Dectin-1 rs3901533 and rs7309123 Polymorphisms Increase Susceptibility to Pulmonary Invasive Fungal Disease in Patients with Acute Myeloid Leukemia from a Chinese Han Population.

This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1 (Dectin-1), Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) influence the susceptibility to pulmonary invasive fungal disease (IFD) in patients with acute myeloid leukemia (AML) from a Chinese Han population. Eight single nucleotide polymorphisms (SNPs) of Dectin-1 (rs16910526, rs3901533, and rs7309123), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791) and MyD88 (rs4988453 and rs4988457) in the genomic DNA of 172 adult AML patients were genotyped. Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus guidelines. SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD. The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR (qRT-PCR), and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed. Two Dectin-1 intron SNPs (rs3901533 and rs7309123) were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population. Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model (G/T+G/G vs. T/T, OR: 2.158; 95% CI: 1.109-4.2, P=0.02), Dectin-1 rs3901533 G allele (OR: 2.201; 95% CI: 1.206-4.019, P=0.01), or Dectin-1 rs7309123 C allele (OR: 1.919; 95% CI: 1.047-3.518, P=0.03). There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs (rs16910526), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791) or MyD88 (rs4988453 and rs4988457). In conclusion, two Dectin-1 SNPs (rs3901533 and rs7309123) are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.

Coccidioidomycosis: Experience From a Children's Hospital in an Area of Endemicity.

The incidence of coccidioidomycosis is increasing, and published pediatric experience is limited. This study further characterizes pediatric coccidioidomycosis by describing experience with 64 patients cared for at Children's Hospital of Los Angeles over 20 years, with focus on sites of involvement and severity, as well as serologic profiles of affected children.

Mannose-binding lectin serum levels are low in persons with clinically active coccidioidomycosis.

BACKGROUND: Mannose-binding lectin (MBL) is a circulating collectin that is part of the innate immune response. We explored the serum levels of MBL in persons with different forms of coccidioidomycosis. METHODS: Serum MBL was measured by ELISA from samples obtained from healthy donors with immunity to Coccidioides, and those with various forms of active coccidioidomycosis. Blood cell specimens from a subgroup of subjects with active coccidioidomycosis were examined for single nucleotide polymorphisms of the MBL gene and promoter regions. RESULTS: The control group comprised 29 healthy immune subjects. Patient groups with active coccidioidomycosis consisted of 20 patients with symptomatic primary pulmonary coccidioidomycosis, 26 with non-meningeal disseminated coccidioidomycosis, and nine with coccidioidal meningitis. The group with active coccidioidomycosis was significantly older and more likely to be male than the control group (for both, P < 0.001). The mean +/- SEM level of serum MBL in the healthy controls was 169.4 +/- 28.6 ng/ml, significantly higher than the 79.2 +/- 10.9 ng/ml for all active groups (P < 0.001). Moreover, the active coccidioidomycosis group was significantly more likely to have serum MBL level

Pulmonary coccidioidomycosis found in healthy Japanese individuals.

BACKGROUND AND OBJECTIVE: Coccidioidomycosis is endemic in the south-western USA. This study described the clinicopathological features of pulmonary coccidioidomycosis found in otherwise healthy Japanese individuals. METHODS: Four male patients with pulmonary coccidioidomycosis were assessed by clinical examination, serology, PCR assay, high-resolution computed tomography and histopathological findings. RESULTS: All patients had returned to Japan from the USA and all presented with an abnormal CXR during routine assessment; two of the patients were symptomatic. High-resolution computed tomography showed a well-defined homogenous nodule or mass adjacent to the pleura. All patients underwent surgical wedge resection. Histopathological examination revealed encapsulated caseating epithelioid cell granulomas containing spherules and endospores. Serum IgG antibody was negative in all patients, but PCR assay using DNA from resected specimens demonstrated the presence of coccidioides-specific DNA. CONCLUSIONS: Pulmonary coccidioidomycosis is very rare in Japan, but it can be found incidentally during routine evaluation. The main high-resolution computed tomography findings are a well-defined homogenous nodule adjacent to the pleura, reflecting the histological feature of encapsulated granulomas. PCR assay is useful for confirming the presence of coccidioides.

Cryptococcal pneumonia in African miners at autopsy.

SETTING: Deceased miners from South Africa whose cardiorespiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: To 1) calculate the prevalence of cryptococcal pneumonia in 8421 autopsied miners, a population with a high prevalence of human immunodeficiency virus (HIV) infection; 2) document the association of cryptococcal pneumonia with other pulmonary infection; 3) document the association of cryptococcal pneumonia with a clinical diagnosis of cryptococcal meningitis; and 4) determine the accuracy of the clinical diagnosis of cryptococcal pneumonia. DESIGN: Case series of 589 black miners with histological evidence of cryptococcal pneumonia at autopsy, defined as the presence of cryptococcal organisms in the lung parenchyma, identified by staining of the mucinous capsule. RESULTS: The incidence of cryptococcal pneumonia at autopsy was 7%. Ninety-seven of the 589 cases (16.5%) had a concomitant respiratory infection, most commonly Pneumocystis jirovecii pneumonia (51.5%), followed by mycobacterial infection (42.3%). In life, cryptococcal meningitis was diagnosed in 46.9% and cryptococcal pneumonia in only 2.7%. CONCLUSION: Although tuberculosis remains the most common HIV-associated respiratory disease in Africa, it is important to consider the diagnosis of cryptococcal pneumonia in acquired immune-deficiency syndrome (AIDS) patients, and to bear in mind the possibility of dual pathology.

[HIV-associated histoplasmosis with pulmonary manifestation in Europe]. / HIV-assoziierte Histoplasmose in Europa mit pulmonaler Manifestation.

A 35-year-old man developed weight loss, lower abdominal pain, diarrhoea, cough, fever and general deterioration in his health. He had been born and resident in the USA until 1991, when he moved to Germany. Since 1991 he had known that he was HIV-positive. The chest radiograph showed bilateral diffuse spotty marking and a rounded cardiac silhouette, the latter echocardiographically due to pericardial effusion. Tuberculostatic drugs were started because miliary tuberculosis was suspected. But as his condition worsened and he was thought to have Pneumocystis pneumonia high doses of co-trimoxazole were administered. Perbronchial lung biopsy showed nonspecific chronic inflammatory changes. Periodide acid-Schiff reaction and Grocott staining demonstrated numerous histoplasma in alveolar macrophages and connective tissue. The organism was also cultured from bronchial secretions. Treatment was now changed to itraconazole (400 mg daily), 2 weeks later changed to liposomal amphotericin B (100 mg daily) because of renewed fever. After 6 weeks the patient became free of symptoms and the radiological changes had largely regressed. To prevent recurrence, treatment with itraconazole (400 mg daily) is being continued.

[Pulmonary mycoses and parasitosis]. / Les mycoses et parasitoses pulmonaires.

Lungs can be the target of many fungal parasitic organisms. Some of them are specific to the lung (Pneumocystis); while others will migrate there in the course of their life cycle (Ascaris) or be caught in it (Paragonimus, Echinococcus). Sometimes, they also generate hypersensitivity reactions (fungi). In making a diagnosis one has to consider the present state of health or the disease history of the patient. A great number of parasites or mycetes are opportunist agents found in immuno-compromised patients. The epidemiological investigation giving details of a trip, even a long time ago, in a tropical region allows the suspicion of an imported parasitosis or an exotic mycosis. At present, we have on one hand, the mixing of populations, and on the other hand, many immuno-compromised situations which has given rise to a renewed interest in fungal and parasitic lung diseases.