Chapter 3Infectious Diseases Related To Travel
Mark D. Gershman, J. Erin Staples
Yellow fever virus (YFV) is a single-stranded RNA virus that belongs to the genus Flavivirus.
Vectorborne transmission occurs via the bite of an infected mosquito, primarily Aedes or Haemagogus spp. Nonhuman and human primates are the main reservoirs of the virus, with anthroponotic (human-to-vector-to-human) transmission occurring. There are 3 transmission cycles for yellow fever: sylvatic (jungle), intermediate (savannah), and urban.
- The sylvatic (jungle) cycle involves transmission of the virus between nonhuman primates and mosquito species found in the forest canopy. The virus is transmitted via mosquitoes from monkeys to humans when the humans encroach into the jungle during occupational or recreational activities.
- In Africa, an intermediate (savannah) cycle involves transmission of YFV from tree hole-breeding Aedes spp. to humans living or working in jungle border areas. In this cycle, the virus may be transmitted from monkeys to humans or from human to human via these mosquitoes.
- The urban cycle involves transmission of the virus between humans and urban mosquitoes, primarily Aedes aegypti.
Humans infected with YFV experience the highest levels of viremia and can transmit the virus to mosquitoes shortly before onset of fever and for the first 3–5 days of illness. Given the high level of viremia, bloodborne transmission theoretically can occur via transfusion or needlesticks.
Yellow fever occurs in sub-Saharan Africa and tropical South America, where it is endemic and intermittently epidemic (see Tables 3-21 and Tables 3-22 for a list of countries with risk of YFV transmission). Most yellow fever disease in humans is due to sylvatic or intermediate transmission cycles. However, urban yellow fever occurs periodically in Africa and sporadically in the Americas. In Africa, natural immunity accumulates with age, and thus, infants and children are at highest risk for disease. In South America, yellow fever occurs most frequently in unimmunized young men who are exposed to mosquito vectors through their work in forested areas.
Table 3-21. Countries with risk of yellow fever virus (YFV) transmission1
|AFRICA||CENTRAL AND SOUTH AMERICA|
Central African Republic
Congo, Republic of the
Democratic Republic of the Congo2
Trinidad and Tobago2
1Countries or areas where “a risk of yellow fever transmission is present,” as defined by the World Health Organization, are countries or areas where “yellow fever has been reported currently or in the past, plus vectors and animal reservoirs currently exist” (see the current country list within the International Travel and Health publication (Annex 1) at www.who.int/ith/en/index.html).
2These countries are not holoendemic (only a portion of the country has risk of yellow fever transmission). See Maps 3-16 and 3-17 and yellow fever vaccine recommendations (Yellow Fever and Malaria Information, by Country) for details.
Table 3-22. Countries with low potential for exposure to yellow fever virus (YFV)1
São Tomé and Príncipe3
1Countries listed in this table are not contained on the official WHO list of countries with risk of YFV transmission (Table 3-21). Therefore, proof of yellow fever vaccination should not be required if traveling from one of these countries to another country with a vaccination entry requirement (unless that country requires proof of yellow fever vaccination from all arriving travelers; see Table 3-25). An exception is South Africa, which requires YF vaccination for people traveling from or transiting through any of the 5 countries with low potential for exposure.
2 These countries are classified as “low potential for exposure to YFV” in only some areas; the remaining areas of these countries are classified as having no risk of exposure to YFV.
3 The entire area of these countries is classified as “low potential for exposure to YFV.”
RISK FOR TRAVELERS
A traveler’s risk for acquiring yellow fever is determined by various factors, including immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and local rate of virus transmission at the time of travel. Although reported cases of human disease are the principal indicator of disease risk, case reports may be absent because of a low level of transmission, a high level of immunity in the population (because of vaccination, for example), or failure of local surveillance systems to detect cases. This “epidemiologic silence” does not equate to absence of risk and should not lead to travel without taking protective measures.
YFV transmission in rural West Africa is seasonal, with an elevated risk during the end of the rainy season and the beginning of the dry season (usually July–October). However, YFV may be episodically transmitted by Ae. aegypti even during the dry season in both rural and densely settled urban areas.
The risk for infection in South America is highest during the rainy season (January–May, with a peak incidence in February and March). Given the high level of viremia that may occur in infected humans and the widespread distribution of Ae. aegypti in many towns and cities, South America is at risk for a large-scale urban epidemic.
From 1970 through 2011, a total of 9 cases of yellow fever were reported in unvaccinated travelers from the United States and Europe who traveled to West Africa (5 cases) or South America (4 cases). Eight (89%) of these 9 travelers died. There has been only 1 documented case of yellow fever in a vaccinated traveler. This nonfatal case occurred in a traveler from Spain who visited several West African countries in 1988.
The risk of acquiring yellow fever is difficult to predict because of variations in ecologic determinants of virus transmission. For a 2-week stay, the risks for illness and death due to yellow fever for an unvaccinated traveler visiting an endemic area in:
- West Africa are 50 per 100,000 and 10 per 100,000, respectively
- South America are 5 per 100,000 and 1 per 100,000, respectively
These estimates are a rough guideline based on the risk to indigenous populations, often during peak transmission season. Thus, these risk estimates may not accurately reflect the true risk to travelers, who may have a different immunity profile, take precautions against getting bitten by mosquitoes, and have less outdoor exposure.
The risk of acquiring yellow fever in South America is lower than that in Africa, because the mosquitoes that transmit the virus between monkeys in the forest canopy in South America do not often come in contact with humans. Additionally, there is a relatively high level of immunity in local residents because of vaccine use, which might reduce the risk of transmission.
Asymptomatic or clinically inapparent infection is believed to occur in most people infected with YFV. For people who develop symptomatic illness, the incubation period is typically 3–6 days. The initial illness presents as a nonspecific influenzalike syndrome with sudden onset of fever, chills, headache, backache, myalgias, prostration, nausea, and vomiting. Most patients improve after the initial presentation. After a brief remission of hours to a day, approximately 15% of patients progress to a more serious or toxic form of the disease, characterized by jaundice, hemorrhagic symptoms, and eventually shock and multisystem organ failure. The case-fatality ratio for severe cases with hepatorenal dysfunction is 20%–50%.
The preliminary diagnosis is based on the patient’s clinical features, places and dates of travel, and activities. Laboratory diagnosis is best performed by:
- Serologic assays to detect virus-specific IgM and IgG antibodies. Because of cross-reactivity between antibodies raised against other flaviviruses, more specific antibody testing, such as a plaque reduction neutralization test, should be done to confirm the infection.
- Virus isolation or nucleic acid amplification tests performed early in the illness for YFV or yellow fever viral RNA. However, by the time more overt symptoms are recognized, the virus or viral RNA is usually undetectable. Therefore, virus isolation and nucleic acid amplification should not be used for ruling out a diagnosis of yellow fever.
Clinicians should contact their state or local health department or call the CDC Arboviral Diseases Branch at 970-221-6400 for assistance with diagnostic testing for yellow fever infections and for questions about antibody response to vaccination.
There are no specific medications to treat YFV infections; treatment is directed at symptomatic relief or life-saving interventions. Rest, fluids, and use of analgesics and antipyretics may relieve symptoms of fever and aching. Care should be taken to avoid certain medications, such as aspirin or nonsteroidal anti-inflammatory drugs, which may increase the risk for bleeding. Infected people should be protected from further mosquito exposure (staying indoors or under a mosquito net) during the first few days of illness, so they do not contribute to the transmission cycle.
Personal Protection Measures
The best way to prevent mosquitoborne diseases, including yellow fever, is to avoid mosquito bites (see Chapter 2, Protection against Mosquitoes, Ticks, & Other Insects & Arthropods).
Yellow fever is preventable by a relatively safe, effective vaccine. All yellow fever vaccines currently manufactured are live-attenuated viral vaccines. Only 1 yellow fever vaccine is licensed for use in the United States (Table 3-23).
Studies comparing the reactogenicity and immunogenicity of various yellow fever vaccines, including those manufactured outside the United States, suggest that there is no substantial difference in the reactogenicity or immune response generated by the various vaccines. Thus, people who receive yellow fever vaccines in other countries should be considered protected against yellow fever.
Indications for Use
Yellow fever vaccine is recommended for people aged ≥9 months who are traveling to or living in areas with risk for YFV transmission in South America and Africa. In addition, some countries require proof of yellow fever vaccination for entry. See the Travel Vaccines & Malaria Information, by Country section at the end of this chapter for more detailed information on the requirements and recommendations for yellow fever vaccination for specific countries.
Because of the risk of serious adverse events that can occur after yellow fever vaccination, clinicians should only vaccinate people who 1) are at risk of exposure to YFV or 2) require proof of vaccination to enter a country. To further minimize the risk of serious adverse events, clinicians should carefully observe the contraindications and consider the precautions to vaccination before administering yellow fever vaccine (Table 3-24). For additional information, refer to the yellow fever vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) at www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/yf.html.
For all eligible people, a single injection of reconstituted vaccine should be administered subcutaneously. The International Health Regulations (IHR) published by the World Health Organization (WHO) require revaccination at 10-year intervals.
Vaccine Safety and Adverse Reactions
Common adverse reactions
Reactions to yellow fever vaccine are generally mild; 10%–30% of vaccinees report mild systemic adverse events. Reported events typically include low-grade fever, headache, and myalgias that begin within days after vaccination and last 5–10 days. Approximately 1% of vaccinees temporarily curtail their regular activities because of these reactions.
Severe adverse reactions
Immediate hypersensitivity reactions, characterized by rash, urticaria, bronchospasm, or a combination of these, are uncommon. Anaphylaxis after yellow fever vaccine is reported to occur at a rate of 1.8 cases per 100,000 doses administered.
Yellow fever vaccine–associated neurologic disease (YEL-AND)
YEL-AND represents a conglomerate of different clinical syndromes, including meningoencephalitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and rarely, bulbar and Bell palsies. Historically, YEL-AND was seen primarily among infants as encephalitis, but more recent reports have been among people of all ages.
The onset of illness for documented cases is 3–28 days after vaccination, and almost all cases were in first-time vaccine recipients. YEL-AND is rarely fatal. The incidence of YEL-AND in the United States is 0.8 per 100,000 doses administered. The rate is higher in people aged ≥60 years, with a rate of 1.6 per 100,000 doses in people aged 60–69 years and 2.3 per 100,000 doses in people aged ≥70 years.
Yellow fever vaccine–associated viscerotropic disease (YEL-AVD)
YEL-AVD is a severe illness similar to wild-type disease, with vaccine virus proliferating in multiple organs and often leading to multisystem organ failure and death. Since the initial cases of YEL-AVD were published in 2001, >60 confirmed and suspected cases have been reported throughout the world.
YEL-AVD has been reported to occur only after the first dose of yellow fever vaccine; there have been no reports of YEL-AVD following booster doses. The median time from YF vaccination until symptom onset for YEL-AVD cases was 4 days (range, 0–8 days). The case-fatality ratio for all reported YEL-AVD cases worldwide is 63%. The incidence of YEL-AVD in the United States is 0.4 cases per 100,000 doses of vaccine administered. The rate is higher for people aged ≥60 years, with a rate of 1.0 per 100,000 doses in people aged 60–69 years and 2.3 per 100,000 doses in people aged ≥70 years.
Infants younger than 6 months
Yellow fever vaccine is contraindicated for infants aged <6 months. This contraindication was instituted in the late 1960s in response to a high rate of YEL-AND documented in vaccinated young infants (50–400 per 100,000). The mechanism of increased neurovirulence in infants is unknown but may be due to the immaturity of the blood-brain barrier, higher or more prolonged viremia, or immune system immaturity.
Yellow fever vaccine is contraindicated for people with a history of hypersensitivity to any of the vaccine components, including eggs, egg products, chicken proteins, or gelatin. The stopper used in vials of vaccine also contains dry natural latex rubber, which may cause an allergic reaction.
If vaccination of a person with a questionable history of hypersensitivity to one of the vaccine components is considered essential because of a high risk for acquiring yellow fever, skin testing, as described in the vaccine package insert, should be performed under close medical supervision. If a person has a positive skin test to the vaccine or has severe egg sensitivity and the vaccination is recommended, desensitization, as described in the package insert, can be performed under direct supervision of a physician experienced in the management of anaphylaxis.
Altered immune status
Yellow fever vaccine is contraindicated for people with a thymus disorder that is associated with abnormal immune cell function, such as thymoma or myasthenia gravis. If travel to a yellow fever–endemic area cannot be avoided in a person with such a thymus disorder, a medical waiver should be provided and counseling on protective measures against mosquito bites should be emphasized. Because there is no evidence of immune dysfunction or increased risk of yellow fever vaccine–associated serious adverse events in people who have undergone incidental surgical removal of their thymus or have had indirect radiation therapy in the distant past, these people can be given yellow fever vaccine if recommended or required.
Yellow fever vaccine is contraindicated for people with AIDS or other clinical manifestations of HIV, including people with CD4 T-lymphocyte values <200/mm3 or <15% of total lymphocytes for children aged <6 years. This recommendation is based on a theoretical increased risk of encephalitis in this population (see HIV infection under the following section, Precautions).
If travel to a yellow fever–endemic area cannot be avoided by a person with severe immune suppression based on CD4 counts (<200/mm3 or <15% total for children aged <6 years) or symptomatic HIV, a medical waiver should be provided, and counseling on protective measures against mosquito bites should be emphasized. See the following section, Precautions, for other HIV-infected people not meeting the above criteria.
Immunodeficiencies (other than thymus disorder or HIV infection)
Yellow fever vaccine is contraindicated for people with primary immunodeficiencies, malignant neoplasms, and transplantation. While there are no data on the use of yellow fever vaccine in these people, they presumably are at increased risk for yellow fever vaccine–associated serious adverse events (see the section on Immunocompromised Travelers in Chapter 8).
If someone with an immunodeficiency cannot avoid travel to a yellow fever–endemic area, a medical waiver should be provided, and counseling on protective measures against mosquito bites should be emphasized.
Immunosuppressive and immunomodulatory therapies
Yellow fever vaccine is contraindicated for people whose immunologic response is either suppressed or modulated by current or recent radiation therapies or drugs. Drugs with known immunosuppressive or immunomodulatory properties include, but are not limited to, high-dose systemic corticosteroids, alkylating drugs, antimetabolites, tumor necrosis factor-α inhibitors (such as etanercept), interleukin-1 and interleukin-6 blocking agents (such as anakinra and tocilizumab), or other monoclonal antibodies targeting immune cells (such as rituximab or alemtuzumab; see Table 8-4 in Chapter 8, Immunocompromised Travelers for a longer list of immunosuppressive biologic agents). There are no specific data on the use of yellow fever vaccine in people receiving these therapies. However, these people are presumed to be at increased risk for yellow fever vaccine–associated serious adverse events, and the use of live attenuated vaccines is contraindicated in the package insert for most of these therapies (see Chapter 8, Immunocompromised Travelers).
Live viral vaccines should be deferred in people who have discontinued these therapies until immune function has improved. If travel to a yellow fever–endemic area cannot be avoided for someone receiving immunosuppressive or immunomodulatory therapies, a medical waiver should be provided and counseling on protective measures against mosquito bites should be emphasized.
Family members of people with altered immune status, who themselves have no contraindications, can receive yellow fever vaccine.
Infants aged 6–8 months
Age 6–8 months is a precaution for yellow fever vaccination. Two cases of YEL-AND have been reported among infants aged 6–8 months. In infants <6 months of age, the rates of YEL-AND are elevated (50–400 per 100,000). By 9 months of age, risk for YEL-AND is believed to be substantially lower. ACIP generally recommends that, whenever possible, travel to yellow fever-endemic countries should be postponed or avoided for children aged 6–8 months. If travel is unavoidable, the decision of whether to vaccinate these infants needs to balance the risks of YFV exposure with the risk for adverse events after vaccination.
Adults 60 years of age or older
Age ≥60 years is a precaution for yellow fever vaccination, particularly if this is the first dose of the yellow fever vaccine given. A recent analysis of adverse events passively reported to the Vaccine Adverse Events Reporting System (VAERS) from 2000 through 2006 indicates that people aged ≥60 years are at increased risk for any serious adverse event after vaccination, compared with younger people. The rate of serious adverse events in people aged ≥60 years was 8.3 per 100,000 doses distributed, compared with 4.7 per 100,000 for all vaccine recipients. The risk of YEL-AND and YEL-AVD is also increased in this age group, at 1.8 and 1.4 per 100,000 doses, respectively, compared with 0.8 and 0.4 per 100,000 for all vaccine recipients. Given that YEL-AVD has been reported exclusively, and YEL-AND almost exclusively, in primary vaccine recipients, more caution should be exercised with older travelers who may be receiving yellow fever vaccine for the first time. If travel is unavoidable, the decision to vaccinate travelers aged ≥60 years needs to weigh the risks and benefits of the vaccination in the context of their destination-specific risk for exposure to YFV.
Asymptomatic HIV infection with CD4 T-lymphocyte values 200–499/mm3 or 15%–24% of total lymphocytes for children aged <6 years is a precaution for yellow fever vaccination (see also the discussion of HIV infection in the Contraindications section above). Large prospective, randomized trials have not been performed to adequately address the safety and efficacy of yellow fever vaccine among this group. Several retrospective and prospective studies including >500 people infected with HIV have reported no serious adverse events among patients considered moderately immunosuppressed based on their CD4 counts. However, HIV infection has been associated with a reduced immunologic response to a number of inactivated and live attenuated vaccines, including yellow fever vaccine. The mechanisms for the diminished immune response in HIV-infected people are uncertain but appear to be correlated with HIV RNA levels and CD4 T-cell counts.
Because vaccinating asymptomatic HIV-infected people might be less effective than vaccinating people not infected with HIV, measuring their neutralizing antibody response to vaccination should be considered before travel. Contact the state health department or the CDC Arboviral Diseases Branch (970-221-6400) to discuss serologic testing.
If an asymptomatic HIV-infected person with moderate immune suppression (CD4 T-lymphocyte values 200–499/mm3 or 15%–24% of total lymphocytes for children aged <6 years) is traveling to a yellow fever–endemic area, vaccination may be considered. Vaccinated people should be monitored closely after vaccination for evidence of adverse events, and the state health department or CDC should be notified if an adverse event occurs. However, if international travel requirements—not risk of yellow fever—are the only reason to vaccinate an HIV-infected person, the person should be excused from immunization and issued a medical waiver to fulfill health regulations.
If an asymptomatic HIV-infected person has no evidence of immune suppression based on CD4 counts (CD4 T-lymphocyte values ≥500/mm3 or ≥25% of total lymphocytes for children aged <6 years), yellow fever vaccine can be administered if recommended.
Pregnancy is a precaution for yellow fever vaccine administration. The safety of yellow fever vaccination during pregnancy has not been studied in a large prospective trial. However, a recent study of women who were vaccinated with yellow fever vaccine early in their pregnancies found no major malformations in their infants. A slight increased risk was noted for minor, mostly skin, malformations in infants. A higher rate of spontaneous abortions in pregnant women receiving the vaccine was reported but not substantiated. The proportion of women vaccinated during pregnancy who develop YFV-specific IgG antibodies is variable depending on the study (39% or 98%) and may be correlated with the trimester in which they received the vaccine. Because pregnancy may affect immunologic function, serologic testing can be considered to document a protective immune response to the vaccine.
If travel is unavoidable and the vaccination risks are felt to outweigh the risks of YFV exposure, pregnant women should be excused from immunization and issued a medical waiver to fulfill health regulations. Pregnant women who must travel to areas where YFV exposure is likely should be vaccinated. Although there are no specific data, ACIP recommends that a woman wait 4 weeks after receiving the yellow fever vaccine before conceiving.
Breastfeeding is a precaution for yellow fever vaccine administration. Three YEL-AND cases have been reported in exclusively breastfed infants whose mothers were vaccinated with yellow fever vaccine. All 3 infants were aged <1 month at the time of exposure. Further research is needed to document the risk of potential vaccine exposure through breastfeeding. Until more information is available, yellow fever vaccine should be avoided in breastfeeding women. However, when travel of nursing mothers to a yellow fever–endemic area cannot be avoided or postponed, these women should be vaccinated.
Chronic medical conditions that may be associated with varying degrees of immune deficit include, but are not limited to, chronic renal disease, chronic liver disease (including hepatitis C), and diabetes mellitus. Because no information is available regarding possible increased adverse events or decreased vaccine efficacy after administration of yellow fever vaccine to patients with these diseases, caution should be used if considering vaccination of such patients. Factors to consider in assessing patients’ general level of immune competence include disease severity, duration, clinical stability, complications, and comorbidities.
Simultaneous Administration of Other Vaccines and Drugs
Determination of whether to administer yellow fever vaccine and other immunobiologics simultaneously (administration on the same day but at a different injection site) should be made on the basis of convenience to the traveler in completing the desired vaccinations before travel and on information regarding potential immune interference. No evidence exists that inactivated vaccines interfere with the immune response to yellow fever vaccine. Therefore, inactivated vaccines can be administered either simultaneously or at any time before or after yellow fever vaccination. ACIP recommends that yellow fever vaccine be given at the same time as other live-virus vaccines. Otherwise, the clinician should wait 30 days between vaccinations, as the immune response to one live-virus vaccine might be impaired if administered within 30 days of another live-virus vaccine. A recent study involving the simultaneous administration of yellow fever and measles-mumps-rubella (MMR) vaccines in children found a decrease in the immune response against yellow fever, mumps, and rubella when the vaccines were given on the same day versus 30 days apart. Additional studies are needed to confirm these findings, but they suggest that if possible, yellow fever and MMR should be given 30 days apart. Because of the different routes of administration, oral Ty21a typhoid vaccine can be administered simultaneously or at any interval before or after yellow fever vaccine.
Table 3-23. Vaccine to prevent yellow fever
|VACCINE||TRADE NAME (MANUFACTURER)||AGE||DOSE||ROUTE||SCHEDULE||BOOSTER|
|17D yellow fever vaccine||YF-Vax (Sanofi Pasteur)||≥9 months1||0.5 mL2||SC||1 dose||10 years3|
Abbreviation: SC, subcutaneous.
1Ages 6–8 months and ≥60 years are precautions for use of yellow fever vaccine.
2YF-Vax is available in single-dose and multiple-dose (5-dose) vials.
3Revaccination every 10 years is recommended for people at continued risk of exposure to yellow fever virus and is required for entry by certain countries under the International Health Regulations of the World Health Organization.
Table 3-24. Contraindications and precautions to yellow fever vaccine administration
1Symptoms of HIV are classified in 1) Adults and Adolescents, Table 1. CDC. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.MMWR Recomm Rep 1992 Dec 18: 41(RR-17). Available from: www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm and 2) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2010. Available from: http://aidsinfo.nih.gov/ContentFiles/PediatricGuidelines.pdf (PDF). p. 20-2.
INTERNATIONAL CERTIFICATE OF VACCINATION OR PROPHYLAXIS (ICVP)
The IHR allow countries to require proof of yellow fever vaccination as a condition of entry for travelers arriving from certain countries, even if only in transit, to prevent importation and indigenous transmission of YFV. Some countries require evidence of vaccination from all entering travelers, which includes direct travel from the United States (Table 3-25). Travelers who arrive in a country with a yellow fever vaccination entry requirement without proof of yellow fever vaccination may be quarantined for up to 6 days, refused entry, or vaccinated on site. A traveler who has a specific contraindication to yellow fever vaccine and who cannot avoid travel to a country requiring vaccination should request a waiver from a physician before embarking on travel (see the Medical Waivers [Exemptions] section below).
Authorization to Provide Vaccinations and to Validate the ICVP
Under the revised IHR (2005), effective December 15, 2007, all state parties (countries) are required to issue a new ICVP. This is intended to replace the former International Certificate of Vaccination against Yellow Fever (ICV). People who received a yellow fever vaccination after December 15, 2007, must provide proof of vaccination on the new ICVP. If the person received the vaccine before December 15, 2007, the original ICV card is still valid, provided that the vaccination was given <10 years previously. Vaccinees should receive a completed ICVP (Figure 3-01), validated (stamped and signed) with the stamp of the center where the vaccine was given (see below). An ICVP must be complete in every detail; if incomplete or inaccurate, it is not valid. Failure to secure validations can cause a traveler to be quarantined, denied entry, or possibly revaccinated at the point of entry to a country. Revaccination at the point of entry is not a recommended option for the traveler.
Clinics may purchase ICVPs, CDC 731 (formerly PHS 731), from the US Government Printing Office (http://bookstore.gpo.gov/, 866-512-1800). This certificate of vaccination is valid for a period of 10 years, beginning 10 days after the date of vaccination. When a booster dose of the vaccine is given within this 10-year period, the certificate is considered valid from the date of revaccination.
People Authorized to Sign the ICVP and Designated Yellow Fever Vaccination Centers
The ICVP must be signed by a medical provider, who may be a licensed physician or a health care worker designated by the physician, supervising the administration of the vaccine (Figure 3-01). A signature stamp is not acceptable. Yellow fever vaccination must be given at a certified center in possession of an official “uniform stamp,” which can be used to validate the ICVP.
State health departments are responsible for designating nonfederal yellow fever vaccination centers and issuing uniform stamps to clinicians. Information about the location and hours of yellow fever vaccination centers may be obtained by visiting CDC’s website at wwwnc.cdc.gov/travel/yellow-fever-vaccination-clinics-search.aspx.
Medical Waivers (Exemptions)
Some countries do not require an ICVP for infants younger than a certain age (<6 months, <9 months, or <1 year of age, depending on the country). Age requirements for vaccination for individual countries can be found in the Travel Vaccines & Malaria Information, by Country section at the end of this chapter. For medical contraindications, a clinician who has decided to issue a waiver should fill out and sign the Medical Contraindications to Vaccination section of the ICVP (Figure 3-02). The clinician should also do the following:
- Give the traveler a signed and dated exemption letter on the physician’s letterhead stationery, clearly stating the contraindications to vaccination and bearing the stamp used by the yellow fever vaccination center to validate the ICVP.
- Inform the traveler of any increased risk for yellow fever infection associated with lack of vaccination and how to minimize this risk by avoiding mosquito bites.
Reasons other than medical contraindications are not acceptable for exemption from vaccination. The traveler should be advised that issuance of a waiver does not guarantee its acceptance by the destination country. On arrival at the destination, the traveler may be faced with quarantine, refusal of entry, or vaccination on site. To improve the likelihood that the waiver will be accepted at the destination country, clinicians can suggest that the traveler take the following additional measures before beginning travel:
- Obtain specific and authoritative advice from the embassy or consulate of the destination country or countries.
- Request documentation of requirements for waivers from embassies or consulates and retain these, along with the completed Medical Contraindication to Vaccination section of the ICVP.
Table 3-25. Countries that require proof of yellow fever vaccination from all arriving travelers1
Central African Republic
Congo, Repubic of the
Democratic Republic of Congo
São Tomé and Príncipe
1 Country requirements for yellow fever vaccination are subject to change at any time; therefore, CDC encourages travelers to check with the destination country’s embassy or consulate before departure.
Figure 3-01. Example international certificate of vaccination or prophylaxis (ICVP)
(1) Name should appear exactly as on the patient’s passport.
(2, 5, 7) All dates should be entered with the day in numerals, followed by the month in letters, then the year. For example: in the above example, the patient’s date of birth is 22 March 1960.
(3) This space is for the patient’s signature.
(4) For a yellow fever vaccination, ‘Yellow Fever’ should be written in both spaces. Should the ICVP be used for a required vaccination or prophylaxis against another disease or condition (following an amendment to the International Health Regulations or by recommendation of WHO), that disease or condition should be written in this space. Other vaccinations may be listed on the other side.
(5) The date on which the vaccination is given should be entered as shown above.
(6) A handwritten signature of the clinician—either the stamp holder or another health care provider authorized by the stamp holder—administering or supervising the administration of the vaccine (or prophylaxis) should appear in this box. A signature stamp is not acceptable.
(7) The certificate of yellow fever vaccination is valid for 10 years, beginning 10 days after the date of primary vaccination. The ending date for a valid vaccination recorded on the ICVP is 1 calendar day prior to the calendar day on which the vaccine became valid. For example, a vaccination given on 15 June 2012 will be valid on 25 June 2012 and will expire on 24 June 2022. In the case of revaccination, the certificate of yellow fever vaccination is valid immediately if documentation exists on an ICVP demonstrating that the previous yellow fever vaccination was given within the last 10 years.
(8) The Uniform Stamp of the vaccinating center should appear in this box.
Figure 3-02. Medical contraindication to vaccination section of the international certificate of vaccination or prophylaxis (ICVP)
REQUIREMENTS VERSUS RECOMMENDATIONS
Country entry requirements for proof of yellow fever vaccination under the IHR differ from CDC’s recommendations. Yellow fever vaccine entry requirements are established by countries to prevent the importation and transmission of YFV and are allowed under the IHR. Travelers must comply with these to enter the country, unless they have been issued a medical waiver. Certain countries require vaccination from travelers arriving from all countries (Table 3-25), while some countries require vaccination only for travelers coming from “a country with risk of yellow fever transmission” (see Travel Vaccines & Malaria Information, by Country at the end of this chapter). WHO defines those areas “with risk of yellow fever transmission” as countries or areas where yellow fever has been reported currently or in the past, plus where vectors and animal reservoirs exist. Country requirements are subject to change at any time; therefore, CDC encourages travelers to check with the relevant embassy or consulate before departure.
The information in the section on yellow fever vaccine recommendations is advice given by CDC to prevent yellow fever infections among travelers. Recommendations are subject to change at any time because of changes in YFV circulation; therefore, CDC encourages travelers to check the destination pages for up-to-date vaccine information and to check for relevant travel notices on the CDC website before departure (www.cdc.gov/travel).
RECENT CHANGES TO YELLOW FEVER RISK CLASSIFICATION
In 2010, CDC, WHO, and other yellow fever experts completed a comprehensive review of available data and revised the criteria and global maps designating the risk of YFV transmission. The new criteria established 4 categories of risk for YFV transmission that apply to all geographic areas: endemic, transitional, low potential for exposure, and no risk.
Yellow fever vaccination is recommended for travel to endemic and transitional areas. Although vaccination is generally not recommended for travel to areas with low potential for exposure, it might be considered for a small subset of travelers whose itinerary could place them at increased risk for exposure to YFV (such as prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites).
Based on the revised criteria for yellow fever risk classification, the current maps (Maps 3-16 and 3-17) and country-specific information (see Travel Vaccines & Malaria Information, by Country at the end of this chapter) designate 3 levels of yellow fever vaccine recommendations: recommended, generally not recommended, and not recommended. Note: The revised yellow fever Maps 3-16 and 3-17 depict areas where yellow fever vaccination is recommended rather than yellow fever risk.
Countries that only contain areas with low potential for exposure to YFV (Table 3-22) are not included on the official WHO list of countries with risk of YFV transmission (Table 3-21). Therefore, proof of yellow fever vaccination should not be required if traveling from a country with low potential for exposure to YFV to a country with a vaccination entry requirement (unless that country requires proof of yellow fever vaccination from all arriving travelers; see Table 3-25). An exception is South Africa, which since the end of 2011 has required yellow fever vaccination for people traveling from or transiting through any of the 5 countries with low potential for exposure, in addition to those with risk of YFV transmission.
VACCINATION FOR TRAVEL ON MILITARY ORDERS
Because military requirements may exceed those indicated in this publication, any person who plans to travel on military orders (civilians and military personnel) should contact the nearest military medical facility to determine the requirements for his or her trip (see also Chapter 8, Special Considerations for US Military Deployments).
CDC website: www.cdc.gov/yellowfever
Map 3-16. Yellow fever vaccine recommendations in Africa1
1Current as of September 2012. This map, which aligns with recommendations also published by the World Health Organization (WHO), is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.
Map 3-17. Yellow fever vaccine recommendations in the Americas1
1Current as of September 2012. This map, which aligns with recommendations also published by the World Health Organization (WHO), is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.
- Barwick R. History of thymoma and yellow fever vaccination. Lancet. 2004 Sep 11–17;364(9438):936.
- Cavalcanti DP, Salomao MA, Lopez-Camelo J, Pessoto MA. Early exposure to yellow fever vaccine during pregnancy. Trop Med Int Health. 2007 Jul;12(7): 833–7.
- CDC. General recommendations on immunization—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(2):1–64.
- CDC. Transmission of yellow fever vaccine virus through breast-feeding—Brazil, 2009. MMWR Morb Mortal Wkly Rep. 2010 Feb 12;59(5):130–2.
- Hayes EB. Acute viscerotropic disease following vaccination against yellow fever. Trans R Soc Trop Med Hyg. 2007 Oct;101(10):967–71.
- Jentes ES, Poumerol G, Gershman MD, Hill DR, Lemarchand J, Lewis RF, et al. The revised global yellow fever risk map and recommendations for vaccination, 2010: consensus of the Informal WHO Working Group on Geographic Risk for Yellow Fever. Lancet Infect Dis. 2011 Aug;11(8):622–32.
- Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Marano N, et al. Adverse event reports following yellow fever vaccination. Vaccine. 2008 Nov 11;26(48):6077–82.
- McMahon AW, Eidex RB, Marfin AA, Russell M, Sejvar JJ, Markoff L, et al. Neurologic disease associated with 17D-204 yellow fever vaccination: a report of 15 cases. Vaccine. 2007 Feb 26;25(10):1727–34.
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- Nascimento Silva JR, Camacho LA, Siqueira MM, Freire Mde S, Castro YP, Maia Mde L, et al. Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella. Vaccine. 2011 Aug 26;29(37):6327–34.
- Nasidi A, Monath TP, Vandenberg J, Tomori O, Calisher CH, Hurtgen X, et al. Yellow fever vaccination and pregnancy: a four-year prospective study. Trans R Soc Trop Med Hyg. 1993 May–Jun;87(3):337–9.
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- Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Jul 30;59(RR-7):1–27.
- Suzano CES, Amaral E, Sato HK, Papaiordanou PM, Campinas Group on Yellow Fever Vaccination. The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil. Vaccine. 2006 Feb 27;24(9):1421–6.
- Whittembury A, Ramirez G, Hernandez H, Ropero AM, Waterman S, Ticona M, et al. Viscerotropic disease following yellow fever vaccination in Peru. Vaccine. 2009 Oct 9;27(43):5974–81.
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