TNF microsatellite alleles may confer protection against the development of lipodystrophy syndrome in Brazilian HIV patients

P>The aim of this study was to evaluate the frequency of TNFa-e microsatellites and the promoter region (TNF-308 and TNF-238) in HIV/AIDS-infected patients presenting or not lipodystrophy syndrome (LS). The design is the genetic case-control association study. Microsatellite and the TNF promoter region polymorphisms were amplified by PCR and submitted to polyacrylamide gel electrophoresis. The genotypes and allele frequencies for 67 HIV-positive patients with lipodystrophy were compared with 50 HIV-positive patients with no evidence of lipodystrophy and with 131 healthy HIV-negative individuals. The presence of the TNFa5 allele could provide HIV/AIDS patients with protection against developing LS. The presence of TNF-308G allele, as well as of its homozygote TNF-308GG, were associated with susceptibility to developing LS. In addition, the presence of the haplotype TNFe3-d3-238G-308A-c1-a5-b7 suggests protection against developing that syndrome. This study highlights that polymorphic sites spanning the region nearby the TNF locus are associated with LS development in HIV/AIDS patients.

Kallmann syndrome and mirror movements: White matter quantitative evaluation with magnetic resonance imaging

Kallmann syndrome (KS), characterized by the association of hypogonadotropic hypogonadism and anosmia, may present many other phenotypic abnormalities, including neurologic features as involuntary movements, called mirror movements (MM). MM etiology probably involves a complex mechanism comprising corticospinal tract abnormal development associated with deficient contralateral motor cortex inhibitory system. In this study, in order to address previous hypotheses concerning MM etiology, we identified and quantified white matter (WM) alterations in 21 KS patients, comparing subjects with and without MM and 16 control subjects, using magnetization transfer ratio (MTR) and T2 relaxometry (R2). Magnetization transfer and 12 double-echo images were acquired in a 1.5 T system. MTR and R2 were calculated pixel by pixel to initially create individual maps, and then, group average maps, co-registered with MNI305 stereotaxic coordinate system. After analysis of selected regions of interest, we demonstrated areas with higher 12 relaxation time and lower MTR values in KS patients, with and without MM, differently involving corticospinal tract projection, frontal lobes and corpus callosum. Higher MTR was observed only in pyramidal decussation when compared in both groups of patients with controls. In conclusion, we demonstrated that patients with KS have altered WM areas, presenting in a different manner in patients with and without MM. These data suggest axonal loss or disorganization involving abnormal pyramidal tracts and other associative/connective areas, relating to the presence or absence of MM. We also found a different pattern of alteration in pyramidal decussation, which can represent the primary area of neuronal disarrangement. (C) 2010 Elsevier B.V. All rights reserved.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Cutaneous mycoflora and CD4:CD8 ratio of cats infected with feline immunodeficiency virus

This study was designed to compare cutaneous mycoflora isolation and CD4+:CD8+ ratio in feline immunodeficiency virus (FIV)-infected cats with that in FIV-uninfected cats. Sixty cats were examined. Twenty-five were Fly-infected cats and 35 were RV-uninfected cats. All 60 cats were FeLV-negative. Fungi were speciated and immunophenotyping of peripheral CD4+ and CD8+ T lymphocytes was performed. At least one fungal colony was isolated from 22/25 (88%) FIV-infected cats. Among the FIV-uninfected cats fungal colonies were recovered from 13/35 (37%) specimens. Dermatophytes were recovered from 2/25 (8%) FIV-infected cats (one Microsporum gypseum, one Microsporum can is) and 3/35 (8.5%) FIV-uninfected cats (M gypseum). Malassezia species was the most commonly isolated organism from both groups of cats (51.6%). Malassezia species was more commonly isolated from FIV-infected cats than RV-uninfected cats (84% vs 28.6%). The CD4+ to CD8+ lymphocyte ratio for FIV-infected cats was significantly lower than the CD4+ to CD8+ ratio in the FIV-uninfected cats. The CD4+ to CD8+ lymphocyte ratio for FIV-infected cats with cutaneous overall fungal isolation was significantly lower than the CD4:CD8 lymphocyte ratio in the FIV-infected cats but without cutaneous fungal isolation. We can conclude that immunologic depletion due to retroviral infection might represent a risk factor to cutaneous fungal colonization in cats. (C) 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Kaposi sarcoma and paracoccidioidomycosis in the same fragment of oral mucosa biopsy: a rare association in human immunodeficiency virus-positive patient. A case report

The immunossuppression caused by HIV infection makes the affected individuals more susceptible to some diseases including infections, neoplasms, or even the association between them. Kaposi sarcoma (KS) is the most common AIDS-related neoplasm, featured as an angioproliferative disorder. Its cause seems to be related to the human herpesvirus type 8 and it is usually associated with lower CD4+ T cell count. Oral involvement is frequent, presenting red to blue-purplish plaques, maculaes, and nodules. On the other hand, paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in Latin America, caused by Paracoccidioides brasiliensis. This mycosis is not commonly related to human immunodeficiency virus (HIV) infection, although PCM can be present in immunosuppression cases. Oral lesions, as granulomatous ulcers, are often identified in seropositive patients with PCM. A rare case, in which a male HIV-positive patient presented simultaneously Kaposi sarcoma and PCM in the same fragment of oral mucosa biopsy, is described. To the best of our knowledge, this concomitant association had not been previously described. (C) 2011 Elsevier Inc. All rights reserved.

Oral manifestations after immune reconstitution in HIV patients on HAART

In order to verify possible association between immune reconstitution inflammatory syndrome (IRIS) and oral manifestations (OMs), we selected AIDS patients who had low CD4 count before the initiation of highly active antiretroviral therapy (HAART) and who returned three months later for therapy evaluation. The oral lesions observed three months after the initiation of HAART were evaluated and associated with the type of antiretroviral therapy (ART), CD4 count and HIV-RNA load levels (before and three months after HAART initiation). A total of 105 patients matched the selected criteria. Immune reconstitution (IR) was identified in 35.2%. Among these patients, the mean CD4 cell count rose from 105.97 to 330.29 and the mean viral load dropped from 168.005 (log 5.22) to 21.852 (log 4.33). There was no significant difference in age (P=0.78), sex (P=0.41) or previous history of ART (P=0.55) between IR and non-IR patients. In the IR group, the most common OM was. parotid enlargement (57.14%) (P=0.619), whereas in the non-IR group candidiasis (46.15%) was the most common OM. The results of our study suggest that the parotid gland enlargement found in the studied population might be an IRIS event, as it was found in patients with IR three months after the initiation of HAART.

Drug targets and mechanisms of resistance in the anaerobic protozoa

The anaerobic protozoa Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica infect up to a billion people each year. G. duodenalis and E. histolytica are primarily pathogens of the intestinal tract, although E. histolytica can form abscesses and invade other organs, where it can be fatal if left untreated. T. vaginalis infection is a sexually transmitted infection causing vaginitis and acute inflammatory disease of the genital mucosa. T. vaginalis has also been reported in the urinary tract fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and oral lesions. Respiratory infections can be acquired perinatally. T. vaginalis infections have been associated with preterm delivery, low birth weight, and increased mortality as well as predisposing to human immunodeficiency virus infection, AIDS, and cervical cancer. All three organisms lack mitochondria and are susceptible to the nitroimidazole metronidazole because of similar low-redox-potential anaerobic metabolic pathways. Resistance to metronidazole and other drugs has been observed clinically and in the laboratory. Laboratory studies have identified the enzyme that activates metronidazole, pyruvate:ferredoxin oxidoreductase, to its nitroso form and distinct mechanisms of decreasing drug susceptibility that are induced in each organism. Although the nitroimidazoles have been the drug family of choice for treating the anaerobic protozoa, G. duodenalis is less susceptible to other antiparasitic drugs, such as furazolidone, albendazole, and quinacrine. Resistance has been demonstrated for each agent and the mechanism of resistance has been investigated. Metronidazole resistance in T. vaginalis is well documented, and the principal mechanisms have been defined Bypass metabolism, such as alternative oxidoreductases, have been discovered in both organisms. Aerobic versus anaerobic resistance in T. vaginalis is discussed. Mechanisms of metronidazole resistance in E. histolytica have recently been investigated ruing laboratory-induced resistant isolates. Instead of downregulation of the pyruvate:ferredoxin oxidoreductase and ferredoxin pathway as seen in G. duodenalis and T. vaginalis, E. histolytica induces oxidative stress mechanisms, including superoxide dismutase and peroxiredoxin. The review examines the value of investigating both clinical and laboratory-induced syngeneic drug-resistant isolates and dissection of the complementary data obtained. Comparison of resistance mechanisms in anaerobic bacteria and the parasitic protozoa is discussed as well as the value of studies of the epidemiology of resistance.

Community-acquired Klebsiella pneumoniae bacteremia: Global differences in clinical patterns

We initiated a worldwide collaborative study, including 455 episodes of bacteremia, to elucidate the clinical patterns of Klebsiella pneumoniae. Historically, community-acquired pneumonia has been consistently associated with K. pneumoniae. Only four cases of community-acquired bacteremic K. pneumoniae pneumonia were seen in the 2-year study period in the United States, Argentina, Europe, or Australia; none were in alcoholics. In contrast, 53 cases of bacteremic K. pneumoniae pneumonia were observed in South Africa and Taiwan, where an association with alcoholism persisted (p=0.007). Twenty-five cases of a distinctive syndrome consisting of K. pneumoniae bacteremia in conjunction with community-acquired liver abscess, meningitis, or endophthalmitis were observed. A distinctive form of K. pneumoniae infection, often causing liver abscess, was identified, almost exclusively in Taiwan.

An investigation into support for restrictions on HIV carriers in the Chicago metropolitan area

An investigation into support for restrictions on people testing seropositive for HIV is reported on. Data were collected during telephone interviews with two-hundred adults aged eighteen to sixty-five in the Chicago metropolitan area. Using the analytic technique of LISREL, six models which attempt to explain support for restrictions were tested. It was found that the model best supported by the data indicates that two groups contribute to support for restrictions on HIV carriers - one due to intolerance of homosexuality and one to mistrust of public health officials regarding their control and management of the AIDS epidemic. The relevance of these findings for public health policy makers is discussed.

Central obesity and dietary intake in HIV/AIDS patients

OBJECTIVE: To assess the association between dietary intake and central obesity among people living with HIV/AIDS and receiving highly active antiretroviral therapy. METHODS: A cross-sectional study was conducted involving 223 adult individuals in the city of São Paulo city in 2002. The study population was classified according to central obesity, defined as waist-to-hip ratio >0.95 for men and >0.85 for women. The dietary variables studied were energy consumption (in calories and calories/kilo of body weight), macronutrients (in grams and % of energy intake), total fiber (grams) and fruit and vegetables intake (grams). The potential confounders examined were sex, skin color, age, schooling, income, body mass index, physical activity, smoking habits, peripheral CD4+ T lymphocyte count and length of protease inhibitor use. The multiple logistic regression model was performed in order to evaluate the association between central obesity and dietary intake. RESULTS: The prevalence of central obesity was 45.7% and it was associated with greater consumption of lipids: for every increase of 10g of lipid intake the odds of central obesity increased 1.28 times. Carbohydrate consumption showed negative association (OR=0.93) with central obesity after adjustment for control variables. CONCLUSIONS: The results suggest that the amount of carbohydrates and lipids in the diet, regardless of total energy intake, may modify the chance of developing central obesity in the studied population. Nutritional interventions may be beneficial for preventing central obesity among HIV/AIDS patients.

Respiratory complications in Brazilian patients infected with human immunodeficiency virus

PURPOSE: To determine how often and by what means an indentifiable pulmonary pathogen can be recognized in human immunodeficiency virus (HIV) infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms and what impact specific therapy has on these agents. PATIENTS AND METHODS: Thirty-five HIV seroposiüve subjects with respiratory complaints were studied. All patients had a complete history, physical examination and blood counts. The pulmonary assessment included chest radiograms; sputum examination for bacterial and fungal pathogens; bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Patients with treatable complications received standard antimicrobial therapy. RESULTS: One or more microorganisms were found in 24 subjects and another 3 individuals showed nonspecific interstitial pneumonitis. The sputum examination identified the pulmonary pathogens in 7 cases. The bronchoalveolar lavage and the histopathologic examination were diagnostic in 14% and 83%, respectively, of the 28 individuals that were submitted to bronchoscopy. The most frequently identified microorganism was P. carinii (55%), followed by M. tuberculosis (41%) and cytomegalovirus (8%). The clinical, laboratory and radiographic findings failed to distinguish the specific pulmonary pathogens. Twenty-three individuals with P. carinii pneumonitis and/or tuberculosis received specific therapy; among the evaluable patients the therapeutic response rates were 79% for PCP and 100% for TB. CONCLUSIONS: We have determined that tuberculosis, P. carinii and cytomegalovirus pneumonitis are the most common respiratory opportunistic diseases in Brazilian patients infected with HIV. The histologic evaluation was crucial in order to identify the pulmonary pathogens. Tuberculosis in AIDS individuals displayed clinical and radiographic findings atypical for reactivation disease. However, most of the features observed in HIV infected patients had been previously described in infection of the normal host. Furthermore, the AIDS subjects showed a good therapeutic response to anti-tuberculous drugs.

Drug resistance of M. Tuberculosis isolated from patients with HIV infection seen at an AIDS Reference Center in São Paulo, Brazil

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

Neutralizing antibodies in Brazilian sera against three strains of human immunodeficiency virus type 1 (HIV-1)

The MN strain of HIV-1 is known to be more prevalent in Brazil, the BRU strain is more prevalent in Europe, and the NDK strain in Africa. It has been suggested in the literature to include different strains in the same vaccine against HIV-1. To contribute to the studies for the development of a universal vaccine, the occurrence of antibodies (Ab) against three HIV-1 strains (MN, BRU and NDK) was determined in serum samples from 85 HIV-1-positive patients, adult volunteers seen at the University Hospital of the Faculty of Medicine of Ribeirão Preto-USP. One-hundred tissue culture infective unit (TCIU) of the viruses reacted with serial dilutions of the sera (2x) and with MT4 cells added at a final concentration of 0.3 × 106 cells/ml, and a cytopathic effect was observed on the 7th and 11th days of incubation. Titres of less than 1/50 were considered to be negative. In 129 tests, the sera were negative for one of the three strains: 40 for MN, 29 for BRU and 60 for NDK. There was a predominance of strains MN and BRU, most of them presenting titres from 1/50 to 1/200. Titres for NDK were detected in 25 sera. We conclude that there seems to be a predominance of strains MN and BRU among the individuals from the region tested; however, the detection of sera with positive NKD titres indicates the need for further studies of this strain in other populations and regions of Brazil

Development of Secondary Resistance to Fluconazole in Cryptococcus neoformans Isolated from a Patient with AIDS

Cryptococcus neoformans is the fifth most common opportunistic agent of infection in patients with AIDS in the USA, exceeded only by Candida species, Pneumocystis carinii, cytomegalovirus and Mycobacterium avium1, 2, 6, 10, 11. In Brazil is the sixth, exceeded by Candida species, P. carinii, Mycobacterium species, Toxoplasma gondii, and herpes simplex virus (AIDS, Boletim Epidemiológico, set/nov 96, Ministério da Saúde, Brasil). During 30 years, the treatment of C. neoformans meningitis was based on the use of amphotericin B with or without flucytosine13. Nowadays, with the immunodepression caused by human immunodeficiency virus (HIV) infection and the availability of new antifungal drugs as the triazoles, the concept related to cure and relapses of cryptococcosis has been altered7, 20. Patients are treated with amphotericin B with or without flucytosine as initial therapy, but maintenance therapy is always necessary in AIDS patients with C. neoformans infections

Bacillary angiomatosis: description of 13 cases reported in five reference centers for AIDS treatment in Rio de Janeiro, Brazil

The aim of this case series was to describe the clinical, laboratory and epidemiological characteristics and the presentation of bacillary angiomatosis cases (and/or parenchymal bacillary peliosis) that were identified in five public hospitals of Rio de Janeiro state between 1990 and 1997; these cases were compared with those previously described in the medical literature. Thirteen case-patients were enrolled in the study; the median age was 39 years and all patients were male. All patients were human immunodeficiency virus type 1 (HIV-1) infected and they had previous or concomitant HIV-associated opportunistic infections or malignancies diagnosed at the time bacillary angiomatosis was diagnosed. Median T4 helper lymphocyte counts of patients was 96 cells per mm³. Cutaneous involvement was the most common clinical manifestation of bacillary angiomatosis in this study. Clinical remission following appropriate treatment was more common in our case series than that reported in the medical literature, while the incidence of relapse was similar. The frequency of bacillary angiomatosis in HIV patients calculated from two of the hospitals included in our study was 1.42 cases per 1000 patients, similar to the frequencies reported in the medical literature. Bacillary angiomatosis is an unusual opportunistic pathogen in our setting.