International-Related Vaccines

Chokechai RongkavilitPediatric Infectious DiseasesChildren’s Hospital of Michigan

Objectives

Make aware of other commonly-used vaccines overseas

Know the relevance of a specific vaccine to the international travel

Share your personal experience on vaccine use overseas

Nigeria China India Thailand Brazil WHO

BCG birth birth birth birth birth birth

DPT 6, 10, 14 wk

3, 4, 5, 18 mo

6, 10, 14 wk, 16-24 mo

2, 4, 6 mo, 1.5-2 y, 4-5 y

2, 4, 6, 15 mo

6, 10, 14 wk, 1.5-4 y

OPV birth, 6, 10, 14 wk

2, 3, 4 mo, 4 y

6, 10, 14 wk, 16-24 mo

2, 4, 6 mo, 1.5-2 y, 4-5 y

2, 4, 6, 15 mo

birth, 6, 10, 14 wk

HIB - - - - 2, 4, 6, 15 mo

6, 10, 14 wk

Hep B birth, 6, 14 wk

birth, 1, 6 mo

6, 10, 14 wk

birth, 2, 6 mo

birth, 1, 6 mo

birth, 6, 14 wk6, 10, 14 wk

Measles 9 mo 8 mo, 7 y 9 mo 9-12 mo, MMR 6 y

MMR 1 y 9 mo

Yellow fever 9 mo - - - 9 mo 9 mo

Japanese encephalitis

- - - 1.5-2 y, 1.5-2 y, 2.5-3 y

- *

WHO Vaccines & Biologicals 2002 Update

Source: WHO/UNICEF joint reporting form, 2002data from 192 WHO member states

Hib vaccine not introduced (108 countries)

Hib3 < 80% (10 countries) Hib vaccine introduced but no coverage data reported (29 countries)

Hib3 > 80% (45 countries)

2002 (84 countries introduced 44%)

Hib vaccine not introduced (167 countries)

Hib vaccine introduced but no coverage data reported (25 countries)

1997 (25 countries introduced)

Countries having introduced Hib vaccineand reported Hib3 coverage, 2002

Slide Date: October 03

Important vaccines used overseas

BCG Yellow fever vaccine Oral polio vaccine Japanese encephalitis vaccine

BCG (Bacille Calmette-Guérin)

One of the most controversial vaccines

WHO estimates >80% of infants received BCG in 2002.

Contains a live-attenuated strain of M. bovis.

It was originally isolated from a cow with tuberculosis by Calmette and Guerin at Pasteur Institute in Paris.

The strain was subcultured every 3 weeks for 13 years to reduce its virulence (undefined genetic changes).

BCG Use of BCG oral vaccination began in France in 1921 among

infants who were exposed to active TB.

Oral vaccination induced slight tuberculin sensitivity, therefore intradermal vaccination was proposed.

The original French BCG vaccine was later subcultured and distributed to several labs worldwide.

The BCG vaccines that are currently in use are produced at several (7?) sites worldwide.

These vaccines are not identical. To what extent they differ in efficacy and safety is not clear.

BCG: Special Considerations

Adverse reactions are rare even in asymptomatic, HIV+

infants BCG should be given to all infants even in HIV

endemic area.

Infants with TB exposure at birth should not receive BCG

until TB prophylaxis is complete.

BCG may be considered in unavoidable and close contacts

of multidrug-resistant TB cases (contact should have

negative PPD).

HIV-TB interaction and emerging multidrug-resistant TB

raise more interest in BCG vaccines.

BCG vaccination It contains both live and dead organisms; the number of

bacilli per dose varies.

Intradermal injection at deltoid area is preferred.

Correct vaccination almost always results in local

reactions, small ulceration and eventually scar formation.

Presence of a scar does not indicate protection.

Benefits of booster BCG is unclear.

Benefits of revaccination in those with negative skin tests

is also unproven.

BCG: Efficacy

Documented protection against TB meningitis and disseminated

TB in children (64-86%).

Meta-analysis of 1200 articles showed overall efficacy of 50%.

A study in American Indians Alaska Natives showed 48-62%

efficacy for 50-60 years.

Duration of protection is unknown.

In Saudi Arabia, 82% protection in children <15 y, 67% by 15-24

years of age, and 20% by 25-34 years of age.

Colditz GA. JAMA 1994;271:698Aronson NE. JAMA 2004;291:2086

BCG: Efficacy

Very likely, it does not prevent primary infection.

It does not prevent reactivation of latent TB impact on

TB transmission is limited.

Some efficacy against leprosy (M. leprae) and Buruli ulcer

(M. ulcerans) and bladder cancer.

BCG: Adverse Effects Fatal dissemination: 0.2-1.5 per million vaccinees, mostly

in compromised host.

Extensive ulceration and regional lymphadenitis: <1:1000 (more in neonates neonates usually get a reduced dose)

Current BCG has no impact on TB control.

New TB vaccines on horizon: recombinant BCG, DNA vaccines

Yellow Fever

Yellow Fever, Etiology It is a member of the flavivirus family (group B arbovirus).

Two types of yellow fever

jungle type: transmitted by Haemagogus mosquitoes in South America and Aedes africanus in Africa, which acquire the disease from monkeys.

urban type: humans serve as viremic hosts and the disease is spread between humans by the domestic mosquito vector, Aedes aegypti.

Yellow Fever, Epidemiology Predominately in sub-Saharan Africa and South

America.

Epidemics are underreported. They commonly include 30-1000 cases and have fatality rates of 20-50%.

Severity ranges from a self-limited infection to hemorrhagic fever that carries a 50% mortality rate.

Yellow Fever, Clinical Findings Initial phase

Fever with relative bradycardia (Faget sign), conjunctival injection severe headache, back pain and myalgia.

Transient remission (up to 24 h)

The toxic phase develops as the fever returns.

The above symptoms but more severe. Hepatic-induced coagulopathy and hemorrhage

(hematemesis, epistaxis, and petechiae).

Yellow Fever, Clinical Findings

Systemic manifestations include jaundice and albuminuria.

Hypotension, shock, metabolic acidosis, acute tubular necrosis, myocardial dysfunction, and arrhythmia dominate the picture in late stage.

Yellow Fever, Lab Findings Leukopenia and thrombocytopenia.

Elevated direct bilirubin and hepatic transaminases.

PT, PTT and INR are prolonged invariably.

Positive DIC panel: Diminished levels of factor VIII, fibrinogen,

and platelets, along with the presence of fibrin split products.

Albuminuria and elevated BUN.

Immunoglobulin M (IgM) testing by ELISA is the preferred

method of testing. This assay is 95% sensitive 7-10 days after

the onset of illness.

PCR can be used in the first week (limited trials).

Yellow Fever Vaccine

Injectable, live-attenuated 17D vaccine prepared in eggs

Efficacy is almost 100%

This is the only internationally regulated immunization

(International Certificate of Vaccination).

Schedule: single subcutaneous dose (booster every 10

years) in patients > 9 months of age

It should be given at least 10 days before travel.

Yellow Fever Vaccine

Side effects Fever, headache, muscle ache Rare encephalitis in very young infants

Precautions Immunocompromised host Pregnancy Given at the same time with, or 4 weeks apart

from other live vaccines Given 3 weeks apart from cholera vaccine

Oral Polio Vaccine

Dr. Sabin administered Sabin’s oral polio vaccine (1960s)

Oral Polio Vaccine (OPV)

Live-attenuated

Single-dose dispenser

Multiple-dose dispenser: 2 drops per dose (10

doses)

Must store in –20 oC

Thawed vaccine is good for 4 months in 2-8 oC.

Once open, it is good for 3 days in 2-8 oC.

Polio Eradication

The number of polio-endemic countries has decreased to 6 in 2003 (Afghanistan, Egypt, India, Niger, Nigeria and Pakistan; 682 cases)

As of April 2004, 89 cases have been reported this year; 63 are in Nigeria.

There has been a significant decrease in cases in India and no cases in Egypt in 2004.

Polio Eradication

WHO Global Polio Eradication Initiative aims to interrupt

transmission of wild polio by end 2004 and for global

polio-free certification in 2008.

Supplementary immunization activities (National

Immunization Days) in 2004

Kano, Nigeria did not participate in NID as it reviewed

reports on OPV safety.

Importation of wild polio from northern Nigeria in

February 2004 in Botswana (free of polio since 1991).

Polio Eradication: Challenges ahead for OPV

OPV: Advantage Low cost Easy to use in mass immunization High efficacy & durability Mucosal immunity to stop viral transmission

(outbreak control) Confer secondary community protection

(contact immunization) Resulted in drastic reduction of polio globally

Polio Eradication: Challenges ahead for OPV

OPV: Disadvantage

OPV can mutate and become virulent and transmissible

Vaccine-associated paralytic poliomyelitis (neurovirulence)

Circulating vaccine-derived poliovirus (neurovirulence and transmissibility)

Vaccine-associated paralytic poliomyelitis (VAPP)

Clinically indistinguishable from wild polio Frequently associated with OPV serotypes 2 and 3 Risk in a highly immune community is 1 in 2.5 million

doses Higher risk in low vaccine coverage and after the first

dose of OPV Usually occurs only in vaccine recipients and close

contacts; not been associated with an outbreak. Annual cases of VAPP in developing countries is

unknown (400-800 worldwide).Jacob John T. Bull World Health Organ 2004;82:53

Circulating vaccine-derived poliovirus (cVDPV)

OPV transmits from one unimmunized individual to another, and it accumulates mutations to gain neurovirulence and transmissibility.

This could occur in regions with declining OPV coverage and could result in outbreak.

Outbreaks of cVDPV

Country Year OPV serotype Cases

Poland 1968 3

Egypt 1983-93 2 32

Hispaniola 2000-1 1 21

Phillippines 2001 1 3

Madagascar 2001-2 2 5

• cVDPV can circulate indefinitely if OPC coverage is low.

• Transient immunity gaps may permit cVDPV emergence.

• Outbreak can be stopped by mass OPV campaign.

Polio Eradication: Challenges ahead for OPV

Mass OPV campaign to eliminate the last pockets of wild type polioviruses.

Once global eradication of

wild polio has been achieved, OPV will be the only potential source of live poliovirus in communities (cVDPV).

Total eradication of poliomyelitis requires a synchronous and prompt cessation of OPV use.

WT

OPV

cVDPV

Japanese Encephalitis Vaccine

Japanese encephalitis

Case fatality 30-40%

Neurologic morbidity 50%

Risk increases among travelers living for

prolonged periods in places where the disease is

endemic or epidemic (rural area with flooded rice

farms)

Pigs are the reservoir.

Culex mosquito is the vector.

Japanese encephalitis vaccine

Live-attenuated vaccine (China): Efficacy 95-100%

Inactivated, mouse-brain derived, whole-virus vaccine

(JE-VAX, USA): Efficacy 76-95%

Schedule: 0, 7, 14 (30) days

Reduced dose by half in children 1-3 y

Safety and efficacy is unknown in children < 1 y

Adverse effects: Allergic reaction (<1%, delay up to 2

wks)Bista MB. Lancet 2001;358:791

Japanese encephalitis vaccine

New vaccine (chimeric virus)

Yellow fever virus vaccine with envelop gene of Japanese encephalitis virus

Protective levels were seen after one dose in phase II study

DNA vaccine, poxvirus-based vaccine

Monath TP. J Infect Dis 2003;188:1213