SEROLOGIC METHODS FOR THE EARLY DIAGNOSIS OF PNEUMOCYSTIS CARINII INFECTION IN RENAL ALLOGRAFT RECIPIENTS

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Abstract
Because of the nephrotoxic action of trimethoprim-sulfamethoxazole (TMP-SMX) in cyclosporine (CsA)-treated patients, combined with the possibility of selecting resistant gram-negative or Nocardia asteroides organisms, a monitoring tool to detect early Pneumocystis carinii (PC) infection permitting a selective treatment approach is highly desirable. A review of 401 consecutive renal transplants revealed 26 cases (18 suspected and 8 histologically proved) of PC infection in 21 cadaver and 5 living-related renal recipients. The diagnosis was confirmed in 8/18 patients who were inva-sively studied by open-lung biopsy (1/2), bronchoscopy with transbronchial biopsy (4/9), bronchoscopy with brushing (1/2), bronchoscopy with bronchoalveolar lavage (2/5), and transpleural needle biopsy (0/1)-yielding a confirmed incidence of 2% (8/401). All positive invasive studies had been performed prior to or within 24 hr of the inception of TMP-SMX therapy. Nine of ten negative invasive studies were performed after more than 24 hr of treatment. The mean time from transplantation to the onset of clinical symptoms was 2.5pM1.5 months. The infection rate would be 6.5%, assuming all 18 suspected cases would be PC-positive if studied pre-treatment. In order to assess the efficacy of a variety of serologic methods of PC detection, qualitative counter-immunoelectrophoresis (CIE) for P carinii antigen (PC-Ag), IgG antibody reactive with PC (enzyme-linked immunosorbent assay [EI,ISA]), and a latex particle agglutination test (LPA) were performed on 279 sera; 85 sera from the 26 suspected or proved cases, 100 sera from normal age-matched controls, and 94 sera from 78 asymptomatic allograft recipients followed as outpatients. In the eight histologically proven cases, CIE was positive in only 3/8 and turned positive late in the clinical course. LPA was positive in all histologically proved cases; however, it was also positive in 60% of asymptomatic renal recipients. In cases that developed clinical disease, LPA increased in titer weeks to months prior to the onset of symptoms. Additionally, LPA titers decreased or stabilized during successful TMP-SMX therapy, providing an early therapeutic index. Measurement of anti-PC IgG was not useful per se, as it was elevated in both controls and documented PC infection. The combination of very low antibody titer (≤1:16) with a positive or increasing LPA PC-Ag titer appeared to be disease-predictive. Both histologic and serologic criteria appeared to indicate an increase in P carinii pneumonia (PCP) incidence in this transplant population. Serial studies of LPA PC-Ag and ELISA PC antibody titers will aid in the development of monitoring tools to improve the care of transplant recipients at high risk for PC infection.