Chagas disease in immunocompromised patients.

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

Adaptation of Chagas Disease Screening Recommendations for a Community of At-risk HIV in the United States.

Chagas disease (CD), caused by Trypanosoma cruzi, is underdiagnosed in the United States. Improved screening strategies are needed, particularly for people at risk for life-threatening sequelae of CD, including people with human immunodeficiency virus (HIV, PWH). Here we report results of a CD screening strategy applied at a large HIV clinic serving an at-risk population.

Chagas disease in the immunocompromised host.

PURPOSE OF REVIEW: To highlight recent advances in our understanding of Trypanosoma cruzi infection in immunocompromised individuals, a condition that is increasingly recognized as populations shift and use of immunosuppressive medications becomes more commonplace. RECENT FINDINGS: Chagas disease screening programs should include people at risk for both Chagas disease and immunocompromise, e.g. people who have resided for ≥6 months in endemic Latin America who have an immunocompromising condition such as HIV or who are planned to start an immunosuppressive medication regimen. The goal of identifying such individuals is to allow management strategies that will reduce their risk of T. cruzi reactivation disease. For people with HIV- T. cruzi coinfection, strict adherence to antiretroviral therapy is important and antitrypanosomal treatment is urgent in the setting of symptomatic reactivation. People at risk for T. cruzi reactivation due to immunosuppression caused by advanced hematologic conditions or postsolid organ transplantation should be monitored via T. cruzi qPCR and treated with preemptive antitrypanosomal therapy if rising parasite load on serial specimens indicates reactivation. Reduction of the immunosuppressive regimen, if possible, is important. SUMMARY: Chronic Chagas disease can lead to severe disease in immunocompromised individuals, particularly those with advanced HIV (CD4 + < 200 cells/mm 3 ) or peri-transplantation.

Impact of the COVID-19 Pandemic on Medical Education during Inpatient Internal Medicine Rounds.

OBJECTIVES: Inpatient rounding is a foundational component of medical education in academic hospitals. The coronavirus 2019 (COVID-19) pandemic disrupted traditional inpatient rounding practices. The objectives of this study were to describe how Internal Medicine inpatient team rounding changed because of COVID-19-related precautions and the effect of these changes on education during rounds. METHODS: During February to March 2021, we conducted four virtual focus groups with medical and physician assistant students, interns, upper-level residents, and attending physicians at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, and designed a codebook to categorize focus group commentary. RESULTS: Focus groups revealed that students believed that certain physical-distancing measures in place early on during the pandemic were ineffective and significantly limited their ability to evaluate patients in person. Residents described increased stress levels related to potential severe acute respiratory-coronavirus 2 exposure and limited time at the bedside, which affected their confidence with clinical assessments. Rounding-team fragmentation precluded the entire team learning from all of the patients on the team's census. Loss of intrateam camaraderie impaired the development of comfortable learning environments. CONCLUSIONS: This study evaluated Internal Medicine team member focus groups to describe how the COVID-19 pandemic affected medical education during rounds. Academic teaching programs can adapt the findings from this study to address and prevent pandemic-related gaps in medical education during rounds now and during future potential disruptions to medical education.

Screening for Chagas Disease Should Be Included in Entry-to-Care Testing for At-Risk People With Human Immunodeficiency Virus (HIV) Living in the United States.

Chagas disease screening of at-risk populations is essential to identify infected individuals and facilitate timely treatment before end-organ damage occurs. Coinfected people with human immunodeficiency virus (PWH) are at risk for dangerous sequelae, specifically Trypanosoma cruzi reactivation disease. Recently published national recommendations indicate that at-risk PWH, particularly those from endemic areas or born to women from endemic areas, should be screened via a sensitive anti-T. cruzi IgG assay. However, immunocompromised patients with negative serologic results may warrant further investigation. Reactivation should be suspected in at-risk, untreated PWH with low CD4 cell counts presenting with acute neurologic or cardiac symptoms; these patients should be promptly evaluated and treated. One pragmatic solution to improve Chagas disease screening among PWH and thereby reduce T. cruzi-related morbidity and mortality is to incorporate Chagas disease screening into the panel of tests routinely performed during the entry-to-care evaluation for at-risk PWH.

Updated Estimates and Mapping for Prevalence of Chagas Disease among Adults, United States.

We combined American Community Survey data with age-specific Trypanosoma cruzi prevalence derived from US surveys and World Health Organization reports to yield estimates of Chagas disease in the United States, which we mapped at the local level. In addition, we used blood donor data to estimate the relative prevalence of autochthonous T. cruzi infection. Our estimates indicate that 288,000 infected persons, including 57,000 Chagas cardiomyopathy patients and 43,000 infected reproductive-age women, currently live in the United States; 22-108 congenital infections occur annually. We estimated ≈10,000 prevalent cases of locally acquired T. cruzi infection. Mapping shows marked geographic heterogeneity of T. cruzi prevalence and illness. Reliable demographic and geographic data are key to guiding prevention and management of Chagas disease. Population-based surveys in high prevalence areas could improve the evidence base for future estimates. Knowledge of the demographics and geographic distribution of affected persons may aid practitioners in recognizing Chagas disease.

Why Contact Tracing Efforts Have Failed to Curb Coronavirus Disease 2019 (COVID-19) Transmission in Much of the United States.

By late April 2020, public discourse in the United States had shifted toward the idea of using more targeted case-based mitigation tactics (eg, contact tracing) to combat coronavirus disease 2019 (COVID-19) transmission while allowing for the safe "reopening" of society, in an effort to reduce the social, economic, and political ramifications associated with stricter approaches. Expanded tracing-testing efforts were touted as a key solution that would allow for a precision approach, thus preventing economies from having to shut down again. However, it is now clear that many regions of the United States were unable to mount robust enough testing-tracing programs to prevent major resurgences of disease. This viewpoint offers a discussion of why testing-tracing efforts failed to sufficiently mitigate COVID-19 across much of the nation, with the hope that such deliberation will help the US public health community better plan for the future.

Veteran Women Living With Human Immunodeficiency Virus Have Increased Risk of Human Papillomavirus (HPV)-Associated Genital Tract Cancers.

BACKGROUND: Disparities in access to screening often confound observed differences in human papillomavirus (HPV)-associated female genital tract cancer (FGTC) incidence between women living with human immunodeficiency virus (HIV; WLWH) and their HIV-negative counterparts. We aimed to determine if there have been changes in cancer risk among WLWH during the antiretroviral era in a single-payer health system. METHODS: We retrospectively selected WLWH and HIV-negative controls receiving care between 1999 and 2016 at the US Department of Veterans Affairs (VA) and identified FGTC diagnoses via Cancer Registry and International Classification of Diseases-9/10 codes. We extracted demographic and clinical variables from the VA's Corporate Data Warehouse; evaluated incidence rates (IRs), incidence rate ratios, hazard ratios, and 95% confidence intervals (CIs) for cancer risk; and conducted survival analyses. RESULTS: We identified 1454 WLWH and compared them with 5816 matched HIV-negative controls. More WLWH developed HPV-associated FGTCs (total n = 28 [2.0%]; cervical = 22, vulvovaginal = 4, and anal/rectal = 2) than HIV-negative women (total n = 32 [0.6%]; cervical = 24, vulvovaginal = 5, and anal/rectal = 5) (log rank P < .0001). Cervical cancer IR was >6-fold higher for WLWH (204.2 per 100 000 person-years [py] [95% CI, 83.8-324.7]) than HIV-negative women (IR = 31.2 per 100 000 py [95% CI, 17.9-44.5]). The IRs for vulvovaginal and anal cancers were also higher in WLWH. Overall, WLWH were more likely to develop HPV-associated FGTCs compared with their HIV-negative counterparts (all log rank P values < .0001). CONCLUSIONS: Veteran WLWH are more likely to develop HPV-associated FGTCs despite equal access to health care. Even in single-payer health systems, WLWH continue to require special attention to ensure guideline-based high-risk HPV screening for prevention of FGTCs.

Strongyloides stercoralis Infection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study.

BACKGROUND: Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease. METHODS: In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens ("crude antigen") using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid-binding protein (IFABP). RESULTS: We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman's r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively). CONCLUSIONS: This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.

Chronic Chagas Disease in the US.

This JAMA Insights provides recommendations for Chagas disease screening, diagnosis, and management in the US.

A new framework for understanding stress and disease: the developmental model of stress as applied to multiple sclerosis.

This paper proposes a new model of stress that integrates earlier models and adds insights from developmental psychology. Previous models describe the behavioral and physical effects of stress events, but have not explained the translation of experiences into stress itself. The Developmental Model of Stress shows how psychosocial developmental challenges in childhood create persistent negative beliefs and behaviors that increase threat perception and maladaptive stress responses. These developmental challenges produce early psychological and physiological predispositions for increased stress responses over time. Ongoing stress leads to dysregulation of physical stress-response systems (allostatic load), which is associated with multiple diseases. High allostatic load provides the necessary preconditions for the diathesis-stress model, which says the addition of an acute stressor to a weakened or predisposed system can lead to disease development. The paper also documents the evolving measurement of stress to better understand the stress-disease relationship, helping to resolve conflicting results between studies. The Developmental Model of Stress was combined with clinician insight and patient reports to build an integrative framework for understanding the role of stress in the development and progression of multiple sclerosis (MS). It includes the first mapping of maladaptive beliefs and behaviors arising from developmental challenges that are common to people with MS. An initial comparison shows these may be distinct from those of people with other chronic diseases. These beliefs and behaviors form the predisposing factors and contribute to the triggering factors, which are the acute stressors triggering disease onset. These often took two forms, a prolonged incident experienced as feeling trapped or stuck, and threat of a breach in a relationship. The reinforcing factors add the stress of a chronic disease with a poor prognosis and seemingly random symptom fluctuation, still managed with the same beliefs and behaviors developed in childhood, increasing physiological dysregulation and symptom severity. A pilot study is described in which these three categories of stress factors in MS were explicitly addressed. This study noted clinically important improvements in physical and mental well-being, providing preliminary support for the Developmental Model. Future research might expand on the pilot using a more robust sample and design.

Risk and predictors of penile cancer in US Veterans with HIV.

OBJECTIVES: People with HIV (PWH) may have an increased burden of penile cancer. We aimed to evaluate the risk of penile cancer in PWH compared with that of the general population. DESIGN: We conducted a nationwide retrospective matched cohort study of penile cancer incidence among veterans with HIV (VWH) compared with veterans without HIV. METHODS: We compared penile cancer incidence rates in 44 173 VWH to those of veterans without HIV ( N  = 159 443; 4 : 1 matched in age). We used Cox regression models to estimate hazard ratios and 95% confidence intervals (CIs) for associations with HIV infection and for penile cancer risk factors. RESULTS: HIV positivity was associated with an increased risk of penile cancer, with adjusted hazard ratios of 2.63 (95% CI 1.64-4.23) when adjusting for age, race/ethnicity, baseline BMI, smoking and alcohol use, economic means test, and history of condyloma. The risk increased to hazard ratio = 4.25 (95% CI 2.75-6.57) when adjusting for all factors except history of condyloma. Risk factors for penile cancer in VWH included lower nadir CD4 + count, less than 50% of follow-up time with undetectable HIV viral load, and history of condyloma. CONCLUSION: VWH - particularly those with low CD4 + counts, detectable HIV viral loads, or history of condyloma - are at increased risk of penile cancer, suggesting the penile cancer prevention activities are needed in this population.

Herminthology: promoting gender equity in science and parasitology.

Gender inequity in Science, Technology, Engineering, and Medicine (STEM) fields, including parasitology, continues to limit the participation of women in scientific leadership and development. Here we highlight the aims and activities of Herminthology, an initiative promoting the work of women in parasitology, alongside the current status quo of men and women scientists in the discipline.

Plasmodium falciparum malaria in the Peruvian Amazon, a region of low transmission, is associated with immunologic memory.

The development of clinical immunity to Plasmodium falciparum malaria is thought to require years of parasite exposure, a delay often attributed to difficulties in developing protective antibody levels. In this study, we evaluated several P. falciparum vaccine candidate antigens, including apical membrane antigen 1 (AMA-1), circumsporozoite protein (CSP), erythrocyte binding antigen 175 (EBA-175), and the 19-kDa region of merozoite surface protein 1 (MSP1(19)). After observing a more robust antibody response to MSP1(19), we evaluated the magnitude and longevity of IgG responses specific to this antigen in Peruvian adults and children before, during, and after P. falciparum infection. In this low-transmission region, even one reported prior infection was sufficient to produce a positive anti-MSP1(19) IgG response for >5 months in the absence of reinfection. We also observed an expansion of the total plasmablast (CD19(+) CD27(+) CD38(high)) population in the majority of individuals shortly after infection and detected MSP1-specific memory B cells in a subset of individuals at various postinfection time points. This evidence supports our hypothesis that effective antimalaria humoral immunity can develop in low-transmission regions.

Can statins lessen the burden of virus mediated cancers?

BACKGROUND: Oncogenic viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), Epstein Barr virus (EBV), and Kaposi Sarcoma Herpes virus (KSHV) contribute to a significant proportion of the world's cancers. Given the sizeable burden of virus mediated cancers, development of strategies to prevent and/or treat these cancers is critical. While large population studies suggest that treatment with hydroxymethylglutaryl-CoA reductase inhibitors, commonly known as statins, may reduce the risk of many cancer types including HBV/HCV related hepatocellular carcinoma, few studies have specifically evaluated the impact of statin use in populations at risk for other types of virus mediated cancers. MAIN BODY: Studies of populations with HBV and HCV suggest a protective, dose-dependent effect of statins on hepatocellular carcinoma risk and support the theory that statins may offer clinical benefit if used as chemoprophylactic agents to reduce liver cancer incidence. However, no population level data exists describing the impact of statins on populations with other oncogenic viral infections, such as HPV, EBV, and KSHV. CONCLUSION: Further study of statin use in diverse, global populations with or at high risk for oncogenic viral infections is essential to determine the impact of statin therapy on virus mediated cancer risk.

The role of helminths in the development of non-communicable diseases.

Non-communicable diseases (NCDs) like cardiovascular disease, chronic respiratory diseases, cancers, diabetes, and neuropsychiatric diseases cause significant global morbidity and mortality which disproportionately affect those living in low resource regions including low- and middle-income countries (LMICs). In order to reduce NCD morbidity and mortality in LMIC it is imperative to understand risk factors associated with the development of NCDs. Certain infections are known risk factors for many NCDs. Several parasitic helminth infections, which occur most commonly in LMICs, have been identified as potential drivers of NCDs in parasite-endemic regions. Though understudied, the impact of helminth infections on the development of NCDs is likely related to helminth-specific factors, including species, developmental stage and disease burden. Mechanical and chemical damage induced by the helminth in combination with pathologic host immune responses contribute to the long-term inflammation that increases risk for NCD development. Robust studies from animal models and human clinical trials are needed to understand the immunologic mechanisms of helminth-induced NCDs. Understanding the complex connection between helminths and NCDs will aid in targeted public health programs to reduce helminth-induced NCDs and reduce the high rates of morbidity that affects millions of people living in parasite-endemic, LMICs globally.

Evaluation of Adherence to Guideline-Based Bone Mineral Density Screening in Veterans with HIV.

People with HIV (PWH) have a higher prevalence of bone mineral density (BMD) loss compared to people without HIV. The Infectious Diseases Society of America (IDSA) recommends BMD screening through dual energy X-ray absorptiometry (DXA) in PWH starting at age 50. We aimed to evaluate adherence to this recommendation in a population of Veterans with HIV (VWH). Retrospective cross-sectional analysis of VWH followed from 2014 to 2018 at the Michael E. DeBakey VA Medical Center Infectious Diseases Clinic, Houston, Texas. We collected data through registry extraction and chart review. We calculated the percentage of VWH with timely BMD loss screening by DXA within 5 years of turning 50. Secondary outcomes included prevalence of osteopenia, osteoporosis, and vitamin D deficiency. We included data from 1,243 VWH. Their average age was 52 years (range 18-86). Most were male (95%), and 59% were black. Of the 346 VWH who turned 50 years old during the study period, 78 (22.5%) underwent DXA within 5 years. Of these, 42 (53.8%) had normal BMD, 28 (35.9%) had osteopenia, and 8 (10.3%) had osteoporosis. Nine hundred ninety-three (79.9%) VWH had available 25-hydroxyvitamin D levels; of these, 453 (45%) had normal levels, 304 (30.6%) had vitamin D insufficiency, 184 (18.5%) had vitamin D deficiency, and 52 (5.2%) had severe vitamin D deficiency. Fewer than 25% of eligible VWH underwent timely BMD loss screening by DXA per IDSA guidelines. Almost half of screened VWH showed evidence of BMD loss. Although limited by lack of follow-up and fracture data, this study emphasizes the importance of improving BMD loss screening in this vulnerable population.