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Fifty Years Ago in The Journal of Pediatrics
MALE ET AL
THE JOURNAL OF PEDIATRICS VOLUME 134, NUMBER 2 tion Committee of the ISTH. Thromb Haemost 1995;74:1185-90. 32. Bajaj SP, Rapaport SI, Fierer DS, Herbst KD, Schwartz DB. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemialupus anticoagulant syndrome. Blood 1983;61:684-92. 33. Jäger U, Kapiotis S, Pabinger I, Puchhammer E, Kyrle PA, Lechner K. Transient lupus anticoagulant associated with hypoprothrombinemia and factor XII deficiency following adenovirus infection. Ann Hematol 1993;67:95-9.
34. Andrews PA, Frampton G, Cameron JS. Antiphospholipid syndrome and systemic lupus erythematosus [letter]. Lancet 1993;342:988-9. 35. Finazzi G, Brancaccio V, Moia M, Ciaverella N, Mazzucconi MG, Schinco PC, et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 1996;100:530-6. 36. Ehrenstein MR, Swana M, Keeling D, Asherson R, Hughes GRV, Isenberg DA. Anti-DNA antibodies in the pri-
mary antiphospholipid antibody syndrome (PAPS). Br J Rheumatol 1993;32:362-5. 37. Cassidy JT, Petty RE. Pediatric rheumatology. 3rd ed. Toronto: WB Saunders Co; 1995. 38. Manco Johnson MJ, Nuss R, Key N, Moertel C, Jacobson L, Meech S, et al. Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis. J Pediatr 1996;128:319-23.
Fifty Years Ago in The Journal of Pediatrics ACTIVE IMMUNIZATION AGAINST TUBERCULOSIS Blattner RJ. J Pediatr 1949;34:263-5 This comment on current literature puts, into the context of the time, a carefully performed study of immunization and long-term follow-up of children at high risk for acquisition of tuberculosis in the United States (Aronson JD. Am Rev Tuberc 1948;58:255). In working with cattle, Calmette and Guerin had found that resistance to mycobacterial reinfection was due to the presence of viable tubercle bacilli and that when animals were injected with a vaccine prepared from an attenuated strain of tubercle bacilli, protection against infection occurred. Results of this animal experimentation suggested the possible use of this bovine vaccine, called BCG, for active immunization of human beings. Experimentation with route of administration in humans showed lack of immunogenicity (measured by conversion to positive Mantoux tuberculin skin test result) when the oral route was used and excessive abscess formation when the subcutaneous route was used. Aronson’s project was carried out as a prospective, controlled study in cooperation with the Health Division of the Office of Indian Affairs, Department of the Interior. It was a trial of BCG vaccine given by the intracutaneous route to approximately 1500 of 3000 children (by alternating assignment) whose Mantoux test result was negative. Follow-up included repeated Mantoux tests, chest radiographs, and clinical observation of the cohort of 3000 children over 6 to 8 years. One year after entry, 93% of vaccinated versus 13% of nonvaccinated children had positive Mantoux test results. Tuberculosis and deaths were significantly increased in the nonvaccinated group. Mortality rate per 1000 person-years from tuberculosis was 0.4 in the vaccinated group versus 3.5 in the control group. In an important subset analysis, 123 newborns immunized with BCG within 7 days of birth had a skin test conversion rate of 91%, similar to that of older children, and also had evidence of protection from tuberculosis through the 6 to 8 years of follow-up. As implementation of BCG vaccination began in high-risk populations in the United States, isoniazid and other antituberculous agents became available for treatment of symptomatic and asymptomatic infection, supplanting use of BCG. Research to develop a better and safer vaccine has been thwarted by difficulties in eliciting mucosal protection that is long-lived. BCG vaccines continue to be used in many countries where tuberculosis is endemic. Although vaccination has been successful in some of those countries, problems with BCG vaccine include: (1) lack of standardization of products, (2) effectiveness ranging from 0% to greater than 80%, (3) confounding of the Mantoux skin test results for use in diagnosis of tuberculosis, (4) safety issues ranging from the common local abscess and ulcer that occurs in healthy individuals to disseminated and distant infection in immunocompromised individuals and, rarely, in healthy individuals as well. Sarah S. Long, MD Section of Infectious Diseases St. Christopher’s Hospital for Children Philadelphia, PA 19134-1095
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THE JOURNAL OF PEDIATRICS VOLUME 134, NUMBER 2 tion Committee of the ISTH. Thromb Haemost 1995;74:1185-90. 32. Bajaj SP, Rapaport SI, Fierer DS, Herbst KD, Schwartz DB. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemialupus anticoagulant syndrome. Blood 1983;61:684-92. 33. Jäger U, Kapiotis S, Pabinger I, Puchhammer E, Kyrle PA, Lechner K. Transient lupus anticoagulant associated with hypoprothrombinemia and factor XII deficiency following adenovirus infection. Ann Hematol 1993;67:95-9.
34. Andrews PA, Frampton G, Cameron JS. Antiphospholipid syndrome and systemic lupus erythematosus [letter]. Lancet 1993;342:988-9. 35. Finazzi G, Brancaccio V, Moia M, Ciaverella N, Mazzucconi MG, Schinco PC, et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 1996;100:530-6. 36. Ehrenstein MR, Swana M, Keeling D, Asherson R, Hughes GRV, Isenberg DA. Anti-DNA antibodies in the pri-
mary antiphospholipid antibody syndrome (PAPS). Br J Rheumatol 1993;32:362-5. 37. Cassidy JT, Petty RE. Pediatric rheumatology. 3rd ed. Toronto: WB Saunders Co; 1995. 38. Manco Johnson MJ, Nuss R, Key N, Moertel C, Jacobson L, Meech S, et al. Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis. J Pediatr 1996;128:319-23.
Fifty Years Ago in The Journal of Pediatrics ACTIVE IMMUNIZATION AGAINST TUBERCULOSIS Blattner RJ. J Pediatr 1949;34:263-5 This comment on current literature puts, into the context of the time, a carefully performed study of immunization and long-term follow-up of children at high risk for acquisition of tuberculosis in the United States (Aronson JD. Am Rev Tuberc 1948;58:255). In working with cattle, Calmette and Guerin had found that resistance to mycobacterial reinfection was due to the presence of viable tubercle bacilli and that when animals were injected with a vaccine prepared from an attenuated strain of tubercle bacilli, protection against infection occurred. Results of this animal experimentation suggested the possible use of this bovine vaccine, called BCG, for active immunization of human beings. Experimentation with route of administration in humans showed lack of immunogenicity (measured by conversion to positive Mantoux tuberculin skin test result) when the oral route was used and excessive abscess formation when the subcutaneous route was used. Aronson’s project was carried out as a prospective, controlled study in cooperation with the Health Division of the Office of Indian Affairs, Department of the Interior. It was a trial of BCG vaccine given by the intracutaneous route to approximately 1500 of 3000 children (by alternating assignment) whose Mantoux test result was negative. Follow-up included repeated Mantoux tests, chest radiographs, and clinical observation of the cohort of 3000 children over 6 to 8 years. One year after entry, 93% of vaccinated versus 13% of nonvaccinated children had positive Mantoux test results. Tuberculosis and deaths were significantly increased in the nonvaccinated group. Mortality rate per 1000 person-years from tuberculosis was 0.4 in the vaccinated group versus 3.5 in the control group. In an important subset analysis, 123 newborns immunized with BCG within 7 days of birth had a skin test conversion rate of 91%, similar to that of older children, and also had evidence of protection from tuberculosis through the 6 to 8 years of follow-up. As implementation of BCG vaccination began in high-risk populations in the United States, isoniazid and other antituberculous agents became available for treatment of symptomatic and asymptomatic infection, supplanting use of BCG. Research to develop a better and safer vaccine has been thwarted by difficulties in eliciting mucosal protection that is long-lived. BCG vaccines continue to be used in many countries where tuberculosis is endemic. Although vaccination has been successful in some of those countries, problems with BCG vaccine include: (1) lack of standardization of products, (2) effectiveness ranging from 0% to greater than 80%, (3) confounding of the Mantoux skin test results for use in diagnosis of tuberculosis, (4) safety issues ranging from the common local abscess and ulcer that occurs in healthy individuals to disseminated and distant infection in immunocompromised individuals and, rarely, in healthy individuals as well. Sarah S. Long, MD Section of Infectious Diseases St. Christopher’s Hospital for Children Philadelphia, PA 19134-1095
205