Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation.

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.

Use of human induced pluripotent stem cell-derived neurons as a model for Cerebral Toxoplasmosis.

Toxoplasma gondii is a ubiquitous protozoan parasite with approximately one-third of the worlds' population chronically infected. In chronically infected individuals, the parasite resides primarily in cysts within neurons in the central nervous system. The chronic infection in immunocompetent individuals has been considered to be asymptomatic but increasing evidence indicates the chronic infection can lead to neuropsychiatric disorders such as Schizophrenia, prenatal depression and suicidal thoughts. A better understanding of the mechanism(s) by which the parasite exerts effects on human behavior is limited due to lack of suitable human neuronal models. In this paper, we report the use of human neurons derived from normal cord blood CD34+ cells generated via genetic reprogramming, as an in vitro model for the study T. gondii in neurons. This culture method resulted in a relatively pure monolayer of induced human neuronal-like cells that stained positive for neuronal markers, MAP2, NFL, NFH and NeuN. These induced human neuronal-like cells (iHNs) were efficiently infected by the Prugniad strain of the parasite and supported replication of the tachyzoite stage and development of the cyst stage. Infected iHNs could be maintained through 5 days of infection, allowing for formation of large cysts. This induced human neuronal model represents a novel culture method to study both tachyzoite and bradyzoite stages of T. gondii in human neurons.

Analysis of cerebral toxoplasmosis in a series of 170 allogeneic hematopoietic stem cell transplant patients.

INTRODUCTION: Cerebral toxoplasmosis is a rare but fatal complication in hematopoietic stem cell transplant patients, which mostly is caused by reactivation of latent disease. METHODS: In this study, we report an analysis of cerebral toxoplasmosis in a series of 170 allogeneic stem cell transplant patients during a 30-month period at our institution. RESULTS: Among these allogeneic stem cell transplant patients, 5 were diagnosed with cerebral toxoplasmosis by brain magnetic resonance imaging and polymerase chain reaction of Toxoplasma gondii DNA. The incidence of cerebral toxoplasmosis was found to be 2.94%. CONCLUSION: Mortality rate is known to be very high in cerebral toxoplasmosis; therefore, it is life saving to diagnose the disease in the early stages and start treatment promptly, especially in high-endemic countries like Turkey.

Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: voxel-based-morphometry (VBM) study.

OBJECTIVES: To address the role of latent T. gondii infection in schizophrenia we studied the influence of latent toxoplasmosis on brain morphology. METHODS: An optimized voxel-based morphometry of magnetic resonance imaging was analyzed by analysis of variance with diagnosis and seropositivity as factors in 44 schizophrenic patients (12 T. gondii positive) and 56 controls (13 T. gondii positive). RESULTS: Grey matter (GM) volume was reduced in schizophrenia patients compared with controls in the cortical regions, hippocampus and in the caudate. In the schizophrenia sample we found a significant reduction of GM volume in T. gondii positive comparing with T. gondii-negative patients bilaterally in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres. T. gondii-positive and -negative controls did not differ in any cluster. Among participants seropositive to T. gondii the reduction of GM in the schizophrenia subjects was located in the same regions when comparing the entire sample (11,660 over-threshold voxels (P ≤ 0.05, FWR corrected). The differences between T. gondii-negative patients and controls consisted only of 289 voxels in temporal regions. CONCLUSIONS: Our study is the first to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls.

Imaging of neuro-AIDS.

The pathogenesis of the human immunodeficiency virus (HIV) infection of the central nervous system and the imaging presentation of patients with neurological complications from HIV/AIDS are discussed. Imaging findings are often nonspecific; however, correlations with patient's clinical signs and CD4 count allow a working diagnosis to be made.

Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome.

Microglial nodules associated with opportunistic and HIV-related lesions are frequently found in the brains of AIDS patients. However, in many cases, the causative agent is only presumptively suspected. We reviewed 199 brains of AIDS patients with micronodular lesions to clarify their etiology by immunohistochemistry (to Toxoplasma gondii, cytomegalovirus, herpes simplex virus I/II, varicella zoster virus and HIV-p24 core protein), PCR (for herpetic viruses and Mycobacterium tuberculosis) and electron microscopy. Productive HIV infection was observed in 110 cases (55.1%): 30 cases with Toxoplasma gondii encephalitis, 30 with cytomegalovirus encephalitis, eight with multiple cerebral diseases, while in the remaining 42 cases HIV was the only pathogenetic agent. Multinucleated giant cells (hallmark of HIV infection) were found in the MGNs of 85/110 cases with HIV-related lesions; the remaining 25 cases had only p24 positive cells but no multinucleated giant cells. In these latter cases the micronodular lesions had been initially attributed to the main opportunistic agent found in the brain, or defined as subacute encephalitis. Individual microglial nodules positive for an opportunistic pathogen were generally negative for HIV antigens. In 13 cases no opportunistic agent or HIV productive infection was found. In these cases, PCR and electron microscopy examination for HIV and other viral infections were negative. Our data suggest that HIV-immunohistochemistry should be used for the etiological diagnosis of micronodular lesions in AIDS brains, even in the presence of other pathogens. After extensive search, the etiology of the microglial nodules remains unknown in only a small percentage of cases.

[Recurrence of cerebral toxoplasmosis in 15 AIDS patients]. / Rechutes de toxoplasmose cérébrale chez 15 malades atteints de SIDA.

Relapse of brain toxoplasmosis in AIDS patients continue to occur despite maintenance therapy. The characteristics of 15 patients who experienced a relapse were reviewed. Mean delay of relapse was 7 months (2-20). Maintenance therapy for the 2 months prior to the relapse was pyrimethamine alone (n = 4), pyrimethamine plus dapsone (n = 3), pyrimethamine plus spiramycine (n = 1), pyrimethamine plus clindamycine (n = 4), pyrimethamine plus sulfadiazine (n = 1) and no treatment (n = 2). Strict compliance was ascertained for only 5 patients. Compared with the first episode of brain toxoplasmosis, all 15 patients had new neurological signs, and new lesions of the brain were detected by CT scan in 67% patients. This study showed that poor compliance to maintenance therapy is a major factor of relapse, and the less favourable response to acute therapy could be due to progression of immunodeficiency.

[Cerebral toxoplasmosis primarily diagnosed as a tumor]. / Cerebral toksoplasmose primaert diagnosticeret som tumor.

Three cases of cerebral toxoplasmosis as the presenting manifestation of AIDS are reported. The initial diagnoses were brain tumors because of the cerebral mass lesions which resembled glioblastoma. In the light of the increasing occurrence of AIDS, attention is drawn to cerebral toxoplasmosis as a differential diagnosis from glioblastoma multiforme.

[Detection of Toxoplasma gondii by "Polymerase Chain Reaction" (PCR) technique in AIDS infected patients using the repetitive sequence TGR1E]. / Détection de Toxoplasma gondii chez des patients sidéens par la technique de "Polymerase Chain Reaction" (PCR), à l'aide de la séquence répétée TGR1E.

A repetitive original DNA sequence, TGR1E, was cloned and sequenced, then used to develop a polymerase chain reaction (PCR) test for detecting Toxoplasma gondii. Preliminary studies were performed using purified T. gondii DNA or a lysate of purified T. gondii cells [7], with or without a leukocyte lysate. A negative correlation was evidenced between sensitivity of the test and the amount of cellular debris contaminating the DNA to be amplified. Nevertheless, the method was tested on 100 clinical specimens subjected to lysis using the same method. Among the 88 specimens from AIDS patients, four were positive by conventional diagnostic tests and by PCR. Among the 12 specimens tested as part of evaluations for the prevention of congenital toxoplasmosis, PCR failed to detect the positive results yielded by conventional tests on two amniotic fluid specimens. No false positive result was seen with the PCR method.