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New Insights into Rickettsia and Related Organisms

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A Special Issue of Pathogens (ISSN 2076-0817) belonging to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (20 January 2026) | Viewed by 18031

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Editors

Dr. Alison Luce-Fedrow

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Guest Editor

Department of Biology, Shippensburg University of Pennsylvania, Shippensburg, PA 7257, USA
Interests: Rickettsia; Orientia; Ehrlichia; ectoparasites; immunology

Dr. Kristin E. Mullins

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Guest Editor

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Interests: Rickettsia; Bartonella; vector borne diseases; clinical diagnostics

Special Issue Information

Dear Colleagues,

The causative agents of rickettsial (and related) diseases (including Rickettsia, Orientia, Ehrlichia, Anaplasma, and Coxiella) have historically plagued both civilian and military populations due to the cosmopolitan distribution of their associated vectors (ticks, fleas, mites, and lice). Similarly, vector-transmitted microbes such as Borrelia, Babesia, and Bartonella are also capable of causing infections in humans/animals, which can be chronic and difficult to treat. Among the aforementioned micro-organisms, new species are consistently being described, detection is being reported beyond regions of endemicity, antibiotic-resistant strains have emerged, and the responsible vector populations have experienced shifting patterns due to environmental/climatic changes. Moreover, the “flu-like” nature of these diseases can lead to potential delays in diagnosis/treatment, resulting in detriments to the patient. Despite a wealth of ongoing advances geared towards better understanding these vector-borne pathogens, additional research is needed to explicitly refine the knowledge surrounding details such as host–microbe relationships, virulence mechanisms, genomics, genetic manipulation, immunological processes, vector populations/dynamics, model development, and microbe–microbe interactions. It is the combination of these research outcomes that will ultimately boost our ongoing quest to develop superior diagnostic/therapeutic tools and will lead to the development of broadly protective vaccines. The collaborative efforts of scientists worldwide are imperative to mitigate the global disease burden associated with these challenging microbes.

Consequently, for this Special Issue, we invite manuscripts dedicated to all facets of research concerning Rickettsia, Orientia, Ehrlichia, Anaplasma, Coxiella, Borrelia, Babesia, and Bartonella. We look forward to your submission(s) and continuing to be part of the collaborative community of Rickettsia (and related diseases) research.

Dr. Alison Luce-Fedrow
Dr. Kristin E. Mullins
Guest Editors

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Keywords

Rickettsia
Orientia
Ehrlichia
Anaplasma
Coxiella
Borrelia
Bartonella
Babesia

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Published Papers (10 papers)

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22 pages, 2714 KB

Open AccessArticle

Orientia tsutsugamushi Alters Mitochondrial Function and Selectively Associates with VDAC

by Savannah E. Sanchez, Travis J. Chiarelli, John S. Billingsley, Richard T. Marconi and Jason A. Carlyon

Pathogens 2026, 15(4), 372; https://doi.org/10.3390/pathogens15040372 - 31 Mar 2026

Cited by 1 | Viewed by 935

Abstract

Orientia tsutsugamushi is an obligate intracellular alphaproteobacterium and the causative agent of the potentially fatal rickettsiosis, scrub typhus. During infection, O. tsutsugamushi replicates exclusively in the eukaryotic cytosol near mitochondria and alters host metabolic pathways governed by mitochondria. We report that O. tsutsugamushi induces mitochondrial enzymatic impairment and structural abnormalities without altering mitochondrial abundance or the levels of proteins that maintain mitochondrial homeostasis. Confocal and structured illumination microscopy revealed a selective spatial association between O. tsutsugamushi and the mitochondrial membrane protein, voltage-dependent anion channel (VDAC) but not other mitochondrial proteins. Immunosignal for VDAC paralogs 1 and 3 colocalized with cytosolic O. tsutsugamushi organisms whereas VDAC2 did not. Additionally, the antibody specific for VDAC1 and VDAC3 detected proteins of the expected sizes in Orientia membrane fractions. These findings indicate that O. tsutsugamushi negatively impacts mitochondrial function without overt organelle loss and selectively associates with VDAC1/VDAC3. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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23 pages, 3032 KB

Open AccessArticle

A Compact Closed Genome of Orientia tsutsugamushi from Hainan Island, China Provides a TA763_A Reference and Reveals Repeat-Driven Remodeling

by Yi Niu, Yijia Guo, Zhao Xu, Siqi Chen, Liyuan Zhang, Xiuji Cui, Dachuan Lin, Kwok-Yung Yuen, Jasper Fuk-Woo Chan, Chuanning Tang and Feifei Yin

Pathogens 2026, 15(3), 318; https://doi.org/10.3390/pathogens15030318 - 16 Mar 2026

Cited by 1 | Viewed by 1614

Abstract

Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi (O. tsutsugamushi), remains a major public-health concern in the Asia–Pacific region. Genome-wide inference is complicated by extensive repetitive DNA and frequent genome rearrangement. We isolated O. tsutsugamushi HMU_001 from a scrub typhus patient on Hainan Island, China. Intracellular morphology was examined and replication was quantified in endothelial cells. Using long-read sequencing with short-read polishing, we generated a closed circular genome and performed standardized comparative analyses across all available complete O. tsutsugamushi genomes. HMU_001 assembled as a 1,895,724 bp genome and, among the 17 complete genomes analyzed in this study, represented the most compact genome. Repeats comprised 873,550 bp (46.08%) and included 72 RAGE loci (4 relatively complete) and 283 insertion sequences (54 intact). Repeat content varied widely and largely explained genome size differences. A core-gene phylogeny resolved four clades with partial geographic structure, while tsa56 genotypes were only partly congruent with it. Genome synteny was generally limited across strains but markedly higher among the closest relatives, consistent with ongoing rearrangement. HMU_001 expands representation of complete O. tsutsugamushi genomes by adding a TA763_A lineage strain from a high-incidence island setting. Comparative analyses support a model in which repeat proliferation and decay drive genome evolution and structural remodeling. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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19 pages, 1860 KB

Open AccessArticle

Assessment of the Pathogenicity of Candidatus Rickettsia Colombiensis in a Syrian Hamster Model and Serological Cross-Reactivity Between Spotted Fever Rickettsia Species

by Jorge Miranda, Alejandra García, Cristina Cervera-Acevedo, Sonia Santibañez, Aránzazu Portillo, José A. Oteo and Salim Mattar

Pathogens 2026, 15(2), 146; https://doi.org/10.3390/pathogens15020146 - 29 Jan 2026

Cited by 1 | Viewed by 821

Abstract

Candidatus Rickettsia colombiensis is a new candidate species of Rickettsiae spotted fever group that have been isolated only from ticks. The pathogenicity of Ca. R. colombiensis to human and animals is unknown. This study evaluated the pathogenic potential of Ca. R. colombiensis in Syrian hamsters and assessed the cross-reactivity between Ca. R. colombiensis and other Rickettsia in human and hamster sera. Shell vial technique was employed to isolate Ca. R. colombiensis. Subsequently, five male Syrian hamsters were inoculated intraperitoneally (IP) and five intradermally (ID) with 1 × 10⁶ Vero cells infected with Ca. R. colombiensis. One control hamster was used in each group. The health status was assessed daily, and necropsies were performed. Serum samples were tested by indirect immunofluorescence and tissues were processed by qPCR and histological stains. All Syrian hamsters remained healthy during the trial. No histopathological damages associated with rickettsial infection were observed. No Rickettsial DNA was detected in tissues. Syrian hamsters showed IgG antibody titers ranging from 1:64 to 1:1024. Control hamsters were negative. Regarding human sera, 56% (84/150) had IgG cross-reactivity antibodies against Ca. R. colombiensis. Subsequently, in a selected subset of 30 sera with moderate to high titers, all samples reacted with Ca. R. colombiensis antigen. Under specific conditions of this study, Ca. R. colombiensis did not behave as a highly virulent pathogen in the hamster model, although all infected Syrian hamsters developed IgG antibodies responses. Regarding cross-reactivity, it is possible to serologically diagnose rickettsial infection using Ca. R. colombiensis as an antigen. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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12 pages, 860 KB

Open AccessArticle

Autonomic Dysfunction in Patients with Acute Infection with Coxiella burnetii

by Branislav Milovanović, Nikola Marković, Elizabeta Ristanović, Sonja Atanasievska Kujović, Nikoleta Đorđevski, Masa Petrovic, Milica Milošević, Sulin Bulatovic and Milovan Bojić

Pathogens 2026, 15(1), 3; https://doi.org/10.3390/pathogens15010003 - 19 Dec 2025

Cited by 2 | Viewed by 1856

Abstract

Background: Coxiella burnetii is a common zoonotic pathogen that can lead not only to acute or chronic Q fever but also to post-infectious syndromes, where autonomic nervous system (ANS) dysfunction has been suggested as a contributing mechanism. This study aimed to assess autonomic function in patients presenting with polymorphic symptoms, dysautonomia, or ME/CFS who had serological evidence of acute infection with Coxiella burnetii. Methods: A total of 156 participants were evaluated, including 100 seropositive patients and 56 matched controls. All subjects underwent standardized cardiovascular reflex tests (CART), beat-to-beat analysis of heart rate and blood pressure with baroreflex indices, 24 h Holter ECG with HRV assessment, and, in the Coxiella group, head-up tilt testing (HUTT). Results: A significantly higher prevalence of autonomic dysfunction was observed in the Coxiella group, predominantly affecting parasympathetic regulation, with abnormal CART scores, reduced LF power and baroreflex effectiveness, and a high rate of positive HUTT findings characterized by extreme blood pressure variability. Although long-term HRV measures did not differ significantly between groups, short-term indices consistently indicated ANS impairment. Conclusions: These findings suggest that Coxiella burnetii infection may trigger persistent autonomic dysfunction, potentially contributing to the development of ME/CFS and syncope in affected individuals. Further longitudinal studies are needed to clarify pathophysiological mechanisms and clinical implications. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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16 pages, 4970 KB

Open AccessArticle

A Field Study Examining the Attraction of Adult Dermacentor variabilis to Heat Stimuli Associated with Road Edge Habitats

by Noah L. Stewart, Hannah Stahlman, Richard L. Stewart, Marcie L. Lehman and Alison Luce-Fedrow

Pathogens 2025, 14(11), 1147; https://doi.org/10.3390/pathogens14111147 - 12 Nov 2025

Viewed by 904

Abstract

Ticks use multiple sensory organs to facilitate host detection, including Haller’s organs (HOs) that allow ticks to sense infrared (IR) radiation from potential hosts. Additionally, ticks have primitive eyes to sense light sources. The possibility exists that these senses may detect stimuli that attract ticks to road edge habitat, where IR radiation tends to be elevated. We investigated the role of the HOs and eyes in the attraction of adult American dog ticks, Dermacentor variabilis, towards road edge habitat(s). Adult D. variabilis were collected from multiple study sites and separated into three groups: (1) Haller’s organs removed; (2) eyes painted with black nail polish; and (3) unmodified ticks (control). All tick groups were marked with a unique fluorescent paint color and released 7.5 m from the road edge at two study sites. Tick movements were tracked at night using ultraviolet lights, tick position(s) were recorded using flags, and measurements were recorded to track tick movement in relation to the release point and road edge. Surface temperatures were recorded at the road edge and in the field to detect a potential thermal stimulus. Mixed-effects models were applied to investigate the significance of tick proximity to the road edge between the groups and sites. Our results demonstrated that the control unmodified group was significantly closer to the road edge than the modified groups lacking Haller’s organ or eyes (p ≤ 0.0001, p = 0.0049), leading to the conclusion that unmodified ticks move towards road edges. Modifying ticks, either by removing the HO or eyes of adult D. variabilis decreased tick movement toward road edges. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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15 pages, 2319 KB

Open AccessArticle

Spatial Distribution of Equid Exposure to Rickettsia spp. in Goiás State, Midwestern Brazil

by Gracielle Teles Pádua, Mariana Avelar Tavares, Nicolas Jalowitzki de Lima, Warley Vieira de Freitas Paula, Gabriel Cândido dos Santos, Lucianne Cardoso Neves, Raphaela Bueno Mendes Bittencourt, Raquel Loren dos Reis Paludo, Ennya Rafaella Neves Cardoso, Bianca Barbara Fonseca da Silva, Bruno Rodrigues de Pádua, Ana Carolina Borsanelli, Filipe Dantas-Torres, Gina Paola Polo and Felipe da Silva Krawczak

Pathogens 2025, 14(5), 449; https://doi.org/10.3390/pathogens14050449 - 2 May 2025

Cited by 1 | Viewed by 1793

Abstract

This study sought to investigate the presence of anti-Rickettsia spp. antibodies in georeferenced serum samples from equids across all regions of the state of Goiás, while also presenting variables that indicate risk factors for the circulation of rickettsiae, and evaluating the presence of rickettsial DNA in ticks collected from equids and the surrounding environment in the municipalities of Uruaçu and Porangatu, located in the northern region of the state. A total of 1156 equid serum samples provided by the Goiás Agricultural Defense Agency (Agrodefesa) were analyzed for antibodies against 4 Rickettsia antigens. Additionally, 39 blood samples were collected from equids during a 3-day field expedition in January 2024, alongside 938 ticks collected from both animals and the environment. In total, 297 adult ticks were randomly selected for molecular analysis and tested by qPCR targeting the rickettsial gltA gene. Positive samples were further analyzed using cPCR to target the ompA and gltA genes. Results revealed that 9.6% (111/1156) of the serum samples were seroreactive to at least one Rickettsia antigen. Among these, 36% had antibodies against Rickettsia rickettsii, 18.9% against Rickettsia parkeri, 69.4% against Rickettsia amblyommatis, and 14.4% against Rickettsia bellii. Furthermore, the possible antigen responsible for a homologous reaction was found in 3.6% of equids for R. rickettsii, and in the same proportion for R. bellii, while 23.4% of animals showed antibodies for R. amblyommatis, and none exhibited a homologous reaction to R. parkeri. Meanwhile, 28.2% of the serum samples collected during the field expedition had antibodies against R. amblyommatis, with 72.7% identifying R. amblyommatis as the antigen involved in the homologous reaction. In the logistic regression analysis, the variables of education level, altitude below 500 m, and presence of female mules demonstrated a positive effect on seropositivity. Ticks from animals were identified as Amblyomma cajennense sensu lato, Amblyomma sculptum, Dermacentor nitens, and Rhipicephalus microplus, while environmental ticks were identified as A. cajennense s.l., A. sculptum, and Amblyomma nodosum. In the qPCR assays, two specimens of A. cajennense s.l., one of A. sculptum, and one of D. nitens amplified a fragment of the gltA gene. Of these, one A. cajennense s.l. specimen amplified a fragment of both the ompA and gltA genes, and one A. sculptum specimen amplified a fragment of the gltA gene through conventional PCR. Sequencing confirmed the detection of R. amblyommatis. These findings highlight the presence of anti-Rickettsia spp. antibodies in equid serum samples from all regions of the state of Goiás, emphasizing the important role of equids as sentinels for Rickettsia spp. To our knowledge, this study represents the largest effort to detect anti-Rickettsia spp. antibodies in equid serum samples in Brazil. Additionally, it is the first nationwide investigation of its kind conducted in collaboration with the Agricultural Defense Agency (Agrodefesa), serving as a significant example of the One Health approach. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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9 pages, 2179 KB

Open AccessArticle

Rickettsia asembonensis Isolated from Four Human Cases with Acute Undifferentiated Febrile Illness in Peru

by Steev Loyola, Rosa Palacios-Salvatierra, Omar Cáceres-Rey and Allen L. Richards

Pathogens 2024, 13(6), 489; https://doi.org/10.3390/pathogens13060489 - 8 Jun 2024

Cited by 16 | Viewed by 3015

Abstract

Rickettsioses, often underreported, pose public health challenges. Rickettsia asembonensis is a potential emerging pathogen that was previously detected in humans, animals, and a variety of arthropods. While its pathogenicity in humans remains unclear, it poses a potential public health threat. Here, we present an extended epidemiological, diagnostic, and genetic analysis of the information provided in a preliminary report on the investigation of rickettsiae in Peru. In particular, we report the detection of R. asembonensis in blood specimens collected from four human patients with an acute undifferentiated fever of a seven- to nine-day duration, all of whom tested negative for other vector-borne pathogens. Additionally, we describe the replicative capacity of the R. asembonensis isolates in cell cultures. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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10 pages, 1112 KB

Open AccessCase Report

The Paucity of Typical Pathology: An Autopsy Series of Typhus Group Rickettsiosis-Associated Hemophagocytic Lymphohistiocytosis

by Joshua Klinnert, Vasily Ovechko, Michelle M. Felicella, April McDougal, Sarah E. Muir, Patricia A. Crocquet-Valdes, David H. Walker and Lucas S. Blanton

Pathogens 2026, 15(2), 230; https://doi.org/10.3390/pathogens15020230 - 19 Feb 2026

Cited by 1 | Viewed by 734

Abstract

Murine typhus (also called flea-borne or endemic typhus) is an undifferentiated febrile illness caused by the bacterium Rickettsia typhi. The disease, transmitted by rat and cat fleas, is endemic to seaboard regions worldwide. Recently, murine typhus has reemerged as an increasingly recognized cause of febrile illness in the United States, especially in Texas and Southern California. In addition to fever, manifestations often include headache, malaise, myalgias, and a maculopapular rash in approximately half of cases. Although usually considered a mild illness, when untreated, symptoms can last up to 3 weeks. Severe manifestations such as pneumonitis, acute kidney injury, and meningoencephalitis may occur. Historically, death has occurred in 0.4%, but in Southern California, the case fatality rate has been recently recorded at 1.8%. As murine typhus has reemerged, there have been growing reports that this infection has triggered hemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome. We herein report two fatal cases of hemophagocytic lymphohistiocytosis secondary to murine typhus. Autopsy revealed typhus group rickettsial antigen in tissues via immunohistochemistry, along with hemophagocytosis. Interestingly, the classic vascular and perivascular histopathologic findings associated with disseminated rickettsial infection were absent. These findings highlight an aberrant inflammatory cascade leading to hemophagocytic lymphohistiocytosis. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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8 pages, 494 KB

Open AccessCase Report

Acute Rickettsiosis Triggering Plasmodium vivax Relapse in a Returned Traveler: A Case Report and Clinical Review of Travel-Related Coinfections

by Ruchika Bagga, Charlotte Fuller, Kalsoom Shahzad, Ezra Bado, Judith Joshi, Dileesha Fernando, Amanda Hempel and Andrea K. Boggild

Pathogens 2025, 14(8), 768; https://doi.org/10.3390/pathogens14080768 - 3 Aug 2025

Cited by 1 | Viewed by 1715

Abstract

Given the overlap of epidemiological and clinical presentations of both rickettsioses and malaria infections, diagnostic testing where malaria is confirmed or excluded, without subsequent rickettsial testing, specifically in the case of Plasmodium vivax or P. ovale infection, may mask the possibility of relapse. A lack of clinical suspicion of co-infections, absence of knowledge on the geographic distribution of diseases, and lack of availability of point-of-care diagnostic testing for other tropical diseases can often lead to missed diagnosis or misdiagnosis of common tropical infections, including rickettsioses. We herein describe a case of confirmed intercurrent rickettsial and P. vivax infection, with the former potentially triggering a relapse of the latter in a febrile traveler returning to Canada from South America, and review the literature on tropical coinfections in returning travelers. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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9 pages, 1917 KB

Open AccessCase Report

Scrub Typhus and Influenza A Co-Infection: A Case Report

by Chie Yamamoto, Ayano Maruyama, Jun Munakata, Tasuku Matsuyama, Keitaro Furukawa, Ryosuke Hamashima, Motohiko Ogawa, Yuki Hashimoto, Akiko Fukuda, Tohru Inaba and Yoko Nukui

Pathogens 2025, 14(1), 64; https://doi.org/10.3390/pathogens14010064 - 13 Jan 2025

Cited by 2 | Viewed by 3297

Abstract

Scrub typhus, caused by Orientia tsutsugamushi, is a neglected and reemerging disease that causes considerable morbidity and mortality. It now extends beyond the Tsutsugamushi Triangle, the region wherein it has traditionally been endemic. Influenza has also resurged since the infection control measures against COVID-19 were relaxed. A few cases of scrub typhus and influenza co-infection have been reported. Herein, we report the case of a 74-year-old woman with fever and upper respiratory symptoms diagnosed with influenza A and treated with oseltamivir; however, her fever persisted, and she developed respiratory failure, liver dysfunction, headache, diarrhea, and an erythematous skin rash. She lived in a forested area where scrub typhus was endemic and worked on a farm. Physical examination revealed an eschar on her posterior neck, and she was diagnosed with scrub typhus and influenza A co-infection. After minocycline treatment, her symptoms improved within a few days. This is the first reported case of scrub typhus and influenza A co-infection in Japan. This case illustrates that co-infection should be suspected in patients with fever persisting after their initial infection has been treated and that in patients living in endemic areas, scrub typhus can occur concurrently with influenza. The symptoms of scrub typhus are flu-like and nonspecific, which may delay diagnosis and treatment. Full article

(This article belongs to the Special Issue New Insights into Rickettsia and Related Organisms)

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