Publications by authors named "Caleb Skipper"

Cryptococcal meningitis is a fungal infection that is typically caused by and most commonly seen in severely immunosuppressed patient. This disease causes severe neurologic disease due to elevated intracranial pressures. In this case report, we describe a patient with newly diagnosed HIV presenting to the hospital with cryptococcal meningitis complicated by sudden vision loss.

View Article and Find Full Text PDF
Article Synopsis
  • Multisystem inflammatory syndrome in children (MIS-C) is a serious condition linked to COVID-19, causing inflammation and affecting multiple organs.
  • Research indicates that while antibodies are produced, there are issues with cell-mediated immune responses, particularly with natural killer (NK) cells, which show reduced functionality.
  • Possible treatments, like using CD16 cellular engagers, may improve NK cell function and help address the immune system's dysregulation associated with MIS-C.
View Article and Find Full Text PDF
Article Synopsis
  • Individuals with HIV and cryptococcal antigenemia face a high risk of developing cryptococcal meningitis or death, with factors like baseline CrAg titer and CRP levels being crucial for assessing outcomes.* -
  • In a study of 182 participants, those with elevated CRP levels had a higher rate of meningitis or death compared to those with normal CRP levels, specifically revealing that elevated CRP impacted low CrAg titer individuals more significantly.* -
  • The research indicates a complex relationship between CrAg titers and CRP levels, suggesting that future studies should further explore this interaction to improve patient risk assessments and outcomes.*
View Article and Find Full Text PDF
Article Synopsis
  • Cryptococcal meningitis poses a significant risk for individuals with AIDS, and the study aims to evaluate if adding a high-dose of liposomal amphotericin B to fluconazole can reduce the incidence of meningitis among asymptomatic CrAg-positive individuals.
  • In a trial with participants from Uganda, those with low plasma CrAg titers were given either liposomal amphotericin B with fluconazole or fluconazole alone for 24 weeks to assess meningitis-free survival.
  • Results showed no significant difference in meningitis or death rates between the two groups, suggesting that for asymptomatic patients with low CrAg levels, adding liposomal amphotericin B does not improve outcomes and may lead to
View Article and Find Full Text PDF

Background: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.

View Article and Find Full Text PDF
Article Synopsis
  • Cryptococcal meningitis is a significant cause of mortality in individuals with late-stage HIV, and the relationship between cerebrospinal fluid (CSF) immune responses and leukocyte infiltration's impact on survival is being studied.
  • A study involving 401 adults in Uganda showed that those with a higher CSF leukocyte count (≥50/μL) had a 68% survival rate at 18 weeks, compared to 52% for those with lower counts, indicating that immune response is critical for survival.
  • Increased survival correlates with elevated levels of specific immune markers, including T helper cytokines and certain chemokines, suggesting that a robust immune response in CSF is vital for improving outcomes in patients with HIV
View Article and Find Full Text PDF

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection.

View Article and Find Full Text PDF

Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity.

View Article and Find Full Text PDF
Article Synopsis
  • Adults with HIV-associated cryptococcal meningitis frequently have concurrent infections with cytomegalovirus (CMV) and tuberculosis (TB), which can complicate their health outcomes.
  • A study of 497 Ugandan patients revealed that 42% either developed TB or died within a median follow-up of 4.6 months, with a notable risk increase linked to high levels of CMV viremia at diagnosis.
  • Specifically, participants with high CMV viremia (≥1000 IU/mL) were more than twice as likely to experience TB or death compared to those with lower or no detectable CMV levels.
View Article and Find Full Text PDF
Article Synopsis
  • Amphotericin B is the primary treatment for severe fungal infections, and a new less-toxic oral formulation called lipid nanocrystal (LNC) amphotericin has been developed for potential use.
  • A clinical trial tested LNC amphotericin against traditional intravenous amphotericin for treating cryptococcal meningitis in HIV patients, focusing on safety, efficacy, and survival rates.
  • Results showed that the oral formulation had comparable effectiveness and was associated with fewer severe side effects compared to intravenous treatment, suggesting it could be a safer alternative for patients.
View Article and Find Full Text PDF
Article Synopsis
  • * This study investigates the impact of hyponatremia in asymptomatic individuals who have cryptococcal antigenemia (the presence of cryptococcal antigens in the blood).
  • * It finds that having serum hyponatremia levels at or below 130 mmol/L independently raises the risk of developing meningitis and increases mortality in these individuals.
View Article and Find Full Text PDF

Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019-January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre-coronavirus disease 2019 period).

View Article and Find Full Text PDF

Introduction: The role of cytomegalovirus (CMV) infection as a co-factor in HIV disease has been a topic of considerable interest since the beginning of the HIV pandemic. CMV is believed to function both as a co-factor in the progression of HIV infection, and as a contributor to enhanced disease for other opportunistic infections.

Areas Covered: In this special article, we review several recent studies that have enhanced our understanding of the role that CMV infection plays in the natural history of other HIV-related opportunistic infections.

View Article and Find Full Text PDF

Cryptococcus is the leading cause of AIDS-related meningitis in sub-Saharan Africa. The clinical implications of a sterile cerebrospinal fluid (CSF) culture among individuals diagnosed with cryptococcal meningitis using CSF cryptococcal antigen (CrAg) are unclear. We prospectively enrolled 765 HIV-positive Ugandans with first-episode cryptococcal meningitis from November 2010 to May 2017.

View Article and Find Full Text PDF
Article Synopsis
  • Cryptococcal meningitis is a significant cause of death in AIDS patients, and understanding the reasons for symptom recurrence is challenging.
  • A study in Uganda classified recurrent cases into categories like microbiological relapse and paradoxical immune reconstitution inflammatory syndrome (IRIS), enrolling 724 participants.
  • Findings showed that patients with relapse had lower immune markers (CD4 and cerebrospinal fluid white blood cell counts) compared to those with IRIS, with higher mortality rates associated with the first episodes of meningitis and relapses.
  • The results suggest that monitoring these lab values can guide early antifungal treatment.
View Article and Find Full Text PDF
Article Synopsis
  • A study in Uganda assessed the outcomes of HIV patients with cryptococcal meningitis, comparing those diagnosed through routine CrAg screening to those with symptomatic meningitis who went directly to the hospital.
  • Results indicated that CrAg-screened individuals had significantly lower 14-day mortality rates (12% vs 21%) and better overall health indicators, such as lower altered mental status and CSF burden.
  • The findings suggest that CrAg screening allows for earlier detection of cryptococcal meningitis, leading to better survival outcomes compared to those diagnosed without screening.
View Article and Find Full Text PDF

Objectives: CMV viremia is associated with increased mortality in persons with HIV. We previously demonstrated that CMV viremia was a risk factor for 10-week mortality in antiretroviral therapy (ART)-naïve persons with cryptococcal meningitis. We investigated whether similar observations existed over a broader cohort of patients with HIV-associated meningitis at 18 weeks.

View Article and Find Full Text PDF

Background: During the coronavirus disease 2019 (COVID-19) pandemic, clinical trials necessitated rapid testing to be performed remotely. Dried blood spot (DBS) techniques have enabled remote HIV virologic testing globally, and more recently, antibody testing as well. We evaluated DBS testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing in outpatients to assess seropositivity.

View Article and Find Full Text PDF

Bacteremia is a rare complication of infection. To our knowledge, there are only two case reports to date of , both hypothesized to be secondary to a gastrointestinal source. Herein, we report a case of an elderly man with genome sequence-proven bacteremia from a possible cutaneous source without neuromuscular symptoms.

View Article and Find Full Text PDF

Unlabelled: Cryptococcal antigen (CrAg) screening and pre-emptive antifungal therapy for people with CD4 cell counts <100 cells/μl are recommended by the World Health Organization and several national HIV guidelines. We sought to evaluate CrAg screening program implementation across Uganda, in relation to health center level and distance from the capital. We conducted a cross-sectional study of 22 health centers across southern Uganda from April to June 2019.

View Article and Find Full Text PDF
Article Synopsis
  • A new cryptococcal antigen semiquantitative (CrAgSQ) lateral flow assay (LFA) offers rapid results for diagnosing cryptococcal meningitis without needing time-consuming serial dilutions.
  • The study compared the CrAgSQ assay's diagnostic performance with existing CrAg LFA in cerebrospinal fluid samples from HIV-associated meningitis patients, showing 100% sensitivity and specificity.
  • Higher grades of CrAgSQ correlate with increased fungal culture positivity and disease severity, implying that this test not only identifies infection accurately but also provides insights into the patient's condition.
View Article and Find Full Text PDF

As the severe acute respiratory syndrome coronavirus 2 pandemic evolved, it was apparent that well designed and rapidly conducted randomized clinical trials were urgently needed. However, traditional clinical trial design presented several challenges. Notably, disease prevalence initially varied by time and region, and the pockets of outbreaks evolved geographically over time.

View Article and Find Full Text PDF
Article Synopsis
  • C-reactive protein (CRP) is produced by the liver in response to inflammation and can serve as a biomarker to track infection outcomes, particularly in HIV-infected individuals with cryptococcal meningitis.
  • A study involving 168 HIV-infected Ugandans indicated that higher baseline CRP levels were linked to increased mortality rates at 18 weeks, highlighting a significant correlation between CRP levels and disease severity.
  • The findings suggest that monitoring CRP could help identify patients at higher risk of mortality due to potential coinfections or immune system factors impacting individuals with advanced AIDS and cryptococcal meningitis.
View Article and Find Full Text PDF

Background: Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials.

Methods: We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design.

View Article and Find Full Text PDF