Cross-sectional study of hepatitis B virus infection in rural communities, Central African Republic

Despite the availability of an effective vaccine, infection with hepatitis B virus (HBV) remains a major worldwide health problem: over 2 billion people have been in contact with the virus, and there are 400 million chronic carriers and 1 million deaths per year [1]. It is hyperendemic in sub-Saharan Africa and Asia [2–5]. HBV is the type species of the Hepadnaviridae family and is categorized into eight genotypes (A to H) on the basis of a divergence of more than 8% in the entire nucleotide sequence of the viral DNA. Recently, two additional genotypes, I and J, were tentatively proposed [6, 7].

There are several routes of HBV transmission in sub-Saharan Africa. The highest prevalence is reported in 20–40-year-olds, and horizontal transmission in early life, as a consequence of close family contact, is the most common route of infection [8, 9]. In the Central African Republic (CAR), E is the prevalent genotype among HBV-infected patients, although genotypes A1, D4 and a genotype E and D recombinant have also been reported [10].

Most studies of the seroprevalence of HBV in the CAR have been conducted in urban areas, mainly Bangui [10–12], with only a few in rural areas [13, 14]. In order to obtain a more precise idea of the impact of HBV infection in rural communities, we performed a survey in four prefectures of the country.

The overall prevalence of HBV detected in the present study was slightly higher than that reported in blood donors in Burkina Faso (14.96%) [18], lower than those reported in pregnant women in the United Republic of Tanzania (56.2%) [19] and in Ghana (67.1%) [20], in a cohort of students in Bangui (42.3%) [11], in blood donors in Cameroon (86.8%) and Sudan (36%) [21, 22] and in the staff of a public hospital in Luanda (79.7%) [23]. The diversity of the observed prevalence is probably due to the diversity of patients and population groups and differences in sampling method, test kit sensitivity and specificity or differences between rural areas and large cities. In large cities, population movement and a permissive lifestyle increase the risk for exposure to this disease.

Dried blood spots are now commonly used for serology and molecular biology testing. The only problem encountered so far is a slightly lower sensitivity, although reliable results are obtained. The technique permits surveys to be conducted in remote areas, as it requires little equipment, the cost of sampling is low, and it is widely accepted as it is almost painless [11].

A better estimate of the prevalence of HBV infection in rural areas throughout the country would have been obtained if we had surveyed all 16 prefectures; however, this was not possible because of the absence of practicable roads and wide insecurity. Nevertheless, the prevalences of HBV in the four prefectures studied (Lobaye 29%, Nana-Mambéré 28%, Ouaka 29% and Ouham 23%) are similar and lower than the only previous prevalence data published more than two decades ago in the prefecture of Ouham-Pendé (61% in 1984 and 48% in 1988) [13]. Similarly, the HBsAg prevalence was lower than in Ouham-Pendé (20.9%) [14] in all prefectures except for Ouaka (19%, Figure 1). The high HBsAg prevalence in Ouaka prefecture was not statistically different from that in the other three prefectures, probably because of the relatively small number of people investigated. Individuals positive for antibodies against HBc but HBsAg negative were found commonly (16.5%), and viral DNA was detected in five. Thus, the number of patients with active HBV infection is underestimated if only HBsAg prevalence is considered. Inability to detect HBsAg may be due to a mutation (G145R for example, which abolishes HBsAg specificity); however, such mutants are unlikely to be selected by vaccination [24], which in the CAR is given only to young children within the expanded programme of immunization (EPI) . A high prevalence of HBV DNA in the absence of HBsAg was previously described among students in Benin, which was not explained by mutations in the S gene sequence [25], and has also been observed previously in the CAR [10]. A certain characteristic of the population that favours occult infection is a possibility and requires additional investigation [26]. Occult infections are often overlooked, as these patients are considered uninfected on the basis of HBsAg test results. As a consequence, a diagnosis of chronic hepatitis B should systematically include screening for HBV DNA when antibodies to HBc are present and HBsAg is not.

Analysis of the socio-demographic data did not reveal any significant risk factor for acquiring HBV infection in rural areas of the CAR. Nevertheless, small traders were more often affected than people in other professions (50%); sexual practices (30–40%), tattooing (29%), blood transfusion (13%) and dental surgery (10%) were other possible risk factors. These percentages were much lower than in a cohort of students in Bangui [11] (sexual practices, 38.2–53.3%; tattooing, 42.4%; blood transfusion, 39.4%; dental surgery; 38%). It is possible that other unknown or unstudied risk factors contribute to the transmission of HBV in rural CAR, and large-scale studies should be performed, including more risk factors.

In contrast to other studies [4, 21, 23] that showed a certain diversity of HBV genotypes in Central African countries, this study confirms that genotype E is highly predominant, not only in Bangui [10] but also in rural areas of the CAR, supporting the hypothesis that this country is part of the vast genotype E crescent, spanning Africa from Senegal to Angola [25]. Characterization of HBV nucleotide sequences from a large sampling in rural CAR should be undertaken to better evaluate the genetic variability of this virus in these areas.

HBV infection is a major health issue in the CAR, as shown by high prevalence rates. The prevalence in the four prefectures is close to that in Bangui, and only genotype E sequences were found. This high prevalence confirms that HBV is responsible for high rates of morbidity and mortality in CAR. The results underline the necessity for adult vaccination against hepatitis B in addition to HBV vaccination included in the EPI since November 2008.