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Reversible diabetes in patient with AIDS-related Kaposi's sarcoma treated with interferon α-2a
Giant-cell arteritis was confirmed in 30 patients: 28 (93%) met at least three of the American College of Rheumatology classification criteria for giant-cell arteritis. Diagnosis of polymyalgia rheumatica, without temporal arteritis, was accepted in 44 patients, none of whom fulfilled the American College of Rheumatology classification criteria for giant-cell arteritis, and 70% of whom had had at least one negative temporal artery biopsy. In 6 patients, DFS was not followed by temporal artery biopsy because a different diagnosis had been confirmed in the meantime. The overall results of DFS in the patients with or without giant-cell arteritis were: Positive DFS
Giant-cell arteritis
No
23
10
giant-cell arteritis
Negative DFS 7 40 The sensitivity of DFS was thus 77%, the specificity 80%, and the positive and negative predictive values 70% and 85%, respectively. We conclude that the DFS score in giant-cell arteritis has a higher sensitivity and specificity than the commonly used clinical or biological diagnostic criteria in this disease. It is particularly useful because of its high negative predictive value, but for diagnosis cannot replace temporal artery biopsy which has a better specificity. Whether the morphological abnormalities shown by colour doppler improve the diagnostic accuracy when compared with continuous-wave doppler examination, which is less time consuming, remains to be established.
frequently identified in many white populations’ of the USA, the UK, Denmark, South Africa, Austria, Australia, the Netherlands, Canada, France, Italy, Switzerland, Belgium, and Germany. Yet FDB is rarely reported in other populations, and never found in Finland, the former Soviet Union, and Israel. According to haplotype analysis of the apoB gene, ethnic diversity of FDB frequency suggests that most apoB 3500 mutations are derived from a single common ancestral mutation that occurred at least 10 000 years ago,’ probably in a Caucasian. Our results suggest that the apoB 3500 mutation is a rare cause of genetic hypercholesterolaemia in Japan and are consistent with this explanation. The
apoB
3500 mutation has been
*Atsushi Nohara, Kunimasa Yagi, Akihiro Inazu, Kouji Kajinami, Junji Koizumi, Hiroshi Mabuchi Second Department of Internal Medicine, School of Medicine, Kanazawa Kanazawa 920, Japan
1
2
3
4
University,
Myant NB. Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolemia. Atherosclerosis 1993; 104: 1-18. Defesche JC, Pricker KL, Hayden MR, van der Ende BE, Kastelein JP. Familial defective apolipoprotem B-100 is clinically indistinguishable from familial hypercholesterolemia. Arch Intern Med 1993; 153: 2349-56. Hansen PS, Rudiger N, Tybjaerg-Hansen A, et al. Detection of the apo-B-3500 mutation (glutamine for arginine) by gene amplification and cleavage with MspI. J Lipid Res 1991; 32: 1229-33. Miserez AR, Laager R, Chiodetti N, et al. High prevalence of familial defective apolipoprotein B-100 in Switzerland. J Lipid Res 1994; 35: 574-83.
*Xavier Puéchal, Michel Chauveau, Charles J Menkès Rhumatologie A, and Service d’Exploration Fonctionnelle Vasculaire, Hôpital Cochin, Université René Descartes, Paris 75674, France *Service de
1
2
Menkès CJ, Branche I, Feldmann JL, Chauveau M, Delbarre F. Application de l’effet Doppler au dépistage de l’artérite de Horton. Nouv Presse Med 1981; 10: 2371. Puéchal X, Chauveau M, Hilliquin P, Perrot S, Job-Deslandre C, Menkès CJ. Superficial temporal Doppler flow studies in suspected giant cell arteritis: validation of a diagnostic score. Arthritis Rheum 1994; 37 (suppl 9): S409 (abstr).
Absence of familial defective apolipoprotein B-100 in Japanese patients with familial hypercholesterolaemia SiR-Familial defective apolipoproteinB-100 (FDB) is a form of genetic hypercholesterolaemia. A single-base substitution (G to A) at nucleotide 10 708 in exon 26 of the apoB-100 gene creates a glutamine for arginine substitution in position 3500 aminoacid, resulting in reduced affinity of low-density lipoproteins (LDL) to the LDL receptor.’ FDB has been shown to be clinically indistinguishable from familial hypercholesterolaemia.2 To estimate the frequency of FDB in the Japanese population, we searched for this apoB mutation among clinically diagnosed 385 heterozygous familial hypercholesterolaemia patients from 350 unrelated families (197 men and 188 women, mean age 45 years). The mean (SD) concentrations of total cholesterol, triglyceride, and high-density lipoprotein cholesterol were 7-73 (2-15), 1-78 (1-11), and 1-27 (0-75) mmol/L, respectively. 85% of the subjects had Achilles tendon xanthoma, and 18% had coronary heart disease. We used PCR followed by cleavage with Mspl to detect the apoB 3500 mutation as described by Hansen et al.3 DNA samples from patients already diagnosed as FDB (provided by N B Myant, Hammersmith Hospital, UK and D R Illingworth, Oregon Health Sciences University, USA) were included in each PCR assay. No individuals with apoB 3500 mutation were detected. 1438
Reversible diabetes in patient with AIDSrelated Kaposi’s sarcoma treated with interferon &agr;-2a SiR-The development of type 1 diabetes in a patient treated with recombinant interferon a-2b for chronic type C hepatitis has been described, but its pathogenesis remains unclear.’1 We describe a reversible insulin-dependent diabetes occurring in an HIV-positive man 2 weeks after recombinant interferon (IFN) a-2a treatment was started for cutaneous
Kaposi’s
sarcoma.
A 54-year-old homosexual man had been positive for HIV-1 antibodies since 1990 without any notable disease in his previous medical history and no familial evidence of diabetes. Cutaneous Kaposi’s sarcoma localised to the fingers and the soles of the feet was diagnosesd in June, 1993. The CD4 cell count was 384/jjbL. In July, 1993, the patient began local radiotherapy and at the same time was started on 500 mg daily zidovudine because of a decline in his CD4 cell count (337/µL). From December, 1993, he was prescribed 10 million units of subcutaneous IFN three times weekly plus 5 million units injected intralesionally twice weekly because of Kaposi’s sarcoma relapse that had occurred 5 months after the end of radiotherapy. At baseline, biochemical analysis was normal and organ and non-organ specific autoantibodies were negative. None of the commonly observed transient side-effects caused by IFN were observed. After 10 days, he had sudden onset of polyuria, polydipsia, and fatigue. Fasting blood glucose was 45 mmol/L and glycosuria was 17-2 mmol/L. IFN a-2a and zidovudine were stopped and a hypoglycaemic diet was introduced without improvement of glycaemia. The patient was admitted to hospital and given regular insulin 30 U plus Lente insulin 15 U per day. At this time, thyroid microsomal, thyroglobulin, and islet-cell autoantibodies were negative. Insulin autoantibodies were just above normal (10-52% compared with normal value of radiobinding assay method <10%) and the C-peptide value was
normal. 7 days later, the insulin doage was gradually reduced, because of a rapid improvement in glycaemia. In January, 1994, insulin was stopped and oral hypoglycaemic treatment
(glibenclamide
5
mg+phenformin
50 mg
daily)
started. This treatment was discontinued in February, 1994, given the persistent normal levels of glycaemia and the absence of glycosuria. At this time, insulin autoantibodies were within the normal range (< 10%). During the 12 months the remained of follow-up normal, zidovudine was glycaemia reintroduced and the patient received chemotherapy (bleomycin plus vincristine) for Kaposi’s sarcoma. An intriguing side-effect of IFN is the induction of autoimmunity. In a high proportion of patients low levels of autoantibodies develop; these are usually not associated with clinical symptoms. However, some patients have developed autoimmune diseases during IFN therapy.2,3 Fabris et al described the development of type 1 diabetes in a patient 6 months after IFN a-2b was started for chronic hepatitis C.’ Although the patient had markers of autoimmune destruction of &bgr;-cells and insulin autoantibodies, the role of IFN in the pathogenesis of the autoimmune reaction was unclear. In our patient, the temporal relation between therapy and development of type 1 diabetes makes it likely that the disease was induced by IFN treatment. Nevertheless, the absence of markers of autoimmune destruction of (3-cells makes autoimmune pathogenesis of the disease unlikely. It has also been suggested that IFN may induce peripheral insulin resistance either directly or mediated by other immunomodulators or factors stimulated by IFN.4,5 Our case of reversible insulin-dependent diabetes might reflect insulin resistance induced by IFN. was
*Andrea Gori, Francesco Caredda, Fabio Franzetti, Annalisa Ridolfo, Stefano Rusconi, Mauro Moroni Clinic of Infectious Diseases, "L Sacco" Hospital, University of Milan,
20157 Milan,
Italy 1 Fabris P, Betterle C, Floreani A, et al. Development of type 1 diabetes mellitus during interferon alfa therapy for chronic HCV hepatitis. Lancet 1992; 340: 548. 2 Conlon KC, Urba WJ, Smith JW, et al. Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 1990; 65: 2237-42. 3 Schultz M, Muller R, Muhlem A, Brabant G. Induction of hyperthyroidism by interferon-alfa-2b. Lancet 1989; i: 1452. 4 Koivisto VA, Pelkonen R, Cantell K. Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes 1989; 38: 641-47. 5 Koivisto VA. Interferon alfa and development of type 1 diabetes mellitus. Lancet 1992; 340: 1236.
Preventive therapy for tuberculosis SIR—De Cock and
colleagues’ (April 1, p 833) review of for tuberculosis in HIV-infected persons preventive therapy was very illuminating. However, the issue of compliance with preventive therapy, especially in developing countries, could have been given greater emphasis. What is the noncompliance rate for preventive therapy in developing countries? What steps can be taken to ensure adherence to preventive therapy in such countries? Very often, the medical profession blames the patient for not complying with therapeutic instructions, thus shifting the blame from the doctor to the patient and not placing a greater responsibility on the doctor to assist the patient to comply with treatment. There could be very legitimate and rational reasons why a patient might be unable to take preventive therapy in its entirety. Possible reasons for non-compliance with preventive therapy could include factors related to the patient’s environment, the local health service provided, and individual factors related to the patient’s socioeconomic circumstances, his knowledge, beliefs, and practices.
non-compliance is high in a locality, then instituting preventive therapy for HIV-infected individuals might encourage the emergence of resistant strains of bacilli, and in the long-term undermine the control of tuberculosis in the community. We need to investigate and find out reasons for non-compliance locally so as to be in a position to rationally provide solutions and thus improve the success rate of preventive therapy. If the
rate
of
Patrick Twumasi Jr Teaching Hospital, Kumasi,
Komfo Anokye
Ghana
SIR—In describing preventive measures available for tuberculosis control in HIV-infected persons, De Cock and colleagues understandably concentrate on the role of drug prophylaxis. Although HIV infection is the strongest risk factor for the development of tuberculosis, other potentially controllable host factors may play a part. In a recent case-control study of tuberculosis in adult immigrants from the Indian subcontinent, we noted a trend for increasing tuberculosis with decreasing frequency of meat or fish consumption. Lactovegetarians had an 8-5-fold increased risk (95% CI 1-8-45-4) compared with daily meat/fish eaters. Adjustment for a range of potentially confounding socioeconomic, migration, and lifestyle variables made little difference to the relative risks derived.’ AIDS is rare in Asian immigrants, and none of the Asian patients studied was known to be HIV infected. However, the pattern of tuberculosis seen in immigrant Asians in the UK, with frequent glandular and non-pulmonary involvement, is well described and has similarities to that of tuberculosis seen in immunosuppression with AIDS.2 Our findings indicate that a vegetarian diet is an independent risk factor for tuberculosis in immigrant Asians. The mechanism is unexplained, but vitamin D deficiency, which is common among vegetarian Asians in south London, is known to affect cellular immune competence.3 Decreased immunocompetence associated with a vegetarian diet might result in increased mycobacterial reactivation among Asians from the Indian subcontinent, and contribute to their greatly increased risk of developing tuberculosis. If reactivation of tuberculosis is determined by a single micronutrient such as vitamin D, our findings could have important implications for the prevention of tuberculosis in other settings. Vitamin D supplements are cheap and nontoxic, in comparison with antituberculous drugs. It would be worth evaluating in properly controlled studies whether such micronutrient supplements (alone or in conjunction with standard drug prophylaxis regimens) had an effect in preventing tuberculosis or altering the progress of HIV infection in co-infected individuals. Such studies would be easier to do and more likely to be informative in northern (industrialised) countries, where seasonal changes in photosynthesis, and vitamin D deficiency, are well
recognised.4 David P Strachan, John F C Millard, *J
Douglas Maxwell
Departments of Public Health Sciences and *Medicine, St George’s Hospital and Medical School, London SW17 0RE, UK
1
2 3
4
Strachan DP, Powell KJ, Thaker A, Millard FJC, Maxwell JD. Vegetarian diet as a risk factor for tuberculosis in immigrant south London Asians. Thorax 1995; 50: 175-80. Harries AD. Tuberculosis and human immunodeficiency virus infection in developing countries. Lancet 1990; 335: 387-90. Yang S, Smith C, Prahl JM, Luo X, DeLuca HF. Vitamin D deficiency suppresses cell mediated immunity in vivo. Arch Biochem Biophys 1993; 303: 98-106. Maxwell JD. Seasonal variation in vitamin D. Proc Nutr Soc 1994; 53: 515-25.
1439
Giant-cell arteritis
No
23
10
giant-cell arteritis
Negative DFS 7 40 The sensitivity of DFS was thus 77%, the specificity 80%, and the positive and negative predictive values 70% and 85%, respectively. We conclude that the DFS score in giant-cell arteritis has a higher sensitivity and specificity than the commonly used clinical or biological diagnostic criteria in this disease. It is particularly useful because of its high negative predictive value, but for diagnosis cannot replace temporal artery biopsy which has a better specificity. Whether the morphological abnormalities shown by colour doppler improve the diagnostic accuracy when compared with continuous-wave doppler examination, which is less time consuming, remains to be established.
frequently identified in many white populations’ of the USA, the UK, Denmark, South Africa, Austria, Australia, the Netherlands, Canada, France, Italy, Switzerland, Belgium, and Germany. Yet FDB is rarely reported in other populations, and never found in Finland, the former Soviet Union, and Israel. According to haplotype analysis of the apoB gene, ethnic diversity of FDB frequency suggests that most apoB 3500 mutations are derived from a single common ancestral mutation that occurred at least 10 000 years ago,’ probably in a Caucasian. Our results suggest that the apoB 3500 mutation is a rare cause of genetic hypercholesterolaemia in Japan and are consistent with this explanation. The
apoB
3500 mutation has been
*Atsushi Nohara, Kunimasa Yagi, Akihiro Inazu, Kouji Kajinami, Junji Koizumi, Hiroshi Mabuchi Second Department of Internal Medicine, School of Medicine, Kanazawa Kanazawa 920, Japan
1
2
3
4
University,
Myant NB. Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolemia. Atherosclerosis 1993; 104: 1-18. Defesche JC, Pricker KL, Hayden MR, van der Ende BE, Kastelein JP. Familial defective apolipoprotem B-100 is clinically indistinguishable from familial hypercholesterolemia. Arch Intern Med 1993; 153: 2349-56. Hansen PS, Rudiger N, Tybjaerg-Hansen A, et al. Detection of the apo-B-3500 mutation (glutamine for arginine) by gene amplification and cleavage with MspI. J Lipid Res 1991; 32: 1229-33. Miserez AR, Laager R, Chiodetti N, et al. High prevalence of familial defective apolipoprotein B-100 in Switzerland. J Lipid Res 1994; 35: 574-83.
*Xavier Puéchal, Michel Chauveau, Charles J Menkès Rhumatologie A, and Service d’Exploration Fonctionnelle Vasculaire, Hôpital Cochin, Université René Descartes, Paris 75674, France *Service de
1
2
Menkès CJ, Branche I, Feldmann JL, Chauveau M, Delbarre F. Application de l’effet Doppler au dépistage de l’artérite de Horton. Nouv Presse Med 1981; 10: 2371. Puéchal X, Chauveau M, Hilliquin P, Perrot S, Job-Deslandre C, Menkès CJ. Superficial temporal Doppler flow studies in suspected giant cell arteritis: validation of a diagnostic score. Arthritis Rheum 1994; 37 (suppl 9): S409 (abstr).
Absence of familial defective apolipoprotein B-100 in Japanese patients with familial hypercholesterolaemia SiR-Familial defective apolipoproteinB-100 (FDB) is a form of genetic hypercholesterolaemia. A single-base substitution (G to A) at nucleotide 10 708 in exon 26 of the apoB-100 gene creates a glutamine for arginine substitution in position 3500 aminoacid, resulting in reduced affinity of low-density lipoproteins (LDL) to the LDL receptor.’ FDB has been shown to be clinically indistinguishable from familial hypercholesterolaemia.2 To estimate the frequency of FDB in the Japanese population, we searched for this apoB mutation among clinically diagnosed 385 heterozygous familial hypercholesterolaemia patients from 350 unrelated families (197 men and 188 women, mean age 45 years). The mean (SD) concentrations of total cholesterol, triglyceride, and high-density lipoprotein cholesterol were 7-73 (2-15), 1-78 (1-11), and 1-27 (0-75) mmol/L, respectively. 85% of the subjects had Achilles tendon xanthoma, and 18% had coronary heart disease. We used PCR followed by cleavage with Mspl to detect the apoB 3500 mutation as described by Hansen et al.3 DNA samples from patients already diagnosed as FDB (provided by N B Myant, Hammersmith Hospital, UK and D R Illingworth, Oregon Health Sciences University, USA) were included in each PCR assay. No individuals with apoB 3500 mutation were detected. 1438
Reversible diabetes in patient with AIDSrelated Kaposi’s sarcoma treated with interferon &agr;-2a SiR-The development of type 1 diabetes in a patient treated with recombinant interferon a-2b for chronic type C hepatitis has been described, but its pathogenesis remains unclear.’1 We describe a reversible insulin-dependent diabetes occurring in an HIV-positive man 2 weeks after recombinant interferon (IFN) a-2a treatment was started for cutaneous
Kaposi’s
sarcoma.
A 54-year-old homosexual man had been positive for HIV-1 antibodies since 1990 without any notable disease in his previous medical history and no familial evidence of diabetes. Cutaneous Kaposi’s sarcoma localised to the fingers and the soles of the feet was diagnosesd in June, 1993. The CD4 cell count was 384/jjbL. In July, 1993, the patient began local radiotherapy and at the same time was started on 500 mg daily zidovudine because of a decline in his CD4 cell count (337/µL). From December, 1993, he was prescribed 10 million units of subcutaneous IFN three times weekly plus 5 million units injected intralesionally twice weekly because of Kaposi’s sarcoma relapse that had occurred 5 months after the end of radiotherapy. At baseline, biochemical analysis was normal and organ and non-organ specific autoantibodies were negative. None of the commonly observed transient side-effects caused by IFN were observed. After 10 days, he had sudden onset of polyuria, polydipsia, and fatigue. Fasting blood glucose was 45 mmol/L and glycosuria was 17-2 mmol/L. IFN a-2a and zidovudine were stopped and a hypoglycaemic diet was introduced without improvement of glycaemia. The patient was admitted to hospital and given regular insulin 30 U plus Lente insulin 15 U per day. At this time, thyroid microsomal, thyroglobulin, and islet-cell autoantibodies were negative. Insulin autoantibodies were just above normal (10-52% compared with normal value of radiobinding assay method <10%) and the C-peptide value was
normal. 7 days later, the insulin doage was gradually reduced, because of a rapid improvement in glycaemia. In January, 1994, insulin was stopped and oral hypoglycaemic treatment
(glibenclamide
5
mg+phenformin
50 mg
daily)
started. This treatment was discontinued in February, 1994, given the persistent normal levels of glycaemia and the absence of glycosuria. At this time, insulin autoantibodies were within the normal range (< 10%). During the 12 months the remained of follow-up normal, zidovudine was glycaemia reintroduced and the patient received chemotherapy (bleomycin plus vincristine) for Kaposi’s sarcoma. An intriguing side-effect of IFN is the induction of autoimmunity. In a high proportion of patients low levels of autoantibodies develop; these are usually not associated with clinical symptoms. However, some patients have developed autoimmune diseases during IFN therapy.2,3 Fabris et al described the development of type 1 diabetes in a patient 6 months after IFN a-2b was started for chronic hepatitis C.’ Although the patient had markers of autoimmune destruction of &bgr;-cells and insulin autoantibodies, the role of IFN in the pathogenesis of the autoimmune reaction was unclear. In our patient, the temporal relation between therapy and development of type 1 diabetes makes it likely that the disease was induced by IFN treatment. Nevertheless, the absence of markers of autoimmune destruction of (3-cells makes autoimmune pathogenesis of the disease unlikely. It has also been suggested that IFN may induce peripheral insulin resistance either directly or mediated by other immunomodulators or factors stimulated by IFN.4,5 Our case of reversible insulin-dependent diabetes might reflect insulin resistance induced by IFN. was
*Andrea Gori, Francesco Caredda, Fabio Franzetti, Annalisa Ridolfo, Stefano Rusconi, Mauro Moroni Clinic of Infectious Diseases, "L Sacco" Hospital, University of Milan,
20157 Milan,
Italy 1 Fabris P, Betterle C, Floreani A, et al. Development of type 1 diabetes mellitus during interferon alfa therapy for chronic HCV hepatitis. Lancet 1992; 340: 548. 2 Conlon KC, Urba WJ, Smith JW, et al. Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 1990; 65: 2237-42. 3 Schultz M, Muller R, Muhlem A, Brabant G. Induction of hyperthyroidism by interferon-alfa-2b. Lancet 1989; i: 1452. 4 Koivisto VA, Pelkonen R, Cantell K. Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes 1989; 38: 641-47. 5 Koivisto VA. Interferon alfa and development of type 1 diabetes mellitus. Lancet 1992; 340: 1236.
Preventive therapy for tuberculosis SIR—De Cock and
colleagues’ (April 1, p 833) review of for tuberculosis in HIV-infected persons preventive therapy was very illuminating. However, the issue of compliance with preventive therapy, especially in developing countries, could have been given greater emphasis. What is the noncompliance rate for preventive therapy in developing countries? What steps can be taken to ensure adherence to preventive therapy in such countries? Very often, the medical profession blames the patient for not complying with therapeutic instructions, thus shifting the blame from the doctor to the patient and not placing a greater responsibility on the doctor to assist the patient to comply with treatment. There could be very legitimate and rational reasons why a patient might be unable to take preventive therapy in its entirety. Possible reasons for non-compliance with preventive therapy could include factors related to the patient’s environment, the local health service provided, and individual factors related to the patient’s socioeconomic circumstances, his knowledge, beliefs, and practices.
non-compliance is high in a locality, then instituting preventive therapy for HIV-infected individuals might encourage the emergence of resistant strains of bacilli, and in the long-term undermine the control of tuberculosis in the community. We need to investigate and find out reasons for non-compliance locally so as to be in a position to rationally provide solutions and thus improve the success rate of preventive therapy. If the
rate
of
Patrick Twumasi Jr Teaching Hospital, Kumasi,
Komfo Anokye
Ghana
SIR—In describing preventive measures available for tuberculosis control in HIV-infected persons, De Cock and colleagues understandably concentrate on the role of drug prophylaxis. Although HIV infection is the strongest risk factor for the development of tuberculosis, other potentially controllable host factors may play a part. In a recent case-control study of tuberculosis in adult immigrants from the Indian subcontinent, we noted a trend for increasing tuberculosis with decreasing frequency of meat or fish consumption. Lactovegetarians had an 8-5-fold increased risk (95% CI 1-8-45-4) compared with daily meat/fish eaters. Adjustment for a range of potentially confounding socioeconomic, migration, and lifestyle variables made little difference to the relative risks derived.’ AIDS is rare in Asian immigrants, and none of the Asian patients studied was known to be HIV infected. However, the pattern of tuberculosis seen in immigrant Asians in the UK, with frequent glandular and non-pulmonary involvement, is well described and has similarities to that of tuberculosis seen in immunosuppression with AIDS.2 Our findings indicate that a vegetarian diet is an independent risk factor for tuberculosis in immigrant Asians. The mechanism is unexplained, but vitamin D deficiency, which is common among vegetarian Asians in south London, is known to affect cellular immune competence.3 Decreased immunocompetence associated with a vegetarian diet might result in increased mycobacterial reactivation among Asians from the Indian subcontinent, and contribute to their greatly increased risk of developing tuberculosis. If reactivation of tuberculosis is determined by a single micronutrient such as vitamin D, our findings could have important implications for the prevention of tuberculosis in other settings. Vitamin D supplements are cheap and nontoxic, in comparison with antituberculous drugs. It would be worth evaluating in properly controlled studies whether such micronutrient supplements (alone or in conjunction with standard drug prophylaxis regimens) had an effect in preventing tuberculosis or altering the progress of HIV infection in co-infected individuals. Such studies would be easier to do and more likely to be informative in northern (industrialised) countries, where seasonal changes in photosynthesis, and vitamin D deficiency, are well
recognised.4 David P Strachan, John F C Millard, *J
Douglas Maxwell
Departments of Public Health Sciences and *Medicine, St George’s Hospital and Medical School, London SW17 0RE, UK
1
2 3
4
Strachan DP, Powell KJ, Thaker A, Millard FJC, Maxwell JD. Vegetarian diet as a risk factor for tuberculosis in immigrant south London Asians. Thorax 1995; 50: 175-80. Harries AD. Tuberculosis and human immunodeficiency virus infection in developing countries. Lancet 1990; 335: 387-90. Yang S, Smith C, Prahl JM, Luo X, DeLuca HF. Vitamin D deficiency suppresses cell mediated immunity in vivo. Arch Biochem Biophys 1993; 303: 98-106. Maxwell JD. Seasonal variation in vitamin D. Proc Nutr Soc 1994; 53: 515-25.
1439