Disseminated coccidioidomycosis presenting with intramedullary spinal cord abscesses: Management challenges

Coccidioides species are endemic to the southwestern United States and typically cause a mild or asymptomatic primary infection. In some instances, infection can disseminate and involve the central nervous system with meningitis being the most common manifestation. Non-osseous spinal cord involvement is exceedingly rare. We report a case of disseminated coccidioidomycosis in an otherwise healthy 20 year old man with diffuse leptomeningeal enhancement, cerebrospinal fluid findings suggestive of meningitis, and intramedullary spinal cord abscesses. Response to treatment occurred with prolonged systemic liposomal amphotericin B and voriconazole. An extended course of steroids was needed to blunt inflammation

The need for sexual health clinics, their future role, and contribution to public health

Specialised sexual health clinics (SHCs) play an important role in addressing the staggering rates of STIs seen in many high-income nations. Despite increasing healthcare coverage in the US and nationalised health care in some countries, there is a continued need for SHCs to meet the needs of patients and the community, especially for high-priority populations: those at high risk of STI acquisition and/or groups historically marginalised and underserved in the traditional healthcare system. We need to mobilise resources to support a stronger clinical infrastructure in specialised SHCs. This review describes the importance of SHCs, their future role, and some of the innovative programs housed within SHCs in the US, Australia, and the Netherlands to address both STI and HIV prevention for the populations they serve

Adaptation of the collaborative care model to integrate behavioral health care into a low-barrier HIV clinic

Background The collaborative care management (CoCM) model is an evidence-based intervention for integrating behavioral health care into nonpsychiatric settings. CoCM has been extensively studied in primary care clinics, but implementation in nonconventional clinics, such as those tailored to provide care for high-need, complex patients, has not been well described. Method We adapted CoCM for a low-barrier HIV clinic that provides walk-in medical care for a patient population with high levels of mental illness, substance use, and housing instability. The Exploration, Preparation, Implementation, and Sustainment model guided implementation activities and support through the phases of implementing CoCM. The Framework for Reporting Adaptations and Modifications to Evidence-Based Interventions guided our documentation of adaptations to process-of-care elements and structural elements of CoCM. We used a multicomponent strategy to implement the adapted CoCM model. In this article, we describe our experience through the first 6 months of implementation. Results The key contextual factors necessitating adaptation of the CoCM model were the clinic team structure, lack of scheduled appointments, high complexity of the patient population, and time constraints with competing priorities for patient care, all of which required substantial flexibility in the model. The process-of-care elements were adapted to improve the fit of the intervention with the context, but the core structural elements of CoCM were maintained. Conclusions The CoCM model can be adapted for a setting that requires more flexibility than the usual primary care clinic while maintaining the core elements of the intervention

In vivo expansion of CD4(+)CD45RO–CD25(+) T cells expressing foxP3 in IL-2-treated HIV-infected patients

Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4(+)CD45RO(–)CD25(+) cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4(+)CD45RO(–)CD25(+) cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45RO(–)CD25(–) or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25(+) cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45RO(+)CD25(+high) cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4(+)CD45RO(–)CD25(+) cells that express high levels of foxP3 but exert weak suppressive function. These CD4(+)CD25(+) cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4(+) T cell pool

Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses

The alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole virus, protein, and peptide levels, consistent with bi-directional cross-reactivity. HSV-specific CD4 T cells recovered from HSV seronegative persons can be partially explained by such VZV cross-reactivity. HSV-1-reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, and kill VZV-infected dermal fibroblasts. Mono- and cross-reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T-cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV-VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10-50%. Based on these findings, we hypothesize host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens, and that cross-reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy