Meetings and publications | |
>> Viral Hepatitis newsletters |
VIRAL HEPATITIS
PUBLISHED BY THE VIRAL HEPATITIS PREVENTION BOARD
July 1997
Volume 5 - Number 3
Contents
Editorial
Meeting news
VHPB Consensus Statement on Surveillance
Editorial
This issue of Viral Hepatitis tackles the subject of surveillance and monitoring of viral hepatitis in Europe. It also provides an overview of the current status of epidemiological surveillance programmes in countries in the WHO European Region, detailing the different approaches and regulations from country to country. In addition, a review of the hepatitis G virus is also included.
All countries in Europe have systems for epidemiological surveillance in place. However, these systems vary so widely in terms of method and completeness that it is difficult to arrive at meaningful numbers and to make international comparisons. Case definitions - if used at all - vary between countries, laboratory confirmation is the exception rather than the norm, and the reporting criteria differ.
Without reliable, standardised surveillance systems for viral hepatitis it is difficult to have a clear picture of the burden of disease and to monitor the progress made towards meeting targets for disease reduction and prevention.
The VHPB advocates the standardisation of surveillance of viral hepatitis across Europe. In the consensus statement (pages ---), the VHPB has set down guidelines for surveillance that include recommendations on formulating case definitions, submitting surveillance reports, monitoring vaccine coverage and impact, and reporting severe adverse events. It is the aim of the VHPB that all countries in Europe work to incorporate these recommendations into their surveillance programmes so that systems in the region become more effective, accurate and uniform.
Dr Colette Roure
WHO Regional Office for Europe
This edition of Viral Hepatitis is prepared from material presented at the Viral Hepatitis Prevention Board Meeting held 24-26 June, 1996 in Athens, Greece.
Core Members
Dr Johannes Hallauer
WHO Collaborating Centre on Public Health Research
Institute for Health Systems Research
Kiel, Germany
Dr Mark Kane
WHO, Global Programme for Vaccines and Immunization
Geneva, Switzerland
Dr Elizabeth McCloy
(Formerly) Civil Service Occupational Health and Safety Agency
London, United Kingdom
Prof André Meheus
WHO Collaborating Centre for Prevention and Control of Viral Hepatitis
Department of Epidemiology and Community Medicine
University of Antwerp, Belgium
Dr Colette Roure
WHO Regional Office for Europe
Copenhagen, Denmark
Executive Secretary
Dr Pierre Van Damme
WHO Collaborating Centre for Prevention and Control of Viral Hepatitis
Department of Epidemiology and Community Medicine
University of Antwerp, Belgium
VHPB Standing Advisors
Prof Paolo Bonanni
Public Health Department
University of Florence, Italy
Prof Pietro Crovari*
Institute of Hygiene and Preventive Medicine
University of Genoa, Italy
Dr José de la Torre
Ministry of Health and Consumer Affairs
Madrid, Spain
Prof Alain Goudeau
Department of Medical and Molecular Microbiology
University of Tours, France
Prof Peter Grob
Department of Medicine
University Hospital Zurich, Switzerland
Prof Wolfgang Jilg
Institute for Medical Microbiology and Hygiene
University of Regensburg, Germany
Dr Daniel Lavanchy*
BVI Unit, Division of Communicable Diseases
World Health Organization
Geneva, Switzerland
Dr Harold Margolis*
CDC, Hepatitis Branch
Atlanta, Georgia, United States
Prof Georges Papaevangelou
National Centre for Viral Hepatitis
Athens School of Hygiene, Greece
Invited Advisors and Speakers
Dr Bill Carman
Institute of Virology
Glasgow, UK
Dr Nicole Guérin
Communicable Diseases & Immunization Unit
International Children’s Centre
Paris, France
Prof Stephanos Hadziyannis
Academic Department of Medicine
Hippokration General Hospital
Athens, Greece
Dr Stanislava Popova
Ministry of Public Health
Sofia, Bulgaria
Dr Mary Ramsay
Public Health Laboratory Service - Communicable Disease Surveillance Centre
London, UK
Dr Pedro Reis
ICIL
Lisbon, Portugal
Dr Adam Vass
Department of Epidemiology
Office of the Chief Medical Officer of State
Budapest, Hungary
Rapporteur
Margaret Van der Elst
Antwerp, Belgium
VHPB Secretariat
Mrs Emmy Engelen
Mr Gino Verwimp
WHO Collaborating Centre for Prevention and Control of Viral Hepatitis
Department of Epidemiology and Community Medicine
University of Antwerp, Belgium
*Not present at the meeting
Report on the Viral Hepatitis Prevention Board meeting held 24-26 June, 1996 in Athens, Greece.
Surveillance systems in Europe need strengthening and uniformity
The results of a survey carried out by the European Regional Office of the World Health Organization (WHO) indicate that surveillance systems for hepatitis B (HBV) across Europe vary in their methods and completeness. In most European countries notification of HBV infections is mandatory; however, case definitions vary, laboratory confirmation is not always used, reporting systems differ, and distinctions are not always made between the types of viral hepatitis. In addition, because of the short-comings in surveillance systems, and because under-reporting of HBV infection is commonplace, it is difficult to draw meaningful comparisons from the data provided.
The WHO European Region encompasses 50 countries and a population of approximately 840 million. Fifty government officials responsible for surveillance and control of infectious diseases were surveyed in 1993 to obtain information on surveillance systems, notification of cases, incidence of acute hepatitis, and estimates of hepatitis B carriage and infection.
Of the 50 countries polled, 41 responded to the survey, covering approximately 91 percent of the population of the area. The response rate was 86% for Western and Central Europe and 50% for Eastern Europe. An overview of the information submitted is as follows:
Despite the variations in data provided, a pattern of disease can be found. The average annual incidence of acute hepatitis B for Europe is estimated at 20 per 100,000. In the western part of the region, rates increase from north to south. Central Europe has markedly higher rates; and - with rates ranging from 41 to 120 per 100,000 - the Central Asian Republics are the most affected.
It is obvious that there is underreporting of acute hepatitis. From the available data, the average number of reported cases of acute hepatitis B for the years 1991-1995 in Europe has been approximately:
1991 |
1992 |
1993 |
1994 |
1995 |
133,000 |
124,000 |
123,000 |
121,000 |
89,000 |
According to the average annual incidence rate, about 185,000 acute cases would have been expected for 1993. As sub-clinical cases are not properly identified or reported, it can be assumed that reported cases represent as little as one-sixth of total cases.
Although most countries do report cases of acute hepatitis B, without adherence to standard case definitions and without laboratory confirmation tests (which in some countries are not readily available) it is difficult to know the real situation. Surveillance systems throughout the region therefore need to be strengthened and standardised, and should also include monitoring of HBsAg prevalence in the general population as well as the incidence of acute hepatitis B.
As presented by Dr Colette Roure of the WHO Regional Office for Europe, Copenhagen, Denmark
References:
Mangtani, P., Hepatitis B: Incidence and Vaccine Policy in Europe. Results of the 1993 WHO Euro Study (report).
See also Viral Hepatitis, 1996. Vol. 4, no. 2.
Surveillance: the France model
Surveillance and monitoring of infectious and vaccine-preventable diseases in France is carried out using a number of different systems and approaches. These include a mandatory notification system collected by the national health authority; a laboratory confirmation and notification system also aggregated at the national level; and a sentinel surveillance network.
Sentinel surveillance is the method used to monitor hepatitis B infections, although viral hepatitis experts in the country recommend that mandatory reporting of hepatitis infections be introduced.
A variety of methods are also in place for assessing vaccine coverage in France. The principle means is a system in which certificates of health detailing immunization history must be filed by physicians for all children 24 months of age. The form has recently been updated to include information on hepatitis B immunization. Although this method is compulsory and theoretically exhaustive, data from 1993 (the most recent information available) indicate a 56% reporting rate. This underreporting may in part be the result of the delivery system. In France, immunization is largely carried out by the private sector, which increases the likelihood of underreporting.
Supplemental information on immunization is gleaned from vaccine sales figures, prescriptions for vaccine doses, and from a national survey of children at age six. 1997 will be the first year this survey covers all antigens and not MMR only. Other surveys are also used to augment vaccine coverage information. These include immunization surveys of families, military recruits, healthcare workers and other at-risk professionals, and blood donors.
Since 1995, immunization against hepatitis B has been recommended for pre-adolescents between 11 and 13 years of age. Vaccination coverage for this age group is currently monitored through school-based reporting systems in which information is collected at a national level, and through surveys.
As reported by Dr Nicole Guérin, International Children’s Centre, Paris, France.
Surveillance: the UK model
Laboratory reporting forms the basis of the hepatitis B surveillance system in England and Wales. Surveillance of vaccine preventable disease includes disease incidence, vaccine coverage, and adverse events, as well as routine and ad hoc serological surveillance and special surveillance systems.
Under the UK system, the main sources of data used to determine disease incidence are statutory notification information provided by physicians, and reports submitted by laboratories performing the serological confirmation tests. In the case of physician reporting, no case definition is required, and information is submitted to the local public health department and passed on weekly to the Office of National Statistics (ONS); laboratories report information to the Communicable Disease Surveillance Centre (CDSC).
Laboratories report a data set on all clinically significant infections. It includes patient demographics, micro-organism name and species, specimen type, date, method of identification, lab name, district and region, and clinical and epidemiological features. Follow-up information would include the method of identification, reason for testing, diagnosis, clinical features, occupational information, relevant risk factors, information on overseas travel, and contact information.
Auxiliary sources of information include sentinel general practitioner reporting, hospital reporting, paediatric surveillance, and the death registry.
Surveillance system of vaccine coverage can be monitored as vaccine usage or doses distributed by routine and ad hoc sampling population assessment and total target population assessment. In the UK, a computerised child health registry is maintained in each district; information is reported quarterly and aggregated at both the regional and national levels. The information is used to monitor trends over time; to pinpoint pockets of poor vaccine coverage; to compare disease epidemiology; and to estimate vaccine efficacy. The system has proven useful in tracking epidemics and for studying the impact of the vaccination programme.
In addition, serological surveillance is collected annually for children aged 1-15, and every five years for adults over 16. Opportunistic samples are collected and examined for antibody to vaccine preventable diseases.
Since 1995, a surveillance programme for blood donors has been underway. The goal of this programme is to measure disease prevalence and incidence; to describe the epidemiology of infections in a selected, low-risk adult population; to identify risk factors not excluded by pre-donation donor selection; and to provide the potential basis for further study.
As presented by Dr Mary Ramsay, Immunization Division of the Communicable Disease Surveillance Centre
An overview of surveillance systems in selected countries in Europe1,2*
Country |
System |
Institution |
Source |
Case definition |
Type of report |
Reported |
Disseminated |
Austria |
Mandatory Notification |
Ministry of Health |
Physician |
No |
Summary |
Monthly |
Monthly |
Belgium |
Mandatory Notification |
Ministry of Health |
Physician + Lab |
No
|
Individual
|
Per case
|
Quarterly |
|
Physician Sentinel |
IHE |
|
Yes |
Individual |
Weekly |
Annually |
Denmark |
Mandatory Notification |
STS |
Physician |
Yes |
Individual |
Daily |
Weekly |
Finland |
Mandatory Notification |
Ministry of Health |
Physician |
Yes |
Individual |
Weekly |
Annually |
|
Voluntary Lab |
Ministry of Health |
Labs |
Yes |
Summary |
Bi-weekly |
Annually |
France |
Physician Sentinel |
Ministry of Health |
450 Physicians |
Yes |
Individual |
Weekly |
|
|
Voluntary Lab |
LNS |
30 Labs |
Yes |
Individual |
|
|
Germany |
Mandatory Notification |
Ministry of Health |
Physician |
No |
Individual |
Weekly |
|
Greece |
Mandatory Notification |
Ministry of Health |
Physician |
No |
Summary |
Monthly |
Annually |
|
Sero Survey |
SOH |
|
|
|
|
|
Ireland |
Mandatory Notification |
Ministry of Health |
Physician |
No |
Individual |
Daily |
Monthly |
Italy |
Mandatory Notification |
ISS |
Physician |
No |
Summary |
Monthly |
Annually |
Luxembourg |
Mandatory Notification |
Depart-ment of Health |
Physician |
No |
Individual |
Per case |
Monthly |
Nether-lands |
Mandatory Notification |
Ministry of Health |
Physician |
No |
Individual |
Weekly |
Quarterly |
Norway |
Mandatory Notification |
National Institute of Health |
Lab + Physician |
Yes |
Individual |
Weekly |
Weekly |
Portugal |
Mandatory Notification |
Ministry of Health |
Physician |
No |
Individual |
Daily |
Annually |
Spain |
Mandatory Notification |
CE |
Physician |
No
|
Summary |
Weekly
|
Weekly |
|
Voluntary Lab |
|
20% Labs |
Yes |
Individual |
Weekly |
Weekly |
Sweden |
Mandatory Notification |
NBL |
Physician |
Yes
|
Individual |
Weekly
|
Monthly |
|
Voluntary Lab |
|
100% Labs |
No |
Summary |
Monthly |
Annually |
Switzer-land |
Mandatory Notification |
FOPH |
Physician |
Yes |
Individual |
Per case |
Monthly |
United Kingdom |
Mandatory Notification |
OPCS |
Physician |
Yes |
Individual |
Weekly |
Weekly |
|
Voluntary Lab |
CDSC |
Physician |
Yes |
Summary |
Weekly |
Quarterly |
(caption to previous chart)
A comparison of surveillance systems for monitoring hepatitis B incidence and prevalence in Europe shows that the commonest approach to surveillance in the region is mandatory notification by treating physicians. In some countries, notification by physicians is accompanied by laboratory confirmation.
Case definitions are used in very few countries; those that do use case definitions may use the WHO definition or a country-specific definition. The frequency of reporting also varies; reports may be submitted on a daily, weekly, or monthly basis, or only when there is a case to report. Data is generally collected and aggregated by the ministry of health, although in some cases, this is the responsibility of a public health agency working on behalf of the government.
*Some information may have changed since the publication of the reference documents.
Evaluating immunization programmes
It is necessary to monitor immunization programmes to determine how successfully they are being carried out, to establish what percentage of the targeted population is being reached, and to pinpoint gaps or weaknesses in the delivery system. In order for the data collected to be considered comparable and complete, immunization programmes should include clear guidelines which establish the parameters (indices) against which these programmes can be evaluated. For example:
Determining vaccination coverage
Immunization coverage is defined as the proportion of the target population which is vaccinated.3 The immunization coverage is expressed as a ratio in which the numerator is the number of vaccinees in the target population (e.g. calculated band on the reported number of doses administered during the year), and the denominator is the (estimated) size of the target population.
Immunization coverage = |
number of vaccinees in the target population |
|
size of the target population |
Information is not always easy to obtain and many countries simply use the data at hand. To measure or estimate the percentage of vaccination coverage, various methods can be used to determine the numerator and the denominator.
To establish the numerator, countries use, for example, the number of children immunised by age two; the number of doses of vaccine delivered, imported or licensed; the number of immunised children at school entry; the number of immunizations by certificate; or the number of doses distributed to the public health service. The denominator can be based on the number of children living in the district; the resident population; the number of births from previous years; the number of live births from the current year; the number of immunization cards surveyed; the number of school entrants; or the number of certificates received. The numerator and denominator must be relevant to one another. Obviously, the accuracy of these parameters differs widely.
Investigating outbreaks and adverse events
A well defined scheme is also needed to investigate outbreaks of disease and adverse reactions following immunization. Procedures are already in place for investigating polio, diphtheria and measles outbreaks, and these can serve as models for hepatitis B.
Monitoring systems which are already in place for tracking adverse events following immunization should be applied to hepatitis B immunization programmes as well.
Any programme for monitoring adverse reactions to immunization should include parameters on:
As presented by Dr Johannes Hallauer, Institute for Health Systems Research,
Kiel, Germany.
References:
Facts on Hepatitis G Virus
A sixth, infectious viral hepatitis - hepatitis G - was identified in 1995. The hepatitis G virus (HGV) is an RNA virus, and, as a member of the Flaviviridae family of viruses, is closely related to HCV. It has been associated with acute and chronic hepatitis, although a major issue is to what extent, if at all, HGV causes hepatitis or any other disease.
Transmission
Hepatitis G is transmitted parenterally through blood and blood products, and through intravenous drug use. HGV is prevalent in the blood donor population, and donor-recipient links have been clearly established. High rates of HGV are seen in patients who have received multiple blood transfusions, and prevalence rates for HGV in haemodialysis units can be quite high. Currently, studies are underway to determine if HGV is transmitted from mother to child; as yet there are no data on intra-familial transmission.
Epidemiology
The distribution of the virus varies world-wide: in Europe, Japan and the United States the prevalence of HGV is estimated at between 1% and 2.5%; in Egypt, where HGV is thought to be the most widespread, prevalence is estimated at approximately 22%. These figures are estimates because, as of now, no serologic assay to identify HGV is available. Diagnosis of HGV currently depends on the use of polymerase chain reaction to detect viral RNA in infected fluids or tissues. Attempts to develop an antibody detection system have thus far been unsuccessful.
Clinical picture
Although the clinical significance of the virus is still not fully known, HGV appears to cause both self-limited and chronic disease. Disease is generally mild and infected persons frequently have normal or only slightly raised liver enzyme levels. Evidence suggests that HGV can clear over time, although a higher proportion of males than females do not clear the virus.
The virus is not an important cause of fulminant hepatitis. Presently, it is unknown if a normal carrier state exists, and the potential role of HGV in cirrhosis and hepatocellular carcinoma remains to be investigated.
HGV and HCV can be simultaneously transmitted and result in persistent co-infection. Co-infection with HCV or HBV is commonly seen, presumably because of shared risk factors. ‘HGV does not give rise to classical hepatitis,’ says Dr Hadziyannis of the Hippodration General Hospital in Athens, Greece. ‘The view is that it causes infection but little liver damage.’ It is also possible that hepatitis G could play a role in certain systemic or non-hepatic disorders.
Treatment
The effectiveness of alfa interferon as a treatment for HGV infection has been studied. Although the hepatitis G virus appeared to be sensitive to interferon, all cases relapsed on cessation of therapy. This may be related to the amount of interferon or to the duration of treatment. Patients co-infected with HGV and HCV showed a poorer response to treatment for HCV than those infected with HCV only; in other studies, however, the efficacy of alfa interferon therapy on chronic hepatitis C was not affected by concurrent HGV infection.
Conclusions
Hepatitis G virus was identified in 1995. Based on the data available today, it is thought that the virus:
As presented by Dr S.J. Hadziyannis of the Academic Department of Medicine, Hippodration General Hospital, Athens, Greece.
Further recommended reading:
Lemon, S. M., Thomas, D. L. Vaccines to Prevent Viral Hepatitis. The New England Journal of Medicine, 1997; 336: 196-204.
Di Bisceglie, A.M. Hepatitis G Virus Infection: A Work in Progress. Annals of Internal Medicine, 1996; 125: 772-773.
VHPB recommendations on surveillance of hepatitis B
Surveillance is necessary to determine the incidence, prevalence and burden of a disease. The success of any surveillance system is dependent on the willingness of doctors to report cases of infectious disease. Feedback to reporting physicians is an integral part of any surveillance system. The role and purpose of surveillance should be stressed from the start of medical training.
Surveillance systems for hepatitis B are necessary to:
Surveillance may also alert health officials to outbreaks of disease.
In most European countries notification of acute hepatitis is mandatory, but wide differences between case definitions, and the completeness and methods of reporting exist, making it extremely difficult to draw meaningful conclusions from country-to-country comparisons.
For better standardisation of surveillance systems across Europe, the VHPB recommend greater uniformity in formulating case definitions, in submitting surveillance reports, in monitoring vaccine coverage and impact, and in reporting severe adverse events.
1. Formulating case definitions
The VHPB recommend that all countries formulate a case definition, and support the case definition of viral hepatitis B put forward by the World Health Organization:
The serological quality of the tests used is crucial for a firm diagnosis of infection. It is understood, however, that case definitions based on serological tests pose a problem for countries without widespread access to these tests. Methods to detect HBsAg using test procedures such as reverse passive hemagglutination (RPHA) or latex bead technology are very inexpensive, and while not as sensitive as radioimmunoassay (RIA) antigen tests or the enzyme-linked immunosorbent assay (ELISA), are far better than not testing at all.
2. Submitting surveillance reports
Regardless of the availability of serological tests, all countries are advised to report all cases of jaundice and suspected viral hepatitis. Countries with laboratory facilities can further differentiate between hepatitis A, B, C and other types of hepatitis. Surveillance reports should be submitted on a regular basis, and at a minimum, once a month.
Data from acute disease reporting systems underestimate the true incidence of hepatitis B virus infection in the community because:
Although surveillance of acute disease can be an essential parameter, it is insufficient to give a clear picture of the burden of disease. Surveillance of the chronic consequences of HBV (for instance, cirrhosis and HCC) and reporting of disease-specific mortality data is useful to document the burden of disease in the community. Acute case notification should be followed up by further epidemiological investigation and implementation of appropriate control measures. All outbreaks should be investigated immediately and confirmed serologically.
Outbreak investigation and sentinel surveillance may serve as supplementary sources of data on disease surveillance. In addition, sero-surveillance systems are very cost-effective ways of looking at the epidemiological situation of an infectious disease.
Although screening of blood donors is a very efficient system for preventing transmission of bloodborne pathogens, prevalence data from blood donors are not representative of the general population. Certain population groups - such as pregnant women and military personnel - are easily accessible for hepatitis screening, and data collected from these groups are relevant and should be incorporated into surveillance systems. In addition, hospital diagnosis systems should also be considered as additional sources of information.
3. Monitoring vaccine coverage and impact
All countries should have coverage assessment systems in place for the vaccine-preventable diseases included in the national immunization schedule. The target age for assessing vaccine coverage is dependent on the chosen vaccination programme and should be clearly defined.
The impact of vaccination programmes on acute and chronic disease cannot be measured until many years after implementation. However, countries may decide to conduct serological studies to measure the effectiveness of the vaccination programme: taking serological assessment of markers such as surface antigen and core antibody can document a reduction in chronic carrier rates and acute disease.
4. Reporting severe adverse events
Adverse events monitoring systems are already in place for tracking adverse events following immunization; these guidelines should be applied to hepatitis B immunization programmes.