Disseminated leishmaniasis (DL) caused by L. braziliensis is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against Leishmania is mediated by macrophages upon activation by IFN-γ produced by CD4+T cells, the pathology of disseminated leishmaniasis (DL) could be mediated by macrophages, NK, and CD8+T cells. Herein, we evaluate the participation of senescent CD8+T cells in the pathogenesis of DL. Methods: Peripheral blood mononuclear cells (PBMCs), biopsies, co-cultures of CD8+T cells with uninfected and infected macrophages (MØ), and PBMC cultures stimulated with soluble L. braziliensis antigen (SLA) for 72 h from patients with cutaneous leishmaniasis (CL) and DL were used to characterize senescent CD8+T cells. Statistical analysis was performed using the Mann-Whitney and Kruskal-Wallis tests, followed by Dunn\'s. Results: Patients with DL have an increase in the frequency of circulating CD8+T cells that present a memory/senescent phenotype, while lesions from DL patients have an increase in the frequency of infiltrating CD8+T cells with a senescent/degranulation phenotype. In addition, after specific stimuli, DL patients\' circulating CD8+T with memory/senescent profile, showing degranulation characteristics, increased upon SLA stimuli, and those specific CD8+T cells from DL patients had an increased degranulation phenotype, causing more apoptosis of infected target cells. Conclusions: DL patients show a higher frequency of cytotoxic senescent CD8+T cells compared to CL patients, and that could promote the lysis of infected cells, although without parasite killing, releasing Leishmania to the extracellular compartment, contributing to the spread of parasites.

Cat scratch disease (CSD) is an infection caused by Bartonella henselae, presents with non-specific symptoms like lymphadenopathy, fever, and fatigue. It can progress to disseminated disease, leading to complications such as liver and splenic micro abscesses, osteomyelitis, encephalitis, and uveitis. Diagnosis is challenging due to varied presentations and limited tests. Treatment involves supportive care, with severe cases requiring antimicrobial therapy. In this report, we present a case of Cat scratch disease characterized by an atypical clinical manifestation, hepatosplenic and paravertebral involvement.

Angiosarcoma-like Kaposi sarcoma represents a recently delineated rare histomorphologic variant of Kaposi sarcoma that can be difficult to distinguish from other vasoproliferative lesions. Conventional lesions of Kaposi sarcoma encompass patches, plaques, and nodules; however, rarely vesiculobullous lesions have been described. Angiosarcoma-like Kaposi sarcoma has never been previously reported to present with vesiculobullous lesions. Herein, we describe a unique case of disseminated angiosarcoma-like Kaposi sarcoma with vesiculobullous lesions as the initial manifestation of human immunodeficiency virus infection.

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted (tps1Δ) Cryptococci are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (tps1Δ:TPS1) strains expand in the lungs and disseminate, causing 100% mortality. Rapid pulmonary clearance of tps1Δ mutant is T-cell independent and relies on its susceptibility to lung resident factors and innate immune factors, exemplified by tps1Δ but not H99 inhibition in a coculture with dispersed lung cells and its rapid clearance coinciding with innate leukocyte infiltration. In the disseminated model of infection, which bypasses initial lung-fungus interactions, tps1Δ strain remains highly attenuated. Specifically, tps1Δ mutant is unable to colonize the lungs from the bloodstream or expand in spleens but is capable of crossing into the brain, where it remains controlled even in the absence of T cells. In contrast, strains H99 and tps1Δ:TPS1 rapidly expand in all studied organs, leading to rapid death of the infected mice. Since the rapid pulmonary clearance of tps1Δ mutant resembles a response to acapsular strains, the effect of tps1 deletion on capsule formation in vitro and in vivo was examined. Tps1Δ cryptococci form capsules but with a substantially reduced size. In conclusion, TPS1 is an important virulence factor, allowing C. neoformans evasion of resident pulmonary and innate defense mechanisms, most likely via its role in cryptococcal capsule formation.

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A 79-year-old man with type II diabetes mellitus and recently diagnosed idiopathic thrombocytopenic purpura presented to the Emergency Department with progressive dyspnea over the course of two weeks. He was found to have diffuse miliary nodules, dense cavitary consolidation, and widespread cystic changes on chest imaging and died within 48 hours of admission to the hospital. His serum Coccidioides antibody and urine Histoplasma antigen were both positive. He later grew Coccidioides immitis from the blood, supporting the theory that Histoplasma positivity was likely the result of antigen test cross-reactivity. Coccidioidomycosis typically presents with mild, self-limited symptoms, but may also disseminate rapidly, causing fulminant, life-threatening disease. Prompt recognition of risk factors for fulminant coccidioidomycosis and understanding flaws in serologic testing are essential to the appropriate diagnosis and management of this disease.

UNASSIGNED: Melioidosis is an infection caused by Burkholderia pseudomallei, a Gram-negative bacterium. It is a disease endemic to Southeast Asia and northern Australia although its global incidence has been rising. It most commonly infects people with certain identified risk factors such as diabetes, alcoholism, thalassemia, and underlying chronic disease involving lungs, kidney and liver. This bacterium is capable of producing a wide array of clinical manifestations ranging from asymptomatic disease to localised infections such as in the lung, bone or skin to disseminated infection.
UNASSIGNED: This is a case, from United Arab Emirates, of a 40-year-old male recently diagnosed with diabetes who presented with multiple abscesses and was eventually diagnosed with disseminated melioidosis. He was treated successfully with antibiotics and drainage of abscesses.
UNASSIGNED: In non-endemic regions, melioidosis can be easily missed in common diagnostic approaches. This gap of awareness could delay the diagnosis and allow further deterioration of the patient due to complications. Thus, case reports like this can enlighten internists about changing incidences and complexity of clinical presentations, thus preparing them to better handle such patients in the future.
CONCLUSIONS: Owing to its considerably rare incidence in non-endemic regions including the United Arab Emirates, melioidosis can easily be overlooked or misdiagnosed.Moreover, due to similarity with multiple other diseases and infections as well as significant absence from standard medical curricula, melioidosis is rarely on the differential list of an internist.This report aims to enhance awareness and alertness to aid earlier detection and avoid severe complications.

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Coccidioidomycosis is a fungal infection primarily Endemic in the Southwest United States. Disseminated Coccidioidomycosis is a life-threatening variant that mainly occurs in an immunocompromised host. This report describes an unusual presentation of disseminated Coccidioidomycosis in an immunocompetent individual. The patient was admitted with a subacute cough, progressively worsening shortness of breath, significant weight loss, nodular skin lesions in upper extremities, and acute hypoxemic respiratory failure. Chest imaging revealed extensive nodularity and mass-like lesions. What sets this case apart is the significant endotracheal and endobronchial involvement, which mimicked metastatic lung cancer. The diagnosis was confirmed through serology and bronchoscopy biopsy. This case underscores the critical importance of considering detailed travel history and maintaining a high index of suspicion for fungal infections in patients with endobronchial lesions, particularly in regions where Coccidioidomycosis is endemic.

Nocardia farcinica, an aerobic, Gram-positive bacterium belonging to the genus Nocardia, is a challenging opportunistic pathogen, particularly impacting immunocompromised individuals. The prevalence of human disease has witnessed a notable rise over the past two decades, correlating with an expanding population of immunocompromised individuals and advancements in the detection and identification of Nocardia spp. within clinical laboratories. This case is of a 59-year-old male with compromised immunity due to immunosuppressive medication use following a renal transplant who had an array of presentations before confirming a diagnosis of disseminated nocardiosis. The challenges faced in our case provide valuable insights into the complexities associated with diagnosing and managing Nocardia infections in immunocompromised populations, informing future clinical practice and research endeavors.