Prevalence and risk factors of hepatitis B infection among mothers and children with hepatitis B infected mother in upper Dolpa, Nepal

Hepatitis B Virus (HBV) infection is a worldwide public health problem. Two hundred and forty million people are estimated to be chronically infected, particularly in low and middle income countries [1‐3].HBV poses a serious concern worldwide as the virus is the major cause of chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma (HCC). The prevalence of HBV is highest in Sub-Saharan Africa and East Asia where 5–10% of the general population is infected, while in the Indian Subcontinent prevalence is estimated to be 2–5% [3]. Although most of the infections are self-limiting, the remainder persist as chronic infections in carrier individuals [2]. Around 15–40% of HBV infected patients develop cirrhosis, liver failure, or HCC [4]. Approximately 500,000 to 1.2 million people die of complications related to HBV infection annually [5].

In Nepal, the prevalence of HBV in the general population is believed to be heterogeneous, though there is no representative study or survey to confirm the national prevalence among the adults [6‐8]. Most of the studies have depicted low prevalence of hepatitis B surface antigen (HBsAg) seroprevalence among the general population and blood donors, ranging from 0.4–1.2% [9‐11].

A serosurvey of children born before and after hepatitis B vaccine introduction revealed that the prevalence of infection in pre-vaccination (10–12 years) and post-vaccination (5–6 years) cohorts of children were 0.28 and 0.13% respectively [12]. However, the prevalence of HBV infection is not homogenous due to differences observed within regions as well as ethnic groups. The Sherpas and Gurung residing at northern border of the country have a higher prevalence. HBsAg seroprevalence was found to be 7.35% of healthy individuals in Manang and 3.5% of individuals in Gurung at Mt. Everest Base camp [13]. Similarly, many other studies have suggested that there is high prevalence (≥8%) of hepatitis B infection among subgroups in mountain region of Nepal, ranging from 21 to 38% [8, 14‐16].

In endemic areas, most infections occur in infants and children as a result of maternal-neonatal transmission or close childhood contact [17]. Children who are not HBV infected at birth remain at risk from long-term interpersonal contact with their infected mothers [18]. The disease outcome is determined by the time of exposure as early neonatal exposure has high morbidity and mortality rates [19, 20].

The determining factor for progression of acute HBV infection to the chronic lifelong carrier stage is the patient’s age at acquisition of the virus. Thus children acquiring infection perinatally or within 6 years of age are prone to develop chronic infection [21].

This study was conducted to determine the prevalence and identify the risk factors of hepatitis B infection among the children with a hepatitis B infected mother in upper part of Dolpa district, the most remote part of Nepal.

The prevalence of HBsAg, if equal or greater than 8% is considered as high endemic [1]. This study showed that the prevalence of hepatitis B infection is very high among the mothers, and the youngest children under 5-years living with HBsAg sero-positive mothers in the upper part of the district, whereas the national prevalence of the infection in the general population is considered low (0.9%) [6]. Hence, it can be described as an issue of health disparity affecting indigenous mothers and children in Nepal.

Among HBV infected mothers, 40% were carried HBeAg seroprevalence. The majority of the children living with HBeAg positive mothers were HBsAg positive. Obviously, in highly endemic areas with HBeAg positive mothers, HBV is most commonly spread from mother-to-child at birth or perinatal transmission (WHO, #1292;Li, 2015 #1200;WHO, 2017 #1424). But in this study the proportion of positivity has increased with age group, so it can be assumed that there was other horizontal mode of transmission along with vertical one, which calls for a further study to know the relationship.

In our study 60% of children living with HBeAg positive mothers were found to be HBsAg positive, which was higher than sub-Sahara Africa (38.3%) between 3 and 12 months of age and lower than many other studies (70–90%) in Asia; whereas 40% of children living with HBeAg negative mothers were HBsAg positive, it is higher than sub-Saharan Africa (4.8%) [24] but in concordance with many other studies (< 10–40%), in the absence of post exposure immunoprophylaxis [25‐27].

A significant proportion of children were HBsAg negative who were living with HBeAb positive mothers as in other studies [28]. It is due to the seroconversion from HBeAg to HBeAb, which usually indicates lower viral loads [29]. Further studies are required whether the seroconversion was due to spontaneous or local food or medicines as the “Thikpa or Thigba”, a local name of disease which is characterized by loss of appetite, distension of abdomen, yellowish discoloration of the conjunctiva/skin, dark urine are extensively treated by the local Amchi (a traditional doctor) and Lama with a various local herbs [8]. They perform wide ranges of health care activities such as chanting mantras for well-being and prescribing local herbal pills to cure the diseases as per their own diagnosis criteria and disease classification system [8, 14]. The Amchis also provide various surgical interventions to cure Thigba/Thikpa to their community through sucking, cutting and letting the blood from the big veins of the body but they are still unaware of proper sterilization practices and procedures [8], the impact of intervention needs to be assessed whether it has risked the transmission or prevented the infection in the community.

In this study male children were more infected than female ones. The proper explanations are not known, but male child is prone to most of infections compared to female child [30, 31]. Some of the studies had identified behavioral differences between sexes as an influencing factor, while other hypothesized that double X chromosome in females and random activation is also a factor for antibody development which may have protected the female child [32]. The explanation behind the cause of disparity of the prevalence of hepatitis B among sexes is not known. However, the disparity could have an impact on public health as it is estimated that the lifetime risk of death from Chronic Hepatitis B Infection (CHB) was 40–50% in men, and about 15% in women [33].

Using condom in their last sexual intercourse was nil. Utilization of ANC services was poor. It could be due to lack of awareness, unavailability of health care services and a far-flung settlement from the health post and district hospital. Only few (4%) mothers used a new/boiled blade to cut their newborns’ umbilical cord, majority of the mothers used old scissors and knives to cut the baby cord. There is a high chance of transmission of the infection while using the unsterilized contaminated scissors and knives. Furthermore, the poor availability of indicated items for infection prevention (0.2%) at health facilities in the mountain ecological region [34] could be a contributor to the high prevalence of the infection.

The National Immunization Program (NIP) has administered hepatitis B vaccine starting at 6 weeks of age [35] considering the low prevalence of the infection and other feasibility issues. Mothers were not screened for the HBsAg, an overwhelming numbers of participants had never had vaccinated against the HBV. Newborns were neither administered hepatitis B vaccine at birth nor hepatitis B immunoglobulin by the NIP. In the high endemicity setting (HBsAg prevalence ≥ 8%), the infection is mainly transmitted at birth or during early childhood (< 5 years), the first vaccine dose at birth are recommended, which prevent transmission of the infection by more than 90% of cases [36].

Only one-third of the children were administered three dose of hepatitis vaccine, among them more than half children were infected. The proportion of infection among the children increased with an increase in age groups. It has suggested that there is a horizontal transmission of hepatitis B infection among the children in addition to perinatal transmission. However, the perinatal and early neonatal transmission could be effectively prevented by at birth vaccination and immunoglobulin [2, 37]. Likewise, the horizontal transmission could be prevented with effective vaccination, awareness and education program. The finding has raised questions on the coverage of the NIP, the timing of the vaccination and effectiveness of the program.

Alcohol consumption was very common among the women and the infection prevalence was high among the children living with mothers who consumed drinks containing alcohol during their pregnancy compared to non drinkers. Generally, an alcohol use is associated with sexual risk behavior [38], though it requires a research for culture-specific and context-specific ways of dealing with the problems. There is a need for an in-depth understanding of the alcohol consumption that influences the risk behaviors for hepatitis B transmission and its consequences on them. Furthermore, both heavy alcohol consumption and hepatitis B are independent risk factors for the hepatocellular carcinoma [39, 40].

The majority of the infected mothers belonged to Janajati followed by Dalit and others. Janajati is Nepali word for indigenous people [41]. Indigenous and Tribal Peoples Convention, 1989 defines the indigenous people as the, tribal peoples in independent countries whose social, cultural and economic conditions distinguish them from other sections of the national community, and whose status is regulated wholly or partially by their own customs or traditions or by special laws or regulations.” In Nepali history the Janajatis have been excluded from the mainstream and these people are living in abject poverty [41]. Likewise, these people have been excluded from the modern health care services as they live in the remotest areas from the hospitals, have poor access to other promotive and preventive health care services [8].

This study revealed that the prevalence of HBsAg is high among mothers and children living with hepatitis B positive mothers in the indigenous community of the upper Dolpa. In this endemic setting, the infection is mainly transmitted at birth or during early childhood. The hepatitis B vaccine series with the first dose at birth prevents the transmission of the infection in greater than 90% of cases.

A comprehensive intervention on prevention, control, and treatment are required in endemic areas to address the current and future associated liver health problems considering the high prevalence of the infection and additional risk factors, such as alcohol abuse, lack of safe sexual practices, poor access to modern health care services, and harmful traditional health care practices.