Pinho-Nascimento Carlos Augusto, Bratschi Martin W, Höfer Rene, Soares Caroline Cordeiro, Warryn Louisa, Pečerska Jūlija, Minyem Jacques C, Paixão Izabel C N P, Baroni de Moraes Marcia Terezinha, Um Boock Alphonse, Niel Christian, Pluschke Gerd, Röltgen Katharina
Swiss Tropical and Public Health Institute, Molecular Immunology, Basel, Switzerland.
University of Basel, Basel, Switzerland.
mSystems. 2018 Sep 18;3(5). doi: 10.1128/mSystems.00120-18. eCollection 2018 Sep-Oct.
According to the World Health Organization (WHO), an estimated 257 million people worldwide are chronically infected with hepatitis B virus (HBV), with approximately 15 million of them being coinfected with hepatitis D virus (HDV). To investigate the prevalence and transmission of HBV and HDV within the general population of a rural village in Cameroon, we analyzed serum samples from most (401/448) of the villagers. HBV surface antigen (HBsAg) was detected in 54 (13.5%) of the 401 samples, with 15% of them also containing anti-HDV antibodies. Although Cameroon has integrated HBV vaccination into their Expanded Program on Immunization for newborns in 2005, an HBsAg carriage rate of 5% was found in children below the age of 5 years. Of the 54 HBsAg-positive samples, 49 HBV pre-S/S sequences (7 genotype A and 42 genotype E sequences) could be amplified by PCR. In spite of the extreme geographical restriction in the recruitment of study participants, a remarkable genetic diversity within HBV genotypes was observed. Phylogenetic analysis of the sequences obtained from PCR products combined with demographic information revealed that the presence of some genetic variants was restricted to members of one household, indicative of intrafamilial transmission, which appears to take place at least in part perinatally from mother to child. Other genetic variants were more widely distributed, reflecting horizontal interhousehold transmission. Data for two households with more than one HBV-HDV-coinfected individual indicate that the two viruses are not necessarily transmitted together, as family members with identical HBV sequences had different HDV statuses. This study revealed that the prevalence of HBV and HDV in a rural area of Cameroon is extremely high, underlining the pressing need for the improvement of control strategies. Systematic serological and phylogenetic analyses of HBV sequences turned out to be useful tools to identify networks of virus transmission within and between households. The high HBsAg carriage rate found among children demonstrates that implementation of the HBV birth dose vaccine and improvement of vaccine coverage will be key elements in preventing both HBV and HDV infections. In addition, the high HBsAg carriage rate in adolescents and adults emphasizes the need for identification of chronically infected individuals and linkage to WHO-recommended treatment to prevent progression to liver cirrhosis and hepatocellular carcinoma.
据世界卫生组织(WHO)估计,全球约有2.57亿人长期感染乙型肝炎病毒(HBV),其中约1500万人同时感染丁型肝炎病毒(HDV)。为了调查喀麦隆一个乡村普通人群中HBV和HDV的流行情况及传播方式,我们分析了该村庄大多数(401/448)村民的血清样本。在401份样本中,54份(13.5%)检测到HBV表面抗原(HBsAg),其中15%还含有抗HDV抗体。尽管喀麦隆于2005年将HBV疫苗接种纳入其新生儿扩大免疫规划,但在5岁以下儿童中仍发现HBsAg携带率为5%。在54份HBsAg阳性样本中,49份HBV前S/S序列(7份基因型A序列和42份基因型E序列)可通过PCR扩增。尽管研究参与者的招募存在极大的地域限制,但仍观察到HBV基因型内存在显著的遗传多样性。对PCR产物获得的序列进行系统发育分析并结合人口统计学信息表明,一些遗传变异体仅存在于一个家庭的成员中,这表明存在家庭内传播,且似乎至少部分是在围产期从母亲传给孩子。其他遗传变异体分布更广泛,反映了家庭间的水平传播。两个有不止一名HBV-HDV合并感染个体的家庭的数据表明,这两种病毒不一定同时传播,因为具有相同HBV序列的家庭成员HDV状态不同。 本研究表明,喀麦隆农村地区HBV和HDV的流行率极高,凸显了改进控制策略的迫切需求。对HBV序列进行系统的血清学和系统发育分析被证明是识别家庭内部和家庭之间病毒传播网络的有用工具。在儿童中发现的高HBsAg携带率表明,实施HBV首剂疫苗接种并提高疫苗接种覆盖率将是预防HBV和HDV感染的关键因素。此外,青少年和成年人中的高HBsAg携带率强调了识别慢性感染个体并与WHO推荐的治疗方法建立联系以预防进展为肝硬化和肝细胞癌的必要性。