scholarly journals High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection

2021 ◽  
Vol 15 (3) ◽  
pp. e0009283
Author(s):  
Carol S. Devamani ◽  
John A. J. Prakash ◽  
Neal Alexander ◽  
William Stone ◽  
Karthik Gunasekaran ◽  
...  

Background Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk. Methods/principal findings We studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (<1.0), intermediate (1.0 to 2.9), and high (≥3.0). OD was also modelled as a continuous variable (cubic spline). Median age of cases was 41 years (range 0–85), with 37% having severe infection. Compared to the low category, the age-adjusted risk of severe infection was 1.5 times higher in the intermediate category (95%CI 1.2, 1.9), and 1.3 times higher in the high category (95%CI 1.0, 1.7). The effect was stronger in cases <40 years, doubling the risk in the intermediate and high categories compared to the low category. The effect was more pronounced in cases tested within 7 days of fever onset when IgG ODs are more likely to reflect pre-infection levels. Conclusions/Significance Intermediate and high IgG antibody levels at the time of diagnosis are associated with a higher risk of severe scrub typhus infection. The findings may be explained by severe infection eliciting an accelerated IgG response or by previous scrub typhus infection enhancing the severity of subsequent episodes.

2016 ◽  
Vol 5 (09) ◽  
pp. 4896
Author(s):  
Sripriya C.S.* ◽  
Shanthi B. ◽  
Arockia Doss S. ◽  
Antonie Raj I. ◽  
Mohana Priya

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. 


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 422
Author(s):  
Rajendra Gautam ◽  
Keshab Parajuli ◽  
Mythili Tadepalli ◽  
Stephen Graves ◽  
John Stenos ◽  
...  

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.


Author(s):  
Sophia G de Vries ◽  
Louise E van Eekeren ◽  
Hans van der Linden ◽  
Benjamin J Visser ◽  
Martin P Grobusch ◽  
...  

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.


2019 ◽  
Author(s):  
Meghnath Dhimal ◽  
Shyam Prakhas Dumre ◽  
Guna Niddhi Sharma ◽  
Pratik Khanal ◽  
Kamal Ranabhat ◽  
...  

ABSTRACTBackgroundScrub typhus is a severely ignored tropical disease and a leading cause of undifferentiated febrile illness worldwide caused by infection of an obligate intracellular bacteria Orientia tsutsugamushi. It has been rapidly expanding in South Asian countries, although clear epidemiological information is not available from Nepal. After the 2015 earthquake in Nepal, a sudden upsurge in scrub typhus cases was reported. The objective of this study was to investigate scrub typhus and its causative agents in human, rodent and chigger mites to better understand the ongoing transmission ecology.MethodsScrub typhus cases with confirmed diagnosis throughout the country were included in the analysis. Studies were concentrated in the Chitwan district, the site of a major outbreak in 2016. Additional country-wide data from 2015 to 2017 was made available from the government database to analyse the disease distribution using geographical mapping.ResultsDuring 2015-2017, 1,239 scrub typhus cases were confirmed with the largest outbreak occurring in 2016 with 831 (67.1%) cases. The remainder 267 cases were reported in 2017. The case fatality rate was 5.7% in 2015 and declined to 1.1% in 2017. Nationwide outbreak of scrub typhus was identified as the cases were found from 52 of the 75 districts of Nepal. A seasonal trend was observed with a peak during August and September (p = 0.01). In addition to the human cases, the presence of O. tsutsugamushi was also confirmed in rodents and chigger mites from the outbreak areas of southern Nepal.ConclusionThe detection of O. tsutsugamushi in human, rodent, and chigger mites from outbreak locations and wide-spread reports of scrub typhus throughout the country over two years confirms the ongoing transmission of O. tsutsugamushi with a firmly established ecology in Nepal. The country’s health system needs to be strengthened for systematic surveillance, early outbreaks detection, and immediate response actions including treatment and preventive measures.Author SummaryScrub typhus is a disease caused by a bacteria called Orientia tsutsugamushi and transmitted to people through bites of infected chiggers (larval mites). After the 2015 Gorkha earthquake in Nepal, a sudden upsurge in scrub typhus cases was reported with repeated outbreaks from different parts of the country. This study has documted epidemiology of scrub typhus and its causative agents in human, rodent and chigger mites confimring the local transmission O. tsutsugamushi with a firmly established ecology in Nepal. The local transmission of the diseases from most parts of the country demands strengthening for systematic surveillance, early outbreaks detection, and immediate response actions including treatment and preventive measures.


2021 ◽  
Vol 8 (25) ◽  
pp. 2216-2221
Author(s):  
Kiranmayi Bogarapu ◽  
Aruna P

BACKGROUND Coronavirus disease - 19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Anti-SARS-CoV-2 IgM and IgG antibodies can be detected in almost all patients of COVID-19. We sought to evaluate the antibody responses in COVID19 patients and also analyse their potential role in disease prognostication. METHODS All consecutive COVID-19 patients, between ages 20 - 65 years, encountered between April and July 2020 were included and compared to age-matched controls. Severity of the SARS-CoV-2 infection was categorized as none, mild and severe, based on the presence of symptoms, oxygen saturation and need for respiratory support. Serum levels of IgM and IgG antibody assays were obtained, using chemiluminescence immunoassay, after the 2nd week of presentation (range 14 - 60 days). Antibody titres above 10 AU/ml were taken as elevated. RESULTS Of 50 eligible patients, majority (40/50, 80 %) had mild symptoms and oxygen saturations above 94 %. Of the remainder, 10 % (5/50) had severe infection with need for either high flow nasal cannula oxygen or mechanical ventilation while the remainder (10 %; 5/50) were asymptomatic. IgM and IgG seroconversion were noted in almost all COVID-19 patients (46/50, 92 %) compared to healthy controls. While elevated IgG antibody levels were noted in 76 % (38/50), combined elevation of IgM and IgG antibodies is seen in 16 % (8/50) of patients. Seroconversion was markedly profound in patients with severe infection than those with mild infection. Also, greater seroconversion was noted after 21 days of testing compared to 14th day, especially for IgG. CONCLUSIONS Antibody seroconversion to SARS-CoV-2 occurred in majority of patients with COVID-19, with most salient increase in the IgG antibody levels. Antibody titres correlated directly to the disease severity, suggestive of the potential value of antibodies not only in diagnosis but also in prognostication. KEYWORDS COVID-19, Chemiluminescence Immunoassay, Invasive Mechanical Ventilation, High Flow Nasal Oxygen


2018 ◽  
Vol 38 (1) ◽  
pp. 59-62
Author(s):  
Madiha Zainab ◽  
Atul Kumar Gupta ◽  
Suparna Guha

Introduction: Scrub typhus is an acute febrile illness caused by infection with rickettsial bacilli Orientia tsutsugamushi. This was a retrospective observational study to study the clinical profile of paediatric scrub typhus, its associated complications and response to treatmentMaterial and Methods: Record files of all patients diagnosed with positive Weil felix (OXK>1:80) and Scrub IgM positive over a period of one year were analysed. Total of 10 cases were diagnosed as scrub with median age of presentation 4.1 years.Results: Fever was present in all followed by pain abdomen (50%), rash. Anaemia (90%), lymphadenopathy (70%) hepatomegaly (100%), Leukopenia was present in those cases with fever <1 week while leucocytosis was found thereafter. Most common complication were hepatitis (100%) shock (50%), acute kidney injury (AKI) 30%, DIC in 20% cases. Secondary HLH was found in 20% and pancarditis in one case. All the cases showed dramatic response to doxycycline.Conclusion: So a high index of suspicion is required to diagnose scrub and early initiation of treatment is essential to prevent mortality from the disease.


2020 ◽  
Vol 18 (2) ◽  
pp. 282-287
Author(s):  
Ram Hari Chapagain ◽  
Sumit Agrawal ◽  
Sunita Pokharel ◽  
Madhusudhan Kayastha ◽  
Susan Bhattrai ◽  
...  

Background: Scrub typhus, an important cause of undifferentiated fever, is grossly neglected and often misdiagnosed in low and middle income countries like Nepal. The main aim of this study was to describe the clinico-laboratory profile, drug used in treatment, predictor of PICU admission and therapeutic outcome of serologically confirmed scrub typhus among Nepalese children.Methods: A prospective observational study was carried out in children aged up to 14 years with serologically (IgM ELISA) diagnosed Scrub typhus, admitted in a tertiary care hospital of central Nepal between Jan 2019 to Dec 2019.Results: All 100 children with scrub typhus presented with fever. Other symptoms and sign were cough (29%), abdominal distension (22%) hepatomegaly (45%), splenomegaly (28%), crepitation (10%) and eschar (6%). Similarly, thrombocytopenia (72%), and increased liver enzymes SGPT (51%) and SGOT (62%) were found. Co-infection with dengue (5%) brucella (5%) and UTI (5%) were seen. Thirty six percent has some form of complication. Fifty eight percent of children were treated with azithromycin and 25% treated with doxycycline. The mean length of hospital stay was 6.68 ±2.97 days with a mean duration of defervescence being 30.07 ± 26.65 hours. The increased risk of PICU admission was found in those children with crepitation in chest (OR: 15.17, 95% CI: 3.4-66.8) during presentation and those children not getting azithromycin as treatment (OR: 3.8, 95% CI: 1.2-11.7)Conclusions: Scrub typhus should be considered as a differential diagnosis in any community acquired acute undifferentiated febrile illness regardless of the presence of an eschar. Sepsis, meningitis and pneumonia are important complications. Child having crepitation on presentation has an increased chance admission in critical care unit. The child receiving azithromycin has less chance to land in PICU.Keywords: Clinico-laboratory profile; complications; fever; scrub typhus.


Author(s):  
Shiv Kumar Pandey ◽  
Vishal Malviya ◽  
Kumar Girendra ◽  
Abhijeet Khandelwal

Background & Method: 20 patients with scrub typhus who visited Index Medical College Hospital & Research Centre, Indore. Diagnosis of scrub typhus was made from blood samples based on serology (scrub typhus IgM / IgG antibody). We observed the following symptoms – eschar, cough, SOB, fever, chest pain, nausea /vomiting, abdominal pain, seizures, & the various laboratory investigations were done (TLC, ESR, S.CREATINE, LFT, SERUM ELECTROLYTES ETC.). CXR (PA / AP) were analysed on the basis of the presence, location and zonal predilection for consolidations, reticulo nodular shadows, hilar shadows and lower lobe haziness. Conclusion: Pulmonary manifestation of Scrub typhus is uncommon. But can be fatal, particulary in the form of ARDS. Antibiotic therapy may prove beneficial in initial phase. In acute febrile illness (SCRUB TYPHUS), pulmonary symptoms and radiological menifestations should be rule out in early stages to prevent the mortality. Keywords: Prevalance, Pulmonary, Radiological & Scrub Typhus.


2018 ◽  
Vol 16 (3) ◽  
pp. 533-541
Author(s):  
Le Thi Lan Anh ◽  
Trinh Van Toan ◽  
Pham Thi Ha Giang ◽  
Bui Thi Thanh Nga ◽  
Vo Viet Cuong ◽  
...  

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, transmitted to humans by the bite of the larva of trombiculid mites. Diagnosis of scrub typhus is normally based on the clinical presentations. However, it is difficult to differentiate scrub typhus from other acute febrile illnesses, such as dengue fever, malaria and leptospirosis due to similar symptoms. For differential diagnosis of scrub typhus from other acute febrile diseases, a rapid and reliable serological diagnosis is important. In order to produce an ELISA kit for detection of antibodies against O. tsutsugamushi in Vietnam, four truncated 56 kDa antigenic genes of O. tsutsugamushi including Karp (HT-09), Gilliam (HT-11), TA763 (HT-49), and Kato (YB-50) íolated from the most prevalent cases in Vietnam were cloned and expressed in E. coli Rosetta 1 cells. The recombinant proteins formed inclusion bodies when expressed in E. coli. The recombinant 56 kDa proteins in insoluble form were solubilized in 6M urea and were successfully purified by Ni2+affinity column. The purity of four recombinant proteins,HT-09, HT-11, HT-49 and YB-50,reached more than 95% and their concentrations are 12,57 mg/ml; 11,6 mg/ml; 8,98 mg/ml và 8,02 mg/ml, respectively.


2020 ◽  
Author(s):  
Jian-Jun Liu ◽  
Sharon LT Pek ◽  
Jiexun Wang ◽  
Sylvia Liu ◽  
Keven Ang ◽  
...  

<b>Objective: </b>Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein which potentially involves in several pathways related with pathogenesis of heart failure (HF). We aim to study whether plasma LRG1 is associated with risk of incident HF and hospitalization attributable to HF (HHF) in individuals with type 2 diabetes. <p><b>Design and Methods</b>: 1978 individuals with type 2 diabetes were followed for a median of 7.1 (IQR 6.1-7.6) years. Association of LRG1 with HF was studied by cause-specific Cox regression models. </p> <p><b>Results</b>: 191 incident HF and 119 HHF events were identified in follow-up. As compared to quartile 1, participants with LRG1 in quartile 3 and 4 had 3.60 (95% CI 1.63- 7.99) and 5.99 (95% CI 2.21-16.20) folds increased risk for incident HF, and 5.88 (95% CI 1.83-18.85) and 10.44 (95% CI 2.37- 45.98) folds increased risk for HHF after adjustment for multiple known cardio-renal risk factors. As a continuous variable, 1- SD increment in natural log-transformed LRG1 was associated with 1.78 (95% CI 1.33-2.38) folds adjusted risk for incident HF and 1.92 (95% CI 1.27- 2.92) folds adjusted risk for HHF. Adding LRG1 onto clinical variable- based model improved risk discrimination for incident HF (AUC 0.79 to 0.81, P=0.02) and HHF (AUC 0.81 to 0.84, P=0.02).</p> <p><b>Conclusion</b>: Plasma LRG1 is associated with risk of incident HF and HHF, suggesting that it may potentially involve in pathogenesis of HF in individuals with type 2 diabetes. Further studies are warranted to determine whether LRG1 may be a novel biomarker for HF risk-stratification.</p>


Sign in / Sign up

Export Citation Format

Share Document