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The Past and Present Threat of Rickettsial Diseases (Volume II)

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A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 41959

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Special Issue Editor

Prof. Dr. Daniel H. Paris

E-Mail Website1 Website2
Guest Editor

1. Swiss Tropical and Public Health Institute, CH-4123 Allschwil, Switzerland
2. University of Basel, P.O. Box, CH-4003 Basel, Switzerland
Interests: rickettsia; scrub typhus; murine typhus; diagnostics; pathophysiology; vaccine; host response and immune response

Special Issue Information

Dear Colleagues,

Tropical rickettsial illnesses are severely neglected tropical diseases that have substantial impact on both rural and urban populations. For scrub typhus, all countries with established surveillance systems—available for South Korea, Japan, China, and Thailand—have reported increasing minimum incidence rates over the past decade. Recent reports from South America and Africa suggest a wider distribution outside of Asia. For murine typhus, an equally important and even more neglected disease with a more urban distribution, a lot of clinically relevant information on the natural history, disease burden, diagnostics and pathogen characterization is lacking. Spotted fever group rickettsia transmitted largely by ticks should also receive more attention, especially concerning reports from tropical and subtropical regions. Scrub typhus and murine typhus together are responsible for a substantial proportion of undiagnosed febrile illnesses in humans in many parts of the tropics.

Unfortunately, there are many limitations on the amount and quality of available epidemiological data, natural history, mathematical modeling, or mapping approaches. Furthermore, the control of these vector-borne diseases is challenging due to humans being dead-end hosts, vertical maintenance of the pathogen in the vector itself, a potentially large rodent reservoir of unclear significance, coupled with non-specific clinical features upon presentation and diagnostic difficulties.

In this Special Issue of “Tropical Medicine and Infectious Disease”, we invite the submission of reviews, reports and original research articles on the currently relevant aspects of tropical rickettsial illnesses—with emphasis on diagnostic developments, epidemiology, fever studies, bacterial virulence, genomics and potential antimicrobial resistance issues—aiming at improving the awareness and understanding of physicians and researchers alike, about these neglected but important diseases.

Prof. Dr. Daniel Paris
Guest Editor

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Keywords

Tropical rickettsial illnesses
Scrub typhus
Murine typhus
Spotted fever group rickettsiae
Orientia tsutsugamushi
Rickettsiales
Trombiculid mites
Fleas and ticks
Diagnostics
Cell biology
Unraveling genomic issues
Aetiology of fever studies
Epidemiology

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Published Papers (9 papers)

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Research

Jump to: Review, Other

14 pages, 1254 KiB

Open AccessArticle

A Use of 56-kDa Recombinant Protein of Orientia tsutsugamushi Karp Serotype in Serodiagnosis of Scrub Typhus by Enzyme-Linked Immunosorbent Assay in Thais

by Phanita Chankate, Thareerat Kalambaheti, Nathamon Kosoltanapiwat, Ampai Tanganuchitcharnchai, Stuart D. Blacksell, Narisara Chantratita and Pornsawan Leaungwutiwong

Trop. Med. Infect. Dis. 2023, 8(1), 10; https://doi.org/10.3390/tropicalmed8010010 - 23 Dec 2022

Viewed by 2898

Abstract

Scrub typhus is a mite-borne disease caused by a Gram-negative obligately intracellular bacillus, Orientia tsutsugamushi. The disease is endemic in the Asia–Australia–Pacific region, including Thailand. Scrub typhus generally manifests as acute undifferentiated febrile fever along with myalgia, rash, and lymphadenopathy. An eschar can be a valuable diagnostic clue, but this skin lesion may be missed in some patients. The disease symptoms resemble those of other febrile illnesses such as leptospirosis, typhoid, murine typhus, malaria, and dengue fever, making a laboratory diagnosis necessary for the definitive diagnosis. In this study, we expressed a recombinant protein derived from 56-kDa type-specific antigen of O. tsutsugamushi Karp serotype and tested its ability to detect and differentiate scrub typhus infection. IgM and IgG antibodies were determined in sera from scrub typhus (n = 92) and other febrile illness patients (murine typhus (n = 25), melioidosis (n = 36), leptospirosis (n = 42), and dengue (n = 35)) from Thailand. Sensitivities of 87.0% and 59.8% with a specified assay cut-off were obtained for IgM and IgG indirect ELISAs, respectively, with a specificity of 100% in both tests. The sensitivity was increased to 95.7% when a combination of IgM and IgG ELISAs results was considered. Our study suggested a potential of the 56-kDa recombinant protein for further development and evaluation for use in scrub typhus serodiagnosis. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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14 pages, 2607 KiB

Open AccessArticle

Rickettsial Infections Are Neglected Causes of Acute Febrile Illness in Teluk Intan, Peninsular Malaysia

by Muhamad Yazli Yuhana, Borimas Hanboonkunupakarn, Ampai Tanganuchitcharnchai, Pimpan Sujariyakul, Piengchan Sonthayanon, Kesinee Chotivanich, Sasithon Pukrittayakamee, Stuart D. Blacksell and Daniel H. Paris

Trop. Med. Infect. Dis. 2022, 7(5), 77; https://doi.org/10.3390/tropicalmed7050077 - 18 May 2022

Cited by 6 | Viewed by 3485 | Correction

Abstract

Rickettsial infections are among the leading etiologies of acute febrile illness in Southeast Asia. However, recent data from Malaysia are limited. This prospective study was conducted in Teluk Intan, Peninsular Malaysia, during January to December 2016. We recruited 309 hospitalized adult patients with acute febrile illness. Clinical and biochemistry data were obtained, and patients were stratified into mild and severe infections based on the sepsis-related organ failure (qSOFA) scoring system. Diagnostic assays including blood cultures, real-time PCR, and serology (IFA and MAT) were performed. In this study, pathogens were identified in 214 (69%) patients, of which 199 (93%) patients had a single etiology, and 15 (5%) patients had >1 etiologies. The top three causes of febrile illness requiring hospitalization in this Malaysian study were leptospirosis (68 (32%)), dengue (58 (27%)), and rickettsioses (42 (19%)). Fifty-five (18%) patients presented with severe disease with a qSOFA score of ≥2. Mortality was documented in 38 (12%) patients, with the highest seen in leptospirosis (16 (42%)) followed by rickettsiosis (4 (11%)). While the significance of leptospirosis and dengue are recognized, the impact of rickettsial infections in Peninsular Malaysia remains under appreciated. Management guidelines for in-patient care with acute febrile illness in Peninsular Malaysia are needed. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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23 pages, 12084 KiB

Open AccessArticle

Comparison of Lethal and Nonlethal Mouse Models of Orientia tsutsugamushi Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection

by Alison Luce-Fedrow, Suchismita Chattopadhyay, Teik-Chye Chan, Gregory Pearson, John B. Patton and Allen L. Richards

Trop. Med. Infect. Dis. 2021, 6(3), 121; https://doi.org/10.3390/tropicalmed6030121 - 2 Jul 2021

Cited by 10 | Viewed by 5199

Abstract

The antigenic diversity of Orientia tsutsugamushi as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of O. tsutsugamushi infection using the two strains, Karp (New Guinea) and Woods (Australia). The models included the lethal model: Karp intraperitoneal (IP) challenge; and the nonlethal models: Karp intradermal (ID), Woods IP, and Woods ID challenges. We monitored bacterial trafficking to the liver, lung, spleen, kidney, heart, and blood, and seroconversion during the 21-day challenge. Bacterial trafficking to all organs was observed in both the lethal and nonlethal models of infection, with significant increases in average bacterial loads observed in the livers and hearts of the lethal model. Multicolor flow cytometry was utilized to analyze the CD4+ and CD8+ T cell populations and their intracellular production of the cytokines IFNγ, TNF, and IL2 (single, double, and triple combinations) associated with both the lethal and nonlethal murine models of infection. The lethal model was defined by a cytokine signature of double- (IFNγ-IL2) and triple-producing (IL2-TNF-IFNγ) CD4+ T-cell populations; no multifunctional signature was identified in the CD8+ T-cell populations associated with the lethal model. In the nonlethal model, the cytokine signature was predominated by CD4+ and CD8+ T-cell populations associated with single (IL2) and/or double (IL2-TNF) populations of producers. The cytokine signatures associated with our lethal model will become depletion targets in future experiments; those signatures associated with our nonlethal model are hypothesized to be related to the protective nature of the nonlethal challenges. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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16 pages, 1299 KiB

Open AccessEditor’s ChoiceReview

A Review of Rickettsial Diseases Other Than Scrub Typhus in India

by Sivanantham Krishnamoorthi, Shriya Goel, Jasleen Kaur, Kamlesh Bisht and Manisha Biswal

Trop. Med. Infect. Dis. 2023, 8(5), 280; https://doi.org/10.3390/tropicalmed8050280 - 16 May 2023

Cited by 9 | Viewed by 4316

Abstract

Rickettsial diseases (RD) are widely reported all over the world. Scrub typhus (ST) is a major tropical infection which is well documented all over India. Therefore, the index of suspicion of scrub typhus is high among physicians with regard to patients presenting with acute febrile illness (AFI) and acute undifferentiated febrile illness (AUFI) in India. Rickettsial diseases other than ST (non-ST RDs), which include spotted fever group (SFG) rickettsioses and typhus group (TG) rickettsioses are not uncommon in India, but the index of suspicion is not as high as ST unless there is a history of the presence of fever with rashes and/or recent arthropod bites. This review aims to look into the Indian scenario on the epidemiology of non-ST RDs, especially the SFG and TG rickettsioses based on various investigations, spectrum of clinical presentation, challenges and gaps in knowledge to suspect and diagnose these infections. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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19 pages, 1089 KiB

Open AccessReview

Moonlighting in Rickettsiales: Expanding Virulence Landscape

by Ana Luísa Matos, Pedro Curto and Isaura Simões

Trop. Med. Infect. Dis. 2022, 7(2), 32; https://doi.org/10.3390/tropicalmed7020032 - 19 Feb 2022

Cited by 17 | Viewed by 4499

Abstract

The order Rickettsiales includes species that cause a range of human diseases such as human granulocytic anaplasmosis (Anaplasma phagocytophilum), human monocytic ehrlichiosis (Ehrlichia chaffeensis), scrub typhus (Orientia tsutsugamushi), epidemic typhus (Rickettsia prowazekii), murine typhus (R. typhi), Mediterranean spotted fever (R. conorii), or Rocky Mountain spotted fever (R. rickettsii). These diseases are gaining a new momentum given their resurgence patterns and geographical expansion due to the overall rise in temperature and other human-induced pressure, thereby remaining a major public health concern. As obligate intracellular bacteria, Rickettsiales are characterized by their small genome sizes due to reductive evolution. Many pathogens employ moonlighting/multitasking proteins as virulence factors to interfere with multiple cellular processes, in different compartments, at different times during infection, augmenting their virulence. The utilization of this multitasking phenomenon by Rickettsiales as a strategy to maximize the use of their reduced protein repertoire is an emerging theme. Here, we provide an overview of the role of various moonlighting proteins in the pathogenicity of these species. Despite the challenges that lie ahead to determine the multiple potential faces of every single protein in Rickettsiales, the available examples anticipate this multifunctionality as an essential and intrinsic feature of these obligates and should be integrated into available moonlighting repositories. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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11 pages, 556 KiB

Open AccessReview

Rickettsiosis in Southeast Asia: Summary for International Travellers during the COVID-19 Pandemic

by Thundon Ngamprasertchai, Borimas Hanboonkunupakarn and Watcharapong Piyaphanee

Trop. Med. Infect. Dis. 2022, 7(2), 18; https://doi.org/10.3390/tropicalmed7020018 - 27 Jan 2022

Cited by 4 | Viewed by 6147

Abstract

Rickettsiosis is an important cause of febrile illness among travellers visiting Southeast Asia (SEA). The true incidence of rickettsiosis is underestimated; however, murine typhus and scrub typhus are widely distributed across SEA. Among travellers visiting SEA, scrub typhus was mostly reported from Thailand, whereas murine typhus was frequently found in Indonesia. Although most cases are self-limited or present with mild symptoms, a few cases with severe clinical manifestations have been reported. Doxycycline remains the key treatment of rickettsiosis. Some travellers, such as backpackers, trekkers, or cave explorers, are at a higher risk for rickettsiosis than others. Therefore, in resource-limited conditions, empirical treatment should be considered in these travellers. The coronavirus disease 2019 (COVID-19) pandemic has contributed to difficulty in the diagnosis of rickettsiosis because of the clinical similarities between these diseases. In addition, physical distancing mandated by COVID-19 management guidelines limits accurate physical examination, resulting in misdiagnosis and delayed treatment of rickettsiosis. This review summarises the characteristics of murine typhus and scrub typhus, describes travel-associated rickettsiosis, and discusses the impact of the COVID-19 pandemic on rickettsiosis. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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17 pages, 5245 KiB

Open AccessReview

Mediterranean Spotted Fever: Current Knowledge and Recent Advances

by Nikolaos Spernovasilis, Ioulia Markaki, Michail Papadakis, Nikolaos Mazonakis and Despo Ierodiakonou

Trop. Med. Infect. Dis. 2021, 6(4), 172; https://doi.org/10.3390/tropicalmed6040172 - 24 Sep 2021

Cited by 23 | Viewed by 7728

Abstract

Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar (“tache noire”). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF. Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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Other

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1 pages, 167 KiB

Open AccessCorrection

Correction: Yuhana et al. Rickettsial Infections Are Neglected Causes of Acute Febrile Illness in Teluk Intan, Peninsular Malaysia. Trop. Med. Infect. Dis. 2022, 7, 77

Trop. Med. Infect. Dis. 2022, 7(7), 134; https://doi.org/10.3390/tropicalmed7070134 - 13 Jul 2022

Cited by 1 | Viewed by 1176

Abstract

The authors wish to make the following correction to this paper [...] Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

12 pages, 846 KiB

Open AccessSystematic Review

Rickettsiosis with Pleural Effusion: A Systematic Review with a Focus on Rickettsiosis in Italy

by Cristoforo Guccione, Raffaella Rubino, Claudia Colomba, Antonio Anastasia, Valentina Caputo, Chiara Iaria and Antonio Cascio

Trop. Med. Infect. Dis. 2022, 7(1), 11; https://doi.org/10.3390/tropicalmed7010011 - 14 Jan 2022

Cited by 6 | Viewed by 3351

Abstract

Background: Motivated by a case finding of Mediterranean spotted fever (MSF) associated with atypical pneumonia and pleural effusion in which Rickettsia conorii subsp. israelensis was identified by molecular methods in the pleural fluid, we wanted to summarize the clinical presentations of rickettsiosis in Italy by systematic research and to make a systematic review of all the global cases of rickettsiosis associated with pleural effusion. Methods: For the literature search, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. We chose to select only the studies published in last 25 years and confirmed both with serological and molecular assays. Results: Human cases of rickettsiosis in Italy were reported in 48 papers describing 2831 patients with very different clinical presentations; the majority was MSF accounted to R. conorii and was reported in Sicily. Pleural effusion associated with infection with microorganisms belonging to Rickettsiales was described in 487 patients. It was rarely associated with microorganisms different from O. tsutsugamushi; also rarely, cases of scrub typhus were reported outside Southeast Asia and in the largest majority, the diagnosis was achieved with serology. Conclusions: MSF, especially when caused by R. conorii subsp. israelensis, may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis Full article

(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases (Volume II))

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