Coccidioidomycosis: A Contemporary Review.

Coccidioidomycosis, colloquially known as Valley Fever, is an invasive dimorphic fungal infection caused by Coccidioides immitis and C. posadasii. The fungi are found in the arid desert soils of the southwestern US, as well as in parts of Mexico and Central and South America. Acquisition is typically via inhalation of arthroconidia which become airborne after both natural (e.g., earthquakes, dust storms, and fires) and human-related events (e.g., military maneuvers, recreational activities, agriculture, and construction). The incidence of infection in increasing likely a result of both climatic and populational changes. Further, the recognized geographic distribution of Coccidioides spp. is expanding, as cases are being diagnosed in new areas (e.g., eastern Washington, Oregon, and Utah). Most coccidioidal infections are asymptomatic (60%); however, approximately one-third develop a pulmonary illness which is a leading cause of community-acquired pneumonia in highly endemic areas. Uncommonly (0.5-2% of cases), the infection disseminates to extrapulmonary locations (e.g., skin, bones/joints, and the central nervous system), and is most commonly seen among persons with cellular immunodeficiencies (e.g., transplant recipients, HIV, and pregnancy) and non-Caucasian races (especially African Americans and Filipinos). The diagnosis of coccidioidomycosis requires astute clinical suspicion and laboratory findings, including positive serology, cultures, and/or histopathology results. Treatment is warranted among persons with pneumonia who have risk factors for complicated disease and among those with extrapulmonary disease. Novel antifungals with improved fungicidal activity and rapidity of action with fewer side effects and drug interactions are needed. Preventive strategies (e.g., education regarding the disease, dust avoidance, mask wearing, including among select groups, antifungal prophylaxis, and surveillance laboratory testing) are advised for residents and travelers to endemic areas. Currently, no preventive vaccine is available. Coccidioidomycosis has been recognized for over a century, and an expanding wealth of knowledge has been gained regarding this emerging infectious disease which will be reviewed here.

Fifteen-year study of the changing epidemiology of methicillin-resistant Staphylococcus aureus.

PURPOSE: The study's purpose was to elucidate the evolutionary, microbiologic, and clinical characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infections. METHODS: MRSA cases from military medical facilities in San Diego, from 1990 to 2004, were evaluated and categorized as community-acquired or nosocomial. Sequence type, staphylococcal chromosomal cassette gene type, and Panton-Valentine leukocidin gene status were determined for a subset of isolates. RESULTS: Over the 15-year period, 1888 cases of MRSA were identified; 65% were community acquired. The incidence (155 infections/100000 person-year in 2004) and household-associated cases rapidly increased since 2002. Among persons with community-acquired MRSA, 16% were hospitalized and only 17% were initially given an effective antibiotic. Community-acquired MRSA cases compared with nosocomial MRSA cases were more often soft-tissue and less often urinary, lung, or bloodstream infections (P<.001). Patients with community-acquired MRSA were younger (22 vs 64 years, P<.001) and less likely to have concurrent medical conditions (9% vs 98%, P<.001). Clindamycin resistance increased among community-acquired MRSA isolates during 2003 and 2004 compared with previous years (79% vs 13%, P<.001). Genetically, nosocomial MRSA isolates were significantly different than those acquired in the community. Although community-acquired MRSA isolates were initially diverse by 2004, one strain (staphylococcal chromosomal cassette type IV, sequence type 8, Panton-Valentine leukocidin gene positive) became the predominant isolate. CONCLUSIONS: Community-acquired and intrafamilial MRSA infections have increased rapidly since 2002. Our 15 years of surveillance revealed the emergence of distinct community-acquired MRSA strains that were genetically unrelated to nosocomial MRSA isolates from the same community.

Coccidioidomycosis in pregnancy: case report and review of the literature.

BACKGROUND: Coccidioidomycosis is an uncommon fungal infection during pregnancy. We report a case and review the literature on coccidioidomycosis in pregnancy. METHODS: We searched MEDLINE (1966-2005), PubMed (1950-2005), Embase (1974-2005), the Cochrane Library, and the Index-Catalogue of the Library of the Surgeon-General's Office United States Army (1880-1961) for cases of coccidioidomycosis occurring during pregnancy. We describe a woman with disseminated coccidioidomycosis during the last trimester of pregnancy with fungemia, respiratory failure, a miliary pattern on chest radiograph, and skin and bony involvement. RESULTS: We identified 80 additional cases of coccidioidomycosis occurring with pregnancy in the literature. The mean age of patients was 26 years (range 16-38 years). Disseminated disease was strongly associated with the trimester of pregnancy; 40% of the cases diagnosed before pregnancy, 50% of the cases diagnosed in the first trimester, 62% of the cases diagnosed in the second trimester, and 96% of the cases diagnosed in the third trimester had dissemination (P<.001). In addition, African American women had a 13-fold increased risk of dissemination compared with white women (P=.007). CONCLUSIONS: Mortality rates have improved over time in association with the timely administration of antifungal therapy. Disseminated coccidioidomycosis may occur during pregnancy, especially during the third trimester. Improved maternal and fetal survival is associated with early disease recognition and administration of amphotericin B.

Epstein Barr virus hepatitis: case series and review.

Epstein Barr virus (EBV) infection causes asymptomatic liver-associated enzyme abnormalities in 80 to 90% of cases which are often unrecognized. Patients with acute EBV infections may also develop cholestatic hepatitis with associated jaundice and hepatitis with moderate elevations in the transaminase levels. Other gastrointestinal complications associated with EBV may include splenic rupture, liver failure due to acute and/or chronic EBV infection, and perhaps, autoimmune hepatitis and hepatocellular carcinoma. This article presents a case series of EBV infections with clinically significant hepatitis and reviews the literature on the gastrointestinal complications of EBV.

Efficacy of Cyto-Chex blood preservative for delayed manual CD4 testing using Dynal T4 Quant CD4 test among HIV-infected persons in Zambia.

BACKGROUND: Manual CD4 tests such as Dynal T4 Quant (Dynabeads, Dynal Biotech, Oslo, Norway) are less expensive alternatives to flow cytometry in resource-limited countries. Whereas blood preservatives have proven useful for stabilizing blood samples to allow delayed CD4 testing by flow cytometry, they have not been verified for manual tests. A method for preservation of blood prior to manual CD4 testing is needed for long-distance transport or sample batching. METHODS: Blood from HIV-positive Zambian military beneficiaries was mixed (1:1) with Cyto-Chex (Streck Laboratories, La Vista, NE) blood preservative, and the blood was stored at refrigerated, ambient, and incubator (37 degrees C) temperatures prior to Dynabeads CD4 testing at 0, 3, 6, and 9 days after collection. Baseline flow cytometry and Dynabeads testing without preservative were performed for comparison. RESULTS: Twenty-seven patient samples were analyzed. Dynabeads vs. flow cytometry had a correlation coefficient (r) of 0.84. There was excellent correlation (r = 0.96) between baseline Dynabeads testing and Cyto-Chex-preserved samples. Refrigerated samples showed strong correlation with baseline Dynabeads (r = 0.93-0.95) on days 3, 6, and 9 without decline in CD4 count (P = 0.73). Samples stored at ambient temperature yielded inferior results (r = 0.76-0.81), with a significant decline in CD4 count by day 3 (P < 0.001). The incubator arm had especially poor correlation (r = 0.30-0.49). CONCLUSIONS: Addition of Cyto-Chex to peripheral blood (1:1) adequately preserves refrigerated blood samples for up to 9 days for subsequent testing with Dynabeads CD4 test. Cyto-Chex, however, cannot be recommended for delayed Dynabeads CD4 testing with storage at 37 degrees C or ambient temperatures in tropical areas similar to the site of this study.

Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras.

METHODS: Comparisons of death-related variables during the 3 eras were performed. RESULTS: The number of deaths declined over the study period, with 987 deaths in the pre-HAART era, 159 deaths in the early HAART era (1997-1999), and 78 deaths in the late HAART era (2000-2003) (P < 0.01). The annual death rate peaked in 1995 (10.3 per 100 patients) and then declined to <2 deaths per 100 persons in the late HAART era (P < 0.01). The proportion of deaths attributable to infection decreased, but infection remained the leading cause of death in our cohort, followed by cancer. Of those who died, there was an increasing proportion of non-HIV-related deaths (32% vs. 9%; P < 0.01), including cardiac disease (22% vs. 8%; P < 0.01) and trauma (8% vs. 2%; P = 0.01) in the post-HAART versus pre-HAART era. Despite the absence of intravenous drug use and the low prevalence of hepatitis C coinfection in our cohort, an increasing proportion of deaths in the HAART era were attributable to liver disease, although the numbers are small. CONCLUSIONS: Despite increasing concerns regarding antiretroviral resistance, the death rate among HIV-infected persons in our cohort continues to decline. Our data show a lower death rate than that reported among many other US HIV-infected populations; this may be the result of open access to health care. A shift in the causes of death toward non-HIV-related causes suggests that a more comprehensive health care approach may be needed for optimal life expectancy; this may include enhanced screening for malignancy and heart disease as well as preventive measures for liver disease and accidents.

Non-typhi Salmonella empyema: case report and review of the literature.

A case of non-typhi Salmonella empyema is reported. A review of the literature over the past century found only 13 other empyemas due to Salmonella typhimurium and 25 cases of other non-typhi Salmonella. A review of pleuropulmonary disease due to non-typhi Salmonella is provided along with management recommendations.

A review of hypogonadism and erectile dysfunction among HIV-infected men during the pre- and post-HAART eras: diagnosis, pathogenesis, and management.

Hypogonadism and erectile dysfunction (ED) appear to be more common among men infected with HIV compared to age-matched men within the general U.S. population. HIV providers should consider these conditions and utilize standardized evaluation and diagnostic criteria. Treatment of both hypogonadism and ED increases sexual function and quality of life; testosterone supplementation in the setting of hypogonadism may also improve lean body mass, mental status, and anemia. We review the epidemiology, diagnosis, pathogenesis, and treatment options of both hypogonadism and ED among HIV-infected men.

Infections associated with tumor necrosis factor-alpha antagonists.

Tumor necrosis factor (TNF)-alpha antagonists are promising therapeutic agents for patients with severe autoimmune and rheumatologic conditions. Unfortunately, their use has been associated with an increased rate of tuberculosis, endemic mycoses, and intracellular bacterial infections. Infliximab, 1 of 3 available drugs in this novel class, appears to be associated with the greatest risk of infection, likely because of its long half-life and induction of monocyte apoptosis. Prospective trials are necessary to determine the exact risk associated with these agents, particularly the newer TNF-alpha antagonists. More specific TNF-alpha blockers, which reduce inflammation while maintaining adequate immunity, are needed. In the meantime, a thorough work-up is mandatory for all febrile illness occurring in TNF-alpha blocker recipients. We present 4 patients who developed severe infections during TNF-alpha antagonist therapy, review the literature, and discuss current guidelines for surveillance and prophylaxis.

The emergence of severe, community-acquired methicillin-resistant Staphylococcus aureus infections.

The number of community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections is rapidly increasing. Most CA-MRSA infections are localized soft tissue infections; however, severe life-threatening infections have been occasionally described. This report serves to increase the awareness of severe CA-MRSA infections by presenting a fulminant CA-MRSA infection with sepsis, endocarditis, septic pulmonary emboli, and extensive soft tissue and bone destruction. A review of the literature revealed 14 cases of severe CA-MRSA infections with a median age of 13 y; 93% had no underlying medical condition. Only 1 case was initially treated with antibiotics effective for MRSA. The fatality rate was 64%, and 40% of patients who survived had significant disabilities.

Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals.

BACKGROUND: The objective of this study was to determine the rates and predictors of non-AIDS-defining cancers (NADCs) among a cohort of human immunodeficiency virus (HIV)-infected individuals. METHODS: The authors conducted a retrospective study of 4144 HIV-infected individuals who had 26,916 person-years of follow-up and who had open access to medical care at 1 of the United States military HIV clinics during the years 1988-2003. Cancer incidence rates were race specific and were adjusted for age; these were compared with national rates using logistic regression to assess predictors of NADC development. RESULTS: One hundred thirty-three NADCs were diagnosed with a rate of 980 diagnoses per 100,000 person-years. The most frequent NADCs were skin carcinomas (basal cell and squamous cell), Hodgkin disease, and anal carcinoma. The results showed that there were higher rates of melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease among the HIV-infected cohort compared with age-adjusted rates for the general United States population. Predictors of NADCs included age older than 40 years (odds ratio [OR], 12.2; P < 0.001), Caucasian/non-Hispanic race (OR, 2.1; P < 0.001), longer duration of HIV infection (OR, 1.2; P < 0.001), and a history of opportunistic infection (OR, 2.5; P < 0.001). The use of highly active antiretroviral therapy (HAART) was associated with lower rates of NADCs (OR, 0.21; P < 0.001). A low CD4 nadir or CD4 count at diagnosis (< 200 cells/mL) was not predictive of NADCs. CONCLUSIONS: The most frequent NADCs were primary skin malignancies. Melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease occurred at higher rates among HIV-infected individuals. The implementation of screening programs for these malignancies should be considered. Most risk factors for the development of NADCs are nonmodifiable; however, the use of HAART appeared to be beneficial in protecting against the development of malignant disease.

History of U.S. military contributions to the study of parasitic diseases.

U.S. military researchers have made major contributions to the discovery, diagnosis, treatment, and prevention of a number of parasitic diseases. We review the paramount U.S. military contributions to the understanding of leishmaniasis, filariasis, schistosomiasis, trypanosomiasis, gastrointestinal parasites, intestinal capillariasis, and angiostrongyliasis.

Cytomegalovirus retinitis after immune reconstitution.

Cytomegalovirus (CMV) infection is the most common opportunistic infection that affects the retina in HIV-positive patients; it typically occurs in the setting of severe immune suppression (CD4 count less than 50 cell/microL). We present a case report of an HIV-infected patient in whom recurrent CMV retinitis developed after HAART and apparent immune reconstitution (CD4 count of greater than 500 cells/microL). This case report underscores that CMV infection may occur despite high CD4 counts among patients who experience only partial immune reconstitution.