Preferential recognition of human myocardial antigens by T lymphocytes from rheumatic heart disease patients.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune sequelae of upper respiratory infections with group A streptococci (GAS). To gain a better understanding of the pathogenesis of these diseases, we examined the in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) from RHD patients to human myocardial proteins in a T-cell Western assay. A number of myocardial proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were recognized by PBMC from both patients and controls. However, PBMC from a significant percentage of RHD patients (40%) responded to a discrete band of myocardial proteins migrating with an apparent molecular mass of 50 to 54 kDa while none of the control subject PBMC responded to this protein band (P < or = 0.0001). To further investigate the link between infections with GAS and autoimmune carditis, we studied the proliferative responses of PBMC from patients and controls to myocardial proteins before and after in vitro stimulation of the cells with opsonized GAS isolated from ARF patients. Priming of PBMC with rheumatogenic GAS caused the percentage of RHD patients responding to the 50- to 54-kDa myocardial proteins to increase from 43 to 90% (P < or = 0.0284). By contrast, PBMC from control subjects failed to recognize the 50- to 54-kDa myocardial proteins even after stimulation with the opsonized streptococci (P < or = 0.0001). The assay sensitivity was increased from 40 to 90% after priming of a patient's cells with opsonized GAS, but the positive predictive value was 100% in both unprimed and primed cultures. Antibodies generated to partially purified 50- to 54-kDa myocardial proteins did not cross-react with either streptococcal homogenates, purified M protein, myosin, laminin, or vimentin, suggesting a lack of cross-reactivity at the humoral level. This study suggests that the 50- to 54-kDa myocardial proteins contain a putative antigen that is preferentially recognized by T cells from RHD patients and demonstrates that exposure to streptococcal antigens enhances the ability of patients to recognize these proteins.

Resistance patterns of Streptococcus pneumoniae and Haemophilus influenzae isolates recovered in Egypt from children with pneumonia. The Antimicrobial Resistance Surveillance Study Group.

Treatment of childhood pneumonia in developing countries requires knowledge of susceptibility patterns for Streptococcus pneumoniae and Haemophilus influenzae. Between October 1991 and April 1993, a surveillance survey of antimicrobial resistance was performed at two fever hospitals in Egypt; nasopharyngeal swab and blood specimens obtained from 1,635 children with pneumonia were cultured for these organisms. Susceptibility testing of these organisms was performed. At least one of these organisms was isolated from nasopharyngeal swab specimens from 73% of the children; 3.7% of blood cultures were positive. For S. pneumoniae strains, 70.9% of nasopharyngeal isolates were calculated to be susceptible to penicillin vs. 77.6% of blood isolates; the percentages of isolates susceptible to co-trimoxazole were 73.0% and 75.0%, respectively. For H. influenzae strains, 93.0% of nasopharyngeal isolates were calculated to be susceptible to ampicillin vs. 100% of blood isolates; the percentages of isolates susceptible to co-trimoxazole were 84.9% and 100%, respectively. Although most S. pneumoniae and H. influenzae strains associated with childhood pneumonia in Cairo were susceptible to penicillins and co-trimoxazole, antimicrobial resistance did not occur.

Identification and characterization of Schistosoma mansoni antigens recognized by T and B lymphocytes of humans with early active intestinal and/or urinary schistosomiasis.

Schistosome antigens selected as vaccine candidates should induce in the majority of humans T and B cell-mediated immunity that results in protection against infection. As a first step towards the identification of such antigens, we attempted to define and characterize the soluble adult Schistosoma mansoni worm antigen (SAWA) bands that are recognized by serum antibodies and/or peripheral blood mononuclear cells of Egyptian children with early active S. mansoni and/or S. haematobium infection. Considerable inter-subject variation was observed in the SAWA bands recognized by antibodies and T lymphocytes, as demonstrated by Western blotting and T cell Western assays, respectively. The humoral response rate for the separated SAWA bands varied between 0% and 88% of infected subjects. The bands of 153, 144, 38 and 32 kDa reacted with the sera of 60 to 88% of infected subjects but not with the sera of uninfected controls. The bands of 144, 38, 32 and 18 kDa elicited proliferative responses in the lymphocytes of 42-63% of infected subjects. It was thus concluded that the SAWA bands of 144, 38 and 32 kDa are likely to carry T and B cell epitopes that could stimulate immune responses in a majority of individuals. The selected bands (144, 38 and 32 kDa) were found to include glycoproteins containing D-mannopyranosyl or glycosyl residues, and respectively 62.5, 46 and 55% amino acids by weight. The amino acid molar ratios of these bands were completely different.

Hemophilus influenzae and Streptococcus pneumoniae as causative agents of pneumonia in Egyptian preschool children: analysis and serotyping of Hemophilus isolates from hospital patients in Cairo, 1991-93.

The Hemophilus influenzae blood culture and nasopharyngeal isolates, collected during a limited Surveillance of Antimicrobial Resistance in 1991-1993 from 1,635 Egyptian children under 5 years of age, presenting with pneumonia to Embaba and Abbassia Fever Hospitals, were serotyped. The 8 blood culture isolates confirmed H. influenzae to be responsible for 0.5% of the cases of pneumonia, versus 50 Streptococcus pneumoniae blood culture isolates from the same population that confirmed it responsible for 3.1% of the cases. The invasive Hemophilus strains were exclusively isolated from infants below 1 year, from one hospital (Embaba), on one winter season (January to March, 1992). On serotyping, 50% of the blood culture isolates were found to be non-b by latex agglutination. Some 297 nasopharyngeal isolates from cases of pneumonia were also serotyped and 45% were found to be non-b, thus confirming the invasive strains findings. Furthermore, the typing results from ARI-free controls nasopharyngeal isolates--though limited--were consistent with the findings and showed a 43% proportion of non-b. These findings put a question mark on the benefit of a large scale use of the available H. influenzae type b polysaccharide and conjugated vaccines in Egypt. But before interpreting out data in terms of vaccine needs, more specifically designed epidemiological studies need to be conducted to assess the role of H. influenzae as a pathogen in Egypt.

A suggested vaccine formulation for the control of pneumococcal meningitis in Egypt.

Mortality rates of pneumococcal meningitis ranges from 13-60% in different parts of the world. Reports of pneumococci with multiple antibiotic resistance add urgency to the need for developing means of primary prevention. A 14-valent pneumococcal vaccine was licensed in 1977, and a 23-valent pneumococcal vaccine in 1983. In the present work 131 strains of pneumococci isolated from meningitis cases in Egypt were identified and serotyped by Quellung reaction. The most frequently isolated serotype was serotype 1 (32%). Serotypes 6A, 9L, 12A, 19A and 29 were next in prevalence. The age groups 0-18 years were the most frequently affected groups (79%) and over 18 years of age were only 21% of total cases. A vaccine formulation is suggested to have a coverage rate against pneumococcal meningitis cases of 79.3% and 89.3% of a proposed 14-valent vaccine and 23-valent vaccine versus to coverage rate of 48% and 54% of 14-valent and 23-valent International vaccines respectively. According to the age distribution of cases and the isolated serotypes a vaccination could be recommended during the first two years of age in order to protect the most frequently infected groups.

Newly recognized distinctive M protein associated with certain M type 1 group A streptococci.

Immunological and epidemiological characteristics of M1T1 and M1T8 (T8, 25, Imp.19) group A streptococci isolated in Egypt have been described. Both strains possess a common M1 antigen. The M1T8 strains possess a second antigen which has the immunological and biological characteristics of M protein. The M1T1 strains do not possess this second M antigen. Absorbed rabbit antisera which are specific for this second antigen do not react with extracts of any of the known M protein serotypes. This second antigen is therefore a newly recognized M protein. The M1T1 and M1T8 strains had mutually exclusive geographical and temporal distributions. This finding may have been a consequence of the immunity which occurred after the initial occurrence of the M1T8 strain.