Humoral and cellular immune responses to an envelope-associated antigen of herpes simplex virus.

The humoral and cellular immune responses of rabbits and guinea pigs to the envelope-associated antigen of herpes simplex virus type I were studied. Neutralizing antibody (at high titer) and lymphocytes reactive to herpes simplex virus were detected in both guinea pigs and rabbits after immunization with the antigen. In a standard assay of cellular immunity to herpes simplex virus, the antigen stimulated blast transformation of herpes simplex virus-reactive splenic lymphocytes in vitro. Furthermore, immunization of rabbits with the envelope-associated antigen protected the animals from a lethal dose of live herpes simplex virus. Thus an antigen of herpes simplex virus can be prepared which contains neither infectious nor noninfectious viral particles and which stimulates immunity to the virus in laboratory animals.     

Dissemination of Pneumocystis carinii in patients with AIDS.

Extrapulmonary Pneumocystis carinii infections in AIDS are still rare although the number of cases is increasing. We present 2 cases of extrapulmonary pneumocystosis detected at our institution during an 8-month period. The first was a patient treated for P. carinii pneumonia (PCP) disseminated to liver, spleen and kidneys. The second patient had widely dissemination of P. carinii diagnosed at autopsy. Both patients had received aerosolised pentamidine (AP) for PCP prophylaxis. Totally we have treated patients with AP prophylaxis for 122 patient years and found a frequency of extrapulmonary spread of 1.6% compared to none in the 116 patient years on sulfamethoxazole-trimethoprim.     

Pneumocystis carinii and Toxoplasma gondii infections in patients with AIDS

Pneumocystis carinii and Toxoplasma gondii are the commonest protozoans causing infections in patients with acquired immunodeficiency syndrome (AIDS). P. carinii is almost exclusively a pulmonary pathogen and caused the commonest serious infection experienced by AIDS patients. The clinical findings are those of progressive pneumonia. Diagnosis requires microscopic examination of lower respiratory secretions or lung tissue. Pentamidine or combinations of trimethoprim and sulfamethoxazole are equally effective (85% recovery), but about one-half of patients thus treated experience severe toxicity. T. gondii infections occur primarily in the brain; patients present with focal seizures or neurologic deficit and have focal abnormalities as assessed by computed tomography. Serologic tests for toxoplasmosis are rarely diagnostic in AIDS patients, and most patients are treated empirically with a combination of pyrimethamine and sulfonamide. Less invasive diagnostic tests and better chemotherapeutic agents are required for both pneumocystosis and toxoplasmosis.     

Pneumocystis carinii pneumonia in patients with AIDS in the Congo

Forty-five bronchoalveolar lavages (BAL) were performed in Brazzaville in AIDS patients who did not expectorate acid- and alcohol-resistant bacilli (AARB). All patients presented with respiratory symptoms (cough, dyspnoea or chest pain), and all but 6 of them had abnormal radiography of the chest. Four cases of pneumocystosis were diagnosed (9%); 3 of these patients had interstitial pneumonia and dyspnoea. No AARB was found at microscopic examination of BAL which showed Pneumocyctis carinii; no culture on L?wehstein's medium could be made. The authors consider that the low prevalence of pneumocystosis in Africa, compared with industrial countries, is due to a smaller dissemination of the parasite in Africa rather than to immunodepression which is known to be more pronounced in AIDS patients from industrial countries.     

Bronchial responsiveness in AIDS patients with Pneumocystis carinii pneumonia.

OBJECTIVE: To study bronchial responsiveness to inhaled histamine among HIV-infected patients. DESIGN: A prospective study in a regional infectious diseases unit. METHODS: Three groups of patients were studied. Group A consisted of AIDS patients (n = 7) who had had Pneumocystis carinii pneumonia (PCP), group B of AIDS patients (n = 7) not known to have had PCP, and group C of asymptomatic HIV-positive patients (n = 7). Inhalational histamine challenge in cumulative doses (0.03-3.91 mumol) was administered by a nebulizer. It was stopped when the forced expiratory volume in 1 sec (FEV1) had fallen by more than 20% of the baseline value or when the cumulative dose administered exceeded 3.91 mumol. Response was measured as percentage change in FEV1 from the baseline value, and plotted on a linear scale against log dose histamine to enable the dose of histamine causing a 20% fall in FEV1 (PD20-FEV1) to be determined. Statistical analysis was performed by analysis of variance. RESULTS: AIDS patients previously infected with PCP (group A) had a significantly lower PD20-FEV1 [(mean, 0.31 mumol; range, 0.07-0.95; s.d., 0.31; s.e., 0.12; 95% confidence interval (CI), 0.03-0.60)] than AIDS patients without PCP (group B; mean, 1.01 mumol; range, 0.20-2.00; s.d., 0.67; s.e., 0.25; 95% CI, 0.39-1.64) or asymptomatic HIV-positive patients (group C; mean, 1.28 mumol; range, 0.49-1.80; s.d., 0.51; s.e., 0.19; 95% CI, 0.81-1.76) (P < 0.05). There was no significant difference between groups B and C. All patients recorded PD20-FEV1 within the asthmatic range of bronchial hyper-responsiveness. CONCLUSIONS: These results suggest that development of PCP in a small group of HIV-infected patients induces a significantly greater degree of bronchial hyper-responsiveness.     

Pneumocystis carinii pneumonia treated with eflornithine in AIDS patients resistant to conventional therapy

Eflornithine (DFMO) was used to treat 31 AIDS patients with confirmed Pneumocystis carinii pneumonia who had clinically failed treatment with pentamidine, sulphamethoxazole-trimethoprim or both agents as their first-line therapy. Twenty-one of 31 (68%) responded to second-line treatment with 400mg/kg per day of eflornithine. Five patients discontinued treatment because of bone marrow toxicity. Eflornithine appears to be a useful salvage therapy in patients failing first-line treatments.     

Pneumocystis carinii pneumonia in patients with AIDS in Central Africa.

Over a period of 11 months, 37 patients infected with the Human Immunodeficiency Virus (HIV) presenting with symptoms of bronchopulmonary disease were investigated. Patients presented with cough, weight loss, fever and dyspnoea. Investigations included fibreoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. In eight patients (22%) Pneumocystis carinii was found. Pulmonary infiltrates were found on chest radiographs of six patients, while in the remaining two patients chest radiographs showed clear lung fields. P. carinii was found in two patients with pulmonary Kaposi's sarcoma. Infection with P. carinii often occurred with other pathogens: Streptococcus pneumoniae was found in four patients, Staphylococcus aureus in two and tuberculosis in two. P. carinii pneumonia does occur in patients with HIV infection in Africa and the diagnosis is relatively simple to make provided that transbronchial biopsy and bronchoalveolar lavage are carried out through a fibreoptic bronchoscope and specimens examined after appropriate staining. However, the prevalence of P. carinii in patients with HIV infection in Africa appears to be lower than that found in patients with HIV infection in Europe and North America.     

Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS

We reviewed the initial and follow-up chest roentgenograms (CXR) of 104 patients with the acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) diagnosed between 1981 and 1985 in order to determine the relative frequencies of its various roentgenographic patterns. Although a diffuse bilateral interstitial infiltrate is most common, it was concluded that unusual and atypical roentgenographic manifestations of PCP occur in AIDS. These include localized infiltrate, cystic or honeycomb lesions, hilar enlargement and spontaneous pneumothorax.     

Improved survival in patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure

Pneumocystis carinii pneumonia (PCP) causing acute respiratory failure (ARF) in patients with acquired immunodeficiency syndrome (AIDS) has been reported in several studies to have a mortality of 84 to 100 percent. A recent report found a 42 percent survival rate. We followed 58 patients with AIDS who required positive pressure ventilation and identified 33 patients with PCP and ARF who had a PaO2/FIo2 level less than 150 mmHg. We report the survival of 12 of these 33 (36 percent). The mean duration of survival after discharge from the hospital was 7.9 +/- 1.8 months, which is an improvement over previous reports. These data suggest that we should reevaluate the reported recommendations that patients with AIDS, PCP and ARF should not receive intensive care or mechanical ventilation.     

The outcome of Pneumocystis carinii pneumonia in Danish patients with AIDS

A total of 100 consecutive patients with AIDS were evaluated for efficacy and safety of treatment and secondary prophylaxis directed against Pneumocystis carinii pneumonia (PCP). 89 episodes of PCP were recorded in 75 patients. 63 of the 75 patients (84%) with a first episode of PCP were discharged. Of 72 patients with a first episode of PCP who were initially treated with trimethoprim-sulfamethoxazole. 76% completed therapy successfully. Side effects were common, but generally mild and tolerated during continued treatment. 7/11 patients (64%) with a first episode of PCP who required mechanical ventilation were discharged. Long term prognosis for these patients was not worse than for patients who did not require mechanical ventilation. Relapse of PCP occurred in 3/50 patients (6%) during secondary prophylaxis, 160 mg trimethoprim and 800 mg sulfamethoxazole (TMP-SMZ) every 24 h, compared to 11/16 (69%) patients who were not receiving prophylaxis (p less than 0.00001). No patients discontinued prophylaxis because of side effects. It is concluded that for most patients with AIDS and PCP, treatment and secondary prophylaxis with TMP-SMZ is safe and effective.     

Pneumocystis carinii pneumonia in young children with AIDS

We present our experience with 54 episodes of Pneumocystis carinii pneumonia in 50 young children with AIDS, all but one representing congenitally acquired infection. Findings at history and physical examination are not helpful in suggesting the diagnosis. The diagnosis is suggested by marked hypoxemia, diffuse disease on chest radiograph, and elevated serum LDH level. Because important aspects of the history may be withheld, a high index of suspicion may be necessary for the correct diagnosis. The mortality rate for ventilated patients was 50%.     

Transmission of Pneumocystis carinii from AIDS patients to other immunosuppressed patients: a cluster of Pneumocystis carinii pneumonia in renal transplant recipients.

Five renal transplant recipients developed Pneumocystis carinii pneumonia (PCP) over a 22-month period, while no cases had been observed over a 5-year period in 114 transplanted patients treated with the same immunosuppressive protocol. All patients were HIV-negative, and no modification in diagnostic techniques for P. carinii could account for this observation. All five patients developed PCP within 2 months of an acute graft rejection episode. All of them attended the same outpatient facility as AIDS patients attending the hospital, where they shared the waiting and treatment rooms. Comparison of cases with matched controls was possible in three instances and revealed that the cases had had more outpatient clinic encounters with AIDS patients who had presented, or subsequently developed, PCP. This observation suggests that AIDS patients developing PCP may transmit the infection to other immunosuppressed patients.     

Humoral response to herpes simplex virus is complement-dependent

The complement system represents a cascade of serum proteins, which provide a major effector function in innate immunity. Recent studies have revealed that complement links innate and adaptive immunity via complement receptors CD21/CD35 in that it enhances the B cell memory response to noninfectious protein antigens introduced i.v. To examine the importance of complement for immune responses to virus infection in a peripheral tissue, we compared the B cell memory response of mice deficient in complement C3, C4, or CD21/CD35 with wild-type controls. We found that the deficient mice failed to generate a normal memory response, which is characterized by a reduction in IgG antibody and germinal centers. Thus, complement is important not only in the effector function of innate immunity but also in the stimulation of memory B cell responses to viral-infected cell antigens in both blood and peripheral tissues.     

Hypertrophic osteoarthropathy associated with Pneumocystis carinii pneumonia in AIDS

Hypertrophic osteoarthropathy (HOA) is a systemic disorder primarily affecting the bones, joints, and soft tissues and developing in association with another disease process. Acute pyogenic pulmonary processes (empyema, lung abscess) are occasionally accompanied by transient HOA, but reversible HOA has not previously been reported in the setting of PCP in AIDS.     

Aerosolized pentamidine as second line therapy in patients with AIDS and Pneumocystis carinii pneumonia

The use of aerosolized pentamidine was investigated in ten patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who had previous or concurrent severe adverse reactions or contraindications to trimethoprim-sulfamethoxazole or parenteral pentamidine. A dose of 600 mg pentamidine in 6 ml sterile water, aerosolized in a small-particle producing jet nebulizer was administered for 25 minutes once daily for an average of 10.5 days to these ten patients. All patients improved their arterial O2 saturation and showed clinical and roentgenographic improvement within six to 21 days of aerosol pentamidine therapy. No adverse systemic reactions occurred. The results of this small open trial indicate that aerosolized pentamidine is effective and can be given safely to AIDS patients with PCP who have had adverse reactions to trimethoprim-sulfamethoxazole or parenteral pentamidine.