Visceral Leishmaniasis in Immunocompetent Hosts in Brescia: A Case Series and Analysis of Cytokine Cascade.

Visceral leishmaniasis (VL) is a parasitic zoonosis caused by Leishmania spp. that usually manifests itself in immunocompromised subjects. It is a rare and neglected disease, and it is not endemic in the province of Brescia (Italy). Three cases of human VL occurred in Brescia from October to December 2021 in immunocompetent patients. We evaluated the patients looking for signs of underlying immunodeficiencies and conducted further epidemiological evaluations in the province of Brescia without success. An analysis of the sera levels of the main cytokines involved in the immune response to VL was performed. All patients presented a significant augmentation of CXCL-10, CCL-4, and IL-6. The patients tested during the acute phase showed an elevation of IL-1α, IL-5, IL-10, and IL-12, while in the recovery phase, higher levels of TNF-α and IL-7 were detected. Altogether, a predominant activation of the T-helper-2 pathway emerged during the acute phase of the parasite infection, while the cytokines associated with the T-helper-1 pathway were less represented. This imbalanced immune response to the parasite infection might play a crucial role in the development of VL in immunocompetent patients.

Disseminated Histoplasmosis as AIDS-presentation. Case Report and Comprehensive Review of Current Literature.

Progressive disseminated histoplasmosis (PDH) is an AIDS-defining illness with a high lethality rate if not promptly treated. The wide range of its possible clinical manifestations represents the main barrier to diagnosis in non-endemic countries. Here we present a case of PDH with haemophagocytic syndrome in a newly diagnosed HIV patient and a comprehensive review of disseminated histoplasmosis focused on epidemiology, clinical features, diagnostic tools and treatment options in HIV-infected patients.

Effectiveness of kidney transplantation in HIV-infected recipients under combination antiretroviral therapy: a single-cohort experience (Brescia, Northern Italy).

PURPOSE: Kidney transplantation was recently introduced for the treatment of end stage renal disease (ESRD) in HIV-infected patients. We report the results of the first 28 procedures at our centre. METHODS: A retrospective study was conducted on HIV-infected patients evaluated for kidney transplantation between January 2005 and October 2016. Patients were selected and monitored by the kidney transplantation and infectious diseases teams, according to the national protocol. RESULTS: 60 patients were evaluated; 32 entered the list and 28 were transplanted. Median CD4+ count was 337 cell/µL at transplantation and 399 cell/µL 12 months thereafter. HIV RNA was undetectable at transplantation in 27/28 patients and became undetectable within 24 weeks in the only patient starting antiretroviral combination therapy (cART) after surgery. Four patients experienced virological failure, but reached again undetectability after cART regimen change. At last available point of follow-up (median 126.1 weeks), HIV RNA was undetectable in all patients. Three patients experienced AIDS-defining events. We observed a cumulative number of 19 acute rejections in 16 patients (median time from transplantation to first rejection 5.2 weeks). Survival rate was 82.1%. To avoid pharmacokinetics (PK) interactions, cART regimen was changed from a protease inhibitor (PI)/non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to an integrase inhibitor (InSTI)-based regimen in 11/20 alive patients with functioning graft. CONCLUSIONS: Kidney transplantation appears to be safe in HIV-infected patients carefully selected. As previously reported, we observed a high incidence of acute rejection. We expect that the recent implementation of the immunosuppressive protocols will allow a better immunologic control. Moreover, the introduction of InSTI permits a better strategy of cART, with lower incidence of PK interactions with immunosuppressive drugs.

Lymphoproliferative disease with mixed cryoglobulinemia and hyperviscosity syndrome in an HIV-infected patient: HCV is the only culprit.

The availability of direct antiviral agents (DAAs) offers the possibility to treat HCV-infected patients with a high rate of efficacy and a good safety profile. Little is known about the benefit of DAAs on HCV-related hematological diseases and their complications. We describe the case of an HIV/HCV-infected patient with HCV-related chronic lymphoproliferative disease, mixed cryoglobulinemia and hyperviscosity syndrome. Treatment with direct antiviral agents (DAAs) cured HCV infection and its complications, while HCV re-infection caused recrudescence of the associated diseases.

Colitis during new direct-acting antiviral agents (DAAs) therapy with sofosbuvir, simeprevir and ribavirin for genotype 1b hepatitis C.

Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

Antibiotics for the newborn.

Because of the high susceptibility to infections, antibiotics are the most widely used drugs in newborns. The result of antibiotic use, however, may be strongly influenced by the peculiar physiology of the neonate, characterized by the delicate process of adaptation from intra- to extra-uterine life. Additional important factors that may affect antibiotic therapy are gestational age, birth weight, the intrauterine growth restriction, chronological age and, especially, the kidney and liver function immaturity. Dosing, timing and route of administration must, therefore, take in careful consideration the neonatal variability of bioavailability, distribution, metabolism, biotransformation, and excretion. The fine adjustment of dosing and duration of therapy should be based on pharmacokinetic and pharmacodynamic parameters. In spite of significant variations of sepsis etiology, the best initial empiric therapy of a suspected systemic infection still remains, as several years ago, the association of ampicillin and gentamicin. Other very effective and useful antibiotics, as cephalosporins, carbanepems or glycopeptides should be administered judiciously to infants, following the recommendations of a restricted use, to obtain maximal efficacy and minimal toxicity. Finally, because of their peculiar features, macrolide antibiotics have recently been proposed for different indications than the antibacterial activity. Use of oral erythromycin for the treatment of gastrointestinal dysmotility in preterm infants could reduce the incidence of parenteral nutrition-associated cholestasis by almost 50%, while azithromycin because of the combined antibiotic and anti-inflammatory effects, has been successfully used in a pilot study in the extremely low birth weight infant for the prevention of bronchopulmonary dysplasia.