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New Insights into the Pathogenesis, Immunology and Treatment of Human...
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New Insights into the Pathogenesis, Immunology and Treatment of Human Babesiosis and Other Erythrocytic Pathogens

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4517

Special Issue Editors

Dr. Luis A. Marcos

E-Mail Website
Guest Editor
Division of Infectious Diseases, Department of Medicine & Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY 11794, USA
Interests: clinical diseases caused by tick-borne diseases and co-infections
Dr. Dana G. Mordue

E-Mail Website
Guest Editor
Department of Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA
Interests: understanding host and pathogen determinants as well as treatments that impact human babesiosis including parasite carriage and disease complications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Erythrocytic protozoa parasites, including Babesia and Plasmodium, occupy a unique cellular niche that impacts clinical disease, including pathogenesis, and mechanisms important for their control and clearance. Host and parasite determinants that impact disease caused by piroplasms, including Babesia microti, are largely unknown. More effective treatments for babesiosis, particularly in immune suppressed individuals, are needed. Co-infections with Babesia microti and other tick-transmitted infections, such as Lyme disease, continue to increase, yet the impact of co-infection on clinical disease remains unclear. The goal for this Special Issue is to highlight emerging themes broadly related to the pathogenesis, immunology, and treatment of clinical babesiosis and other erythrocytic protozoa in humans.

The papers in this Special Issue will be focused on the following areas.

  1. Clinical studies in humans with babesiosis that provide new insights into the pathogenesis, immunology and/or management of disease.
  2. Translational studies involving basic science studies of babesiosis likely to provide important insight into human disease
  3. Studies that provide important information on the impact of co-infection of Babesia and other tick-transmitted co-infections.
  4. Studies of other erythrocytic pathogens that provide important new information that is likely also applicable to erythrocytic pathogens in general including Babesia microti.

Dr. Luis A. Marcos
Dr. Dana G. Mordue
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • piroplasms
  • Babesia species
  • erythrocytic pathogens
  • human babesiosis
  • host response
  • diagnosis
  • epidemiology
  • management

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Published Papers (3 papers)

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Research

14 pages, 998 KiB  
Article
Tumor Necrosis Factor Receptors and C-C Chemokine Receptor-2 Positive Cells Play an Important Role in the Intraerythrocytic Death and Clearance of Babesia microti
by Dana G. Mordue, Adiya S. Katseff, Andrew J. Galeota, Synthia J. Hale, Shaaf Rezaee, Ilana Schwartz, Mariya Sambir and Paul M. Arnaboldi
Pathogens 2024, 13(10), 858; https://doi.org/10.3390/pathogens13100858 - 1 Oct 2024
Viewed by 636
Abstract
Babesia microti is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. B. microti can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune [...] Read more.
Babesia microti is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. B. microti can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune compromised state, age greater than 50, and asplenia. However, increasing cases of severe disease and hospitalization in otherwise healthy individuals suggests that there are unknown risk factors. The immunopathology of babesiosis is poorly described. CD4+ T cells and the spleen both play a critical role in parasite clearance, but few other factors have been found that significantly impact the course of disease. Here, we evaluated the role of several immune mediators in B. microti infection. Mice lacking TNF receptors 1 and 2, the receptors for TNFα and LTα, had a higher peak parasitemia, reduced parasite killing in infected red blood cells (iRBCs), and delayed parasite clearance compared to control mice. Mice lacking CCR2, a chemokine receptor involved in the recruitment of inflammatory monocytes, and mice lacking NADPH oxidase, which generates superoxide radicals, demonstrated reduced parasite killing but had little effect on the course of parasitemia. These results suggest that TNFR-mediated responses play an important role in limiting parasite growth, the death of parasites in iRBCs, and the clearance of iRBCs, and that the parasite killing in iRBCs is being primarily mediated by ROS and inflammatory monocytes/macrophages. By identifying factors involved in parasite killing and clearance, we can begin to identify additional risk factors for severe infection and newer therapeutic interventions. Full article
(This article belongs to the Special Issue New Insights into the Pathogenesis, Immunology and Treatment of Human Babesiosis and Other Erythrocytic Pathogens)
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12 pages, 1598 KiB  
Article
Immune Mediators Important for a Protective Secondary Response to Babesia microti
by Joseph Conti, Thomas Gagliardi, Paul M. Arnaboldi, Synthia J. Hale, Sini Skariah, Ali A. Sultan and Dana G. Mordue
Pathogens 2024, 13(2), 123; https://doi.org/10.3390/pathogens13020123 - 28 Jan 2024
Cited by 1 | Viewed by 1578
Abstract
Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk [...] Read more.
Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti. Full article
(This article belongs to the Special Issue New Insights into the Pathogenesis, Immunology and Treatment of Human Babesiosis and Other Erythrocytic Pathogens)
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6 pages, 492 KiB  
Communication
Reduced Cholesterol Levels during Acute Human Babesiosis
by Luis A. Marcos, Charles Kyriakos Vorkas, Inderjit Mann, Evan Garry, Pooja Lamba, Sophia K. Pham, Rachel Spector, Aikaterini Papamanoli, Sara Krivacsy, Michael Lum, Aleena Zahra, Wei Hou and Eric D. Spitzer
Pathogens 2023, 12(4), 613; https://doi.org/10.3390/pathogens12040613 - 18 Apr 2023
Viewed by 1654
Abstract
Background: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe [...] Read more.
Background: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. Methods: We reviewed the medical records of adult patients with babesiosis diagnosed by identification of Babesia parasites on a thin blood smear and confirmed by polymerase chain reaction from 2013 to 2018, who also had available a lipid profile drawn at the time of clinical presentation. Additional lipid profile levels were considered as “baseline” if they were drawn within 2 months before or after the infection as part of routine care. Results: A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician’s clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, p = 0.02). The median levels of low-density lipoprotein (LDL) and HDL were significantly reduced in admitted patients compared to non-admitted patients (46 vs. 76 mg/dL, p = 0.04; and 9 vs. 28.5 mg/dL, p = 0.03, respectively). In addition, LDL and HDL levels returned to baseline values following resolution of acute babesiosis. Conclusion: LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis. Full article
(This article belongs to the Special Issue New Insights into the Pathogenesis, Immunology and Treatment of Human Babesiosis and Other Erythrocytic Pathogens)
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