435
BCG is low. As far as possible, for every patient with a clinical diagnosis of tuberculosis, we try to obtain microbiological confirmation (sputum, gastric lavage, or biopsy examination by the National Chest Disease Laboratories). The clinical presentation of tuberculosis in HIV-infected patients is different from the classic situation in an immunologically competent host.9,10 Most tuberculosis cases in HIV-infected children simulate the adult or reactivation type, with cavitatory lesions, extensive pneumonias, and dissemination. The tuberculosis is difficult to treat and there is a high number of allergic drug reactions." We are trying to determine why the clinical presentation of tuberculosis is so different in HIV-infected children, and whether these children develop "BCGaemia" after vaccination, whereby the strain of BCG vaccine propagates, disseminates, and causes infection and death. Because of financial and technical restraints, most investigators like us will be unable to obtain satisfactory answers.
But the facts are that 30-40% of babies bom to HIV-positive mothers can be infected with HIV-1, BCG could disseminate in an immunocompromised host, and it is difficult to diagnose AIDS in newborn babies. Therefore, is it advisable to immunise all babies at birth with BCG vaccine, irrespective of their or their maternal HIV-antibody status, as advocated by WHO in developing countries? And how ethical is it to immunise all when the incidence of HIV infection is high? We suggest immunising children at 1 year of age, because by then full-blown AIDS or HIV infection will be evident and provide the basis for exclusion from immunisation. We are currently investigating the role of tuberculosis as a cause of pneumonia in early infancy. Department of Paediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia 1. 2.
UMA H. ATHALE CHEWE LUO-MUTTI C. CHINTU
Speck WT Tuberculosis In Berhman RE, Vaughan VC III, eds. Nelson textbook of pediatrics 13th ed. Philadelphia; WB Saunders, 1990: 629-38 Bhat GJ, Diwan VK, Chintu C, Kabika M, Masona J. BCG provides no protection in HIV positive children a case control study. J Trop Pediatr (in press )
3 Ten DHG BCG vaccination and HIV infection. Bull Int Union Tuberc Lung Dis 1990;
65: 38-39
B, Morenco S, Burdach R, et al Clinical presentation of Bacillus Calmette-Guerin infection in patients with immunodeficiency syndromes Paediatr Intect Dis J 1989, 8: 201-06. 5 Bregene P BCG vaccination and AIDS. Bull Int Union Tuberc Lung Dis 1988, 63: 40-41 6. Nunn P HIV associated pulmonary tuberculosis. Africa Health 1991; 14: 10-11. 7. Luo C HIV disease amongst hospitalised children in University Teaching Hospital, Lusaka. diagnosis and risk of transmission through therapeutic practices M Med Dissertation, 1991. 8 Elliot AM, Luo N, Tembo G, et al Impact of HIV on tuberculosis in Zambia across sectional study BMJ 1990, 301: 412-15. 9. Elliot AM The changing face of tuberculosis in HIV endemic areas Postgrad Doctor 1992; 14: 15-19 10. Chintu C, Bhat GJ, Luc C, Kabika M, Raviglione MC, O’Brien R Fatal skin reactions in children treated for tuberculosis in Zambia VIIIth International Conference on AIDS, Amsterdam, July, 1992 abstr POB 3859 4 Gonzale
Contribution of maternal viral load to HIV-1 transmission SIR,-The European Collaborative Study on HIV-1 (April 25, p24-antigenaemia and low CD4
p 1007) has shown that detectable
risk factors for mother-to-child transmission of HIV-1. Plasma viral load is known to be inversely related to CD4 number, and these observations suggest that maternal viral load might be relevant to HIV-1transmission.’To study this possibility, we have examined infectious HIV-1 load in plasma and peripheral blood mononuclear cells (PBMC) in six HIV-1 seropositive mothers attending St Mary’s Hospital. Infectious virus titre was measured during the pregnancy, at delivery, or in the immediate puerperium, depending on the time of presentation. Titration of viral load was done by limiting dilution co-culuvanon with donor PBMCs and endpoint assessment of HIV replication by p24 detectionThe HIV status of the infants was established by clinical observation, nested PCR sensitive enough to detect one provirus,3 and by virus culture. So far, no infant has shown any HIV-related disease up to age three months. The table shows the results of the nested PCR at month zero (case 1), one month cases 3,4, 5, 6), and two months (case 2). The positive HIV
NESTED PCR TESTING OF MATERNAL AND INFANT HIV STATUS
Neg = negative, Pos= positive, ND—not detected *Plasma TCID per ml/PBMC TCID per 106 cells, tOn three occasions, tOn two occasions
transmission in case 6 was confirmed by repeat PCR at three months and by positive virus culture. We found no association between maternal infectious viral load in plasma or in PBMCs and outcome of transmission to the child. In cases 2 and 5 (the mothers with the highest titres of infectious plasma and provirus) there was no evidence of HIV transmission. The only positive transmission in this series was from a mother with undetectable levels of infectious virus, on two occasions within 3 months after delivery. We have shown that plasma viraemia is unrelated to p24 antigenaemia/ and we and others have demonstrated the association between CD4 number and plasma viraemia: patients with CD4 counts above 200 x lQ6jl are only rarely viraemic by infectious assays.’1 The association found between p24 antigen and transmission may not therefore involve the quantity of infectious virus. We believe that the results of the European Collaborative Study accord with our observations: there was no significant difference in HIV transmission rate between the mothers with CD4 count of less than 400 and 400-699 in the study, and 5 mothers whose CD4 count was greater than 700 transmitted HIV to their infants. These findings together with our limited data persuade us that infectious virus titres in peripheral blood do not correlate with mother-to-child transmission of HIV-1. Even if a mother has no or very low levels of infectious virus in peripheral blood, there is still a substantial risk of HIV-1vertical transmission. Wolinsky et aP have shown that only certain variants among maternal viruses are transmitted. The quality of the virus may therefore be more important than the quantity in determining transmission. Departments of Genito-urinary Medicine and Communicable Diseases, and Paediatrics, St Mary’s Hospital Medical School, London W2 1NY, UK
K. ARIYOSHI JONATHAN WEBER S. WALTERS
Saag M, Cram M, Decker D, et al. High level viraemia in adults and children infected with HIV relation to disease stage and CD4 + level. JInfect Dis 1991; 164: 72-80 2. Ho D, Mougdil T, Alam M. Quantitation of HIV-1 in the blood of infected persons. N Engl J Med 1989, 321: 1621-25 3 Simmonds P, Balfe P, Peutherer J, el al. HIV-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol 1.
1990; 64: 864-72. J, Ariyoshi K Lack of correlation between acidified HIV p24Ag and plasma viraemia AIDS 1992; 6: 428-29. Wolinsky S, Wike C, Korber B, et al. Selective transmission of HIV-1 variants from mothers to infants. Science 1992, 255: 1134-37
4 Weber
5
Bone minerals and
counts are
and
levothyroxine
SIR,-Dr Franklyn colleagues (July 4, p 9) found that bone mineral density (BMD) during treatment with levothyroxine is not reduced if the patients are compared with correctly matched controls. This confirms results with single photon absorptiometry (Nuclear Data transmission scanner ND 1100 B). To avoid varying influences by oestrogen reduction in postmenopausal women-and thus the need for much larger groups-our study was restricted to premenopausal women. All had undergone total thyroidectomy and radioiodine ablation for differentiated thyroid cancer 5 or more years earlier. In contrast to publications describing bone loss after an obscure history of levothyroxine treatment,’ thyrotropin suppression had been carefully monitored and serum triiodothyronine (T3) increases had been avoided. Controls were selected on premenopausal state, age, body weight, and smoking habits. Further information about possible acceleration of bone metabolism was obtained by
BCG is low. As far as possible, for every patient with a clinical diagnosis of tuberculosis, we try to obtain microbiological confirmation (sputum, gastric lavage, or biopsy examination by the National Chest Disease Laboratories). The clinical presentation of tuberculosis in HIV-infected patients is different from the classic situation in an immunologically competent host.9,10 Most tuberculosis cases in HIV-infected children simulate the adult or reactivation type, with cavitatory lesions, extensive pneumonias, and dissemination. The tuberculosis is difficult to treat and there is a high number of allergic drug reactions." We are trying to determine why the clinical presentation of tuberculosis is so different in HIV-infected children, and whether these children develop "BCGaemia" after vaccination, whereby the strain of BCG vaccine propagates, disseminates, and causes infection and death. Because of financial and technical restraints, most investigators like us will be unable to obtain satisfactory answers.
But the facts are that 30-40% of babies bom to HIV-positive mothers can be infected with HIV-1, BCG could disseminate in an immunocompromised host, and it is difficult to diagnose AIDS in newborn babies. Therefore, is it advisable to immunise all babies at birth with BCG vaccine, irrespective of their or their maternal HIV-antibody status, as advocated by WHO in developing countries? And how ethical is it to immunise all when the incidence of HIV infection is high? We suggest immunising children at 1 year of age, because by then full-blown AIDS or HIV infection will be evident and provide the basis for exclusion from immunisation. We are currently investigating the role of tuberculosis as a cause of pneumonia in early infancy. Department of Paediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia 1. 2.
UMA H. ATHALE CHEWE LUO-MUTTI C. CHINTU
Speck WT Tuberculosis In Berhman RE, Vaughan VC III, eds. Nelson textbook of pediatrics 13th ed. Philadelphia; WB Saunders, 1990: 629-38 Bhat GJ, Diwan VK, Chintu C, Kabika M, Masona J. BCG provides no protection in HIV positive children a case control study. J Trop Pediatr (in press )
3 Ten DHG BCG vaccination and HIV infection. Bull Int Union Tuberc Lung Dis 1990;
65: 38-39
B, Morenco S, Burdach R, et al Clinical presentation of Bacillus Calmette-Guerin infection in patients with immunodeficiency syndromes Paediatr Intect Dis J 1989, 8: 201-06. 5 Bregene P BCG vaccination and AIDS. Bull Int Union Tuberc Lung Dis 1988, 63: 40-41 6. Nunn P HIV associated pulmonary tuberculosis. Africa Health 1991; 14: 10-11. 7. Luo C HIV disease amongst hospitalised children in University Teaching Hospital, Lusaka. diagnosis and risk of transmission through therapeutic practices M Med Dissertation, 1991. 8 Elliot AM, Luo N, Tembo G, et al Impact of HIV on tuberculosis in Zambia across sectional study BMJ 1990, 301: 412-15. 9. Elliot AM The changing face of tuberculosis in HIV endemic areas Postgrad Doctor 1992; 14: 15-19 10. Chintu C, Bhat GJ, Luc C, Kabika M, Raviglione MC, O’Brien R Fatal skin reactions in children treated for tuberculosis in Zambia VIIIth International Conference on AIDS, Amsterdam, July, 1992 abstr POB 3859 4 Gonzale
Contribution of maternal viral load to HIV-1 transmission SIR,-The European Collaborative Study on HIV-1 (April 25, p24-antigenaemia and low CD4
p 1007) has shown that detectable
risk factors for mother-to-child transmission of HIV-1. Plasma viral load is known to be inversely related to CD4 number, and these observations suggest that maternal viral load might be relevant to HIV-1transmission.’To study this possibility, we have examined infectious HIV-1 load in plasma and peripheral blood mononuclear cells (PBMC) in six HIV-1 seropositive mothers attending St Mary’s Hospital. Infectious virus titre was measured during the pregnancy, at delivery, or in the immediate puerperium, depending on the time of presentation. Titration of viral load was done by limiting dilution co-culuvanon with donor PBMCs and endpoint assessment of HIV replication by p24 detectionThe HIV status of the infants was established by clinical observation, nested PCR sensitive enough to detect one provirus,3 and by virus culture. So far, no infant has shown any HIV-related disease up to age three months. The table shows the results of the nested PCR at month zero (case 1), one month cases 3,4, 5, 6), and two months (case 2). The positive HIV
NESTED PCR TESTING OF MATERNAL AND INFANT HIV STATUS
Neg = negative, Pos= positive, ND—not detected *Plasma TCID per ml/PBMC TCID per 106 cells, tOn three occasions, tOn two occasions
transmission in case 6 was confirmed by repeat PCR at three months and by positive virus culture. We found no association between maternal infectious viral load in plasma or in PBMCs and outcome of transmission to the child. In cases 2 and 5 (the mothers with the highest titres of infectious plasma and provirus) there was no evidence of HIV transmission. The only positive transmission in this series was from a mother with undetectable levels of infectious virus, on two occasions within 3 months after delivery. We have shown that plasma viraemia is unrelated to p24 antigenaemia/ and we and others have demonstrated the association between CD4 number and plasma viraemia: patients with CD4 counts above 200 x lQ6jl are only rarely viraemic by infectious assays.’1 The association found between p24 antigen and transmission may not therefore involve the quantity of infectious virus. We believe that the results of the European Collaborative Study accord with our observations: there was no significant difference in HIV transmission rate between the mothers with CD4 count of less than 400 and 400-699 in the study, and 5 mothers whose CD4 count was greater than 700 transmitted HIV to their infants. These findings together with our limited data persuade us that infectious virus titres in peripheral blood do not correlate with mother-to-child transmission of HIV-1. Even if a mother has no or very low levels of infectious virus in peripheral blood, there is still a substantial risk of HIV-1vertical transmission. Wolinsky et aP have shown that only certain variants among maternal viruses are transmitted. The quality of the virus may therefore be more important than the quantity in determining transmission. Departments of Genito-urinary Medicine and Communicable Diseases, and Paediatrics, St Mary’s Hospital Medical School, London W2 1NY, UK
K. ARIYOSHI JONATHAN WEBER S. WALTERS
Saag M, Cram M, Decker D, et al. High level viraemia in adults and children infected with HIV relation to disease stage and CD4 + level. JInfect Dis 1991; 164: 72-80 2. Ho D, Mougdil T, Alam M. Quantitation of HIV-1 in the blood of infected persons. N Engl J Med 1989, 321: 1621-25 3 Simmonds P, Balfe P, Peutherer J, el al. HIV-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol 1.
1990; 64: 864-72. J, Ariyoshi K Lack of correlation between acidified HIV p24Ag and plasma viraemia AIDS 1992; 6: 428-29. Wolinsky S, Wike C, Korber B, et al. Selective transmission of HIV-1 variants from mothers to infants. Science 1992, 255: 1134-37
4 Weber
5
Bone minerals and
counts are
and
levothyroxine
SIR,-Dr Franklyn colleagues (July 4, p 9) found that bone mineral density (BMD) during treatment with levothyroxine is not reduced if the patients are compared with correctly matched controls. This confirms results with single photon absorptiometry (Nuclear Data transmission scanner ND 1100 B). To avoid varying influences by oestrogen reduction in postmenopausal women-and thus the need for much larger groups-our study was restricted to premenopausal women. All had undergone total thyroidectomy and radioiodine ablation for differentiated thyroid cancer 5 or more years earlier. In contrast to publications describing bone loss after an obscure history of levothyroxine treatment,’ thyrotropin suppression had been carefully monitored and serum triiodothyronine (T3) increases had been avoided. Controls were selected on premenopausal state, age, body weight, and smoking habits. Further information about possible acceleration of bone metabolism was obtained by
