Search

Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome-related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985-1994) and HAART (1997-2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome-related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era.

An unusual case of epididymal and prostatic histoplasmosis is reported from Karnataka State of southern India, in a 37-year-old male renal transplant recipient, who had presented with gastrointestinal histoplasmosis a year before the second presentation and had responded successfully to 9 months' treatment with itraconazole. The patient presented a second time with high-grade fever and pain in the scrotum and the lower abdomen. Ultrasound of the abdomen revealed a retrotrigonal abscess, which was confirmed on computed tomography scan of the pelvis. Pus was drained via transrectal route and biopsy specimens were taken from the epididymis and the prostate. Histopathology revealed the picture suggestive of histoplasmosis, and the pus on culture confirmed the infection with Histoplasma capsulatum. To our knowledge, only 5 cases of epididymal histoplasmosis have been reported in the literature, our case being the second report from India and sixth in the world; prostatic histoplasmosis is also a rare occurrence., (© 2011 John Wiley & Sons A/S.)

Histoplasmosis, an infection caused by the fungus Histoplasma capsulatum, has been reported all over the world and is considered endemic in the American continent, including Cuba. This fungus grows on the soils contaminated with bird and bat excreta, where it produces a great number of microconidia that could cause the infection when they are inhaled. The clinical spectrum varies from asymptomatic infections to serious disseminated diseases involving one or many organ systems and affects mainly AIDS patients, patients with hematological neoplasias, transplant recipients or other immunosuppressed patients. The main risk groups include those individuals whose working activities make them be exposed to aerosols contaminated with H. capsulatum. Lab diagnosis is based on the microscopic observation, isolation and identification of the fungus in fluid or tissue samples of patients, and on specific antigen and antibodies detection. The molecular methods based on polymerase chain reaction have not been sufficiently defined, and they could be an important advance in the early diagnosis of this mycosis. Itraconazole is recommended for treatment of moderate, localized and chronic infection whereas amphotericin B is the drug of choice for disseminated and serious manifestations, particularly in its lipidic formulations. At present, histoplasmosis is considered one of the most important systemic mycoses in the Americas, and it is widely spread over all regions of Cuba.

The pathogen ecology of Amazonian regions may lead to specific differences in the most frequent clinical presentations of acquired immunodeficiency syndrome (AIDS). A retrospective cohort study was thus conducted to describe the main AIDS-defining events in French Guiana. Disseminated histoplasmosis was the most frequent opportunistic infection (15.4/1000 person years).

Cutaneous diseases occur in most people infected with human immunodeficiency virus (HIV) and at a higher rate than people not infected with HIV. Common HIV-related rashes and rashes made unusual by HIV infection are reviewed., (Copyright 2010 Elsevier Inc. All rights reserved.)

Histoplasmosis is recognized to occur in the Ohio and Mississippi River Valleys of the United States, but less widely appreciated is its worldwide distribution. We report a case of disseminated histoplasmosis with disease involving skin, lungs, and epiglottis in a renal transplant patient 6 months after a trip to Bangladesh, to highlight the potential risk of acquisition of this infection in the Indian subcontinent.

We report the case of 48 year old female patient without a history of significance importance.(refuses blood transfusion). She complaint of diarrhea of four months of duration and weight loss of 8 kg. she added episodes of hematochezia and severe anemia requiring transfusion. An intrahemorrhagic colonoscopy was performed detecting three ulcerated lesions. First at 10 cm from the anus, one in transverse colon distal, another similar ulcer in the proximal transverse The biopsies showed ulcer granulation tissue, abundant macrophages with intracytoplasmic structures consistent with histoplasmosis. Tests showed no tuberculosis or intestinal parasitosis. HIV testing (ELISA and Western Blot) were positive. The CD4 (78 cells) and extrapulmonary histoplasmosis were the criteria defined stage AIDS. The extrapulmonary histoplasmosis defines stage IV in immunosuppressed patients with HIV. Lower gastrointestinal bleeding colonic ulcer secondary to Histoplasma is a rare form presentation as a diagnostic manifestation of AIDS.

Life-threatening histoplasmosis is one of the most common opportunistic infections in patients receiving tumor necrosis factor (TNF) blockers. Delays in considering the diagnosis may lead to increased morbidity and mortality. Most affected patients present with pneumonitis, usually accompanied by additional signs of progressive dissemination, or with signs of progressive dissemination alone. The diagnosis often can be promptly established using antigen detection or direct examination of bronchoalveolar lavage specimens. If histoplasmosis is diagnosed promptly, antifungal therapy is highly effective. After a favorable clinical response, the safety of both discontinuation of antifungal therapy and the resumption of TNF blocker remains undetermined. The management of the immune reconstitution inflammatory syndrome that may follow discontinuation of TNF blockers also requires investigation. Prescribers should become aware of the recognition, diagnosis, and treatment of histoplasmosis and educate recipients about decreasing their risk of exposure and both recognizing and reporting signs of early infection.

Histoplasmosis is systemic mycosis caused by a small fungus, Histoplasma capsulatum var. capsulatum, whose natural habitat is soil contaminated by bat or bird excrement. The incidence of histoplasmosis is worldwide. In Brazil, the disease is found in all regions; however, the state of Rio de Janeiro is responsible for most of the microepidemics described. Human infection occurs when airborne spores of H. capsulatum are inhaled. The most common clinical presentation is asymptomatic. The symptoms of acute or epidemic histoplasmosis are high fever, cough, asthenia and retrosternal pain, as well as enlargement of the cervical lymph nodes, liver and spleen. The most common radiological findings are diffuse reticulonodular infiltrates in both lungs, as well as hilar and mediastinal lymph node enlargement. In chronic pulmonary histoplasmosis, the clinical and radiological manifestations are identical to those of reinfection with pulmonary tuberculosis. Histoplasmosis is diagnosed by means of the identification or culture growth of the fungus in sputum or fiberoptic bronchoscopy specimens. Histopathological examination reveals the fungus itself within or surrounding macrophages, as well as granulomatous lesions with or without caseous necrosis. Double agar gel immunodiffusion is the most easily used and readily available serologic test for making the immunological diagnosis. Acute histoplasmosis with prolonged symptoms requires treatment, as do the disseminated or chronic pulmonary forms of the disease. The drug of choice is itraconazole.

Background: Many clinical scenarios have been encountered by patients who developed histoplasmosis after receiving a solid organ transplant at a large transplant center in an endemic area., Methods: Cases of posttransplantation histoplasmosis were identified by use of multiple methods, including reviews of microbiology test results, transplant databases, and billing codes. Data were obtained retrospectively. Descriptive statistics were used., Results: During the 1997-2007 study period, 3436 patients received a solid organ transplant, and 38 patients were identified as having posttransplantation histoplasmosis. Of these 38 patients, 9 were excluded from our study because the diagnosis was solely clinical. Of the remaining 29 patients, 14 had posttransplantation histoplasmosis (incidence, 1 case per 1000 person-years); 14 showed histologic evidence of histoplasmosis in the recipient or donor tissue, which was encountered unexpectedly at the time of transplantation; and 1 had histoplasmosis before receiving the transplant. Of the 14 patients who developed histoplasmosis after transplantation, 5 were heart transplant recipients, 3 were lung transplant recipients, 3 were kidney transplant recipients, 1 was a liver transplant recipient, 1 was a pancreas transplant recipient, and 1 was a kidney-pancreas transplant recipient. The median time from transplantation to diagnosis was 17 months (interquartile range, 8.1-46 months), and the median time from onset of symptoms to diagnosis 3 weeks (interquartile range, 1.9-6.5 weeks). All recipients had disseminated disease. The most common treatment was amphotericin B and itraconazole. All were cured, or still on treatment, but symptom-free. Of the 14 patients who had an explanted organ or donor tissue that showed histologic evidence of histoplasmosis, 13 (93%) were lung transplant recipients, and 1 (7%) was a liver transplant recipient. None of these patients developed active histoplasmosis, but all received prophylactic treatment. Finally, 1 patient had histoplasmosis before transplantation; he was treated with itraconazole 3 months before and after transplantation, and he did well., Conclusions: In conclusion, posttransplantation histoplasmosis is rare (1 case per 1000 transplant-person-years; 95% confidence interval, 0.6-1.7), even in endemic areas. Prognosis is good but requires protracted therapy. Patients with latent infection did not develop posttransplantation histoplasmosis when prophylaxis was used.

We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial. This trial was designed to evaluate intraarticular delivery of a tumor necrosis factor alpha (TNF-alpha) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's receipt of concurrent anti-TNF-alpha therapy and other immunosuppressive therapy while she was living in an area where histoplasmosis was endemic was thought to be the most likely explanation for the infection; the evidence presented suggests that this fatal infection was unlikely to have been related to exposure to the agent administered in the gene-therapy trial. This case reinforces the importance of considering infectious complications, such as those from endemic mycoses, in patients receiving treatment with a TNF-alpha antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724.), (2009 Massachusetts Medical Society)

Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum. It is classically considered an endemic mycosis, even though the fungus has an opportunistic behavior in immunocompromised patients. People acquired the infection through the inhalation of conidial forms present in the environmental, such as caves dwelling bats and soils inhabited by chickens. The clinical features may vary from asymptomatic infections to disseminated severe forms that affect patients with acquired immunodeficiency syndrome or hematological malignancies and allograft recipients. The diagnosis is based on the detection of the fungus in organic fluids (sputum, blood, liquor) or tissues (histopathological assays), in the culture of biological samples and serological assays. The treatment of severe chronic respiratory acute or localized forms can be performed with oral azolic (itraconazol) and in the disseminated forms, the amphotericin B (preferentially the lipidic formulations) consists in the elected drug to initiate the therapy. Nowadays, histoplasmosis represents one of the most important systemic mycosis in the Americas, with broad distribution in all regions of Brazil.

Soft-tissue masses are rarely associated with Histoplasma capsulatum infection. We describe a heart transplant patient who presented with a large right-sided chest wall mass as a manifestation of disseminated histoplasmosis. A successful clinical outcome was achieved upon recognition of the fungal pathogen.

A 58-year-old man was admitted with complaints of pain in the right upper right side of the chest. Chest radiography and computed tomography (CT) revealed a cavitary lesion in the right upper lobe. A CT-guided percutaneous lung biopsy and transbronchial lung biopsy of this lesion did not yield a definitive diagnosis; therefore, we performed video assisted thoracic surgery (VATS). We also investigated various types of mycosis because he had several records of overseas travel. At a later day, the histoplasma immunodiffusion test showed positive results. We finally diagnosed pulmonary histoplasmosis based on the clinical course, CT and radiographic images and serological tests. Voriconazole improved the patient's subjective symptoms and laboratory findings. A positive reaction was obtained for anti-human T-cell leukemia virus type 1 (HTLV-1) antibody and the HTLV-1 carrier, confirming his immunodeficiency disorder. We raised the possibility that the development of pulmonary histoplasmosis might be associated with the HTLV-1 carrier.

Drug resistance to Tuberculosis is an emerging problem but proper exhaustive workup needs to be done before confirming the diagnosis. The case of a 5 year old male child who presented with low grade fever and lymphadenopathy and was being treated with anti TB drugs with no satisfactory response is presented. A detail workup including a biopsy gave the diagnosis of histoplasmosis.

A 66-year-old Columbian man presented with a 15-day history of generalized weakness, cough, fever, and verrucous, ulcerating plaques of the face, upper chest and back, and arms. The patient proved to be HIV positive. Histopathologic examination showed a diffuse lymphocytic infiltrate coupled with a striking number of yeast forms within macrophages. The clinical presentation and histopathologic alterations are consistent with the diagnosis disseminated Histoplasma capsulatum. This case emphasizes the importance of increasing awareness of histoplasmosis in nonendemic areas as a result of the large subgroup of immunocompromised patients at risk. Disseminated histoplasmosis can be a treatable HIV complication if recognized early, though is unfortunately a harbinger for an overall poor prognosis.

We report a case of disseminated histoplasmosis in a 33-year old Ecuadorian patient with AIDS and a CD4 lymphocyte count of 39 cells/microl. He presented with prolonged fever and cough, was diagnosed with hemophagocytic syndrome and multiple organ failure and died 18 days after admission. Histoplasma capsulatum was isolated post-mortem from bone marrow biopsy and blood culture. In a literature review we found 22 published cases of disseminated histoplasmosis in patients with AIDS in Spain since 1988. All but two were men under 50 years old. Nineteen had been born or had lived in endemic areas. The diagnosis of histoplasmosis was established by culture of bone marrow biopsy in 10 cases. Itraconazole was introduced as a second drug after amphotericin B in ten of the thirteen patients who survived.

Opportunistic infections are well documented in states of steroid excess. To our knowledge, histoplasmosis has not been previously reported in Cushing's disease, and has rarely been reported in patients with exogenous glucocorticoid use. We report a novel presentation of Histoplasmosis as pulmonary nodules in a patient with Cushing's disease. A 45-year-old man with a pituitary macroadenoma and Cushing's disease was treated with transsphenoidal hypophysectomy and radiation therapy. He was receiving Ketoconazole and basal steroid replacement, when he presented with dyspnea. Chest radiograph showed nodular lesions and subsequent biopsy revealed Histoplasma capsulatum. Itraconazole was administered and the patient recovered. The case not only demonstrates the protean manifestations of Histoplasmosis in patients with glucocorticoid excess but it also emphasizes the importance of intensive control of the hypercortisolemia in achieving a favorable outcome.

The Platelia Aspergillus assay tested positive in 8 of 11 patients with disseminated histoplasmosis. While other available methods for diagnosis have several drawbacks, this cross-reactivity is particularly valuable in the perspective of practitioners outside the USA who cannot use the test detecting antigen of Histoplasma capsulatum.

The second-generation Histoplasma antigen immunoassay is semiquantitative, expressing results as a comparison to a negative control, which requires repeat testing of the prior specimen with the current specimen to accurately determine a change in antigen. Reporting results in this manner often is confusing to the ordering physician and laboratory. Development of a quantitative assay could improve accuracy, reduce interassay variability, and eliminate the need to test the prior sample with the current sample in the same assay. Calibrators with known concentrations of Histoplasma antigen were used to quantitate antigen in specimens from patients with histoplasmosis and from controls. Samples from cases of disseminated histoplasmosis or other mycoses and controls were tested to evaluate the performance characteristics of the quantitative assay. Paired specimens were evaluated to determine if quantitation eliminated the need to test the current and prior specimens in the same assay to assess a change in antigen. The sensitivity in samples from patients with AIDS and disseminated histoplasmosis was 100% in urine and 92.3% in serum. Cross-reactions occurred in 70% of other endemic mycoses, but not in aspergillosis. Specificity was 99% in controls with community-acquired pneumonia, medical conditions in which histoplasmosis was excluded, or healthy subjects. A change in antigen level categorized as an increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in nanograms/milliliter determined from testing current and prior specimens in different assays. Sensitivity, specificity, and interassay precision are excellent in the new third-generation quantitative Histoplasma antigen immunoassay.

Fungal infections in solid organ transplant recipients continue to be a significant cause of morbidity and mortality. Candida spp. and Aspergillus spp. account for most invasive fungal infections. The incidence of fungal infection varies with type of solid organ transplant. Liver transplant recipients have highest reported incidence of candida infections while lung transplant recipients have highest rate of Aspergillus infections. Recent epidemiological studies suggest the emergence of resistant strains of candida as well as mycelial fungi other than Aspergillus in these patients. The current review incorporates the recent changes in the epidemiology of fungal infections in solid organ transplant recipients and highlights the newer data on the diagnosis, prophylaxis and treatment of fungal infections in these patients.

Histoplasmosis is an endemic and systemic mycosis, caused by the dimorphic fungus Histoplasma capsulatum var capsulatum. Disseminated disease in immunocompromised patients generally results from the reactivation of latent foci after a prolonged period of asymptomatic infection. We report a case of laryngeal histoplasmosis as the unique clinical manifestation of a progressive form of the disease in a patient with advanced HIV/AIDS disease. Histopathological analysis of laryngeal biopsy smears revealed granulomas containing Histoplasma-like organisms. Treatment with amphotericin B followed by itraconazole resulted in complete remission of laryngeal lesions. To our knowledge, this is the third case report of laryngeal histoplasmosis in a patient with AIDS.

Histoplasmosis is a usually asymptomatic deep fungal infection of tropical origin with respiratory entry and possible oral, pharyngeal, or metastatic localization. The condition represents an important imported systemic mycosis with oral involvement. We report the case of a patient who developed an oropharyngeal reactivation of a latent Histoplasma infection after receiving local antitumoral radiation therapy of the neck. H capsulatum was shown to be present in the lesion by both histopathology and staining, and was deduced to be the causative organism of the disease.

Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that is critically important in host defenses to a number of pathogenic microbes. Among those, this cytokine is necessary for control of infection with the pathogenic fungus, Histoplasma capsulatum. Antagonism of endogenous cytokine is associated with an enhanced susceptibility to histoplasmosis in both mice and humans. The mechanisms by which TNF-alpha modulates the protective immune response will be discussed.

Objective: Spinal intramedullary histoplasmosis is an extremely rare condition. We report a case of isolated intramedullary histoplasmosis as the initial manifestation of human immunodeficiency virus (HIV) infection., Clinical Presentation: A 27-year-old man presented with a rapidly progressive paraparesis. Magnetic resonance imaging scans revealed an enhancing lesion at C7-T1 with edema extending as far as the cervicomedullary junction. He improved with steroid medications., Intervention: The patient underwent laminectomy and biopsy of the lesion. The diagnosis of histoplasmosis was made by histology, culture, and polymerase chain reaction identification of fungal deoxyribonucleic acid. The patient did not have disseminated histoplasmosis. Subsequent to the biopsy, the patient was discovered to have HIV infection., Conclusion: The isolated spinal histoplasmosis lesion thus represented the initial presentation of HIV infection. Management of the case and diagnostic issues are discussed.

Background: Thrombotic microangiopathies (TMA) are systemic vasoocclusive disorders associated with significant morbidity and mortality. Rapid and reliable diagnosis of TMA is critical. The diagnosis is complicated by a lack of objective and sensitive laboratory testing as well as multiple concurrent diseases, including infectious processes., Case Study: We report two cases of disseminated histoplasmosis associated with TMA manifestations in renal transplant recipients, including one patient with histologically documented renal microthrombi; both patients were referred for plasma exchange. After the diagnosis of histoplasmosis, the treatment plan was changed to antifungal medications, reduced immuno-suppression, and supportive care, with progressive resolution of TMA manifestations., Conclusion: TMA occurs in transplant populations in association with infections, medications, and other factors. Appropriate management includes recognition and treatment of possible etiological factors. Disseminated histoplasmosis should be considered in transplant patients presenting with TMA.

We reviewed the clinical, microbiologic, and outcome characteristics of 72 patients with human immunodeficiency virus (HIV)-associated histoplasmosis (4 newly described) reported in Europe over 20 years (1984-2004). Seven cases (9.7%) were acquired in Europe (autochthonous), whereas the majority involved a history of travel or arrival from endemic areas. The diagnosis of progressive disseminated histoplasmosis (PDH) was made during life in 63 patients (87.5%) and was the acquired immunodeficiency syndrome (AIDS)-presenting illness in 44 (61.1%). Disease was widespread in 66 patients (91.7%) and localized in 6 (8.3%), with the skin being the most frequent site of localized infection. Overall skin involvement was reported in 47.2% of the patients regardless of whether histoplasmosis was acquired in Africa or South America. Reticulonodular or diffuse interstial infiltrates occurred in 52.8%. The diagnosis was made during life by histopathology plus culture in 44 patients (69.8%), histopathology alone in 18 (28.5%), and culture alone in 1 (1.5%). During the induction phase amphotericin B and itraconazole (74.6%) were the single most frequently used drugs. Both drugs were also used either in combination (10.2%) or in sequential therapy (11.8%). Cumulative mortality rate during the induction phase of treatment was 15.2%. Overall, 37 patients died (57.8%); death occurred early in the course in 18 (28.1%). Seven of 40 patients (17.5%) who responded to therapy subsequently relapsed. Autopsy data in 13 patients confirmed the widespread disseminated nature of histoplasmosis (85%) among AIDS patients with a median of 4.5 organs involved. The results of the present report highlight the need to consider the diagnosis of PDH among patients with AIDS in Europe presenting with a febrile illness who have traveled to or who originated from an endemic area.

The host response to infection is the outcome of a complex interaction between a microbe and a host's innate and adaptive immune system. In this context, the role of antibody in the endemic mycoses is relatively poorly understood. Recently, a monoclonal antibody to a cell surface protein has been shown to be protective in a murine histoplasmosis model. The findings with Histoplasma capsulatum may provide a paradigm for antibody protection against endemic fungi. This paper reviews the recent data on protective antibody in histoplasmosis and previous data supporting a role for antibody in protective responses in other dimorphic fungi.

Objective: The objective of this study was to determine the etiology and risk factors for acute histoplasmosis in two outbreaks in Illinois among laborers at a landfill in 2001 and at a bridge reconstruction site in 2003., Design: We performed environmental investigations during both outbreaks and also performed an analytic cohort study among bridge workers., Participants: Workers at the landfill during May 2001 and those at the bridge site during August 2003 participated in the study. At the landfill, workers moved topsoil from an area that previously housed a barn; at the bridge, workers observed bat guano on bridge beams., Evaluations/measurements: We defined a case by positive immunodiffusion serology, a > or = 4-fold titer rise in complement fixation between acute and convalescent sera, or positive urinary Histoplasma capsulatum (HC) antigen. Relative risks (RR) for disease among bridge workers were calculated using bivariate analysis., Results: Eight of 11 landfill workers (73%) and 6 of 12 bridge workers (50%) were laboratory-confirmed histoplasmosis cases. Three bridge workers had positive urinary HC antigen. At the bridge, seeing or having contact with bats [RR = 7.0; 95% confidence interval (CI), 1.1-43.0], jack-hammering (RR = 4.0; 95% CI, 1.2-13.3), and waste disposal (RR = 4.0; 95% CI, 1.2-13.3) were the most significant job-related risk factors for acquiring histoplasmosis., Conclusions: Workers performing activities that aerosolized topsoil and dust were at increased risk for acquiring histoplasmosis. Relevance to professional and clinical practice: Employees should wear personal protective equipment and use dust-suppression techniques when working in areas potentially contaminated with bird or bat droppings. Urinary HC antigen testing was important in rapidly identifying disease in the 2003 outbreak.

Introduction: Histoplasma capsulatum var capsulatum is a dimorphic fungi predominating on the American continent. It is responsible for disseminated histoplasmosis associated with AIDS. The presentation in the form of cutaneous ulceration is uncommon and misleading., Observation: A 25 year-old man presented with 3 ulcerations, of 2 to 4 cm in diameter, localized on the lower lip and knees. The patient exhibited fever, alteration in his general status of health and a pulmonary interstitial syndrome. He was seropositive for the human immunodeficiency syndrome (HIV). His lymphocyte CD4+ level was of 1/mm3. Diagnosis of histoplasmosis was established by direct examination and culture of the cutaneous ulcerations and bronchoalveolar washing fluid., Discussion: The clinical aspect of cutaneous localizations of disseminated histoplasmosis is usually multiple, disseminated, papular or nodular-type lesions. Ulcerations represent less than 20% of the cases described. In our patient, the aspect of the lesions at first evoked cutaneous leishmaniosis. Direct mycological examination followed by culture confirmed the final diagnosis.

The case of a Spanish kidney transplant patient who developed disseminated histoplasmosis approximately one year and a half after transplantation without having previously visited or travelled to endemic areas of histoplasmosis is presented. To our knowledge this is the first case of this disease in a kidney transplant patient in Spain without epidemiologic antecedent. The study of anti-histoplasm antibodies by complement fixation of the donor and recipient did not safely clarify the mechanism of contagion.

The clinical data of 21 patients, suffering AIDS-related histoplasmosis, who were able to interrupt antifungal secondary prophylaxis, after achieving a partial restoration of the cell mediated immunity by HAART administration, are presented. They were 16 males and five females, whose ages varied between 32 and 54 years (mean = 38.5 years). All of them presented disseminated progressive forms of histoplasmosis, with multiple locations (skin, mucous membranes, liver, spleen, lymph nodes and lungs). The majority of the cases suffered other concomitant diseases (specially tuberculosis and Kaposi sarcoma), 66.6 % of the patients had less than 50 CD4+ cells/microl at the start of treatment and the average viral burden was 278,385 RNA copies/ml. The initial treatment consisted in 400 mg/day of itraconazole, by oral route, in 14 cases and the remaining seven patients were treated with amphotericin B, intravenously, at a daily dose of 0.7 mg/kg of body weight. One patient who did not tolerate amphotericin B and presented a partial response to itraconazole, was treated with posaconazole orally at a daily dose of 800 mg. Fourteen patients received oral itraconazole at a daily dose of 200 mg as a secondary prophylaxis, the remaining three patients were treated with intravenous amphotericin B, 50 mg twice a week. After HAART for an average lapse of 16.7 months (10 to 32 months), five cases showed CD4+ cells counts above 150 cells/microl and the remaining 16 presented more than 200 cells/microl; 18 of them had undetectable viral burden and all cases were asymptomatic. The follow up after secondary prophylaxis discontinuation varied between six months and six years (mean= 33.6 months). Twenty out of 21 patients (95 %) were clinically stable, without any manifestation of relapses, including two patients who abandoned HAART. One patient, who discontinued HAART, contracted a fatal bacterial pneumonia. Even though the limited number of cases, the data presented in this study seem to suggest that it is possible to interrupt antifungal secondary prophylaxis of histoplasmosis, when the patient is clinically asymptomatic and the CD4+ cells counts are above 150 cells/microl.

Leukotrienes are classical mediators of inflammatory response. New aspects of leukotriene function have recently been described. We examine here the previously unreported role that leukotrienes play in the regulation of cytokines in a murine model of histoplasmosis. We demonstrate that administration of MK 886, a leukotriene synthesis inhibitor, caused Histoplasma capsulatum-infected mice to die by the day 15 of infection, whereas the correlating death rate in untreated infected mice was 0%. Treating infected animals with MK 886 inhibited leukotriene synthesis but increased leukocyte recruitment to the lungs. Subsequent to this phenomenon, levels of tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and KC chemoattractant cytokines and fungi in the lung parenchyma increased, as did inflammatory response. In contrast, IL-2, IL-5, IL-12, and gamma interferon cytokine levels actually decreased. Thus, murine response to pulmonary histoplasmosis may be leukotriene modulated. This finding may enable us to alter the course of the immune response and inflammation caused by histoplasmosis. The data from the present study suggest an important new strategy for immunologic or drug intervention in human patients.

In countries where highly active antiretroviral therapy (HAART) is widely available, a decrease in the incidence of fungal infections has been observed in the last 5 years compared with countries that cannot afford this treatment. Even refractory fungal infections may be controlled when HAART is given to patients, and end-stage AIDS infections, such as aspergillosis, are now only infrequently seen. In contrast, fungal infections in certain regions, such as penicilliosis in Southeast Asia or cryptococcosis in Sub-Saharan Africa, are a growing problem. Antifungal therapy for documented infections has not changed very much during recent years; however, new drugs such as caspofungin and voriconazole may be more effective in the treatment of opportunistic fungal infections, in particular, those involving resistant organisms. Secondary antifungal prophylaxis for many opportunistic pathogens can now be temporarily or even permanently discontinued in many HIV-positive patients who have a marked improvement in immune function parameters, such as CD4(+) cell counts, after initiation of HAART. The link between effective virustatic control of HIV infection and a decreasing incidence of fungal infections has been recognised; and so, despite the availability of very effective new antifungal drugs, the cornerstone of treatment and prevention of opportunistic fungal infections in patients with HIV infection is effective antiretroviral therapy including protease inhibitors.

We aimed to identify prognostic factors for AIDS-associated disseminated histoplasmosis. In a multivariate analysis, we found that dyspnea, a platelet count of <100,000 platelets/mm3, and lactate dehydrogenase levels of >2 times the upper limit of the normal range were significantly independently associated with the death of the patient during the first 30 days of antifungal treatment.