Reversible dilated cardiomyopathy associated with amphotericin B therapy.

WHAT IS KNOWN AND OBJECTIVE: Amphotericin B (AmB) is commonly used to treat a broad spectrum of fungal infections and leishmaniasis. Its use is limited by numerous adverse effects. Reversible dilated cardiomyopathy associated with AmB is a rare disorder with only four previously reported cases, and all of them referring to patients who presented with a predisposing factor for heart failure. CASE SUMMARY: A previously healthy 45-year-old man with visceral leishmaniasis treated with AmB developed acute dilated cardiomyopathy. Other causes of heart failure as well-known predisposing factors for this condition were ruled out. As with previously reported cases, the cardiac function of our patient returned to normal shortly after. WHAT IS NEW AND CONCLUSION: We describe the first case of dilated cardiomyopathy associated with the administration of AmB in a patient without any known predisposing factor for developing cardiac dysfunction. Available evidence suggests that AmB may induce cardiotoxicity. Further investigations are needed to clarify this issue.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center.

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Ultrasound and CT findings in hepatic and pancreatic parenchyma in acute schistosomiasis.

A case of acute toxaemic schistosomiasis is presented. Abdominal ultrasound examination revealed hepatosplenomegaly, lymphadenomegaly, heterogeneous hepatic parenchyma and heterogeneous focal lesions in the pancreas. CT confirmed lymph node enlargement and hepatosplenomegaly, and showed multiple small focal nodular lesions in the liver and focal lesions in the pancreas. To our knowledge, this is the first description of pancreatic lesions associated with acute Schistosoma mansoni infection.

Mixed inflammatory/regulatory cytokine profile marked by simultaneous raise of interferon-gamma and interleukin-10 and low frequency of tumour necrosis factor-alpha(+) monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagasi infection.

Considering the complexity of the immunological events triggered during active visceral Leishmaniasis (VL), the relevance of the segregation of the immune response during human VL into type 1 and type 2 still remains unclear. For this purpose, in individuals living in risk areas for VL, we have evaluated especially asymptomatic individuals and patients with active VL, the plasmatic levels of cytokines and reactive nitrogen species under ex vivo conditions. In addition, we have also performed an analysis of intracellular cytokine patterns of circulating leucocytes after short-term culture, particularly in the absence of antigenic-specific stimulation, in order to reflect dynamic events of immune response in vivo during Leishmania chagasi infection. Although asymptomatic individuals and non-infected subjects presented a similar immunological profile, an outstanding inflammatory/regulatory profile, based on higher plasmatic levels of cytokines such as interleukin (IL)-8, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-6 and IL-10, was associated with clinical status observed in active VL. In this context, we hypothesize that IL-10, through its ability to inhibit anti-leishmanial macrophage activation, associated with the lower frequency of TNF-alpha(+) monocytes and ordinary levels of nitrite and nitrate are the major mechanisms associated with disease onset.

Clinical value of anti-live Leishmania (Viannia) braziliensis immunoglobulin G subclasses, detected by flow cytometry, for diagnosing active localized cutaneous leishmaniasis.

OBJECTIVE: To evaluate the clinical value of flow cytometry anti-live promastigate antibody (FC-ALPA), for diagnosing active cutaneous leishmaniasis. METHOD: Serum samples from 145 individuals living in endemic areas for localized cutaneous leishmaniasis (population 1) were classified as having the disease or not and then tested for their IgG reactivity by indirect immunofluorescence assay and FC-ALPA-IgG. The results of FC-ALPA-IgG were expressed as percentage of positive fluorescent parasite. Both tests were also evaluated in serum samples of people with visceral leishmaniasis and Chagas disease (population 1A). RESULTS: In population 1, FC-ALPA-IgG performed better than the immunofluorescence assay regarding sensitivity, specificity and predictive values. Analysis of the results according to the likelihood ratios indicated that a percentage of positive fluorescent parasite 60% it reinforces diagnosis of the disease (likelihood ratio = 7.0). Immunofluorescent assay is of little value (likelihood ratio=2.04). In population 1A, both tests performed worse, but FC-ALPA-IgG achieved better statistical indexes than immunofluorescent assay. CONCLUSION: The FC-ALPA-IgG is a valuable method for serological diagnosis of localized cutaneous leishmaniasis. FC-ALPA-IgG1/ALPA-IgG2 combined analysis is an additional serological tool for discriminating localized visceral leishmaniasis, Chagas disease and visceral leishmaniasis in areas where these infections co-exist.

Immune response in human visceral leishmaniasis: analysis of the correlation between innate immunity cytokine profile and disease outcome.

We investigated the cytokine profile of cells of the innate immune response and its association with active (ACT), asymptomatic (AS) and cured (CUR) human visceral leishmaniasis (VL), as well as noninfected (NI) subjects. The frequency of cytokine-producing cells was determined after short-term in vitro incubation of whole peripheral blood samples with soluble Leishmania antigen (SLA). Our data demonstrated a predominant type 2 cytokine profile in NI and ACT. In NI, we observed an increase of IL-4+ neutrophils, IL-10+ eosinophils besides a decrease of tumour necrosis factor (TNF)-alpha+ eosinophils/monocytes. Yet in ACT, we observed an increase of IL-4+ neutrophils and natural killer (NK) cells and IL-10+ monocytes, a reduced frequency of IL-12+ and IFN-gamma+ eosinophils and lower levels of TNF-alpha+ and IL-12+ monocytes. AS presented a mixed profile, characterized by an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, of IL-12+ eosinophils/monocytes, as well as increase of IL-4+ neutrophils and NK cells and IL-10+ eosinophils/monocytes. In contrast, CUR was characterized by a type 1 response with an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, associated with an increase in IL-12+ monocytes. In conclusion, we show a correlation between innate immune cytokine patterns and clinical status of VL, suggesting that these cells, in addition to other factors, may contribute to the cytokine microenvironment in which Leishmania-specific T cells are primed and to disease outcome.

Immunological and clinical evaluation of chagasic patients subjected to chemotherapy during the acute phase of Trypanosoma cruzi infection 14-30 years ago.

We recently evaluated the in vitro proliferative response and interferon (IFN)-gamma production of peripheral blood mononuclear cells from a group of 25 people who were treated for Chagas' disease during the acute phase of Trypanosoma cruzi infection and followed up for a period of 14-30 years. On the basis of the parasitological and serological tests, the individuals were classified as cured (C), dissociated, or not cured (NC). Members of group C (the group without cardiac alterations) presented significantly stronger proliferative response against the parasite antigens, with secretion of high levels of IFN-gamma in comparison with the NC group, raising a question about the role of this cytokine in the curing of human T. cruzi infection. Severe cardiac alterations were observed only in 1 of 25 patients, which suggests that treatment benefited the patients.

Actinomycosis of the colon: a rare form of presentation.

Actinomycosis is an uncommon entity, caused by an anaerobic bacterium, Actinomyces israelii, which is a component of the human oral and gastrointestinal flora. The cervicofacial region is the commonest site of disease, and the abdomen is the second commonest. In this situation the disease is almost always unifocal and restricted to the right colon, especially to the cecum. We report here the case of a patient with a very rare form of this entity, characterized by multiple foci of abdominal involvement with the most severe lesions localized in the transverse and sigmoid colon. The clinical presentation resembled a picture of colon perforation by cancer or diverticulitis, and the diagnosis was made by histopathologic examination of the lesions removed at surgery. No predisposing factor was found. The infection was successfully treated with a prolonged course of penicillin, after the surgical removal of the lesions.

Spinal cord schistosomiasis. A report of 2 cases and review emphasizing clinical aspects.

Schistosomal myeloradiculopathy (SMR) is a severe and little known form of presentation of schistosomiasis mansoni and hematobic schistosomiasis. The literature concerning the entity is scarce, and most publications are limited to isolated case reports. Thus, to consolidate and analyze the knowledge currently available about the disease, I reviewed 231 cases, with emphasis on clinical aspects. Although variations occur, in most cases the clinical picture of SMR is highly suggestive in individuals with epidemiologic antecedents of the infection. Thus, a patient with SMR is usually a young male with no other manifestations of schistosomal infection who presents with lumbar pain, often of a radicular nature, soon followed by weakness and sensory loss of rapid progression in the lower limbs associated with autonomic dysfunction, particularly bladder dysfunction. The most suggestive elements of the entity, and therefore of higher diagnostic value, are the low localization of the spinal cord lesion, the acute or subacute onset of the disease, and the association of manifestations due to medullary and radicular involvement. SMR is commonly classified into clinical or anatomoclinical forms. However, I observed no consensus in this classification even in terms of the terminology used. The analysis performed in this review permitted the introduction of a new concept not yet reported in the literature regarding the possibility that the disease consists of a continuous spectrum, with asymptomatic egg laying in the spinal cord at 1 end of the spectrum and devastating forms at the other end, with most cases occupying an intermediate position and with the various types of damage overlapping and associated to different degrees. This concept applies not only to different patients but also to the same patient at different stages of the disease. Chemical and cytomorphologic examination of cerebrospinal fluid (CSF) almost always revealed mildly or moderately increased total protein concentration and predominantly lymphocytic pleocytosis. Eosinophils, the least nonspecific finding, were detected in the CSF of less than half (40.8%) the patients. Myelography and computed tomography-myelography were altered in 63.3% of cases, but this proportion may be an overestimate. The most frequent changes were images of a filling defect due to expansion of the spinal cord and were almost always demonstrated by the 2 imaging modalities. Although still few in number, early reports suggest that magnetic resonance imaging is more sensitive; however, the changes are also nonspecific, such as those revealed by myelography and computed tomography-myelography. Parasite eggs were demonstrated frequently in a biologic specimen (88.3%), but difficulty in detection was not uncommon. Peripheral blood eosinophilia was detected in 64.5% of patients and represented a nonspecific finding. The detection of anti-Schistosoma antibodies in the serum or CSF was also frequent (94.9% and 84.8%, respectively). The presence of anti-Schistosoma antibodies in serum is of limited value for the diagnosis of schistosomiasis in general, especially among individuals living in endemic areas; however, their quantification in the CSF has proved to be promising for diagnosis in the few studies conducted for this purpose. The large number of variables concerning treatment (such as drugs used and duration of disease at the beginning of treatment), together with the relative lack of information about the natural history of the disease, limit the analysis of aspects related to treatment and prognosis. Nevertheless, it was possible to conclude that corticosteroids and antischistosomotic drugs have a favorable effect on disease outcome and should be administered as early as possible. In addition to early treatment, factors linked to the disease itself affect prognosis. The new cases of SMR reported here are typical and illustrate the data discussed in this literature survey.

Evaluation of enzyme-linked immunosorbent assay for the diagnosis of Helicobacter pylori infection in children from different age groups with and without duodenal ulcer.

BACKGROUND: Although enzyme-linked immunosorbent assay (ELISA) is highly sensitive and specific for the diagnosis of Helicobacter pylori infection in adults, their performance in children is still controversial. METHODS: A second-generation ELISA was used to evaluate the IgG response to H. pylori in the serum of 130 consecutive children who underwent upper gastrointestinal endoscopy. The presence of H. pylori was determined in antral biopsy specimens by culture, urease test, and histologic analysis. RESULTS: Sixty-eight children (all of the 20 who had duodenal ulcer) were H. pylori positive by microbiologic test. Immunoglobulin G antibodies to H. pylori were detected in 79.4% of the infected children and in 8.1% of the noninfected ones. The sensitivity of the test was higher in patients with duodenal ulcer (100%) than in those without (70.8%). When used in children of different ages the test also presented differences in sensitivity: 44.4% in children 2 to 6 years old; 76.7% in children 7 to 11 years old, and 93.1% in children 12 to 16 years old (p = 0.006). The serum immunoglobulin G concentration was significantly higher (p = 0.0003) in children with duodenal ulcer than in those without and was higher in older children than in younger ones without duodenal ulcer (p = 0.05). CONCLUSIONS: The accuracy of the test in children with duodenal ulcer and in children more than 12 years old was good; however, in children up to 12 years of age without duodenal ulcer, the sensitivity of the test was too low to be used for screening purposes or to rule out the presence of infection.

Estimation of the local synthesis of immunoglobulin G (IgG) in the central nervous system of patients with spinal cord schistosomiasis by the IgG index.

By analogy with other infections of the central nervous system (CNS), it is believed that schistosomal myeloradiculopathy (SMR) is an entity that may involve a mild-to-moderate degree of impairment of the blood-brain barrier along with intrathecal synthesis of antibodies. The first of these aspects is obvious but the second has not been clearly demonstrated. This study was undertaken in Brazil with the aim of investigating the production of immunoglobulin G (IgG) within the CNS in patients with SMR, by the determination of the cerebrospinal fluid (CSF) IgG index. The study population included 54 patients with SMR, evaluated prospectively. The CSF IgG index was increased in 43 of them (80%). Preliminary results from our laboratory suggest that these antibodies are reactive against Schistosoma mansoni antigens. Thus, this finding also suggests that this index may be useful in the differential diagnosis of SMR.

Serodiagnosis of Helicobacter pylori infection by Cobas Core ELISA in adults from Minas Gerais, Brazil

We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infection in adults from a developing country in view of variations in sensitivity and specificity reported for different populations. We studied 97 non-consecutive patients who underwent endoscopy for evaluation of dispeptic symptoms. The presence of H. pylori was determined in antral biopsy specimens by culture, by the preformed urease test and in carbolfuchsin-stained smears. Patients were considered to be H. pylori positive if at least two of the three tests presented a positive result or if the culture was positive, and negative if the three tests were negative. Sixty-five adults (31 with peptic ulcer) were H. pylori positive and 32 adults were H. pylori negative. Antibodies were detected by Cobas Core anti-H. pylori EIA in 62 of 65 H. pylori-positive adults and in none of the negative adults. The sensitivity, specificity and positive and negative predictive values of the test were 95.4, 100, 100 and 91.4 per cent, respectively. The Cobas Core anti-H. pylori EIA presented high sensitivity and specificity when employed for a population in Brazil, permitting the use of the test both to confirm the clinical diagnosis and to perform epidemiologic surveys.

Serodiagnosis of Helicobacter pylori infection by Cobas Core ELISA in adults from Minas Gerais, Brazil.

We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infection in adults from a developing country in view of variations in sensitivity and specificity reported for different populations. We studied 97 non-consecutive patients who underwent endoscopy for evaluation of dispeptic symptoms. The presence of H. pylori was determined in antral biopsy specimens by culture, by the preformed urease test and in carbolfuchsin-stained smears. Patients were considered to be H. pylori positive if at least two of the three tests presented a positive result or if the culture was positive, and negative if the three tests were negative. Sixty-five adults (31 with peptic ulcer) were H. pylori positive and 32 adults were H. pylori negative. Antibodies were detected by Cobas Core anti-H. pylori EIA in 62 of 65 H. pylori-positive adults and in none of the negative adults. The sensitivity, specificity and positive and negative predictive values of the test were 95.4, 100, 100 and 91.4%, respectively. The Cobas Core anti-H. pylori EIA presented high sensitivity and specificity when employed for a population in Brazil, permitting the use of the test both to confirm the clinical diagnosis and to perform epidemiologic surveys.

An atypical isolate of Paracoccidioides brasiliensis.

An atypical strain of Paracoccidioides brasiliensis was obtained from a patient with disseminated paracoccidioidomycosis. This isolate, which has been maintained in the laboratory for 4 years by successive subcultures (30-40 days) in Fava Netto medium, produces cerebriform colonies characteristic of the yeast phase of the fungus when left at room temperature. Microscopy shows a predominance of yeasts with multiple buds, side by side with some branching filamentous structures presenting intercalary chlamydospores. The strain does not develop well at 37 degrees C, suggesting heat sensitivity. Storage at 4 degrees C does not change its macro- or microscopic characteristics. These findings support the hypothesis raised by others that the dimorphism of P. brasiliensis may not be exclusively heat dependent. Studies are currently being developed in our laboratory to better characterize this isolate in terms of biochemical peculiarities, degree of virulence and susceptibility/resistance to antifungal drugs.

The value of an enzyme-linked immunosorbent assay for the diagnosis of schistosomiasis mansoni myeloradiculopathy.

The role of serological tests on cerebrospinal fluid (CSF) in the diagnosis of neuroschistosomiasis has not been fully elucidated; the condition is essentially diagnosed on the basis of circumstantial evidence, which may lead to an erroneous diagnosis, especially in highly endemic areas. We therefore carried out a prospective case-control study in which we compared the concentrations of immunoglobulin G (IgG) specific for schistosome soluble egg antigen (SEA) present in the CSF of 54 patients with schistosomiasis mansoni myeloradiculopathy (SMMR) with those observed in a control group consisting of 41 patients with epidemiological and serological evidence of exposure to schistosomes, and with other neurological disorders that result in mild to moderate impairment of the blood-brain barrier. Anti-SEA IgG was estimated by an enzyme-linked immunosorbent assay. The sensitivity, specificity and positive and negative predictive values were 56%, 95%, 94% and 62% respectively. Likelihood ratios and the corresponding post-test probabilities were determined for 4 levels of anti-SEA IgG in CSF. A value below 0.1 micrograms/mL practically excluded the possibility of SMMR (post-test probability < 5%), a value above 1.4 micrograms/mL practically confirmed the diagnosis of SMMR (post-test probability > 96%), values of 0.1 to 0.5 microgram/mL had no diagnostic value (post-test probability approximately 45%), and values of 0.6 to 1.4 micrograms/mL were useful in some situations (post-test probability approximately 70%). We conclude that the estimation of anti-SEA IgG in the CSF is useful for the diagnosis of SMMR.

Isolation Leishmania sp from aqueous humor of a patient with cutaneous disseminated leishmaniasis and bilateral iridocyclitis (preliminary report)

Os autores descrevem um caso raro de leishmaniose con lesoes cutaneas disseminadas, manifestacoes sistemicas e comprometimento ocular, sendo este caracterizado por iridociclite bilateral nao granulomatosa. A gravidade do quadro oftalmologico e a ausencia de resposta ao tratamento, a despeito da melhora das manifestacoes cutaneas e sistemicas, levaram a realizacao de puncao propedeutica da camada anterior ocular. A partir do humor aquoso isolou-se Leishmania sp. Os autores desconhecem na literatura qualquer outro caso onde tal achado tenha sido demonstrado