Pulmonary pathogens in HIV-infected patients

On well defined criteria a total of 102 fiberoptic bronchoscopies (FB) were done on HIV-infected patients with pulmonary symptoms. A microbiological agent was identified in 85 patients (83%). Pneumocystis carinii (PC) was histologically verified in 61 patients, bacteria cultured in 22 patients, and cytomegalovirus (CMV) cultured in 17 patients. A histological diagnosis of CMV was only established in 2/17 patients. In the present study, a CMV positive culture from bronchial lavage fluid did not appear related to the clinical picture. Patients with P. carinii pneumonia (PCP) had significantly higher IgA, lower CD4-count, more commonly dyspnea and an X-ray showing diffuse interstitial infiltration than patients without PCP. Patients with bacterial pneumonia had significantly higher CD4-count, lower IgA, more commonly productive cough and an X-ray showing focal infiltration. In more than 75% of the patients, microorganisms identified were responsible for the pulmonary symptoms leading to bronchoscopy. Mainly PC and bacterial pathogens, both of which are treatable, were responsible for these infections. Pulmonary infections of clinical relevance besides PCP and bacterial infections were rare (3%, 95% confidence limit 1-8%).     

Results and complications of fiber bronchoscopy in HIV positive patients

Fibreoptic bronchoscopy is an established diagnostic procedure for HIV-associated pulmonary infections. We retrospectively evaluated the diagnostic effectivity and safety of fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in 153 patients with late-stage HIV infection and clinical signs of pulmonary infection or abnormal chest radiograph. Bronchoscopy leads to diagnosis in 82.4% and changed therapy in 54%. 45 patients (30%) were found to have pneumocystis carinii pneumonia (PCP), the most common bronchoscopic finding, followed by bacterial lung disease (29.3%). BAL had a sensitivity of 78% for PCP. Diagnostic yield of BAL for PCP was higher in patients without previous treatment (positive results in 82%) with regard to PCP independend of the prior treatment. Serious complication occurred in 22 cases (pneumothorax: 6 (3.9%), bleeding: 12 (7.8%), hypoxaemia: 4 (2.6%)). High serum levels of lactate dehydrogenase (LDH) correlated with pulmonary complications like pneumothorax. Age, sex and kind of pulmonary infection did not influence complication rates. 6 (3.9%) episodes of spontaneous pneumothorax occurred in the further course, 3 of them concurrently with PCP or prior history of PCP. We conclude that fibreoptic bronchoscopy is of great value for diagnosing pulmonary infection in HIV-seropositive patients. TBB provides incremental diagnostic information not available from BAL, especially in patients pretreated with cotrimoxazol or pentamidin. For that reason we believe that TBB should be performed in these patients.     

Diagnosis of pulmonary diseases

A broad spectrum of lung disease occurs in association with HIV infection. Included are both infectious and neoplastic processes and idiopathic disorders. To insure prompt, accurate, and efficient diagnosis, a logical, staged sequence of tests should be applied. Chest films and, in some instances, pulmonary function tests and gallium-67 citrate lung scans serve to provide objective indications of lung disease. Each of these tests is sensitive but nonspecific. Specific infecting organisms, particularly P. carinii, can be identified by examining sputum induced by inhalation of 3 per cent saline. Bronchoscopic procedures, including BAL and TBB, are highly sensitive and should be performed in patients having nondiagnostic sputum examinations. Tests involving antigen and antibody detection are of little use in the evaluation of individual patients. Detection of recurrent episodes of PCP is difficult because abnormalities in the usual screening tests may be residual from previous episodes. Finding P. carinii in sputum or bronchoscopic specimens soon (within 2 to 3 months) after a confirmed episode of PCP likely represents residual organisms rather than recrudescence of the infection. Empiric diagnosis of P. carinii should be employed only in limited circumstances when specific diagnostic studies are not available, are contraindicated, or are refused.     

Occurrence of Pneumocystis carinii in HIV-positive patients with suspected pulmonary tuberculosis in Ethiopia

OBJECTIVE: To investigate the prevalence of Pneumocystis carinii in consecutive HIV-positive patients with suspected pulmonary tuberculosis (PTB) attending a university hospital in Ethiopia. METHODS: A PCR for P. carinii and an indirect immunoflorescence (IF) assay were performed on expectorated sputum samples from: 119 HIV-1-positive patients with negative smears and sputum cultures for Mycobacterium tuberculosis; 96 HIV-1-positive patients with culture-verified PTB; and 97 HIV-negative patients with negative mycobacterial cultures and 72 HIV-negative patients with culture-verified PTB, serving as controls. Outcome of PCR and IF were compared with the chest radiographic (CXR) and initial clinical diagnosis. RESULTS: In the HIV+PTB- group, P. carinii was found in 10.9% by IF, 8.4% by single PCR (sPCR) and 30.3% by nested PCR (nPCR). In the HIV+PTB+ group, 3.1% were P. carinii positive by IF and sPCR and 13.5% by nPCR. All IF- and sPCR-positive samples were nPCR positive. In the HIV-PTB+ and HIV-PTB- groups, 4.2% and 3.1% were nPCR positive, respectively. Six out of eight HIV+PTB- patients with CXR suggesting P. carinii pneumonia (PCP) were IF and/or nPCR positive for P. carinii. In the IF-positive and nested PCR-positive HIV+PTB- patients more than one-third were interpreted as PTB by CXR whereas only one patient was diagnosed with clinical PCP. CONCLUSIONS: P. carinii is prevalent in HIV-positive PTB suspects, suggesting that PCP may be an important, but not well recognized, differential diagnosis. Our findings have implications for treatment and primary prophylaxis for PCP in Ethiopia.     

Clinical correlation of variations in the internal transcribed spacer regions of rRNA genes in Pneumocystis carinii f.sp. hominis

OBJECTIVES: To analyse the importance of sequence variations in the internal transcribed spacer (ITS) regions 1 and 2 of the nuclear rRNA operon in AIDS patients with Pneumocystis carinii pneumonia (PCP). DESIGN AND METHODS: ITS 1 and 2 genotypes were determined in 162 bronchoalveolar lavage samples from 130 patients participating in a prospective cohort study of PCP. RESULTS: A total of 49 different ITS genotypes were detected. ITS genotype was not associated with the clinical severity or outcome of PCP. In 37 of 162 (23%) samples infection with two or more genotypes was observed. A genotype switch was detected in six of 10 patients (60%) with recurrent episodes of PCP. However, genotype changes were also seen in 10 of 19 patients (53%) who had repeated bronchoscopies within the same episode of PCP. The same ITS type was observed twice in 13 (46%) of the 28 patients with repeat bronchoscopies during single or recurrent episodes of pneumonia, but in only 14 of 81 (17%) randomly selected pairs (P < 0.01). CONCLUSION: Although the detection of ITS genotypes is not a random event, changes in genotype can be detected in a single episode of disease, with 23% of PCP patients being infected with more than one P. carinii genotype, thus complicating the use of this locus as a genetic marker to separate new infection from the reactivation of latent infection. ITS genotypes are not associated with the clinical severity of PCP.     

Correlation of bronchoalveolar lavage findings to severity of Pneumocystis carinii pneumonia in AIDS. Evidence for the development of high-permeability pulmonary edema.

We correlated bronchoalveolar lavage findings with the clinical course and outcome of Pneumocystis pneumonia. Forty-eight patients with AIDS and a confirmed diagnosis of P carinii pneumonia were studied. Patients with additional pulmonary infections were excluded. On the basis of BAL findings, they were divided into those with a low neutrophil count (less than 5 percent) and those with a high neutrophil count (greater than or equal to 5 percent). Sixteen patients with AIDS but without PCP served as a control group. All BAL fluid samples from the control group showed a low neutrophil count. The group with PCP and a high neutrophil count had more severe respiratory compromise and greater morbidity than the group with PCP and a low neutrophil count. Mortality rate was not different. The group showing a high BALF neutrophil count also showed a higher BALF protein concentration, a higher ratio of BALF protein concentration to plasma protein concentration, and the presence of alpha 2-globulins compared with other groups. These findings suggest that increased alveolar-capillary permeability occurs during severe PCP.     

Nonspecific interstitial pneumonitis without evidence of Pneumocystis carinii in asymptomatic patients infected with human immunodeficiency virus (HIV)

STUDY OBJECTIVE: To assess how often Pneumocystis carinii organisms, P. carinii pneumonia, or other pulmonary pathologic processes were present in persons infected with human immunodeficiency virus (HIV) without pulmonary symptoms or previous history of P. carinii, and with a normal chest roentgenogram. DESIGN: Serial, prospective assessment of eligible HIV-seropositive patients over 21 months. PATIENTS: Twenty-four HIV-seropositive patients with either a nonpulmonary manifestation of the acquired immunodeficiency syndrome (AIDS) (n = 12) or an absolute CD4 lymphocyte count of 0.200 X 10(9) cells/L or less (n = 12), no pulmonary symptoms, a normal chest roentgenogram, no history of P. carinii pneumonia, and no history of treatment with antipneumocystis prophylaxis. INTERVENTIONS: Pulmonary assessment with arterial blood gases, pulmonary function tests, gallium-67 citrate scans, and bronchoscopy with bronchoalveolar lavage and transbronchial biopsies. MEASUREMENTS AND MAIN RESULTS: Mean alveolar-arterial gradient was 11.1 mm Hg +/- 8.5 and mean diffusion capacity was 73.0% +/- 20.0% of predicted. None of the 24 patients showed P. carinii or other pathogens on stains of bronchoalveolar lavage fluid. No patient had histologic evidence of P. carinii pneumonia. Transbronchial biopsy specimens showed chronic, nonspecific interstitial pneumonitis (11 of 23) and no pathologic abnormality (12 of 23). Six patients have developed P. carinii pneumonia during 2 to 18 months of follow-up. CONCLUSIONS: HIV-infected patients without pulmonary symptoms did not have detectable Pneumocystis organisms in bronchoalveolar lavage fluid or transbronchial biopsy specimens; but 11 of 23 had evidence of chronic, nonspecific interstitial pneumonitis. Pneumocystis organisms in a pulmonary specimen from a symptomatic patient probably indicate the cause of the pulmonary dysfunction even if only a few are detected.     

Bronchoalveolar lavage as the exclusive diagnostic modality for Pneumocystis carinii pneumonia. A prospective study among patients with acquired immunodeficiency syndrome

Pneumocystis carinii pneumonia (PCP) is the most common life-threatening opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS). Because retrospective studies suggested that bronchoalveolar lavage (BAL) compared favorably to lung biopsy in the diagnosis of PCP, we prospectively evaluated the utility of BAL in 40 consecutive patients with AIDS or risk of AIDS who presented with respiratory complaints. The BAL revealed P carinii in 36 of 42 episodes of pneumonia (86 percent) among 40 patients. Clinical follow-up of the six patients whose BAL was negative for PCP suggested only one possible false negative BAL for PCP. Therefore, BAL detected PCP in 36 of 37 patients for a sensitivity of 97 percent. BAL detected cytomegalovirus in 15 of 38 patients, as well as Mycobacterium avium-intracellulare and Cryptococcus (each in one patient). By virtue of accuracy and lack of morbidity demonstrated in our study, BAL should supplant lung biopsy techniques in the evaluation of AIDS patients with pulmonary symptoms.     

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia.

Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response was higher (mean optical density ratio: 0.6 vs. 0.23 and 0.2, respectively; P less than .01). Changes in antibody response were investigated in 78 patients for whom serial serum samples taken around the time of bronchoscopy were available. Of the 47 patients with verified PCP, 20 (43%) mounted an antibody response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody response to P. carinii.     

Detection of Pneumocystis carinii by DNA amplification in patients with connective tissue diseases: re-evaluation of clinical features of P. carinii pneumonia in rheumatic diseases

OBJECTIVES: We evaluated the polymerase chain reaction (PCR) detection of Pneumocystis carinii DNA in induced sputum of patients with connective tissue diseases and assessed the clinical features of patients positive for P. carinii. METHODS: Sputum was induced by nebulization in 29 in-patients with various connective tissue diseases who presented with symptoms suggestive of P. carinii pneumonia (PCP), and was examined by PCR. RESULTS: Detection of P. carinii DNA by PCR was significantly more sensitive than cytology; 54.5% patients were positive by PCR and only 4.5% by cytology. The prevalence of PCP was higher than previously considered and was especially high in patients receiving > 30 mg/day prednisolone with or without other immunosuppressants. P. carinii-positive patients had significant lymphocytopenia and a low serum IgG level compared with P. carinii-negative patients. P. carinii disappeared within 7-10 days after therapy with trimethoprim/sulfamethoxazole. CONCLUSION: We propose that the use of PCR for detection of P. carinii using induced sputum is a useful and non-invasive method that has high sensitivity and specificity for the early diagnosis of PCP.     

Role of multiple induced sputum examination in the diagnosis of Pneumocystis carinii pneumonia

We evaluated the usefulness of repeated nebulized saline induced sputum examinations among 60 HIV infected patients clinically suspected to have Pneumocystis carinii pneumonia (PCP). We found that the first sample was positive for 15 episodes (21.4%); the second sample was positive in 33 episodes (47.1%); the third sample was positive in 22 episodes (31.4%). Repeated nebulized saline induced sputum examination imporved the yield of Pneumocystis carinii and enhanced the sensitivity of a positive result. This technique is simple, cost-effective, non-invasive, and reliable. We recommend the examination of multiple induced samples of nebulized saline induced sputum in all HIV infected patients with suspected PCP. This recommendation may decrease the need for invasive procedures.     

Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation to diagnosis and prognosis

Bronchoalveolar lavage (BAL) cell differentials and T-lymphocyte subpopulations were analysed in 95 HIV-infected patients with pulmonary symptoms to determine whether the type of cellular inflammatory response could be useful in diagnosis or as a prognostic marker. Patients with Pneumocystis carinii pneumonia (PCP) had more BAL fluid lymphocytes, mainly comprising CD8+ cells, and patients with bacterial infection had more neutrophils than other patients. Neither of these changes were mirrored in peripheral blood. Seven patients who died after their acute episode of PCP had significantly higher BAL fluid neutrophils than 53 patients with PCP who survived (P = 0.002). There seems to be correlation between BAL fluid neutrophilia, PCP and concomitant bacterial infection since four out of seven patients with a fatal outcome had coinfection with bacteria, whereas only one patient with PCP and bacterial coinfection survived (P = 0.0007).     

肾移植术后并发卡氏肺孢子虫肺炎

目的:讨论肾移植术后并发卡氏肺孢子虫肺炎(PCP)的早期诊断和治疗。方法:对6例肾移植术后并发PCP患者的临床资料进行分析和总结。结果:6例患者经支气管镜肺泡穿刺活检和支气管肺泡灌洗确诊。PCP发病于术后95～172d,一经确诊,根据肾功能及耐受情况予以复方新诺明[SMZco(SMZ50～70mg/(kg.d)TMP10～14mg/(kg.d)治疗3周,同时根据患者外周血CD4+计数及CD4+/CD8+比值调整免疫抑制方案,6例患者均治愈。结论:PCP确诊有赖于肺组织活检或肺泡灌洗找到病原体,必要时诊断性治疗不失为有效方法。治疗首选SMZco,但剂量应结合患者肾功能和耐受情况,并根据患者免疫状态调整免疫抑制方案。     

Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia.

To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.     

Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia.

Cases of paradoxical worsening of opportunistic infections shortly after the beginning of highly active antiretroviral therapy (HAART) prompted questions on the optimal timing of introduction of HAART in patients with inaugural AIDS-related opportunistic infections. We describe three cases of acute respiratory failure after early introduction of HAART in patients treated for Pneumocystis carinii pneumonia (PCP). The three patients had severe PCP that initially improved with anti-PCP and adjunctive steroid therapy. HAART was introduced 1 to 16 d after diagnosis of PCP, and steroids were stopped on Day 15. Seven to 17 d after HAART introduction, the three patients developed a second episode of severe acute respiratory failure with high-grade fever and patchy alveolar opacities on the chest roentgenogram. PCP resistant to cotrimoxazole, pulmonary superinfection, and drug-related pneumonitis were suspected but subsequently ruled out. Bronchoalveolar lavage and lung pathologic findings showed severe nonspecific pulmonary inflammatory foci surrounding a few persistent P. carinii cysts. All three patients recovered after HAART interruption or steroid reintroduction. We conclude that acute respiratory failure can recur after initiation of antiretroviral therapy in patients being treated for severe PCP. This phenomenon could result from rapid pulmonary recruitment of fully competent immune and inflammatory cells responding to a few persistent P. carinii cysts. A short course of steroid therapy may suppress this reaction.     

Impact of Pneumocystis carinii and cytomegalovirus on the course and outcome of atypical pneumonia in advanced human immunodeficiency virus disease.

Patients undergoing bronchoscopy for possible pneumocystis pneumonia were studied retrospectively to characterize the impact of common viral pathogens on the course of advanced human immunodeficiency virus (HIV) disease and atypical pneumonia. In 327 episodes, Pneumocystis carinii was found in 220 (67%), cytomegalovirus (CMV) in 145 (44%), and herpes simplex virus in 16 (5%). Early deterioration in oxygenation and use of intensive care was less common in CMV-positive patients. Neither CMV nor P. carinii was a predictor of mortality in multivariate analyses. CMV was not associated with an increased prevalence of later CMV disease. Isolation of CMV from the bronchoalveolar lavage fluid of these patients was not an indication for antiviral therapy. Pulmonary shedding of CMV may be associated with a decreased inflammatory response to P. carinii. The outcome of HIV-associated atypical pneumonia where no clear pulmonary pathogen is found on routine evaluation was no better than that of treated P. carinii pneumonia.     

Improved outcome of Pneumocystis carinii pneumonia in AIDS patients: a multifactorial treatment effect.

Factors determining the outcome of an episode of Pneumocystis carinii pneumonia (PCP) in 149 AIDS patients treated at St Mary's Hospital were identified and their importance on improved survival evaluated between 1984 and 1989. The proportion of fatal episodes of PCP decreased over time. Fatal compared with nonfatal episodes had lower mean alveolar-arterial oxygen gradient (82.5 mmHg vs 53.8 mmHg, P less than 0.001), mean haemoglobin level (11.2 g/dl vs 12.1 g/dl, P = 0.01), mean lymphocyte count (0.68 x 10(9)/l vs 0.92 x 10(9)/l, P = 0.05) and more coinfections (31% vs 5%, P less than 0.001). Over time, the most significant change which occurred was a reduction in alveolar-arterial oxygen gradient at time of first presentation with PCP (r = -0.37, P less than 0.001). Mean alveolar-arterial oxygen gradient declined from 79.9 mmHg in 1984 to 45.3 mmHg in 1989 (r = -0.88, P = 0.02), independently of zidovudine therapy or PCP prophylaxis. Patients were being treated at an earlier stage in their disease course as indicated by their reduced alveolar arterial oxygen gradient. This is due either to earlier patient presentation, earlier medical diagnosis or both. The widespread introduction of zidovudine and PCP prophylaxis may further contribute to improve morbidity and mortality patterns in the future.     

Genetic diversity of Pneumocystis carinii in HIV-positive and -negative patients as revealed by PCR-SSCP typing

OBJECTIVE: To describe the epidemiology of severe Pneumocystis carinii pneumonia (PCP) in HIV-infected and non HIV-infected patients. METHODS: Bronchoalveolar lavage specimens from 212 European patients with PCP were typed using PCR--single strand conformation polymorphism analysis of four genomic regions of P. carinii f. sp. hominis. Demographic and clinical information was obtained from all patients. RESULTS: Twenty-three per cent of the patients were presumably infected with a single P. c. hominis type. The other patients presented with two (50%) or more (27%) types. Thirty-five genetically stable and ubiquitous P. c. hominis types were found. Their frequency ranged from 0.4% to 10% of all isolates, and up to 15% of those from a given hospital. There was no significant association between the P. c. hominis type or number of co-infecting types per patient and geographical location, year of collection, sex, age, or HIV status. No more than three patients infected with the same type were observed in the same hospital within the same 6 month period, and no epidemiological link between the cases was found. CONCLUSIONS: The broad diversity of types observed seems to indicate that multiple sources of the pathogen co-exist. There was no evidence that in our study population inter-human transmission played a significant role in the epidemiology of P. carinii.     

Pulmonary complications in patients with AIDS: a report from a Beijing hospital

OBJECTIVE: The aim of this study was to improve the awareness of pulmonary complications in patients with AIDS. METHODOLOGY: Nine patients with AIDS with pulmonary involvement from March 1992 to March 2000 were analysed. RESULTS: Of the nine cases, there were eight cases complicated with Pneumocystis carinii pneumonia (PCP). The clinical presentation of PCP was fever (8/8), dyspnoea on exertion or at rest (7/8), and hypoxaemia with a mean PaO2 of 58 mmHg. Chest X-ray films showed bilateral diffuse interstitial or alveolar infiltrates. Pulmonary tuberculosis, tuberculous lymphadenitis and bronchial fungal infection were found in three cases. CONCLUSIONS: AIDS patients are at high risk of suffering from pulmonary complications, of which PCP is most common. If young patients who were healthy in the past suddenly suffered from pneumonia and respiratory failure, PCP should be considered. When opportunistic pulmonary infection is diagnosed under special circumstances, one should be alert to the possibility of AIDS and examine serum antihuman immunodeficiency virus (HIV) antibody.