Immune reconstitution inflammatory syndrome associated with disseminated Mycobacterium sherrisii infection

Mycobacterium sherrisii is a recently described mycobacterium closely related to Mycobacterium simiae. There have been only a few reports of this organism causing disease, predominantly in the setting of HIV with severe immunosuppression. We report the first case of disseminated M. sherrisii associated with immune reconstitution inflammatory syndrome.     

Immune reconstitution inflammatory syndrome in HIV-infected patients with disseminated histoplasmosis

Four HIV-1-infected patients presented with unusual clinical manifestations in the course of disseminated histoplasmosis, including liver abscesses, compressive lymphadenitis, intestinal obstruction, uveitis and arthritis within a median of 45 days after initiation of highly active antiretroviral therapy (HAART). They had a median increase of 106 CD4 cells/mul and granulomas with caseation in three. Partial immune reconstitution induced by HAART during disseminated histoplasmosis either related to the variety capsulatum or duboisii may be associated with immune reconstitution inflammatory syndrome.     

Immune reconstitution inflammatory syndrome associated with Mycobacterium tuberculosis infection: a systematic review

HIV and tuberculosis (TB) are leading global causes of mortality and morbidity. Highly active antiretroviral therapy (HAART) is often initiated in patients being treated for TB. The immune recovery associated with HAART results in dramatic clinical benefits, but this restoration of immunity may result in immunopathological reactions. The immune reconstitution inflammatory syndrome can result in fever, nodal enlargement, and worsening pulmonary infiltrates observed on a chest radiograph, with or without recurrent respiratory symptoms. Several other manifestations have also been described. As a consequence, the use of HAART might not be appropriate during the first weeks of anti-TB therapy in HIV-infected patients. In this review, we summarize the incidence, clinical presentations, and potential mechanisms of these conditions and we describe therapeutic methods.     

Immune reconstitution inflammatory syndrome in HIV-infected patients with Pneumocystis jirovecii pneumonia

Introduction

The incidence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after an episode of Pneumocystis jirovecii pneumonia (PJP) seems to be lower than with other opportunistic infections. We conducted an observational study in order to determine the incidence, clinical characteristics and outcome of patients diagnosed with PJP-related IRIS.

Paradoxical immune reconstitution inflammatory syndrome associated with disseminated tuberculosis infection in an unrelated donor cord blood transplant recipient

Tuberculosis (TB) is an infrequent infection after hematopoietic cell transplant (HCT), with associated mortality up to 30%. The utility of universal screening for latent TB in HCT candidates is controversial due to the lack of sensitive screening tests. We describe a case of disseminated TB infection complicated by immune reconstitution inflammatory syndrome in an adult double unit umbilical cord blood transplant recipient who originated from the United Arab Emirates.     

Immune reconstitution inflammatory syndrome in HIV

PURPOSE OF REVIEW: The purpose of this review is to describe the epidemiology, clinical features, putative immune mechanisms and management of immune reconstitution inflammatory syndrome (IRIS) using data published in the last 2 years. RECENT FINDINGS: Ever more conditions are reported as IRIS events. These most frequently occur with mycobacterial (tuberculosis or Mycobacterium avium complex infection) or cryptococcal disease (each in approximately 30% of cases). Definitions have been proposed for its clinical diagnosis. These suffer from a lack of prospective studies to support their predictive value. The immunopathogenesis of IRIS appears to be related to the interaction between HAART-induced changes in host immune response and the presence of (usually microbial) antigen. Increasing evidence exists that this might be an anatomically compartmentalized phenomenon, such that immune responses may be localized to specific tissue sites such as the brain. This has implications for the use of simple blood tests, such as CD4 count or change in viral load, when assessing risk of IRIS. Treatment options include immune modulation, though supportive care is typically all that is required, unless symptoms are prolonged, significant or life-threatening. SUMMARY: IRIS is common and will become more so as HAART is rolled out worldwide. Clear clinical definitions are required to avoid its over-diagnosis due to misclassification of other conditions.     

Immune reconstitution inflammatory syndrome associated with Aspergillus terreus pulmonary infection in an autologous stem cell transplant recipient

S. Antinori, M. Corbellino, A. Necchi, P. Corradini, C. Vismara, V. Montefusco, A.M. Gianni. Immune reconstitution inflammatory syndrome associated with Aspergillus terreus pulmonary infection in an autologous stem cell transplant recipient.
Transpl Infect Dis 2010: 12: 64–68. All rights reserved
Abstract: We describe an autologous stem cell transplant recipient who developed immune reconstitution inflammatory syndrome (IRIS) associated with Aspergillus terreus invasive pulmonary infection after recovery from neutropenia. Clinical and radiological worsening of pulmonary invasive aspergillosis coincident with a robust decline of serum galactomannan values and rising neutrophil counts should be interpreted as IRIS and should not require changes to antifungal therapy.     

Immune reconstitution inflammatory syndrome in HIV-infected patients with and without prior tuberculosis

We conducted a nested case-control study in a cohort of patients initiating antiretroviral therapy (ART) to identify risk factors and common manifestations of immune reconstitution inflammatory syndrome (IRIS) and to validate the Robertson criteria for IRIS prediction. HIV-infected patients at the Tuberculosis Research Centre clinics, Chennai and Madurai, India, initiating ART between July 2004 and June 2005 were prospectively studied. Of 97 patients (62% men, median age 32 years, median CD4 count 63 cells/μL) included, 34 developed IRIS. IRIS was more common in patients with a prior history of tuberculosis (74% versus 52%, P = 0.04), median time to development was 46 days and the sensitivity and specificity of the Robertson criteria to predict IRIS were 91% and 22%, respectively. In this population, IRIS was a common event, more so among patients with prior tuberculosis, and neither the rate of CD4 increase nor the Robertson criteria were useful in predicting its development.     

Immune reconstitution syndrome associated with opportunistic mycoses

Host immunity is essential in facilitating the eradication of infection. However, immunological recovery and an imbalance characterised by either suboptimum or excessive expression of immune responses can also be harmful to the host. Inflammatory responses triggered by rapid resolution of immunosuppression can lead to a series of localised and systemic reactions, termed immune reconstitution syndrome (IRS), that are often misconstrued as failure of specific antifungal therapy to eliminate the offending fungal pathogen. Recognition of IRS has become increasingly relevant in the context of our current use of potent immunosuppressive agents and immunostimulators that allow rapid manipulation of the immune system. Whereas the conceptual principles of IRS underscore the adverse effects of an overzealous and dysregulated immune response, they also support a role of immunotherapies to augment immunity if induction of endogenous responses is inadequate for the control of infection.     

Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals

Immune reconstitution disease (IRD) in HIV-infected patients is an adverse consequence of the restoration of pathogen-specific immune responses during the initial months of highly active antiretroviral treatment (HAART). Previously subclinical infections are "unmasked" or pre-existing opportunistic infections clinically deteriorate as host immunopathological inflammatory responses are "switched on". IRD is most frequently associated with mycobacterial infections. Our literature search identified 166 published cases of IRD associated with mycobacterial infections. We review the underlying immunological mechanisms, difficulties surrounding case definition and diagnosis, the wide diversity of clinical manifestations, and treatment. The importance of screening patients for mycobacterial disease before starting HAART and the critical impact of the timing of commencement of HAART in patients receiving treatment for tuberculosis are highlighted. We also discuss the problem of IRD associated with mycobacterial diseases in developing countries where tuberculosis prevalence is high and access to HAART is currently expanding.     

T lymphocyte responses to mycobacterial antigen in AIDS patients with disseminated Mycobacterium avium-Mycobacterium intracellulare infection

Patients with acquired immunodeficiency syndrome (AIDS) who have Mycobacterium avium-Mycobacterium intracellulare (MAI) infection typically have widely disseminated disease, often fail to respond to multi-drug chemotherapeutic regimens, and show little or no inflammatory tissue response. To determine if this clinicopathologic state correlates with in vitro lymphocyte responses to specific antigen, peripheral blood mononuclear cells from 18 patients with AIDS who had MAI bacillemia were stimulated with either particulate (heat-killed bacille Calmette Guérin [BCG]) or soluble (M intracellulare) mycobacterial antigens. In comparison to reactive cells from healthy control subjects testing positive with purified protein derivative of tuberculin (PPD) or from MAI-colonized (non-AIDS) control subjects, cells from 16 (89 percent) patients with AIDS essentially failed to show any antigen-induced proliferative activity or secretion of gamma-interferon; however, in two patients, antigen-stimulated proliferation of gamma-interferon production was modest but within the range of responses of normal healthy control subjects. Thus, although an occasional patient with AIDS can develop disseminated MAI infection despite the presence of antigen-reactive cells in vitro, most MAI-infected patients with AIDS display a striking defect in responsiveness to both particulate and soluble mycobacterial antigens. Since treatment with gamma-interferon activates the mononuclear phagocyte in vivo, these results suggest a rationale for a trial of gamma-interferon therapy in patients with AIDS who have disseminated MAI infection.     

The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS)

We analyzed cases of disseminated nontuberculous mycobacterial infection (DNTM) in patients with AIDS reported to the Centers for Disease Control. Between 1981 and 1987, 2,269 cases were reported. In 96% of cases, infection was caused by M. avium complex (MAC). The number of cases has risen steadily since 1981, but the rate as a percentage of AIDS cases has remained stable at 5.5%. DNTM was seen less frequently in AIDS cases with Kaposi's sarcoma than in other AIDS cases (p less than 0.01). Rates of DNTM were lower in Hispanics and declined with age but were not significantly different by patient sex or means of acquiring HIV infection. Rates of disseminated MAC varied by geographic region from 3.9% to 7.8% (p less than 0.0001). As assessed by helper/suppressor T-cell ratios, AIDS patients with DNTM were not more immunologically impaired than those with other opportunistic infections. Life table analysis revealed that AIDS patients with DNTM survived a shorter time (median, 7.4 months) than did other AIDS patients (median, 13.3 months; p less than 0.0001). We conclude that DNTM is acquired by unpreventable environmental exposures. Because DNTM adversely affects survival of AIDS patients, effective therapeutic agents must be vigorously sought.     

Immune reconstitution inflammatory syndrome in the lung in non-human immunodeficiency virus patients

BackgroundWe evaluated immune reconstitution inflammatory syndrome (IRIS) in the lung in non-human immunodeficiency virus (HIV) patients.MethodsWe reviewed articles related to IRIS occurrence in the lung in non-HIV patients using a PubMed search. The keywords used for the search were “immune reconstitution syndrome” and “non-HIV.” Only patients with lung involvement were included. Those with suggested IRIS caused by white blood cell recovery were excluded.ResultsThere were 37 cases of IRIS in the lung in non-HIV patients. Complicating infections included tuberculosis (n = 17), histoplasmosis (n = 9), aspergillosis (n = 5), cryptococcosis (n = 4), and Pneumocystis pneumonia (n = 2). We also evaluated the underlying diseases, IRIS pathogenesis, management, and prognosis. IRIS was most commonly encountered in patients treated with anti-tumor necrosis factor (TNF) antibody who developed disseminated or extrapulmonary tuberculosis, leading to treatment discontinuation.ConclusionsThe diagnosis and management of IRIS in the lung in non-HIV patients should be investigated further, especially in the era of anti-TNF treatment.     

Immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in an HIV-infected patient: an immunohistochemical study

Sarcoidosis has been rarely described in literature as a cause of interstitial pulmonary disease associated with AIDS. This study reports a case of immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in a patient with a history of previous pulmonary tuberculosis concomitant with HIV infection. Results of the immunohistochemical study of samples from the resected right lower lobe are described. Pathological findings suggest a role of Th1, Th2 and Th17 response in IRIS associated sarcoidosis.     

Immune reconstitution inflammatory syndrome among HIV/AIDS patients during highly active antiretroviral therapy in Addis Ababa, Ethiopia

Suppression of viral replication is followed by increases in CD4+ lymphocytes, and this has been shown to result in decreased susceptibility to opportunists after initiation of highly active antiretroviral therapy (HAART). However, clinical aggravations after the initiation of HAART have been thought to be due to the restored ability to mount an inflammatory response, or the immune reconstitution inflammatory syndrome (IRIS). The degree of IRIS observed in human immunodeficiency virus (HIV)-infected patients following initiation of HAART is variable. This prospective study was aimed at determining the proportion of IRIS and the pattern of opportunistic infections among 186 HIV/AIDS patients receiving HAART between December 2006 and July 2007 at Zewditu Memorial Hospital, Addis Ababa, Ethiopia. The proportion of IRIS was 17.2% (32/186). The mean number of days of IRIS occurrence for each disease ranged from 26 to 122 days with a mean of 80. Opportunistic diseases associated with IRIS were tuberculosis (68.8%, 22/32), herpes zoster rash (12.5%, 4/32), cryptococcosis (9.4%, 3/32), toxoplasmosis (6.3%, 2/32) and bacterial pneumonia (3.1%, 1/32). Compared to baseline readings there were significant increases in CD4 count, aspartate aminotransferase and alanine aminotransferase levels while hemoglobin values decreased during the development of IRIS. In summary, the proportion of IRIS and the pattern of opportunistic infections in HAART-treated patients in Ethiopia mirrored those reported in other countries. Further prospective surveys on epidemiological, immunological, microbial and clinical studies are imperative to assess the proportion and pattern of IRIS and effect of HAART in Ethiopia.