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

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.

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

Clinical Infectious Diseases ◽

10.1093/cid/ciaa091 ◽

2020 ◽

Cited By ~ 1

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.

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Seroepidemiologic survey of Orientia tsutsugamushi, Rickettsia typhi, and TT118 spotted fever group rickettsiae in rubber estate workers in Malaysia.

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.1999.61.73 ◽

1999 ◽

Vol 61 (1) ◽

pp. 73-77 ◽

Cited By ~ 17

Author(s):

T S Tee ◽

S Devi ◽

K A Suan ◽

S S Chun ◽

H T Ming ◽

...

Keyword(s):

Spotted Fever ◽

Spotted Fever Group ◽

Orientia Tsutsugamushi ◽

Rickettsia Typhi ◽

Spotted Fever Group Rickettsiae

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Antibodies to Orientia tsutsugamushi, Rickettsia typhi and spotted fever group rickettsiae among febrile patients in rural areas of Malaysia

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1016/s0035-9203(00)90322-5 ◽

2000 ◽

Vol 94 (3) ◽

pp. 280-284 ◽

Cited By ~ 30

Author(s):

S.T. Tay ◽

T.M. Ho ◽

M.Y. Rohani ◽

S. Devi

Keyword(s):

Rural Areas ◽

Spotted Fever ◽

Spotted Fever Group ◽

Orientia Tsutsugamushi ◽

Rickettsia Typhi ◽

Spotted Fever Group Rickettsiae

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Seroprevalence of spotted fever group and typhus group rickettsiae in individuals with acute febrile illness from Gorakhpur, India

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2018.10.024 ◽

2019 ◽

Vol 79 ◽

pp. 195-198 ◽

Cited By ~ 7

Author(s):

Arati Mane ◽

Suchit Kamble ◽

Manish Kumar Singh ◽

Manisha Ratnaparakhi ◽

Amit Nirmalkar ◽

...

Keyword(s):

Spotted Fever ◽

Febrile Illness ◽

Spotted Fever Group ◽

Acute Febrile Illness

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

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008747 ◽

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.

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Rickettsial Diseases: Not Uncommon Causes of Acute Febrile Illness in India

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5020059 ◽

2020 ◽

Vol 5 (2) ◽

pp. 59

Author(s):

Manisha Biswal ◽

Sivanantham Krishnamoorthi ◽

Kamlesh Bisht ◽

Amit Sehgal ◽

Jasleen Kaur ◽

...

Keyword(s):

Spotted Fever ◽

Febrile Illness ◽

Epidemiological Studies ◽

North India ◽

Rickettsia Conorii ◽

Spotted Fever Group ◽

Acute Febrile Illness ◽

Serological Tests ◽

Loss Of Appetite ◽

Rickettsial Diseases

Rickettsial diseases (RDs) are major under-diagnosed causes of arthropod borne acute febrile illness (AFI) presenting with a range of symptoms from mild self-limiting fever to fatal sepsis. The spotted fever group (SFG) and typhus group (TG) are major RDs, which are commonly caused by Rickettsia conorii and Rickettsia typhi, respectively. The limited availability and role of serological tests in the acute phase of illness warrants rapid reliable molecular methods for diagnosis and epidemiological studies. Two hundred patients with AFI in whom the routine fever diagnostics were negative, were enrolled over a period of two months (April 2019 to May 2019). DNA was extracted and in-house nested PCR using primers specific for both SPG and TG pathogens was used. The positive amplified products were sequenced for species identification and phylogenetic analysis was performed using MEGA 7.0.14 software (iGEM, Temple University, Philadelphia, PA 19122, USA). The demographic details of the RD cases were documented. The prevalence of RD among AFI cases was 7% (14/200); SFG and TG were identified as the cause in 4% and 3% of AFI cases, respectively. The median age of the RD cases was 22 years (range 2–65). The median duration of fever was 3 days (range 1–12). The RD cases presented with respiratory symptoms or signs (44.44%), jaundice (22.22%), abdominal pain (22.22%), diarrhea (22.22), vesicular rash (11.11%), vomiting (11.11%), loss of appetite (11.11%), headache (11.11%), leukocytosis (88.88% with mean count 22,750/mm3), and thrombocytopenia (33.33%). The cases were treated empirically with piperacillin-tazobactam (66.66%), clindamycin (44.44%), cefotaxime (33.33%), meropenem (33.33%), metronidazole (33.33%), doxycycline (22.22%), azithromycin (22.22%), ceftriaxone (11.11%), and amoxicillin-clavulanic acid (11.11%). The mortality among the RD cases was 11.11%. The present pilot study shows that RD is not an uncommon cause of AFI in north India. The febrile episodes are usually transient, not severe and associated with heterogenous clinical presentation without documented history of tick exposure in the hospitalized patients. The transient, non-severe, febrile illness could be due to transient rickettsemia resulting from empirical antimicrobial therapy as the rickettsial organisms are expected to be more susceptible to higher doses of β-lactam antibiotics. The study emphasizes the molecular method as a useful tool to identify rickettsial etiology in AFI.

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Scrub Typhus and Molecular Characterization of Orientia tsutsugamushi from Central Nepal

Pathogens ◽

10.3390/pathogens10040422 ◽

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.

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