Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system

Chemokines are chemoattractant cytokines involved in the immune response of a wide variety of diseases. There are few studies assessing their role in opportunistic infections in HIV-infected patients. In this study, we measured CC and CXC chemokines in cerebrospinal fluid (CSF) samples obtained from 40 HIV-infected patients with or without opportunistic infections of the central nervous system (CNS). CSF samples were also analyzed for quantification of total protein, cell count and HIV-1 RNA. HIV+ patients with cryptococcal meningitis had higher levels of CCL2, CCL3, CCL5, CXCL9 and CXCL10 when compared to patients without opportunistic neurological infections. Furthermore, HIV+ patients with associated cryptococcal meningitis had higher levels of CCL3, CXCL9 and CXCL10 when compared to HIV+ patients with associated toxoplasmic encephalitis. CCL3 and CXCL9 levels were positively correlated with CSF HIV-1 RNA levels, CSF protein concentration, and CSF cell count. CXCL10 level was correlated with the CSF viral load and the CSF cell count and CCL5 level was correlated with the CSF cell count. In conclusion, the profile of chemokines in CSF of HIV patients may differ according to the modality of the presented opportunistic infection and according to other biological markers, such as viral load in CSF. These differences are probably related to different patterns of neuroinflammatory responses displayed by patients with different opportunistic neurological infections. (C) 2009 Elsevier B.V. All rights reserved.

Intestinal cryptosporidiosis. association with Pneumocystis carinii, cytomegalovirus and Candida sp. Infections

This is a case report of intestinal cryptosporidiosis diagnosed in histological specimen collected from autopsy. The patient was a child of 5 months admitted to the hospital with severe acute diarrhea associated with Pneumocystis carinii pneumonia, cytomegalic sialadenitis, oral and dermal candidiasis. The presence of multiple opportunistic infections in this case indicated immunodeficiency state. Cryptosporidium sp is a possible etiology of acute diarrhea in both immunodeficient and immunocompetent patients and has to be searched for at autopsy when diagnosis was not possible "in vivo".

Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

The question of whether HIV-1 RNA in cerebrospinal fluid (CSF) is derived from viral replication in the central nervous system or simply reflects the transit of infected lymphocytes from the blood compartment has long been a matter of debate. Some studies found no correlation between CSF and plasma viral load, whereas others did. The lack of a correlation between the two compartments suggests that the presence of HIV-1 RNA is not simply due to the passive passage of the virus from blood to CSF but rather due to intrathecal replication. To evaluate the correlation between plasma and CSF HIV-1 RNA levels and to identify situations in which there is no correlation between the two compartments, seventy patients were prospectively studied. The association between CSF and plasma viral load was evaluated in the total population and in subgroups of patients with similar characteristics. A correlation between the CSF and plasma compartments was observed for patients undergoing highly active antiretroviral therapy (HAART), those with a CD4 T lymphocyte count lower than 200 cells/mm³, and those with increased CSF protein content. On the other hand, no correlation was observed for patients without adequate virological control, who had a CD4 count higher than 200 cells/mm³ and who did not use HAART. The correlation between the two compartments observed in some patients suggests that CSF HIV-1 RNA levels may reflect plasma levels in these subjects. In contrast, the lack of a correlation between the two compartments in patients who were not on HAART and who had normal CSF proteins and a poor virological control possibly indicates compartmentalization of the virus in CSF and, consequently, plasma-independent intrathecal viral replication.

Evaluation of the histopathological hepatic lesions and opportunistic agents in Brazilian HIV patients

INTRODUCTION: to evaluated the type histopathological hepatic lesions and opportunistic agents in Brazilian HIV-infected patients. METHODS: we examined 52 percutaneous liver biopsies of 50 HIV-infected patients who had at least two of the following conditions: fever of unknown origin, unexplained severe emaciation, hepatomegaly or abnormal liver chemistry. The specimens were cultured for mycobacteria and fungi and stained by standard procedures. RESULTS: reactive patterns, granulomatous hepatitis and chronic active hepatitis were verified in 28 (54%), 11 (21%) and 8 (15%) of the patients respectively. Opportunistic infections were diagnosed in 18 (36%) patients: mycobacteria in 12 (24%), Cryptococcus neoformans in 5 (10%) patients and mycobacteria and yeast was isolated from the same liver fragment in one patient. CONCLUSIONS: mycobacteriosis was the most common opportunistic infection and liver tissue culture is an important method to detect opportunistic agents, even in the absence of histological lesions.

Strategies to combat infections of Acinetobacter baumannii biofilms

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Thymoma, immunodeficiency, and herpes simplex virus infections.

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

Prise en charge par le praticien des infections après transplantation d'organes solides [Management of infection after organ transplantation by the primary care physician]

The primary care physician is frequently consulted in first line for infectious complications in organ transplant recipients. Many infections without signs of severity can nowadays be managed on an outpatient basis. However, a number of clinical situations specific to transplant recipients may require special attention and knowledge. In particular, the general practitioner must be aware of the potential interactions between immunosuppressive and antimicrobial therapies, the risk of renal dysfunction as a consequence of diarrhea or urinary tract infection, and the diagnostic of CMV disease as a cause of fever without obvious source occurring several months after transplantation. Collaboration with the transplantation specialists is recommended in order to assure an optimal management of these patients.

Infections by protozoa in immunocompromised hosts

Protozoa are among the most important pathogens that can cause infection in immunocompromised patients. They infect particularly individuals with impaired cell immunity, such as those with hematologic neoplasias, those submitted to transplant of solid organs, those under high-dose corticosteroid therapy, and carriers of the human immunodeficiency virus. Among the protozoa that most commonly cause disease in immunocompromised individuals are Toxoplasma gondii, Trypanosoma cruzi, Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis and microsporidia; the former two cause severe encephalitis and myocarditis, and the others cause gastrointestinal infections. Early diagnosis and prompt institution of specific therapy for each of these organisms are basic measures to decrease morbidity and mortality associated with these infections.

Some Aspects of Protozoan Infections in Immunocompromised Patients: A Review

Protozoa are among the most important pathogens that can cause infections in immunocompromised hosts. These microorganisms particularly infect individuals with impaired cellular immunity, such as those with hematological neoplasias, renal or heart transplant patients, patients using high doses of corticosteroids, and patients with acquired immunodeficiency syndrome. The protozoa that most frequently cause disease in immunocompromised patients are Toxoplasma gondii, Trypanosoma cruzi, different Leishmania species, and Cryptosporidium parvum; the first two species cause severe acute meningoencephalitis and acute myocarditis, Leishmania sp. causes mucocutaneous or visceral disease, and Cryptosporidium can lead to chronic diarrhea with hepatobiliary involvement. Various serological, parasitological, histological and molecular methods for the diagnosis of these infections are currently available and early institution of specific therapy for each of these organisms is a basic measure to reduce the morbidity and mortality associated with these infections.

Bloodstream infections in late-stage acquired immunodeficiency syndrome patients evaluated by a lysis centrifugation system

Opportunistic infections, which affect acquired immunodeficiency syndrome (Aids) patients, are frequently disseminated and may cause bloodstream infections (BSI). The aim of this study was to evaluate the main causes of BSI in Aids patients with advanced stage of the disease, with special emphasis on the identification of fungemia. During a 21 months period, all patients with Aids (CD4 < 200) and febrile syndrome admitted to 3 university hospitals were systematically evaluated. For each patient presenting fever, a pair of blood cultures was collected and processed by using a commercial lysis-centrifugation system. One hundred and eleven patients (75 males) with a mean age of 36 years (median 33 years) and mean CD4 count of 64 cells/ml were included. Among the 111 patients evaluated we documented 54 episodes of BSI, including 46 patients with truly systemic infections and 8 episodes considered as contaminants. BSI were caused by gram-positive bacteria (43%), fungi (20%), gram-negative bacteria (15%), mycobacteria (15%), and mixed flora (7%). The crude mortality rate of our patients was 39%, being 50% for patients with BSI and 31% for the others. In conclusion, BSI are a common related to systemic infections on Aids patients with advanced stage of disease and is associated with a high rate of mortality.

Lung infections: the radiologist's perspective.

Imaging plays a key role in lung infections. A CT scan must be carried out when there is a strong clinical suspicion of pneumonia that is accompanied by normal, ambiguous, or nonspecific radiography, a scenario that occurs most commonly in immunocompromised patients. CT allows clinicians to detect associated abnormalities or an underlying condition and it can guide bronchoalveolar lavage or a percutaneous or transbronchial lung biopsy. An organism can vary in how it is expressed depending on the extent to which the patient is immunocompromised. This is seen in tuberculosis in patients with AIDS. The infective agents vary with the type of immune deficiency and some infections can quickly become life-threatening. Clinicians should be aware of the complex radiological spectrum of pulmonary aspergillosis, given that this diagnosis must be considered in specific settings.

Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.

Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.

T cell reactivity against mycolyl transferase antigen 85 of M. tuberculosis in HIV-TB coinfected subjects and in AIDS patients suffering from tuberculosis and nontuberculous mycobacterial infections.

The mycolyl transferase antigen 85 complex is a major secreted protein family from mycobacterial culture filtrate, demonstrating powerful T cell stimulatory properties in most HIV-negative, tuberculin-positive volunteers with latent M.tuberculosis infection and only weak responses in HIV-negative tuberculosis patients. Here, we have analyzed T cell reactivity against PPD and Ag85 in HIV-infected individuals, without or with clinical symptoms of tuberculosis, and in AIDS patients with disease caused by nontuberculous mycobacteria. Whereas responses to PPD were not significantly different in HIV-negative and HIV-positive tuberculin-positive volunteers, responses to Ag85 were significantly decreased in the HIV-positive (CDC-A and CDC-B) group. Tuberculosis patients demonstrated low T cell reactivity against Ag85, irrespective of HIV infection, and finally AIDS patients suffering from NTM infections were completely nonreactive to Ag85. A one-year follow-up of twelve HIV-positive tuberculin-positive individuals indicated a decreased reactivity against Ag85 in patients developing clinical tuberculosis, highlighting the protective potential of this antigen.

The spectrum of opportunistic diseases complicating sarcoidosis.

Sarcoidosis is an inflammatory disease marked by a paradoxical immune status. The anergic state, which results from various immune defects, contrasts with the inflammatory formation of granulomas. Sarcoidosis patients may be at risk for opportunistic infections (OIs) and a substantial number of cases have been reported, even in untreated sarcoidosis. It is not clear how OIs in patients with sarcoidosis are different from other groups at risk. In this review, we discuss the most common OIs: mycobacterial infection (including tuberculosis), cryptococcosis, progressive multifocal leukoencephalopathy, and aspergillosis. Unlike peripheral lymphocytopenia, corticosteroids are a major risk factor for OIs but the occurrence of Ols in untreated patients suggests more complex predisposing mechanisms. Opportunistic infections presenting with extrapulmonary features are often misdiagnosed as new localizations of sarcoidosis. Aspergillomas mostly develop on fibrocystic lungs. Overall, physicians should be aware of the possible occurrence of OIs during sarcoidosis, even in untreated patients.

Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death.

BACKGROUND: A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown. METHODS: Immunological and clinical endpoints were evaluated in 2491 participants of the Swiss HIV Cohort Study initiating ART during a mean follow-up of 7.1 years. Data were analysed in persons with treatment interruptions (n = 1271; group A), continuous ART, but intermittent HIV-1 RNA at least 1000 copies/ml (n = 469; group B) and continuous ART and HIV-1 RNA constantly less than 1000 copies/ml (n = 751; group C). Risk factors for low CD4 T-cell counts and clinical events were analysed using Cox proportional hazards models. RESULTS: In groups A-C, CD4 T lymphocytes increased to a median of 427, 525 and 645 cells/μl at 8 years. In group A, 63.0 and 37.2% reached above 350 and 500 CD4 T cells/μl, whereas in group B 76.3 and 55.8% and in group C 87.3 and 68.0% reached these thresholds (P < 0.001). CD4 T-cell recovery directly depended on the cumulative duration of treatment interruptions. In addition, participants of group A had more Centers for Disease Control and Prevention B/C events, resulting in an increased risk of death. Major risk factors for not reaching CD4 T cells above 500 cells/μl included lower baseline CD4 T-cell count, higher age and hepatitis C virus co-infection. CONCLUSION: In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed. CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months.