RESUMEN

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.

Asunto(s)

Antígenos de Histocompatibilidad Clase I , Péptidos y Proteínas de Señalización Intracelular , Orientia tsutsugamushi , Orientia tsutsugamushi/metabolismo , Orientia tsutsugamushi/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , Animales , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Citoplasma/metabolismo , Células HEK293 , Proteolisis , Tifus por Ácaros/inmunología , Tifus por Ácaros/microbiología , Tifus por Ácaros/metabolismo , Ratones , Ubiquitinación , Interacciones Huésped-Patógeno/inmunología

RESUMEN

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.

Asunto(s)

Tifus por Ácaros , Centros de Atención Terciaria , Humanos , Tifus por Ácaros/epidemiología , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/tratamiento farmacológico , India/epidemiología , Estudios Prospectivos , Niño , Preescolar , Masculino , Femenino , Prevalencia , Centros de Atención Terciaria/organización & administración , Centros de Atención Terciaria/estadística & datos numéricos , Lactante , Orientia tsutsugamushi/patogenicidad

RESUMEN

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.

Asunto(s)

Borrelia , Orientia tsutsugamushi , Rickettsia , Roedores , Musarañas , Garrapatas , Animales , Musarañas/parasitología , Musarañas/microbiología , Roedores/microbiología , Roedores/parasitología , Rickettsia/aislamiento & purificación , Rickettsia/genética , República de Corea/epidemiología , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/aislamiento & purificación , Borrelia/aislamiento & purificación , Borrelia/genética , Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/veterinaria , Reacción en Cadena de la Polimerasa , Animales Salvajes/microbiología , Animales Salvajes/parasitología , Tifus por Ácaros/epidemiología , Tifus por Ácaros/veterinaria , Tifus por Ácaros/microbiología

RESUMEN

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.

Asunto(s)

Larva , Rickettsia , Rickettsiosis Exantemáticas , Trombiculidae , Animales , Rickettsia/genética , Rickettsia/clasificación , Rickettsia/aislamiento & purificación , Trombiculidae/microbiología , Larva/microbiología , Rickettsiosis Exantemáticas/microbiología , Genoma Bacteriano , Humanos , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/clasificación , Orientia tsutsugamushi/aislamiento & purificación , Femenino , Filogenia , Japón , Factores de Virulencia/genética , Tifus por Ácaros/microbiología , Tifus por Ácaros/transmisión , Línea Celular

RESUMEN

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.

Asunto(s)

Antibacterianos , Doxiciclina , Tifus por Ácaros , Humanos , Tifus por Ácaros/complicaciones , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/tratamiento farmacológico , Masculino , Doxiciclina/uso terapéutico , Antibacterianos/uso terapéutico , Anemia Hemolítica/etiología , Anemia Hemolítica/diagnóstico , Adulto , Orientia tsutsugamushi/aislamiento & purificación

RESUMEN

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.

Asunto(s)

Tifus por Ácaros , Tifus por Ácaros/epidemiología , Tifus por Ácaros/mortalidad , Humanos , Estudios Seroepidemiológicos , Factores de Riesgo , Incidencia , Orientia tsutsugamushi/inmunología , Salud Global , Animales

RESUMEN

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.

Asunto(s)

Tifus por Ácaros , Humanos , Tifus por Ácaros/complicaciones , Tifus por Ácaros/diagnóstico , Masculino , Adulto , Femenino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/diagnóstico , India , Meningoencefalitis/diagnóstico

RESUMEN

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.

Asunto(s)

Antibacterianos , Accidente Cerebrovascular Hemorrágico , Tifus por Ácaros , Humanos , Tifus por Ácaros/complicaciones , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/tratamiento farmacológico , Femenino , Adulto , Accidente Cerebrovascular Hemorrágico/diagnóstico , Antibacterianos/uso terapéutico , Diagnóstico Diferencial , Orientia tsutsugamushi , Tomografía Computarizada por Rayos X

RESUMEN

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.

Asunto(s)

Fluorodesoxiglucosa F18 , Lupus Eritematoso Sistémico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tifus por Ácaros , Humanos , Tifus por Ácaros/diagnóstico por imagen , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Bazo/diagnóstico por imagen , Bazo/patología , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/metabolismo , Diagnóstico Diferencial , Radiofármacos , Adulto Joven

RESUMEN

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

Asunto(s)

Anticuerpos Antibacterianos , Inmunoglobulina G , Inmunoglobulina M , Orientia tsutsugamushi , Tifus por Ácaros , Tifus por Ácaros/epidemiología , Tifus por Ácaros/inmunología , Humanos , India/epidemiología , Estudios Seroepidemiológicos , Nepal/epidemiología , Inmunoglobulina G/sangre , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Orientia tsutsugamushi/inmunología , Inmunoglobulina M/sangre , Incidencia , Adulto , Masculino , Femenino , Tailandia/epidemiología , Adolescente , Adulto Joven , Teorema de Bayes , Persona de Mediana Edad

RESUMEN

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.

Asunto(s)

Infecciones Bacterianas del Ojo , Glaucoma de Ángulo Abierto , Presión Intraocular , Tifus por Ácaros , Humanos , Masculino , Persona de Mediana Edad , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Presión Intraocular/fisiología , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/tratamiento farmacológico , Tifus por Ácaros/microbiología , Tifus por Ácaros/complicaciones , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/microbiología , Antibacterianos/uso terapéutico , Orientia tsutsugamushi/aislamiento & purificación , Doxiciclina/uso terapéutico , Uveítis Anterior/microbiología , Uveítis Anterior/diagnóstico , Uveítis Anterior/tratamiento farmacológico , Trabeculectomía

RESUMEN

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.

Asunto(s)

Antibacterianos , Tifus por Ácaros , Humanos , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/tratamiento farmacológico , Tifus por Ácaros/complicaciones , Masculino , Adolescente , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Doxiciclina/uso terapéutico , Doxiciclina/administración & dosificación , Orientia tsutsugamushi/aislamiento & purificación , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/microbiología

RESUMEN

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.

Asunto(s)

Antibacterianos , Orientia tsutsugamushi , Tifus por Ácaros , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/efectos de los fármacos , Tifus por Ácaros/microbiología , Tifus por Ácaros/tratamiento farmacológico , Antibacterianos/farmacología , Humanos , Adaptación Fisiológica , Animales

RESUMEN

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.

Asunto(s)

Heces , Orientia tsutsugamushi , Tifus por Ácaros , Bazo , Animales , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/aislamiento & purificación , India/epidemiología , Tifus por Ácaros/epidemiología , Tifus por Ácaros/microbiología , Ratas , Heces/microbiología , Estudios Transversales , Prevalencia , Bazo/microbiología , Hígado/microbiología , Enfermedades de los Roedores/epidemiología , Enfermedades de los Roedores/microbiología , Reacción en Cadena de la Polimerasa , ADN Bacteriano/genética

RESUMEN

Acute encephalitis syndrome (AES) is a major public health concern in India as the aetiology remains unknown in the majority of cases with the current testing algorithm. We aimed to study the incidence of Japanese encephalitis (JE) and determine the aetiology of non-JE AES cases to develop an evidence-based testing algorithm. Cerebrospinal fluid (CSF) samples were tested for Japanese encephalitis virus by ELISA and polymerase chain reaction (PCR). Multiplex real-time PCR was done for Dengue, Chikungunya, West Nile, Zika, Enterovirus, Epstein Barr Virus, Herpes Simplex Virus, Adenovirus, Cytomegalovirus, Herpesvirus 6, Parechovirus, Parvovirus B19, Varicella Zoster Virus, Scrub typhus, Rickettsia species, Leptospira, Salmonella species, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Plasmodium species and by ELISA for Mumps and Measles virus. Of the 3173 CSF samples, 461 (14.5%) were positive for JE. Of the 334 non-JE AES cases, 66.2% viz. Scrub typhus (25.7%), Mumps (19.5%), Measles (4.2%), Parvovirus B19 (3.9%) Plasmodium (2.7%), HSV 1 and 2 (2.4%), EBV and Streptococcus pneumoniae (2.1% each), Salmonella and HHV 6 (1.2% each) were predominant. Hence, an improved surveillance system and our suggested expanded testing algorithm can improve the diagnosis of potentially treatable infectious agents of AES in India.

Asunto(s)

Encefalopatía Aguda Febril , Humanos , India/epidemiología , Masculino , Adolescente , Femenino , Preescolar , Niño , Adulto Joven , Adulto , Encefalopatía Aguda Febril/epidemiología , Encefalopatía Aguda Febril/diagnóstico , Encefalopatía Aguda Febril/etiología , Encefalopatía Aguda Febril/virología , Lactante , Incidencia , Persona de Mediana Edad , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/diagnóstico , Encefalitis Japonesa/virología , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Anciano , Tifus por Ácaros/epidemiología , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/microbiología

RESUMEN

INTRODUCTION: The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India. METHODS: We conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever. RESULTS: The demographic profile predominantly included individuals aged 21-40 years, with a male-to-female ratio of 1.9:1; 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%); malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases. CONCLUSION: Our findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use.

Asunto(s)

Fiebre , Humanos , Estudios Transversales , Femenino , Masculino , Adulto , India/epidemiología , Fiebre/etiología , Adulto Joven , Persona de Mediana Edad , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/epidemiología , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/epidemiología , Dengue/diagnóstico , Dengue/epidemiología , Dengue/complicaciones , Factores de Tiempo , Malaria/diagnóstico , Malaria/epidemiología , Centros de Atención Terciaria , Adolescente , Atención Terciaria de Salud

RESUMEN

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-ß. 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.

Asunto(s)

Interferón gamma , Orientia tsutsugamushi , Tifus por Ácaros , Transducción de Señal , Animales , Ratones , Modelos Animales de Enfermedad , Interferón gamma/metabolismo , Interferón gamma/inmunología , Ratones Endogámicos C57BL , Ratones Noqueados , Orientia tsutsugamushi/inmunología , Tifus por Ácaros/inmunología , Tifus por Ácaros/microbiología , Piel/microbiología , Piel/patología , Piel/inmunología , Factor de Transcripción STAT1/metabolismo , Receptor de Interferón gamma/genética , Receptor de Interferón gamma/metabolismo

RESUMEN

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

Asunto(s)

Linfohistiocitosis Hemofagocítica , Orientia tsutsugamushi , Tifus por Ácaros , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/complicaciones , Humanos , Femenino , Niño , Orientia tsutsugamushi/aislamiento & purificación , Orientia tsutsugamushi/genética , Linfohistiocitosis Hemofagocítica/diagnóstico , China , Masculino , Doxiciclina/uso terapéutico

RESUMEN

Background: Scrub typhus has become widespread across various regions in China in recent decades, causing a considerable burden on residents. While meteorological variables significantly impact the spread of scrub typhus, there is insufficient quantitative evidence illustrating this association in known high-endemic areas. Methods: A distributed lag non-linear model was applied to explore the relationship between meteorological parameters and scrub typhus incidence from 2010 to 2019 in Baoshan City, western Yunnan Province, China. Results: High monthly mean (20°C) and maximum (30°C) temperatures were associated with a peak risk of scrub typhus in the current month. Higher minimum temperatures and higher relative humidity were followed by increasing cumulative risks over the ensuing 3 months. Higher precipitation was followed by increasing cumulative risk over the ensuing 2-month period, peaking at around 30 cm. Conclusion: The non-linear lag associations between meteorological parameters and scrub typhus incidence suggest that higher monthly minimum temperature and relative humidity could be associated with an increased risk of scrub typhus in the subsequent several months, while warm temperature is more likely to impact the occurrence of scrub typhus in the current month.

Asunto(s)

Humedad , Conceptos Meteorológicos , Tifus por Ácaros , Tifus por Ácaros/epidemiología , Humanos , China/epidemiología , Incidencia , Temperatura , Dinámicas no Lineales , Estaciones del Año , Factores de Riesgo

RESUMEN

Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia-Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27-26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05-53.40) for males and 48.84% (45.87-51.80) for females. Eschar prevalence was observed to be 30.34% (22.54-38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions.

Asunto(s)

Tifus por Ácaros , Tifus por Ácaros/epidemiología , Humanos , Estudios Seroepidemiológicos , Femenino , Masculino , Prevalencia , Orientia tsutsugamushi/inmunología , Salud Global