Prevalence of and factors associated with scrub typhus exposure among the hill tribe population living in high incidence areas in Thailand: a cross-sectional study.

BACKGROUND: Scrub typhus is a significant tropical disease, occurring in rural settings and therefore usually afflicting remote agricultural populations who have lower socioeconomic status and limited access to medical care. A large proportion of the hill tribe people in Thailand are financially poor, have limited education, and do not have adequate health care access. This study aimed to estimate the prevalence of and determine factors associated with scrub typhus exposure among the hill tribe population living in high-incidence areas in northern Thailand. METHODS: A cross-sectional study design was used to gather information from hill tribe people aged 18 years and over living in ten hill tribe villages in Mae Fah Luang, Chiang Rai Province, Thailand. Participants who met the inclusion criteria were invited to participate in the study. A validated questionnaire was used as the research instrument, and 5 mL blood samples were taken. Orientia tsutsugamushi IgM and IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and then confirmed by immunofluorescence assay (IFA). Logistic regression was used to detect associations between variables at a significance level of α = 0.05. RESULTS: A total of 485 hill tribe people participated in the study; 57.1% were female, 29.9% were over 60 years of age, 46.4% were from the Akha tribe, and 74.2% had never attended school. The overall prevalence of scrub typhus exposure was 48.0%. In the multivariate model, five variables were found to be associated with scrub typhus exposure. Participants aged over 60 years had a 4.31-fold increased risk (95% CI = 1.73-10.72) of scrub typhus exposure compared to those who were younger than 30 years. Those who were illiterate had a 3.46-fold increased risk (95% CI = 1.93-6.21) of scrub typhus exposure than those who had at least a primary education level. Participants from the Akha tribe had a 2.20-fold increased risk (95% CI = 1.31-3.72) of scrub typhus exposure than those from the Lahu tribe. Subjects who had a history of cutting grass had a 1.85-fold increased risk (95% CI = 1.20-2.84) of scrub typhus exposure. Those who never wore gloves for farming had a 2.12-fold increased risk (95% CI = 1.28-3.49) of scrub typhus exposure than those who wore gloves daily. CONCLUSIONS: There is a high prevalence of scrub typhus exposure among the hill tribe in Thailand. Effective public health interventions to promote scrub typhus awareness and prevention are urgently needed in these populations.

Role of hinge motion and ATP dynamics in factors for inversion stimulation FIS protein deduced while targeting drug resistant Orientia tsutsugamushi.

Orientia tsutsugamushi, the causative agent of scrub typhus has been found resistant to various classes of antibiotics such as penicillins, gentamycin and cephalosporins. Review of current literature suggests that the prevalence of scrub typhus has increased globally. Therefore, the current study has aimed at exploring the genome of O. tsutsugamushi to identify potential drug target proteins that can be used for developing novel antibiotics against the pathogen. Subtractive proteomics approach has revealed FIS as a potential drug target protein involved in two component system (TCS), a signaling pathway crucial for bacteria to survive and adjust in changing environmental conditions. Molecular docking studies have revealed compound-356 (CHEMBRIDGE-10040641-3710.356) as a potential inhibitor in both chains A and B of the FIS protein. Simulation results suggest that the docked complex has remained stable and compact throughout the 200 ns run. Significant conformational changes including the hinge motion was observed in the DNA binding domain. Furthermore, the presence of salt bridge between GLU910 and ARG417, rearrangement of interaction residues and displacement of ATP in the central AAA + domain upon binding to the inhibitor were also observed playing a role in stabilizing the protein structure.

Multiple Orientia clusters and Th1-skewed chemokine profile: a cross-sectional study in patients with scrub typhus from Nepal.

OBJECTIVES: Scrub typhus is an emerging infectious disease in Asia caused by Orientia tsutsugamushi (Ot). From Nepal, only scant data on the genetic epidemiology of this agent is available, and determinants of immunoregulation are poorly understood. METHODS: Patients (n = 238) referred to the National Public Health Laboratory (Kathmandu, Nepal) from all over Nepal for suspected scrub typhus were enrolled upon positive immunoglobulin (Ig)M testing between July and October 2015. From Ot 16S and 47 kD polymerase chain reaction (PCR)-positive samples, the variable domain I of the 56 kD gene was sequenced and phylogenetically analyzed. T helper (Th) cell-associated cytokines (n = 13) and chemokines (n = 12) were quantified by multiplex bead arrays. RESULTS: In 93/238 (39.1%) IgM-positive samples, Ot DNA was detected by quantitative PCR. Phylogenetic analysis of 56 kD sequences revealed seven distinct clusters, six of them with high homologies to strains detected in other countries. The Th1-related cytokines interferon-γ and C-X-C motif chemokine ligand 10 were strongly upregulated and correlated with bacteremia, while levels of Th2-associated chemokines were reduced. Bacteremia also correlated with concentrations of interleukin (IL)-6 and IL-10 but not tumor necrosis factor-α. CONCLUSION: We identified a considerable genetic heterogeneity of human-pathogenic Ot strains circulating in Nepal. Acute Nepalese scrub typhus patients showed strong Th1 but impaired Th2 responses, especially on the chemokine level.

Neurological Manifestations of Scrub Typhus.

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

Simple clinical and laboratory predictors to improve empirical treatment strategies in areas of high scrub typhus and dengue endemicity, central Vietnam.

BACKGROUND: Dengue fever is highly endemic in Vietnam, but scrub typhus-although recognized as an endemic disease-remains underappreciated. These diseases together are likely to account for more than half of the acute undifferentiated fever burden in Vietnam. Scrub typhus (ST) is a bacterial disease requiring antimicrobial treatment, while dengue fever (DF) is of viral etiology and does not. The access to adequate diagnostics and the current understanding of empirical treatment strategies for both illnesses remain limited. In this study we aimed to contribute to the clinical decision process in the management of these two important etiologies of febrile illness in Vietnam. METHODS: Using retrospective data from 221 PCR-confirmed scrub typhus cases and 387 NS1 protein positive dengue fever patients admitted to five hospitals in Khanh Hoa province (central Vietnam), we defined predictive characteristics for both diseases that support simple clinical decision making with potential to inform decision algorithms in future. We developed models to discriminate scrub typhus from dengue fever using multivariable logistic regression (M-LR) and classification and regression trees (CART). Regression trees were developed for the entire data set initially and pruned, based on cross-validation. Regression models were developed in a training data set involving 60% of the total sample and validated in the complementary subsample. Probability cut points for the distinction between scrub typhus and dengue fever were chosen to maximise the sum of sensitivity and specificity. RESULTS: Using M-LR, following seven predictors were identified, that reliably differentiate ST from DF; eschar, regional lymphadenopathy, an occupation in nature, increased days of fever on admission, increased neutrophil count, decreased ratio of neutrophils/lymphocytes, and age over 40. Sensitivity and specificity of predictions based on these seven factors reached 93.7% and 99.5%, respectively. When excluding the "eschar" variable, the values dropped to 76.3% and 92.3%, respectively. The CART model generated one further variable; increased days of fever on admission, when eschar was included, the sensitivity and specificity was 95% and 96.9%, respectively. The model without eschar involved the following six variables; regional lymphadenopathy, increased days of fever on admission, increased neutrophil count, increased lymphocyte count, platelet count ≥ 47 G/L and age over 28 years as predictors of ST and provided a sensitivity of 77.4% and a specificity of 90.7%. CONCLUSIONS: The generated algorithms contribute to differentiating scrub typhus from dengue fever using basic clinical and laboratory parameters, supporting clinical decision making in areas where dengue and scrub typhus are co-endemic in Vietnam.

Association of leptospirosis and scrub typhus in acute encephalitis syndrome in a tertiary care hospital in Odisha, India.

BACKGROUND: Acute encephalitis syndrome (AES) is a major public health concern in India, causing febrile illness principally associated with viral infection. Bacteria-like scrub typhus and leptospirosis also cause acute febrile illness. Therefore, this study was conceived to address the possible etiological agents contributing to sporadic AES in a tertiary care center in Odisha, India. METHOD: This was a prospective hospital-based study that enrolled 92 consecutive patients with clinically diagnosed AES whose blood/cerebrospinal fluid samples were tested for IgM antibodies to dengue, Japanese encephalitis (JE), herpes simplex virus (HSV), Epstein-Barr virus (EBV), leptospirosis and scrub typhus. RESULTS: Viral antibodies to dengue were detected in three (3.26%) cases, HSV1 in four (4.34%) and HSV2 in three (3.26%) cases. Significantly, antibodies to EBV in 22 (23.591%) and to JE in 27 (29.34%) cases were detected. Notably, 30 (32.60%) and 11(12.0%) of patients had IgM antibodies to leptospirosis and scrub typhus, respectively. CONCLUSION: This observation indicates an association of leptospirosis and scrub typhus infection in sporadic cases of AES, besides other viruses.

Splenic infarction and infectious diseases in Korea.

BACKGROUND: The spleen contains immune cells and exhibits a pattern of infarction different from other organs; as such, splenic infarction (SI) may provide important clues to infection. However, the nature of the relationship between SI and infectious disease(s) is not well understood. Accordingly, this retrospective study investigated the relationship between SI and infection. METHODS: Hospital records of patients with SI, who visited Inha University Hospital (Incheon, Republic of Korea) between January 2008 and December 2018, were reviewed. Patient data regarding clinical presentation, causative pathogens, risk factors, and radiological findings were collected and analyzed. RESULTS: Of 353 patients with SI, 101 with infectious conditions were enrolled in this study, and their data were analyzed to identify associations between SI and infection. Ten patients were diagnosed with infective endocarditis (IE), and 26 exhibited bacteremia without IE. Twenty-seven patients experienced systemic infection due to miscellaneous causes (negative result on conventional automated blood culture), including the following intracellular organisms: parasites (malaria [n = 12], babesiosis [n = 1]); bacteria (scrub typhus [n = 5]); viruses (Epstein-Barr [n = 1], cytomegalovirus [n = 1]); and unidentified pathogen[s] (n = 7). Splenomegaly was more common among patients with miscellaneous systemic infection; infarction involving other organs was rare. Thirty-eight patients had localized infections (e.g., respiratory, intra-abdominal, or skin and soft tissue infection), and most (35 of 38) had other risk factors for SI. CONCLUSIONS: In this study, various infectious conditions were found to be associated with SI, and intracellular organisms were the most common causative pathogens. Further studies are needed to examine other possible etiologies and the underlying pathophysiological mechanisms.

A Concise Review of the Epidemiology and Diagnostics of Rickettsioses: Rickettsia and Orientia spp.

Rickettsioses are globally distributed and caused by the family Rickettsiaceae, which comprise a diverse and expanding list of organisms. These include two genera, Rickettsia and Orientia Serology has been traditionally the mainstay of diagnosis, although this has been limited by cross-reactions among closely related members and diminished sensitivity/utility in the acute phase of illness. Other techniques, such as nucleic acid amplification tests using blood specimens or tissue swabs/biopsy specimens, sequencing, and mass spectrometry, have emerged in recent years for both pathogen and vector identification. This paper provides a concise review of the rickettsioses and the traditional and newer technologies available for their diagnosis.

Prevalence of scrub typhus in pyrexia of unknown origin and assessment of interleukin-8, tumor necrosis factor-alpha, and interferon-gamma levels in scrub typhus-positive patients.

BACKGROUND: Scrub typhus is lesser known cause of fever of unknown origin in India. Even if there have been reports documenting the prevalence of scrub typhus in different parts of India, it is still an unknown entity, and clinicians usually do not consider it as differential diagnosis. The present study was performed to document the prevalence of scrub typhus among febrile patients in western part of Uttar Pradesh and to assess the clinical profile of infected patients on the one hand and knowledge, attitude, and practices among clinicians on the other. MATERIALS AND METHODS: A total of 357 adult patients with fever of more than 5-day duration were recruited. All patients underwent complete physical examination, and detailed clinical history was elicited as per predesigned pro forma. After primary screening to rule out malaria, enteric fever, and leptospirosis infection, secondary screening for scrub typhus was done by rapid screen test and IgM ELISA. RESULTS: Scrub typhus infection was positive in 91 (25.5%) cases. The most common symptoms among the patients were fever (100%), pain in abdomen (79.1%), pedal edema 56 (61.5%), rash 44 (48.3%), headache 44 (48.3%), vomiting 42 (46.1%), constipation 33 (36.2%), cough 28 (30.7%), and lymphadenopathy 20 (21.9%). The median values of interleukin-8, interferon-gamma, and tumor necrosis factor-alpha in healthy controls were 15.54 pg/ml, 7.77 pg/ml, and 54.1 pg/ml, respectively, while the median values of these cytokines in scrub typhus-positive patients were 21.04 pg/ml, 8.74 pg/ml, and 73.8 pg/ml, respectively. CONCLUSION: Our results highlight that scrub typhus infection is an important cause of pyrexia of unknown origin, and active surveillance is necessary to assess the exact magnitude and distribution of the disease.

Tifus de los matorrales, una enfermedad emergente en Chile / Scrub typhus, an emerging infectious disease in Chile

Resumen El tifus de los matorrales, causado por Orientia tsutsugamushi y transmitido por larvas de ácaros trombicúlideos de roedores silvestres es una rickettsiosis endémica en el Asia Pacífico. Luego del primer caso identificado en Chile en el año 2006, nuestro grupo ha identificado más de 30 casos a partir del año 2015. Los casos se han presentado con un marcado predominio en meses de verano, y su presentación clínica incluye fiebre, exantema y una mancha negra en el sitio de inoculación. Otros hallazgos frecuentes han sido cefalea intensa, sudoración nocturna, aumento de PCR, VHS y transaminasas hepáticas. La gran mayoría de los pacientes se han diagnosticado en el sur de Chile (principalmente la isla de Chiloé), pero recientemente también se han presentado casos en la Región Metropolitana, en personas volviendo de viajes al sur de Chile. Los médicos clínicos deben estar informados de esta enfermedad emergente en el país, de modo de sospecharla e iniciar terapia empírica con doxiciclina. La confirmación de estos casos con los métodos diagnósticos disponibles en Chile contribuirá a una mejor comprensión del rango epidemiológico y la relevancia clínica de esta infección nueva en el país.

Scrub typhus, caused by Orientia tsutsugamushi and transmitted by larvae of trombiculid mites, is an endemic rickettsiosis in the Asia Pacific region. After the first identification of a case in Chile in 2006, more than 30 cases have been diagnosed by our group since 2015. Cases were detected predominantly during the Chilean summer months. Patients presented with fever, rash, and a typical eschar at the inoculation site; other frequent findings were intense headache, night sweats, increased laboratory markers of inflammation and transaminases. The vast majority of cases have been diagnosed in southern Chile (mainly Chiloé Island), although recently some cases were also identified in the central Metropolitan Region in patients returning from trips to southern Chile. Physicians attending Chilean patients should be aware of this emerging infection to be able to initiate empirical therapy with doxycycline. The confirmation of cases by the diagnostic methods available in Chile will contribute to a better understanding of the epidemiological and clinical relevance of this emerging infection in South America.

Neurological manifestations of scrub typhus in adults.

In order to study the neurological manifestations in adult patients suffering from scrub typhus, 323 patients aged over 18 years, admitted with a positive diagnosis, were screened for neurological dysfunction; 37 patients with symptoms and/or signs suggestive of neurological dysfunction were included in the study. Of these, 31 (84%) patients had altered sensorium, four (11%) had cerebellitis, one (2%) patient had acute transverse myelitis and one (2%) had bilateral papilloedema without focal neurological deficit. Of the 31 patients with altered sensorium, 15 (40%) had meningoencephalitis, three (8%) had seizures, two (5%) had cerebral haemorrhages, one (2%) had a presentation likened to neuroleptic malignant syndrome (NMS) and one (2%) had a 6th nerve palsy with inflammation of the right cavernous sinus. Cerebrospinal fluid (CSF) analysis was abnormal in 23 patients (raised lymphocytes in 68%, raised protein in 80%). All patients improved with anti-rickettsial therapy.

Diagnostic evaluation of rapid tests for scrub typhus in the Indian population is needed.

BACKGROUND: Owing to frequent outbreaks witnessed in different parts of the country in the recent past, scrub typhus is being described as a re-emerging infectious disease in India. Differentiating scrub typhus from other endemic diseases like malaria, leptospirosis, dengue fever, typhoid, etc. is difficult due to overlapping clinical features and a lower positivity for eschars in Asian populations. Hence, the diagnosis heavily relies on laboratory tests. DISCUSSION: Costs and the need of technical expertise limit the wide use of indirect immunoperoxidase or immunofluorescence assays, ELISA and PCR. The Weil-Felix test is the most commonly used and least expensive serological test, but lacks both sensitivity and specificity. Hence, the diagnosis of scrub typhus is often delayed or overlooked. With due consideration of the cost, rapidity, single test result and simplicity of interpretation, rapid diagnostic tests have come into vogue. However, evaluation of rapid diagnostic tests for scrub typhus in the Indian population is needed to justify or discourage their use. CONCLUSION: Research studies are needed to find the most suitable test in terms of the rapidity of the result, simplicity of the procedure, ease of interpretation and cost to be used in the Indian populace.

Diagnostic Accuracy of the InBios Scrub Typhus Detect Enzyme-Linked Immunoassay for the Detection of IgM Antibodies in Northern Thailand.

In this study, we examined the diagnostic accuracy of the InBios Scrub Typhus Detect IgM enzyme-linked immunosorbent assay (ELISA) and determined the optimal diagnostic optical density (OD) cutoffs for screening and diagnostic applications based on prospectively collected, characterized samples from undifferentiated febrile illness patients in northern Thailand. Direct comparisons with the serological gold standard, indirect immunofluorescence assay (IFA), revealed strong statistical correlation of ELISA OD values and IFA IgM titers. Determination of the optimal ELISA cutoff for seroepidemiology or screening purposes compared to the corresponding IFA reciprocal titer of 400 as previously described for Thailand was 0.60 OD, which corresponded to a sensitivity (Sn) of 84% and a specificity (Sp) of 98%. The diagnostic performance against the improved and more-stringent scrub typhus infection criteria (STIC), correcting for low false-positive IFA titers, resulted in an Sn of 93% and an Sp of 91% at an ELISA cutoff of 0.5 OD. This diagnostic ELISA cutoff corresponds to IFA reciprocal titers of 1,600 to 3,200, which greatly reduces the false-positive rates associated with low-positive IFA titers. These data are in congruence with the recently improved serodiagnostic positivity criteria using the Bayesian latent class modeling approach. In summary, the InBios Scrub Typhus Detect IgM ELISA is affordable and easy-to-use, with adequate diagnostic accuracy for screening and diagnostic purposes, and should be considered an improved alternative to the gold standard IFA for acute diagnosis. For broader application, regional cutoff validation and antigenic composition for consistent diagnostic accuracy should be considered.

[Clinical analysis of scrub typhus-associated hemophagocytic syndrome].

OBJECTIVE: To analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome. METHOD: The medical records for the onset time of hemophagocytic syndrome, the clinical course, the chest radiographic findings, laboratory data, antibiotic therapy, clinical outcome and its prognosis were retrospectively reviewed. RESULT: (1) Four patients were diagnosed as scrub typhus based on clinical manifestations only, while 15 patients met the criteria of laboratory diagnosis. All 19 patients with scrub typhus had hemophagocytic syndrome. Eschar lesion was identified in 12 patients, 7 patients were described as an ulcer. A seasonal pattern (78.9% from June through September in 15 patients) was observed. Clinical misdiagnosis was common (all 19 cases). There were 9 patients with admitting diagnosis of scrub typhus, 10 patients were not diagnosed as scrub typhus after admission. In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus. Until discharge from the hospital, 5 cases were not diagnosed with scrub typhus. In this study, the length of time from the illness onset (beginning of fever) to the occurrence of clinical symptoms was (9 ± 4) days. (2) All 19 patients had changed AST levels (149 ± 37) U/L, albumin levels (23 ± 4) g/L, C-reactive protein levels (103 ± 51) mg/L, and platelet count (48 ± 41) × 109/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis. Weil-Felix agglutination test revealed positive results in 6 of 15 cases. Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion. (3) Five cases with failure to diagnose the disease had ineffective antibiotics treatment (imipenem or ß-lactam-based regimens). These patients did not receive appropriate treatment with antibiotics against scrub typhus. Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics, 8 cases with chloramphenicol, 3 cases with azithromycin, and in 3 patients (2 cases of azithromycin and one case of erythromycin), therapy was then switched to chloramphenicol. Four patients were treated with methylprednisolone and 10 patients with dexamethasone. (4) During their hospitalization, the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS, four of five cases died. However, the course in 14 patients were relieved and did not progress to MODS. CONCLUSION: The diagnosis of scrub typhus was frequently delayed, the early course of scrub typhus could be associated with hemophagocytic syndrome. Serious complications of MODS generally occur without antibiotic treatment. Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness, significant increases in levels of CRP, hypoalbuminemia, thrombocytopenia, splenomegaly, pneumonitis with pleural effusion, especially those with suspected exposure history. It was not easily recognized without careful observation and was present for a few days in each patient.

Clinical profile of scrub typhus in children and its association with hemophagocytic lymphohistiocytosis.

OBJECTIVE: To study the clinical profile of children with scrub typhus and its association with hemophagocytic lymphohistiocytosis. METHODS: Children presenting with unexplained fever and multi-systemic involvement between May to December 2011 were tested for scrub typhus using IgM ELISA kits. Occurrence of Hemophagocytic lymphohistiocytosis in IgM positive cases of scrub typhus was studied. RESULTS: Of the 35 children with unexplained fever and multi-systemic involvement, 15 children (9 boys) tested positive for scrub typhus. Thrombocytopenia, hypoalbuminemia and raised hepatic transaminases were observed in all children. Out of seven children evaluated for hemophagocytic lymphohistiocytosis. 3 met the criteria for hemophagocytosis. Two children (one with hemophagocytic lymphohistiocytosis) died. CONCLUSIONS: Scrub typhus is a common cause of unexplained fever in children in northern India. Hemophagocytic lymphohistiocytosis can occasionally complicate scrub typhus in children.

Rickettsiosis transmitidas por garrapatas en las Américas: avances clínicos y epidemiológicos, y retos en el diagnóstico / Tick-borne rickettsioses in the Americas: clinical and epidemiological advances, and diagnostic challenges

Las rickettsiosis son entidades clínicas de tipo zoonótico, causadas por bacterias intracelulares estrictas de los géneros Rickettsia y Orientia, pertenecientes a la familia Rickettsiaceae. Su ecología está determinada por factores ambientales y la presencia de vectores específicos que condicionan el establecimiento y la epidemiología en diferentes regiones del mundo. En las Américas, durante el siglo XX, únicamente eran reconocidas tres de estas enfermedades: la fiebre manchada de las Montañas Rocosas, el tifus epidémico y el tifus endémico, Sin embargo, a partir del año 2000 se han descrito mas de 10 especies diferentes previamente desconocidas en este continente, tanto en artrópodos como en casos clínicos, hecho que permite clasificarlas como entidades clínicas emergentes y reemergentes. Dadas las manifestaciones clínicas de las enfermedades causadas por rickettsias, siendo la gran mayoría inespecíficas y, por lo mismo, compartidas con otras enfermedades infecciosas, especialmente virales y bacterianas, han sido enmarcadas entre los diagnósticos diferenciales del síndrome febril agudo, tanto en áreas urbanas como tropicales. En la actualidad, se cuenta con métodos diagnósticos directos e indirectos, que son útiles en la identificación del agente infeccioso, en este caso, causante de rickettsiosis.

Rickettsioses are a group of zoonotic diseases caused by strict intracellular bacteria of the genus Rickettsia and Orientia which belong to the Rickettsiaceae family. Their ecology is influenced by environmental factors and the presence of specific vectors that determine the establishment and epidemiology in different world regions. In America, during the 20 th century, only three of these diseases were recognized: Rocky Mountain spotted fever, epidemic typhus and endemic typhus. However, since 2000, more than 10 different species that had previously been unknown in this continent have been described, both in arthropods and in clinical cases, fact that classifies them as emerging and re-emerging diseases. Given the clinical manifestations of the diseases caused by rickettsias, being the majority unspecific and, therefore, shared with other infectious diseases, especially viral and bacterial, they have been framed within the differential diagnoses of acute febrile syndrome in urban and tropical areas. Nowadays, there are direct and indirect diagnostic methods, which are useful in the definition of the infectious agent, in this case, the cause of rickettsioses.

Endemic scrub typhus-like illness, Chile.

We report a case of scrub typhus in a 54-year-old man who was bitten by several terrestrial leeches during a trip to Chiloé Island in southern Chile in 2006. A molecular sample, identified as related to Orientia tsutsugamushi based on the sequence of the16S rRNA gene, was obtained from a biopsy specimen of the eschar on the patient's leg. Serologic analysis showed immunoglobulin G conversion against O. tsutsugamushi whole cell antigen. This case and its associated molecular analyses suggest that an Orientia-like agent is present in the Western Hemisphere that can produce scrub typhus-like illness. The molecular analysis suggests that the infectious agent is closely related, although not identical, to members of the Orientia sp. from Asia.

Antigenic types of Orientia tsutsugamushi in Malaysia.

The seroprevalence of various Orientia tsutsugamushi (OT) strains among Malaysian patients with suspected scrub typhus infections was determined using an indirect immunoperoxidase (IIP) assay. IgG against a single OT strain were detected in six sera (3 Karp, 1 Gilliam and 2 TC586), whereas IgM antibodies against a single OT strain (Gilliam) were noted in 3 sera (Gilliam). IgG reactive to all OT strains were present in 33 (47.1%) of the 70 sera and IgM reactive to all OT strains were present in 22 (78.6%) of the 28 sera. The fact that most sera were reactive to multiple OT strains suggests that group-specific antigens are involved in scrub typhus infections, whereas very few were due to strain-specific epitopes present on these strains. Peak IgG and IgM titers were noted more frequently against Gilliam, Karp, and TA763 strains: this suggests that these strains may be the commonest infecting strains among Malaysian patients. Two predominant OT polypeptides consistently reacted with patients' sera were the 70 kDa and 56 kDa proteins.

Evaluation of a newly developed dipstick test for the rapid diagnosis of scrub typhus in febrile patients.

Scrub typhus is a potentially fatal, febrile disease prevalent in rural Asia. The etiological agent, Orientia tsutsugamushi, is transmitted to humans by the bite of a larval trombiculid mite. No current diagnostic test is sufficiently practical for use by physicians working in rural areas. A new dipstick test using a dot blot immunoassay format has been developed for the serodiagnosis of scrub typhus. We evaluated this test on 83 patients presenting with acute fever of unknown origin at Maharaj Hospital, a tertiary care medical center in Nakhon Ratchasima, Northeast Thailand. The diagnosis of scrub typhus was confirmed in 30 of these patients (36%) by the indirect immunoperoxidase test. The sensitivity of the test was 87% and its specificity was 94%. The dot blot immunoassay dipstick is accurate, rapid, easy to use, and relatively inexpensive. It appears to be the best currently available test for diagnosing scrub typhus in rural areas where this disease predominates.