According to the World Health Organization (WHO), the Ministry of Health in Kenya has reported 32 cases of Rift Valley fever resulting in 19 deaths. The outbreak is occurring in remote parts of northeastern Kenya, primarily in flood-affected areas of Garissa, including Korakora, Chanta Abak, Shell Gulliet, and Shimbirey. An investigation and response measures are underway, with the help of several international organizations and agencies.
Recommendations for Travelers
Generally, the risk of Rift Valley fever infection is low for travelers, unless they are in areas where an outbreak is occurring and are bitten by infected insects or come in contact with body fluids and aerosols from infected animals (primarily livestock).
There are no preventive medications or licensed vaccines for Rift Valley fever, but travelers to affected areas can take the following steps to reduce their risk of infection:
Rift Valley fever is a viral disease generally found in sub-Saharan Africa where sheep and cattle are raised, but the virus has also occurred in Egypt, the Arabian Peninsula and in Madagascar. Rift Valley fever virus primarily affects livestock and can cause disease in a large number of domestic animals. Although the virus is usually transmitted by infected mosquitoes and possibly other biting insects that have virus contaminated mouthparts, Rift Valley Fever virus is occasionally transmitted to humans through contact with the blood, body fluids, or tissues of the infected animals (e.g., exposure through veterinary or obstetric procedures or direct exposure during slaughter).
Rift Valley fever (RVF) is an acute, fever-causing viral disease that affects domestic animals (such as cattle, buffalo, sheep, goats, and camels) and humans. RVF is most commonly associated with mosquito-borne epidemics during years of unusually heavy rainfall.
The disease is caused by the RVF virus, a member of the genus Phlebovirus in the family Bunyaviridae. The disease was first reported among livestock by veterinary officers in Kenya in the early 1900s.
RVF is generally found in regions of eastern and southern Africa where sheep and cattle are raised, but the virus also exists in most countries of sub-Saharan Africa and in Madagascar. In September 2000, a RVF outbreak was reported in Saudi Arabia and subsequently Yemen. These cases represent the first Rift Valley fever cases identified outside Africa.
RVF virus primarily affects livestock and can cause disease in a large number of domestic animals (this situation is referred to as an "epizootic"). The presence of an RVF epizootic can lead to an epidemic among humans who are exposed to diseased animals. The most notable epizootic of RVF, which occurred in Kenya in 1950-1951, resulted in the death of an estimated 100,000 sheep. In 1977, the virus was detected in Egypt (probably exported there in infected domestic animals from Sudan) and caused a large outbreak of RVF among animals and humans. The first epidemic of RVF in West Africa was reported in 1987 and was linked to construction of the Senegal River Project. The project caused flooding in the lower Senegal River area and altered interactions between animals and humans resulting in transmission of the RVF virus to humans.
An epizootic of RVF is generally observed during years in which unusually heavy rainfall and localized flooding occur. The excessive rainfall allows mosquito eggs, usually of the genus Aedes, to hatch. The mosquito eggs are naturally infected with the RVF virus, and the resulting mosquitoes transfer the virus to the livestock on which they feed. Once the livestock is infected, other species of mosquitoes can become infected from the animals and can spread the disease. In addition, it is possible that the virus can be transmitted by other biting insects.
Humans can get RVF as a result of bites from mosquitoes and possibly other bloodsucking insects that serve as vectors. Humans can also get the disease if they are exposed to either the blood or other body fluids of infected animals. This exposure can result from the slaughtering or handling of infected animals or by touching contaminated meat during the preparation of food. Infection through aerosol transmission of RVF virus has resulted from contact with laboratory specimens containing the virus.
RVF virus can cause several different disease syndromes. People with RVF typically have either no symptoms or a mild illness associated with fever and liver abnormalities. However, in some patients the illness can progress to hemorrhagic fever (which can lead to shock or hemorrhage), encephalitis (inflammation of the brain, which can lead to headaches, coma, or seizures), or ocular disease (diseases affecting the eye). Patients who become ill usually experience fever, generalized weakness, back pain, dizziness, and extreme weight loss at the onset of the illness. Typically, patients recover within two days to one week after onset of illness.
The most common complication associated with RVF is inflammation of the retina (a structure connecting the nerves of the eye to the brain). As a result, approximately 1% - 10% of affected patients may have some permanent vision loss.
Approximately 1% of humans that become infected with RVF die of the disease. Case-fatality proportions are significantly higher for infected animals. The most severe impact is observed in pregnant livestock infected with RVF, which results in abortion of virtually 100% of fetuses.
There is no established course of treatment for patients infected with RVF virus. However, studies in monkeys and other animals have shown promise for ribavirin, an antiviral drug, for future use in humans. Additional studies suggest that interferon, immune modulators, and convalescent-phase plasma may also help in the treatment of patients with RVF.
Studies have shown that sleeping outdoors at night in geographical regions where outbreaks occur could be a risk factor for exposure to mosquito and other insect vectors. Animal herdsmen, abattoir workers, and other individuals who work with animals in RVF-endemic areas (areas where the virus is present) have an increased risk for infection. Persons in high-risk professions, such as veterinarians and slaughterhouse workers, have an increased chance of contracting the virus from an infected animal. International travelers increase their chances of getting the disease when they visit RVF-endemic locations during periods when sporadic cases or epidemics are occurring.
A person's chances of becoming infected can be reduced by taking measures to decrease contact with mosquitoes and other bloodsucking insects through the use of mosquito repellents and bednets. Avoiding exposure to blood or tissues of animals that may potentially be infected is an important protective measure for persons working with animals in RVF-endemic areas.
A number of challenges remain for the control and prevention of RVF. Knowledge regarding how the virus is transmitted among mosquitoes and the role of vertebrates in propagating the virus must be answered to predict and control future outbreaks of RVF. Vaccines for veterinary use are available, but they can cause birth defects and abortions in sheep and induce only low-level protection in cattle. The human live attenuated vaccine, MP-12, has demonstrated promising results in laboratory trials in domestic animals, but more research will be needed before the vaccine can be used in the field. In addition, surveillance (close monitoring for RVF infection in animal and human populations) is essential to learning more about how RVF virus infection is transmitted and to formulate effective measures for reducing the number of infections.
Chikungunya fever is a viral disease transmitted to humans by the bite of infected mosquitoes. Chikungunya virus (CHIKV) is a member of the genus Alphavirus, in the family Togaviridae. CHIKV was first isolated from the blood of a febrile patient in Tanzania in 1953, and has since been identified repeatedly in west, central and southern Africa and many areas of Asia, and has been cited as the cause of numerous human epidemics in those areas since that time. The virus circulates throughout much of Africa, with transmission thought to occur mainly between mosquitoes and monkeys.
CHIKV infection can cause a debilitating illness, most often characterized by fever, headache, fatigue, nausea, vomiting, muscle pain, rash, and joint pain. The term ‘chikungunya’ is Swahili for ‘that which bends up.’
The incubation period (time from infection to illness) can be 2-12 days, but is usually 3-7 days. “Silent” CHIKV infections (infections without illness) do occur; but how commonly this happens is not yet known.
Acute chikungunya fever typically lasts a few days to a couple of weeks, but as with dengue, West Nile fever, o'nyong-nyong fever and other arboviral fevers, some patients have prolonged fatigue lasting several weeks. Additionally, some patients have reported
incapacitating joint pain, or arthritis which may last for weeks or months. The prolonged joint pain associated with CHIKV is not typical of dengue. Co-circulation of dengue fever in many areas may mean that chikungunya fever cases are sometimes clinically misdiagnosed as dengue infections, therefore the incidence of chikungunya fever could be much higher than what has been previously reported.
No deaths, neuroinvasive cases, or hemorrhagic cases related to CHIKV infection have been conclusively documented in the scientific literature.
CHIKV infection (whether clinical or silent) is thought to confer life-long immunity.
CHIKV is spread by the bite of an infected mosquito. Mosquitoes become infected when they feed on a person infected with CHIKV. Monkeys, and possibly other wild animals, may also serve as reservoirs of the virus. Infected mosquitoes can then spread the virus to other humans when they bite.
Aedes aegypti (the yellow fever mosquito), a household container breeder and aggressive daytime biter which is attracted to humans, is the primary vector of CHIKV to humans. Aedes albopictus (the Asian tiger mosquito)may also play a role in human transmission is Asia, and various forest-dwelling mosquito species in Africa have been found to be infected with the virus.
The geographic range of the virus is Africa and Asia. For information on current outbreaks, consult CDC’s Travelers’ Health website (www.cdc.gov/travel). Given the current large CHIKV epidemics and the world wide distribution of Aedes aegypti, there is a risk of importation of CHIKV into new areas by infected travelers.
No vaccine or specific antiviral treatment for chikungunya fever is available. Treatment is symptomatic--rest, fluids, and ibuprofen, naproxen, acetaminophen, or paracetamol may relieve symptoms of fever and aching. Aspirin should be avoided.
Infected persons should be protected from further mosquito exposure (staying indoors and/or under a mosquito net during the first few days of illness) so that they can't contribute to the transmission cycle.
The best way to avoid CHIKV infection is to prevent mosquito bites. There is no vaccine or preventive drug. Prevention tips are similar to those for dengue or West Nile virus:
Yellow fever is a viral disease that is transmitted to humans through the bite of infected mosquitoes. Illness ranges in severity from an influenza-like syndrome to severe hepatitis and hemorrhagic fever. The yellow fever virus is maintained in nature by mosquito-borne transmission between nonhuman primates. Transmission by mosquitoes from one human to another occurs during epidemics of "urban yellow fever."
The disease occurs only in sub-Saharan Africa and tropical South America, where it is endemic and intermittently epidemic. (See Table 4-22 for a list of countries that lie within the endemic zone, which is defined as those areas where there is active yellow fever transmission as well as those in which yellow fever may be more likely to occur because of the presence of the vector and infection in nonhuman primates.) In Africa, where most cases are reported, a variety of vectors are responsible for transmitting the virus. The case-fatality rate is >20%, and infants and children are at greatest risk for infection.
A traveler's risk of acquiring yellow fever is determined by immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and the local rate of yellow fever virus transmission at the time. Although reported cases of human disease are the principal indicator of disease risk, they may be absent (because of a high level of immunity in the population) or not detected as a result of poor surveillance. Only a small proportion of yellow fever cases are officially reported because of the occurrence of the disease in remote areas and lack of specific diagnostic facilities.
|Table 4-22. Countries in the Yellow Fever-Endemic Zone|
Central African Republic
Democratic Republic of Congo
São Tomé and Principe
1These countries are not holo-endemic. Please see Map 4-13 and yellow fever vaccine recommendations for details.
During interepidemic periods, low-level transmission may not be detected by public health surveillance. Such interepidemic conditions may last years or even decades in certain countries or regions. This "epidemiologic silence" may provide a sense of false security and lead to travel without the benefit of vaccination. Surveys in rural West Africa during "silent" periods have estimated an incidence of yellow fever of 1.1-2.4 cases per 1,000 persons and an incidence of death due to yellow fever of 0.2-0.5 deaths per 1,000 persons; both these ranges are less than the threshold of detection of the surveillance systems in place.
The incidence of yellow fever in South America is lower than that in Africa because the mosquitoes that transmit the virus between monkeys in the forest canopy do not often come in contact with humans and because immunity in the indigenous human population is high. Urban epidemic transmission has not occurred in South America for many years, although the risk of introduction of the virus into towns and cities is ever present. For travelers, the risks of illness and death due to yellow fever are probably 10 times greater in rural West Africa than in South America; these risks vary greatly according to specific location and season. In West Africa, the most dangerous time of year is during the late rainy and early dry seasons (July-October). Virus transmission is highest during the rainy season (January-March) in Brazil.
The risks of illness and of death due to yellow fever in an unvaccinated traveler in endemic areas in Africa are estimated to be 1:1,000 and 1:5,000 per month, respectively. (For a 2-week stay, the risks of illness and death are 1:2,000 and 1:10,000, respectively.) The risks of illness and death to travelers to South America are probably 10 times lower (1:20,000 and 1:100,000, respectively for a two week trip). These estimates are based on risk to indigenous populations and may overestimate the risk to travelers, who may have a different immunity profile, take precautions against getting bitten by mosquitoes, and have less outdoor exposure. Based on data for U.S. travelers, the risk for illness in a traveler due to yellow fever has been estimated to be 0.4-4.3 cases per million travelers to yellow fever-endemic areas.
In addition to vaccination, travelers to areas with yellow fever transmission should be advised to take precautions against exposure to mosquitoes. Staying in air-conditioned or well-screened quarters and wearing long-sleeved shirts and long pants will help to prevent mosquito bites. Insect repellents containing DEET should be used on exposed skin. Permethrin-containing repellents should be applied to clothing. (For further prevention information, see Protection against Mosquitoes and Other Arthropods.)
Yellow fever is preventable by a relatively safe, effective vaccine. To meet international vaccination requirements, yellow fever vaccines must be manufactured under approval by the World Health Organization and administered at an approved yellow fever vaccination center. For all eligible persons, a single injection of 0.5 mL of reconstituted vaccine should be administered subcutaneously. Authorized U.S. vaccination centers can be identified by contacting state or local health departments or by visiting CDC's Travelers' Health website, where there is a listing of current authorized yellow fever vaccination providers in the United States. (http://www2.ncid.cdc.gov/travel/yellowfever/).
Reactions to yellow fever vaccine are generally mild. Vaccine recipients have reported mild headaches, myalgia, low-grade fevers, or other minor symptoms that may begin within days after vaccination and last 5-10 days after vaccination. In clinical trials, the incidence of mild adverse events has been ∼25%, but many events may have been unrelated, as the trials were not placebo-controlled. Approximately 1% of vaccinees find it necessary to curtail regular activities. Immediate hypersensitivity reactions, characterized by rash, urticaria, or asthma or a combination of these, are uncommon (incidence <1 case per 131,000 vaccinees). Unrecognized allergy to eggs or chicken or to the hydrolyzed gelatin used to stabilize the vaccine may be responsible for hypersensitivity reactions. Persons who have allergies to egg, chicken, or gelatin should be evaluated by an allergist to determine whether they can safely receive yellow fever vaccine.
Historically, yellow fever vaccine-associated adverse events were seen primarily among infants, and presented as encephalitis. Since 1992, five cases of encephalitis among adult recipients of yellow fever vaccine have been reported to the U.S. Vaccine Adverse Event Reporting System (VAERS). In addition, ten cases of autoimmune neurologic disease have been reported to VAERS, including patients with Guillian-Barré syndrome and acute disseminated encephalomyelitis. All patients with yellow fever vaccine-associated neurologic disease (YEL-AND) had an onset of illness 4-23 days after vaccination. All cases were in first-time vaccine recipients. The risk for vaccine-associated neurologic disease does not appear to be limited to infants, and crude estimates in the United States of the reported frequency range from 4 to 6 cases per 1,000,000 doses distributed.
A serious adverse reaction syndrome has recently been described among recipients of yellow fever vaccines produced by several different manufacturers. This syndrome was previously reported as febrile multiple organ system failure and is now called yellow fever vaccine-associated viscerotropic disease (YEL-AVD). Since 1996, nine cases of yellow fever vaccine-associated viscerotropic disease, a disease clinically and pathologically resembling naturally acquired yellow fever, have been reported in the U.S.; an additional 17 cases have been identified worldwide as of October 2004. All U.S. cases required intensive care after experiencing fever, hypotension, respiratory failure, elevated hepatocellular enzymes, hyperbilirubinemia, lymphocytopenia, and thrombocytopenia; eight of the nine also had renal failure, which required hemodialysis. Six (67%) of the U.S. cases have been fatal. In several cases for which tissue samples were available, immunohistochemistry demonstrated viral dissemination throughout the body, including liver, lung, spleen, lymph node, brain, and smooth muscle; however, in many cases, tissue samples were not available for histopathologic review or detection of virus. All cases reported thus far have occurred in primary vaccinees. Yellow fever vaccines must be considered as a possible, but rare, cause of yellow fever vaccine-associated viscerotropic disease that is similar to fulminant yellow fever caused by wild-type yellow fever virus. Accurately measuring the incidence of vaccine-associated viscerotropic disease is currently precluded by lack of adequate prospective data; however, crude estimates in the United States of the reported frequency range from 3 to 5 cases per 1,000,000 doses distributed. This frequency appears to be higher for persons >60 years of age, as much as 19 cases per million doses distributed.
Because of recent reports of deaths from yellow fever among unvaccinated travelers to areas endemic for yellow fever and of these reports of vaccine-associated viscerotropic disease, yellow fever vaccination of travelers to high-risk areas should be encouraged as a key prevention strategy; however, physicians should be careful to administer the vaccine only to persons truly at risk for exposure to yellow fever. Additional surveillance to better monitor and quantify wild-type yellow fever activity, as well as yellow fever vaccine-specific adverse outcomes, should be established. Studies are being conducted to clarify the cause and risk factors for these rare adverse events associated with the yellow fever vaccines.
The risk for adverse reactions appears to be age related. Infants <6 months of age should not be vaccinated because they are more susceptible to the serious adverse reaction of yellow fever vaccine-associated neurotropic disease (also known as postvaccinal encephalitis) than are older children. Immunization should be delayed until an infant is at least 9 months of age. In unusual circumstances, physicians considering vaccinating infants aged <9 months should contact the Division of Vector-Borne Infectious Diseases (970-221-6400) or the Division of Global Migration and Quarantine (404-498-1600) at CDC for advice.
A recent analysis of adverse events passively reported to the Vaccine Adverse Event Reporting System (VAERS) during 1990-2002 indicates that persons >60 years of age may be at increased risk for systemic adverse events following vaccination compared with younger persons. Travelers aged >60 years should discuss with their physicians the risks and benefits of vaccination in the context of their destination-specific risk for exposure to yellow fever virus.
Recently, a history of thymus disease has been identified as a contraindication to yellow fever vaccine. Four (15%) of the 26 vaccine recipients with YEL-AVD worldwide have had a history of diseases involving the thymus, all of which are extremely rare, suggesting that compromised thymic function may be another independent risk factor for YEL-AVD. One fatal case in the United States occurred in a 67-year-old woman who had a history of thymectomy for a malignant thymoma approximately 2 years before vaccination. A second case in the United States occurred in a 70-year-old man who had a history of hyperthyroidism, myasthenia gravis, and thymectomy for thymoma 20 years before vaccination. This patient survived. A third case was reported from Switzerland and occurred in a 50-year-old man who had a history of thymectomy due to thymoma 8 years prior to vaccination. This patient also survived. Most recently, a fatal case (male, age 44 years) of viscerotropic disease with fulminant hepatic failure temporally associated with yellow fever vaccine was reported from Colombia. This patient had a thymectomy due to benign thymoma 2 years before vaccination.
In addition to concerns about vaccinating elderly travelers, health-care providers should be careful to ask about a history of thymus disorder, including myasthenia gravis, thymoma, or prior thymectomy, when screening a patient before administering yellow fever vaccine. For persons with such a history, alternative means of prevention should be recommended, if travel plans cannot be altered to avoid yellow fever-endemic areas.
The safety of yellow fever vaccination during pregnancy has not been established, and the vaccine should be administered only if travel to an endemic area is unavoidable and if an increased risk for exposure exists. If international travel requirements, rather than an increased risk for infection, are the only reason to vaccinate a pregnant woman, efforts should be made to obtain a waiver letter from the traveler's physician. Pregnant women who must travel to areas where the risk for yellow fever infection is high should be vaccinated. Despite the apparent safety of this vaccine, infants born to these women should be monitored closely for evidence of congenital infection and other possible adverse effects resulting from yellow fever vaccination. If vaccination of a pregnant woman is deemed necessary, serologic testing to document an immune response to the vaccine can be considered, because the seroconversion rate for pregnant women in a developing nation has been reported to be substantially lower than that observed for other healthy adults and children. To discuss the need for serologic testing, the appropriate state health department or CDC's Division of Vector-Borne Infectious Diseases at 970-221-6400 or Division of Global Migration and Quarantine at 404-498-1600 should be contacted for more information.
Whether this vaccine is excreted in breast milk is not known. There have been no reports of adverse events or transmission of the vaccine viruses from nursing mother to infant. As a precautionary measure, vaccination of nursing mothers should be avoided, because of the theoretical risk of the transmission of virus to the breastfed infant. When travel of nursing mothers to high-risk yellow fever endemic areas cannot be avoided or postponed, these women may be vaccinated.
Infection with yellow fever vaccine virus poses a theoretical risk for travelers with immunosuppression in association with AIDS or other manifestations of HIV infection; leukemia, lymphoma, or generalized malignancy; with a history of thymus disease or thymectomy; or with the administration of corticosteroids, alkylating drugs, antimetabolites, or radiation. There is a single report of a 53 year-old patient with undiagnosed HIV infection who had a low CD4+ count (108 cells/mm3) and who developed YEL-AND and died of meningoencephalitis. Immunosuppressed patients should not be vaccinated. If travel to a yellow fever-infected zone is necessary, patients should be advised of the risks posed by such travel, instructed in methods for avoiding vector mosquitoes, and supplied with vaccination waiver letters by their physicians. Low-dose (i.e., 20 mg prednisone or equivalent/day), short-term (i.e., <2 weeks) systemic corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids and intranasal corticosteroids should not be sufficiently immunosuppressive to constitute an increased hazard to recipients of yellow fever vaccine.
Persons who are HIV-infected but do not have AIDS or other symptomatic manifestations of HIV infection, who have established laboratory verification of adequate immune system function (e.g. CD4+ T lymphocyte cell counts >200/mm3), and who cannot avoid potential exposure to yellow fever virus should be offered the choice of vaccination. If international travel requirements are the only reason to vaccinate an asymptomatic HIV-infected person, rather than an increased risk for infection, efforts should be made to obtain a waiver letter from the traveler's physician. Asymptomatic HIV-infected persons who must travel to areas where the risk for yellow fever infection is high should be offered the choice of vaccination and monitored closely for possible adverse effects. Family members of immunosuppressed or HIV-infected persons who themselves have no contraindications can receive yellow fever vaccine.
Data regarding seroconversion rates after yellow fever vaccination among asymptomatic HIV-infected persons are limited, but they do indicate that the seroconversion rate among such persons is reduced. Because vaccination of asymptomatic HIV-infected persons might be less effective than that of persons not infected with HIV, measurement of the neutralizing antibody response to vaccination should be considered before travel. Physicians should consult the applicable state health department or CDC's Division of Vector-Borne Infectious Diseases at 970-221-6400 or Division of Global Migration and Quarantine at 404-498-1600, for more information.
Live yellow fever vaccine is produced in chick embryos and should not be given to persons hypersensitive to eggs. Generally, persons who are able to eat eggs or egg products may receive the vaccine. However, some egg-sensitive persons are not allergic to cooked eggs and may not know they are susceptible to allergic reactions following raw eggs or egg-containing vaccines. If vaccination of a person with a questionable history of egg or chicken hypersensitivity is considered essential because of high risk for exposure, an intradermal test dose may be administered under close medical supervision. Specific directions for skin testing are found in the package insert. In some instances, small test doses for vaccine administered intradermally have led to an antibody response. Gelatin is used as a stabilizer in several vaccines, including yellow fever vaccine, and might be the stimulus for some allergic reactions to yellow fever vaccine. If international travel regulations are the only reason to vaccinate a traveler hypersensitive to eggs or gelatin, efforts should be made to obtain a waiver.
Studies have shown that the immune response to yellow fever vaccine is not inhibited by administration of certain other live, attenuated vaccines concurrently or at various intervals of a few days to one month. Smallpox, measles, BCG, and oral (live) typhoid vaccines have been administered in combination with yellow fever vaccines without interference. Additionally, reactions to vaccination are no more severe when these vaccines are administered concurrently. Hepatitis A, hepatitis B, Vi capsular polysaccharide typhoid, meningococcal, inactivated poliovirus, diphtheria-pertussis-tetanus and yellow fever vaccines may be given concurrently. If live-virus vaccines are not given concurrently, 4 weeks should be allowed to elapse between sequential vaccinations.
No data are available on possible interference between yellow fever vaccine and influenza, pneumococcal polysaccharide or conjugate, rabies, or Japanese encephalitis vaccines.
A prospective study of persons given yellow fever vaccine along with 5 mL of commercially available immune globulin showed no alteration of the immunologic response to yellow fever vaccine when compared with controls. Although chloroquine inhibits replication of yellow fever virus in vitro, it does not adversely affect antibody responses to yellow fever vaccine in persons receiving the drug as antimalarial prophylaxis.
International regulations require proof of vaccination for travel to and from certain countries. For purposes of international travel, yellow fever vaccine produced by different manufacturers worldwide must be approved by WHO and administered at an approved yellow fever vaccination center. In the United States, state and territorial health departments have authority to designate nonfederal vaccination centers; these can be identified by contacting state or local health departments or by visiting CDC's Travelers' Health website, where there is a listing of current authorized yellow fever vaccination providers (http://www2.ncid.cdc.gov/travel/yellowfever/). Vaccinees should receive a completed International Certificate of Vaccination, signed and validated with the center's stamp where the vaccine was given. This certificate is valid 10 days after vaccination and for a subsequent period of 10 years.
To prevent importation and transmission, a number of countries require a certificate from travelers arriving from infected areas or from countries with infected areas, even if only in transit. Such requirements may be strictly enforced, particularly for persons traveling from Africa or South America to Asia. Some countries in Africa require evidence of vaccination from all entering travelers; others may waive the requirements for travelers coming from nonendemic areas and staying in the country <2 weeks. Travelers with a specific contraindication to yellow fever vaccine should be advised to obtain a waiver before traveling to countries requiring vaccination.
Vaccination is also recommended for travel to countries that do not officially report the disease but lie in the yellow fever-endemic zone (see Maps 4-12 and 4-13 and Table 4-22). The actual areas of yellow fever virus activity can extend beyond the officially reported endemic zones.
An International Certificate of Vaccination must be complete in every detail; if incomplete or inaccurate, it is not valid. Revisions of this certificate dated 9-66, 9-69, 9-71, 1-74, 9-77, 1-82, or 11-91 are acceptable. A copy of the International Certificate of Vaccination, PHS-731, may be purchased for $1.25 ($15.00 per 100) from the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402, telephone 1-202-512-1800. The stock number is 017-001-00483-9.
A yellow fever vaccination must be given at an official yellow fever vaccination center as designated by respective state health departments or the Division of Global Migration and Quarantine, CDC. The accompanying certificate must be validated by the center that administers the vaccine. The certificate can be validated at most city, county, and state health departments or by vaccinating physicians who possess a "Uniform Stamp." State health departments are responsible for designated nonfederal yellow fever vaccination centers and issuing Uniform Stamps to be used to validate the International Certificate of Vaccination. Information about the location and hours of yellow fever vaccination centers may be obtained by contacting local or state health departments or visiting CDC's Travelers' Health website at http://www2.ncid.cdc.gov/travel/yellowfever/. Health-care providers administering vaccine to travelers should emphasize that an International Certificate of Vaccination must be validated to be acceptable to quarantine authorities. Failure to secure validations can cause a traveler to be revaccinated, quarantined, or denied entry.
The following section should be completed at the time of vaccination:
The International Certificate of Vaccination must be signed by a licensed physician or by a person designated by the physician. A signature stamp is not acceptable.
For direct travel from the United States, only the following countries require an International Certificate of Vaccination against yellow fever.
Table 4-23: Countries that require proof of vaccination against yellow fever
|Benin||Côte d'Ivoire||Liberia||São Tomé and Principe|
|Burkina Faso||Democratic Republic of Congo||Mali||Togo|
|Cameroon||French Guiana||Mauritania (for a stay >2 weeks)|
|Central African Republic||Gabon||Niger|
For travel to and between other countries, individual country requirements should be checked. No vaccinations are currently required for return to the United States.
Travelers who do not have the required vaccinations or appropriate documentation of a vaccination waiver upon entering a country might be subject to vaccination, medical follow-up, isolation, or quarantine, or a combination of these. In a few countries, unvaccinated travelers are denied entry.
Some countries do not require an International Certificate of Vaccination for infants <6 months of age, <9 months of age, or <1 year of age. Travelers should be advised to check the individual country requirements in Yellow Fever Vaccine Requirements and Information on Malaria Risk and Prophylaxis, by Country.
If a physician concludes that a particular vaccination should not be administered for medical reasons, the traveler should be given a signed and dated statement of the reasons on the physician's letterhead stationary.
No other reasons are acceptable for exemption from vaccination.
A physician's letter clearly stating the contraindications to vaccination is acceptable to some governments. Ideally, it should be written on letterhead stationery and bear the stamp used by health department and official immunization centers to validate the international certificate of vaccination. Under these conditions, it is also useful for the traveler to obtain specific and authoritative advice from the embassy or consulate of the country or countries he or she plans to visit. Waivers of requirements obtained from embassies or consulates should be documented by appropriate letters and retained for presentation with the International Certificate of Vaccination and the section on Medical Contraindication to Vaccination completed.
Because military requirements may exceed those indicated in this publication, any person who plans to travel on military orders (civilians and military personnel) should be advised to contact the nearest military medical facility to determine the requirements for the trip.
Patients should receive supportive care. In general, no specific treatments or established cures have proven benefit for patients with yellow fever or yellow fever vaccine-related illness.
- Michelle Russell, Rachel Barwick Eidex, Edward Hayes, Anthony Marfin, Thomas Monath, Dirk Teuwen, Megan Ranney, and Martin Cetron
Yellow Fever Vaccine Risk and Updated Yellow Fever Vaccine Information Statement (VIS)
Released: December 3, 2004
According to a September 2004 letter in the journal Lancet , a history of thymic dysfunction may be an independent risk factor for yellow fever vaccine-associated viscerotropic disease (YEL-AVD), a disease that clinically and pathologically resembles naturally acquired yellow fever. As of July 2004, 23 cases of YEL-AVD have been reported worldwide, of which 14 have been fatal. Four (17%) of the 23 patients reported a history of thymectomy due to thymoma.* Before administering yellow fever vaccine, health-care providers are advised to ask travelers about any history of thymus disorder or dysfunction (i.e., myasthenia gravis, thymoma, thymectomy, or DiGeorge syndrome), regardless of the age of the traveler. Persons 60 years of age or older are at increased risk for YEL-AVD, and health-care providers are reminded to consider the risks/benefits of vaccinating such travelers.
CDC has updated the Vaccine Information Statement (VIS) for yellow fever vaccine to include a caution about vaccinating persons with a history of thymic disease (see http://www.cdc.gov/nip/publications/VIS/#yf ).
*As of November 2004, 28 cases of YEL-AVD have been reported worldwide, of which 17 have been fatal.
For a copy of the published letter, see http://www.thelancet.com .
For more information about YEL-AVD, see:
For more information about yellow fever, see http://www.cdc.gov/travel/diseases/yellowfever.htm
Barwick Eidex R for the Yellow Fever Vaccine Safety Working Group. History of thymoma and yellow fever vaccination [letter]. Lancet. 2004:364:936.
Trypanosomiasis is a systemic disease caused by the parasite Trypanosoma brucei . East African trypanosomiasis is caused by T. b. rhodesiense and West African trypanosomiasis by T. b. gambiense . Both forms are transmitted by the bite of the tsetse fly, a gray-brown insect about the size of a honeybee.
African trypanosomiasis is confined to tropical Africa between 15° north latitude and 20° south latitude, or from north of South Africa to south of Algeria, Libya, and Egypt. According to WHO, 25,000-45,000 cases of trypanosomiasis are reported annually; however, the actual prevalence of cases is estimated to be 300,000 to 500,000.
Tsetse flies inhabit rural areas, living in the woodland and thickets of the savannah and the dense vegetation along streams. Infection of international travelers is rare. Approximately 1 case per year is reported among U.S. travelers. Most of these infections are caused by T. b. rhodesiense and they are acquired in East African game parks. Travelers visiting game parks and remote areas should be advised to take precautions. Travelers to urban areas are not at risk.
Signs and symptoms are initially nonspecific (fever, skin lesions, rash, edema, or lymphadenopathy); however, the infection progresses to meningoencephalitis. Symptoms generally appear within 1 to 3 weeks of infection. East African trypanosomiasis is more acute clinically, with earlier central nervous system involvement than in the West African form of the disease. Untreated cases are eventually fatal.
No vaccine is available to prevent this disease. Tsetse flies are attracted to moving vehicles and dark, contrasting colors. They are not affected by insect repellents and can bite through lightweight clothing. Areas of heavy infestation tend to be sporadically distributed and are usually well known to local residents. Avoidance of such areas is the best means of protection. Travelers at risk should be advised to wear clothing of wrist and ankle length that is made of medium-weight fabric in neutral colors that blend with the background environment.
Travelers who sustain tsetse fly bites and become ill with high fever or other manifestations of African trypanosomiasis should be advised to seek early medical attention. The infection can usually be cured by an appropriate course of anti-trypanosomal therapy. The drug of choice for treatment of East African trypanosomiasis is suramin (for the hemolymphatic stage) or melarsoprol (for late disease with central nervous system involvement). These drugs are available under an Investigational New Drug protocol from the CDC Drug Service. West African trypanosomiasis is best treated with pentamidine isethionate (for the hemolymphatic stage) or eflornithine. Travelers should be advised to consult an infectious disease or tropical medicine specialist.
- Anne Moore
Mycobacterium tuberculosis is a rod-shaped bacterium that can cause disseminated disease but is most frequently associated with pulmonary infections. The bacilli are transmitted by the airborne route and, depending on host factors, may lead to latent tuberculosis infection (sometimes abbreviated LTBI) or tuberculosis disease (TB). Both conditions can usually be treated successfully with medications.
In many other countries, tuberculosis is much more common than in the United States, and it is an increasingly serious public health problem.
To become infected, a person usually has to spend a relatively long time in a closed environment where the air was contaminated by a person with untreated tuberculosis who was coughing and who had numerous M. tuberculosis organisms (or tubercle bacilli) in secretions from the lungs or voice box (larynx). Infection is generally transmitted through the air; therefore, there is virtually no danger of its being spread by dishes, linens, and items that are touched, or by most food products. However, it can be transmitted through unpasteurized milk or milk products obtained from infected cattle.
Travelers who anticipate possible prolonged exposure to tuberculosis (e.g., those who could be expected to come in contact routinely with hospital, prison, or homeless shelter populations) should be advised to have a tuberculin skin test before leaving the United States. If the reaction is negative, they should have a repeat test approximately 12 weeks after returning. Because persons with HIV infection are more likely to have an impaired response to the tuberculin skin test, travelers who are HIV positive should be advised to inform their physicians about their HIV infection status. Except for travelers with impaired immunity, travelers who already have a positive tuberculin reaction are unlikely to be reinfected.
Travelers who anticipate repeated travel with possible prolonged exposure or an extended stay over a period of years in an endemic country should be advised to have two-step baseline testing and, if the reaction is negative, annual screening, including a tuberculin skin test.
CDC and state and local health departments have published the results of six investigations of possible tuberculosis transmission on commercial aircraft. In these six instances, a passenger or a member of a flight crew traveled on commercial airplanes while infectious with tuberculosis. In all six instances, the airlines were unaware that the passengers or crew members were infected with tuberculosis. In two of the instances, CDC concluded that tuberculosis was probably transmitted to others on the airplane. The findings suggested that the risk of tuberculosis transmission from an infectious person to others on an airplane was greater on long flights (8 hours or more). The risk of exposure to tuberculosis was higher for passengers and flight crew members sitting or working near an infectious person because they might inhale droplets containing M. tuberculosis bacteria.
Based on these studies and findings, WHO issued recommendations to prevent the transmission of tuberculosis in aircraft and to guide potential investigations. The risk of tuberculosis transmission on an airplane does not appear to be greater than in any other enclosed space. To prevent the possibility of exposure to tuberculosis on airplanes, CDC and WHO recommend that persons known to have infectious tuberculosis travel by private transportation (that is, not by commercial airplanes or other commercial carriers), if travel is required. CDC and WHO have issued guidelines for notifying passengers who might have been exposed to tuberculosis aboard airplanes. Passengers concerned about possible exposure to tuberculosis should be advised to see their primary health-care provider for a tuberculosis skin test.
Based on WHO recommendations, the Bacille Calmette-Guérin (BCG) vaccine is used in most developing countries to reduce the severe consequences of tuberculosis in infants and children. However, BCG vaccine has variable efficacy in preventing the adult forms of tuberculosis and interferes with testing for latent tuberculosis infection. Therefore, it not routinely recommended for use in the United States.
Travelers should be advised to avoid exposure to known tuberculosis patients in crowded environments (e.g., hospitals, prisons, or homeless shelters). Travelers who will be working in hospitals or health-care settings where tuberculosis patients are likely to be encountered should be advised to consult infection control or occupational health experts about procedures for obtaining personal respiratory protective devices (e.g., N-95 respirators), along with appropriate fitting and training. Additionally, tuberculosis patients should be educated and trained to cover coughs and sneezes with their hands or tissues to reduce spread. Otherwise, no specific preventive measures can be taken or are routinely recommended for travelers.
Persons who are infected or who become infected with M. tuberculosis can be treated to prevent progression to tuberculosis disease. Updated American Thoracic Society (ATS)/CDC recommendations for treatment of latent tuberculosis infection recommend 9 months of isoniazid as the preferred treatment and suggest that 4 months of rifampin is a reasonable alternative. Travelers who suspect that they have been exposed to tuberculosis should be advised to inform their physicians of the possible exposure and receive appropriate medical evaluation. CDC and ATS have published updated guidelines for targeted tuberculin skin testing and treatment of latent tuberculosis infection. Recent data from the WHO suggest that resistance is relatively common in some parts of the world. Travelers who have tuberculin skin test conversion associated with international travel should consult experts in infectious diseases or pulmonary medicine.
- Michael Iademarco
Cholera is an acute intestinal infection caused by toxigenic Vibrio cholerae O-group 1 or O-group 139. The infection is often mild and self limited or subclinical. Patients with severe cases respond dramatically to simple fluid- and electrolyte-replacement therapy. Infection is acquired primarily by ingesting contaminated water or food; person-to-person transmission is rare.
Since 1961, V. cholerae has spread from Indonesia through most of Asia into Eastern Europe and Africa, and from North Africa to the Iberian Peninsula. In 1991, an extensive epidemic began in Peru and spread to neighboring countries in the Western Hemisphere. In 2003, 111,575 cases from 45 countries were reported to the WHO.
Travelers who follow usual tourist itineraries and who observe food safety recommendations while in countries reporting cholera have virtually no risk. Risk increases for those who drink untreated water or eat poorly cooked or raw seafood in disease-endemic areas.
The risk of cholera to U.S. travelers is so low that vaccination is of questionable benefit. The manufacture and sale of the only cholera vaccine licensed in the United States (by Wyeth Ayerst) have been discontinued. The vaccine is not recommended for travelers because of the brief and incomplete immunity it confers.
Two recently developed oral vaccines for cholera are licensed and available in other countries (Dukoral from Biotec AB and Mutacol from Berna). Both vaccines appear to provide somewhat better immunity and have fewer adverse effects than the previously available vaccine. However, CDC does not recommend either of these two vaccines for most travelers, nor are they available in the United States. Further information on these vaccines can be obtained from the manufacturers: Dukoral, Active Biotec AB, P.O. Box 724, SE-220 07, Lund, Sweden; telephone: 46 46 19 20 00; fax: 46 46 19 20 50; e-mail: firstname.lastname@example.org ; and website: http://www.activebiotech.com ; and Mutacol, Berna, Switzerland Division, P.O. Box CH-3001, Bern, Switzerland; telephone: 41 31 981 22 11; fax: 41 31 981 20 66. E-mail information is available at http://www.bernaproducts.com/contact.cfm and from the website http://www.bernaproducts.com .
Currently, no country or territory requires vaccination against cholera as a condition for entry. Local authorities, however, may continue to require documentation of this vaccination. In such cases, a single dose of either oral vaccine is sufficient to satisfy local requirements, or the traveler may request a medical waiver from a physician.
Travelers to cholera-affected areas should be advised to avoid eating high-risk foods, especially fish and shellfish. Food that is cooked and served hot, fruits and vegetables peeled by the traveler personally, beverages and ice that are made from boiled or chlorinated water, or carbonated beverages are usually safe. (See Risks from Food and Water, for additional information.) Chemoprophylaxis is almost never indicated.
Rehydration is the cornerstone of therapy for cholera; antibiotics are an adjunct useful in severe cases only. Oral rehydration salts, and when necessary intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce case-fatality rates to well under 1%.
- Eric Mintz
Update on Cholera Vaccine
Two recently developed vaccines for cholera are licensed and available in other countries (Dukoral®, Biotec AB and Mutacol®, Berna). Both vaccines appear to provide a somewhat better immunity and fewer side-effects than the previously available vaccine. However, neither of these two vaccines is recommended for travelers nor are they available in the United States. Further information on these vaccines can be obtained from the manufacturers at:Dukoral®
Active Biotec AB (publ)
Postal Address: P.O. Box 724, SE-220 07 Lund, Sweden
Office address: Scheelevagen 22
Tel: +46 46 19 20 00,
Fax +46 46 19 20 50
Home page: http://www.activebiotech.com/ Mutacol®
Berna, Switzerland Division
Tel. +41 31 981 22 11
Fax +41 31 981 20 66
Home page: http://www.berna.org/
Use of trade names is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
See the Diseases section for more information on cholera.
|Date: August 11, 2003|
|Content Source: National Center for Infectious Diseases, Division of Global Migration and Quarantine|
Malaria in humans is caused by one of four protozoan species of the genus Plasmodium: P. falciparum , P. vivax , P. ovale , or P. malariae . All species are transmitted by the bite of an infected female Anopheles mosquito. Occasionally, transmission occurs by blood transfusion, organ transplantation, needle-sharing, or congenitally from mother to fetus. Although malaria can be a fatal disease, illness and death from malaria are largely preventable.
Malaria is a major international public health problem, causing 300-500 million infections worldwide and approximately 1 million deaths annually. Information about malaria risk in specific countries (Yellow Fever Vaccine Requirements and Information on Malaria Risk and Prophylaxis, by Country) is derived from various sources, including WHO. The information presented herein was accurate at the time of publication; however, factors that can change rapidly and from year to year, such as local weather conditions, mosquito vector density, and prevalence of infection, can markedly affect local malaria transmission patterns. Updated information may be found on the CDC Travelers' Health website: http://www.cdc.gov/travel .
Malaria transmission occurs in large areas of Central and South America, the island of Hispaniola (the Dominican Republic and Haiti), Africa, Asia (including the Indian Subcontinent, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific.
The estimated risk for a traveler's acquiring malaria differs substantially from area to area. This variability is a function of the intensity of transmission within the various regions and of the itinerary and time and type of travel. From 1985 through 2002, 11,896 cases of malaria among U.S. civilians were reported to CDC. Of these, 6,961 (59%) were acquired in sub-Saharan Africa; 2,237 (19%) in Asia; 1,672 (14%) in the Caribbean and Central and South America; and 822 (7%) in other parts of the world. During this period, 76 fatal malaria infections occurred among U.S. civilians; 71 (93%) were caused by P. falciparum , of which 52 (73%) were acquired in sub-Saharan Africa.
Thus, most imported P. falciparum malaria among U.S. travelers was acquired in Africa, even though only 467,940 U.S. residents traveled to countries in that region in 2002. In contrast, that year 21 million U.S. residents traveled from the United States to other countries where malaria is endemic (including 19 million travelers to Mexico). This disparity in the risk for acquiring malaria reflects the fact that the predominant species of malaria transmitted in sub-Saharan Africa is P. falciparum , that malaria transmission is generally higher in Africa than in other parts of the world, and that malaria is often transmitted in urban areas as well as rural areas in sub-Saharan Africa. In contrast, malaria transmission is generally lower in Asia and South America, a larger proportion of the malaria is P. vivax , and most urban areas do not have malaria transmission.
Estimating the risk for infection for various types of travelers is difficult. Risk can differ substantially even for persons who travel or reside temporarily in the same general areas within a country. For example, travelers staying in air-conditioned hotels may be at lower risk than backpackers or adventure travelers. Similarly, long-term residents living in screened and air-conditioned housing are less likely to be exposed than are persons living without such amenities, such as Peace Corps volunteers. Travelers should also be reminded that even if one has had malaria before, one can get it again and so preventive measures are still necessary.
Persons who have been in a malaria risk area, either during daytime or nighttime hours, are not allowed to donate blood in the United States for a period of time after returning from the malarious area. Persons who are residents of nonmalarious countries are not allowed to donate blood for 1 year after they have returned from a malarious area. Persons who are residents of malarious countries are not allowed to donate blood for 3 years after leaving a malarious area. Persons who have had malaria are not allowed to donate blood for 3 years after treatment for malaria.
Malaria is characterized by fever and influenza-like symptoms, including chills, headache, myalgias, and malaise; these symptoms can occur at intervals. Malaria may be associated with anemia and jaundice, and P. falciparum infections can cause seizures, mental confusion, kidney failure, coma, and death. Malaria symptoms can develop as early as 7 days after initial exposure in a malaria-endemic area and as late as several months after departure from a malarious area, after chemoprophylaxis has been terminated.
No vaccine is currently available. Taking an appropriate drug regimen and using anti-mosquito measures will help prevent malaria. Travelers should be informed that no method can protect completely against the risk for contracting malaria.
Because of the nocturnal feeding habits of Anopheles mosquitoes, malaria transmission occurs primarily between dusk and dawn. Travelers should be advised to take protective measures to reduce contact with mosquitoes, especially during these hours. Such measures include remaining in well-screened areas, using mosquito bed nets (preferably insecticide-treated nets), and wearing clothes that cover most of the body. Additionally, travelers should be advised to purchase insect repellent for use on exposed skin. The most effective repellent against a wide range of vectors is DEET (N, N-diethylmetatoluamide), an ingredient in many commercially available insect repellents. The actual concentration of DEET varies widely among repellents. DEET formulations as high as 50% are recommended for both adults and children >2 months of age (See Protection against Mosquitoes and Other Arthropod Vectors).
Travelers not staying in well-screened or air-conditioned rooms should be advised to use a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours. They should take additional precautions, including sleeping under bed nets (preferably insecticide-treated bed nets). In the United States, permethrin (Permanone) is available as a liquid or spray. Overseas, either permethrin or another insecticide, deltamethrin, is available and may be sprayed on bed nets and clothing for additional protection against mosquitoes. Bed nets are more effective if they are treated with permethrin or deltamethrin insecticide; bed nets may be purchased that have already been treated with insecticide. Information about ordering insecticide-treated bed nets is available at http://www.travmed.com , telephone 1-800- 872 8633, fax: 413-584-6656; or http://www.travelhealthhelp.com , telephone 1-888-621-3952.
Chemoprophylaxis is the strategy that uses medications before, during, and after the exposure period to prevent the disease caused by malaria parasites. The aim of prophylaxis is to prevent or suppress symptoms caused by blood-stage parasites. In addition, presumptive anti-relapse therapy (also known as terminal prophylaxis) uses medications towards the end of the exposure period (or immediately thereafter) to prevent relapses or delayed-onset clinical presentations of malaria caused by hypnozoites (dormant liver stages) of P. vivax or P. ovale .
In choosing an appropriate chemoprophylactic regimen before travel, the traveler and the health-care provider should consider several factors. The travel itinerary should be reviewed in detail and compared with the information on areas of risk in a given country to determine whether the traveler will actually be at risk for acquiring malaria. Whether the traveler will be at risk for acquiring drug-resistant P. falciparum malaria should also be determined. Resistance to antimalarial drugs has developed in many regions of the world. Health-care providers should consult the latest information on resistance patterns before prescribing prophylaxis for their patients. (See section "Malaria Hotline" below for details about accessing this information from CDC.)
The resistance of P. falciparum to chloroquine has been confirmed in all areas with P. falciparum malaria except the Dominican Republic, Haiti, Central America west of the Panama Canal, Egypt, and some countries in the Middle East. In addition, resistance to sulfadoxine-pyrimethamine (e.g., Fansidar) is widespread in the Amazon River Basin area of South America, much of Southeast Asia, other parts of Asia, and, increasingly, in large parts of Africa. Resistance to mefloquine has been confirmed on the borders of Thailand with Burma (Myanmar) and Cambodia, in the western provinces of Cambodia, and in the eastern states of Burma (Myanmar).
Malaria chemoprophylaxis with mefloquine or chloroquine should begin 1-2 weeks before travel to malarious areas; prophylaxis with doxycycline, atovaquone/proguanil, or primaquine can begin 1-2 days before travel. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites. Chemoprophylaxis can be started earlier if there are particular concerns about tolerating one of the medications. Starting the medication 3-4 weeks in advance allows potential adverse events to occur before travel. If unacceptable side effects develop, there would be time to change the medication before the traveler's departure.
The drugs used for antimalarial chemoprophylaxis are generally well tolerated. However, side effects can occur. Minor side effects usually do not require stopping the drug. Travelers who have serious side effects should see a health-care provider. See the section below on "Adverse Reactions and Contraindications" for more detail on safety and tolerability of the drugs used for malaria prevention. The health-care provider should establish whether the traveler has previously experienced an allergic or other reaction to one of the antimalarial drugs of choice. In addition, the health-care provider should determine whether medical care will be readily accessible during travel should the traveler develop intolerance to the drug being used and need to change to a different agent.
Chemoprophylaxis should continue during travel in the malarious areas and after leaving the malarious areas (4 weeks after travel for chloroquine, mefloquine, and doxycycline, and 7 days after travel for atovaquone/proguanil and primaquine). In comparison with drugs with short half-lives, which are taken daily, drugs with longer half-lives, which are taken weekly, offer the advantage of a wider margin of error if the traveler is late with a dose. For example, if a traveler is 1-2 days late with a weekly drug, prophylactic blood levels can remain adequate; if the traveler is 1-2 days late with a daily drug, protective blood levels are less likely to be maintained.
- Monica Parise, Ann Barber, and Sonja Mali
Hepatitis E, which is caused by the hepatitis E virus (HEV), cannot be distinguished reliably from other forms of acute viral hepatitis except by specific serologic testing.
HEV, which is transmitted by the fecal-oral route, occurs both in epidemic and sporadic forms. Transmission is associated primarily with ingestion of fecally contaminated drinking water. The potential for HEV transmission from contaminated food is still under investigation, and there is no evidence of transmission by percutaneous or sexual exposures.
Hepatitis E occurs primarily in adults. The highest rates of symptomatic disease (jaundice) have been reported in young to middle-aged adults. Lower disease rates in younger age groups may be the result of subclinical HEV infection. Chronic infection does not occur.
Epidemics and sporadic cases of hepatitis E have been reported from areas of Asia (Afghanistan, Bangladesh, Burma [Myanmar], China, India, Indonesia, Kazakhstan, Kyrgyzstan, Malaysia, Mongolia, Nepal, Pakistan, Tajikistan, Turkmenistan, and Uzbekistan), Mexico, the Middle East, Northern Africa, and sub-Saharan Africa. No outbreaks have been recognized in Europe, the United States, Australia, or South America. Hepatitis E usually occurs in persons who travel to or live in an endemic area. However, three cases have been identified in U.S. residents who had no history of recent international travel. Studies are in progress to determine if hepatitis E is an endemic disease in the United States.
The incidence of hepatitis E among travelers is unknown but likely low. As with hepatitis A, risk for infection is highest for those who frequently eat or drink in settings of poor sanitation.
The incubation period averages 40 days (range 15-60 days). Signs and symptoms, if they occur, include fatigue, loss of appetite, nausea, abdominal pain, and fever. Most patients with hepatitis E have a self-limiting course. Hepatitis E has a low (0.5%-4.0%) case-fatality rate in the general population. Fulminant hepatitis, however, is more commonly associated with hepatitis E than with other types of viral hepatitis, particularly among pregnant women in the second or third trimester. Fetal loss is common. Case-fatality rates as high as 15%-25% have been reported among pregnant women. Perinatal transmission of HEV has also been reported.
No FDA-approved diagnostic test is available, although some U.S. commercial laboratories offer serologic tests for HEV infection. Several of these tests have been shown to perform well in detecting anti-HEV in known positive sera, such as from travelers to an HEV-endemic country who develop acute hepatitis but have negative test results for other potential infectious and noninfectious causes of hepatitis. However, these tests provide highly discordant results when used on panels of U.S. blood donor sera, indicating that use of currently available serologic tests in persons without signs or symptoms of hepatitis and recent travel to an endemic country is unreliable, and results in this setting should be interpreted with caution.
Vaccines to prevent hepatitis E are being developed, but none are yet available. Immune globulin prepared from plasma collected in HEV-endemic areas has not been effective in preventing clinical disease during HEV outbreaks. IG prepared from plasma collected from parts of the world where HEV is not an endemic disease is unlikely to be effective. The best prevention of infection is to avoid potentially contaminated water and food, using measures recommended to prevent hepatitis A and other enteric infections.
No specific treatment is available for hepatitis E. Treatment is supportive.
- Anthony Fiore and Beth Bell
Hepatitis C is caused by the hepatitis C virus (HCV). Most persons who acquire acute HCV infection either have no symptoms or have a mild clinical illness. However, chronic HCV infection develops in 75%-85% of those acutely infected, with chronic liver disease developing in 60%-70% of chronically infected persons. Chronic hepatitis C is the leading cause for liver transplantation in the United States.
HCV is transmitted primarily through activities that result in the exchange of blood; it is less commonly transmitted by sexual activity. The most frequent mode of transmission in the United States is through sharing of drug-injecting equipment among injecting drug users. For international travelers, the principal activities that can result in blood exposure include receiving blood transfusions that have not been screened for HCV; having medical or dental procedures or engaging in activities (e.g., acupuncture, tattooing, or injecting drug use) in which equipment has not been adequately sterilized or disinfected or in which contaminated equipment is reused; and working in health-care fields (e.g., medical, dental, or laboratory) that entail direct exposure to human blood.
Approximately 3% (170 million) of the world's population has been infected with HCV. For most countries, the prevalence of HCV infection is <3%. Prevalence is higher (up to 15%) in some countries in Africa and Asia, and highest (>15%) in Egypt.
Travelers' risk for contracting HCV infection is generally low. To assess risk, travelers should be advised to consider the extent of their direct contact with blood, particularly receipt of blood transfusions from unscreened donors, or exposure to contaminated equipment used in health care-related or cosmetic (e.g., tattooing) procedures.
Most persons (80%) with acute HCV infection have no symptoms. If symptoms occur, they may include loss of appetite, abdominal pain, fatigue, nausea, dark urine, and jaundice. Chronic infection occurs in 75%-85% of infected persons, leading to chronic liver disease in 60%-70%. The most common symptom of chronic hepatitis C is fatigue, although severe liver disease develops in 10%-20% of infected persons.
No vaccine is available. 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). HCV 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 if they are thinking about getting a tattoo or body piercing in areas where adequate sterilization or disinfection procedures might not be available or practiced. (See section on Seeking Health Care Abroad.)
No specific treatment is available for acute hepatitis C. Antiviral drugs are available for the treatment of chronic hepatitis C in persons >18 years of age.
- Anthony Fiore and Beth Bell
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.
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.
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. In the United States and many other developed countries, children and adolescents are routinely vaccinated against hepatitis B. The highest incidence of disease 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 Amazon 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).
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. Factors to consider in assessing risk include 1) the prevalence of chronic HBV infection in the local population, 2) the extent of direct contact with blood or secretions, or of sexual contact with potentially infected persons, and 3) the duration of travel. 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. However, unprotected sex and sharing illegal drug injection equipment are also risks for HBV infection in these areas.
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.
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%) who will have close contact with the local populations. In particular, travelers who will have sex contact or will have daily physical contact with the local population; or who are likely to seek medical, dental, or other treatment in local facilities; or any combination of these activities during their stay should be advised to receive the vaccine.
Hepatitis B vaccination is currently recommended for all United States residents who work in health-care fields (medical, dental, laboratory, or other) that involve potential exposure to human blood. All unvaccinated United States children and adolescents (<19 years old) should receive hepatitis B vaccine. 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.
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 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. 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, particularly among travelers to areas with intermediate or high levels of endemic HBV transmission, when considering if hepatitis B vaccine should be offered.
Two monovalent hepatitis B vaccines are currently licensed in the United States: Recombivax HB, manufactured Merck and Co., Inc., and Engerix B, manufactured by GlaxoSmithKline. These vaccines are produced through recombinant DNA technology by baker's yeast into which the gene for HBsAg has been inserted. 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 4-8). 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.
Twinrix, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for persons 18 years of age or more. 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 4-6). Twinrix consists of inactivated hepatitis A virus and recombinant HBsAg protein, with aluminum phosphate and aluminum hydroxide as adjuvant and 2-phenoxyethanol as a preservative.
Individual 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) for travelers who will depart before an approved vaccination schedule can be completed. The FDA has not approved accelerated schedules that involve vaccination at more than one time during a single month for hepatitis B vaccines currently licensed in the United States. Persons who receive a vaccination on an accelerated schedule that is not FDA approved should also receive a booster dose at one year after the start of the series to promote long-term immunity.
Table 4-8. Recommended doses of currently licensed Hepatitis B vaccines 1
|All infants (regardless of mother's HBsAg status), children, adolescents, and adults, birth through 19 years||5 µg||10 µg|
|Adults < 20 years of age||10 µg||20 µg|
|Dialysis patients and other immunocompromised persons||40 µg 3||40 µg 4|
1 Both vaccines are routinely administered in a three-dose series. Engerix-B also has been licensed for a four-dose series administered at 0, 1, 2, and 12 months.
2 Recombivax-HB is now approved in a two-dose schedule for 11- to 15-year-olds (see "Preventive Measures").
3 Special formulation (40 µg in 1.0 mL)
4 Two 1.0 mL doses given at one site, in a four-dose schedule at 0, 1, 2, 6 months
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 Vaccine Recommendations for Infants and Children, for a discussion of the hepatitis B immunization schedule for infants who will be traveling.)
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 >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 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 (56% among adults and 8% among children) and headache (14% among adults and 4% among children). 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.
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.
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 if they are considering getting a tattoo or body piercing in areas where adequate sterilization or disinfection procedures might not be available or practiced. (See Seeking health care abroad.)
No specific treatment is available for acute illness caused by hepatitis B. Antiviral drugs are approved for the treatment of chronic hepatitis B.
- Anthony Fiore and Beth Bell