Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism

THE TREATMENT OF COCCIDIOIDOMYCOSIS

Therapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection.A terapia da coccidioidomicose continua a evoluir. Para a doença pulmonar primária, o tratamento antifúngico frequentemente não é necessário, enquanto períodos prolongados de tratamento antifúngico são geralmente necessários para aqueles nos quais houve disseminação extratorácica. A anfotericina B intravenosa deve ser reservada para pacientes com doença grave. Antifúngicos triazólicos orais têm tido um grande impacto no manejo da coccidioidomicose. Tanto fluconazol quanto itraconazol em doses diárias de 400 mg foram eficazes contra várias formas de coccidioidomicose, incluindo a meníngea, embora recaídas após a interrupção da terapia ainda constituam um problema. Indivíduos com supressão da imunidade celular apresentam risco aumentado para a coccidioidomicose sintomática, incluindo pacientes infectados pelo HIV, em uso de medicações imunossupressoras, e os que receberam transplantes de órgãos sólidos. Mulheres grávidas e homens afro-americanos foram identificados como dois outros grupos que apresentam risco aumentado de infecção sintomática e grave

Coccidioidomycosis: Changing Concepts and Knowledge Gaps

Although first described more than 120 years ago, much remains unknown about coccidioidomycosis. In this review, new information that has led to changing concepts will be reviewed and remaining gaps in our knowledge will be discussed. In particular, new ideas regarding ecology and epidemiology, problems and promises of diagnosis, controversies over management, and the possibility of a vaccine will be covered

Central Nervous System Infections Due to Coccidioidomycosis

Coccidioidomycosis is a common infection in the western and southwestern United States as well as parts of Mexico and Central and South America and is due to the soil-dwelling fungi Coccidioides. Central nervous system (CNS) infection is an uncommon manifestation that is nearly always fatal if untreated. The presentation is subtle, commonly with headache and decreased mentation. The diagnosis should be considered in patients with these symptoms in association with a positive serum coccidioidal antibody test. The diagnosis can only be established by analysis of cerebrospinal fluid (CSF), which typically demonstrates a lymphocytic pleocytosis, hypoglycorrhachia, elevated protein, and positive CSF coccidioidal antibody. Cultures are infrequently positive but a proprietary coccidioidal antigen test has reasonable sensitivity. Current therapy usually begins with fluconazole at 800 mg daily but other triazole antifungals also have efficacy and are often used if fluconazole fails. Triazole therapy should be lifelong. Intrathecal amphotericin B, the original treatment, is now reserved for those in whom triazoles have failed. There are several distinct complications of CNS coccidioidal infection, the most common of which is hydrocephalus. This is nearly always communicating and requires mechanical shunting in addition to antifungal therapy. Other complications include cerebral vasculitis, brain abscess, and arachnoiditis. Management of these is difficult and not well established

Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells▿

Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P = 0.03). When monocyte-derived mature dendritic cells pulsed with T27K (mDCT27K) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDCT27K did significantly increase the concentrations of IL-2 and IFN-γ released by PBMC from nonimmune donors (P = 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low- and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P = 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis

Cellular Immune Suppressor Activity Resides in Lymphocyte Cell Clusters Adjacent to Granulomata in Human Coccidioidomycosis

The in situ immunologic response in human coccidioidomycosis remains undefined. To explore this further, pulmonary necrotizing coccidioidal granulomata were examined using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-γ). Discrete perigranulomatous lymphocytic clusters were seen in eight of nine tissues examined. In these tissues, T lymphocytes (CD3(+)) significantly outnumbered B lymphocytes (CD20(+)) in the mantle area of the granulomata (P = 0.028), whereas the clusters were composed of roughly equal numbers of T and B lymphocytes. While the number of cells in the mantle expressing IL-10 was similar to those in the perigranulomatous clusters, there were significantly more cells expressing IFN-γ in the mantle than in the clusters (P = 0.037). Confocal microscopy revealed that CD4(+) T lymphocytes and B lymphocytes are associated with IL-10 production. CD4(+)CD25(+) T lymphocytes were identified in the perigranulomatous clusters but were not associated with IL-10 production. This is the first report noting perigranulomatous lymphocyte clusters and IL-10 in association with human coccidioidal granulomata and suggests that down-regulation of the cellular immune response is occurring within coccidioidal granulomata