Evolving epidemiology of hepatitis C virus.

More than 20 years after the discovery of the hepatitis C virus (HCV), it is now well established that HCV is of global importance affecting all countries, leading to a major global health problem that requires widespread active interventions for its prevention and control. Chronic hepatitis C was linked to the development of cirrhosis and hepatocellular carcinoma in many areas of the world. Current epidemiological assessments have identified complex patterns with highly variable local prevalence rates between countries and within countries. HCV infection patterns have not significantly changed in most parts of the world since 1997, when first analyzed, partly due to the lack of new and more accurate data. The assessment of the national HCV prevalence and transmission modes should be completed to enable national authorities to prioritize preventive measures and to make the most appropriate use of available resources. The 'patchy' epidemiological situation in some areas will continue to complicate the task of the establishment of global, regional and national base line data. The present assessment finds a global prevalence of 2.35%, affecting 160 million chronically infected individuals. There is an urgent need for more accurate Information on the costs and burden of HCV to society. Twenty-one year after the discovery of HCV, the assessment is far from being complete and little progress has been made in the past 10 years in many countries. In some countries significant increases have been reported and this may also apply to countries were insufficient data exist. A safe and efficient vaccine against HCV is urgently needed.

Hepatitis B virus infection in dentistry: a forgotten topic.

More than two billion people have been infected with hepatitis B virus (HBV). Globally, 350-400 million suffer from chronic HBV infection. It is postulated that dentists and dental staff are infected and transmit the virus to their patients more than any other occupation. The aim of this article is to review the HBV incidence in dental society, the points of view of dentists and their patients regarding transmission of the virus during dental procedures, the occurrence of HBV outbreaks in dental clinics and the importance of methods of preventing HBV infection in dentistry.

Hepatitis B virus, hepatitis C virus and other blood-borne infections in healthcare workers: guidelines for prevention and management in industrialised countries.

The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international experts from the public and private sectors in order to review and evaluate the epidemiology of blood-borne infections in healthcare workers, to evaluate the transmission of hepatitis B and C viruses as an occupational risk, to discuss primary and secondary prevention measures and to review recommendations for infected healthcare workers and (para)medical students. This VHPB meeting outlined a number of recommendations for the prevention and control of viral hepatitis in the following domains: application of standard precautions, panels for counselling infected healthcare workers and patients, hepatitis B vaccination, restrictions on the practice of exposure-prone procedures by infected healthcare workers, ethical and legal issues, assessment of risk and costs, priority setting by individual countries and the role of the VHPB. Participants also identified a number of terms that need harmonization or standardisation in order to facilitate communication between experts.

Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention.

Worldwide, hepatitis B virus (HBV) is the most common among those hepatitis viruses that cause chronic infections of the liver in humans, and it represents a global public health problem. Chronic hepatitis caused by HBV is the major cause of hepatocellular carcinoma (HCC) worldwide, and remains therefore a major public health problem globally. This fact is related to both the continuing occurrence of frequent new infections and to the presence of a large reservoir of persons chronically infected, which may develop severe and fatal complications of chronic liver disease. Hepatitis B and all of the complications resulting from it, as well hepatitis D (HDV) and its complications, are globally preventable by hepatitis B vaccination, and therefore elimination of HBV transmission and of new acute and chronic infections is a feasible goal.

Prevention of hepatitis C virus infection.

In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13-14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations.

Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures.

Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Safe and effective vaccines against HBV infection have been available since 1982. The implementation of mass immunization programs, which have been recommended by the World Health Organization since 1991, have dramatically decreased the incidence of HBV infection among infants, children, and adolescents in many countries. However, not all countries have adopted these recommendations and there remains a large number of persons that were infected with HBV prior to the implementation of immunization programs. Antiviral treatment is the only way to reduce morbidity and mortality from chronic HBV infection. Conventional interferon alfa and lamivudine have been the primary treatments to date. Conventional interferon alfa produces a durable response in a moderate proportion of patients but has undesirable side-effects and must be administered subcutaneously three times per week. Lamivudine also produces a response in a modest proportion of patients and causes few side-effects. However, prolonged treatment is often necessary to prevent relapse on cessation of therapy, and continuous treatment can lead to the development of lamivudine resistance. Promising emerging new treatments include adefovir, entecavir and peginterferon alfa-2a (40 kDa).

Influenza and the work of the World Health Organization.

Before World War I, influenza was not considered a particularly serious problem. The great pandemic of 1918-1919 changed all that, and the possibility that such a catastrophe could occur again has conditioned all subsequent developments. In epidemiological terms, the hallmark of an influenza is the excess mortality that it causes combined with an enormous burden of ill-health that saps the energy of individuals, families and communities throughout the whole world. In order to engage in influenza prevention and control, the global influenza surveillance network was set up by World Health Organization (WHO) in 1948 as a worldwide alert system for the identification of new influenza viruses, gathering information from 110 participating laboratories in 82 countries and four WHO Collaborating Centers for Influenza reference and research: Centers for Disease Control and Prevention, Atlanta (USA), National Institute for Medical Research, London (UK), WHO Collaborating Centre for Influenza Reference and Research, Melbourne (Australia) and the National Institute for Infectious Diseases, Tokyo (Japan). This network helps WHO to monitor influenza activity all over the world and provides the organization with the viral isolates and information it requires to decide which new virus strains will be used to produce influenza vaccines during the following season. Each year, information about the isolates over the previous 12 months is analyzed and used to determine the composition of the influenza vaccine to be administered during the coming influenza season both for the northern and southern hemisphere. If necessary, the recommendations for the southern hemisphere differ from the ones formulated for the northern hemisphere vaccine. The information supplied by this network enables the organization to regularly update its World Wide Web (WWW) site (FluNet), which reports on the situation of diseases. This network will also enable the WHO to detect a new influenza pandemic as early as possible.

Planning for the next pandemic of influenza.

Worldwide influenza pandemics have occurred at irregular and unpredictable intervals throughout history and it is confidently expected that they will continue to occur in the future. It is now recognised that these pandemics result when avian influenza A viruses succeed in adaptation to and transmission between humans. The impact of pandemic influenza is substantial in terms of morbidity, mortality and economic cost and there is the potential for serious social disruption. Influenza vaccines remain the most effective defence against influenza but will be in short supply during a pandemic, as will the new specific anti-influenza drugs, due to the lead-time required for production and rapid spread of the virus. To minimise the impact of pandemics it is imperative to maximise the availability of both vaccines and antivirals and to ensure that they are used optimally. This requires planning at both the international and national levels. The World Health Organization has, therefore, developed a staged plan for responding to a pandemic threat which is based principally on its surveillance program. It has also prepared guidelines to assist national agencies in their planning. However, there may be further options for increasing our preparedness which should also be considered.

Hepatitis C.

Hepatitis C has been identified as the most common cause of post-transfusion hepatitis worldwide, accounting for approximately 90% of this disease in Japan, the United States and Western Europe. Hepatitis C is a major global public health problem. New infections continue to occur, and the source of infection includes transfusion of blood or blood products from unscreened donors; transfusion of blood products that have not undergone viral inactivation; parenteral exposure to blood through use of contaminated and inadequately sterilized instruments and needles used in medical, dental and 'traditional' medicine; procedures such as hemodialysis; high risk sexual practices; household or sexual contacts of hepatitis C virus (HCV)-infected persons; and infants of HCV-infected mothers. In many countries, the relative contribution of the various sources of infection has not been defined with population-based epidemiological studies. Such studies are necessary to enable countries to prioritize their preventive measures and to make the most appropriate use of available resources. Given the substantial morbidity and mortality attributable to HCV-related chronic liver disease, each country, irrespective of economic status, should develop a plan of HCV-related public health activities for the prevention of new HCV infections and the treatment of established chronic infections.

Neuraminidase inhibitors: progress in the management of influenza.

Influenza is a serious respiratory illness and represents a significant clinical burden. As well as being debilitating, influenza can often cause complications leading to hospitalisation and death. Prophylaxis by vaccination is the preferred method of disease management, but because influenza viruses are constantly changing their antigenic properties, influenza outbreaks occur regularly as epidemics. Neuraminidase inhibitors are a new class of anti-influenza drugs designed to block influenza virus replication. Two neuraminidase inhibitors, zanamivir and oseltamivir, have been licensed for clinical use in the treatment of influenza. Both drugs significantly reduce the severity and duration of the illness when treatment is started within two days of the onset of symptoms. However, while zanamivir and oseltamivir have apparently similar efficacy, they differ in their modes of delivery and tolerability. Zanamivir is delivered direct to the lungs by inhalation and is well tolerated. Oseltamivir is taken in the form of a pill but has the side-effect of producing nausea and vomiting in some patients. In the absence of a demonstrable difference in efficacy, uptake of the two drugs will depend on evaluation of the relative merits of mode of delivery and tolerability.

The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt.

BACKGROUND: The population of Egypt has a heavy burden of liver disease, mostly due to chronic infection with hepatitis C virus (HCV). Overall prevalence of antibody to HCV in the general population is around 15-20%. The risk factor for HCV transmission that specifically sets Egypt apart from other countries is a personal history of parenteral antischistosomal therapy (PAT). A review of the Egyptian PAT mass-treatment campaigns, discontinued only in the 1980s, show a very high potential for transmission of blood-borne pathogens. We examine the relative importance of PAT in the spread of HCV in Egypt. METHODS: The degree of exposure to PAT by cohort was estimated from 1961-86 Ministry of Health data. A cohort-specific exposure index for PAT was calculated and compared with cohort-specific HCV prevalence rates in four regions. FINDINGS: HCV prevalence was calculated for 8499 Egyptians aged 10-50 years. A significant association between seroprevalence of antibodies to HCV and the exposure index (1.31 [95% CI 1.08-1.59]; p=0.007) was identified across four different regions. In all regions cohort-specific HCV prevalence was lowest in children and young adults than in older cohorts. These lower prevalence rates coincided with the gradual and final replacement of PAT with oral antischistosomal drugs at different points in time in the four regions. INTERPRETATION: The data suggest that PAT had a major role in the spread of HCV throughout Egypt. This intensive transmission established a large reservoir of chronic HCV infection, responsible for the high prevalence of HCV infection and current high rates of transmission. Egypt's mass campaigns of PAT may represent the world's largest iatrogenic transmission of blood-borne pathogens.

Decrease in the prevalence of hepatitis B and a low prevalence of hepatitis C virus infections in the general population of the Seychelles.

A serological survey of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was carried out on a random sex- and age-stratified sample of 1006 individuals aged 25-64 years in the Seychelles islands. Anti-HBc and anti-HCV antibodies were detected using commercially available enzyme-linked immunosorbent assays (ELISA), followed by a Western blot assay in the case of a positive result for anti-HCV. The age-adjusted seroprevalence of anti-HBc antibodies was 8.0% (95% CI: 6.5-9.9%) and the percentage prevalence among males/females increased from 7.0/3.1 to 19.1/13.4 in the age groups 25-34 to 55-64 years, respectively. Two men and three women were positive for anti-HCV antibodies, with an age-adjusted seroprevalence of 0.34% (95% CI: 0.1-0.8%). Two out of these five subjects who were positive for anti-HCV also had anti-HBc antibodies. The seroprevalence of anti-HBc was significantly higher in unskilled workers, persons with low education, and heavy drinkers. The age-specific seroprevalence of anti-HBc in this population-based survey, which was conducted in 1994, was approximately three times lower than in a previous patient-based survey carried out in 1979. Although there are methodological differences between the two surveys, it is likely that the substantial decrease in anti-HBc prevalence during the last 15 years may be due to significant socioeconomic development and the systematic screening of blood donors since 1981. Because hepatitis C virus infections are serious and the cost of treatment is high, the fact that the prevalence of anti-HCV antibodies is at present low should not be an argument for not screening blood donors for anti-HCV and eliminating those who are positive.

PIP: This study examined the prevalence of anti-hepatitis Bc virus (HBc) and anti-hepatitis C virus (HCV) antibodies in a random sex- and age-stratified sample of 1006 individuals aged 25-64 years in the Seychelles. The anti-HBc and anti-HCV antibodies were detected using an enzyme-linked immunosorbent assay, followed by a Western blot assay in the case of a positive result for anti-HCV antibodies. Findings revealed that the age-adjusted prevalence of anti-HBc antibodies was 10.4% and 5.8%, respectively, among men and women aged 25-63 years. The presence of anti-HBc antibodies was associated significantly with employment, educational level, and alcohol intake, marginally with economic status, and not at all with ethnic origin. 2 men and 3 women were positive for anti-HCV antibodies, with an age-adjusted seroprevalence of 0.34%. 2 out of these 5 subjects who were positive for anti-HCV antibodies were also positive for anti-HBc antibodies. The age-specific seroprevalence of anti-HBc antibodies in this population study conducted in 1994 was approximately 3 times lower than in a previous patient-based survey carried out in 1979. Although there were methodological differences between the two surveys, it is likely that the substantial decrease in the anti-HBc antibody prevalence during the last 15 years may be due to significant socioeconomic development and the systematic screening of blood donors since 1981.

Microheterogeneity of serum glycoproteins in patients with chronic alcohol abuse compared with carbohydrate-deficient glycoprotein syndrome type I.

BACKGROUND: Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrate-deficient transferrin isoforms. This alteration could be similar to that present in patients with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1). We thus compared the alterations of N-glycans present in patients with alcoholism and patients with CDG1. METHODS: The N-glycans of serum glycoproteins were compared in sera of patients with alcoholism, patients with CDG1, and controls by two-dimensional electrophoresis, neuraminidase, peptide:N-glycosidase F, and endoglycosidase F2 treatments. A specific antibody directed against the amino acid sequence surrounding the N-432 N-glycosylation site of transferrin was prepared (SZ-350 antibody). RESULTS: In patients with alcoholism, the abnormal transferrin and alpha(1)-antitrypsin isoforms were devoid of a variable number of entire N-glycan moieties and were identical with those present in CDG1. In the serum of patients with alcoholism, this finding was less pronounced than in CDG1. In contrast to CDG1, there was no decrease in clusterin or serum amyloid P in patients with alcoholism. The SZ-350 antibody recognized only transferrin isoforms with one or no N-glycan moieties. CONCLUSION: Antibodies directed against specific N-glycosylation sites of glycoproteins could be useful for developing more specific immunochemical tests for the diagnosis of chronic alcohol abuse.

Hepatitis C: public health strategies.

Hepatitis C virus (HCV) is a major global public health problem. As with many recently discovered diseases, there is still considerable controversy within the scientific community regarding the prevalence, incidence and socio-economic burden of acute and chronic hepatitis C. New infections continue to occur. Given the substantial morbidity and mortality attributable to HCV-related chronic liver disease, each country, irrespective of its economic status, should develop an HCV-related public health plan for the prevention of new HCV infections. The source of HCV infection includes transfusion of blood or blood products from unscreened donors, transfusion of blood products that have not undergone viral inactivation, parenteral exposure to blood through the use of contaminated and inadequately sterilized instruments and needles used in medical, dental and "traditional" medicine, individuals undergoing procedures such as haemodialysis, persons who participate in high risk sexual practices, household or sexual contacts with HCV-infected persons and infants of HCV-infected mothers. In many countries, the relative contribution of the various sources of infection has not been defined with population-based epidemiological studies. Wherever possible, such studies should be performed to enable countries to prioritise their preventive measures and to make the most appropriate use of available resources.

[Drug therapy of chronic hepatitis B]. / Medikamentöse Therapie der chronischen Hepatitis B.

Medical therapy of chronic hepatitis B aims at halting progression towards cirrhosis/hepatocellular carcinoma by inhibiting replication of hepatitis B virus in a sustained fashion (viral elimination). The sole therapy of proven efficacy is interferon-alpha (5-10 Mio IU sc TIW) which leads within 4 months to viral elimination (seroconversion from HBeAg to anti-HBe-antibody; serum HBV-DNA negative by hybridisation) in approximatively 40% of patients. Interferon-alpha therapy has been shown to decrease hepatitis B associated morbidity/mortality and to be cost-effective. Certain nucleoside analoga such as lamivudine or famciclovir are able to stop hepatitis B virus replication in a large proportion of patients; replication promptly resumes however after cessation of treatment and resistance develops in approximatively 15% of patients treated for one year. The clinical value, in particular for interferon-alpha non-responders, of a combination of interferon-alpha and/or nucleoside analoga remains to be seen.