Guy Dequesne

Treatment of infections

Nowadays Pneumocystis carinii pneumonia most commonly occurs in those at risk of HIV infection who fail to take adequate prophylaxis or in those who are newly diagnosed with advanced disease, where it is frequently the presenting illness. Clinical suspicion is aroused early in patients who are under regular medical supervision, leading to earlier diagnosis. Later diagnosis is asssociated with more severe disease and poorer treatment outcome. Techniques of diagnosis include sputum induction with nebulised saline; this obviates the need for bronchoscopy but the diagnostic sensitivity is lower. The use of lavage alone at bronchoscopy avoids transbronchial biopsy with its complications of haemorrhage and pneumothorax. Exercise oximetry and alternative imaging techniques with radiolabelled compounds are also being used in diagnosis. Monoclonal antibodies to pneumocystis proteins and sensitive DNA probes have been developed but have yet to reach the bedside. In the absence of a confirmatory test, a presumptive diagnosis may be made based on the clinical presentation and chest x ray appearances in a patient severely immunosuppressed and at risk. Prophylaxis for Pneumocystis carinii pneumonia is essential after a first attack (secondary prophylaxis) but is also recommended for all patients once their CD4 cell counts falls

The Lyme disease vaccine candidate outer surface protein A (OspA) in a formulation compatible with human use protects mice against natural tick transmission of B. burgdorferi

Development of a vaccine for the Lyme disease spirochete, Borrelia burgdorferi, has focused on the bacterial lipoprotein, major outer surface protein A (OspA). With few exceptions, testing of OspA vaccines in animal models has involved challenge with needle inoculation of cultured spirochetes. Recombinant OspA proteins from two OspA divergent strains of B. burgdorferi were tested for their vaccine potential in three different strains of mice challenged with laboratory reared ticks with a high rate of B. burgdorferi infection. All formulations of the B. burgdorferi sensu stricto derived OspA vaccine protected all strains of mice when challenged by ticks infected with an OspA homologous strain of the spirochete, whereas heterologous OspA from B. afzelii did not protect. Furthermore, ticks feeding on protected mice had reduced OspA levels compared to unvaccinated controls.

Detection and characterization of pediatric serum antibody to the OMP P5-homologous adhesin of nontypeable Haemophilus influenzae during acute otitis media.

We reported earlier that antibody in sera collected from seven children with acute otitis media (AOM) due to nontypeable Haemophilus influenzae (NTHI) recognized immunodominant regions of P5-fimbrin just as we had observed in a chinchilla model of experimental NTHI-induced AOM. To expand upon those preliminary findings, we further characterized pediatric serum antibodies directed against this adhesin during AOM. Collectively, the data show that children respond immunologically to P5-fimbrin and they do so in a manner that allows for the distinction of sequence diversity within short linear peptides representing a focused region of this surface-exposed protein. The immune recognition we observed encourages us to further develop a P5-fimbrin based vaccine component.