecticides quickly kill flying insects, including mosquitoes.
o Bed nets treated with permethrin, if you will not be sleeping in an air-conditioned or wellscreened room and will be in malaria-risk areas. For use and purchasing information, see
Insecticide Treated Bed Nets on the CDC malaria site. Overseas, permethrin or another
insecticide, deltamethrin, may be purchased to treat bed nets and clothes.
See other suggested over-the-counter medications and first aid items for a travelers' health kit.
Note: Check the Air Travel section of the Transportation Security Administration website for the latest
information about airport screening procedures and prohibited items.
Other Diseases Found in Mexico and Central
America
Risk can vary between countries within this region
and also within a country; the quality of in-country
surveillance also varies.
The following are disease risks that might affect travelers; this is not a complete list of diseases that can be
present. Environmental conditions may also change, and up to date information about risk by regions within
a country may also not always be available.
Dengue epidemics have affected most countries in Central America in the past 5 years. Filariasis,
leishmaniasis, onchocerciasis (River blindness), and American trypanosomiasis (Chagas' disease) are
diseases carried by insects that also occur in this region, mostly in rural areas. Risk to the usual traveler is
low. Myiasis (botfly) is endemic in Central America. Protecting yourself against insect bites (see below) will
help to prevent these diseases.
Gnathostomiasis (roundworms) has increased in Mexico, with many cases being reported from the
Acapulco area, infection has been reported in travelers. Humans become infected by eating undercooked fish
or poultry, or reportedly by drinking contaminated water.
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Foci of active transmission of leishmaniasis (predominantly cutaneous) are present in all countries in
Central America. West Nile virus has been found in Mexico and may spread in Central America.
Diarrhea in travelers is common and may be caused by bacteria, viruses, and parasites. Diarrhea caused by
enterotoxigenic E. coli predominates, but other bacteria and protozoa (including Giardia, Cryptosporidia,
and Entamoeba histolytica) can also cause diarrhea.
Cases of hantavirus pulmonary syndrome have been reported from Panama.
Outbreaks of leptospirosis have occurred in travelers to the area (including whitewater rafters in Costa Rica
and U.S. troops training in Panama). Sporadic cases and outbreaks of coccidioidomycosis and
histoplasmosis have occurred in travelers to Central America. Risky activities include disturbing soil and
entering caves and abandoned mines. Cutaneous larva migrans occurs in visitors, especially those visiting
beaches.
For more information, see the Geographic Distribution of Potential Health Hazards to Travelers and
Goals and Limitations in determining actual disease risks by destination
Staying Healthy During Your Trip
Prevent Insect Bites
Many diseases, like malaria and dengue, are spread through insect bites. One of the best protections is to
prevent insect bites by:
Using insect repellent (bug spray) with 30%-50% DEET. Picaridin, available in 7% and 15%
concentrations, needs more frequent application. There is less information available on how effective
picaridin is at protecting against all of the types of mosquitoes that transmit malaria.
Wearing long-sleeved shirts, long pants, and a hat outdoors.
Remaining indoors in a screened or air-conditioned area during the peak biting period for malaria
(dusk and dawn).
Sleeping in beds covered by nets treated with permethrin, if not sleeping in an air-conditioned or wellscreened room.
Spraying rooms with products effective against flying insects, such as those containing pyrethroid.
For detailed information about insect repellent use, see Insect and Arthropod Protection.
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Be Careful about Food and Water
Diseases from food and water are the leading cause of illness in travelers. Follow these tips for safe eating
and drinking:
Wash your hands often with soap and water, especially before eating. If soap and water are not
available, use an alcohol-based hand gel (with at least 60% alcohol).
Drink only bottled or boiled water, or carbonated (bubbly) drinks in cans or bottles. Avoid tap water,
fountain drinks, and ice cubes. If this is not possible, learn how to make water safer to drink.
Do not eat food purchased from street vendors.
Make sure food is fully cooked.
Avoid dairy products, unless you know they have been pasteurized.
Diseases from food and water often cause vomiting and diarrhea. Make sure to bring diarrhea medicine with
you so that you can treat mild cases yourself.
Avoid Injuries
Car crashes are a leading cause of injury among travelers. Protect yourself from these injuries by:
Not drinking and driving.
Wearing your seat belt and using car seats or booster seats in the backseat for children.
Following local traffic laws.
Wearing helmets when you ride bikes, motorcycles, and motor bikes.
Not getting on an overloaded bus or mini-bus.
Hiring a local driver, when possible.
Avoiding night driving.
Other Health Tips
To avoid animal bites and serious diseases (including rabies and plague) do not handle or pet animals,
especially dogs and cats, If you are bitten or scratched, wash the wound immediately with soap and
water and seek medical attention to determine if mediation or anti-rabies vaccine is needed.
To avoid infections such as HIV and viral hepatitis do not share needles for tattoos, body piercing, or
injections.
To reduce the risk of HIV and other sexually transmitted diseases always use latex condoms.
To prevent fungal and parasitic infections, keep feet clean and dry, and do not go barefoot, especially
on beaches where animals may have defecated.
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After You Return Home
If you are not feeling well, you should get medical attention and mention that you have recently traveled.
If you have visited a malaria-risk area, continue taking your chloroquine for 4 weeks after leaving the risk
area.
Malaria is always a serious disease and may be a deadly illness. If you become ill with a fever or flu-like
illness either while traveling in a malaria-risk area or after you return home (for up to 1 year), you should
seek immediate medical attention and should tell the physician your travel history.
Important Note: This document is not a complete medical guide for travelers to this region. Consult with
your doctor for specific information related to your needs and your medical history; recommendations may
differ for pregnant women, young children, and persons who have chronic medical conditions.
Map Disclaimer - The boundaries and names shown and the designations used on maps do not imply the
expression of any opinion whatsoever on the part of the Centers for Disease Control and Prevention
concerning the legal status of any country, territory, city or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries. Approximate border lines for which there may not yet be full
agreement are generally marked.
Page Located on the Web at http://wwwn.cdc.gov/travel/destinationBelize.aspx
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Outbreak Notice
Update: Dengue, Tropical and Subtropical Regions
This information is current as of today, January 29, 2008 at 12:23
Updated: September 19, 2007
Dengue has become one of the most common viral diseases transmitted to humans by the bite of infected
mosquitoes (usually Aedes aegypti); it is the most common cause of fever in travelers returned from the
Caribbean, Central America, and South Central Asia.* Symptoms of dengue include fever, severe headache,
retro-orbital eye pain (pain behind the eye), joint and muscle pain, and rash. Dengue can produce a range of
illness from mild to severe, as well as fatal hemorrhagic fever. Travelers are at risk for dengue infection if
they travel to or reside in areas where dengue virus is transmitted; the preventive measures outlined below
can reduce their risk.
Dengue Risk Areas
The range of areas where dengue is located has rapidly expanded in recent years. Today it includes many
tropical countries in Southeast Asia, the Indian Subcontinent, the South Pacific, the Caribbean, South and
Central America, northeastern Australia, and Africa. See the Distribution of dengue maps for areas where
it is present most of the time. Risk of infection is related to mosquito exposure, which can vary with the
season. The mosquitoes that transmit dengue breed in man-made and natural containers, which are especially
common in and around houses; therefore, dengue is common where many houses are clustered.
Currently, an outbreak of dengue is being reported in French Polynesia and Palau in the South Pacific.
Singapore is also experiencing an increase in dengue cases this year. As of June 30, 2007, the outbreak of
dengue in Paraguay was reported to be subsiding. Other areas in South and Central America and the
Caribbean, such as Brazil, Guadeloupe, Martinique, Mexico, Nicaragua, and Puerto Rico, are experiencing
an increase in dengue cases in 2007.
Prevention Measures for Travelers
No vaccine is available to prevent dengue, and there is no specific treatment other than therapeutic support.
Travelers can reduce their risk by protecting themselves from mosquito bites:
Use insect repellent containing DEET or Picaridin on exposed skin. DEET concentrations of 30% to
50% are effective for several hours. Picaridin, available in 7% and 15% concentrations, must be
applied more frequently. When using sunscreen, apply it before insect repellent.
o DEET formulations as high as 50% are recommended for both adults and children over 2
months of age. Protect infants less than 2 months of age by using a carrier draped with
mosquito netting with an elastic edge for a tight fit.
Wear loose, long pants and long-sleeved shirts when outdoors.
Indoors, spray insecticide where the Aedes mosquito likes to linger: closets, behind curtains, and under
beds. If practical, empty or cover containers containing water.
Air conditioned, screened rooms furnished with mosquito nets provide further protection.
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Empty or cover containers that can collect water (e.g., uncovered barrels, flower vases, or cisterns),
because mosquitoes that transmit dengue breed in standing water.
Aedes mosquitoes, the principal mosquito vector, usually are active at dusk and dawn, but may feed at any
time during the day, especially indoors, in shady areas, or when the weather is cloudy. Unlike malaria,
dengue is often transmitted in urban as well as in rural areas.
Additional Information
Proper diagnosis of dengue is important; many other diseases may mimic dengue and health-care providers
should consider dengue, malaria, and (in South Asia and countries bordering the Indian Ocean), chikungunya
in the differential diagnosis of patients who have fever and a history of travel to tropical areas during the 2
weeks before symptom onset. See Dengue and Dengue Hemorrhagic Fever: Information for HealthCare Practitioners for information regarding reporting dengue cases and instructions for specimen
shipping. Serum samples obtained for viral identification and serologic diagnosis can be sent through state or
territorial health departments to CDC's Dengue Branch, Division of Vector-Borne Infectious Diseases,
National Center for Zoonotic, Vector-Borne and Enteric Diseases, 1324 Calle Cañada, San Juan, Puerto Rico
00920-3860; telephone, 787-706-2399; fax, 787-706-2496.
For more information about dengue and protection measures, see the following links:
Dengue Fever in CDC Health Information for International Travel 2008
Insect and Arthropod Protection
Questions and Answers: Insect Repellent Use and Safety
Overview of dengue from CDC Division of Vector-Borne Infectious Diseases
For more information about dengue in travelers, see
Travel-Associated Dengue—United States, 2005 [MMWR 2006, 55 (25)].
Travel-Associated Dengue Infections—United States, 2001-2004 [MMWR 2005, 54 (22)]
For more information about recent dengue outbreaks, see
Pan American Health Organization http://www.paho.org/english/ad/dpc/cd/dengue.htm
South East Asia-Region/WHO (SEARO)
http://www.searo.who.int/EN/Section10/Section332_1098.htm
* Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, et al.; for the
GeoSentinel Surveillance Network. Spectrum of disease and relation to place of exposure among ill
returned travelers. N Engl J Med 2006;354:119-130
Page Located on the Web at http://wwwn.cdc.gov/travel/contentDengueTropicalSubTropical.aspx
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Dengue Fever
Description
Dengue fever and dengue hemorrhagic fever (DHF) are viral diseases transmitted by Aedes mosquitoes,
usually Aedes aegypti. The four dengue viruses (DEN-1 through DEN-4) are immunologically related, but
do not provide cross-protective immunity against each other.
Occurrence
Dengue, a disease found in most tropical and subtropical areas of the world, has become the most common
arboviral disease of humans. More than 2.5 billion persons now live in areas where dengue infections can be
locally acquired (1). Reported attack rates for disease during epidemics range from 1 per hundred to 1 per
thousand of the population (2). However, because persons with milder illness may not seek medical attention
and subsequently be reported, the actual number of infections in a population may be 5 to 10 times greater
than the number reported. Epidemics caused by all four virus serotypes have become progressively more
frequent and larger in the past 25 years. As of 2005, dengue fever is endemic in most tropical countries of
the South Pacific, Asia, the Caribbean, the Americas, and Africa (see Maps 4-1, 4-2). Additionally, most
tropical urban centers in these regions have multiple dengue virus serotypes co-circulating
(hyperendemicity), which is associated with increased dengue transmission and the appearance of DHF.
Future dengue incidence in specific locales cannot be predicted accurately, but a high level of dengue
transmission is anticipated in all tropical areas of the world for the indefinite future. The incidence of the
severe disease, DHF, has increased dramatically in Southeast Asia, the South Pacific, and the American
tropics in the past 25 years, with major epidemics occurring in many countries every 3-5 years. The first
major epidemic in the Americas occurred in Cuba in 1981, and a second occurred in Venezuela in 19891990 (3,4). Since then, outbreaks and rates of endemic, confirmed DHF have occurred in most tropical
American countries. After an absence of 35 years, several locally acquired cases of dengue fever occurred in
southern Texas in 1980 associated with epidemic dengue in adjacent states in Mexico (5). In the last decade,
such dengue cases have been identified in Texas every 1 to 5 years. The most recent cases in 2005 included
the first locally acquired DHF case in the continental United States (6). After an absence of 56 years, a
limited outbreak of dengue fever occurred in Hawaii in 2001, associated with imported cases arriving from
areas with epidemic dengue in the South Pacific (7).
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MAP 4-01 Distribution of dengue, Western Hemisphere.
Risk for Travelers
The principal mosquito vector, Ae. aegypti, is most frequently found in or near human habitations and
prefers to feed on humans during the daytime. It has two peak periods of biting activity: in the morning for
several hours after daybreak and in the late afternoon for several hours before dark. Nevertheless, the
mosquito may feed at any time during the day, especially indoors, in shady areas, or when it is overcast.
Mosquito breeding sites include artificial water containers such as discarded tires, uncovered water storage
barrels, buckets, flower vases or pots, cans, and cisterns.
Cases of dengue fever and DHF are confirmed every year in travelers returning to the United States after
visits to tropical and subtropical areas (8). Studies of military and relief workers placed the estimated risk for
travelers returning from dengue-endemic areas near one illness per thousand travelers (9, 10). This estimate
may overstate the danger for tourists who may have less contact with the vector when they stay only a few
days in air-conditioned hotels with well-kept grounds, or when they participate in outdoor recreational
activities where the vector mosquito may be absent (such as sunbathing or playing golf in the middle of the
day). A recent study of tourists visiting Hawaii during a dengue outbreak in 2001 failed to identify serologic
evidence of dengue infection among over 3,000 travelers; however, this study was limited by the fact that
only persons sick enough to seek medical attention received dengue testing (11). As a result, milder dengue
infections that did not require medical attention might have been missed. Moreover, travelers who stay in the
homes of friends and relatives in locations with intense disease transmission may have a higher risk of
illness. Therefore, travelers to endemic and epidemic areas should take precautions to avoid mosquito bites
(see Chapter 2).
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Current data suggest that co-circulation of all four dengue strains in the same geographic region, virus
genotype, and host factors such as immune status (i.e., having had a previous dengue infection), age, and
genetic background are the most important risk factors for developing DHF (12). In Asia, where a high
proportion of the population has experienced a dengue infection early in life, DHF is observed most
commonly in infants and children younger than 15 years of age who are experiencing a second dengue
infection. In the Americas and the Pacific, where primary infection at a young age is less common, DHF is
typically observed in older children and adults. Therefore, international travelers from nonendemic areas
(such as the United States) are generally at low risk for DHF.
There is little information in published reports about the consequences of dengue infection for pregnant
women. No convincing evidence demonstrating an association between dengue infection during pregnancy
and congenital malformations has been reported. However, if the mother is ill with dengue at the time of
delivery, the child can be born with dengue infection or can acquire dengue through the delivery process
itself, and then develop the manifestations of dengue fever or DHF (13). Passive transplacental transfer of
maternal anti-dengue antibodies acquired from a previous maternal infection can also place infants at greater
risk of DHF with their first dengue infection, but these maternal antibodies are cleared by 9-12 months of
age (14,15). Transfusion-related dengue infection is a theoretical possibility (16).
MAP 4-02 Distribution of dengue, Eastern Hemisphere.
Clinical Presentation
Dengue fever is characterized by sudden onset after an incubation period of 3-14 days (most commonly 4-7
days) of high fevers, severe frontal headache, and joint and muscle pain. Many patients have nausea,
vomiting, and a maculopapular rash, which appears 3-5 days after onset of fever and can spread from the
torso to the arms, legs, and face. The disease is usually self-limited, although convalescence can be
Page | 13
prolonged. Most patients report a nonspecific viral syndrome or a flu-like illness. Asymptomatic infections
are also common. Although these patients do not experience symptoms at the time of the acute infection, the
immunity that results increases the risk for DHF during a subsequent infection. Approximately 1% of
patients with dengue infection progress to DHF. As the patient’s fever resolves, usually 3-5 days following
the onset of fever, patients may develop leaky capillaries, which allow serum proteins and fluid to
accumulate in the pleural and abdominal cavities. Thrombocytopenia and hemorrhagic manifestations, which
can range from microscopic hematuria or increased menstrual flow to hemetemesis, are part of the
syndrome. Neutropenia, elevated liver enzymes, and disseminated intravascular coagulation are also
common. The case-fatality ratio for DHF averages about 5% worldwide, but can be kept below 1% with
proper clinical management. Dengue shock syndrome is the progression of DHF to a hypotensive state.
Despite the name, the progression of DHF to DSS is primarily due to capillary leakage rather the
hemorrhaging (12).
Physicians should consider dengue in the differential diagnosis of all patients who have fever and a history
of travel to a tropical area within 2 weeks of onset of symptoms. Commercial tests are available for serologic
diagnosis, but their results must be interpreted with care. Sensitivity and specificity of kits may vary among
manufacturers, laboratories, and over time. In combination with a compatible travel history and symptom
profile, anti-dengue IgM positivity suggests a recent dengue infection, but IgG positivity may only indicate
infection at an indeterminate time in the past. Both anti-dengue IgM and IgG antibodies cross-react with
anti-West Nile, -yellow fever, -Japanese encephalitis, and -other flavivirus anti-bodies; therefore, prior
infection or vaccination with another flavivirus may also result in positive anti-dengue antibody results. If
testing at CDC is requested, acute- and convalescent-phase serum samples (collected 0-5 days and 6-30 days
from fever onset, respectively) should be obtained and sent through state or territorial health department
laboratories to CDC’s Dengue Branch, Division of Vector-Borne Infectious Diseases (DVBID), National
Center for Infectious Diseases, 1324 Calle Cañada, San Juan, Puerto Rico 00920-3860. Serum samples
should be accompanied by clinical and epidemiologic information, including the date of disease onset, the
date of collection of the sample, and a detailed recent travel history. For additional information, the Dengue
Branch can be contacted by telephone 1-787-706-2399; fax 1-787-706-2496; e-mail hseda@cdc.gov; or the
DVBID website at http://www.cdc.gov/ncidod/dvbid/dengue/index.htm.
Prevention
No vaccine is available. Travelers should be advised that they can reduce their risk of acquiring dengue by
remaining in well-screened or air-conditioned areas when possible, wearing clothing that adequately covers
the arms and legs, and applying insect repellent to both skin and clothing. The most effective repellents are
those containing N,N-diethylmetatoluamide (DEET) (see Chapter 2).
Treatment
Acetaminophen products are recommended for managing fever. Acetylsalicyclic acid (aspirin) and
nonsteroidal anti-inflammatory agents (such as ibuprofen) should be avoided because of their anticoagulant
properties. Salicylates (e.g., aspirin) should be especially avoided in children due to the association with
Reye syndrome. Patients should be encouraged to rest and take fluids. Warning signs of progression to
severe disease include abrupt change from fever to hypothermia, severe abdominal pain, prolonged
vomiting, and altered mental status (e.g., irritability, confusion, lethargy). Prompt treatment of DHF with
intravenous fluid can improve patient outcomes. In such cases, hospitalization with close monitoring of vital
signs, fluid balance, and hematologic parameters is indicated, as well as additional supportive measures (12).
Page | 14
References
1. Gubler DJ. The global emergence/resurgence of arboviral diseases as public health problems. Arch
Med Res. 2002;33:330-42.
2. Pan American Health Organization. 2005: Number of reported cases of dengue & dengue hemorrhagic
fever (DHF), Region of the Americas (by country and subregion). Available at:
http://wwwn.cdc.gov/travel/forward.aspx?t=http://www.paho.org/English/AD/DPC/CD/dengue
-cases-2005.htm. Accessed 12 July 2006.
3. Kouri GP, Guzman MG, Bravo JR, Triana C. Dengue haemorrhagic fever/dengue shock syndrome:
lessons from the Cuban epidemic, 1981. Bull World Health Organ. 1989;67:375-80.
4. Pan American Health Organization. Dengue hemorrhagic fever in Venezuela. Epidemiol Bull.
1990;11:7-9.
5. CDC. Dengue–Texas. MMWR Morbid Mortal Wkly Rep. 1980;29:451.
6. Lacayo M, Taylor R, Duran H, Abell A, et al. Outbreak investigation of dengue—Texas, 2005 (Latebreaker). Presented at 54th Annual Meeting: American Society of Tropical Medicine and Hygiene.
Washington, DC, December 11-15, 2005.
7. Effler PV, Pang L, Kitsutani P, Vorndam V, Nakata M, Ayers T, et al., and Hawaii Dengue Outbreak
Investigation Team. Dengue Fever, Hawaii, 2001–2002. Emerg Infect Dis. 2005;11:5:742-749.
8. CDC. Travel-associated dengue —United States, 2005. MMWR Morbid Mortal Wkly Rep.
2006;55:22:700-2.
9. Trofa AF, DeFraites RF, Smoak BL, Kanesathasan N, King AD, Burrous JM, et al. Dengue fever in
US military per-sonnel in Haiti. JAMA. 1997;277:1546-8.
10. O’Leary DR, Rigau-Pérez JG, Hayes EB, Vorndam AV, Clark GG, Gubler DJ. Assessment of
Dengue risk in relief workers in Puerto Rico after Hurricane Georges. Am J Trop Med Hyg.
2002;66:35-39.
11. Smith CE, Tom Tammy, Sasaki J, Ayers T, Effler PV. Dengue risk among visitors to Hawaii during
an outbreak. Emerg Infect Dis. 2005;11:750-66.
12. Rigau-Pérez JG, Clark GC, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue
haemorrhagic fever. Lancet. 1998;352:971-7.
13. García-Rivera EJ, Rigau-Pérez JG. Dengue virus. In: Scott GB, Hutto SC, eds. Diagnosis of
congenital and perinatal infections: a concise guide. Totowa, NJ: Humana Press, 2005:189-99.
14. Kliks SC, Nimmanitya S, Nisalak A, Burke DS. Evidence that maternal dengue antibodies are
important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg.
1988;38:411–9.
15. Fernandez R, Rodriguez T, Borbonet F, Vasquez S, Guzman M, Kouri G. Estudio de la relacion
dengue-embarazo en un grupo de madres cubanas. Rev Cubana Med Trop. 1994;46:76–8.
16. Beatty ME, Biggerstaff B, Rigau J, Petersen L. Estimated risk of transmission of dengue virus
through blood transfusion in Puerto Rico (#126). At 5th International Conference on Emerging
Infectious Diseases. Atlanta, GA. March 19-22, 2006.
MARK E BEATTY, GARY G CLARK
Page Located on the Web at http://wwwn.cdc.gov/travel/yellowBookCh4-DengueFever.aspx
Page | 15
Outbreak Notice
Update: 2007 Measles and Mumps Outbreaks
This information is current as of today, January 29, 2008 at 12:25
Updated: May 17, 2007
Measles and mumps remain common diseases in many parts of the world. For US travelers, the risk for
exposure to measles and mumps can be high, and both diseases can be prevented by the MMR (measles,
mumps, rubella) vaccine.
Worldwide, more than 20 million people get sick with measles each year; of these cases, 345,000 are fatal.
Measles cases occur in all regions of the world: Southeast Asia (14 million cases), Africa (3.5 million
cases), Eastern Mediterranean (2 million cases), Western Pacific (1 million cases), Europe (170,000
cases) and the Americas (<1,000 cases). Mumps is endemic in all regions of the world, including in many
developed countries.
Currently, numerous measles outbreaks are ongoing worldwide, including an outbreak in Japan in the
Western Pacific Region, that has resulted in imported cases into the U.S. However, in 2007, the majority of
US import-associated cases have been linked to India.
Recent cases of mumps have been reported in Nova Scotia, New Brunswick, Prince Edward Island, and
Ontario, Canada . The large outbreak of mumps that occurred in the United Kingdom in 2005-6 has waned,
although mumps remains endemic there.
Recommendations for travelers
All travelers should be fully immunized and keep a copy of their immunization records with them as
they travel.
Children
o 12 months or older should receive 2 doses of MMR vaccine separated by at least 28 days,
with the first dose administered on or after the first birthday.
o 6–11 months of age, if they must travel outside the US, should receive single-antigen measles
vaccine before departure if it is available, or MMR if single-antigen measles vaccine is not
available. (Note: MMR given before 12 months of age should not be counted as part of the
series. Children who receive MMR before age 12 months will need 2 more doses of MMR,
the first of which should be administered at 12 months of age.)
Adolescents and Adults
o who have received 2 doses of live measles- or mumps-containing vaccine are generally
considered immune to measles and mumps.
o are also considered immune to measles and mumps if they have had the diagnosis documented
by a physician, laboratory evidence of immunity, or were born before 1957.
o who cannot be considered immune based on the above criteria should receive 2 doses of MMR
vaccine, separated by at least 28 days.
Page | 16
Information about Measles
Measles is a serious disease. Some people who become sick with measles also get an ear infection (7%-9%),
diarrhea (8%), or a serious lung infection, such as pneumonia (1%-6%). One of 1,500 people with measles
develops inflammation of the brain. In the United States in recent years, approximately 1-3 of every 1,000
people with measles have died . Measles can cause especially severe disease in people who are malnourished
or immunosuppressed (i.e., HIV infection, leukemia, lymphoma, or generalized malignancy) or in persons
receiving certain drugs or radiation therapies.
Information about Mumps
Mumps is an infection of the salivary glands caused by a virus. It spreads through direct contact with
respiratory droplets or saliva from an infected person. Early symptoms include fever, headache, and muscle
aches; fewer than half of infected people may have the characteristic swelling of the glands close to the jaw.
Mumps infection can lead to meningitis, inflammation of the testicles or ovaries, inflammation of the
pancreas, and deafness, which may be permanent.
Information about the Vaccine
The MMR vaccine also provides protection against rubella (German measles). Rubella is caused by a virus
that is spread through droplet transmission. It can cause a rash, mild fever, and arthritis (mostly in women).
If a woman gets rubella while she is pregnant, she could have a miscarriage or her baby could be born with
serious birth defects, such as deafness, cataracts, or mental retardation.
Since the introduction of vaccines containing measles, rubella, or mumps vaccine viruses—and later the
combined measles-mumps-rubella (MMR) vaccine—in the United States, the numbers of reported cases of
measles, mumps, and rubella, and of birth defects caused by rubella infection (congenital rubella syndrome)
have decreased substantially. However, routine surveillance and vaccination remain necessary because of the
continuing possibility that these diseases may be introduced from other countries.
For more information, see the following links:
Lancet 2007; 369:191-200
General Information on Outbreaks of Mumps in Canada
MMR vaccine (MMWR Recommendations and Reports, May 22, 1998)
Measles, mumps, and rubella (National Immunization Program website)
Measles outbreaks in Europe (Eurosurveillance website)
Measles (Health Information for International Travel)
Mumps (Health Information for International Travel)
Rubella (Health Information for International Travel)
Page Located on the Web at http://wwwn.cdc.gov/travel/contentMeaslesMumpsOutbreaks.aspx
Page | 17
Hepatitis, Viral, Type A
Description
Hepatitis A is a viral infection of the liver caused by hepatitis A virus (HAV). HAV infection may be
asymptomatic or its clinical manifestations may range in severity from a mild illness lasting 1-2 weeks to a
severely disabling disease lasting several months. Clinical manifestations of hepatitis A often include fever,
malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice (1).
Occurrence
HAV is shed in the feces of persons with HAV infection. Transmission can occur through direct person-toperson contact; through exposure to contaminated water, ice, or shellfish harvested from sewagecontaminated water; or from fruits, vegetables, or other foods that are eaten uncooked and that were
contaminated during harvesting or subsequent handling.
HAV infection is common (high or intermediate endemicity) throughout the developing world, where
infections most frequently are acquired during early childhood and usually are asymptomatic or mild. In
developed countries, HAV infection is less common (low endemicity), but communitywide outbreaks still
occur in some areas of the United States. Map 4-3 indicates the seroprevalence of antibody to HAV (total
anti-HAV) as measured in selected cross-sectional studies among each country’s residents. The
seroprevalence of anti-HAV provides an estimate of the endemicity of HAV infections, including
asymptomatic infections, within a population (2).
Page | 18
MAP 4-03 Prevalence of antibody to hepatitis A virus, by country, 2006.
Risk for Travelers
Hepatitis A is one of the most common vaccine-preventable infections acquired during travel (3,4). The
number of cases associated with travel, as well as the overall incidence, has decreased in recent years,
according to notifiable disease data in the United States and Europe (3,5). However, the proportion of overall
cases attributed to travel has increased in the United States. Among reported cases in persons younger than
15 years old, 40% were associated with travel (5). The risk for acquiring HAV infection for U.S. residents
traveling abroad varies with living conditions, length of stay, and the incidence of HAV infection in the area
visited. Travelers to North America (except Mexico), Japan, Australia, New Zealand, and developed
countries in Europe are at no greater risk for infection than in the United States. For travelers to other
countries, risk for infection increases with duration of travel and is highest for those who live in or visit rural
areas, trek in back-country areas, or frequently eat or drink in settings of poor sanitation. Nevertheless, many
cases of travel-related hepatitis A occur in travelers to developing countries with â¬Sstandardâ¬ý tourist
itineraries, accommodations, and food consumption behaviors (2).
Clinical Presentation
The incubation period for hepatitis A averages 28 days (range 15-50 days). Hepatitis A typically has an
abrupt onset of symptoms that can include fever, malaise, anorexia, nausea, abdominal discomfort, dark
urine, and jaundice. The likelihood of having symptoms with HAV infection is related to the infected
person’s age. In children younger than 6 years old, most (70%) infections are asymptomatic; if illness does
occur, its duration is usually less than 2 months. No chronic or long-term infection is associated with
hepatitis A, but 10% of infected persons will have prolonged or relapsing symptoms over a 6- to 9-month
Page | 19
period. The overall case-fatality rate among cases reported to CDC is 0.3%; however, the rate is 1.8% among
adults older than 50 years of age (1).
Prevention
Hepatitis A vaccine, immune globulin (IG), or both, are recommended for all susceptible persons traveling to
or working in countries with an intermediate or high endemicity of HAV infection. Health-care providers
should administer hepatitis A vaccination for persons traveling for any purpose, frequency or duration to
countries that have high or intermediate endemicity of HAV infection (1). In addition, health-care providers
should be alert to opportunities to provide vaccination for all travelers whose plans might include travel at
some time in the future to an area of high or intermediate endemicity, including those whose current medical
evaluation is for travel to an area where hepatitis A vaccination is not currently recommended.
VACCINE AND IMMUNE GLOBULIN
Two monovalent hepatitis A vaccines are currently licensed in the United States for persons at least 12
months of age: HAVRIX, manufactured by GlaxoSmithKline (Table 4-3), and VAQTA (manufactured by
Merck & Co., Inc.) (Table 4-4). Both vaccines are made of inactivated hepatitis A virus adsorbed to
aluminum hydroxide as an adjuvant. HAVRIX is prepared with 2-phenoxyethanol as a preservative, while
VAQTA is formulated without a preservative. All hepatitis A vaccines should be administered
intramuscularly in the deltoid muscle (1).
TWINRIX, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed
for persons >18 years of age, containing 720 EL.U. of hepatitis A antigen (50% of the HAVRIX adult dose)
and 20 µg of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose)
(Table 4-5). Primary immunization consists of three doses, given on a 0-, 1-, and 6-month schedule, the same
schedule as that commonly used for monovalent hepatitis B vaccine. TWINRIX contains aluminum
phosphate and aluminum hydroxide as adjuvants and 2-phenoxyethanol as a preservative. An accelerated
schedule of Twinrix (i.e., doses at days 0, 7, and 21) for travelers has been approved by the FDA. A booster
dose should be given at 1 year.
The first dose of hepatitis A vaccine should be administered as soon as travel to countries with high or
intermediate endemicity is considered. One month after receiving the first dose of monovalent hepatitis A
vaccine, 94%-100% of adults and children will have protective concentrations of antibody. The final dose in
the hepatitis A vaccine series is necessary to promote long-term protection. The immunogenicity of
TWINRIX is equivalent to that of the monovalent hepatitis vaccines when tested after completion of the
licensed schedule.
Many persons will have detectable antibody to hepatitis A virus (anti-HAV) response to the monovalent
vaccine by 2 weeks after the first vaccine dose. The proportion of persons who develop a detectable antibody
response at 2 weeks may be lower when smaller vaccine dosages are used, such as with the use of
TWINRIX. Travelers who receive hepatitis A vaccine less than 2 weeks before traveling to an endemic area
and who do not receive immune globulin (either by choice or because of lack of availability) likely will be at
lower risk of infection than those who do not receive hepatitis A vaccine or IG. In the case of travel within 4
weeks of vaccine administration, a dose of immune globulin (0.02 mL/kg) may be given alone or in addition
to hepatitis A vaccine, at a different site, for optimal protection. In the case of unavailability or refusal of
immune globulin, administration of hepatitis A vaccine alone for this group is recommended, but they should
be informed that they are not optimally protected from acquiring hepatitis A in the immediate future (i.e., the
subsequent 2-4 weeks) (1,2).
Page | 20
Although vaccination of an immune traveler is not contraindicated and does not increase the risk of adverse
effects, screening for total anti-HAV before travel can be useful in some circumstances to determine
susceptibility and eliminate unnecessary vaccination or IG prophylaxis of immune travelers. Such serologic
screening for susceptibility might be indicated for adult travelers who are likely to have had prior HAV
infection if the cost of screening (laboratory and office visit) is less than the cost of vaccination or IG
prophylaxis and if testing will not delay vaccination and interfere with timely receipt of vaccine or IG before
travel. Such travelers may include those older than 40 years of age and those born in areas of the world with
intermediate or high endemicity. Postvaccination testing for serologic response is not indicated (1).
Using the vaccines according to the licensed schedules is preferable. However, an interrupted series does not
need to be restarted. Given their similar immunogenicity, a series that has been started with one brand of
monovalent vaccine (i.e., HAVRIX or VAQTA) may be completed with the other brand. Hepatitis A vaccine
may be administered at the same time as IG or other commonly used vaccines for travelers, at different
injection sites (1,2).
In adults and children who have completed the vaccine series, anti-HAV has been shown to persist for at
least 5-12 years after vaccination. Results of mathematical models indicate that after completion of the
vaccination series, anti-HAV will likely persist for 20 years or more. For children and adults who complete
the primary series, booster doses of vaccine are not recommended (6). Serologic testing to assess antibody
levels after vaccination is not indicated.
Travelers who are younger than 12 months of age, are allergic to a vaccine component, or otherwise elect not
to receive vaccine should receive a single dose of IG (0.02 mL/kg), which provides effective protection
against HAV infection for up to 3 months (Table 4-6). Those who do not receive vaccination and plan to
travel for longer than 3 months should receive an IG dose of 0.06 mL/kg, which must be repeated if the
duration of travel is longer than 5 months (1,7).
Adverse Reactions
Among adults, the most frequently reported side effects occurring 3-5 days after a vaccine dose are
tenderness or pain at the injection site (53%-56%) or headache (14%-16%). Among children, the most
common side effects reported are pain or tenderness at the injection site (15%-19%), feeding problems (8%
in one study), or headache (4% in one study). No serious adverse events in children or adults that could be
definitively attributed to the vaccine or increases in serious adverse events among vaccinated persons
compared with baseline rates have been identified (1).
Immune globulin for intramuscular administration prepared in the United States has few side effects
(primarily soreness at the injection site) and has never been shown to transmit infectious agents (hepatitis B
virus, hepatitis C virus [HCV], or HIV). Since December 1994, all IG products commercially available in the
United States have had to undergo a viral inactivation procedure or be negative for HCV RNA before release
(1).
Precautions and Contraindications
These vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine
component. HAVRIX or TWINRIX should not be administered to travelers with a history of hypersensitivity
reactions to the preservative 2-phenoxyethanol. TWINRIX should not be administered to persons with a
history of hypersensitivity to yeast. Because hepatitis A vaccine consists of inactivated virus and hepatitis B
vaccine consists of a recombinant protein, no special precautions need to be taken for vaccination of
immunocompromised travelers (1).
Page | 21
Pregnancy
The safety of hepatitis A vaccine for pregnant women has not been determined. However, because hepatitis
A vaccine is produced from inactivated HAV, the theoretical risk to either the pregnant woman or the
developing fetus is thought to be very low. The risk of vaccination should be weighed against the risk of
hepatitis A in women travelers who might be at high risk for exposure to HAV. Pregnancy is not a
contraindication to using IG.>
OTHER PREVENTION TIPS
Boiling or cooking food and beverage items for at least 1 minute to 185°F (85°C) inactivates HAV. Foods
and beverages heated to this temperature and for this length of time cannot serve as vehicles for HAV
infection unless they become contaminated after heating. Adequate chlorination of water as recommended in
the United States will inactivate HAV. Travelers should be advised that, to minimize their risk of hepatitis A
and other enteric diseases in developing countries, they should avoid potentially contaminated water or food.
Travelers should also be advised to avoid drinking beverages (with or without ice) of unknown purity, eating
uncooked shellfish, and eating uncooked fruits or vegetables that are not peeled or prepared by the traveler
personally (see Chapter 2) (8).
TABLE 4-03. Licensed schedule for HAVRIX1
AGE GROUP DOSE
NO. OF SCHEDULE
2 VOLUME
(YRS)
(EL.U.)
DOSES (MONTHS)
1-18
720
0.5 mL
2
0, 6 to 12
≥19
1,440
1.0 mL
2
0, 6 to 12
1
2
Hepatitis A vaccine, inactivated, GlaxoSmithKline
EL.U. = enzyme-linked immunosorbent assay (ELISA) units
TABLE 4-04. Licensed schedule for VAQTA1
AGE GROUP DOSE
NO. OF SCHEDULE
VOLUME
(YRS)
(EL.U.)2
DOSES (MONTHS)
1-18
25 units 0.5 mL
2
0, 6 to 18
≥19
50 units 1.0 mL
2
0, 6 to 18
1
Hepatitis A vaccine, inactivated, Merck & Co., Inc.
TABLE 4-05. Licensed schedule for TWINRIX1
AGE GROUP
DOSE
NO. OF SCHEDULE
VOLUME
2
(YRS)
(EL.U.)
DOSES (MONTHS)
2
≥18
720 EL.U / 20 μg 1.0 mL
3
0, 1, 6 months
0, 7, 21 days
≥18
720 EL.U2 / 20 μg 1.0 mL
4
+ 1 year
1
2
Combined hepatitis A and hepatitis B vaccine, GlaxoSmithKline
EL.U. = enzyme-linked immunosorbent assay (ELISA) units
Page | 22
TABLE 4-06. Recommended doses of immune globulin (IG) for protection against
Hepatitis A
DURATION OF
DOSE (mL/kg)*
COVERAGE
Short-term (1–2 mos) 0.02
Pre-exposure
Long-term (3–5 mos) 0.06†
Postexposure --0.02
SETTING
*IG should be administered by intramuscular injection into either the deltoid or gluteal muscle. For children
aged <12 months, IG can be administered in the anterolateral thigh muscle.
†Repeat every 5 months if continued exposure to hepatitis A virus occurs.
Treatment
No specific treatment is available for persons with hepatitis A. Treatment is supportive.
References
1. CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR Morbid Mortal Wkly Rep. 2006;
RR 55:1-23.
2. Bell BP, Feinstone SM. Hepatitis A vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th
edition. Philadelphia: W.B. Saunders, 2004.
3. Mutsch M, Spicher VM, Gut C, Steffen R. Hepatitis A virus infections in travelers, 1988-2004. Clin
Infect Dis. 2006;42:490-7.
4. Bacaner N, Stauffer B, Boulware DR, Walker PF, Keystone JS. Travel medicine considerations for
North American immigrants visiting friends and relatives. JAMA. 2004;291:2856-64.
5. CDC. Hepatitis Surveillance Report No. 61. 2005. Atlanta: U.S. Department of Health and Human
Services. Centers for Disease Control and Prevention. 2006.
6. van Damme P, Banatvala J, Fay O, Iwarson S, McMahon B, Van Herck K, et al. Hepatitis A booster
vaccination: is there a need? Lancet. 2003;362:1065–71.
7. Winokur PL, Stapleton JT. Immunoglobulin prophylaxis for hepatitis A. Clin Infect Dis. 1992;14:5806.
8. Fiore AE. Hepatitis A transmitted by food. Clin Infect Dis. 2004;38:705-15.
ANTHONY FIORE, BETH BELL
Page Located on the Web at http://wwwn.cdc.gov/travel/yellowBookCh4-HepA.aspx
Page | 23
Hepatitis, Viral, Type B
Description
Hepatitis B is caused by the hepatitis B virus (HBV). The clinical manifestations of HBV infection range in
severity from no symptoms to fulminant hepatitis. Signs and symptoms of hepatitis B may include fever,
malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice (1).
Occurrence
HBV is transmitted through activities that involve contact with blood or blood-derived fluids. Such activities
can include unprotected sex with an HBV-infected partner; shared needles used for injection of illegal drugs;
work in health-care fields (medical, dental, laboratory, or other) that entails direct exposure to human blood;
receiving blood transfusions that have not been screened for HBV; or having dental, medical, or cosmetic (e.g.,
tattooing or body piercing) procedures with needles or other equipment that are contaminated with HBV. In
addition, open skin lesions, such as those due to impetigo, scabies, or scratched insect bites, can play a role in
HBV transmission if direct exposure to wound exudates from HBV-infected persons occurs (1,2).
The prevalence of chronic HBV infection is low (<2%) in the general population in Northern and Western
Europe, North America, Australia, New Zealand, Mexico, and Southern South America (Map 4-4). In the
United States and many other developed countries, children and adolescents are routinely vaccinated against
hepatitis B. The highest incidence of dis-ease is in younger adults, and most HBV infections are acquired
through unprotected sex with HBV-infected partners or through shared needles used for injection drug use. The
prevalence of chronic HBV infection is intermediate (2%-7%) in South Central and Southwest Asia, Israel,
Japan, Eastern and Southern Europe, Russia, most areas surrounding the Ama-zon River basin, Honduras, and
Guatemala. The prevalence of chronic HBV infection is high (>8%) in all socioeconomic groups in certain
areas: all of Africa; Southeast Asia, including China, Korea, Indonesia, and the Philippines; the Middle East,
except Israel; South and Western Pacific islands; the interior Amazon River basin; and certain parts of the
Caribbean (Haiti and the Dominican Republic) (1,2).
Risk for Travelers
The risk of HBV infection for international travelers is generally low, except for certain travelers in countries
where the prevalence of chronic HBV infection is high or intermediate. Modes of HBV transmission in areas
with high or intermediate prevalence of chronic HBV infection that are important for travelers to consider are
contaminated injection and other equipment used for health care-related procedures and blood transfusions from
unscreened donors. Unprotected sex and sharing illegal drug injection equipment are also risks for HBV
infection in these areas (1,2).
Page | 24
Clinical Presentation
The incubation period of hepatitis B averages 120 days (range 45-160 days). Constitutional symptoms such as
malaise and anorexia may precede jaundice by 1-2 weeks. Clinical symptoms and signs include nausea,
vomiting, abdominal pain, and jaundice. Skin rashes, joint pains, and arthritis may occur. The case-fatality rate
is approximately 1%. Acute HBV infection causes chronic (long-term) infection in 30%-90% of persons
infected as infants or children and in 6%-10% of adolescents and adults. Chronic infection can lead to chronic
liver disease, liver scarring (cirrhosis), and liver cancer (1).
MAP 4-04 Prevalence of chronic infection with hepatitis B virus, by country, 2006
Prevention
VACCINE
Hepatitis B vaccination is currently recommended for all U.S. residents who work in health-care fields
(medical, dental, laboratory, or other) that involve potential exposure to human blood (3,4). All unvaccinated
United States children and adolescents (younger than 19 years old) should receive hepatitis B vaccine (5). In
addition, unvaccinated persons who have indications for hepatitis B vaccination independent of travel should be
vaccinated, such as men who have sex with men, injection drug users, and heterosexuals who have recently had
a sexually transmitted disease or have had more than one partner in the previous 6 months (4,6).
Hepatitis B vaccination should be administered to all unvaccinated persons traveling to areas with
intermediate to high levels of endemic HBV transmission (i.e., with hepatitis B surface antigen [HBsAg]
prevalence >2%). As part of the pre-travel education process, all travelers should be given information about
the risks of hepatitis B and other bloodborne pathogens from contaminated medical equipment, injection
Page | 25
drug use, or sexual activity, and informed of prevention measures (see below), including hepatitis B
vaccination, that can be used to prevent transmission of HBV. Regardless of destination, all persons who might
engage in practices that might put them at risk for HBV infection during travel should receive hepatitis B
vaccination if previously unvaccinated. It is reasonable for physicians to consider their ability to accurately
assess these potential risks when considering if hepatitis B vaccine should be offered. Any adult seeking
protection from HBV infection should be vaccinated. Acknowledgment of a specific risk factor is not a
requirement for vaccination (4).
Two monovalent hepatitis B vaccines are currently licensed in the United States: Recombivax HB,
manufactured by Merck and Co., Inc., and Engerix B, manufactured by GlaxoSmithKline. Vaccines available in
the United States use recombinant DNA technology to express HBsAg in yeast, which is then purified from the
cells by biochemical and bio-physical separation techniques. The usual schedule of primary vaccination consists
of three intramuscular doses of vaccine. The recommended dose varies by product and the recipient’s age
(Table 4-7). The vaccine is usually administered as a three-dose series on a 0-, 1-, and 6-month schedule. The
second dose should be given 1 month after the first dose; the third dose should be given at least 2 months after
the second dose and at least 4 months after the first dose. Alternatively, the vaccine produced by
GlaxoSmithKline is also approved for administration on a four-dose schedule at 0, 1, 2, and 12 months. There is
also a two-dose schedule for a vaccine produced by Merck & Co., Inc., which has been licensed for children
and adolescents 11-15 years of age. Using the two-dose schedule, the adult dose of Recombivax-HB is
administered, with the second dose given 4-6 months after the first dose. An interrupted hepatitis B vaccine
series does not need to be restarted. A three-dose series that has been started with one brand of vaccine may be
completed with the other brand (1,5).
Twinrix, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for
persons 18 years of age or older. Primary immunization consists of three doses, given on a 0-, 1-, and 6-month
schedule, the same schedule as that used for single-antigen hepatitis B vaccine (Table 4-5). Twinrix consists of
inactivated hepatitis A virus and recombinant HBsAg protein, with aluminum phosphate and aluminum
hydroxide as adjuvants and 2-phenoxyethanol as a preservative (1,5).
Clinicians may choose to use an accelerated schedule (for either the hepatitis B vaccine or Twinrix) (i.e., doses
at days 0, 7, and 21). The FDA has approved the accelerated schedule for Twinrix, but not for the monovalent
hepatitis B vaccine. Persons who receive a vaccination on an accelerated schedule should also receive a booster
dose at 1 year after the start of the series to promote long-term immunity (7).
Ideally, vaccination should begin at least 6 months before travel so the full vaccine series can be completed
before departure. Because some protection is provided by one or two doses, the vaccine series should be
initiated, if indicated, even if it cannot be completed before departure. Optimal protection, however, is not
conferred until after the final vaccine dose. There is no interference between hepatitis B vaccine and other
simultaneously administered vaccine(s) or with IG. The optimum site of injection in adults is the deltoid
muscle. Long-term studies of healthy adults and children indicate that immunologic memory remains intact for
at least 15 years and confers protection against chronic HBV infection, even though hepatitis B surface antibody
(anti-HBs) levels can become low or decline below detectable levels. For children and adults whose immune
status is normal, booster doses of vaccine are not recommended. Serologic testing to assess antibody levels is
not necessary for most vaccinees. (See Chapter 8, for a discussion of the hepatitis B immunization schedule for
infants who will be traveling [5,8].)
Adverse Reactions
Hepatitis B vaccines have been shown to be very safe for persons of all ages. Pain at the injection site (3%29%) and elevated temperature higher than 37.7°C (99.9°F) (1%-6%) are the most frequently reported side
effects among vaccine recipients. In placebo-controlled studies, these side effects were reported no more
Page | 26
frequently among persons receiving hepatitis B vaccine than among those receiving placebo. Among children
receiving both hepatitis B vaccine and diphtheria-tetanus-pertussis (DTP) vaccine, these mild side effects have
been observed no more frequently than among children receiving DTP vaccine alone. For hepatitis A vaccine (a
component of the combination hepatitis A/hepatitis B vaccine Twinrix), the most frequently reported adverse
reactions occurring within 3-5 days were soreness or pain at the injection site and headache. No serious adverse
events among children or adults that could be definitively attributed to hepatitis A vaccine or increases in
serious adverse events among vaccinated persons compared with baseline rates have been identified (1,5).
Precautions and Contraindications
These vaccines should not be administered to persons with a history of hypersensitivity to any vaccine
component, including yeast. The vaccine contains a recombinant protein (HBsAg) that is noninfectious. Limited
data indicate that there is no apparent risk of adverse events to the developing fetus when hepatitis B vaccine is
administered to pregnant women. HBV infection affecting a pregnant woman can result in serious disease for
the mother and chronic infection for the newborn. Neither pregnancy nor lactation should be considered a
contraindication for vaccination (1,5).
Behavioral preventive measures are similar to those for HIV infection and AIDS. When seeking medical or
dental care, travelers should be advised to be alert to the use of medical, surgical, and dental equipment that has
not been adequately sterilized or disinfected, reuse of contaminated equipment, and unsafe injecting practices
(e.g., reuse of disposable needles and syringes). HBV and other bloodborne pathogens can be transmitted if
tools are not sterile or if the tattoo artist or piercer does not follow other proper infection-control procedures
(e.g., washing hands, using latex gloves, and cleaning and disinfecting surfaces and instruments). Travelers
should be advised to consider the health risks in deciding to get a tattoo or body piercing in areas where
adequate sterilization or disinfection procedures might not be available or practiced (see Chapter 2).
Page | 27
TABLE 4-07. Recommended doses of currently licensed formulations of hepatitis B vaccine
GROUP
SINGLE-ANTIGEN VACCINE
COMBINATION VACCINE
RECOMBIVAX
ENGERIX-B COMVAX1 PEDIARIX2 TWINRIX3
HB
DOSE (μg)4
Infants (<1 year)
Children (1 - 10 years)
Adolescents
VOLUME (mL)
DOSE
(μg)44
VOLUME
(mL)
DOSE
(μg)44
VOLUME
(mL)
DOSE
(μg)44
VOLUME
(mL)
DOSE
(μg)44
VOLUME
(mL)
57
5
0.5
0.5
107
10
0.5
0.5
5
5
0.5
0.5
10
10
0.5
0.5
NA5 NA
NA NA
106
1.0
NA
NA
NA
NA
NA
NA
NA
NA
5
10
0.5
1.0
10
20
0.5
1.0
NA
NA
NA
NA
NA
NA
NA
NA
203
20
1.03
1.0
5
0.5
10
0.5
NA
NA
NA
NA
NA
NA
408
10
409
2.0
NA
NA
NA
NA
NA
NA
11 - 15 years
11 - 19 years
Adults (>20 years)
Hemo- dialysis patients and
other immuno- compromised persons
<20 years7
≥20 years
1
1Combined hepatitis B-Haemophilus influenzae type b conjugate vaccine. This vaccine cannot be
administered before age 6 weeks or after age 71 months.
2
Combined hepatitis B-diphtheria, tetanus, pertussis-inactivated poliovirus vaccine. This vaccine cannot be
administered at birth, before age 6 weeks, or after age 7 years.
3
Combined hepatitis A and hepatitis B vaccine. This vaccine is recommended for persons older than 18 years
who are at increased risk for both hepatitis A virus and hepatitis B virus infections.
4
Recombinant hepatitis B surface antigen dose.
5
Not applicable.
6
Adult formulation administered on a 2-dose schedule.
7
Higher doses might be more immunogenic, but no specific recommendations have been made.
8
Dialysis formulation administered on a 3-dose schedule at 0, 1, 6 months.
9
Two 1.0-mL doses administered at one site, on a 4-dose schedule at 0, 1, 2, and 6 months.
Treatment
No specific treatment is available for acute illness caused by hepatitis B. Antiviral drugs are approved for the
treatment of chronic hepatitis B (9).
References
Page | 28
1. Mast E, Mahoney F, Kane M, et al. Hepatitis B vaccine. In: Plotkin SA, Orenstein WA, editors.
Vaccines. 4th ed. Philadelphia: W.B. Saunders; 2004.
2. Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M. Unsafe injections in the developing world and
transmission of bloodborne pathogens: a review. Bull World Health Organ. 1999;77:789-800.
3. CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to
HBV, HCV and HIV and recommendations for postexposure prophylaxis. MMWR Morbid Mortal Wkly
Rep. 2001;50(RR-11):1-54.
4. CDC. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States
through universal childhood vaccination. Recommendations of the Immunization Practices Advisory
Committee (ACIP). MMWR Morbid Mortal Wkly Rep. 1991;40 (RR-13):1-25.
5. CDC. A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus
Infection in the United States. Recommendations of the Advisory Committee on Immunization Practices
(ACIP) Part 1: Immunization of Infants, Children, and Adolescents. MMWR Morbid Mortal Wkly Rep.
2005;54(RR16);1-23
6. CDC. Provisional Recommendations for Hepatitis B Vaccination of Adults—October 2005. Available
at: http://www.cdc.gov/nip/recs/provisional_recs/hepB_adult.pdf. Accessed 31 October 2006.
7. Bock HL, Loscher T, Scheiermann N, Baumgarten R, Wiese M, Dutz W, et al. Accelerated schedule for
hepatitis B immunization. J Travel Med. 1995;2:213-7.
8. European Consensus Group on Hepatitis B Immunity. Are booster immunisations needed for lifelong
hepatitis B immunity? Lancet. 2000;355:561-5.
9. Lok AS, McMahon BJ; Practice Guidelines Committee, American Association for the Study of Liver
Diseases (AASLD). Chronic hepatitis B: update of recommendations. Hepatology. 2004:39:857-61.
ANTHONY FIORE, BETH BELL
Page Located on the Web at http://wwwn.cdc.gov/travel/yellowBookCh4-HepB.aspx
Page | 29
Typhoid Fever
Description
Typhoid fever is an acute, life-threatening febrile illness caused by the bacterium Salmonella enterica
serotype Typhi.
Occurrence
An estimated 22 million cases of typhoid fever and 200,000 related deaths occur worldwide each year (1).
Approximately 400 cases of typhoid fever among persons with onset of illness in the United States, most of
whom are recent travelers, are reported to CDC each year.
Risk for Travelers
Risk is greatest for travelers to South Asia and developing countries in Asia, Africa, the Caribbean, and
Central and South America. Travelers to South Asia are at highest risk for infections that are nalidixic acidresistant or multidrug-resistant (i.e., resistant to ampicillin, chloramphenicol, and trimethoprimsulfamethoxazole) (2). Travelers who are visiting relatives or friends and who may be less likely to eat only
safe foods (cooked and served hot) and beverages (carbonated beverages or those made from water that has
been boiled) are at greater risk. Travelers have acquired typhoid fever even during brief visits of less than 1
week to countries where the disease is endemic (3).
Clinical Presentation
The hallmark of typhoid infection is persistent, high fever as high as 103° to 104° F (39° to 40° C). Other
common symptoms and signs include headache, malaise, anorexia, splenomegaly, a rash of flat, rose-colored
spots, and relative bradycardia (4). Many mild and atypical infections occur.
Prevention
Typhoid vaccination is not required for international travel, but CDC recommends it for travelers to areas
where there is a recognized risk of exposure to S. Typhi. Vaccination is particularly recommended for those
who will be traveling in smaller cities, villages, and rural areas off the usual tourist itineraries, where food
and beverage choices may be more limited. While immunization is recommended, travelers should be
cautioned that none of the available typhoid vaccines is 100% effective, nor do they provide cross-protection
against other common causes of gastrointestinal infections. Typhoid vaccination is not a substitute for
careful selection of food and drink (see Chapter 2).
VACCINE
Page | 30
Two typhoid vaccines are currently available in the United States: an oral live, attenuated vaccine (Vivotif
Berna vaccine, manufactured from the Ty21a strain of S. Typhi by the Swiss Serum and Vaccine Institute)
and a Vi capsular polysaccharide vaccine (ViCPS) (Typhim Vi, manufactured by sanofi pasteur) for
intramuscular use. Both vaccines protect 50%-80% of recipients (5,6). The intramuscular heat-phenolinactivated vaccine (manufactured by Wyeth-Ayerst) was discontinued in 2000. Combined hepatitis
A/typhoid fever vaccines are not licensed in the United States, but may be available in other countries (7).
Table 4-21 provides information on vaccine dosage, administration, and revaccination. The time required for
primary vaccination differs for the two vaccines, as do the lower age limits.
Primary vaccination with oral Ty21a vaccine consists of four capsules, one taken every other day. The
capsules should be kept refrigerated (not frozen), and all four doses must be taken to achieve maximum
efficacy. Each capsule should be taken with cool liquid no warmer than 37° C (98.6° F), approximately 1
hour before a meal. This regimen should be completed 1 week before potential exposure. The vaccine
manufacturer recommends that Ty21a not be administered to infants or children younger than 6 years of age.
Primary vaccination with ViCPS consists of one 0.5-mL (25-µg) dose administered intramuscularly. One
dose of this vac-cine should be given at least 2 weeks before expected exposure. The manufacturer does not
recommend the vaccine for infants and children younger than 2 years of age. (See Chapter 8 for a discussion
of typhoid immunization for infants who will be traveling.)
Adverse Reactions
Information on adverse reactions is presented in Table 4-22. Information is not available on the safety of
these vaccines in pregnancy; it is prudent on theoretical grounds to avoid vaccinating pregnant women (see
Chapter 9). Live, attenuated Ty21a vaccine should not be given to immunocompromised travelers, including
those infected with HIV. The intramuscular vaccine presents a theoretically safer alternative for this group.
The only contraindication to vaccination with ViCPS vaccine is a history of severe local or systemic
reactions after a previous dose. Neither of the available vaccines should be given to persons with an acute
febrile illness.
Precautions and Contraindications
Theoretical concerns have been raised about the immunogenicity of live, attenuated Ty21a vaccine in
persons concurrently receiving antibiotics, immune globulin, or viral vaccines (9). The growth of the live
Ty21a strain is inhibited in vitro by various antibacterial agents. Vaccination with Ty21a should be delayed
for >24 hours after the administration of any antibacterial agent. Available data do not suggest that
simultaneous administration of oral polio or yellow fever vaccine decreases the immunogenicity of Ty21a. If
typhoid vaccination is warranted, it should not be delayed because of administration of viral vaccines.
Simultaneous administration of Ty21a and immune globulin does not appear to pose a problem.
OTHER PREVENTION
See Risks from food and drink in Chapter 2.
Page | 31
TABLE 4-21. Dosage and schedule for typhoid fever vaccination
VACCINATION
AGE
(YRS)
DOSE/MODE OF
ADMINISTRATION
NO. OF
DOSES
DOSING
INTERVAL
BOOSTING
INTERVAL
Oral, live, attenuated
Ty21a vaccine
≥6
1 capsule1, oral
4
48 hrs
Not applicable
Booster
≥6
Vi Capsular
polysaccharide vaccine
1 capsule1, oral
4
48 hrs
Every 5 yrs
Primary series
Primary series
≥2
0.50 mL,intramuscular
1
Not applicable
Not applicable
Booster
≥2
0.50 mL,intramuscular
1
Not applicable
Every 2 yrs
1
Administer with cool liquid no warmer than 37°C (98.6°F).
TABLE 4-22. Common adverse reactions to typhoid fever vaccines
VACCINATION
Ty21a*
Vi Capsular
polysaccharide>
AGE
(YRS)
0%-5%
REACTIONS
DOSE/MODE OF
ADMINISTRATION
0%-5%
0%-1%/td> 16%-20%/td>
NO. OF DOSES
Not applicable
7% erythema or induration 1
cm
*The side effects of Ty21a are rare and mainly consist of abdominal discomfort, nausea, vomiting, and rash
or urticaria.
Treatment
Specific antimicrobial therapy shortens the clinical course of typhoid fever and reduces the risk of death.
Persons who may have been exposed to Salmonella enterica serotype Typhi and who develop symptoms of
typhoid fever should seek medical care. Antimicrobial therapy should be guided by data on antimicrobial
sensitivity, particularly for travelers to South Asia. Patients should be monitored to ensure that fever wanes
within a few days of starting treatment. If fever does not subside, alternative antimicrobial agents or other foci
of infection should be considered.
References
1. Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ.
2004;82(5):346-53.
2. Ackers ML, Puhr ND, Tauxe RV, Mintz ED. Laboratory-based surveillance of Salmonella serotype
Typhi infections in the United States: antimicrobial resistance on the rise. JAMA. 2000;283(20):266873.
Page | 32
3. Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM, et al. Typhoid fever in
travelers: who should be targeted for prevention? Clin Infect Dis. 2004;39:186-91.
4. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347:1770-82.
5. Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, et al. Protective
activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987;2:1165-9.
6. Simanjuntak CH, Paleologo FP, Punjabi NH, Darmowigoto R, Soeprawoto, Totosudirjo H, et al. Oral
immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet. 1991;338:1055-9.
7. Beeching NJ, Clarke PD, Kitchin NR, Pirmohamed J, Veitch K, Weber F. Comparison of two combined
vaccines against typhoid fever and hepatitis A in healthy adults. Vaccine. 2004;23:29-35.
8. CDC. Typhoid immunization: Recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR Morbid Mortal Wkly Rep. 1994;43(RR-14):1-7.
9. Kollaritsch H, Que JU, Kunz C, Wiedermann G, Herzog C, Cryz SJ Jr. Safety and immunogenicity of
live oral cholera and typhoid vaccines administered alone or in combination with antimalarial drugs, oral
polio vaccine, or yellow fever vaccine. J Infect Dis. 1997;175:871-5.
SHARON GREENE, ERIC MINTZ
Page Located on the Web at http://wwwn.cdc.gov/travel/yellowBookCh4-Typhoid.aspx
Page | 33
Rabies
Description
Rabies is an acute, progressive, fatal encephalomyelitis caused by neurotropic viruses in the family
Rhabdoviridae, genus Lyssavirus (1,2). The disease is almost always transmitted by an animal bite that
inoculates the virus into wounds. Very rarely, rabies has been transmitted by exposures other than bites that
introduce the virus into open wounds or mucous membranes (3-5). All mammals are believed to be
susceptible, but reservoirs are carnivores and bats. Although dogs are the main reservoir in developing
countries, the epidemiology of the disease differs sufficiently from one region or country to another to
warrant the medical evaluation of all mammal bites (6-8).
Occurrence
Rabies is found on all continents except Antarctica. In certain areas of the world, canine rabies remains
highly endemic, including (but not limited to) parts of Africa, Asia, and Central and South America (8,9).
Table 4-14 lists countries that have reported no cases of rabies during the most recent period for which
information is available (formerly referred to as “rabies-free countries”).
Additional information can be obtained from the World Health Organization
(http://wwwn.cdc.gov/travel/forward.aspx?t=http://www.who.int/rabies/rabnet/en/), the Pan American
Health Organization
(http://wwwn.cdc.gov/travel/forward.aspx?t=http://www.paho.org/english/ad/dpc/vp/rabia.htm), the
Rabies Bulletin-Europe (http://wwwn.cdc.gov/travel/forward.aspx?t=http://www.rbe.fli.bund.de), the
World Organization for Animal Health
(http://wwwn.cdc.gov/travel/forward.aspx?t=http://www.oie.int/eng/en_index.htm), local health
authorities of the country, the embassy, or the local consulate’s office in the United States. Lists are provided
only as a guide, because up to date information may not be available, surveillance standards vary, and
reporting status can change suddenly as a result of disease re-introduction or emergence (10,11).
Page | 34
TABLE 4-14. Countries and political units reporting no indigenous cases of rabies during
20051
REGION
COUNTRIES
Africa
Cape Verde, Libya, Mauritius, Réunion, São Tome and Principe, and Seychelles
North: Bermuda, St. Pierre and Miquelon
Americas
Caribbean: Antigua and Barbuda, Aruba, Bahamas, Barbados, Cayman Islands, Dominica,
Guadeloupe, Jamaica, Martinique, Montserrat, Netherlands Antilles, Saint Kitts (Saint Christopher)
and Nevis, Saint Lucia, Saint Martin, Saint Vincent and Grenadines, Turks and Caicos, and Virgin
Islands (UK and US)
South: Uruguay
Asia
Hong Kong, Japan, Kuwait, Lebanon, Malaysia (Sabah), Qatar, Singapore, United Arab Emirates
Austria, Belgium, Cyprus, Czech Republic2, Denmark2, Finland, France2, Gibraltar, Greece, Iceland,
Europe Ireland, Isle of Man, Italy, Luxemburg, Netherlands2, Norway, Portugal, Spain2 (except Ceuta/
Melilla), Sweden, Switzerland, and United Kingdom2
Australia2, Northern Mariana Islands, Cook Islands, Fiji, French Polynesia, Guam, Hawaii, Kiribati,
Oceania
Micronesia, New Caledonia, New Zealand, Palau, Papua New Guinea, Samoa, and Vanuatu
1
Bat rabies may exist in some areas that are reportedly free of rabies in other animals.
2
Bat lyssaviruses are known to exist in these areas that are reportedly free of rabies in other animals.
3
Most of Pacific Oceania is reportedly rabies-free.
Risk for Travelers
Rabies vaccination is not a requirement for entry into any country. However, travelers to rabies-endemic
countries should be warned about the risk of acquiring rabies and educated in animal bite prevention
strategies (12-16). Travelers with extensive unprotected outdoor exposure such as might be experienced
while bicycling, camping, hiking, or engaging in certain occupational activities, might be at higher risk even
if their trip is brief. Also, children are considered at higher risk because of their tendencies to play with
animals and to not report bites. Casual exposure to cave air is not a concern, but cavers should be warned not
to handle bats (3).
Clinical Presentation
After infection, the incubation period is highly variable, but lasts approximately 1-3 months. The disease
progresses from a nonspecific prodromal phase to paresis or paralysis; spasms of swallowing muscles can be
stimulated by the sight, sound, or perception of water (hydrophobia); delirium and convulsions can develop,
followed rapidly by coma and death. No treatment is effective after the development of clinical signs, but the
extremely rare case of recovery after extensive medical intervention offers hope that future experimental
therapeutics may be developed (17-18).
Prevention
Pre-exposure vaccination with human diploid cell rabies vaccine (HDCV), or purified chick embryo cell
(PCEC) vaccine, may be recommended for international travelers based on the local incidence of rabies in
Page | 35
the country to be visited, the availability of appropriate antirabies biologicals, and the intended activity and
duration of stay of the traveler (19). Different schedules, alternative routes of administration, and other
rabies vaccines besides HDCV and PCEC may be found abroad (20,21). Pre-exposure vaccination may be
recommended for veterinarians, animal handlers, field biologists, spelunkers, missionaries, and certain
laboratory workers. Table 4-15 provides criteria for pre-exposure vaccination. Pre-exposure vaccination does
not eliminate the need for additional medical attention after a rabies exposure but simplifies postexposure
prophylaxis in populations at risk by eliminating the need for rabies immune globulin (RIG) and by
decreasing the number of doses of vaccine required. Pre-exposure vaccination is of particular importance for
travelers at risk of exposure to rabies in countries where biologicals are in short supply and locally available
rabies vaccines might carry a higher risk of adverse reactions (20). Pre-exposure vaccination may also
provide some degree of protection when there is an unapparent or unrecognized exposure to rabies and when
postexposure prophylaxis might be delayed. Planning is needed to ensure compliance in completion of the
three pre-exposure vaccine doses, prior to commencing travel (22).
Travelers should be advised that any animal bite or scratch should receive prompt local treatment by
thorough cleansing of the wound with copious amounts of soap and water (and povidone iodine, if
available). This local treatment will substantially reduce the risk of rabies. Travelers who might have been
exposed to rabies should be advised to always contact local health authorities immediately for advice about
postexposure prophylaxis and should also contact their personal physician or state health department as soon
as possible thereafter.
Equine rabies immune globulin (ERIG), or purified fractions of ERIG, has been used effectively in some
developing countries where human rabies immune globulin (RIG) might not be available (20). If necessary,
such heterologous products are preferable to no RIG administration in human rabies postexposure
prophylaxis. The incidence of adverse reactions after the use of these products has been low (0.8%-6.0%),
and most of those reactions were minor. However, such products are neither evaluated by U.S. standards nor
regulated by the U.S. Food and Drug Administration, and their use cannot be unequivocally recommended at
this time (19). In addition, unpurified antirabies serum of equine origin might still be used in some countries
where neither human RIG nor ERIG is available. The use of this antirabies serum is associated with higher
rates of serious adverse reactions, including anaphylaxis.
Tables 4-16 and 4-17 provide information on pre-exposure and postexposure prophylaxis. Routine serologic
testing is not necessary for travelers who receive the recommended pre-exposure or postexposure regimen
with HDCV or PCEC vaccines. Exposed travelers previously vaccinated with vaccines other than those
produced by cell culture should receive the complete postexposure regimen unless they have developed a
laboratory-confirmed virus neutralizing antibody response to the primary vaccination. Serologic testing is
still recommended for travelers whose immune response might be diminished by drug therapy or by
diseases. Rabies pre-exposure prophylaxis may not be indicated for travelers to the countries in Table 4-14,
and postexposure prophylaxis is rarely necessary after exposures to domestic animals in these countries.
Practitioners are urged to follow established current guidelines for schedules and doses of vaccine used in
rabies prophylaxis (23).
ADVERSE REACTIONS
Travelers should be advised that they may experience local reactions after vaccination, such as pain,
erythema, swelling, or itching at the injection site, or mild systemic reactions, such as headache, nausea,
abdominal pain, muscle aches, and dizziness (19,20). Approximately 6% of persons receiving booster
vaccinations with HDCV may experience an immune complex-like reaction characterized by urticaria,
pruritus, and malaise. Once initiated, rabies postexposure prophylaxis should not be interrupted or
discontinued because of local or mild systemic reactions to rabies vaccine.
Page | 36
PRECAUTIONS AND CONTRAINDICATIONS
Pregnancy
Pregnancy is not a contraindication to postexposure prophylaxis (19,20).
Age
In infants and children, the dose of HDCV or PCEC for pre-exposure or postexposure prophylaxis is the
same as that rec-ommended for adults (19,20). The dose of RIG for postexposure prophylaxis is based on
body weight (Table 4-17).
TABLE 4-15. Criteria for pre-exposure immunization for rabies
RISK
CATEGORY
NATURE OF RISK
TYPICAL POPULATIONS
PREEXPOSURE
REGIMEN
Virus present
continuously, often in
high concentrations
Continuous
Specific exposures
likely to go
unrecognized
Bite, non-bite, or
aerosol exposure
Exposure usually
episodic with source
recognized, but
exposure might also
be unrecognized
Frequent
Infrequent
(greater than
general
population)
Rare (general
population)
Bite, nonbite, or
aerosol exposure
possible
Exposure nearly
always episodic with
source recognized
Bite or nonbite
exposure
Exposure always
episodic, with source
recognized
Rabies research laboratory workers1,
rabies biologics production workers
Primary course: Serologic
testing every 6 months;
booster vaccination if
antibody titer is below
acceptable level2
Rabies diagnostic laboratory workers1,
cavers, veterinarians and staff, and
animal control and wildlife workers in
rabiesepizootic areas
Primary course: Serologic
testing every 2 years;
booster vaccination if
antibody titer is below
acceptable level2
Veterinarians, animal control and
wildlife workers in areas with low rabies
rates; veterinary students; and travelers Primary course: No
visiting areas where rabies is enzootic
serologic testing or booster
and immediate access to appropriate
vaccination
medical care, including biologics, is
limited.
U.S. population at large, including
individuals in rabies-epizootic areas
No pre-exposure
immunization necessary
Page | 37
1
Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the
responsibility of the laboratory supervisor (see U.S. Department of Health and Human Service’s Biosafety in
Microbiological and Biomedical Laboratories, 1999).
2
Preexposure booster immunization consists of one dose of human diploid cell [rabies] vaccine (HDCV), or
purified chick embryo cell (PCEC) vaccine, 1.0-mL dose, intramuscular (IM) (deltoid area). Minimum
acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent
focus inhibition test. A booster dose should be administered if titer falls below this level.
TABLE 4-16. Pre-exposure immunization for rabies1
VACCINE DOSE (mL) NO. OF DOSES SCHEDULE (DAYS) ROUTE
HDCV
1.0
3
0, 7, 21 or 28
Intramuscular
PCEC
1.0
3
0, 7, 21 or 28
Intramuscular
HDCV, human diploid cell vaccine; PCEC, purified chick embryo cell.1Patients who are immunosuppressed
by disease or medications should postpone pre-exposure vaccinations and consider avoiding activities for
which rabies pre-exposure prophylaxis is indicated. When this course is not possible, immunosuppressed
persons who are at risk for rabies should have their antibody titers checked after vaccination.
TABLE 4-17. Postexposure immunization for rabies1
IMMUNIZATION
STATUS
VACCINE /
PRODUCT
RIG plus
SCHEDULE
(DAYS)
ROUTE
1
0
Infiltrated at bite site (if
possible); remainder
intramuscular.
HDCV or PCEC 1.0 mL
5
0, 3, 7, 14, 28
Intramuscular
HDCV PCEC
2
0, 3
Intramuscular
Not previously
immunized
Previously
immunized2, 3
NO. OF
DOSES
DOSE
20 IU/kg
body
weight
1.0 mL
RIG, rabies immune globulin; HDCV, human diploid cell (rabies) vaccine; PCEC, purified chick embryo
cell.
1
All postexposure prophylaxis should begin with immediate, thorough cleansing of all wounds with soap and
water.
2
Pre-exposure immunization with HDCV or PCEC; prior postexposure prophylaxis with HDCV or PCEC; or
persons previously immunized with any other type of rabies vaccine and a documented history of positive
antibody response to the prior vaccination.
3
RIG should not be administered.
References
1. Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet. 2004;363:959-69.
2. Nel L. Vaccines for lyssaviruses other than rabies. Expert Rev Vaccines. 2005;4:533-40.
3. Gibbons RV. Cryptogenic rabies, bats, and the question of aerosol transmission. Ann Emerg Med.
2002;39:528-36.
4. Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, et al. Transmission of
rabies virus from an organ donor to four transplant recipients. N Engl J Med. 2005;352:1103-11.
Page | 38
5. Hellenbrand W, Meyer C, Rasch G, Steffens I, Ammon A. Cases of rabies in Germany following
organ transplantation. Euro Surveill. 2005;10:E050224.6.
6. Fooks AR, McElhinney LM, Pounder DJ, Finnegan CJ, Mansfield K, Johnson N, et al. Case report:
isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med
Virol. 2003;71:281-9.
7. Taplitz RA. Managing bite wounds. Currently recommended antibiotics for treatment and prophylaxis.
Postgrad Med. 2004;116:49-52, 55-6, 59.
8. Gupta RK. Recent outbreak of rabies infections in Brazil transmitted by vampire bats. Euro Surveill.
2005;10:E051110.3.
9. Knobel DL, Cleaveland S, Coleman PG, Fevre EM, Meltzer MI, Miranda ME et al. Re-evaluating the
burden of rabies in Africa and Asia. Bull World Health Organ. 2005;83:360-8.
10. Hore C. Important unusual infections in Australia: a critical care perspective. Crit Care Resusc.
2001;3:262-72.11.
11. Kim CH, Lee CG, Yoon HC, Nam HM, Park CK, Lee JC, et al. Rabies, an emerging disease in
Korea. J Vet Med B Infect Dis Vet Public Health. 2006;53:111-5.12.
12. Wilde H, Briggs DJ, Meslin FX, Hemachudha T, Sitprija V. Rabies update for travel medicine
advisors. Clin Infect Dis. 2003;37:96-100.
13. Strauss R, Granz A, Wassermann-Neuhold M, Krause R, Bago Z, Revilla-Fernandez S, et al. A
human case of travel-related rabies in Austria, September 2004. Euro Surveill. 2005;10:225-6.
14. Smith A, Petrovic M, Solomon T, Fooks A. Death from rabies in a UK traveler returning from India.
Euro Surveill. 2005;10:E050728.5.
15. Rendi-Wagner P, Jeschko E, Kollaritsch H, osterreichische Expertengruppe fur Reisemedizin. Travel
vaccination recommendations for Central and Eastern European countries based on country-specific
risk profiles. Wien Klin Wochenschr. 2005;117 Suppl 4:11-9.
16. Richardson M. The management of animal and human bite wounds. Nurs Times. 2006;102:34-6.
17. Jackson AC, Warrell MJ, Rupprecht CE, Ertl HC, Dietzschold B, O’Reilly M, et al. Management of
rabies in humans. Clin Infect Dis. 2003;36:60-3.
18. Willoughby RE Jr, Tieves KS, Hoffman GM, Ghanayem NS, Amlie-Lefond CM, Schwabe MJ, et al.
Survival after treatment of rabies with induction of coma. N Engl J Med. 2005;352:2508-14.
19. CDC. Human rabies prevention — United States, 1999. Recommendations of the Advisory
Committee on Immuniza-tion Practices (ACIP). MMWR Morbid Mortal Wkly Rep. 1999;48(RR1):1-21.
20. World Health Organization Expert Consultation on Rabies. World Health Organ Tech Rep Ser.
2005;931:1-88.
21. Khawplod P, Wilde H, Sirikwin S, Benjawongkulchai M, Limusanno S, Jaijaroensab W, Chiraguna
N, et al. Revision of the Thai Red Cross intradermal rabies post-exposure regimen by eliminating the
90-day booster injection. Vaccine. 2006;24:3084-6.
22. Heudorf U, Tiarks-Jungk P, Stark S. Travel medicine and vaccination as a task of infection
prevention. Gesundheitswesen. 2006;68:316-22.
23. Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against rabies. N Engl J Med.
2004;351:2626-35.
CHARLES E. RUPPRECHT
Page Located on the Web at http://wwwn.cdc.gov/travel/yellowBookCh4-Rabies.aspx
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