RARE DISEASE
Scrub typhus
Scrub typhus
Scrub typhus
Synonyms: Tsutsugamushi disease, Tsutsugamushi fever
Synonyms: Tsutsugamushi disease, Tsutsugamushi fever
Synonyms: Tsutsugamushi disease, Tsutsugamushi fever
Drug discovery
0
drugs
With orphan designations
Overview
Scrub typhus is a mite-borne zoonotic disease caused by Orientia tsutsugamushi, transmitted through infected chigger bites. Clinical features include fever, eschar (at bite sites), rash, lymphadenopathy, and complications such as multi-organ failure or meningoencephalitis [1][6]. Diagnosis relies on clinical suspicion, serological testing (IgM ELISA), and PCR, with early doxycycline therapy critical to reducing mortality [1][3][11].
Burden
Annual global incidence: ≈1 million cases, with underreporting in resource-limited settings [2][5][7].
Accounts for 25% of acute undifferentiated febrile illnesses in Asia; seroprevalence reaches 34.2% in Indian communities [4][7][9].
Economic impact: Hospitalization rates of 17.4% and ICU admissions of 20.4% in severe cases [4][6].
Therapies
First-line treatment: Doxycycline (100 mg twice daily for 7 days), effective if initiated early [1][3][11].
Alternatives: Azithromycin (preferred in pregnancy/children) and rifampicin (reserved for doxycycline-resistant regions, with caution in TB-endemic areas) [3][8][12].
Delayed treatment increases mortality (up to 6.3% overall CFR, rising to 38.9% in multi-organ dysfunction) [4][6].
Categories: rare infectious diseases
Research Papers
532 drug discovery papers about Scrub typhus, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
532 drug discovery papers about Scrub typhus, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
vaccines
2026-03-15 | From obstacles to opportunities: Innovations and evolution of strategies in scrub typhus vaccine research.
Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, remains a major public health burden in the Asia-Pacific region and is increasingly reported beyond its traditional endemic range. Despite its clinical significance, progress toward vaccine has been limited, largely due to extensive antigenic diversity and the difficulty of inducing durable cross-protective immunity. This review attempts to retrace the historical path of scrub typhus vaccine development from whole-cell killed preparations to subunit proteins, recombinant constructs, and epitope-driven strategies. Recent advances in reverse vaccinology, structural modeling, and nanotechnology-based delivery systems including virus-like particles and mucosal nanoparticles offer rational strategies to enhance immunogenicity and broaden strain coverage. Together, these approaches reflect a transition from empirical vaccine design to rational, biology-informed strategies aimed at clinical translation. Success along this pathway will require increased orbiting of computational design, advanced delivery platforms, and clinical validation toward the fulfilment of effective solutions to endemic populations.
2025-12-30 | Analysis of outer membrane protein from Orientia tsutsugamushi for epitope mining.
Scrub typhus, caused by Orientia tsutsugamushi, is an emerging health threat that can lead to severe complications if untreated. Therefore, it is of interest to analyse 130 sequences of the 56 kDa outer membrane protein, a key immunodominant antigen. SNP profiling identified 300 conserved and 8 highly variable residues. Epitope prediction revealed 73 conserved and 6 variable B cell epitopes, along with 4 conserved and 1 variable CD8+ T cell epitopes and 3 conserved and 1 variable CD4+ T cell epitopes. Notably, five immunogenic regions were predicted to activate B cells and both CD8+ and CD4+ T cells simultaneously. Thus, we show valuable insight into immune recognition and evasion strategies of O. tsutsugamushi. Subject to experimental validation, the identified epitopes represent promising candidates for rational vaccine development, improved serodiagnostics and novel therapeutic interventions against scrub typhus.
2025-10-25 | Recombinant Dabie bandavirus as a bivalent vaccine platform inducing protective immunity against intracellular pathogens and cancer.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen endemic to East Asia, associated with high mortality and lacking approved vaccines or therapies. We developed a live-attenuated vaccine platform based on a recombinant SFTSV, which lacks the nonstructural protein on the S segment (NSs) gene, a key virulence factor that suppresses type I interferon responses. The resulting ΔNSs viruses, reassorted with the prevalent genotype B, showed attenuated replication in interferon-competent cells while retaining the ability to infect and activate antigen-presenting cells (APCs). Immunization with the ΔNSs virus elicited robust SFTSV-specific humoral and cellular immune responses in mice and non-human primates, conferring complete protection against lethal challenge across multiple SFTSV genotypes, with immunity lasting up to 12 months. Additionally, recombinant ΔNSs viruses encoding heterologous antigens, such as ovalbumin (OVA) or type-specific antigen 56 (TSA56) from Orientia tsutsugamushi, induced strong antigen-specific T cell responses and conferred protection against OVA-expressing melanoma or scrub typhus, respectively. Mechanistically, ΔNSs viruses enhanced APC activation, improved antigen presentation, and reduced apoptosis in infected cells, supporting effective T cell priming. These findings establish SFTSV ΔNSs as an immunogenic and broadly protective vaccine candidate and a versatile bivalent vector platform for targeting viral, intracellular bacterial, and tumor-associated antigens.
2025-07-09 | Exploring OmpA of Orientia tsutsugamushi to design novel multi-epitope vaccine against scrub typhus: an immunoinformatics approach.
Scrub typhus is a commonly neglected infectious febrile illness caused by an obligate intracellular bacterium known as Orientia tsutsugamushi. It is a major health problem, affecting one million people annually, and poses threat to one billion people worldwide. There is always the escalating threat posed by the development of antibiotic resistance in the forthcoming future which emphasizes on urgency of the development of vaccine against Orientia tsutsugamushi. Despite eight decades of research and development, currently there is no viable vaccine available against scrub typhus. Outer membrane protein A (OmpA) is highly conserved and immunogenic across 51 geographically diverse isolates of Orientia tsutsugamishi. The multi-epitope vaccine was constructed by integrating four B-cell, four MHC-I, and four MHC-II epitopes linked together using specific linkers. The cholera enterotoxin subunit B is linked with the vaccine construct at N-terminal as an adjuvant. The constructed vaccine is 329 amino acid long, highly antigenic, non-allergen, non-toxic, soluble and has 36.3 kDa molecular weight. The molecular docking of vaccine construct with TLR receptors showed strong binding affinity. The interactions among vaccine and TLR receptors were analyzed using PDBsum. The in silico immune simulation of constructed vaccine showed ability to trigger immune response as shown by augmentation in T-cell and B-cell population. The current study provides the way forward for controlling the febrile disease scrub typhus.
2025-04-04 | A systemic immunoinformatics approach to design combinatorial multiepitope vaccine candidates against vector-borne bacterial infections exploiting the proteomes of the causative agent and vector for scrub typhus
An effective vaccine to prevent disease progression and transmission remains unavailable for most vector-borne bacterial infections. Recent comprehensive studies have explored not only the role of bacterial proteins in infection but also the significance of vector salivary proteins, underscoring the potential of combinatorial vaccines incorporating both bacterial and vector-derived antigens. Scrub typhus (ST), caused by the bacterium Orientia tsutsugamushi , is a mite-borne infection and a significant public health concern in eastern and southeastern Asia. Similar to other vector-borne bacterial diseases, the lack of an effective vaccine hampers prophylaxis against ST. Vaccine development is particularly challenging due to the extreme genetic diversity of major surface antigens, which limits cross-protection. In this study, a proteome-wide immunoinformatic approach was employed to identify immunodominant outer membrane proteins of O. tsutsugamushi , mapping conserved regions enriched in B-cell, Tc-cell, and Th-cell epitopes. Additionally, immunodominant regions from vector salivary proteins were identified. Using these segments, fifteen multi-epitope vaccines (MEVs) were designed and assessed for their physicochemical and immunological properties. The tertiary structure of the prioritized MEV was modelled, and its interactions with Toll-like receptors (TLR2, TLR4, and TLR5) were analyzed through molecular docking and molecular dynamics (MD) simulations. A glycosylation-deficient variant of the MEV was also designed and evaluated using the same methods. Immune simulations suggested that both MEVs could elicit a strong immune response. Furthermore, in silico cloning and expression analyses were conducted for bacterial expression system. While the proteome-wide combinatorial approach using immunodominant segments shows promise, experimental validation is necessary to confirm its efficacy against ST and other vector-borne bacterial infections. Strategy to configure a multiepitope vaccine for scrub typhus exploiting bacterial proteme and salivary proteome of the insect vector. • There is lack of an effective vaccine for Scrub typhus, a significant public health concern in eastern and southeastern Asia. • A strategy was adopted to identify immunodominant proteins and segments from bacterial proteome and salivary proteome of the insect vector. • 15 multiepitope vaccines (MEV) were configured by combining the immunodominant segments and evaluated to prioritize the most potent MEV. • Structural analysis and immune simulation highlighted prospect of the MEV to get translated in to an effective vaccine.
small molecules
2026-07-03 | Small-molecule inhibition of the Orientia tsutsugamushi deubiquitylating enzyme OtDUB impairs bacterial reproduction.
Scrub typhus is a potentially fatal infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi . While antibiotic treatment is generally effective, it requires extended treatment, and drug resistance and treatment failures have emerged. O. tsutsugamushi encodes a deubiquitylating enzyme, OtDUB, which interferes with host ubiquitin-dependent pathways. OtDUB cleaves ubiquitin from various substrates, but whether this activity can be selectively targeted by small molecules is unknown. Here we have screened a chemically diverse small-molecule library using a fluorescence-based deubiquitylation assay to identify potential inhibitors of OtDUB. Two compounds, gentisic acid and amiloride hydrochloride, inhibited OtDUB activity at low dosage, with little effect on the related Wolbachia CidB or yeast Ulp1 enzymes. Computational docking predicted the compounds engage regions near the OtDUB catalytic pocket, suggesting a competitive mode of inhibition; this was supported by enzyme kinetic analyses. Neither compound caused detectable cytotoxicity in mammalian cells. Amiloride hydrochloride treatment reduced both total cellular deubiquitylating activity and the O. tsutsugamushi bacterial load in infected cells. While the identified compounds are not optimized inhibitors, they establish that bacterial pathogen-encoded deubiquitylating enzymes can be targeted by small molecules. Overall, our results provide a framework for using selective inhibitors as tools to study DUB function in genetically intractable intracellular bacteria and as potential treatments for scrub typhus.
2026-06-30 | Ruxolitinib combined with azithromycin for scrub typhus-associated hemophagocytic lymphohistiocytosis in a child: a case report and narrative literature review.
Scrub typhus-associated hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening complication in children, with reported mortality of 11.9%-30%. Conventional immunomodulation with corticosteroids and intravenous immunoglobulin often provides insufficient control of the hyperinflammatory state, while etoposide-based chemotherapy carries significant toxicity. JAK1/2 inhibition targeting the interferon-gamma pathway represents a promising therapeutic strategy, but its application in scrub typhus-associated HLH has not been previously reported. A 5-year-11-month-old girl with no prior medical history presented with persistent fever, tachypnea, hepatosplenomegaly, and a 0.5 cm eschar in the left axilla after travel to Yunnan Province, China. Laboratory findings revealed pancytopenia (platelets 40× 109/L), hyperferritinemia (>2,000 ng/mL), hypofibrinogenemia (1 g/L), and elevated interferon-gamma (135.48 pg/mL). Bone marrow aspiration demonstrated hemophagocytosis. Metagenomic next-generation sequencing confirmed Orientia tsutsugamushi infection. The patient met six of eight HLH-2004 diagnostic criteria. She was treated with oral ruxolitinib (5 mg twice daily) initiated on the day of admission, followed by intravenous azithromycin (10 mg/kg once daily) after confirmatory testing. Fever resolved within 72 h. Ruxolitinib was temporally associated with rapid clinical improvement, although causal attribution cannot be established due to concurrent therapies. By day 8, platelet count normalized to 240× 109/L, ferritin declined to 1,246 ng/mL, and fibrinogen recovered to 2.4 g/L. The patient was discharged on day 13 with ruxolitinib tapered to 2.5 mg daily. At 3-month follow-up, she remained well with normal laboratory parameters. Narrative literature review of 66 previously reported pediatric cases from Chinese and English databases (inception to May 2026) plus the present case revealed an overall mortality of 11.94% (8/67). Among these patients, 43 (64.2%) received corticosteroids, 34 (50.7%) received intravenous immunoglobulin, and only 3 (4.5%) received etoposide. The published cases suggest that absence or delay of anti-rickettsial therapy is associated with poor outcomes, though the evidence is limited by case-report bias and confounding. This is the first report of successful JAK1/2 inhibitor therapy in scrub typhus-associated HLH. This case raises a hypothesis worth investigating further-that ruxolitinib combined with azithromycin may achieve rapid disease control with good tolerability. Prospective studies are needed to evaluate the role of targeted JAK inhibition in infection-triggered HLH.
2026-06-29 | Corneal injury associated with scrub typhus following mite exposure in a child in Taiwan: a case report.
Scrub typhus is a mite-borne zoonosis endemic to the Asia-Pacific region. Although ocular complications are occasionally reported during later stages of infection, direct mechanical ocular injury related to mite exposure has rarely been reported. Recognition of early ocular manifestations may facilitate timely diagnosis and treatment of this potentially serious infection. We describe a rare case of a 9-year-old Taiwanese boy who developed acute ocular and systemic symptoms after exposure to mites during a visit to Alishan Forest, Taiwan. Live mites were identified attached to the lower eyelid margins and ocular surface. The left eye showed multiple linear corneal epithelial abrasions with stromal edema, causing severe photophobia, tearing, and reduced visual acuity. The following day, the patient developed fever, headache, myalgia, and a necrotic eschar at the bite site, clinically suggestive of scrub typhus. The diagnosis was primarily based on clinical presentation and endemic exposure history because confirmatory serologic or PCR testing was not performed. Early administration of topical antibiotics, corticosteroids, and systemic doxycycline led to complete resolution of both ocular and systemic symptoms within 10 days without residual deficits. To our knowledge, few reports have described concurrent corneal injury and clinically suspected scrub typhus following direct mite exposure at the initial stage of contact. This case highlights the importance of considering mite-related ocular injury and scrub typhus in the differential diagnosis of acute ocular trauma and febrile illness following outdoor activities in endemic areas. Early recognition and prompt initiation of appropriate therapy may help prevent complications and improve clinical outcomes.
2026-06-28 | A proteome-driven strategy to discover novel therapeutic targets in Orientia tsutsugamushi.
Orientia tsutsugamushi (OT), an obligate intracellular Gram-negative bacterium of the Rickettsiaceae family, causes scrub typhus (ST), a re-emerging vector-borne infectious disease with significant morbidity and mortality in South and Southeast Asia. Despite its widespread prevalence and mortality rates reaching up to 30% in untreated individuals, no effective vaccines or targeted therapeutics are currently available.Compounding these challenges are limitations in existing diagnostic methods, increasing antibiotic resistance, and complex interactions among host, pathogen, and vector. To address these critical gaps, this study conducted a comprehensive genome-wide comparative analysis across 23 OT strains, including UT 76, Karp, Kato, Gilliam, and Wuj/2014, using an in-house R-based computational pipeline. This analysis identified a conserved core genome of 744 genes, of which 19 are unique and pathogen- specific proteins. Subcellular localisation analyses revealed that nine of these proteins are membrane- associated, highlighting their potential accessibility to therapeutic agents. Additionally, proteins were prioritised through an integrative analysis that incorporates protein- protein interaction networks, druggability assessments, and antigenicity profiling. Six key proteins- dnaK, fusA, fabG, infB, nuoN and fabI were identified based on their essential roles in pathogen- specific pathways. These proteins are involved in membrane transport, transcription regulation, and biosynthesis, making them promising drug targets. Notably, this study employs in silico methodologies to overcome limitations inherent to traditional wet-lab approaches. Computational strategies are cost-effective for identifying conserved targets and supporting hypothesis- driven drug discovery. The findings presented here not only reveal previously uncharacterized therapeutic targets but also establish a genomic framework to improve diagnostic accuracy and guide future drug development against ST.
2026-06-26 | Multimodal imaging of ASHH in a case of Scrub Typhus Retinopathy.
To report a case of scrub typhus retinopathy presenting with angular sign of Henle layer hyperreflectivity (ASHH) on optical coherence tomography (OCT). This is a retrospective case report with multimodal imaging. A 43-year-old Indian man presented with sudden, painless diminution of vision in both eyes,(left more than right) following a febrile illness. He was diagnosed with scrub typhus based on positive IgM ELISA. Fundus examination revealed scattered intraretinal haemorrhages in both eyes and a yellowish foveal lesion in the left eye. Optical coherence tomography (OCT) demonstrated angular sign of Henle layer hyperreflectivity (ASHH) in both eyes, with a hard exudate clump at the fovea in the left eye and corresponding areas of blocked fluorescence on fluorescein angiography. A diagnosis of scrub typhus retinopathy was made. After treatment with oral corticosteroids, at one-month follow-up, visual acuity, with marked resolution of haemorrhages and regression of ASHH on OCT. Scrub typhus can present with retinopathy associated with ASHH, a marker of deep retinal ischemia. Multimodal imaging, particularly OCT, plays a crucial role in identifying ischemic retinal changes and may help in assessing disease severity and visual prognosis.
proteins
2025-04-14 | Scrub Typhus Combined With Septic Shock Disseminated Intravascular Coagulation and Significant Hyperfibrinolysis: A Case Report and Review of the Literature.
Introduction: Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi, whose pathophysiology is characterized by systemic small-vessel vasculitis. Its high misdiagnosis rate stems from its nonspecific clinical features. If not diagnosed and treated in time, patients may rapidly progress to multiorgan dysfunction syndrome (MODS) or even disseminated intravascular coagulation (DIC), posing a severe threat to life. Case Presentation: The patient was a 68-year-old male with "recurrent fever and dry cough for six days." He was admitted to the hospital with a diagnosis of scrub typhus. After admission, he developed severe acute respiratory distress syndrome (ARDS), MODS, septic shock, DIC with thrombocytopenia, hypofibrinogenemia, significant hyperfibrinolysis, and myocardial depression. The patient improved following treatment with doxycycline, moxifloxacin, renal replacement therapy, blood transfusion, antifibrinolysis, invasive mechanical ventilation, and other supportive therapies. The patient's coagulation profile in DIC caused by scrub typhus demonstrated significant hyperfibrinolysis, differing from that of garden-variety sepsis, and no similar cases were identified in a search of medical literature/databases. Conclusion: The fibrinolytic system in DIC caused by scrub typhus is excessively active, and antifibrinolytic therapy may benefit such patients. Further research on the distinct coagulation abnormalities in scrub typhus-associated DIC would be highly valuable compared to sepsis-associated DIC.
2025-04-01 | Immunogenic proteins of Orientia tsutsugamushi and implications for scrub typhus intervention: A narrative review
Scrub typhus is an acute undifferentiated febrile infectious disease transmitted by a chigger (genus Leptotrombidium) bite carrying Orientia (O.) tsutsugamushi , affecting millions of people annually while more than one billion people are susceptible. Endemic areas are expanding to Africa, Europe, Middle East, and South America which is concerning, as despite best efforts, there is no vaccine to combat the bacteria. There are now three species of Orientia and over 20 strains of O. tsutsugamushi. The past attempts to develop a vaccine have been ineffective as they confer homologous strain-specific immunity. Various immunogenic proteins of O. tsutsugamushi have been identified that interact with the extracellular matrix (fibronectin) or vMLL5 receptor and modify the cytoskeleton of non-phagocytic host cells, which aids in host cell adhesion and invasion. These highly conserved proteins involve type specific antigen 56 (TSA56), 47 kDa, OmpA, and autotransporter proteins (ScaA, ScaB and ScaC). TSA56 is the most immunogenic and contains four types of hypervariable regions. Out of all autotransporter proteins, ScaA provides the homologous strains specific immunity and when coupled with TSA56 it shows better protective immunity against heterologous strains. The review provides detailed insight into the potential immunogenic proteins of Orientia which can be utilized to develop the vaccine. Furthermore, studies focused on highly antigenic proteins will provide more insight into their roles in developing therapeutics and easy-to-handle rapid diagnostic kits.
2024-07-17 | CARBIMAZOLE-INDUCED AGRANULOCYTOSIS WITH CONCURRENT SCRUB TYPHUS
INTRODUCTIONWhile carbimazole is an effective treatment for hyperthyroidism, it carries a risk of agranulocytosis. Concurrently, rickettsial infections like scrub typhus can worsen neutropenia. We reviewed case notes, investigation results, imaging studies and treatment options based on a literature review. CASEA 55-year-old male farmer with hyperthyroidism on highdose carbimazole treatment sustained a machete injury to his left middle finger. Upon presentation, he had fever, normal thyroid function, stable hemodynamics, severe neutropenia (total white count 0.4 × 109 /L, absolute neutrophil count 0.02 × 103/µL) and typhus eschars. He was treated with doxycycline, piperacillin-tazobactam and subcutaneous granulocyte-colony stimulating factor (G-CSF). Abnormal thyroid function (FT4 46 pmol/L and TSH <0.01 m IU/L) and elevated C-reactive protein (234 mg/L) were also observed. Carbimazole was discontinued and replaced with oral cholestyramine and lithium. Positive serologic findings confirmed scrub typhus. With targeted treatment and G-CSF support, the patient's condition improved, as evidenced by normalized blood counts. Radioactive iodine therapy was contemplated once thyroid function was controlled. CONCLUSIONCarbimazole carries the risk of severe adverse effects, including agranulocytosis. This risk may be compounded with a concurrent rickettsial infection, which can also cause neutropenia. Diagnosis relies on clinical suspicion and profound neutropenia, requiring thorough evaluation including serological tests and PCR to differentiate between agranulocytosis-related and rickettsial infections. Immediate discontinuation of carbimazole and replacement with alternative antithyroid drugs is necessary, often supplemented with broad-spectrum antibiotics and G-CSF to prevent overwhelming infection risks. Tailored antibiotic therapy should also be administered for the rickettsial infection. Prompt recognition and intervention are crucial, particularly in endemic areas. Early diagnosis and aggressive management can help mitigate morbidity and mortality. Educating patients on symptom recognition remains the most effective preventive measure.
2024-05-24 | Lack of the IFN-γ signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions.
Scrub typhus is an acute febrile disease due to Orientia tsutsugamushi (Ot) infection and can be life-threatening with organ failure, hemorrhage, and fatality. Yet, little is known as to how the host reacts to Ot bacteria at early stages of infection; no reports have addressed the functional roles of type I versus type II interferon (IFN) responses in scrub typhus. In this study, we used comprehensive intradermal (i.d.) inoculation models and two clinically predominant Ot strains (Karp and Gilliam) to uncover early immune events. Karp infection induced sequential expression of Ifnb and Ifng in inflamed skin and draining lymph nodes at days 1 and 3 post-infection. Using double Ifnar1-/-Ifngr1-/- and Stat1-/- mice, we found that deficiency in IFN/STAT1 signaling resulted in lethal infection with profound pathology and skin eschar lesions, which resembled to human scrub typhus. Further analyses demonstrated that deficiency in IFN-γ, but not IFN-I, resulted in impaired NK cell and macrophage activation and uncontrolled bacterial growth and dissemination, leading to metabolic dysregulation, excessive inflammatory cell infiltration, and exacerbated tissue damage. NK cells were found to be the major cellular source of innate IFN-γ, contributing to the initial Ot control in the draining lymph nodes. In vitro studies with dendritic cell cultures revealed a superior antibacterial effect offered by IFN-γ than IFN-β. Comparative in vivo studies with Karp- and Gilliam-infection revealed a crucial role of IFN-γ signaling in protection against progression of eschar lesions and Ot infection lethality. Additionally, our i.d. mouse models of lethal infection with eschar lesions are promising tools for immunological study and vaccine development for scrub typhus.
2024-05-01 | Lack of IFN-g signaling leads to enhanced susceptibility to eschar-associated scrub typhus in mice
Abstract Scrub typhus is an infectious disease caused by the bacteria Orientia tsutsugamushi (Ot). Severe infection can lead to organ failure and hemorrhage, resulting in fatality without proper treatment. The mechanism of how the host innate immune system responds to this infection remains elusive. By using an intradermal (i.d.) inoculation mouse model, we found that dendritic cells (DCs) and macrophages (MФ) were the major cell subsets responsible for bacterial uptake in dermis and dissemination into draining lymph nodes (dLN), leading to a systemic infection. This process was dependent on the chemokine receptor CCR7. Interferons (IFNs) are known to play a crucial role in microbial infection defense. Our data showed that the levels of IFNs increased significantly in the skin and lymph nodes after infection. To investigate the role of IFNs in Ot infection, we i.d. infected Ifnar1- or Ifngr-deficient mice and found that the lack of IFN-γ, but not IFN-I signaling, resulted in visible skin eschar lesions, higher bacterial burdens in dLN, exacerbated systemic infection, and animal lethality. Our in vitro study demonstrated that IFN-γ restricted bacterial growth in DCs and MФ, suggesting that IFN-γ may inhibit bacterial dissemination in vivo by signaling on bacteria-carrying myeloid cells. Overall, our findings reveal a Trojan horse mechanism of bacterial transmission and highlight the crucial role of IFN-γ signaling in host protection against scrub typhus.
antibodies
2026-06-11 | A Case of Adult-Onset Still's Disease Diagnosed Following Treatment for Scrub Typhus.
A 28-year-old woman, previously diagnosed with seronegative rheumatoid arthritis, was admitted with fever, vomiting, and diarrhea. She developed septic shock with disseminated intravascular coagulation and was treated with antibiotics, noradrenaline, prednisolone, and thrombomodulin. On day 3, a rash appeared, and polymerase chain reaction detected Orientia tsutsugamushi deoxyribonucleic acid, thus confirming the diagnosis of scrub typhus. Her symptoms resolved after minocycline treatment. After tapering the prednisolone, fever, rash, and arthralgia recurred. Laboratory tests revealed elevated ferritin and interleukin-18 levels. After excluding other causes, adult-onset Still's disease (AOSD) was diagnosed in this patient. The patient exhibited a rapid improvement following tocilizumab treatment. Scrub typhus and AOSD share overlapping features that complicate diagnosis.
2026-05-15 | Successful management of scrub typhus-associated hemophagocytic lymphohistiocytosis with doxycycline and immunomodulation: a case report.
Hemophagocytic lymphohistiocytosis (HLH) is a fatal hyperinflammatory complication of scrub typhus, often with delayed diagnosis. This case report aims to detail the clinical trajectory and successful management of scrub typhus-associated HLH in a child, highlighting key diagnostic clues. A previously healthy 14-year-old boy from a scrub typhus-endemic area presented with prolonged high fever, cough, and lethargy. Physical examination revealed a pathognomonic eschar. Laboratory findings fulfilled HLH-2004 diagnostic criteria, including cytopenias, hyperferritinemia (>3,000 ng/mL), hypofibrinogenemia, and hemophagocytosis on bone marrow aspirate. The patient was diagnosed with secondary HLH triggered by scrub typhus. Immediate treatment with oral doxycycline, combined with immunomodulation using intravenous immunoglobulin and dexamethasone, led to fever resolution within 72 h and full recovery. This case highlights that in pediatric scrub typhus, a rapid decline in platelets/fibrinogen and a sharp rise in ferritin/LDH should alert clinicians to possible HLH. Early combined therapy targeting both the infection (e.g., doxycycline) and the cytokine storm (e.g., immunomodulators) may be beneficial for favorable outcomes.
2026-02-09 | Orientia tsutsugamushi binds to multiple C-type lectin receptors.
Orientia tsutsugamushi, the agent of scrub typhus, is an obligate intracellular bacterium whose atypical cell wall lacks many classical pathogen-associated molecular patterns but is enriched in neutral glycans. Its recognition by phagocytes is driven by a heat-stable ligand that triggers innate cytokine responses, yet the nature of this ligand and the receptors sensing it remain incompletely understood. While activation of innate immunity via toll-like (TLR) and nucleotide-binding and oligomerization domain-like receptors has been described, recognition via C-type lectin receptors (CLRs) has remained largely unexplored. Using a flow cytometry-based screening assay with a library of CLR-Fc fusion proteins, we demonstrate binding of Orientia to four mouse CLRs, including Mincle, Dectin-1, Langerin, and DCL-1, as well as to human DC-SIGN. Binding to Mincle was Ca²+-dependent, indicating carbohydrate-specific recognition. In bone marrow-derived dendritic cells (BMDC), heat-inactivated Orientia induced transcriptional upregulation of Mincle in a MyD88-dependent manner, suggesting cross talk between TLR and CLR pathways. Mincle was dispensable for TNF-α induction in BMDC stimulated with Orientia but contributed to the induction of interleukin-27 and cxcl-10 mRNA, indicating an immunomodulatory rather than a classical pro-inflammatory role. We also discuss in vivo data that demonstrated upregulation of Mincle and concomitant downregulation of Dectin-1 during Orientia infection. Together, this study identifies multiple CLRs as receptors for Orientia, highlights Mincle as a modulator of innate immunity, and suggests that Mincle-driven immunoregulation helps to shape the inflammatory environment during scrub typhus.
2025-10-06 | Guillain–Barré syndrome with anti-GM4 seropositivity after scrub typhus: a first case report
Abstract Background Scrub typhus, a major tropical febrile disease in Asia, rarely triggers Guillain–Barré syndrome (GBS)—an immune-mediated neuropathy typically post-antecedent infections or vaccinations. Only 16 global cases of this association were documented by 2024. Case presentation We present a case of a 72-year-old woman who developed progressive limb weakness and numbness following scrub typhus infection, accompanied by peripheral facial palsy, dysphagia, and dysphonia. Neurophysiological studies and cerebrospinal fluid analysis confirmed GBS diagnosis. Serological testing demonstrated positivity for anti-GM4 antibodies. Administration of immunotherapy resulted in improvement of the patient's clinical symptoms. Conclusions Vigilance for concomitant GBS is warranted during scrub typhus infection, as prompt immunotherapy typically yields favorable clinical outcomes.
2025-04-22 | Scrub typhus-associated movement and gait disorders: A systematic review with principal component analysis and in silico mechanistic modelling.
Orientia tsutsugamushi, the causative agent of scrub typhus, is increasingly recognised for its neurological complications. Among these, movement and gait disorders are poorly understood. We systematically examined their clinical spectrum and explored underlying mechanisms through in-silico protein-protein interaction modelling. A systematic review was conducted following PRISMA guidelines, including studies published up to 5 November 2024. Principal component analysis was used to identify clinical patterns among neurological features. In-silico protein-protein interaction modelling was used to examine potential cross-reactivity between Orientia tsutsugamushi proteins and human targets proteins. Among 76 cases, 50 presented with either isolated or combined movement disorders, most commonly opsoclonus (64.0%, 32/50), with the opsoclonus-myoclonus combination predominating (59.4%, 19/32). Other hyperkinetic features included tremor (4.0%, 2/50) and distinct forms of myoclonus (without opsoclonus) (8.0, 4/50%). Parkinsonism was present in 26.0% (13/50) of cases. Gait disorders, excluding parkinsonian gait and instability due to myoclonus, were well-characterised in 27 patients, one of whom had concomitant opsoclonus and cerebellar ataxia. Ataxic gait was the predominant pattern, observed in 96.3% (26/27), primarily cerebellar in origin. Principal component analysis revealed five principal components reflecting distinct clinical clusters: cerebellar dysfunction, tremor and parkinsonism, sensory ataxia and spinal involvement, myoclonus (diaphragmatic/action/segmental), and prolonged recovery and cranial nerve involvement. In-silico analyses revealed high-confidence interactions between bacterial epitopes and host proteins, including fibronectin-1 and Golgi-associated molecules, suggesting mechanisms of immune-mediated injury and neuroinflammation. Scrub typhus may lead to a range of movement and gait disorders through neuroimmune mechanisms and molecular mimicry. Principal component analysis offered a data-driven framework to classify these manifestations, highlighting clinically relevant patterns. Early recognition and targeted treatment are critical to improving outcomes. Future studies should validate the molecular targets identified and evaluate immunomodulatory strategies for therapeutic intervention.
other
2025-06-25 | Reversible high-grade AV block in a patient with scrub typhus.
A man in his late 30s presented with a prolonged febrile illness and recurrent syncopal episodes. Physical examination revealed hypotension, bradycardia and eschars on the bilateral thighs. A 12-lead ECG showed complete heart block with wide QRS escape rate of 30 beats per minute. Laboratory tests confirmed scrub typhus with elevated cardiac markers. The patient was managed with a temporary transvenous pacemaker and intravenous doxycycline which led to rapid resolution of symptoms and complete normalisation of cardiac conduction within 48 hours. This case highlights the importance of scrub typhus in the differential diagnosis of febrile illnesses with conduction abnormalities, especially in endemic areas.
2017-07-19 | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i.v.) disseminated infection mouse model, we observed that more CD8+ T cells than CD4+ T cells were present in the spleen of infected mice at 12 dpi. We also determined that Treg cells and the proportion of T cells producing IL-10 were significantly increased from 6 dpi, which correlated with the onset of illness, body weight loss, and increased bacterial loads. We further studied CD8-/-, MHC I-/- and wild type control (WT) C57BL/6J mice to determine the importance of CD8+ T cells and MHC I molecules. After infection with an ordinarily sub-lethal dose of O. tsutsugamushi, all CD8-/- and MHC I-/- mice were moribund between 12 and 15 dpi, whereas all WT mice survived. Bacterial loads in the lung, kidney, liver and spleen of CD8-/- and MHC I-/- mice were significantly greater than those in WT mice. Interferon-γ (IFN-γ) and granzyme B mRNA levels in the liver of CD8-/- and MHC I-/- mice were significantly greater than in WT mice. In addition, more severe histopathologic lesions were observed in CD8-/- mice. Finally, adoptive transfer confirmed a major role of immune CD8+ T cells as well as a less effective contribution by immune CD8 T cell-depleted splenocytes in protection against O. tsutsugamushi infection. These studies demonstrated the critical importance of CD8+ T cells in the host immune response during O. tsutsugamushi infection.
2016-09-08 | Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection
T cells are known to contribute to immune protection against scrub typhus, a potentially fatal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to protection and pathogenesis during O. tsutsugamushi infection is still unknown. Using our recently developed BALB/c mouse model that is based on footpad inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T cells infiltrate spleen and lung during the third week of infection. Depletion of CD8+ T cells with monoclonal antibodies resulted in uncontrolled pathogen growth and mortality. Adoptive transfer of CD8+ T cells from infected animals protected naïve BALB/c mice from lethal outcome of intraperitoneal challenge. In C57Bl/6 mice, the pulmonary lymphocyte compartment showed an increased percentage of CD8+ T cells for at least 135 days post O. tsutsugamushi infection. Depletion of CD8+ T cells at 84 days post infection caused reactivation of bacterial growth. In CD8+ T cell-deficient beta 2-microglobulin knockout mice, bacterial replication was uncontrolled, and all mice succumbed to the infection, despite higher serum IFN-γ levels and stronger macrophage responses in liver and lung. Moreover, we show that CD8+ T cells but not NKT cells were required for hepatocyte injury: elevated concentrations of serum alanine aminotransferase and infection-induced subcapsular necrotic liver lesions surrounded by macrophages were found in C57Bl/6 and CD1d-deficient mice, but not in beta 2-microglobulin knockout mice. In the lungs, peribronchial macrophage infiltrations also depended on CD8+ T cells. In summary, our results demonstrate that CD8+ T cells restrict growth of O. tsutsugamushi during acute and persistent infection, and are required to protect from lethal infections in BALB/c and C57BL/6 mice. However, they also elicit specific pathologic tissue lesions in liver and lung.
2000-03-01 | Reducing the risk of transfusion-transmitted rickettsial disease by WBC filtration, using Orientia tsutsugamushiin a model system.
BACKGROUND: Careful donor screening and infectious disease marker testing have significantly reduced the incidence of transfusion‐transmitted diseases and improved the safety of the blood supply. However, transfusion‐transmitted diseases resulting from the use of asymptomatic yet infectious donors continue to put patients at risk. This study was undertaken to determine if third‐generation WBC filters could remove Orientia tsutsugamushi ‐infected cells from contaminated blood. STUDY DESIGN AND METHODS: Packed RBCs were inoculated with human MNCs infected with O. tsutsugamushi at levels estimated to occur in asymptomatic infectious donors. WBC reduction was accomplished with a third‐generation WBC filter. Prefiltration and postfiltration specimens were collected, serially diluted, and injected into mice to determine the infectivity of the samples. RESULTS: Mice receiving WBC‐reduced packed RBCs showed no signs of illness or markers of infectivity, which suggested that a reduction of as much as 10 5 infectious rickettsiae could be achieved by filtration. CONCLUSION: The high‐efficiency, third‐generation, WBC‐reduction filters that were tested may provide protection against the transfusion transmission of scrub typhus rickettsiae by removing from contaminated blood cells that contain intracellular bacteria.
1987-01-01 | Immunological Studies of Rickettsial Infection Establishment and Characterization of Rickettsia tsutsugamushi Antigen-Specific T Cell Line
T cell line specific for R. tsutsugamushi antigen was established by the long term culture of splenocytes from mice immunized with live Gilliam strain of R. tsutsugamushi and was propagated in the presence of homologous rickettsial antigen and syngeneic filler cells. The characteristics and the capacity to induce anti-rickettsial protection in vivo of the T cell line were studied. Flow cytometrical analysis demonstrated the T cell line had a phenotype of Thy 1.2+, L3T4+, and Lyt2-. The T cell line produced gamma interferon, one of macrophage activating factors, in cultures with specific antigen and could adoptively mediate anti-rickettsial protection in vivo. It is concluded that antigen-specific helper T cells play an, important, g role in the protection anainst rickettsial infection.
vaccines
2026-03-15 | From obstacles to opportunities: Innovations and evolution of strategies in scrub typhus vaccine research.
Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, remains a major public health burden in the Asia-Pacific region and is increasingly reported beyond its traditional endemic range. Despite its clinical significance, progress toward vaccine has been limited, largely due to extensive antigenic diversity and the difficulty of inducing durable cross-protective immunity. This review attempts to retrace the historical path of scrub typhus vaccine development from whole-cell killed preparations to subunit proteins, recombinant constructs, and epitope-driven strategies. Recent advances in reverse vaccinology, structural modeling, and nanotechnology-based delivery systems including virus-like particles and mucosal nanoparticles offer rational strategies to enhance immunogenicity and broaden strain coverage. Together, these approaches reflect a transition from empirical vaccine design to rational, biology-informed strategies aimed at clinical translation. Success along this pathway will require increased orbiting of computational design, advanced delivery platforms, and clinical validation toward the fulfilment of effective solutions to endemic populations.
2025-12-30 | Analysis of outer membrane protein from Orientia tsutsugamushi for epitope mining.
Scrub typhus, caused by Orientia tsutsugamushi, is an emerging health threat that can lead to severe complications if untreated. Therefore, it is of interest to analyse 130 sequences of the 56 kDa outer membrane protein, a key immunodominant antigen. SNP profiling identified 300 conserved and 8 highly variable residues. Epitope prediction revealed 73 conserved and 6 variable B cell epitopes, along with 4 conserved and 1 variable CD8+ T cell epitopes and 3 conserved and 1 variable CD4+ T cell epitopes. Notably, five immunogenic regions were predicted to activate B cells and both CD8+ and CD4+ T cells simultaneously. Thus, we show valuable insight into immune recognition and evasion strategies of O. tsutsugamushi. Subject to experimental validation, the identified epitopes represent promising candidates for rational vaccine development, improved serodiagnostics and novel therapeutic interventions against scrub typhus.
2025-10-25 | Recombinant Dabie bandavirus as a bivalent vaccine platform inducing protective immunity against intracellular pathogens and cancer.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen endemic to East Asia, associated with high mortality and lacking approved vaccines or therapies. We developed a live-attenuated vaccine platform based on a recombinant SFTSV, which lacks the nonstructural protein on the S segment (NSs) gene, a key virulence factor that suppresses type I interferon responses. The resulting ΔNSs viruses, reassorted with the prevalent genotype B, showed attenuated replication in interferon-competent cells while retaining the ability to infect and activate antigen-presenting cells (APCs). Immunization with the ΔNSs virus elicited robust SFTSV-specific humoral and cellular immune responses in mice and non-human primates, conferring complete protection against lethal challenge across multiple SFTSV genotypes, with immunity lasting up to 12 months. Additionally, recombinant ΔNSs viruses encoding heterologous antigens, such as ovalbumin (OVA) or type-specific antigen 56 (TSA56) from Orientia tsutsugamushi, induced strong antigen-specific T cell responses and conferred protection against OVA-expressing melanoma or scrub typhus, respectively. Mechanistically, ΔNSs viruses enhanced APC activation, improved antigen presentation, and reduced apoptosis in infected cells, supporting effective T cell priming. These findings establish SFTSV ΔNSs as an immunogenic and broadly protective vaccine candidate and a versatile bivalent vector platform for targeting viral, intracellular bacterial, and tumor-associated antigens.
2025-07-09 | Exploring OmpA of Orientia tsutsugamushi to design novel multi-epitope vaccine against scrub typhus: an immunoinformatics approach.
Scrub typhus is a commonly neglected infectious febrile illness caused by an obligate intracellular bacterium known as Orientia tsutsugamushi. It is a major health problem, affecting one million people annually, and poses threat to one billion people worldwide. There is always the escalating threat posed by the development of antibiotic resistance in the forthcoming future which emphasizes on urgency of the development of vaccine against Orientia tsutsugamushi. Despite eight decades of research and development, currently there is no viable vaccine available against scrub typhus. Outer membrane protein A (OmpA) is highly conserved and immunogenic across 51 geographically diverse isolates of Orientia tsutsugamishi. The multi-epitope vaccine was constructed by integrating four B-cell, four MHC-I, and four MHC-II epitopes linked together using specific linkers. The cholera enterotoxin subunit B is linked with the vaccine construct at N-terminal as an adjuvant. The constructed vaccine is 329 amino acid long, highly antigenic, non-allergen, non-toxic, soluble and has 36.3 kDa molecular weight. The molecular docking of vaccine construct with TLR receptors showed strong binding affinity. The interactions among vaccine and TLR receptors were analyzed using PDBsum. The in silico immune simulation of constructed vaccine showed ability to trigger immune response as shown by augmentation in T-cell and B-cell population. The current study provides the way forward for controlling the febrile disease scrub typhus.
2025-04-04 | A systemic immunoinformatics approach to design combinatorial multiepitope vaccine candidates against vector-borne bacterial infections exploiting the proteomes of the causative agent and vector for scrub typhus
An effective vaccine to prevent disease progression and transmission remains unavailable for most vector-borne bacterial infections. Recent comprehensive studies have explored not only the role of bacterial proteins in infection but also the significance of vector salivary proteins, underscoring the potential of combinatorial vaccines incorporating both bacterial and vector-derived antigens. Scrub typhus (ST), caused by the bacterium Orientia tsutsugamushi , is a mite-borne infection and a significant public health concern in eastern and southeastern Asia. Similar to other vector-borne bacterial diseases, the lack of an effective vaccine hampers prophylaxis against ST. Vaccine development is particularly challenging due to the extreme genetic diversity of major surface antigens, which limits cross-protection. In this study, a proteome-wide immunoinformatic approach was employed to identify immunodominant outer membrane proteins of O. tsutsugamushi , mapping conserved regions enriched in B-cell, Tc-cell, and Th-cell epitopes. Additionally, immunodominant regions from vector salivary proteins were identified. Using these segments, fifteen multi-epitope vaccines (MEVs) were designed and assessed for their physicochemical and immunological properties. The tertiary structure of the prioritized MEV was modelled, and its interactions with Toll-like receptors (TLR2, TLR4, and TLR5) were analyzed through molecular docking and molecular dynamics (MD) simulations. A glycosylation-deficient variant of the MEV was also designed and evaluated using the same methods. Immune simulations suggested that both MEVs could elicit a strong immune response. Furthermore, in silico cloning and expression analyses were conducted for bacterial expression system. While the proteome-wide combinatorial approach using immunodominant segments shows promise, experimental validation is necessary to confirm its efficacy against ST and other vector-borne bacterial infections. Strategy to configure a multiepitope vaccine for scrub typhus exploiting bacterial proteme and salivary proteome of the insect vector. • There is lack of an effective vaccine for Scrub typhus, a significant public health concern in eastern and southeastern Asia. • A strategy was adopted to identify immunodominant proteins and segments from bacterial proteome and salivary proteome of the insect vector. • 15 multiepitope vaccines (MEV) were configured by combining the immunodominant segments and evaluated to prioritize the most potent MEV. • Structural analysis and immune simulation highlighted prospect of the MEV to get translated in to an effective vaccine.
small molecules
2026-07-03 | Small-molecule inhibition of the Orientia tsutsugamushi deubiquitylating enzyme OtDUB impairs bacterial reproduction.
Scrub typhus is a potentially fatal infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi . While antibiotic treatment is generally effective, it requires extended treatment, and drug resistance and treatment failures have emerged. O. tsutsugamushi encodes a deubiquitylating enzyme, OtDUB, which interferes with host ubiquitin-dependent pathways. OtDUB cleaves ubiquitin from various substrates, but whether this activity can be selectively targeted by small molecules is unknown. Here we have screened a chemically diverse small-molecule library using a fluorescence-based deubiquitylation assay to identify potential inhibitors of OtDUB. Two compounds, gentisic acid and amiloride hydrochloride, inhibited OtDUB activity at low dosage, with little effect on the related Wolbachia CidB or yeast Ulp1 enzymes. Computational docking predicted the compounds engage regions near the OtDUB catalytic pocket, suggesting a competitive mode of inhibition; this was supported by enzyme kinetic analyses. Neither compound caused detectable cytotoxicity in mammalian cells. Amiloride hydrochloride treatment reduced both total cellular deubiquitylating activity and the O. tsutsugamushi bacterial load in infected cells. While the identified compounds are not optimized inhibitors, they establish that bacterial pathogen-encoded deubiquitylating enzymes can be targeted by small molecules. Overall, our results provide a framework for using selective inhibitors as tools to study DUB function in genetically intractable intracellular bacteria and as potential treatments for scrub typhus.
2026-06-30 | Ruxolitinib combined with azithromycin for scrub typhus-associated hemophagocytic lymphohistiocytosis in a child: a case report and narrative literature review.
Scrub typhus-associated hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening complication in children, with reported mortality of 11.9%-30%. Conventional immunomodulation with corticosteroids and intravenous immunoglobulin often provides insufficient control of the hyperinflammatory state, while etoposide-based chemotherapy carries significant toxicity. JAK1/2 inhibition targeting the interferon-gamma pathway represents a promising therapeutic strategy, but its application in scrub typhus-associated HLH has not been previously reported. A 5-year-11-month-old girl with no prior medical history presented with persistent fever, tachypnea, hepatosplenomegaly, and a 0.5 cm eschar in the left axilla after travel to Yunnan Province, China. Laboratory findings revealed pancytopenia (platelets 40× 109/L), hyperferritinemia (>2,000 ng/mL), hypofibrinogenemia (1 g/L), and elevated interferon-gamma (135.48 pg/mL). Bone marrow aspiration demonstrated hemophagocytosis. Metagenomic next-generation sequencing confirmed Orientia tsutsugamushi infection. The patient met six of eight HLH-2004 diagnostic criteria. She was treated with oral ruxolitinib (5 mg twice daily) initiated on the day of admission, followed by intravenous azithromycin (10 mg/kg once daily) after confirmatory testing. Fever resolved within 72 h. Ruxolitinib was temporally associated with rapid clinical improvement, although causal attribution cannot be established due to concurrent therapies. By day 8, platelet count normalized to 240× 109/L, ferritin declined to 1,246 ng/mL, and fibrinogen recovered to 2.4 g/L. The patient was discharged on day 13 with ruxolitinib tapered to 2.5 mg daily. At 3-month follow-up, she remained well with normal laboratory parameters. Narrative literature review of 66 previously reported pediatric cases from Chinese and English databases (inception to May 2026) plus the present case revealed an overall mortality of 11.94% (8/67). Among these patients, 43 (64.2%) received corticosteroids, 34 (50.7%) received intravenous immunoglobulin, and only 3 (4.5%) received etoposide. The published cases suggest that absence or delay of anti-rickettsial therapy is associated with poor outcomes, though the evidence is limited by case-report bias and confounding. This is the first report of successful JAK1/2 inhibitor therapy in scrub typhus-associated HLH. This case raises a hypothesis worth investigating further-that ruxolitinib combined with azithromycin may achieve rapid disease control with good tolerability. Prospective studies are needed to evaluate the role of targeted JAK inhibition in infection-triggered HLH.
2026-06-29 | Corneal injury associated with scrub typhus following mite exposure in a child in Taiwan: a case report.
Scrub typhus is a mite-borne zoonosis endemic to the Asia-Pacific region. Although ocular complications are occasionally reported during later stages of infection, direct mechanical ocular injury related to mite exposure has rarely been reported. Recognition of early ocular manifestations may facilitate timely diagnosis and treatment of this potentially serious infection. We describe a rare case of a 9-year-old Taiwanese boy who developed acute ocular and systemic symptoms after exposure to mites during a visit to Alishan Forest, Taiwan. Live mites were identified attached to the lower eyelid margins and ocular surface. The left eye showed multiple linear corneal epithelial abrasions with stromal edema, causing severe photophobia, tearing, and reduced visual acuity. The following day, the patient developed fever, headache, myalgia, and a necrotic eschar at the bite site, clinically suggestive of scrub typhus. The diagnosis was primarily based on clinical presentation and endemic exposure history because confirmatory serologic or PCR testing was not performed. Early administration of topical antibiotics, corticosteroids, and systemic doxycycline led to complete resolution of both ocular and systemic symptoms within 10 days without residual deficits. To our knowledge, few reports have described concurrent corneal injury and clinically suspected scrub typhus following direct mite exposure at the initial stage of contact. This case highlights the importance of considering mite-related ocular injury and scrub typhus in the differential diagnosis of acute ocular trauma and febrile illness following outdoor activities in endemic areas. Early recognition and prompt initiation of appropriate therapy may help prevent complications and improve clinical outcomes.
2026-06-28 | A proteome-driven strategy to discover novel therapeutic targets in Orientia tsutsugamushi.
Orientia tsutsugamushi (OT), an obligate intracellular Gram-negative bacterium of the Rickettsiaceae family, causes scrub typhus (ST), a re-emerging vector-borne infectious disease with significant morbidity and mortality in South and Southeast Asia. Despite its widespread prevalence and mortality rates reaching up to 30% in untreated individuals, no effective vaccines or targeted therapeutics are currently available.Compounding these challenges are limitations in existing diagnostic methods, increasing antibiotic resistance, and complex interactions among host, pathogen, and vector. To address these critical gaps, this study conducted a comprehensive genome-wide comparative analysis across 23 OT strains, including UT 76, Karp, Kato, Gilliam, and Wuj/2014, using an in-house R-based computational pipeline. This analysis identified a conserved core genome of 744 genes, of which 19 are unique and pathogen- specific proteins. Subcellular localisation analyses revealed that nine of these proteins are membrane- associated, highlighting their potential accessibility to therapeutic agents. Additionally, proteins were prioritised through an integrative analysis that incorporates protein- protein interaction networks, druggability assessments, and antigenicity profiling. Six key proteins- dnaK, fusA, fabG, infB, nuoN and fabI were identified based on their essential roles in pathogen- specific pathways. These proteins are involved in membrane transport, transcription regulation, and biosynthesis, making them promising drug targets. Notably, this study employs in silico methodologies to overcome limitations inherent to traditional wet-lab approaches. Computational strategies are cost-effective for identifying conserved targets and supporting hypothesis- driven drug discovery. The findings presented here not only reveal previously uncharacterized therapeutic targets but also establish a genomic framework to improve diagnostic accuracy and guide future drug development against ST.
2026-06-26 | Multimodal imaging of ASHH in a case of Scrub Typhus Retinopathy.
To report a case of scrub typhus retinopathy presenting with angular sign of Henle layer hyperreflectivity (ASHH) on optical coherence tomography (OCT). This is a retrospective case report with multimodal imaging. A 43-year-old Indian man presented with sudden, painless diminution of vision in both eyes,(left more than right) following a febrile illness. He was diagnosed with scrub typhus based on positive IgM ELISA. Fundus examination revealed scattered intraretinal haemorrhages in both eyes and a yellowish foveal lesion in the left eye. Optical coherence tomography (OCT) demonstrated angular sign of Henle layer hyperreflectivity (ASHH) in both eyes, with a hard exudate clump at the fovea in the left eye and corresponding areas of blocked fluorescence on fluorescein angiography. A diagnosis of scrub typhus retinopathy was made. After treatment with oral corticosteroids, at one-month follow-up, visual acuity, with marked resolution of haemorrhages and regression of ASHH on OCT. Scrub typhus can present with retinopathy associated with ASHH, a marker of deep retinal ischemia. Multimodal imaging, particularly OCT, plays a crucial role in identifying ischemic retinal changes and may help in assessing disease severity and visual prognosis.
proteins
2025-04-14 | Scrub Typhus Combined With Septic Shock Disseminated Intravascular Coagulation and Significant Hyperfibrinolysis: A Case Report and Review of the Literature.
Introduction: Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi, whose pathophysiology is characterized by systemic small-vessel vasculitis. Its high misdiagnosis rate stems from its nonspecific clinical features. If not diagnosed and treated in time, patients may rapidly progress to multiorgan dysfunction syndrome (MODS) or even disseminated intravascular coagulation (DIC), posing a severe threat to life. Case Presentation: The patient was a 68-year-old male with "recurrent fever and dry cough for six days." He was admitted to the hospital with a diagnosis of scrub typhus. After admission, he developed severe acute respiratory distress syndrome (ARDS), MODS, septic shock, DIC with thrombocytopenia, hypofibrinogenemia, significant hyperfibrinolysis, and myocardial depression. The patient improved following treatment with doxycycline, moxifloxacin, renal replacement therapy, blood transfusion, antifibrinolysis, invasive mechanical ventilation, and other supportive therapies. The patient's coagulation profile in DIC caused by scrub typhus demonstrated significant hyperfibrinolysis, differing from that of garden-variety sepsis, and no similar cases were identified in a search of medical literature/databases. Conclusion: The fibrinolytic system in DIC caused by scrub typhus is excessively active, and antifibrinolytic therapy may benefit such patients. Further research on the distinct coagulation abnormalities in scrub typhus-associated DIC would be highly valuable compared to sepsis-associated DIC.
2025-04-01 | Immunogenic proteins of Orientia tsutsugamushi and implications for scrub typhus intervention: A narrative review
Scrub typhus is an acute undifferentiated febrile infectious disease transmitted by a chigger (genus Leptotrombidium) bite carrying Orientia (O.) tsutsugamushi , affecting millions of people annually while more than one billion people are susceptible. Endemic areas are expanding to Africa, Europe, Middle East, and South America which is concerning, as despite best efforts, there is no vaccine to combat the bacteria. There are now three species of Orientia and over 20 strains of O. tsutsugamushi. The past attempts to develop a vaccine have been ineffective as they confer homologous strain-specific immunity. Various immunogenic proteins of O. tsutsugamushi have been identified that interact with the extracellular matrix (fibronectin) or vMLL5 receptor and modify the cytoskeleton of non-phagocytic host cells, which aids in host cell adhesion and invasion. These highly conserved proteins involve type specific antigen 56 (TSA56), 47 kDa, OmpA, and autotransporter proteins (ScaA, ScaB and ScaC). TSA56 is the most immunogenic and contains four types of hypervariable regions. Out of all autotransporter proteins, ScaA provides the homologous strains specific immunity and when coupled with TSA56 it shows better protective immunity against heterologous strains. The review provides detailed insight into the potential immunogenic proteins of Orientia which can be utilized to develop the vaccine. Furthermore, studies focused on highly antigenic proteins will provide more insight into their roles in developing therapeutics and easy-to-handle rapid diagnostic kits.
2024-07-17 | CARBIMAZOLE-INDUCED AGRANULOCYTOSIS WITH CONCURRENT SCRUB TYPHUS
INTRODUCTIONWhile carbimazole is an effective treatment for hyperthyroidism, it carries a risk of agranulocytosis. Concurrently, rickettsial infections like scrub typhus can worsen neutropenia. We reviewed case notes, investigation results, imaging studies and treatment options based on a literature review. CASEA 55-year-old male farmer with hyperthyroidism on highdose carbimazole treatment sustained a machete injury to his left middle finger. Upon presentation, he had fever, normal thyroid function, stable hemodynamics, severe neutropenia (total white count 0.4 × 109 /L, absolute neutrophil count 0.02 × 103/µL) and typhus eschars. He was treated with doxycycline, piperacillin-tazobactam and subcutaneous granulocyte-colony stimulating factor (G-CSF). Abnormal thyroid function (FT4 46 pmol/L and TSH <0.01 m IU/L) and elevated C-reactive protein (234 mg/L) were also observed. Carbimazole was discontinued and replaced with oral cholestyramine and lithium. Positive serologic findings confirmed scrub typhus. With targeted treatment and G-CSF support, the patient's condition improved, as evidenced by normalized blood counts. Radioactive iodine therapy was contemplated once thyroid function was controlled. CONCLUSIONCarbimazole carries the risk of severe adverse effects, including agranulocytosis. This risk may be compounded with a concurrent rickettsial infection, which can also cause neutropenia. Diagnosis relies on clinical suspicion and profound neutropenia, requiring thorough evaluation including serological tests and PCR to differentiate between agranulocytosis-related and rickettsial infections. Immediate discontinuation of carbimazole and replacement with alternative antithyroid drugs is necessary, often supplemented with broad-spectrum antibiotics and G-CSF to prevent overwhelming infection risks. Tailored antibiotic therapy should also be administered for the rickettsial infection. Prompt recognition and intervention are crucial, particularly in endemic areas. Early diagnosis and aggressive management can help mitigate morbidity and mortality. Educating patients on symptom recognition remains the most effective preventive measure.
2024-05-24 | Lack of the IFN-γ signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions.
Scrub typhus is an acute febrile disease due to Orientia tsutsugamushi (Ot) infection and can be life-threatening with organ failure, hemorrhage, and fatality. Yet, little is known as to how the host reacts to Ot bacteria at early stages of infection; no reports have addressed the functional roles of type I versus type II interferon (IFN) responses in scrub typhus. In this study, we used comprehensive intradermal (i.d.) inoculation models and two clinically predominant Ot strains (Karp and Gilliam) to uncover early immune events. Karp infection induced sequential expression of Ifnb and Ifng in inflamed skin and draining lymph nodes at days 1 and 3 post-infection. Using double Ifnar1-/-Ifngr1-/- and Stat1-/- mice, we found that deficiency in IFN/STAT1 signaling resulted in lethal infection with profound pathology and skin eschar lesions, which resembled to human scrub typhus. Further analyses demonstrated that deficiency in IFN-γ, but not IFN-I, resulted in impaired NK cell and macrophage activation and uncontrolled bacterial growth and dissemination, leading to metabolic dysregulation, excessive inflammatory cell infiltration, and exacerbated tissue damage. NK cells were found to be the major cellular source of innate IFN-γ, contributing to the initial Ot control in the draining lymph nodes. In vitro studies with dendritic cell cultures revealed a superior antibacterial effect offered by IFN-γ than IFN-β. Comparative in vivo studies with Karp- and Gilliam-infection revealed a crucial role of IFN-γ signaling in protection against progression of eschar lesions and Ot infection lethality. Additionally, our i.d. mouse models of lethal infection with eschar lesions are promising tools for immunological study and vaccine development for scrub typhus.
2024-05-01 | Lack of IFN-g signaling leads to enhanced susceptibility to eschar-associated scrub typhus in mice
Abstract Scrub typhus is an infectious disease caused by the bacteria Orientia tsutsugamushi (Ot). Severe infection can lead to organ failure and hemorrhage, resulting in fatality without proper treatment. The mechanism of how the host innate immune system responds to this infection remains elusive. By using an intradermal (i.d.) inoculation mouse model, we found that dendritic cells (DCs) and macrophages (MФ) were the major cell subsets responsible for bacterial uptake in dermis and dissemination into draining lymph nodes (dLN), leading to a systemic infection. This process was dependent on the chemokine receptor CCR7. Interferons (IFNs) are known to play a crucial role in microbial infection defense. Our data showed that the levels of IFNs increased significantly in the skin and lymph nodes after infection. To investigate the role of IFNs in Ot infection, we i.d. infected Ifnar1- or Ifngr-deficient mice and found that the lack of IFN-γ, but not IFN-I signaling, resulted in visible skin eschar lesions, higher bacterial burdens in dLN, exacerbated systemic infection, and animal lethality. Our in vitro study demonstrated that IFN-γ restricted bacterial growth in DCs and MФ, suggesting that IFN-γ may inhibit bacterial dissemination in vivo by signaling on bacteria-carrying myeloid cells. Overall, our findings reveal a Trojan horse mechanism of bacterial transmission and highlight the crucial role of IFN-γ signaling in host protection against scrub typhus.
antibodies
2026-06-11 | A Case of Adult-Onset Still's Disease Diagnosed Following Treatment for Scrub Typhus.
A 28-year-old woman, previously diagnosed with seronegative rheumatoid arthritis, was admitted with fever, vomiting, and diarrhea. She developed septic shock with disseminated intravascular coagulation and was treated with antibiotics, noradrenaline, prednisolone, and thrombomodulin. On day 3, a rash appeared, and polymerase chain reaction detected Orientia tsutsugamushi deoxyribonucleic acid, thus confirming the diagnosis of scrub typhus. Her symptoms resolved after minocycline treatment. After tapering the prednisolone, fever, rash, and arthralgia recurred. Laboratory tests revealed elevated ferritin and interleukin-18 levels. After excluding other causes, adult-onset Still's disease (AOSD) was diagnosed in this patient. The patient exhibited a rapid improvement following tocilizumab treatment. Scrub typhus and AOSD share overlapping features that complicate diagnosis.
2026-05-15 | Successful management of scrub typhus-associated hemophagocytic lymphohistiocytosis with doxycycline and immunomodulation: a case report.
Hemophagocytic lymphohistiocytosis (HLH) is a fatal hyperinflammatory complication of scrub typhus, often with delayed diagnosis. This case report aims to detail the clinical trajectory and successful management of scrub typhus-associated HLH in a child, highlighting key diagnostic clues. A previously healthy 14-year-old boy from a scrub typhus-endemic area presented with prolonged high fever, cough, and lethargy. Physical examination revealed a pathognomonic eschar. Laboratory findings fulfilled HLH-2004 diagnostic criteria, including cytopenias, hyperferritinemia (>3,000 ng/mL), hypofibrinogenemia, and hemophagocytosis on bone marrow aspirate. The patient was diagnosed with secondary HLH triggered by scrub typhus. Immediate treatment with oral doxycycline, combined with immunomodulation using intravenous immunoglobulin and dexamethasone, led to fever resolution within 72 h and full recovery. This case highlights that in pediatric scrub typhus, a rapid decline in platelets/fibrinogen and a sharp rise in ferritin/LDH should alert clinicians to possible HLH. Early combined therapy targeting both the infection (e.g., doxycycline) and the cytokine storm (e.g., immunomodulators) may be beneficial for favorable outcomes.
2026-02-09 | Orientia tsutsugamushi binds to multiple C-type lectin receptors.
Orientia tsutsugamushi, the agent of scrub typhus, is an obligate intracellular bacterium whose atypical cell wall lacks many classical pathogen-associated molecular patterns but is enriched in neutral glycans. Its recognition by phagocytes is driven by a heat-stable ligand that triggers innate cytokine responses, yet the nature of this ligand and the receptors sensing it remain incompletely understood. While activation of innate immunity via toll-like (TLR) and nucleotide-binding and oligomerization domain-like receptors has been described, recognition via C-type lectin receptors (CLRs) has remained largely unexplored. Using a flow cytometry-based screening assay with a library of CLR-Fc fusion proteins, we demonstrate binding of Orientia to four mouse CLRs, including Mincle, Dectin-1, Langerin, and DCL-1, as well as to human DC-SIGN. Binding to Mincle was Ca²+-dependent, indicating carbohydrate-specific recognition. In bone marrow-derived dendritic cells (BMDC), heat-inactivated Orientia induced transcriptional upregulation of Mincle in a MyD88-dependent manner, suggesting cross talk between TLR and CLR pathways. Mincle was dispensable for TNF-α induction in BMDC stimulated with Orientia but contributed to the induction of interleukin-27 and cxcl-10 mRNA, indicating an immunomodulatory rather than a classical pro-inflammatory role. We also discuss in vivo data that demonstrated upregulation of Mincle and concomitant downregulation of Dectin-1 during Orientia infection. Together, this study identifies multiple CLRs as receptors for Orientia, highlights Mincle as a modulator of innate immunity, and suggests that Mincle-driven immunoregulation helps to shape the inflammatory environment during scrub typhus.
2025-10-06 | Guillain–Barré syndrome with anti-GM4 seropositivity after scrub typhus: a first case report
Abstract Background Scrub typhus, a major tropical febrile disease in Asia, rarely triggers Guillain–Barré syndrome (GBS)—an immune-mediated neuropathy typically post-antecedent infections or vaccinations. Only 16 global cases of this association were documented by 2024. Case presentation We present a case of a 72-year-old woman who developed progressive limb weakness and numbness following scrub typhus infection, accompanied by peripheral facial palsy, dysphagia, and dysphonia. Neurophysiological studies and cerebrospinal fluid analysis confirmed GBS diagnosis. Serological testing demonstrated positivity for anti-GM4 antibodies. Administration of immunotherapy resulted in improvement of the patient's clinical symptoms. Conclusions Vigilance for concomitant GBS is warranted during scrub typhus infection, as prompt immunotherapy typically yields favorable clinical outcomes.
2025-04-22 | Scrub typhus-associated movement and gait disorders: A systematic review with principal component analysis and in silico mechanistic modelling.
Orientia tsutsugamushi, the causative agent of scrub typhus, is increasingly recognised for its neurological complications. Among these, movement and gait disorders are poorly understood. We systematically examined their clinical spectrum and explored underlying mechanisms through in-silico protein-protein interaction modelling. A systematic review was conducted following PRISMA guidelines, including studies published up to 5 November 2024. Principal component analysis was used to identify clinical patterns among neurological features. In-silico protein-protein interaction modelling was used to examine potential cross-reactivity between Orientia tsutsugamushi proteins and human targets proteins. Among 76 cases, 50 presented with either isolated or combined movement disorders, most commonly opsoclonus (64.0%, 32/50), with the opsoclonus-myoclonus combination predominating (59.4%, 19/32). Other hyperkinetic features included tremor (4.0%, 2/50) and distinct forms of myoclonus (without opsoclonus) (8.0, 4/50%). Parkinsonism was present in 26.0% (13/50) of cases. Gait disorders, excluding parkinsonian gait and instability due to myoclonus, were well-characterised in 27 patients, one of whom had concomitant opsoclonus and cerebellar ataxia. Ataxic gait was the predominant pattern, observed in 96.3% (26/27), primarily cerebellar in origin. Principal component analysis revealed five principal components reflecting distinct clinical clusters: cerebellar dysfunction, tremor and parkinsonism, sensory ataxia and spinal involvement, myoclonus (diaphragmatic/action/segmental), and prolonged recovery and cranial nerve involvement. In-silico analyses revealed high-confidence interactions between bacterial epitopes and host proteins, including fibronectin-1 and Golgi-associated molecules, suggesting mechanisms of immune-mediated injury and neuroinflammation. Scrub typhus may lead to a range of movement and gait disorders through neuroimmune mechanisms and molecular mimicry. Principal component analysis offered a data-driven framework to classify these manifestations, highlighting clinically relevant patterns. Early recognition and targeted treatment are critical to improving outcomes. Future studies should validate the molecular targets identified and evaluate immunomodulatory strategies for therapeutic intervention.
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2025-06-25 | Reversible high-grade AV block in a patient with scrub typhus.
A man in his late 30s presented with a prolonged febrile illness and recurrent syncopal episodes. Physical examination revealed hypotension, bradycardia and eschars on the bilateral thighs. A 12-lead ECG showed complete heart block with wide QRS escape rate of 30 beats per minute. Laboratory tests confirmed scrub typhus with elevated cardiac markers. The patient was managed with a temporary transvenous pacemaker and intravenous doxycycline which led to rapid resolution of symptoms and complete normalisation of cardiac conduction within 48 hours. This case highlights the importance of scrub typhus in the differential diagnosis of febrile illnesses with conduction abnormalities, especially in endemic areas.
2017-07-19 | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i.v.) disseminated infection mouse model, we observed that more CD8+ T cells than CD4+ T cells were present in the spleen of infected mice at 12 dpi. We also determined that Treg cells and the proportion of T cells producing IL-10 were significantly increased from 6 dpi, which correlated with the onset of illness, body weight loss, and increased bacterial loads. We further studied CD8-/-, MHC I-/- and wild type control (WT) C57BL/6J mice to determine the importance of CD8+ T cells and MHC I molecules. After infection with an ordinarily sub-lethal dose of O. tsutsugamushi, all CD8-/- and MHC I-/- mice were moribund between 12 and 15 dpi, whereas all WT mice survived. Bacterial loads in the lung, kidney, liver and spleen of CD8-/- and MHC I-/- mice were significantly greater than those in WT mice. Interferon-γ (IFN-γ) and granzyme B mRNA levels in the liver of CD8-/- and MHC I-/- mice were significantly greater than in WT mice. In addition, more severe histopathologic lesions were observed in CD8-/- mice. Finally, adoptive transfer confirmed a major role of immune CD8+ T cells as well as a less effective contribution by immune CD8 T cell-depleted splenocytes in protection against O. tsutsugamushi infection. These studies demonstrated the critical importance of CD8+ T cells in the host immune response during O. tsutsugamushi infection.
2016-09-08 | Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection
T cells are known to contribute to immune protection against scrub typhus, a potentially fatal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to protection and pathogenesis during O. tsutsugamushi infection is still unknown. Using our recently developed BALB/c mouse model that is based on footpad inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T cells infiltrate spleen and lung during the third week of infection. Depletion of CD8+ T cells with monoclonal antibodies resulted in uncontrolled pathogen growth and mortality. Adoptive transfer of CD8+ T cells from infected animals protected naïve BALB/c mice from lethal outcome of intraperitoneal challenge. In C57Bl/6 mice, the pulmonary lymphocyte compartment showed an increased percentage of CD8+ T cells for at least 135 days post O. tsutsugamushi infection. Depletion of CD8+ T cells at 84 days post infection caused reactivation of bacterial growth. In CD8+ T cell-deficient beta 2-microglobulin knockout mice, bacterial replication was uncontrolled, and all mice succumbed to the infection, despite higher serum IFN-γ levels and stronger macrophage responses in liver and lung. Moreover, we show that CD8+ T cells but not NKT cells were required for hepatocyte injury: elevated concentrations of serum alanine aminotransferase and infection-induced subcapsular necrotic liver lesions surrounded by macrophages were found in C57Bl/6 and CD1d-deficient mice, but not in beta 2-microglobulin knockout mice. In the lungs, peribronchial macrophage infiltrations also depended on CD8+ T cells. In summary, our results demonstrate that CD8+ T cells restrict growth of O. tsutsugamushi during acute and persistent infection, and are required to protect from lethal infections in BALB/c and C57BL/6 mice. However, they also elicit specific pathologic tissue lesions in liver and lung.
2000-03-01 | Reducing the risk of transfusion-transmitted rickettsial disease by WBC filtration, using Orientia tsutsugamushiin a model system.
BACKGROUND: Careful donor screening and infectious disease marker testing have significantly reduced the incidence of transfusion‐transmitted diseases and improved the safety of the blood supply. However, transfusion‐transmitted diseases resulting from the use of asymptomatic yet infectious donors continue to put patients at risk. This study was undertaken to determine if third‐generation WBC filters could remove Orientia tsutsugamushi ‐infected cells from contaminated blood. STUDY DESIGN AND METHODS: Packed RBCs were inoculated with human MNCs infected with O. tsutsugamushi at levels estimated to occur in asymptomatic infectious donors. WBC reduction was accomplished with a third‐generation WBC filter. Prefiltration and postfiltration specimens were collected, serially diluted, and injected into mice to determine the infectivity of the samples. RESULTS: Mice receiving WBC‐reduced packed RBCs showed no signs of illness or markers of infectivity, which suggested that a reduction of as much as 10 5 infectious rickettsiae could be achieved by filtration. CONCLUSION: The high‐efficiency, third‐generation, WBC‐reduction filters that were tested may provide protection against the transfusion transmission of scrub typhus rickettsiae by removing from contaminated blood cells that contain intracellular bacteria.
1987-01-01 | Immunological Studies of Rickettsial Infection Establishment and Characterization of Rickettsia tsutsugamushi Antigen-Specific T Cell Line
T cell line specific for R. tsutsugamushi antigen was established by the long term culture of splenocytes from mice immunized with live Gilliam strain of R. tsutsugamushi and was propagated in the presence of homologous rickettsial antigen and syngeneic filler cells. The characteristics and the capacity to induce anti-rickettsial protection in vivo of the T cell line were studied. Flow cytometrical analysis demonstrated the T cell line had a phenotype of Thy 1.2+, L3T4+, and Lyt2-. The T cell line produced gamma interferon, one of macrophage activating factors, in cultures with specific antigen and could adoptively mediate anti-rickettsial protection in vivo. It is concluded that antigen-specific helper T cells play an, important, g role in the protection anainst rickettsial infection.
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