Pneumocystis carinii and parasitic infections in transplantation

Pneumocystis carinii remains an important pathogen in organ transplantation. New therapeutic options have been developed for the prevention and treatment of P. carinii pneumonia. Parasitic infections are recognized more frequently in potential organ donors or recipients as travel and technology for transplantation extend into endemic regions. Parasites important to transplantation are largely those that can replicate in humans and that cause infection, the intensity of which is regulated by immune mechanisms in the normal host. The spectrum of parasitic infections is likely to increase with improved diagnostic methods, expansion of intestinal transplantation, and xenotransplantation.     

Granulomatous Pneumocystis carinii in AIDS patients

Seven cases of Pneumocystis carinii pneumonia with granulomatous reaction in patients infected with the human immunodeficiency virus are described. The patients were all adult men between the ages of 32 and 45 years, with different high-risk factors. Clinically, all the patients presented with a history of non-productive cough and shortness of breath. Two of the patients had a past history of pulmonary pneumocystosis. Radiologically, six patients had diffuse pulmonary infiltrates and one nodular pulmonary infiltrate. Transbronchial lung biopsies were obtained in four patients and open lung biopsies in three. All presented a predominant granulomatous reaction composed of epithelioid and multinucleated giant cells. Several other special stains to detect the presence of other microorganisms to account for the granulomatous reaction were negative.     

Viral and Pneumocystis carinii infections of the lung in the immunocompromised host

Viruses and Pneumocystis carinii are significant causes of pneumonia in immunocompromised patients, particularly patients with impaired cell-mediated immunity. They are often simultaneously considered in the differential diagnosis of diffuse pneumonitis in these patients and, because radiographic appearances and the periods of vulnerability to these infections may overlap, may be difficult to differentiate. This article will correlate radiographic findings to evolving histopathologic changes in select specific infections, as they affect three different immune impaired populations: (a) acquired immunodeficiency syndrome, (b) immunosuppression secondary to therapy for underlying malignancy or with solid organ transplantation, and (c) immune impairment in the bone marrow transplant patient. Appreciation of the specific clinical setting in which to consider these infections will be emphasized.     

Fulminant Pneumocystis carinii pneumonia in 4 patients with dermatomyositis

Between 1989 and 1996, 4 cases of Pneumocystis carinii pneumonia (PCP) were observed in patients seronegative for the human immunodeficiency virus who were receiving corticosteroid therapy for dermatomyositis in our institution. These cases were considered unusual in light of the short delay of their onset after initiation of immunosuppressive therapy and their fulminant course: 3 of these patients died of PCP occurring during the first month of treatment with prednisone. In all 4 patients lymphopenia was observed before the initiation of corticosteroid treatment and low CD4 and CD8 cell counts were evident at the time of PCP. These observations support the view of an increase in both the severity and incidence of PCP in patients without human immunodeficiency virus infection and question the need for a primary prophylaxis in patients with connective tissue diseases receiving high-dose corticosteroid therapy.     

Pneumocystis carinii meningoradiculitis in a patient with AIDS

Pneumocystis carinii is a common opportunistic pathogen in patients infected with the human immunodeficiency virus (HIV). Pneumocystis carinii pneumonia is common, while extrapulmonary infections with Pneumocystis carinii have been reported sparingly. The clinical features are frequently nonspecific. The detection of Pneumocystis carinii in cerebrospinal fluid (CSF) has not been reported thus far. In this report, an unusual case of Pneumocystis carinii meningoradiculitis in an HIV-infected patient who had previously received primary prophylaxis with trimethoprim-sulfamethoxazole is presented.     

Uptake and metabolism of L-serine by Pneumocystis carinii carinii

Serine is an important amino acid that is utilized in the biosyntheses of proteins and lipids. It is directly incorporated into the head group of phosphatidylserine, which in turn can be converted to other phospholipids. Also, it is required for the formation of long chain bases, precursors of sphingolipids. Uptake and incorporation of radiolabeled serine into both lipids and acid-precipitable material were demonstrated in Pneumocystis carinii carinii organism preparations freshly isolated from infected rat lungs. Radioactivity in proteins was about double that observed in lipids. Liquid scintillation spectrometry of metabolically radiolabeled lipids separated by thin-layer chromatography showed 53% of the total radioactivity were in phosphatidylserine, 12% in phosphatidylethanolamine, 24% in ceramides, and 11% in long chain bases and other compounds. Four long chain bases were detected by thin-layer chromatography in hydrolyzed P. carinii ceramides metabolically labeled with radioactive serine. Phytosphingosine and dihydrosphingosine were tentatively identified by their migrations on thin-layer plates. Radiolabeled ethanolamine was incorporated into P. carinii phosphatidylethanolamine, but relatively low incorporation of radiolabeled choline into phosphatidylcholine occurred. The observations made in this study indicated that P. carinii has the biosynthetic capacity to metabolize phospholipid head groups and to de novo synthesize sphingolipids. L-Cycloserine and beta-Cl-D-alanine, inhibitors of long chain base synthesis, reduced the incorporation of serine into P. carinii long chain bases and ceramides, which supported the conclusion that the pathogen synthesizes sphingolipids.     

Radiographic findings in Pneumocystis carinii pneumonia and its complications in HIV patients

Despite their increasing representation in the population, little is known about the neuropsychological test performance of the oldest old, particularly those who live in residential settings. Limited published data and clinical experience suggest that this group is more likely to perform in the impaired range on standardized tests when cut-offs developed with younger groups are used. We examined the Dementia Rating Scale (DRS) performance of 82 nondemented nursing home residents, aged 80 to 99, with a mean education level of 11 years. Using published norms and cutoffs, a large percentage of this sample performed in the impaired range, particularly on the initiation and conceptualization subtests and on the total score. Education, but not age, was significantly related to performance in this sample. Percentages of patients misclassified were substantial in all groups, but were higher in those with less than 13 years of education. Using a lower total-score cutoff of 110 reduced the percentage of misclassifications markedly. We recommend the development and use of revised cutoff scores for the evaluation of very elderly nursing home residents.     

Incidence of symptomatic urinary tract infections in HIV seropositive patients and the use of cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia

A case of complete synostosis of the cervical spine in a 12-year-old girl is described. Differential diagnosis included dysontogenetic forms of synostosis, Klippel-Feil syndrome, rheumatic synostosis and synostosis of other inflammatory origin. This severe case, the first of its type to be described, appeared to be due to tuberculosis of the cervical spine.     

Dihydropteroate synthase polymorphisms in Pneumocystis carinii

Sulfa drugs are widely used in the treatment and prophylaxis of Pneumocystis carinii pneumonia. The nucleotide sequences of the sulfa target enzyme, dihydropteroate synthase (DHPS), differed substantially in human-, rat-, and mouse-derived P. carinii. Sequence variation also existed in the DHPSs from human-derived isolates. Six nucleotide changes were found in 6 human isolates; each was nonsynonymous and resulted in an amino acid change. Several of these changes were in highly conserved regions and are similar to those that cause sulfa resistance in other organisms. These data suggest that the human-derived P. carinii DHPS may be evolving under positive selective pressure from sulfa drugs.     

Neutrophil chemotactic activity in bronchoalveolar lavage fluid of patients with AIDS-associated Pneumocystis carinii pneumonia

Of the various classes of human genetic disorders, aneuploidy is the most prevalent. Besides its association with maternal age and its predominant origin during maternal meiosis I, little is known about the etiology of aneuploidy. Although various classes of chemicals have been shown to induce aneuploidy in experimental systems, there is no definitive evidence for the role of chemically induced aneuploidy and adverse human health effects, particularly germ cell effects. Thus, it is important to understand the potential of chemicals for inducing aneuploidy in germ cells. There are conflicting data in the literature about the ability of thiabendazole (TBZ) to induce aneuploidy; therefore, we investigated the potential of TBZ for inducing aneuploidy in oocytes. Superovulated ICR female mice were administered 0, 50, 100, or 150 mg/kg TBZ by intraperitoneal injection. The frequencies and percentages of hyperploid oocytes were 0/472 (0), 2/410 (0.5), 6/ 478 (1.3), and 3/427 (0.7) for control, 50, 100, and 150 mg/kg TBZ, respectively. The difference between controls and the 100 mg/kg dose was statistically significant. Also, the proportions of ovulatory mice and the number of oocytes collected per ovulatory female were reduced in the TBZ groups relative to controls. Based on these results, we conclude that TBZ induces a small, but significant increase in the frequency of aneuploid oocytes at toxic doses that also impair ovulation.     

Hyperkalaemia with renal tubular dysfunction by sulfamethoxazole-trimethoprim for Pneumocystis carinii pneumonia in patients with lymphoid malignancy

The prenatal diagnosis of an 11q;22q translocation in a triplet pregnancy detected at the time of chorionic villus sampling (CVS) because of advanced maternal age is reported. Karyotypes obtained from two apparently different CV samples showed the balanced form of translocation, while the one obtained from a third empty sac showed the unbalanced form: 46,XX,-22,+der(22)t(11;22). Second-trimester amniocentesis confirmed the balanced translocation in one of the two viable fetuses and a normal karyotype in the other. The detected karyotypes derived from two different types of meiotic segregation, alternate and adjacent 1. To our knowledge, this is the first reported case of an unbalanced karyotype not due to a 3:1 meiotic segregation of this specific translocation.     

DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora

Samples of ambient air collected with three different types of spore traps in a rural location were examined for the presence of Pneumocystis carinii by screening for P. carinii-specific DNA sequences by DNA amplification. Eleven spore trap samples were analyzed by nested PCR, using oligonucleotide primers designed for the gene encoding the mitochondrial large subunit rRNA of P. carinii f. sp. carinii and P. carinii f. sp. hominis. The samples were collected over a 3-year period during the months of May to September, with a range of sampling times from 9 to 240 h. One air sample from an animal facility housing P. carinii-infected rats was also examined. P. carinii-specific amplification products were obtained from samples from each of the spore traps. The amplification products from eight air samples were cloned and sequenced. The majority of the recombinants from each of these samples had sequences identical to those of P. carinii f. sp. carinii and P. carinii f. sp. hominis, and a number of clones had single-base differences. These data suggest that sequences identical to those of P. carinii f. sp. carinii and P. carinii f. sp. hominis can be detected in samples of air collected in a rural location and that P. carinii may be a component of the air spora of rural Oxfordshire.     

Advances in the treatment and prophylaxis of Pneumocystis carinii pneumonia

Pneumocystis carinii pneumonia (PCP) is the most common illness associated with the acquired immunodeficiency syndrome (AIDS) in the United States and also occurs in immunocompromised persons not infected with the human immunodeficiency virus.. Several advances have taken place in the treatment and prophylaxis of PCP, with most clinical trials conducted in patients with AIDS. Treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMX). Desensitization regimens are available for those who have a fever or rash associated with the agent. Patients with severe PCP who cannot tolerate TMP-SMX may be treated successfully with pentamidine or trimetrexate. Those with mild to moderate disease may receive dapsone-trimethoprim, clindamycin-primaquine, or atovaquone if they cannot take TMP-SMX. Adjunctive therapy with corticosteroids improves the outcome in patients with AIDS and severe PCP.