Atypical Pneumocystis carinii infection in AIDS: massive cervical lymphadenitis and fever of unknown origin

Pulmonary Pneumocystis carinii infections are relatively common in patients with the acquired immunodeficiency syndrome (AIDS). Extrapulmonary pneumocystis is a less common manifestation, particularly when it occurs without concurrent Pneumocystis carinii pneumonia. Disseminated pneumocystis is most commonly found in lymph nodes, the liver, and the spleen and may result in nonspecific debilitating illness, which is often overlooked in the absence of pulmonary symptoms. We present the case of an AIDS patient who had massive cervical pneumocystis lymphadenitis and minimal pulmonary infiltrates of undetermined etiology and a clinical picture of severe wasting and fever of unknown origin.     

Pneumocystis carinii pneumonia: an opportunistic infectious risk associated with systemic diseases and their treatment

Pneumocystis carinii, an opportunistic pathogen, often causes pneumonia in persons with human immunodeficiency virus (HIV) infection. In patients free of HIV infection, the risk is clearly associated with certain diseases and immunosuppressive therapy. Pneumocystis carinii pneumonia can complicate solid or hematologic malignancies, organ transplantation and connective tissue diseases. Recent therapeutic strategies based on aggressive immunosuppression have increased the risk of opportunistic infection with Pneumocystis carinii, particularly in patients with Wegener's syndrome and systemic lupus erythematosus. The risk of interhuman nosocomial transmission of Pneumocystis carinii in units caring for HIV-infected patients and patients with immunosuppressive diseases should also be considered. The undeniable progress in therapeutic immunosuppression has increased the risk of opportunistic infections. The gravity of Pneumocystis carinii pneumonia demonstrates the importance of optimizing treatment choice in order to strike the right balance between beneficial effect and risk of opportunistic infection.     

Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection

We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.     

AIDS pathology: infections and neoplasms in 55 fatal AIDS cases. A postmortem study

The study evaluated the incidence of infections and neoplasms in 55 out of 104 patients with AIDS who died in Poland from January 1986 to April 1994 (the estimated autopsy rate-52.8%). Histopathological examination revealed 103 infections and 11 neoplasms. In 40 persons (73%) either multiple infections or a neoplasm and an infection were diagnosed. Cytomegalovirus infection was most common. (65.5% of cases) followed by Pneumocystis carinii (24% of cases). These infections were the leading cause of death in 20% and 16% of cases, respectively. The results of this study showed a significantly lower incidence of Pneumocystis carinii, Kaposi's sarcoma and non-Hodgkin's lymphoma in comparison with the results of similar studies in countries with a large number of AIDS cases.     

Microsurgical and prosthetic reconstruction of patient with recurrent ameloblastoma extending into the skull base

Pneumocystis carinii pneumonia is a common cause of death in patients with AIDS. Diagnosis is based on cytological examination of smears prepared from induced sputum samples and bronchoalveolar lavage (BAL) specimens which have been stained with methenamine silver. We have examined 46 BAL/induced sputum specimens from patients who had clinical symptoms and signs suggestive of P. carinii pneumonia and measured the diameter of a minimum 100 cysts in each specimen. We found that cyst size correlated with response to treatment with co-trimoxazole. This observation has implications for the therapeutic management of patients with this infection.     

Extrapulmonary pneumocystosis

Extrapulmonary pneumocystosis is an exceedingly rare complication of Pneumocystis carinii pneumonia (PCP). Prior to the advent of the human immunodeficiency virus type 1 (HIV-1) epidemic, only 16 cases of extrapulmonary pneumocystosis in individuals who were immunocompromised by a variety of underlying diseases had been reported. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported. This review briefly presents a history of the discovery of P. carinii and its recognition as a human pathogen, the controversy regarding its taxonomy, and the epidemiology of this organism. A more detailed analysis of the incidence of extrapulmonary pneumocystosis in HIV-1-infected individuals and its occurrence despite widespread prophylaxis for PCP with either aerosolized pentamidine or systemic dapsone-trimethoprim is presented. The clinical features of published cases of extrapulmonary pneumocystosis in non-HIV-1-infected individuals are summarized and contrasted with those in HIV-1 infected individuals. The diagnosis of extrapulmonary pneumocystosis is discussed, and because clinical microbiologists and pathologists are the key individuals in establishing the diagnosis, the characteristic microscopic morphology of P. carinii as its appears when stained with a variety of stains is presented and reviewed. The review concludes with a brief discussion of treatments for extrapulmonary pneumocystosis.     

Cavitary pulmonary lesions in patients infected with human immunodeficiency virus

The differential diagnosis of cavitary pulmonary lesions in individuals infected with human immunodeficiency virus (HIV) is broad, especially in patients with advanced disease. In patients with Pneumocystis carinii pneumonia, cavitation is an uncommon manifestation of a common disease. It is unusual in patients with pulmonary cryptococcosis, coccidioidomycosis, and histoplasmosis but occurs frequently in patients with invasive pulmonary aspergillosis. In patients with pulmonary tuberculosis, cavities are more common during earlier stages of HIV disease, when cellular immunity is relatively preserved. Mycobacterium avium complex is an uncommon cause of lung disease and infrequently produces cavities. However, Mycobacterium kansasii, is often associated with cavitation. Cavities can complicate any bacterial pneumonia and are especially common with pneumonia due to Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi. Noninfectious causes of cavitary lesions are rare, but cavitary lesions caused by pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported. Because of the broad differential diagnosis and because most cavities are caused by treatable opportunistic infections, a definitive diagnosis is essential.     

The diagnosis and management of a perianesthetic cerebral aneurysmal rupture aided with transcranial Doppler ultrasonography

To further elucidate the extent of variation among Pneumocystis carinii obtained from different mammalian hosts, polymerase chain reaction (PCR) analysis of the genes encoding two antigens of P. carinii was done. Using primers based on the ferret P. carinii glycoprotein (gp)A gene and the rat P. carinii 45- to 55-kDa antigen gene, amplification was attempted with DNA isolated from P. carinii-infected ferret, rat, mouse, and human lungs. For both genes, amplification was successful only with P. carinii DNA isolated from the same host species from which the P. carinii gene was originally isolated. The presence of P. carinii DNA in each sample was documented by PCR using primers based on the conserved mitochondrial ribosomal RNA gene sequence. These results were confirmed for P. carinii gpA by Southern blot analysis using a labeled fragment of the ferret P. carinii gpA gene as a probe. Thus, in addition to the previously reported phenotypic variation among antigens of P. carinii, there is also genotypic variation of these same antigens.     

Malignant uterine smooth muscle tumors: role of etoposide, cisplatin, and doxorubicin (EPA) chemotherapy

Fungal infections, in addition to bacterial and opportunistic infections such as Pneumocystis carinii pneumonia, may evolve in patients with infectious complications due to iatrogenic immunosuppression. Aside from common Candida and Aspergillus species, rare fungi like Mucor must be considered in patients with neutropenia or prolonged impaired T-cell function. Here we report on a patient with a low grade lymphoma who was treated with 2-chlorodeoxyadenosine because of disease progression. After recovery from Pneumocystis carinii pneumonia he presented again with clinical signs of pneumonia. No pathogen was found on bronchoscopy and he died rapidly. In the lungs a massive necrosis was seen in which nonseptated hyphae identified as Mucor species were demonstrated.     

Structure of a new neutral O-specific polysaccharide of Proteus penneri 34

Since Pneumocystis carinii cannot be cultured in vitro, the introduction of polymerase chain reaction (PCR) has been an enormous advantage for research purposes. It is now possible to detect P. carinii in specimens containing low numbers of organisms where conventional detection methods using microscopic examination of histochemical stains has been insufficient. PCR has been used to detect P. carinii in bronchoalveolar lavage, induced sputum, spontaneous expectorates, oropharyngeal gargles, nasopharyngeal aspirates, serum, blood and in environmental samples. The use of PCR will enable the study of the epidemiology of P. carinii infection by detecting the organism in environmental samples, permitting molecular typing and thereby the study of the transmission of the organism. Furthermore PCR will facilitate studies on the response to therapy, studies monitoring for the emergence of drug resistant strains of P. carinii and in the diagnosis of P. carinii pneumonia in noninvasive specimens, in patients unable to undergo more invasive diagnostic procedures.     

A 25-week placebo-controlled study of eptastigmine in patients with Alzheimer disease

Studies of Pneumocystis carinii have been limited by our inability to propagate it in continuous culture. In this context, studies of P. carinii antigens have provided significant insight into the biology of this organism. The mannose-rich surface major surface glycoprotein of P. carinii termed glycoprotein A (gpA) is the best studied of these P. carinii antigens. Significant genetic and immunologic diversity exists between the gpA molecules expressed by P. carinii derived from different mammalian sources. The molecular and biochemical nature of gpA and other P. carinii antigens including p55 are reviewed. In addition, available information concerning the role of P. carinii gpA and other antigens in host-organism interactions are also discussed.     

Management of hypoparathyroidism during pregnancy--report of twelve cases

Rats exposed to Pneumocystis carinii mount antibody responses to a broad band migrating on western blot with an apparent molecular weight of 45-55 kDa. One antigen within this band, designated p55, is uniformly recognized by P. carinii exposed rats. Although the gene encoding the p55 antigen had been previously cloned, the location of this antigen within the organism was unknown. Prior attempts to localize the protein were unsuccessful. A monospecific polyclonal antiserum raised against a carboxyl-terminal 15-oligomer peptide yielded specific reactivity with a single 55 kDa band on a western blot of P. carinii. Using this antiserum, little to no reactivity could be detected with P. carinii organisms by immunofluorescence assay (IFA). However, zymolyase treatment of P. carinii dramatically increased the intensity and proportion of organisms reactive by IFA. Zymolyase, an enzyme with beta-1,3 glucanase activity, has previously been shown to remove the electron dense outer layer of the P. carinii cell wall, exposing an electron lucent layer. Immunoelectron microscopy performed on zymolyase treated organisms showed the majority of labeling occurs within the cell wall.     

Pneumonia caused by granulomatous Pneumocystis carinii in a patient with the acquired immunodeficiency syndrome

A 54-year-old man was admitted to the hospital because of fever and general fatigue. A chest roentgenogram on admission showed lobular opacities and ill-defined opacities in both lower lobes. The pneumonia was successfully treated with antibiotics. The acquired immunodeficiency syndrome was diagnosed because ELISA and PCR tests for antibodies to the human immunodeficiency virus were positive and the CD 4+ lymphocyte count was 39 per cubic millimeter. Examination of bronchoalveolar lavage fluid revealed no Pneumocystis carinii. Trimethoprim and sulfamethoxazole were given prophylactically, but were withdrawn because of a rash. The patient began to receive aerosolized pentamindine and was discharged. On the next day, he was readmitted to the hospital because of a high fever. A chest roentgenogram showed diffuse miliary opacities. Chest CT scan also showed diffuse small nodular opacities in both lungs. Examination of a transbronchial biopsy specimen revealed well-defined, noncaseating granulomas with pneumocystis organisms in their centers. Cultures for tuberculosis and fungi were all negative. We diagnosed granulomatous pneumonia caused by Pneumocystis carinii, which is an atypical manifestation of Pneumocystis carinii pneumonia. The patient died of sepsis and cardiac tamponade. Microscopically, the lung tissue was found to have foamy intra-alveolar exdates, which is a typical histological feature of Pneumocystis carinii pneumonia.     

Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat

Pneumocystis carinii is a major opportunistic pathogen and a leading cause of morbidity in patients with AIDS. CD4+ cells have been shown to be important in host defenses against P. carinii, but the antigen(s) involved with this response have not been identified. We undertook the present study to determine whether the major surface glycoprotein (MSG) of P. carinii contains epitopes that can elicit a protective cellular immune response. Spleen cells and purified CD4+ cells isolated from Lewis rats, pulsed 1-4 d with MSG, and injected into corticosteroid-treated Lewis rats with pneumocystosis resulted in significant reduction in the P. carinii burden, as judged by organism quantitation and lung histology. The protective response demonstrated by the donor cells was dependent on previous exposure to P. carinii, cell concentration, and time of incubation with MSG. In addition, reconstitution with MSG-specific CD4+ cells resulted in an early hyperinflammatory response within the lungs of these animals with a high percentage of mortality. Thus, in this model, MSG can elicit an immune response mediated by CD4+ cells, which has a harmful as well as helpful effect on the host, and these responses occur despite the presence of corticosteroids.     

Cultured rat and purified human Pneumocystis carinii stimulate intra- but not extracellular free radical production in human neutrophils

The production of free radicals in human neutrophils was studied in both Pneumocystis carinii derived from cultures of L2 rat lung epithelial-like cells and Pneumocystis carinii purified from human lung. Using the cytochrome C technique, which selectively measured extracellular superoxide generation, hardly any free radical production was observed after stimulation with cultured rat-derived P. carinii. A chemiluminescence technique, which separately measured intra- and extracellular free radical production, was subsequently employed to differentiate the free radical generation. It was established that 1) P. carinii stimulated intra- but not extracellular free radical production in human neutrophils, 2) opsonized cultured rat-derived P. carinii stimulated human neutrophils to a strong intracellular response of superoxide production, and 3) opsonized P. carinii, purified from human lung also stimulated human neutrophils to produce intracellular free radicals.     

The diagnosis of Pneumocystis carinii pneumonia by cytologic evaluation of Papanicolaou and Leishman-stained bronchoalveolar specimens in patients with the acquired immunodeficiency syndrome

The presence of foamy alveolar casts or flocculent material in Papanicolaou and Leishman-stained smears of bronchoalveolar lavage (BAL) fluid is said to be indicative of infection with Pneumocystis carinii. We have investigated the sensitivity and specificity of this method of diagnosing pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Patients (n = 114) with diffuse lung infiltrates were submitted to fibreoptic bronchoscopy and BAL. Seventy of them were patients with AIDS. The other 44 individuals were not infected by the human immunodeficiency virus (HIV). Pneumocystis carinii organisms were identified on Grocott's methenamine silver (GMS)-stained BAL smears in 30 patients with AIDS. Flocculent material was present in the Papanicolaou and Leishman-stained smears from all of these cases. Conversely, P. carinii were not seen on GMS-stained smears in the remaining 84 individuals with or without AIDS. No flocculent material was observed in Papanicolaou or Leishman-stained smears in these 84 patients. We concluded that the presence of flocculent material in Papanicolaou or Leishman-stained smears of BAL fluid is indicative of P. carinii pneumonia in patients with AIDS.     

Suppurative Acinetobacter baumanii thyroiditis with bacteremic pneumonia: case report and review

Suppurative thyroiditis is rare, and the major pathogens are Staphylococcus and Streptococcus species. We present a case caused by Acinetobacter baumanii, which has never before been reported. We review another 191 cases from the English-language literature (1980 to April 1997) and make a comparison with a review of 224 cases (1900-1980). As the numbers of immunocompromised patients increase, cases of suppurative thyroiditis are increasing. Pneumocystis carinii has become an important pathogen. Most patients (83.1%) with bacterial infections were euthyroid, whereas those with fungal or mycobacterial infections tended to be hypothyroid (62.5%) and hyperthyroid (50%), respectively.     

Characterizations of Pneumocystis carinii and rat lung lipids: glyceryl ethers and fatty alcohols

Pneumocystis carinii carinii and rat lung phospholipids contained 3-6% 1-alkyl-2-acyl glycerols composed of the glyceryl ether species, 1-O-octadecyl glycerol (batyl alcohol), 1-O-octadec-9-enyl glycerol (selachyl alcohol), 1-O-hexadecyl glycerol (chimyl alcohol), and 1-O-hexadec-9-enyl glycerol. Of the major phospholipid classes, phosphatidylinositol (PI) and phosphatidylserine contained the highest percentage of alkyl acyl glycerols. Methylprednisolone treatment caused an increase in alkyl acyl PI of rat lung lipids from 12% to 45%. As the PI concentration in lung phospholipids increases in rats treated with methylprednisolone, the increase in alkyl acyl PI was substantial; the proportions of alkyl acyl phosphatidylethanolamine and alkyl acyl lyso phosphatidylcholine (PC) also increased. Pneumocystis phospholipids contained higher proportions of alkyl acyl PC than the phospholipids of the lungs from normal and immunosuppressed uninfected rats. The glyceryl ether compositions of P. carinii carinii PC and lyso PC were similar, which suggests that lyso PC in the organism is derived by phospholipase A2 action on PC. This was not the case for PC and lyso PC of the lung controls. Analysis of the free fatty alcohols, precursors of glyceryl ethers identified only saturated species in P. carinii carinii and rat lung controls. Thus, the introduction of a double bond in the alcohol moiety of glyceryl ethers occurs after formation of the ether linkage between fatty alcohol and the glyceryl backbone.     

Potential impact of Pneumocystis genetic diversity on the molecular detection of the parasite in human host

Our aim was to evaluate if genetic diversity of Pneumocystis carinii could influence the detection by molecular techniques in bronchoalveolar lavage (BAL) fluids and in non-invasive specimens (induced sputum, oropharyngeal washing and serum/blood). P. carinii is morphologically similar in different hosts although several strains have been identified by biomolecular techniques. Variations of mt-LSU and ITSs sequences could determine a lack of hybridization of some clinical samples and could have diagnostic consequences with loss in sensitivity and specificity of available molecular tests, but at the moment no data support a significant impact of genetic diversity in these sequences on molecular detection of P. carinii for clinical purposes.     

Comments: overview of the 5th international workshop on Pneumocystis and the 5th general meeting of the European Concerted Action on Pneumocystis Research

The major highlights of the meetings were the initiation of efforts to assign different species names to certain Pneumocystis organisms, and the invitation for international participation in a project to map and sequence the genome of P. carinii carinii. The oral and poster presentations demonstrated important advances have been achieved in the past year.