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Sandercock (Edinburgh); Dr C. Gardner-Thorpe (Exeter); Dr W. F. Durward, Dr I. Melville, Dr M. Thomas (Glasgow); Dr M. A. Barrie (Harlow); Dr J. E. Rees, Dr M. Rice-Oxley (Haywards Heath): Dr A. M. Butterfill, Dr N. Fraser (Hereford); Dr M. D. Rawson (Hull); Dr C. H. Hawkes (Ipswich); Dr A. I. Mukhtar (Kettering); Dr E. G. S. Spokes (Leeds); Dr B. Kendall, Dr P. Millac, Dr J. R. Moore, Dr I. F. Pye (Leicester); Dr J. W. Garry (Lincoln); Dr J. Andrews, Dr L. D. Blumhardt, Dr M. Hand, Prof F. Harris, Dr M. Hayward, Dr D. P. Heaf, Dr S. J. Howell, Dr P. R. D. Humphrey, Dr A. D. Kindley, Dr I. Lewis, Dr P. MacFarlane, Dr T. McKendrick, Dr N. Marlow, Dr P. Minchom, Dr I. Morgan, Dr J. R. Roberts, Dr L. Rosenbloom, Dr S. R. Sadik, Dr J. Sills, Dr W. B. Spry, Dr P. Stutchfield, Dr A. P. Thomson, Dr A. J. Williams, Dr E. H. Yousif, Dr T. D. Yuille (Liverpool); Dr P. Chesterman, Dr C. R. A. Clarke, Dr F. Clifford Rose, Dr P. Crawford, Dr C. Dellaportas, Dr R. Elwes, Dr T. D. C. Fox, Dr D. Hall, Dr A. Hellier, Dr N. Legg, Dr P. Monro, Dr G. D. Perkin, Dr E. H. Reynolds, Dr de Silva, Dr T. Steiner, Dr S. Wilson (London); Dr W. J. K. Gumming, Dr R. W. Newton, Dr M. Noronha, Dr D. I. Shepherd (Manchester); Dr P. Newman, Dr M. Saunders (Middlesbrough); Dr D. Bates, Dr N. E. F. Cartlidge, Dr D. GardnerMedwin, Dr D. W. A. Milligan (Newcastle upon Tyne); Dr D. R. Knight (Northampton); Dr R. Greenhall, Dr N. M. Hyman, Dr E. Spalding (Oxford); Dr P. I. Tomlin (Preston); Dr G. Venables (Sheffield); Dr A. W. Pantlin (South Ockendon); Dr B. Crossley, Dr C. Tyrie (Southampton); Dr H. G. Boddie, Dr R. A. Cooper, Dr S. L. Manawadu, Dr R. P. Murphy (Stoke-on-Trent); Dr A. C. Butler (Stourbridge); Dr P. Cleland (Sunderland); Dr C. A. R. Bainton (Torquay); Dr L. Loizou (Wakefield); Dr G. P. McMullin (Warrington); Dr J. Platt (Whitehaven); Dr R. Corston (Wolverhampton); Study participants Europe: Dr B. Pedersen (Denmark); Dr O. Dulac (France); Dr M. Conran (Ireland); Dr P. Zagnoni (Cuneo); Dr G. Zaccara (Florence); Dr A. van Lierde and Prof F. Viani (Milan, Italy); Dr J. Overweg (the Netherlands). REFERENCES

JF, Hauser WA, Elverbalk LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia 1979; 20: 729-37. 2. Chadwick D. The discontinuation of antiepileptic therapy. In: Meldrum BS, Pedley TA, eds. Recent advances in epilepsy 2. Edinburgh: 1. Annegers

3.

Churchill Livingstone, 1985: 111-24. Pedley TA. Discontinuing antiepileptic drugs. N Engl J Med 1988; 318: 982-84.

Goodridge DMG, Shorvon SD. Epilepsy in a population of 6000. II: treatment and prognosis. Br Med J 1983; 287: 645-47. 5. Commission on Classification and Terminology of the International League against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 4.

1981; 22: 489-501. on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30: 389-98. 7. White SJ, Freedman LS. Allocation of patients to treatment groups in a controlled clinical trial. Br J Cancer 1978; 37: 849-57. 8. Janz D. When should antiepileptic drug treatment be terminated? In: Wolf P, Dam M, Janz D, Dreifuss FE, eds. Advances in epileptology, vol 16. New York: Raven, 1987: 365-72. 9. Shafer SQ, Hauser WA, Annegers JF, Klass DW. EEG and other early predictors of epilepsy remission: a community study. Epilepsia 1988;

6. Commission

29: 590-600. 10. Oller-Daurella

L, Pamies R, Oller L. Reduction or discontinuance of antiepileptic drugs in patients seizure-free for more than 5 years. In. Janz D, ed. Epileptology. Stuttgart: Thieme-Verlag, 1976: 218-27. 11. Arts WFM, Visser LH, Loonen MCB, et al. Follow-up of 146 children with epilepsy after withdrawal of antiepileptic therapy. Epilepsia 1988; 29: 244-50.

12. Overweg J, Rowan AJ, Binnie CD, Oosting J, Nagelkerke NJD. Prediction of seizure recurrence after withdrawal of antiepileptic drugs. In: Dam M, Gram L, Penry JK, eds. Advances in epileptology: XII Epilepsy International Symposium. New York: Raven, 1987: 503-08. 13. Shinnar S, Vining EPG, Mellits ED, et al. Discontinuing antiepileptic medication in children with epilepsy after two years without seizures. N Engl J Med 1985; 313: 976-80. 14. Emerson R, D’Souza BJ, Vining EP, Holden KR, Mellits ED, Freeman JM. Stopping medication in children with epilepsy: predictors of outcome. N Engl J Med 1981; 304: 1125-29. 15. Todt H. The late prognosis of epilepsy in childhood: results of a prospective follow-up study. Epilepsia 1984 25: 137-44.

Scheduling of revaccination against hepatitis B virus

Studies have shown that to maintain protection against infection after a primary course of hepatitis B immunisation, revaccination can be scheduled on the basis of an anti-hepatitis B virus surface antigen (anti-HBs) titre obtained 1 month after the booster dose. However, schemes which require post-booster testing may present practical difficulties. We applied a random-effects regression model to data from 118 Senegalese infants given three injections of hepatitis B vaccine about 6 weeks apart and a booster injection at 13 months, and show that revaccination can be scheduled on the basis of an anti-HBs titre recorded at the time of the booster dose. We also show that titre-at-booster is no less accurate in predicting future titre than 1-month post-booster titre. In several other studies the post-booster decline in anti-HBs conforms to the same mathematical description, indicating the generality of our findings. Lancet 1991; 337: 1180-83.

Introduction The duration of protection from hepatitis B virus (HBV) infection afforded by a primary course of immunisation depends on the titre of antibody against HBV surface

antigen (anti-HBs) attained shortly after the booster dose.1-5 To maintain protection whilst conserving vaccine, it has been proposed that revaccination should be scheduled on the basis of an anti-HBs titre obtained 1 month after boosting,1-4 and this strategy has been endorsed for adults from non-endemic areas.After finding evidence of. substantial random variation amongst vaccinees in the rate of loss of antibody, Nommensen et al’ proposed that revaccination should be scheduled on the basis of anti-HBs titres obtained on two separate occasions after

boosting. Revaccination strategies which involve post-booster testing may be criticised on logistic and financial grounds. We have shown previously that anti-HBs titre at vaccination has a strong effect on the subsequent antibody response.8 Here we use a formal statistical model to investigate the possibility of scheduling revaccination on the basis of an ADDRESSES Institut de Virologie de Tours and Laboratoire de Microbiologie, Faculte de Pharmacie, Tours, France (P. Coursaget, PhD, B. Yvonnet, PhD, Prof J-P Chiron, PhD); Medical Research Council Biostatistics Unit, Fair View Lodge, 5 Shaftesbury Road, Cambridge CB2 2BW, UK (W. R. Gilks, PhD, Prof N E Day, PhD); Institute of Statistics, Academia Sinica,

Taipei, Taiwan (C. C. Wang, PhD); and Faculte de Medecine et de Pharmacie, Dakar, Senegal (Profl Diop-mar, MD) Correspondence to Dr W R. Gilks

,

1181

anti-HBs titre determined at the time of boosting. Such scheme should be feasible in many situations.

a

Methods The study population and serological methods have been described previously.9lo 156 Senegalese infants were each given three injections of hepatitis B vaccine about 6 weeks apart, with a booster dose about 13 months after the first dose. We analysed data from 118 infants whose anti-HBs titres at booster were known. Anti-HBs titres were recorded during annual surveys for 6 years after the booster injection. 43 infants had one post-booster anti-HBs titre recorded, 33 had two recorded, 24 had three recorded, 12 had four recorded, and 6 had five recorded. Thus, 259 post-booster blood samples were included in the analysis. The statistical analysis was designed to evaluate average postbooster trends in anti-HBs titres, and the importance of individual departures from average trends. Data were analysed with a Bayesian random-effects regression model (appendix). An alternative model in which titre at booster was replaced by an estimate of 1-month post-booster titre was fitted to see if this would decrease the variance of the random components of the model. Each infant’s 1-month post-booster titre was estimated from the first titre recorded post-booster, but infants without a titre recorded during the first post-booster year were excluded. 139 blood samples were included in this alternative analysis.

Results The data analysed are summarised in fig 1, which shows the decline in anti-HBs titre in three groups of infants divided according to their anti-HBs titre at booster injection. The three groups have a roughly linear decline in log-titre with log time-since-booster; moreover, the three trends are

nearly parallel. Results from model (1) (appendix) concerning each model parameter are summarised in table I in the form of a probability distribution. For example, table I shows that the average rate of decline in titre was precisely determined by the analysis: there was a 90% probability that oc2 lay between 1 05 and - 0-84 (ie, about —1-0). The titre at booster had a substantial positive effect on subsequent titres (tl3 ’" 0’6), but the rate of decline in titre after booster was not affected by titre at booster (tl4 ",0). There was considerable -

10 000r

*Mean of differences between observed and expected

log titres

random variation amongst infants in their response to the booster injection (standard deviation of &bgr;li ’" 1-2), but little random variation amongst infants in their rates of decline in titre (standard deviation of 02i ",0,2) compared with the baseline of decline (a2). Model (1) assumed a linear relationship between log anti-HBs titre and log time, as shown in fig 1. This assumption was checked more rigorously by examining the model residuals-ie, the differences between observed and expected log titres (table II). The residuals were close to zero (well within two standard errors) for the first, fourth, and subsequent years of follow-up. For the second year, the residuals indicated a small but significant over-estimation of anti-HBs titres, and for the third year a small but significant under-estimation. (This kink in the time trend is also evident in fig 1.) This may reflect a change in the anti-HBs assay during the study. However, the residuals showed no systematic time trend, supporting the assumption of a linear trend in log titre with log time. Also, the estimated random effects did not show significant departure from the assumed normal distribution. TABLE III-PREDICTED DISTRIBUTION (%) OF ANTI-HBs TITRES FOR A GIVEN TITRE AT BOOSTER

LVLe

Illu[IL"z SIIIGC UVVJtCI

Fig 1-Decline

in anti-HBs titre after booster for infants with anti-HBs titres at booster of less than 30 mlUjml (A), 30-199 mlUjml (B), or greater than or equal to 200 mlUjml (C).

The geometric mean titre and SE are plotted as a vertical bar at the mean observation time for each year Data for the fourth post-booster year are omitted as there were fewer than 7 observations in each group for that year

1182

The parameter estimates in table I lead to the prediction that: amongst individuals with a given titre at booster, log anti-HBs titres will have a normal distribution with: mean

=9-2+0-6xlog titre at booster - log time since booster (in days) (standard deviation =1-2)

The slope of each line plotted in fig 1 and fig 2 is equal to 1 -0, implying that a tenfold increase in time since booster induces a tenfold reduction in geometric mean titre (GMT). This can also be seen by rewriting model (2): -

(2)

time after the post-booster peak titre. The standard deviation in this model reflects the random variation in the response of infants to the booster injection (the standard deviation of &bgr;li), but ignores variation due to short-term fluctuations in immunity and measurement imprecision ("noise"). We used model (2) to predict the distribution of anti-HBs titres 2-5, 5, 10, 20, and 40 years after booster, for four titres at booster (table III). A tenfold increase in titre at booster was shown to induce a fourfold increase in duration of protection. The alternative analysis suggested that predictions based on 1-month post-booster anti-HBs titres instead of titres at booster would not reduce the spread of distribution shown in table III. at any

Discussion The linear relationship shown in fig 1 was also found when we plotted log titre against log time-since-booster for previous long-term follow-up studies of hepatitis B immunisation2,4,5,10-18 (fig 2) (Yvonnet et al10 contains the data analysed here). All the previous studies show the same rate of antibody decay. The variation in vertical placement of the lines is not surprising in view of the variety of immunisation protocols and subjects employed in these studies (fig 2). The lower lines are mostly from studies in which only three vaccine doses were given, or in which the vaccinees were patients. This analysis may indicate that natural boosting during the first 5 years after immunisation is not significant in maintaining immunity in endemic areas, since lines for endemic10,16 and non-endemic2,4,11-14 areas are similar.

GMT ~ 10 000x

Titre at booster 0 66 Time since booster (in days) .

(3)

This expression also shows that a tenfold increase in titre at booster induces a fourfold increase in post-booster titre

(100 6~4). We found that the rate of loss of antibody does not depend titre at booster. Other studies have shown that rate of loss of antibody does not depend on the 1-month post-booster titre.1-5In contrast with Nommensen et al,’we also found that there was no substantial random variation amongst vaccinees in the rate of loss of antibody. Though our objectives were in several respects similar to those of Nommensen et al,’7 our results are quite different. Nommensen et al were criticised for their untested assumption of an exponential decline in log titre which is inconsistent with published data .3,11,19 In reply,20 they suggested that at extended follow-up published GMTs may be upwardly biased because of the omission of individuals with no detectable antibody. However, we would not expect this to greatly influence the course of anti-HBs decline in infants with high titre after booster injection. Moreover, since the same rate of decline in log titres is seen irrespective of response to the booster,1-5 we doubt whether published data suffer seriously from this bias. Our results indicate that post-booster sampling would not give better predictions (ie, smaller spread within each of the distributions in table III) than blood sampling at the time of the booster. Thus, titre at booster could be used as a basis for scheduling revaccinations (table III). For example, to maintain anti-HBs titres above 10 mIU/ml for at least 90% of vaccinees, subjects should be revaccinated after 2-5, 10, or 40 years, depending on whether titre at booster is around 10, 100, or 1000 mIU/ml, respectively. Alternatively, titres in a greater proportion of vaccinees could be allowed to fall below 10 mIU/ml before revaccinating, in view of evidence that protection outlasts detectable antibody.6,21,22 A revaccination strategy based on titre at booster would avoid the cost of revaccinating the whole target population at fixed intervals regardless of individual need, yet overcome some of the practical difficulties inherent in schemes which involve post-booster testing. However, the model described here should be validated prospectively before scheduling revaccination on the basis of anti-HBs titre at booster. Such a study might also evaluate directly the relationship between titre at booster and incidence of acute hepatitis or HBV surface antigen carriage. on

Bayesian random-effects regression model:

LOGSAMP1. &agr;4

x

where

= al + a2

LOGTIMEij

x

x

LOGTIME,,

LOGBOOSTi +

+

a3

x

LOGBOOST,

× LOGTIMEij + ∈1j

+

(1)

LOGSAMPij = log anti-HBs titre at jth blood sample from infant i;

LOGTIMEï =log days from booster to jth blood sample for infant 1; and Fig 2-Previous studies of decline

in anti-HBs titre after

booster.

(A) Healthy adults: Gesemann and Scheiermann" (220 subjects; &Dgr;), Goudeau et al12 (178; •), Grob et al4 (86; 0), Laplanche et al5 and Crosnier et al" (80; []), Oon et al" (31; 8),Zachoval etal" (195; V). (B) Patients and children: Benhamou et al2 and Courouce et al’8 (69 haemodialysis patients; []),Grob et al’ (62 haemodialysis patients; V), Zanetti et al’5 (67 anti-human immunodeficiency virus negative haemophiliacs; 0),Dentico et al’6 (40 Italian children; &Dgr;), Yvonnet et a]" (125 Senegalese infants; .).

LOGBOOSTi =

log titre at booster for infant i. All logarithms are to base e. Anti-HBs titres of 0 mIU/ml (11 at booster, 7 post-booster) were considered to be 1 mIU/ml for calculations to avoid taking logarithms of zero. For numerical stability, log 620 days was subtracted from and log 87 mIU/ml was subtracted from LOGBOOST1, yielding zero means for the two variables. al and a2 x LOGTIME1i describe the average anti-HBs trajectory after boosting; in paticular, a2 x LOGTIMEij describes an average rate of loss of x antibody. &agr;3 x LOGBOOSTi and &agr;4 x LOGBOOST, describe an adjustment to the average trajectory due to titre at booster; thus, a3 x LOGBOOSTi represents an overall (time-independent) adjustment to

LOGTIMEij

LOGTIMEij

1183

x the average trajectory, and &agr;4 x LOGBOOSTi represents an of the rate to average antibody decay. adjustment &bgr;1i and &bgr;2i x LOGTIMEij describe an infant-specific adjustment to the average trajectory due to factors other than titre at booster. Random effects &bgr;1i and &bgr;2i take on potentially different values for each infant i; they were assumed to be normally distributed over mfants i. Thus, &bgr;1irepresents an overall (time-independent) is an adjustment for infant i to the average trajectory, and &bgr;2i x adjustment for infant i to the average rate of antibody decay (suggested by Nommensen et aF). ∈ij describes purely random variation or "noise" caused by measurement imprecision and, perhaps, short-term random fluctuations in titre. Other parameters included the standard deviations for &bgr;1i and &bgr;2i over infants i, the correlation between &bgr;1i and &bgr;2i over infants i, and the standard deviation of the noise ∈ij. We estimated all model parameters from the data Further details are available from the authors using Gibbs (W. R. G.). To assess the adequacy of the model, a residual (an estimate of was calculated for each blood sample, and residuals were compared between post-booster time intervals. The estimated random effects &bgr;1i and &bgr;2i were tested for normality with the Kolmogorov-Smimov statistiC.25

LOGTIMEij

LOGTIMEij

sampling.23,24

∈ij)

REFERENCES 1. Grob PJ, Steffen R, Joller-Jemelka HI, Fierz W, Tschopp A, Schneider C. Hepatitis B vaccination campaign of Zurich: clinical consequences and booster strategy. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. France: Editions John Libbey Eurotext, 1990: 437-45. 2. Benhamou E, Courouce A-M, Laplanche A, Jungers P, Tron JF, Crosnier J. Long-term results of hepatitis B vaccination in patients on dialysis. N Engl J Med 1986; 314: 1710-11. 3. Jilg W, Schmidt M, Deinhardt F. Decline of anti-HBs after hepatitis B

vaccination and timing of revaccination. Lancet 1990; 335: 173-74. 4. Grob PJ, Dufek A, Joller-Jemelka HI. Hepatitis-B-immunisation— when is a booster injection necessary? Schweiz Med Wochenschr 1985; 115: 394-402. 5. Laplanche A, Courouce A-M. Benhamou E, Jungers P. Timing of hepatitis B revaccination in healthy adults. Lancet 1987; i: 1206-07. 6. International Group. Immunisation against hepatitis B. Lancet 1988; i: 875-76. 7. Nommensen FE, Go ST, MacLaren DM. Half-life of HBs antibody after hepatitis B vaccination: an aid to timing of booster vaccination. Lancet 1989; ii: 847-50. 8. Gilks WR, Coursaget P, Yvonnet B, et al. Response to hepatitis B vaccinations: some new insights. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. France: Editions John Libbey Eurotext, 1990: 409-18. 9. Coursaget P, Yvonnet B, Chotard J, et al. Seven-year study of hepatitis B

vaccine efficacy in infants from an endemic area (Senegal). Lancet 1986; ii: 1143-45. 10. Yvonnet B, Coursaget P, Chotard J, et al. Hepatitis B vaccine in infants from an endemic area: long-term anti-HBs persistance and revaccination. J Med Virol 1987; 22: 315-21. 11. Gesemann M, Scheiermann N. Timing of booster doses of hepatitis B vaccine. Lancet 1989; ii: 1274. 12. Goudeau A, Dubois F, Asou P. Long-term persistence of anti-HBs after hepatitis B immunization in adults. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. France: Editions John Libbey Eurotext, 1990: 123-37. 13. Oon CJ, Goh KT, Tan KL, Chan SH, Lim GK. Experience of hepatitis B prevention and control programme in Singapore. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. France: Editions John Libbey Eurotext, 1990: 475-89. 14. Zachoval R, Jilg W, Lorbeer B, Schmidt M, Deinhardt F. Passive/active immunisation against hepatitis B. J Infect Dis 1984; 150: 112-17. 15. Zanetti AR, Tanzi E, Romano L, Mari D, Colombo M, Mannucci PM. Anti-pre-S2 and anti-HBs responses in hemophiliacs vaccinated with a plasma-derived vaccine. A four year follow-up study. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. France: Editions John Libbey Eurotext, 1990: 79-86. 16. Dentico P, Buongiorno R, Zavoianni A, Volpe A, Pastore G, Schiraldi O. Immunogenicity of HEVAC-B Pasteur vaccine in infants: comparison of2 and 5 mcg. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. France: Editions John Libbey Eurotext, 1990: 325-32. 17. Crosnier J, Jungers P, Courouce A-M, et al. Randomised placebocontrolled trial of hepatitis B surface antigen vaccine in French haemodialysis units: I, medical staff. Lancet 1981; i: 455-59. 18. Courouce A-M, Jungers P, Benhamou E, Crosnier J. Hepatitis B vaccine in dialysis patients. N Engl J Med 1984; 311: 1515-16. 19. Gilks WR, Hall AJ, Day NE. Timing of booster doses of hepatitis B vaccine. Lancet 1989; ii: 1273-74. 20. Nommensen FE, MacLaren DM, Go ST. Timings of booster doses of hepatitis B vaccine. Lancet 1990; 335: 479-80. 21. Rawal BK, Kurtz JB. Timing of booster doses of hepatitis B vaccine. Lancet 1989; ii: 1274. 22. Wainwright RB, McMahon BJ, Bulkow LR. Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population. JAMA 1989; 261: 2362-66. 23. Geman S, Geman D. Stochastic relaxation, Gibbs distributions, and the Bayesian restoration of images. IEEE Transactions on Pattern Analysis and Machine Intelligence 1984; PAMI-6: 721-41. 24. Gelfand AE, Smith AFM. Sampling based approaches to calculating marginal densities. J Am Statist Assoc 1990; 85: 398-409. 25. Siegel S. Nonparametric statistics: for the behavioural sciences. Tokyo: McGraw-Hill, 1956: 47-52.

Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals

To

identify factors contributing to the pathogenesis of autoimmune chronic active hepatitis (CAH) healthy relatives of 13 patients with the disorder were followed prospectively for 4 years. 58 relatives were monitored for various serological markers and for T-lymphocyte migration inhibitory activity every 2 months. 3 cases of subclinical acute hepatitis A occurred during the study. In 2 of the 3 subjects, before hepatitis A virus (HAV) infection, there was a defect in suppressor-inducer T lymphocytes specifically controlling immune responses to the asialoglycoprotein receptor, an antigen expressed on the hepatocyte surface. In these 2 subjects, specific helper T cells and antibodies to the asialoglycoprotein receptor persisted and increased after acute hepatitis A, and autoimmune CAH type 1

5 months. Thus, in susceptible individuals HAV is a trigger for autoimmune CAH.

developed within

Lancet 1991; 337:1183-87.

Introduction Autoimmune chronic active hepatitis (CAH) type 1 is characterised by periportal piecemeal necrosis accompanied by high serum titres (reciprocal titre 40 or higher) of non-organ-specific autoantibodies (antinuclear antibodies ADDRESSES: Infectious Diseases Unit, A. Pugliese Hospital, Catanzaro (S. Vento, MD, T Garofano, MD); Department of Microbiology, BorgoTrento Hospital, Verona (L. Dolci, MD); and Department of Infectious Diseases, Borgo Trento Hospital, University of Verona, Italy (G. Di Perri, MD, E. Concia, MD, Prof D Bassetti, MD). Correspondence to Dr S. Vento, Infectious Diseases Unit, A. Pugliese Hospital, 88100 Catanzaro, Italy.

Scheduling of revaccination against hepatitis B virus.

Studies have shown that to maintain protection against infection after a primary course of hepatitis B immunisation, revaccination can be scheduled on...
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