Open Journal of Gastroenterology, 2013, 3, 237-240 OJGas
doi:10.4236/ojgas.2013.34040 Published Online August 2013 (http://www.scirp.org/journal/ojgas/)
Prevalence of hepatitis B infection and factors associated in
children of Ivorian HBsAg carrier subjects
Koffi Alain Attia1*, Ya Henriette Kissi1, Stanislas Doffou1, Demba Bangoura1, Roseline Flora Wilson1,
Georges Bougha1, Fulgence Yao Bathaix1, Kouame Alassan Mahassadi1, Mohamed Sayegh2,
Therese N’dri-Yoman1
1Department of General Medicine and Hepato-Gastroenterology, Teaching Hospital of Yopougon, Abidjan, Côte d’Ivoire
2Medical Private hospital of Danga, Cocody, Abidjan, Côte d’Ivoire
Email: *attia_alain@yahoo.fr
Received 13 May 2013; revised 16 June 2013; accepted 1 July 2013
Copyright © 2013 Koffi Alain Attia et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Aims of the Study: 1) Determine the Prevalence of
Hepatitis B virus (HBV) infection in children (contact
subjects) of chronic Hepatitis B surface antigen
(HBsAg) carrier subjects (index subjects); 2) Search
for factors associated with HBV infection in these
children. Patients and Methods: Retrospective-cross-
sectional study (January 5th, 2006 through December
31st, 2012). Studied parameters: biological and clini-
cal characteristics of index subjects; Prevalence of
HBsAg and Hepatitis B core antibody (HBcAb) in
their children. Search for the HBV infection associa-
ted factors in the children (univariate analyses through
Chi-square or Fisher’s exact test; multivariate analy-
sis through a backward logistic regression). Results:
Our 44 subjects’ median age was 43.1 ± 7.49 years
and 88.6% of them lived with a spouse. Average
number of children per index subjects was 2.3 ± 1.1.
Our 92 children’s median age was 9.3 ± 4.55 (ranging
from 1 to 15 years), and 43 (44.8%) were vaccinated
against HBV. HBV infection prevalence was 24%
(23/96 of which, 4 were HBsAg positive and 19 HBcAb
positive subjects without HBsAg). Independent fac-
tors associated with HBV infection in children of in-
dex subjects were HBV DNA for index subjects >2000
IU/ml (OR = 11.5; p = 0.001), existence of HBV in two
parents (OR = 7.9; p = 0.03) and absence of HBV
vaccination in the children (OR = 30.9; p = 0.003).
Conclusion: Immunization coverage for children of
index subjects was insufficient, especially before the
introduction of HBV vaccine into the enlarged vacci-
nation program. Outside vertical transmission, those
children were more exposed to HBV intrafamilial
transmission risk when they were not immunized
against HBV, when both parents were infected and
when HBV viremia in index subjects was higher than
2000 IU/ml.
Keywords: Hepatitis B Infection; Intrafamilial
Transmission; Screening
1. INTRODUCTION
Hepatitis B virus (HBV) infection is a real public health
problem worldwide and more particularly in high preva-
lence areas, such as sub-Saharan Africa [1-7], because of
its progressive complications (cirrhosis and hepatocellu-
lar carcinoma), comorbidity frequency (especially HIV
infection) and management difficulties in the particular
context of our countries with limited financial resources.
In sub-Saharan Africa, both main transmission ways are
vertical or perinatal and intrafamilial horizontal in early
childhood [5,7]. Introduction of HBV universal immuni-
zation for newborns into enlarged vaccination programs
(EVP) of our countries in Sub-Sahara dates generally from
at least two decades. In most EVP of our countries, HBV
immunization only starts from the 6th week after birth
(pentavalent or hexavalent vaccine). Moreover, owing to
anti-HBs immunoglobulins (Ig) availability problems in
our countries, passive immunoprophylaxis is almost never
associated with active immunization. Vertical and in-
trafamilial horizontal transmission risks of HBV infec-
tion remain a concern before HBV immunization, espe-
cially during children’s first six weeks of life. This study
aims to determine HBV infection prevalence among chil-
dren (contact subjects) of hepatitis B surface antigen
(HBsAg) chronic carrier subjects (index subjects) through
familial screening of HBV infection and search for fac-
tors associated with HBV infection in these children.
*Corresponding author.
Published Online August 2013 in SciRes. http://www.scirp.org/journal/ojgas
K. A. Attia et al. / Open Journal of Gastroenterology 3 (2013) 237-240
238
2. PATIENTS AND METHODS
It’s about a retrospective cross-sectional study (January
5th, 2006 through December 31st, 2012). Records of
HBsAg chronic carrier patients, with ambulatory follow-
up in two medical centers in Abidjan (University Hospi-
tal of Yopougon and Clinique Médicale Danga), were
analyzed. All the HBsAg-positive patients (index sub-
jects), whose family surrounding (contacts subjects: spouses
and children) was subjected to systematic screening for
HBV infection, were included in our study (search for
HBsAg and hepatitis B core antibody (HBcAb) in con-
tact subjects: Mini Vidas; Biomerieux, Marcy l’Etoile,
France). Subjects whose children were more than 15
years old were excluded from the study.
A systematic and minimal biological checkup was re-
alized for every index subject; the checkup included
transaminases determination (Cobas Integra 400 plus;
Roche diagnostics, Mannheim, Germany), a search for
HBeAg, anti-HBeAb and anti-HBcAb, anti-HCV Anti-
bodies (Mini Vidas; Biomerieux, Marcy l’Etoile, Fran-
ce), DNA HBV determination using a real-time PCR as-
say (Cobas Amplicor HBV Monitor assay, threshold of
detectability 35 copies/ml or 6 IU/ml; Roche Diagnostics)
and HIV test (screening test using Determine and con-
firmation test using Genie II).
Main evaluation criteria was the existence of HBV in-
fection in index subjects’ children testified by presence
of HBcAb. The infection was past when HBsAg was
negative and present when HBsAg was positive.
We searched for HBV associated factors in children
through univariate analyses (Chi-square or Fisher’s exact
test) and a multivariate analysis (backward logistic re-
gression). All variables of which “p” was under 0.30 in
univariate analysis were included in initial model of mul-
tivariate analysis. Alpha threshold was 5% for bilateral
formulation.
3. RESULTS
HVB infection screening among the family circle of the
44 studied index subjects was about 39 spouses and 96
children. Index subjects’ median age was 43.1 7.49
years ranging from 28 to 58. Average number of children
per subject index was 2.3 1.1 ranging from 1 to 5 chil-
dren. HIV test was negative in all their parents. Charac-
teristics of index subjects and their children at inclusion
are summed up in Tables 1 and 2.
The 96 children’s median age was 9.3 ± 4.55 years
ranging from 1 to 15 years. HBV infection in children
was 24% (HBcAb were presents in 23 out of 96). HBsAg
was present in only 4 of these 23 children (17.4%), that
is an overall prevalence of 4.2% (4 children out of 96).
Three of these 4 HBsAg-positive children had not re-
ceived any Hepatitis B vaccine (one aged 14 years old
Table 1. Baseline characteristics of 44 index subjects.
Baseline characteristics of 44 in d ex su b jects
Median age, years (IQR*) 42 38 - 47
Female gender, n (%) 20/44 (45.5)
Positive HBe antigen (Ag), n (%) 11/44 (25)
Positive anti-HBe antibodies (Ab), n (%) 33/44 (75)
HBV DNA 2000 IU/ml, n (%) 18/44 (40.9)
Serum transaminase level (ALT*) > UNV*, n (%) 14/44 (31.8)
Spouse at home, n (%) 39/44 (88.6)
HBV complete vaccination of spouses, n (%) 05/39 (12.8)
HBV serological status of spouses:
Positive HBsAg and positive HBcAb, n (%) 06/39 (15.4)
Positive HBcAb without HBsAg, n (%) 17/39 (43.6)
Negative HBsAg and negative HBcAb, n (%) 16/39 (41)
Median number of children (IQR) 2 (1 - 3)
*IQR = Interquartile range; HBV DNA = Hepatitis B virus DNA; ALT =
Alanine aminotransferase (UNV: 50 UI/mL); UNV = Upper normal value.
Table 2. Baseline characteristics of 96 children.
Baseline characteristics of 96 children
Median age, years (IQR*) 9 (5 - 14)
Female gender, n (%) 52/96 (54.2)
HBV vaccination coverage of children, n (%) 43/96 (44.8)
HBV serological status of children:
Positive HBsAg and positive HBcAb, n (%) 04/96 (4.2)
Positive HBcAb without HBsAg, n (%) 19/96 (19.8)
Negative HBsAg and negative HBcAb, n (%) 73/96 (76)
*IQR = Interquartile range.
and two aged 15 years old). The 4th one aged 2 years old
was immunized within the framework of the enlarged
vaccination program (3 doses at the 6th, 10th and 14th
week after birth). Vaccination coverage was 44.8% (43
children out of 96). These vaccination coverage among
children above 12 years was significantly less than that
of those aged 12 or less (1 of 37 children >12 years, that
is 2.7% versus 42 of 59 children 12 years, that is 71.2%;
p < 0.001). None of the 96 children had drug addiction
history or risk sexual behavior. Relationship between
HBV serological status of children and baseline charac-
teristics of index subjects and their children is summed
up in Table 3.
4. DISCUSSION
In HBV high-endemic areas, like Côte d’Ivoire, the two
main transmission ways are perinatally or vertical trans-
mission and intrafamilial hor zontal transmission in early i
Copyright © 2013 SciRes. OJGas
K. A. Attia et al. / Open Journal of Gastroenterology 3 (2013) 237-240
Copyright © 2013 SciRes.
239
OJGas
Table 3. Relationship between HBV serological status of children and baseline characteristics of index subjects and their children.
Univariate analyses
Multivariate analysis
HBV serological status of children
Infected Uninfected p HR (95% CI) p Baseline characteristics
n (%) n (%)
Children >12 years 16/23 (69.6) 21/73 (28.8) <0.001
Male gender children 10/23 (43.5) 34/73 (46.6) 0.795
Unvaccined children 22/23 (95.7) 31/73 (42.5) <0.001 30.9 (3.8 - 95.2) 0.003
Index subjects >42 years* 17/23 (73.9) 30/73 (41.1) 0.006
Female gender index subjects 5/23 (21.7) 36/73 (49.3) 0.02
Both parents’ infected* 22/23 (95.7) 34/65 (52.3) <0.001 7.9 (1.9 - 60.2) 0.03
Vaccined spouses* 1/23 (4.4) 8/65 (12.3) 0.436
Biological results of index subjects
ALT* > UNV* 14/23 (60.9) 21/73 (28.8) 0.005
Positive HBeAg 14/23 (60.9) 9/73 (12.3) <0.001
HBV DNA* 2000 IU/ml 17/23 (73.9) 21/73 (28.8) <0.001 11.5 (2.7 - 25.2) 0.001
*Median age of index subjects, results for 88 children of 39 index subjects living with a regular spouse; ALT = Alanine aminotransferase (UNV: 50 UI/mL);
UNV = Upper normal value; HBV DNA = Hepatitis B virus DNA.
childhood [5,7]. From teenage, there exist other HBV
transmission additional risks, especially sexual transmis-
sion during unprotected intercourse and drug addiction
[5,7]. We excluded from our study all parents whose
children were above 15 years old to limit weight of all
these additional factors.
Most of index subjects were married and had at least
two children. HBV infection prevalence in children of
index subjects in our study was 24%. That just shows the
importance of HBV infection systematic screening of the
HBsAg-positive subjects’ family circle.
Out of 96 children of index subjects, only 43 were
immunized (44.8%). This weak immunization coverage
was above all observed before HBV vaccine integration
of into the EVP in 2000. Indeed, rate of immunized chil-
dren aged above 12 years was 2.7% and that of the chil-
dren aged 12 years or less was 71.2% (p < 0.001).
Among the 43 immunized children, only one aged 2
years had been screened HBsAg positive. The latter must
have been infected during perinatal period, before ad-
ministration of the 1st HBV vaccine dose of the 6th week.
HBV vaccine must therefore be privileged in delivery
room to be more efficient (immunization at birth and par-
ticularly during the 12 first hours). Indeed, in two obser-
vational cross-sectional studies made in sub-Saharan
Africa, HBV infection vertical transmission rate in new-
borns of HBsAg mothers was 32.8% [8] and 37.1% [9].
Transmission rate was significantively associated with
HBeAg mother status. When HBeAg was present in the
mother, infected newborns rate was respectively 66.7%
[8] and 54.5% [9] whereas it was respectively 26.9% [8]
et 29.2% [9] when HBeAg was absent in mother. In ad-
dition, in children who escaped form vertical transmis-
sion, there exist a risk of horizontal intrafamilial trans-
mission before immunoprophylaxis through vaccination;
that risk of horizontal intrafamilial transmission is fa-
vored by promiscuity and share of objects between par-
ents and children or between children themselves [10].
Three independent factors were significantively asso-
ciated with HBV in children of index subjects: a HBV
viremia higher than 2000 IU/ml in index subjects, exis-
tence of HBV infection in two parents and absence of
HBV vaccine for children. Many works have showed
that the key risk factor for HBV infection vertical trans-
mission was viremia in mother within perinatal period
[11-15]. Viremia in parents is as well an important risk
factor for horizontal intrafamilial transmission of HBV
infection [16], especially in children who escaped from
vertical transmission and who did not receive HBV vac-
cine. Owing to promiscuity, intrafamilial transmission
risk for the infection is all the more important since both
parents are infected. Even though it is not always easy in
studies to put things in perspective between vertical
transmission and horizontal intrafamilial transmission,
there seems the existence of a significative association
between female index subjects and HBV high prevalence
in these parents’ children [17-19]. Of these three risk
factors identified in our study, the most easily controlla-
K. A. Attia et al. / Open Journal of Gastroenterology 3 (2013) 237-240
240
ble is HBV vaccine. Current vaccinal strategy must be
modified on the one hand starting immunization from
birth in all children whatever HBV status the mother has,
on the other hand, prescribing a nucleosidic analogs from
the 28th week to HBsAg-positive mothers who have
strong HBV viremia. So, even if children are systemati-
cally immunized at birth, searching for HBsAg in preg-
nant women must be made compulsory and quantify
HBV load in HBsAg-positive pregnant women in order
to identify those to whom a treatment through nucleosi-
dic analogs will be proposed for maximal reduction of
HBV infection perinatal transmission. Acquired immu-
nization through vaccination will allow to later prevent-
ing children from other HBV transmission risks, espe-
cially horizontal intrafamilial transmission.
5. CONCLUSION
Immunization coverage for children of our index subjects
was insufficient, especially before introduction of HBV
vaccine into the EVP. Outside vertical transmission,
those children were more exposed to HBV intrafamilial
transmission when they were not immunized against
HBV, when both parents were infected and when HBV
viremia of index subjects was higher than 2000 IU/ml.
Immunization coverage must therefore be improved, im-
munization must be started at birth and nucleosidic ana-
logs must be proposed to HBsAg-positive pregnant wo-
men with strong viremia.
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