Chapter one-Introduction

1.1. Background
Hepatitis is inflammation of liver most commonly caused by viruses. Of these viruses Hepatitis
B virus (HBV) account substantial proportion and can cause both acute and chronic disease. The
main pathogenesis mechanism that cause sign and symptoms of acute HBV infection is the
host’s cell mediated immunity and inflammation (1).

Hepatitis B virus (HBV) is an envelope virus with a viral genome of partially double stranded
circular DNA which belongs to the family Hepadnaviridae (2, 3).The virus consists of a
nuclocaspsid and an outer envelope composed mainly of three hepatitis B surface antigen (HBs
Ags) that play a central role in diagnosis of HBV infection. The nuclocaspid contains hepatitis B
core antigen (HBcAg) a deoxyribonucleic acid DNA polymerase reverse transcriptase, the viral
genome as well as cellular proteins(4).

HBV is contagious and easily transmitted from infected individual to another by blood to blood
contact, semen and other body fluids ,unprotected sexual intercourse ,reuse of needles and
syringes either in health care institution or through tattooing, sharing of eating utensils and other
barber shop and beauty salon equipment mother to child(5).

Infections by HBV in pregnancy come with its attendant effect on both mother and child (6). It
has been reported that 10-20% of HBsAg positive pregnant women transmit the virus to their
babies and women, who are positive for both HBsAg and HBeAg, have a chance of transmitting
HBV to their newborns at birth nearly 100%. Up to 90% of the newborns born to these mothers
go on to develop chronic hepatitis B if they do not receive hepatitis B immune globulin and
hepatitis B vaccine at birth(7). Although this means of transmission has not been reported to be
teratogenic, a higher incidence of low birth weight, low intelligence quotient, liver cirrhosis and
hepatocellular carcinoma in young adulthood may result (8).

Sign and symptoms of acute HBV infection include fever malaise, and anorexia followed by
nausea and vomiting, abdominal pain and chills are also possible classic enteric symptoms of
liver damage s many as 10% of patients with chronic hepatitis may develop cirrhosis and liver
failure or cancer(9). Several vaccines have been developed for the prevention of HBV infection.
These rely on the use of one of the viral envelop protein HBsAg(hepatitis B surface antigen or
HBV).The vaccine was originally prepared from plasma obtained from patients who had long
standing hepatitis B virus infection. However, currently, it is made using a synthetic recombinant
deoxyribonucleic acid DNA technology that does not contain blood products. one cannot be
infected with hepatitis B from this vaccine(10) .HBV infections are diagnosed mainly by
serologic technique either by enzyme linked immunosorbent serologic assay(ELISA)or rapid test
kits, the diagnosis of HBV is conducted by detection of viral antigen like HBsAg, Hepatitis
antigen(HBeAg)and HBcAg and serum pattern of antibody to individual antigen. When neither
HBsAg nor anti HBsAg can be detected (window) diagnosis depend on measure of IgM anti
HBcAg. HBV has no specific treatment; interferon alpha may be effective to treat HBV chronic
infection. Immunoglobulin against HBV also can be administered as post exposure prophylaxis,
especially prescribed for infants. To prevent and control HBV infection there should be pre
transfusion blood screening, avoiding life style that facilitate viral transmission, avoiding life
style that facilitate viral transmission avoid intimate contact with chronic carriers for HBV,
vaccine is also available and prescribed for high risk groups and infants as special case(11).
1.2 Statement of the problem
Hepatitis B virus (HBV) is major global health problem over 20 million people are infected
annually with this virus globally and there are 350-400 million chronic carrier of Hepatitis B
virus (HBV) (12). Globally, there are 400 million people infected with HBV, and the risk
continuous to rise as prenatal and early childhood infections revamp which risk over 95%of the
infected persons to change to chronicity. (13) In Africa burden of hepatitis B virus (HBV),
between 56%and98percent of the adult population show evidence of past exposure to HBV
infection has been estimated to range from 6% to 20%. According to WHO 2017 report, HBV
infection in pregnancy can result in occurrence of pre term delivery and low birth weight in
addition to vertical transmission.(14 15 16) one of the major causes of death in the continent.
HBV have great impact on economy as they mainly attack working age group (30-45) with
virtual mortality rate of 100% (17). Infections of HBV are by far the most prevalent, and their
consequences can be serious. Long term chronic infection with one or both of these viruses is the
most common cause of liver fibrosis and cirrhosis, leading to liver failure and hepatocellular
carcinoma (18). Liver diseases are common in Africa and account for high morbidity and
mortality. Hospital based analysis indicate that acute viral hepatitis, chronic hepatitis, cirrhosis
and hepatocellular carcinoma are responsible for at least 12% of medical admissions and over
20% of hospital mortality in many parts of Africa(19).

Most countries in Africa have a high HBV endemicity, with the exception of Morocco and
Tunisia, which have intermediate endemicity.(20)A prevalence rate of 10% of HBV was found
among pregnant women in Hong Kong,(21) 2% in Taiwan,(22)n and17.3% in Burkina Faso(23)

In Ethiopia as in other Sub-Saharan Africa, the prevalence of liver disease is high. They account
for 12% of the hospital admissions and 31% of the mortality in medical wards of
Ethiopian Hospitals (24). In an earlier study done to define the mode of transmission of Hepatitis
B infection in Ethiopia, 5% of pregnant women were reported to be positive for HBsAg (25). A
study among Ethiopian women attending antenatal care (ANC) in Addis Ababa hospitals, the
prevalence of HBsAg was 5% (26). Blood and blood products are the main routes through which
the virus is transmitted. Only a very small amount of blood is needed for transmission (down to
0.00004 ml intra dermally). The risk for transfusion-associated HBV infection has been greatly
reduced since the screening of blood for HBV markers a2nd the exclusion of donors who
engage in high-risk activities, the transmission is still possible when the blood donors are
asymptomatic carrier with HBsAg positive (27).

Since HBV infected pregnant women are at risk of infecting their babies, knowing magnitude of
HBV status and its risk factors in the area is very important. However, there is paucity of
information on prevalence of HBV and associated factors among pregnant women in Ethiopia.

An improved understanding of HBV infection routes among the population reduce the risk of
HBV infection, which isa especially true for young people serving in the military. Young males
and females in the military are one group in which it is important to recognize risk behaviors
associated with parentally transmitted diseases. Military personnel often live in camps,
predisposing them to expose to common routes HBV transmission sharing daily utensils, such as
hairbrushes, combs, razors, is common among people living in groups and is behavior that may
facilitate the transmission of viruses(28).

Soldiers frequently travel for professional reasons and may spend extended periods of time apart
from their family. This may encourage soldiers to have multiple sexual partners, increasing their
risk of exposure to sexually transmitted infection (29)
1.3 Significant of the study
The purpose of this study to assist Hospital medical directors, governmental and non-
governmental organizations in collaboration with Defense Health head office to be aware of the
prevalence and help to develop appropriate strategies for promoting awarenesscreation in the
defense force personnel and improving HBV vaccine coverage, based on the magnitude and
identified associated factor.And also such data are fundamental for health planers and care givers
for evidence-based intervention. And also to health professional improve managing the pregnant
mothers and their new born.In general to plan vaccination and other preventive strategies and
also end results of this study will be used as a base line for further study.
 Chapter two-Literature review
2.1 Prevalence for Hepatitis B virus

Hepatitis B virus (HBV) was identified more than 50 years ago, and it was soon found that the
infection is among the most frequent and important in humans. It causes a wide spectrum of liver
diseases, spanning from fulminate hepatitis to cirrhosis and hepatocellular carcinoma. In the last
couple of decades, the understanding of HBV infection, especially the management of chronic
infection, has evolved drastically. The pathogenesis of this virus has become clearer after basic,
clinical, and epidemiological studies. More constructively, the infection can now be prevented
effectively, and the chronic infection can be suppressed efficiently, shedding light at the end of the
tunnel toward the elimination of HBV infection. (30)
Hepatitis B virus (HBV) is major global health problem over 20 million people are infected
annually with this virus globally and there are 350-400 million chronic carrier of Hepatitis B virus
(HBV)(12).Globally, there are 400 million people infected with HBV,and the risk continuous to rise
as prenatal and early childhood infections revamp which risk over 95%of the infected persons to
change to chronicity(13). In Africa burden of hepatitis B virus(HBV),between 56%and98% of the
adult population show evidence of past exposure to HBV infection has been estimated to range
from 6% to 20%. According to WHO 2017 report.

Global epidemiology of HBV infection is based on prevalence of HBV surface antigen (HBsAg)
in the population. Countries are classified into three categories of HBV endemicity: low (<2%),
intermediate (2- 7%), and high (=8%) prevalence of HBsAg (31).

The study conducted in Gambia to assess hepatitis B virus sero prevalence among pregnant
women showed that prevalence of HBsAg was 9.20% among all pregnant women. Based on
these report women who were likely to have been vaccinated had a prevalence rate of 2.30%,
while those unlikely to have been vaccinated had a prevalence of 13.71%. There was statistically
significant between those likely to have been vaccinated and those unlikely to have been
vaccinated. (32)
Study conducted in dawro zone southern region to assess sero-prevalence of hepatitis b virus
surface antigen and factors associated among pregnant women by cross sectional study showed
that the prevalence was 3.5%.the risk factors identified in this study abortion history and
multiple sexual partner were most significant associated with HBV infection among pregnant
mothers(33).

In a study done at the Muhimbili National Hospital (MNH) in Tanzania, the sero-prevalence of
HBV showed no association with marital status, previous history of jaundice, history of blood
transfusion and age (34).Studies conducted at São Luís, Maranhão in Brazil was observed that
only family history of hepatitis and low level of education was positively associated. Family
history could be explained by the possibility that some patients have family members with HBV
infection, who could have transmitted the disease to them and then cleared the virus (remaining
the markers of contact). Such occurrence is frequent after five years of age, which already clearly
shown in some regions of the world, including Brazil (35).

Relatively many studies on sero-epidemiology of HBV prevalence among pregnant women in

Ethiopia have been previously done in Northern part of the country. The study that was
conducted on sero-prevalence of sexually transmitted infections (STIs) among antenatal care
attendees in Gondar (Northwest Ethiopia) reported as 7.3% was accounted for HBV(36), where
as in more recent studies in this region of Ethiopia determined the prevalence of 4.9% and 3.8%
in Dessie referral hospital and in Bahir Dar city, respectively(37,38).Moreover, a study from
Southern Ethiopia reported a sero-prevalence rate of 6.1% (39); where there are scarce
published studies on HBV among pregnant women in this region which is also similar for eastern
part of Ethiopia.
2.2 Magnitude of HBV infection
In a study conducted in Greece by Papaevangelou et al, in [2006] on a screening program for
HBV infection in a total of 3,760 delivering pregnant women, shows that prenatal screening for
HBsAg was documented in 91.3%. HBsAg prevalence was 2.89%. Higher prevalence of HBV
infection was noted in immigrant women 9.8%. Other risk factors associated with maternal
HBsAg positivity included young maternal age and absence of prenatal testing. No prenatal or
prenatal HBsAg testing was performed in 3.2% women. Delivering in public hospital and
illiteracy were identifiable risk factors for never being tested (40).

In Iran, a study done on the prevalence of HBV infection among pregnant women in 2015 on a
total of 24853 women shows that Prevalence of HBV infection among pregnant women was
estimated as 1.2%. Among different risk factors assessed, only familial history in four studies out
of five relevant evidences was statistically significant (41).

Other study done in Jazan region, kingdom of Saudi Arabia, by Ibrahim B et al, in 2012 on the
prevalence and risk factors of HBV among pregnant women shows an overall HBV prevalence

of 4.1%. The study identified past history of hospitalization and jaundices are important risk
factors for transmission of the infection (42).

In a cross sectional study conducted in Southwest Nigeria by Chinenye Gloria A.et al, in 2013
prevalence, socio-demographic features and risk factors of Hepatitis B virus infection among 180
pregnant women were determined. Sero prevalence of HBsAg was 8.3% out of which 26.7%
were positive for HBeAg, 53.3% had HBeAb, 20% had neither HBeAg nor HBeAb. The highest
HBV infection rate occurred in 25-29 age groups. Multiple sexual partners (OR= 3.987) and
early age at sexual debut (OR- 11.996) were independent risk factors for HBV infection (43).

A study conducted on the sero prevalence of HBsAg and factors associated in 289 pregnant
women in Dawro zone, SNNPR, Southwest Ethiopia by Chernet et al, in 2015 shows an overall
prevalence of 3.5%. Multiple sexual partner (AOR = 6.923), and abortion history (AOR =
4.975), were significantly associated with hepatitis B virus surface antigen (HBsAg) infection
(44).
In a hospital-based cross-sectional study conducted in Southern Ethiopia, by Metaferia Y.et al, in
2015, among the 269 pregnant women investigated the overall seroprevalence of HBsAg was
7.8% and the prevalence of HIV infection was 5.2%, of whom two participants (14.2%) were
also positive for HBsAg. Pregnant women with no formal education (odds ratio, 3.68) were more
likely to be infected with HBV than those who had completed at least secondary school.
Although HBsAg was detected more often in pregnant women who had multiple exposure
factors (8.8%) than in pregnant women who had not experienced possible risk factors (4%,), this
difference was not statistically significant (OR, 2.33) (45).

2.3. Factors Associated with Infection of HBV

A variety of risk factors have been found to be associated with high prevalence rates for HBV;
however, the emphasis on these risk factors varies greatly from one country to another. As HBV
is a blood-borne virus, blood and its products remain major causes of HBV transmission. Sexual
and parenteral routes(46) also reported as main routes of HBV transmission. Studies from
Nigeria have reported that HBV infection was found to be associated mainly with blood
transfusion among pregnant women (47). In contrast to the above-mentioned findings, studies of
HBV infection in pregnant women in Sudan, Yemen, and Mauritania have failed to show any
evidence of blood transfusion being a factor for transmission(48,49,50).However, previous
history of blood transfusion was reported as significant risk factor among pregnant women in
Bahir Darcity, Northwest Ethiopia( 38)

Maternal screening programs and universal active and passive immune-prophylaxis of newborn
have reduced dramatically the HBV transmission rates by 95% (51) ; Vertical transmission of
HBV is defined as positivity at6–12 months of life for the hepatitis B surface antigen (HBsAg) or
of HBV-DNA in an infant born to an infected mother(52). In fact, detection of the infection
when the child is 6 months old correlates with infection when the child is one year old and
indicates chronicity of the infection. Without prophylaxis, the risk of HBV vertical transmission
is high. The risk is highest in HBsAg and HBeAg-positive mothers (transmission rate:70%–
90%), and low for HBsAg-positive but HBeAg-negative mothers (transmission rate:10%–40%)
(53); also the risk of trans-placental transmissions known to be increased among HBeAg positive
mothers as well as those with high HBsAg titer and HBV DNA level (54).
In some studies socio-demographic factors such as age, education level, and gravidity have been
found not to be significant factors associated with transmission of HBV(48,49,50), however,
some reports have stated that history of multiple partners and becoming sexually active at an
early age is a risk factor as has been found among Nigerian pregnant women (55).

Similar finding was reported in Ethiopia, Dessie referral hospital and Jimma Zone. Cross
sectional study was conducted in Dessie; multivariate analysis showed that history of nose
piercing (AOR 18.1; 95%CI 2.9-114, P= 0.002) and history of having multiple sexual partners
(AOR 13.5; 95% CI 2.3-78, P =0.004) were significantly associated with HBV infection.
Nevertheless, there was no statistically significant association between gravidity status, home
delivery by traditional birth attendants and HIV status with that of HBV infection (37).Same
study in Jimma showed that pregnant women who experienced abortion had higher prevalence of
HBsAg (7.3%) and the odds of having HBsAg was more than twice with those pregnant women
that had history of abortion (56). High parity, polygamy, multiple sexual partners and previous
history of sexually transmitted disease(57) were shown to be a significant risk factors for HBV
infection in Nigerian pregnant women.

As tattooing and body arts have become more prevalent in recent years, their popularity
increasing among young adults. Findings of the current systematic review and meta-analysis
indicate that tattooing is associated with hepatitis B transmission (58).

Since HIV and HBV share the modes of HIV transmission, it is plausible that HBV and HIV co-
infection can occur, and this has been documented. A study done among pregnant women
showed that one out of sixteen HIV infected had HBV infection as well(59). Ethiopia being one
of the countries with high burden of HIV infection and also found in a region classified as high
endemic area for HBV; the likelihood of HBV/HIV co infection is highly anticipated(60). The
frequency of HBV and HIV co-infection was19.0% in Northwest Ethiopia (38), and the
prevalence of HIV infection among HBsAg positive pregnant women was 33.3%.

Dental treatment can be included among the risk factors of HBV infection and it is more
important in developing countries where the rate of hepatitis infected individuals is higher (61).
Dentists and dental health care workers are at a high risk of infection with both HBV and HCV
during their daily occupational experiences (62). Similarly, they can infect their patients by such
agents if adequate infection control policies are not applied(63)

Medical and surgical risk factors such as surgical procedures, home delivery, dental procedures,
and history of jaundice were all found not to be significant in some studies(56,50,51), but the
study in Northern Ethiopia among pregnant women those came to hospital and health centers for
ANC follow-up in Bahir Dar administrative city, Previous history of blood transfusion (AOR =
3.7, 95% CI, 9.02-14.84), body tattooing (AOR= 5.7, 95% CI, 1.24-26.50) and history of surgery
(AOR = 11.1, 95% CI, 2.64-46.88) were significantly associated with HBV infection (38).But in
an Indian study found no association between HBsAg status and dental treatment in a group of
71 HBV positive blood donors after multivariate analysis(64).
2.4 Conceptual framework

Related factors that exposed Socio demographic

HBV:- data:-
Multiple sexual partners Religion
Blood transfusion history Age
Surgical procedure history marital status
Uvuloctomy, HBV
occupational
Ear/nose piercing, status of
Status
Female circumcision, pregnant
income
Contact with jaundiced women
patients,
Dental extraction,
Tattooing,
Shaving by barbers,
History of abortion , Co morbidity:-
HIV AIDS status,
chemotherapy,
cancer

Fig 1, Conceptual frame work is adopted from different literature

 Chapter Three-Objective
3.1 General objective

 To assess prevalence of hepatitis B virus infection and associated factor, among pregnant
women attending selected antenatal follows up at armed force comprehensive specialized
and teaching hospital.

3.2. Specific objectives

 To determine HBV prevalence among pregnant who visit the respective study area.
 To identify associated factors to HBV infection among pregnant in the study area.
 Chapter Four-Methodology
4.1Study Area
This study will be conducted at Army force compressive specialized teaching hospital
(AFCSTH). Formerly, known as princess Tsehai memorial Hospital .The Armed Force General
Hospital was renamed after the 1974 revolution Emperor Haile Selasiel.Founded the hospital in
memory of his daughter princes Tsehai Haile Selasie, she died of illness in 1942. Addis Ababa is
the capital city of Ethiopia, which had 127 years old with surface area 527 square kilometer and
2355m above sea level on a plateau surrounded by heals and mountains. The total population is
3,384,569 according to the 2007 census. Male population was 1.31 million and female
population was 1.43 million people in 2007. The population density is estimated to be near 5,165
individual per square kilometer available. It has 10 sub city and 116 wereda. Approximately 82%
of the population orthodox Christian religions, 12.7% of residents are Muslim, 3.9% protestant,
less than 1% catholic and a smaller percentage following other faiths. Army force compressive
specialized teaching referral hospital has been established in Addis Ababa the marrow of Ethno-
Italian war their through its journey nearly 71 years ago. It is located western part of Lideta sub
city kebeles 2 and far from Federal court of Lideta 1.5 kilometer western. 8 command referral
hospitals refer to the hospitals additionally 25 health center and clinics around Addis Ababa use
this facility as referral center. The hospital has 600 beds and well organized human resources,
instruments and infrastructure. This Hospital gives medical, surgical, pediatric, psychiatric all
human immune viruses related services obstetrics & gynecology, etc.

4.2 Study Design

A cross sectional study will be conducted among pregnant women attending antenatal Clinic in
Armed force general teaching and referral hospital in Addis Ababa, Ethiopia

4.3 Study Period

The study will be conducted from May 10 –May 21/ 2021.

4.4 Population

All pregnant women who will be attended in army force comprehensive specialized teaching
hospital (AFCSTH).

4.4.1 Source population

The source populations are Mothers attending ANC program at AFGTH

4.4.2 Study Population

Those who will be attend antenatal care unit in army force comprehensive specialized teaching
hospital during the study period and who fulfill inclusion selection criteria and selected will be
considered as study population.

4.3 Eligibility Criteria

4.3.1Inclusion criteria
All pregnant women who came for antenatal care were told about the study and those randomly
selected were recruited if they consented to be a part of the study. Willing to participate in the
research by giving consent.

4.3.2Exclusion criteria
 Any pregnant woman who declined to be part of the study..
 Any woman already in labor
 Any woman who is very ill or admitted in the ICU
 Women who are not pregnant
 Women who have been vaccinated HBV

4.4. Sample size and sampling procedure

4.4.1 Sample size

Sample size will be determined by using the prevalence of Hepatitis B virus infection in
pregnancy that is reported in Hawassa (8.2%).The sample size will be determined using a single
population proportion formula considering the following assumptions: standard normal
distribution with confidence interval (CI) of 95% (Z=1.96), absolute precision or tolerable
margin of error (d=0.05), and added 10 % non-response rate; so, the final sample size will be
128.

n= (1.96)2 *0.082(1-0.082) = 116

(0.05)2
n=116

n= 116 by considering 10% for non-response then, the final sample size will be 128.

An initial sample size was 116. After considering 10% non-response, the final sample size will
be determined to be (116×10)/100 = 11.6 ≈ 17 then total

116+ 17 = 128.

Where: -

n = Sample size required

Z: Standard normal distribution value corresponding to 95% confidence interval (1.96)

d= desired level of precision/Marginal error (0.05).

P= Proportion in the target population to have HBV.

4.4.2Sampling procedure
Systematic random sampling technique will be used until calculated sample size achieved from
antenatal care. The first sample will be selected by lottery method which is3.

(N=1100 a 3month report of 3 hospitals

n=128 / calculated sample size.

K=N/n=8 so every 8 screened patient is target for data collection.

4.5 Sampling technique

Mothers attending the ANC (excluding those attending for post-natal reasons) will be selected
every 8 mother.

The Research Assistants and researcher did not want to interfere with the flow of the mother in
receiving antenatal care. Therefore, the first two women coming from each of the doctors were
asked to participate in the study by the two Research Assistants and the investigator.

Following their consent, each interviewed individually and the HBV test result will see from
card. A Research Assistant ensured that all mothers coming out of Doctor’s rooms will be
appropriately directed for study inclusion. The research assistants or the researcher picked
another woman after finishing the previous one.

4.6 Study Variables

4.6.1 Dependent variables

 Hepatitis B surface antigen

4.6.2 Independent variable

 Age
 Religion
 Occupation
 Monthly Income
 Multiple Sexual Partners,
 Blood Transfusion History,
 Surgical Procedure History,
 Uvulotomy,
 Ear/Nose Piercing,
 Female Circumcision,
 Contact With .Jaundiced Patients,
  Dental Extraction,
 Tattooing,
 History of Abortion
 History of Alcohol Consumption

4.7 Operational definitions

Antibody: is a protein that produced after hepatitis virus inter in to the body

Antigen: is substance which released by hepatitis b.

Hepatitis B virus: is a type of virus which causes liver disease

Co-infection: is an Infection caused by more than two organisms

Prevalence: is a method of measure that indicates total number of hepatitis cases.

4.8 Data quality assurance

Structured questionnaire will be prepared based on independent variables and used to obtain
demographic data, and associated factors with HBV infection which include sex, age residence;
occupation religion, maternal status, history of blood transfusion through systematic random
sampling method .pretest will be conducted in Bishoftu hospital general hospital.

The data will be collected by data collectors after training provided for data collectors by using
interviewing technique of the patient after informing the objective of data collection and will be
cheeked completeness of data by principal investigators as well as will be held securely and
placed on hard copy and soft ware files .the result will be presented by frequency and presents.

4.9 Data processing and analyzing

The collected data will be clear and check by the principal investigator for completeness and
consistency. Statistical soft ware SPSS version will be used. Finally data will be presented in
tables and graphs.

4.10 Ethical consideration

Official letter from Defense University College of health science department of nursing IRB
(institutional review board) of research committee to army specialized comprehensive hospital.
Verbal consent will be Health will be obtained and submit to army specialized comprehensive
hospital2, obtained from all patients after the information of the study subjects and result will be
dealt with confidentiality. All information will be collected, held securely and placed on hard
copy and soft ware files.

4.11 Dissemination of findings

After completion of the research the finding of the study willbe submitted to Defense University
college of health science, Department of Armed force comprehensive referral hospital, other
administration office in order to conduct further study and take an action to prevent
transmission and if it is possible will be sent to publication in scientific journal..
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