The guidance does not include any indication of which markers of hepatitis B virus infection are necessary to determine a student's acceptability. It is perhaps not surprising therefore that a survey of medical schools reveals some confusion (p426).( 6) Most of the schools required the results of hepatitis B virus markers before registering a new student, and half required that the student should have at least started the course of immunisation. Which hepatitis B virus tests were required varied, in some cases suggesting a lack of understanding of hepatitis B virus serology. This was demonstrated by a question asking under what circumstances a student would be refused entry, or removed from a course; two schools replied that students would be excluded if hepatitis B virus surface antibody tests were positive, which would exclude students who were immune, and five schools replied that they would exclude students if hepatitis B virus surface antigen tests were positive, regardless of "e" marker status, which goes much further than required by the NHSguidance.
In a low prevalence population, such as medical students, the most economical strategy for achieving confirmed immunity to hepatitis B is to immunise all and to test serologically after the third dose. To screen before immunisation and confirm immunity afterwards requires more tests and saves very little vaccine, but this would identify carriers of hepatitis B virus infection earlier.
Which tests should be used? Detectable antibody to hepatitis B virus surface antigen indicates immunity to infection, whether natural or vaccine induced, and a lack of infectivity (table 1). If antibody to surface antigen is not detectable after vaccination, this may be due to a failure to respond to the vaccine or due to the individual already being infected; a test for hepatitis B virus surface antigen, if positive, would confirm current infection. If neither surface antigen nor antibody are detected, a test for antibodies to hepatitis B virus core antigen will distinguish non-responders to the vaccine (hepatitis B core antibody negative) from those who have had hepatitis B in the past but do not have a detectable response to hepatitis B surface antigen (hepatitis B core antibody detectable). Non-responders to vaccine may be given one or more further doses, but a residual group of non-responders will remain.
Most students found to have hepatitis B surface antigen in their serum will prove to be carriers (defined as someone with detectable surface antigen for more than six months) rather than to have acute infection. The critical question is whether a carrier is to be considered infectious. The guidance from the NHS Management Executive is for this to be determined by tests for hepatitis B e antigen( 4) ; if this marker is detectable, the individual should be considered infectious and is not permitted to undertake exposure prone procedures. For medical students, the implication is that if the guidance from the Committee of Vice-Chancellors and Principals is followed, they should be refused entry, or not allowed to continue to the clinical course. If hepatitis B e antigen is not detectable, whether or not hepatitis B e antibody is detected, there should be no restriction on students' activity, unless they have been associated with transmission of hepatitis B to a patient. Transmissions from health care workers who are negative for hepatitis B e antigen have been reported, associated with mutations in the precore gene of the hepatitis B virus, which permits viral replication in the absence of e antigen expression.( 7-9) In the future, recommendations maybe amended to take this into account.
| Table 1-Interpretation of the common patternsof serological markers of hepatitis B virus infection | ||||||
| Hepatitis B surface | Hepatitis B core | Hepatitis B 'e' | ||||
| Antigen | Antibody | Antibody (IgG) | Antibody (IgM)(*) | Antigen | Antibody | |
| Neverinfected | - | - | - | |||
| Vaccinated | - | + | - | |||
| Immune by natural infection | - | +(**) | + | |||
| Acute infection: | ||||||
| Early | +(***) | - | - | - | +/- | |
| Late | + | - | + | +++ | + | |
| Carrier (****): | ||||||
| High infectivity | + | - | + | +/- | + | - |
| Low infectivity | + | - | + | - | - | + |
| (*)Tests for IgM are usually strongly reactive during acute infection; weaker reactivity may also be present in carriers, particularly if they are also positive for e antigen.
(**) Not detectable in 10-15% of those who have had hepatitis B in the past; core antibody may be the only marker detectable. (***) The first marker to become detectable during acute infection, and before any symptoms. (****) Someone with detectable surface antigen more than six months after acute hepatitis B or first detection of antigen. | ||||||
The Committee of Vice-Chancellors and Principals should provide more detailed guidance if its policy is to have credibility.Universities should ensure that their policies are appropriate, and some need to take advice-discussing policy with their own departments of virology and occupational health would seem to be a good start. Some may yet consider that excluding all students positive for hepatitis B virus e antigen is not necessary. None would disagree with the committee that medical students, like health care workers, have a duty of care to their patients, including a duty not to expose them to hepatitis B virus infection-but are they necessarily a hazard to patients? There have been no reported cases of hepatitis B transmission from medical students to patients in Britain. Provided there is the safeguard that the hepatitis B virus status of all medical students is known, a more flexible approach should be possible, especially if the universities and the General Medical Council accept that it is not essential for medical students to carry out exposure prone procedures in order to qualify and complete a preregistration year. Might hepatitis B virus not be considered along with other disabilities which may lead to a limited career choice but which leave open the possibility that those affected can safely qualify and contribute to medicine in one of its many fields?
R J C GILSON
Senior lecturer
Department of Sexually Transmitted Diseases,
Division of Pathology and Infectious Diseases,
University College London Medical School,
London WC1E 6AU
REFERENCES
1 Committee of Vice-Chancellors and Principals of the Universities of the United Kingdom. Guidance on fitness to practise: hepatitis B. London: The Committee, 1994.
2 Lever AML. Hepatitis B and medical student admission.BMJ 1994;308:870-1.
3 Entry to medical school: by examination and vaccination?Lancet 1994;343:927-8.
4 NHS Management Executive. Protecting health care workers and patients from hepatitis B. Lancashire: Department of Health,1993. (Health Services Guidelines HSG (93)40.)
5 Committee of Vice-Chancellors and Principals of the Universities of the United Kingdom. Guidance on fitness to practise: hepatitis B. London: The Committee, 1995.
6 Parker G, Jenkins S. Hepatitis B and admission to medical school: an audit of British medical school policy. Student BMJ 1996;4:426.
7 Carman WF, Jacyna MR, Hadziyannis S, Karayiannis P, McGarvey M J, Makris A, et al. Mutation preventing the formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 1989;ii:588-91.
8 Hawkins A E, Gilson R J C, Beath S V, Boxall E H, Kelly DA, Tedder R S, et al. Novel application of a point mutation assay:evidence for transmission of hepatitis B viruses with precore mutations and their detection in infants with fulminant hepatitis B. J Med Virol 1994;44:13-21.
9 Zuckerman MA, Hawkins A E, Briggs M, Waite J, Balfe P, Gilson R J C, et al. The investigation of hepatitis B transmission in an health care setting-application of direct sequence analysis. J Inf Dis1995;172:1080-3.