Yellow Fever Vaccine

department of health and human services

Centers for Disease Control and Prevention

Recommendations and Reports July 30, 2010 / Vol. 59 / No. RR-7

Morbidity and Mortality Weekly Report

www.cdc.gov/mmwr

Yellow Fever Vaccine

Recommendations of the Advisory Committee

on Immunization Practices (ACIP)

MMWR

e MMWR series of publications is published by the Oﬃce of

Surveillance, Epidemiology, and Laboratory Services, Centers for

Disease Control and Prevention (CDC), U.S. Department of Health

and Human Services, Atlanta, GA 30333.

Suggested Citation: Centers for Disease Control and Prevention.

[Title]. MMWR 2010;59(No. RR-#):[inclusive page numbers].

Centers for Disease Control and Prevention

omas R. Frieden, MD, MPH

Director

Harold W. Jaﬀe, MD, MA

Associate Director for Science

James W. Stephens, PhD

Oﬃce of the Associate Director for Science

Stephen B. acker, MD, MSc

Deputy Director for

Surveillance, Epidemiology, and Laboratory Services

Editorial and Production Staff

Frederic E. Shaw, MD, JD

Editor, MMWR Series

Christine G. Casey, MD

Deputy Editor, MMWR Series

Teresa F. Rutledge

Managing Editor, MMWR Series

David C. Johnson

Lead Technical Writer-Editor

Jeﬀrey D. Sokolow, MA

Project Editor

Martha F. Boyd

Lead Visual Information Specialist

Malbea A. LaPete

Stephen R. Spriggs

Terraye M. Starr

Visual Information Specialists

Quang M. Doan, MBA

Phyllis H. King

Information Technology Specialists

Editorial Board

William L. Roper, MD, MPH, Chapel Hill, NC, Chairman

Virginia A. Caine, MD, Indianapolis, IN

Jonathan E. Fielding, MD, MPH, MBA, Los Angeles, CA

David W. Fleming, MD, Seattle, WA

William E. Halperin, MD, DrPH, MPH, Newark, NJ

King K. Holmes, MD, PhD, Seattle, WA

Deborah Holtzman, PhD, Atlanta, GA

John K. Iglehart, Bethesda, MD

Dennis G. Maki, MD, Madison, WI

Patricia Quinlisk, MD, MPH, Des Moines, IA

Patrick L. Remington, MD, MPH, Madison, WI

Barbara K. Rimer, DrPH, Chapel Hill, NC

John V. Rullan, MD, MPH, San Juan, PR

William Schaﬀner, MD, Nashville, TN

Anne Schuchat, MD, Atlanta, GA

Dixie E. Snider, MD, MPH, Atlanta, GA

John W. Ward, MD, Atlanta, GA

On the Cover: Aedes aegypti mosquito, the urban vector of yellow

fever virus; vervet monkey (Chlorocebus pygerythrus), present in east

and south Africa; and man receiving vaccine.

CONTENTS

Introduction .............................................................................. 1

Methods

................................................................................... 2

Background

.............................................................................. 2

Yellow Fever Vaccine

................................................................. 6

Summary of Rationale for YF Vaccine Recommendations

............ 13

Recommendations for the Use of YF Vaccine in Laboratory

Workers

................................................................................ 14

Recommendations for Prevention of YF Among Travelers

............ 14

Requirements for Vaccination Before International Travel

............ 15

Administration of Yellow Fever Vaccine

..................................... 16

Contraindications

.................................................................... 18

Precautions

............................................................................. 20

Special Populations

................................................................. 21

Reporting of Vaccine Adverse Events......................................... 22

Future Research

....................................................................... 22

Additional Information

............................................................. 22

References

.............................................................................. 22

Vol. 59 / RR-7 Recommendations and Reports 1

Introduction

Yellow fever virus (YFV), a mosquito-borne ﬂavivirus, is pres-

ent in tropical areas of Africa and South America. In humans,

the majority of YFV infections are asymptomatic. Clinical

disease varies from a mild, undiﬀerentiated febrile illness to

severe disease with jaundice and hemorrhagic manifestations

(1). After an incubation period of 3–6 days, symptomatic

yellow fever (YF) infections typically manifest with an abrupt

onset of fever and headache (2). As the illness progresses, other

symptoms might occur, including photophobia, myalgias,

e material in this report originated in the National Center for

Emerging and Zoonotic Infectious Diseases, omas Hearn, PhD,

Director, and the Division of Vector-borne Diseases, Lyle Petersen,

MD, Director.

Corresponding preparer: J. Erin Staples, MD, PhD, National Center

for Emerging and Zoonotic Infectious Diseases, CDC, 3150 Rampart

Road, MS P-02, Fort Collins, CO 80521. Telephone: 970-225-4235;

Fax: 970-266-3568; E-mail: [email protected].

Yellow Fever Vaccine

Recommendations of the Advisory Committee

on Immunization Practices (ACIP)

Prepared by

J. Erin Staples, MD, PhD,

Mark Gershman, MD,

Marc Fischer, MD

Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases

Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases

Summary

is report updates CDC’s recommendations for using yellow fever (YF) vaccine (CDC. Yellow fever vaccine: recommendations

of the Advisory Committee on Immunizations Practices: MMWR 2002;51[No. RR-17]). Since the previous YF vaccine recom-

mendations were published in 2002, new or additional information has become available on the epidemiology of YF, safety proﬁle

of the vaccine, and health regulations related to the vaccine. is report summarizes the current epidemiology of YF, describes

immunogenicity and safety data for the YF vaccine, and provides recommendations for the use of YF vaccine among travelers and

laboratory workers.

YF is a vectorborne disease resulting from the transmission of yellow fever virus (YFV) to a human from the bite of an infected

mosquito. It is endemic to sub-Saharan Africa and tropical South America and is estimated to cause 200,000 cases of clinical

disease and 30,000 deaths annually. Infection in humans is capable of producing hemorrhagic fever and is fatal in 20%–50%

of persons with severe disease. Because no treatment exists for YF disease, prevention is critical to lower disease risk and mortality.

A traveler’s risk for acquiring YFV is determined by multiple 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.

All travelers to countries in which YF is endemic should be advised of the risks for contracting the disease and available methods

to prevent it, including use of personal protective measures and receipt of vaccine. Administration of YF vaccine is recommended

for persons aged ≥9 months who are traveling to or living in areas of South America and Africa in which a risk exists for YFV

transmission. Because serious adverse events can occur following YF vaccine administration, health-care providers should vaccinate

only persons who are at risk for exposure to YFV or who require proof of vaccination for country entry. To minimize the risk for

serious adverse events, health-care providers should observe the contraindications, consider the precautions to vaccination before

administering vaccine, and issue a medical waiver if indicated.

arthalgias, epigastric pain, anorexia, vomiting, and jaundice

(3,4). In some persons, multisystem organ failure with hem-

orrhagic signs and symptoms occurs. e case-fatality ratio of

severe yellow fever with hepatorenal dysfunction is 20%–50%

(1). Because no speciﬁc antiviral treatment exists for YF, preven-

tion is critical to lower disease risk and mortality.

YFV has three transmissiotn cycles: jungle (sylvatic), inter-

mediate (savannah), and urban (5). All cycles involve the trans-

mission of YFV between primates (nonhuman or human) and

mosquitoes. Depending on the transmission cycle and location,

diﬀerent mosquito species are involved, and humans or nonhu-

man primates serve as the primary reservoir of the virus.

e World Health Organization (WHO) estimates that

YFV causes 200,000 cases of clinical disease and 30,000 deaths

each year (6). However, the majority of cases and deaths are

not recognized because of the predominantly rural nature of

the disease and inadequate surveillance and reporting (4,7). In

recent decades, hundreds of cases have been reported annually

in South America, primarily among men with occupational

2 MMWR July 30, 2010

exposures in forested areas (8). In Africa, the number of cases

reported from the continent annually varies substantially

(range: 1–5,000 cases). Most of the ﬂuctuation in the annual

case numbers from Africa likely is attributable to variations

in reporting and recognition. However, because the natural

occurrence of disease also can ﬂuctuate, being absent in certain

areas for years before reappearing, delineation of aﬀected areas

depends on surveillance for animal reservoirs and vectors, accu-

rate diagnosis, and prompt reporting of all human cases.

Evaluation of a traveler’s risk should take into account the

traveler’s immunization status and planned itinerary, including

location of travel, season, duration of exposure, occupational

and recreational activities, and local rate of virus transmission

at the time of travel. All travelers should be provided advice on

prevention of mosquito bites. Health-care providers weighing

a decision as to whether to administer YF vaccine to travelers

must take into account multiple factors (e.g., the risk for travel-

associated YFV disease, the high morbidity and mortality when

YF does occur, country-entry requirements for YF vaccine, and

the risk for serious adverse events following vaccination). is

report provides recommendations for use of YF vaccine for

prevention of YF among travelers and laboratory workers.

Methods

e Advisory Committee on Immunization Practices (ACIP)

Yellow Fever Vaccine Work Group* (the ACIP Work Group)

ﬁrst met in September 2008 to review available information

on the risk for YF for travelers and to revise recommendations

for the use of the vaccine. In addition to ACIP members, the

ACIP Work Group included participants from the American

Academy of Family Physicians, CDC, the U.S. Department

of Defense, the U.S. Department of State, the Food and

Drug Administration (FDA), the Infectious Diseases Society

of America, the International Society of Travel Medicine, the

Public Health Agency of Canada (PHAC), Boston Medical

Center, and the Harvard School of Public Health.

Issues reviewed and considered by the ACIP Work Group

included YF epidemiology; incidence of and risk factors for

travel-associated YF disease; measures available to prevent YF

disease; and YF vaccine immunogenicity, safety, and incidence

of vaccine adverse events. Further consideration was given to

potential contraindications and precautions to the use of YF

vaccine and International Health Regulations (IHRs) for the

vaccine. Published, peer-reviewed studies were the primary

source of data used. Articles were identiﬁed through searches of

the PubMed, Global Health, and EMBASE databases; review

of relevant bibliographies; and consultation with subject-matter

experts. When relevant to issues under discussion, unpublished

data available at CDC also were considered.

e ACIP Work Group held monthly conference calls until

May 2009. Recommendation options were developed and

discussed by the Work Group. When evidence from clinical

trials or other research studies was lacking, the recommenda-

tions incorporated expert opinion of the ACIP Work Group

members. A short overview presentation was made to ACIP

at the June 2009 meeting. Proposed recommendations and a

draft statement were presented to ACIP and approved at the

October 2009 meeting.

Background

Yellow Fever Virus Transmission

YFV is a ribonucleic acid (RNA) virus that belongs to the

genus Flavivirus. It is related antigenically to West Nile virus,

St. Louis encephalitis virus, and Japanese encephalitis virus

(9). YFV is transmitted to humans primarily through the bite

of an infected Aedes or Haemagogus species mosquito (10–14).

Mosquitoes acquire the virus by feeding on infected nonhuman

or human primates and then can transmit the virus to naïve

nonhuman or human primates.

YFV has three transmission cycles: jungle (sylvatic), inter-

mediate (savannah), and urban (5) (Figure 1). e jungle

(sylvatic) cycle involves transmission of the virus between

nonhuman primates (e.g., monkeys) and tree-hole–breeding

mosquito species found in the forest canopy (15). e virus

is transmitted via mosquitoes from monkey to human when

the humans encroach into the jungle during occupational or

recreational activities. In Africa, an intermediate (savannah)

cycle exists that involves transmission of the YFV from tree-

hole–breeding Aedes spp. to humans living or working in jungle

border areas (16,17). In this cycle, the virus can be transmitted

from monkey to human or from human to human via these

mosquitoes. e urban cycle involves anthroponotic trans-

mission of the virus between humans and urban mosquitoes,

primarily Ae. aegypti.

Humans infected with YFV experience the highest levels of

viremia and are infectious to mosquitoes shortly before the

onset of fever and for 3–5 days thereafter (18). Given the high

level of viremia attained in humans, bloodborne transmission

theoretically could occur through transfusions or needlestick

injuries.

* A list of the members of the work group appears on page 27 of this report.

Vol. 59 / RR-7 Recommendations and Reports 3

FIGURE 1. Transmission cycles for yellow fever virus

* The jungle (sylatic) transmission cycle involves transmission of the virus between nonhuman primates and mosquito species found in the forest canopy. The virus is

transmitted via mosquitoes from nonhuman primates to human when the humans encroach into the jungle during occupational or recreational activities.

†

The urban transmission cycle involves transmission of the virus between human and urban mosquitoes, primarily Ae. aegypti. Viremic humans traveling from one region

to another can feed into and serve as a source of infection for mosquitoes in other transmission cycles (dotted line).

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 can be transmitted from nonhuman primate to humans or from human to human via these mosquitoes.

Jungle

(sylvatic)

Urban

Nonhuman

primate

Mosquito

Nonhuman

primate

Mosquito

Africa:

S. America: spp.

and spp.

Aedes africanus

Haemagogus

Sabethes

Semi-domestic

pp.Aedes s

Nonhuman

or human

primate

Mosquito Mosquito

Nonhuman

or human

primate

Human

Mosquito Mosquito

Human

Intermediate

(savannah)

Africa only

Aedes aegypti

†

Epidemiology of Yellow Fever

Geographic Distribution and Spread

YF occurs in sub-Saharan Africa and tropical South America,

where it is endemic and intermittently epidemic (Figure 2).

Most YF disease in these areas is attributable to sylvatic or

intermediate transmission cycles. However, urban transmis-

sion of YF does occur periodically in Africa and sporadically

in South America (19–21).

In Africa, the majority of outbreaks have been reported from

West Africa; fewer outbreaks have been reported from Central

and East Africa (22). e reasons for this are unknown but

might include higher densities of humans and Ae. aegypti in

the west, genetic diﬀerences between YFV strains (genotypes)

between the east and west, the presence of antibodies against

other ﬂaviviruses contributing to cross-protection, and mos-

quito species transmitting the disease in East Africa being

less likely to bite humans (5,22,23). During West African

outbreaks, up to 30% of the population is infected with YFV,

and 3%–4% develop clinical disease (24,25). Since 2008, an

increased number of YF cases have been reported from Central

African countries (e.g., the Central African Republic, Congo,

and Chad) (26,27; WHO, unpublished data, 2009). Many

of these countries have reported YF cases infrequently in the

past, and whether the recent reports of cases in these countries

are attributable to improved surveillance or to increased dis-

ease activity either locally or via extension from neighboring

endemic areas is unclear.

In South America, transmission of YFV occurs predomi-

nantly in sparsely populated forested areas rather than in urban

areas. Most YF cases are reported from the Orinoco, Amazon,

and Araguaia river basins and contiguous grasslands (28).

Peru and Bolivia have the highest cumulative incidence of YF

over the past 20 years (29). In Brazil, most cases are reported

from the Amazon and western Brazil. However, starting in

2007, cases have been identiﬁed in more southern and eastern

provinces, including Sao Paulo, Rio Grande do Sul, and Goias

states (30–32). During this same time, areas contiguous with

4 MMWR July 30, 2010

southern Brazil in northern Argentina and Paraguay also have

had conﬁrmed cases of YF, representing the ﬁrst reemergence of

the virus in these regions since the 1970s (31). In addition to

the expansion of the endemic zone of the disease in recent years,

Ae. aegypti also have reinfested many urban centers in South

America, increasing the risk for urban outbreaks of YF in the

Americas, as occurred in 2007 in Asunción, Paraguay (21).

Although urban outbreaks of YF occurred in North America

and Europe until the early 1900s, autochthonous transmission

has not been reported over the past several decades. Local YFV

transmission never has been identiﬁed in Asia or Australia.

However, these areas are at risk for importation, as many

urban areas in these regions have Ae. aegypti and have a large

susceptible human population (33). As a result, some countries

in which the disease is not endemic (e.g., India and Australia)

require proof of YF vaccination from travelers arriving from

regions in which YFV is endemic (34).

Incidence and Burden of Disease

WHO estimates that 200,000 cases of YF and 30,000 deaths

attributable to YF occur annually worldwide (6). However, only

a limited percentage of these cases are identiﬁed because of

underreporting (24,25). During 1988–2007, a total of 26,356

YF cases were reported to WHO, including 23,056 (87%)

cases from sub-Saharan Africa and 3,300 (13%) from South

America (1,35–37). In Africa, the number of cases reported

annually varies widely (range: 1–5,000), which suggests incon-

sistencies in surveillance and reporting. In South America, as

many as 524 cases per year have been reported to WHO. e

case-fatality ratio is highly variable but is approximately 20%

in Africa and approximately 50% in South America (1). e

higher case-fatality ratio in South America is believed to be

the result of enhanced diagnostic testing of persons with fatal

disease rather than an indication of a more virulent form of

the disease (5).

Ecologic and Seasonal Patterns

e ecology of YFV is complex, and multiple factors con-

tribute to its transmission. In general, increased temperature,

humidity, and rainfall lead to higher mosquito abundance and

consequently an increase in viral circulation (38,39). In South

America, YF incidence is highest during months of increased

rainfall, humidity, and temperature (January–May) (40). In

intermediate zones of West Africa, YFV activity increases dur-

ing the middle of the rainy season (around August) and peaks

during the early dry season (October) (40,41). is period

corresponds to the period of maximum longevity of mosquito

vectors. Because Ae. aegypti breed in containers used for water

storage, mosquito activity and reproduction patterns are less

dependent on rainfall (41). As a result, when Ae. aegypti are

involved in virus transmission, YF also can occur in the dry

season.

FIGURE 2. Areas* at risk for yellow fever transmission — Africa and South America, 2009

Source: Brunette GW, Kozarsky PE, Magill AJ, Shlim DR, Whatley AD, eds. CDC health information for international travel 2010. Atlanta. GA: US Department of Health

and Human Services, Public Health Service, CDC; 2009.

* As dened by the World Health Organization, countries/areas where yellow fever has been reported currently or in the past, plus areas where vectors and animal

reservoirs currently exist.

Brazil

Argentina

Peru

Bolivia

Chile

Colombia

Venezuela

Paraguay

Ecuador

Guyana

Uruguay

Suriname

French Guiana

Falkland Islands

Trinidad and Tobago

Panama

SOUTH AMERICA

Areas at risk for yellow fever transmission

Areas of no risk

Algeria

Libya

Egypt

Western

Sahara

Namibia

Mozambique

Zambia

Eritrea

Malawi

Saudi Arabia

Ye men

Oman

Djibouti

Democratic

Republic

of the Congo

Sudan

Mali

Angola

Ethiopia

Nigeria

Mauritania

Kenya

Somalia

Republic

of the Congo

Gabon

Guinea

Tanzania

Senegal

Burkina

Faso

Liberia

Togo

Sierra Leone

Burundi

Rwanda

Guinea-

Bissau

Equatorial Guinea

he Gambia

Cape

Verde

Algeria

Libya

Egypt

Namibia

Botswana

Madagascar

Zambia

Malawi

Zimbabwe

Saudi Arabia

Ye men

Democratic

Republic

of the Congo

Sudan

Mali

Niger

Angola

Ethiopia

Nigeria

Mauritania

Kenya

Somalia

Cameroon

Gabon

Ghana

Guinea

Tanzania

Uganda

Senegal

Burkina

Faso

Burundi

Rwanda

Chad

Central

African

Republic

AFRICA

Côte

São Tomé and Principe

d’lvoire

Benin

Red

Sea

Vol. 59 / RR-7 Recommendations and Reports 5

Age-Speciﬁc Patterns

e age-speciﬁc patterns of YF disease in Africa and South

America diﬀer and are aﬀected by sex and occupation. In Africa,

cases often occur in villages in the savannah region contiguous

with the forest. Children are predominantly aﬀected, as older

persons in the community frequently have naturally acquired

or vaccine-acquired immunity (24). In South America, YF

disease occurs most frequently in unvaccinated young men

who are exposed to mosquito vectors through their work in

forested or jungle areas (42,43). Occupations involving lum-

bering and forest clearing for building or road construction

have been linked to human infection (28). e age and sex

distribution of YF cases in urban areas of South America diﬀers

from that observed in jungle areas, with a higher prevalence of

infections occurring among children and women attributable

to Ae. aegypti breeding around homes (21).

Clinical Manifestations and Diagnosis

Signs and Symptoms

In the majority of persons infected with YFV, infections are

believed to be asymptomatic (24,25). Clinical disease varies

from a mild, undiﬀerentiated febrile illness to severe disease

with jaundice and hemorrhagic manifestations. e incubation

period is usually 3–6 days (1,2). In its mildest form, YF is a

self-limited infection characterized by sudden onset of fever

and headache without other symptoms (3). Other patients

experience an abrupt onset of a high fever (up to 104°F [40°C]),

chills, severe headache, generalized myalgias, lumbosacral pain,

anorexia, nausea, vomiting, and dizziness (4,43). e patient

appears acutely ill, and examination might demonstrate bra-

dycardia in relation to the elevated body temperature (Faget’s

sign). e patient is usually viremic during this period, which

lasts for approximately 3 days. Many patients have an unevent-

ful recovery, but in approximately 15% of infected persons,

the illness recurs in more severe form within 48 hours follow-

ing the viremic period (44). Symptoms include fever, nausea,

vomiting, epigastric pain, jaundice, renal insuﬃciency, and

cardiovascular instability (4). Viremia generally is absent during

this phase of symptom recrudescence. A bleeding diathesis can

occur, with hematemesis, melena, metrorrhagia, hematuria,

petechiae, ecchymoses, epistaxis, and oozing blood from the

gingiva and needle-puncture sites. Physical ﬁndings include

scleral and dermal icterus, hemorrhages, and epigastric tender-

ness without hepatic enlargement (44).

Clinical Laboratory Findings

Multiple laboratory abnormalities can be observed in patients

with YF; these can vary depending on the severity and stage of

illness. In the ﬁrst week of the illness, leukopenia might occur;

however, leukocytosis also can occur during the second week

of the disease (3). Bleeding dyscrasias also can occur, together

with elevated prothrombin and partial thromboplastin times,

decreased platelet count, and presence of ﬁbrin-split products

(45,46). Hyperbilirubinemia might be present as early as the

third day but usually peaks toward the end of the ﬁrst week

of illness. Elevations of serum transaminase levels occur in

severe hepatorenal disease and might remain elevated for up

to 2 months after onset (47).

Preliminary diagnosis is based on the patient’s clinical

features, YF vaccination status, and travel history, includ-

ing destination, time of year, and activities. Mild YF cannot

be distinguished clinically from a range of other infections.

Cases of YF with jaundice must be diﬀerentiated from viral

hepatitis, malaria, leptospirosis, Congo-Crimean hemorrhagic

fever, Rift Valley fever, typhoid, Q fever, and typhus, as well as

surgical, drug-induced, and toxic causes of jaundice (17). e

other viral hemorrhagic fevers, which usually manifest with-

out jaundice, include dengue hemorrhagic fever, Lassa fever,

Marburg and Ebola virus diseases, and Bolivian, Argentinean,

and Venezuelan hemorrhagic fevers (48,49).

Laboratory Conﬁrmation

Laboratory diagnosis generally is accomplished by testing

serum to detect virus-speciﬁc immunoglobulin M (IgM) and

immunoglobulin G (IgG) antibodies by serologic assays (50).

Serologic cross-reactions occur with other ﬂaviviruses (e.g.,

West Nile or dengue viruses), so positive results should be

conﬁrmed with a more speciﬁc test (e.g., plaque reduction neu-

tralization test) (49). Early in the illness (during the ﬁrst 3–4

days), YFV or YFV RNA often can be detected in the serum

by virus isolation or nucleic acid ampliﬁcation testing (e.g.,

reverse transcription-polymerase chain reaction [RT-PCR]).

However, by the time overt symptoms are recognized, the virus

or viral RNA usually is undetectable. erefore, virus isolation

and RT-PCR should not be used for excluding the diagnosis of

YF. Immunohistochemical staining of formalin-ﬁxed material

can detect YFV antigen on histopathologic specimens (51).

Health-care providers should contact their state or local health

department and CDC (at telephone 1-970-221-6400) for

assistance with diagnostic testing for YFV infections.

Treatment and Management

Although multiple drugs have been evaluated or used

empirically to treat YF disease, to date, none has demonstrated

speciﬁc beneﬁt (52). Management is supportive and based

on symptoms and the organ systems involved. Patients with

multisystem organ involvement likely will require critical-care

support with possible mechanical ventilation or hemodialysis.

6 MMWR July 30, 2010

Rest, ﬂuids, and nonsteroidal anti-inﬂammatory drugs or acet-

aminophen can relieve milder symptoms of fever and myalgias.

Aspirin should be avoided because of the risk for hemorrhagic

complications. 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 they do

not contribute to the transmission cycle.

Outcome and Sequelae

e majority of persons with mild YF illness recover without

long-term sequelae. For those with severe disease involving

hepatorenal dysfunction, the length of illness is variable, and

the case-fatality ratio is 20%–50% (1). Risk factors for death

include hypotension, shock, renal failure, severe hemorrhagic

disease, coma, and convulsions (44). For those who survive,

convalescence often is prolonged, lasting several weeks. Rarely,

death can occur at the end of convalescence or even weeks after

complete recovery from the acute illness. ese late deaths

are thought to be attributable to myocardial damage and

cardiac arrhythmia (53). Secondary bacterial infections (e.g.,

pneumonia) also can complicate recovery. Jaundice has been

observed for up to 3 months after recovery from serologically

documented YF (45).

Yellow Fever Among Travelers

During 1970–2009, nine cases of YF were reported in

unvaccinated travelers from the United States and Europe

who traveled to West Africa (ﬁve cases) or South America (four

cases) (54–63). Eight of these nine travelers died (19,40). Only

one case of YF has been documented in a vaccinated traveler,

a female aged 37 years from Spain who visited several West

African countries during 1988 (56).

A traveler’s risk for acquiring YF is determined by multiple

factors, including immunization status, use of personal protec-

tion measures against mosquito bites, location of travel, dura-

tion of exposure, occupational and recreational activities while

traveling, and local rate of virus transmission at the time of

travel. In both West Africa and South America, YFV transmis-

sion typically is seasonal and is associated with the mid-to-late

rainy season (

). However, YFV can be transmitted by Ae.

aegypti even during the dry season in both rural and densely

settled urban areas (41). Although the number of reported

cases of human disease often is used to estimate the crude level

of endemic transmission, cases might not be reported because

of a low level of transmission, a high level of immunity in the

local population (e.g., because of vaccination), or cases not

being detected by local surveillance systems. erefore, a lack

of human disease cases in an area does not equate to absence

of risk for transmission.

e risk for acquiring YF is diﬃcult to predict because of

variations in ecologic determinants of virus transmission. For

a 2-week stay, the estimated risks for illness and death attribut-

able to YF for an unvaccinated traveler traveling to an area of

West Africa where the disease is endemic are 50 and 10 cases

per 100,000 population, respectively; for South America,

the risks for illness and death are ﬁve cases and one case per

100,000 population, respectively (40). ese crude estimates

for unvaccinated travelers are based on risk to indigenous

populations, often during peak transmission season. us,

these risk estimates might not reﬂect accurately the actual risk

to travelers, who might have a diﬀerent immunity proﬁle, take

precautions against getting bitten by mosquitoes, and have less

outdoor exposure. e risk for acquiring YF in South America

might be lower than that in Africa because the mosquitoes that

transmit the virus between monkeys in the forest canopy do not

come in contact with humans often, and local residents have

a relatively high level of immunity secondary to widespread

vaccine use.

Yellow Fever Vaccine

YF vaccine was ﬁrst developed in the 1930s after success-

ful attenuation of the Asibi strain of YFV (64). Two vaccines

were established: the 17D and the French neurotropic vac-

cines. e French neurotropic vaccine was manufactured

until 1982, when production was stopped because of higher

rates of neurologic adverse events reported following use of

the vaccine (1).

Two 17D substrain vaccines are manufactured today: the

17DD and 17D-204 YF vaccines. e YFV strains in these

two vaccines share 99.9% sequence homology (65). e 17DD

YF vaccine is manufactured in Brazil and is used in Brazil and

many other South American countries. e 17D-204 vaccine

is manufactured and used outside of Brazil, including in the

United States. Studies comparing the various 17D YF vaccines

produced by multiple manufacturers suggest that the reacto-

genicity or immune responses generated by these vaccines do

not diﬀer (66–70). us persons who receive YF vaccines in

countries other than the United States should be considered

protected against YF.

Vaccine Composition, Storage,

and Handling

e 17D-204 strain vaccine, YF-VAX (manufactured by

sanoﬁ pasteur, Swiftwater, Pennsylvania), is a freeze-dried

supernatant of centrifuged embryo homogenate, packaged in

1-dose and 5-dose vials for domestic use. e vaccine should

be stored at temperatures of 35

F–46

F (2

C–8

C) until it is

Vol. 59 / RR-7 Recommendations and Reports 7

reconstituted by the addition of diluent (sterile, physiologic

saline) supplied by the manufacturer. Multidose vials of recon-

stituted vaccine should be stored at 35

F–46

F (2

C–8

C) for

up to 1 hour. Any unused vaccine that is not used within 1

hour of reconstitution must be discarded (71).

Correlates of Protection

No human studies have been performed to determine the

correlates of protection for YFV infection. However, dose-

response studies conducted in rhesus monkeys have established

the minimal level of neutralizing antibodies needed to protect

the monkeys against virulent YFV. Testing was conducted with

constant amounts of serum and varying dilutions of virus to

establish a log

neutralization index (LNI). ese studies

demonstrated that LNI >0.7 was correlated strongly with

protection (1,72). Although the amount of serum needed for

LNI testing is suitable for animal studies or clinical trials, it

precludes routine screening among humans (1). erefore,

a similar test, plaque reduction neutralization test (PRNT),

which uses a constant amount of virus and varying dilutions

of serum, is used most frequently in diagnostic tests to deter-

mine the absence or presence of neutralizing antibodies and

the speciﬁc serum antibody titer.

Efﬁcacy and Immunogenicity

No human eﬃcacy studies have been performed with YF

vaccine. However, several observations support YF vaccine

being protective in humans, including 1) the reduction of

laboratory-associated infections in vaccinated workers, 2) the

observation following initial use of the vaccine in Brazil and

other South American countries that YF occurred only in

unvaccinated persons, and 3) the rapid disappearance of cases

during YF vaccination campaigns initiated during epidemics.

Unpublished reports comparing YF incidence among vacci-

nated and unvaccinated populations during a 1986 epidemic

in Nigeria estimated vaccine eﬀectiveness to be approximately

85% (1). Worldwide, only ﬁve cases of YF have been reported

in vaccine recipients since YF vaccine has been in use; whether

any or all of them were vaccinated properly with appropriately

handled YF vaccine is uncertain (1).

Following YF vaccine administration, primary vaccine recipi-

ents often develop a low-level viremia with the vaccine virus.

e viremia usually occurs within 3–7 days and persists for 1–3

days, abating as YFV IgM antibodies are developed (73,74).

e level of viremia following vaccination is high enough to

be transmitted through blood products. Transfusion-related

transmission of YF vaccine virus has been documented in three

persons who received blood products that were collected from

persons vaccinated 4 days before their blood donation (75).

Studies have demonstrated that 80%–100% of vaccinated

persons develop neutralizing antibodies by 10 days after

vaccination (74,76,77). Most studies indicate that >99% of

vaccinated persons developed YFV neutralizing antibodies by

28 days after vaccination (1). Overall, the vaccine-induced

antibodies are delayed in their formation and at lower titers

compared with antibodies developed in response to wild-type

YFV infection (1).

A study of two YF vaccines (YF-VAX and Arilvax) in 1,440

healthy adults found diﬀerent neutralizing antibody responses

to the vaccine, depending on sex and race. For both vaccines,

males and Caucasians were noted to have higher LNI levels

when compared with females, blacks, and Hispanics (66). e

age at which a person is vaccinated with YF vaccine does not

appear to aﬀect immunologic response to the vaccine (1).

IHRs allow countries to require proof of YF vaccination as a

condition of entry for travelers arriving from certain countries

to prevent importation and indigenous transmission of YFV.

IHRs stipulate that the vaccination certiﬁcate for YF is valid

beginning 10 days after administration of YF vaccine for pri-

mary vaccine recipients (78). is time period corresponds to

the time at which the majority of vaccinees demonstrate immu-

nity. e YF vaccination certiﬁcate for international travel is

valid for 10 years. is interval was based on published studies

indicating that neutralizing antibodies were present in >90%

of persons 16–19 years after vaccination (79). Later studies of

U.S. military veterans from World War II tested 30–35 years

after a single dose of YF vaccine demonstrated that >80% had

neutralizing antibody; in certain subgroups, >95% still had

neutralizing antibodies (80).

Healthy persons rarely fail to develop neutralizing antibod-

ies following YF vaccination. In controlled clinical trials, the

primary failure rate is generally about 1% (66). Persons who

fail to develop antibody after their ﬁrst vaccination can develop

antibody upon revaccination (81).

ree host factors have been associated with failure to

respond immunologically to YF vaccine: pregnancy, human

immunodeﬁciency virus (HIV) infection, and malnutrition.

In one study, only 39% of pregnant women seroconverted

after receiving the vaccine in their third trimester (82). is

diﬀerence was attributed to the altered immune state associated

with pregnancy and suggests the need to revaccinate at-risk

women who were vaccinated during pregnancy. However, a

more recent study indicated that 425 (98%) of 441 women

who were vaccinated inadvertently with YF vaccine, primarily

during their ﬁrst trimester, developed YFV-speciﬁc neutral-

izing antibodies (83). erefore, revaccination might not be

necessary in women who received vaccine during pregnancy,

but antibody titers should be checked to ensure an appropriate

immune response in women still at risk for the disease.

8 MMWR July 30, 2010

HIV infection has been associated with a reduced immu-

nologic response to a number of inactivated and live, attenu-

ated vaccines, including YF vaccine (84). Some case reports

have suggested that vaccinating HIV-infected persons who

are not immunosuppressed (CD4

T-cell count [CD4 count]

>500/mm

) results in seroconversion (85). However, a recent

retrospective cohort study indicated that signiﬁcantly fewer

HIV-infected persons had YFV neutralizing antibodies at 1

year after vaccination compared with vaccinated uninfected

persons (83% and 97%, respectively; p=0.01) (86). e study

measured YFV neutralizing antibodies in HIV-infected persons

with median baseline CD4 count of 496 cells/mm

(range:

72–1,730 cells/mm

) and varying levels of HIV RNA detected

in their blood (52% had HIV RNA levels ≥50 copies/mL).

Among HIV-infected infants in one developing nation, only

17% developed neutralizing antibodies within 10 months of

YF vaccine compared with 74% of HIV-uninfected controls

matched for age and nutritional status (87). e mechanisms

for this observed diﬀerence in immune response among HIV-

infected persons are uncertain but appear to correlate with

HIV RNA level and CD4 count. Further studies are required

to assess the relevance of these ﬁndings.

Adverse Events

General Events

After YF vaccination, vaccinees have reported mild head-

aches, myalgia, low-grade fevers, or other minor symptoms for

5–10 days (71). Localized pain, swelling, erythema, or warmth

might occur at the injection site for up to a week following

vaccination. In one large study of 1,440 vaccine recipients,

the most common systemic side eﬀects were headache (33%

of subjects), myalgia (25%), malaise (19%), fever (15%),

and chills (11%) (66). ese side eﬀects generally were mild,

and only 1% of vaccinees curtailed their regular activities as

a result. In the only placebo-controlled trial of 1,007 adults

vaccinated with either YF vaccine (the 17-DD vaccine virus

strain) or placebo, 3% of reported local reactions and 7% of

systemic reactions were attributed to vaccine (88).

e Vaccine Adverse Event Reporting System (VAERS)

is a passive surveillance system for adverse events following

vaccination operated collaboratively by CDC and FDA.

Adverse event reports can be submitted to VAERS from a

variety of sources, including vaccine providers and recipients,

medical practitioners, and manufacturers. e rate of any

adverse events following YF vaccine as reported to VAERS

is 43 adverse events per 100,000 doses distributed (89). e

majority of reported adverse events are classiﬁed as nonserious

(rate: 38 per 100,000 population) and include reports of fever,

injection-site pain, injection-site erythema, pruritis, headache,

urticaria, and rash. e majority of events occur a median of

1 day after vaccination; roughly 60% occur within the ﬁrst 2

days after vaccination.

During 2000–2006, a rate of 4.7 serious adverse events per

100,000 doses distributed was derived from VAERS data.

Reporting rates were highest among persons aged ≥60 years

(8.3 per 100,000 doses). ree well-characterized serious

adverse events occur following YF vaccine administration: 1)

immediate hypersensitivity or anaphylactic reactions, 2) YF

vaccine-associated neurologic disease (YEL-AND), and 3) YF

vaccine-associated viscerotropic disease (YEL-AVD).

In 2002, CDC formed the Yellow Fever Vaccine Safety

(YFVS) Working Group, consisting of vaccine safety experts

from CDC and partner organizations. e YFVS Working

Group systematically reviewed VAERS reports for YF vaccine

and devised a surveillance case deﬁnition for YEL-AND and

YEL-AVD (Boxes 1 and 2) to help classify cases and determine

rates of these adverse events.

Hypersensitivity and Anaphylactic Reactions

Multiple components of YF vaccine have been cited as pos-

sible allergens, including eggs, chicken proteins, gelatin, or

latex (found in vial stopper) (71). Immediate hypersensitivity

reactions or anaphylaxis, characterized by urticaria and respira-

tory symptoms (e.g., dyspnea, bronchospasm, or pharyngeal

edema) are uncommon and occur principally among persons

with histories of allergies to egg or other substances (90).

However, anaphylaxis has been reported to occur in persons

with no history of reactions to the vaccine’s components. Rates

of anaphylaxis from VAERS data vary (range: 0.8–1.8 events

per 100,000 doses distributed) (89,90).

YEL-AND

YEL-AND is a serious but rarely fatal adverse event. YEL-

AND manifests as several distinct clinical syndromes, includ-

ing meningoencephalitis (neurotropic disease), Guillain-Barré

syndrome (GBS), acute disseminated encephalomyelitis

(ADEM), and bulbar palsy (91,92). Meningoencephalitis

occurs as a result of direct YF vaccine viral invasion of the

central nervous system (CNS) with infection of the meninges

and/or the brain. e other neurologic syndromes (e.g., GBS

and ADEM) represent autoimmune manifestations in which

antibodies and/or T-cells produced in response to the vac-

cine cross-react with neuronal epitopes and lead to central or

peripheral nerve damage.

rough the attenuation process, YF vaccine virus strains

were determined to develop neurovirulence (93,94). Early in

the vaccine’s history, multiple cases of encephalitis associated

with vaccine administration were noted and determined to

be attributable to too few or too many passages of the virus

Vol. 59 / RR-7 Recommendations and Reports 9

BOX 1. CDC’s Yellow Fever Vaccine Safety (YFVS) Working Group case denition* for yellow fever vaccine-associated neurologic disease

(YEL-AND)

Case ascertainment

Level 1: neurologic disease

• Oneormoreofthefollowingsignsandsymptoms:

– fever (≥100.5°F [>38.1°C] for >24 hours) and headache

(>24 hours)

– focal neurologic dysfunction (including but not limited to

ataxia, aphasia, and paresis)

– mental status change (confusion, lethargy, or personality

change lasting >24 hours)

– new onset seizure or recurrence of previously controlled

seizures

– cerebrospinal ﬂuid (CSF) pleocytosis (>5 WBC/mm

)

– elevated CSF protein (>1.5 times the normal limit)

Level 2: neurotropic disease

• Level1neurologicdisease,and

• oneormoreofthefollowing:

– neuroimaging consistent with inﬂammation, (with or with-

out demyelination)

– electroencephalogram ﬁnding consistent with

encephalopathy

Level 2: autoimmune disease with central nervous system

involvement

• Level1neurologicdisease,and

• neuroimagingconsistentwithmultifocalordisseminated

areas of demyelination

Level 2: autoimmune disease with peripheral nervous system

involvement

• Level1neurologicdisease,

†

and

• twoormoreofthefollowingsignsandsymptoms:

– limb weakness with decreased or absent tendon reﬂexes

– cranial nerve abnormalities

– autonomic dysfunction (including but not limited to

postural hypotension, arrhythmias, abnormal sweating, and

gastric motility abnormalities)

– numbness or paresthesias in the extremities

– electromyography ﬁnding consistent with Guillain-Barré

syndrome

Case deﬁnitions

Yellow fever vaccine-associated neurotropic disease

Suspect neurotropic disease

• Onsetofsymptomsandsignsoccurswithin1–30daysof

vaccination with yellow fever vaccine, either given alone or in

combination with other vaccinations;

• level2neurotropicdisease;and

• noevidenceofotherdiagnoses

Probable neurotropic disease

• SuspectYEL-AND,and

• oneormoreofthefollowing:

– vaccine-type yellow fever viral isolation from blood (>7

days postvaccination)

– yellow fever 17D

virus concentration in serum on any day

exceeds 3 log

pfu/mL

Deﬁnite neurotropic disease

• SuspectYEL-AND,and

• oneormoreofthefollowing:

– YF-speciﬁc CSF IgM

– yellow fever 17D

virus isolation from CSF

– ampliﬁcation of vaccine type virus

from CSF

Yellow fever vaccine-associated autoimmune disease with

central nervous system involvement (YEL-AAD-CNS)

Suspect YEL-AAD-CNS

• Onsetofsymptomsandsignsoccurswithin1–30daysof

vaccination with yellow fever vaccine, either given alone or in

combination with other vaccinations;

• level2autoimmunediseasewithcentralnervoussystem

involvement; and

• noevidenceofotherdiagnoses

Probable YEL-AAD-CNS

• Suspectautoimmunediseasewithcentralnervoussystem

involvement, and

• YELadministeredalone

Yellow fever vaccine-associated autoimmune disease with

peripheral nervous system involvement (YEL-AAD-PNS)

Suspect YEL-AAD-PNS

• Onsetofsymptomsandsignsoccurswithin1–30daysof

vaccination with yellow fever vaccine, either given alone or in

combination with other vaccinations;

• level2autoimmunediseasewithPNSinvolvement;and

• noevidenceofotherdiagnoses

Probable YEL-AAD-PNS

• SuspectautoimmunediseasewithPNSinvolvement,and

• YELadministeredalone

* A modiﬁed version of the case deﬁnitions has been published (Monath T, Cetron MS, Teuwen DE. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Oﬃt

PA, eds. Vaccines. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008:959–1055). ese case deﬁnitions 1) deﬁne cases of neurologic disease, 2) deﬁne cases

with autoimmune involvement in the central nervous system or peripheral nervous system, and 3) describe causal linkage to yellow fever vaccine. Another

laboratory-conﬁrmed diagnosis that explains the clinical picture fully might be suﬃcient to exclude yellow fever vaccine-associated disease. Given the challenges

in procuring suﬃcient evidence to make a deﬁnitive diagnosis, it might be necessary to combine suspect, probable, and deﬁnite cases for risk factor analysis

and case counting.

†

Does not require presence of altered mental status or seizures.

Conﬁrmed as 17D virus by monoclonal antibody analysis or nucleotide sequencing when a possibility of wild-type YF infection exists, inclusive of all

17D-derived vaccines.

10 MMWR July 30, 2010

during the attenuation process. is observation led to the

establishment of a vaccine seed lot system in 1945 that clearly

deﬁned the number of passages allowed for certain strains of

the vaccine (95). However, even after the implementation of

the seed lot system, additional cases of encephalitis associated

with YF vaccine continued to be reported. Studies conducted

during the early 1950s identiﬁed four cases of encephalitis out

of 1,000 children aged <6 months vaccinated with YF vaccine

(96). An additional 10 cases of encephalitis associated with YF

vaccine administered to infants aged <4 months were reported

worldwide during the 1950s (1). Consequently, recommenda-

tions were made in the 1960s restricting the use of YF vaccine

to infants aged ≥6 months (97). Subsequently, the number of

cases of encephalitis reported in infants diminished.

A total of 29 cases of YEL-AND (nine of meningoencepha-

litis, eight of GBS, three of ADEM, one of bulbar palsy, and

eight cases with insuﬃcient data to classify) that occurred dur-

ing 1990–2006 were reviewed retrospectively or prospectively

by the YFVS Working Group (91,92,98,99). e 29 cases

had a varied time from vaccination to symptom onset (range:

Case ascertainment

Level 1: viscerotropic disease (for surveillance)

• Fever(≥100.5°F[(>38.1°C]for>24hours),and

• oneormoreofthefollowingsignsandsymptoms:

– nausea

– vomiting

– malaise (duration >72 hours)

– myalgia (duration >24 hours)

– arthralgia (duration >24 hours)

– dyspnea

Level 2: viscerotropic disease

• Level1viscerotropicdisease;and

• oneormoreofthefollowingsigns:

– jaundice (total bilirubin elevated 1.5 times normal)

– liver dysfunction (elevation of AST and ALT three times

above normal)

– renal impairment (decrease in glomerular ﬁltration rate, as

measured by an elevation over 1.5 times in BUN or creati-

nine and no history of renal disease)

– tachycardia (heart rate >100 beats per minute) or bradycar-

dia (<50 beats per minute)

– rhabdomyolysis (>5 times normal CPK)

– respiratory distress (shortness of breath, ventilation

or oxygenation impairment)

– thrombocytopenia (platelets <100,000/µL)

– hypotension (systolic blood ≤90 mm Hg for adults

or less than ﬁfth percentile by age for children aged <16

years; orthostatic drop in diastolic blood pressure ≥15 mm

Hg from lying to sitting, orthostatic syncope, or orthostatic

dizziness)

– myocarditis (compatible abnormalities including

electrocardiogram, echocardiogram, or cardiac enzyme

changes, or inﬂammation by tissue biopsy)

– disseminated intravascular coagulation (elevation of pro-

thrombin time or activated partial thromboplastin time

with ﬁbrin split products)

– hemorrhage

Case deﬁnitions

Yellow fever vaccine-associated viscerotropic disease (YEL-

AVD)

Suspect YEL-AVD

• Onsetofsymptomsandsignsoccurswithin1–10daysof

vaccination with yellow fever vaccine, either given alone or in

combination with other vaccinations;

• level2viscerotropicdisease,withevidenceofliver

dysfunction; and

• noevidenceofotherdiagnoses

Probable YEL-AVD

• SuspectYEL-AVD,and

• oneormoreofthefollowing:

– histopathology consistent with yellow fever (e.g.,

liver midzonal necrosis, Councilman bodies)

– yellow fever 17D

†

isolation from blood (>7 days

postvaccination)

– yellow fever 17D

†

virus concentration in serum on any day

exceeds 3 log

pfu/mL

Deﬁnite YEL-AVD

• SuspectYEL-AVD,and

• oneormoreofthefollowing:

– YF-speciﬁc antigen in tissue demonstrated by

immunohistochemistry (IHC)

– yellow fever 17D

†

virus isolation from tissue

– ampliﬁcation of yellow fever 17D

†

virus from tissue

BOX 2. CDC’s Yellow Fever Vaccine Safety (YFVS) Working Group case denition* for yellow fever vaccine-associated viscerotropic disease

(YEL-AVD)

* A modiﬁed version of these case deﬁnitions has been published (Monath T, Cetron MS, Teuwen DE. Yellow fever vaccine. In: Plotkin SA, Orenstein WA,

Oﬃt PA, eds. Vaccines. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008:959–1055.) ese case deﬁnitions deﬁne cases of viscerotropic disease and levels

of certainty that might be causally linked to yellow fever vaccine. Absence of inclusion criteria does not exclude diagnosis of vaccine-associated viscerotropic

disease (YEL-AVD); however, another laboratory-conﬁrmed diagnosis that explains the clinical picture fully might be suﬃcient to exclude YEL-AVD. Given

the challenges in procuring suﬃcient evidence to make a deﬁnitive diagnosis of YEL-AVD, it may be necessary to combine suspect, probable, and deﬁnite

cases for risk factor analysis and case counting.

†

Conﬁrmed as 17D virus by monoclonal antibody analysis or nucleotide sequencing when a possibility of wild-type YF infection exists, inclusive of all

17D-derived vaccines.

Vol. 59 / RR-7 Recommendations and Reports 11

3–28 days). For the 25 cases with data available on age, there

again was a wide variation in age range (range: 6–78 years). All

cases were reported to occur in ﬁrst-time vaccine recipients.

One death was reported in a male aged 53 years who had

unrecognized asymptomatic human immunodeﬁciency virus

(HIV) infection and CD4 count <200/mm

(98). e patient

developed fever and malaise 3 days after his vaccination and

became encephalopathic at 5 days postvaccination. He died

at 9 days following vaccination.

Data regarding the speciﬁc age and illness onset for the dif-

ferent neurologic presentations can be derived from VAERS

reports (91). Of six reported encephalitis cases, the median age

was 54 years (range: 16–78 years), and median time to onset

after vaccination was 14 days (range: 5–24 days). For the six

GBS cases, the median age was 53 years (range: 17–68 years),

and median time to onset after vaccination was 13 days (range:

7–27 days). Finally, for the three ADEM cases, the median age

was 19 years (range: 18–61 years), and median time to onset

after vaccination was 15 days (range: 7–20 days).

A recently published report has included the ﬁrst report of

a case of longitudinal myelitis in a male aged 56 years who

received no other vaccines (100). YFV IgM antibodies were

detected in his cerebrospinal ﬂuid (CSF) and serologic test-

ing for other regional ﬂaviviruses was negative. However, the

time to symptom onset was 45 days after vaccination, which

is longer than that reported for all other YEL-AND cases. A

second recently published report concerned a male aged 23

years who presented originally with meningoencephalitis but

was later determined to have ADEM (101). e diagnosis of

ADEM was determined by magnetic resonance imaging of

the brain.

e diagnostic testing for YEL-AND is speciﬁc to the clini-

cal presentation. For cases with meningitis or encephalitis, the

detection of the YF vaccine virus in CSF either by culture

or nucleic acid ampliﬁcation is diagnostic. e detection of

YFV IgM and speciﬁc neutralizing antibodies in the CSF also

supports the diagnosis. YFV IgM antibodies are not believed

to cross the blood-brain barrier normally, so their production

in CSF is considered indicative of local CNS infection. For

autoimmune mediated events, no speciﬁc YF testing is avail-

able. e diagnosis of these conditions should be made using

appropriate studies (e.g., neuroimaging, electroencephalog-

raphy, electromyelography, and nerve conduction studies).

Because no conﬁrmatory YFV-speciﬁc laboratory test exists for

the autoimmune syndromes of ADEM and GBS, the YFVS

Working Group case deﬁnition only speciﬁes “suspect” and

“probable” levels of causality. If no evidence of another diag-

nosis exists, a case is classiﬁed further depending on whether

YF vaccine was the only vaccine administered. Diagnostic

testing for suspected YEL-AND cases is available from CDC

at http://www.cdc.gov/ncidod/dvbid/yellowfever/vaccine/

special-testing.htm.

Treatment for YEL-AND also depends on the particular

clinical syndrome. Treatment for meningoencephalitis is sup-

portive, and manifestations such as seizures or autonomic

dysfunction should be managed according to acceptable medi-

cal standards for each disorder. For autoimmune neurologic

manifestations associated with YF vaccine, treatment often

includes intravenous immune globulin (IVIG) or plasmaphere-

sis for GBS, and corticosteroids, IVIG, or plasmapheresis for

ADEM (102,103).

YEL-AND rarely is fatal. In addition to the case described

previously of fatal encephalitis in a person with HIV, four

other deaths have been reported attributable to YEL-AND

(1,104). One fatal case of encephalitis occurred in a girl aged

3 years who was vaccinated in 1965 (104). Molecular studies

of the YF vaccine virus isolated from the brain of this patient

demonstrated that the virus had mutated and become more

neurovirulent as documented in monkey studies (105). is is

the only case in which a mutation of the vaccine virus has been

linked to an adverse outcome in a recipient. ree other fatal

YEL-AND cases were reported unoﬃcially from a hospital-

based surveillance system for postvaccine encephalitis in Kenya

after a mass vaccination campaign in 1993 (1).

e incidence rate of YF vaccine-associated encephalitis in

very young infants has been estimated on the basis of reports

from the time period before institution of the age restriction

for vaccination to be 50–400 cases per 100,000 population

(96,106). From VAERS data, the reporting rate for YEL-AND

is 0.4–0.8 cases per 100,000 doses distributed (89,107). e

reporting rate was higher for persons aged ≥60 years, with a

rate of 1.6 cases per 100,000 doses distributed in persons aged

60–69 years and 1.1–2.3 cases per 100,000 doses distributed

for persons aged ≥70 years. ese estimates most likely are low

given underreporting. In countries in which YF is endemic, a

national vaccine adverse event surveillance system might not

exist or, if one does exist, be consistent and sensitive enough to

detect the majority of YEL-AND cases that do occur. However,

an unoﬃcial report from a hospital-based surveillance system

for postvaccine encephalitis in Kenya after a mass vaccination

campaign estimated the incidence of YEL-AND to be 0.6 cases

per 100,000 doses (1).

YEL-AVD

In 2001, a previously unrecognized serious adverse reaction

among recipients of YF vaccine was ﬁrst described (48,108–

113

). is syndrome initially was termed febrile multiple organ

system failure; the name subsequently was changed to YEL-

AVD. YEL-AVD mimics naturally acquired YF disease, with

12 MMWR July 30, 2010

the vaccine virus proliferating and disseminating throughout

the host’s tissues.

As of February 2010, a total of 57 cases of YEL-AVD have

been reported to CDC from 14 countries (Australia, Belgium,

Brazil, China, Colombia, Ecuador, France, Germany, Japan,

Peru, Spain, Switzerland, the United Kingdom, and the United

States). e cases have occurred in association with the diﬀerent

substrains of YF vaccine produced by several manufacturers.

On the basis of an analysis of cases for which information is

available, YEL-AVD has occurred only following a recipient’s

ﬁrst YF vaccination; no cases of YEL-AVD occurring in persons

receiving booster doses of the vaccine have been reported. Of

the 53 persons with YEL-AVD cases whose sex is known, 32

(60%) were male. e overall median age was 50 years (range:

3–81 years) but diﬀered by sex, with a median age of 62 years

(range: 4–81 years) in males and 24 years (range: 3–79 years)

in females. e median time from vaccination until symptom

onset was 3 days (range: 1–8 days). Of 57 patients, 37 (65%)

died, with a higher case-fatality ratio in females (19 [90%])

than males (16 [50%]) (sex was unknown in two fatal cases).

e median time from YF vaccination until death was 10

days (range: 7–30 days). Whether age and case-fatality ratio

diﬀerences between sexes reﬂect sex-speciﬁc host factors or are

a function of surveillance or reporting bias is unclear.

Patients with YEL-AVD typically develop fever and other

nonspeciﬁc signs and symptoms (including headache, malaise,

myalgias, nausea, vomiting, or diarrhea) within 1 week of

vaccination. As the illness progresses, jaundice and laboratory

abnormalities (e.g., thrombocytopenia, elevations of hepatic

transaminases, total bilirubin, and creatinine) might occur.

Leukopenia or leukocytosis might be present, depending on

the stage and severity of the illness. Persons with severe cases

can develop hypotension, hemorrhage, renal failure requiring

hemodialysis, and respiratory failure requiring mechanical ven-

tilation. Less frequent complications include rhabdomyolysis

and disseminated intravascular coagulation. No speciﬁc therapy

exists for YEL-AVD, and, assuming other diseases have been

excluded, treatment is supportive.

YF vaccine-speciﬁc laboratory testing can assist in making the

diagnosis. Documentation of high levels of YF vaccine virus in

the serum of patients within the ﬁrst 7 days of vaccination or

prolonged presence of replicating YF vaccine virus in blood >7

days postvaccination is consistent with YEL-AVD (probable

case). In fatal cases, when an autopsy has been performed,

immunohistochemistry can be performed on ﬁxed tissues

to detect YFV antigen, and RT-PCR can be performed on

RNA extracted from frozen tissues to verify the presence of

YF vaccine virus versus wild-type YFV. Liver tissue can have

characteristic histopathologic ﬁndings (e.g., midzonal necrosis,

microvesicular fatty changes, and Councilman bodies) (114).

Diagnostic testing for suspect YEL-AVD cases is available

from CDC at http://www.cdc.gov/ncidod/dvbid/yellowfever/

vaccine/special-testing.htm.

Several risk estimates for YEL-AVD have been published.

On the basis of VAERS data, the reporting rate of YEL-AVD is

0.3–0.4 cases per 100,000 doses distributed (89,107). Similar

to YEL-AND, reporting rates also are highest among persons

aged ≥60 years, with rates of 1.0–1.1 cases per 100,000 doses

distributed in persons aged 60–69 years and 2.3–3.2 cases

per 100,000 doses distributed for persons aged ≥70 years.

An analysis of YEL-AVD cases that occurred in Europe dur-

ing 1996–2003 yielded an overall incidence of 0.3 cases per

100,000 doses distributed (92). A Brazilian analysis based on

four fatal cases of YEL-AVD derived risk estimates of fatal

YEL-AVD ranging from <0.01 to 0.21 per 100,000 doses

administered (115). However, more recent risk estimates from

Brazil have identiﬁed overall YEL-AVD rates similar to those

from the United States and Europe (CDC, unpublished data,

2010).

Almost all cases of YEL-AVD have occurred in persons

who received diﬀerent lots of vaccine. However, at least one

known cluster has been reported involving ﬁve cases of YEL-

AVD associated with the same lot of YF vaccine (116). is

cluster occurred in 2007 after a vaccination campaign in

an area of Peru in which the disease was not endemic. Four

patients died of conﬁrmed YEL-AVD. e overall incidence

of YEL-AVD in this campaign was 7.9 cases per 100,000

doses distributed, compared with a lot-speciﬁc incidence of

11.7 cases per 100,000 doses distributed for the implicated

lot. A thorough investigation detected no abnormalities of the

implicated vaccine lot and no common risk factors among the

ﬁve case patients. e incidence of YEL-AVD associated with

this campaign in Peru is substantially higher than previous risk

estimates from other countries and remains unexplained.

To date, two speciﬁc risk factors for YEL-AVD have been

identiﬁed: older age and a history of thymus disease or thymec-

tomy. e two analyses of VAERS reports of YEL-AVD in the

United States yielded reporting rates of YEL-AVD for persons

aged ≥60 years of 1.4–1.8 cases per 100,000 doses distributed

(89,107). is age-speciﬁc rate is several-fold higher than the

overall reported rate of 0.3–0.4 cases per 100,000 doses dis-

tributed. Four (17%) of the ﬁrst 23 patients with YEL-AVD

identiﬁed had a history of thymectomy for either a benign or

malignant thymoma (117). e details of these cases suggest

that a history of thymus disease is a risk factor for YEL-AVD.

In 2003, the package insert for YF vaccine available in the

United States was updated to include a history of thymus

disorder as a contraindication to vaccine administration (71).

No additional cases of YEL-AVD identiﬁed since 2004 have

involved a history of thymus disease.

Vol. 59 / RR-7 Recommendations and Reports 13

A number of cases of YEL-AVD have involved a history of

autoimmune disease or diseases with potential autoimmune

etiology. ese include three patients with systemic lupus

erythematosis, two with Addison’s disease, one with Crohn’s

disease in remission, one with a history of polymyalgia rheu-

matica and hypothyroidism, one with ulcerative colitis, and

one with myasthenia gravis (108,116,117; CDC, unpublished

data, 2010). ese cases suggest that autoimmune disease

might be a risk factor for YEL-AVD. However, four patients

with underlying autoimmune disease were aged >60 years, two

of whom had a history of thymectomy for a thymoma; both of

these factors are associated with increased risk for YEL-AVD.

erefore, more information is needed regarding the number

of patients with underlying autoimmune disease who are vac-

cinated safely to better address the potential risk for YEL-AVD

in persons with autoimmune disease.

Although studies on certain cases of YEL-AVD have identi-

ﬁed potential genetic risk factors (118), no common genetic

abnormality has been demonstrated. No conclusive evidence

has been reported that demonstrates that YEL-AVD has been

caused by a reversion to increased virulence in the vaccine

(114,119).

Vaccination of Women During

Pregnancy and Breastfeeding

No data are available on the YF disease risk for pregnant or

breastfeeding women and their fetuses or infants. However,

on the basis of surveillance and outbreak data, pregnant and

breastfeeding women do not appear to be at risk for more

severe YF disease.

e use of YF vaccine during pregnancy has not been

studied in a large prospective trial (FDA Pregnancy Category

C). Limited data are available from a number of studies in

which pregnant women either were vaccinated inadvertently

or administered the vaccine in outbreak settings. Two studies

involving 81 infants whose mothers had received YF vaccine

identiﬁed YFV IgM antibodies in the cord blood of one infant

shortly after birth (82,120). ese ﬁndings suggest that infec-

tion of the fetus with YF vaccine can occur, albeit at a low inci-

dence (i.e., one of 81). A study of 304 infants born to women

who were vaccinated with YF vaccine early in their pregnancies

found no increased risk for major malformations (121). An

increased risk was identiﬁed for minor malformations (e.g.,

pigmented nevi), but the ﬁnding could have resulted from

assessment bias. One study of 39 pregnant women who were

vaccinated with YF vaccine identiﬁed a higher rate of spontane-

ous abortions in pregnant women receiving the vaccine, with

a relative risk of 2.3, but the diﬀerence was not statistically

signiﬁcant (95% conﬁdence interval = 0.7–8.0; p=0.2) (122).

A more recent study of 441 women inadvertently vaccinated

early in their pregnancy did not ﬁnd an increased risk for fetal

death (7.4/1,000 in vaccinated women versus 18.5/1,000

unvaccinated women in the general population) (83).

e proportion of women vaccinated during pregnancy who

develop YFV antibodies is variable and might be related to the

trimester in which they received vaccine. Of 101 pregnant

women receiving YF vaccine predominantly in their third

trimester, 39% had evidence of seroconversion to YFV (82).

Of 433 women vaccinated predominantly in the ﬁrst trimester,

425 (98%) developed YFV-speciﬁc neutralizing antibodies

(83). Because pregnancy might aﬀect immunologic function,

serologic testing to document an immune response to the vac-

cine should be considered.

No evidence exists that breastfeeding mothers have an altered

response to YF vaccine. Very limited safety data are available on

the use of YF vaccine in breastfeeding women and their infants.

One probable and one conﬁrmed case of YEL-AND have been

reported in infants whose mothers were vaccinated with YF

vaccine (PHAC, unpublished data, 2008; 123). Both infants

were breastfed exclusively, were aged <1 month at the time of

the exposure, and had not received the vaccine themselves. YF

vaccine virus was recovered from the CSF of the conﬁrmed

case patient, and YFV-speciﬁc IgM antibodies were detected

in the probable case-patient’s CSF. Testing was not performed

on the breast milk in either case to conﬁrm the presence of

vaccine virus. RNA from West Nile virus, a related ﬂavivirus,

has been identiﬁed in breast milk, which suggests that this is

a plausible mode of transmission (124,125). Further research

is needed to document the risk for potential vaccine exposure

through breastfeeding.

Summary of Rationale

for YF Vaccine Recommendations

YF is a vectorborne disease resulting from the transmission

of YFV to a human from the bite of an infected mosquito. It

is endemic to sub-Saharan Africa and tropical South America.

Infection in humans is capable of producing hemorrhagic

fever and is fatal in 20%–50% of persons with severe disease.

Because no treatment exists for YF disease, prevention is critical

to lower disease risk and mortality.

e risk for acquiring YF for travelers is determined by mul-

tiple factors, including vaccination 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 only 10 cases of imported YF in

travelers from Europe (seven cases) or the United States (three

cases) have been reported since 1970, the low number of cases

14 MMWR July 30, 2010

is likely, at least in part, to be a result of the routine use of the

vaccine. In attempts to minimize the potential importation and

spread of the disease into new areas, many countries enforce

the IHR and have vaccine requirements for entry.

Decisions regarding the use of YF vaccine for travelers

must take into account the overall risk for travel-associated

YFV disease, the high mortality when it does occur, vaccine

requirements per IHR, contraindications or precautions for

vaccination, and risk for serious adverse events following YF

vaccine administration.

Recommendations for the Use of

YF Vaccine in Laboratory Workers

YF vaccine is recommended for laboratory personnel who

might be exposed to virulent YFV or to concentrated prepara-

tions of YF vaccine virus strains by direct or indirect contact

or by aerosols.

Recommendations for Prevention

of YF Among Travelers

All travelers to countries in which YF is endemic should be

advised of the risks for the disease and available methods to pre-

vent it, including personal protective measures and vaccine.

Personal Protective Measures

All travelers should take precautions to avoid mosquito bites

to reduce the risk for YF and other vector-borne infectious

diseases. ese precautions include using insect repellent,

wearing permethrin-impregnated clothing, and staying in

accommodations with screened or air-conditioned rooms.

Additional information on protection against mosquitoes and

other arthropods is available at http://wwwnc.cdc.gov/travel/

yellowbook/2010/chapter-2/protection-against-mosquitoes-

ticks-insects-arthropods.aspx.

Recommendations for the Use

of YF Vaccine in Travlers

YF vaccine is recommended for persons aged ≥9 months who

are traveling to or living in areas at risk for YFV transmission

in South America and Africa. Countries with risk for YFV

transmission have been listed (Table 1). For many of these

countries, only a portion of the country is at risk for YFV

transmission (Figure 2). Given that changes in the designation

of endemic regions can occur, travelers and health-care provid-

ers should obtain updated information from CDC, available

at http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/

yellow-fever.aspx.

YF vaccine may be required for entry into certain countries.

A list of country-speciﬁc requirements is available at http://

wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/yellow-

fever-vaccine-requirements-and-recommendations.aspx.

Requirements are mandatory and are intended primarily to

prevent importation into and transmission of YFV within a

given country. However, IHRs stipulate that a medical provider

may issue a waiver of YF vaccination to a traveler to fulﬁll

these requirements if the provider judges that YF vaccination

is medically contraindicated.

Because of the risk for serious adverse events that can occur

following YF vaccine administration, health-care providers

should vaccinate only persons who are at risk for exposure to

YF virus or require proof of vaccination for country entry. To

minimize further the risk for serious adverse events, health-care

providers should observe the contraindications carefully and

TABLE 1. Countries with risk for yellow fever virus (YFV) transmission*

Africa Central and South America

Angola

Benin

Burkina Faso

Burundi

Cameroon

Central African Republic

Chad

†

Congo, Republic of the

Côte d’Ivoire

Democratic Republic of the Congo

Equatorial Guinea

Ethiopia

Gabon

The Gambia

Ghana

Guinea

Guinea-Bissau

Kenya

Liberia

Mali

†

Mauritania

†

Niger

†

Nigeria

Rwanda

Sierra Leone

São Tomé and Principe

Senegal

Somalia

Sudan

†

Tanzania

Togo

Uganda

Argentina

†

Bolivia

†

Brazil

†

Colombia

Ecuador

†

French Guiana

Guyana

Panama

†

Paraguay

Peru

†

Suriname

Trinidad and Tobago

†

Venezuela

†

* As dened by the World Health Organization, countries/areas where yellow fever has been reported currently or in the past, plus areas where vectors and animal

reservoirs currently exist.

†

These countries are not holoendemic (i.e., only a portion of the country has risk for YFV transmission). Information about which areas are endemic is available at

http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/yellow-fever.aspx.

Vol. 59 / RR-7 Recommendations and Reports 15

consider the precautions to vaccination before administration

of YF vaccine and provide a medical waiver when needed

(Table 2).

Requirements for Vaccination

Before International Travel

Certain countries require evidence of vaccination from all

entering travelers, which includes direct travel from the United

States (34). Travelers who arrive in a country with a YF vac-

cination entry requirement without proof of vaccination may

be quarantined for up to 6 days.

Country-entry requirements for proof of YF vaccination

under IHRs are diﬀerent from ACIP or CDC recommenda-

tions. Requirements are mandatory and are intended primarily

to prevent importation into and transmission of YFV within

a given country. CDC’s recommendations are public health

advice provided to travelers on the basis of the best available

epidemiologic data to prevent YFV infection among travelers

visiting countries with a risk for YFV transmission.

For purposes of international travel, YF vaccines must be

administered at an approved YF vaccination center. In the

United States, state and territorial health departments have

the authority to designate nonfederal vaccination centers

and to issue YF vaccination stamps to those centers. A list of

designated vaccine centers is available from CDC at http://

wwwnc.cdc.gov/travel or can be obtained from state or local

health departments.

As proof of receipt of YF vaccine, all vaccinees should

possess a completed International Certiﬁcate of Vaccination or

Prophylaxis (ICVP), validated with the provider’s signature and

oﬃcial YF vaccination center stamp (Figure 3). An ICVP must

be complete in every detail; if it is 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. Some countries do not require

an ICVP for infants younger than a certain age (e.g. aged <6

months, <9 months, or <1 year, depending on the country).

Information on age requirements for vaccination by individual

countries is available at http://wwwnc.cdc.gov/travel.

e certiﬁcate of vaccination is valid beginning 10 days after

the date of vaccination and extending for a period of 10 years.

When a booster dose of the vaccine is administered within this

10-year period, the certiﬁcate is considered valid from the day

of the most recent vaccination.

IHRs stipulate that a medical provider may issue a waiver

of YF vaccination to a traveler if the provider judges that YF

vaccination is medically contraindicated (see Contraindications

and Precautions). In this case, the physician should ﬁll out and

sign the “Medical Contraindications to Vaccination” section

of the ICVP (Figure 4), provide a signed and dated letter on

letterhead stationary clearly stating the contraindication, and

bearing that center’s oﬃcial YF vaccination stamp. e pro-

vider should inform the traveler of any increased risk for YF

infection associated with nonvaccination and how to minimize

this risk. Reasons other than medical contraindications are not

acceptable for exemption from vaccination. e traveler also

should be advised of the possibility that the medical waiver

might not be accepted by the destination country.

Because requirements and recommendations might change,

all travelers should seek up-to-date information before travel

from health departments, CDC, and WHO. Travel agencies,

international airlines, or shipping lines also might have up-

to-date information. Updated information on requirements

and recommendations for vaccination are available at http://

wwwnc.cdc.gov/travel.

TABLE 2. Contraindications and precautions to yellow fever vaccine administration

Contraindications Precautions

Allergy to vaccine component Age 6–8 months

Age less than 6 months Age ≥60 years

†

Symptomatic HIV infection or CD4

T-lymphocytes <200/mm

(or <15% of total in

children aged <6 years)

Asymptomatic HIV infection and CD4

T-lymphocytes 200–499/mm

(or 15%–24% of total in children aged <6 years)*

Thymus disorder associated with abnormal immune function

†

Pregnancy

Primary immunodeciencies Breastfeeding

Malignant neoplasms

Transplantation

Immunosuppressive and immunomodulatory therapies

†

* Symptoms of HIV have been classied (Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected

adults and adolescents; US Department of Health and Human Services; 2008. Available at http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=

Guidelines&Search=O&GuidelineID=7&ClassID=1. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the

Use of Antiretroviral Agents in Pediatric HIV Infection; 2009. Available at http://aidsinfo.nih.gov/ContentFiles/PediatricGuidelines.pdf.)

†

New contraindication or precaution since the ACIP’s recommendations for the use of yellow fever vaccine were published in 2002 (CDC. Yellow fever vaccine: recom-

mendations of the Advisory Committee on Immunizations Practices: MMWR 2002;51[No. RR-17]).

16 MMWR July 30, 2010

Administration of Yellow Fever

Vaccine

Dosage and Administration

For persons of all ages for whom vaccination is indicated,

a single subcutaneous injection of 0.5 mL of reconstituted

vaccine is used. According to the package insert, the vaccine

needs to be administered within 1 hour of reconstitution (71).

Once reconstituted, a multidose vial should be maintained at

35°F–46°F (2°C–8°C), and the remaining doses should be

used or discarded within 1 hour.

Although limited data suggest YF vaccine might retain its

potency following the expiration date (126), the package

insert states that the vaccine should not be used after its expi-

ration date. According to ACIP’s General Recommendations

on Immunization, a dose of an expired vaccine should not

be counted as valid, and the dose should be repeated with

a nonexpired vaccine following a 28-day interval (127). For

more guidance on the inadvertent administration of an expired

vaccine, health-care providers should contact the vaccine

manufacturer.

If the vaccine is administered inadvertently via the intra-

muscular route, the response to vaccine probably will not

be aﬀected. Repeating doses of vaccine administered by the

intramuscular route rather than by the subcutaneous route is

not necessary (127).

Anaphylaxis has been reported to occur in persons with no

history of reactions to the components of the vaccine. Given

this, all persons should be observed for at least 15 minutes

following the administration of the vaccine, and epinephrine

FIGURE 3. International Certicate of Vaccination or Prophylaxis (ICVP)*

Source: Brunette GW, Kozarsky PE, Magill AJ, Shlim DR, Whatley AD, eds. CDC health information for international travel 2010. Atlanta. GA: US Department of Health

and Human Services, Public Health Service, CDC; 2009.

* International Health Regulations allow countries to require proof of yellow fever vaccination for entry and from travelers arriving from certain countries to prevent

importation and indigenous transmission of yellow fever vaccine. As proof of vaccination, vaccinees should receive a completed ICVP, validated (stamped and signed)

with the stamp of the center where the vaccine was administered.

INTERNATIONAL CERTIFICATE OF VACCINATION OR PROPHYLAXIS

Certicat international de vaccination ou de prophylaxie

This is to certify that

Nous certitions que (name - nom) (date of birth - né(e) le) (sex - de sexe) (nationality - et de nationalité)

whose signature follows

(national identication document, if applicable - document d’identication nationale, le cas échéant) dont la signature suit

has on the date indicated been vaccinated or received prophylaxis against in accordance with the International Health Regulations.

a éré vacciné(e) ou a reçu une prophylaxie à la date indiguée (name of disease or condition - nom de la maladie ou de l’aection) conformément au Règlement sanitaire international.

Vaccine or prophylaxis

Vaccine ou agent

prophylactique

Date Signature and professional

status of supervising

clinician

Signature et litre du

professopnel de santé

responsable

Manufacturer and batch no.

of vaccine or prophylaxis

Fabricant du vaccin ou de

l’agent prophlactique et

numéro du lot

Certicate valid

from:

until:

Certicat valable

à partie du:

jusqu’au:

Ocial stamp of the administering center

Cachet ociel du centre habilité

Vol. 59 / RR-7 Recommendations and Reports 17

injection (1:1,000) should be readily available in case of a seri-

ous allergic reaction. Furthermore, because reactions have been

delayed up to several hours following YF vaccine, all patients

should be advised of signs and symptoms of an allergic reac-

tion (e.g., urticaria, angioedema, rash, dyspnea, bronchospasm,

pharyngeal edema, wheezing, and throat tightness). In addi-

tion, vaccinated persons should be advised to seek immediate

medical care if any symptoms of an allergic reaction develop

following vaccination.

Transfusion-related transmission of yellow fever vaccine

virus has been documented among persons receiving blood

products that were collected from recently vaccinated persons

(75). Blood donation centers should screen blood donors to

determine if they received a yellow fever vaccine within the

preceding 2 weeks and defer these donors. However, practices

vary between blood collection centers, and questions about

vaccination history might not be asked routinely. erefore,

health-care providers should advise persons to defer blood

donation for 2 weeks after receiving YF vaccine.

Booster Doses

IHRs require revaccination at intervals of 10 years to boost

antibody titer. Evidence from multiple studies demonstrates

that YF vaccine immunity persists for many decades and might

provide life-long protection (79,80,128,129).

To minimize the occurrence of adverse events and optimize

the immune response, eﬀorts should be taken to observe a

10-year interval between YF vaccine doses. However, limited

data suggest that revaccination occurring <10 years after the

previous dose does not increase the risk for adverse events

(74), particularly as serious adverse events occur primarily

after the initial vaccination of YF vaccine. Although the level

of YFV-speciﬁc antibodies formed following revaccination

appears to be correlated inversely to the amount of preexisting

antibodies (130), no data suggest that earlier revaccination will

have a negative impact on seroprotection. If the date of the

most recent vaccination cannot be ascertained, and the patient

requires vaccination, a booster dose should be administered.

Simultaneous Administration of Other

Vaccines or Drugs

Determination of whether to administer YF vaccine and

other immunobiologics simultaneously (i.e., 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

FIGURE 4. Medical contraindication section of the International Certicate of Vaccination or Prophylaxis (ICVP)*

Source: Brunette GW, Kozarsky PE, Magill AJ, Shlim DR, Whatley AD, eds. CDC health information for international travel 2010. Atlanta. GA: US Department of Health

and Human Services, Public Health Service, CDC; 2009.

* A health-care provider who identies a medical contraindication to yellow fever vaccination and wants to issue a medical waiver should ll out and sign the Medical

Contraindications to Vaccination section of the ICVP. The health-care provider also should give the traveler a signed and dated exemption letter.

MEDICAL CONTRAINDICATION TO VACCINATION

Contre-indication médicale à la vaccination

This is to certify that immunication against

Je soussigné(e) certie que ia vaccination contre

for

(Name of disease - Nom de la maladie) pour

is medically

(Name of traveler - Nom du voyageur) est medicalement

contraindicated because of the following conditions:

contre-indiquée pour les raisons suivantes:

(Signature and address of physician)

(Signature et adresse du médecin)

18 MMWR July 30, 2010

desired vaccinations before travel and on information regarding

possible immune interference.

No evidence exists that inactivated vaccines and YF vaccine

interfere with the immune response to the vaccine. erefore,

inactivated vaccines can be administered either simultaneously

or at any time before or after YF vaccination (127). YF vaccine

should be administered either simultaneously or 30 days apart

from other live viral vaccines because the immune response to

one live virus vaccine might be impaired if administered within

30 days of another live-virus vaccine (131,132). Limited data

suggest that the serologic response to YF vaccine is not inhib-

ited by administration of measles vaccine nonsimultaneously

within 30 days of YF vaccine administration (133). However,

the serologic response to measles vaccine was not assessed in

this study. Oral Ty21a typhoid vaccine can be administered

simultaneously or at any interval before or after YF vaccine

attributable to the diﬀerent routes of administration (34).

Vaccines that have been administered simultaneously with

YF vaccine without interfering in the immune response to the

vaccines or resulting in unusual safety proﬁles include Bacillius

Calmette-Guerin (134), diphtheria (135,136), hepatitis A

(137,138), hepatitis B (139), inﬂuenza (140), measles (133),

meningococcal (Menomune) (141), pertussis (136), polio

(135), smallpox (136,142), tetanus (135,136), and typhoid

(both injectable [138] and oral [143,144]). No data exist

regarding possible interference between YF vaccine and rabies,

human papillomavirus, Japanese encephalitis, live attenuated

inﬂuenza, or varicella virus vaccines (145).

Studies of persons administered YF vaccine and immune

globulin simultaneously found no alteration of the immuno-

logic response to YF vaccine when compared with controls (i.e.,

YF vaccine alone) (146,147). Although chloroquine inhibits

replication of YFV in vitro, it does not aﬀect antibody responses

to YF vaccine adversely among persons receiving antimalarial

prophylaxis (148).

No data exist for YF vaccine and the potential suppression

of the tuberculin skin test (TST) response. However, because

the use of live attenuated measles vaccine theoretically can

suppress TST reactivity resulting in a false-negative reaction,

ACIP’s General Recommendations on Immunization suggest

that TST should be administered at the same time as YF vac-

cine or 4 weeks after receipt of YF vaccine (127). Alternatively,

TST screening can be performed and read before administer-

ing YF vaccine. However, if YF vaccine has been administered

recently, TST screening should be delayed for at least 4 weeks

after vaccination (127).

Contraindications

Allergy to Vaccine Components

YF vaccine is contraindicated for persons with a history of

hypersensitivity to any of the vaccine components, including

eggs, egg products, chicken proteins, or gelatin. e stopper

used in vials of vaccine also contains dry latex rubber, which

might cause an allergic reaction (71).

According to the manufacturer, persons who are able to

eat eggs or egg products may receive the vaccine. However,

potential hypersensitivity reactions might occur in persons

with a history of minor reactions to eggs. For egg-sensitive

persons, a scratch test or intradermal test can be performed

before administering the vaccine to check for reactivity. If a

person has a severe egg-sensitivity or has a positive skin test

to the vaccine, but the vaccination is recommended because

of their travel destination-speciﬁc risk, desensitization can be

performed under direct supervision of a physician experienced

in the management of anaphylaxis. e desensitization proce-

dure is detailed in the product insert (71).

Given the risk for anaphylaxis, even among persons with

no history of reactions to components of the vaccine, all

persons should be observed for at least 15 minutes following

the administration of the vaccine, and epinephrine (1:1,000)

should be readily available in case of a serious allergic reac-

tion. Vaccinated persons should be advised of symptoms of

an allergic reaction and should be advised to seek immediate

medical care if any symptoms of an allergic reaction develop

following vaccination.

Infants Aged <6 Months

YF vaccine is contraindicated for infants aged <6 months.

is contraindication was instituted in the late 1960s in

response to a high rate of YEL-AND documented in vacci-

nated young infants (97

). e mechanism of increased neu-

rovirulence in infants is unknown but might be attributable

to the immaturity of the blood-brain barrier, higher or more

prolonged viremia, or immune system immaturity.

Altered Immune Status

Thymus Disorder

YF vaccine is contraindicated for persons with a thymus

disorder that is associated with abnormal immune cell function

(e.g., thymoma or myasthenia gravis) (149). Four (17%) of

the initial 23 YEL-AVD reported cases were noted to occur in

persons who had had thymectomies performed for thymomas

(117). In 2003, thymus disorder was added to the YF vaccine

package insert as a contraindication. To date, no evidence has

Vol. 59 / RR-7 Recommendations and Reports 19

been identiﬁed of immune dysfunction or increased risk for YF

vaccine-associated serious adverse events in persons who have

undergone incidental surgical removal of their thymus or have

had indirect radiation therapy in the distant past. erefore,

YF vaccine can be administered, if indicated based on their

destination-speciﬁc YF risk, in persons who underwent inci-

dental surgical removal of the thymus or have a remote history

of radiation therapy to the thymus.

AIDS and HIV Infection with Severe Immune

Suppression

YF vaccine is contraindicated for persons with acquired

immunodeﬁciency syndrome (AIDS) or other clinical mani-

festations of HIV (150,151), including persons with CD4

counts <200 per mm

or <15% of total lymphocytes for

children aged <6 years. is recommendation is based on a

theoretic increased risk for encephalitis in this population.

One fatal YEL-AND case has been reported in a person with

a previously undiagnosed HIV infection and a CD4 count

of 108 cells/mm

who was vaccinated with YF vaccine (98).

No large prospective, randomized trials have been performed

to address the safety and eﬃcacy of YF vaccine among this

group adequately. Several retrospective and prospective stud-

ies that included a total of approximately 450 HIV-infected

persons who received YF vaccine reported no additional seri-

ous adverse events. However, these studies included a limited

subset of adults (n = 10) with a CD4 counts <200 per mm

(84–87,98,152–155).

If travel to an area in which YF is endemic cannot be avoided

in a person with severe immune suppression based on CD4

counts (<200 per mm

or <15% total) or symptomatic HIV, a

medical waiver should be provided, and counseling on protec-

tive measures against mosquito bites should be emphasized.

(See Precautions for other HIV-infected persons not meeting

these criteria.)

Immunodeﬁciencies Other than Thymus

Disorder or HIV Infection

YF vaccine is contraindicated for persons with primary

immunodeﬁciencies, malignant neoplasms, and transplanta-

tion (127). Although no data exist on the use of YF vaccine

in these persons, they are presumed to have an increased risk

for YF vaccine-associated serious adverse events. More speciﬁc

information on primary immunodeﬁciencies for which the use

of live viral vaccines, such as YF vaccine, is contraindicated

will be published (127). In general, solid organ transplant or

hematopoietic stem cell transplant recipients within 2 years

of transplantation, or persons whose transplants occurred >2

years ago but who are still taking immunosuppressive drugs, are

considered to be immunosuppressed (156). Live viral vaccines

should be deferred in persons with a history of malignant neo-

plasm or transplantation until immune function has improved

substantially. is is best determined by a physician who is

familiar with the patient and the patient’s underlying medical

condition and treatments in consultation with a YF vaccination

center. If a person with an immunodeﬁciency cannot avoid

travel to an area in which YF is endemic, a medical waiver

should be provided, and counseling on protective measures

against mosquito bites should be emphasized.

Immunosuppressive and

Immunomodulatory Therapies

YF vaccine is contraindicated for person whose immunologic

response is either suppressed or modulated by current or recent

radiation therapies or drugs. Drugs with known immunosup-

pressive or immunomodulatory properties include high-dose

systemic corticosteroids, alkylating drugs, antimetabolites,

TNF-α inhibitors (e.g., etanercept), IL-1 blocking agent (e.g.,

anakinra), and other monoclonal antibodies targeting immune

cells (e.g., rituximab, alemtuzumab). No speciﬁc data exist

on the use of YF vaccine in persons receiving these therapies.

However, these persons are presumed to be at an increased risk

for YF vaccine-associated serious adverse events, and the use

of live attenuated vaccines in these persons is contraindicated

according to the package insert for most of these therapies

(127).

Although the immunosuppressive eﬀects of corticosteroids

can vary, a dose of either ≥2 mg/kg of body weight or a total

≥20 mg/day of prednisone or its equivalent for persons who

weigh >10 kg when administered for ≥2 weeks is considered

suﬃciently immunosuppressive to contraindicate the use

of live attenuated vaccines (127). Corticosteroids are not a

contraindication when administration is under any of the

following circumstances: short-term (i.e., <2 weeks); a low-

to-moderate dose (<20 mg of prednisone or its equivalent per

day); long-term, alternate-day treatment with short-acting

preparations; maintenance physiologic doses (replacement

therapy); or administered topically (skin or eyes), inhaled, or

by intra-articular, bursal, or tendon injection (127).

Administration of live viral vaccines should be deferred in

persons who have discontinued these therapies until immune

function has improved. is is best determined by a physician

who is familiar with the patient’s underlying medical conditions

and by the patient’s pharmacist, who can assist in determining

the speciﬁc half-lives of the immunosuppressive drugs and

the potential duration of immune suppression. If someone

receiving immunosuppressive or immunomodulatory therapies

cannot avoid travel to an area in which YF is endemic , a medi-

cal waiver should be provided, and counseling on protective

measures against mosquito bites should be emphasized.

20 MMWR July 30, 2010

Precautions

Infants Aged 6–8 Months

Age 6–8 months is a precaution for YF vaccine administra-

tion. In infants aged <6 months, the rates of YEL-AND are

substantially elevated (50–400 cases per 100,000 infants vac-

cinated) (96,106). Two cases of YEL-AND have been reported

among infants aged 6–8 months (96). By age 9 months, the risk

for YEL-AND is believed to be substantially lower. In general,

whenever possible, travel of children aged 6–8 months to coun-

tries in which YF is endemic should be postponed or avoided.

If travel is unavoidable, the decision of whether to vaccinate

these infants needs to balance the risks for YFV exposure with

the risk for adverse events following vaccination.

Adults Aged ≥60 Years

Age ≥60 years is a precaution for YF vaccine administra-

tion, particularly if the ﬁrst dose of the YF vaccine is to be

administered. A recent analysis of adverse events reported to

VAERS during 2000–2006 indicates that persons aged ≥60

years are at increased risk for any serious adverse events after

vaccination, compared with younger persons (89). e rate

of serious adverse events in persons aged ≥60 years was 8.3

events per 100,000 doses distributed compared with 4.7 events

per 100,000 doses distributed for all YF vaccine recipients.

is reinforces ﬁndings from VAERS data from 1990–1998

that reported the rate of serious adverse events was 7.5 times

higher in persons aged ≥60 years than in the reference group

(persons aged 19–29 years) (107). e risk for YEL-AND

and YEL-AVD also are increased in this age group, at 1.8 and

1.4 reported cases per 100,000 doses distributed, respectively,

compared with 0.8 and 0.4 reported cases per 100,000 doses

distributed for all YF vaccine recipients. Given that YEL-AND

and YEL-AVD are seen almost exclusively in primary vaccine

recipients, caution should be exercised with older travelers

who might be receiving YF 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

Moderate Immune Suppression

Asymptomatic HIV infection with moderate immune sup-

pression (i.e., CD4 counts of 200–499 per mm

for persons

aged ≥6 years or 15%–24% of total lymphocytes for children

aged <6 years) is a precaution for YF vaccine administration.

Large prospective randomized trials have not been performed

to address the safety and eﬃcacy of YF vaccine adequately

among this group. Several retrospective and prospective studies

including approximately 450 persons infected with HIV have

reported no serious adverse events among patients considered

moderately immunosuppressed based on the their CD4 counts

(84–87,152–155).

HIV infection has been associated with a reduced immuno-

logic response to a number of inactivated and live-attenuated

vaccines, including YF vaccine (84). In a recent retrospective

cohort study, 65 (83%) of 78 HIV-infected persons developed

speciﬁc antibodies against YFV in the ﬁrst year after vaccina-

tion; however, this was signiﬁcantly lower than vaccinated

persons without HIV infection (97% [64/66]; p=0.01) (86).

Among HIV-infected infants in developing nations, only three

(17%) of 18 developed YFV-speciﬁc neutralizing antibodies

within 10 months of vaccination compared with 42 (74%) of

57 HIV-uninfected controls matched for age and nutritional

status (87). e mechanisms for the diminished immune

response in HIV-infected persons are uncertain but appear to

be correlated with HIV RNA levels and CD4 counts. Because

vaccination of asymptomatic HIV-infected persons might be

less eﬀective than that for persons not infected with HIV,

measurement of their neutralizing antibody response to vac-

cination should be considered before travel. Health-care pro-

viders should contact the appropriate state health department

or CDC (at telephone 1-970 221-6400) to discuss serologic

testing further.

For HIV-infected persons who experience immune recon-

stitution in response to antiretroviral therapy, their current

CD4 count and symptoms of HIV infection (if stable over

3 month time period) rather than a CD4 count nadir and a

history of prior opportunistic infections/symptomatic HIV

should be used to categorize their HIV status (156). Of note,

one YEL-AVD case was reported in a person determined to

have a genetic polymorphisms in chemokine receptor CCR5

(118). Consequently, concern has been raised that despite

having adequate immune function, persons with HIV infec-

tion who are receiving an antiretroviral regimen containing a

CCR5-receptor antagonist could be at increased risk for adverse

events after YF vaccination (157). Further research is needed

to address this concern.

If an asymptomatic HIV-infected person with moderate

immune suppression is traveling to an area in which YF is

endemic, vaccination can be considered. Vaccinated persons

should be monitored closely after vaccination for evidence of

adverse events. If an adverse event occurs, a VAERS report

should be ﬁled, and the state health department or CDC should

be notiﬁed to obtain technical support and assistance with

diagnostic testing. If international travel requirements rather

than an increased risk for acquiring YFV infection are the only

Vol. 59 / RR-7 Recommendations and Reports 21

reason to vaccinate HIV-infected persons, the person should be

excused from vaccination 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 count ≥500 per mm

or ≥25% of total lymphocytes

for children aged <6 years), YF vaccine can be administered,

if recommended on the basis of their destination-speciﬁc YF

risk. (See Contraindications for other HIV-infected persons

not meeting these criteria.)

Pregnancy

Pregnancy is a precaution for YF vaccine administration,

compared with most other live vaccines, which are contrain-

dicated in pregnancy. If travel is unavoidable, and the risks

for YFV exposure are felt to outweigh the vaccination risks,

a pregnant woman should be vaccinated. If the risks for

vaccination are felt to outweigh the risks for YFV exposure,

pregnant women should be issued a medical waiver to fulﬁll

health regulations. Although no speciﬁc data are available, a

woman should wait 4 weeks after receiving YF vaccine before

conceiving. (See Vaccination of Women During Pregnancy

and Breastfeeding.)

Breastfeeding

Breastfeeding is a precaution for YF vaccine administration.

Two serious adverse events have been reported in exclusively

breastfed infants whose mothers were vaccinated with YF vac-

cine (123; PHAC, unpublished data, 2008). Further research

is needed to document the risk for potential vaccine exposure

through breastfeeding. Until more information is available,

YF vaccine should be avoided in breastfeeding women.

However, when travel of nursing mothers to a YF endemic

area cannot be avoided or postponed, these women should be

vaccinated. (See Vaccination of Women During Pregnancy

and Breastfeeding.)

Special Populations

Age

YF vaccine is approved for use in persons aged ≥9 months.

e vaccine is contraindicated for infants aged <6 months. (See

Contraindications for more information.) Age 6–8 months and

adults aged ≥60 years are precautions for YF vaccine adminis-

tration. (See Precautions.)

Pregnancy

Limited data are available regarding the safety and immuno-

genicity of YF vaccine in pregnancy. Pregnancy is a precaution

for YF vaccine administration. (See Vaccination of Women

During Pregnancy and Breastfeeding and Precautions.)

Breastfeeding Women

Although no data are available on the immune response in

breastfeeding mothers, no alteration to the immune response in

these women are suspected. Limited data are available regarding

the safety of YF vaccine in breastfed infants. Breastfeeding is

a precaution for YF vaccine administration. (See Vaccination

of Women During Pregnancy and Breastfeeding and

Precautions.)

Altered Immune Status

e following conditions are a contraindication for YF vac-

cine administration: 1) thymus disorders associated with abnor-

mal immune cell function, 2) symptomatic HIV-infection or

CD4

T-lymphocyte values <200 per mm

or <15% of total

lymphocytes for children aged <6 years, 3) primary immuno-

deﬁciencies, 4) malignant neoplasms, 5) transplantation, and

6) immune suppression or modulation attributable to current

or recent radiation therapies or drugs. e following condi-

tion with altered immune status is a precaution for YF vaccine

administration: asymptomatic HIV-infection with CD4

T-lymphocyte values 200–499 per mm

or 15%–24% of total

lymphocytes for children aged < 6 years. (See Contraindications

and Precautions.)

Complete details are not available regarding what medications

the nine patients with reported YEL-AVD who had a history

of autoimmune disease or diseases with potential autoimmune

etiology were taking; these might have included immunosup-

pressive medications. Four of the nine patients were aged >60

years, including two who also had a history of thymectomy for

thymoma (see YEL-AVD). Older age and history of thymoma

are both risk factors for YEL-AVD. Nonetheless, the fact that

nine (16%) of 57 persons with reported cases of YEL-AVD had

a history of autoimmune disease is a concern and suggests that

autoimmune disease, either by itself of in conjunction with

other risk factors, including immunosuppressive medication,

could increase the risk for YEL-AVD. Deﬁnitive data are lack-

ing to guide decision-making about YF vaccination in these

patients. Health-care providers should consider the possibility

of diminished immune function resulting from the autoim-

mune disease state itself and/or the medication used in deciding

whether or not to administer YF vaccine to these patients.

22 MMWR July 30, 2010

Reporting of Vaccine Adverse

Events

Even if a causal relation to vaccination is not certain, all

adverse events following receipt of vaccine that are thought

to be clinically signiﬁcant by health-care providers or vaccine

recipients should be reported to VAERS at http://vaers.hhs.gov

or by telephone at 1-800-822-7967. To promote better timeli-

ness and quality of safety data, secure web-based reporting is

available and health-care providers are encouraged to report

electronically at https://vaers.hhs.gov/esub/step1.

Surveillance to monitor, characterize, and quantify YF

vaccine-speciﬁc adverse outcomes are ongoing. Because cur-

rent reporting mechanisms are strictly passive, detection of

of YEL-AVD and YEL-AND in recently vaccinated persons

who experience new symptoms largely depends on health-

care providers being familiar with these conditions and with

reporting requirements. An education program regarding the

vaccine and possible serious adverse events is being developed

and will be made available to all health-care providers by fall

2010 through CDC’s Travelers’ Health website. State health

departments are encouraged to incorporate requirements for

completion of these programs into their certiﬁcation and

recertiﬁcation processes for issuance of YF vaccination stamps

to health-care providers.

Future Research

Research focusing on suspected risk factors for serious adverse

events or suboptimal response to YF vaccine for which few

or no data exist should be designed and implemented. is

should include HIV, immunosuppressive diseases, autoim-

mune diseases, and use of immunosuppressive and immuno-

modulatory drugs. Ethical considerations might limit these to

observational studies. If possible, studies geared to collecting

population-based data would be the most useful, though also

the most diﬃcult to implement. Further research also is needed

to determine if YF vaccine virus is present in breast milk and

the exact route of transmission involved (e.g., ingested milk

or blood).

Studies addressing the duration of immune response to the

vaccine, in particular the duration of IgM antibodies following

vaccination and the duration of protective antibody levels, are

warranted. ese studies would help resolve issues related to

possible YF disease in vaccinated travelers as well as provide

updated evidence on the dosing interval needed for booster

doses of the vaccine. Finally, studies examining the immune

response to an inactivated yellow fever vaccine are underway.

If successful, the inactivated vaccine potentially could be

administered to persons with contraindications to the use of

a live viral vaccine.

Additional Information

Information about YF for travelers and health-care providers

has been published previously (34). Additional information

about YF is available at http://www.cdc.gov/ncidod/dvbid/

yellowfever/index.html. Additional licensure information for

the YF vaccine that is approved in the United States is avail-

able at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/

ApprovedProducts/ucm094074.htm.

Acknowledgments

is report is based in part on contributions by Nicole Lindsey,

MPH, Susan Hills, MBBS, Division of Vector-Borne Diseases,

National Center for Emerging and Zoonotic Infectious Diseases,

CDC.

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Vol. 59 / RR-7 Recommendations and Reports 27

Advisory Committee on Immunization Practices

Membership List, October 2009

Chair: Carol Baker, MD, Baylor College of Medicine, Houston, Texas.

Executive Secretary: Larry Pickering, MD, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia.

Members: Lance Chilton, MD, University of New Mexico, Albuquerque, New Mexico; Paul Cieslak, MD, Oregon Public Health Division, Portland, Oregon;

Kristen Ehresmann, MPH, Minnesota Department of Health, St. Paul, Minnesota; Janet Englund, MD, University of Washington and Children’s Hospital

and Regional Medical Center, Seattle, Washington; Franklyn Judson, MD, University of Colorado Health Sciences Center, Denver, Colorado; Wendy Keitel,

MD, Baylor College of Medicine, Houston, Texas; Susan Lett, MD, Massachusetts Department of Public Health, Boston, Massachusetts; Michael Marcy,

MD, UCLA Center for Vaccine Research, Torrance, California; Cody Meissner, MD, Tufts Medical Center, Boston, Massachusetts; Kathleen Neuzil, MD,

University of Washington, Seattle, Washington; Sara Rosenbaum, JD, George Washington University, District of Columbia; Mark Sawyer, MD, University

of California - San Diego, California; Ciro Valent Sumaya, MD, Texas A&M Health Science Center, College Station, Texas; Jonathan Temte, MD, University

of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

ExOﬃcio Members: James E. Cheek, MD, Indian Health Service, Albuquerque, New Mexico; Wayne Hachey, DO, Department of Defense, Falls Church,

Virginia; Geoﬀrey S. Evans, MD, Health Resources and Services Administration, Rockville, Maryland; Bruce Gellin, MD, National Vaccine Program Oﬃce,

District of Columbia; Linda Murphy, Centers for Medicare and Medicaid Services, Baltimore, Maryland; George T. Curlin, MD, National Institutes of

Health, Bethesda, Maryland; Norman Baylor, MD, Food and Drug Administration, Bethesda, Maryland; Linda Kinsinger, MD, Department of Veterans

Aﬀairs, Durham, North Carolina.

Liaison Representatives: American Academy of Family Physicians, Doug Campos-Outcalt, MD, Phoenix, Arizona; American Academy of Pediatrics,

Joseph Bocchini, MD, Shreveport, Louisiana, David Kimberlin, MD, Birmingham, Alabama; American College Health Association, James C. Turner, MD,

Charlottesville, Virginia; American College of Obstetricians and Gynecologists, Stanley Gall, MD, Louisville, Kentucky; American College of Physicians,

Gregory Poland, Rochester, Minnesota; American Geriatrics Society, Kenneth Schmader, MD, Durham, North Carolina; America’s Health Insurance Plans,

Mark Netoskie, MD, Houston, Texas; American Medical Association, Litjen Tan, PhD, Chicago, Illinois; American Osteopathic Association, Stanley Grogg,

DO, Tulsa, Oklahoma; American Pharmacists Association, Stephan L. Foster, PharmD, Memphis, Tennessee; Association for Prevention Teaching and Research,

W. Paul McKinney, MD, Louisville, Kentucky; Biotechnology Industry Organization, Clement Lewin, PhD, Cambridge, Massachusetts; Canadian National

Advisory Committee on Immunization, Joanne Langley, MD, Halifax, Nova Scotia, Canada; Council of State and Territorial Epidemiologists, Christine Hahn,

MD, Boise, Idaho; Department of Health, United Kingdom David M. Salisbury, MD, London, United Kingdom; Healthcare Infection Control Practices

Advisory Committee, Alexis Elward, MD, St Louis, Missouri; Infectious Diseases Society of America, Samuel L. Katz, MD, Durham, North Carolina;

National Association of County and City Health Oﬃcials, Jeﬀ Duchin, MD, Seattle, Washington; National Association of Pediatric Nurse Practitioners,

Patricia Stinchﬁeld, St Paul, Minnesota; National Foundation for Infectious Diseases, William Schaﬀner, MD, Nashville, Tennessee; National Immunization

Council and Child Health Program, Mexico, Vesta Richardson, MD, Mexico City, Mexico; National Medical Association, Patricia Whitley-Williams, MD,

New Brunswick, New Jersey; National Vaccine Advisory Committee, Guthrie Birkhead, MD, Albany, New York; Pharmaceutical Research and Manufacturers

of America, Damian A. Braga, Swiftwater, Pennsylvania, Peter Paradiso, PhD, Collegeville, Pennsylvania; Society for Adolescent Medicine, Amy Middleman,

MD, Houston, Texas; Society for Healthcare Epidemiology of America, Harry Keyserling, MD, Atlanta, Georgia.

Yellow Fever Vaccine Work Group

Chair: Carol J. Baker, MD, Houston, Texas.

Members: Elizabeth Barnett, MD, Boston, Massachusetts; Louisa Chapman, MD, Atlanta, Georgia; Eileen Farnon, MD, Atlanta, Georgia; Patrick Garmon,

PharmD, PhD, Falls Church, Virginia; Mark D. Gershman, MD, Atlanta, Georgia; Christina Greenaway, MD, Toronto, Canada; Kristen B. Janusz, DVM,

Fort Collins, Colorado; James F. Jones, MD, Atlanta, Georgia; Franklyn N. Judson, MD, Denver, Colorado; Katrin S. Kohl, MD, Atlanta, Georgia; Nina

Marano, DVM, Atlanta, Georgia; Michael E. Neseman, MD, Lima, Peru; Karen O’Brien, MD, Fort Monroe, Virginia; Michele Sabourin, Ottawa, Ontario,

Canada; Betsy Schroeder, MPH, Atlanta, Georgia; Barbara A. Slade, MD, Atlanta, Georgia; J. Erin Staples, MD, PhD, Fort Collins, Colorado; Andrea

Sutherland, MD, Silver Springs, Maryland; Mary E. Wilson, MD, Boston, Massachusetts.

U.S. Government Printing Oﬃce: 2010-623-026/41263 Region IV ISSN: 1057-5987

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