Scrub Typhus Patients Research Articles

Application of Nested PCR and Loop-Mediated Isothermal Amplification (LAMP) to Target 56kDa gene in Scrub Typhus Patients and Phylogenetic Analysis to Identify Orientia tsutsugamushi Strains Circulating In and Around Puducherry

Scrub typhus (ST) is a re-emerging zoonotic disease caused by Orientia tsutsugamushi and is transmitted by chiggers. Serological tests targeting IgM and/or IgG antibodies play a major role in the detection of ST cases. Orientia 56kDa genome is common target for the molecular diagosis of ST to identify the prevalence of specific serotypes of O. tsutsugamushi in and around Puducherry by targeting 56kDa gene with the application of phylogenetic analysis. This prospective laboratory-based study was conducted in a tertiary care teaching hospital, from November 2105 to March 2018. Blood samples were collected from out-patients/in-patients, and those tested positive for ST IgM ELISA (n=140) and an equal number of negative samples were archived and anonymized. Genomic DNA was extracted and analyzed by using Nested PCR and LAMP assay. The positive products were purified and sequenced. Phylogenetic tree was constructed based on the sequences. Among 280 samples, 45 (16.1%) N-PCR and 102 LAMP (36.43%) positivity was observed for 56kDa gene. Forty-one N-PCR positive products were sequenced and accession numbers were obtained (MG601875 to MG601917) for the isolates. Phylogenetic analysis was done by Maximum Likelihood methods and this study has showed that 32.3% are similar to the Karp isolates. Molecular diagnosis of Scrub typhus has become essential in case of doubtful serology and early acute phase of illness. Gene sequencing result indicates that most of them were different from the existing ones, which may belong to the newer strains. The identification of newer strains will be helpful in future for development of scrub typhus vaccine.

The Liver Function Score – “ALBI” Sets Apart Melioidosis, Scrub Typhus from Viral Hepatitis, Tuberculosis, Enteric Fever in a III-II Grade Score: Useful in Machine Learning and AI

ALBI (Albumin-Bilirubin) score is routinely used in grading liver function of hepatocarcinoma and hepatitis patients. In this purposive review, the published values of serum albumin, bilirubin in Viral hepatitis, Tuberculosis, Scrub typhus, Enteric fever has been compared with that of melioidosis. Since PubMed yielded zero searches with key words “albumin, bilirubin, melioidosis”, it was searched in Google Scholar, a better retrievable search engine. This yielded 46 relevant articles with 53 ALBI scores for Melioidosis. An equivalent search to retrieve 53 ALBI scores was made in Google Scholar for other confounding diseases of Melioidosis with search words “albumin, bilirubin, hepatitis” “albumin, bilirubin, tuberculosis”, “albumin, bilirubin, scrub typhus”, “albumin, bilirubin, enteric fever”. This raw data was deposited in Harvard dataverse (https://doi.org/10.7910/DVN/QEW20J) and subsequent analysis done is documented in this article. This placed Melioidosis patients and Scrub typhus patients to be on an average grade III ALBI and the patients of Viral hepatitis, Tuberculosis, and Enteric fever in grade II ALBI.
 GRAPHICAL ABSTRACT

Clinical, laboratory, and molecular epidemiology of Orientia tsutsugamushi infection from Southwestern India.

Scrub typhus is a vector borne disease which in a proportion of patients causes multiorgan involvement and death if untreated. Infecting genotype and virulence factors play a role in severity of infection and outcome. The current prospective cohort study was undertaken to elucidate the severity of illness in scrub typhus patients and to identify the circulating genotypes in Karnataka, India. A total of 214 patients of either gender from 9 districts of Karnataka and one patient each from Andhra Pradesh and Kerala, India were enrolled in the study. With a predefined severity criterion, 132 patients were segregated to the severe group. Multi organ involvement was seen in 59 (44.69%) patients. Phylogenetic analysis revealed JG-v like (48.97%), Karp-like (26.53%), JG-like (22.44%), and Kato-like (2.04%) strains in Karnataka. Patients infected with Orientia tsutsugamushi Karp-like strains had respiratory involvement (69.2%), cardiovascular involvement (46.2%) and thrombocytopenia (23.1%) and required higher hospital resource utilization.

Scrub Typhus Re-Emergence of The Neglected, Silent Killer in Himachal Pradesh (India)

Scrub typhus is one of the common causes of fever in the foothills of the Himalayan region of India, affecting almost all age groups of patients. Scrub typhus is a zoonotic mite-borne bacterial disease that is transmitted to the population by the bite of larvae of the infected trombiculid mites that bite humans. Currently, scrub typhus appears to be re-emerging and spreading in the non-endemic areas with alarming antibiotic resistance patterns. It is a threat to more than a billion people and causes significant mortality worldwide. Clinical features can present in a variety of ways in patients suffering with scrub typhus. It causes multiple organ dysfunction syndrome and mortality can range 60-70% without effective therapy. Scrub Typhus presenting with bicytopenia, pancytopenia, hepatomegaly, and splenomegaly. This present study aims to know the varied clinical presentation in scrub typhus patients with Pancytopenia and Bicytopenia and the incidence of hepatomegaly and splenomegaly in the paediatric age group. Prospective observational study conducted in the Department of Paediatrics in Dr. RPGMC Tanda Himachal Pradesh (India). The study included all patients except those falling in the exclusion criteria and only after informed written consent. A total of 37 children admitted with scrub typhus bicytopenia and pancytopenia were enrolled for one year, that is from March 2013 to March 2014. Bicytopenia was observed in 30 patients (81.08%) and pancytopenia in 7 (18.91%) cases in typhus patients. Hepatomegaly was observed in 28 patients (73.68%) and splenomegaly in 16 patients (42.10%). Anaemia was seen in 35 (94.59%) patients. Males 13 were less affected than females 24 with a male-to-female ratio of .54 to 1. The most common age group affected was 11-15 years with female prudence with a male: female ratio of 0.54:1. Pallor was the most common sign in 35 (94.59%) followed by hepatomegaly 28(73.68%) and splenomegaly in 16(42.10%) patients. It is very important to start empirical therapy in a patient with fever and multiorgan dysfunction syndrome for scrub typhus to reduce mortality. There is an urgent need to establish next-generation metagenomic sequencing centers in the region at the tertiary-level institutes for the detection of new antigenic variations.

A CROSS SECTIONAL STUDY TO EVALUATE ACUTE KIDNEY INJURY IN SCRUB TYPHUS PATIENTS

Objective: This study was conducted with the objective of estimating the incidence and severity of acute kidney injury (AKI) in scrub typhus patients. Methods: This was a cross-sectional study conducted on 90 patients diagnosed with scrub typhus in a tertiary care center. Basic demographic and treatment details of the patients were recorded. Routine hematological investigations and biochemical profiles were performed upon admission and follow-up. AKI was defined and classified based on the RIFLE criteria. Results: The mean age of the patients was 49.0±19.5 year and a female preponderance was observed. The hemoglobin level was significantly lower in AKI patients as compared to non-AKI patients. Meanwhile, there was a significant increase in mean TLC count, C-reactive protein, and total bilirubin in AKI patients as compared to non-AKI patients. Was significantly higher as compared to those without AKI. Increasing age, Intensive care unit admission, shock, urinary abnormalities, and mechanical ventilation were the factors significantly associated with AKI. Conclusion: AKI is a frequently reported complication in scrub typhus patients. In evaluating febrile illnesses associated with AKI, scrub typhus should be considered.

Estimation of Serum Albumin Level and its Prognostic Significance in Scrub Typhus Patients in Districts of Lower Assam

Estimation of Serum Albumin Level and its Prognostic Significance in Scrub Typhus Patients in Districts of Lower Assam

Coagulation Abnormalities in Severe Scrub Typhus and Their Association with Complications.

To describe coagulation abnormalities and their association with complications in patients with severe scrub typhus. A cohort study was conducted among all patients of severe scrub typhus [immunoglobulin M (IgM) positive] who reported to this facility from 1st August 2019 to 31st July 2020 and met our inclusion criteria. We estimated the incidence of severe thrombocytopenia (<50,000/µL) and overt disseminated intravascular coagulation (DIC) (DIC score of ≥5). We determined the association [risk (RR) ratios] of these abnormalities with complications of scrub typhus, namely-septic shock, multiple organ dysfunction syndrome (MODS), and septic shock with MODS. In total, 71 patients were studied with a mean age of 50 ± 15.5 years, of which 45 (63.4%) were females. On presentation, fever 70 (98.5%), myalgias 22 (31.0%), loose stools 13(18.3%), cough, vomiting, headache 11 (15.5%), altered sensorium 10(14.1%), and pain abdomen 9 (12.7%) were main symptoms. On examination, hypotension 31 (43.7%), eschar 25 (35.2%), icterus 17 (23.9%), and rash 16 (22.5%) were noted. The d-dimer (>0.5 µg/mL) levels were increased in all (100%) patients. Thrombocytopenia (91.5%) was the commonest hematological abnormality and 31 (43.6%) of them had severe thrombocytopenia, 25 (35.2%) patients had low fibrinogen levels (<200 mg/dL) and prothrombin time (PT >16.7 seconds) was prolonged in 20 (28.1%). A total of 42 (59.1%) patients developed MODS, 33 (46.4%) developed septic shock, 24 (33.8 %) had MODS with septic shock, 17 (23.9%) developed overt DIC, and eight (11.2%) died. Severe thrombocytopenia (p = -0.028) and overt DIC (p = 0.045) were significantly associated with septic shock development. In the patients admitted with severe scrub typhus; thrombocytopenia was the commonest hematological abnormality. The development of septic shock was significantly associated with severe thrombocytopenia and overt DIC.

Alterations in Germinal Center (GC) Formation and B Cell Activation during Severe Orientia tsutsugamushiInfection in Mice

Abstract Scrub typhus is a poorly studied, but life-threatening, disease caused by the bacterium Orientia tsutsugamushi (Ot). Humoral immunity in scrub typhus patients wanes as early as one-year post-infection; yet its underlying mechanisms remain unclear. The objective of this study is to delineate mechanisms underlying humoral immune dysregulation and B cell dysfunction during acute Ot infection. Using a lethal scrub typhus C57BL/6 murine model, we evaluated splenic GC responses by immunofluorescent staining. Splenic germinal centers (GL-7 +cells) were formed at D4, but were nearly absent at D8, accompanied by randomly scattered T cells. Both infection days had comparable numbers of GC B cells and T follicular helper (Tfh) cells, indicating that GC loss at D8 was less likely due to cell death, but rather dysregulation in GC formation. To confirm this hypothesis, we performed RNAseq analysis of purified B220 +B cells and revealed a set of differentially expressed genes associated with B cell adhesion (S1PR1, ICAM1, GPR183) and co-stimulation (CD40, ICOS-L, SLAMF1) at D8. Notably, the downregulation of S1PR2 (a GC-specific adhesion gene) was most evident at D8, correlating to disrupted GC formation. Furthermore, transcriptomic data revealed significant downregulation of 71% B cell activation genes on D8, suggesting attenuation of B cell activation. Additional studies with low- and high-virulence Ot strains and comparative flow cytometry revealed significant differences in both B cell subsets (plasmablasts, marginal zone B cells) and T cell subsets (Tfh and Tfr cells). This is the first study showing marked dysregulation of B cell responses during Ot infection, which helps understand the transient immunity associated with scrub typhus. Supported by grants from NIH (R01 AI132674, R21 AI156536, R21 AI153586, R01 EY028773, T32 AI007526), Department of Defense Threat Reduction Agency grant (HDTRA1-19-1-0043), UTMB IHII Data Acquisition (CIRWH&IHII Pilot/ Phase II Research grant) and UTMB Center for Biodefense and Emerging Infectious Diseases (Pilot grant)

EFFECT OF SCRUB TYPHUS DISEASE ON LIVER FUNCTION – A HOSPITAL BASED OBSERVATIONAL STUDY AT A TERTIARY CARE CENTRE, ASSAM, INDIA

Background And Objectives : Scrub typhus is a chigger-borne zoonotic disease, caused by Orientia tsutsugamushi. Humans are accidental hosts. It occurs all along East Asia with many recent outbreaks in North-East India. It shows similar symptoms to other tropical infections and its disease spectrum ranges from mild febrile illness to severe life-threatening illness with multi organ dysfunctions. This study was done to observe relationship between scrub typhus and liver function. Methods : A hospital based observational study was conducted on randomly selected 40 scrub typhus patients ( between 12 and 60 years) diagnosed by detecting IgM antibody using enzyme linked immunosorbent assay (ELISA) over a period of 1 year at a tertiary care centre, Assam. Liver function tests were performed on the diagnosed cases using reectance spectrophotometry method on automated analyser. The values of LFT were estimated and p-values were calculated to establish statistical signicance. Results : Total 40 number of cases of scrub typhus was taken for our study with a mean age of 29.28 years among which, males were 57.5% and females were 42.5%. Bilirubin elevation was seen in 25 patients (62.5%), AST was increased in 36 patients (90%), ALT was increased in 35 patients (87.5%), ALK was high in 25patients (62.5%), 32 pateints (80%) had hypoalbuminemia, with a p value of < 0.05, which is statistically signicant. Interpretation And Conclusion : Our study concluded that scrub typhus could to be taken into consideration in patients with undifferentiated fever with abnormal liver function tests.

A CROSS-SECTIONAL STUDY TO EVALUATE ACUTE KIDNEY INJURY IN SCRUB TYPHUS PATIENTS

Objective: This study was conducted with the objective to estimate the incidence and severity of acute kidney injury (AKI) scrub typhus patients. Methods: This was a cross-sectional study conducted 90 patients diagnosed with scrub typhus in a tertiary care center. Basic demographic and treatment details of the patients were recorded. Routine hematological investigations and biochemical profiles were performed upon admission and follow-up. AKI was defined and classified based on the RIFLE criteria. Results: Mean age of the patients was 49.0±19.5 years and female preponderance was observed. The hemoglobin level was significantly lower in AKI patients as compared to non-AKI patients. Meanwhile, there was a significant increase in mean TLC count, CRP, total bilirubin in AKI patients as compared to non-AKI patients. was significantly higher as compared to those without AKI. Increasing age, ICU admission, shock, urinary abnormalities, and mechanical ventilation were the factors significantly associated with AKI. Conclusion: AKI is a frequently reported complication in scrub typhus patients. In evaluating febrile illness associated with AKI, scrub typhus should be considered.

CLINICAL PROFILE AND TREATMENT OUTCOME IN SCRUB TYPHUS PATIENTS IN UDAIPUR

Background: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, an obligate intracellular gram-negative bacterium. It is transmitted via the larval stage of trombiculid mites (chigger, a primary reservoir). It is prevalent across southern and eastern India including Rajasthan. Therefore present research was carried out with an objective to study the clinical prole and treatment outcome in scrub typhus patients in Udaipur. Method: In this study, total 100 patients with an acute febrile illness diagnosed as scrub typhus by positive IgM antibodies against O. tsutsugamushi were enrolled, over a period of two months (August to October 2022). All relevant data were recorded and analyzed. Results: Among 100 cases, 52% patients reported from urban area and 48% patients from rural area. The mean age of patients was 43.75±16.82 years, ranged from 12-83 years with female predominance (male: female-1:1.37). Fever (100%), cough (40%) breathlessness (40%), altered sensorium (13%) and headache (11%) were the predominant clinical features. Eschar was seen in 33 patients. Renal (63%) and hepatic dysfunction (58%) was the commonest followed by respiratory dysfunction (49%). All patients (except pregnant patients) were treated with oral or inj.doxycycline. Seventeen patients needed mechanical ventilation and ve patients required dialysis. Total 24 patients died during the study period. Conclusion: Scrub typhus has become a leading infectious disease causing acute febrile illness. It should be considered as a differential diagnosis with high index of suspicion for acute febrile illness in patients from this region, as early diagnosis and intervention may reduce mortality.

A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus.

Assessment of cellular immune responses by combining intracellular cytokine staining and immunophenotyping using flow cytometry enables the simultaneous measurement of T cell phenotype and effector function in response to pathogens and vaccines. The use of whole blood samples rather than peripheral blood mononuclear cells avoids both the need for immediate processing and loss of functional antigen presenting cells due to processing and cryopreservation. Using whole blood provides the possibility to stimulate peripheral T cells in situ, and is more suitable for studies where sample volume is limited, such as those involving children, the elderly and critically ill patients. The aim of this study was to provide a robust tool for the assessment of antigen-specific T cell responses in a field site setting with limited resources. We optimised a flow cytometry-based whole blood intracellular cytokine assay (WBA) with respect to duration of antigen stimulation and intracellular protein retention time. We demonstrate the ability of the WBA to capture polyfunctional T cell responses in the context of acute scrub typhus infection, by measuring IFN-γ, TNF and IL-2 in CD4+ and CD8+ T cells in response to the causative agent O. tsutsugamushi (OT). Using an optimised OT antigen preparation, we demonstrate the presence of polyfunctional antigen-specific memory CD4+ T cells in the blood of scrub typhus patients. In conclusion, this flow cytometry-based WBA is well-suited for use at field study sites, and enables the assessment of polyfunctional T cell responses to infectious agents and vaccines through delineation of antigen-specific cytokine secretion at the single cell level.

ECHOLOGICAL ABNORMALITIES IN SEVERE SCRUB TYPHUS PATIENTS

Background: Jhalawar is an endemic area for scrub typhus.Scrub typhus presents as an acute,febrile,exanthematous illness.If not treated early,it can lead to life threatening complications,affecting various systems of the body.Hence,this study was done with an objective to study the cardiovascular abnormalities in patients of severe scrub typhus. Methods: We conducted a hospital-based study in the Department of Medicine, of a tertiary care hospital in jhalawar medical college in patients of severe scrub typhus from July 2021 to November 2021. Results: Echocardiographic changes included tricuspid regurgitation in 8(16.66%), pericardial effusion in 5(10.41%), myocarditis in 11(22.91%) and Regional wall motion abnormality in 4(8.33%). Left ventricular ejection fraction >45% in 38 (79.16%) and <45% in 10(20.83%). Conclusions: Severe scrub typhus manifested with tricuspid regurgitation, myocarditis, pericardial effusion and Regional wall motion abnormality.

Genetic recombination of Orientia tsutsugamushi strains from scrub typhus patients in Guangxi, Southwest China, and the analysis of clinical features

Three Orientia tsutsugamushi genotypic groups belonging to two prototypes (Gilliam and Karp) were identified in scrub typhus patients from Guangxi, Southwest China. Fever, headache, pneumonia, fatigue, chill, and anorexia were the most common clinical signs. Frequent recombination was observed for their 47-kDa gene compared to 56-kDa and 16S genes. Furthermore, patients infected with the Gilliam prototype represent a much higher proportion of pneumonia (6/6, 100%) than those infected with the Karp prototype (4/8, 50%) (p-value = 0.040). This discrepancy is consistent with recent animal tests on rhesus and may indicate different virulence and tissue tropism between different O. tsutsugamushi prototypes.

Cytokine Profile of Scrub Typhus Patients during the Acute Phase of Illness

Background: An early and effective immune response has a role in disease presentation and clearance of pathogen. Chemokine and cytokine responses in the immunopathogenesis of scrub typhus (ST) are the least explored aspect. This study aimed to analyze interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-α), IL-10, transforming growth factor (TGF)-β, and human macrophage inflammatory protein-1 (HMIP-1) β cytokine levels in ST-positive patients during the acute phase of illness. Materials and Methods: A total of 112 ST-positive patients were included in the study with 30 healthy controls (HC). Diagnosis was confirmed by immunoglobulin M enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay. The serum levels of cytokines were measured using the ELISA. Statistical analysis was performed with the IBM SPSS Statistics 20 and MedCalc 16.1 Software. Results: The mean level of IL-6, IL-10, TNF-α, and HMIP1-β (72 pg/ml, 86.7 pg/ml, 187.05 pg/ml, and 12.23 pg/ml vs. 7.30 pg. ml, 8.73 pg/ml, 56.62 pg/ml, and 6.94 pg/ml, respectively) was significantly raised among the ST patients compared to the control group (P < 0.001) However, the mean and median levels of IL-2 and TGF-β were not differed significantly between ST patients and HC (P = 0.0207 and 0.0386, respectively). The severity of the disease involved respiratory complications. Around 90.1% (101/112) of patients showed high levels of IL-6, whereas IL-10, TNF-α, and HMIP-1 β levels were raised in 97 (86.6%), 63 (56.2%), and 69 (61.6%) cases, respectively. There was a higher TNF-α level in severe cases with a few values up to 298.77 pg/ml. Conclusion: Proinflammatory cytokines and IL-10 were found to be increased in ST patients during the acute phase of infection. A proper balance of these cytokines is required for a better outcome. These findings suggest that the status of TNF-α levels in the acute phase may predict the severity of ST disease.

Field epidemiology, clinical findings and outcome of Scrub typhus patients admitted at Gedu District Hospital, Chhukha, Bhutan.

This study aimed to understand the field epidemiology, clinical findings, diagnostic reports and outcome of Scrub typhus patients admitted at Gedu District Hospital, Bhutan. The researcher extracted data from the records of patients admitted at the hospital from 1 January 2017 to 31 December 2020, with diagnosis of Scrub typhus. A total of 185 records were used to study the demographic distribution, results of rapid diagnostic test for Scrub typhus, presence of eschar, treatment outcome and duration of admission in the hospital. The months of May to October had increased admissions of 137 (74%) patients with a peak in September. Three gewogs (sub-districts) had 173 (93.5%) patients; age range was 6 months to 84 years and a greater proportion of patients were females. Scrub typhus is endemic in the district. The absence of recorded fever or a negative rapid diagnostic test report may not exclude the diagnosis of Scrub typhus.

A Use of 56-kDa Recombinant Protein of Orientia tsutsugamushi Karp Serotype in Serodiagnosis of Scrub Typhus by Enzyme-Linked Immunosorbent Assay in Thais.

Scrub typhus is a mite-borne disease caused by a Gram-negative obligately intracellular bacillus, Orientia tsutsugamushi. The disease is endemic in the Asia-Australia-Pacific region, including Thailand. Scrub typhus generally manifests as acute undifferentiated febrile fever along with myalgia, rash, and lymphadenopathy. An eschar can be a valuable diagnostic clue, but this skin lesion may be missed in some patients. The disease symptoms resemble those of other febrile illnesses such as leptospirosis, typhoid, murine typhus, malaria, and dengue fever, making a laboratory diagnosis necessary for the definitive diagnosis. In this study, we expressed a recombinant protein derived from 56-kDa type-specific antigen of O. tsutsugamushi Karp serotype and tested its ability to detect and differentiate scrub typhus infection. IgM and IgG antibodies were determined in sera from scrub typhus (n = 92) and other febrile illness patients (murine typhus (n = 25), melioidosis (n = 36), leptospirosis (n = 42), and dengue (n = 35)) from Thailand. Sensitivities of 87.0% and 59.8% with a specified assay cut-off were obtained for IgM and IgG indirect ELISAs, respectively, with a specificity of 100% in both tests. The sensitivity was increased to 95.7% when a combination of IgM and IgG ELISAs results was considered. Our study suggested a potential of the 56-kDa recombinant protein for further development and evaluation for use in scrub typhus serodiagnosis.

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

ObjectivesScrub 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. MethodsPatients (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. ResultsIn 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. ConclusionWe 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.

1167. Changing spectrum of aetiology of Acute Fever with Jaundice (Tropical Jaundice) in Adults presenting to Emergency Care--- A study from a Tertiary Care Hospital in North India

Abstract Background The spectrum of infections causing the above acute onset fever with jaundice has changed over the last few years from the conventional hepatotropic viruses to new emerging infections. Methods 250 adult patients ≥ 14 years of age) with acute fever (body temperature > 101ᵒF of 14 days or less in duration) without any localized source of infection on initial clinical evaluation accompanied with jaundice (hyperbilirubinemia ≥ 1.5 mg/dl or elevation of ALT or AST ≥ three times upper limit) were enrolled.All these patients with fever and jaundice were evaluated on the basis of a standard proforma and were evaluated for malaria (peripheral smears/rapid diagnostic kits), scrub typhus( PCR /IgM ELISA), leptospirosis(IgM ELISA), enteric fever by blood cultures and dengue by dengue (NS1 antigen test and IgM ELISA), Hepatitis(IgM ELISA of EBV/HSV, IgM ELISA of HAV/HEV and HBsAg with IgM HBc ELISA if HBsAg positive) Results 62.5 % were males and 37.5 % were females. The mean duration of fever before the presentation was 8.1 ± 2.58 days. 10 patients (4%) died, while 133 patients (96%) improved with treatment. Scrub typhus 57 (22.8%), Hepatitis E 33 (13.2%), malaria 9 (3.6%), dengue fever, enteric fever, hepatitis A and leptospirosis in 26 (10.4%), 6 (2.4%), 6 (2.4%) patients and 4 (1.6%) patient respectively were the prominent aetiology a patient presenting with fever and jaundice. Probable sepsis (Fulfilling SIRS criteria with a negative culture) accounted for 40(16%) patients. In 69(27.6%) cases no diagnosis could be made on serological testing Conjunctival suffusion (OR=23.17), respiratory crepitations (OR=5.17), thrombocytopenia (OR=1.14), normal INR (OR=0.29) were significant predictors of a diagnosis of scrub typhus in patients with fever and jaundice. Severe anaemia (Hb< 8), Hypoalbuminemia, severe thrombocytopenia (Platelet count < 50,000) and a near-normal INR at admission were predictors of a malarial vs a viral aetiology of Tropical jaundice. Co-infection with scrub typhus and malaria was seen in 6 patients (vivax-5 and falciparum-1) and viral hepatitis A & E was observed in 10 patients. Conclusion Neglected Tropical diseases like Scrub typhus infection is emerging as common aetiology of acute onset tropical jaundice in adults presenting to emergency services. Disclosures All Authors: No reported disclosures.

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

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