Chapter 4: Hepatitis E – Epidemiology, transmission and natural history

Johannes Lenz

Introduction

Like hepatitis A, the hepatitis E virus is a non-enveloped single stranded RNA virus of an icosahedral shape, measuring 27-34 nm in diameter. It is the sole member of the genus Hepevirus in the family of Hepeviridiea (Emerson 2004). Its existence was hy-pothesised when a retrospective analysis of clinical samples collected during hepatitis outbreaks in India in 1955 with newly developed essays for hepatitis A and B showed a high prevalence of close to 100% for anti-HAV IgG but no sign of acute hepatitis A or B. Thus the conclusion was that there must be another infectious agent for en- terically transmitted non-A non-B hepatitis (ET-NANB) (Khuroo 1980; Wong 1980). HEV was frst visualised in 1983. It was transmitted to a human volunteer in Russia and to cynomologus monkeys, causing acute hepatitis in both, and thus establishing its etiologic role in ET-NANB hepatitis (Balayan 1983).

Three large open reading frames (ORFs) of the positive-sense RNA of HEV have been described. While the largest ORF consisting of 1693 codons encodes for non- structural proteins responsible for the processing and replication of the virus, the oth- er two ORFs (660 and 123 codons, respectively) encode for structural polypeptides (Koonin 1992). Four genotypes and multiple subtypes of HEV have been identifed by phylogenetic analysis of stored HEV sequences.

Genotype 1 HEV is the main cause of hepatitis E in developing regions of Asia, Africa, and South America. In patients in Mexico, Chad, and Nigeria genotype 2 has been identified (Buisson 2000; Cuyck-Gandre 1997; Tam 1991). Genotype 3 has been found in cases of autochthonous hepatitis E in many developed regions (Banks 2004; Garkavenko 2001; Wibawa 2004) while genotype 4 has been found in industrialized regions of Asia (Lu 2006; Wang 2002). Genotypes 1 and 2 HEV appear to be confined to humans only, genotype 3 and 4 have been found in swine and wild animals (Lu 2006). Only one serotype of HEV is known.

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Sample

Hepatitis B – Epidemiology, transmission and natural history

J.C. Wasmuth

Introduction

It is estimated that 40% of the world’s population has had contact with or are carriers of the hepatitis B virus (HBV). This corresponds to an estimated 350 million HBV carriers (Goldstein 2005). Thus, HBV infection is one of the most important infectious diseases worldwide. Around one million persons die of HBV-related causes annually. There is a wide range of HBV prevalence rates in different parts of the world. HBV prevalence varies from 0.1% up to 20%. Low prevalence areas (0.1-2%) are Western Europe (with wide variation within Europe), United States and Canada, Australia and New Zealand; intermediate prevalence (3-5%) are the Mediterranean countries, Japan, Central Asia, the Middle East, and Latin and South America; and high prevalence areas (10-20%) southeast Asia, China, and sub-Saharan Africa. This diversity is probably related to differences in the age at infection, which correlates with the risk of chronicity. The progression rate from acute to chronic HBV infection decreases with age. It is approximately 90% for an infection acquired perinatally, and is as low as 5% (or even lower) for adults (Stevens 1975; Wasley 2008).

The incidence of new infections has decreased in most developed countries, most likely due to the implementation of vaccination strategies (Rantala 2008). However, exact data are difficult to generate as many cases will remain undetected due to the asymptomatic nature of many acute and chronic infections (RKI 2007). Nevertheless, in Germany 2524 cases of acute hepatitis B were documented in the year 2006, corresponding to an incidence rate of 1.4 per 100,000 inhabitants. In 1997 there were 6135 documented cases of acute hepatitis B. Likewise, the incidence of acute hepatitis B in the United States has decreased by 78% from 1990 to 2005 (Wasley 2008). It is expected that this number will further decrease in countries with implementation of vaccination programs. In Germany 87% of all children starting school were completely vaccinated in 2006 with a trend toward increasing coverage (Poethko-Muller 2007).

Although the incidence of acute HBV infection has decreased in most countries due to the implementation of vaccination programs, HBV-related complications such as cancers and deaths have been on the increase (Gomaa 2008). Reasons might be the delay of vaccination effects, improved diagnosis, and better documentation of HBV cases. Although a drop in prevalence has been observed in many countries, estimates are difficult due to a continuously growing migration from high or medium prevalence areas to low prevalence areas (Belongia 2008).

Transmission

The routes of HBV transmission:

• Sexual
• Percutaneous (Intravenous Drug Use)
• Perinatal
• Horizontal
• Transfusion
• Nosocomial infection (including needle-stick injury)
• Organ transplantation

There is considerable variation in the predominance of transmission modes in different geographic areas. For example, in low prevalence areas such as Western Europe, the routes are mainly unprotected sexual intercourse and intravenous drug use. In high prevalence areas like Sub-Saharan Africa perinatal infection is the predominant mode of transmission. Horizontal transmission, particularly in early childhood, is regarded as the major route of transmission in intermediate prevalence areas.

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