Eskild A. Petersen

Raised serum levels of tumour necrosis factor in parasitic infections.

In a study of serum levels of endogenous tumour necrosis factor (TNF) in healthy people and patients with neoplastic or infectious disease, only patients with kala-azar (visceral leishmaniasis) and malaria were found to have a strikingly increased frequency of raised TNF levels (66.6% and 70.0%, respectively). 7.9% of samples from both healthy subjects and patients with neoplastic disease contained measurable TNF. The discovery of elevated TNF levels in the sera of patients with parasitic diseases suggests that this cytokine may play a part in host defences against parasitic infections.

Coccidioidomycosis in the Acquired Immunodeficiency Syndrome

Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS.

Coccidioidomycosis during human immunodeficiency virus infection: A review of 77 patients

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature

We have reported 7 new cases of Bipolaris infection and 2 of Exserohilum infection, which demonstrate the capability of these 2 genera to cause invasive as well as allergic disease. As noted previously, it is likely that all of the cases of Helminthosporium and Drechslera infections reported in the literature were caused by Bipolaris or Exserohilum. Infections due to these 2 genera are probably more common than previously recognized. They should be included in the differential diagnosis of central nervous system and disseminated fungal disease, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, and allergic bronchopulmonary disease. These various entities have distinct histopathologic characteristics. With disseminated disease in the immunocompromised patient, the most frequent findings are acute inflammation with prominent vascular invasion, thrombosis, and infarction. In contrast, granulomatous inflammation and leukocytoclastic vasculitis are seen in meningoencephalitis caused by these fungi. The histologic features of allergic bronchopulmonary disease and sinusitis are similar. A chronic inflammatory infiltrate of lymphocytes, plasma cells and eosinophils within edematous granulation tissue is found in addition to squamous metaplasia and thickening of the basement membrane. Infections caused by Bipolaris/Exserohilum and Aspergillus show many clinical and pathologic similarities despite the lack of taxonomic relationship between these fungi. Both cause disseminated disease in immunocompromised patients that is characterized by tissue necrosis and vascular invasion. Both cause central nervous system disease, osteomyelitis, and sinusitis and are associated with allergic bronchopulmonary disease. Sinusitis, the most common form of disease caused by Bipolaris and Exserohilum, occurs in otherwise healthy patients with nasal polyposis and allergic rhinitis. Although pathologic evidence of bone invasion may not be found, there frequently is radiographic evidence of invasive disease. Most patients who are treated initially with surgical debridement and amphotericin B have apparently been cured. However, longer follow-up will be necessary in these patients. Amphotericin B appears to be the treatment of choice for invasive infections caused by Bipolaris/Exserohilum species. Ketoconazole and other imidazole derivatives may also be effective in certain of the disease entities caused by these black moulds; however, their role has yet to be defined.(ABSTRACT TRUNCATED AT 400 WORDS)

Specific Inhibition of Lymphocyte-Proliferation Responses by Adherent Suppressor Cells in Diffuse Cutaneous Leishmaniasis

Diffuse cutaneous leishmaniasis is characterized by multiple nonulcerative skin lesions. Histologically, these lesions are dominated by vacuolated, heavily infected macrophages, with only a few lymphocytes present. A unique focus of diffuse cutaneous leishmaniasis is present in the Dominican Republic. We studied four patients with this disease. None had a delayed reaction to leishmanial antigen on skin tests. The total numbers of lymphocytes and T cells were normal. None of these patients had a lymphocyte-proliferation response to leishmanial antigens, although their responses to other antigens were normal. Adding indomethacin to cultures or decreasing the number of adherent cells by passage of cells over nylon wool reconstituted the lymphocyte responses to leishmanial antigens. Thus, our studies demonstrate that patients with diffuse cutaneous leishmaniasis have a selective anergy to leishmanial antigen, and that an adherent suppressor cell is one mechanism by which this selective immunosuppressive state is modulated.

Visceral leishmaniasis in the Sudan: comparative parasitological methods of diagnosis

Patients with suspected kala-azar had aspirations of spleen, lymph node and bone marrow performed to compare the relative merit of each procedure. Splenic aspiration remains the method most likely to provide microscopic proof of leishmanial infection (18 of 19 samples) and was the only site positive in 5 patients. Lymph node aspirates contained parasites in 20 of 29 patients, whereas bone marrow aspirates provided the diagnosis in 18 of 28. Therefore, lymph node aspiration, with its minimal morbidity, is indicated as the primary diagnostic method in patients in the Sudan with suspected kala-azar. If negative, splenic aspiration should be performed.

Pulmonary Infections in Cardiac Transplant Patients: Modes of Diagnosis, Complications, and Effectiveness of Therapy

Eighteen serious pulmonary infections have been encountered in 10 of 16 surviving cardiac transplant recipients. Fourteen of 18 infections (78%) occurred within the first six months after transplant and the remaining 4 (22%) after the first six months (p less than 0.05). There was no correlation between the number of rejections per patient and propensity toward infection. Transtracheal aspiration or percutaneous lung aspiration established the diagnosis in all but two episodes. Percutaneous lung aspiration appeared more accurate as a diagnostic tool but was associated with 6 complications in 13 attempts (46%), while no complications occurred in 17 attempts with transtracheal aspiration (p less than 0.05). Five of the 10 patients had multiple episodes of pulmonary infection; 2 of these 5 (40%) had concurrent infections. Nocardia organisms were encountered most frequently, accounting for 7 of 18 (39%) infections; 6 of 10 patients (60%) were infected with Nocardia at some point after transplant. Nine of 10 patients (90%) were cured of infection. Eight are still alive without evidence of infection. We conclude from these data that pulmonary infection is common in transplant recipients, that early definitive diagnosis, in spite of the potential complications, is warranted, and that cure of infection and long-term survival are possible if treatment is timely and aggressive.

Hantavirus Pulmonary Syndrome in Pregnancy

This comprehensive case review of hantavirus pulmonary syndrome (HPS) during pregnancy in 5 women characterizes the effect of Sin Nombre virus infection on maternal and fetal outcomes. Histopathologic, serological, and clinical information were evaluated for evidence of vertical transmission. Maternal ages ranged from 20 to 34 years and gestational ages from 13 to 29 weeks. Symptoms, physical findings, and laboratory values other than those related to pregnancy were not noticeably different from those of nonpregnant patients with HPS, although fevers were somewhat lower. One maternal death and 2 fetal losses occurred. Gross, microscopic, and immunohistochemical examination for hantavirus antigen were done on 2 fetal autopsies and 3 placentas showing no evidence of transplacental hantavirus transmission. There was no serological evidence of conversion in the 3 surviving children. Maternal and fetal outcomes of HPS appear similar to those of nonpregnant HPS patients and of pregnant patients with other causes of acute respiratory distress syndrome. No evidence of vertical transmission of Sin Nombre virus was found.

In vitro susceptibility of Plasmodium falciparum malaria to pyrimethamine, sulfadoxine, trimethoprim and sulfamethoxazole, singly and in combination

Two isolates of Plasmodium falciparum (F 32 and K 1) were tested against sulfadoxine (SDX), sulfamethoxazole (SMZ), pyrimethamine (PYR) and trimethoprim (TMP), using a 48 h microtest, with RPMI-1640 low in PABA and folic acid. The IC50 for F 32 was: PYR 6.1 X 10(-9) M (mol/litre), TMP 1.3 X 10(-7) M, Fansidar (SDX/PYR 80:1) less than 10(-8) to 1.3 X 10(-10) M and cotrimoxazole (SMZ/TMP 20:1) 2.6 X 10(-7) to 1.3 X 10(-8) M. The IC50 for K 1 was: PYR greater than 10(-6) M, TMP 8.2 X 10(-7) M, Fansidar 4.1 X 10(-7) to 1.1 X 10(-9) M and cotrimoxazole 1.8 X 10(-6) to 9.0 X 10(-8) M. The difference in IC50 between F 32 and K 1 against TMP and cotrimoxazole is much less than the difference between the IC50 values against PYR and Fansidar, indicating that cross-resistance between PYR and TMP exists, but is not complete. A method for calculating the IC50 by linear regression analysis is described.

Coccidioidouria: Clinical Significance

Abstract Twelve patients had urine cultures positive forCoccidioides immitis. Ten patients showed the usual criteria for dissemination, but 2 were believed, before urine culture, to have only chron...