The major late promoter and bipartite leader sequence of fowl adenovirus

Invasive pulmonary aspergillosis in immunocompromised patients (ICP) is the second most frequent opportunistic fungal infection. The causative organism includes 16 species of Aspergillus, of which A. fumigatus dominates the ubiquitous incidence of invasive or allergic broncho-pulmonary aspergillosis (ABPA). The definitive diagnosis of invasive aspergillosis is difficult. We have analyzed 24 strains of A. fumigatus recovered from ICP using the RAPD technique. The profiles generated with the 20 primers tested were mostly unique. These results may have a profound impact on the management of aspergillosis, especially in the ICP.     

Anti-obesity drugs

In patients with hematological malignancies invasive mycoses occur frequently. In this retrospective study autopsy and histopathology material of 171 patients with hematological malignancy who had died between 1994 and 1996 at the 1st Department of Internal Medicine (Hematology), St. László Hospital, Budapest was analysed. In cases with invasive fungal infection post mortem results were compared to clinical and microbiological data. Through the three years' period an invasive mycosis could be confirmed in 33 patients by autopsy. Aspergillosis occurred in 21, candidiasis in 11, other fungal infections in 2 cases, a double infection was seen in 1 patient. The incidence was 19.2% (in invasive candidiasis: 6.4%, in aspergillosis 12.2%). Invasive aspergillosis most frequently was seen in the lung (71%), while candidiasis occurred mainly in the intestinal tract (42%). Cultures for mycology were collected from the autopsy material of 9 patients, of which 8 gave positive results. A previous fungal colonisation results was confirmed in 23 patients, but based on colonisation conclusions rarely could be driven concerning the species causing invasive infection. Sensitivity of Aspergillus antigen and antibody tests was 45 and 50%, respectively. Predisposing factors for invasive aspergillosis and candidiasis were similar, except for duration of neutropenia (24 vs. 12 days, p < 0.004). The antifungal drug most frequently used was amphotericin B. We observed a persisting infection in invasive pulmonary aspergillosis and chronic disseminated candidiasis in spite of the administration of a cumulative dosis of 1-2 g. Most frequently Aspergillus infections--primarily that of the lung--can be seen. Presence of invasive mycoses can usually be confirmed in vivo, but an early diagnosis still remains unsolved.     

Cavitary pulmonary lesions in patients infected with human immunodeficiency virus

The differential diagnosis of cavitary pulmonary lesions in individuals infected with human immunodeficiency virus (HIV) is broad, especially in patients with advanced disease. In patients with Pneumocystis carinii pneumonia, cavitation is an uncommon manifestation of a common disease. It is unusual in patients with pulmonary cryptococcosis, coccidioidomycosis, and histoplasmosis but occurs frequently in patients with invasive pulmonary aspergillosis. In patients with pulmonary tuberculosis, cavities are more common during earlier stages of HIV disease, when cellular immunity is relatively preserved. Mycobacterium avium complex is an uncommon cause of lung disease and infrequently produces cavities. However, Mycobacterium kansasii, is often associated with cavitation. Cavities can complicate any bacterial pneumonia and are especially common with pneumonia due to Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi. Noninfectious causes of cavitary lesions are rare, but cavitary lesions caused by pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported. Because of the broad differential diagnosis and because most cavities are caused by treatable opportunistic infections, a definitive diagnosis is essential.     

Opportunistic fungal infections: filamentous fungi and cryptococcosis

Older patients with diabetes mellitus or pulmonary diseases and those receiving immunosuppressive drugs are at an increased risk of infection with environmentally-acquired, opportunistic fungal diseases. Aspergillus most often produces invasive pulmonary or sinus infection in severely immuno-compromised patients. Chronic necrotizing pulmonary and sino-orbital aspergillosis present subacutely and are often misdiagnosed. Mucormycosis classically presents with rhinocerebral disease in diabetic patients with ketoacidosis, whereas pulmonary infection mimics invasive pulmonary aspergillosis and occurs mostly in patients who are neutropenic. Cryptococcal meningitis in the older patient may manifest simply as confusion. Amphotericin B is the preferred initial treatment for all three fungal infections.     

Changes in the natural history of invasive pulmonary aspergillosis in neutropenic leukemic patients

We describe five patients with acute leukemia who during the period of chemotherapy-induced neutropenia developed invasive pulmonary aspergillosis. Amphotericin B was initiated early in the febrile neutropenic episode at a dose of 1-1.5 mg/kg per day. Four of the five patients had normal chest films at the time amphotericin B was started and only later developed infiltrates, which subsequently progressed to cavitation formation with resolution of the infiltrates around the cavitations. This is compatible with primary aspergilloma or invasive pulmonary aspergillosis. The patients experienced partial (2 patients) or complete resolution (3 patients) of the process, and none died of the fungal infection. In the past, infection with invasive aspergillosis carried a high mortality. We believe that this positive outcome constitutes a change in the natural history of invasive pulmonary aspergillosis in neutropenic patients as a result of the early initiation of high dose amphotericin B. We recommend the early empiric use of amphotericin B therapy in febrile neutropenic patients not responding to broad-spectrum antibiotics, and that the minimal initial dose be 1 mg/kg per day especially in institutions carrying a high incidence of aspergillosis.     

Selenocysteine inserting RNA elements modulate GTP hydrolysis of elongation factor SelB

Invasive pulmonary aspergillosis (IPA) is associated with a high mortality. In 27 consecutive neutropenic patients who underwent lung resection for suspected IPA, we analyzed preoperative diagnostic evaluation, operative procedure, perioperative management, histological findings, outcome concerning recurrence of aspergillosis, and survival to evaluate the morbidity and mortality of a surgical treatment of IPA. Seventeen patients with hematologic diseases had previously undergone high-dose chemotherapy and four stem cell transplantation. Six patients with aplastic anemia were treated with antilymphocyte globulin. IPA was suspected if localized infiltrates developed on thoracic CT scan, and fever persisted under antibiotic therapy in neutropenic patients. In only one case a diagnosis of IPA could be made preoperatively. Twenty patients underwent lobectomy and seven wedge resection. At day of surgery the neutrophil count was below 500 x 10(9)/L in 78% of patients, and the platelet count below in 50 x 10(9)/L in 58% of patients. Invasive fungal infection was confirmed histologically in 22 of 27 patients (81.5%); in five patients no fungal infection was documented. The median duration of surgery was 120 min. Postoperatively, patients stayed one night in the intensive care unit, and chest tubes were removed after 2 d. Within 7 d a median of four erythrocyte packs and two platelet packs per patient were replaced. Major surgical complications occurred in two patients (bronchial dehiscence; pleural aspergillosis). Minor surgical complications included prolonged chest tube drainage (recurrent pneumothorax, n = 2; air leakage, n = 1; hematothorax, n = 1), pleural effusion (n = 4), and seroma (n = 2). Postoperatively, two patients suffered from histologically proven disseminated aspergillosis (pleural aspergillosis, renal aspergilloma) and another patient from suspected orbital aspergillosis. At 30 d postoperative mortality was 11% and 3-mo survival was 77%. After lung resection, seven patients underwent stem cell transplantation without recurrence of IPA. In conclusion, we suggest lung resection is a therapeutic option for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases and is associated with a low surgery-related morbidity and mortality.     

Evaluation of PCR for detection of DNA specific for Aspergillus species in sera of patients with various forms of pulmonary aspergillosis

Pulmonary aspergillosis is classified into invasive, saprophytic, and allergic forms. In this study, we evaluated the usefulness of PCR for differentiating between different forms of aspergillosis or in monitoring disease activity during treatment by detecting DNA specific for Aspergillus species in the serum. Nested PCR was used to detect Aspergillus DNA in the sera of 30 patients with various forms of pulmonary aspergillosis. The results were compared with those of latex agglutination tests for detecting galactomannan antigen. We also examined the serial changes in the results of nested PCR during and after treatment of a subgroup of patients with invasive pulmonary aspergillosis with amphotericin B. The highest proportion of positive nested PCR results were in patients with invasive aspergillosis (10 of 12; 83%), while patients with pulmonary aspergilloma had the lowest frequency of positive tests (1 of 9; 11%). These results suggested that the sensitivity of the nested PCR depends on the extent of invasion by Aspergillus species. Serial assays showed that the results of nested PCR became negative shortly after commencement of antifungal treatment and that such changes did not correlate with clinical responsiveness to treatment. Our results indicate the potential usefulness of nested PCR with serum samples for the diagnosis of invasive aspergillosis and the detection of a shift in the status of infection from a noninvasive type to invasive aspergillosis. However, the results of the nested PCR did not correlate with the response to antifungal treatment.     

The changing role of village health volunteers in northeast Thailand: an ethnographic field study

Aspergillus sinusitis is an uncommon complication of advanced human immunodeficiency virus (HIV) infection. We describe 2 patients with AIDS who developed histologically proven invasive Aspergillus sinusitis. We also review the findings of 14 histologically documented and 5 probable cases of invasive Aspergillus sinusitis. The literature on the prevalence, predisposing factors, diagnosis, treatment, and prognosis of the infection is reviewed. Major risk factors for the disease are advanced AIDS, chronic sinusitis or otitis, neutropenia, use of corticosteroids and prolonged use of broad spectrum antibiotics. The most common presenting symptoms are nonspecific and include fever, local pain, and swelling. Despite the newer diagnostic and therapeutic approaches discussed herein, the infection is usually fatal in HIV-infected patients. Early diagnosis and aggressive treatment remain the only available means to improve the currently dismal prognosis of Aspergillus sinusitis.     

Central venous catheter infection by Aspergillus fumigatus in a patient with B-type non-Hodgkin lymphoma

Invasive Aspergillus infection is still a major problem in immunocompromised patients. A central venous catheter infection by Aspergillus fumigatus, however, has not yet been reported. We describe the case of a 10-year-old female patient with B-type non-Hodgkin lymphoma treated according to the German chemotherapy protocol NHL-BFM 90. Isolation of Aspergillus fumigatus from the blood was the first hint of invasive aspergillosis. A central venous catheter-associated infection was suggested, since Aspergillus was also isolated from the thrombotic tip of the removed catheter. Secondary pulmonary aspergillosis was documented radiologically. The patient was treated successfully by Ampho-thericin B and Itraconazol and explantation of the central venous catheter under conditions of complete hematopoietic regeneration of the bone marrow with omission of the final chemotherapeutic cycle.     

Invasive pulmonary aspergillosis in an apparently nonimmunocompromised host

Invasive aspergillosis generally occurs in patients with hematologic malignancies, neutropenia or other severe derangements of host defense. An adult patient without such a predisposition, and without a previous history of susceptibility to infections, had rapidly progressive respiratory failure associated with repeated growth of Aspergillus fumigatus on culture of sputum and bronchoscopy specimens. At autopsy he proved to have invasive pulmonary aspergillosis.     

Placement of screws in subtalar arthrodesis: a simplified technique

Risk factor for invasive pulmonary aspergillosis in HIV-negative patients include neutropenia, corticosteroid therapy, and chemotherapy. Corresponding risk factors in HIV-positive patients have not yet been reported. A case-control study was conducted at the Bichat-Claude Bernard Teaching Hospital, Paris, France, between 1991 and 1996. Eight cases were identified. In three cases, the diagnosis was documented histologically. Of the remaining five patients, four had a de novo lung cavity with a positive bronchoscopy sample, and one had a pulmonary infiltrate with a positive bronchoscopy sample in the absence of any other potential pathogen. Each case was matched with three controls who were admitted during the same period and had CD4 counts lower than 50/mm3. Median age was 38.1 years in the cases and 38.4 years in the controls. Median CD4 counts were 12.5 +/- 19.2 in the cases versus 19.3 +/- 16.3 in the controls (P = 0.14). No case-control differences were found for AIDS duration, neutrophil counts at diagnosis or during the previous six months, history of corticosteroid therapy or chemotherapy, or number of previous opportunistic infections. Cases were more likely than controls to have a preexisting lung cavity (3/8 versus 0/24; P = 0.01) and had spent more time in the hospital during the previous year (7 +/- 4.5 versus 2.8 +/- 3.2 weeks; P = 0.02). These data do not support a role for neutropenia or immunosuppressive treatments as risk factors for invasive aspergillosis in AIDS. They suggest that AIDS patients with a lung cavity or frequent hospital stays are at increased risk for invasive aspergillosis.     

Aspergillus laryngotracheobronchitis presenting as stridor in a patient with peripheral T cell lymphoma

Invasive aspergillosis is a serious opportunistic infection in immunocompromised patients. The case history is described of a 44 year old patient with peripheral T cell lymphoma who developed hoarseness and stridor after chemotherapy. Aspergillus fumigatus was isolated repeatedly from the sputum. Bronchoscopic examination showed symmetrical creamy-white exophytic lesions involving both vocal cords and the supraglottic area. There was diffuse tracheobronchitis with multiple raised cream-coloured plaques in the trachea which histologically consisted of numerous septate branching hyphae consistent with Aspergillus species. The lesions responded to systemic treatment with amphotericin B.     

Outcome of ICU treatment in invasive aspergillosis

OBJECTIVE: To assess the outcome of intensive care treatment in invasive aspergillosis. DESIGN: Retrospective study. SETTING: University Hospital, Medical Intensive Care Unit (ICU). PATIENTS: Twenty-five patients with invasive aspergillosis who were admitted to the medical ICU in a 5 1/2 year period. Twenty-two had received high-dose chemotherapy for (mainly hematologic) malignancies, one had been treated with cyclosporine and prednisolone for systemic lupus erythematosus, one with high-dose methylprednisolone for polyarteritis nodosa and one had an ARDS after near-drowning. MEASUREMENTS AND RESULTS: The medical records were reviewed for patient and disease characteristics, outcome, reasons for admission to the ICU, supportive care and antifungal therapy as well as for the results of cultures and autopsy. Out of 25 patients, a definite ante mortem diagnosis could be established in seven. When autopsied patients were included, a total of 15 suffered from proven invasive aspergillosis. Although standard antifungal treatment and maximal available supportive care were given, 23 of 25 patients (92%) died after a mean of 15 (1-51) days in the ICU. Both patients who recovered had received high-dose chemotherapy for hematologic malignancy and showed bone marrow recovery and/or had a localized pulmonary infection. CONCLUSIONS: In patients with highly suspected or proven invasive aspergillosis, admission to an ICU and mechanical ventilation should be considered in cases of localized infection and obvious signs of hematologic recovery. In most other circumstances ICU admission for mechanical ventilation does not seem to improve survival.     

Gangrene of the anterior abdominal wall after orthotopic liver transplantation: invasive cutaneous candidiasis

Fungal infections following liver transplantation are not uncommon and may be life-threatening. Superficial candidal infections of the bronchus, oesophagus and urinary tract are the most common mode of presentation. Invasive cutaneous and subcutaneous candidiasis is, however, very rare. We report two patients with invasive cutaneous and subcutaneous candidiasis after orthotopic liver transplantation.     

Spectrum of immunodeficiency in HIV-1-infected patients with pulmonary tuberculosis in Zaire

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/microL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.     

Invasive pulmonary aspergillosis in AIDS: radiographic, CT, and pathologic findings

PURPOSE: To review the radiographic and computed tomographic (CT) manifestations of invasive pulmonary aspergillosis and to correlate the imaging and pathologic findings in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Chest radiographs, CT scans, and pathologic specimens were reviewed retrospectively in 10 AIDS patients with proved invasive pulmonary aspergillosis. RESULTS: The most common radiographic finding was the presence of thick-walled cavitary lesions. Less common findings included nodules, consolidation, and pleural effusion. CT depicted more nodules and cavities than did radiography. The predominant pathologic abnormalities consisted of tissue invasion and abscess formation and angioinvasion with or without infarction. All patients had infection with Aspergillus fumigatus as well as other pathogens, the most common being cytomegalovirus and Pseudomonas aeruginosa. CONCLUSION: Thick-walled cavitary lesions are the most common radiologic manifestation of invasive pulmonary aspergillosis in AIDS. The findings are more numerous and better defined on CT scans. The radiologic findings reflect a spectrum of pathologic abnormalities.     

Structure-based design of ligands for protein basic domains: application to the HIV-1 Tat protein

OBJECTIVES: to describe the clinical, microbiological and pathological features of invasive sinus aspergillosis affecting immunocompetent hosts, and to identify the risk factors for mortality. METHODS: we report three apparently immunocompetent patients with invasive sinus aspergillosis, and review all cases reported in the English literature since 1987, the year in which the triazole antifungal agents were introduced. RESULTS: twenty-nine patients (including three of our own) were identified. The presenting symptoms were non-specific and indistinguishable from viral, bacterial or allergic causes of sinusitis. The findings on computed tomography scan were also non-specific, and histopathology and culture of sinus tissue biopsy had low yield. These factors, along with the mistaken impression that Aspergillus can only affect immunocompromised hosts, frequently delayed the diagnosis. Fifty-nine percent of patients either failed therapy or died. The following factors were associated with a poor prognosis: delayed diagnosis, intracranial extension of infection, and histopathology demonstrating hyphal invasion of blood vessel or tissue. Complete surgical extirpation was the key element of successful therapy; antifungal agents played an adjunctive role. CONCLUSIONS: invasive sinus aspergillosis carries high morbidity and mortality, even in immunocompetent hosts. To improve outcome, the diagnosis must be recognized early, before the organism can invade the central nervous system or vascular structures. Aggressive surgical resection of the infected areas is of utmost importance in the management of this infection.     

Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience and review of the literature

A 12-year retrospective analysis was done to identify and evaluate in detail cases of invasive pulmonary aspergillosis (IPA) caused by Aspergillus terreus. We identified 13 A. terreus infections among 133 total cases of confirmed invasive aspergillosis; 11 were IPA and 2 were primary peritoneal infections. Of the 11 patients with IPA, 7 developed neutropenia during hospitalization, and the remaining four were receiving immunosuppressive agents. Ten patients with IPA died; one liver transplantation patient without neutropenia survived after treatment with amphotericin B, itraconazole, and a pulmonary lobectomy. Six patients developed disseminated disease, with the heart the most common extrapulmonary site identified (four patients). These cases demonstrate that IPA caused by A. terreus rapidly progresses in immunocompromised patients receiving amphotericin B and illustrate the need for sensitive diagnostic tests and more effective antifungal agents.     

The infectious complications of sarcoidosis: a current perspective

The incidence of indections requiring hospitalization was determined in 122 patients with sarcoidosis. The group was remarkably free of infection except for three patients with Aspergillus mycetoma occurring in areas of long-standing parenchymal involvement with cystic degeneration. There was a single instance of complicating pulmonary tuberculosis, and the only extrathoracic infection was a single instance of disseminated herpes zoster. This study confirms that aspergillosis, not tuberculosis, is currently the most common infectious complication of sarcoidosis. Although previous case reports have suggested an increased incidence of invasive fungal infection in patients with sarcoidosis, there is little to support this concept. None of the patients in the present study group developed these fungal infections during a mean 7.2-year follow-up. The clinical presentation of many of the previously reported cases suggests that the entire course of the granulomatous illness was infectious in nature rather than sarcoidosis with complicating infection.     

Therapy of sinuorbital aspergillosis with amphotericin B colloidal dispersion

Invasive aspergillosis is a feared complication in the management of patients with malignancies. We report a 13-year-old boy with acute myelogenous leukaemia and chronic sinusitis who developed a sinuorbital fungal infection during cytostatic and prolonged antibiotic treatment. The clinical findings, diagnostic measures and treatment and its adverse effects are described and discussed. Special emphasis is given to our experience of the use of colloidal dispersed amphotericin B (Amphocil).