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Pneumococcal vaccine efficacy in selected populations in the United States
6
Abstracts
J. ALLERGY CLIN. IMMUNOL. AUGUST 1986
a protective effect against subsequent infection challenge with hepatitis B virus (HBV). The idiotypic determinant (Id) of an antibody represents the variable region of the antibody molecule. Id to human Id antibody to HB~Ag contained a sequence that conformed to the internal image portion of HB~Ag and immunization of mice to this anti-Id produced anti-HB~Ag that resembled the human ld antibody to HB~Ag. In the present study rabbits were immunized with human anti-HBAg (the Id, or Ab-1) and produced rabbit anti-ld (or Ab-2) that was affinity purified and injected into two chimpanzees. These animals mounted an anti-HB~ response. One control monkey was treated with nonimmune rabbit lgG, and a second control chimpanzee was left untreated. Neither control animal produced anti-HB~ after infection with HBV, whereas the anti-ld-treated animals were protected from infection. The authors were able to demonstrate by RIA that before challenge with HBV, the rabbit anti-Id recipients developed anti-isotypic, antiallotypic, and anti-idiotypic antibody activity to rabbit anti-Id. The antiHBV immunity induced by the anti-Id immunization was long lasting. It is believed that a monoclonally produced anti-ld would help to obviate the need for large doses of the anti-ld vaccine used in these experiments with polyclonal anti-Id and thereby reduce the possibility of anaphylactic or serum serum sickness type of reactions to heterologous antiserum. Potential uses of such vaccines to protect children from infection with pathogenic capsule-forming bacteria is discussed.
D.S.
Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease Rowntree S, Cogswell J, Platts-Mills T, Mitchell E: Arch Dis Child 60:727, 1985. In this study, 92 infants, selected for investigation before birth, had at least one parent who gave a history of atopic disease. Children were examined at birth, 3, 6, and 12 months and, thereafter, annually, up to 5 years of age. Parents were asked to keep a daily record of symptoms involving the respiratory tract or skin as well as a careful record of the feeding regimen in order to insure that infants who were breast-fed did not receive cow's milk. Skin prick tests for immediate hypersensitivity were performed annually from 1 to 5 years with Dermatophagoides pteronyssinus, grass pollens, cat fur, dog hair, cows' milk, and hens' eggs. RAST with egg, milk, and crude D. pteronyssinus antigens was done as well. Antigen-binding assays were used to quantitate specific IgG and IgE antibody, and samples of dust collected from homes of 66 patients were assayed for dust mite antigen. Specific IgE to ovalbumin occurred in 30% of the children with the mean concentration found at 12 months ',and an increase in prevalence by the second year with decrease in mean concentration. Specific IgE antibody to milk could not be demonstrated in any subject, including four subjects with positive skin tests to milk. Specific IgG antibody to food was noted by antigen-
binding radioimmunoassays at 3 months in most children, peaking by the fifth year. Inhalant allergies, on the other hand, were demonstrated by detectable IgE or IgG antibody and were rare before the first 2 years of life. However, the concentration and prevalence of specific antibody increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Subjects developing positive skin prick test responses or specific lgE during the 5-year observation period were more likely to develop allergic diseases than subjects who had no evidence of sensitivity. Eczema was present at some time in 36% of the children. In these children the prevalence of skin test responses to inhalants and egg protein was comparable throughout the 5-year period. During the first 2 years, however, the prevalence of eczema appeared to correlate with the presence of egg-specific lgE antibody. In later years the overall incidence of eczema was lower. A large proportion of these children, however, who still had symptoms, also had respiratory tract symptoms. The incidence of antibodies to inhalant allergy in this group was high after 5 years. The mean concentration of total IgE for the group rose progressively during the 5 years and correlated significantly with specific IgE antibody responses to inhalant allergens but not with IgE antibody to food allergens. It was noted that a high level of exposure to dust mites was associated with an increased prevalence of positive resuits from skin tests to dust mite and appreciably higher antibody concentration. The incidence of disease appeared to be lowest in children whose bedroom dust contained smaller numbers of house dust mites. Breast-feeding was associated with increased positive results from skin tests but was not associated with detectable lgE antibody to both of the food proteins tested and was not associated with protection against the development of disease. It was noted that both egg and milk protein-positive skin tests were more common in breast-fed infants who were exposed to small quantities of food protein via mother's milk. The authors imply that these small quantities of food antigens are more likely to induce positive results from skin tests. At the end of the first years, there were no obvious differences, either in results of skin tests or serum antibodies to food and inhalant allergens or between breast- or bottle-fed infants. It is postulated that for breast-feeding to be successful, quantities of cow's milk and egg protein in the mother's diet would have to be controlled, and breast-feeding for the first 3 months would probably not alter the antibody response to inhalant allergens at 2 to 5 years.
A.J.C.
Pneumococcal vaccine efficacy in selected populations in the United States Bolan G, Broome CV, Facklam RR, Plikaytis BD, Fraser DW, Schlech WF: Ann Intern Med 104:1, 1986. Pneumococcal vaccine, 14-valent (14-V-PCV) was in use in the United States from 1977 until 1983 when it was replaced by a 23-valent vaccine (23-V-PCV). These authors
VOLUME 72 NUMBER 2
collected and serotyped blood and cerebrospinal fluid isolates of pneumocci from 249 patients who received 14-VPCV and from 1638 unvaccinated patients. Patients were stratified by the serotype of the infecting pneumococcus, the site of infection (blood versus cerebrospinal fluid), patient's age, underlying disease, and the time elapsed between vaccination and onset of infection. Vaccine efficacy (VE) was defined as the reduction in the risk of "vaccine pneumococcus-type" infections occurring in immunized persons as compared to infections occurring in unvaccinated subjects. Post hoc analysis of the data allowed the authors to group serologically "vaccine related"-type infections with "vaccine unrelated"-type infections. Thus VE was poor (<2(1%) for the pneumococcal serotypes 6A, 23F, and 25 in both adults and children (ages 2 to 5 years), whereas VE was similarly effective in young adults and in patients more than 65 years of age. The vaccine was inefficient in patients with Hodgkins disease, renal disease, alcoholism, and multiple myeloma. In patients with splenic dysfunction that was not due to sickle-cell disease, the VE was found to be quite high, and it was noted that VE did not decline during a 5-year postinocculation period in healthy individuals. The authors conclude that PCV vaccination is warranted. J.S.
Serum antibody responses to indigenous oral mucosal antigens and selected laboratory-maintained bacteria in recurrent aphthous ulceration Lindemann R, Riviere G, Sapp J: Oral Surg
59: 585, 1985. Recurrent aphthous ulceration (RAU) is the most common oral ulcerative disease in man. Oral streptococci have been implicated as the causative agent of RAU. The purpose of this study was to test the hypothesis that subjects with RAU have higher serum antibody levels to S. sanguis than do control subjects. In addition, sera were tested against particulate material from nonkeratinizing oral mucosa of each subject with active RAU and control subject in order to test an alternate hypothesis; that is, serum antibody levels to indigenous antigenic material from oral mucosa would disclose differences between subjects with RAU and control subjects. Twenty-one patients with RAU and 12 normal control subjects were studied. Sera from subjects with RAU and control subjects were tested for relative levels of IgM, IgG, and IgA antibodies against eight selected laboratory-maintained bacteria, including S. sanguis. There were no differences in relative serum antibody levels for any isotype against any bacteria between the controi and the RAU groups. Subjects with RAU with active lesions were paired with control subjects, andserum from each group was tested against sedimentable material derived from the oral mucosa of each pair member. Subjects with RAU and control subjects were demonstrated to have similar levels of serum antibodies to indigenous mucosal antigens. Mouths of sub-
Abstracts
7
jects with RAU yielded significantly less antigenic material than did control subjects. A difference was noted in subjects with RAU with active lesions compared to those in remission. The group of patients in RAU remission was found to have a significantly lower level of IgE to S. salivarius and two strains of S. sanguis. Tiffs implies, according to the authors, that humoral immunity to certain oral bacteria may be restricted in the absence of ulceration. A.J.C.
Pharmacology, physiology, and pathology Anaphylactoid reactions associated with parenteral cyclosporine use: Possible role of Cremophor EL Howrie DL, Ptachcinski RJ, Griffith BP, Hardesty RJ, Rosenthal JT, Burckart GJ, Venkataramanan R: Drug Intell Clin Pharm
19:425, 1985. Too rapid intravenous infusion of cyclosporine (CS), a potent immunosuppressive drug that is used in the prevention of organ graft rejection as well as in the amelioration of graft-versus-host disease, may cause flushing, headache, and nausea that usually resolves on slowing the rate of infusion. This article describes three patients with cyclosporine-induced anaphylactoid reactions occurring during infusion of the drug. Two of the subjects had tolerated previous oral doses of the drug, whereas the third individual had received seven parenteral doses of CS before reacting on the eighth postoperative day. Signs and symptoms of adver,;e reaction included pruritus, chest pain, respiratory distress, nausea, headache, urticaria, hypertension, and high alveolar arterial D2 gradients. The authors implicated the drug solubilizing agent Cremophor EL that is used in the preparation of parenteral CS. This material has been implicated similarly in the parenteral forms of miconazole, and diezapam, especially during rapid intravenous infusion. It is suggested, therefore, that these drugs be infused slowly into sensitized patients who should be premedicated with antihistamines. These measures along with close monitoring may allow safe administration of important drugs. J.S.
Passage of undegraded dietary antigen into the blood of healthy adults Husby S, Jensenius J, Svehag S: Scand J Immunol 22:83, 1985, Dietary antigen (ovalbumin) has been demonstrated to be taken up in increased amounts in both allergic and normal children, during and after acute gastroenteritis. The amount and quality of abosrbed antigen may have implications for the development of food allergy. The passage of dietary antigens into the circulation has also been suggested to be
Abstracts
J. ALLERGY CLIN. IMMUNOL. AUGUST 1986
a protective effect against subsequent infection challenge with hepatitis B virus (HBV). The idiotypic determinant (Id) of an antibody represents the variable region of the antibody molecule. Id to human Id antibody to HB~Ag contained a sequence that conformed to the internal image portion of HB~Ag and immunization of mice to this anti-Id produced anti-HB~Ag that resembled the human ld antibody to HB~Ag. In the present study rabbits were immunized with human anti-HBAg (the Id, or Ab-1) and produced rabbit anti-ld (or Ab-2) that was affinity purified and injected into two chimpanzees. These animals mounted an anti-HB~ response. One control monkey was treated with nonimmune rabbit lgG, and a second control chimpanzee was left untreated. Neither control animal produced anti-HB~ after infection with HBV, whereas the anti-ld-treated animals were protected from infection. The authors were able to demonstrate by RIA that before challenge with HBV, the rabbit anti-Id recipients developed anti-isotypic, antiallotypic, and anti-idiotypic antibody activity to rabbit anti-Id. The antiHBV immunity induced by the anti-Id immunization was long lasting. It is believed that a monoclonally produced anti-ld would help to obviate the need for large doses of the anti-ld vaccine used in these experiments with polyclonal anti-Id and thereby reduce the possibility of anaphylactic or serum serum sickness type of reactions to heterologous antiserum. Potential uses of such vaccines to protect children from infection with pathogenic capsule-forming bacteria is discussed.
D.S.
Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease Rowntree S, Cogswell J, Platts-Mills T, Mitchell E: Arch Dis Child 60:727, 1985. In this study, 92 infants, selected for investigation before birth, had at least one parent who gave a history of atopic disease. Children were examined at birth, 3, 6, and 12 months and, thereafter, annually, up to 5 years of age. Parents were asked to keep a daily record of symptoms involving the respiratory tract or skin as well as a careful record of the feeding regimen in order to insure that infants who were breast-fed did not receive cow's milk. Skin prick tests for immediate hypersensitivity were performed annually from 1 to 5 years with Dermatophagoides pteronyssinus, grass pollens, cat fur, dog hair, cows' milk, and hens' eggs. RAST with egg, milk, and crude D. pteronyssinus antigens was done as well. Antigen-binding assays were used to quantitate specific IgG and IgE antibody, and samples of dust collected from homes of 66 patients were assayed for dust mite antigen. Specific IgE to ovalbumin occurred in 30% of the children with the mean concentration found at 12 months ',and an increase in prevalence by the second year with decrease in mean concentration. Specific IgE antibody to milk could not be demonstrated in any subject, including four subjects with positive skin tests to milk. Specific IgG antibody to food was noted by antigen-
binding radioimmunoassays at 3 months in most children, peaking by the fifth year. Inhalant allergies, on the other hand, were demonstrated by detectable IgE or IgG antibody and were rare before the first 2 years of life. However, the concentration and prevalence of specific antibody increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Subjects developing positive skin prick test responses or specific lgE during the 5-year observation period were more likely to develop allergic diseases than subjects who had no evidence of sensitivity. Eczema was present at some time in 36% of the children. In these children the prevalence of skin test responses to inhalants and egg protein was comparable throughout the 5-year period. During the first 2 years, however, the prevalence of eczema appeared to correlate with the presence of egg-specific lgE antibody. In later years the overall incidence of eczema was lower. A large proportion of these children, however, who still had symptoms, also had respiratory tract symptoms. The incidence of antibodies to inhalant allergy in this group was high after 5 years. The mean concentration of total IgE for the group rose progressively during the 5 years and correlated significantly with specific IgE antibody responses to inhalant allergens but not with IgE antibody to food allergens. It was noted that a high level of exposure to dust mites was associated with an increased prevalence of positive resuits from skin tests to dust mite and appreciably higher antibody concentration. The incidence of disease appeared to be lowest in children whose bedroom dust contained smaller numbers of house dust mites. Breast-feeding was associated with increased positive results from skin tests but was not associated with detectable lgE antibody to both of the food proteins tested and was not associated with protection against the development of disease. It was noted that both egg and milk protein-positive skin tests were more common in breast-fed infants who were exposed to small quantities of food protein via mother's milk. The authors imply that these small quantities of food antigens are more likely to induce positive results from skin tests. At the end of the first years, there were no obvious differences, either in results of skin tests or serum antibodies to food and inhalant allergens or between breast- or bottle-fed infants. It is postulated that for breast-feeding to be successful, quantities of cow's milk and egg protein in the mother's diet would have to be controlled, and breast-feeding for the first 3 months would probably not alter the antibody response to inhalant allergens at 2 to 5 years.
A.J.C.
Pneumococcal vaccine efficacy in selected populations in the United States Bolan G, Broome CV, Facklam RR, Plikaytis BD, Fraser DW, Schlech WF: Ann Intern Med 104:1, 1986. Pneumococcal vaccine, 14-valent (14-V-PCV) was in use in the United States from 1977 until 1983 when it was replaced by a 23-valent vaccine (23-V-PCV). These authors
VOLUME 72 NUMBER 2
collected and serotyped blood and cerebrospinal fluid isolates of pneumocci from 249 patients who received 14-VPCV and from 1638 unvaccinated patients. Patients were stratified by the serotype of the infecting pneumococcus, the site of infection (blood versus cerebrospinal fluid), patient's age, underlying disease, and the time elapsed between vaccination and onset of infection. Vaccine efficacy (VE) was defined as the reduction in the risk of "vaccine pneumococcus-type" infections occurring in immunized persons as compared to infections occurring in unvaccinated subjects. Post hoc analysis of the data allowed the authors to group serologically "vaccine related"-type infections with "vaccine unrelated"-type infections. Thus VE was poor (<2(1%) for the pneumococcal serotypes 6A, 23F, and 25 in both adults and children (ages 2 to 5 years), whereas VE was similarly effective in young adults and in patients more than 65 years of age. The vaccine was inefficient in patients with Hodgkins disease, renal disease, alcoholism, and multiple myeloma. In patients with splenic dysfunction that was not due to sickle-cell disease, the VE was found to be quite high, and it was noted that VE did not decline during a 5-year postinocculation period in healthy individuals. The authors conclude that PCV vaccination is warranted. J.S.
Serum antibody responses to indigenous oral mucosal antigens and selected laboratory-maintained bacteria in recurrent aphthous ulceration Lindemann R, Riviere G, Sapp J: Oral Surg
59: 585, 1985. Recurrent aphthous ulceration (RAU) is the most common oral ulcerative disease in man. Oral streptococci have been implicated as the causative agent of RAU. The purpose of this study was to test the hypothesis that subjects with RAU have higher serum antibody levels to S. sanguis than do control subjects. In addition, sera were tested against particulate material from nonkeratinizing oral mucosa of each subject with active RAU and control subject in order to test an alternate hypothesis; that is, serum antibody levels to indigenous antigenic material from oral mucosa would disclose differences between subjects with RAU and control subjects. Twenty-one patients with RAU and 12 normal control subjects were studied. Sera from subjects with RAU and control subjects were tested for relative levels of IgM, IgG, and IgA antibodies against eight selected laboratory-maintained bacteria, including S. sanguis. There were no differences in relative serum antibody levels for any isotype against any bacteria between the controi and the RAU groups. Subjects with RAU with active lesions were paired with control subjects, andserum from each group was tested against sedimentable material derived from the oral mucosa of each pair member. Subjects with RAU and control subjects were demonstrated to have similar levels of serum antibodies to indigenous mucosal antigens. Mouths of sub-
Abstracts
7
jects with RAU yielded significantly less antigenic material than did control subjects. A difference was noted in subjects with RAU with active lesions compared to those in remission. The group of patients in RAU remission was found to have a significantly lower level of IgE to S. salivarius and two strains of S. sanguis. Tiffs implies, according to the authors, that humoral immunity to certain oral bacteria may be restricted in the absence of ulceration. A.J.C.
Pharmacology, physiology, and pathology Anaphylactoid reactions associated with parenteral cyclosporine use: Possible role of Cremophor EL Howrie DL, Ptachcinski RJ, Griffith BP, Hardesty RJ, Rosenthal JT, Burckart GJ, Venkataramanan R: Drug Intell Clin Pharm
19:425, 1985. Too rapid intravenous infusion of cyclosporine (CS), a potent immunosuppressive drug that is used in the prevention of organ graft rejection as well as in the amelioration of graft-versus-host disease, may cause flushing, headache, and nausea that usually resolves on slowing the rate of infusion. This article describes three patients with cyclosporine-induced anaphylactoid reactions occurring during infusion of the drug. Two of the subjects had tolerated previous oral doses of the drug, whereas the third individual had received seven parenteral doses of CS before reacting on the eighth postoperative day. Signs and symptoms of adver,;e reaction included pruritus, chest pain, respiratory distress, nausea, headache, urticaria, hypertension, and high alveolar arterial D2 gradients. The authors implicated the drug solubilizing agent Cremophor EL that is used in the preparation of parenteral CS. This material has been implicated similarly in the parenteral forms of miconazole, and diezapam, especially during rapid intravenous infusion. It is suggested, therefore, that these drugs be infused slowly into sensitized patients who should be premedicated with antihistamines. These measures along with close monitoring may allow safe administration of important drugs. J.S.
Passage of undegraded dietary antigen into the blood of healthy adults Husby S, Jensenius J, Svehag S: Scand J Immunol 22:83, 1985, Dietary antigen (ovalbumin) has been demonstrated to be taken up in increased amounts in both allergic and normal children, during and after acute gastroenteritis. The amount and quality of abosrbed antigen may have implications for the development of food allergy. The passage of dietary antigens into the circulation has also been suggested to be