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

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.

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A study on serodiagnosis of scrub typhus in a Teaching Hospital of South India

PERSPECTIVES IN MEDICAL RESEARCH - 2 ◽

10.47799/pimr.0902.03 ◽

2021 ◽

Vol 9 (2) ◽

pp. 10-14

Author(s):

Santosha Kelamane Kelamane ◽

Cheruku Mispah ◽

Sri Sandhya K.

Keyword(s):

South India ◽

Scrub Typhus ◽

Clinical Symptoms ◽

Febrile Illness ◽

Unknown Origin ◽

Elisa Test ◽

Public Health Issue ◽

Serum Samples ◽

Igm Elisa ◽

Sera Samples

Background: crub typhus is caused by Orientia tsutsugamushi (rickettsial disease) commonly transmitted by the bite of larval chiggers of trombiculid mites. It has been one of the important causes of febrile illness, especially in south India. The clinical diagnosis is difficult owing to the non-specific presentation. We in the current study tried to evaluate the serodiagnosis of scrub typhus with the Weil Felix test and IgM ELISA. Methods: This study was conducted in the Department of Microbiology, Prathima Institute of Medical Sciences, Naganoor, Karimnagar. All the sera samples were subjected to the Weil Felix test using Proteus OX2, OX19, OX-K strain agglutination test, and subsequently, Scrub typhus IgM ELISA test. Results: All the samples were subjected to the Weil Felix test n=4(6.06%) were positive for scrub typhus (OXK antigen) n=11(16.67%) were positive for the spotted group of fever (OX2 antigen) and n=10 (15.15%) were positive of typhus group (OX19 antigen). N=5 sera samples were positive for more than one type of antigens. All the n=66 serum samples were subjected to IgM ELISA for scrub typhus. Out of n=66, only two serum samples (3.03%) were positive by IgM ELISA. Conclusion: Scrub typhus is emerging as an important public health issue. It is one of the important causes of acute febrile illness. Although it is difficult to distinguish scrub typhus based on the clinical symptoms alone a simple test such as Weil Felix was found to be promising in the diagnosis of scrub typhus. ELISA IgM test may be performed additionally in laboratories with adequate facilities. Hence for clinicians, any case with a fever of unknown origin should arouse suspicion of scrub typhus

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Scrub typhus and lateral rectus palsy: an uncommon presentation of a common illness

BMJ Case Reports ◽

10.1136/bcr-2020-240882 ◽

2021 ◽

Vol 14 (5) ◽

pp. e240882

Author(s):

Ajay Chauhan ◽

Aditya Jandial ◽

Kundan Mishra ◽

Rajeev Sandal

Keyword(s):

Scrub Typhus ◽

Clinical Manifestations ◽

Central Nervous System Involvement ◽

Febrile Illness ◽

Acute Febrile Illness ◽

Orientia Tsutsugamushi ◽

Cranial Nerve Involvement ◽

Uncommon Presentation ◽

Life Threatening ◽

Multiorgan Dysfunction Syndrome

Scrub typhus is a zoonosis, which usually manifests as an acute febrile illness. It is caused by a rickettsia, Orientia tsutsugamushi, which is endemic in the Asian region. It can present with varied clinical manifestations, ranging from acute febrile illness to life-threatening multiorgan dysfunction syndrome. Central nervous system involvement in the form of altered sensorium and/or meningitis is frequently observed in scrub typhus. However, isolated cranial nerve involvement is uncommon and so far only a few such cases have been reported in the literature. We present a rare case of scrub typhus with fever and diplopia at presentation, which completely improved with doxycycline-based treatment.

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Scrub typhus: as it stands today

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20193958 ◽

2019 ◽

Vol 7 (9) ◽

pp. 3605

Author(s):

Raman Sharma ◽

Mayank Gupta ◽

Sunil K. Mahavar ◽

Madhulata Agarwal

Keyword(s):

Scrub Typhus ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Febrile Illness ◽

Late Presentation ◽

Presumptive Treatment ◽

Appropriate Treatment ◽

Trombiculid Mite ◽

Common Causes ◽

Specific Symptoms

Scrub typhus is one of the three most common causes of prolonged fever in Southeast Asia and Pacific affecting almost 1 million people annually worldwide out of 1 billion exposed. Scrub typhus is a rickettsial infection caused by Orientia Tsutsugamushi transmitted through bite of Chiggers (larval stage of trombiculid mite). It 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 and death. Deaths are attributable to late presentation, delayed diagnosis, and drug resistance. Scrub typhus, though endemic in India; yet is under reported. It should be considered as an important differential diagnosis in a febrile patient with thrombocytopenia, deranged liver or renal functions, and B/L chest opacities. Relapse is not uncommon. Presumptive treatment with Doxycycline can be a suitable option in febrile patients from Typhus pockets. Alert physician should keep an eye on deviation from usual presentation to changing spectrum of the disease. Early diagnosis and appropriate treatment is rewarding and prevents morbidity and mortality.

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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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Diagnostic Accuracy of the InBios Scrub Typhus Detect™ ELISA for the Detection of IgM Antibodies in Chittagong, Bangladesh

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed3030095 ◽

2018 ◽

Vol 3 (3) ◽

pp. 95 ◽

Cited By ~ 7

Author(s):

Stuart Blacksell ◽

Hugh Kingston ◽

Ampai Tanganuchitcharnchai ◽

Meghna Phanichkrivalkosil ◽

Mosharraf Hossain ◽

...

Keyword(s):

General Population ◽

Diagnostic Accuracy ◽

Diagnostic Tests ◽

Scrub Typhus ◽

Febrile Illness ◽

High Sensitivity ◽

Immunofluorescence Assay ◽

Immunoglobulin M ◽

Regional Assessment ◽

Igm Elisa

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.

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Evaluation of a Genus Specific rGroEL 1-524 IgM-ELISA and Commercially ELISA Kits During Course of Leptospirosis in Thailand

10.21203/rs.3.rs-352195/v1 ◽

2021 ◽

Author(s):

Santi Maneewatchararangsri ◽

Galayanee Doungchawee ◽

Thareerat Kalambaheti ◽

Viravarn Luvira ◽

Ngamphol Soonthornworasiri ◽

...

Keyword(s):

Early Detection ◽

Early Diagnosis ◽

Screening Test ◽

Scrub Typhus ◽

Acute Infection ◽

Febrile Illness ◽

High Sensitivity ◽

Elisa Assay ◽

Igm Elisa ◽

Post Onset

Abstract This work, we developed a genus-specific rGroEL1-524 IgM-ELISA assay for using as screening diagnosis of suspected leptospirosis among acute undifferentiated febrile illness patients during acute fever. Ddiagnostic accuracies of rGroEL1–524 IgM-ELISA, and commercial Panbio IgM-ELISA, and Virion-Serion Classic IgG-ELISA were evaluated with Thai 107 leptospirosis sera, and 189 controls, compared to reference culture and/or MAT methods. Sensitivities were 91.7%, 59.6%, and 17.7% for acute- infection, and were 97.1%, 54.8%, and 9.7% for early detection at 1-3 days post-onset of symptoms (DPO1-3), and the specificities were 87.5%, 86.6%, and 74.8% among controls, respectively. The rGroEL1-524 IgM-ELISA had high sensitivity, at 95.9% and 91.2% among culture and MAT negative cases. Impaired specificity on scrub typhus, possibly from antibody-cross reaction to ortholog GroEL. Commercial Panbio IgM-ELISA had sensitivities of 50%, 63.2%, and 89.9% compared with culture, MAT-negative and single MAT-positive cases whereas Virion-Serion IgG-ELISA provided sensitivities of 13.3%, 10.5% and 71.4%, respectively. A rGroEL1-524 IgM-ELISA could be useful as a screening test for early diagnosis. The performance of the commercial ELISA suggests the applicability of IgM-ELISA for diagnosis, while IgG-ELISA is useful for seroprevalence surveys. However, confirmation by reference tests is recommended.

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Correlation between Clinical Symptoms of Coeliac Disease, Serum IgA Anti TTG and Biopsy in Pediatric Population of Northern India

Asian Journal of Clinical Pediatrics and Neonatology ◽

10.47009/ajcpn.2020.8.1.16 ◽

2020 ◽

Vol 8 (1) ◽

pp. 65-68

Author(s):

Sumit Jeena ◽

Jaswinder Kaur ◽

Nishant Wadhwa

Keyword(s):

Coeliac Disease ◽

Clinical Symptoms ◽

Tissue Transglutaminase ◽

Pediatric Population ◽

Clinical Manifestations ◽

North India ◽

P Value ◽

Serum Iga ◽

Significant Difference ◽

The Mean

Background: Celiac disease is basically an immune-mediated enteropathic condition produced by permanent sensitivity to gluten in genetically susceptible subjects. There is paucity of data in north India regarding clinical symptoms of coeliac disease, Serum IgA Anti TTG and Biopsy in pediatric population. The present study was conducted with the aim to determine the correlation between clinical symptoms of coeliac disease, Serum IgA Anti TTG and Biopsy in pediatric population of northern India.Materials and Methods: The present study was conducted in prospective including 73 pediatric patients at Department of Pediatric Gastroenterology, Institute of Child Health, Sir Gangaram Hospital, New Delhi, India. Esophagogastroduodenoendoscopy and serum anti Ig A tissue transglutaminase were performed. The characteristic scalloping of the folds were looked for in endoscopy followed by four duodenal biopsies performed from second part of duodenum and histological grading was performed as per modified marsh system. Patients with Serum IgA anti tTG>20 U/ml were confirmed to be at risk. Complete histological work up was done including hemoglobin, RBC indices and peripheral blood smear examination. The association of clinical manifestations with disease grade was also established with correlation coefficient. All the data thus obtained was arranged in a tabulated form and analyzed using SPSS software. Probability value of less than 0.05 was regarded as significant.Results: There were 4 males and 16 females with marsh grade 1 and 2 and mean age of 7.3±1.9 years. There were 5 males and 8 females with marsh grade 3a and mean age of 6.8±2.3 years. The mean weight of 18.11±3.89, height of 103.17±8.73 and BMI of 16.26±3.78 was observed amongst subjects with Marsh grade 1 and 2. The mean weight of 15.12±3.17, height of 99.28±9.19 and BMI of 15.02±3.20was observed amongst subjects with Marsh grade 3a. Diarrhoea was maximum amongst subjects with grade 3c and 4(70%) and minimum amongst Grade 1 and 2 (40%). There was a significant difference between the frequency of anemia amongst different grades as the p value was less than 0.05.Conclusion: The most common presenting signs and symptoms were diarrhea and abdominal pain. The study also concluded that the incidence of anemia increases with higher marsh grades.

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Diagnostic evaluation of IgM ELISA and IgM Immunofluorescence assay for the diagnosis of Acute Scrub Typhus in central Nepal

10.21203/rs.2.10024/v5 ◽

2020 ◽

Author(s):

Rajendra Gautam ◽

Keshab Parajuli ◽

Tshokey Tshokey ◽

John Stenos ◽

Jeevan Bahadur Sherchand

Keyword(s):

Likelihood Ratio ◽

Predictive Value ◽

Gold Standard ◽

Scrub Typhus ◽

Febrile Illness ◽

Immunofluorescence Assay ◽

Acute Febrile Illness ◽

Central Nepal ◽

Igm Elisa ◽

Typhus Fever

Abstract Introduction Scrub typhus is an acute febrile illness caused by the obligate intracellular bacterium,Orientia tsutsugamushi. Given their affordability and ease of use, antibody based diagnostic assays can be important diagnostic tools for early detection of scrub typhus fever in resource poor countries like Nepal. Immunochromatography (ICT) and IgM ELISA are two of the routinely employed antibody based assays for diagnosis of Scrub typhus fever in Nepal, although the recommended gold standard diagnostic test is IgM Immunofluorescence assay (IFA). This study evaluated the InBios Scrub Typhus Detect™ Immunoglobulin M (IgM) ELISA and IgM Immunofluorescence assays in single serum sample at the time of admission. Methodology Study participants (1585 suspected cases), were enrolled based on acute febrile illness with suspected scrub typhus cases in central Nepal from April 2017 to March 2018. Blood sample was collected from the suspected patients of scrub typhus, presenting with acute febrile illness. IgM antibody to Orientia tsusugamushi was detected by using Scrub Typhus Detect™ Kit (In Bios International, USA) and an in-house IgM IFA (Australian Rickettsial Reference Laboratory, Geelong, Australia. The IFA assay was performed with the Gilliam, Karp, Kato strains and O. chuto antigens following the ARRL protocol. Result Statistical analysis of ELISA IgM results when compared to reference test, IgM IFA results demonstrated the following characteristics, sensitivity 84.0% (95%CI: 79.73%-87.68%), specificity 94.82% (95% CI: 93.43%-95.99%), positive likelihood ratio 16.21% (95% CI: 12.71%-20.67%), negative likelihood ratio 0.17% (95% CI: 0.13-0.21%), disease prevalence 22.08% (95% CI: 20.06%-24.21%), positive predictive value 82.12% (95% CI: 78.28-85.42%) and negative predictive value 95.44% (95% CI: 94.27%-96.38%) respectively. Conclusion The study indicated that the IgM ELISA has the sensitivity 84.0% (95% CI: 79.73%-87.68%) and specificity 94.82% (95% CI: 93.43%-95.99%). Although IgM IFA is considered the gold standard test for the diagnosis of scrub typhus cases, it is relatively expensive, requires trained personal and a microscope with fluorescence filters. Scrub typhus IgM ELISA with appropriate OD cut–off values may be the best alternative test and possible viable option for resource limited endemic countries like Nepal.

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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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Clinical presentation of scrub typhus during a major outbreak in central Nepal

Asian Journal of Medical Sciences ◽

10.3126/ajms.v8i4.17163 ◽

2017 ◽

Vol 8 (4) ◽

pp. 27-31 ◽

Cited By ~ 5

Author(s):

Arun Sedhain ◽

Gandhi R. Bhattarai

Keyword(s):

Acute Kidney Injury ◽

Scrub Typhus ◽

Clinical Manifestations ◽

Kidney Injury ◽

Continuous Variables ◽

Neurologic Manifestation ◽

Igm Elisa ◽

Clinical Presentations ◽

Tertiary Teaching ◽

Major Outbreak

Background: Scrub typhus, an emerging rickettsial disease caused by the organism Orientiatsutsugamushi, is associated with multi-organ involvement. We prospectively studied the clinical manifestations of the disease during a major outbreak in central part of Nepal.Aims and Objective: This study was carried out with an aim to analyze the clinical presentations, laboratory parameters, complications and outcomes of scrub typhus.Materials and Methods: A prospective observational study was conducted in the Department of Medicine in a tertiary teaching hospital. A total of 1398 patients admitted with acute febrile illness were subjected for Scrub Typhus Detect™ IgM ELISA test, among which 502 (35.90%) patients tested positive and were included in the study. Acute kidney injury was defined according to KDIGO guideline. Statistical analysis was done with SAS University Studio package using t-test for continuous variables and chi-square test for categorical variables.Results: Mean age of the patients was 30.37±18.81 years with 26.29% in the pediatric age group (<14 years). Females comprised of 55.98% of the patients. Majority (97.98%) of the patients were seen between July to November. Clinical presentations in the descending order of frequency were anorexia (55.18%), headache (53.39%), lymphadenopathy (15.73%), jaundice (13.35) and eschar (6.57%). Mean scrub typhus IgM ELISA value was 2.17. Leukocytosis was seen in 5.78% and thrombocytopenia in 66.73% of patients. Transaminitis was found in 80.68% of patients. Urinary abnormalities were recorded in 42.3% of patients. Acute kidney injury (AKI) was seen in 35.8% of patients followed by acute respiratory distress syndrome (24.1%), pneumonia (22.1%), shock (14.74%), neurologic manifestation (6.37%) and cardiac manifestations (4.38%). ICU admission was required for 18.73% of patients and 8.57% required ventilator support. Mortality rate was 1.79%.Conclusion: Scrub typhus, being an emerging vector borne infectious disease in Nepalese context, is associated with multiple organ involvement.Asian Journal of Medical Sciences Vol.8(4) 2017 27-31

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