Special Issue "The Past and Present Threat of Rickettsial Diseases"

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366).

Deadline for manuscript submissions: closed (31 May 2018).

Special Issue Editor

Prof. Dr. Daniel H. Paris
E-Mail Website1 Website2
Guest Editor
1. Nuffield Department of Medicine, University of Oxford, UK
2. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, 3rd Floor, 60th Anniversary Chalermprakiat Building, 420/6 Ratchawithi Rd., Ratchathewi District, Bangkok 10400, Thailand
3. Swiss Tropical and Public Health Institute, Basel, Switzerland
4.University Basel, 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 of 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—report increasing minimum incidence rates over the past decade. Recent reports from South America and Africa suggest a wider distribution outside Asia. It is a potentially severe disease, with mortality reports around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. 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 characterisation are lacking. 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, limited conclusions, mathematical modeling, or mapping approaches. Further, 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. Daniel H. Paris
Guest Editor

Manuscript Submission Information

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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

Published Papers (21 papers)

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Research

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Open AccessArticle
Epidemiology, Risk Factors and Seasonal Variation of Scrub Typhus Fever in Central Nepal
Trop. Med. Infect. Dis. 2019, 4(1), 27; https://doi.org/10.3390/tropicalmed4010027 - 02 Feb 2019
Cited by 1
Abstract
Scrub typhus is a mite-borne acute febrile illness caused by Orientia. tsutsugamushi, a zoonotic bacterial infection common in the region known as the tsutsugamushi triangle. This study aims to determine the seroprevalence, seasonal variation, and risk factors of scrub typhus among the acute [...] Read more.
Scrub typhus is a mite-borne acute febrile illness caused by Orientia. tsutsugamushi, a zoonotic bacterial infection common in the region known as the tsutsugamushi triangle. This study aims to determine the seroprevalence, seasonal variation, and risk factors of scrub typhus among the acute febrile illness patients attending different hospitals of central Nepal. Blood samples were collected from hospitalized patients of acute febrile illness suspected of scrub typhus infection attending different hospitals of central Nepal from April 2017 to March 2018. The IgM antibody to Orientia tsutsugamushi was detected by using the Scrub Typhus Detect™ Kit. Among the total cases (1585), 358 (22.58%) were positive for IgM Antibodies. Multivariate analysis identified several risks factors to be significantly associated with the scrub typhus infection, including gender (female) (odds ratio [OR] = 1.976, p ≤ 0.001, confidence interval [CI] = 1.417–2.756), rural residential location (odds ratio [OR] = 0.431, p = 0.001, confidence interval [CI] = 0.260–0.715), house near grassland (odds ratio [OR] = 3.288, p ≤ 0.001, confidence interval [CI] = 1.935–5.587), and working in the field (odds ratio [OR] = 9.764, p = 0.004, confidence interval [CI] = 2.059–46.315). The study findings indicate scrub typhus infection to be a significant health problem in Nepal. The proper diagnosis of infection cases, timely institution of therapy, public awareness, and vector control are important measures to be taken for the prevention and management of scrub typhus. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Diagnostic Accuracy of the InBios Scrub Typhus Detect™ ELISA for the Detection of IgM Antibodies in Chittagong, Bangladesh
Trop. Med. Infect. Dis. 2018, 3(3), 95; https://doi.org/10.3390/tropicalmed3030095 - 01 Sep 2018
Cited by 1
Abstract
Here we estimated the accuracy of the InBios Scrub Typhus Detect™ immunoglobulin M (IgM) ELISA to determine the optimal optical density (OD) cut-off values for the diagnosis of scrub typhus. Patients with undifferentiated febrile illness from Chittagong, Bangladesh, provided samples for reference testing [...] Read more.
Here we estimated the accuracy of the InBios Scrub Typhus Detect™ immunoglobulin M (IgM) ELISA to determine the optimal optical density (OD) cut-off values for the diagnosis of scrub typhus. Patients with undifferentiated febrile illness from Chittagong, Bangladesh, provided samples for reference testing using (i) qPCR using the Orientia spp. 47-kDa htra gene, (ii) IFA ≥1:3200 on admission, (iii) immunofluorescence assay (IFA) ≥1:3200 on admission or 4-fold rise to ≥3200, and (iv) combination of PCR and IFA positivity. For sero-epidemiological purposes (ELISA vs. IFA ≥1:3200 on admission or 4-fold rise to ≥3200), the OD cut-off for admission samples was ≥1.25, resulting in a sensitivity (Sn) of 91.5 (95% confidence interval (95% CI: 96.8–82.5) and a specificity (Sp) of 92.4 (95% CI: 95.0–89.0), while for convalescent samples the OD cut-off was ≥1.50 with Sn of 66.0 (95% CI: 78.5–51.7) and Sp of 96.0 (95% CI: 98.3–92.3). Comparisons against comparator reference tests (ELISA vs. all tests including PCR) indicated the most appropriate cut-off OD to be within the range of 0.75–1.25. For admission samples, the best Sn/Sp compromise was at 1.25 OD (Sn 91.5%, Sp 92.4%) and for convalescent samples at 0.75 OD (Sn 69.8%, Sp 89.5%). A relatively high (stringent) diagnostic cut-off value provides increased diagnostic accuracy with high sensitivity and specificity in the majority of cases, while lowering the cut-off runs the risk of false positivity. This study underlines the need for regional assessment of new diagnostic tests according to the level of endemicity of the disease given the high levels of residual or cross-reacting antibodies in the general population. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Differential Susceptibility of Male Versus Female Laboratory Mice to Anaplasma phagocytophilum Infection
Trop. Med. Infect. Dis. 2018, 3(3), 78; https://doi.org/10.3390/tropicalmed3030078 - 23 Jul 2018
Cited by 3 | Correction
Abstract
Human granulocytic anaplasmosis (HGA) is a debilitating, non-specific febrile illness caused by the granulocytotropic obligate intracellular bacterium called Anaplasma phagocytophilum. Surveillance studies indicate a higher prevalence of HGA in male versus female patients. Whether this discrepancy correlates with differential susceptibility of males [...] Read more.
Human granulocytic anaplasmosis (HGA) is a debilitating, non-specific febrile illness caused by the granulocytotropic obligate intracellular bacterium called Anaplasma phagocytophilum. Surveillance studies indicate a higher prevalence of HGA in male versus female patients. Whether this discrepancy correlates with differential susceptibility of males and females to A. phagocytophilum infection is unknown. Laboratory mice have long been used to study granulocytic anaplasmosis. Yet, sex as a biological variable (SABV) in this model has not been evaluated. In this paper, groups of male and female C57Bl/6 mice that had been infected with A. phagocytophilum were assessed for the bacterial DNA load in the peripheral blood, the percentage of neutrophils harboring bacterial inclusions called morulae, and splenomegaly. Infected male mice exhibited as much as a 1.85-fold increase in the number of infected neutrophils, which is up to a 1.88-fold increase in the A. phagocytophilum DNA load, and a significant increase in spleen size when compared to infected female mice. The propensity of male mice to develop a higher level of A. phagocytophilum infection is relevant for studies utilizing the mouse model. This stresses the importance of including SABV and aligns with the observed higher incidence of infection in male versus female patients. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Serological Cross-Reactivity among Orientia tsutsugamushi Serotypes but Not with Rickettsia japonica in Japan
Trop. Med. Infect. Dis. 2018, 3(3), 74; https://doi.org/10.3390/tropicalmed3030074 - 05 Jul 2018
Cited by 3 | Correction
Abstract
The rickettsial diseases Japanese spotted fever (JSF) and scrub typhus (ST) are caused by Rickettsia japonica and Orientia tsutsugamushi, respectively. The diseases share clinical symptoms, such as fever, rash, and eschar. However, there are no systematical investigations of the serological cross-reactivity between [...] Read more.
The rickettsial diseases Japanese spotted fever (JSF) and scrub typhus (ST) are caused by Rickettsia japonica and Orientia tsutsugamushi, respectively. The diseases share clinical symptoms, such as fever, rash, and eschar. However, there are no systematical investigations of the serological cross-reactivity between R. japonica and O. tsutsugamushi. Also, the serological cross-reactivity among O. tsutsugamushi serotypes is still unclear. We analyzed 1406 cases tested by indirect immunoperoxidase assay using seven rickettsial antigens—one R. japonica and six O. tsutsugamushi serotypes—between 2003 and 2016 at two reference centers in Japan. Of these, 167 JSF and 190 ST cases were serologically diagnosed. None of the ST cases had a significant increase in IgM titers against R. japonica. Six JSF cases showed IgG titers of ≥40 against O. tsutsugamushi, but no IgG titer showed a significant elevation in the convalescent phase sample. We observed a substantial degree of cross-reactivity between O. tsutsugamushi serotypes. Cross-reactivity was significant among Karp, Hirano/Kuroki, and Kato types and between Gilliam and Irie/Kawasaki types in IgM, while the Shimokoshi type was less cross-reactive than the others. In conclusion, there is no serological cross-reaction between R. japonica and O. tsutsugamushi. The cross-reactivity among O.tsutsugamushi varies depending on serotypes. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Outer Membrane Protein A Conservation among Orientia tsutsugamushi Isolates Suggests Its Potential as a Protective Antigen and Diagnostic Target
Trop. Med. Infect. Dis. 2018, 3(2), 63; https://doi.org/10.3390/tropicalmed3020063 - 11 Jun 2018
Cited by 1
Abstract
Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium Orientia tsutsugamushi. A vaccine that affords heterologous protection and a [...] Read more.
Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially-available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically-related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs and blood of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly-protective scrub typhus vaccine. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Spotted Fever Rickettsiosis in a Wildlife Researcher in Sabah, Malaysia: A Case Study
Trop. Med. Infect. Dis. 2018, 3(1), 29; https://doi.org/10.3390/tropicalmed3010029 - 06 Mar 2018
Cited by 2
Abstract
We present evidence for a case of spotted fever rickettsiosis with severe complications in a young adult male. Although spotted fever group rickettsiae (SFGR) have been reported as the most prevalent cause of rickettsiosis in rural areas of Sabah, Malaysia since the 1980s, [...] Read more.
We present evidence for a case of spotted fever rickettsiosis with severe complications in a young adult male. Although spotted fever group rickettsiae (SFGR) have been reported as the most prevalent cause of rickettsiosis in rural areas of Sabah, Malaysia since the 1980s, this is the first detailed case report of suspected SFGR in the state. Current data on the prevalence, type, and thorough clinical reports on complications of SFGR and other rickettsioses in Sabah is lacking and required to raise the awareness of such diseases. There is a need to emphasize the screening of rickettsioses to medical personnel and to encourage the use of appropriate antibiotics as early treatment for nonspecific febrile illnesses in this region. Suspected rickettsioses need to be considered as one of the differential diagnoses for patients presenting with acute febrile illness for laboratory investigations, and early treatment instituted. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Development and Clinical Validation of a Multiplex Real-Time Quantitative PCR Assay for Human Infection by Anaplasma phagocytophilum and Ehrlichia chaffeensis
Trop. Med. Infect. Dis. 2018, 3(1), 14; https://doi.org/10.3390/tropicalmed3010014 - 29 Jan 2018
Abstract
Background: Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, and human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, often present as undifferentiated fever but are not treated by typical empiric regimens for acute febrile illness. Their role as agents of vector-borne [...] Read more.
Background: Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, and human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, often present as undifferentiated fever but are not treated by typical empiric regimens for acute febrile illness. Their role as agents of vector-borne febrile disease in tropical regions is more poorly studied than for other rickettsial infections. Limitations in diagnosis have impaired epidemiologic and clinical research and needless morbidity and mortality occur due to untreated illness. Methods: We designed and clinically validated a multiplex real-time quantitative PCR assay for Anaplasma phagocytophilum and Ehrlichia chaffeensis using samples confirmed by multiple gold-standard methods. Results: Clinical sensitivity and specificity for A. phagocytophilum were 100% (39/39) and 100% (143/143), respectively, and for E. chaffeensis 95% (20/21) and 99% (159/161), respectively. Conclusions: These assays could support early diagnosis and treatment as well as the high-throughput testing required for large epidemiologic studies. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Rickettsial Infections and Q Fever Amongst Febrile Patients in Bhutan
Trop. Med. Infect. Dis. 2018, 3(1), 12; https://doi.org/10.3390/tropicalmed3010012 - 25 Jan 2018
Cited by 1
Abstract
There is limited evidence of rickettsial diseases in Bhutan. We explored the contribution of rickettsioses as a cause of undifferentiated febrile illness in patients presenting to 14 Bhutanese hospitals from October 2014 to June 2015. Obvious causes of fever were excluded clinically. Clinico-demographic [...] Read more.
There is limited evidence of rickettsial diseases in Bhutan. We explored the contribution of rickettsioses as a cause of undifferentiated febrile illness in patients presenting to 14 Bhutanese hospitals from October 2014 to June 2015. Obvious causes of fever were excluded clinically. Clinico-demographic information and acute blood samples were collected. Samples were tested by immunofluorescence assay (IFA) and qPCR against scrub typhus group (STG), spotted fever group (SFG) and typhus group (TG) rickettsiae, and Q fever (QF). Of the 1044 patients, 539 (51.6%) were female and the mean age was 31.5 years. At least 159 (15.2%) of the patients had evidence of a concurrent rickettsial infection. Of these, 70 (6.7%), 46 (4.4%), 4 (0.4%), and 29 (2.8%) were diagnosed as acute infections with STG, SFG, TG, and QF respectively. Ten (1.0%) patients were seropositive for both SFG and TG. Seven of the 70 STG patients were positive by qPCR. Eschar (p < 0.001), myalgia (p = 0.003), and lymphadenopathy (p = 0.049) were significantly associated with STG, but no specific symptoms were associated with the other infections. Disease incidences were not different between age groups, genders, occupations, and districts, except for students with significantly lower odds of infection with STG (OR = 0.43; 95% CI = 0.20, 0.93; p = 0.031). Rickettsioses were responsible for at least 15% of undifferentiated febrile illnesses in Bhutan, scrub typhus being the commonest. Health authorities should ensure that health services are equipped to manage these infections. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessArticle
Clinical Manifestations and Outcomes of Rickettsia australis Infection: A 15-Year Retrospective Study of Hospitalized Patients
Trop. Med. Infect. Dis. 2017, 2(2), 19; https://doi.org/10.3390/tropicalmed2020019 - 20 Jun 2017
Cited by 2
Abstract
Queensland tick typhus (QTT; Rickettsia australis) is an important cause of community-acquired acute febrile illness in eastern Australia. Cases of QTT were identified retrospectively from 2000 to 2015 at five sites in Northern Brisbane through a pathology database. Those included had a [...] Read more.
Queensland tick typhus (QTT; Rickettsia australis) is an important cause of community-acquired acute febrile illness in eastern Australia. Cases of QTT were identified retrospectively from 2000 to 2015 at five sites in Northern Brisbane through a pathology database. Those included had a fourfold rise in spotted fever group (SFG)-specific serology, a single SFG-specific serology ≥ 256 or SFG-specific serology ≥ 128 with a clinically consistent illness. Cases were excluded on the basis of clinical unlikelihood of QTT infection. Thirty-six cases were included. Fever was found in 34/36 (94%) patients. Rash occurred in 83% of patients with maculopapular being the dominant morphology (70%). Thrombocytopenia, lymphopenia, and raised transaminases were common and occurred in 58%, 69%, and 89% of patients, respectively. Thirty-one of 36 (86%) patients received antibiotic therapy (usually doxycycline) and the time to correct antibiotic (from admission) ranged from 3 to 120 h (mean 45.5 h). Four of 36 (11%) required intensive care unit (ICU) admission for severe sepsis and end-organ support. There were no deaths. QTT has a wide range of clinical and laboratory features. Early and appropriate antimicrobial therapy is important and may prevent severe disease. Further prospective studies are required to identify factors associated with severe infection and sepsis. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Review

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Open AccessReview
Origins, Importance and Genetic Stability of the Prototype Strains Gilliam, Karp and Kato of Orientia tsutsugamushi
Trop. Med. Infect. Dis. 2019, 4(2), 75; https://doi.org/10.3390/tropicalmed4020075 - 30 Apr 2019
Abstract
Scrub typhus, a chigger-borne febrile illness, occurs primarily in countries of the Asia-Pacific rim and islands of the Western Pacific. The etiologic agent is the obligate intracellular rickettsial bacterium Orientia tsutsugamushi. Research on O. tsutsugamushi has relied on the availability of several [...] Read more.
Scrub typhus, a chigger-borne febrile illness, occurs primarily in countries of the Asia-Pacific rim and islands of the Western Pacific. The etiologic agent is the obligate intracellular rickettsial bacterium Orientia tsutsugamushi. Research on O. tsutsugamushi has relied on the availability of several prototype strains, which were isolated from human cases of scrub typhus in the 1940s and 1950s. We review the history of the three original, and most important, prototype strains, Gilliam, Karp and Kato, including information on their isolation, their culture history, their clinical characteristics, their importance within the research literature on scrub typhus, and recent advances in elucidating their molecular genomics. The importance of these strains to the research and development of clinical tools related to scrub typhus is also considered. Finally, we examine whether the strains have been genetically stable since their isolation, and whether prototype strains maintained in separate laboratories are identical, based on pairwise comparisons of several sequences from four genes. By using genetic information archived in international DNA databases, we show that the prototype strains used by different laboratories are essentially identical, and that the strains have retained their genetic integrity at least since the 1950s. The three original prototype strains should remain a standard by which new diagnostic procedures are measured. Given their fundamental position in any comparative studies, they are likely to endure as a critical part of present and future research on scrub typhus and Orientia. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
Hemophagocytic Lymphohistiocytosis Associated with Scrub Typhus: Systematic Review and Comparison between Pediatric and Adult Cases
Trop. Med. Infect. Dis. 2018, 3(1), 19; https://doi.org/10.3390/tropicalmed3010019 - 14 Feb 2018
Cited by 3
Abstract
Background: Scrub typhus is a mite-borne bacterial infection caused by Orientia tsutsugamushi. Hemophagocytic lymphohistiocytosis (HLH) is a potential severe complication. Most reported cases of HLH associated with scrub typhus were single cases or case series with a small sample sizes. Thus, no [...] Read more.
Background: Scrub typhus is a mite-borne bacterial infection caused by Orientia tsutsugamushi. Hemophagocytic lymphohistiocytosis (HLH) is a potential severe complication. Most reported cases of HLH associated with scrub typhus were single cases or case series with a small sample sizes. Thus, no clear consensus exists on clinical manifestations and differences between pediatric and adult cases of this condition. Methods: a systematic search of English and Japanese articles from PubMed, PubMed Central, and Directory of Open Access Journals databases was performed from 3 December 2016 to 28 December 2017. The primary outcome was mortality in patients with HLH associated with scrub typhus; secondary outcomes were differences in clinical symptoms, laboratory findings, and treatment between pediatric and adult patients with HLH associated with scrub typhus. Results: thirty cases of HLH associated with scrub typhus were identified (age range: 2 months to 75 years; median age: 21.5 years, male:female ratio, 1:1). Eschar was frequently observed in the pediatric group (p = 0.017), whereas acute kidney injury was more prevalent in the adult group (p = 0.010). Two patients died of intracranial hemorrhage complicated with multiple organ failure; overall mortality rate was 6.7%. Conclusions: HLH associated with scrub typhus could be cured with remarkable improvement using single antibiotic therapy in approximately half the cases, with the mortality rate being relatively lower than that of HLH associated with other secondary causes. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
Scrub Typhus: No Longer Restricted to the Tsutsugamushi Triangle
Trop. Med. Infect. Dis. 2018, 3(1), 11; https://doi.org/10.3390/tropicalmed3010011 - 25 Jan 2018
Cited by 4
Abstract
Scrub typhus is the most important rickettsial disease in the world. Its previous endemic region was considered to be in Asia, Australia and islands in the Indian and Pacific Oceans; this area was referred to as the Tsutsugamushi Triangle. Accumulation of serological, molecular, [...] Read more.
Scrub typhus is the most important rickettsial disease in the world. Its previous endemic region was considered to be in Asia, Australia and islands in the Indian and Pacific Oceans; this area was referred to as the Tsutsugamushi Triangle. Accumulation of serological, molecular, genetic, and culture data have shown that not only is scrub typhus not limited to the Tsutsugamushi Triangle, but can be caused by orientiae other than Orientia tsutsugamushi. This review describes evidence currently available that will be instrumental to researchers, healthcare providers and medical leaders in developing new research projects, performing diagnosis, and preventing scrub typhus in locations not previously thought to be endemic. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow
Trop. Med. Infect. Dis. 2018, 3(1), 8; https://doi.org/10.3390/tropicalmed3010008 - 17 Jan 2018
Cited by 11
Abstract
Scrub typhus and the rickettsial diseases represent some of the oldest recognized vector-transmitted diseases, fraught with a rich historical aspect, particularly as applied to military/wartime situations. The vectors of Orientia tsutsugamushi were once thought to be confined to an area designated as the [...] Read more.
Scrub typhus and the rickettsial diseases represent some of the oldest recognized vector-transmitted diseases, fraught with a rich historical aspect, particularly as applied to military/wartime situations. The vectors of Orientia tsutsugamushi were once thought to be confined to an area designated as the Tsutsugamushi Triangle. However, recent reports of scrub typhus caused by Orientia species other than O. tsutsugamushi well beyond the limits of the Tsutsugamushi Triangle have triggered concerns about the worldwide presence of scrub typhus. It is not known whether the vectors of O. tsutsugamushi will be the same for the new Orientia species, and this should be a consideration during outbreak/surveillance investigations. Additionally, concerns surrounding the antibiotic resistance of O. tsutsugamushi have led to considerations for the amendment of treatment protocols, and the need for enhanced public health awareness in both the civilian and medical professional communities. In this review, we discuss the history, outbreaks, antibiotic resistance, and burgeoning genomic advances associated with one of the world’s oldest recognized vector-borne pathogens, O. tsutsugamushi. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
Tick-, Flea-, and Louse-Borne Diseases of Public Health and Veterinary Significance in Nigeria
Trop. Med. Infect. Dis. 2018, 3(1), 3; https://doi.org/10.3390/tropicalmed3010003 - 03 Jan 2018
Cited by 1
Abstract
Mosquito-borne diseases are common high-impact diseases in tropical and subtropical areas. However, other non-mosquito vector-borne pathogens (VBPs) may share their geographic distribution, seasonality, and clinical manifestations, thereby contributing their share to the morbidity and mortality caused by febrile illnesses in these regions. The [...] Read more.
Mosquito-borne diseases are common high-impact diseases in tropical and subtropical areas. However, other non-mosquito vector-borne pathogens (VBPs) may share their geographic distribution, seasonality, and clinical manifestations, thereby contributing their share to the morbidity and mortality caused by febrile illnesses in these regions. The purpose of this work was to collect and review existing information and identify knowledge gaps about tick, flea-, and louse-borne diseases of veterinary and public health significance in Nigeria. Full-length articles about VBPs were reviewed and relevant information about the vectors, their hosts, geographic distribution, seasonality, and association(s) with human or veterinary diseases was extracted. Specific laboratory tools used for detection and identification of VBPs in Nigeria were also identified. A total of 62 original publications were examined. Substantial information about the prevalence and impacts of ticks and fleas on pet and service dogs (18 articles), and livestock animals (23 articles) were available; however, information about their association with and potential for causing human illnesses was largely absent despite the zoonotic nature of many of these peri-domestic veterinary diseases. Recent publications that employed molecular methods of detection demonstrated the occurrence of several classic (Ehrlichia canis, Rickettsia africae, Bartonella sp.) and emerging human pathogens (R. aeschlimannii, Neoehrlichia mikurensis) in ticks and fleas. However, information about other pathogens often found in association with ticks (R. conorii) and fleas (R. typhi, R. felis) across the African continent was lacking. Records of louse-borne epidemic typhus in Nigeria date to 1947; however, its current status is not known. This review provides an essential baseline summary of the current knowledge in Nigeria of non-mosquito VBPs, and should stimulate improvements in the surveillance of the veterinary and human diseases they cause in Nigeria. Due to increasing recognition of these diseases in other African countries, veterinary and public health professionals in Nigeria should expand the list of possible diseases considered in patients presenting with fever of unknown etiology. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
Suspected and Confirmed Vector-Borne Rickettsioses of North America Associated with Human Diseases
Trop. Med. Infect. Dis. 2018, 3(1), 2; https://doi.org/10.3390/tropicalmed3010002 - 03 Jan 2018
Cited by 3
Abstract
The identification of pathogenic rickettsial agents has expanded over the last two decades. In North America, the majority of human cases are caused by tick-borne rickettsioses but rickettsiae transmitted by lice, fleas, mites and other arthropods are also responsible for clinical disease. Symptoms [...] Read more.
The identification of pathogenic rickettsial agents has expanded over the last two decades. In North America, the majority of human cases are caused by tick-borne rickettsioses but rickettsiae transmitted by lice, fleas, mites and other arthropods are also responsible for clinical disease. Symptoms are generally nonspecific or mimic other infectious diseases; therefore, diagnosis and treatment may be delayed. While infection with most rickettsioses is relatively mild, delayed diagnosis and treatment may lead to increased morbidity and mortality. This review will discuss the ecology, epidemiology and public health importance of suspected and confirmed vector-transmitted Rickettsia species of North America associated with human diseases. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
Open AccessReview
The Re-Emergence and Emergence of Vector-Borne Rickettsioses in Taiwan
Trop. Med. Infect. Dis. 2018, 3(1), 1; https://doi.org/10.3390/tropicalmed3010001 - 21 Dec 2017
Cited by 1
Abstract
Rickettsial diseases, particularly vector-borne rickettsioses (VBR), have a long history in Taiwan, with studies on scrub typhus and murine typhus dating back over a century. The climatic and geographic diversity of Taiwan’s main island and its offshore islands provide many ecological niches for [...] Read more.
Rickettsial diseases, particularly vector-borne rickettsioses (VBR), have a long history in Taiwan, with studies on scrub typhus and murine typhus dating back over a century. The climatic and geographic diversity of Taiwan’s main island and its offshore islands provide many ecological niches for the diversification and maintenance of rickettsiae alike. In recent decades, scrub typhus has re-emerged as the most prevalent type of rickettsiosis in Taiwan, particularly in eastern Taiwan and its offshore islands. While murine typhus has also re-emerged on Taiwan’s western coast, it remains neglected. Perhaps more alarming than the re-emergence of these rickettsioses is the emergence of newly described VBR. The first case of human infection with Rickettsia felis was confirmed in 2005, and undetermined spotted fever group rickettsioses have recently been detected. Taiwan is at a unique advantage in terms of detecting and characterizing VBR, as it has universal health coverage and a national communicable disease surveillance system; however, these systems have not been fully utilized for this purpose. Here, we review the existing knowledge on the eco-epidemiology of VBR in Taiwan and recommend future courses of action. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
Rickettsia felis: A Review of Transmission Mechanisms of an Emerging Pathogen
Trop. Med. Infect. Dis. 2017, 2(4), 64; https://doi.org/10.3390/tropicalmed2040064 - 19 Dec 2017
Cited by 3
Abstract
Rickettsia felis is an emerging pathogen of the transitional group of Rickettsia species and an important cause of febrile illness in Africa. Since the organism’s original discovery in the early 1990s, much research has been directed towards elucidating transmission mechanisms within the primary [...] Read more.
Rickettsia felis is an emerging pathogen of the transitional group of Rickettsia species and an important cause of febrile illness in Africa. Since the organism’s original discovery in the early 1990s, much research has been directed towards elucidating transmission mechanisms within the primary host and reservoir, the cat flea (Ctenocephalides felis). Several mechanisms for vertical and horizontal transmission within this vector have been thoroughly described, as well as transmission to other arthropod vectors, including other species of fleas. However, while a growing number of human cases of flea-borne spotted fever are being reported throughout the world, a definitive transmission mechanism from arthropod host to vertebrate host resulting in disease has not been found. Several possible mechanisms, including bite of infected arthropods and association with infectious arthropod feces, are currently being investigated. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessReview
The Historical Case for and the Future Study of Antibiotic-Resistant Scrub Typhus
Trop. Med. Infect. Dis. 2017, 2(4), 63; https://doi.org/10.3390/tropicalmed2040063 - 15 Dec 2017
Cited by 6
Abstract
Scrub typhus is an acute, and sometimes fatal, human febrile illness, typically successfully treated using chloramphenicol or one of the tetracyclines. Over the past several years, descriptions of strains of Orientia tsutsugamushi with reduced susceptibility to antibiotics have appeared. Because case-fatality ratios approached [...] Read more.
Scrub typhus is an acute, and sometimes fatal, human febrile illness, typically successfully treated using chloramphenicol or one of the tetracyclines. Over the past several years, descriptions of strains of Orientia tsutsugamushi with reduced susceptibility to antibiotics have appeared. Because case-fatality ratios approached 50% during the pre-antibiotic era, antibiotic-resistant scrub typhus is concerning. Herein, we review the data on resistant scrub typhus, describe how the theoretical existence of such resistance is affected by interpretation of treatment outcomes, and propose a plan to further identify whether true drug resistance is present and how to deal with drug resistance if it has evolved. Limited resistance is not unambiguous, if present, and antibiotic resistance in scrub typhus is not a dichotomous trait. Rather, evidence of resistance shows a continuous gradation of increasing resistance. The availability of genomes from isolates of O. tsutsugamushi allows the search for loci that might contribute to antibiotic resistance. At least eighteen such loci occur in all genomes of O. tsutsugamushi examined. One gene (gyrA) occurs as a quinolone-resistant form in the genome of all isolates of O. tsutsugamushi. At least 13 other genes that are present in some members of the genus Rickettsia do not occur within O. tsutsugamushi. Even though reports of scrub typhus not responding appropriately to chloramphenicol or a tetracycline treatment have been in the literature for approximately 23 years, the existence and importance of antibiotic-resistant scrub typhus remains uncertain. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessCorrection
Correction: Naimi, W.A., et al. Differential Susceptibility of Male versus Female Laboratory Mice to Anaplasma phagocytophilum Infection. Trop. Med. Infect. Dis. 2018, 3, 78
Trop. Med. Infect. Dis. 2019, 4(1), 51; https://doi.org/10.3390/tropicalmed4010051 - 23 Mar 2019
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
Open AccessCase Report
Diagnosis of Murine Typhus by Serology in Peninsular Malaysia: A Case Report Where Rickettsial Illnesses, Leptospirosis and Dengue Co-Circulate
Trop. Med. Infect. Dis. 2019, 4(1), 23; https://doi.org/10.3390/tropicalmed4010023 - 31 Jan 2019
Abstract
Murine typhus is a rarely diagnosed cause of acute febrile illness in Malaysia, and its true disease burden is unknown. We report a case of an acute murine typhus infection in a patient living in a small city in Peninsular Malaysia, presenting with [...] Read more.
Murine typhus is a rarely diagnosed cause of acute febrile illness in Malaysia, and its true disease burden is unknown. We report a case of an acute murine typhus infection in a patient living in a small city in Peninsular Malaysia, presenting with fever, rash, and headache. Unresponsive to the initial empirical treatment for leptospirosis, he showed a rapid response to doxycycline when murine typhus was diagnosed later. This case highlights the importance of considering murine typhus as a diagnostic in cases of acute febrile illness in urban and sub-urban areas, such as that of in Peninsular Malaysia. Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Open AccessCorrection
Correction: Sando E. et al. Serological Cross-Reactivity among Orientia tsutsugamushi Serotypes but Not with Rickettsia japonica in Japan. Trop. Med. Infect. Dis. 2018, 3, 74.
Trop. Med. Infect. Dis. 2018, 3(4), 113; https://doi.org/10.3390/tropicalmed3040113 - 25 Oct 2018
Cited by 1
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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