Scrub Typhus Patients Research Articles

Clinical profile and biochemical abnormalities in Scrub Typhus: A cross-sectional study.

Scrub Typhus (ST) is an acute febrile illness caused by obligate intracellular bacteria of the family Rickettsia. It is often unrecognized and neglected but prevalent in tropical regions of endemic areas. The tragedy behind this diagnostic dilemma is non-specific clinical signs and symptoms, limited awareness, unavailability of diagnostic facilities, and low index of suspicion among the physicians. To address the knowledge gap, we tried to find out a proper panel of laboratory investigations to diagnose the disease and predict its progression because of the uncertainty of the course of the disease in a tertiary care hospital in western Nepal. This is a hospital laboratory-based prospective study conducted at Gandaki Medical College- Teaching Hospital (GMC-TH) for a period of two years. Among 988 cases of acute febrile illness, 40 seropositive cases of ST were enrolled in the study. We excluded those who did not give consent for the participation, those who were under 17 years of age, and those who had preexisting liver dysfunctions and other co-morbidities and dual seropositive with other infectious etiologies. We used descriptive statistics to analyze the data in terms of demography, clinical features, and laboratory parameters. Out of 988 febrile patients, we included 40 confirmed cases of ST aged between 17 and 70 years during the study-period. Maximum seropositive cases were from Tanahun district 14 (35%), with predominance among the women (70%). The cases were prevalent in the age group 30-60 years, 19 (47.5%), and in the month of October 15 (37.5%). The commonest complaints were fever in 40 (100%), headache in 20 (50%), eschar in 11 (27.5%). Laboratory parameters showed anemia in 22 (55%), hypoalbuminemia in 11 (27.5%), leukopenia in 5 (12.5%), leukocytosis in 9 (22.5%), thrombocytopenia in 13 (32.5%), raised transaminase levels, SGPT in 21 (52.5%) and SGOT in 14 (26%) ST patients. We found clinical and laboratory profiles in patients with ST were varied and nonspecific. However, knowledge of these findings may evoke the recognition of ST and give a clue to the progression of the disease.

Neurological manifestations of scrub typhus infection: A systematic review and meta-analysis of clinical features and case fatality.

Scrub typhus has become a leading cause of central nervous system (CNS) infection in endemic regions. As a treatable condition, prompt recognition is vital. However, few studies have focused on describing the symptomology and outcomes of neurological scrub typhus infection. We conducted a systematic review and meta-analysis to report the clinical features and case fatality ratio (CFR) in patients with CNS scrub typhus infection. A search and analysis plan was published in PROSPERO [ID 328732]. A systematic search of PubMed and Scopus was performed and studies describing patients with CNS manifestations of proven scrub typhus infection were included. The outcomes studied were weighted pooled prevalence (WPP) of clinical features during illness and weighted CFR. Nineteen studies with 1,221 (656 adults and 565 paediatric) patients were included. The most common clinical features in CNS scrub typhus were those consistent with non-specific acute encephalitis syndromes (AES), such as fever (WPP 100.0% [99.5%-100.0%, I2 = 47.8%]), altered sensorium (67.4% [54.9-78.8%, I2 = 93.3%]), headache (65.0% [51.5-77.6%, I2 = 95.1%]) and neck stiffness 56.6% (29.4-80.4%, I2 = 96.3%). Classical features of scrub typhus were infrequently identified; an eschar was found in only 20.8% (9.8%-34.3%, I2 = 95.4%) and lymphadenopathy in 24.1% (95% CI 11.8% - 38.9%, I2 = 87.8%). The pooled CFR (95% CI) was 3.6% (1.5%- 6.4%, I2 = 67.3%). Paediatric cohorts had a CFR of 6.1% (1.9-12.1%, I2 = 77%) whilst adult cohorts reported 2.6% (0.7-5.3%, I2 = 43%). Our meta-analyses illustrate that 3.6% of patients with CNS manifestations of scrub typhus die. Clinicians should have a high index of suspicion for scrub typhus in patients presenting with AES in endemic regions and consider starting empiric treatment whilst awaiting results of investigations, even in the absence of classical signs such as an eschar or lymphadenopathy.

Clinical Spectrum and Outcome of Scrub Typhus Patients in a Tertiary Care Teaching Hospital of Western Maharashtra

Introduction: Acute febrile illness (AFI) is the most common presenting complaint in the emergency and outpatient clinics in developing countries. Scrub typhus is currently one of the most covert re-emerging infections and it is one of the commonly occurring rickettsial diseases in India. Objectives: To determine the clinical profile and outcome of scrub typhus patients admitted at a tertiary care centre of western Maharashtra for treatment. Material and Method: Present descriptive cross sectional study conducted over period of three years from October 2019 to October 2022. Study commenced after obtaining Institutional Ethical Permission (IEC). Clinically suspected patients undergone Weil-Fliex test followed by IgM ELISA for confirmation of diagnosis. Total 148 patients were included as inclusion and exclusion criteria. Results: Out of 148 patients 58.10% (86) and 41.89% (62) were male and female respectively. The commonest age group of patients was 21 to 30 years. Fever was the most common (81.75%) symptom and eschar (skin lesion) was seen in 16.21% (24) patients. Conclusion: Scrub typhus is an important cause of undifferentiated acute febrile illness should be considered in the differential diagnosis of pyrexia of unknown. Adequate knowledge about demographic and clinical profile scrub typhus helps in early diagnosis.

Epidemiological, clinical and genetic characterization of scrub typhus in patients presenting with acute febrile illness in New Delhi

PurposeScrub typhus (ST) is a zoonotic disease, caused by O. tsutsugamushi is a major cause of acute febrile illness (AFI) in India. There is a need to study the prevalence and risk factors in various regions of India. MethodsA study to estimate the prevalence and study the risk factors of ST in patients presenting with acute febrile illness (AFI) was performed. All patients underwent serology for IgM antibodies to Orientia tsutsugamushi (In Bios International Inc, Seattle, WA) as per the manufacturers’ protocol. Following this, Polymerase Chain reaction (PCR) (real time SYBR green based targeting groEL gene and conventional PCR targeting 56 ​kDa type specific antigen gene) was performed from stored serum samples. ResultsDuring the study period, 473 patients were admitted. Of these 56 (11.8%) patients were ST positive by IgM serology. The conventional PCR targeting 56 ​kDa type specific antigen gene of O. tsutsugamushi was positive in six patients while Ot groEL SYBR green based PCR) was positive in five. PCR was positive in patients who had demonstrated a higher OD value in ELISA. Conventional PCR positive amplicons were sent for Sanger sequencing and confirmed to be O. tsutsugamushi. The mean age of the patients was 49 ​± ​18.3 years and males constituted a higher number of patients (67.9%, n ​= ​38). The pathognomonic eschar was present in 7 (12.5%) patients. Phylogenetic analysis revealed that sequences clustered close to Kato-like Hualein-20 strain and Karp-like Linh DT strains. All patients were administered doxycycline in our study. Mortality was recorded in 8.9% of the patients. ConclusionsIn patients presenting with acute febrile illness, ST should be considered as a differential diagnosis, especially in post-monsoon season. Along with serology, serum can also be used as sample for PCR in an intracellular bacterium like O. tsutsugamushi.

CLINICAL CHARACTERISTICS, MANAGEMENT PRACTICES AND IN-HOSPITAL OUTCOMES OF SCRUB TYPHUS PATIENTS IN A TERTIARY CARE CENTER IN THE NORTH EASTERN STATE, TRIPURA

Background- With the changing epidemiology, scrub typhus is now among the commonest causes of AFI in India and a high suspicion should be maintained, and an early diagnosis and promt management is warranted to prevent complications. Objective - Clinical characteristics, management practices and in-hospital outcomes of scrub typhus patients. Methods- a Cross-sectional retrospective study was conducted among 110 scrub typhus patients attending Agartala Government Medical College and GB Pant Hospital, a tertiary care centre of Tripura in last one year period. Their clinical profile, laboratory studies and management has been recorded and data has been evaluated with SPSS 21.0 for windows with p- value <0.05. Results- the commonest presenting symptoms of scrub typhus are high-grade fever with chills , headache and it most commonly effects farmers. Most commonly effected age group was 40-50 years of age. Most of the patients were from West Tripura followed by Khowai Tripura and least patients were from North Tripura. Predominately it occured in September, October and November i.e. in post monsoon period. The pathognomonic eschar was present in 43% patients and rarest presentation was paraparesis (0.9%). Lymphadenopathy (9%), neck rigidity (6%), hepatomegaly (10%), splenomegaly (4%), acute respiratory distress syndrome was seen in 14% patients. Hepatic involvement was the most common complication seen in our study (42%). Anemia was present in 25% and thrombocytopenia was present in 22% patients. Subside of fever to doxycycline injection seen in 73% on day1 and 84% on day2. 19% Patient required icu admission. 9% developed ARDS and 6% required ET tube intubation and mechanical ventilation. 6% developed hypotension requiring inotropic support. 4% developed severe thrombocytopenia(<10,000) required platelet transfusion. 11% developed acute kidney injury requiring haemodialysis. Survival rate were 93% and mortality 7%. In conclusion, scrub typhus became the leading infectious cause of acute febrile illness in North eastern state, Tripura. A high suspicion should be maintained, and an early diagnosis and promt management is warranted to prevent mortality and morbidity of patients.

Neurological Manifestations of Scrub Typhus.

The occurrence of cases of scrub typhus is on the rise in South Asian and Southeast Asian countries. The present review discusses neurological complications following scrub typhus to appraise clinicians practicing in endemic regions about considering this treatable disease in the differential diagnosis of acute febrile illnesses, especially when accompanied with clinical neurological features. While the association of aseptic meningitis, encephalitis, and meningoencephalitis with scrub typhus is well known, more recently described neurological syndromes associated with scrub typhus include acute disseminated encephalomyelitis, various cranial nerve palsies, cerebellitis, cerebrovascular diseases including cerebral venous sinus thrombosis, transverse myelitis, longitudinally extensive transverse myelitis, Guillain-Barré syndrome, opsoclonus-myoclonus syndrome, parkinsonism, and many more. Early diagnosis is key to successful treatment. While diagnostic confirmation is generally made by the detection of IgM antibody by either ELISA or indirect fluorescent antibody tests, conventional PCR using 56kDa gene (cPCR) and loop-mediated isothermal amplification assay (LAMP assay), as well as a newly introduced metagenomic next-generation sequencing (mNGS), are currently available for detection of Orientia tsutsugamushi infection in clinically suspected cases. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The cutaneous hallmark of the disease is the "eschar." Scrub typhus results in multisystem involvement. Neurological compromise is present in about 20% of scrub typhus patients and affects both the central nervous system and the peripheral nervous system. The postulated underlying mechanisms include direct invasion of the organism, a vasculitis-like process, or an immune-mediated injury. Diagnosis of scrub typhus is confirmed by detection of O. tsutsugamushiIgM antibody in serum. Awareness among clinicians regarding the varied presentations of this disease is very important in order to reduce morbidity and mortality. Co-infection with dengue and/or chickungunya viruses may occur in endemic regions. The history of an acute febrile illness preceding the neurological illness is crucial. A very careful search for the eschar is essential; however, the absence of the skin lesion cannot exclude the diagnosis of scrub typhus. Neurological manifestations mostly respond to doxycycline therapy.

Scrub Typhus in Intensive Care Unit in Kathmandu – A case series from a tertiary center

Scrub typhus is a rickettsial zoonosis caused by Orientia tsutsugamushi which can cause focal or disseminated vasculitis & perivasculitis in various body systems. It is endemic in many parts of Nepal & has been neglected & under-detected. We clinically assessed six patients from a intensive care unit in a tertiary hospital in Nepal that tested positive for scrub typhus using IgM ELISA & analyzed their profiles.
 Out of six patients, three were male & three were female with a mean age of 44.6 years. All six patients had chief complaints of fever & myalgia. Four patients presented with eschar. Three patients presented with septic shock while one presented with septicemia and meningoencephalitis. Only one patient had elevated white cell counts. Four out of six patients had transaminitis. Thrombocytopenia was present in two patients. Hypoalbuminemia was present in three patients. All cases tested negative for dengue, malaria, brucella, Leptospira, leishmania, salmonella & tuberculosis.
 This study points out the need for raising the index of suspicion & early screening of scrub typhus in patients with fever & laboratory findings of liver dysfunction or thrombocytopenia even with normal white cell counts.

Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study’s scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.’s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.

Development of paper-based DNA sensor for detection of O. tsutsugamushi using sustainable GQDs@AuNPs nanocomposite

The graphene quantum dots (GQDs) was synthesized using potato starch and water by hydrothermal method and further used for reduction of tetracholoroauric acid to form graphene quantum dots-gold (GQDs@AuNPs) nanocomposite. The GQDs/GQDs@AuNPs were analyzed using FTIR, UV–Vis, Flourometry and HR-TEM. The synthesized GQDs@AuNPs were further used for fabrication of cost-effective screen-printed paper electrode (SPPE) based DNA sensor for the detection of O. tsutsugamushi using htrA gene specific 5′NH2 linked DNA probe. Modification of SPPE using GQDs@AuNPs nanocomposite and ssDNA probe was monitored using EIS, FTIR, FE-SEM and AFM. The sensor detection limit (LOD) was assessed as 0.002 ng/μl from the standard calibration curve with the correlation coefficient, R2 = 0.993. The sensitivity of the DNA sensor was calculated as 7700 μA/cm2/ng for ssGDNA of O. tsutsugamushi using cyclic voltammetry. The sensor validation was done using scrub typhus patient's blood DNA samples. The sensor showed good storage stability at 4 °C for six months with just a loss of 12% of the initial current values. The SPPE/DNA sensor developed is very specific, sensitive, stable and detects O. tsutsugamushi in less time.

Acute renal failure in scrub typhus patients

Scrub typhus, a bacterial infection caused by Orientia Tsutsugamushi (formally Rickettsia) due to bite of the mite, and is increasing every year, and becomes a important cause of acute febrile illnesses. Due to lack of specific diagnostic facilities in most rural setups and non-specific clinical presentations, it becomes a challenge for clinician to correctly diagnose it on clinical examination. Clinically it presents with non-specific febrile illnesses with constitutional symptoms such as fever, rash, myalgia and headache or with organ dysfunction involving kidneys, lungs, liver, central nervous system or with circulatory collapse with hemorrhagic features. Eschar is the characteristic lesion which is present at the bite site of mite. Later an ulcer with black necrotic centre and regional lymphadenopathy occurs. Renal involvement in the form of Acute Renal Failure is seen very occasionally in these patients. So this Case-control study is designed for a period of six months which are october-2018 to march-2019, comparing 80 ELISA(Enzyme Linked Immune Sorbent Assay) confirmed cases of scrub typhus and 50 healthy controls. Statistically significant difference in Urea, Creatinine and Uric acid levels were found between two groups, using 't'-test with the significance value of P<0.0001.

An unusual presentation of scrub typhus in a child: a case report

BackgroundScrub Typhus (ST) is an acute, febrile zoonotic disease caused by the bacterium Orientia tsutsugamushi which is endemic to the Asia-Pacific region. Infected adults rarely present with sensorineural hearing loss and otalgia. Though few cases of pediatric cases are known to present with otalgia, no pediatric cases of sensorineural deafness complicating ST have been reported to date.Case presentationA 5-year-old, previously healthy girl presented with a one-week history of high-grade intermittent fever, Headache and right ear pain with a recent onset of reduced hearing. She had a fever up to 39 °C, cervical lymphadenopathy, bilateral pleural effusion with diffuse infiltrations, and mild hepatosplenomegaly with no evidence of rash. Her initial examination was normal except for mildly enlarged tonsils. Unilateral right ear hearing loss was noted using Weber’s test. Evidence of progressive, mild anemia, and raised inflammatory markers was noted. Diagnosis of scrub typhus was confirmed by positive detection of Orentia tsutsugamushi IgM antibodies on rapid diagnostic test and the presence of chigger mite in the right external auditory canal on repeat examination. She responded dramatically to the empirical treatment of ceftriaxone and doxycycline. On follow-up, she did not have any residual hearing loss and her ear pain had resolved completely.ConclusionAcute onset hearing loss or severe otalgia with or without findings should be an important diagnostic clue for suspecting scrub typhus in patients who present with a history of fever especially in endemic areas.

Study of Clinical Profile and Treatment Pattern of Scrub Typhus Patients in Tertiary Care Hospital

Objectives: To assess the clinical features, complications and treatment of scrub typhus patients in tertiary care hospital. Material and Methods: A total of 100 patients with scrub typhus, aged >12 years admitted in medicine wards and intensive care units of Government Medical College, Nagpur, were included in the study. A detailed history was taken; clinical examination, all relevant investigations, and IgM ELISA test were done for the diagnosis of scrub typhus. Results: The most common presenting symptoms were high-grade fever with chills (80%). The most common complication was lung involvement (35%), liver damage (28%), and acute kidney injury (27%) with six cases requiring renal replacement therapy. Multisystem organ dysfunction syndrome was seen in 19% of cases. About 27% of patients had acute respiratory distress syndrome of which 16 cases needed mechanical ventilation. Of 100 patients included, 82 (82%) cases survived and were discharged, while 18 (18%) patients succumbed during hospital admission. Among the risk factor studied, systemic hypertension was associated with an increase in mortality (P = 0.014). There was a statistically significant increase in mortality (P = 0.006) in patients having electrocardiogram abnormalities in the forms of low-voltage complexes and tachycardia. Early diagnosis and rapid treatment with doxycycline (93.90%) and ceftriaxone (87.80%) were found to be associated with more survival rate. Conclusion: Scrub typhus is a significant disease in this part of the country; therefore, it should be kept in mind as a possible diagnosis in undifferentiated fevers even though an eschar is not found. An early diagnosis and timely antibiotic therapy may prevent further complications.

Unraveling scrub encephalitis: A study on the clinical profile and investigations of scrub encephalitis

Introduction: Scrub encephalitis (SE) is one of the known causes of acute encephalitis syndrome (AES). Although central nervous system involvement is known in scrub typhus, its association with AES is less understood and lesser diagnosed. In the absence of a point of care test for scrub typhus, cases of SE can be easily missed. A clinical approach using detailed history and clinical profiling of SE will help to diagnose SE in our region, using minimum resources, within a reasonable period. Aims: To analyze the clinical spectrum in patients of SE and to evaluate the investigations required to diagnose SE. Methodology: This is a retrospective study that analyzed Scrub typhus patients over 2 years from January 2018 to December 2019. A total of 370 patients were screened and 23 patients who satisfied the study criteria were included in the study and analyzed. Results: Among the cases of scrub typhus admitted in the hospital, the prevalence of SE was 6%. The most common presenting complaint was fever in 21 patients (91%) followed by altered sensorium in 16 (70%) and seizures in 9 patients (39%). An eschar was noted in 66% of the cases. The mean Glasgow Coma scale was 11 among the cases with almost 70% of cases showing signs of meningeal irritation. Organ involvement was noted as thrombocytopenia in 21 patients (91%), 16 patients (69%) with jaundice, and 1 (4%) with acute kidney injury. Conclusion: SE is an AES which, if detected early, is easily treatable with no residual neurological sequelae. Hence, identification of this condition and prompt diagnosis of SE becomes crucial to the management of this complication of scrub typhus.

A clinico-epidemiological profile of scrub typhus cases admitted in a tertiary hospital in South India

Scrub typhus (ST) is a consistently underreported disease. The disease is spreading to newer areas, and an understanding of disease epidemiology is needed in the local Indian and current context. This study describes the demographic characteristics, monthly distribution, clinical and laboratory presentations, and treatment outcome of the ST cases recently identified. Case sheets of 15 ST patients diagnosed from January 2019 to December 2020 were analyzed. The majority of the patients were male. Eighty percent of the patients were from rural or suburban areas. Higher admission was observed from September to December. Fever (100%), skin rash (73.3%), body ache (53.3%), and vomiting (53.3%) were the most common clinical features. The onset of fever till the appearance of skin rash was 3 ± 1.2 days. The mean day from onset of symptoms till diagnosis was 6.8 ± 3.9 days. Eschar was found in only two patients. Nine (60%) patients already had complications at the time of admission. Most patients presented a laboratory picture of thrombocytopenia, neutrophilic leukocytosis, and anemia. Complications such as septic shock, acute kidney injury, and hepatic involvement were observed. All responded to doxycycline within 48 h. No fatalities were observed. Early clinical suspicion of ST among those with high fever, skin rash and thrombocytopenia, and transaminitis showed positive clinical outcome.

Seroprevalence of Scrub Typhus in Patients Attending Dhulikhel Hospital, Kavre

Background Scrub typhus is a largely ignored tropical disease and a leading cause of undifferentiated febrile illness. It is caused by Orientia tsutsugamushi. Scrub Typhus is frequently observed in South Asian countries. However, clear epidemiological information of this disease is lacking in case of Nepal. Nepal has shown steady increase in cases of Scrub Typhus since 2015. The epidemiological data related to this disease would support the decision making and surveillance design for early outbreak detection and immediate responses including prevention and treatment of scrub typhus in Nepal.
 Objective To understand prevalence of Scrub Typhus in subjects who had visited outpatient department at Dhulikhel Hospital.
 Method In this study, we have studied antibody test data (n=784) for Scrub Typhus from 2019 to 2021. The tests were performed on serum samples of patients who had visited OPD at Dhulikhel Hospital with fever lasting more than 5 days. The kit used in analysis was Scrub Typhus Detect™ IgM ELISA Kit from InBios International.
 Result Out of the total subjects (n=784), 133 were positive (16.9%) for IgM antibody of Scrub Typhus. The positivity in female (18.6%) was higher than the male subjects (15.3%). The positivity rate was variable among the different age groups, with highest positivity for age group 0-14 years (25%). The seasonal variation was also observed among the seropositive cases.
 Conclusion Scrub Typhus being a neglected tropical disease has high prevalence. It can be postulated that female subjects and subjects of age group 0-14 years are vulnerable to the infection with Scrub Typhus. There is need to increase the surveillance of Scrub Typhus to add the knowledge for diagnosis and treatment.

Demographic variables and clinical profile of scrub typhus patients: experience from a tertiary care center in Udaipur, Rajasthan

Background: Scrub typhus is an acute febrile bacterial zoonoses, caused by Orientia tsutsugamushi and is associated with a range of complications, including sepsis, Acute respiratory distress syndrome (ARDS), pre-renal azotemia and Multiorgan dysfunction syndrome (MODS). The objective of this study was to study the demographic variables and clinical profile of the patients diagnosed with scrub typhus. admitted in a tertiary care hospital in Udaipur, Rajasthan.Methods: It was a longitudinal, observational study, conducted in a tertiary care centre in Udaipur, Rajasthan from January 2020-June 2021. All patients, diagnosed (positive for antibody IgM) with scrub typhus in the hospital during the study period were included in the study. Information about the patients was collected using a pre-tested questionnaire and clinical examination, after taking the informed consent from the study participants.Results: Mean age of the patients was 36.4±19 years. Majority (69.4%) of the patients were from rural area and fever was the most common (83.9%) symptom experienced. Eschar was found in only 1.6% of patients. About 87.1% of the patients had complications, with MODS, being the most common affecting about 34% of the total patients. The patients from rural areas were found to have significantly higher odds (OR=1.61) of having complications as compared to urban area patients (CI=1.09-4.3). Conclusions: This article draws attention to the fact that scrub typhus is quite on rise and most of the cases are associated with complications. There is a need to develop effective strategies and interventions to stop this rampant rise of the cases in India.

A Prospective Study in Scrub Typhus Patients with Cardiac Manifestationsin- A Tertiary Care Center

A Prospective Study in Scrub Typhus Patients with Cardiac Manifestationsin- A Tertiary Care Center

The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing.

Introduction: Scrub typhus is a mite-borne infection widespread in Southeast Asia, with clinical symptoms such as fever, chills, skin rash, eschar at the bite site, and other signs of acute febrile illness. The Rickettsia pathogen (Orientia tsutsugamushi) is always difficult to be diagnosed at an early stage by traditional clinical diagnostic methods, especially for patients without typical eschar. This greatly increases the mortality of patients with scrub typhus. A new approach should be introduced to improve its clinical diagnosis.Methods: During May 2018 to March 2021, 13 samples from 10 patients with suspected scrub typhus were collected. Metagenomic next-generation sequencing (mNGS) and other diagnostic methods (including serology using Weil–Felix reaction and indirect immunofluorescence test (IIFT) for scrub typhus and respiratory tract profile IgM as well as culture for routine bacteria) were used to identify the pathogens in this study.Results: The results of mNGS were all positive, with mapped reads of O. tsutsugamushi ranging from 1 to 460. Eight patients (80%) were diagnosed as scrub typhus. The other two were diagnosed as suspected scrub typhus due to the limited number of reads of the pathogen (one and two, respectively). According to clinical evidences, nine of the 10 patients were finally diagnosed as scrub typhus, except for patient 9 (suspected scrub typhus by mNGS with one specific reads of the pathogen) diagnosed as acute exacerbation of chronic obstructive pulmonary disease. For the five scrub typhus patients without typical eschar, mNGS gave all positive results (4–460 specific reads). For other methods, only Weil–Felix reaction of one patient detected the pathogen. In addition, the respiratory tract profile (IgM) detected various pathogens, but all were confirmed to be false positive.Conclusions: mNGS performed better than conventional clinical methods to early diagnose scrub typhus. This approach can be routinely carried out for early and precise diagnosis in clinical infections, especially for those hard to be identified by traditional diagnostic methods.

Systematic review of the scrub typhus treatment landscape: Assessing the feasibility of an individual participant-level data (IPD) platform.

BackgroundScrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions.Methodology/principal findingsWe conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology.Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women.Conclusions/significanceThere were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.

Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal Orientia tsutsugamushi Transmission Time by Leptotrombidiumchiangraiensis Chiggers.

Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, Orientia tsutsugamushi-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated O. tsutsugamushi in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit O. tsutsugamushi to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host’s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of O. tsutsugamushi within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that O. tsutsugamushi infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia.