Surfactant analysis during Pneumocystis carinii pneumonia in HIV-infected patients.

Pulmonary surfactant is altered in experimental Pneumocystis carinii pneumonia. Although P carinii is a major causative agent of pneumonia in immunocompromised patients, the pathophysiology of lung injury caused by this organism is poorly understood. Therefore, we studied bronchoalveolar lavage specimens obtained from 19 HIV-infected subjects with PCP compared with specimens from ten healthy control subjects. As iterative BAL was performed, 37 BAL specimens were analyzed for protein and phospholipid. The BAL samples were divided into two groups as follows: 22 BAL samples with the presence of P carinii and 15 BAL samples without P carinii. Compared to control subjects, HIV+ BAL presented a significant increase of PR and a decrease of total PL in both P carinii+ and P carinii- BAL, but in P carinii+ BAL, the fall of PL/PR ratio was significantly more pronounced compared to P carinii- (0.09 +/- 0.02 vs 0.19 +/- 0.04, p less than 0.02). The BAL performed during the recovery of PCP showed an improvement of initial biochemical abnormalities. Surfactant composition was also altered, with a phosphatidylcholine and phosphatidylglycerol drop and a sphingomyelin and lysophosphatidylcholine increase. The presence, even in P carinii- BAL, of less polar compounds of undetermined nature, was revealed. We concluded that in HIV+ patients, abnormalities of pulmonary surfactant were present before PCP, and that the development of PCP enhances these abnormalities. These surfactant alterations may contribute to the saprophyte-pathogen transformation of P carinii, but this hypothesis requires further investigation that is presently in progress.     

Low levels of IgG antibodies against pneumocystis carinii among HIV-infected patients

IgG antibodies against Pneumocystis carinii (P. carinii) were detected by an ELISA method using urea-extracted material from human and rat P. carinii as the antigen. Carbohydrate formed a major part of the antigen responsible for reactivity in the ELISA assay, since periodate treatment reduced the reactivity of most sera tested. Cross-reactivity between human and rat P. carinii was detected. However, human serum recognized antigens specific for human P. carinii. With the ELISA method IgG antibody levels were compared between blood donors (n = 40), asymptomatic HIV-antibody positive patients (n = 30) and AIDS patients with (n=22) and without previous P. carinii pneumonia (PCP) (n=21). HIV-infected patients had significantly lower antibody reactivity against the microorganism compared with blood donors. Among HIV-antibody positive patients the highest antibody reactivity was seen in PCP patients. The antibody response to PCP was impaired, since an equal number of patients had an increase and a decrease in antibody reactivity. In conclusion, carbohydrate formed an important part of the P. carinii immunogenic antigen. Cross-reactivity between rat and human P. carinii was demonstrated, but reactivity was somewhat lower using antigen from rats. The antibody level was lower in HIV-infected patients and the ability to mount an antibody response to the infection was impaired, suggesting that the poor antibody response may contribute to the liability of HIV-infected patients to have PCP.     

Pneumocystis carinii infection in non-AIDS patients

Infection with the opportunist fungus Pneumocystis carinii remains a significant cause of morbidity and mortality in non-HIV-infected individuals immunosuppressed by a wide range of malignancies, transplantation and inflammatory conditions. Glucocorticoid use appears to be an independent risk factor for the development of Pneumocystis carinii pneumonia. Transmission from infected to susceptible patients may occur, albeit infrequently. A diagnosis of Pneumocystis carinii pneumonia may be achieved in the majority of cases by DNA detection using polymerase chain reaction on oropharyngeal mouth washes.     

Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era

Since the advent of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections (OI) in patients with HIV has markedly decreased. Despite this, there are still large numbers of Pneumocystis carinii pneumonia (PCP) cases at Cook County Hospital (CCH). To better understand this patient group, we performed a retrospective chart review of 120 pathologically proven cases of PCP from January 1998 to June 2001. One hundred four patients were included in the study. Sixty-nine percent of our patients were active substance abusers and 50% had previous knowledge of HIV disease. Of our patients, fewer than 5% were on HAART or PCP prophylaxis on study admission. The overall mortality rate was 14%. Of discharged patients, 65% were placed on HAART therapy and 59% of these achieved a viral load of less than 1000 copies per milliliter in the year postdischarge. Patients who failed to achieve a viral load less than 1000 copies per milliliter were more likely active substance abusers or had a viral load greater than 100,000 copies per milliliter prior to study admission. Our study shows that patients are still being admitted with PCP in the HAART era. Active substance abuse and failure to recognize HIV status contributed heavily to this late presentation of HIV disease. An aggressive approach toward HIV identification and substance abuse treatment may decrease admissions to the hospital for PCP and improve response to HAART therapy.     

Improved survival with highly active antiretroviral therapy in HIV-infected patients with severe Pneumocystis carinii pneumonia

BACKGROUND: Although the incidence of pneumonia (PCP) has declined, mortality of patients who require intensive care for this disease remains high. Highly active antiretroviral therapy (HAART) might alter the course of PCP either via effects on the immune system or through anti- actions; however, HAART has not been studied in patients acutely ill with PCP. OBJECTIVE: To assess the effects of HAART on outcome of patients admitted to the intensive care unit (ICU) with PCP. DESIGN AND SETTING: Retrospective cohort study carried out at a University-affiliated county hospital. PARTICIPANTS: Fifty-eight HIV-infected adults with PCP admitted to an ICU from 1996 to 2001. MEASUREMENTS: A standardized chart review was performed to collect information on demographic variables, hospital course, and use of antiretroviral therapy. Outcome measured was death while in the ICU or hospital. RESULTS: A total of 20.7% of patients were either receiving HAART or were started on therapy while hospitalized. Mortality in this group was 25%, whereas mortality in those not receiving therapy was 63% (P = 0.03). Multiple logistic regression analyses adjusting for potential confounders showed that HAART started either before or during hospitalization was associated with a lower mortality [odds ratio (OR), 0.14; 95% confidence interval (95% CI), 0.02-0.84; = 0.03). The need for mechanical ventilation and/or development of a pneumothorax (OR, 20.9; 95% CI, 1.9-227.2; = 0.01) and delayed ICU admission (OR, 9.7; 95% CI, 2.2-42.1; = 0.002) were associated with increased mortality. CONCLUSIONS: Use of HAART is an independent predictor of decreased mortality in severe PCP and may represent a potential therapy to improve outcome in this disease.     

Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients

OBJECTIVE: To describe clinical experience with atovaquone suspension for the treatment of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: A retrospective chart review. METHODS: The medical records of 54 HIV-infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day). RESULTS: The proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated. CONCLUSION: Atovaquone suspension is effective and well tolerated for the treatment of PCP.     

Pneumocystis carinii pneumonia in patients without HIV infection

Pneumocystis carinii is an important, but sporadic, opportunistic pulmonary pathogen in immunosuppressed HIV seronegative persons. Historically, patients at highest risk for P. carinii pneumonia are included infants with severe malnutrition, children with primary immunodeficiencies, patients with hematological malignancies, and recipients of solid organ or bone marrow transplants. Recently, solid tumor patients, in particular those receiving high-dose corticosteroids for brain neoplasms, and patients with inflammatory or collagen-vascular disorders, especially patients with Wegener granulomatosis receiving immunosuppressive therapy, have been identified as subgroups at increased risk for P. carinii pneumonia. Other factors associated with P. carinii pneumonia include the intensity of the immunosuppressive regimen and tapering doses of corticosteroids. Because P. carinii pneumonia is associated with significant morbidity and mortality, it is important to identify high-risk patient populations to administer effective chemoprophylactic agents, such as trimethoprim-sulfamethoxazole.     

Development of murine monoclonal antibodies to Pneumocystis carinii

Relatively little is known about the antigenic structure of Pneumocystis carinii and the immunopathogenesis of pneumonitis caused by P. carinii. To begin to define the antigenic character of the surface of this organism, we have produced murine monoclonal antibodies that react with the surface of P. carinii (obtained from rats), as detected by immunofluorescence and immunoelectron microscopy. Immunoblot analysis revealed that the six antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons. Although all six monoclonal antibodies bound P. carinii obtained from rats, only one (5E12) was also able to bind P. carinii obtained from rabbits, ferrets, and a human; this result demonstrated that isolates of P. carinii obtained from different species are not antigenically identical.     

Pneumocystis carinii pneumonia in HIV-infected patients: diagnostic yield of induced sputum and immunofluorescent stain with monoclonal antibodies.

The purpose of this study was to evaluate the diagnostic yield of induced sputum (IS), assessing the reliability of indirect immunofluorescent stain with monoclonal antibodies (IFMoAb) and methenamine silver (Met-Ag) and analysing factors likely to influence the sensitivity of these techniques. An analysis was prospectively carried out on IS specimens collected from 61 human immunodeficiency virus (HIV)-infected patients during 69 episodes of suspected Pneumocystis carinii pneumonia. Ultrasonic nebulizers with hypertonic 2% saline were used. IFMoAb to P. carinii and Met-Ag were performed after cytocentrifugation of the specimen. Results were compared with those of bronchoalveolar lavage (BAL) with/without transbronchial biopsy (TBB), performed not more than seven days after induction of sputum. P. carinii pneumonia was confirmed in 32 episodes, of which IS was diagnostic in 23. The sensitivity of the staining procedures was 69% for IFMoAb, and 28% for Met-Ag. The three episodes of P. carinii pneumonia in patients on oral chemoprophylaxis yielded negative IS results; in contrast, IS was negative in only 6 of the 29 cases not receiving chemoprophylaxis. IS is a non-aggressive procedure that diagnosed P. carinii pneumonia in 72% of our cases. The yield increased significantly when IFMoAb was used in patients not receiving oral chemoprophylaxis.     

S-adenosylmethionine concentrations in diagnosis of Pneumocystis carinii pneumonia

Pneumocystis carinii is unable to synthesise S-adenosylmethionine and thus scavenges this intermediate. We aimed to test whether measurement of concentrations of this metabolic intermediate in plasma could provide a new method for rapid diagnosis of Pneumocystis carinii pneumonia (PCP). We measured S-adenosylmethionine plasma concentrations in 12 healthy controls, 16 patients with confirmed or suspected PCP, and 36 patients with other infections. Median concentration in healthy controls was 106 nmol/L (range 86-128), but the protein was undetectable in eight patients with histologically proven and seven with suspected PCP, and was 8 nmol/L in another confirmed case (p<0.0001). In 36 patients with other infections, S-adenosylmethionine concentrations were much the same as in controls: 18 had bacterial pneumonia, two tuberculosis, five cryptococcal meningitis, three had other infections, and eight had asymptomatic HIV-1 infection. After treatment for PCP, S-adenosylmethionine concentrations rose rapidly in all but one patient who died of the disease. Measurement of plasma S-adenosylmethionine concentrations could prove useful for diagnosis of PCP and assessment of patients' response to treatment.     

肺癌患者卡氏肺孢子虫感染情况初步观察

卡氏肺孢子虫是一种机会致病性原虫 ,其所致的卡氏肺孢子虫肺炎 (Ｐｎｅｕｍｏｃｙｓｔｉｓｃａｒｉｎｉｉｐｎｅｕｍｏｎｉａ,ＰＣＰ)常见于艾滋病患者、恶性肿瘤晚期患者、器官移植者等免疫功能低下者。本文报道肺癌患者ＰＣＰ的感染情况的初步观察。1　材料与方法1 .1　临床材料　肺癌患者 50例 ,其中男性 35例 ,女性 1 5例 ,年龄 30～ 69岁 ,术前未进行任何抗肿瘤治疗。1 .2　病理学及ＰＣＰ感染观察　快速冰冻检查肺癌的根治术大标本 ,肉眼分型后 ,分别切取肺癌肿块、癌周组织及各组淋巴结 ,石蜡包埋 ,4μｍ连续切片 ,分别行ＨＥ、吉氏…     

Evidence for destruction of lung tissues during Pneumocystis carinii infection

Five cases of Pneumocystis carinii infection with evidence of lung tissue destruction that occurred in patients with the acquired immunodeficiency syndrome were reviewed. None of the patients had a history of cigarette smoking, but all five had either cavitarylike lesions in the lungs or had pneumothorax at the time of presentation to the hospital. All patients had P carinii identified in specimens obtained either from bronchial washings or from open-lung biopsy. In four of the five patients, no other pathogens were involved in the lungs, while the fifth patient had concomitant cytomegalovirus infection. Findings on chest roentgenograms included large thin-walled cavitarylike lesions, multiple cavitary lesions, or pneumothorax. These presentations of the infection have not been previously described, and the mechanisms for lung tissue damage are as yet unknown. Cavitary lung disease found on chest roentgenograms in patients should not exclude the diagnosis of P carinii pneumonia, and patients with the acquired immunodeficiency syndrome presenting with pneumothorax should have the possibility of P carinii infection included in the differential diagnosis.     

The estimation of Pneumocystis carinii in HIV-infected patients occurrence based on three different methods

The frequency of Pneumocystis carinii occurrence in BAL of 38 HIV-infected patients was determined with three different method. BAL sediments were stained with Giemsa method, silvered according to Gomori-Grocott method and studied with indirect immunofluorescence assay. Using Giemsa method staining Pneumocystis carinii was diagnosed in 81.6% of patients, in Gomori-Grocott method--in 31.6% of patients, but results of indirect immunofluorescence assay were positive only in 23.,7%. In our study staining BAL sediments with Giemsa method allowed to detect Pneumocystis carinii in the highest percentage of examined patients.     

IgG anti-toxoplasma antibodies among asymptomatic HIV-infected patients in Marrakesh-Morocco

Detection and monitoring of anti-Toxoplasma gondii antibodies are of a great interest among human immunodeficiency virus (HIV)-infected patients, since cerebral toxoplasmosis is a life-threatening opportunistic infection within this vulnerable population. The IgG anti-T. gondii seroprevalence was assessed in 95 asymptomatic HIV-infected adults living in Marrakesh city and its surrounding areas. Our results showed a seroprevalence of 62.1%, which is high compared to most other countries. The mean of CD(4+) T-cells count of involved patients was 381.9cells/μl. Given these results, HIV-infected patients in Marrakesh region could be at high risk to develop toxoplasmosis disease, especially when CD(4+) T-cells count falls below 100cells/μl. Accordingly, there is a serious need of widening antiretroviral therapy and chemoprophylaxis against toxoplasmosis, when indicated, to ovoid toxoplasmosis reactivation among this population.     

Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia in HIV-infected patients.

Serum lactate dehydrogenase levels, alveolar-arterial oxygen gradient, and percentage of neutrophils in bronchoalveolar lavage correlate most strongly with early mortality in Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. However, the individual outcome can not be predicted by these parameters due to a considerable overlap between survivors and nonsurvivors. We prospectively investigated a PCP severity score, which has been developed earlier based on a retrospective analysis. Seven of 94 consecutively examined HIV-infected patients died within 14 days after diagnosis of PCP. A PCP severity score greater than 7 had a positive predictive value for early fatal outcome of 66.7 percent (6/9) and a negative predictive value of 98.8 percent (84/85). The overall diagnostic accuracy was 95.7 percent (90/94). The positive predictive value for early fatal outcome of a P(A-a)O2 > 35 mm Hg was 24 percent (6/25); the negative predictive value was 98.6 percent (68/69). However, the overall diagnostic accuracy was only 78.7 percent (74/94). The PCP severity score is a valuable tool for clinical decision making, for the early identification of patients with a prognostic unfavorable course, and for the comparison of patient populations in future studies of HIV-associated PCP.     

Geographic clustering of Pneumocystis carinii pneumonia in patients with HIV infection

To detect whether there was geographic clustering of Pneumocystis carinii pneumonia cases among patients with human immunodeficiency virus (HIV) infection, we performed a retrospective analysis of a clinical database. The rates of pneumocystosis were analyzed by zip code zones for evidence of geographical clustering. During the study period, 118 patients at our AIDS Treatment Center had a first episode of P. carinii pneumonia. An analysis of the 24 zip code zones for which a P. carinii pneumonia rate was calculated (requiring a denominator of at least 10 known HIV- infected individuals residing in that zone) showed a trend toward geographic clustering (p = 0.07); when all 45 Cincinnati zip code zones were included in the analysis, clustering of cases was observed (p = 0. 02). By contrast, no clustering was observed for 52 HIV-infected control subjects with respiratory disease or for 960 HIV-infected patients treated at our center during the same time period. These data raise intriguing questions about exposure to exogenous sources of P. carinii and suggest the need for prospective studies.     

Pneumocystis carinii pneumonia in HIV-infected patients: effect of steroid therapy on surfactant level.

Previous studies have suggested alterations in pulmonary surfactant lipid in the setting of Pneumocystis carinii pneumonia in HIV-infected patients. Because pulmonary surfactant lipid is composed of a variety of lipid products and because other phospholipids might be present in bronchoalveolar lavage (BAL) lipid determinations, a single molecular species of phospholipid which comprises a substantial portion of the surfactant lipid fraction, dipalmitoyl phosphatidylcholine (DPPC), was measured by capillary column gas chromatography in BAL samples taken at the time of the diagnosis of P. carinii pneumonia, and 10 days after treatment for P. carinii pneumonia. DPPC was measured at day 0 and day 10 in seven patients who had been randomized to receive methylprednisolone adjuvant therapy for P. carinii pneumonia and in six patients who had been randomized to not receive methylprednisolone therapy. The level of DPPC in BAL from all patients at day 0 was 0.49 +/- 0.06 microgram ml-1 BAL. This level is significantly lower that the level of DPPC determined in BAL from five normal volunteers 2.48 +/- 0.40 micrograms ml-1. At day 0, the BAL level of DPPC in patients treated with methylprednisolone was not different from the BAL level of DPPC in patients not treated with methylprednisolone. By day 10 of therapy for P. carinii pneumonia, BAL levels of DPPC in all patients had increased to 1.05 +/- 0.19 micrograms ml-1 BAL. At day 10 DPPC levels in the methylprednisolone treated group were not different from the group not treated with methylprednisolone. We conclude that in HIV-infected patients, lung surfactant lipid is reduced in the setting of P. carinii pneumonia. The lipid levels return toward normal levels with treatment. Adjuvant therapy with corticosteroids does not alter the rate of recovery of surfactant lipid levels at least after 10 days of therapy.     

Outcome and survival in HIV-infected infants with Pneumocystis carinii pneumonia and respiratory failure

A retrospective chart review (January 1987-December 1994) of cases of histologically proven Pneumocystis carinii pneumonia (PCP) in 9 infants (ages 1.1-7 months) who had perinatally acquired human immunodeficiency-1 virus (HIV) infection was performed. None of the children was suspected of having HIV or had received PCP prophylaxis. Respiratory failure requiring mechanical ventilation developed in all 9 children. Comparison of survivors (5) with nonsurvivors (4) showed no significant differences in the age of onset, weight for length, hemoglobin level, total protein/albumin, lactic dehydrogenase (LDH), liver function tests, lymphocyte numbers and functions, time on mechanical ventilation, treatment received (including the use of steroids), and other complications occurring during the acute phase of pneumonia. The survivors had significantly higher platelet counts than nonsurvivors (mean 516 K versus 237 K, p = 0.02), a trend toward lower arterial-alveolar (A-a) gradient (mean 415 versus 218, p = 0.07), and earlier use of steroids after the onset of illness (2.5 versus 1 day, p = 0.06). Four of 5 children treated after December 1989 survived compared to 1 of 4 prior to that. Four survivors followed for a median length of 29 months (range 28-32 months) had stable physical and neurocognitive development, improvement in CD4+ T cell counts [mean 27% (range 23-36%), absolute count-mean 1631 (range 1427-1631)] and immunologic functions, and decrease in p24 Ag in 3 of 4. The cellular proviral load measured by DNA quantitative polymerase chain reaction (QC-PCR) decreased (40 K to 17.3 K copies) in one of two patients studied at two time points. PCP continues to be a serious complication of HIV infection in infancy and aggressive preventive approaches seem warranted. In our institution no single factor was responsible for improved survival following PCP after 1989. Four of 5 survivors continued to do well 28-32 months after the acute episode.     

实验动物肺孢子菌隐性感染状况调查

目的调查实验动物肺内肺孢子菌隐性感染情况,为其质量监测及选择标准提供依据。方法从本校实验动物部培育的3种6个品系普通级实验动物中随机抽取大鼠、小鼠和兔,取肺脏制成印片标本,分别用姬姆萨(Giemsa)和改良的六亚甲基四胺银(GMS)染色,镜检肺孢子菌的包囊型和滋养体型;用PCR方法检测肺孢子菌特异性DNA。结果①大鼠Giem-sa染色和改良的GMS法阳性率分别为22.6%(12/53)和30.2%(16/53);PCR检测阳性率为49.1%(26/53)。②小鼠Giemsa染色检查全为阴性;GMS染色法检查阳性率为8.5%(8/94)。③用Giemsa和GMS染色检查日本大耳白兔,结果全为阴性。④对比3种动物不同品系的肺孢子菌感染率,GMS染色大鼠、小鼠两者差异显著(P<0.05)。Wistar和SD两种品系大鼠间无显著性差异(P>0.05);昆明株,BALB/c和C57BL/6三个品系小鼠间感染率无显著性差异(P>0.05)。⑤3种检查方法对比:PCR,GMS和Giemsa的阳性率分别为49.1%(26/53),13.6%(24/177)和6.8%(12/177),三者间检出率存在显著性差异(P<0.05)。结论肺孢子菌在普通级实验大鼠及小鼠体内的隐性感染现象较为普遍,其中大鼠的感染率明显高于小鼠。PCR灵敏性高于Giemsa和GMS染色法。