1192 FAILURE OF PNEUMOCOCCAL VACCINE TO PREVENT STREPTOCOCCUS PNEUMONIÆ SEPSIS IN NEPHROTIC CHILDREN
SIR,-Immunisation with polyvalent pneumococcal polysaccharide vaccine is recommended for certain high-risk groups, including children with the nephrotic syndrome.’ These children, even when in relapse or receiving steroids, have been reported to respond to this vaccine as well as control children do.2 We have observed two episodes of sepsis with Streptococcus pneumonice among a group of nineteen children vaccinated since January, 1979. One child had infection with a vaccine-covered strain, type 4. The other child had sepsis due to type 19A, against which the vaccine theoretically protects, and which is the principal capsular type reported to develop antibiotic resistance.3 A 4-year-old boy with a 1-Lyear history of nephrotic syndrome due to focal segmental glomerulosclerosis, received 14-valent pneumococcal vaccine (’Pneumovax’; Merck, Sharp and Dohme, lot 526A). At the time he was on prednisone 0-8 mg/kg four times daily, had 3+ proteinuria, serum albumin of 1.3 g/dl, IgG 204 mg/dl (normal 585-1381), and serum-creatinine 0-5mg/dl. He had had a 6-week course of cyclophosphamide, 2 mg/kg, one year before vaccination. 5 weeks after immunisation primary peritonitis developed. Strep. pneumonix type 4 was isolated from peritoneal fluid and blood. Recovery without sequelae followed penicillin therapy. Antibody concentration against type 4 pneumococcal antigen in sera obtained at the time of vaccination, 3 days after diagnosis of sepsis, and 2 months after discharge were 139, 140, and 128 ng antibody
N/ml, respectively.4 A 4-year-old girl had pneumonitis during a relapse of her steroid-responsive nephrotic syndrome. She had received pneumovax 4 i months earlier, at a time when she had been off corticosteroid therapy for 2 months. Strep. pneumoniae type 19A was identified in a blood culture. Antibody concentration against type 19 at the time of infection was 0-2 ng antibody N/ml.
levels may be due to the immunosuppressive medication used to treat the nephrotic syndrome. Similar impaired immune responsiveness persists for several years after chemotherapy in patients with Hodgkin’s disease.5 Perhaps a second, or booster, vaccination will allow development of more protective levels of
antibody. Type 19A is not included in pneumovax although type 19F is. Data suggest that types 19A and 19F are cross-antigenic and cross-immunogenic in rabbits.6 The lack of protection against type 19A infection afforded the second patient by immunisation with type 19F may be due to low levels of antibody in nephrotic children, as discussed above. However, it may indicate that immunisation with type 19F provides insufficient protection against type 19A pneumococci in man. Most of the multiply antibiotic resistant Strep. pneumonice, which are and with wider geobeing reported with increasing frequency 3 are 19A.3 distribution, type graphic Reformulation of the vaccine to include type 19A should be considered, and, despite the use of polyvalent pneumococcal polysaccharide vaccine, physicians must remain alert for serious pneumococcal infection in high-risk individuals. We thank Sandra
Fleming for ensuring specimen collection.
Department of Pediatrics, Wayne State University School of Medicine, Children’s Hospital of Michigan, Detroit, Michigan 48201, U.S.A. Department of Microbiology and Immunology, Downstate Medical Center,
GERALD SCHIFFMAN
Brooklyn, N.Y.
PERITONEAL DRAINAGE
SIR,-Your editorial (Nov. 3, p. 941), in condemning fails to specify the type of drain. In one prospective trial cited, corrugated drains were used after cholecystectomy, an entirely different matter from fine vacuum tube drainage, which is our practice. I would say that corrugated or even large rubber tube trains will never evacuate blood except when liquefied by pancreatic ferments, any blood appearing down them originating from the stab wound and probably the dermis. Elsewhere blood clots too soon to be removed, so intraperitoneal collection will not be prevented. Although when we close up after cholecystectomy we leave the scene clean, tidy, and dry, we are occasionally surprised by a bottle half filled with blood or bile the next day. Without drainage it could have been troublesome, whereas a fine plastic tube is most unlikely
drainage,
The boy had a 2-fold or greater increase in antibody concentration in response to the vaccine for 7 of the 11 pneumococcal capsular types assayed (table). The persistently low antibody levels of type 4 suggest a specific inability to respond to this capsular type. This may be age related or due to an underlying specific immunological defect. The levels of pneumococcal capsular antibody necessary to prevent infection are not known. While nephrotic children respond immunologically to pneumovax, they have much lower absolute pre-vaccination (table) and post-vaccination antibody concentrations2 than control children have. This may explain the continued susceptibility to pneumococcal infection in vaccinated children. These low O, Mortimer EA. Use of pneumococcal vaccine in children. Pediatrics 1978; 61: 321-22. 2. Fikrig SM, Schiffman G, Phillip JC, Moel D. Antibody response to capsular polysaccharide vaccine of streptococcus pneumoniae in patients with nephrotic syndrome.J Infect Dis 1972; 126: 507-13. 3. Pabst HF, Nigrin J. Penicillin resistance of pneumococci and immune deficiency. Lancet 1979; ii: 359-60. 4. Schiffman G, Austrian R. FedProc 1971; 30: 658. abstr. 1. Klein
5. Minor DR, Schiffman G, McIntosh LS. Response of patients with Hodgkins’s disease to pneumococcal vaccine. Ann Intern Med 1979; 90: 892-95. 6. Krishnamurthy T, Henrichsen J, Carlo DJ, Stoudt TM, Robbins JB. Characterization of the cross-reaction between type 19F (19) and 19 (57) pneumococcal capsular polysaccharides: Compositional analysis and immunological relation determined with rabbit typing antisera. Infect Immun
1978; 22: 727-35.
ANTIBODY CONCENTRATIONS BEFORE AND AFTER IMMUNISATION IN
Results expressed
WILLIAM A. PRIMACK MYRNA ROSEL M. C. THIRUMOORTHI LARRY E. FLEISCHMANN
as
ng antibody N/ml serum. Control and nephrotic children’s data from
Fikrig et al.2
4-YEAR-OLD
BOY
SIR,-Immunisation with polyvalent pneumococcal polysaccharide vaccine is recommended for certain high-risk groups, including children with the nephrotic syndrome.’ These children, even when in relapse or receiving steroids, have been reported to respond to this vaccine as well as control children do.2 We have observed two episodes of sepsis with Streptococcus pneumonice among a group of nineteen children vaccinated since January, 1979. One child had infection with a vaccine-covered strain, type 4. The other child had sepsis due to type 19A, against which the vaccine theoretically protects, and which is the principal capsular type reported to develop antibiotic resistance.3 A 4-year-old boy with a 1-Lyear history of nephrotic syndrome due to focal segmental glomerulosclerosis, received 14-valent pneumococcal vaccine (’Pneumovax’; Merck, Sharp and Dohme, lot 526A). At the time he was on prednisone 0-8 mg/kg four times daily, had 3+ proteinuria, serum albumin of 1.3 g/dl, IgG 204 mg/dl (normal 585-1381), and serum-creatinine 0-5mg/dl. He had had a 6-week course of cyclophosphamide, 2 mg/kg, one year before vaccination. 5 weeks after immunisation primary peritonitis developed. Strep. pneumonix type 4 was isolated from peritoneal fluid and blood. Recovery without sequelae followed penicillin therapy. Antibody concentration against type 4 pneumococcal antigen in sera obtained at the time of vaccination, 3 days after diagnosis of sepsis, and 2 months after discharge were 139, 140, and 128 ng antibody
N/ml, respectively.4 A 4-year-old girl had pneumonitis during a relapse of her steroid-responsive nephrotic syndrome. She had received pneumovax 4 i months earlier, at a time when she had been off corticosteroid therapy for 2 months. Strep. pneumoniae type 19A was identified in a blood culture. Antibody concentration against type 19 at the time of infection was 0-2 ng antibody N/ml.
levels may be due to the immunosuppressive medication used to treat the nephrotic syndrome. Similar impaired immune responsiveness persists for several years after chemotherapy in patients with Hodgkin’s disease.5 Perhaps a second, or booster, vaccination will allow development of more protective levels of
antibody. Type 19A is not included in pneumovax although type 19F is. Data suggest that types 19A and 19F are cross-antigenic and cross-immunogenic in rabbits.6 The lack of protection against type 19A infection afforded the second patient by immunisation with type 19F may be due to low levels of antibody in nephrotic children, as discussed above. However, it may indicate that immunisation with type 19F provides insufficient protection against type 19A pneumococci in man. Most of the multiply antibiotic resistant Strep. pneumonice, which are and with wider geobeing reported with increasing frequency 3 are 19A.3 distribution, type graphic Reformulation of the vaccine to include type 19A should be considered, and, despite the use of polyvalent pneumococcal polysaccharide vaccine, physicians must remain alert for serious pneumococcal infection in high-risk individuals. We thank Sandra
Fleming for ensuring specimen collection.
Department of Pediatrics, Wayne State University School of Medicine, Children’s Hospital of Michigan, Detroit, Michigan 48201, U.S.A. Department of Microbiology and Immunology, Downstate Medical Center,
GERALD SCHIFFMAN
Brooklyn, N.Y.
PERITONEAL DRAINAGE
SIR,-Your editorial (Nov. 3, p. 941), in condemning fails to specify the type of drain. In one prospective trial cited, corrugated drains were used after cholecystectomy, an entirely different matter from fine vacuum tube drainage, which is our practice. I would say that corrugated or even large rubber tube trains will never evacuate blood except when liquefied by pancreatic ferments, any blood appearing down them originating from the stab wound and probably the dermis. Elsewhere blood clots too soon to be removed, so intraperitoneal collection will not be prevented. Although when we close up after cholecystectomy we leave the scene clean, tidy, and dry, we are occasionally surprised by a bottle half filled with blood or bile the next day. Without drainage it could have been troublesome, whereas a fine plastic tube is most unlikely
drainage,
The boy had a 2-fold or greater increase in antibody concentration in response to the vaccine for 7 of the 11 pneumococcal capsular types assayed (table). The persistently low antibody levels of type 4 suggest a specific inability to respond to this capsular type. This may be age related or due to an underlying specific immunological defect. The levels of pneumococcal capsular antibody necessary to prevent infection are not known. While nephrotic children respond immunologically to pneumovax, they have much lower absolute pre-vaccination (table) and post-vaccination antibody concentrations2 than control children have. This may explain the continued susceptibility to pneumococcal infection in vaccinated children. These low O, Mortimer EA. Use of pneumococcal vaccine in children. Pediatrics 1978; 61: 321-22. 2. Fikrig SM, Schiffman G, Phillip JC, Moel D. Antibody response to capsular polysaccharide vaccine of streptococcus pneumoniae in patients with nephrotic syndrome.J Infect Dis 1972; 126: 507-13. 3. Pabst HF, Nigrin J. Penicillin resistance of pneumococci and immune deficiency. Lancet 1979; ii: 359-60. 4. Schiffman G, Austrian R. FedProc 1971; 30: 658. abstr. 1. Klein
5. Minor DR, Schiffman G, McIntosh LS. Response of patients with Hodgkins’s disease to pneumococcal vaccine. Ann Intern Med 1979; 90: 892-95. 6. Krishnamurthy T, Henrichsen J, Carlo DJ, Stoudt TM, Robbins JB. Characterization of the cross-reaction between type 19F (19) and 19 (57) pneumococcal capsular polysaccharides: Compositional analysis and immunological relation determined with rabbit typing antisera. Infect Immun
1978; 22: 727-35.
ANTIBODY CONCENTRATIONS BEFORE AND AFTER IMMUNISATION IN
Results expressed
WILLIAM A. PRIMACK MYRNA ROSEL M. C. THIRUMOORTHI LARRY E. FLEISCHMANN
as
ng antibody N/ml serum. Control and nephrotic children’s data from
Fikrig et al.2
4-YEAR-OLD
BOY
