[Systemic antifungal drugs].
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Biomedical subjects
Publications and source records attributed to P Ruutu.
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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.
Viral causes of acute lower respiratory tract infection were studied prospectively between 15 June and 31 October 1984 in 312 Filipino children less than 5 years old living in periurban slums and middle-class housing. The cause was based on viral antigen detection, virus isolation, and antibody assays. There were 131 children (41.2%) who were admitted to the hospital, and 150 (47%) had an infiltrate on chest radiograph. A total of 198 viral infections were confirmed in 162 patients (51.9%), 42.3% with single viral infection and 9.6% with mixed (two or more) infection. The infections were measles (21.4%), influenza A (15.9%), parainfluenza types 1, 2, and 3 (8.8%), respiratory syncytial virus (7.1%), influenza B (5.8%), enteroviruses (5.1%), adenoviruses (3.9%), herpes simplex virus (1.6%), and cytomegalovirus (1.3%). Viral infections other than measles were seen in 39.7% of the cases. The presence of viral infection correlated with better nutritional status. Influenza A or B diagnosis was associated with mild forms of acute respiratory tract infection, measles and a preceding rash with severe disease.
The acute phase response induced by 19 episodes of Pneumocystis carinii pneumonia (PCP) was analysed in a retrospective study. There were 9 men and 1 woman with HIV, aged 25-45 years (mean 37.2) and 4 men and 4 women with other immunodeficiencies, aged 18-35 years (mean 26.2). The outcome of these two groups with PCP did not differ: in the HIV group 4 died and in the non-HIV group 2 died. In the HIV group, peak serum C-reactive protein (S-CRP) ranged 41-228 mg/l, mean 126 (77.3), and in the non-HIV group 19-290 mg/l, mean 105 (89.1) (NS). The patients with a fatal outcome had higher mean peak S-CRP: 186 (73.8) mg/l versus 85.3 (63.5) mg/l in the survivors (p = 0.007). The HIV infection itself did not increase the S-CRP concentration, which was normal before or after PCP in all 7 survivors of the 11 episodes. Thus, PCP induces a clear-cut S-CRP response, which may be used for monitoring the treatment and evaluating the prognosis of the patient.
Indications for use of influenza and pneumococcal vaccines are reviewed in view of current knowledge of the incidence, risk factors and etiology of pneumonia in adults. It appears that both vaccines contribute equally in an almost additive fashion to predicted benefits of vaccination; therefore, both should be used for maximum benefit. Target groups for vaccination include both elderly persons (e.g. 65 years and older) and younger ones who have medical risk factors that increase the likelihood or severity of pneumonia.
The two methods commonly used to diagnose cytomegalovirus (CMV) infections, conventional tissue culture and detection of early CMV nuclear antigen by immunofluorescence from cell culture, were performed in parallel on 597 clinical specimens. CMV was detected by the early-antigen test in 108 samples, of which 102 (94%) were detected 1 to 3 days after inoculation. Of these 108 CMV-positive specimens, seven were negative on conventional culture. Two samples negative in the early-antigen test were positive on conventional culture. Thus, CMV was detected in 110 specimens. A cytopathic effect in conventional tissue culture occurred 9 to 42 days after inoculation. The diagnosis of CMV infection was possible by the conventional method 29.6 +/- 12.7 days and by early-antigen immunofluorescence 1.9 +/- 1.5 days after obtaining the specimen. The rapid early-antigen test was slightly more sensitive than culture, and fewer samples were lost due to bacterial or fungal infections during incubation. Detection of CMV by conventional culture usually requires several weeks and provides a diagnosis only retrospectively. The main advantage of the early-antigen test is that a virologically proven diagnosis of CMV infection is available at an early stage.
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Heme synthesis was studied by measuring the activity of delta-aminolevulinic acid synthase (AmLev synthase) in granulocytes, the activity of delta-aminolevulinic acid dehydratase (AmLev dehydratase) and of uroporphyrinogen I synthase in erythrocytes as well as the concentrations of coproporphyrin and protoporphyrin in erythrocytes of 6 patients with Pelger-Huët anomaly. 3 of these patients from the same kindred had a syndrome of recurrent attacks of fever and abdominal pains, a tendency to skin infections, delayed wound healing and impaired neutrophil motility. The other 3 patients were asymptomatic. The activity of AmLev synthase was depressed in all 3 symptomatic patients and normal in the asymptomatic patients. 1 symptomatic patient had a decreased erythrocyte protoporphyrin concentration. These findings indicate a derangement of heme synthesis in the symptomatic patients. Their abdominal pain attacks could be due to heme depletion. The findings suggest that the abdominal pains of patients with porphyria could be due to decreased heme synthesis rather than due to accumulation of porphyrin precursors in tissues. The cause of the impaired neutrophil motility may be a defect in energy metabolism due to decreased supply of heme for oxidative metabolism.
Within a period of 15 months 8 cases of invasive pulmonary aspergillosis were seen in a haematologic unit; 7 of them between January and October 1984. No previous cases of invasive aspergillosis had been encountered during the existence of the unit since 1979. Environmental studies did not prove a single likely source for the fungal spores. Previous window renovation with concomitant fiber deposits on ventilation grids, poor sealing of air filter fittings in patient rooms, occasional ventilation through windows in the ward, and low speed of booster fans in the ventilation system may have created a condition favourable for the entry of Aspergillus fumigatus spores into the patient rooms. Environmental sanitation including cleaning of the ventilation ducts and change of filters in the ventilation system stopped the outbreak. Two sporadic cases have appeared during a follow-up period of 26 months.
A 47-year-old female with acute myeloid leukemia received HIV positive platelets during induction chemotherapy. 18 days later, coincident with the recovery of the bone marrow function, she developed an erythematous rash, mild lymphadenopathy, and nausea which disappeared within 10 days. A week later mild CSF pleocytosis consisting of mature lymphocytes and macrophages together with elevated CSF protein levels (1,080 mg/l) were observed suggesting mild aseptic meningitis, and the HIV was concomitantly isolated from CSF. The CSF abnormalities have improved and the patient is well and in remission after 3 cycles of chemotherapy. This case expands the clinical spectrum of HIV infection to include a primary syndrome during immunosuppression from an unrelated cause.
Eight patients with haematologic malignancies contracted fatal invasive aspergillosis during an outbreak. Five patients were neutropenic. Bronchofiberoscopic examination with microbiology specimen brush and bronchoalveolar lavage yielded Aspergillus fumigatus in only 2/5 patients examined. The specific diagnosis reached during lifetime in 5 patients was based on a combination of invasive procedures (lung biopsy in 2, percutaneous lung puncture in 1), the presence of a lung abscess (3 patients), seroconversion (1 patient), and purulent maxillary sinusitis caused by A. fumigatus together with repeated abundant growth of A. fumigatus in the sputum (1 patient). Six patients received amphotericin B. The infection was temporarily controlled only in 2 bone marrow transplant recipients whose granulocyte counts recovered. In 3/8 patients the pneumonia was of polymicrobial aetiology, Mycobacterium tuberculosis (2 patients), Pneumocystis carinii (1 patient), and Legionella pneumophila (1 patient) being the other microbes involved. 3/4 bone marrow transplant recipients with aspergillosis had been transplanted for chronic myeloid leukaemia, supporting the previously reported association of bone marrow transplantation for chronic myeloid leukaemia and the risk of invasive aspergillosis. Improved diagnostic methods for earlier definitive diagnosis of invasive aspergillosis as well as more efficacious and less toxic antifungal agents are needed to allow early treatment.
Bone marrow transplantation recipients who were cytomegalovirus (CMV) seropositive and/or had a CMV seropositive donor were randomized for treatment with CMV hyperimmune plasma (n = 27) or no treatment at all (n = 27). The CMV hyperimmune plasma had neutralization titers greater than 250 and enzyme-linked immunosorbent assay titers greater than 18,000. Plasma (200 mg/kg body weight) was given on four occasions (during 2 days) from day 3 to day 76 after transplantation. Patient characteristics were similar in the two groups. After transplantation, the median CMV titers increased with greater than 100% in the group receiving the CMV plasma and decreased to less than 50% in the controls (p less than 0.01). Asymptomatic CMV infections occurred in 26% of the patients in the plasma group and 33% of the controls. The frequency of patients with symptomatic CMV infections was also the same in the two groups (51% vs 33%). Three patients each in the two groups developed CMV-associated interstitial pneumonitis. Patient survival and causes of death were similar in the two groups. To conclude, no beneficial effect of CMV hyperimmune plasma was seen in patients at high risk of developing CMV infections.