The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Children's Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P < 0.001). Among isolates with identical multilocus sequence types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Children's Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P ؍ 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine.
Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.
Background
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) expressing Panton-Valentine Leukocidin (PVL) cause severe skin and soft tissue infections (SSTI), necrotizing pneumonia and other invasive infections. PVL toxin has been implicated as a virulence factor and antibody to a component of this toxin is under investigation as a vaccine candidate. The role of PVL in pathogenesis remains controversial and it is unknown if human serum antibody to PVL modulates infection.
Methods
We determined antibody levels to PVL in sera from children aged 0-18 years presenting with PCR-confirmed PVL-positive MRSA SSTI with or without prior MRSA infection or SSTI, PVL-positive MRSA invasive infections, PVL-negative MRSA infections and uninfected controls. We also measured antibody-mediated neutralization of PVL-induced lysis of human polymorphonuclear cells.
Results
Antibody to PVL was present in healthy children reaching adult levels by 4-6 years with a nadir at 4-6 months likely due to loss of maternal antibody. Children with a primary PVL-positive MRSA infection had moderate levels of antibody to PVL that increased following infection. Children with prior MRSA or SSTI infections had high levels of antibody to PVL at the onset of infection. There was no increase in antibody to PVL in this populations’ sera after the onset of infection. Sera from children with PVL-positive MRSA SSTIs, particularly those with prior MRSA or SSTI, and convalescent sera from children with invasive PVL-positive MRSA infection, potently inhibited PVL-induced lysis of PMNs.
Conclusions
Neutralizing antibody to PVL does not protect children against primary or recurrent CA-MRSA SSTI.
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