Estimation of scrub typhus incidence and spatiotemporal multicomponent characteristics from 2016 to 2023 in Zhejiang Province, China.

Background: China is one of the main epidemic areas of scrub typhus, and Zhejiang Province, which is located in the coastal area of southeastern China, is considered a key region of scrub typhus. However, there may be significant bias in the number of reported cases of scrub typhus, to the extent that its epidemiological patterns are not clearly understood. The purpose of this study was to estimate the possible incidence of scrub typhus and to identify the main driving components affecting the occurrence of scrub typhus at the county level. Methods: Data on patients with scrub typhus diagnosed at medical institutions between January 2016 and December 2023 were collected from the China Disease Control and Prevention Information System (CDCPIS). The kriging interpolation method was used to estimate the possible incidence of scrub typhus. Additionally, a multivariate time series model was applied to identify the main driving components affecting the occurrence of scrub typhus in different regions. Results: From January 2016 to September 2023, 2,678 cases of scrub typhus were reported in Zhejiang Province, including 1 case of reported death, with an overall case fatality rate of 0.04%. The seasonal characteristics of scrub typhus in Zhejiang Province followed an annual single peak model, and the months of peak onset in different cities were different. The estimated area with case occurrence was relatively wider. There were 41 counties in Zhejiang Province with an annual reported case count of less than 1, while from the estimated annual incidence, the number of counties with less than 1 case decreased to 21. The average annual number of cases in most regions fluctuated between 0 and 15. The numbers of cases in the central urban area of Hangzhou city, Jiaxin city and Huzhou city did not exceed 5. The estimated random effect variance parameters σ λ 2 , σ ϕ 2 , and σ ν 2 were 0.48, 1.03 and 3.48, respectively. The endemic component values of the top 10 counties were Shuichang, Cangnan, Chun'an, Xinchang, Pingyang, Xianju, Longquan, Dongyang, Yueqing and Qingyuan. The spatiotemporal component values of the top 10 counties were Pujiang, Anji, Pan'an, Dongyang, Jinyun, Ninghai, Yongjia, Xiaoshan, Yinwu and Shengzhou. The autoregressive component values of the top 10 counties were Lin'an, Cangnan, Chun'an, Yiwu, Pujiang, Longquan, Xinchang, Luqiao, Sanmen and Fuyang. Conclusion: The estimated incidence was higher than the current reported number of cases, and the possible impact area of the epidemic was also wider than the areas with reported cases. The main driving factors of the scrub typhus epidemic in Zhejiang included endemic components such as natural factors, but there was significant heterogeneity in the composition of driving factors in different regions. Some regions were driven by spatiotemporal spread across regions, and the time autoregressive effect in individual regions could not be ignored. These results that monitoring of cases, vectors, and pathogens of scrub typhus should be strengthened. Furthermore, each region should take targeted prevention and control measures based on the main driving factors of the local epidemic to improve the accuracy of prevention and control.

Unveiling the burden of scrub typhus in acute febrile illness cases across India: A systematic review & meta-analysis.

Background & objectives Scrub typhus is an emerging mite-borne zoonotic infection that has been overlooked, despite being one of the most widespread severe vector-borne diseases. With an estimated one billion people at risk worldwide and one million annual cases, it poses a significant public health concern. While various studies have investigated the prevalence of scrub typhus in different regions of India, a comprehensive regional systematic review and meta-analysis on the seropositivity of scrub typhus among acute febrile cases has been lacking. To address this gap, we conducted a systematic review and meta-analysis to compile information on the current seroprevalence of scrub typhus in acute febrile illness cases in India. Methods A literature search of multiple databases on prevalence of scrub typhus in acute febrile illness in India, 60 eligible studies out of 573 studies. The prevalence of individual studies was double arcsine transformed, and the pooled prevalence was calculated using inverse variance method. Results In total, these studies encompassed 34,492 febrile cases. The overall seroprevalence of scrub typhus among acute febrile illness cases in India was found to be 26.41 per cent [95% confidence interval (CI): 22.03-31.03]. Additionally, the pooled case fatality rate (based on data from six studies) among scrub typhus-positive cases yielded a case fatality rate of 7.69 per cent (95% CI: 4.37-11.72). Interpretation & conclusions This meta-analysis shows that scrub typhus is a significant health threat in India. Preventive measures to control scrub typhus need to be given priority.

Usefulness of next-generation sequencing for laboratory diagnosis of rickettsiosis.

Rickettsiosis includes a diversity of culture-negative non-specific systemic infections. Laboratory diagnosis of rickettsiosis is often not easy. In this 12-month study, six patients with a variety of rickettsia infections of the spotted fever group, typhus group and scrub typhus were diagnosed directly or indirectly by metagenomic next-generation sequencing (mNGS). The patient with Japanese spotted fever was rapidly made when mNGS analysis of the patient's blood revealed Rickettsia japonica sequences. For the two patients with Rickettsia felis chest infections, the bacterium was detected in the bronchoalveolar lavage of one case and lung biopsy of the other. Both patients had underlying malignancies, carcinoma of the breast and carcinoma of the lung respectively, and were on chemotherapy with immunosuppressive effect. For the remaining three patients who presented over a period of 13 weeks, all had fever, headache and the typical eschar. They also had increased serum transaminases and responded promptly to doxycycline. However, the Weil-Felix test results of all three patients were negative. Since we considered the three cases typical of rickettsiosis, we submitted their serum samples for mNGS analysis. Results showed that Orientia tsutsugamushi sequences were present in the serum of one case. In view of the positive mNGS results, we repeated the Weil-Felix test for the residual sera of all three patients and it revealed that those of the other two cases showed OX-19 titers of 1:640 and 1:160 respectively, inferring that these two patients probably had rickettsiosis of the typhus group. As for the patient positive for O. tsutsugamushi sequences, we also detected IgM for O. tsutsugamushi in the serum, which double confirmed that it was a case of scrub typhus. mNGS is an important molecular tool and can complement serology for laboratory diagnosis of rickettsiosis.

Scrub typhus meningoencephalitis in children: an experience from Eastern India.

Scrub typhus meningoencephalitis (STME) is an uncommon but fatal complication of scrub typhus that requires extra diligence in early identification and treatment. The goal of this study was to look at the clinical characteristics, laboratory results, and outcome of STME in children. A retrospective study was conducted in the paediatric intensive care unit of a tertiary care hospital in Eastern India between April 2021 and September 2022. It was carried out in children aged 1 month-12 years. Sixteen children were diagnosed with STME out of 75 acute encephalitis syndrome (AES) cases. The male-to-female ratio was 3:1, with a mean age of 4.28 ± 3.36 years. All the children hailed from rural areas. Fever (100%), convulsions (87.5), altered sensorium (93.75%), nuchal stiffness (25%), vomiting (75%), pallor (75%), and hepatomegaly (50%) were the most prevalent clinical manifestations. The average duration of fever upon presentation was 8.25 ± 2.11 days and the average length of hospital stay was 9.00 ± 4.59 days. The complications encountered were shock (3), interstitial pneumonia (1), myocarditis (1), raised intracranial pressure (1), and right-sided hemiplegia (1). Fifteen children recovered completely, whereas one child suffered from residual right-sided neurodeficit. A high index of suspicion needs to be maintained for STME as a possible AES entity, as anti-scrub measures administered promptly can go a long way in mitigating the related morbidity and mortality especially in resource-constrained settings.

Prevalence, Clinico-Laboratory Features and Outcomes of Paediatric Scrub Typhus Cases in a Tertiary Care Centre in Eastern India: A prospective observational study.

Objectives: Scrub typhus is the most common rickettsial disease in India, caused by Orientia tsutsugamushi and transmitted by chigger mites. Previously prevalent in South India, a resurgence of scrub typhus cases has recently affected Eastern India. This study aimed to estimate the prevalence and describe the clinico-laboratory profile of scrub typhus in paediatric patients (1-12 years old) living in Eastern India. Methods: This prospective observational study was conducted from January to December 2019 at the Dr B C Roy Post Graduate Institute of Paediatric Sciences, Kolkata, India. All acute undifferentiated cases of febrile illness, in patients aged between 1-12 years, were tested using scrub typhus serology by ELISA. Demographic details, clinical features, laboratory findings, complications and treatment outcomes of these scrub typhus patients were extracted and analysed. Results: Out of 1,473 patients with acute febrile illness, 67 (4.5%) children were diagnosed with scrub typhus. The mean age of the selected patients was 5.22 ± 3.05 years, and the majority (64.2%) had been running a fever since the preceding 7-14 days. Gastrointestinal symptoms such as vomiting (43.3%) and abdominal pain (32.8%) were most frequently observed. Major clinical signs of scrub typhus were hepatomegaly (41.8%) and splenomegaly (31.3%). Complications were observed in 74.6% of patients, with thrombocytopenia (40.3%) and meningoencephalitis (29.9%) occurring more frequently. The case fatality rate of the study sample was 1.5%. Conclusion: Classical eschar was absent in three-fourth of the studied patients. Hence, this study advocates laboratory scrub typhus tests for all suspected cases in the endemic region (Eastern India). Prompt treatment with doxycycline and/or azithromycin could prevent complications such as thrombocytopenia/meningoencephalitis and reduce mortality.

Two complicated cases of severe scrub typhus, eschar- a non-negligible sign: Case reports and literature review.

RATIONALE: Scrub typhus is a mite-borne, acute febrile disease caused by Orientia tsutsugamushi. The endemic areas of scrub typhus are expanding, both globally and in China. Patients who are not treated promptly, are likely to die of multiple organ dysfunction syndrome. PATIENT CONCERNS: Case I A 61-year-old female patient complained of sudden chest tightness and shortness of breath accompanied by fever for 6 days. Case II A 54-year-old male patient complained of fever and cough for 4 days and renal insufficiency for 2 days. DIAGNOSES: Scrub typhus, multiple organ dysfunction syndrome. INTERVENTIONS: After the definite diagnosis, both patients were treated with doxycycline and various organ supports. OUTCOMES: The patient in case I was ultimately not salvageable. The patient in case II was successfully cured by the prompt administration of doxycycline along with continuous renal replacement therapy. LESSONS: With early diagnosis and treatment, patients can completely recover. Eschar, a characteristic sign of scrub typhus, is often overlooked, leading to delayed diagnosis and regrettable outcomes.

Changes in seasonality and sex ratio of scrub typhus: a case study of South Korea from 2003 to 2019 based on wavelet transform analysis.

BACKGROUND: Scrub typhus (ST, also known as tsutsugamushi disease) is a common febrile vector-borne disease in South Korea and commonly known as autumn- and female-dominant disease. Although understanding changes in seasonality and sex differences in ST is essential for preparing health interventions, previous studies have not dealt with variations in periodicity and demographic characteristics in detail. Therefore, we aimed to quantify the temporal dynamics of seasonal patterns and sex differences in the incidence of ST in South Korea. METHODS: We extracted epidemiological week (epi-week)-based ST cases from 2003 to 2019 Korean National Health Insurance Service data (ICD-10-CM code: A75.3). To determine changes in seasonality and sex differences, year-, sex-, and age-group-stratified male-to-female ratios and wavelet transform analyses were conducted. RESULTS: Between 2003 and 2019, 213,976 ST cases were identified. The incidence per 100,000 population increased by 408.8% from 9.1 in 2003 to 37.2 in 2012, and subsequently decreased by 59.7% from 2012 to 15.0 in 2019. According to the continuous wavelet transform results, ST exhibited a dual seasonal pattern with dominant seasonality in autumn and smaller seasonality in spring from 2005 to 2019. Overall, the periodicity of seasonality decreased, whereas its strength decreased in autumn and increased in spring. With an overall male-to-female ratio being 0.68:1, the ratio has increased from 0.67:1 in 2003 to 0.78:1 in 2019 (Kendall's τ = 0.706, p < 0.001). However, interestingly, the ratio varied significantly across different age groups. CONCLUSIONS: Our findings quantitatively demonstrated changes in seasonality with dual seasonal pattern and shortened overall periodicity and a decrease in sex differences of ST in South Korea. Our study suggests the need for continuous surveillance on populations of vector and host to address ST dynamics to preemptively prepare against global warming.

Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression.

How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacterium Orientia tsutsugamushi uses its effector protein, Ank5, to inhibit nuclear translocation of the MHC class I gene transactivator, NLRC5, and orchestrate its proteasomal degradation. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of NLRC5 in the leucine-rich repeat region that dictates susceptibility to Orientia- and Ank5-mediated degradation. The ability of O. tsutsugamushi strains to degrade NLRC5 correlates with ank5 genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator during Orientia infection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and reduce surface MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression.

Tick-borne pathogens isolated from ticks, rodents, and a shrew in Gangwon and Gyeonggi provinces in the Republic of Korea.

The prevalence of tick-borne pathogens (TBP), Orientia tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals, namely wild rodents, is now widely investigated. This study is to present the prevalence and distribution of O. tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals and ticks collected from Gyeonggi and Gangwon provinces, Republic of Korea (ROK) in 2014. A total of 131 wild small animals, rodents and shrews, and 2,954 ticks were collected from Gyeonggi and Gangwon provinces from May to November 2014. The wild small animals (KR1-9) and ticks (K1-17) were grouped in accordance with capture dates and locations. Among the wild small animals, a total of 393 tissues and blood samples were extracted from six selected small animal series (KR1-3, KR6-8). Also, each date and location-grouped ticks were identified for its species and pooled according to the stage of development. Molecular identification for Rickettsia, Orientia, and Borrelia species was performed using polymerase chain reaction (PCR). To detect TBPs among wild small animals and ticks, primer sets targeting the 56 kDa protein encoding gene of Orientia spp., outer membrane protein B gene (OmpB) of Rickettsia spp., and 5S-23S intergenic spacer region (IGS) gene of Borrelia spp. were used. Of the 393 wild small animals' blood and tissue samples, 199 (50.6%) were positive for Orientia spp., 158 (40.2%) were positive for Borrelia spp., and 55 (14.0%) were positive for Rickettsia spp. Moreover, a total of 14 tick pools (n = 377) was positive for Rickettsia spp. (n=128, 34.0%) and Borrelia spp. (n=33, 8.8%). High prevalence of Orientia spp. and Rickettsia spp. in rodents and shrews were observed. This study presents significant insights by presenting data collected in 2014 that the prevalence of TBP was already high in mid 2010s. This study highlights the sustainable routine surveillance model for TBP.

Scrub typhus with hemorrhagic stroke: a case report.

BACKGROUND: Scrub typhus, caused by Orientia tsutsugamushi, rarely leads to central nervous system involvement. Although intracerebral bleeding is rare due to endemicity and a significant proportion of underdiagnoses, it should be considered a noteworthy differential diagnosis in endemic regions in patients with relevant history and clinical findings. CASE PRESENTATION: We present the case of a 40-year-old Nepali woman who visited the emergency department with complaints of left-sided weakness for 6 hours and an acute febrile illness with an eschar for 7 days and was diagnosed with scrub typhus by immunoglobulin M enzyme-linked immunosorbent assay of the serum. Imaging revealed a right-sided frontotemporal hematoma, and further examination revealed pulmonary edema with multiple organ dysfunction syndrome. The patient was mechanically ventilated and was treated with antibiotics, steroids, vasopressors, and antipyretics. However, the hematoma was treated conservatively, with ongoing neurological recovery at the 6-month follow-up. CONCLUSION: Although neurological complications and intracranial hemorrhage are uncommon, physicians must be cautious when making differential diagnoses and initiating appropriate therapies to avoid serious or fatal complications.

Acute intravascular haemolysis associated with scrub typhus.

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.

Comparative analysis of F-18 FDG PET/CT images between scrub typhus and systemic lupus erythematosus.

This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions.

Flea-Borne Rickettsioses and Scrub Typhus in Patients with Suspected Arbovirus Infection in Bangkok, Thailand.

Background: In urban Thailand, arboviral infections dominate diagnoses of acute undifferentiated fevers (AUFs) owing to their well-defined epidemiology and characteristic clinical presentations. However, rickettsial diseases, also endemic in this setting, remain under-recognized owing to challenges in early detection. Objective: This study aimed to identify potential rickettsial infections among patients with AUF in Bangkok and vicinity utilizing leftover nucleic acid extracted from serum samples from patients initially suspected of but negative for arbovirus infections. Materials and Methods: A total of 609 nucleic acid samples were screened for rickettsial bacteria using real-time PCR, targeting the 17-kDa common antigen gene of Rickettsia spp. and the 47-kDa gene of Orientia tsutsugamushi. Results: Nine samples were positive for Rickettsia spp. and two were positive for O. tsutsugamushi. DNA sequence and phylogenetic analyses based on partial 17-kDa antigen and citrate synthase (gltA) genes identified the Rickettsia-positive samples as R. typhi in eight cases and R. felis in one case. Analysis of the 56-kDa type-specific antigen gene identified the two O. tsutsugamushi isolates as Gilliam-related genotypes. Although rickettsial diseases typically present with mild symptoms, two patients with R. typhi infection (murine typhus) developed respiratory distress syndrome, highlighting the potential for rare but serious complications. Conclusion: This study underscores the critical importance of differential diagnosis and prompt, effective intervention to prevent complications in suspected cases.

Global and regional seroprevalence, incidence, mortality of, and risk factors for scrub typhus: A systematic review and meta-analysis.

OBJECTIVES: Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. We aimed to provide the first comprehensive review on the seroprevalence, incidence, mortality of and risk factors for scrub typhus. METHODS: We searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases. Trended incidence and median mortality were calculated and pooled seroprevalence and risk factors for scrub typhus were evaluated using the random-effects meta-analysis. RESULTS: We included 663 articles from 29 countries/regions. The pooled seroprevalence was 10.73% (95%CI 9.47-12.13%) among healthy individuals and 22.58% (95%CI: 20.55%-24.76%) among febrile patients. Mainland China reported the highest number of cases and South Korea and Thailand had the highest incidence rates. Median mortalities were 5.00% (range: 0.00-56.00%) among hospital inpatients, 6.70% (range: 0.00-33.33%) among patients without specified admission status and 2.17% (range: 0.00-22.22%) among outpatients. The significant risk factors included agricultural work, specific vegetation exposure, other outdoor activities, risky personal health habits, and proximity to rodents, livestock, or poultry. CONCLUSIONS: Our comprehensive review elucidates the significant yet variable burden of scrub typhus across different regions, underscoring its emergence as a critical public health concern globally.

The Spectrum of Neurological Manifestations in Scrub Typhus.

BACKGROUND: Scrub typhus is a mite-borne zoonotic disease caused by Orientia tsutsugamushi and commonly presents with fever, rash, and eschar. Systemic complications develop later in the illness including, meningoencephalitis, pericardial effusion, myocarditis, and pneumonitis. In this article, we will be presenting different neurological manifestations of scrub typhus along with functional outcomes studied at a tertiary care center in New Delhi. METHODS: This ambispective observational study was conducted at Army Hospital Research and Referral, New Delhi, during January 2018- January 2020. Febrile illness, serologically confirmed as scrub typhus and developing neurological complications were included. A predesigned clinical proforma was recorded for demographics, clinical features, neurological examination, supported with laboratory and/or radiology evaluation, and functional outcomes using the modified Rankin Scale (mRS). RESULTS: In our cohort of 7 patients' majority were male (71%) with mean age at presentation being 42.5 years. Eschar was present in only 2 cases (28%) and a syndromic clinical diagnosis of meningoencephalitis was made in 3 (43%), acute flaccid quadriparesis in 2 (28%); and symptomatic seizure and parkinsonism in 1 patient each (14%). CSF showed lymphocytic pleocytosis with protein elevation in 57% cases. Systemic dysfunction was noted in the form of thrombocytopenia (57%), hyponatremia (42%), elevated transaminases (57%). Symptoms resolved with Doxycycline ± Rifampicin therapy in all cases, with good functional outcomes in majority of (89%) cases. CONCLUSION: Neurological complications in scrub typhus have a wide spectrum involving meninges, encephalon, basal ganglia, cranial, and peripheral nerves. High index of suspicion with early serological testing (ELISA) is a must in undifferentiated fevers. Timely initiation of appropriate therapy leads to good clinical outcomes, in majority of cases with neurological involvement.

Discovery of a novel spotted fever group Rickettsia, "Candidatus Rickettsia kedanie," in unfed larval chigger mites, Leptotrombidium scutellare.

Spotted fever group (SFG) rickettsia, the causative agent of SFG rickettsiosis, is predominantly carried by ticks, whereas Orientia tsutusgamushi, the causative agent of scrub typhus, is primarily transmitted by chigger mites in Japan. In this study, we attempted to isolate intracellular eubacteria from Leptotrombidium scutellare, a major vector of O. tsutsugamushi; moreover, we isolated an SFG rickettsia using a mosquito-derived cell line. Draft genome sequences of this unique isolate, by applying criteria for species delimitation, classified this isolate as a novel strain, proposed as "Rickettsia kedanie." Further genetic analysis identified conserved virulence factors, and the isolate successfully propagated in mammalian cells, suggesting its ability to cause diseases in humans. The presence of SFG rickettsia in unfed larvae implies potential dual-pathogen carriage and reflects a symbiotic relationship similar to that between the mites and O. tsutsugamushi, indicating possibility of its transovarial transmission from female adults. Furthermore, conserved genomic similarity of the novel isolate to known SFG rickettsia suggests potential multiple hosts, including chiggers and ticks. In the natural environment, ticks, chigger mites, and wild animals may carry new isolates, complicating the infection cycle and increasing the transmission risks to humans. This discovery challenges the conventional association of SFG rickettsia with ticks, emphasizing its implications for research and disease control. However, this study was confined to a particular species of chigger mites and geographic area, underscoring the necessity for additional studies to comprehend the ecological dynamics, host interactions, and health implications linked to this newly identified SFG rickettsia.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

A cross sectional study on molecular prevalence of Orientia tsutsugamushi in household rat population of South India.

This study aimed to assess the molecular prevalence of mite-borne zoonotic pathogen O. tsutsugamushi in household rats of South India through nested polymerase chain reaction amplification of O. tsutsugamushi 47-kDa htrA gene and to determine the most suitable sample type for screening of O. tsutsugamushi in rats. Out of 85 rats trapped in Tamil Nadu, Karnataka, and Puducherry regions, 47 rats were found positive for the O. tsutsugamushi genome with prevalence of 55.29 %. Among different sample types screened, faecal samples exhibited the highest positivity rate, followed by liver, spleen, kidney, and blood samples. Agreement between faecal and spleen samples of rats for the presence of O. tsutsugamushi was the highest. Principal component analysis revealed a positive correlation between the spleen, liver, and faeces and a negative correlation between blood and faeces for the presence of O. tsutsugamushi genome. These findings underscore the varied distribution of O. tsutsugamushi among different samples and indicate that the faecal and liver samples of rats are an ideal choice of samples for epidemiological studies. This is the first study to report a high level of presence of O. tsutsugamushi in faecal samples of rats.

Orientia tsutsugamushi: An Unusual Intracellular Bacteria-Adaptation Strategies, Available Antibiotics, and Alternatives for Treatment.

During evolution Orientia tsutsugamushi became a smarter obligate bacterium to establish as intracellular pathogens. O. tsutsugamushi is a human pathogenic bacterium responsible for 1 billion infections of scrub typhus. Several novel mechanisms make this bacterium unique (cell wall, genetic constitutions, secretion system, etc.). In 2007, O. tsutsugamushi Boryong was pioneer strain for whole-genome sequencing. But the fundamental biology of this bacterial cell is a mystery till date. The unusual biology makes this organism as model for host cell interaction. Only a few antibiotics are effective against this intracellular pathogen but emergence of less susceptibility toward antibiotics make the situation alarming. The review was captivated to highlight the unusual aspects of adaptation, antibiotics, and drugs beyond antibiotics.

Ocular inflammation in tsutsugamushi disease - a case report.

A 64-year-old male, working at a mountain site in Taitung County, suffered from primary open angle glaucoma (POAG) post trabeculectomy with well-controlled intraocular pressure (IOP) in both eyes (OU). He presented with headache accompanied by red eyes (OU) for 10 days. Physical examination revealed fever up to 38.2°C, neck stiffness, one eschar at the left forearm and another at the left ankle. Abnormal laboratory data indicated bacterial infection with central nervous system involvement. Ophthalmic examination showed elevated IOP, moderate conjunctival congestion, subconjunctival hemorrhage, anterior uveitis, cotton-wool spots on the retina and multiple white dots on the temporal retina (OU). Under the impression of uveitis in tsutsugamushi disease with atypical meningitis, oral doxycycline, anti-glaucoma and anti-inflammation eye drugs were prescribed. IOP returned to 12 mmHg and anterior uveitis subsided. The lesions of cotton-wool spots on the retina disappeared within 2 weeks, but multiple white dots remained persistently on the temporal retina.