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 inhibitor (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 a BTKi is now the first-line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the International Classification of Diseases, Tenth Revision code (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 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 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 Pneumocystis jirovecii pneumonia (PJP) (0.5% vs 0.3%, P = .02) and invasive candidiasis (3.5% vs 2.7%, P = .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 BTKis are required to identify at-risk patients and preventive, cost-effective interventions.

Clinical Characteristics and Outcomes of Disseminated Strongyloidiasis in the United States-A Multicenter Network Analysis.

Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.

Coccidioidomycosis in Oklahoma: A retrospective case series.

BACKGROUND: Coccidioidomycosis is a systemic fungal disease endemic to arid regions of the Western Hemisphere. In the south-western US, Coccidioides spp. may account for up to 20%-25% of all cases of community acquired pneumonia. Clinical manifestations vary widely, from asymptomatic infection to life-threatening disease, especially in immunocompromised hosts. OBJECTIVES: The primary objective of the study was to characterise cases of coccidioidomycosis in an area of the United States not considered traditionally endemic for the disease. METHODS: We performed a single-centre retrospective study of all cases of coccidioidomycosis from 1 January 2000 to 31 December 2020, in the University of Oklahoma Health Sciences Medical Center. RESULTS: A total of 26 patients were included for analysis. The central nervous system (CNS) and the lungs were the sites most frequently involved. Twenty (77%) had travelled to a coccidioidomycosis endemic region. Most were male (81%) with a median age of 42 years (range: 3-78 years). The majority (46%) were Caucasians, 19% were African American, 19% Hispanic, and 12% Native American. The most common comorbidities were diabetes mellitus and acquired immunodeficiency syndrome, identified in 27% and 23% of patients, respectively. Patients on immunosuppressive therapy accounted for 12% of all cases. CONCLUSION: Our study is one of the largest single-centre case series of coccidioidomycosis from a non-endemic area. Diabetes mellitus was the most frequent comorbidity. Compared to other case series of coccidioidomycosis, our patient population had higher rates of immunosuppression and had both a higher rate of disseminated disease and overall mortality.

Chagas disease in the United States: a call for increased investment and collaborative research.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a highly overlooked parasitic infection within the United States. It affects an estimated 300,000 individuals, often remaining asymptomatic for years before triggering severe complications such as cardiomyopathy in 30-40% of cases. While many contract the disease in Latin America, its transmission by local vectors in the southern U.S. presents a significant challenge. Unfortunately, limited access to diagnosis and treatment persists, alongside unresolved gaps in healthcare systems and disease pathogenesis. In this viewpoint, we discuss the need for focused research and public health initiatives, with U.S. research institutions playing a crucial role in developing new treatments and identifying biomarkers. Furthermore, investigating the genetic variations of T. cruzi between North and South America is vital for improving diagnostic and treatment strategies. Urgent action is required to implement national and local programs, bolstering healthcare responses and advancing research efforts.Q4As per journal style section heading 'Introduction' is mandatory, hence we have introduced the heading. Please check, and correct if necessary.ResolvedQ5If there are any drug dosages in your article, please verify them and indicate that you have done so by initialing this query.ResolvedQ6Please supply the year of publication.ResolvedFootnoteView Edit Log9.

Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis.

BACKGROUND: Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda. METHODS: We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648). FINDINGS: Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I2=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals. INTERPRETATION: Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries. FUNDING: None. TRANSLATIONS: For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Hematopoietic stem cell transplantation and the noncytomegalovirus herpesviruses.

Although hematopoietic stem cell transplantation (HSCT) and other cellular therapies have significantly improved outcomes in the management of multiple hematological and nonhematological malignancies, the resulting impairment in humoral and cellular response increases the risk for opportunistic infection as an undesirable side effect. With their ability to establish latent infection and reactivate when the host immune system is at its weakest point, the Herpesviridae family constitutes a significant proportion of these opportunistic pathogens. Despite recent advancements in preventing and managing herpesvirus infections, they continue to be a common cause of significant morbidity and mortality in transplanted patients. Herein, we aim to provide and update on herpesvirus other than cytomegalovirus (CMV) affecting recipients of HSCT and other cellular therapies.

Migrants in transit across Central America and the potential spread of chloroquine resistant malaria-a call for action.

Human migration has shaped the distribution and patterns of infectious diseases transmission throughout history. Migration is one of the contributing factors that has played an important role in the dissemination of drug-resistant Plasmodium falciparum. Central America and Mexico are important transit points of an increasing migrant flow originating from countries where chloroquine-resistant P. falciparum and vivax are prevalent. Surveillance systems, as well as detection and diagnostic capacities in the Central American region, are limited. The additional challenges imposed by the increasingly mobile population in the region are creating the perfect scenario for the emergence or re-emergence of infectious diseases, such as the introduction of chloroquine-resistant malaria. The development and implementation of transborder, collaborative, and ethical migrant health initiatives in the region are urgently needed. The health of migrant people in transit during their migratory route is of our collective interest and responsibility; their exclusion from health programs based on their legal status contradicts international human rights treaties and is inconsistent with ethical global public health practice.

Chagas Disease and Domestic Medical Screening Guidance for Newly Arrived Individuals Under a Humanitarian-Based Immigration Status: A Call for Action.

Chagas disease is considered one of the most important neglected tropical diseases in the Western Hemisphere, given its morbidity, mortality, and societal and economic burden. The United States has the fifth highest global burden of Chagas disease. Every year, thousands of migrant people from Latin America and throughout the globe travel to the U.S.- Mexico border searching for asylum. The U.S. CDC's Guidance for the U.S. Domestic Medical Examination for Newly Arriving Refugees provides recommendations to safeguard the health of individuals who enter the United States with a humanitarian-based immigration status as defined by the CDC's guidance under Key Considerations and Best Practices. We encourage the inclusion of Trypanosoma cruzi infection screening recommendations in this guidance as an important step toward understanding the risk and burden of Chagas disease in this vulnerable population, strengthening their access to care and contributing to the 2030 objectives of the WHO's neglected tropical diseases road map.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study

BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1,164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age [≥] 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63-4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FundingNIH RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe did a systematic search of the PubMed database from January 1st, 2020 until April 24th, 2022 using the search terms: "hospitalized" AND "SARS-CoV-2" OR "COVID-19" AND "Pro-spective" AND "Antibody" OR "PCR" OR "long term follow up" and applying the following filters: "Multicenter Study" AND "Observational Study". No language restrictions were applied. While clinical, laboratory, and radiographic features associated with severe COVID-19 in hospitalized adults have been described, description of the kinetics of SARS-CoV-2 specific assays available to clinicians (e.g. PCR and binding antibody) and their integration with other variables is scarce for both short and long term follow up. The current literature is comprised of several studies with small sample size, cross-sectional design with laboratory data typically only recorded at a single point in time (e.g., on admission), limited clinical characteristics, variable duration of follow up, single-center setting, retrospective analyses, kinetics of either PCR or antibody testing but not both, and outcomes such as death or, mechanical ventilation that do not allow delineation of variations in clinical course. Added value of this studyIn our large longitudinal multicenter cohort, the description of outcome severity, was not limited to survival versus death, but encompassed a clinical trajectory approach leveraging longitudinal data based on time in hospital, disease severity by ordinal scale based on degree of respiratory illness, and presence or absence of limitations at discharge. Fatal COVID-19 cases had the lowest ratio of antibody to viral load levels over time as compared to non-fatal cases. Integration of PCR cycle threshold and antibody values with demographics, baseline comorbidities, and laboratory/radiographic findings identified additional risk factors for outcome severity over the first 28 days. However, female sex was the only variable associated with persistence of symptoms over time. Persistence of symptoms was not associated with clinical trajectory over the first 28 days, nor with antibody/viral loads from the acute phase. Implications of all the available evidenceThe described calculated ratio (binding IgG/PCR Ct value) is unique compared to other studies, reflecting host pathogen interactions and representing an accessible approach for patient risk stratification. Integration of SARS-CoV-2 viral load and binding antibody kinetics with other laboratory as well as clinical characteristics in hospitalized COVID-19 patients can identify patients likely to have the most severe short-term outcomes, but is not predictive of symptom persistence at one year post-discharge.

Chagas disease in Oklahoma.

Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, is one of the leading public health problems in the Western Hemisphere. The parasite is mainly transmitted by contact with infected insect vectors but other forms of transmission are important in endemic areas. In the United States, while the disease is largely restricted to immigrants from endemic countries in Latin America, there is some risk of local acquisition. T. cruzi circulates in a sylvatic cycle between mammals and local triatomine insects in the southern half of the country, where human residents may be at risk for incidental infection. There are several reported cases of locally-acquired Chagas disease in the United States, but there is a paucity of information in Oklahoma. We present a brief summary of the available data of Chagas disease in Oklahoma to raise awareness and serve as a foundation for future research.

Burden of serious fungal infections in Honduras.

BACKGROUND: The burden of serious fungal infections in Honduras is unknown. The diagnosis of fungal diseases relies on almost exclusively on microscopy and culture limiting an accurate estimate of the burden of disease. OBJECTIVES: The primary objective of the study was to estimate the burden of serious fungal infections in Honduras using previously described methods. METHODS: National and international demographic data on population, HIV, tuberculosis, asthma, COPD and cancer were obtained. A thorough literature search was done for all epidemiological studies and case series of serious fungal diseases. Using these risk populations and whatever incidence and prevalence could be found that was most pertinent to Honduras, a burden estimate was derived. RESULTS: The estimated number of serious fungal infection was estimated to be between 178,772 and 179,624 with nearly 2300 cases of these representing opportunistic infections in people living with HIV. The incidence of histoplasmosis and cryptococcosis in people living with HIV is high and estimated to be 4.3 and 4.6 cases per 100,000 population respectively. Approximately 12,247-13,099 cases of aspergillosis and 164,227 of other serious fungal infections were estimated to occur each year. CONCLUSION: An accurate estimate of the burden of serious fungal infections in Honduras is unknown but based on our results, likely significant. Serious fungal infections represent an important public health problem in Honduras affecting approximately 1.8% of the population. There is a clear need for better access to diagnostic tools and antifungals to conduct research to better understand the impact of fungal diseases in Honduras.

Evaluation of I-TAC as a potential early plasma marker to differentiate between critical and non-critical COVID-19.

The COVID-19 pandemic has led to significant global health and economic consequences. There is an unmet need to define a molecular fingerprint of severity of the disease that may guide an early, rational and directed intervention preventing severe illness. We collected plasma from patients with moderate (nine cases), severe (22 cases) and critical (five cases) COVID-19 within three days of hospitalization (approximately one week after symptom onset) and used a cytokine antibody array to screen the 105 cytokines included in the array. We found that I-TAC, IP-10, ST2 and IL-1ra were significantly upregulated in patients with critical disease as compared to the non-critical (moderate and severe combined). ELISA further quantified I-TAC levels as 590.24±410.89, 645.35±517.59 and 1613.53±1010.59 pg/ml in moderate, severe and critical groups, respectively. Statistical analysis showed that I-TAC levels were significantly higher in patients with critical disease when compared with moderate (p = 0.04), severe (p = 0.03) or the combined non-critical (p = 0.02) group. Although limited by the low sample numbers, this study may suggest a role of I-TAC as a potential early marker to discriminate between critical and non-critical COVID-19 cases. Such knowledge is urgently needed for appropriate allocation of resources and to serve as a platform for future research towards early interventions that could mitigate disease severity and save lives.

Rapid health evaluation in migrant peoples in transit through Darien, Panama: protocol for a multimethod qualitative and quantitative study.

BACKGROUND: The world is currently unprepared to deal with the drastic increase in global migration. There is an urgent need to develop programs to protect the well-being and health of migrant peoples. Increased population movement is already evident throughout the Americas as exemplified by the rising number of migrant peoples who pass through the Darien neotropical moist broadleaf forest along the border region between Panama and Colombia. The transit of migrant peoples through this area has an increase in the last years. In 2021, an average of 9400 people entered the region per month compared with 2000-3500 people monthly in 2019. Along this trail, there is no access to health care, food provision, potable water, or housing. To date, much of what is known about health needs and barriers to health care within this population is based on journalistic reports and anecdotes. There is a need for a comprehensive approach to assess the health care needs of migrant peoples in transit. This study aims to describe demographic characteristics, mental and physical health status and needs, and experiences of host communities, and to identify opportunities to improve health care provision to migrant peoples in transit in Panama. STUDY DESIGN AND METHODS: This multimethod study will include qualitative (n = 70) and quantitative (n = 520) components. The qualitative component includes interviews with migrant peoples in transit, national and international nongovernmental organizations and agencies based in Panama. The quantitative component is a rapid epidemiological study which includes a questionnaire and four clinical screenings: mental health, sexual and reproductive health, general and tropical medicine, and nutrition. CONCLUSION: This study will contribute to a better understanding of the health status and needs of migrant peoples in transit through the region. Findings will be used to allocate resources and provide targeted health care interventions for migrant peoples in transit through Darien, Panama.

Mortality risk in chronic Chagas cardiomyopathy: a systematic review and meta-analysis.

AIMS: This study aimed to estimate the annual mortality risk and its determinants in chronic Chagas cardiomyopathy. METHODS AND RESULTS: We conducted a systematic search in MEDLINE, Web of Science Core Collection, Embase, Cochrane Library, and LILACS. Longitudinal studies published between 1 January 1946 and 24 October 2018 were included. A random-effects meta-analysis using the death rate over the mean follow-up period in years was used to obtain pooled estimated annual mortality rates. Main outcomes were defined as all-cause mortality, including cardiovascular, non-cardiovascular, heart failure, stroke, and sudden cardiac deaths. A total of 5005 studies were screened for eligibility. A total of 52 longitudinal studies for chronic Chagas cardiomyopathy including 9569 patients and 2250 deaths were selected. The meta-analysis revealed an annual all-cause mortality rate of 7.9% [95% confidence interval (CI): 6.3-10.1; I2  = 97.74%; T2  = 0.70] among patients with chronic Chagas cardiomyopathy. The pooled estimated annual cardiovascular death rate was 6.3% (95% CI: 4.9-8.0; I2  = 96.32%; T2  = 0.52). The annual mortality rates for heart failure, sudden death, and stroke were 3.5%, 2.6%, and 0.4%, respectively. Meta-regression showed that low left ventricular ejection fraction (coefficient = -0.04; 95% CI: -0.07, -0.02; P = 0.001) was associated with an increased mortality risk. Subgroup analysis based on American Heart Association (AHA) classification revealed pooled estimate rates of 4.8%, 8.7%, 13.9%, and 22.4% (P < 0.001) for B1/B2, B2/C, C, and C/D stages of cardiomyopathy, respectively. CONCLUSIONS: The annual mortality risk in chronic Chagas cardiomyopathy is substantial and primarily attributable to cardiovascular causes. This risk significantly increases in patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D.

An update on prevention of malaria in travelers.

Malaria, a parasitic disease caused by protozoa belonging to the genus Plasmodium, continues to represent a formidable public health challenge. Despite being a preventable disease, cases reported among travelers have continued to increase in recent decades. Protection of travelers against malaria, a potentially life-threatening disease, is of paramount importance, and it is therefore necessary for healthcare professionals to be up to date with the most recent recommendations. The present review provides an update of the existent measures for malaria prevention among travelers.

Pulmonary cannonballs in a patient with Acquired Immunodeficiency Syndrome (AIDS).

Pneumocystis jirovecii pneumonia (PJP) remains one of the most common and life-threatening complications in patients with AIDS. PJP typically presents subacutely with a dry cough, shortness of breath with exertion, fever, and bilateral ground-glass opacities on imaging. However, atypical imaging findings have been reported including cysts, isolated lymphadenopathy, and small to large nodules. This case highlights the importance of considering unusual presentations of a relatively common entity in order to prevent delays in diagnosis and treatment.

Dermatologic Manifestations of Tick-borne Diseases in Travelers.

PURPOSE OF REVIEW: International and domestic travelers may acquire a wide variety of infectious diseases transmitted by exposure to insects. Exposure to ticks may be associated with systemic infections clinically suspected through skin and soft tissue manifestations along with fever, myalgia, headache, and other related symptoms. Cutaneous lesions may include eschars at the site of initial contact, maculopapular rashes, or others as the result of systemic dissemination of viral, Rickettsial, parasitic, and protozoan infections acquired by exposure to different types of ticks. RECENT FINDINGS: Ticks represent the second most common global vector of transmission of infectious diseases to humans after mosquitoes. In some endemic regions, ticks are the most important vector of transmission of a great variety of infectious pathogens including protozoan (Babesia spp.), viral (Coltivirus), rickettsia, and bacterial infections (Francisella tularensis). With increasing international travel, different tick-borne diseases continue to emerge and being identified. SUMMARY: Identifying the cutaneous signs associated with tick-borne diseases is crucial to clinically suspect the diagnosis of a specific tick-borne illness. Minimizing the exposure to ticks during domestic or international travel represents the most important intervention to reducing the risk of tick-borne illnesses.