This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

Histoplasmosis: a Clinical and Laboratory Update

The incidence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. Such infections may be broken into two broad categories: opportunistic and endemic. The most important agents of the opportunistic mycoses are Candida spp., Cryptococcus neoformans, Pneumocystis jirovecii, and Aspergillus spp. (although the list of potential pathogens is ever expanding); while the most commonly encountered endemic mycoses are due to Histoplasma capsulatum, Coccidioides immitis/posadasii, and Blastomyces dermatitidis. This review discusses the epidemiologic profiles of these invasive mycoses in North America, as well as risk factors for infection, and the pathogens' antifungal susceptibility.

Epidemiology of Invasive Mycoses in North America

The USPHS/IDSA Prevention of Opportunistic Infections Working Group has recently formulated disease-specific recommendations for 17 opportunistic infections (OIs) or groups of OIs in HIV-infected persons [1]. The purpose of this article is to synthesize these recommendations and to offer the health care provider an organized approach to the prevention of OIs in this population. The authors recognize that preventing all exposures to opportunistic pathogens or all disease due to these pathogens is not possible. The avoidance of all behaviors and environments that can result in exposure to opportunistic pathogens would excessively restrict the patient's lifestyle. Furthermore, drugs active against many opportunistic pathogens are not available; even if they were, the multitude of agents required to reduce the risk of all OIs-with the attendant problems of toxicities, interactions, cost, and adherence to chemoprophylactic regimens-would render a complete preventive strategy impossible. This article is therefore intended to guide the provider in establishing priorities for the various preventive measures available.

USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus: Introduction

Population-based active laboratory surveillance for invasive mycotic infections was conducted during 1992 and 1993 in three California counties: Alameda, Contra Costa, and San Francisco (population, 2.94 million). The cumulative incidence of invasive mycotic infections was 178.3 per million per year. Invasive mycoses were most commonly caused by Candida (72.8 per million per year), Cryptococcus (65.5), Coccidioides (15.3), Aspergillus (12.4), and Histoplasma (7.1). The clinical significance of other, less common fungi was determined by detailed chart review. The cumulative incidence was determined for zygomycosis (1.7 per million per year), hyalohyphomycosis (1.2), and phaeohyphomycosis (1.0). The most common underlying conditions were human immunodeficiency virus infection (47.4%), nonhematologic malignancy (14.7%), diabetes mellitus (9.9%), and chronic lung disease (9.3%). This represents the first population-based epidemiological assessment of invasive mycoses in the United States.

The Epidemiological Features of Invasive Mycotic Infections in the San Francisco Bay Area, 1992–1993: Results of Population-Based Laboratory Active Surveillance

M E Eads

Papers

Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature.