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1.  Clinic HIV-Focused Features and Prevention of Pneumocystis Carinii Pneumonia 
To examine the association of clinic HIV-focused features and advanced HIV care experience with Pneumocystis carinii pneumonia (PCP) prophylaxis and development of PCP as the initial AIDS diagnosis.
Nonconcurrent prospective study.
New York State Medicaid Program.
Medicaid enrollees diagnosed with AIDS in 1990–1992.
We collected patient clinical and health care data from Medicaid files, conducted telephone interviews of directors of 125 clinics serving as the usual source of care for study patients, and measured AIDS experience as the cumulative number of AIDS patients treated by the study clinics since 1986. Pneumocystis carinii pneumonia prophylaxis in the 6 months before AIDS diagnosis and PCP at AIDS diagnosis were the main outcome measures. Bivariate and multivariate analyses adjusted for clustering of patients within clinics. Of 1,876 HIV-infected persons, 44% had PCP prophylaxis and 38% had primary PCP. Persons on prophylaxis had 20% lower adjusted odds of developing PCP (95% confidence interval [CI] 0.64, 0.99). The adjusted odds of receiving prophylaxis rose monotonically with the number of HIV-focused features offered by the clinic, with threefold higher odds (95% CI 1.6, 5.7) for six versus two or fewer such features. Patients in clinics with three HIV-focused features had 36% lower adjusted odds of PCP than those in clinics with one or none. Neither clinic experience nor specialty had a significant association with prophylaxis or PCP.
PCP prevention in our study cohort appears to be more successful in clinics offering an array of HIV-focused features.
PMCID: PMC1496898  PMID: 9462490
Pneumocystis carinii pneumonia (PCP); AIDS; clinical competence; ambulatory care; case management
2.  The role of a nested polymerase chain reaction in the diagnosis of Pneumocystis carinii pneumonia 
Clinical Molecular Pathology  1995;48(6):M347-M350.
Aim—To compare the techniques and results of a nested PCR and an immunofluorescence assay (IFA) for the detection of Pneumocystis carinii infection; to consider the role of the nested PCR in the diagnosis of P carinii pneumonia (PCP).
Methods—Serial dilutions of two known P carinii positive samples were tested by IFA and PCR to determine their relative sensitivities. Seventy eight respiratory samples (15 from 11 patients with HIV infection/acquired immunodeficiency syndrome (AIDS) and 63 from 42 patients with other forms of immunodeficiency) were tested using both assays, and the costs and technical requirements of each assay were assessed.
Results—The PCR had a greater relative sensitivity over the IFA of 2 × 101 to 2 × 103 fold in a postmortem lung sample and 2 × 105 to 2 × 106 fold in a bronchoalveolar lavage sample from a patient with PCP. P carinii was detected in all 15 samples from the patients with HIV/AIDS by both IFA and PCR. Of the 63 samples from the patients with immunodeficiencies other than HIV/AIDS, the PCR was more sensitive than IFA.
Conclusions—The nested PCR is a more sensitive assay than the IFA. It may be useful in the diagnosis of PCP in patients with immunodeficiencies other than HIV/AIDS. Similarly, PCR may be of benefit for this patient group as less invasive specimens are needed. PCR has an increasing role to play in the diagnosis of PCP in the routine laboratory.
PMCID: PMC408003  PMID: 16696036
Pneumocystis carinii; PCR; immunofluorescence assay; acquired immunodeficiency syndrome
3.  Decreased Production of Local Immunoglobulin A to Pneumocystis carinii in Bronchoalveolar Lavage Fluid from Human Immunodeficiency Virus-Positive Patients 
Infection and Immunity  2000;68(3):1054-1060.
An enzyme-linked immunosorbent assay and a Western blot analysis were developed to study the antibody response to Pneumocystis carinii in serum and bronchoalveolar lavage fluid from 27 human immunodeficiency virus 27 (HIV)-infected patients with P. carinii pneumonia (Pcp), 32 patients without Pcp, and 51 HIV-negative controls. Urea was used for the correct dilution of epithelial lining fluid, and albumin was used to evaluate transudation from plasma for the assessment of local production of antibodies to P. carinii. By contrast with those of immunoglobulin G (IgG), IgA responses to P. carinii were increased in serum from HIV-positive patients compared to negative controls. Local production of antibodies to P. carinii, especially IgA, was decreased in patients with Pcp. In a study of 10 patients of each group, IgG and IgA responses to gp116 from P. carinii were lower in patients with Pcp than in other groups. These results suggest that, in addition to alveolar macrophages, local antibodies may play a role in host defense against P. carinii.
PMCID: PMC97248  PMID: 10678907
4.  Usefulness of PCR for diagnosis of Pneumocystis carinii pneumonia in different patient groups. 
Journal of Clinical Microbiology  1997;35(6):1445-1449.
Pneumocystis carinii pneumonia (PCP) is one of the most predominant opportunistic infectious diseases in patients with AIDS. Nested PCR has been described as a sensitive and specific tool for detecting P. carinii DNA in clinical specimens. Little is known about the correlation of positive PCR results and clinical evidence of PCP in patients with different forms of immunosuppression. One hundred and thirty-six sputum samples, 26 tracheal-bronchial aspirate samples, 35 bronchoalveolar lavage samples, and 11 lung biopsy samples from (i) human immunodeficiency virus (HIV)-infected patients with AIDS, (ii) immunocompromised patients with leukemia or lymphoma, and (iii) immunocompetent control patients were investigated by a nested PCR amplifying DNA from the mitochondrial large subunit of P. carinii. All patients suffered from acute episodes of respiratory disease. The resulting data were correlated with clinical evidence of PCP. A high degree of association of positive P. carinii PCR results and clinical evidence of PCP in HIV-infected patients with AIDS was found. When calculated for bronchoalveolar lavage and lung biopsy samples, the positive and the negative predictive values of P. carinii PCR for PCP diagnosis in HIV-infected patients with AIDS were 1 and the specificity and the sensitivity were 100%. In contrast, in the group of patients with leukemia or lymphoma, the positive predictive value of the nested PCR for these materials was found to be as low as 0.09, the negative predictive value was 0.73, the specificity was 44.4%, and the sensitivity was 25.0%. No P. carinii DNA could be detected in specimens from immunocompetent patients. In summary, in contrast to patients with leukemia and lymphoma, nested PCR seems to be a sensitive and specific tool for PCP diagnosis in HIV-infected patients with AIDS.
PMCID: PMC229764  PMID: 9163459
5.  Recovery of Pseudomonas aeruginosa in respiratory specimens from HIV positive patients being evaluated for Pneumocystis carinii pneumonia. 
Thorax  1995;50(5):548-550.
BACKGROUND--Despite the immune suppression, frequent hospital admissions, and many intercurrent illnesses associated with HIV infection, Pseudomonas aeruginosa has been cited relatively infrequently as a respiratory pathogen in HIV positive patients. METHODS--The microbiological isolates, medical records, radiographic reports, and laboratory data from 224 patients undergoing sputum induction and/or bronchoalveolar lavage for evaluation of respiratory symptoms suspicious for Pneumocystis carinii pneumonia (PCP) from 1989 to 1992 were reviewed retrospectively. RESULTS--An increasing number of respiratory isolates with Pseudomonas aeruginosa was found over this time period. Eighteen of the 224 patients were identified in whom P aeruginosa was recovered on at least one occasion. These patients were more likely to have a history of smoking and prior PCP than those in whom Pseudomonas was not recovered. Mean CD4 counts were also significantly lower in these patients. CONCLUSIONS--Pseudomonas aeruginosa may be recovered from a substantial number of respiratory isolates from HIV positive patients suspected of having PCP. The prevalence of this phenomenon may be increasing.
PMCID: PMC1021227  PMID: 7597670
6.  Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS. 
BMJ : British Medical Journal  1991;302(6770):203-207.
OBJECTIVE--To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN--A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS--347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING--Departments of immunology and genitourinary medicine, St Mary's Hospital, London. MAIN OUTCOME MEASURES--Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposi's sarcoma. RESULTS--The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposi's sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposi's sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS--The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.
PMCID: PMC1669078  PMID: 1998759
7.  Identification of Pneumocystis carinii f. sp. hominis Gene Sequences in Filtered Air in Hospital Environments 
Journal of Clinical Microbiology  1998;36(6):1737-1740.
To evaluate the risk of a nosocomial spread of Pneumocystis carinii f. sp. hominis (P. carinii hominis), air filter samples from rooms of P. carinii pneumonia (PCP) patients, adjacent corridors, and other hospital environments have been investigated for the presence of P. carinii hominis. Amplified DNA from air filters and sputum or bronchoalveolar lavage samples from the PCP patients have been genotyped with the P. carinii hominis genes of the mitochondrial large-subunit (mtLSU) rRNA and the internal transcribed spacers (ITS1 and ITS2) of the rRNA. Genotypes of the two loci were identified by direct sequencing, and for site 85 of the mtLSU locus, three allele-specific PCR assays were used. P. carinii hominis DNA was identified in the air of five of seven PCP patient rooms and in the air of two of four air filtrations from the ward corridors. The P. carinii hominis genotypes were the same in four of the five room air samples as those in the corresponding patients, suggesting a risk of person-to-person transmission of P. carinii hominis from PCP patients. Three of 16 air samples collected in infectious disease wards without the presence of PCP patients and one sample from a cardiology unit in a separate hospital building were also positive, which further strengthens the possibility of acquisition of P. carinii hominis from the environment.
PMCID: PMC104910  PMID: 9620410
8.  Evidence for depressed humoral immunity to Pneumocystis carinii in homosexual males, commercial plasma donors, and patients with acquired immunodeficiency syndrome. 
Journal of Clinical Microbiology  1987;25(6):991-995.
Heterosexual controls were found to have significantly higher titers of immunoglobulin G antibody to Pneumocystis carinii than did patients with the acquired immunodeficiency syndrome (AIDS) and P. carinii pneumonitis, human immunodeficiency virus (HIV) antibody-positive or -negative homosexual male "gay bar" patrons, and HIV antibody-positive or -negative commercial plasma donors. The T-helper/T-suppressor lymphocyte ratios of HIV antibody-negative homosexual male gay bar patrons were slightly depressed (mean = 1.31 +/- 0.54) compared with those of heterosexual controls (mean = 1.79 +/- 0.32). In addition to other recognized factors, preexisting humoral as well as cell-mediated immune deficits before infection with HIV may help to explain the prevalence of and morbidity and mortality associated with P. carinii pneumonitis in AIDS patients.
PMCID: PMC269122  PMID: 2954997
9.  Bronchoalveolar lavage cell analysis in patients with human immunodeficiency virus related diseases. 
Thorax  1989;44(4):289-291.
The value of differential cell counts in bronchoalveolar lavage fluid in patients who were serologically positive for the human immunodeficiency virus (HIV) was studied in 30 patients with classified into four groups according to the severity of illness: (1) seven subjects with the AIDS related complex without clinical or radiological evidence of pulmonary infection; (2) eight patients with the AIDS related complex and pulmonary tuberculosis; (3) eight patients with AIDS and Pneumocystis carinii pneumonia; and (4) seven patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure. All four groups had a similar percentage of lymphocytes, significantly higher than that of a control group of 15 healthy volunteers. A significant increase in the percentage of neutrophils was observed in groups 2, 3, and 4. The lavage fluid differential cell count does not therefore appear to help in the differential diagnosis of pulmonary infections in HIV positive patients. The abnormal percentage of lymphocytes observed in some patients with the AIDS related complex without clinical evidence of pulmonary infection suggests that lung injury may exist before clinical or radiological abnormalities develop. This might be related to an immunological mechanism or might be caused by an undetected subclinical infection.
PMCID: PMC461795  PMID: 2788319
10.  Reduced carbon monoxide transfer factor (TLCO) in human immunodeficiency virus type I (HIV-I) infection as a predictor for faster progression to AIDS. 
Thorax  1993;48(5):481-485.
BACKGROUND--In addition to the acute fall in carbon monoxide transfer factor (TLCO) associated with Pneumocystis carinii pneumonia (PCP) or other opportunistic lung infections, reduced TLCO occurs in HIV-I seropositive individuals without active pulmonary disease. Abnormal TLCO, in the absence of lung disease, may be a surrogate marker of HIV-I induced immunosuppression and, therefore, a predictor for a more rapid progression to AIDS. METHODS--Eighty four individuals with AIDS, who had regular pulmonary function tests before the diagnosis of AIDS was made, were identified from a cohort of patients with HIV-I infection. None had evidence of active pulmonary disease at the time of initial pulmonary function testing. The relation between the time taken to progress to AIDS and initial pulmonary function tests was examined with life table survival analysis. RESULTS--Patients with a TLCO value of < 80% of predicted normal (n = 46) progressed significantly faster to AIDS, with a median time of 8.0 months compared with 16.5 months for those with a TLCO value of > or = 80% (n = 38). When stratified by AIDS defining diagnosis (PCP or non-PCP), median time to PCP was also significantly related to initial TLCO values (TLCO of < 80% = 9.0 months, TLCO of > or = 80% = 19.0 months). Reductions in other measurements of lung function (FEV1, FVC, KCO) were not temporally associated with the development of AIDS. CONCLUSIONS--HIV-I seropositive individuals with TLCO values of < 80% predicted and no evidence of lung disease progress more rapidly to AIDS than those with TLCO values of > or = 80%.
PMCID: PMC464497  PMID: 8322232
11.  Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis pneumonia: A strategy for prevention 
Pneumocystis pneumonia (PCP) is an increasing problem amongst patients on immunosuppression with autoimmune inflammatory disorders (AID). The disease presents acutely and its diagnosis requires bronchoalveolar lavage in most cases. Despite treatment with intravenous antibiotics, PCP carries a worse prognosis in AID patients than HIV positive patients. The overall incidence of PCP in patients with AID remains low, although patients with Wegener's granulomatosis are at particular risk.
In adults with AID, the risk of PCP is related to treatment with systemic steroid, ill-defined individual variation in steroid sensitivity and CD4+ lymphocyte count. Rather than opting for PCP prophylaxis on the basis of disease or treatment with cyclophosphamide, we argue the case for carrying out CD4+ lymphocyte counts on selected patients as a means of identifying individuals who are most likely to benefit from PCP prophylaxis.
Corticosteroids, lymphopenia and a low CD4+ count in particular, have been identified as risk factors for the development of PCP in adults with AID. Trimethoprim-sulfamethoxazole (co-trimoxazole) is an effective prophylactic agent, but indications for its use remain ill-defined. Further prospective trials are required to validate our proposed prevention strategy.
PMCID: PMC526257  PMID: 15488151
12.  AIDS and antibodies to human immunodeficiency virus (HIV) in children and their families: clinical experience at Yale-New Haven Hospital. 
As of December 1986, we have identified 23 symptomatic children with human immunodeficiency virus (HIV) infection in New Haven. Twelve developed AIDS as manifested by lymphocytic interstitial pneumonitis, Pneumocystis carinii pneumonia (PCP), and/or disseminated mycobacterial infections; seven of them have died. The remainder have milder clinical syndromes, which include failure to thrive, diffuse lymphadenopathy, and parotid swelling. When compared to adults with AIDS, children often have hypergammaglobulinemia and normal numbers of T4 lymphocytes. Intravenous drug abuse by the mother or mother's consort is the risk factor in 87 percent of these children. Two families have now been identified with more than one symptomatic child, but in no family is there evidence of spread from symptomatic children to uninfected siblings. A prospective study was begun to attempt to assess the risk of developing symptomatic HIV infection when a child is born to a mother with antibodies to HIV.
PMCID: PMC2590383  PMID: 3481146
13.  Pulmonary coinfection by Pneumocystis jiroveci and Cryptococcus neoformans 
We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.
PMCID: PMC3609199  PMID: 23569840
Cryptococcus neoformans; Pneumocystis jiroveci; Pulmonary coinfection; Diagnosis test; Opportunistic pathogen; Pneumonia; Definitive diagnosis
14.  Changing patterns of respiratory disease in HIV positive patients in a referral centre in the United Kingdom between 1986-7 and 1990-1. 
Thorax  1993;48(3):204-207.
BACKGROUND: Respiratory illness is a significant contributor to morbidity and mortality in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). It has been suggested that Pneumocystis carinii pneumonia is no longer the most frequent cause of respiratory disease in this group because of widespread use of prophylaxis and anti-retroviral drugs. METHODS: A retrospective comparison of the diagnoses in HIV 1 antibody positive patients with respiratory illness admitted to a major UK centre in 1986-7 and 1990-1 was carried out to identify changes in patterns of respiratory disease. RESULTS: In the 1986-7 period there were 73 patients, of whom none received zidovudine or prophylaxis for pneumocystis pneumonia while in the 1990-1 period there were 122 patients. One hundred and ninety patients (98%) were male homosexuals. Pneumocystis pneumonia remained the commonest respiratory disease, comprising 68% of all diagnoses in the 1986-7 period and 48% in the 1990-1 period. Bacterial infections (bronchitis and pneumonia) were seen more commonly in the 1990-1 period (23%) than in the 1986-7 period (14%), as was pulmonary Kaposi's sarcoma (12% in 1990-1 and 4% in 1986-7). Mycobacterial infection remained uncommon (4% in 1986-7 and 6.5% in 1990-1). CONCLUSION: Despite widespread use of zidovudine and prophylaxis, pneumocystis pneumonia remains the commonest respiratory disease in homosexual men.
PMCID: PMC464354  PMID: 8497816
15.  Sterols of Pneumocystis carinii hominis Organisms Isolated from Human Lungs 
The opportunistic pathogen Pneumocystis carinii causes pneumonia (P. carinii pneumonia, or PCP) in immunocompromised individuals such as AIDS patients. Rat-derived P. carinii carinii organisms have distinct sterols which are not synthesized by mammals and not found in other microbes infecting mammalian lungs. The dominant sterol present in the organism is cholesterol (which is believed to be scavenged from the host), but other sterols in P. carinii carinii have an alkyl group at C-24 of the sterol side chain (C28 and C29 24-alkylsterols) and a double bond at C-7 of the nucleus. Recently, pneumocysterol (C32), which is essentially lanosterol with a C-24 ethylidene group, was detected in lipids extracted from a formalin-fixed human P. carinii-infected lung, and its structures were elucidated by gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectrometry in conjunction with analyses of chemically synthesized authentic standards. The sterol composition of isolated P. carinii hominis organisms has yet to be reported. If P. carinii from animal models is to be used for identifying potential drug targets and for developing chemotherapeutic approaches to clear human infections, it is important to determine whether the 24-alkylsterols of organisms found in rats are also present in organisms in humans. In the present study, sterol analyses of P. carinii hominis organisms isolated from cryopreserved human P. carinii-infected lungs and from bronchoalveolar lavage fluid were performed. Several of the same distinct sterols (e.g., fungisterol and methylcholest-7-ene-3β-ol) previously identified in P. carinii carinii were also present in organisms isolated from human specimens. Pneumocysterol was detected in only some of the samples.
PMCID: PMC95807  PMID: 10548595
16.  Quantitative and qualitative comparison of DNA amplification by PCR with immunofluorescence staining for diagnosis of Pneumocystis carinii pneumonia. 
Journal of Clinical Pathology  1993;46(2):140-144.
AIM: To compare the results of DNA amplification by the polymerase chain reaction (PCR) with immunofluorescence staining for detecting Pneumocystis carinii in bronchoalveolar lavage specimens taken from symptomatic HIV seropositive patients with suspected P carinii pneumonia (PCP). METHODS: Bronchoalveolar lavage specimens were obtained from 28 symptomatic HIV seropositive patients. Specimens were examined for P carinii using immunofluorescence, and by DNA amplification with PCR to obtain results on gel electrophoresis (gel) and a more sensitive Southern hybridisation (blot) technique. Specimens positive by immunofluorescence and gel electrophoresis were serially diluted to a 10(-6) concentration and each dilution strength tested for P carinii using PCR to compare quantitatively immunofluorescence with PCR. RESULTS: Of the 28 specimens analysed, 18 were negative for P carinii by both immunofluorescence and PCR, two were positive only by the blot technique of PCR, four were equivocally positive and four unequivocally positive by immunofluorescence. Three of the four equivocally positive patients tested by immunofluorescence were negative for P carinii by PCR, although one was positive by PCR (blot) technique. This patient had clinically confirmed PCP. Of the four unequivocally positive patients tested by immunofluorescence, three were gel and blot positive by PCR and had PCP clinically, but one was negative by both gel and blot techniques, although the patient certainly had PCP on clinical grounds. This patient had received nine days of treatment with high dose co-trimoxazole before bronchoalveolar lavage specimens were obtained. The three specimens positive by gel and blot techniques remained gel positive down to dilutions of between 10(-4) and 10(-6). CONCLUSIONS: PCR results may become negative soon after starting treatment for PCP. Specimens should therefore be taken before, or soon after, starting treatment. PCR seems to be between 10(4) and 10(6) times more sensitive than immunofluorescence.
PMCID: PMC501145  PMID: 8459034
17.  Granulomatous Pneumocystis carinii pneumonia in patients with malignancy 
Thorax  2002;57(5):435-437.
Background: A review was undertaken of the clinical features and results of diagnostic tests in non-HIV infected patients who developed granulomatous Pneumocystis carinii pneumonia (PCP).
Methods: A retrospective review was performed of the charts and radiographs of patients with a granulomatous reaction to P carinii identified from computerised pathology records at Memorial Sloan Kettering Cancer Center, a university affiliated tertiary care hospital.
Results: Three cases were identified; the incidence of granulomatous PCP was 3%. All patients had risk factors for PCP and had received high dose corticosteroids which had been stopped. Two patients had received chemotherapy. Presentation was insidious with only mild symptoms; only one patient had fever. Chest radiographs showed a reticulonodular pattern. Bronchoscopy was negative for PCP in all cases and open lung biopsy was necessary.
Conclusion: A granulomatous pathological reaction to PCP occurs rarely in patients with malignancy. In these cases the clinical presentation may be atypical and bronchoscopy can be non-diagnostic.
PMCID: PMC1746334  PMID: 11978921
18.  Lethal exacerbation of Pneumocystis carinii pneumonia in severe combined immunodeficiency mice after infection by pneumonia virus of mice 
The Journal of Experimental Medicine  1993;177(4):1193-1198.
Mice homozygous for the mutant allele scid (severe combined immunodeficiency) have been described as excellent models for Pneumocystis carinii (Pc) pneumonia (PCP), a major health problem in patients with acquired immune deficiency syndrome (AIDS) and other immunodeficiency states. Other microorganisms have been shown to infect AIDS patients simultaneously with Pc, but whether one opportunist is able to directly influence the pathogenicity of another has not been determined previously. We have deliberately coinfected scid mice (with extent Pc infection) with a variety of primarily pneumotropic viruses and bacteria and have identified pneumonia virus of mice as causing a dramatic increase in the density of Pc organisms and the morbidity due to PCP in immunodeficient scid mice. This finding has clinical significance in the management of PCP, in that the identification and treatment of coinfecting pneumotropic pathogens may be as important as treatment targeted at Pc. A search for other synergistic (or antagonistic) microorganisms and determination of their mechanism(s) of action in altering the progression of PCP is indicated.
PMCID: PMC2190992  PMID: 8459214
19.  Pneumocystis carinii pneumonia in vertically acquired HIV infection in the British Isles. 
Archives of Disease in Childhood  1994;70(3):241-244.
In order to review the clinical course, laboratory findings, and outcome of children with vertically acquired HIV infection and Pneumocystis carinii pneumonia, questionnaires were sent to paediatricians in the British Isles who had reported P carinii pneumonia and HIV infection through the British Paediatric Surveillance Unit (BPSU). Paediatric reports from the BPSU are linked to reports of pregnancies in HIV positive women and laboratory reports. P carinii pneumonia was the most frequently reported AIDS indicator disease at AIDS diagnosis, occurring in 22/56 (40%) children born in the British Isles; in a further two children P carinii pneumonia occurred after another AIDS indicator disease. The median age at P carinii pneumonia diagnosis was 4.1 (1.4-27.3) months and in 48% it occurred with other AIDS indicator diseases. Despite intensive treatment the three month survival was only 38%. The nine children surviving P carinii pneumonia subsequently developed further AIDS indicator diseases, in particular HIV encephalopathy and four have since died. P carinii pneumonia was present at AIDS diagnosis in 65% of children developing AIDS in the first year of life and caused 82% of infant deaths. Most children were not known to be at risk of HIV until they presented with P carinii pneumonia. Children with HIV infection develop P carinii pneumonia at an early age and have a poor outcome. Increased awareness of the condition is required to initiate early treatment. Prevention may be a compelling incentive for screening in pregnancy, but further study is required to quantify the risks and benefits of initiating early P carinii pneumonia prophylaxis as well as the impact this might have on life expectancy.
PMCID: PMC1029752  PMID: 8135571
20.  Current understanding of Pneumocystis immunology 
Future microbiology  2010;5(1):43-65.
Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP.
PMCID: PMC3702169  PMID: 20020829
adaptive immunity; chemokine; cytokine; fungal; HAART; HIV+; inflammatory response; innate immunity; Pneumocystis pneumonia
21.  Effect of a Bis-Benzyl Polyamine Analogue on Pneumocystis carinii 
Pneumocystis carinii is the causative agent of P. carinii pneumonia (PCP), an opportunistic infection associated with AIDS and other immunosuppressed conditions. Although polyamine metabolism of this fungus has been shown to be a chemotherapeutic target, this metabolism has not been thoroughly investigated. Reported here is the effect of one polyamine analogue, N,N′-bis{3-[(phenylmethyl)amino]propyl}-1,7-diaminoheptane (BBS), on P. carinii. BBS inhibits the growth of P. carinii in culture, but at concentrations higher than those required to inhibit the growth of other pathogens. However, BBS is at least as active in an animal model of PCP as in other models of diseases studied. BBS causes some reduction in P. carinii polyamine content and polyamine biosynthetic enzyme activities, but the effect is less than that observed with other pathogens and very much less than the effect of the polyamine biosynthesis inhibitor dl-α-difluoromethylornithine. BBS enters P. carinii cells via a polyamine transporter, unlike all other cells that have been studied. P. carinii cells do not remove the benzyl groups of BBS, as is reported for mammalian cells. The most likely mode of action is displacement of natural polyamines. Overall, the activity of BBS provides further evidence that polyamines and polyamine metabolism are rational targets for the development of drugs to treat PCP. Because the details of BBS-P. carinii interaction differ from those of other cells studied, polyamine analogues may provide a highly specific treatment for PCP.
PMCID: PMC89680  PMID: 10639359
22.  Ploidy of Cell-Sorted Trophic and Cystic Forms of Pneumocystis carinii 
PLoS ONE  2011;6(6):e20935.
Once regarded as an AIDS-defining illness, Pneumocystis pneumonia (PcP) is nowadays prevailing in immunocompromised HIV-negative individuals such as patients receiving immunosuppressive therapies or affected by primary immunodeficiency. Moreover, Pneumocystis clinical spectrum is broadening to non-severely-immunocompromised subjects who could be colonized by the fungus while remaining asymptomatic for PcP, thus being able to transmit the infection by airborne route to susceptible hosts. Although the taxonomical position of the Pneumocystis genus has been clarified, several aspects of its life cycle remain elusive such as its mode of proliferation within the alveolus or its ploidy level. As no long-term culture model exists to grow Pneumocystis organisms in vitro, an option was to use a model of immunosuppressed rat infected with Pneumocystis carinii and sort life cycle stage fractions using a high-through-put cytometer. Subsequently, ploidy levels of the P. carinii trophic and cystic form fractions were measured by flow cytometry. In the cystic form, eight contents of DNA were measured thus strengthening the fact that each mature cyst contains eight haploid spores. Following release, each spore evolves into a trophic form. The majority of the trophic form fraction was haploid in our study. Some less abundant trophic forms displayed two contents of DNA indicating that they could undergo (i) mating/fusion leading to a diploid status or (ii) asexual mitotic division or (iii) both. Even less abundant trophic forms with four contents of DNA were suggestive of mitotic divisions occurring following mating in diploid trophic forms. Of interest, was the presence of trophic forms with three contents of DNA, an unusual finding that could be related to asymmetrical mitotic divisions occurring in other fungal species to create genetic diversity at lower energetic expenses than mating. Overall, ploidy data of P. carinii life cycle stages shed new light on the complexity of its modes of proliferation.
PMCID: PMC3114859  PMID: 21695077
23.  HIV-Associated Pneumocystis Pneumonia 
During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).
PMCID: PMC3132788  PMID: 21653531
acquired immune deficiency syndrome; HIV; Pneumocystis; Pneumocystis pneumonia; dihydropteroate synthase
24.  Predictors of Early Hospital Readmission in HIV-infected Patients with Pneumonia 
Although hospitalization patterns have been studied, little is known about hospital readmission among HIV-infected patients in the era of highly active antiretroviral therapy. We explored the risk factors for early readmission to a tertiary care inner-city hospital among HIV-infected patients with pneumonia in Vancouver, Canada.
Case-control study.
Tertiary care, university-affiliated, inner-city hospital.
All HIV-infected patients who were hospitalized with Pneumocystis carinii pneumonia (PCP) or bacterial pneumonia (BP) between January 1997 and December 2000. Case patients included those who had early readmissions, defined as being readmitted within 2 weeks of discharge (N = 131). Control patients were randomly selected HIV-infected patients admitted during the study period who were not readmitted within 2 weeks of discharge (N = 131), matched to the cases by proportion of PCP to BP.
Sociodemographic, HIV risk category, and clinical data were compared using χ2 test for categorical variables, and the Wilcoxon rank-sum test was used for continuous variables. Multivariable logistic regression was performed to determine the factors independently associated with early readmission. We also reviewed the medical records of 132 patients admitted to the HIV/AIDS ward during the study period and collected more detailed clinical data for a subanalysis.
Patients were at significantly increased odds of early readmission if they left the hospital against medical advice (AMA) (adjusted odds ratio [OR], 4.26; 95% confidence interval [95% CI], 2.13 to 8.55), lived in the poorest urban neighborhood (OR, 2.03; 95% CI, 1.09 to 3.77), were hospitalized in summer season (May though October, OR, 2.36; 95% CI, 1.36 to 4.10), or had been admitted in the preceding 6 months (OR, 2.55; 95% CI, 1.46 to 4.47). Gender, age, history of AIDS-defining illness, and injection drug use status were not significantly associated with early readmission.
Predictors of early readmission of HIV-infected patients with pneumonia included: leaving hospital AMA, living in the poorest urban neighborhood, being hospitalized in the preceding 6 months and during the summer months. Interventions involving social work may address some of the underlying reasons why these patients leave hospital AMA and should be further studied.
PMCID: PMC1494845  PMID: 12709090
case-control; hospital readmission; HIV; AIDS; bacterial pneumonia; PCP; antiretroviral therapy
25.  Pneumocystis carinii pneumonia: detection of parasites in sputum and bronchoalveolar lavage fluid by monoclonal antibodies. 
BMJ : British Medical Journal  1988;297(6645):381-384.
Diagnosis of pneumocystis pneumonia is based on identifying Pneumocystis carinii cytochemically in material from the lung. The silver methenamine staining methods most commonly used are technically difficult and lack specificity. The diagnostic value of immunocytological identification of the parasite was evaluated by using mouse monoclonal antibody 3F6, specific for human pneumocystis, to identify P carinii in bronchoalveolar lavage fluid and sputum by immunofluorescence and was compared with that of other variables. Bronchoalveolar lavage was performed on 25 patients positive for HIV antibody with clinically suspected pneumocystis pneumonia and 40 patients negative for HIV antibody who presented with interstitial disorders of the lung. Lavage fluid showed pneumocystis only in the patients positive for antibody, the parasite being detected in 19 by immunofluorescence and in 17 by a modified silver methenamine staining method. Chest x ray films obtained at the time of bronchoscopy showed interstitial or alveolar shadowing in 17 of the 19 patients, but clinical symptoms and the presence of antibodies to pneumocystis did not seem to be predictive. Sputum samples were collected during 43 episodes of clinically suspected pneumocystis pneumonia in patients positive for HIV antibody. Pneumocystis was detected consistently more commonly by immunofluorescence than the silver strain in sputum collected routinely and induced by inhalation of saline. In 17 patients bronchoalveolar lavage followed sputum collection, and the sensitivity of detection of pneumocystis in immunofluorescence in sputum compared with lavage fluid was 57% (8/14). Immunofluorescence was suitable for specimens fixed in ethanol and seemed highly specific and more sensitive than the standard cytochemical methods for identifying pneumocystis.
PMCID: PMC1834294  PMID: 3044514

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