Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients.

Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1 µg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2 µg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.

Coronavirus Disease 2019 (COVID-19) in a Patient with Disseminated Histoplasmosis and HIV-A Case Report from Argentina and Literature Review.

The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care.

Identificación de citomegalovirus y varicela zoster virus en lesiones cutáneas en una paciente con sida Presentación de un caso y revisión de la bibliografía / CENTRAL NERVOUS SYSTEM INVOLVEMENT DUE TO HERPESVIRUS REACTIVATION IN AIDS PATIENTS

Las reactivaciones de las infecciones latentes por virus de la familia Herpes originan variadas y graves manifestaciones clínicas en los enfermos con sida. Las lesiones mucocutáneas son comunes en las infecciones por Herpes simple 1 y 2 y por varicela-zóster (VZV). En cambio, son infrecuentes en infecciones por citomegalovirus (CMV). La coexistencia de más de un patógeno en la misma lesión ha sido escasamente referida en la literatura. Presentamos una paciente con enfermedad VIH/sida avanzada que desarrolló lesiones cutáneas diseminadas, en una de las cuales se identificó por técnica de PCR el genoma de VZV y CMV. El diagnóstico precoz seguido del tratamiento antiherpético y la reconstitución inmunológica alcanzada con la TARGA pueden mejorar el pronóstico de esta clase de pacientes

The reactivation of latent infections due to Herpesviridae is associated with a serious compromise in HIV/AIDS patients. Mucocutaneous lesions are frequent in disseminated infections due to Herpes simple 1 and 2 and varicella-zoster virus (VZV). However, cutaneous involvement is rare in cytomegalovirus infections. The coexistence of VZV and CMV in the same lesion has been little reported in the literature. Here, we describe a female with advanced HIV/AIDS disease who developed disseminated cutaneous lesions, in one of yhem we detected VZV and CMV by PCR. Early diagnosis followed by specific antiherpetic therapy and the immune reconstitution associated with HAART can improve the prognosis of these kind of patients.

Ventriculoperitoneal shunts for treating increased intracranial pressure in cryptococcal meningitis with or without ventriculomegaly.

INTRODUCTION: Cryptococcosis is an opportunistic mycosis, especially in patients that are human immunodeficiency virus (HIV)-positive, and frequently involves the central nervous system. METHODS: We assessed the potential of ventriculoperitoneal shunting (VPS) in preventing mortality due to uncontrollable intracranial hypertension (ICH) in 15 patients with acquired immunodeficiency syndrome (AIDS)-related cryptococcal meningitis. RESULTS: After 2 weeks of antifungal therapy consisting of amphotericin B deoxycholate with or without fluconazole, patients with persistent ICH underwent VPS, despite having persistent Cryptococcus neoformans infection. In 12 patients, the uncontrollable ICH was resolved by VPS. CONCLUSIONS: Patients with cryptococcal meningoencephalitis who have ICH must be considered for VPS even with positive cerebrospinal fluid cultures.

Anal squamous cell carcinoma in HIV/AIDS patients in the HAART era: Report of 8 cases and literature review.

BACKGROUND: Anal squamous cell carcinoma is a rare neoplasm with a higher incidence in the HIV-seropositive population. PATIENTS AND METHODS: Epidemiologic, clinic, immunologic, virologic and therapeutic characteristics of 8 HIV-positive patients with anal squamous cell carcinoma were descriptively and retrospectively analyzed from 2005 to 2011. RESULTS: Median of age ofpatients was 39 years, 75% were male and 83% were men who have sex with men. Median elapsed time from HIV infection to anal cancer diagnosis was 10.5 ± 9.5 years. Anal pain and local large tumors detected by physical examination were the most common clinical manifestations; pain with or without itching was marginally correlated with poor survival. The median of CD4 T-cell countfor the whole study group was 330 cells/µL. At the time ofthe neoplasm diagnosis, CD4 T-cell count was more than 200 cell/µL in 62.5% of the patients. In the descriptive analysis, higher CD4 T-cell count was significantly associated with a prolonged survival. In the overall population, 71% were receiving highly active antiretroviral therapy (HAART) and all of them had undetectable viral load at the time ofneoplasm diagnosis. HAART was correlated with better survival in the overallpopulation. Histopathologic examination showed that 4 cases (50%) had in situ carcinoma and 4 patients (50%) had diagnosis of invasive anal carcinoma. One patient underwent surgical tumorectomy plus HAART, 2 patients received chemotherapy plus HAART and 3 patients were treated with fractionated radiotherapy plus systemic chemotherapy plus HAART. One patient died without the possibility of treatment due to his poor clinical condition and for one patient was no available data. After a follow up of 2 years, overall survival rate was 71%. CONCLUSION: A carefully evaluation of anal infiltrative or tumoral lesions is necessary to achieve an early diagnosis and to improve the survival in this kind of patients.

[Clinical problems in medical mycology: Problem number 47]. / Problemas clínicos en micología médica: problema número 47.

A 66 year-old man, who had lived in Paraguay and was a rural worker, was admitted to Infectious Diseases Hospital F. J. Muñiz in Buenos Aires. He presented fever, loss of body weight, cough, mucopurulent expectoration, wide perianal ulceration, paresthesia and paresis of both legs as well as vesical and anal sphincter dysfunction. He was a heavy smoker and drinker. Thorax X-ray examination showed bilateral micronodular interstitial lesions. With a NMR of the dorsolumbar spine region a nodular lesion outside the spinal cord (which produced compression of this organ) was shown. The diagnosis of disseminated paracoccidiodomycosis was based on the finding of Paracoccidioides brasiliensis in the skin ulcer in histopathology and mycology studies, and on the positive results of serologic tests with paracoccidioidin antigen. The patient was treated with trimethoprim-sulfamethoxazole with good clinical outcome.