Case Report: Fulminant Myocarditis Successfully Treated With Extracorporeal Membrane Oxygenation in Ikeda Strain Orientia tsutsugamushi Infection

Scrub typhus is an acute zoonotic febrile illness caused by Orientia tsutsugamushi having a specific geographic endemic area. This infection could be complicated with multi-organ involvement including myocarditis with variable severity. Here, we report a rare case of scrub typhus with biopsy-proven acute fulminant myocarditis which progressed very rapidly to cardiac arrest and was treated successfully with extracorporeal cardiopulmonary resuscitation. Clinicians should be alert to possible rapid progression of scrub typhus myocarditis to fulminant form and be prepared for close monitoring and temporary mechanical support if indicated.

Detection of Orientia tsutsugamushi in Novel Trombiculid Mite Species in Northern Tamil Nadu, India: Use of Targeting the Multicopy traD Gene

Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it might be a potential vector of scrub typhus in an endemic area. Over a period of 20 mo, 85 rats were trapped, 57 had chiggers that were identified by standard morphometric techniques. The chigger pools were assessed by performing PCR assays targeting fragments of the single-copy genes 56 kDa type-specific antigen gene (TSA56) by nested PCR and the 47 kDa (htrA) quantitative real-time PCR (qPCR). The novel traD SYBR green assay that detects a multicopy gene was also performed. In total, 27 chigger pools were positive by traD qPCR, of which only 7 were positive by 47 kDa qPCR and in 3 of these, 56 kDa gene was amplified by nested PCR. Orientia tsutsugamushi-specific DNA was detected in Ascoschoengastia spp., Schoengastiella ligula, Leptotrombidium rajasthanense, Leptotrombidium deliense, and Leptotrombidium jayawickremei chigger pools. Therefore, they could be potential vectors of scrub typhus in Southern India. The three 56 kDa sequences belonged to TA716 genotype and Kato genogroup. Further studies are needed to confirm these chigger species as scrub typhus vectors in Northern Tamil Nadu.

Orientia tsutsugamushi dynamics in vectors and hosts: ecology and risk factors for foci of scrub typhus transmission in northern Thailand

Background Scrub typhus is an important neglected vector-borne zoonotic disease across the Asia–Pacific region, with an expanding known distribution. The disease ecology is poorly understood, despite the large global burden of disease. The key determinants of high-risk areas of transmission to humans are unknown. Methods Small mammals and chiggers were collected over an 18-month period at three sites of differing ecological profiles with high scrub typhus transmission in Chiang Rai Province, northern Thailand. Field samples were identified and tested for Orientia tsutsugamushi by real-time PCR. The rates and dynamics of infection were recorded, and positive and negative individuals were mapped over time at the scale of single villages. Ecological analyses were performed to describe the species richness, community structure and interactions between infected and uninfected species and habitats. Generalised linear modelling (GLM) was applied to examine these interactions. Results The site with the highest rates of human infection was associated with the highest number of infected chigger pools (41%), individual chiggers (16%), proportion of the known vector species Leptotrombidium deliense (71%) and chigger index (151). Chigger species diversity was lowest (Shannon diversity index H′: 1.77) and rodent density appeared to be high. There were no consistent discrete foci of infection identified at any of the study sites. The small mammals Rattus tanezumi and Bandicota indica and the chiggers L. deliense and Walchia kritochaeta emerged as central nodes in the network analysis. In the GLM, the end of the dry season, and to a lesser extent the end of the wet season, was associated with O. tsutsugamushi-infected small mammals and chiggers. A clear positive association was seen between O. tsutsugamushi-positive chigger pools and the combination of O. tsutsugamushi-positive chigger pools and O. tsutsugamushi-positive small mammals with lowland habitats. Conclusions These findings begin to reveal some of the factors that may determine high-risk foci of scrub typhus at a fine local scale. Understanding these factors may allow practical public health interventions to reduce disease risk. Further studies are needed in areas with diverse ecology. Graphical abstract

Elevated Extracellular Levels of Granzymes in Patients with Scrub Typhus

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi, which is transmitted through chigger mites. Delayed treatment results in various complications and, in severe cases, death. Granzymes are secreted by cytotoxic T lymphocytes or natural killer cells and are known to play an important role in controlling intracellular pathogens. To date, few studies have been done on granzymes in patients with scrub typhus. In this study, granzymes A and B showed a significant increase during the acute stage of scrub typhus compared with healthy control subjects, and decreased sharply after treatment. In addition, granzymes A and B were significantly high in the moderately elevated liver enzyme group. In conclusion, it appears that the host during the acute phase of scrub typhus increases cytotoxic T-cell activity to control infection.

Epidemiological Distribution and Potential Risk Factors of Orientia tsutsugamushi Infection in Eastern Uttar Pradesh, India

Background: Scrub typhus (ST) is a rickettsial infection caused by Orientia tsutsugamushi, which presents with flu like symptoms. This disease has been reported from all over India but with slight variations in its pattern. For decreasing the prevalence, preventing new incidences, and predicting the course of the ST, therefore, it is crucial to gain knowledge and perception of local risk components associated with the disease. The present study aimed to investigate the epidemiological distribution and potential risk factors of O. tsutsugamushi Infection in Eastern Uttar Pradesh (EUP), India. Methods: The serums of 211 samples were collected from the suspected cases along with the detailed information about the participants such as age, location, and place recorded in case history form (CRF). IgM estimation was performed using enzyme-linked immunosorbent assay (ELISA) assay. Results: A total of 58 samples (27.4%) out of 211 ones were found to be positive for IgM antibodies against O. tsutsugamushi bacterium. Furthermore, the results were correlated with epidemiological data such as gender, rural or urban background, pets, and occupation. The results showed that 76.7% of the study participants were from rural areas or had bushes around their houses, 88.3% of them had pets/cattle or frequent encounter with rodents at their houses, and 30.3% of them had no toilet facilities at home. Conclusions: It was concluded that the proximity to pets/cattle, having rodents in closer vicinity, residing in places surrounded by vegetation/farm/bushy areas, and following occupations involving field work increased the chances of getting bitten by mites/chiggers. Overall, Orientia tsutsugamushi prevalence increased in EUP, with respect to clinical features, disease presentation, and laboratory diagnosis can help our community to reduce the mortality caused by this infectious disease.

Scrub Typhus – A Threatening Scenario in North Bengal

BACKGROUND Scrub typhus is a mite borne zoonotic bacterial disease caused by Orientia tsutsugamushi. It is transmitted by bite of chiggers of trombiculid mite. Clinical features generally include fever, headache, and myalgia, with or without eschar/rash. People with severe illness may develop organ failure and bleeding which can be fatal if left untreated. This study was done to detect outbreak of cases of scrub typhus in Eastern India. These mites generally live in paddy fields of forested area and people visiting those areas are generally affected. Now a days these mites migrate to urban area resulting in increased incidence of scrub typhus infection in urban area. This study was conducted in collaboration with another institute. The purpose of this study was to find out the incidence of scrub typhus in our area and the relationship between occurrence of scrub typhus and seasonal, age and sex variation. METHODS This study was carried out in our tertiary care hospital with 441 samples for a period of one year (01.01.2019 to 31.12.19). All the blood samples collected from febrile patients were subjected to Weil Felix test. If the titre is > 1 : 160; this was further confirmed by specific IgM testing. Both Weil-Felix tests and IgM scrub typhus positive tests were noted. RESULTS Out of 441 samples, 98 (22.2 %, n = 441) samples were positive for both WeilFelix and scrub typhus IgM by enzyme linked immunosorbent assay (ELISA) testing. Most of the cases were seen in males. Seasonal distribution showed higher cases in the months of September and October. CONCLUSIONS In our study, the highest numbers of scrub typhus cases were found in rural areas, during the harvesting period of July–September specially in monsoon or post monsoon period when there is abundance of mite larva. This infection is also reported high in cases among children in the age group of 1 - 14 years. Patients who tested positive for scrub typhus improved radically with doxycycline. KEYWORDS Orientia Tsutsugamushi, Scrub Typhus, IgM ELISA

Analysis of Orientia tsutsugamushi promoter activity

ABSTRACT Orientia tsutsugamushi is an obligate intracellular bacterium that causes scrub typhus, a potentially fatal rickettsiosis, and for which no genetic tools exist. Critical to addressing this technical gap is to identify promoters for driving expression of antibiotic resistance and fluorescence reporter genes in O. tsutsugamushi. Such promoters would need to be highly conserved among strains, expressed throughout infection, and exhibit strong activity. We examined the untranslated regions upstream of O. tsutsugamushi genes encoding outer membrane protein A (ompA), 22-kDa type-specific antigen (tsa22) and tsa56. The bacterium transcribed all three during infection of monocytic, endothelial and epithelial cells. Examination of the upstream noncoding regions revealed putative ribosome binding sites, one set of predicted −10 and −35 sequences for ompA and two sets of −10 and −35 sequences for tsa22 and tsa56. Comparison of these regions among geographically diverse O. tsutsugamushi patient isolates revealed nucleotide identities ranging from 84.8 to 100.0%. Upon examination of the candidates for the ability to drive green fluorescence protein expression in Escherichia coli, varying activities were observed with one of the tsa22 promoters being the strongest. Identification and validation of O. tsutsugamushi promoters is an initial key step toward genetically manipulating this important pathogen.

Scrub typhus associated acute kidney injury in a 33-year-old male

Scrub typhus or bush typhus is caused by Orientia tsutsugamushi. An eschar at the site of bite is evidentiary of scrub typhus. Increased mortality is seen in cases presenting with acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), pneumonitis, meningitis, myocarditis and multi-organ dysfunction. Renal impairment in scrub typhus should be identified and management initiated early to prevent the progress of the damage. Scrub typhus if left undiagnosed and untreated results in high morbidity and mortality. Here we report a case of a 33-year-old male with AKI following scrub typhus fever. In our case early diagnosis and management led the patient to recovery.