Hepatitis Ebook

Alternative Hepatitis C Treatments

The therapeutic goals of Natural treatment for Hepatitis C are as follows: Decrease iral load Normalize liver enzyme levels. Enhance/regulate immune system function. Strengthen and promote healthy liver function. Protect the liver, prevent further damage. Virological response; i.e. viral clearance, viral reduction or elimination of the virus. Starve the virus by limiting levels of iron. Optimizing cellular levels of glutathione in the body, making detoxification of the liver possible and enhancing the immune system. Stimulate regeneration of the damaged liver cells. Use of antioxidants to combat the effects of free-radicals generated by the virus. Reduce inflammation. Slow viral replication. Replace all of the inflammation-damaged liver cells. Regulate immune function/prevent auto-immune problems. Cancer preventative measures. Reverse fibrosis to prevent and improve cirrhosis

Alternative Hepatitis C Treatments Summary


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Hepatitis A Introduction and Definitions

Epidemics of jaundice have been reported for many centuries and the term 'infectious hepatitis' was coined in 1912 to describe these outbreaks. The term 'hepatitis type A' was adopted by the World Health Organization (WHO) in 1973 to describe this form of hepatitis, and the virus was visualised by electron microscopy in human faecal extracts in the same year. Hepatitis A virus (HAV) is spread by the faecal-oral route. It remains endemic throughout the world and is hyperendemic in areas with poor standards of sanitation and hygiene. Since the end of World War II in 1945, the seroprevalence of antibodies to HAV has declined in many countries. Infection results most commonly from person-to-person contact, but large epidemics do occur. For example, in 1988, an outbreak of hepatitis A associated with the consumption of raw clams in Shanghai resulted in almost 300 000 cases.

Hepatitis B Introduction and Definitions

Hepatitis B was referred to originally as 'serum hepatitis' it is the most common form of parenterally transmitted viral hepatitis, and an important cause of acute and chronic infection of the liver in many countries. More than a third of the world's population had been infected with hepatitis B virus (HBV), and WHO estimates that it results in 1-2 million deaths every year. The clinical features of acute infection resemble those of the other viral hepatitides. The virus persists in approximately 5-10 of immunocompetent adults, and in as many as 90 of infants infected perinatally. Persistent carriage of hepatitis B, defined by the presence of hepatitis B surface antigen (HBsAg) in the serum for more than 6 months, has been estimated to affect about 350 million people worldwide, although not all carriers are infectious. Long-term continuing virus replication may lead to progression to chronic liver disease, cirrhosis and hepatocel-lular carinoma. Primary liver cancer is one of the 10...

Prevention of Hepatitis B

General measures are based on knowledge of the mode of transmission of hepatitis B and include measures to prevent blood-to-blood contact, the use of sterile syringes, needles and other implements, screening of blood and blood products, protected casual sexual intercourse and other precautions dictated by the propensity for spread of this infection and the huge number of asymptomatic carriers of HBV in the population. The single most effective measure for prevention is active immunisation.

Hepatitis B and the Traveller

The risk of hepatitis A and hepatitis B to the traveller should not be underestimated. Travellers must take commonsense precautions to reduce the risk of hepatitis B, as outlined above. Great caution is required in any casual intimate or sexual contact, particularly with prostitutes and male homosexuals. All procedures involving penetration of the skin or mucous surfaces must be avoided if possible, including any injections, tattooing, ear and other body piercing, blood transfusion and medical and dental procedures carried out under questionable hygienic conditions. Immunisation against hepatitis A and hepatitis B is strongly recommended for all travellers to hyperendemic areas, and it is a sensible precaution in case of accidents that require treatment. Combined hepatitis A and B vacines are available, are highly effective and are strongly recommended for all travellers.

Hepatitis D Introduction and Definitions

Delta hepatitis was first recognised following the detection of a novel protein, termed delta antigen, by immunof-luorescent staining in the nuclei of liver cells in biopsy specimens from patients with chronic active hepatitis B. Later this antigen was found to be a component of a new RNA virus enveloped by the surface antigen of HBV. Hepatitis delta virus (HDV) requires a helper function of HBV for its transmission. Two forms of delta hepatitis infection are known. In the first, a susceptible individual is coinfected with HBV and HDV, often leading to a more severe form of acute hepatitis caused by HBV. In the second, an individual infected chronically with HBV becomes superinfected with HDV. This may cause a second episode of clinical hepatitis and accelerate the course of the chronic liver disease, or cause overt disease in asymptomatic carriers of hepatitis B. HDV is cytopathic and HDAg may be directly cytotoxic. Delta hepatitis is common in the Mediterranean region, parts of...

Hepatitis E Introduction and Definitions

Epidemic hepatitis, which resembles hepatitis A but is caused by a distinct and different virus, has been reported in the Indian subcontinent, Central and Southeast Asia, the Middle East, North and East Africa and Central America. Outbreaks involving tens of thousands of cases have been reported, and Hepatitis E virus (HEV) is also a common cause of sporadic acute hepatitis in these countries. Sporadic cases have been seen in other countries and in the highly developed (industrialised) countries in returning travellers from the areas listed above and among migrant labourers. The infection is acute and self-limiting but it is associated with high mortality (10-20 ) in pregnant women during the third trimester of pregnancy.

Hepatitis C Introduction and Definitions

Specific laboratory diagnosis of hepatitis types A, B and delta revealed an unrecognised form of hepatitis that was clearly unrelated to any of these three types of viruses. Surveys of post-transfusion hepatitis, after the administration of blood and blood products screened for hepatitis B by highly sensitive techniques, provided strong epidemiological evidence of 'guilt by association' of an infection of the liver referred to as non-A, non-B hepatitis. Attempts to clone the agent ofparenterally transmitted non-A, non-B hepatitis were made from a plasma known to contain high titre of the agent by experimental transmission to nonhuman primates. Because it was not known whether the genome was DNA or RNA, a de-naturation step was included before the synthesis of complementary DNA so that either DNA or RNA could serve as a template. The resultant cDNA was then inserted into the bacteriophage expression vector X gt 11 and the libraries screened using serum from a patient with chronic...

The Hepatitis C Virus

HCV is a small enveloped single-stranded RNA virus belonging to the Flaviviridae family and Hepacivirus genus 12 . Other Flaviviridae members include the flaviviruses such as yellow fever virus, and pestiviruses, which are responsible, for example, for bovine viral diarrhea 13 . The most closely related virus identified to date is GBV-B, which infects the tamarind, a new world monkey. GBV-B has also been tentatively classified as a Hepacivirus 12 . The HCV genome consists of approximately 9,600 bases, encoding a single polyprotein of approximately 3,000 amino acids, flanked by conserved 5'- and 3'-untranslated regions essential for replication and translation (Figure 2.1A). The genome is replicated in the cytoplasm by a virally encoded polymerase and translated by cellular machinery directed to the viral RNA by a highly structured internal ribosomal entry sequence (IRES)

Current Therapies For The Treatment Of Hcv Infections

The primary therapy for HCV infection is the intravenous administration of type-I interferon. Interferons are a group of endogenous proteins, which form part of the innate immune response 25 . Use of type I interferon-a was approved in 1990 and can reduce viral load and in some cases eliminate the virus completely. Many individuals do not respond, however, and many of those who respond initially do not clear their infections completely. The prolonged (up to 48-96 weeks) treatment course also has numerous side effects, including flu-like symptoms and psychiatric disorders 26 . Thus, in addition to those who fail to respond to treatment, many individuals are forced to discontinue therapy due to these side effects. Subsequent years have seen significant developments in interferon therapy. The most important have been the use of pegylated interferons, which have increased stability, and the introduction of combination therapy with the nucleoside analogue ribavirin 27 . Ribavirin is a...

Viral hepatitis E HEV

Like HAV, HEV causes malaise, anorexia, jaundice and liver enzyme serum elevation. The first outbreak occurred in India in 1955 involving over 30 000 people and was associated with a breach in the city's water supply system. The incubation period is around 40 days, a case fatality rate of 20 occurred in pregnant women in India, while 60 of sporadic cases of fulminant hepatitis seen in the country are all due to HEV. Subsequent to the Indian epidemic, hepatitis E has been reported from a number of countries in the tropics ranging from China to Mexico. The source of infection has been contaminated drinking water. The peak age specific sero-prevalence in endemic countries is in the over-16 years group - unlike hepatitis A, which usually occurs before the age of 5 years. Clinical manifestations occur in persons 25A10 years of age. Autochthonous cases of hepatitis E are rare in Western Europe and the USA.

Background and Epidemiology of Hepatitis Viruses in Correctional Settings

Hepatitis A Virus Infection Clinical Description of HAV Infection HAV infection is usually acquired by the fecal-oral route, produces a self-limited disease that does not result in chronic infection or long-term liver disease, and usually produces symptoms of acute viral hepatitis after an average incubation period of 28 days (range 15-50 days). Signs and symptoms usually last less than 2 months, although 10-15 of symptomatic persons have prolonged or relapsing disease lasting up to 6 months (Glikson, Galun, Oren, Tur-Kaspa, & Shouval, 1992). Peak infectivity occurs during the 2 weeks prior to onset of jaundice or elevation of liver enzymes, when the concentration of virus in stool is highest (Fiore et al., 2006). Persons with chronic liver disease who acquire hepatitis A are at increased risk for fulminant hepatitis (Vento et al., 1998). Following the implementation of routine hepatitis A vaccination of children, overall hepatitis A rates have declined approximately 75 from 1990-1997...

Prevention of Viral Hepatitis

Primary prevention of infection with HAV and HBV can be achieved through immunization. For HCV, primary prevention of infection activities includes screening and testing of blood donors, virus inactivation of plasma-derived products, risk reduction counseling and services (e.g., substance abuse treatment) for injection-drug users, and implementation and maintenance of infection control practices to prevent exposure to blood. Identification of persons with chronic HBV and HCV infection provides an opportunity to initiate primary prevention activities including vaccination of household, sex, and needle-sharing contacts of persons with chronic HBV infection and counseling to reduce risks for transmitting HBV and HCV to others. In addition, persons with chronic HBV and HCV infection can be provided medical management that can reduce the progression of chronic liver disease. This section summarizes current information, practices, and recommendations to prevent infection with hepatitis...

Combined Hepatitis A and B Vaccine

Recent advances in combination vaccines have resulted in the availability of two different multivalent vaccines, one containing hepatitis A and hepatitis B antigen (see below, Hepatitis B) and the other being hepatitis A and typhoid antigen (see below and Typhoid). These vaccines may be suitable for those travellers at dual risk of exposure to these diseases. The combined hepatitis A and B vaccine is licensed for both paediatric (0.1 ml 1-15 years) and adult (1.0ml over 16 years) use by the intramuscular route, with the primary course being administered at day 0, 1 month and 6 months. The corresponding levels of antibody protection achieved at each of these time points are 94 , 99 and 100 for hepatitis A, and 34 , 97 and 99 for hepatitis B. Booster doses of the monovalent hepatitis A vaccine should be administered at 10-yearly intervals, with that of the monovalent hepatitis B recommended at 5-yearly intervals at present for those travellers at continued high risk. No serious...

Combined Hepatitis A and Typhoid Vaccine

Another combination vaccine recently licensed in the United Kingdom is that of hepatitis A and typhoid. Licensed currently for those aged 15 years and over, 1.0 ml of vaccine administered intramuscularly will confer protection against hepatitis A and typhoid within 14 days. Booster doses of the monovalent typhoid vaccine must be administered at 3-yearly intervals, while that of the monovalent hepatitis A vaccine must be given at 6-12 months initially, followed by 10-yearly intervals. Again, no serious side-effects have been reported with the use of this vaccine. The future development of routine universal immunisation programmes against hepatitis A, such as those being introduced in the United States and several southern Mediterranean countries, will be of benefit to future generations of travellers, who will be protected well in advance of their travels. It could also be surmised that future universal immunisation programmes will include the use of the combination hepatitis A and B...

HIV and Viral Hepatitis in Corrections A Public Health Opportunity

Inmates are disproportionately impacted by communicable diseases such as HIV and viral hepatitis (Hammett et al., 2002, BOJ Statistics, 2002). Once incarcerated, the conditions that exist in most of the world's jails and prisons create an ideal environment for the transmission of contagious diseases. Overcrowded communal living environments, delays in medical treatment, insufficient access to clean laundry, soap, and water, and prohibitions against the use of harm reduction measures such as condoms and needle exchange increase the probability that infectious diseases will be transmitted from one inmate to another. The transient status of inmates who are frequently and often abruptly moved from one location to another complicates the diagnosis of infection, recognition of an outbreak, interruption of transmission, performance of a contact investigation, and eradication of disease. In this chapter, I will explore the disproportionate impact of infectious diseases in jails and prisons on...

Hepatitis A Vaccine

Several inactivated and attenuated hepatitis A vaccines have been developed and evaluated in human clinical trials and in nonhuman primate models of hepatitis A virus infection (D'Hondt, 1992) however, only inactivated vaccines have been evaluated for efficacy in controlled clinical trials (Innis et al., 1994). The vaccines licensed currently are Havrix (SmithKline Beecham Bio-logicals), Vaqta (Merck and Co., Inc.), Avaxim (Pasteur Merieux Connaught) and Epaxal (Berna Products). All four are inactivated vaccines.

Acute Hepatitis

Acute hepatitis is an inflammatory condition of the liver that is caused by viruses or hepatotoxins. In acute viral hepatitis, inflammatory changes in the hepatocyte are generally mild and transient, although they can be chronic (chronic active hepatitis) and severe, resulting in cirrhosis or death. Blaschke and Williams and their colleagues (12-15) have conducted informative studies of the effects of acute viral hepatitis on drug disposition. These investigators used a longitudinal study design in which each of a small number of patients was studied initially during the time that they had acute viral hepatitis and subsequently after recovery (Table 7.1). The drugs that were administered included phenytoin (12), tolbutamide (13), warfarin (14), and lidocaine (15). The most consistent significant finding was that the plasma protein binding of both phenytoin and tolbu-tamide was reduced during acute hepatitis. For both drugs, this was partly attributed to drug displacement from protein...

Viral hepatitis

There are six types of viral hepatitis - A and E, which are transmitted by the faeco-oral route, and B, C, D and G, which are blood-borne infections. Viral hepatitis A (HAV) Viral hepatitis A (HAV) Hepatitis A virus (HAV) Faeco-oral spread is the most important mode of transmission by direct or indirect contact. Sporadic cases are probably caused by person to person contact, but explosive epidemics from water and food occur. Food handlers can disseminate the infection. The ingestion of shellfish grown in polluted waters is attended by a risk of acquiring hepatitis A. Although in most parts of the tropics infective hepatitis is essentially a childhood disease, many adult patients are also seen. In many countries the incidence of infectious hepatitis is rising. Factors affecting the severity of the disease include Pregnancy - exacerbates hepatitis. Glucose-6-phospate deficiency - a high frequency of G6PD deficiency has been found among patients with hepatitis and those it ' this genetic...

Hepatitis A

Vaccination against hepatitis A is recommended for all travellers visiting areas outside northwestern Europe, North America, Australia and New Zealand, where the risks of infection from contaminated food and water and close contact with the local population may be high. Those at risk include a wide group of travellers, e.g. short-and long-term travellers, expatriates, aid health care workers, missionaries and military personnel, and those travellers with underlying medical conditions such as chronic liver disease, where infection with another hepatic virus may result in an increased burden on the liver, leading to morbidity and mortality in this group. The risks of infection with hepatitis A have been estimated as three cases per 1000 travellers per month of travel in a tourist resort, which rises to 20 cases per 1000 travellers per month of travel outside tourist resorts. As the prevalence of infection with hepatitis A has been estimated as 1.4 million cases per annum worldwide, this...

Hepatitis B

Protection against hepatitis B has gained greater importance for all types of travellers who may be exposed to hepatitis B by virtue of many risk activities as well as destination. It has been estimated that there are 2 billion people infected with hepatitis B and more than 350 million carriers of disease throughout the world. The risks of infection to travellers has been estimated to be 80-240 cases per 100 000 travellers per month of stay for long-term travellers and 2-10 times lower among short-term travellers. Therefore, hepatitis B is the second most common vaccine-preventable disease in travellers. The risk factors which may lead to subsequent infection with hepatitis B include sexual behaviour, medical or dental intervention, which may follow an accident or an adventure sports activity, acupuncture, tattooing, body piercing, haircuts, sharing razors and toothbrushes all of these may result in transmission of bloodborne viruses. Travel health care professionals should consider...

Hepatitis viruses

Donors with a history of hepatitis are deferred for 12 months. When serum from an individual with hepatitis B virus is ultra-centrifuged and examined with the electron microscope, three types of particle may be seen. The large (42-nm diameter) Dane particle is the actual virus with its central nucleocapsid core, which has its own antigenic constituent HBc. The core contains partially double-stranded DNA and DNA polymerase, and is surrounded by a lipoprotein coat carrying the surface antigen (HBsAg). The other two types of particles are 20-nm rods and spheres and represent overproduction of surface antigen material. The HBe antigen is in soluble form and is present in the incubation period, during acute infection and during the first years of the carrier phase. HBeAg is a marker of high infectivity. Dane particles are very rare in the plasma of low-infectivity carriers. All donations are tested for the presence of hepatitis B surface antigen (HBsAg) by sensitive enzyme-linked...

Hepatitis C

Hepatitis C infection is on the rise. Travel-associated risks include exposure to blood that has not been screened, sexual transmission, tattooing and occupational exposures of volunteer health care workers or missionaries to blood products or contaminated needles used for administration of medications or intravenous drug use. There is no evidence that pregnancy alters the natural history of hepatitis C or that it interferes with normal pregnancy, unless the woman already has cirrhosis and its associated complications (Reinus and Leikin, 1999). Vertical transmission is uncommon. Pregnant travelers should be advised of at-risk behaviors to decrease risk of infection. Immune globulin is not thought to be effective postexposure.

Hepatitis E

A new hepatitis E virus (HEV) vaccine is in clinical trials in Nepal (Shlim and Innis, 2000). HEV is a major cause of hepatitis in Nepal, India, Burma, Pakistan and China, the former Soviet Union and Africa (Ooi, Gawoski et al., 1999). Transmission of the virus occurs through fecal-oral exposure. HEV acquired during pregnancy has a particularly high case fatality rate (15-30 ). HEV infection is most common in persons of childbearing age (15-40 years). Clinical illness can range from mild to severe. In the non-pregnant, fulminant disease occurs in less than 1 . In pregnant women the disease may be fulminant in 20-30 . The overall fatality rate for nonpregnant patients is 0.5-4.0 . During pregnancy the fatality rate increases from 1.5 during the first trimester, to 8.5 during the second trimester and 21 during the third trimester (Reinus and Leikin, 1999). The reasons why the infection is more severe in pregnancy are not known. HEV infection acquired during the third trimester is also...


Hepatitis A is highly prevalent in the developing world. In general, by the age of 10, the vast majority of children have been exposed and have lifelong protective antibodies. Sometimes, child refugees, some incubating the disease, have caused limited outbreaks in persons having close contacts with them (Castelli et al., 1999). In Asia and Africa, the endemicity of hepatitis B is high, with over 5 carriers of hepatitis B surface antigen. Table 28.2 shows the seroprevalence of hepatitis B in asylum seekers screened in Switzerland at the time of arrival, according to their origin (Raeber et al., 1990). This illustrates its variability as the result of the level of endemicity in their country of origin it is also related to some selection inherent in the migratory process. Counselling and providing medical care to those who are chronically infected, and immunising relatives to prevent intrafamilial infection, should be carried out by medical providers. Hepatitis C is also of concern,...

Hepatitis B HBV

Hepatitis B virus (HBV) Hepatitis B is not transmitted by the faeco-oral route Hit is a blood-borne agent, transmitted by inoculatior. It is only included here for convenience. Hepatitis B virus causes long-incubation hepatitis. It also gives rise to one of the 10 most common cancers, heptocellular carcinoma. There is evidence that HBV is the aetiological agent in up to 80 of cases. Control is carried out by a combination of (i) counselling (ii) hygiene practices in high-risk areas (iii) vaccination of at-risk individuals and (iv) selective use of hepatitis B immunoglobin (HbIG). A recombinant HbsAg vaccine is now widely used. Three doses (at 0, 1 and 6 months) are required for complete protection. Vaccination is required for groups at high risk of infection (e.g. health-care staff in contact with blood or patients, homosexuals, drug users, etc.) depending on epidemiological patterns, socio-economic factors, cultural and sexual practices. In areas of the world where perinatal...

Clinical Trials Of Treatment With Palliative Intent

Bonkovsky et al. (1999) used the Medical Outcomes Study (MOS) SF-36 and additional items, to evaluate the benefit of therapy with interferon for patients with chronic hepatitis C. It was expected that most patients would have a normal life span. It had been shown that patients with hepatitis C have a clinically and socially important reduction in QoL, although it was unclear whether this results from the disease or its associated comorbidity.

Conundrums1 Behind Bars

A second conundrum is how to address the nexus of personal medical care and public health. We have learned lessons at the interface of public health and criminal justice. In the 1980s we learned about HIV and the disproportionate percentage of infected people who were behind bars. In the 1990s we learned about the prevalence and incidence of tuberculosis and the high risk of transmission in correctional facilities. And in the first decade of the twenty-first century, we are learning about viral hepatitis C and community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Every inmate who leaves a correctional facility with untreated sexually transmitted disease, viral hepatitis, HIV, or tuberculosis might be a source of transmission in the community. These are diseases typically addressed by public health authorities, agencies that because of their categorical funding may not have the resources to join efforts with correctional agencies. Every inmate who is treated for...

Substitutional Rna Editing In Mammals

RNA editing in mammals is exclusively of the substitutional type. Two types of substitutional RNA have been reported in mammals, namely adenosine to inosine (A to I) and cytosine to uracil (C to U) RNA editing (1,2). All forms of substitutional RNA editing result in an alteration of the amino acid sequence encoded by the edited mRNA, emphasizing the relevance of this model of genetic regulation in creating diversity at the level of the transcriptome. A to I RNA editing modifies pre-mRNA transcripts of the neuronal calcium-gated glutamate receptor (GluR) and serotonin (5HT) receptor-type 2c mRNA, as well as viral RNA such as hepatitis delta virus (2). A to I RNA editing is mediated through the enzymatic action of distinct members of a family of adenosine deaminases acting on double-stranded RNA (ADARs). At least three members of this gene family have been characterized, each with partially overlapping target specificity, suggesting that a range of potential targets exist for each...


Why do clinicians need to understand pharmacology when treating infections It could reasonably be argued that for the standard bacterial infection, prescribing of an appropriate antibiotic with little more than a rudimentary knowledge of pharmacology usually results in successful eradication. The same is alas not true of antiviral drugs. Unlike most bacteria, viruses utilise host cell mechanisms for their own replication and are as a general rule harder to treat. Drugs not only have to penetrate inside the cell and target these processes, but must also achieve this with minimum detriment to host cell metabolism. Toxicity is consequently increased. Many viruses (e.g. herpesviruses) have the capacity to undergo latency and are difficult to eradicate. Others such as hepatitis C produce chronic infection and require prolonged treatment. Therapeutic alternatives are more limited than for bacterial infection and pharmacological manipulation may be required to minimise toxicity or maximise...

Epidemiology and Geographical Distribution

Hepatitis A occurs endemically in all parts of the world, with frequent reports of minor and major outbreaks. The exact incidence is difficult to estimate because of the high proportion of subclinical infections and infections without jaundice, differences in surveillance, and differing patterns of disease. The degree of underreporting is very high. The mode of transmission of HAV is by the faecal-oral route, most commonly by person-to-person contact in developed countries, and infection occurs readily under conditions of poor sanitation and hygiene and overcrowding. Common source outbreaks are most frequently initiated by faecal contamination of water and food, but waterborne transmission is not a major factor in maintaining this infection in industrialised communities. On the other hand, many foodborne outbreaks have been reported. This can be attributed to the shedding of large quantities of virus in the faeces during the incubation period of the illness in infected food handlers...

Management and Treatment

Since faecal shedding of the virus is at its highest during the late incubation period and prodromal phase of the illness, strict isolation of cases is not a useful control measure. Spread of hepatitis A is reduced by simple hygienic measures and the sanitary disposal of excreta. There is no specific treatment for hepatitis A beyond general supportive measures. Passive immunisation with normal human immuno-globulin, or in selected circumstances active immunisation with hepatitis A vaccine, is indicated as soon as possible after exposure and within 2 weeks to all household and sexual contacts, and for those exposed to contaminated food. Immunoglobulin should be given to all classroom contacts in daycare centres (children under 5 years old), and, if there are infants in nappies, immuno-globulin should be given to all potentially exposed children and staff in the centre. Immunoglobulin has been used effectively for controlling outbreaks such as in homes for the mentally handicapped. It...

Nature of the Virus

The hepatitis B virion is a 42 nm particle comprising an electron-dense nucleocapsid or core (HBcAg) 27 nm in diameter, surrounded by an outer envelope of the surface protein (HBsAg) embedded in membraneous lipid derived from the host cell (Figure 6.2). The surface antigen, originally referred to as Australia antigen, is produced in excess by the infected hepatocytes and is secreted in the form of 22 nm particles and tubular structures of the same diameter. Figure 6.3 The molecular structure of the genome of hepatitis B virus Figure 6.3 The molecular structure of the genome of hepatitis B virus

Surface Antigen mutants

Production of antibodies to the group antigenic determinant a mediates crossprotection against all subtypes, as has been demonstrated by challenge with a second subtype of the virus following recovery from an initial experimental infection. The epitope a is located in the region of amino acids 124-148 of the major surface protein, and appears to have a double-loop conformation. A monoclonal antibody which recognises a region within this a epitope is capable of neutralising the infectivity of HBV for chimpanzees, and competitive inhibition assays using the same monoclonal antibody demonstrate that equivalent antibodies are present in the sera of subjects immunised with either plasma-derived or recombinant hepatitis B vaccine. During a study of the immunogenicity and efficacy of hepatitis B vaccines in Italy, a number of individuals who had apparently mounted a successful immune response and became anti-surface antibody (anti-HBs)-positive, later became infected with HBV. These cases...

Clinical Features and Diagnosis

The clinical features of acute hepatitis B are similar to those of acute hepatitis A and the other hepatitides. and by assay of viral DNA and its amplification by various techniques. All these direct techniques are often impractical in the general diagnostic laboratory, and specific diagnosis must therefore rely on serological tests. Many serological tests, mainly based on ELISA and less commonly used radioimmunoassays, are available for markers of infection with HBV. HBsAg first appears during the late stages of the incubation period and persists during the acute phase, declining rapidly when antibody to the surface antigen (anti-HBs) becomes detectable. Antibody of the IgM class to the core antigen is found in the serum after the onset of clinical symptoms and slowly declines after recovery and is replaced by IgG anticore, which persists for many years. Hepatitis B e antigen appears during the acute phase of illness and anti-e is detectable with recovery. Molecular techniques are...

Passive Immunisation with Immunoglobulin

Hepatitis B immunoglobulin is prepared specifically from pooled plasma with high titre of hepatitis B surface antibody and may confer temporary passive immunity under certain defined conditions. The major indication for the administration of hepatitis B immunoglobulin is a single acute exposure to HBV, such as occurs when blood containing surface antigen is inoculated, ingested or splashed on to mucous membranes and the conjunctiva. It should be administered as early as possible after exposure and preferably within 48 h, usually 3 ml (containing 200IUml_1 anti-HBs) in adults. It should not be administered 7 days or more after exposure. It is generally recommended that two doses of hepatitis B immuno-globulin should be given 30 days apart. Results with the use of hepatitis B immunoglobulin for

Active Immunisation

The major humoral antibody response of recipients of hepatitis B vaccine is to the common a epitope, with consequent protection against all subtypes of the virus. First-generation inactivated vaccines were prepared from 22 nm HBsAg particles purified from plasma donations from chronic carriers. These preparations are safe and immunogenic but have been superseded in some countries by recombinant vaccines produced by the expression of HBsAg in yeast cells. The expression plasmid contains only the 3' portion of the HBV surface ORF and only the major surface protein, without pre-S epitopes, is produced. Vaccines containing pre-S2 and pre-S1 as well as the major surface proteins expressed by recombinant DNA technology are undergoing clinical trial. Immunisation against hepatitis B is now recognised as a high priority in preventive medicine in all countries and strategies for immunisation are being revised. Universal vaccination of infants and adolescents is under examination as the...

Nature of the Infectious Agent

Genotype I is the commonest and isolates have been obtained from all parts of the world. Genotype II represent isolates in Taiwan, and this genotype appears to be associated with less severe disease. Genotype III from South America is associated with a fulminant form of hepatitis.

Passive immunizatioif

For example, travellers to places where infective hepatitis (hepatitis A virus) is highly endemic may be protected by inoculation with immunoglobulin. Passive immunization is also recommended for protecting individuals who are unusually susceptible to infections, for example varicella-zoster immune globulin is indicated in a child under immunosuppressive therapy who is exposed to chickenpox.

Indications and Testing

The evaluation of candidates follows a similar pattern to that of the kidney patient, with emphasis in the diabetic complications that can threaten successful transplantation. Consequently, great emphasis is placed on the cardiac and peripheral vascular workup. Cardiologic workup and clearance usually entails a peripheral vascular evaluation, chest X-rays, an EKG, a dobutamine stress echocardio-gram, and frequently a coronary angiogram. Other common tests with other transplant recipients include serologic testing (i.e., CMV, HIV, HCV, etc.), HLA, blood group testing, complete blood count (CBC), and coagulation studies, to mention a few. Ophthalmologic, neurologic, and urologic workups are performed on a case-by-case basis (Table 4.2). Absolute contraindications include active infection, recent or current history of malignancy, positive crossmatch, and HIV infection. Relative contraindications include advanced age, obesity, and cardiovascular disease. Many centers consider that, in...

Preerythrocytic Sporozoite Vaccines

Pre-erythrocytic vaccine development initially focused on inducing antibodies to the sporozoite surface. Antibodies directed to the circumspor-ozoite protein (CSP) repeat asparagine (N), alanine (A), Proline (P), NANP were shown to neutralize sporozoites in vitro but to give inconsistent protection against P. falciparum infection in vivo (Ballou et al., 1987 Herrington et al., 1987). It is likely that the failure of the early CSP vaccine was due to a failure to induce cellmediated effector mechanisms, such as cytotoxic T lymphocytes and cytokine-mediated inhibition of parasite development. It is encouraging that a hybrid containing the central repeats and most of the C-terminus of the PfCSP fused to hepatitis B surface antigen in a complex adjuvant mixture (RTS,S-SBAS4) was recently shown to be protective (Stoute et al., 1998) and is now undergoing clinical trial in the Gambia.

Diagnostic Frameworks for General Practice

'The masqueraders can be grouped into primary and secondary groups. The primary (most common) masqueraders are depression, diabetes mellitus, drugs, anemia, thyroid disease, spinal dysfunction, and urinary tract infection. A secondary (less common) list includes chronic renal failure, HIV AIDS, rare bacterial infections (e.g. subacute bacterial endocarditis, tuberculosis), systemic viral infections (e.g. infectious mononucleosis, hepatitis A, B, C, D, E), neurological dilemmas (e.g. Parkinson's disease, multiple sclerosis), connective tissue disorders (e.g. systemic lupus erythe-matosus, polymyalgia rheumatica).

Symptomatic treatment

However well children are managed there is a serious risk of blood-borne infection, particularly hepatitis B and C, HIV and, in tropical countries, malaria. Much can be achieved by adequate screening of blood products, but the possibility of these complications should be constantly borne in mind and viral infec

Porphyria Cutanea Tarda

Porphyria cutanea tarda is the most common of the porphyrias, with significant cutaneous involvement. This form may be hereditary but far more frequently is due to an exogenous agent, such as alcohol, oestrogens, iron, antimalarials (high doses), hexachlorobenzene, and chlorinated phenols. Other predisposing factors include diabetes mellitus and hepatitis C. While patients do have photosensitivity, there is some delay between sun exposure and the development of the lesions and they actually complain of skin fragility and, conversely, may appear sun-tanned.

Other Vaccine Components

Thiomersal is a preservative that contains mercury and has been used as an additive in vaccines and biological substances for some 70 years because it prevents bacterial and fungal contamination, particularly in multidose containers. In 1999, the American Academy of Paediatrics and the US Public Health Service recommended, as part of the effort to reduce exposure to mercury, that the thiomersal content of vaccines should be reduced or replaced with formulations which do not contain thiomer-sal as a preservative as soon as possible, without unnecessary disruption of the vaccine system. It should be noted that the risk, if any, to infants from exposure to thiomersal is believed to be slight. The demonstrated risks for not vaccinating children far outweigh the theoretical risk for exposure to vaccines containing thiomersal during the first 6 months of life. Single and multiple antigen vaccine preparations, e.g. Hib and hepatitis B Hib vaccines, are available and others are in preparation.

When Did They Travel and For How Long

At the other end of the scale, disease with long incubation periods may not be recognised as travel-related by either the patient or physician. Hepatitis B transmitted by tattoo during an overland trip through Asia might not cause illness until 6 months later. The increased risk of tuberculosis in immigrants persists for at least 5 years after arrival in Britain (Ormerod, 2000) and the clinical incubation period of symptomatic leprosy is several years. We have seen patients with colonic bleeding due to schistosomiasis presenting for the first time 10 years after travel to Africa. Some infections can persist for many years, such as strongyloidiasis, which we still see in ex-prisoners of war who worked over 50 years ago on the Thai-Burma railway during World War II (Gill and Bell, 1979 Archibald et al., 1993). Knowledge of the biology of the pathogen can also be integrated with the detailed travel history to recognise the limitation of investigation at different phases of the illness....

The Patient Who Has Not Travelled

A 24-year-old woman of Indian ethnic origin was admitted to hospital in Liverpool with 1 week of illness typical of acute viral hepatitis. She and her husband (also of Indian ethnic origin) had both been born and brought up in the UK. Her husband had returned from his first trip to India 2 months before, and had been managed at home with probable hepatitis starting 1 month before. She was confirmed as having hepatitis E, imported by her husband. Hepatitis E is not a common diagnosis in Western countries unless the patient has travelled overseas (Schwartz et al., 1999). This case illustrates the importance of taking a good contact and travel history in all patients.

Hepatocellular carcinoma 103

A HCCs are associated with chronic liver damage (e.g. alcoholic liver disease, hepatitis C, autoimmune disease), metabolic disease (e.g. haemochromatosis) and aflatoxins (from cereals contaminated with fungi or biological weapons). E Common making up 1-2 of all malignancies, but less common than secondary liver malignancies. incidence in regions where hepatitis B and C are endemic (e.g. southern Mediterranean, Far East). History of exposure to carcinogens High alcohol intake, Hepatitis B or C, aflatoxins. _I Bloods FBC, ESR, LFT, clotting, a-fetoprotein, hepatitis serology.

Clinical presentation

The clinical features derive from the decrease in peripheral blood cells and are non-specific. The patient may be feeling completely well at the time when easy bruising or petechiae appear or may have a more or less prolonged period of feeling tired from anaemia. Sometimes infection is the presenting feature, but this is less common in idiosyncratic aplastic anaemia than bleeding manifestations. The spleen, liver and lymph nodes are not enlarged and jaundice is only a feature in those patients with post-hepatitis aplasia who have a prolonged cholestatic phase after the infection.

Preliminary Tests For Ivf And

Preliminary tests for couples undertaking PGD are as for IVF (see Chapter 5). A gynaecological and medical history should be taken. Rubella immunity should be checked and immunization offered if necessary. Haematological screening (sickle cell and thalassaemia) and screening for Tay-Sachs disease is offered if appropriate. The male partner should be asked to produce a semen sample for analysis. As for all patients undergoing IVF, PGD patients are tested for HIV and hepatitis B and C before they undergo treatment.

Comparison With Retropubic Approach

Patients has required a blood transfusion. Recognizing the advantage in transfusion requirements appears important for a generation of surgeons less familiar with the specific advantages of the perineal approach. Blood transfusions constitute a significant cost factor but, more importantly, may be a point of major concern to patients worried about the risk of contracting hepatitis or the human immunodeficiency virus associated with heterologous blood transfusions.

Clinical Management

The first line agent for fascioliasis is bithionol, which is used at a dose of 30-50 mg kg on alternate days for 10-15 doses and has an efficacy ranging from 58 to 100 (Table 17.6) (Arjona et al., 1995 Bacq et al., 1991 Bassiouny et al., 1991 Farag et al., 1988 Farid et al., 1990). Frequent side effects include photosensitivity, vomiting, diarrhea, abdominal pain and urticaria. Rarely, leukopenia or hepatitis may occur. Unfortunately, bithionol is no longer manufactured and its availability is limited. In the USA, the CDC provides bithionol for domestic use only, while in many countries, such as the UK, it is unavailable. While praziquantel is efficacious for most trematode infections, it has had limited success with treating fascioliasis. The results have been disappointing, with cure rates of 0-71 (Arjona et al., 1995 Farid et al., 1986, 1989 Knobloch et al., 1985). Praziquantel is not currently recommended for treatment. Previous to bithionol, the drug of choice was emetine or...

Complications Of Transfusion

The risks of HIV and hepatitis B transmission are small (said to be in the order of I in 200 000 in the US), but are higher in the case of Hepatitis C (c. I in 5000). Septic reactions are rare, but commoner with platelet concentrates which are stored at room temperature.

Impact On Society Of An Aging Population

Immigration from the Third World to the developed countries will increase as countries of aging populations try to replace the loss of their labor pool. This is already happening in Europe and in the USA. This again will put further pressure on Medicare and Medicaid, as many of these immigrants will suffer from tuberculosis, hepatitis, and intestinal disease, endemic to many of their home countries. In 1997, 39 of tuberculosis cases in the USA were in foreign-born parents in California this rose to 67 (Satcher, 1999) and the annual cost of diagnosis and treatment of the 1 million immigrants was 40 million (Muenning et al 1999). This will cause further competition for available health dollars.

Liver transplantation continued

Recurrent liver disease Reinfection in the case of hepatitis B or C (if originally present) is common, the latter having the potential for an aggressive and rapidly progressive course. Hepatitis B can be managed with HB-Ig and immunisation. Other diseases that can recur include PBC, PSC and autoimmune hepatitis as well as recidivism in the case of alcoholic liver disease. Complications of immunosuppression Drug effects, infections, post-transplant malignancies, e.g. risk of skin cancers, lymphomas. Non-A, non-B hepatitis liver failure

IRESmediated Translation Initiation

Although it is clear that canonical cap-dependent initiation plays a central role in the recruitment of ribosomes to a large number of mRNAs, translation can initiate by a cap-independent mechanism on some mRNAs, and under specific conditions. This mode of initiation entails the binding of 40S ribosomes to an internal ribosome entry site, or IRES, which is mostly (but not always) part of the 5'-UTR of the mRNA. IRES-mediated translation was first discovered in picornavirus mRNAs (poliovirus 362 and encephalomyocarditis virus 363 ). Unlike all nuclear-transcribed cellular mRNAs, these viral mRNAs do not possess a cap structure and, therefore, must be translated by a cap-independent mechanism. All picornavirus RNAs (including enteroviruses, rhinoviruses, aphthoviruses and others) contain an IRES. Other viruses that do not contain a cap structure, such as HCV 364 and cricket paralysis virus (CrPV) 365 , also translate by an IRES-mediated mechanism. However, there are striking differences...

Laboratory tests on blood donations Table 165

HCV Anti-HCV ELISA plus NAT on pools of 48 samples All blood donors in the UK are tested at each donation for syphilis, HBsAg, anti-HIV 1 and 2 and antigen, anti-HCV, HCV RNA, and anti-HTLV. ABO and RhD grouping is determined routinely on each occasion. Typing for other Rh antigens (C, E, c and e) and K is now routinely performed on most, although not all blood donations, in the UK. Matching for such antigens is only performed in special cases such as alloimmun-ized patients and sickle cell disease patients. Ideally, girls and women of childbearing age should be matched for c and K, as anti-c and anti-K are, after anti-D, the major causes of severe HDN in the UK.

Relative Contraindications for Travel during Pregnancy

Record with them in case of an emergency and or to get general advice in transit or at the destination. This should include a recent evaluation by the women's health clinician. The following should be included gestational age, presence of an intrauterine pregnancy on ultrasound, fetal growth performance, and appropriate medical and obstetric history. Laboratory data should include blood type and Rh factor. Serology for toxoplasmosis, rubella, measles, chickenpox, cytomegalovirus and hepatitis B should also be considered, if not done previously.

Quantification of viral load

Quantitative PCR analysis of viral nucleic acid is now used by diagnostic laboratories worldwide and is particularly useful for monitoring viral loads in patients to assess the effect of anti-viral therapy and potentially to detect drug-resistant viral strains. In clinical virology, qPCR is commonly used for the detection and quantification of blood-borne viruses, including hepatitis B and C and human immunodeficiency viruses. However, it is also increasingly used to monitor viral pathogens of transplant patients, including Epstein-Barr virus, cytomegalovirus and BK virus. In recent years, our laboratory has used quantitative real-time PCR to investigate BK viral loads in a transplant patient population (see Protocol 14.3). BKV can cause several clinical manifestations in immunocompromised patients including hemorrhagic cystitis and allograft nephropathy. Since adopting qPCR, several limitations of this technology have been identified, including the impact of PCR inhibitors, poor...

Viral infection in transplant patients

Plant recipients is invasive, more frequent, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Epstein-Barr virus (EBV) has its most significant effect in solid organ transplant as the precipitating factor in the development of post-transplant lymphoproliferative disorders (PTLD) as well as rejection (Jabs et al., 2004). Over the past few years, PCR assay has shown that a rapid increase in peripheral blood EBV DNA load is predictive of PTLD (Qu et al., 2000). Identifying patients at high risk or in an early stage of PTLD enables EBV infection to be pre-emptively or promptly dealt with by administering anti-CD20 monoclonal antibody or EBV-CTL, or simply by reducing the immunosuppressive therapy (Wagner et al., 2004 Kuehnle et al., 2000). In conclusion, EBV reactivation, increase in viral-load detection by quantitative real-time PCR, can be managed simply by modulating immunosuppression. Hepatitis B virus (HBV)...

Vaccine Preventable Illnesses

Age alone is not a contraindication to any vaccine, although seroconversion rates may decrease with age. For the healthy older traveler, general recommendations for both routine and travel vaccines apply. Hepatitis A seropositivity rates are higher in older travelers who have lived in or traveled extensively to endemic areas, or have a prior history of jaundice serologic hepatitis A antibody screening prior to immunization in these individuals may be cost-effective (Castelli et al., 1996 Schwartz and Raveh, 1998). Live vaccines (oral typhoid, oral polio, varicella, yellow fever) should not be given routinely to immunocom-promised travelers. Elderly travelers are at higher risk of adverse events related to yellow fever vaccine (Martin et al., 1999). Immunologically impaired individuals, including those on hemodialysis, require a higher vaccine dose for hepatitis B (usually double, but consult the manufacturer's recommendations).

What Should Screening Consist Of History

Medical history taken for expatriates needs some exploration of specific components. These include any unusual health and safety risks, psychosocial factors, failed expectations, causes of sleep disturbance, signs of abnormal stress, sexual health risks, alcohol consumption, risks specific to hostile or dangerous environments and occupational health risks from HIV, hepatitis B or hepatitis C. Structured questionnaires or protocols can provide the majority of the information and make the consultation more effective.

The Migration Process And Health

This is characterised by the influences on health of the environment in which one individual or a group of migrants has lived. This refers to a broad spectrum of factors. One thinks immediately of exposure to endemic diseases such as malaria, tuberculosis, intestinal parasites or hepatitis. Nutritional factors such as sufficient intake of micronutrients, vitamins and proteins will shape the nutritional status and normal growth of children. Social and economic factors such as poverty, illiteracy, unemployment, occupational hazards, poor housing and unhygienic living conditions are among key factors shaping the future health status of migrants, as will exposure to insecurity, war, violence, torture and other human rights violations. Religion and cultural background are of course of key importance in influencing health belief and behaviours. Finally, experiences encountered in contact with the medical services in the country of origin and with other traditional...

First Encounter With Health Services

The introduction of communicable diseases by foreigners and travellers has always been of concern to health authorities. International regulations, quarantine procedures and medical screening have been designed to control the spread of diseases. At a time of worldwide mobility of millions of travellers, medical screening is still implemented for immigrants and refugees before or at the time of entry in the receiving country. It is most frequently mandatory and in some instances it determines acceptance for entering the country. No doubt migrants may be afraid that such a medical examination that may hinder them from reaching their destination. Medical screening is aimed mainly at identifying communicable diseases such as tuberculosis, hepatitis B, syphilis, HIV or other health conditions that may cause a financial burden on the receiving country. Preventive measures such as vaccinations are often implemented at that time. Much of the data available on the health of migrants are drawn...

Future of Gene Therapy

Gene therapy was initially conceived to cure monogenetic disorders, however the spectrum of gene therapeutic approaches is widening very rapidly to include everything from simple genetic disorders to acquired diseases like cancer, human immune deficiency virus (HIV), and hepatitis B virus. Somatic gene therapy has been well accepted among the general public, whereas germline gene therapy is facing ethical dilemmas (106).

Epidemiology Clinical Features and Geographical Distribution

A rotavirus vaccine, a rhesus-based rotavirus vaccine-tetravelent (RRV-TV), has been licensed in the USA and elsewhere. RRV-TV is a live attenuated oral vaccine which incorporates a rhesus monkey rotavirus strain (with human serotype G3 specificity) and three singlegene human-rhesus reassortants. Immunisation early in life, which mimics the child's first natural infection, will not prevent all subsequent disease but should prevent most cases of severe rotavirus diarrhoea including hospital admission for treatment. The US Advisory Committee on Immunization Practices (1999a) recommends routine immunisation with three oral doses of RRV-TV for infants at the age of 2, 4 and 6 months. This vaccine can be administered together with DPT, Hib vaccine, oral polio vaccine, inactivated polio vaccine and hepatitis B vaccine. RRV-TV is effective but has now been withdrawn owing to a number of adverse events.

Gene Delivery Approaches Viral Methods

Gene Delivery Viral Method

Ing application of intramuscular and ballistic plasmid DNA injection is in DNA-based immunization protocols. DNA-based vaccinations are being developed to prevent infectious diseases and cancer 40 . Cells that express a foreign protein and subsequently present that protein on their surfaces are more likely to produce a cell-mediated immune response. Such a response may be more important in fighting viral infections such as those caused by HIV, HSV, CMV, or RSV. Techniques that inject a foreign antigen usually yield an antibody-mediated response. Both the gene gun and direct intramuscular plasmid DNA injection are being used in protocols to immunize against HIV, hepatitis B and C, HSV, influenza, papilloma, tuberculosis, RSV (Rous Sarcoma virus), CMV, Lyme disease, Helicobacter pylori, malaria and Mycoplasma pulmonis.

Effects Of Pathological Conditions

Hepatic disease and damage clearly have the potential to be major factors in the metabolism of foreign compounds. Thus, in patients with liver necrosis due to paracetamol, the half-life of the latter was increased from 2 to 8 h and that of antipyrine from 12 to 24 h. Acute hepatic necrosis in animals caused by the administration of hepatotoxins resulted in the plasma half-lives of barbiturates, diphenylhydantoin and antipyrine being approximately doubled. However, there may be several factors operating such as displacement of a drug from plasma-protein binding sites by bilirubin. In liver damage, plasma-bilirubin levels may be high due to lack of conjugation with glucuronic acid. This may alter elimination of some drugs such as tolbutamide. The level of plasma albumin may often be reduced by liver disease as this is the site of synthesis of albumin, the hence binding to plasma albumin will tend to be reduced. However, the effects of liver disease can be somewhat unpredictable. For...

Druginduced Immune Suppression

The second problem in administering these vaccines is the diminished immune response. In serious immune suppression, serological tests should be carried out before and after vaccination in the case of hepatitis A, hepatitis B, rabies and tick-borne encephalitis. In all these diseases, if seroconversion has not been achieved by vaccination, A 57-year-old man is planning to make a trip through Southeast Asia. At the age of 50 he developed a nephropathy with proteinuria due to Henoch-Schonlein disease. He gradually developed end-stage renal insufficiency for which, after 2 years of dialysis, he received a kidney transplant. Since the transplant 1 year ago, he has been treated with mycophenolate mofetil (500mgt.d.s.) and prednisolone (10mgo.d.). He is in good general condition with only an unchanging mild renal insufficiency. He is advised to have malaria prophylaxis with mefloquine, in adjusted dosage according to the level of renal insufficiency. Mefloquine does not interact with...

Cirrhosis and portal hypertension

Hepatocellular Adenoma Mri

The commonest cause of portal hypertension is cirrhosis secondary to alcoholic liver disease or chronic hepatitis B or C (see Fig. 6.24), further causes are listed in Table 6.3. Imaging features of cirrhosis and portal hypertension include liver nodularity, reversal of portal blood flow (demonstrated on ultrasound), porto-systemic colateral vessels, splenomegaly, ascites and complications such as hepatoma. Porto-systemic colateral vessels occur at many sites (see Table 6.4) as a consequence of portal hypertension (see Fig. 6.25).

Integrated Cell CulturePCR for Detection of Enteric Viruses in Environmental Samples

Cell culture assay is the standard method for the detection of viable human viruses (i.e., poliovirus, coxsackievirus, echovirus, adenovirus, hepatitis A virus, reovirus, and rotavirus) in environmental samples, serving as the method against which all newer technologies are evaluated. Although cell culture is theoretically capable of detecting a single viable virus in relatively large volumes of sample, the time required for confirmed results with conventional cell culture makes it an impractical method for routine monitoring of environmental samples. Furthermore, cell culture does not detect noncytopathogenic viruses (viruses that are viable, infecting cells, and continually spreading to neighboring cells but that do not cause a visible cytopathogenic effect CPE on the cell monolayer). Rotavirus and most wild-type hepatitis A viruses (HAV) are infectious to cell cultures but do not produce a clear CPE. 2 Reynolds, K. A., Gerba, C. P., Abbaszadegan, M., and Pepper, I. L., (2001). ICC...

Assisted Reproductive Technology

The evaluation of the infertile couple often includes a panel of screening tests. This includes a cervical Pap smear, maternal blood type and Rh, antibody screening, rubella status, RPR (syphilis), varicella status, hepatitis B, and cystic fibrosis. Screening for sexually transmitted diseases is also recommended for patients at high risk, and would include hepatitis C, HIV 1 and 2, HTLV, CMV, chlamydia, and gonorrhea.

David J Reich Cosme Manzarbeitia Radi Zaki Jorge A Ortiz and Sergio Alvarez

When the metabolic abnormality is primarily within the liver, transplantation will be curative for metabolic disease transplantation, at present, is indicated only where there is also significant liver disease (e.g., hemophilia with end-stage hepatitic C virus HCV infection). Such indications include alphal-antitrypsin deficiency, antithrombin-III deficiency, protein C deficiency, protein S deficiency, Wilson's disease, tyrosinosis, Byler's disease, galactosemia, hemophilia A and B, and Crigler-Najjar syndrome. Where the disease process is extrahepatic, liver replacement is not always indicated. However, when the disease recurs, transplantation is sometimes indicated, as the effects of disease can be modified, as with genetic hemochromatosis and congenital erythropoietic porphyria. In patients grafted for cystic fibrosis, the disease may affect the graft but medium-term survival is good. In conditions such as the sea-blue histiocyte syndrome or Gaucher's disease, liver replacement is...

Possible Functions of eIF3 in mRNA Binding

Mammalian eIF3 can bind to the hepatitis C virus (HCV) and classical swine fever virus IRES elements, and the eIF3a p170, eIF3b p116, eIF3d p66 and eIF3f p47 subunits were found crosslinked to these mRNA sequences 180, 181 . The binding region for eIF3 in the HCV IRES has been localized to domains IIIa-b 180, 182 and the cryo-EM map of the IRES-40S complex places this domain extending from the platform side of the 40S subunit just below the mid-line of the particle 183 . This location is consistent with the binding site for eIF3 on 40S subunits visualized in three-dimensional (3D) reconstructions of electron micrographs of negatively stained native 40S subunits 31, 184 however, eIF3 also makes extensive contacts with the solvent side of the 40S subunit in the model of Lutsch et al 184 . It is unclear whether conventional mRNAs translated by the scanning mechanism will interact with eIF3 in the same manner utilized by the HCV IRES, as the latter bypasses the requirement for the eIF4...

Nayere Zaeri and lerachmiel Daskal

Banff Schema Liver Rejection

The allograft is susceptible to various opportunistic infections, particularly viral infection. Cytomegaloviral (CMV) hepatitis usually occurs in the first 2 to 3 months after transplantation. On infrequent occasions, CMV hepatitis can mimic rejection. The hallmark of histologic diagnosis is microabscesses (Fig. 21.3) with Hepatitis B and C infections recur in 80-100 of cases. A subfulminant form of hepatitis B, known as fibrosing cholestatic hepatitis, can occur and carries a bad prognosis. End-stage liver disease due to hepatitis C is now the major cause for liver transplant in the United States. Recurrent hepatitis C has overlapping features with rejection and, therefore, may require clinical-pathologic correlation to reach the specific diagnosis. Portal infiltrate with lymphocytic preponderance, bile duct inflammatory changes, and lobular inflammation are constant features of recurrent hepatitis C. Predominant lobular hepatitis and liver cell necrosis (apop-totic liver cells) are...

Improving Public Health Through Correctional Health Care

Section Two is about categorical public health. From a prevention point of view, we address how to reduce morbidity, mortality, and transmission of diseases that are highly prevalent in inmate populations tuberculosis, viral hepatitis, HIV, and sexually transmitted disease.

Introduction and Definitions

Stone Wallpaper Background

The last three decades have witnessed an explosion in knowledge of viral hepatitis, a major public health problem throughout the world affecting several hundreds of millions of people. Viral hepatitis is an important cause of morbidity and mortality, both from acute infection and chronic sequelae which include, with hepatitis B, hepatitis C and hepatitis D (delta) infection, chronic active hepatitis and cirrhosis, and primary liver cancer with hepatitis B and hepatitis C. The hepatitis viruses include a range of unrelated human pathogens. Hepatitis A virus (HAV) is a small unenveloped symmetrical RNA virus which shares many of the characteristics of the family Picornaviridae. It is the cause of infectious or epidemic hepatitis transmitted by the faecal-oral route. The virus is classified within the genus Hepatovirus. Hepatitis B virus (HBV) is a large double-shelled virus of the hepadnavirus group of double-stranded DNA viruses which replicate by reverse transcription. The virus is...

Median absolute RNA copy numbers

Another approach for the simultaneous analysis of multiple codons associated with drug-resistance to HIV-1 RT inhibitors was introduced some years ago 36, 37, 38, 39 , The assay, based on reverse (selective) hybridization of a biotinylated amplified part of the RT gene with specific probes present as lines on a nitrocellulose filter (line-probes), has been applied earlier for the typing of HCV strains and HLA genotypes. Currently, the HIV-1 RT LiPA is capable of detecting an array of mutations associated with resistance mutations to nucleoside and non-nucleoside inhibitors, as well as for protease inhibitors. In small studies comparing the HIV-1 RT LiPA with sequencing, it was demonstrated that the LiPA assay was highly specific and that general concordance existed between both technologies 36, 37,40, 26 , although the technology is extremely sensitive to sequence variation in the probe regions and as such is dependent on the careful selection of the probe sequences. Concordant...

Pathogenesis And Clinical Significance

Almost all of the organs of the human body can be infected by one or more of the spectrum of 14 microsporidian species described in the previous section. Many tissues and cell types are involved (Table 8.1). According to site of infection, clinical manifestations may be diarrhoea, weight loss, cholecystitis, cholangitis, bronchitis, bronchiolitis, pneumonitis, sinusitis, rhinitis, hepatitis, peritonitis, nephritis, ureteritis, cystitis, urethritis, prostatitis, keratoconjunctivitis, corneal ulcer, myositis or encephalitis. The pathology has been reviewed by Weber et al. (1994) and Schwartz et al. (1996). Cardiac disease and probable pancreatic, parathyroid and thyroid dysfunction have been reported for T. anthropophthera (Yachnis et al., 1996). Without treatment, the outcome is likely to be fatal for severely immunocompromised hosts infected with the disseminating species. E. cuniculi has been reported once as a cause of hepatitis (Terada et al., 1987) and once as a cause of...

Acquired Immune Deficiency

A 24-year-old man came for advice before trekking through India and Nepal. He had an IgA deficiency, and had been treated on and off until the age of 18 by a paediatrician with several experimental treatments. He had to be treated regularly for respiratory tract infections and had been plagued by chronic nasal congestion. As a child he had received the usual vaccinations without problems. He received diphtheria-tetanus and polio boosters, typhoid fever vaccine, hepatitis A vaccine, meningococcal A C vaccine and Haemophilus influenzae vaccine. Instructions were given on the use of standby treatment consisting of co-amoxiclav,

Transplant Recipients

Immunosuppressive agents, particularly cyclosporine and tacrolimus used to prevent graft rejection in transplant recipients, have profound effects on T cells. Aza-thioprine and corticosteroids may also be part of an immunosuppressive regimen and further impair neu-trophil function. Intracellular pathogens pose the greatest risk to these individuals. Persons who have undergone allogeneic bone marrow transplantation (e.g. for leukemia) have more severe immunosuppression than solid organ recipients, and are functionally asplenic. Live virus vaccines should be avoided because there is a risk that disease with a vaccine strain of yellow fever or poliomyelitis might emerge. Overall, transplant recipients have weaker and less durable antibody responses than normal individuals. Fortunately, there is no evidence to suggest that immunizations lead to a greater risk of graft rejection. Recent evidence shows that the hepatitis A vaccine is both safe and immunogenic in liver and renal transplant...

Screening of Asymptomatic Individuals

Laboratory testing might also be helpful for children who have spent more than 3 months overseas. A blood count with a leukocyte differential reading could give a clue of nutritional anemia (low hemoglobin concentration with hypochromic, microcytic red blood cells) or of some parasitic diseases (eosinophilia). Hepatitis B testing could help determine if a vaccine course is actually needed (yes, if negative serology) or if further evaluation is indicated (yes, if positive hepatitis B surface antigen) for chronic active hepatitis or for hepatic tumors. HIV serol-ogy would be considered for young children who were A urinalysis could give a clue to urinary schis-tosomiasis (hematuria) in an asymptomatic child returning from a long stay in East Africa or another endemic area. Hepatitis C testing is sometimes recommended for foreign-born adoptees (Miller, 1999). Very young infants and some older children who did not have newborn screening testing might benefit from screening for conditions...

Route of Administration of Vaccines

Intramuscular and subcutaneous injection. With the exception of oral vaccines and BCG, all vaccines available currently should be given by intramuscular injection or by deep subcutaneous injection. The site of injection is important the upper arm (the deltoid region) or the anterolateral aspect of the thigh are strongly recommended, and not the buttock. The injection of vaccine into deep fat in the buttocks is likely, particularly with needles shorter than 5 mm, and there is a lack of phagocytic or antigen-presenting cells in layers of fat. Another factor may involve the rapidity with which antigen becomes available to antigen-processing cells from deposition in fat, leading to delay in presentation to T and B cells. An additional factor may be denaturation of antigen by enzymes as a result of deposition in fat for many hours or days. This is well illustrated in the case of hepatitis B vaccines. There are over 100 reports of low antibody seroconversion rates after hepatitis B...

Chronic Liver Disease and Cirrhosis

Chronic liver disease is usually secondary to chronic alcohol abuse or chronic viral hepatitis. Alcoholic liver disease is most common and begins with the accumulation of fat vacuoles within hepatocytes and hepatic enlargement. There is a decrease in cytochrome P450 content per weight of tissue, but this is compensated for by the increase in liver size so that drug metabolism is not impaired (18). Alcoholic fatty liver may be accompanied or followed by alcoholic hepatitis, in which hepatocyte degeneration and necrosis become evident. In neither of these conditions is there significant diversion of blood flow past functioning hepato-cytes by functional or anatomic shunts. The deposition of fibrous bands also disrupts the normal hepatic vascular architecture and increases vascular resistance and portal venous pressure. This reduces portal venous flow that normally accounts for 70 of total liver blood flow (19). However, the decrease in portal venous flow is compensated for by an...

Aging and Reentry Issues

Older inmates transitioning into the community may also have new health care providers who do not know of their incarceration history. This can pose a significant problem as ex-prisoners are at particularly high risk for certain diseases such as STDs, hepatitis, and HIV (Hornung et al., 2002 http www. ojp.usdoj.gov bjs pub pdf reentry.pdf, 2003). Although all older adults should be screened for these diseases, they often are not because health care providers rarely consider older adults at risk (Skiest & Keiser, 1997). Thus, without knowledge of a history of incarceration, many health care providers might fail to screen older ex-prisoners for STDs or infectious disease.

Primary Biliary Cirrhosis PBC

Chronic Viral Hepatitis Chronic viral hepatitis is one of the most common causes of end-stage liver disease, and this is reflected in the number of patients referred for LT. A better understanding of the mechanism of viral replication and of viral transmission has led to improved results with LT for patients with end-stage liver disease caused by viral hepatitis. Patients with hepatitis fi-related liver disease (HBV) that are HBV-DNA negative can expect excellent survival after LT. Patients with hepatitis D virus (HDV) infection who are HBV-DNA negative can also expect an excellent survival rate. HBV-DNA-positive patients may patients may benefit from the addition of lamivudine to the prophylactic regimen both before and after LT. Lamivudine has proven to be effective in the treatment of both de novo and recurrent HBV infection after LT. However, viral resistance can develop. Cirrhosis due to hepatitis C virus (HCV) infection is now the most common indication of LT in Western...

Signal Amplification Techniques

Branched Dna And Hybrid Capture Assay

Branch DNA (bDNA) analysis is a quantitative technique that is used primarily to quantify levels of certain viruses, such as HIV-1 and HCV, in biological samples. The principle of a bDNA assay is shown in Fig. 11. In this example, the target is an RNA virus molecule. The target RNA is liberated from the virus, and capture extender and label extender molecules are allowed to hybridize to the target. Capture extenders and label extenders are single-strand DNA oligonucleotides that have sequence complementarity to regions of the target RNA. The capture extenders also have a region that can hybridize to immobilized DNA oligonucleotides (capture probes) on the wall of a microtiter plate well. If the target RNA is present in bDNA is a proprietary technology of Bayer. Commercially available assays include quantitative tests for HIV-1, HCV, and HBV. During gene transcription, the usual direction of flow of genetic information is from DNA to RNA. Several enzymes are known that can synthesize...

Residual microbial risk of allogeneic blood transfusion

The calculated residual risks per donation in England and Wales for HIV, HBV and HCV are approximately 1 in 8 million, 1 in 1 million and 1 in 30 million respectively. These calculations are consistent with 'haemovigilence' reports in the UK Serious Hazards of Transfusion (SHOT) scheme. Indeed, acute microbial transmissions now constitute a mere 3 of all reported hazards, with 'incorrect blood component transfused' being the major reported risk. The low microbial risk is a result of a series of incremental safety interventions becoming ever more complex and costly.

Drugs and Vaccinations

Yellow fever vaccination is extremely effective, but cases continue to be imported to Europe and North America from both Africa and South America by travellers who have not been immunised. Active immunisations against hepatitis A and B are both more than 90 effective, whereas currently licensed vaccines against typhoid only have 70 or less protective efficacy. The effectiveness of antimosquito bite measures and antimalarial chemoprophylaxis is variable and highly dependent on adherence by travellers.


The hepatitis C virus (HCV) is responsible for a world-wide epidemic with approximately 170 million people infected. It was identified only in the 1980s and since that time great efforts have been made in the search for treatments. Genetic analysis of the virus revealed coding for a serine protease (NS3) and the first clinical studies on inhibitors of the protease have recently been carried out. Chapter 2 presents a review of the medicinal chemistry approaches to this target. 2 Blunting the Swiss Army Knife of Hepatitis C Virus 65 Inhibitors of NS3 4A Protease


Diabetic patients should be prepared for travel like most other travellers. They can be given all the vaccines indicated. Special attention should be taken to ensure that influenza and pneumococcal immunisations are up to date. Hepatitis B vaccination is strongly recommended as diabetics are at greatest risk of receiving health care and injections abroad. They should carry their own needles, even if they are not taking insulin. For all travellers carrying needles and syringes, a letter on official stationary and signed by the attending physician, should be provided. An example of such letter is shown in Figure 3.1. A Medic-Alert bracelet (engraved with the wearer's allergies or other medical conditions) is also recommended. Malaria prophylaxis should be used when recommended.

Clinical Features

Inapparent or subclinical infections and infection without jaundice are common with all the different hepatitis viruses, particularly in children under the age of 6 years. The clinical picture ranges from an asymptomatic infection to a mild anicteric illness, to acute disease with jaundice, to severe prolonged jaundice, to fulminant hepatitis. Differences between the clinical syndromes of acute hepatitis A, acute hepatitis B and other types of viral hepatitis become apparent on analysis of large numbers of well-documented cases, but these differences are not reliable for the diagnosis of individual patients with jaundice. The following description of the acute illness applies to all types of viral hepatitis. Prodromal nonspecific symptoms, such as fever, chills, headache, fatigue, malaise and aches and pains, are followed a few days later by anorexia, nausea, vomiting and right upper quadrant abdominal pain, followed by the passage of dark urine and clay-coloured stools. Jaundice of...


Diagnosis is based on the detection of specific IgM antibodies by serological tests, usually by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. Specific IgA antibody responses may also be measured. Specialised laboratories have developed sensitive immunoassays for detection of hepatitis A antigen in faecal samples, and molecular hybridization can be employed for detection of HAV RNA in faeces. RNA probes have been used for detection of virus in shellfish and in contaminated water.

Passive Immunisation

Immunoglobulin does not always prevent infection and excretion of HAV and inapparent or subclinical hepatitis may develop. The efficacy of passive immunisation is based on the presence of HAV antibody in the immunoglobulin and the minimum titre of antibody required for protection is believed to be about 10IUl i. Immunoglobulin is used most commonly for close personal contacts of patients with hepatitis A and for those exposed to contaminated food. It has also been used effectively for controlling outbreaks in institutions such as homes for the mentally handicapped and in nursery schools. Prophylaxis with immunoglobulin is recommended for persons without HAV antibody visiting highly endemic areas. After a period of 6 months the administration of immunoglobulin for travellers needs to be repeated, unless it has been demonstrated that the recipient had developed HAV antibodies. Active immunisation for travellers is therefore preferred and is strongly recommended.

HBV Precore Mutants

In 1988, a report was published on the nucleotide sequence of the genome of a strain of HBV cloned from the serum of a naturally infected chimpanzee. A surprising feature was a point mutation in the penultimate codon of the precore region to a termination codon. This mutation was found subsequently in some patients with anti-HBe who were positive for HBV DNA in serum by hybridisation. In most cases there was an additional mutation in the preceding codon. Precore variants have been described in many patients with severe chronic liver disease and some failed to respond to treatment with interferon. It has been suggested that the mutants are more pathogenic than the wild-type virus. A precore variant which produces hepatitis B e antigen has also been described.


Pathological changes in the liver include conspicuous focal activation of sinusoidal cells, accumulation of lymphocytes and histiocytes in the parenchyma, often replacing hepatocytes lost by cytolytic necrosis, mainly in the periportal areas, focal degeneration and occasional co-agulative necrosis. It has been reported that acute hepatitis B is characterised by more extensive parenchymal abnormalities and inflammatory changes than those found in hepatitis A, whereas portal inflammation and cholestasis are less prominent.

Immune Responses

Antibody and cell-mediated immune responses to various types of antigens are induced during acute infection however, not all these are protective and, in some instances, may cause autoimmune phenomena that contribute to disease pathogenesis. The immune response to infection with HBV is directed toward at least three antigens HBsAg, the core antigen, and the e antigen. The view that hepatitis B exerts its damaging effect on hepatocytes by direct cytopathic changes is inconsistent with the persistence of large quantities of the surface antigen in liver cells of many apparently healthy carriers. Additional evidence suggests that the pathogenesis of liver damage in the course of hepatitis B infection is related to the immune response by the host.


General protective measures are similar to those recommended for hepatitis B and other bloodborne viral diseases. Prevention of hepatitis D can be achieved by immunisation against hepatitis B in those who are susceptible to hepatitis B. Healthy individuals who are immunised effectively against hepatitis B cannot be coin-


It is sometimes overlooked that some common forms of cancer may be caused by infection. For example, stomach cancer is often brought on by infection with Helicobacter pylori. Infection with H. pylori, and hence stomach cancer, was especially common in Japan prior to the widespread availability of refrigeration (31,32). Liver cancer is related to hepatitis infection (both B and C strains of the virus), and, thus, reductions in liver cancer hinge on controlling infection as well as curbing excess drinking. A third example is infection by the human papilloma virus, which can cause cervical cancer (33). These three forms of cancer have tended to decline in recent decades and should decline further as the relevant infectious agents are brought under control (e.g., hepatitis B and C). On the other hand, cancers that have become more common include those strongly influenced by individual behaviors (e.g., lung and pancreatic cancer are linked to smoking, and both have tended to increase over...

Yellow Fever

Flaviviridae, genus Flavivirus, classified in the past in the togaviruses. The other two genera in this family are Hepa-civirus and Pestivirus, which include important animal pathogens such as Bovine diarrhoea virus and Hog cholera virus. The medically important flaviviruses are often associated with three major clinical syndromes haemorrhagic fever with hepatitis ( Yellow fever virus) encephalitis (St Louis encephalitis, Japanese encephalitis, Powassan and Tick-borne encephalitis viruses) febrile illness with rash (Dengue virus) and haemorrhagic fever (Kyasanur Forest disease virus and sometimes Dengue virus). Malaria and relapsing fever are usually associated with splenomegaly. Blood smears will reveal malaria parasites or treponemata. Viral hepatitis may present difficulties, but on the whole jaundice is often deeper, proteinuria is uncommon and by the time jaundice appears, the patient is generally afebrile with subjective clinical improvement.

Rift Valley Fever

Rift Valley fever virus is a member of the family Bunyaviridae, genus Phlebovirus, and causes an enzootic infection of sheep, cattle, camels and goats in Africa and Madagascar. The virus (Figure 6.14) is transmitted by mosquitoes and the disease is characterised by necrotic hepatitis and a haemorrhagic state, although infections are frequently inapparent or mild. Humans become infected from contact with blood and tissues of domestic livestock or mosquito bite, and the infection is a mild to severe febrile illness with encephalitis, involvement of the eye, and or haemorrhagic fever in about 1 of cases. Human cases are usually restricted to veterinary surgeons, butchers and others in close contact with the blood of domestic livestock, and there is a potential risk with ritual slaughter.