The Perennial Threat of Yellow Fever

Despite the availability of a safe and effective vaccine, yellow fever remains a major vaccine-preventable disease in endemic regions. Additionally, travelers risk acquiring yellow fever when visiting areas of endemic transmission or locations with ongoing outbreaks. Yellow fever is a viral hemorrhagic fever that has inflicted stigma, illness, and death among human societies. From the 17th to the 19th centuries, yellow fever remained a mysterious illness that predominantly affected tropical regions in Africa, the Caribbean and the Americas. The disease was as feared as cholera or smallpox, and played a significant geopolitical role in shaping modern societies. Epidemics of yellow fever brought out the best and the worst of human nature: the disease spread to new regions during the Atlantic slave trade; while the identification of its causative viral agent and mode of transmission, as well as the development of a vaccine, were made possible by the sacrifice of selfless scientists. Confirmation of the vector transmission of YF paved the way for the development of an effective vaccine in the first half of the 20th century. Encroachment of human settlements into locations with sylvatic transmission has blurred the distinction between the urban and sylvatic cycles. Introduction or expansion of routine immunization activities and reaching hard-to-reach populations consitute public health priorities toward ensuring vaccine equity in endemic areas. It is also critical to ensure the timely immunization of at-risk populations during outbreaks and to promote vaccination of international travelers. We conclude that the threat of YF will linger far into the 21st century as a leading public health emergency of global concern under the International Health Regulations

Primary Extranodal, Extralymphatic Hodgkin Lymphoma of the Mandible

Primary extranodal, extralymphatic Hodgkin lymphomas (PEEHLs) are a rare occurrence. When they are encountered, they become diagnostic challenges. We are describing the uniqueness of a case of PEEHL affecting the mandible with his early response to the available chemotherapy

Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions

Epidemiological trends and clinical outcomes of cryptococcosis in a medically insured population in the United States: a claims-based analysis from 2017 to 2019

Background: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. Objective: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. Methods: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. Results: Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). Conclusion: In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients

Diabetes Mellitus Type 2 as a Risk Factor and Outcome Modifier for Cryptococcosis in HIV Negative, Non-transplant Patients, a Propensity Score Match Analysis

Cryptococcosis is an opportunistic fungal infection of worldwide distribution with significant associated morbidity and mortality. HIV, organ transplantation, malignancy, cirrhosis, sarcoidosis, and immunosuppressive medications are established risk factors for cryptococcosis. Type 2 diabetes mellitus (DM2) has been hypothesized as a risk factor and an outcome modifier for cryptococcosis. We aimed to compare outcomes among HIV-negative, non-transplant (NHNT) patients with and without DM2. We queried a global research network to identify NHNT patients (n = 3280). We performed a propensity score-matched (PSM) analysis comparing clinical outcomes among cryptococcosis patients by DM status. We also characterize adults with cryptococcosis and DM2 as the only risk factor. After PSM, NHNT patients with DM2 were more likely to develop cognitive dysfunction [9% vs. 6%, OR 1.6; 95% CI (1.1–2.3); P = 0.01] but had similar mortality, hospitalization, ICU, and stroke risk after acquiring cryptococcosis when compared to NHNT patients without DM2. Pulmonary cryptococcosis was the most common site of infection. Among 44 cryptococcosis patients with DM2 as the only identifiable risk factor for disease, the annual incidence of cryptococcosis was 0.001%, with a prevalence of 0.002%. DM2 is associated with increased cognitive dysfunction risk in NHNT patients with cryptococcosis. It is rare for DM2 to be the only identified risk factor for developing cryptococcosis. Kidney disease, hyperglycemia, and immune dysfunction can increase the risk of cryptococcosis in patients with DM2

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis

Chagas disease affects approximately 300,000 patients in the United States. We evaluated a multicenter U.S.-based network to obtain clinical characteristics and outcomes of chronic Chagas disease by disease forms. This was a U.S.-based, multicenter, population-based, retrospective cohort study. We queried TriNetX, a global research network, to identify patients with dual-positive IgG serology for Trypanosoma cruzi. We captured outcomes of interest for up to 5 years. We found 429 patients with evidence of dual-positive T. cruzi IgG out of 19,831 patients with an available test result from 31 U.S. medical centers. The positive proportion for those tested was 2.2%, up to 4.6% among Hispanics. We found a prevalence of a positive Chagas serology of 0.02% among Hispanics. Cardiomyopathy risk reached an annual rate of 1.3% during the initial 5 years of follow-up among patients with the indeterminate form. We found no new events for pulmonary embolism, sudden death, or left ventricular aneurysms at 5 years. Annual risks for arrhythmias and stroke for chronic Chagas cardiomyopathy (CCC) were 1.6% and 0.8%, respectively. The yearly mortality and hospitalization rates for CCC were 2.7% and 17.1%, respectively. Only 13 patients had a documented antitrypanosomal therapy course within 6 months after diagnosis. Of those receiving treatment, 10 patients received benznidazole and three nifurtimox. Chagas disease screening in patients from endemic areas living in the United States remains crucial. Chronic Chagas cardiomyopathy carries a considerable disease burden, translating into increased morbidity and mortality and an enlarging medical health service utilization

Zero by 2030 and OneHealth: The multidisciplinary challenges of rabies control and elimination

"Rabies, caused by a negative strand RNA-virus belonging to the genus Lyssavirus (family Rhabdoviridae of the order Mononegavirales), remains of global concern [1]. This vaccine-preventable viral zoonotic disease is present in more than 150 countries and territories [2]. Ac- cording to the World Health Organization (WHO), rabies is estimated to cause ~59,000 human deaths annually, with 95% of cases occurring in Africa and Asia [3,4]. However, rabies still occurs in other regions, such as Latin America and the Caribbean [5–8], Central Asia and the Middle East [9,10]. Whilst a number of animals can host the rabies virus, dogs are the main source of human rabies deaths, contributing up to 99% of all rabies transmissions to humans. Dog-mediated rabies has been eliminated from Western Europe, Canada, the United States of America (USA), Japan and some Latin American countries [11]. Nevertheless, the risk of reintroduction and disease among travellers to risk areas is a matter of concern [12–15]. As occurred with many other communicable and non-communicable diseases, the 2020–2022 COVID-19 pandemic negatively impacted the efforts of control and reemergence of rabies in certain countries [7,16,17]. Post-pandemic challenges to enhance con- trol and prevention are multiple and need urgent actions to achieve the goal in eight years by 2030 [16].

doi:10.1016/j.neulet.2008.04.029

a b s t r a c t Over 160 rare genetic variants in presenilin 1 (PSEN1) are known to cause Alzheimer's disease (AD). In this study we screened a family with early-onset AD for mutations in PSEN1 using direct DNA sequencing. We identified a novel PSEN1 genetic variant which results in the substitution of a Proline with an Alanine at codon 117 (P117A). The P117A variant was present in all demented individuals and fifty percent of at risk individuals. This variant occurs at a site where three other disease-causing variants have been previously observed. In vitro functional studies demonstrate that the P117A variant results in an altered A␤42/total A␤ ratio consistent with an AD causing mutation. The P117A variant is a novel mutation in PSEN1, which causes early-onset AD in an autosomal dominant manner

Hospitalization risk among patients with Mpox infection—a propensity score matched analysis

Background: Monkeypox (Mpox) is a reemerging, neglected viral disease. By May 2023, worldwide Mpox cases surpassed 87,000. Predictive factors for hospitalization with Mpox are lacking. Objective: We aim to compare clinical characteristics and outcomes in hospitalized and nonhospitalized patients with Mpox infection. Design: A multicenter retrospective case-control cohort of patients with Mpox infection. Methods: We performed a propensity score match analysis from a global health network (TrinetX). We compare clinical characteristics and outcomes between hospitalized and nonhospitalized patients with Mpox. Results: Of 1477 patients, 6% were hospitalized, 52% required an ED visit, and 29% received treatment at urgent care. After propensity score matching, 80 patients remained in each group. Hospitalizations were more common among Black persons (51% versus 33%, p = 0.01), people with HIV (50% versus 20%, p < 0.0001), and those with proctitis (44% versus 12.5%, p < 0.001). Conclusion: Independent predictive factors of hospitalization in our cohort for Mpox included people who are Black with a diagnosis of HIV, severe proctitis, pain requiring opioids, and elevated lactate dehydrogenase. Greater recognition of factors associated with increased risk of Mpox severity and hospitalization is paramount.Dr. Boghuma K. Titanji is funded by the NIH BIRCWH program and Emory CFAR grant P30AI050509)