Hepatitis B vaccination of newborns in rural China ......• Among providers who had used the Uniject device: – 98% thought Uniject was easy to carry, transport, and use – 95%

Hepatitis B vaccination of newborns in rural China: evaluation of an out-of-cold-chain delivery strategy

Istanbul, Turkey

March 15-17, 2006

Contents

• Introduction

• Objective

• Methods and Implementation

• Results

• Conclusions

• Next steps

Hepatitis B in China

• Hepatitis B (HB) is one of the four major infectious diseases in China

• 120 million people are chronically infected with hepatitis B virus (HBV)—10% of the population

• An estimated 280,000 deaths annually>33% of global deaths attributed to HB

Sources:State of the World’s Vaccines and Immunization. WHO, UNICEF, The World Bank. 2002.The Global Alliance for Vaccines and Immunization. Progress Report. 2002.1992 National Serosurvey. China.

HBV surface antigen rate among children

7.12%

2.10%

11.40%

8.25%

0%

2%

4%

6%

8%

10%

12%

HB

sAg

Rat

e

Urban2002

Rural2002Urban

1992

Rural1992

Urban: 71%

Rural: 28%

Source: Serosurvey adopting the samples from 2002 national nutrition survey (unpublished)

Increase in on-time administration of HB vaccine birth dose

0102030405060708090

100

National Eastern Middle Western

Cov

erag

e(%

)

1997200120022003

Project Focus

Source: National EPI Coverage Survey. China. 1999 and 2004

Proportion of children receiving the HB vaccine birth dose on 1st or 2nd day of life

0 10 20 30 40 50 60 70 80 90

Place of Birth

Geography

Overall

Percent (Weighted)

PlainsHillsMountains

County Hospital or AboveTownship HospitalHome

Source: National EPI Coverage Survey. China. 1999

Project Focus

Objective

To evaluate strategies for improving on-time delivery (within 24 hours) of the HB vaccine birth dose in remote areas of China, especially among children born at home.

Study design

• Townships situated at least 20 km from the county capital in three counties in Hunan Province were randomly divided into three groups: – Group 1: Ampoule inside the cold chain– Group 2: Ampoule outside the cold chain– Group 3: HB vaccine in Uniject™* (HB-Uniject) outside the cold

chain

• All ampoules of HB vaccine and HB-Uniject packages were marked with vaccine vial monitors (VVMs)

*Uniject is a registered trademark of BD.

Hospital vaccination in the cold chain;home vaccination out of the cold chain

Group 1:– HB vaccine delivered in

township hospitals. Vaccine stored in the cold chain

Group 2 and Group 3:– Village-based doctors and

midwives trained as vaccine providers. Vaccine stored and delivered out of the cold chain

Preparations

• Held trainings with vaccine providers at township and village levels

• Conducted social mobilization to emphasize the importance of hepatitis B immunization and on-time delivery of the birth dose

• Monitored vaccine storage temperatures with data loggers

Evaluation methods

Baseline and final coverage survey– Review of children’s immunization cards– Review of village/township immunization

records

Immunologic response survey– Radioimmunoassay for HBsAg, anti-HBs

Results: Significant improvements in on-time vaccination

11.3 6.8

57.9

77.3

8.78.0

67.667.8

0

20

40

60

80

100

Group 1: AmpouleInside Cold Chain

Group 2: AmpouleOutside Cold Chain

Group 3: HB-UnijectOutside Cold Chain

Total

Perc

ent o

f inf

ants

who

rece

ived

the

first

dos

e of

va

ccin

e w

ithin

24

hour

s of

birt

h

BaselineFinal

Raising awareness

helps

Out-of-cold-chain storage helps more

Unijecthelps even

more

Results: Significant improvements in on-time vaccination

Hospital births—improved Home births—improved by by raising awareness out-of-cold-chain strategy

2.4 2.5 0.6

77.9 80.3

25.2

51.8

66.7

10.711.018.4

87.6

0

20

40

60

80

100

Group 1Ampoule

Inside ColdChain

Group 2Ampoule

Outside ColdChain

Group 3 HB-Uniject

Outside ColdChain

Group 1Ampoule

Inside ColdChain

Group 2Ampoule

Outside ColdChain

Group 3 HB-Uniject

Outside ColdChain

Perc

ent o

f inf

ants

who

rece

ived

the

first

dose

of v

acci

ne

with

in 2

4 ho

urs o

f birt

h

BaselineFinal

Born in the hospital Born at home

Results: Home-born infants better served when vaccinated at home

73.5

32.8

0

20

40

60

80

100

Home-born and immunized athome

Home-born and immunized intownship hospitalPe

rcen

t of i

nfan

ts w

ho re

ceiv

ed th

e fi

rst

dose

of v

acci

ne w

ithin

24

hour

s of

bir

th

Serology results: No difference between in-the-cold-chain and out-of-cold-chain groups

Anti-HBs positive HBsAg positive

Children % 95%CI Children % 95%CI

Group 1 203 194 95.6 91.5-97.8 1 0.5 0.03－3.1

Group 2 203 195 96.1 92.1－98.2 1 0.5 0.03－3.1

Group 3 200 191 95.5 91.4－97.8 3 1.5 0.4－4.7

Total 606 580 96.0 93.7－97.1 5 0.8 0.3－2.0

Groups Children observed

Serology results: No difference between in-the-cold-chain and out-of-cold-chain groups

Anti-HBs>=10 mIU/ml Groups Children

observed

Children with Anti-

HBs +Among Anti-

HBs positive (%)Among children

observed (%)GMT

Group 1 203 194 180(92.8 %)

180(88.7 %) 95.5

Group 2 203 195 184(94.4 %)

184(90.6 %) 93.3

Group 3 200 191 178(93.2 %)

178(89.0 %) 102.3

Inside cold chain 203 194 180

(92.8 %) 180

(88.7 %) 95.5

Outside cold chain 403 386 362

(93.8 %) 362

(89.8 %) 97.7

Total 606 580 542(93.5 %)

542(89.4 %) 97.7

Storage temperatures: freeze and heat exposure

• In the cold chain: 2/3 township refrigerators below 0 °C

• Out of the cold chain: temperatures 2°C–30°C – 0.2% vaccine was discarded due to heat exposure

– VVMs effective in identifying heat exposure

• No serious adverse events following immunization were reported during the study

Acceptability of Uniject• Among providers who had used the Uniject device:

– 98% thought Uniject was easy to carry, transport, and use

– 95% thought Uniject could administer a full dose of HB vaccine

– 88% thought Uniject could save immunization time compared with standard syringes

• Almost all immunization providers thought that the village-based out-of-cold-chain strategy could improve the on-time delivery of the HB vaccine birth dose among children born at home

Conclusion 1

• In remote areas in China and other countries where many children are born at home, on-time administration of HB vaccine has been difficult to achieve through routine immunization service

• Village health workers using an out-of-cold chain immunization strategy can improve the on-time administration of the HB vaccine birth dose among infants born at home

• Training and monitoring of hospital health workers can improve on-time administration of the HB vaccine birth dose to children born in hospitals

Conclusion 2

• Simple tools such as VVMs and Uniject can ensure vaccine quality and injection safety when vaccines are administered by village health workers

• HB vaccine is sufficiently heat stable to withstand routine out-of-cold-chain storage in tropical conditions without loss of immunogenicity

• Taking vaccine out of the cold chain could potentially decrease the risk of vaccine damage due to inadvertent freezing

Next steps

• Improve awareness and coordination of the birth dose in hospital settings through increased supervision

• HB vaccine manufacturer will start application of licensure for use of HB-Uniject stored out of the cold chain

• Introduce VVMs on EPI vaccines, in accordance with UNICEF and WHO recommendations

• Adopt national policy of HB vaccine storage out of the cold chain, initially in warm areas among children born at home

Lixia Wang, MDProgram Officer

Immunization Solutions Strategic ProgramPATH

[email protected]

Increase in coverage of HB3

0102030405060708090

100

National Beijing Hubei Guizhou

Cov

erag

e(%

)

2001 2002 2003

Integration into EPI since 2002

Source: National Coverage Survey, 2004

Progress in Hepatitis B Immunization Western Provinces 1999-2004 *

0

500

1000

1500

2000

2500

3000

3500

4000

1999 2000 2001 2002 2003 2004

Dos

es A

dmin

iste

red

(100

0s)

BCGDTP1DTP3HBV1HBV3HBV1 Ontime

* Adjusted for corrected data Qinghai (2004), Xinjiang (2003-4)