Role of bronchoalveolar lavage in diagnosis of disseminated toxoplasmosis

In three cases of acute disseminated toxoplasmosis developing soon after renal (two patients) or hepatorenal (one patient) transplantation, Toxoplasma gondii trophozoites were visualized on Giemsa-stained smears of bronchoalveolar lavage fluid. Trophozoites were also found in bone marrow smears in one instance. Seroconversion occurred late in two cases and was not detected before the patient's death in the third. These observations underline the potential of bronchoalveolar lavage as a diagnostic procedure for disseminated toxoplasmosis.     

Disseminated toxoplasmosis following T cell-depleted related and unrelated bone marrow transplantation

More than 95% of reported cases of disseminated toxoplasmosis following BMT have occurred following an unmodified transplant. Most have been fatal, diagnosed at autopsy and without antemortem institution of specific therapy. From 1989 to 1999, we identified 10 cases of disseminated toxoplasmosis, in 463 consecutive recipients of a T cell-depleted (TCD) BMT. Transplants were from an unrelated donor (n = 5), an HLA-matched sibling (n = 4) or an HLA-mismatched father (n = 1). In 40%, both the donor and recipient had positive IgG titers against T. gondii pre-transplant; in 30%, only the recipient was sero-positive. Three recipients of an unrelated TCD BMT developed toxoplasmosis despite both donor and host testing negative pretransplant. All 10 patients presented with high grade fever. CNS involvement ultimately occurred in seven patients, with refractory respiratory failure and hypotension developing in nine. Eight of 10 cases were found only at autopsy, involving the lungs (n = 7), heart (n = 5), GI tract (n = 5), brain (n = 8), liver and/or spleen (n = 5). The only survivor, treated on the day of presentation with fever and headache, was diagnosed by detection of T. gondii DNA by polymerase chain reaction (PCR) performed on the blood and spinal fluid. This study demonstrates the similar incidence of toxoplasmosis following TCD BMT and that reported post T cell-replete BMT, and underscores the need for rapid diagnostic tests in an effort to improve outcome.     

Toxoplasma gondii pneumonia in liver transplantation: survival after a severe case of reactivation

Abstract: Toxoplasmosis is an infrequent infection in solid organ transplantation, except in heart transplantation, where the grafting of a positive organ in a negative recipient transmits the infection in a high percentage of cases, in the absence of prophylaxis.
We report a case of pneumonia by Toxoplasma gondii in a woman who received a liver transplant and had pre-transplant positive serology. Diagnosis was made by cytologic examination of bronchoalveolar lavage fluid, where the parasite was observed with hematoxylin–eosin and Giemsa staining. That finding was confirmed by direct immunofluorescence and positive polymerase chain reaction. The patient had a favorable outcome, although she had not initially received first-choice drugs. This was a case of severe illness secondary to reactivation of Toxoplasma infection, diagnosed pre-mortem and with a favorable outcome. Duration of treatment and need for secondary prophylaxis in these patients are discussed in the literature. Although infrequent, toxoplasmosis must be considered among the differential diagnoses of pulmonary infiltrates in solid organ transplantation.     

Severe pneumonia during primary infection with an atypical strain of Toxoplasma gondii in an immunocompetent young man

We report a case of severe acute primary pulmonary toxoplasmosis in an immunocompetent young man living in Nice (Southern France). The Toxoplasma DNA extracted from the broncho-alveolar lavage fluid allowed a genetic characterization of the responsible strain which displayed an atypical genotype of Toxoplasma gondii. This unusual genetic composition of the parasite may have influenced, among other factors, the severity of the disease.     

Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas

Improved diagnostic techniques have been needed for pulmonary aspergillosis, a common opportunistic fungal infection with a high mortality rate. Radioimmunoassay was used in this study to detect Aspergillus antigen in bronchoalveolar lavage fluid. In four patients with invasive aspergillosis or aspergillomas, Aspergillus antigen was detected in bronchoalveolar lavage fluid. In two patients, results of fungal cultures were negative or delayed. The specificity of antigen detection in bronchoalveolar lavage fluid was 91 percent in 35 control patients with a variety of pulmonary disorders. The technique of radioimmunoassay detection of microbial antigen in bronchoalveolar lavage fluid appears promising for the diagnosis of aspergillosis.     

Pulmonary toxoplasmosis: a review.

Toxoplasma pneumonia is being recognized with increased frequency, especially in patients with AIDS. We reviewed the English-, French-, and Spanish-language literature from January 1966 through February 1991 to identify cases of postnatally acquired pneumonia associated with Toxoplasma gondii. We identified two distinct clinical syndromes, one in immunocompetent patients and one in patients with defects in cell-mediated immunity. Shortness of breath and cough were the most common symptoms and fever and rales the most common signs in both groups of patients. Lymphadenopathy and hepatosplenomegaly were reported more frequently for immunocompetent patients. Chest roentgenographs usually revealed bilateral interstitial infiltrates, but a variety of other roentgenographic findings were reported. Serological findings were suggestive of active toxoplasmosis in immunocompetent but not in immunosuppressed patients. In early reports, identification of T. gondii as the etiologic agent of pneumonia was based on serology or autopsy findings. In more recent reports, open lung biopsy and especially bronchoalveolar lavage were used for diagnosis. Mortality among patients with toxoplasma pneumonia was 55%. However, in cases of T. gondii pneumonia diagnosed during life, mortality was 0 for immunocompetent patients and 40% for immunosuppressed patients. In immunosuppressed patients, improvement was associated with specific antitoxoplasma drug therapy. Unfortunately, relapses were common. We also reviewed data on series of patients with disseminated toxoplasmosis manifested predominantly in extrapulmonary sites and found that 33% of these patients had evidence of subclinical pulmonary involvement even though pneumonia had not been diagnosed clinically.     

Toxoplasma gondii pneumopathy in a patient with the acquired immunodeficiency syndrome: demonstration of the parasite by bronchioloalveolar lavage

Toxoplasmosis is an infection frequently observed in patients with acquired immunodeficiency syndrome. Its first manifestations usually are cerebromeningal symptoms, but others may occur. A pulmonary lesion is sometimes present; it is discovered at post-mortem examination in most cases. The authors report a case of pulmonary toxoplasmosis diagnosed by bronchoalveolar lavage (BAL). Three points are emphasized: toxoplasmosis of the lung may produce an interstitial pneumonia similar to that of pneumocystosis; diagnosis can be made non-invasively by BAL, and provided an appropriate treatment is administered, the outcome may be favourable.     

Pulmonary toxoplasmosis in AIDS. Report of 3 cases

Pulmonary toxoplasmosis in AIDS is rare. Its frequency is estimated to be between 0.2 and 3.7% but is probably underestimated; however, it is lower than that of neurotoxoplasmosis and is rarely identified prior to autopsy. We describe herein 3 cases diagnosed in living patients. The clinical presentation is usually severe interstitial pneumonitis, occurring in profoundly immunodeficient patients. Toxoplasma gondii, the infectious agent, must always be sought in the bronchoalveolar lavage of such patients and is sometimes associated with other opportunistic infectious agents, such as Pneumocystis carinii.     

Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients

PURPOSE: The purpose of our work was to evaluate pulmonary complications in autologous bone marrow transplant recipients. PATIENTS AND METHODS: A total of 141 consecutive autologous bone marrow transplant recipients were evaluated. In 29 patients, a clinical syndrome characterized by progressive dyspnea, hypoxia, cough, diffuse consolidation on chest roentgenography, and characteristic bronchoalveolar lavage findings developed over one to seven days. RESULTS: In 29 patients, bronchoalveolar lavage performed by sequential instillation and aspiration of 20-ml aliquots of normal saline resulted in recovered lavage fluid that became progressively bloodier with each recovered aliquot. Autopsy and bronchoalveolar lavage in these patients revealed no pathogens that accounted for the clinical findings. Since the later aliquots sample predominantly alveolar material, this syndrome was termed diffuse alveolar hemorrhage (DAH). DAH was associated with a high inpatient mortality rate (23 of 29 died versus 14 of 112 without DAH, p less than 0.001) and was associated with age over 40 years, solid malignancies, high fevers, severe mucositis, white blood cell recovery, and renal insufficiency (p less than 0.05, compared with patients without DAH). However, DAH was not associated with prolonged prothrombin or partial thromboplastin times or decreased platelet counts compared with patients without DAH. CONCLUSION: DAH is a frequent cause of respiratory compromise and a major cause of mortality in autologous bone marrow transplant recipients.     

Toxoplasmosis in bone marrow transplantation: a report of two cases and systematic review of the literature

Toxoplasma infection represents a rare but often fatal complication in bone marrow transplant (BMT) recipients. We report two cases of toxoplasmosis: one of successfully treated cerebral toxoplasmosis after peripheral blood stem cell transplantation, and a fatal case of pulmonary toxoplasmosis in a BMT recipient. We have systematically reviewed the 110 published cases of toxoplasmosis following BMT. We analyzed the pre-transplant and clinical features of BMT recipients developing toxoplasmosis, together with the diagnostic procedures used and treatment given. By univariate and multivariate statistical analysis we analyzed the risk factors for diagnosis (during life vs post-mortem) and Toxoplasma-related mortality. Ante-mortem diagnosis was made in 47% of cases. Site of infection (P = 0.02; odds ratio 10.8), presence of symptoms at onset (P = 0.01) and conditioning regimen (P = 0.04) were factors influencing whether the diagnosis was made before or after death. Overall mortality rate was 80% and that attributed to toxoplasmosis was 66%. Variables influencing outcome were: site of infection (P = 0.02; odds ratio 5.28), day of onset (P = 0.04) and conditioning regimen (P = 0.04). Underlying disease (P = 0.02; odds ratio 9.45), among patients diagnosed before death, was the most significant factor influencing outcome.     

实时荧光定量聚合酶链反应检测支气管肺泡灌洗液中结核分枝杆菌-DNA对肺结核的诊断价值

目的探讨实时荧光定量聚合酶链反应法（FQ-PCR）检测支气管肺泡灌洗液（BALF）中结核分枝杆菌-DNA（TB-DNA）对肺结核的诊断价值。方法肺结核52例（菌阳20例,菌阴32例）,肺炎35例,采用FQ—PCR法检测其支气管肺泡灌洗液中TB—DNA水平。结果52例肺结核组的阳性率为65．4％（菌阳19例,菌阴15例）,35例非肺结核组的阳性率为5．7％,经统计学比较,FQ-PCR法检出结核杆菌阳性率显著高于痰涂片抗酸染色和培养法（P均〈0．05）,FQ-PCR法特异性高。结论FQ-PCR法检测BALF中TB-DNA为痰涂片阴性及无痰患者提供良好的诊断依据。     

不同方法检测痰和肺泡灌洗液中结核杆菌的分析

目的对比分析不同检测方法和不同检测标本在结核杆菌检测结果中的意义。方法选取本科室收治的初次我院就诊并临床诊断符合"肺结核"标准的158例患者的痰液和肺泡灌洗液,对所有的标本均进行两次抗酸染色涂片、两次快速培养检测结核杆菌(1次及1次以上阳性均记为阳性)。结果 1.快速培养法的结核杆菌检出率高于抗酸染色涂片法;2.肺泡灌洗液的结核杆菌阳性率均高于痰液。结论快速培养法是临床工作中确诊结核病的首选方法,肺泡灌洗液能有效提高肺结核的诊断率。     

Bronchoscopy with bronchoalveolar lavage in the evaluation of pulmonary complications of bone marrow transplantation in children.

Pulmonary complications are a frequent cause of morbidity and mortality following bone marrow transplantation. We examined the results of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) in 27 pediatric bone marrow transplant (BMT) recipients with 29 episodes of pulmonary complications. Bone marrow transplant was performed for a variety of malignancies and hematologic disorders. Median age of BMT was 10.3 years (range, 1.7-17.6 years). Median time of FB following BMT was 60 days (range, 11-1,026 days). Routine cytologic and culture techniques were utilized to detect malignant cells, viruses, fungi, bacteria, and protozoa. Positive results were found in 15 (52%) with cytomegalovirus (CMV), the most common positive finding. In 14 (48%) episodes the results were negative. Fourteen patients had follow-up autopsy or open lung biopsy (OLB). Based on autopsy/OLB results, there were two false negatives and no false positives, giving a diagnostic sensitivity of 75% and specificity of 100%. There was one possible complication of FB and BAL. Survival of both positive and negative patients was poor, only seven patients being alive 90 days post-FB with BAL. We conclude that FB with BAL is a safe and accurate procedure for the diagnosis of pulmonary complications of BMT.     

Alveolo-Capillary Protein Permeability and Lung Function in Patients with Late Pulmonary Complications after Allogeneic Bone Marrow Transplantation

A prospective study was performed to identify markers predictive for the development of pulmonary complications in the early (<50 days) and late (>50 days) phase after bone marrow transplantation (BMT). The characterization of BMT patients with early or late pulmonary complications revealed clear-cut differences. Early and long term increase of alveolo-capillary protein permeability was associated with smoking and was found in 20 patients developing pulmonary complications within 50 days after BMT (group 1). The 22 patients who developed such complications thereafter (group 2) had more acute graft vs host disease than 66 patients who remained free of these complications for a minimum of 1 year. Concentrations of bronchoalveolar lavage (BAL) fluid albumin (alb) and serum β₂-microglobulin (S-β₂m) were determined 10 days before BMT, on days 1, 30, and 40 after BMT, whereas lung function tests were performed before BMT, after discharge from the hospital, and 6 months as well 1 year after BMT. Using cut-off values for BAL fluid alb (>2.3 mg/dl) and S-β₂m (>0.8 mg/liter) we could significantly discriminate 12 patients out of 19 group 1 patients (early pulmonary complications) as well as 9 out of 21 group 2 patients (late pulmonary complications) from 12 out of 64 group 3 patients (without such complications) 1 day after BMT. Our results demonstrate that early increased alveolo-capillary protein permeability defines a patient population at risk to develop pulmonary complications later than 50 days after BMT with up to 1 year significantly decreased lung volumes (FEV1, 73% predicted, VC, 85% predicted). Accepted for publication: 12 June 1997     

Toxoplasma gondii pneumonitis in patients infected with the human immunodeficiency virus.

Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms.     

Cytomegalovirus is frequently isolated in bronchoalveolar lavage fluid of bone marrow transplant recipients without pneumonia

We prospectively studied the presence of cytomegalovirus in bronchoalveolar lavage through virus isolation in 21 bone marrow transplant recipients before and after transplantation. All 14 lavage specimens collected before bone marrow transplantation were negative for cytomegalovirus. During the period from 20 to 90 days after transplantation, 12 of 24 lavage specimens (50%) from 14 patients without lung problems were positive for cytomegalovirus. Cytomegalovirus was isolated from 4 of 10 lavage specimens (40%) in 7 patients with pneumonia during the same interval. We conclude that culture for cytomegalovirus in bronchoalveolar lavage fluid is not a reliable method for establishing the virus's causative role in pneumonia soon after bone marrow transplantation. Among 14 patients in whom bronchoalveolar lavage was done at an asymptomatic stage, 6 of 9 patients with cytomegalovirus and none of 5 without cytomegalovirus in the lavage fluid later developed pneumonia. All of the patients subsequently developing pneumonia also had acute graft-versus-host disease, suggesting an immunopathologic mechanism, possibly triggered by cytomegalovirus, for cytomegalovirus-associated pneumonia.     

Detection ofToxoplasma gondii in AIDS patients by the polymerase chain reaction

Summary In recent years, toxoplasmosis has become one of the most frequent and life-threatening opportunistic infections in AIDS patients. Despite strict clinical follow-up and repeated biological examinations, its diagnosis remains difficult to establish in the context of immunodeficiency because of the poor predictive value of serology. The aim of the study was to compare standard methods of diagnosis with the polymerase chain reaction (PCR), in an attempt to investigate the potential usefulness of PCR in the diagnosis of toxoplasmosis. Twelve biological samples (cerebrospinal fluid, bronchoalveolar lavage fluid, one brain biopsy and one liver biopsy) from 11 unselected AIDS patients were tested by PCR. The results showed good correlation (for eight out of 11 patients) between classical methods and PCR, and confirm the value of bronchoalveolar lavage for the diagnosis of toxoplasmosis in AIDS patients. The pathophysiological significance of the presence ofToxoplasma in samples tested is discussed.

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Nachweis von Toxoplasma gondii unter Anwendung der Polymerasekettenreaktion bei AIDS-Kranken

Zusammenfassung Bei AIDS-Kranken stellt die Toxoplasmose eine der häufigsten lebensbedrohlichen Infektionen dar. Wegen des geringen prädiktiven Wertes der Serologie ist die Diagnose im Zustand der Abwehrschwäche trotz konsequenter klinischer Kontrollen und wiederholter Laboruntersuchungen schwierig. Die vorliegende Studie wurde durchgeführt, um die Methoden der konventionellen Diagnostik mit der Polymerasekettenreaktion (PCR) zu vergleichen und den Nutzen der PCR in der Toxoplasmose-Diagnostik zu beurteilen. Die PCR wurde bei 11 unausgewählten AIDS-Kranken eingesetzt; für die Untersuchungen standen 12 Proben (Liquor cerebrospinalis, bronchoalveoläre Lavage-Flüssigkeit, eine Hirnbiopsie und eine Leberbiopsie) zur Verfügung. Die Ergebnisse zeigten bei acht der 11 Patienten eine gute Korrelation zwischen den klassischen Nachweismethoden und der PCR. Sie bestätigen den Wert der Bronchoalveolar-Lavage für den Nachweis der Toxoplasmose bei AIDS-Kranken. Die pathophysiologische Bedeutung der Toxoplasma-Organismen in den Proben wird diskutiert.

     

Toxoplasmosis in bone marrow-transplant recipients: report of seven cases and review.

We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty-four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases.     

Pathogenesis of T-lymphocyte alveolitis associated with HTLV-I infection]

Pulmonary involvement has been demonstrated in patients with spastic myelopathy associated with HTLV-I infection (HAM/TSP). Pulmonary lesions in these patients are characterized by T-lymphocytosis and increased level of soluble IL-2 receptor in bronchoalveolar lavage fluid. T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid proliferated spontaneously and released IL-2 and IL-2 receptor when cultured in vitro. Spontaneous proliferation of T-lymphocytes was also found in HTLV-I carriers without myelopathy, but less intensely than in HAM/TSP patients. Interestingly, HTLV-I-infected cells were markedly increased in bronchoalveolar lavage fluid from HAM/TSP patients compared to HTLV-I carriers without myelopathy. These results suggest that T-lymphocyte activation and increased HTLV-I-infected cells play an important role in the pathogenesis of pulmonary involvement in patients with HAM/TSP.