Pneumocystis carinii Pneumonia in Patients Without Predisposing Illnesses

Pneumocystis carinii Pneumonia in Patients Without Predisposing Illnesses* Acute Episode and Follow-up of Five Cases Soledad Cano, M.D.; Francisco Capote, M.D .; Antonio ltm3ira, M.D.; Enrique Calderon, M.D.; and jose Castillo, M.D. Pneumocylitis carinii pneumonia (PCP) is described almost exclusively in immunocompromised hosts. This report describes our experience with acute episodes and the followup of five patients with PCP who had no known predisposing conditions. The average follow-up period was 3.6 years (range, 2.6 to 4 years). Lymphocyte subpopulations (CD4, CD8, and CD4:CD8), serum immunoglobulins (IgG, IgM, and IgA), and serologic studies for human immunodeficiency virus were carried out on all patients at least twice, both at the beginning and the end of the follow-up. None of the

patients presented compatible data with AIDS or any other identifiable risk factors. We conclude that PCP can occur in patients who apparently do not have immunosuppression. (Chellt 1993; 104:376-81)

neumocystis carinii is an organism of universal P distribution and presumed low pathogenicity. The

having PCP. These patients were evaluated during the acute pneumonic episode, and later, a follow-up was carried out in periodic visits to the Pneumology Outpatient Department. The initial evaluation included serum immunoglobulins (IgG, IgM, and IgA) and a quantity of lymphocyte subpopulations, serologic study for human immunodeficiency virus (HIV), search for collagenvascular and neoplastic disease indicators, and computed tomography (Cf) of the chest and abdomen. During the fOllow-up, lymphocyte subpopulations, serum immunoglobulins (IgG, lgM, and IgA), and serologic study for HIV were evaluated. The PCP diagnosis was established by the identification of typical organisms in specimens obtained by fiberoptic bronchoscopy (FB) in four cases, transthoracic needle aspiration (TNA) in two cases, and thoracentesis in one case (Table 1). The FB was performed (with the Olympus FB 10-0ES) and the techniques used for taking specimens were identical to those described by other authors. •••• Bronchoalveolar lavage (BAL)•• was performed by wedging the tip of the FB into the third-generation bronchus of the middle lobe or lingula or alternatively in the area shown on the chest radiograph that contained most lung infiltrates. At least 50 ml of saline solution was instilled and then suctioned afterward. Samples for bacterial cultures were obtained with a telescoping plugged catheter (TPC) using the technique of Wimberley et al . 17 A FB 21C forceps was used to perform the transbronchial biopsy (TBB),•• and a 22G spinal needle, connected to a 5-ml syringe, was used for the TNA.•• Specimens were immediately transported in sterile containers for bacterial, fungal , and parasitologic studies. In each case, toluidine blue 0 and modified Giemsa stains ('Thble 1) were used to identify Pcarinii . Up to the end of 1989, lymphocyte subpopulations were analyzed by indirect immunoftuorescence, using monoclonal antibodies of the OKT series against CD4 and CDS. In the last 2 years of the follow-up, lymphocyte subpopulations were measured by means of Row cytometry (FACScan Analysis, Becton Dickinson). Investigations of the anti-HIV-1 antibody (HIVAC 1, Abbott Laboratories) were carried out on all five patients at least twice-both at the beginning and the end of the follow-up-by enzyme immunoassay (EIA). In two patients, the serum was tested for antibodies against the envelope and core pmteins of the HIV-1 by a second-generation recombinant EIA (ENVACOR HIV 1, Abbott Laboratories); and in another patient, for the presence of proteins against HIV-1, by Western-blot (NEW LAV BLOO' I, Diagnostics Pasteur). Investigations of the HIV-1 antigen (Abbott Recombinant HIV 1 EIA) were

high prevalence of antibodies against P cannu m children1. 2 supports the current concept of the epidemiology of infection by P carinii. The most probable epidemiologic sequence is the development of a subclinical infection in infancy, and the later manifestation of the illness when some defect in the immune system is produced. 3 The first reports on P carinii pneumonia (PCP) were published in the mid-1900s, involving premature and young infants. •·s In the following decades, the reports described almost exclusively patients with some predisposing conditions (leukemia, lymphoma, primary immune deficiencies, solid tumors, organ transplants, steroid or cytostatic treatments).6·7 However, PCP was a rare condition until 1981, when the acquired immunodeficiency syndrome (AIDS) was described . There since has been a significant rise in the rate of cases, becoming the most common infection complicating AIDS. 8 ·9 Since P carinii was first described, only exceptional reports have been published on pneumonia by this microorganism in patients with no previous predisposing illness. UHs We believe that it is interesting to share our experience with acute episodes and the follow-up of five patients with PCP who had no known predisposing conditions. METHODS

Between July 1987 and October 1988, five patients with no known immunoc~>mpmmising condition were diagnosed at our hospital as

*Fmm the Pneumology Service, Hospital Universitario Virgen del Rocio, Seville, Spain. Manuscript received July 28; revision accepted January 6. Reprint n!quests: Dr. Cano Gomez, VIllegas y Marnwlejo 9-11, Bloque 2,68, 41005 Seville , Spain

376

ANA= antinuclear antibody; EIA =enzyme immunoassay; FB = &beroptic bronchoscopy; LE =lupus erythemato~~sz PCP= Pneuii!OCfiUU carinii pneumooia; TBB = transbronclliaJ biopsy; TNA =transthoracic needle aspiration; TPC = telescoping plugged catheter

PCP In Patients without Pradlsposlng llinesMa (Cano et al)

Table 1-Method ofDiagnosiB ofP carinii Pneumonio* Method

No. of Patients

Methods to obtain the samplest Bronchoscopy (BA, BAL. TBB) Transthoracic needle aspiration Thoracentesis Staining technical Toluidine blue 0 stain Modified Giemsa Stain

4 2

5 5

*BA =bronchial aspirate; BAL = bronchoalveolar lavage; TBB = transbronchial biopsy. tin two patients, the diagnosis was established by more than one method. also made in four patients; and, in one of the patients, anti-HIV-2 antibody by EIA (ELAVIA II, Diagnostics Pasteur) was determined (Table2). CASE REPORTS CASE

1

A previously healthy, 39-yeaM>ld man, an agricultural worker by profession, manifested an episode of rhinitis and fever some 20 days before hospitalization. The episode was autolimited after 4 days without undergoing treatment. He presented to the hospital in November 1987, 24 h after the onset of chest pain, fever, and dyspnea. At the time of hospital admission, he had a temperature of38•c, a respiratory rate of36 breaths/min, and a heart rate of 120 systoles/min. Auscultation manifested decreased breath sounds over the left side of the chest. A chest radiograph revealed a left pleural

effusion and a bilateral interstitial infiltrate. The initial arterial blood gas measurement, while the patient was breathing room air, revealed partial pressure of oxygen (Po.) of 64 mm Hg and partial pressure of carbon dioxide (Pco.) of 34 mm Hg. The total leukocyte count was 17.8x 10"/L (88 percent neutrophils, 4 percent lymphocytes, 2 percent band forms, and 6 percent monocytes), the hemoglobin level was 15.8 gldl (normal, 11.8 to 18.1), and the platelet count was 277 X 10"/L (normal, 114 to 406). Results of serum biochemical analysis were normal. In the days following hospital admission, the patient developed severe respiratory failure, for which he required respiratory assistance with mechanical ventilation. Chest radiograph showed pleural effusion in two thirds of the left hemithorax and a bilateral alveolointerstitial infiltrate. The pleural Huid was an exudate, cultures were sterile, and a drainage tube was inserted. The patient was given empirical treatment with erythromycin, tobramycin, rifarnpin, and isoniazid, with no results. On the 12th hospital day, FB and TNA were performed, and both the bronchial aspirate and the material obtained by puncture showed P carinii cysts and trophozoites. Treatment every 6 h was begun, administering 320 mg of tnrnethoprim and 1,600 mg of sulfarnethoxazole. One week after start of the anti-Pneumocystis treatment, an improvement was seen on the chest radiograph, and on day 12, we were able to discontinue the mechanical ventilation. Lymphocyte subpopulations (Thble 2) and serum immunoglobulins were normal. Serologic studies for anti-HIV-1 antibody by EIA and Western-blot were negative. Collagen-vascular and neoplastic illness indicators (lupus erythematosus [LE] cells, antinuclear antibody [ANA], rheumatoid factor, serum complement C3 and C4, afetoprotein, and carcinoembryonic antigen) were within normal limits. ACT scan of the chest and abdomen showed no masses or lymphadenopathy.

Table 2-Phenotypic Analysis ofPeripherOl-Blood T CeU. and Serologic Studiafor HI.V*

Control subjects Patient 1 Acute episode First control Last control Anti-HIV-1 (sEIAJ cEIA, WB), HIV-1-Ag Patient2 Acute episode First control Last control Anti-HIV-1 (sEIA,t cEIA, WB), HIV-1-Ag§, anti-HIV-2 Patient 3 Acute episode First control Last control Anti-HIV-1 (sEIAt), HIV-1-Ag§ Patient4 Acute episode First control Last control Anti-HIV-1 (sEIA§), HIV-1-Ag PatientS Acute episode First control Last control Anti-HIV-1 (sEIA§)

Leukocytet

Lymphocytet

CD4•Cellst

CD8•Cellst

CD4:CD8

3.9-10.6

0.8-3.2

0.53-1.46

0.10-0.18

0.58-2.35

17.8 6.9 5.79

0.712 3.374 2.950

1.755 1.138

0.675 0.860

2.6 1.3

21.7 8.8 9.66

3.689 2.72 2.07

1.08 0.873

0.972 0.703

1.1 1.2

28.8 6.1 9.59

1.904 2.434 2.820

1.176 0.570

0.552 0.942

2.13 0.6

12.8 12.5

1.408 2.02

1.22

0.440

2.7

6 .8

2.77

1.01

0 .804

1.25

24.8 13.8 10.3

3.472 2.76 1.96

1.435 0.960

0.580 0.384

2.4 2.5

*Anti-HIV=antibodies to HIV; HIV-Ag=HIV antigen; sEIA=screening enzyme immunoassay; cEIA=competitive enzyme immunoassay (by envolture and core); WB =Western blot; HIV =human immunodeficiency virus. tValues are X IO -•JL. tThree times tested. §Twice tested. CHEST I 104 I 2 I AUGUST, 1993

377

Four years after the acute episode, the patient was clinically healthy. Lymphocyte subpopulations (Table 2) and serum immunoglobulins were within normal limits. During the follow-up, serologic studies for HIV were negative (Table 2). CASE2 A 30-yeaNJld man, a truck driver by profession, had no pathologic history. In January 1988, 5days before entering hospital, he began manifesting fever, chills, a cough, mucous sputum, diffuse thoracic pain, myalgias, and progressive dyspnea. A temperature of 39"C, tachypnea, cyanosis, tachycardia of 130 systoles/min, and bilateral rales were noted on the first physical examination. The leukocyte count was 21.7 x 100/L (79 percent neutrophils, 2 percent band forms, 17 percent lymphocytes, and 22 percent monocytes), the hemoglobin level was 14 gldl, and the platelet count was 350 X 100/L. The arterial blood gas measurement, while the patient was breathing room air, showed a Po1 of 49 mm Hg and Pco. of 33 mg Hg. The chest radiograph revealed a diffuse alveolar infiltrate, predominating in the middle fields. From the beginning, the patient received mechanical ventilation and empirical treatment with erythromycin and tobramycin. Two days after hospital admission, because of the absence of response to treatment, FB was performed to take specimens with BAL and TPC. Bacterial cultures were negative, and in the BAL fluid, blue toluidine 0 and modified Giemsa stains showed P carinll cysts and trophozoites, respectively. Treatment was begun with 320 mg of trimethoprim and 1,600 mg of sulfamethoxazole, every 6 h . At this stage, the patient was in critical condition and presented criteria of adult respiratory distress syndrome (ARDS). After 21 days of anti-Pneumocystis treatment, a slight improvement was noted on the radiograph and in blood gases, and a new FB produced BAL liquid that did not show P carinll. Therefore, the treatment was discontinued. Sev~ral days later, the patient's clinical, radiologic, and gasometric condition worsened and, after a third BF was performed, cysts and trophozoites were again evident in the BAL liquid. The same anti-Pneumocystis treatment was reinstated, and there was a l>rogressive improvement after 5 days, with a clearing of the pulmoitary infiltrates, apyrexia, and a notable gasometric improvement. After 50 days of mechanical ventilation, it was possible to extubate the patient. Lymphocyte subpopulations (Table 2) and serum immunoglobulins were normal. The anti-HIV-1 antibody was negative. Collagen-vascular disease parameters (LE cells, rheumatoid factor, ANA, and complement C3 and C4) were within normal limits. The CT scan of chest and abdomen showed no lymphadenopathy or tumoral masses. We carried out a 4-year follow-up and in this period the patient did not require medical attention for any other condition. Lymphocyte subpopulations (Table 2) and serum immunoglobulins were within normal limits. Throughout the evaluation, serologic studies for HIV-1 and HIV-2 were negative (Table 2). CASE3 A previously healthy 37-yeaNJld woman who had no pathologic history was admitted to the hospital in March 1988. Nine days before admission, she began to manifest fever, a cough, and malaise. She underwent treatment with oral amoxicillin, with no improvement, and the day before entering the hospital, she also had dyspnea. The first physical examination showed a serious illness, agitation, tachypnea, 38.5"C temperature, tachycardia of 140 systoles/min, and diffuse bilateral rales. The chest radiograph showed a bilateral alveolointerstitial infiltrate. The total leukocyte count was 28.8 X 100/L (92 percent neutrophils, 6 percent lymphocytes, and 2 percent monocytes), hemoglobin level was 13.6 gldl, and the platelet count was 523 x 100/L. The arterial blood gas measurement, while the patient was breathing room air was Po1 of 34 mm Hg and Pco1 of 32 mm Hg. Mechanical ventilation and treatment with cefotaxime, erythromycin, and tobramycin were initiated. On hospital day 5, an FB was performed to take a microbiologic

378

specimen by BAL and TPC. In the BAL fluid, P catinii cysts and trophozoites were observed, and a pure Pseudomonas aeroginosa culture was obtained from the TPC . Treatment with ceftazidime, 6 gld, amikacin, 1gld, trimethoprim, 1,280 mgld, and sulfamethoxazole, 6,400 mgld was initiated. Five days after beginning this treatment, an improvement was shown on the chest radiograph, and on the seventh day, apyrexia was attained and it was possible to discontinue the mechanical ventilation. The serologic study, carried out on the tenth day after hospital admission, showed a titer of 11256 for Mycoplasma pneumoniae, by complement fixation. Lymphocyte subpopulations (Table 2) and immunoglobulins were normal. Anti-HIV-1 antibody was negativ~ . Other immunologic studies (LE cells, rheumatoid factor, and ANA) and the tumor markers (afetoprotein and carcinoembryonic antigen) were normal. The CT scan of chest and abdomen was normal. A follow-up of the patient was earned out over 4 years, and she was asymptomatic. Nine months after the acute episode, the titer for Mycoplasma was 1116 by complement fixation. On conclusion of the follow-up, the analysis of lymphocyte subpopulations showed the CD4 to be near the lower limits of normal (Table 2). Serum immunoglobulins were within normal limits except for the lgA, which showed a value of 55 mgldl (normal values, 130 to 310 mgl dl). The serologic study for HIV was negative (Table 2). CASE4 A 37-yeaNJld man had a smoking habit (40 cigarettes a day); the only notable history was chronic expectoration. Twenty days before hospital admission, in October 1988, he manifested a cough and purulent sputum, pain in the right side of the thorax, and fever. A physical examination showed 26 breaths/min, rales over the left side of the chest, and decreased breath sounds over the lower half of the right hemithorax. The first chest radiograph showed a bilateral nonhomogeneous alveolar infiltrate, right diaphragm elevation, and obliteration of both costophrenic angles. The arterial blood gas study, while the patient was breathing room air, showed Po1 of 70 mm Hg and Pco. of 25 mm Hg. The total leukocyte count ~as 12.8 x 100/L (78 percent neutrophils, 11 percent lymphocytes, and 11 percent monocytes), the hemoglobin level was 15.8 g!dl, and the platelet count was 224 X 100/L. Results of the biochemical study of the serum were normal. Empirical treatment was begun with erythromycin. Six days after hospital admission, the patient continued to be febrile, and the chest radiograph showed a diffuse opacity in the right hemithorax. Thoracentesis and TNA were performed. The pleural fluid was an exudate, with negative bacterial cultures. In the pleural fluid and in the specimen obtained by pulmonary puncture, P catinii cysts and trophozoites were identified. Apleural drainage tube was inserted and treatment was begun with 320 mg of trimethoprim and 1,600 mg of sulfamethoxazole, every 6 h . Response to the treatment was favorable and, on the sixth day of treatment, apyrexia was attained. Nevertheless, the pleural drainage was not effective, and it was .necessary to perform pleural lavage by thoracotomy. In the material obtained by lavage, P catinii cysts were identified. Lymphocyte subpopulations (Table 2) and serum immunoglobulins were found to be within normal limits. Anti-HIV antibody and HIV-1 antigen (EIA) were found negative. Collagenvascular and neoplastic disease parameters analyzed (LE cells, ANA, complement, a-fetoprotein, and carcinoembryonic antigen) were normal. The CT scan of chest and abdomen showed no picture compatible with adenopathy or tumoral masses. Three years and 3 months after beginning the follow-up, the patient was healthy. Lymphocyte subpopulations (Table 2) and the immunoglobulin levels were normal. The HIV serologic study was negative (Table 2). CASES A 55-yeaNJld male agricultural worker, with a smoking habit (40 cigarettes per day), was previously diagnosed as suffering from PCP in Patients wtthout Pradisposing Illnesses (Csno et a/)

chronic obstructive pulmonary disease (COPD). He was admitted to the hospital in July 1987. Fifteen days before, he presented with 39"C temperature, chills, profuse sweating, and dyspnea. In the physical examination made at the time of hospital admission, bilateral rales were notable. The chest radiograph showed a bilateral alveolar infiltrate in the middle and lower fields. Total leukocyte count was 24.8 x 10"/L (75 percent neutrophils, 14 percent lymphocytes, 6 percent monocytes, 3 percent band forms, and 2 per<:ent metarnyelocytes), the hemoglobin level was 14.1 !lfdl, and the platelet count was 300 X 10"/L. The arterial blood gas analysis, while the patient was breathing room air, showed a Po, of 52 mm Hg and Pco2 of 36 mm Hg. Fiberoptic bronchoscopy was performed using bronchoaspirate and TPC to take samples. In the bronchial aspirate, P carinii cysts and trophozoites were identified and multiple flora of Gram-negative germs grew in the culture of TPC. Treatment with 320 mg of trimethoprim and 1,600 mg of sulfamethoxazole, every 6 hours, was begun, and there was a favomble response. Defervescence was attained 4 days later and an improvement was evident in the chest radiograph 8 days after beginning the treatment. Lymphocyte subpopulations (Table 2) and serum immunoglobulins were normal. Anti-HIV-1 antibody was negative . ACT scan of the chest and abdomen was performed, and there we re no signs suggesting neoplastic disease. During follow-up (32 months), the patient was not diagnosed as having any other pathologic pnx:ess. Lymphocyte subpopulations (Table 2) and immunoglobulin levels were found to be within normal limits. The serologic study for HIV-1 (Table 2) was negative. RESULTS

The average time of the follow-up period was 3.6 years (between 2.6 and 4 years). CD4 and CD8 lymphocyte subpopulation values, as well as the CD4:CD8 ratio, were within normal limits, in both the first and the last control. Serum immunoglobulin levels (IgG, IgM, and IgA) were normal in all their investigations, except in patient 3, who presented some slightly lower values of lgA in the final evaluation. All serologic studies for HIV (Table 2) were negative. Neoplastic or collagen-vascular disease indicators analyzed were negative. In none of the cases was there enlarged adenopathies or tumoral masses manifested in the Cf scans of chest and abdomen. Finally, all patients were well at the end of the followup period. DISCUSSION

This article describes a group of five patients with PCP in whom no predisposing factor could be detected, either during the acute episode or during the follow-up period (average duration, 3.6 years). Reports of PCP in patients without any known underlying immunosuppressive illnesses have been rare. After careful research, we found 11 cases, 1(}. 15 ·20 ·21 which can be reduced to 9, if homosexual patients with lymphopenia described at the beginning of the AIDS epidemic211·21 are excluded. In 1961, reports were published on the first previously healthy patients who presented with PCP. 10 • 12 Both were diagnosed by necropsy, and no associated predisposing illness was found. However, no immunologic study had been made before death. We have knowledge of only two

healthy subjects who were diagnosed as having PCP with normal results of immunologic study (measurement ofT and B lymphocytes and immunoglobulins, and investigation of the cellular immune response, in vivo and in vitro). 13 • 14 More recently, a cluster of PCP in subjects without predisposing illness was published and the immunologic study carried out on three of them revealed qualitative alterations of the cellular immune system. 15 Although not the most frequent form of presentation, PCP can manifest itself in clusters. Patients described in this series are probably isolated cases of PCP, since the diagnoses were made over a 15-month period and none of them had had a convivial relationship; also, their dates of hospital admission did not coincide. In two of our patients, microorganisms other than P carinii were isolated in respiratory specimens: P aeruginosa in patient 3, and multiple flora of Gramnegative germs in patient 5, the sample being taken with TPC in both cases. From a theoretic point of view, the possibility exists that patients of this report had suffered from pneumonia caused by microorganisms other than P carinii and the role of the latter was only a colonizer of the lung or airway. However, we consider this hypothesis most unlikely. Although there is serologic evidence oflatent infection by P carinii ,2 and the prevalence of this microorganism in adults with no predisposing illnesses is 0 .31 percent according to necropsic studies, 22 ·23 we have no knowledge of its identification in respiratory samples of subjects without pneumonia. On the other hand, patients in this report presented a picture compatible with PCP, the P carinii being identified in all cases using two tincture techniques; and in three cases, the specimens were obtained by two or more methods, and we believe that the response to co-trimoxazole was favorable . We believe, therefore, that the P carinii was the causal agent of the pneumonia in patients from this report. All five patients received the same anti-Pneumocystis treatment and the response was good in patients 1, 3, 4, and 5. Apyrexia and an evident improvement on the chest radiograph were achieved in an average period of 1 week. Patient 2 had a more complex clinical course and a later response to treatment. Patients 1, 2, and 3 developed ARDS . The association of PCP with ARDS is relatively frequent, being found in 25 percent of patients with AIDS admitted to a large metropolitan hospital and having PCP. 24 Although pleural effusion has been described in PCP,25- 27 its presence is infrequent and is usually bilateral and low in quantity.26 Patients 1 and 4 presented unilateral pleural effusion, and in patient 4, the P carinii was identified in the pleural fluid specimen and in the pleural tissue obtained by thoraCHEST I 104 I 2 I AUGUST. 1993

379

cotomy. The P carinii has been isolated in multiple sites other than the lung, 211-31 and only recently has it been isolated in the pleural tissue. 27 There was no evidence that patients in this report had any detectable illness predisposing them to PCP. However, some data suggested previous or simultaneous infection by another agent. Patient 1, before hospital admission, presented a picture compatible with an upper respiratory tract infection of viral cause. On the other hand, in patient 3, the serologic study for M pneumoniae is strongly suggestive of infection caused by this microorganism. It is possible that an infection previous to, or concomitant with, PCP produces a transitory alteration in the immunocompetency condition of the host. In fact, Mycoplasma may originate polyclonal activation of B cells and suppression ofT cells, which would explain the appearance of transitory cutaneous anergy.32 ·33 None of the patients in this study presented data that are compatible with the AIDS diagnosis. They did not belong to any high-risk group, and results of serologic studies for HIV were normal throughout the evaluation (Table 2). On the other hand, the CD4:CD8 ratio was shown to be within normal limits, and CD4 subpopulations were always above 450 mm 3 • A CD4 value of less than 250 mm3 in patients with HIV infection has been related to the risk of contracting PCP. 34 This pneumonia, however, can manifest in patients with a normal CD4 count, 14 • 15 •35 and in these cases, the PCP is probably associated with qualitative alterations of the cellular immune system. In support of this hypothesis, there are these findings in three patients with PCP who were previously healthy: absence of CD25+ , peripheral T cells and low stimulation indexes in the presence of mitogens. 15 We believe that the study of these parameters could serve as the basis for further investigation. Although it has been rarely described , PCP can appear in patients with deficiencies of the humoral immune system. 36 •37 In this respect , patients of this report presented no lowering of the immunoglobulin levels during the pneumonic episode and only patient 3 showed slightly diminished IgA at the end of the follow-up. This isolated alteration, however, has not been described in relation to PCP, and we do not know for certain what their implication is in the development of this pneumonia. To conclude, PCP can occur in patients who apparently show no immunosuppression. Therefore, in previously healthy patients who have serious pneumonia with unclear and poor response to the usual antibiotics, an investigation for P carinii is indicated. REFERENCES

Meuwissen J, Tanl>er I, Leewenber~ A. Parasitolo~ic and serologic observation of infection with Pne umocystis in humans.

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J Infect Dis 1977; 136:43-49 2 Pifer L, Hughes Wf, Stagno SS . Pneumocystis carinii infection: evidence for a high prevalence in normal and immunosuppressed children. Pediatrics 1978; 61 :35-41 3 Young LS . Pneumocystis carinii . In: Pennington JE, ed. Respiratory infections: diagnosis and management. 2d ed. New York: Raven Press, 1988; 570-82 4 Vanek J, Jivorec 0, Luckes J. Interstitial plasma cell pneumonia in infants. Ann Pediatr 1953; 180:1-21 5 Lunseth JH , Kirmse TW, Prezyna AP, Gerth R. Interstitial plasma cell pneumonia. J Pediatr 1955; 46:137-45 6 Walzer PO, Perl DP, Krogstad OJ. Pneumocystis carinii pneumonia in the United States: epidemiologic, diagnostic and clinical features. Ann Intern Med 1974; 80:83-93 7 Hughes Wf. Pneumocystis carinii pneumonitis. Chest 1984; 85:810-13 8 Rothenberg R, Woelfel M, Stoneburner R, Milberg], Parker R, Truman B. Survival with the acquired immunodeficiency syndrome: experience with 5,833 cases in New York city. N Eng! J Med 1987; 317:1297-1302 9 Centers for Disease Control. AIDS Weekly Surveillance Report- United States, October 12, 1987 10 Henningar GR. Pneumocystis carinii pneumonia in an adult. Am J Clin Pathol 1961; 35:353-64 11 Lyons HA. Pneumocystis carinii pneumonia unassociated with other disease. Arch Intern Med 1961; 108:173-80 12 Watanabe JM, Chinchinian H . Pneumocystis carinii pneumonia in a family. JAMA 1965; 193:119-20 13 Rao M, Steiner P. Pneumocystis carinii pneumonia occurrence in a healthy American infant. JAMA 1977; 238:2301 14 Kobayashi M. Association of Pneumocystis carinii pneumonia and scabies. JAMA 1982; 248:1973 15 Jacobs JL, Libby MD , Winters RA . A cluster of Pneumocystis carinii pneumonia in adult without predisposing illnesses. N Eng! J Med 1991; 324:246-50 16 Reynolds HY, Newhall HH . Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage. J Lab Clin Med 1974; 84:559-73 17 Wimberley N, Faling LJ, Bartlett JG . Afiberoptic bronchoscopy technique to obtain uncontaminated lower airway secretions for bacterial culture . Am Rev Respir Dis 1979; 119:337-43 18 Zabala DC. Diagnostic fiberoptic bronchoscopy: techniques and results of biopsy in 600 patients. Chest 1975; 68:12-19 19 Permutt LM, Johnston WW, Dunnick NR. Percutaneous transthoracic needle aspiration: a review. AJR 1989; 152:451-55 20 Waldhorn RE. Pneumocystis carinii pneumonia in a previously healthy adult. JAMA 1982; 247:1060-61 21 Spange nthal S, Beer OJ, Snydman DR. Pneumocystis carinii and cytomegalovirus pne umonia in a previously healthy adult. Am Rev Respir Dis 1982; 125:601-03 22 Hamlin WB. Pneumocystis carinii. JAMA 1968; 204:173-74 23 Esterly LA . Pneumocystis carinii in lungs at autopsy. Am Rev Respir Dis 1968; 97:935-37 24 Braumann WR, Jung RC , Koss M . Incidence and mortality of adult respiratory distress syndrome: a prospective analysis from a large metropolitan hospital . Crit Care Med 1986; 14:1-4 25 Levine SJ, White AD. Pneumocystis carinii . Clin Chest Med 1988; 9:395-423 26 DeLorenzo LJ, Huang CT, Maguire GP, Stone OJ. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS . Chest 1987; 91 :323-27 27 Balachandmn I, Jones DB, Humphrey OM . A case of Pneumocystis carinii in pleural Ruid with cytologic, histologic and ultrastructural documentation. Acta Cytol 1990; 34:486-90 28 Coulman CU, Greene I, Archibald RWR. Cutaneous pneumocystosis. Ann Intern Med 1987; 106:396-98 29 Schinella RA, Breda SO, Hammerschlag PE . Otic infection due PCP in Patients without Predisposing Illnesses (Cano et al)

30 31

32 33

to Pneumocystis carinii in an apparently healthy man with antibody to the human immunodeficiency virus. Ann Intern Med 1987; 106:399-400 Rahimi S. Disseminated Pneumocystis carinii in alymphoplasia. Arch Pathol 1974; 97:162- 65 Telzak EE, Cote JR, Gold JWM, Campbell SW, Armstrong D. Extrapulmonary Pneumocystis carinii infections. Rev Infect Dis 1990; 12:380-86 Cassell GH, Cole BC. Mycoplasmas as agents of human disease. N Eng! J Med 1981; 304:80-89 Fernald GW Immunologic interactions between host cells and mycoplasmas: an introduction. Rev Infect Dis 1982; 4(suppl):201

34 Masur H, Ognibene FP, Yarchoan RY, Shelhamer JH, Baird BF. Travis W. et al. CD4 munts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med 1989; 111:223-31 35 Kennedy CA, Goetz MB, Mathisen GE . Absolute CD4 lymphocyte counts and the risk of opportunistic pulmonary infection. Rev Infect Dis 1990; 12:561-62 36 Burke BA, Good RA. Pneumocystis carinii infection. Medicine 1973; 52:23-51 37 Heinzel FP. Infections in patients with humoral immunodeficiency. Hosp Pract 1989; 15:99-130

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