Prevalence and Identification of Serum Markers Associated with Vertical Transmission of Hepatitis B in Pregnant Women in Yaounde, Cameroon

1. Background and Introduction

Hepatitis is an inflammatory and necrotic liver disease.[1] Six viruses cause hepatitis A, B, C, D, E and G which can all result in acute hepatitis. Only viruses B, C and D lead to chronic hepatitis that can degenerate to cirrhosis and hepatocellular carcinoma cell; they result in about a million deaths each year.[2] Hepatitis B is the most frequent of hepatitis infections and mainly affects the young.[3] The World Health Organization (WHO) estimates that nearly 30% of the world populations are carriers of serological markers of the hepatitis B virus (HBV), among whom 350 million are carriers of the chronic HBs antigen (HBsAg). In many countries, there is no HBV mother to child transmission prevention program (MCTPP). The age of infection onset plays a very important role in carriage.

Children born to mothers with active hepatitis B are under high infection risk in early childhood and become chronic carriers.[1] Later, some of these children are exposed to high risk of death from cirrhosis or hepatocellular carcinoma in adulthood. In Africa, chronic hepatitis B virus has become one of the major causes of cancerous deaths.[4] Cameroon is an area of high endemicity for HBV infection, with an estimated prevalence between 8% and 20% of the population and a high incidence of hepatocellular carcinoma.[5] A prior study from ‘Centre Pasteur’ of Cameroon (CPC) reported a prevalence of 26.11% among women of reproductive age.[6] Another study from International Research Centre (CIRCB) reported a prevalence of 19% with molecular biology techniques and 12% with serology techniques.[7] Most infections occur during the perinatal period and infancy, an age at which a symptomatic acute hepatitis B is unlikely to occur but at which the risk of developing a chronic infection remains high.[8] Pregnancy is therefore a most appropriate period to screen for this disease. Indeed, if the mother is a carrier of HBsAg, the risk of transmission to the child in the perinatal period is high. The objective of our study, therefore, was to determine the prevalence of Hepatitis B Virus (HBV) infection in pregnant women and identify markers associated with vertical transmission of HBV.

2. Methods

This was a prospective, cross-sectional study carried out over a period of 10 months in two health districts of the town of Yaounde, namely, the district hospitals of Cité Verte and Efoulan in Cameroon. These hospitals are located in the outskirts of the city of Yaounde and are frequented by cosmopolitan populations, coming from urban, semi-urban and rural areas. The target population consisted of pregnant women under antenatal consultation in these health districts as well as the babies delivered by these mothers. We obtained ethical clearance No. 2014/12/532/EC/CNERSH/SP from the National Ethics Committee of Research on Human Health. We collected our samples through convenient sampling technique. Standard questionnaires were given (on explanation and consent of recipient) to pregnant women who came to these hospitals for childbirth. The questionnaires which were intended to collect demographic and clinical data were completed by the women after they had been delivered. A dry tube blood collection was performed on all pregnant women and babies born to HBsAg-positive mothers. Serum from the women was used to search for HBsAg through immunochromatography (HexagoneHBsAg Test) and then confirmed by ELISA (Monolisa AgHBsPlus Test). The search for HBeAg, HBeAb and HBcAb through the VIKIAR rapid test and dosage of transaminases were performed on the serum of HBsAg-positive women. Only HBsAg was tested in babies within 24 hours after birth. Biological analyses were carried out at the Laboratory of Epidemiology of the Institute of Medical Research and Medicinal Plants Studies (IMPM). A descriptive analysis was done on the study population and the relative risk and rating ratio of association measures used. The results were analyzed with EPI Info (7.0) with statistical significance fixed at <0.05 for all tests.

3. Results

4. Discussion

Viral hepatitis B is a major public health problem in our community. Our country is among the most affected by the infection given that it is situated in a high endemicity zone.[9] This high endemicity is sustained by an intense vertical transmission (mother-to-child). The woman is therefore the center of this transmission process. We investigated the seroprevalence and factors associated with HBV infection in a rural, semi-rural and urban area of Yaounde city in Cameroon. The information from this study may contribute to improving knowledge on HBV infection epidemiology in pregnant women, and may be used to inform local and national antenatal HBV screening and infant immunization policies.

We believe that the ages of the mothers included in our study were representative of those of the overall population of pregnant women in Cameroon. The rate of HBsAg carriage in mothers (7.70%) was comparable to those reported in other studies in pregnant women in urban areas of Yaounde in Cameroon, such as from studies by Fomulu et al[10] (7.7%) and Kfutwah et al[9] in 2012 (7.85%) but below the 10.2% reported by Noubiap et al. in rural areas in the far north of Cameroon. [11]

Distribution of subjects according to their HBsAg status shows that 23 of the 298 women tested positive, giving a prevalence of 7.7%. This result is close to that of 7.85% obtained in 2012 by Kfutwah[9] which was set as the national prevalence of HBV infection in pregnant women in Cameroon. Given that only 62% of deliveries take place in health centers in the presence of qualified personnel, one would expect that in the absence of any intervention, there would be an increase in the mother-to-child transmission rate of the infection.

Distribution of children according to their HBsAg status shows that vertical transmission is at a rate of 40%. In 2009, the work of Sangaré et al.[12] in Ouagadougou reported a 37.1% rate of HBV vertical transmission. This difference in results may be explained by the fact that the care given to HBsAg-positive women in Burkina Faso may be more effective and efficient.[2]

Distribution of patients according to HBeAg status shows that 30% of HBsAg-positive patients are carriers of HBeAg and 100% of these gave birth to HBsAg-positive childrenthus making HBeAg a serum marker associated with the vertical transmission of HBV with anRR = 7 and P <0.05. These results agree with those reported in 2003 by Berges et al.[13] which showed that HBeAg was a marker associated with the vertical transmission in 100% of cases in France.

HBcAb was found in all our HBsAg-positive women. This could be explained by the fact that HBcAb is the second marker to appear after HBsAg and persists even after recovery. Distribution of women according to their HBeAb status shows that 50% of HBsAg-positive women were carriers of this antibody. All infants born to these positive-tested women tested negative for HBsAg, making a zero percent vertical transmission. This result is statistically significant (P <0.05) showing HBeAb as a protective marker against the vertical transmission of HBV with an Odds Ratio of 0.00 and a Relative Risk of 0.00. These results are in agreement with those reported by Pascal Berges et al.[13] who reported a 100% protection rate for babies born to HBsAg-positive/HBeAb-positive mothers in France. According to Lok et al.[14] the presence of HBeAb in HBsAg-positive subjects was evidence of the absence of viral replication and made the subject a healthy carrier in most cases.

The distribution of infants according to the HIV status of mothers shows that two mothers (10%) were HIV-positive. This HIV/HBV co-infection had no impact on vertical transmission of HBV. However, the works of Sangaré et al.[12] in Burkina Faso showed that HIV among HBsAg-positive pregnant women was a marker associated with the vertical transmission of HBV. They claim that HIV can influence the natural history of HBV infection by increasing occurrence of chronic HBV infections and rates of HBV replication, but reduce anti-HBs and anti-HBe seroconversion rates. These opposing results could be explained by the fact that our subjects were receiving anti-retroviral treatment. The anti-HIV combination therapy seems to affect the mother-to-child transmission of HBV.

Evaluation of transmission based on markers of liver injury (transaminases GOT/GPT) shows that the average value of GOT among mothers who gave birth to negative-tested children was 18.92 IU/L and an average GPT value of 15.58 IU/L in the same subjects as against 32.00 IU/L and 31.51 IU/L as average respectively of GOT and GPT among those mothers whose children tested positive for HBsAg. These statistically significant results show a more marked elevation of transaminase values among mothers with HBsAg who transmitted it to their babies. These results corroborate the findings of Heathcote and colleagues[15] in Canada which reported that a transaminase value greater than 20 IU/L in an HBsAg-positive woman was an indication of hepatic inflammatory activity in progress. According to this study, this activity correlates with the high viral load resulting from viral replication (presence of HBeAg) and was responsible simultaneously for the vertical transmission of HBV and increase of the risk of developing hepatocellular carcinoma.[15]

5. Conclusion and Global Health Implications

The results obtained showed that mother-to-child transmission of HBV is high in Cameroon and may reflect a high risk of developing chronic infections and hepatocellular carcinomas in young adults. The chemotherapy of viral hepatitis B by molecules like Lamivudine or Entecavir is inaccessible to majority of the country’s population who are also highly affected by the HIV pandemic. Screening for HBV in women and immunization of mothers and children in the first day of life should be a priority of the viral hepatitis B programs in Cameroon. Nevertheless, to our knowledge, only the immunization of children six weeks after birth has been effective since 2005.