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Incidence and prognosis of central nervous system infections in a birth cohort of 12,000 children
13 Infectious Diseases Newsletter 6(2) February 1987 cultured and treatment with cefuroxime was started; cardiopulmonary arrest followed, and she was transferred after resuscitation. On arrival, her blood pressure was 50/? (palpation), pulse 170/min, and pink, frothy material poured from her endotracheal tube. A grade 3/6 holosystolic m u r m u r radiated from the infrasternal border to the left axilla; there was palpable hepatomegaly and splenomegaly; she had no skin lesions. She improved with vigorous application of treatment for cardiogenic shock. Electrocardiography revealed nonspecific ST-T changes; by echocardiography, there was a large pedunculated mass on the anterior leaflet of the mitral valve that prolapsed into the left atrium; there was mitral regurgitation. Blood cultures were obtained and treatment was begun using vancomycin, cefotaxime, and gentamicin. Because blood cultures did not yield growth, amphotericin B was added to the regimen of anti-infective drugs. Both lower extremities remained abnormally cool although her cardiopulmonary status continued to improve. Because of undertainty as to the nature of the mass on the mitral valve, and concern as to saddle embolus blocking the iliac arteries, she was transferred to an institution with capability for cardiovascular surgical intervention. Episodic mitral inlet obstruction was demonstrated, and total obstruction of the aorta at its bifur-
COMMENTS
ON CURRENT
cation was found. The mitral valve was resected and replaced with a #19 St. Jude prosthesis. Aortic and right iliac thrombectomy, excision of aortic and left c o m m o n iliac mycotic aneurysms, and patch angioplasty of the aorta and right iliac artery were carried out. Neither histopathology (fibrin, polymorphonuclear leukocytes, and amorpho u s - c o m p a t i b l e with infective endocarditis) nor cultures revealed either bacterial or fungal microorganisms. Treatment with nafcillin, gentamicin, and ampicillin, given by IV injection, was continued for four weeks postoperatively, yielding a total of six weeks of antibacterial therapy. When evaluated six months after discharge, the patient had returned to her pre-illness level of activity and continued to develop normally Comment Infective endocarditis is an uncommon disorder in children, and its occurrence in the absence of underlying heart disease or other predisposing illnesses, distinctly unusual is recognized. Hence, the concern that our patient might have had a tumor, not infective endocarditis, despite, fever, anemia, a new cardiac murmur, and splenomegaly. Because of the size of the vegetation, impaction of a major artery with an embolus, and formation of a mycotic aneurysm, slow growing, fastidious gram-negative bacteria, nutritionally variant viridans Strep-
tococcus spp. and fungi were considered as etiologic agents. Perhaps the failure to demonstrate an etiologic agent by cultures and on examination of the resected tissues can be related to the antimicrobics given prior to surgery. Ultimately, our patient had a favorable outcome. However, her illness serves as a reminder that infective endocarditis, while rare, may occur in a young child without underlying cardiac disease even in this era of ready availability of powerful antibacterial antimicrobics. Bibliography Johnson CM, Rhodes KH: Pediatric endocarditis. Mayo Clin Proc 57:8694, 1982. Johnson DH, Rosenthal A, Nadas AS: Bacterial endocarditis in children under 2 years of age. Am J Dis Child 129:183-186, 1975. Johnson DH, Rosenthal A, Nadas AS: A 40-year review of bacterial endocarditis in infancy and childhood. Circulation 51:581-588, 1975. Mendelsohn G, Hutchins GM: Infective endocarditis during the first decade of life. Am J Dis Child 13:619-622, 1979. Van Scoy RE: Culture-negative endoarditis. Mayo Clin Proc 57:149-154, 1982. Walterspiel JN, Kaplan SL: Incidence and clinical characteristics of "culture-negative" infective endocarditis in a pediatric population. Pediatr Infect Dis 5:328-332, 1986. Gary Gathman, MD Crystie C. Halsted, MD
Department of Pediatrics University of California Davis Medical Center Sacramento, California
PUBLICATIONS
Rantakallio P, Leskinen M, Von Wendt L: Incidence and prognosis of central nervous system infections in a birth cohort of 12,000 children. Scand 3 Infect Dis 18:287-284, 1986. Among 12,058 children forming a cohort by birth in 1966 in northern Finland and followed to 14 years in age, 110 boys and 64 girls had 174
infections that involved the central nervous system (CNS). For overall findings, see Table i. Of identified bacterial causes, Neisseria meningitidis (38.2% and Haemophilus influenzae (14.6%) were the most c o m m o n isolates. Of viral causes, mumps (41%) and Coxsackieviruses (16%) were the commonest identified causes. © 1987 Elsevier Science Publishing Co.. Inc. 0278-2316/87 $0.00 + 2.20
Comment Infections of the CNS continue to be major causes of morbidity and mortality, with bacterial infections carrying a more ominous prognosis than viral infections. The authors noted that both frequency of infection and prognosis have improved in relation to meningococcal disease, a change attributed to use of
14
Infectious Diseases Newsletter 6(2) F e b r u a r y 1987
Table 1.
Overall Findings of Study,
Bacterial Viral
Incidence
Mortality
Sequellae*
63.3/100,000
8/55 (14.5%)
17/55 (30.9%)
688.0/100,000
3/67 (4.5%)
9/67 (8.1%)
*Mental retardation, epilepsy, cerebral palsy, hearing deficit--alone or in some combination. Significantly different from noninfected children only with regard to bacterial infections. meningococcal polysaccharide vaccine and improved therapy. PDH []
Forberg U, Fryden A, Kihlstrom E, et al: Yersinia enterocolitica septicemia: Clinical and microbiological aspects. Scand J Infect Dis 18:269-279, 1986. Brief reports of seven patients (5 men, 46 to 84 years of age; 2 women, 81 to 87 years of age) with bactermia caused by serotype 0:3, biotype 4, Yersinia enterocolitica affirmed association with chills and high fever, abdominal distress with diarrhea, reactive (ie, sterile) arthritis, and pulmonary complications. While 5/6 patients were over 70 years in age, 2/7 were diabetic, and 2/7 previously had surgical gastric resection. Death resulted in 3/7, all over 75 years. One patient was cured of yersinial endocarditis by surgical resection plus antimicrobial therapy. All isolates produced extracellular beta-lactamases yet, by disc testing were susceptible in vitro to piperacillin and mecillinam (resistant to ampicillin). Several cephalosporins were also active in vitro, as was trimethjoprim-sulfamethoxazole, gentamicin, and rifampin. Despite use of antimicrobics effective by testing in vitro, 5/7 relapsed--4 during therapy, usually with one drug. Based on their limited experience, the authors recommended use of combinations synergistic by testing in vitro, eg, an aminocyclitol + ceftazidime; IV
therapy; and treatment for at least 14 days. Comment
Among the authors' cases, there was a relative paucity of an immunocompromised state with but 2/7 in this category, assuming advanced age is not an immunocompromising event (in the 6 patients studied, all had humoral antibody responses). In the United States, about onefifth of the cases reported were in apparently noncompromised patients (Bouza et al: Am J Med Sci 281-35-42, 1979). Serotype 0.8 is predominant in the United States, but no clear association of serotype with virulence has been shown. The authors did not find tolerance in their isolates, yet failures of therapy were frequent. Further experience is needed to define regimens with high probability of success. At this time, a combination of an aminocyclitol with one of the newer cephalosporins would seem reasonable for commencing treatment, with the regimen modified as indicated by the clinical course and the results of testing in vitro. PDH []
Ouaissi MA, Cornette J, Afchain D, et al: Trypanopsoma cruzi infection inhibited by peptides modeled from a fibronectin cell attachment domain. Science 234:603-607, 1986.
The role of fibronectin (Fn), a high molecular weight glycoprotein present at cell surfaces, in the attach© 1987 Elsevier Science Publishing Co., Inc. 0278-2316; 8 7 5 0 . 0 0 + 2.20
ment of the infectious trypomastigote form of T. cruzi to host cells was explored. Using monoclonal antibodies to the attachment site of Fn, and peptides synthesized to conform to the sequence of the attachment domain, it was shown that the sequence Arg-Gly-Asp-Ser was key to attachment. Immunization of mice with a conjugate of tetanal toxoid + a peptide containing the Arg-Gly-Asp-Ser sequence resulted in significant protection on challenge with trypomastigotes. Comment
Fibronectin is present in blood and connective tissues and participates in a number of cell surface phenomena, including attachment of Treponema pallidurn and Leishmania spp. Interesting too, is the role of the sequence Arg-Gly-Asp-Ser as this hydrophilic peptide is found in the phage receptor on the surface of Escherichia coil and in the protein coat of the Sindbis virus. PDH []
Collins FH, Sakai RK, Vernick KD, et al: Genetic selection of a
Plasmodium-refractory strain of the malaria vector Anopheles gambiae. Science 234:607-610, 1986. A strain of Anopheles gambiae isolated in Gambia in 1975 was shown to have reduced susceptibility to Plasmodium cynomolgi through encapsulation of oocysts formed in the midgut, killing the parasite. The property of refractoriness to infection was found to be heritable. Moreover, a strain of A. gambiae selected for resistance to P. cynomolgi was also refractory to infection with other simian species of Plasmodiu. When tested with Plasmodium spp. pathogenic for humans, refractoriness to infection (continued on pa~,,e15)
COMMENTS
ON CURRENT
cation was found. The mitral valve was resected and replaced with a #19 St. Jude prosthesis. Aortic and right iliac thrombectomy, excision of aortic and left c o m m o n iliac mycotic aneurysms, and patch angioplasty of the aorta and right iliac artery were carried out. Neither histopathology (fibrin, polymorphonuclear leukocytes, and amorpho u s - c o m p a t i b l e with infective endocarditis) nor cultures revealed either bacterial or fungal microorganisms. Treatment with nafcillin, gentamicin, and ampicillin, given by IV injection, was continued for four weeks postoperatively, yielding a total of six weeks of antibacterial therapy. When evaluated six months after discharge, the patient had returned to her pre-illness level of activity and continued to develop normally Comment Infective endocarditis is an uncommon disorder in children, and its occurrence in the absence of underlying heart disease or other predisposing illnesses, distinctly unusual is recognized. Hence, the concern that our patient might have had a tumor, not infective endocarditis, despite, fever, anemia, a new cardiac murmur, and splenomegaly. Because of the size of the vegetation, impaction of a major artery with an embolus, and formation of a mycotic aneurysm, slow growing, fastidious gram-negative bacteria, nutritionally variant viridans Strep-
tococcus spp. and fungi were considered as etiologic agents. Perhaps the failure to demonstrate an etiologic agent by cultures and on examination of the resected tissues can be related to the antimicrobics given prior to surgery. Ultimately, our patient had a favorable outcome. However, her illness serves as a reminder that infective endocarditis, while rare, may occur in a young child without underlying cardiac disease even in this era of ready availability of powerful antibacterial antimicrobics. Bibliography Johnson CM, Rhodes KH: Pediatric endocarditis. Mayo Clin Proc 57:8694, 1982. Johnson DH, Rosenthal A, Nadas AS: Bacterial endocarditis in children under 2 years of age. Am J Dis Child 129:183-186, 1975. Johnson DH, Rosenthal A, Nadas AS: A 40-year review of bacterial endocarditis in infancy and childhood. Circulation 51:581-588, 1975. Mendelsohn G, Hutchins GM: Infective endocarditis during the first decade of life. Am J Dis Child 13:619-622, 1979. Van Scoy RE: Culture-negative endoarditis. Mayo Clin Proc 57:149-154, 1982. Walterspiel JN, Kaplan SL: Incidence and clinical characteristics of "culture-negative" infective endocarditis in a pediatric population. Pediatr Infect Dis 5:328-332, 1986. Gary Gathman, MD Crystie C. Halsted, MD
Department of Pediatrics University of California Davis Medical Center Sacramento, California
PUBLICATIONS
Rantakallio P, Leskinen M, Von Wendt L: Incidence and prognosis of central nervous system infections in a birth cohort of 12,000 children. Scand 3 Infect Dis 18:287-284, 1986. Among 12,058 children forming a cohort by birth in 1966 in northern Finland and followed to 14 years in age, 110 boys and 64 girls had 174
infections that involved the central nervous system (CNS). For overall findings, see Table i. Of identified bacterial causes, Neisseria meningitidis (38.2% and Haemophilus influenzae (14.6%) were the most c o m m o n isolates. Of viral causes, mumps (41%) and Coxsackieviruses (16%) were the commonest identified causes. © 1987 Elsevier Science Publishing Co.. Inc. 0278-2316/87 $0.00 + 2.20
Comment Infections of the CNS continue to be major causes of morbidity and mortality, with bacterial infections carrying a more ominous prognosis than viral infections. The authors noted that both frequency of infection and prognosis have improved in relation to meningococcal disease, a change attributed to use of
14
Infectious Diseases Newsletter 6(2) F e b r u a r y 1987
Table 1.
Overall Findings of Study,
Bacterial Viral
Incidence
Mortality
Sequellae*
63.3/100,000
8/55 (14.5%)
17/55 (30.9%)
688.0/100,000
3/67 (4.5%)
9/67 (8.1%)
*Mental retardation, epilepsy, cerebral palsy, hearing deficit--alone or in some combination. Significantly different from noninfected children only with regard to bacterial infections. meningococcal polysaccharide vaccine and improved therapy. PDH []
Forberg U, Fryden A, Kihlstrom E, et al: Yersinia enterocolitica septicemia: Clinical and microbiological aspects. Scand J Infect Dis 18:269-279, 1986. Brief reports of seven patients (5 men, 46 to 84 years of age; 2 women, 81 to 87 years of age) with bactermia caused by serotype 0:3, biotype 4, Yersinia enterocolitica affirmed association with chills and high fever, abdominal distress with diarrhea, reactive (ie, sterile) arthritis, and pulmonary complications. While 5/6 patients were over 70 years in age, 2/7 were diabetic, and 2/7 previously had surgical gastric resection. Death resulted in 3/7, all over 75 years. One patient was cured of yersinial endocarditis by surgical resection plus antimicrobial therapy. All isolates produced extracellular beta-lactamases yet, by disc testing were susceptible in vitro to piperacillin and mecillinam (resistant to ampicillin). Several cephalosporins were also active in vitro, as was trimethjoprim-sulfamethoxazole, gentamicin, and rifampin. Despite use of antimicrobics effective by testing in vitro, 5/7 relapsed--4 during therapy, usually with one drug. Based on their limited experience, the authors recommended use of combinations synergistic by testing in vitro, eg, an aminocyclitol + ceftazidime; IV
therapy; and treatment for at least 14 days. Comment
Among the authors' cases, there was a relative paucity of an immunocompromised state with but 2/7 in this category, assuming advanced age is not an immunocompromising event (in the 6 patients studied, all had humoral antibody responses). In the United States, about onefifth of the cases reported were in apparently noncompromised patients (Bouza et al: Am J Med Sci 281-35-42, 1979). Serotype 0.8 is predominant in the United States, but no clear association of serotype with virulence has been shown. The authors did not find tolerance in their isolates, yet failures of therapy were frequent. Further experience is needed to define regimens with high probability of success. At this time, a combination of an aminocyclitol with one of the newer cephalosporins would seem reasonable for commencing treatment, with the regimen modified as indicated by the clinical course and the results of testing in vitro. PDH []
Ouaissi MA, Cornette J, Afchain D, et al: Trypanopsoma cruzi infection inhibited by peptides modeled from a fibronectin cell attachment domain. Science 234:603-607, 1986.
The role of fibronectin (Fn), a high molecular weight glycoprotein present at cell surfaces, in the attach© 1987 Elsevier Science Publishing Co., Inc. 0278-2316; 8 7 5 0 . 0 0 + 2.20
ment of the infectious trypomastigote form of T. cruzi to host cells was explored. Using monoclonal antibodies to the attachment site of Fn, and peptides synthesized to conform to the sequence of the attachment domain, it was shown that the sequence Arg-Gly-Asp-Ser was key to attachment. Immunization of mice with a conjugate of tetanal toxoid + a peptide containing the Arg-Gly-Asp-Ser sequence resulted in significant protection on challenge with trypomastigotes. Comment
Fibronectin is present in blood and connective tissues and participates in a number of cell surface phenomena, including attachment of Treponema pallidurn and Leishmania spp. Interesting too, is the role of the sequence Arg-Gly-Asp-Ser as this hydrophilic peptide is found in the phage receptor on the surface of Escherichia coil and in the protein coat of the Sindbis virus. PDH []
Collins FH, Sakai RK, Vernick KD, et al: Genetic selection of a
Plasmodium-refractory strain of the malaria vector Anopheles gambiae. Science 234:607-610, 1986. A strain of Anopheles gambiae isolated in Gambia in 1975 was shown to have reduced susceptibility to Plasmodium cynomolgi through encapsulation of oocysts formed in the midgut, killing the parasite. The property of refractoriness to infection was found to be heritable. Moreover, a strain of A. gambiae selected for resistance to P. cynomolgi was also refractory to infection with other simian species of Plasmodiu. When tested with Plasmodium spp. pathogenic for humans, refractoriness to infection (continued on pa~,,e15)