Effectiveness of a "Suppression Bundle" to improve HIV virologic suppression in an outpatient infectious disease clinic: a pilot implementation study.

Despite effectiveness and accessibility of combined anti-retroviral therapy (cART), only 85% of people living with HIV (PLHIV) in the United States are virologically suppressed. Improving suppression is complex. Our objective was to consider unique factors in PLHIV with non-suppressed viral loads in clinic and improve the percentage of suppressed patients by implementing a "Suppression Bundle" consisting of three to five bundled interventions with the goal of improved suppression. Prior to the study, there were 567 HIV-positive patients receiving care in clinic. Of those, 89 had a measurable viral load (>40 copies/mL). In this pilot pre-post implementation, we focused on the 89 non-suppressed patients to (1) determine feasibility of implementing bundles and (2) increase the number of patients with suppressed viral loads pre- to post-intervention. Of non-suppressed patients, 65 were active in care immediately pre-intervention and participated in the pilot. At the completion of the 9-month intervention, 46 had viral loads <40 copies/mL, demonstrating substantial improvement with 70.1% of the previously non-suppressed patients achieving suppression. By considering unique patient factors, an individualized Suppression Bundle is acceptable, feasible, and may increase virally suppressed patients in an outpatient clinic. Next steps include determining whether suppression bundles can be implemented in differing practices.

Re-drawing the Maps for Endemic Mycoses.

Endemic mycoses such as histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, and talaromycosis are well-known causes of focal and systemic disease within specific geographic areas of known endemicity. However, over the past few decades, there have been increasingly frequent reports of infections due to endemic fungi in areas previously thought to be "non-endemic." There are numerous potential reasons for this shift such as increased use of immune suppressive medications, improved diagnostic tests, increased disease recognition, and global factors such as migration, increased travel, and climate change. Regardless of the causes, it has become evident that our previous understanding of endemic regions for these fungal diseases needs to evolve. The epidemiology of the newly described Emergomyces is incomplete; our understanding of it continues to evolve. This review will focus on the evidence underlying the established areas of endemicity for these mycoses as well as new data and reports from medical literature that support the re-thinking these geographic boundaries. Updating the endemic fungi maps would inform clinical practice and global surveillance of these diseases.

Geographical distribution of the Cryptococcus gattii species complex: a systematic review.

The taxonomy of the Cryptococcus gattii species complex continues to evolve, and has been divided into five pathogenic species. The objective of this systematic review was to summarise the geographical distribution of the C gattii species complex and the species within the C gattii species complex. We searched PubMed for articles related to human, animal, ecological, or laboratory-based studies of C gattii species complex isolates with traceable geographical origin published from January, 1970, until September, 2021. Having extracted their geographical origin, we used ArcMap to construct maps according to the highest degree of resolution allowed by their reported taxonomy, to reflect the most likely area of transmission on the basis of published reports of human isolates. 604 such articles were included in the study. This review indicated that although C gattii species complex isolates have been reported globally, understanding their heterogeneous geographical distribution by species can have implications for researchers and clinicians in formulating research questions and considering diagnostic quandaries.

Diagnosis of Pulmonary Infections Due to Endemic Fungi.

Endemic mycoses including Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, and Talaromyces are dimorphic fungi that can cause a variety of clinical manifestations, including respiratory infections. Their pulmonary presentations are variable, and diagnosis is often delayed as they can mimic other infectious and non-infectious causes of pulmonary disease. Delay in diagnosis can lead to unnecessary antibiotic use, repeat hospitalizations, and increased morbidity and mortality. The diagnosis of endemic fungal pulmonary infections often relies on multiple diagnostic tests including culture, tissue histopathology, antigen assays, and antibody assays. Due to the increased use of immunosuppressive agents and the widening geographic ranges where these infections are being found, the prevalence of endemic fungal infections is increasing. Physicians need to be aware of the clinical manifestations of pulmonary infections due to endemic fungal in order to ensure that the proper diagnostic work up is obtained promptly. A high index of suspicion is particularly important in patients with suspected pulmonary infections who have failed to improve despite antibiotics in the appropriate setting. We present a review diagnostic testing for pulmonary infections due to endemic mycoses.

Methods for rapid diagnosis of meningitis etiology in adults.

Infectious meningitis can be caused by viral, bacterial or fungal pathogens. Despite widely available treatments, many types of infectious meningitis are still associated with significant morbidity and mortality. Delay in diagnosis contributes to poor outcomes. Cerebrospinal fluid cultures have been used traditionally but are time intensive and sensitivity is decreased by empiric treatment prior to culture. More rapid techniques such as the cryptococcal lateral flow assay (IMMY), GeneXpert MTB/Rif Ultra (Cepheid) and FilmArray multiplex-PCR (Biofire) are three examples that have drastically changed meningitis diagnostics. This review will discuss a holistic approach to diagnosing bacterial, mycobacterial, viral and fungal meningitis.

Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease.

Antiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment. Recently published studies have emphasized the importance of neutrophils and T cell subtypes in TB-IRIS pathogenesis, alongside the recognized role of CD4 T cells and macrophages. Research has also refined our prognostic understanding, revealing how the disease can impact lung function. While corticosteroids remain the only trial-supported therapy for prevention and management of TB-IRIS, increasing interest has been given to biologic therapies directly targeting the immune pathology. TB-IRIS, especially its unmasking form, remains incompletely described and more data is needed to validate biomarkers for diagnosis. Management strategies remain suboptimal, especially in the highly morbid central nervous system (CNS) form of the disease, and further trials are necessary to refine treatment. In this review we will summarize the current understanding of the immunopathogenesis, the presentation of TB-IRIS and the evidence for management recommendations.

Afatinib-induced Interstitial Lung Disease Successfully Treated with Corticosteroids: Case Report and Review of the Literature.

The first-line treatment for advanced epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) includes the use of afatinib and other EGFR tyrosine kinase inhibitors (EGFR-TKIs). While generally well tolerated, a small subset of patients will develop drug-induced interstitial lung disease (ILD) which could lead to drug discontinuation or even death. A 58-year-old female with stage IV NSCLC treated with afatinib presented with dyspnea and rapidly progressive hypoxemia. Imaging of the lungs demonstrated ground glass opacities. Infectious workup was unrevealing, and since drug-induced ILD was suspected early on presentation, high dose corticosteroids were initiated leading to clinical improvement. While the incidence of afatinib-induced ILD is rare, the consequences may be serious and potentially fatal. The presentation is often non-specific and may mimic other common respiratory pathologies making the diagnosis challenging. If therapeutic measures such as corticosteroids are initiated promptly, they can be life-saving.