scholarly journals Searching and Finding the Hidden Treasure: A Retrospective Analysis of Rickettsial Disease Among Dutch International Travelers

2020 ◽  
Author(s):  
Sophia G de Vries ◽  
Louise E van Eekeren ◽  
Hans van der Linden ◽  
Benjamin J Visser ◽  
Martin P Grobusch ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Medical Records ◽  
Scrub Typhus ◽  
Spotted Fever ◽  
Febrile Illness ◽  
Empiric Antibiotic Therapy ◽  
Spotted Fever Group ◽  
Orientia Tsutsugamushi ◽  
Rickettsial Disease ◽  
Empiric Antibiotic

Abstract Background Rickettsial disease (RD) is a prevalent and underestimated cause of febrile illness worldwide, especially in the absence of an inoculation eschar. We attempted to quantify this underestimation at our clinic, by investigating past cases of febrile illness in travelers who had tested negative for leptospirosis, a disease that can initially present similarly to non-eschar RD, and which we routinely consider when other important causes of unspecified febrile illness have tested negative. Methods We performed a retrospective analysis in febrile returned travelers from Asia, Africa, or the Americas between 2010 and 2017, who had tested negative for leptospirosis. Serologic immunofluorescence assays were performed for Orientia tsutsugamushi (scrub typhus), typhus group, and spotted fever group RD. We performed a medical records review of all patients who tested positive. In case of a fitting medical history, cases were deemed either confirmed (based on convalescent serology) or suspected (based on single serology). Results Among 97 patients, convalescent serology was available in 16 (16.5%) patients, and a single serology in 81 (83.5%) patients. RD was the likely diagnosis in 8 of 16 (50.0%) patients with convalescent serology, and in 8 of 81 (9.9%) with single serology. Of the 16 confirmed/suspected cases, 11 (69%) had been missed and 7 (44%) had not received adequate empiric antibiotic therapy. Conclusions This study shows that non-eschar RD is an important and poorly recognized cause of illness in travelers, even in a specialized travel clinic. A lower threshold to test and treat for RD is warranted in returning travelers with febrile illness.

scholarly journals Optimization and Evaluation of a Multiplex Quantitative PCR Assay for Detection of Nucleic Acids in Human Blood Samples from Patients with Spotted Fever Rickettsiosis, Typhus Rickettsiosis, Scrub Typhus, Monocytic Ehrlichiosis, and Granulocytic Anaplasmosis

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Megan E. Reller ◽  
J. Stephen Dumler
Keyword(s):  
Quantitative Pcr ◽  
Scrub Typhus ◽  
Spotted Fever ◽  
Febrile Illness ◽  
Epidemiologic Studies ◽  
Qpcr Assay ◽  
Spotted Fever Group ◽  
Analytical Sensitivity ◽  
Content Type ◽  
Real Time Quantitative Pcr

ABSTRACT Spotted fever group rickettsioses (SFGR), typhus group rickettsioses (TGR), scrub typhus (caused by Orientia tsutsugamushi), ehrlichiosis, and anaplasmosis often present as undifferentiated fever but are not treated by agents (penicillins and cephalosporins) typically used for acute febrile illness. Inability to diagnose these infections when the patient is acutely ill leads to excess morbidity and mortality. Failure to confirm these infections retrospectively if a convalescent blood sample is not obtained also impairs epidemiologic and clinical research. We designed a multiplex real-time quantitative PCR (qPCR) assay to detect SFGR, TGR, O. tsutsugamushi, and infections caused by Anaplasma phagocytophilum and Ehrlichia chaffeensis with the ompA, 17-kDa surface antigen gene, tsa56, msp2 (p44), and vlpt gene targets, respectively. Analytical sensitivity was ≥2 copies/μl (linear range, 2 to 2 × 105) and specificity was 100%. Clinical sensitivities for SFGR, TGR, and O. tsutsugamushi were 25%, 20%, and 27%, respectively, and specificities were 98%, 99%, and 100%, respectively. Clinical sensitivities for A. phagocytophilum and E. chaffeensis were 93% and 84%, respectively, and specificities were 99% and 98%, respectively. This multiplex qPCR assay could support early clinical diagnosis and treatment, confirm acute infections in the absence of a convalescent-phase serum sample, and provide the high-throughput testing required to support large clinical and epidemiologic studies. Because replication of SFGR and TGR in endothelial cells results in very low bacteremia, optimal sensitivity of qPCR for these rickettsioses will require use of larger volumes of input DNA, which could be achieved by improved extraction of DNA from blood and/or extraction of DNA from a larger initial volume of blood.

Rickettsioses

2020 ◽  
pp. 1230-1251
Author(s):  
Karolina Griffiths ◽  
Carole Eldin ◽  
Didier Raoult ◽  
Philippe Parola
Keyword(s):  
Scrub Typhus ◽  
Spotted Fever ◽  
Intracellular Bacteria ◽  
Spotted Fever Group ◽  
Orientia Tsutsugamushi ◽  
Obligate Intracellular ◽  
Metabolic Characteristics ◽  
The Past ◽  
Life Threatening ◽  
Obligate Intracellular Bacteria

Rickettsioses are mild to life-threatening zoonoses caused by obligate intracellular bacteria of the order Rickettsiales (family Rickettsiaceae). Arthropods, including ticks, fleas, and mites, are implicated as their vectors, reservoirs, or amplifiers. With an increasing number of new pathogens and recognition of new pathogenicity and affected geographical areas over the past few decades, there is a better understanding of the scope and importance of these pathogens, particularly as a paradigm to understanding emerging and remerging infections. The taxonomy has undergone numerous changes, with now three main groups classified as rickettsioses according to morphological, antigenic and metabolic characteristics: (1) Rickettsioses due to the bacteria of the genus Rickettsia, including the spotted fever group, typhus groups (Rickettsiaceae), (2) Ehrlichioses and Anaplasmoses due to bacteria of the Anaplasmataceae and (3) scrub typhus due to Orientia tsutsugamushi.

Spotted Fever Group Rickettsiae among Children with Acute Febrile Illness, in Gorakhpur, India

2020 ◽  
Author(s):  
Siraj A Khan ◽  
Trishna Bora ◽  
Jeromie Wesley Vivian Thangaraj ◽  
Manoj V Murhekar
Keyword(s):  
Spotted Fever ◽  
Uttar Pradesh ◽  
Febrile Illness ◽  
Health Facilities ◽  
Spotted Fever Group ◽  
Acute Febrile Illness ◽  
Orientia Tsutsugamushi ◽  
Spotted Fever Group Rickettsiae ◽  
Acute Encephalitis ◽  
Indian State

Abstract Seasonal outbreaks of acute encephalitis syndrome have been occurring in Gorakhpur division in the Indian state of Uttar Pradesh during monsoon and post-monsoon months. Orientia tsutsugamushi was identified as the major aetiology of these outbreaks. Orientia tsutsugamushi was also identified as one of the important aetiology of febrile illness among children attending peripheral health facilities. The present study was undertaken to detect antibodies against spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) among children with acute febrile illness presenting at peripheral health facilities in Gorakhpur district. Of the 224 blood samples tested, SFGR infection was detected in 13 (6%) patients. None of the samples tested positive for TGR.

scholarly journals Performance of molecular and serologic tests for the diagnosis of scrub typhus

2020 ◽  
Vol 14 (11) ◽  
pp. e0008747
Author(s):  
Kavitha Kannan ◽  
Rebecca John ◽  
Debasree Kundu ◽  
Divya Dayanand ◽  
Kundavaram P. P. Abhilash ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Predictive Value ◽  
Diagnostic Tests ◽  
Scrub Typhus ◽  
Spotted Fever ◽  
Lamp Assay ◽  
Febrile Illness ◽  
Acute Febrile Illness ◽  
Orientia Tsutsugamushi ◽  
Igm Antibodies

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus.

Scrub typhus (Orientia tsutsugamushi), A rapidly spreading epidemic in Chennai - A standalone lab experience

2016 ◽  
Vol 5 (09) ◽  
pp. 4896
Author(s):  
Sripriya C.S.* ◽  
Shanthi B. ◽  
Arockia Doss S. ◽  
Antonie Raj I. ◽  
Mohana Priya
Keyword(s):  
Scrub Typhus ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Febrile Illness ◽  
Orientia Tsutsugamushi ◽  
The Past ◽  
Igm Elisa ◽  
The Mean ◽  
Specific Symptoms ◽  
Symptoms And Signs

Scrub typhus (Orientia tsutsugamushi), is a strict intracellular bacterium which is reported to be a recent threat to parts of southern India. There is re-emergence of scrub typhus during the past few years in Chennai. Scrub typhus is an acute febrile illness which generally causes non-specific symptoms and signs. The clinical manifestations of this disease range from sub-clinical disease to organ failure to fatal disease. This study documents our laboratory experience in diagnosis of scrub typhus in patients with fever and suspected clinical symptoms of scrub typhus infection for a period of two years from April 2014 to April 2016 using immunochromatography and IgM ELISA methods. The study was conducted on 648 patients out of whom 188 patients were found to be positive for scrub typhus. Results also showed that pediatric (0 -12 years) and young adults (20 – 39 years) were more exposed to scrub typhus infection and female patients were more infected compared to male. The study also showed that the rate of infection was higher between September to February which also suggested that the infection rate is proportional to the climatic condition. Statistical analysis showed that the mean age of the patients in this study was 37.6, standard deviation was 18.97, CV % was 50.45. 

scholarly journals Scrub Typhus and Molecular Characterization of Orientia tsutsugamushi from Central Nepal

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 422
Author(s):  
Rajendra Gautam ◽  
Keshab Parajuli ◽  
Mythili Tadepalli ◽  
Stephen Graves ◽  
John Stenos ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Scrub Typhus ◽  
Febrile Illness ◽  
Acute Febrile Illness ◽  
Limited Information ◽  
Orientia Tsutsugamushi ◽  
Health Measures ◽  
Central Nepal ◽  
Vector Borne

Scrub typhus is a vector-borne, acute febrile illness caused by Orientia tsutsugamushi. Scrub typhus continues to be an important but neglected tropical disease in Nepal. Information on this pathogen in Nepal is limited to serological surveys with little information available on molecular methods to detect O. tsutsugamushi. Limited information exists on the genetic diversity of this pathogen. A total of 282 blood samples were obtained from patients with suspected scrub typhus from central Nepal and 84 (30%) were positive for O. tsutsugamushi by 16S rRNA qPCR. Positive samples were further subjected to 56 kDa and 47 kDa molecular typing and molecularly compared to other O. tsutsugamushi strains. Phylogenetic analysis revealed that Nepalese O. tsutsugamushi strains largely cluster together and cluster away from other O. tsutsugamushi strains from Asia and elsewhere. One exception was the sample of Nepal_1, with its partial 56 kDa sequence clustering more closely with non-Nepalese O. tsutsugamushi 56 kDa sequences, potentially indicating that homologous recombination may influence the genetic diversity of strains in this region. Knowledge on the circulating strains in Nepal is important to the development of diagnostic tests and vaccines to support public health measures to control scrub typhus in this country.

scholarly journals A Brief History of the Major Rickettsioses in the Asia–Australia–Pacific Region: A Capstone Review for the Special Issue of TMID

2020 ◽  
Vol 5 (4) ◽  
pp. 165
Author(s):  
Daniel H. Paris ◽  
Daryl J. Kelly ◽  
Paul A. Fuerst ◽  
Nicholas P. J. Day ◽  
Allen L. Richards
Keyword(s):  
Scrub Typhus ◽  
Spotted Fever ◽  
Specific Antigen ◽  
Far East ◽  
Pacific Region ◽  
Special Issue ◽  
Rickettsial Disease ◽  
History Of ◽  
Rickettsial Diseases ◽  
The Impact

The rickettsioses of the “Far East” or Asia–Australia–Pacific region include but are not limited to endemic typhus, scrub typhus, and more recently, tick typhus or spotted fever. These diseases embody the diversity of rickettsial disease worldwide and allow us to interconnect the various contributions to this special issue of Tropical Medicine and Infectious Disease. The impact of rickettsial diseases—particularly of scrub typhus—was substantial during the wars and “police actions” of the last 80 years. However, the post-World War II arrival of effective antibiotics reduced their impact, when recognized and adequately treated (chloramphenicol and tetracyclines). Presently, however, scrub typhus appears to be emerging and spreading into regions not previously reported. Better diagnostics, or higher population mobility, change in antimicrobial policies, even global warming, have been proposed as possible culprits of this phenomenon. Further, sporadic reports of possible antibiotic resistance have received the attention of clinicians and epidemiologists, raising interest in developing and testing novel diagnostics to facilitate medical diagnosis. We present a brief history of rickettsial diseases, their relative importance within the region, focusing on the so-called “tsutsugamushi triangle”, the past and present impact of these diseases within the region, and indicate how historically, these often-confused diseases were ingeniously distinguished from each another. Moreover, we will discuss the importance of DNA-sequencing efforts for Orientia tsutsugamushi, obtained from patient blood, vector chiggers, and rodent reservoirs, particularly for the dominant 56-kD type-specific antigen gene (tsa56), and whole-genome sequences, which are increasing our knowledge of the diversity of this unique agent. We explore and discuss the potential of sequencing and other effective tools to geographically trace rickettsial disease agents, and develop control strategies to better mitigate the rickettsioses.

scholarly journals Epidemiology of Spotted Fever Group Rickettsioses and Acute Undifferentiated Febrile Illness in Villeta, Colombia

2017 ◽  
Vol 97 (3) ◽  
pp. 782-788 ◽  
Author(s):  
Álvaro A. Faccini-Martínez ◽  
Elkin Valbuena ◽  
Christian Barreto ◽  
Ana M. Palomar ◽  
Luis J. Polo-Terán ◽  
...  
Keyword(s):  
Spotted Fever ◽  
Febrile Illness ◽  
Spotted Fever Group

Clinical Features of Rickettsial Infection in Children in Tropical Australia—A Report of 15 Cases

2020 ◽  
Vol 66 (6) ◽  
pp. 655-660 ◽  
Author(s):  
Alexandra G A Stewart ◽  
Simon Smith ◽  
Enzo Binotto ◽  
Josh Hanson
Keyword(s):  
Scrub Typhus ◽  
Spotted Fever ◽  
Case Fatality ◽  
Spotted Fever Group ◽  
Tertiary Referral Hospital ◽  
Admission Rates ◽  
Rickettsial Infections ◽  
Retrospective Audit ◽  
Tropical Australia ◽  
The Tropics

Abstract Rickettsial infections are an under-recognized cause of acute, undifferentiated fever in the tropics. In Asia, intensive care unit (ICU) admission rates as high as 21% and case-fatality rates of up to 5% have been reported. This 20-year retrospective audit of children and adults with serologically confirmed scrub typhus or spotted fever group (SFG) infection was performed at a tertiary-referral hospital in tropical Australia. There were 15 paediatric cases during the study period (11 scrub typhus, 3 SFG and 1 undifferentiated). Hypotension [5/15 (33%)], tachycardia [6/15 (40%)] and tachypnoea [6/15 (40%)] were common at presentation. Children were more likely to be hypotensive at admission than adults [5/15 (33%) vs. 5/118 (4%), p = 0.002]. However, no child died or was admitted to ICU, compared with 18/120 (15%) adults who required ICU support during the study period, one of whom died. Paediatric rickettsial infections have a relatively benign clinical course in tropical Australia with serious complications appearing far less frequently than have been reported in the Asian literature.

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