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De La Hoz, Fernando; (2003) Hepatitis B vaccination in the Columbian Amazon : effectiveness and
factors influencing vaccine coverage. PhD thesis, London School of Hygiene & Tropical Medicine.
DOI: https://doi.org/10.17037/PUBS.01544171
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HEPATITIS B VACCINATION IN THE COLOMBIAN AMAZON.
EFFECTIVENESS AND FACTORS INFLUENCING VACCINATION
COVERAGE.
FERNANDO DE LA HOZ .
Thesis submitted for the degree of Doctor of Philosophy
Department of Infectious and Tropical Diseases
Infectious Disease Epidemiology Unit
London School of Hygiene and Tropical Medicine
University of London
August 2002
2
ABSTRACT
A vaccination coverage survey was carried out in the Colombian Amazon, a former high
endemic area for hepatitis B, involving 3573 children less than II years old. It was carried
out in Leticia, Puerto Narifio, and Araracuara, both urban and rural areas. Children were
selected using a one stage cluster sampling, randomly selecting clusters in urban and rural
areas where all children under 11were surveyed. At the same time blood samples were taken
from all children with known vaccination status (n=1603), and from their mother, when she
was available (n=8l2). These samples were processed for hepatitis B surface antigen
(HBsAg), antibodies to hepatitis B core antigen (Anti-HBc) and antibodies to HBsAg (Anti-
HBs). A sample of children without vaccination data available was also bled to compare
their results with those of children with vaccination data.
Full vaccination coverage was found to range between 39% and 69% among different areas
while hepatitis B vaccination ranged between 73% and 95%. Factors which improve the
likelihood of being fully vaccinated in this study were: Age above one year, living in Leticia,
being. affiliated to the social security, mother's years of schooling. Health worker's
knowledge on vaccine contraindications and perceptions of logistical barriers against
vaccination or importance of hepatitis B as a public health problem were also related to full
vaccine coverage.
Prevalence of hepatitis B infection reached 5% among those who were bled (8211603) while
HBsAg positive status was 1.6% (26/1603). Since the introduction of the vaccine prevalence
of hepatitis B infection has fallen from 40%, an 85% reduction, while carrier prevalence has
fallen from 5%, a 68% reduction. Age above 7 years, living in a rural area, birth delivery
supervised by other than aMD or nurse, and being born from an Anti-HBc+ mother were the
most important general factors related to being infected with HBV. Having an incomplete
schedule for hepatitis B vaccine was associated with an increase in the risk of being Anti-
HBc or HBsAg+. However, some characteristics of the vaccination process were related to
being HBsAg+/Anti-HBc+. Delays in receiving the first dose of hepatitis B after birth and
delays to receiving the second dose after the first dose were associated with an increased risk
of being HBsAg+/Anti-HBc+. None of these characteristics were related to being Anti-Hlic+
alone.
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In conclusion, the introduction of a recombinant Cuban manufactured hepatitis B vaccine has
produced a marked decline in the high infection prevalence of children in the Colombian
Amazon area. A higher coverage has been achieved from the beginning of the program
though intervals from birth to first dose and between doses are too long leading to new
infections that could have been avoided.
There is still room to make improvements in the control program, including the
implementation of a surveillance system of the HBV serological status for pregnant women,
in order to ensure better vaccination schemes for those born to infected or HBsAg+ mothers.
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TABLE OF CONTENTS
Chapter 1: Introduction 16
Chapter 2: Literature Review 22
I.Hepatitis B vaccines 22
1.1.Vaccine development 22
1.2.Efficacy and safety of hepatitis B vaccines 24
1.3. Dose schedule 33
lA. Vaccine types 35
1.5.Immunogenicity 36
1.6.Perspectives 43
1.7.Barriers against hepatitis B vaccination 44
II. Epidemiological aspects of hepatitis B virus infection
in Colombia. 46
ILL North part of the country.
(Zone Bananera de Santa Marta) 47
11.2.Serranfa de los Motilones 47
11.3.The central region of the Country 47
11.4. The Amazon Basin 47
11.5.The Uraba Gulf 47
11.6.Epidemiological studies in the Zone
Bananera de Santa Marta 49
11.7.Epidemiological studies in the Colombian
Amazon Basin 51
11.8. Epidemiological studies in health workers 52
11.9.Other epidemiological studies of HBV infections 53
11.10.Needs for more evaluation on effectiveness
of hepatitis B vaccine 54
III.Methodological issues in postlicensure evaluation
of hepatitis B vaccine effectiveness. 57
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III.I. Outcomes 58
IIL2. Methods for post licensure vaccine evaluation 60
III.3. Variables 66
Chapter 3: Methods 67
3.1 Proposed study 67
3.2. Objectives 67
3.3. Type of study 68
3.4. Localisation of the study 68
3.5. Target population 69
3.6. Sample size and selection 69
3.7. Population survey and logistic aspects 70
3.8. Definitions for vaccination status 71
3.9. Blood sample collection and handling 72
3.10. Serological markers 74
3.11. Definitions for serological study 74
3.12. Data collection from health workers 76
3.13. Data handling and analysis 77
Chapter 4: Results on vaccination coverage 87
L Vaccination coverage and characteristics 88
II. Individual factors related to vaccination coverage 90
ILl. Child factors 90
11.2.Parent factors 93
11.3. Socio-economic factors 94
11.4.Models combining individual variables 96
III. Ecological variables related to vaccination coverage 101
III.I. Results of health worker questionnaire 101
III.2. Relationship between individual vaccination and
characteristics of health workers/centres. 104
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IV. Models combining ecological and individual
variables and not being fully vaccinated 120
V. Models combining ecological and individual
variables and not being hepatitis B vaccinated. 123
Chapter 5: Serological results. 126
I.General description of HBV infection prevalence. 127
II. Overall impact of hepatitis B vaccine in the Amazon. 130
III. Prevalence of hepatitis B infection and related factors. 131
IlLI. Child-related variables. 131
111.2.Mother-related variables. 136
III.3. Vaccination characteristics. 139
IV. Analysis of anti-HBs levels. 151
Chapter 6.Discussion 158
I.Vaccine coverage and related factors: 158
1.1Methodological concerns. 158
1.2.Importance of the results. 160
1.3.Factors related to coverage. 162
1.4.Health workers' (HW) knowledge, perceptions
and their relationship to vaccination coverage. 166
II. Serological results and vaccine effectiveness: 173
11.1.Methodological issues 173
11.2.Hepatitis B infection and vaccine
Effectiveness. 176
11.3.Anti-HBs titres. 183
Annexes
l.Univariable analysis of vaccination coverage and
related factors. 188
2. Questionnaire for vaccination coverage. 193
3. Questionnaire for risk factors. 195
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4. Questionnaire for health workers. 198
Bibliography 203
LIST OF FIGURES
Chapter 2
2.1. Hepatitis B endemicity in Colombia by
geographical area. 48
2.2. Geographical position of Colombia in the
Americas. 49
Chapter 3
3.1. Organization of the statistical analysis for vaccination
coverage and related factors. 80
3.2. Organization of the statistical analysis for HBV prevalence of
infection and related factors. 83
Chapter 4
4.1. Time in days between doses of hepatitis B by area. 89
4.2. Median time between birth and third dose of hepatitis B
by area and age. 89
4.3. Full vaccination coverage by age and area. 90
4.4. Proportion of children completing the basic vaccination
scheme in the first year of life. 91
Chapter 5
5.1. Anti-HBc prevalence by age and area. 127
5.2. Anti-HBc prevalence in rural areas by age and sex 128
5.3. HBsAg prevalence by age and area.
All children. 129
5.4. HBsAg prevalence by age and area.
Only Anti-HBc+. 129
5.5. HBsAg prevalence in rural areas by age and sex.
All children. 130
5.6. HBsAg prevalence in rural areas by age and sex.
Only Anti-HBc+. 130
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5.7. Box plot showing time lag distributions between
hepatitis B doses. 140
5.8. Time from birth to first HB dose by HBsAg status.
Percentiles. 141
5.9. Time from first to second HB dose by HBsAg status.
Percentiles. 141
5.10. Time from second to third HB dose by HBsAg status.
Percentiles. 141
5.11. Time from birth to first dose by Anti-HBc status. 149
5.12. Time from first to second HB dose by Anti-HBc status. 149
5.13. Time from second to third HB dose by Anti-HBc status. 149
5.14. Proportion of people without detectable Anti-HBs by time
from the third dose. 153
5.15. Median of Anti-HBs levels by time from third dose. 153
5.16. Median of Anti-HBs levels by time from birth to
first dose. 154
5.17. Children without detectable anti-HBs by time from birth to
first dose. 154
LIST OF TABLES
Chapter 2
2.1. Summary of studies of hepatitis B vaccine efficacy
in populations other than newborns 28
2.2. Summary of studies on hepatitis B efficacy in
children or newborns 30
2.3. Immunogenicity of hepatitis B vaccine in different trials 38
2.4. Ro values for hepatitis B in Colombia and proportion of
people to be vaccinated to reach eradication. 43
2.5. Serological results of different hepatitis B surveys in Colombia
by region. 59
2.6. Expected effectiveness of HBV vaccine against carrier status
under model 2 of efficacy 64
2.7. Effect on vaccine efficacy of different assumptions about
prevalent cases before vaccine implementation 66
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Chapter 3
3.1. Vaccination schedules recommended by the Colombian
Ministry of Health and by the Amazon 72
3.2. Population distribution in urban and rural areas of
the municipality of Leticia 84
3.3. Population distribution in urban and rural areas of
the municipality of Puerto Narifio. 85
3.4. Population distribution in Leticia by neighbourhood and blocks 85
3.5. Expected results of the serological survey. 86
Chapter 4
4.1. Vaccination coverage by variables related to children. 92
4.2. Children's characteristics and not being fully vaccinated.
Final model. 93
4.3. Children's characteristics and not being vaccinated against
hepatitis B. Final model. 94
4.4. Vaccination coverage according to parents' characteristics. 95
4.5 Parents' characteristics and not being fully vaccinated.
Final model. 96
4.6. Vaccination coverage by socio-economic characteristics. 97
4.7. Socio-economic characteristics and not being fully vaccinated.
Final model. 97
4.8. Socio-economic characteristics and not being vaccinated
against hepatitis B. Final model. 98
4.9. Selected individual variables and not being fully vaccinated.
All children. Final model. 99
4.1O.Selected individual variables and not being fully vaccinated.
Urban area. Final model. 99
4.1l.Selected individual variables and not being fully vaccinated.
Rural area. Final model. 100
4.12.Selected individual variables and not being vaccinated against
hepatitis B. Final model. 101
4.13.Selected individual variables and not being vaccinated against
hepatitis B. Urban area. Final model. 102
Description:knowledge on vaccine contraindications and perceptions of logistical barriers against vaccination or importance of hepatitis B as a public health
