Yellow Fever

Infectious Agent

Yellow fever (YF) virus is a single-stranded RNA virus that belongs to the genus Flavivirus .

Transmission

Vectorborne transmission of YF virus 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 YF virus: sylvatic (jungle), intermediate (savannah), and urban.

  • The sylvatic (jungle) cycle involves transmission of virus between nonhuman primates and mosquito species found in forest canopy. Virus is transmitted via mosquitoes from monkeys to humans when occupational or recreational activities encroach into the jungle.
  • In Africa, an intermediate (savannah) cycle involves transmission of YF virus from tree hole-breeding Aedes spp. to humans in jungle border areas. Virus may be transmitted from monkeys to humans or from human to human via these mosquitoes.
  • The urban cycle involves transmission of virus between humans and peridomestic mosquitoes, primarily Ae. aegypti .

Humans infected with YF virus experience the highest levels of viremia shortly before onset of fever and for the first 3–5 days of illness, during which time they can transmit the virus to mosquitoes. Given the high level of viremia, bloodborne transmission theoretically can occur via transfusion or needlesticks. One case of perinatal transmission of wild-type YF virus has been documented from a woman who developed symptoms of YF, 3 days before giving birth. The infant tested positive for YF viral RNA and died of fulminant YF on the 12th day of life.

Epidemiology

YF occurs in sub-Saharan Africa and tropical South America, where it is endemic and intermittently epidemic (see Tables 4-23 and 4-24 for a list of countries with risk of YF virus transmission). Most YF disease in humans is due to sylvatic or intermediate transmission cycles. However, urban YF occurs periodically in Africa and sporadically in the Americas. In areas of Africa with persistent circulation of YF virus, natural immunity accumulates with age; consequently, infants and children are at highest risk for disease. In South America, YF occurs most frequently in unimmunized young men exposed to mosquito vectors through their work in forested areas.

Table 4-23. Countries with risk of yellow fever (YF) virus transmission 1

Africa



Central and South America

Angola

Benin

Burkina Faso

Burundi

Cameroon

Central African Republic

Chad 2

Congo, Republic of the

Côte d’Ivoire

Democratic Republic of the Congo

Equatorial Guinea

Ethiopia 2

Gabon

The Gambia

Ghana

Guinea

Guinea-Bissau

Kenya 2

Liberia

Mali 2

Mauritania 2

Niger 2

Nigeria

Senegal

Sierra Leone

South Sudan

Sudan 2

Togo

Uganda

Argentina 2

Bolivia 2

Brazil 2

Colombia 2

Ecuador 2

French Guiana

Guyana

Panama 2

Paraguay

Peru 2

Suriname

Trinidad and Tobago 2

Venezuela 2

1 Defined by the World Health Organization as countries or areas where YF “has been reported currently or in the past and vectors and animal reservoirs currently exist.” See current Annex 1 and country list on the WHO International Travel and Health webpage at www.who.int/ith/en.

2 These countries are not holoendemic (only a portion of the country has risk of YF virus + transmission). See Maps 4-13 and 4-14 and YF vaccine recommendations (Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country) for details.

Table 4-24. Countries with low potential for exposure to yellow fever (YF) virus 1

Africa

Eritrea 2

Rwanda

São Tomé and Príncipe

Somalia 2

Tanzania

Zambia 2

1 These countries are not on the World Health Organization list of countries with risk of YF virus transmission (Table 4-23). Therefore, proof of YF vaccination should not be required if traveling from any of these countries to another country with a vaccination entry requirement (unless that country requires proof of YF vaccination from all arriving travelers; see Table 4-27).

2 These countries are classified as “low potential for exposure to YF virus” in only some areas; the remaining areas of these countries are classified as having no risk of exposure to YF virus.

Risk for Travelers

A traveler’s risk for acquiring YF 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. Since “epidemiologic silence” does not mean absence of risk, travelers should not go into endemic areas without taking protective measures.

YF virus 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, Ae. aegypti may transmit YF virus episodically, even during the dry season, in both rural and densely settled urban areas. The risk for infection by sylvatic vectors in South America is highest during the rainy season (January–May, with a peak incidence in February and March).

From 1970 through 2015, 11 cases of YF were reported in travelers from the United States and Europe who traveled to West Africa (6 cases) or South America (5 cases). Eight of 11 travelers (73%) died. Only 1 traveler had a documented history of YF vaccination; that patient survived. Starting in 2016, the number of travel-associated YF cases increased substantially, primarily because of outbreaks in Angola and Brazil. From 2016 through mid-2018, more than 35 travel-associated cases were reported in unvaccinated travelers who were residents of nonendemic areas or countries, including at least 13 European travelers and 1 American traveler to Peru.

The risk of acquiring YF during travel is difficult to predict because of variations in ecologic determinants of virus transmission. For a 2-week stay, the estimated risks for illness and for death due to YF for an unvaccinated traveler visiting an endemic area are as follows:

  • In West Africa, 50 per 100,000 and 10 per 100,000, respectively
  • In South America, 5 per 100,000 and 1 per 100,000, respectively

These estimates are based on the risk to indigenous populations, often during peak transmission season. They may not accurately reflect the risk to travelers who have a different immunity profile, take precautions against mosquito bites, and have less outdoor exposure. However, the risk of infection for travelers is likely higher during outbreaks, as demonstrated with recent outbreaks in Angola and Brazil.

Clinical Presentation

Most people infected with YF virus likely do not seek medical attention because they have minimal or no symptoms. For people who develop symptomatic illness, the incubation period is typically 3–6 days. The initial illness is nonspecific: fever, chills, headache, backache, myalgia, prostration, nausea, and vomiting. Most patients improve after the initial presentation. After a brief remission of up to 24 hours, approximately 12% of those infected progress to a more serious form of the disease, characterized by jaundice, hemorrhagic symptoms, and eventually shock and multisystem organ failure. The case-fatality ratio for severe cases is 30%–60%.

Diagnosis

The preliminary diagnosis is based on the patient’s clinical features and exposure details. Laboratory diagnosis is best performed by:

  • Virus isolation or nucleic acid amplification tests performed early in the illness for YF virus or YF viral RNA. By the time more overt symptoms are recognized, the virus or viral RNA may no longer be detectable. Therefore, virus isolation and nucleic acid amplification should not be used to rule out a diagnosis of YF.
  • 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 performed to confirm the infection.

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 YF virus infections. YF is a nationally notifiable disease.

Treatment

There are no specific medications to treat YF virus infections; treatment is directed at symptomatic relief or life-saving interventions. Rest, fluids, and use of analgesics and antipyretics may relieve symptoms of aching and fever. Care should be taken to avoid 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 (by staying indoors or under a mosquito net) during the first few days of illness, so they do not contribute to the transmission cycle.

Prevention

Personal Protection Measures

The best way to prevent mosquitoborne diseases, including YF, is to avoid mosquito bites (see Chapter 3, Mosquitoes, Ticks & Other Arthropods).

Vaccine

YF is preventable by a relatively safe, effective vaccine. All YF vaccines currently manufactured are live attenuated viral vaccines. Only one YF vaccine (YF-VAX, Sanofi Pasteur) is licensed for use in the United States (Table 4-25). There have been periodic shortages of YF-VAX, including one that started in late 2015 that necessitated the importation and distribution of Stamaril, another YF vaccine produced by Sanofi Pasteur in France, under an expanded-access investigational new drug protocol.

Table 4-25. Vaccine to prevent yellow fever (YF)

Vaccine

Trade Name (Manufacturer)

Age

Dose

Route

Schedule

Booster

17D

YF-VAX (Sanofi Pasteur)

≥9 months 1

0.5mL 2

SC

1 dose

Not recommended for most 3

Abbreviation: SC, subcutaneous.

1 Ages 6–8 months and ≥60 years are precautions and age <6 months is a contraindication to the use of YF vaccine.

2 YF-VAX is available in single-dose and multiple-dose (5-dose) vials.

3 For further details regarding revaccination see “Vaccine Administration” in this section.

There are no substantial differences in reactogenicity or immunogenicity of the different YF vaccine products, including those manufactured outside the United States. People who receive YF vaccines licensed in other countries but not approved by the US Food and Drug Administration (FDA) should be considered protected against YF. For the most up-to-date information on YF vaccine availability, providers should check the CDC Travelers’ Health website at www.cdc.gov/travel.

Indications for Use

YF vaccine is recommended for people aged ≥9 months who are traveling to or living in areas with risk for YF virus transmission in South America and Africa. In addition, some countries require proof of YF vaccination for entry. For country-specific YF vaccination recommendations and requirements, see Chapter 2, Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country.

Because of the risk of serious adverse events after YF vaccination, clinicians should only vaccinate people who are at risk of exposure to YF virus or who require proof of vaccination to enter a country. To minimize further the risk of serious adverse events, clinicians should carefully observe the contraindications and consider the precautions to vaccination before administering YF vaccine (Table 4-26). For additional information, refer to the YF vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) at www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/yf.html.

Table 4-26. Contraindications and precautions to yellow fever vaccine administration

Contraindications

Precautions

  • Allergy to vaccine component 1

  • Age <6 months

  • Symptomatic HIV infection or CD4 T lymphocytes <200/mm3 (or <15% of total lymphocytes in children aged <6 years) 2

  • Thymus disorder associated with abnormal immune-cell function

  • Primary immunodeficiencies

  • Malignant neoplasms

  • Transplantation

  • Immunosuppressive and immunomodulatory therapies

  • Age 6–8 months

  • Age ≥60 years

  • Asymptomatic HIV infection and CD4 T lymphocytes 200–499/mm3 (or 15%–24% of total lymphocytes in children aged <6 years) 2

  • Pregnancy

  • Breastfeeding

1 If vaccination is considered, desensitization can be performed under direct supervision of a physician experienced in the management of anaphylaxis.

2 Symptoms 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;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. pp. 20–2.

Vaccine Administration

For all eligible people, a single 0.5-mL injection of reconstituted vaccine should be administered subcutaneously. Fractional dosing of yellow fever vaccine (administering a partial dose, usually 0.1 mL) has been used recently in several countries to control large yellow fever outbreaks during conditions of limited vaccine availability. In the United States, FDA has not approved fractional dosing of yellow fever vaccine. Furthermore, the World Health Organization (WHO) notes that a fractional dose of yellow fever vaccine does not meet the requirements of a dose of vaccine according to the International Health Regulations (IHR); therefore, proof of vaccination may not be issued to a person who has received only a fractional dose.

In 2014, the WHO Strategic Advisory Group of Experts on Immunization concluded that a single primary dose of YF vaccine provides sustained immunity and lifelong protection against YF disease and that a booster dose is not needed. In 2016, the IHR were officially amended to specify that a completed International Certificate of Vaccination or Prophylaxis (ICVP or “yellow card”) is valid for the lifetime of the vaccinee, and countries cannot require proof of revaccination (booster) against YF as a condition of entry, even if the last vaccination was >10 years prior.

ACIP also stated that a single dose of YF vaccine provides long-lasting protection and is adequate for most travelers. However, these guidelines differ slightly from those of WHO. ACIP guidelines specify that additional doses of YF vaccine are recommended for the following groups of travelers:

  • Women who were pregnant when they received their initial dose of vaccine should receive 1 additional dose before they are next at risk for YF.
  • People who received a hematopoietic stem cell transplant after receiving a dose of YF vaccine should be revaccinated before they are next at risk for YF as long as they are sufficiently immunocompetent.
  • People infected with HIV when they received their last dose of YF vaccine should receive a dose every 10 years if they continue to be at risk for YF.

Consider administering a booster dose for travelers who received their last dose of YF vaccine ≥10 years previously who will be going to higher-risk settings based on season, location, activities, and duration of travel. This includes travelers planning prolonged stays in endemic areas, those traveling to endemic areas such as rural West Africa during peak transmission season, or travelers visiting areas with ongoing outbreaks. Refer to the ACIP website (www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/yf.html) for all current ACIP YF vaccine recommendations.

Although booster doses of YF vaccine are not recommended for most travelers, and despite the recent changes to the IHR, clinicians and travelers should nonetheless review the entry requirements for destination countries. For more information on country-specific recommendations and requirements, see Chapter 2, Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country.

Vaccine Safety and Adverse Reactions

Common Adverse Reactions

Reactions to YF vaccine are generally mild; 10%–30% of vaccinees report mild systemic adverse events, including low-grade fever, headache, and myalgia that begin within days after vaccination and last 5–10 days.

Severe Adverse Reactions

Hypersensitivity

Immediate hypersensitivity reactions, characterized by rash, urticaria, or bronchospasm are uncommon. Anaphylaxis after YF vaccine is reported to occur at a rate of 1.3 cases per 100,000 doses administered.

Yellow Fever Vaccine–Associated Neurologic Disease (YEL-AND)

YEL-AND represents a conglomeration of clinical syndromes, including meningoencephalitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and, rarely, cranial nerve palsies. Historically, YEL-AND was seen primarily among infants as encephalitis, but more recent reports have been among people of all ages. YEL-AND is rarely fatal.

Among all cases of YEL-AND reported globally, almost all occurred in first-time vaccine recipients. The onset of illness for documented cases in the United States is 2–56 days after vaccination. The incidence of YEL-AND in the United States is 0.8 per 100,000 doses administered but is higher (2.2 per 100,000 doses) in people aged ≥60 years.

Yellow Fever Vaccine–Associated Viscerotropic Disease (YEL-AVD)

YEL-AVD is a severe illness similar to wild-type YF disease, with vaccine virus proliferating in multiple organs and often leading to multiorgan dysfunction or failure and occasionally death. Since the initial cases of YEL-AVD were published in 2001, >100 confirmed and suspected cases have been reported throughout the world.

YEL-AVD has been reported to occur only after the first dose of YF vaccine; there have been no laboratory-confirmed reports of YEL-AVD following booster doses. For YEL-AVD cases reported in the United States, the median time from YF vaccination until symptom onset is 4 days (range, 1–18 days). The case-fatality ratio is approximately 48% and the incidence is 0.3 cases per 100,000 doses of vaccine administered. The incidence of YEL-AVD is higher for people aged ≥60 years, 1.2 per 100,000 doses, and is even higher for people aged ≥70 years.

Contraindications

People who have a contraindication to YF vaccine should not be vaccinated. If travel to a YF-endemic area cannot be avoided, a medical waiver (Figure 4-3) should be provided, and protective measures against mosquito bites should be emphasized.

Contraindications to receiving YF vaccine include age <6 months, hypersensitivity to vaccine components, and various forms of altered immunity (including symptomatic HIV infection or HIV infection with severe immunosuppression).

Infants Younger than 6 Months

YF vaccine is contraindicated in infants aged <6 months because the rate of YEL-AND is high (50–400 cases per 100,000 infants vaccinated). 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.

Hypersensitivity

YF vaccine is contraindicated in people with a history of acute hypersensitivity reaction to a previous dose of the vaccine or 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 a vaccine component is considered essential, skin testing and, if indicated, desensitization should be performed by an experienced clinician according to instructions provided by the manufacturer in the vaccine prescribing information.

Altered Immune Status

Thymus Disorder

YF vaccine is contraindicated in people with a thymus disorder associated with abnormal immune cell function, such as thymoma or myasthenia gravis. There is no evidence of immune dysfunction or increased risk of YF vaccine–associated serious adverse events in people who have undergone incidental thymectomy or who have had indirect radiation therapy in the distant past; these people can be vaccinated.

HIV Infection

YF vaccine is contraindicated in people with AIDS or other clinical manifestations of HIV infection, including those with CD4 T lymphocyte values <200/mm3 or <15% of total lymphocytes for children aged <6 years. This recommendation is based on the potential increased risk of encephalitis in this population. See the following section (“Precautions”) for guidance regarding other HIV-infected people not meeting the above criteria.

Immunodeficiencies (other than thymus disorder or HIV infection)

YF vaccine is contraindicated in people who are immunodeficient or immunosuppressed, whether due to an underlying (primary) disorder or medical treatment. This includes organ transplant patients and those with malignant neoplasms. See Chapter 5, Immunocompromised Travelers.

Immunosuppressive and Immunomodulatory Therapies

YF vaccine is contraindicated in people whose immunologic response is either suppressed or modulated by current or recent radiation therapy or drugs. Drugs with known immunosuppressive or immunomodulatory properties include, but are not limited to, high-dose systemic corticosteroids, alkylating agents, antimetabolites, tumor necrosis factor-α inhibitors (such as etanercept), interleukin blocking agents (such as anakinra and tocilizumab), or other monoclonal antibodies targeting immune cells (such as rituximab or alemtuzumab). These people are presumed to be at increased risk for YF 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 5, Immunocompromised Travelers). Live viral vaccines should be deferred in people who have discontinued these therapies until immune function has improved.

Family members of people with altered immune status, who themselves have no contraindications, can receive YF vaccine.

Precautions

If travel to a YF risk area is unavoidable for a person with a precaution to vaccination, the decision to vaccinate should balance the risks of YF virus exposure with the risk for an adverse event after vaccination. If international travel requirements, not risk of YF, are the only reason to vaccinate a person with a precaution to vaccination, the person should not be immunized and should be issued a medical waiver to fulfill health regulations.

Precautions to receiving YF vaccine include age 6–8 months, age ≥60 years, asymptomatic HIV infection with moderate immunosuppression, pregnancy, and breastfeeding.

Infants Aged 6–8 Months

Age 6–8 months is a precaution to receiving YF vaccine. Two cases of YEL-AND have been reported in infants aged 6–8 months. By 9 months of age, risk for YEL-AND is believed to be substantially lower. ACIP recommends that, whenever possible, travel to YF–endemic countries should be postponed or avoided for children aged 6–8 months.

Adults 60 Years of Age or Older

Age ≥60 years is a precaution to receiving YF vaccine, particularly a first ever dose. The rate of reported serious adverse events following YF vaccination in people aged ≥60 years is 7.7 per 100,000 doses distributed, compared with 3.8 per 100,000 for all YF vaccine recipients. The risks of YEL-AND and YEL-AVD are increased in this age group (see above). Given that YEL-AVD has been reported exclusively, and YEL-AND almost exclusively, in primary vaccine recipients, particular caution should be considered for older travelers receiving YF vaccine for the first time.

HIV Infection

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 to receiving YF vaccine (see also the previous discussion of HIV infection as a contraindication to YF vaccine administration). Combined studies of >500 HIV-infected people who had received YF vaccine 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 YF vaccine. The diminished immune response appears to be correlated with HIV RNA levels and CD4 T cell counts.

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), YF vaccine can be administered if recommended. 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.

Pregnancy

Pregnancy is a precaution to receiving YF vaccine. The safety of YF vaccination during pregnancy has not been studied in any large prospective trials. A study of women vaccinated against YF early in their pregnancies detected no major malformations in their infants, although a slight increased risk for minor, mostly skin, malformations was noted. A higher rate of spontaneous abortions in pregnant women receiving the vaccine was reported but not substantiated by a subsequent study.

The proportion of women vaccinated during pregnancy who develop YF virus-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.

Although there are no specific data, ACIP recommends that a woman wait 4 weeks after receiving the YF vaccine before conceiving.

Breastfeeding

Breastfeeding is a precaution to receiving YF vaccine. Three YEL-AND cases have been reported in exclusively breastfed infants whose mothers were vaccinated with YF vaccine. All 3 infants were diagnosed with encephalitis and aged <1 month at the time of exposure. Until specific research data are available, avoid vaccinating breastfeeding women against YF. However, when travel of nursing mothers to YF–endemic areas cannot be avoided or postponed, these women should be vaccinated. Although there are no data, some experts recommend that breastfeeding women who receive YF vaccine should temporarily suspend breastfeeding, pump, and discard pumped milk for at least 2 weeks after vaccination before resuming breastfeeding.

Other Considerations

There are no data regarding possible increased adverse events or decreased vaccine efficacy after administration of YF vaccine to patients with other chronic medical conditions (such as renal disease, liver disease including hepatitis C virus infection, or diabetes mellitus). Limited data suggest that autoimmune disease, either by itself or in conjunction with other risk factors, including immunosuppressive medication, might increase the risk for YEL-AVD. Therefore, use caution if considering vaccination of such patients. Factors to consider in assessing patients’ general level of immune competence include disease severity, duration, clinical stability, complications, comorbidities, and medications that the person is taking.

Simultaneous Administration of other Vaccines and Drugs

No evidence exists that inactivated vaccines interfere with the immune response to YF vaccine. Therefore, inactivated vaccines can be administered either simultaneously or at any time before or after YF vaccination. ACIP recommends that YF vaccine be given at the same time as other live viral vaccines. Otherwise, the clinician should wait 30 days between vaccinations, as the immune response to a live viral vaccine might be impaired if administered within 30 days of another live viral vaccine.

Limited data suggest that coadministration of YF vaccine with measles-rubella (MR) or measles-mumps-rubella (MMR) vaccines might decrease the immune response. One study involving the simultaneous administration of YF and MMR vaccines and a second involving simultaneous administration of YF and MMR vaccines in children demonstrated a decreased immune response against all antigens except measles 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, YF and MMR should be given 30 days apart.

Data suggest oral Ty21a typhoid vaccine, a live bacterial vaccine, can be administered simultaneously or at any interval before or after YF vaccine. There are no data on the immune response to live attenuated oral cholera vaccine (Vaxchora) or nasally administered live attenuated influenza vaccine administered simultaneously with YF vaccine.

International Certificate of Vaccination or Prophylaxis (ICVP)

The IHR allow countries to require proof of YF vaccination documented on an ICVP as a condition of entry for travelers arriving from certain countries, even if only in transit, to prevent importation and indigenous transmission of YF virus. Some countries require evidence of vaccination from all entering travelers, which includes direct travel from the United States (Table 4-27). A traveler who has a specific contraindication to YF 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). Travelers arriving without proof of YF vaccination or a medical waiver to a country that has a YF vaccination entry requirement may be quarantined for up to 6 days, refused entry, or vaccinated on site.

Table 4-27. Countries that require proof of yellow fever (YF) vaccination from all arriving travelers 1

Angola

Ghana

Burundi

Guinea-Bissau

Cameroon

Mali

Central African Republic

Niger

Chad

Sierra Leone

Congo, Republic of the

South Sudan

Côte d’Ivoire

Togo

Democratic Republic of the Congo

Uganda

Gabon


1 Country requirements for YF vaccination are subject to change at any time; therefore, CDC encourages travelers to check with the destination country’s embassy or consulate before departure.

Authorization to Provide Vaccinations and to Validate the Icvp

People who received YF vaccination after December 15, 2007, must provide proof of vaccination on the new ICVP. If the person received the vaccine before December 15, 2007, their original International Certificate of Vaccination against Yellow Fever (ICV) card is still valid as proof of vaccination. Vaccinees should receive a completed ICVP (Figure 4-2), validated (stamped and signed) with the stamp of the center where the vaccine was given (see below). Failure to secure validations can cause a traveler to be quarantined, denied entry, or possibly revaccinated at the point of entry to a country.

Figure 4-2. Example International Certificate of Vaccination or Prophylaxis (ICVP)
Figure 4-2. 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 (YF) 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 the World Health Organization), 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 YF vaccination (ICVP) is valid beginning 10 days after the date of primary vaccination, which should be noted in the box for “certificate valid from.” As of July 2016, the YF vaccine booster requirement was eliminated in the IHR, and a completed ICVP is considered valid for the lifetime of the vaccinee. Suggested wording to write in the ICVP box for “certificate valid until” is “life of person vaccinated.” For the most recent information on YF vaccination entry requirements by country, consult the destination pages of the CDC Travelers’ Health website.(8) The Uniform Stamp of the vaccinating center should appear in this box.

A properly filled out ICVP is valid beginning 10 days after the date of primary vaccination. As of July 2016, the YF vaccine booster requirement was eliminated in the IHR and a completed ICVP is considered valid for the lifetime of the vaccinee. Clinics may purchase ICVPs, CDC 731 (formerly PHS 731), from the US Government Publishing Office website (http://bookstore.gpo.gov) or by phone (866-512-1800).

People Authorized to Sign the Icvp and Designated Yellow Fever Vaccination Centers

The ICVP must bear the signature of a licensed physician or a health care worker designated by the physician to supervise the administration of the vaccine (Figure 4-2). A signature stamp is not acceptable. YF vaccination must be given at an authorized center in possession of an official “uniform stamp,” which can be used to validate the ICVP. In the United States, state health departments are responsible for designating nonfederal YF vaccination centers and issuing uniform stamps to clinicians. Information about the location and hours of YF vaccination centers may be obtained by visiting CDC’s website at wwwnc.cdc.gov/travel/yellow-fever-vaccination-clinics-search.aspx.

Medical Waivers (Exemptions)

A clinician issuing a waiver for YF vaccine should complete and sign the “Medical Contraindications to Vaccination” section of the ICVP (Figure 4-3). Reasons other than medical contraindications are not acceptable for exemption from vaccination. The clinician should also do the following:

Figure 4-3. Medical Contraindication to Vaccination section of the International Certificate of Vaccination or Prophylaxis (ICVP)
Figure 4-3. Medical Contraindication to Vaccination section of the International Certificate of Vaccination or Prophylaxis (ICVP)
  • Provide the traveler with a signed and dated exemption letter on letterhead stationery, clearly stating the contraindications to vaccination and bearing the stamp used by the YF vaccination center to validate the ICVP.
  • Advise the traveler that a medical waiver may not be accepted by the destination country.
  • Inform the traveler of any increased risk for YF infection associated with lack of vaccination and how to minimize this risk by strictly adhering to mosquito bite prevention measures.

To improve the likelihood that the waiver will be accepted at the destination country, the clinician 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.

Requirements Versus Recommendations

Country entry requirements for proof of YF vaccination under the IHR differ from CDC’s recommendations . Countries may establish YF vaccine entry requirements to prevent the importation and transmission of YF virus. Travelers must comply with these requirements to enter the country, unless they have been issued a medical waiver. Certain countries require vaccination from travelers arriving from all countries (Table 4-27), while some countries require vaccination only for travelers above a certain age coming from countries with risk of YF virus transmission (see Chapter 2, Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country). WHO defines those areas with risk of YF virus transmission as countries or areas where YF virus activity has been reported currently or in the past and 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.

CDC bases its advice on how to prevent travel-associated YF virus infections on a destination-specific risk classification for YF virus transmission: endemic, transitional, low potential for exposure, and no risk. CDC recommends YF vaccination for travel to endemic and transitional areas (Maps 4-13 and 4-14). Recommendations are subject to change at any time because of changes in YF virus 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).

Map 4-13. Yellow fever vaccine recommendations in Africa 1
Map 4-13. Yellow fever vaccine recommendations in Africa1

1 Current as of August 2018. This map is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.

2 Yellow fever (YF) vaccination is generally not recommended in areas where there is low potential for YF virus exposure. However, vaccination might be considered for a small subset of travelers to these areas who are at increased risk for exposure to YF virus because of prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites. Consideration for vaccination of any traveler must take into account the traveler’s risk of being infected with YF virus, country entry requirements, and individual risk factors for serious vaccine-associated adverse events (e.g., age, immune status).

Map 4-14.Yellow fever vaccine recommendations in the Americas 1
Map 4-14.Yellow fever vaccine recommendations in the Americas1

1 Current as of August 2018. This map is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.

2 In 2017, CDC expanded yellow fever vaccination recommendations for travelers to Brazil because of a large outbreak of yellow fever in multiple states in that country. Please refer to the CDC Travelers’ Health website (www.cdc.gov/travel) for more information and updated recommendations.

3 Yellow fever (YF) vaccination is generally not recommended in areas where there is low potential for YF virus exposure. However, vaccination might be considered for a small subset of travelers to these areas who are at increased risk for exposure to YF virus because of prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites. Consideration for vaccination of any traveler must take into account the traveler’s risk of being infected with YF virus, country entry requirements, and individual risk factors for serious vaccine-associated adverse events (such as age or immune status).

Countries that contain areas with only low potential for exposure to YF virus (Table 4-24) are not included on the official WHO list of countries with risk of YF virus transmission (Table 4-23). Unless a country requires proof of YF vaccination from all arriving travelers, proof of YF vaccination should not be required of travelers coming from a country with low potential for exposure to YF virus to a country with a vaccination entry requirement.

CDC website: www.cdc.gov/yellowfever

Bibliography

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Authors

Mark D. Gershman, J. Erin Staples