Safety and effectiveness of amphotericin B deoxycholate for the treatment of visceral leishmaniasis in Uganda

Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb-V). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in-hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) =2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI=1.4%-7.9%) among the 161 patients treated with Sb-V (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI= 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI=0.1%-4.4%) of the patients treated with Sb-V (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.

Effect of terbium(III) on the binding of aromatic guests with sodium taurocholate aggregates

The effect of binding Tb(3+) to sodium taurocholate aggregates containing polyaromatic hydrocarbon guests was examined using pyrene and 1-ethylnaphthalene as guests that bind to the primary aggregate, and 1-naphthyl-1-ethanol as a secondary aggregate guest. Time-resolved fluorescence quenching studies were used to study the binding site properties, while laser flash photolysis quenching studies provided information on the dynamics of the guest-aggregate system. Both the primary and secondary aggregate binding sites became more compact in the presence of bound Tb(3+), while only the primary aggregate became more accessible to anionic molecules. The binding dynamics for the guest-primary aggregate system became faster when Tb(3+) was bound to the aggregate. In contrast, for the guest-secondary aggregate the presence of Tb(3+) resulted in a small decrease in the dissociation rate constant. The influence of bound Tb(3+) on the primary and secondary bile salt aggregates is significantly different, which affects how these aggregates can be used as supramolecular host systems to modify guest reactivity.

Rhodotorula spp. isolated from blood cultures: clinical and microbiological aspects

The emergence of less common fungal pathogens has been increasingly reported in the last decade. We describe 25 cases of Rhodotorula spp. isolated from blood cultures at a large Brazilian tertiary teaching hospital from 1996-2004. We also investigated the in vitro activity of four antifungal drugs, using a standardized method. The median age of patients was 43 years. The majority of patients (88%) had a central venous catheter (CVC) and 10 (40%) were recipients of a bone marrow transplant. The episode was classified as a bloodstream infection (BSI) in 80% of the patients. Amphotericin B deoxycholate was the most common antifungal used and CVC was removed in 89.5% of the patients. Death occurred in four patients (17.4%), all classified as BSI. All strains were identified as R. mucilaginosa by conventional methods. Misidentification of the species was observed in 20% and 5% of the strains with the Vitek Yeast Biochemical Card and API 20C AUX systems, respectively. Amphotericin B demonstrated good in vitro activity (MIC(50/90), 0.5 mu g/ml) and the MICs for fluconazole were high for all strains (MIC(50/90), 64 mu g/ml).

Malaria serology: performance of six Plasmodium falciparum antigen extracts and of three ways of determining serum titers in IgG and IgM-ELISA

The study evaluated six Plasmodium falciparum antigen extracts to be used in the IgG and IgM enzyme-linked immunosorbent assays (ELISA), for malaria diagnosis and epidemiological studies. Results obtained with eighteen positive and nine negative control sera indicated that there were statistically significant differences among these antigen extracts (Multifactor ANOVA, p< 0.0001). Urea, sodium deoxycholate and Zwittergent antigen extracts performed better than did the three others, their features being very similar for the detection of IgG antibodies. Urea, alkaline and sodium deoxycholate antigen extracts proved to be better than the others for the detection of IgM antibodies. A straight line relationship was found between the optical densities (or their respective log 10) and the log 10 of antibody dilutions, with a very constant slope. Thus serum titers could be determined by direct titration and by two different equations, needing only one serum dilution. For IgM antibody detections, log 10 expression gave results that better correlated with direct titration (95% Bonferroni). For IgG antibody detections, the titer differences were not significant. The reproducibility of antibody titers and antigen batches was also evaluated, giving satisfactory results.

Measles serodiagnosis: standardization and evaluation of a dot-ELISA

A Dot-ELISA using a measles virus (MV) antigen obtained by sodium deoxycholate treatment was standardized and evaluated for IgM and IgG antibody detection in measles patients and measles-vaccinated subjects. A total of 192 serum samples were studied, comprising 47 from patients with acute and convalescent measles, 55 from 9-month old children prior to measles vaccination and 41 from children of the same age after vaccination, and 49 from patients with unrelated diseases. The diagnostic performances of the IgG Dot-ELISA and IgG immuno fluorescence test (IFT) were found to be close, varying from 0.97 to 1.00 in sensitivity and the specificities were maximum (1.00). Nevertheless, the sensitivity of the IgM Dot-ELISA (0.85) was higher than that (0.63) of the IgM IFT, although both assays had comparably high (1.00) specificities. The IgM Dot-ELISA in particular proved to be more sensitive in relation to other assays studied by revealing antibodies in 80.0% (12/15) of vaccinated children on the 15th day after immunization. In contrast the IgM IFT, failed to detect antibodies in the same group of vaccinated children. The stability of the MV antigen was longer than that of the IFT antigen, and the reproducibility of the Dot-Elisa was satisfactory.

Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture - proven case reported in Brazil

Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV) infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT) showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.

CASE STUDY OF A PATIENT WITH HIV-AIDS AND VISCERAL LEISHMANIASIS CO-INFECTION IN MULTIPLE EPISODES

SUMMARYReport of a 45-year-old male farmer, a resident in the forest zone of Pernambuco, who was diagnosed with human immunodeficiency virus (HIV) in 1999 and treated using antiretroviral (ARV) drugs. In 2005, the first episode of visceral leishmaniasis (VL), as assessed by parasitological diagnosis of bone marrow aspirate, was recorded. When admitted to the hospital, the patient presented fever, hepatosplenomegaly, weight loss, and diarrhea. Since then, six additional episodes of VL occurred, with a frequency rate of one per year (2005-2012, except in 2008). In 2011, the patient presented a disseminated skin lesion caused by the amastigotes of Leishmania, as identified by histopathological assessment of skin biopsy samples. In 2005, he was treated with N-methyl-glucamine-antimony and amphotericin B deoxycholate. However, since 2006 because of a reported toxicity, the drug of choice was liposomal amphotericin B. As recommended by the Ministry of Health, this report emphasizes the need for HIV patients living in VL endemic areas to include this parasitosis in their follow-up protocol, particularly after the first infection of VL.

Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes

Clin Sci (Lond). 2002 Nov;103(5):475-85

Oropharyngeal histoplasmosis: report of eleven cases and review of the literature

INTRODUCTION: Histoplasmosis is a systemic mycosis endemic in Brazil, especially in the State of Rio Grande do Sul, where Histoplasma capsulatum was isolated from the soil. H. capsulatum may compromise unusual areas, including the oropharynx, particularly in patients presenting disseminated histoplasmosis; which is associated with a state of immunosuppression, such as AIDS. METHODS: During database analysis of a total of 265 cases of histoplasmosis, the medical records of 11 patients with histological or microbiological diagnoses of oral histoplasmosis (OH) between 1987 and 2008 were retrospectively reviewed. RESULTS: This work reports 11 cases of OH, the majority presenting histopathological or microbiological evidence of disseminated histoplasmosis (DH). In the patients with DH, OH was the first manifestation of histoplasmosis. Five of the 11 patients discussed were HIV-seropositive with clinical and laboratory findings of AIDS. Four patients presented active pulmonary tuberculosis concomitant with histoplasmosis. Treatment was based on the use of itraconazole and amphotericin B deoxycholate. Eight patients responded successfully to therapy after one year, two did not come back for reevaluation and one died despite adequate therapy. CONCLUSIONS: Oral histoplasmosis is closely associated with immunosuppression status, especially in patients presenting AIDS; moreover, in many cases, OH is the first sign of disseminated histoplasmosis.

Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fungal infections in critically ill patients such as those who are immunosuppressed due to chemotherapy. Diagnostic techniques and effective antifungal therapy have improved the prognosis of these cases.

HIV/AIDS-related visceral leishmaniasis: a clinical and epidemiological description of visceral leishmaniasis in northern Brazil

Introduction: This study aimed to describe the main features of visceral leishmaniasis (VL), both related to and independent of human immunodeficiency virus (HIV) infection, in patients who were registered in Tocantins, Brazil. Methods: Data from 1,779 new patients with VL, 33 of whom were also infected with HIV, were reviewed. Results: The incidence of VL/HIV coinfection increased from 0.32/100,000 inhabitants in 2007 to 1.08/100,000 inhabitants in 2010. VL occurred predominantly in children aged 10 years or younger, while VL/HIV was more common in patients aged between 18 and 50 years. There were more male patients in the VL/HIV group than in the VL group. Relapse rates were also considerably higher in the VL/HIV (9.1%) group than in the VL group (1.5%). Despite a similar clinical presentation, VL/HIV patients exhibited a higher proportion (24.2%) of concomitant infectious diseases and jaundice. Pentavalent antimonials were used for the initial treatment of VL and VL/HIV infections. However, amphotericin B deoxycholate and liposomal amphotericin B were also widely used in the treatment of VL/HIV coinfection. The mortality rate was higher in the VL/HIV coinfection group (19.4%) than in the VL group (5.4%). Furthermore, the mortality rate due to other causes was significantly higher in the VL/HIV group (12.9%) than in the VL group (0.7%). Conclusions: The study showed that the incidence, clinical characteristics and outcomes among the VL and VL/HIV patients in this state are similar to those from other endemic regions, indicating that both infections are emerging with increasing frequency in Brazil.

Ventriculoperitoneal shunts for treating increased intracranial pressure in cryptococcal meningitis with or without ventriculomegaly

Introduction Cryptococcosis is an opportunistic mycosis, especially in patients that are human immunodeficiency virus (HIV)-positive, and frequently involves the central nervous system. Methods We assessed the potential of ventriculoperitoneal shunting (VPS) in preventing mortality due to uncontrollable intracranial hypertension (ICH) in 15 patients with acquired immunodeficiency syndrome (AIDS)-related cryptococcal meningitis. Results After 2 weeks of antifungal therapy consisting of amphotericin B deoxycholate with or without fluconazole, patients with persistent ICH underwent VPS, despite having persistent Cryptococcus neoformans infection. In 12 patients, the uncontrollable ICH was resolved by VPS. Conclusions Patients with cryptococcal meningoencephalitis who have ICH must be considered for VPS even with positive cerebrospinal fluid cultures.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp.

Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin ± Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B-II), liposomal amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B-II), micafungin (B-II) and caspofungin (C-II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A-I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I), anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used.

Purification and characterization of (Na+ + K+)-ATPase from toad kidney

This report describes the partial purification and the characteristics of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) from an amphibian source. Toad kidney microsomes were solubilized with sodium deoxycholate and further purified by sodium dodecyl sulphate treatment and sucrose gradient centrifugation, according to the methods described by Lane et al. [(1973) J. Biol. Chem. 248, 7197--7200], Jørgensen [(1974) Biochim. Biophys. Acta 356, 36--52] and Hayashi et al. [(1977) Biochim. Biophys. Acta 482, 185--196]. (Na+ + K+)-ATPase preparations with specific activities up to 1000 mumol Pi/mg protein per h were obtained. Mg2+-ATPase only accounted for about 2% of the total ATPase activity. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed three major protein bands with molecular weights of 116 000, 62 000 and 26 000. The 116 000 dalton protein was phosphorylated by [gamma-32P]ATP in the presence of sodium but not in the presence of potassium. The 62 000 dalton component stained for glycoproteins. The Km for ATP was 0.40 mM, for Na+ 12.29 mM and for K+ 1.14 mM. The Ki for ouabain was 35 micron. Temperature activation curves showed two activity peaks at 37 degrees C and at 50 degrees C. The break in the Arrhenius plot of activity versus temperature appeared at 15 degrees C.