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Rubella immunity in adolescent girls
332
Letters to the Editor
REFERENCES
1. Dallman, PR: Iron, vitamin E, and folate in the preterm infant, J PEDIATR 85:742, 1974. 2. Committee on Nutrition: Iron balance and requirements in infancy, Pediatrics 43:134, 1969. 3. Committee on Nutrition: Iron-fortified formulas, Pediatrics 47:786, 1971. 4. Weinberg ED: Iron and susceptibility to infectious disease, Science 184:952, 1974. 5. Weinberg ED: Role of iron in host-parasite interactions, J Infect Dis 124:401, 1971. 6. Bulien JJ, et al: Iron binding proteins and infections, Br J Haematol 23:389, 1972. 7. Report of the Sixty-Second Ross Conference on Pediatric Research, Iron nutrition in infancy, Columbus, Ross Laboratories, 1970.
To the Editor: The letter of Levine and Lemons commenting on Dallman's' recent review of hematinic substances in infancy calls attention to an interesting body of investigative data. The possible effects of iron--both deficiency and excess-on the host resistance to infection have been discussed in a number of recent communications?, a There is little doubt that, in a variety of experimental in vitro situations, large excesses of iron may dramatically affect the proliferation of microorganisms. Further, administration of large doses of iron parenterally can increase susceptibility of certain experimental animals to bacterial infection. Exaggerated and uncritical extrapolation of these experimental data, however, into a variety of clinical situations is not warranted. It is over-simplification to attribute rates of infections in different groups of patients to their iron status per se. High serum levels of iron are frequently associated with systemic diseases such as malignancy, bone marrow failure, and extreme hemolysis, whereas iron deficiency usually occurs as a specific nutritional defect in an otherwise healthy person. To attribute iron as the important variable between these two groups seems astigmatic. The crucial importance of iron in other conditions cited by Levine and Lemons is also overstated. For example, the "300fold increased" susceptibility to meningitis of patients with sickle cell anemia is confined to the first few years of life when body stores of iron and serum iron levels are not particularly elevated; whereas later when these patients usually have increased serum concentrations of iron, the risk of meningitis is not increased. To relate sepsis and meningitis in the sickle cell anemia patient to iron ignores this temporal sequence as well as established pathogenetic mechanisms involving abnormal splenic and opsonization functions. Thalassemia major is the prime pediatric disease in which very high levels of serum iron and transferrin saturation occur. In patients maintained on a high transfusion program, susceptibility to infection is not a serious problem unless splenectomy is performed. Finally, increased incidence of infections is not
The Journal of Pediatrics August 1975
reported to be a clinical feature of idiopathic hemochromatosis. Possible contribution of iron to neonatal infection is similarly conjectural. A preliminary communication suggests that administration of iron dextran to Polynesian neonates increased the incidence of gram-negative sepsis? However, such an association was not noted in substantial American experiences? Necrotizing enterocolitis has been attributed to cows' milk feeding. Since human milk has a large amount of unsaturated lactoferrin when compared to cows' milk, this might contribute to possible prophylactic effects of breast milk feeding. The protection attributed to human milk, if it is a real phenomenon, however, is usually attributed to lymphocytes or antibody-and appears to be heat labile? During the last five years the utilization of iron-fortified infant formulas has tripled. A corresponding epidemic increase of neonatal infections has not been recognized. There are doubtless nurseries in the United States which could be matched for most demographic factors except the type of formula used. A simple comparison of rates of infections from a number of these nurseries would be the easiest way to indicate whether a controlled prospective study is likely to yield useful information. Howard A. Pearson Department of Pediatrics 333 Cedar St. New Haven, Conn. 06510
REFERENCES
1. Dallman PR: Iron, vitamin E, and folate in the preterm infant, J PEnIATR 85:742, 1974. 2. Lukens JN: Iron deficiency and infection: Fact or fable? Am J Dis Child 129:160, 1975. 3. Editorial: Iron and resistance to infection, Lancet 2:325, 1974. 4. Barry DMJ, and Reeve AW: Iron and infection in the newborn, Lancet 2:1285, 1974. 5. Leiken SL: The use of intramuscular iron in the prophylaxis of the iron deficiency anemia of prematurity, Am J Dis Child 99:739, 1960. 6. Barlow B, Santuli TV, Heird WC, Pitt J, Branc WA, and Schullinger JN: The experimental study of acute neonatal enterocolitis-the importance of breast milk, J Pediatr Surg 9:587, 1974.
Rubella immunity in adolescent girls To the Editor: Rauh and associates 1 suggest a serious need for routine rubella surveillance of adolescent girls at menarche. The authors demonstrate decreasing hemagglutination-inhibition (HAI) titers in the adolescent years as well as marked variation in the level of immunity from year to year. This, in their opinion, is related to
Volume 87 Number 2
Letters to the Editor
previous exposure to the rubella virus and past immunization practices in the Cincinnati area. A survey conducted at the Walter Reed Army Medical Center further demonstrates the necessity to determine the level of protection afforded the adolescent girl today by present immunization practices. Two hundred and eleven healthy teen-age girls voluntarily participated in the study. Each was questioned with regard to past rubella infection or immunization and a HAl titer was determined. The individual patient was randomly selected from military dependents presenting to the adolescent medicine service of the medical center. Fifty-five (26.1%) of the participants gave a history of past rubella immunization. A protective titer was found in all but 7.3% of this group. Forty (18.5%) girls responded with a past history of clinical disease. Seventeen and one-half percent of patients with a past history of rubella were susceptible to infection by HAI titer. The remainder of the sample population gave no history of disease or immunization or were ignorant of their immune status. Over 27.3% of these individuals were susceptible to rubella. These figures demonstrate medical history to be a tenuous basis for clinical decisions in the adolescent population. The level of protection in this controlled population suggests the inability of present immunization practices to provide a true "herd immunity." Our efforts to ensure protection to the nulliparous female before conception must be equal to our efforts to immunize the preschool child. To this end laboratory documentation of rubellaimmune status must become a routine medical practice. HA1 screening at pubarche and periodically in high-risk populations will permit an accurate assessment of need for immunization and prudent vaccine administration. Peter C. Freis, M.D. Major, M C Chief Pediatric Service U.S. Army Medical Department Activity West Point, N. Y. 10996
REFERENCE 1. Rauh JL, Sehiff GM, and Johnston LB: Follow-up studies of rubella vaccinees at adolescence, J PVDIATR 86:138, 1975.
Death from Torulopsis in chronic granulomatous disease To the Editor: The article by Lazarus and Neu 1 listing microorganisms which have been responsible for morbidity and mortality rates in chronic granulomatous disease (CGD) will be most helpful. We wish to add Torulopsis to the types of fungi causing death in this disease,
CASE REPORT A 2-month-old boy developed diarrhea and fever. He was treated with oral tetracycline, but fever persisted and he was
333
hospitalized, Because of increasing fever and abdominal distention he was then transferred to our hospital. He presented as an irritable, febrile, pale infant with marked abdominal distention. Hemoglobin was 6.6 gm/dl; urinalysis was normal. Multiple cultures of the blood, urine, pharynx, stool, and spinal fluid were negative. A nitroblue tetrazolium dye reduction test revealed very low spontaneous activity in the face of severe septic morphology. Endotoxin did not stimulate the patient's cells. (Subsequently, his mother and maternal grandmother were documented to be carriers of CGD.) Laparotomy revealed much ascitic fluid. There were a number of yellow masses along the ileum extending to the root of the mesentery. Microscopic examination of the masses revealed granulomatous and necrotizing lymphadenitis consistent with CGD. The infant died two days following surgery. Autopsy revealed similar nodules in the lungs, spleen, kidney, alimentary tract, liver, and lymph nodes. Antemortem culture of the ascitic fluid and postmortem culture of the lungs, spleen, and liver grew Torulopsis species. DISCUSSION Torulopsis is a yeast ordinarily considered to be a saprophyte of limited pathogenicity. It has been cultured from the oral cavity, respiratory tract, intestine, urine, and vagina of apparently healthy individuals. It has been reported to cause urinary tract infections and bronchopneumonia. Fungemia has been described. ~ Usually systemic infections have occurred in patients who were debilitated; many were immunosuppressed. One wonders whether the use of tetracycline contributed to infectivity of this usually saprophytic yeast. Jay 34. Orson, M.D. 293 Governor St. Providence, R. L 02906 Richard G. Greco, M.D. Department of Pediatrics Rhode Island Hospital Section on Human Growth and Development Brown University Providence, R. L 02902
REFERENCES 1. Lazarus GM, and Neu HC: Agents responsible for infection in chronic granulomatous disease of childhood, J PEDIATR 86: 415, 1975. 2. Pankey GA, and Daloviso JR: Fungemia caused by Torulopsis glabrata, Medicine 52: 395, 1973.
Proposed readjustment of eponyms for achondrogensis To the Editor: The form of lethal osteochondrodystrophy known as achondrogenesis has been classified into two types on the basis of radiographic 1 and pathologic findings.2 The differentiation,
Letters to the Editor
REFERENCES
1. Dallman, PR: Iron, vitamin E, and folate in the preterm infant, J PEDIATR 85:742, 1974. 2. Committee on Nutrition: Iron balance and requirements in infancy, Pediatrics 43:134, 1969. 3. Committee on Nutrition: Iron-fortified formulas, Pediatrics 47:786, 1971. 4. Weinberg ED: Iron and susceptibility to infectious disease, Science 184:952, 1974. 5. Weinberg ED: Role of iron in host-parasite interactions, J Infect Dis 124:401, 1971. 6. Bulien JJ, et al: Iron binding proteins and infections, Br J Haematol 23:389, 1972. 7. Report of the Sixty-Second Ross Conference on Pediatric Research, Iron nutrition in infancy, Columbus, Ross Laboratories, 1970.
To the Editor: The letter of Levine and Lemons commenting on Dallman's' recent review of hematinic substances in infancy calls attention to an interesting body of investigative data. The possible effects of iron--both deficiency and excess-on the host resistance to infection have been discussed in a number of recent communications?, a There is little doubt that, in a variety of experimental in vitro situations, large excesses of iron may dramatically affect the proliferation of microorganisms. Further, administration of large doses of iron parenterally can increase susceptibility of certain experimental animals to bacterial infection. Exaggerated and uncritical extrapolation of these experimental data, however, into a variety of clinical situations is not warranted. It is over-simplification to attribute rates of infections in different groups of patients to their iron status per se. High serum levels of iron are frequently associated with systemic diseases such as malignancy, bone marrow failure, and extreme hemolysis, whereas iron deficiency usually occurs as a specific nutritional defect in an otherwise healthy person. To attribute iron as the important variable between these two groups seems astigmatic. The crucial importance of iron in other conditions cited by Levine and Lemons is also overstated. For example, the "300fold increased" susceptibility to meningitis of patients with sickle cell anemia is confined to the first few years of life when body stores of iron and serum iron levels are not particularly elevated; whereas later when these patients usually have increased serum concentrations of iron, the risk of meningitis is not increased. To relate sepsis and meningitis in the sickle cell anemia patient to iron ignores this temporal sequence as well as established pathogenetic mechanisms involving abnormal splenic and opsonization functions. Thalassemia major is the prime pediatric disease in which very high levels of serum iron and transferrin saturation occur. In patients maintained on a high transfusion program, susceptibility to infection is not a serious problem unless splenectomy is performed. Finally, increased incidence of infections is not
The Journal of Pediatrics August 1975
reported to be a clinical feature of idiopathic hemochromatosis. Possible contribution of iron to neonatal infection is similarly conjectural. A preliminary communication suggests that administration of iron dextran to Polynesian neonates increased the incidence of gram-negative sepsis? However, such an association was not noted in substantial American experiences? Necrotizing enterocolitis has been attributed to cows' milk feeding. Since human milk has a large amount of unsaturated lactoferrin when compared to cows' milk, this might contribute to possible prophylactic effects of breast milk feeding. The protection attributed to human milk, if it is a real phenomenon, however, is usually attributed to lymphocytes or antibody-and appears to be heat labile? During the last five years the utilization of iron-fortified infant formulas has tripled. A corresponding epidemic increase of neonatal infections has not been recognized. There are doubtless nurseries in the United States which could be matched for most demographic factors except the type of formula used. A simple comparison of rates of infections from a number of these nurseries would be the easiest way to indicate whether a controlled prospective study is likely to yield useful information. Howard A. Pearson Department of Pediatrics 333 Cedar St. New Haven, Conn. 06510
REFERENCES
1. Dallman PR: Iron, vitamin E, and folate in the preterm infant, J PEnIATR 85:742, 1974. 2. Lukens JN: Iron deficiency and infection: Fact or fable? Am J Dis Child 129:160, 1975. 3. Editorial: Iron and resistance to infection, Lancet 2:325, 1974. 4. Barry DMJ, and Reeve AW: Iron and infection in the newborn, Lancet 2:1285, 1974. 5. Leiken SL: The use of intramuscular iron in the prophylaxis of the iron deficiency anemia of prematurity, Am J Dis Child 99:739, 1960. 6. Barlow B, Santuli TV, Heird WC, Pitt J, Branc WA, and Schullinger JN: The experimental study of acute neonatal enterocolitis-the importance of breast milk, J Pediatr Surg 9:587, 1974.
Rubella immunity in adolescent girls To the Editor: Rauh and associates 1 suggest a serious need for routine rubella surveillance of adolescent girls at menarche. The authors demonstrate decreasing hemagglutination-inhibition (HAI) titers in the adolescent years as well as marked variation in the level of immunity from year to year. This, in their opinion, is related to
Volume 87 Number 2
Letters to the Editor
previous exposure to the rubella virus and past immunization practices in the Cincinnati area. A survey conducted at the Walter Reed Army Medical Center further demonstrates the necessity to determine the level of protection afforded the adolescent girl today by present immunization practices. Two hundred and eleven healthy teen-age girls voluntarily participated in the study. Each was questioned with regard to past rubella infection or immunization and a HAl titer was determined. The individual patient was randomly selected from military dependents presenting to the adolescent medicine service of the medical center. Fifty-five (26.1%) of the participants gave a history of past rubella immunization. A protective titer was found in all but 7.3% of this group. Forty (18.5%) girls responded with a past history of clinical disease. Seventeen and one-half percent of patients with a past history of rubella were susceptible to infection by HAI titer. The remainder of the sample population gave no history of disease or immunization or were ignorant of their immune status. Over 27.3% of these individuals were susceptible to rubella. These figures demonstrate medical history to be a tenuous basis for clinical decisions in the adolescent population. The level of protection in this controlled population suggests the inability of present immunization practices to provide a true "herd immunity." Our efforts to ensure protection to the nulliparous female before conception must be equal to our efforts to immunize the preschool child. To this end laboratory documentation of rubellaimmune status must become a routine medical practice. HA1 screening at pubarche and periodically in high-risk populations will permit an accurate assessment of need for immunization and prudent vaccine administration. Peter C. Freis, M.D. Major, M C Chief Pediatric Service U.S. Army Medical Department Activity West Point, N. Y. 10996
REFERENCE 1. Rauh JL, Sehiff GM, and Johnston LB: Follow-up studies of rubella vaccinees at adolescence, J PVDIATR 86:138, 1975.
Death from Torulopsis in chronic granulomatous disease To the Editor: The article by Lazarus and Neu 1 listing microorganisms which have been responsible for morbidity and mortality rates in chronic granulomatous disease (CGD) will be most helpful. We wish to add Torulopsis to the types of fungi causing death in this disease,
CASE REPORT A 2-month-old boy developed diarrhea and fever. He was treated with oral tetracycline, but fever persisted and he was
333
hospitalized, Because of increasing fever and abdominal distention he was then transferred to our hospital. He presented as an irritable, febrile, pale infant with marked abdominal distention. Hemoglobin was 6.6 gm/dl; urinalysis was normal. Multiple cultures of the blood, urine, pharynx, stool, and spinal fluid were negative. A nitroblue tetrazolium dye reduction test revealed very low spontaneous activity in the face of severe septic morphology. Endotoxin did not stimulate the patient's cells. (Subsequently, his mother and maternal grandmother were documented to be carriers of CGD.) Laparotomy revealed much ascitic fluid. There were a number of yellow masses along the ileum extending to the root of the mesentery. Microscopic examination of the masses revealed granulomatous and necrotizing lymphadenitis consistent with CGD. The infant died two days following surgery. Autopsy revealed similar nodules in the lungs, spleen, kidney, alimentary tract, liver, and lymph nodes. Antemortem culture of the ascitic fluid and postmortem culture of the lungs, spleen, and liver grew Torulopsis species. DISCUSSION Torulopsis is a yeast ordinarily considered to be a saprophyte of limited pathogenicity. It has been cultured from the oral cavity, respiratory tract, intestine, urine, and vagina of apparently healthy individuals. It has been reported to cause urinary tract infections and bronchopneumonia. Fungemia has been described. ~ Usually systemic infections have occurred in patients who were debilitated; many were immunosuppressed. One wonders whether the use of tetracycline contributed to infectivity of this usually saprophytic yeast. Jay 34. Orson, M.D. 293 Governor St. Providence, R. L 02906 Richard G. Greco, M.D. Department of Pediatrics Rhode Island Hospital Section on Human Growth and Development Brown University Providence, R. L 02902
REFERENCES 1. Lazarus GM, and Neu HC: Agents responsible for infection in chronic granulomatous disease of childhood, J PEDIATR 86: 415, 1975. 2. Pankey GA, and Daloviso JR: Fungemia caused by Torulopsis glabrata, Medicine 52: 395, 1973.
Proposed readjustment of eponyms for achondrogensis To the Editor: The form of lethal osteochondrodystrophy known as achondrogenesis has been classified into two types on the basis of radiographic 1 and pathologic findings.2 The differentiation,