Latest Updates on Scrub Typhus (Orientia spp.)

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 20 April 2024 | Viewed by 6595

Special Issue Editors


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Guest Editor
Department of Veterinary Medicine, USAMD-AFRIMS, Bangkok, Thailand
Interests: vector-borne diseases; zoonosis; scrub typhus; rickettsia; animal models

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Guest Editor
Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Interests: Rickettsial diseases; scrub typhus; vector-borne diseases; zoonoses

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Guest Editor
1. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
2. Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand
Interests: scrub typhus; rickettsia; zoonoses; diagnostics; biosafety
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Special Issue Information

Dear Colleagues,

Scrub typhus is mite-borne disease caused by Orientia spp., obligate intracellular bacteria in the Rickettsiaceae family. It is previously known to be endemic in the Asia-Pacific region where over a billion people are at risk; however, recent evidences suggest global distribution of scrub typhus beyond tsutsugamushi triangle, for example it has been found in the Middle East, Africa, and South America. Scrub typhus has become more attracted to the research world after being under recognized for many decades. Currently, there are three species of Orientia recognized worldwide including O. tsutsugamushi, Candidatus O. chuto, and Candidatus O. chiloensis. As obligate intracellular bacteria, they have a complex but fascinating life cycle. Orientia spp. can survive in both arthropod and mammalian host cells, and during disease transmission Orientia spp. have to be able to infect a variety of host cells and cope with the immune system of both arthropods and mammals which have different systems and actions. Being intracellular bacteria that require host cells for survival makes it hard to conduct research experiments. However, these days with new cutting-edge technologies and a different point of view to Orientia spp. based on their global distribution map with two new species researchers continue to reveal novel knowledge and unlock some hidden information of Orientia spp.

In this special issue of Pathogens, we would like to invite you to contribute your updates on scrub typhus by submitting original and review articles covering all aspects of scrub typhus.

We look forward to your contribution.

Dr. Piyanate Sunyakumthorn
Prof. Dr. Allen L. Richards
Prof. Dr. Stuart Blacksell
Guest Editors

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Keywords

  • Scrub typhus
  • Orientia
  • Rickettsia
  • mite
  • chigger
  • vector-borne
  • zoonosis

Published Papers (4 papers)

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Research

14 pages, 633 KiB  
Article
Concatenated ScaA and TSA56 Surface Antigen Sequences Reflect Genome-Scale Phylogeny of Orientia tsutsugamushi: An Analysis Including Two Genomes from Taiwan
by Nicholas T. Minahan, Tsai-Ying Yen, Yue-Liang Leon Guo, Pei-Yun Shu and Kun-Hsien Tsai
Pathogens 2024, 13(4), 299; https://doi.org/10.3390/pathogens13040299 - 03 Apr 2024
Viewed by 694
Abstract
Orientia tsutsugamushi is an obligate intracellular bacterium associated with trombiculid mites and is the causative agent of scrub typhus, a life-threatening febrile disease. Strain typing of O. tsutsugamushi is based on its immunodominant surface antigen, 56-kDa type-specific antigen (TSA56). However, TSA56 gene sequence-based [...] Read more.
Orientia tsutsugamushi is an obligate intracellular bacterium associated with trombiculid mites and is the causative agent of scrub typhus, a life-threatening febrile disease. Strain typing of O. tsutsugamushi is based on its immunodominant surface antigen, 56-kDa type-specific antigen (TSA56). However, TSA56 gene sequence-based phylogenetic analysis is only partially congruent with core genome-based phylogenetic analysis. Thus, this study investigated whether concatenated surface antigen sequences, including surface cell antigen (Sca) proteins, can reflect the genome-scale phylogeny of O. tsutsugamushi. Complete genomes were obtained for two common O. tsutsugamushi strains in Taiwan, TW-1 and TW-22, and the core genome/proteome was identified for 11 O. tsutsugamushi strains. Phylogenetic analysis was performed using maximum likelihood (ML) and neighbor-joining (NJ) methods, and the congruence between trees was assessed using a quartet similarity measure. Phylogenetic analysis based on 691 concatenated core protein sequences produced identical tree topologies with ML and NJ methods. Among TSA56 and core Sca proteins (ScaA, ScaC, ScaD, and ScaE), TSA56 trees were most similar to the core protein tree, and ScaA trees were the least similar. However, concatenated ScaA and TSA56 sequences produced trees that were highly similar to the core protein tree, the NJ tree being more similar. Strain-level characterization of O. tsutsugamushi may be improved by coanalyzing ScaA and TSA56 sequences, which are also important targets for their combined immunogenicity. Full article
(This article belongs to the Special Issue Latest Updates on Scrub Typhus (Orientia spp.))
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14 pages, 2864 KiB  
Article
Dual-Antigen Subunit Vaccine Nanoparticles for Scrub Typhus
by Jaeyoung Park, Zhiwen Zhang, Tatyana Belinskaya, Alexandra N. Tsoras, Chien-Chung Chao, Le Jiang and Julie A. Champion
Pathogens 2023, 12(12), 1390; https://doi.org/10.3390/pathogens12121390 - 25 Nov 2023
Cited by 1 | Viewed by 1045
Abstract
Orientia tsutsugamushi is the causative pathogen of scrub typhus, an acute febrile disease prevalent in the Asia–Pacific region that is spread to people through chigger bites. Despite the emerging threat, there is no currently available vaccine against O. tsutsugamushi. Here, we developed [...] Read more.
Orientia tsutsugamushi is the causative pathogen of scrub typhus, an acute febrile disease prevalent in the Asia–Pacific region that is spread to people through chigger bites. Despite the emerging threat, there is no currently available vaccine against O. tsutsugamushi. Here, we developed dual-antigen subunit vaccine nanoparticles using recombinant 47 kD and 56 kD proteins, which are immunogenic outer membrane antigens of O. tsutsugamushi. The biocompatible protein vaccine nanoparticles were formed via desolvation of r56 or r47E antigens with acetone, coating with an additional layer of the 56 kD protein, and stabilization with reducible homobifunctional DTSSP and heterobifunctional SDAD crosslinkers. The dual-antigen subunit vaccine nanoparticles significantly improved antigen-specific antibody responses in vaccinated mice. Most importantly, the dual-antigen nanoparticles coated with an additional layer of the 56 kD protein were markedly more immunogenic than soluble antigens or single-antigen nanoparticles in the context of cellular immune responses. Given the significance of cellular immune responses for protection against O. tsutsugamushi, these results demonstrate the potent immunogenicity of dual-layered antigen nanoparticles and their potential as a promising strategy for developing vaccines against scrub typhus. Full article
(This article belongs to the Special Issue Latest Updates on Scrub Typhus (Orientia spp.))
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16 pages, 3188 KiB  
Article
Orientia tsutsugamushi Infection Stimulates Syk-Dependent Responses and Innate Cytosolic Defenses in Macrophages
by James Fisher, Casey Gonzales, Zachary Chroust, Yuejin Liang and Lynn Soong
Pathogens 2023, 12(1), 53; https://doi.org/10.3390/pathogens12010053 - 29 Dec 2022
Cited by 2 | Viewed by 1914
Abstract
Orientia tsutsugamushi is an obligately intracellular bacterium and an etiological agent of scrub typhus. Human studies and animal models of scrub typhus have shown robust type 1-skewed proinflammatory responses during severe infection. Macrophages (MΦ) play a critical role in initiating such responses, yet [...] Read more.
Orientia tsutsugamushi is an obligately intracellular bacterium and an etiological agent of scrub typhus. Human studies and animal models of scrub typhus have shown robust type 1-skewed proinflammatory responses during severe infection. Macrophages (MΦ) play a critical role in initiating such responses, yet mechanisms of innate recognition for O. tsutsugamushi remain unclear. In this study, we investigated whether Syk-dependent C-type lectin receptors (CLRs) contribute to innate immune recognition and the generation of proinflammatory responses. To validate the role of CLRs in scrub typhus, we infected murine bone marrow-derived MΦ with O. tsutsugamushi in the presence of selective Syk inhibitors and analyzed a panel of CLRs and proinflammatory markers via qRT-PCR. We found that Mincle/Clec4a and Clec5a transcription was significantly abrogated upon Syk inhibition at 6 h of infection. The effect of Syk inhibition on Mincle protein expression was validated via Western blot. Syk-inhibited MΦ had diminished expression of type 1 cytokines/chemokines (Il12p40, Tnf, Il27p28, Cxcl1) during infection. Additionally, expression of innate immune cytosolic sensors (Mx1 and Oas1-3) was highly induced in the brain of lethally infected mice. We established that Mx1 and Oas1 expression was reduced in Syk-inhibited MΦ, while Oas2, Oas3, and MerTK were not sensitive to Syk inhibition. This study reveals that Syk-dependent CLRs contribute to inflammatory responses against O. tsutsugamushi. It also provides the first evidence for Syk-dependent activation of intracellular defenses during infection, suggesting a role of pattern recognition receptor crosstalk in orchestrating macrophage-mediated responses to this poorly studied bacterium. Full article
(This article belongs to the Special Issue Latest Updates on Scrub Typhus (Orientia spp.))
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18 pages, 12308 KiB  
Article
Habitat and Season Drive Chigger Mite Diversity and Abundance on Small Mammals in Peninsular Malaysia
by Hadil Alkathiry, Ahmed Al-Rofaai, Zubaidah Ya’cob, Tamsin S. Cutmore, Siti Nurul Izzah Mohd-Azami, Nurul Aini Husin, Fang Shiang Lim, Sirikamon Koosakulnirand, Nor Hidayana Mahfodz, Siti Nabilah Ishak, Shih Keng Loong, Alexandr Stekolnikov, Farah Shafawati Mohd-Taib, Sazaly Abubakar, Benjamin L. Makepeace, Kittipong Chaisiri and Jing Jing Khoo
Pathogens 2022, 11(10), 1087; https://doi.org/10.3390/pathogens11101087 - 23 Sep 2022
Cited by 6 | Viewed by 2025
Abstract
Chigger mites are vectors of the bacterial disease scrub typhus, caused by Orientia spp. The bacterium is vertically transmitted in the vector and horizontally transmitted to terrestrial vertebrates (primarily wild small mammals), with humans as incidental hosts. Previous studies have shown that the [...] Read more.
Chigger mites are vectors of the bacterial disease scrub typhus, caused by Orientia spp. The bacterium is vertically transmitted in the vector and horizontally transmitted to terrestrial vertebrates (primarily wild small mammals), with humans as incidental hosts. Previous studies have shown that the size of the chigger populations is correlated with the density of small mammals in scrub typhus-endemic regions. Here, we explore interactions between the small mammals and chiggers in two oil palm plantations located in the Perak and Johor states of Peninsular Malaysia. The location in Perak also contained an aboriginal (Orang Asli) settlement. A ~5% sub-sample from 40,736 chigger specimens was identified from five species of small mammals (n = 217), revealing 14 chigger species, including two new records for Malaysia. The abundance and species richness of chiggers were significantly affected by habitat type (highest in forest border), state (highest in Perak), and season (highest in dry). The overall prevalence of Orientia tsutsugamushi DNA in small-mammal tissues was 11.7% and was not significantly affected by host or habitat characteristics, but in Johor, was positively associated with infestation by Leptotrombidium arenicola. These findings highlight the risk of contracting scrub typhus in oil palm plantations and associated human settlements. Full article
(This article belongs to the Special Issue Latest Updates on Scrub Typhus (Orientia spp.))
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