- Email: [email protected]
Association between Graves' ophthalmopathy and smoking
1261
of acute bronchiolitis, cyanosis, crackles, and Sa02 are the best predictors of disease severity, whereas respiratory rate and Pa02 are of less value. Dr E. K. Mulholland was the recipient of Clinical Research Fellowship.
a
Royal Children’s Hospital
We thank Sister J. Keng and the nursing staff of ward 9 East; Dr G. L. Gilbert, Mr E. Uren and the Department of Microbiology; Dr 1. L. Hudson of Biostatistics group; and the Department of Biochemistry; Royal Children’s Hospital, Melbourne.
REFERENCES 1. World Health Organisation. Case management of acute respiratory infections in children in developing countries. Geneva 1985, WHO/
2. World Health
Organisation. Programme for control of acute respiratory infections, Programme Report 1988. Geneva 1989, WHO/ARI/89.3. 3. Reynolds EOR. Arterial blood gas tensions in acute disease of lower respiratory tract in infancy. Br Med J 1963; i: 1192-95. 4. Cherian T, John TJ, Simoes E, Steinhoff MC, John M. Evaluation of simple clinical signs for the diagnosis of acute lower respiratory tract infection. Lancet 1988; ii: 125-28. 5. Simpson H, Matthew DJ, Inglis JM, George EL. Virological findings and blood gas tensions in acute lower respiratory tract infections in children. Br Med J 1974; 2: 629-32. 6. Simpson H, Flenley DC. Arterial blood gas tensions and pH in acute lower respiratory tract infections in infancy and childhood. Lancet 1967; i: 7-12. 7. Kendig E, Chernick V. Disorders of the respiratory tract in children. Philadelphia: WB Saunders, 1983: 284. 8. Nunn JF. Applied respiratory physiology. London: Butterworth, 1987: 229.
RSD-85.15.
EPIDEMIOLOGY Association between Graves’
ophthalmopathy and
smoking
Patients with Graves’ disease were questioned by postal survey about their smoking history. There were significantly more smokers in the group with ophthalmopathy than in the group with Graves’ thyrotoxicosis or controls. Patients with severe eye signs smoked significantly more tobacco than did those with less serious signs.
Introduction Graves’ ophthalmopathy is an autoimmune disease that affects the extraocular muscles.1,2 Most patients with Graves’ thyrotoxicosis have subclinical eye disease, which can be detected by sensitive techniques such as ultrasonography or computed tomography, 3,4 but ophthalmopathy can also develop in patients with Hashimoto’s thyroiditis or even in those without any evidence of thyroid disease.5 These observations have focused interest on factors that may predispose to the development of clinical eye disease, particularly in contrast to patients with thyroid autoimmunity but who have only subclinical disease. The suggestion by Frecker et al6 that there are immunogenetic markers for ophthalmopathy is not supported by others,7,8 and a possible association with blood group P polymorphisms7 has yet to be confirmed. Smoking has been tentatively associated with severe Graves’ ophthalmopathy, based on a retrospective analysis of 12 consecutive patients.9 We here assess smoking habits in a large group of patients with Graves’ ophthalmopathy whose disease was serious enough for referral to a tertiary care centre; we have compared these patients with patients who were referred for treatment of Graves’ thyrotoxicosis, and with a group of controls.
Patients and methods Questionnaire A written questionnaire, which was approved by an ethical committee, was used to gather data. Name, sex, date of birth, and hospital number were recorded. Patients were asked if they had ever smoked as much as 1 cigarette a day (or 1 cigar a week, or 30 g of tobacco a month) for as long as a year. If the response to this was "yes", they were asked to answer further questions about when they had started to smoke, whether and when they had stopped, how much they smoked, and whether this had changed during the previous year. They were also questioned about the occupation of the head of household with a condensed version of the Registrar General’s socioeconomic grouping.l0 The questionnaire was sent with a reply-paid envelope by post to the patients.
Patients Three groups of patients, chosen randomly, were included in the survey. These were: 130 patients referred over a 10-year period (1977-87) to Moorfields Eye Hospital for assessment and treatment of severe Graves’ ophthalmopathy, 89 patients with Graves’ thyrotoxicosis treated over the previous 10 years with radioiodine or antithyroid drugs and who are currently enrolled in the Cambridge automated thyroid follow-up register, and 167 control patients100 without Graves’ disease attending a general outpatient clinic at Moorfields Eye Hospital (Moorfields controls) and 67 enrolled in the Cambridge thyroid register either for follow-up of Hashimoto’s thyroiditis (34) or for radioiodine-treated toxic multinodular goitre
ADDRESSES. Institute of Ophthalmology and Moorfields Eye Hospital, London (B. Shine, MD, P. Fells, FRCS) and University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge (O. M. Edwards, MD, A. P Weetman, MD) Correspondence to Dr A. P. Weetman, Department of Medicine, Level 5, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK.
1262
SMOKING HISTORY
*95% confidence interval
(33) (Cambridge controls). The case notes of all the Cambridge patients were reviewed before an analysis of the returned questionnaires, and the presence and severity of routinely noted eye signs were recorded according to the classification of Van Dyk.11
Analysis Results were analysed with contingency tables and the X2 test; all values are for two-tailed analysis. Binomial probabilities were p used to compare proportions of smokers in the three groups.
Results
Fig 2-Smoking history
in
patients with Graves’ disease and
controls. columns=Graves’ black ophthalmopathy Open (n=59), columns=Graves’ thyrotoxicosis (n=57); grey columns= controls
(n=74).
Replies were received from 85 (65%) of the Graves’ ophthalmopathy group, 62 (70%) of the Graves’ thyrotoxicosis group, 49 (71 %) of the Cambridge controls, and 32 (32%) of the Moorfields controls. Median ages (range) were 68 years (21-80), 56 years (15-81), 69 years (25-95), and 55 years (27-76), respectively. The groups were broadly similar with respect to sex and socioeconomic distribution. There was a significant difference (X2 46-9, p < 0-0001) in smoking history between all the groups (table). When the groups were considered individually, this difference was due to the excess of current smokers with Graves’ =
ophthalmopathy. Smoking history in Cambridge patients with Graves’ thyrotoxicosis did not differ significantly from that of Cambridge controls. Smoking history in Moorfields patients with Graves’ ophthalmopathy was significantly different from that of Moorfields controls (X2 24,3, p < 0-0001). When combined data for all the controls and the Graves’ thyrotoxicosis patients were compared with the Graves’ ophthalmopathy group the difference in smoking habits was even more apparent (=43-06). There was also a significant difference between the Graves’ =
ophthalmopathy group and the Graves’ thyrotoxicosis group (= 18 l,p<0 001). The slight excess of smokers in the Graves’ thyrotoxicosis group compared with the Cambridge controls could have been biased by the inclusion of patients who may also have had severe Graves’ ophthalmopathy. Review of the notes showed that 16 (26%) of the Cambridge controls had ophthalmopathy grade 3 and 3 (5%) had grade 4 eye disease. Enough information was obtained from 59 of the patients with Graves’ ophthalmopathy (19 with grade 3, 40 with grade 4), 57 of the patients with Graves’ thyrotoxicosis, and 74 controls (Cambridge and Moorfields) to estimate total tobacco consumption in pack years-ie, mean daily number of packs (1pack = 20 cigarettes) smoked x number of years of smoking. Graves’ ophthalmopathy patients with the more severe eye signs had a significantly higher consumption of tobacco than did those with less serious signs (grade 3: 10 non-smokers, 5 < 20 pack years, 4 > 20 pack years vs grade >, 4: 8, 11, 21, respectively, p<0 025) (fig 1). Patients with Graves’ ophthalmopathy of grade 3 or less were broadly similar to those with Graves’ thyrotoxicosis and controls with respect to pack years consumed. Fig 2 highlights the heavy consumption in the Graves’ ophthalmopathy patients. Discussion Our findings point to smoking and severe
Fig 1-Smoking history in patients with Graves’ ophthalmopathy. Open columns=grade -$3 (n=19); black columns=grade >3 (n=40)
significant link between current ophthalmopathy. The association is further supported by comparison of the smoking habits of the Graves’ ophthalmopathy group (62% smoked, 95% confidence interval 52-72) with those of British adults12 (40% smoked in 1978, 33% smoked in 1986). More than half our patients were aged over 60; only 30% of the population in this age group smoked in 1978 (25% in 1986).12 How might this association arise? That severity of eye disease may have made patients take up or continue smoking is not supported by the data: there was no significant difference in the numbers of patients who gave up or started smoking after a diagnosis of thyroid disease or eye disease was made, and smoking habits had not changed or had actually decreased in the year before the survey equally in all a
Graves’
1263
patients.
A direct irritant effect of smoke
on
the eye is also
unlikely since grade 3 and greater ophthalmopathy represents significant retrobulbar disease. The immunological effects of smoking include alteration of peripheral blood T-cell phenotypes and function.13 Additionally, production of acute-phase reactants, complement components, and interleukin-1is enhanced by tobacco/3,14 anthracene derivatives in cigarette smoke may have a specific immunological role since 3-methylcholanthrene induces experimental autoimmune thyroiditis in susceptible rats.1s The immunological effect could also be due to enhanced release in smokers of a thyroid autoantigen which then cross reacts with eye muscled that serum thyroglobulin concentrations are higher in smokers probably results from damage to the thyroid by thiocyanates.16 The risk of getting postpartum thyroiditis is similarly increased by smoking.17 Smoking is only one possible environmental association with severe Graves’ ophthalmopathy since one-third of our patients do not smoke. Nonetheless, the effect on ophthalmopathy of stopping smoking should now be assessed. REFERENCES 1. Weetman AP.
Autoimmunity in Graves’ ophthalmopathy: a review. J R Soc Med 1989; 82: 153-58. 2. Jacobson DH, Gorman CA. Endocrine ophthalmopathy: current ideas concerning etiology, pathogenesis and treatment. Endocniol Rev 1984; 5: 200-20. 3. Werner SC, Coleman DJ, Franzen LA. Ultrasonographic evidence of a consistent orbital involvement in Graves’ disease. N Engl J Med 1974; 308: 420-24.
4. Enzmann DR, Donaldson SS, Kriss JP. Appearance of Graves’ eye disease on orbital computed tomography. J Comput Assist Tomogr 1979; 3: 815-19. 5. Teng WSS, Yeo PPB. Ophthalmic Graves’ disease: natural history and detailed thyroid function studies. Br Med J 1977; 1: 273-75. 6. Frecker M, Stenszky V, Bálázs C, Kozma L, Kraszits E, Farid NR. Genetic factors in Graves’ ophthalmopathy. Clin Endocrinol 1986; 25: 479-85. 7. Kendall-Taylor P, Stephenson A, Stratton A, Pipiha SS, Perros P, Roberts DF. Differentiation of autoimmune ophthalmopathy from Graves’ hyperthyroidism by analysis of genetic markers. Clin Endocrinol 1988; 28: 601-10. 8. Weetman AP, So AK, Warner CA, Foroni L, Fells P, Shrine B. Immunogenetic markers in Graves’ ophthalmopathy. Clin Endocrinol 1988; 28: 619-28. 9. Hägg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Br Med J 1987; 295: 634-35. 10. Office of Population Censuses and Surveys. Classification of occupations. London: HM Stationery Office, 1980. 11. Van Dyk HJL. Orbital Graves’ disease: a modification of the "NO SPECS" classification. Ophthalmology 1981; 88: 479-83. 12. Office of Population Censuses and Surveys. Cigarette smoking 1972 to 1986. OPCS Monitor. Government Statistical Service, February 9 1988: 1-10. 13. Holt PG. Immune and inflammatory function in cigarette smokers. Thorax 1987; 42: 241-49. 14. Francus T, Manzo G, Canki M, Thompson LC, Szabo P. Two peaks of interleukin 1 expression in human leukocytes cultures with tobacco glycoprotein. J Exp Med 1989; 170: 327-32. 15. Cohen SB, Weetman AP. Characterization of different types of experimental autoimmune thyroiditis in the Buffalo strain rat. Clin Exp Immunol 1987; 69: 25-32. 16. Christensen SB, Ericsson UB, Janzon L, Tibblin S, Melander A. Influence of cigarette smoking on goiter formation, thyroglobulin and thyroid hormone levels in women. J Clin Endocrinol Metab 1984; 58: 615-18. 17. Fung HYM, Kologlu M, Collison K, et al. Postpartum thyroid dysfunction in Mid Glamorgan. Br Med J 1988; 296: 241-44.
MODERN VACCINES Parasitic diseases
In this brief review we have concentrated on three types of infection in which effective vaccines are desirable and in which some progress has been made. However, as will be seen, nothing is yet on offer which remotely equals the vaccines available for viral and bacterial diseases, and enormous efforts are still required.
parasitic
Malaria Malaria is still a major cause of illness and death in the world; in 1984 over ten million cases were reported, compared with million cases of measles. Mortality is principally in children below the age of 5 and in non-immune (eg, tourist) adults. Control of the mosquito vector is at present impossible, while resistance of the parasite to antimalarial drugs seems to be on the increase. The need for a vaccine, therefore, has never been stronger. The development of clinically effective, though never complete, immunity in young adults from endemic areas, plus the success of vaccines in a range of laboratory animals, suggests that a two
human vaccine ought to be possible, and extraordinary efforts have been made in this direction. It was therefore somewhat of a disappointment when three recent field trials were only partly successful, all directed at Plasmodium falciparum (malignant tertian), the most severe form and the only one whose antigens have been explored in detail. In two of these trials, both from America, the antigen was a 4-aminoacid sequence of which numerous repeats are found in the major surface protein of the sporozoite-the infective stage injected by the mosquito, which subsequently develops in the liver. In one trial a synthetic peptidel and in the other a recombinant one2 were injected, ADDRESSES: Department of Immunology, University College and Middlesex School of Medicine, Arthur Stanley House, Tottenham Street, London W1 P 9PG, UK (Prof J. H. L. Playfair, MB, DSc); Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, London WC1 E 7HT, UK (J M Blackwell, PhD); Moredun Research Institute, 408 Gilmerton Road, Edinburgh EH17 7JH, UK (H. R. P. Miller, BVMS.
PhD).
of acute bronchiolitis, cyanosis, crackles, and Sa02 are the best predictors of disease severity, whereas respiratory rate and Pa02 are of less value. Dr E. K. Mulholland was the recipient of Clinical Research Fellowship.
a
Royal Children’s Hospital
We thank Sister J. Keng and the nursing staff of ward 9 East; Dr G. L. Gilbert, Mr E. Uren and the Department of Microbiology; Dr 1. L. Hudson of Biostatistics group; and the Department of Biochemistry; Royal Children’s Hospital, Melbourne.
REFERENCES 1. World Health Organisation. Case management of acute respiratory infections in children in developing countries. Geneva 1985, WHO/
2. World Health
Organisation. Programme for control of acute respiratory infections, Programme Report 1988. Geneva 1989, WHO/ARI/89.3. 3. Reynolds EOR. Arterial blood gas tensions in acute disease of lower respiratory tract in infancy. Br Med J 1963; i: 1192-95. 4. Cherian T, John TJ, Simoes E, Steinhoff MC, John M. Evaluation of simple clinical signs for the diagnosis of acute lower respiratory tract infection. Lancet 1988; ii: 125-28. 5. Simpson H, Matthew DJ, Inglis JM, George EL. Virological findings and blood gas tensions in acute lower respiratory tract infections in children. Br Med J 1974; 2: 629-32. 6. Simpson H, Flenley DC. Arterial blood gas tensions and pH in acute lower respiratory tract infections in infancy and childhood. Lancet 1967; i: 7-12. 7. Kendig E, Chernick V. Disorders of the respiratory tract in children. Philadelphia: WB Saunders, 1983: 284. 8. Nunn JF. Applied respiratory physiology. London: Butterworth, 1987: 229.
RSD-85.15.
EPIDEMIOLOGY Association between Graves’
ophthalmopathy and
smoking
Patients with Graves’ disease were questioned by postal survey about their smoking history. There were significantly more smokers in the group with ophthalmopathy than in the group with Graves’ thyrotoxicosis or controls. Patients with severe eye signs smoked significantly more tobacco than did those with less serious signs.
Introduction Graves’ ophthalmopathy is an autoimmune disease that affects the extraocular muscles.1,2 Most patients with Graves’ thyrotoxicosis have subclinical eye disease, which can be detected by sensitive techniques such as ultrasonography or computed tomography, 3,4 but ophthalmopathy can also develop in patients with Hashimoto’s thyroiditis or even in those without any evidence of thyroid disease.5 These observations have focused interest on factors that may predispose to the development of clinical eye disease, particularly in contrast to patients with thyroid autoimmunity but who have only subclinical disease. The suggestion by Frecker et al6 that there are immunogenetic markers for ophthalmopathy is not supported by others,7,8 and a possible association with blood group P polymorphisms7 has yet to be confirmed. Smoking has been tentatively associated with severe Graves’ ophthalmopathy, based on a retrospective analysis of 12 consecutive patients.9 We here assess smoking habits in a large group of patients with Graves’ ophthalmopathy whose disease was serious enough for referral to a tertiary care centre; we have compared these patients with patients who were referred for treatment of Graves’ thyrotoxicosis, and with a group of controls.
Patients and methods Questionnaire A written questionnaire, which was approved by an ethical committee, was used to gather data. Name, sex, date of birth, and hospital number were recorded. Patients were asked if they had ever smoked as much as 1 cigarette a day (or 1 cigar a week, or 30 g of tobacco a month) for as long as a year. If the response to this was "yes", they were asked to answer further questions about when they had started to smoke, whether and when they had stopped, how much they smoked, and whether this had changed during the previous year. They were also questioned about the occupation of the head of household with a condensed version of the Registrar General’s socioeconomic grouping.l0 The questionnaire was sent with a reply-paid envelope by post to the patients.
Patients Three groups of patients, chosen randomly, were included in the survey. These were: 130 patients referred over a 10-year period (1977-87) to Moorfields Eye Hospital for assessment and treatment of severe Graves’ ophthalmopathy, 89 patients with Graves’ thyrotoxicosis treated over the previous 10 years with radioiodine or antithyroid drugs and who are currently enrolled in the Cambridge automated thyroid follow-up register, and 167 control patients100 without Graves’ disease attending a general outpatient clinic at Moorfields Eye Hospital (Moorfields controls) and 67 enrolled in the Cambridge thyroid register either for follow-up of Hashimoto’s thyroiditis (34) or for radioiodine-treated toxic multinodular goitre
ADDRESSES. Institute of Ophthalmology and Moorfields Eye Hospital, London (B. Shine, MD, P. Fells, FRCS) and University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge (O. M. Edwards, MD, A. P Weetman, MD) Correspondence to Dr A. P. Weetman, Department of Medicine, Level 5, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK.
1262
SMOKING HISTORY
*95% confidence interval
(33) (Cambridge controls). The case notes of all the Cambridge patients were reviewed before an analysis of the returned questionnaires, and the presence and severity of routinely noted eye signs were recorded according to the classification of Van Dyk.11
Analysis Results were analysed with contingency tables and the X2 test; all values are for two-tailed analysis. Binomial probabilities were p used to compare proportions of smokers in the three groups.
Results
Fig 2-Smoking history
in
patients with Graves’ disease and
controls. columns=Graves’ black ophthalmopathy Open (n=59), columns=Graves’ thyrotoxicosis (n=57); grey columns= controls
(n=74).
Replies were received from 85 (65%) of the Graves’ ophthalmopathy group, 62 (70%) of the Graves’ thyrotoxicosis group, 49 (71 %) of the Cambridge controls, and 32 (32%) of the Moorfields controls. Median ages (range) were 68 years (21-80), 56 years (15-81), 69 years (25-95), and 55 years (27-76), respectively. The groups were broadly similar with respect to sex and socioeconomic distribution. There was a significant difference (X2 46-9, p < 0-0001) in smoking history between all the groups (table). When the groups were considered individually, this difference was due to the excess of current smokers with Graves’ =
ophthalmopathy. Smoking history in Cambridge patients with Graves’ thyrotoxicosis did not differ significantly from that of Cambridge controls. Smoking history in Moorfields patients with Graves’ ophthalmopathy was significantly different from that of Moorfields controls (X2 24,3, p < 0-0001). When combined data for all the controls and the Graves’ thyrotoxicosis patients were compared with the Graves’ ophthalmopathy group the difference in smoking habits was even more apparent (=43-06). There was also a significant difference between the Graves’ =
ophthalmopathy group and the Graves’ thyrotoxicosis group (= 18 l,p<0 001). The slight excess of smokers in the Graves’ thyrotoxicosis group compared with the Cambridge controls could have been biased by the inclusion of patients who may also have had severe Graves’ ophthalmopathy. Review of the notes showed that 16 (26%) of the Cambridge controls had ophthalmopathy grade 3 and 3 (5%) had grade 4 eye disease. Enough information was obtained from 59 of the patients with Graves’ ophthalmopathy (19 with grade 3, 40 with grade 4), 57 of the patients with Graves’ thyrotoxicosis, and 74 controls (Cambridge and Moorfields) to estimate total tobacco consumption in pack years-ie, mean daily number of packs (1pack = 20 cigarettes) smoked x number of years of smoking. Graves’ ophthalmopathy patients with the more severe eye signs had a significantly higher consumption of tobacco than did those with less serious signs (grade 3: 10 non-smokers, 5 < 20 pack years, 4 > 20 pack years vs grade >, 4: 8, 11, 21, respectively, p<0 025) (fig 1). Patients with Graves’ ophthalmopathy of grade 3 or less were broadly similar to those with Graves’ thyrotoxicosis and controls with respect to pack years consumed. Fig 2 highlights the heavy consumption in the Graves’ ophthalmopathy patients. Discussion Our findings point to smoking and severe
Fig 1-Smoking history in patients with Graves’ ophthalmopathy. Open columns=grade -$3 (n=19); black columns=grade >3 (n=40)
significant link between current ophthalmopathy. The association is further supported by comparison of the smoking habits of the Graves’ ophthalmopathy group (62% smoked, 95% confidence interval 52-72) with those of British adults12 (40% smoked in 1978, 33% smoked in 1986). More than half our patients were aged over 60; only 30% of the population in this age group smoked in 1978 (25% in 1986).12 How might this association arise? That severity of eye disease may have made patients take up or continue smoking is not supported by the data: there was no significant difference in the numbers of patients who gave up or started smoking after a diagnosis of thyroid disease or eye disease was made, and smoking habits had not changed or had actually decreased in the year before the survey equally in all a
Graves’
1263
patients.
A direct irritant effect of smoke
on
the eye is also
unlikely since grade 3 and greater ophthalmopathy represents significant retrobulbar disease. The immunological effects of smoking include alteration of peripheral blood T-cell phenotypes and function.13 Additionally, production of acute-phase reactants, complement components, and interleukin-1is enhanced by tobacco/3,14 anthracene derivatives in cigarette smoke may have a specific immunological role since 3-methylcholanthrene induces experimental autoimmune thyroiditis in susceptible rats.1s The immunological effect could also be due to enhanced release in smokers of a thyroid autoantigen which then cross reacts with eye muscled that serum thyroglobulin concentrations are higher in smokers probably results from damage to the thyroid by thiocyanates.16 The risk of getting postpartum thyroiditis is similarly increased by smoking.17 Smoking is only one possible environmental association with severe Graves’ ophthalmopathy since one-third of our patients do not smoke. Nonetheless, the effect on ophthalmopathy of stopping smoking should now be assessed. REFERENCES 1. Weetman AP.
Autoimmunity in Graves’ ophthalmopathy: a review. J R Soc Med 1989; 82: 153-58. 2. Jacobson DH, Gorman CA. Endocrine ophthalmopathy: current ideas concerning etiology, pathogenesis and treatment. Endocniol Rev 1984; 5: 200-20. 3. Werner SC, Coleman DJ, Franzen LA. Ultrasonographic evidence of a consistent orbital involvement in Graves’ disease. N Engl J Med 1974; 308: 420-24.
4. Enzmann DR, Donaldson SS, Kriss JP. Appearance of Graves’ eye disease on orbital computed tomography. J Comput Assist Tomogr 1979; 3: 815-19. 5. Teng WSS, Yeo PPB. Ophthalmic Graves’ disease: natural history and detailed thyroid function studies. Br Med J 1977; 1: 273-75. 6. Frecker M, Stenszky V, Bálázs C, Kozma L, Kraszits E, Farid NR. Genetic factors in Graves’ ophthalmopathy. Clin Endocrinol 1986; 25: 479-85. 7. Kendall-Taylor P, Stephenson A, Stratton A, Pipiha SS, Perros P, Roberts DF. Differentiation of autoimmune ophthalmopathy from Graves’ hyperthyroidism by analysis of genetic markers. Clin Endocrinol 1988; 28: 601-10. 8. Weetman AP, So AK, Warner CA, Foroni L, Fells P, Shrine B. Immunogenetic markers in Graves’ ophthalmopathy. Clin Endocrinol 1988; 28: 619-28. 9. Hägg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Br Med J 1987; 295: 634-35. 10. Office of Population Censuses and Surveys. Classification of occupations. London: HM Stationery Office, 1980. 11. Van Dyk HJL. Orbital Graves’ disease: a modification of the "NO SPECS" classification. Ophthalmology 1981; 88: 479-83. 12. Office of Population Censuses and Surveys. Cigarette smoking 1972 to 1986. OPCS Monitor. Government Statistical Service, February 9 1988: 1-10. 13. Holt PG. Immune and inflammatory function in cigarette smokers. Thorax 1987; 42: 241-49. 14. Francus T, Manzo G, Canki M, Thompson LC, Szabo P. Two peaks of interleukin 1 expression in human leukocytes cultures with tobacco glycoprotein. J Exp Med 1989; 170: 327-32. 15. Cohen SB, Weetman AP. Characterization of different types of experimental autoimmune thyroiditis in the Buffalo strain rat. Clin Exp Immunol 1987; 69: 25-32. 16. Christensen SB, Ericsson UB, Janzon L, Tibblin S, Melander A. Influence of cigarette smoking on goiter formation, thyroglobulin and thyroid hormone levels in women. J Clin Endocrinol Metab 1984; 58: 615-18. 17. Fung HYM, Kologlu M, Collison K, et al. Postpartum thyroid dysfunction in Mid Glamorgan. Br Med J 1988; 296: 241-44.
MODERN VACCINES Parasitic diseases
In this brief review we have concentrated on three types of infection in which effective vaccines are desirable and in which some progress has been made. However, as will be seen, nothing is yet on offer which remotely equals the vaccines available for viral and bacterial diseases, and enormous efforts are still required.
parasitic
Malaria Malaria is still a major cause of illness and death in the world; in 1984 over ten million cases were reported, compared with million cases of measles. Mortality is principally in children below the age of 5 and in non-immune (eg, tourist) adults. Control of the mosquito vector is at present impossible, while resistance of the parasite to antimalarial drugs seems to be on the increase. The need for a vaccine, therefore, has never been stronger. The development of clinically effective, though never complete, immunity in young adults from endemic areas, plus the success of vaccines in a range of laboratory animals, suggests that a two
human vaccine ought to be possible, and extraordinary efforts have been made in this direction. It was therefore somewhat of a disappointment when three recent field trials were only partly successful, all directed at Plasmodium falciparum (malignant tertian), the most severe form and the only one whose antigens have been explored in detail. In two of these trials, both from America, the antigen was a 4-aminoacid sequence of which numerous repeats are found in the major surface protein of the sporozoite-the infective stage injected by the mosquito, which subsequently develops in the liver. In one trial a synthetic peptidel and in the other a recombinant one2 were injected, ADDRESSES: Department of Immunology, University College and Middlesex School of Medicine, Arthur Stanley House, Tottenham Street, London W1 P 9PG, UK (Prof J. H. L. Playfair, MB, DSc); Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, London WC1 E 7HT, UK (J M Blackwell, PhD); Moredun Research Institute, 408 Gilmerton Road, Edinburgh EH17 7JH, UK (H. R. P. Miller, BVMS.
PhD).