Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.

BACKGROUND: Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. METHODS: Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. RESULTS: We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. CONCLUSIONS: In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration.

Primary amebic meningoencephalitis deaths associated with sinus irrigation using contaminated tap water.

BACKGROUND: Naegleria fowleri is a climate-sensitive, thermophilic ameba found in the environment, including warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM), which is almost universally fatal, occurs when N. fowleri-containing water enters the nose, typically during swimming, and N. fowleri migrates to the brain via the olfactory nerve. In 2011, 2 adults died in Louisiana hospitals of infectious meningoencephalitis after brief illnesses. METHODS: Clinical and environmental testing and case investigations were initiated to determine the cause of death and to identify the exposures. RESULTS: Both patients had diagnoses of PAM. Their only reported water exposures were tap water used for household activities, including regular sinus irrigation with neti pots. Water samples, tap swab samples, and neti pots were collected from both households and tested; N. fowleri were identified in water samples from both homes. CONCLUSIONS: These are the first reported PAM cases in the United States associated with the presence of N. fowleri in household plumbing served by treated municipal water supplies and the first reports of PAM potentially associated with the use of a nasal irrigation device. These cases occurred in the context of an expanding geographic range for PAM beyond southern tier states with recent case reports from Minnesota, Kansas, and Virginia. These infections introduce an additional consideration for physicians recommending nasal irrigation and demonstrate the importance of using appropriate water (distilled, boiled, filtered) for nasal irrigation. Furthermore, the changing epidemiology of PAM highlights the importance of raising awareness about this disease among physicians treating persons showing meningitislike symptoms.

Primary cutaneous cryptococcosis in a lung transplant recipient.

Cryptococcal skin lesions are found in 10 to 15% of patients with disseminated cryptococcosis. Primary skin inoculation by Cryptococcus neoformans is rare but has been reported. We report the first known case of primary cutaneous cryptococcosis in a lung transplant recipient. Our patient, a 57-year-old man, underwent left single-lung transplantation and presented with a nonhealing ulcer 50 months later. Skin histopathology and culture confirmed C. neoformans. Serum and cerebrospinal fluid cryptococcal antigen tests were negative. The lesion healed after treatment with fluconazole. To date, disseminated disease is not evident. Primary cutaneous cryptococcosis has been reported in kidney and liver recipients but not in lung transplantation recipients. Nonhealing ulcers in immunocompromised patients mandate aggressive diagnostic procedures. Differential diagnosis of these cutaneous lesions should consider fungi, including C. neoformans.

Innovative medical management with resection for successful treatment of pulmonary mucormycosis despite diagnostic delay.

We present a case of primary pulmonary mucormycosis infection in a renal transplant recipient diagnosed serendipitously by computed tomography scan. Treatment included discontinuation of immunosuppressive regimen, initiation of antifungal therapy with amphotericin B lipid complex, administration of granulocyte-macrophage colony stimulating factor, surgical excision of the involved lobe, and outpatient treatment with amphotericin B with dialysis. The patient ultimately required transplant nephrectomy as a result of immunosuppression discontinuation.