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PubMed2025

Proteome Profiling in Cerebrospinal Fluid Reveals Increased Levels of Peroxiredoxin 2 Discriminating Japanese Encephalitis Virus and Scrub Typhus Infection.

Japanese encephalitis virus (JEV) and scrub typhus (ST) are major etiological agents of acute encephalitis syndrome (AES) in India and South Asia. The pathophysiological changes at the molecular level caused by JEV and ST have yet to be studied in detail. The cerebrospinal fluid (CSF) proteomic landscape is a critical indicator of CNS pathology. Here, we conducted label-free quantitative proteomics on CSF from AES patients (n = 15) to identify etiology-specific differentially expressed proteins (DEPs) linked to encephalitis. The key DEPs were validated via ELISA in CSF (n = 49) and serum (n = 33). Our findings revealed 50 proteins exhibited differential expression across JEV and ST groups, with a notable subset of three proteins, PRDX2, KLK6, and TTR. PRDX2 and KLK6 were markedly elevated in JEV CSF (AUC: 0.8933 and 0.9689) but not in ST or non-JEV AES, while TTR was reduced in JEV yet elevated in ST (AUC: 0.5619 vs. 0.8238). Further, PRDX2 upregulation was validated in JEV-infected mouse brains and cortical neurons. Overexpression of PRDX2 in human neuroblastoma cells correlated with enhanced antiviral gene expression, p-STAT1, p-AKT (ser473), and viral replication. Thus, our comprehensive proteomic analysis of CSF identifies PRDX2 as an important circulatory protein, differentially expressed between JEV and ST, with high specificity and enhancing viral propagation, underscoring its role in viral propagation and pathogenesis.

Humans↗
PubMed1994

HLA-DR+CD3+ and CD8+ cells are increased but CD4+CD45RA+ cells are reduced in the peripheral blood in human scrub typhus.

Immunological studies on scrub typhus (ST) have been limited mostly to animals despite the possible difference in the immune responses among the species of the hosts. To investigate in vivo cellular immune responses to ST in humans, we characterized T-cell subsets in the peripheral blood samples from 30 healthy control subjects (HC), 11 patients with nonrickettsial acute infections (NRAI), and 6 patients with ST by a dual labeling method of flow cytometry. In ST, HLA-DR+CD3+ cells were greatly increased compared with those in HC and NRAI (HC, 2.3 +/- 1.3%; NRAI, 4.5 +/- 4.4%; ST, 32.5 +/- 14.7% values are means +/- SD). CD8+ cells were also significantly increased (HC, 29.5 +/- 5.9%; NRAI, 30.5 +/- 9.4%; ST, 44.9 +/- 11.5%), while CD4+CD45RA+ cells were significantly reduced (HC, 23.6 +/- 8.2%; NRAI, 23.3 +/- 12.3%; ST, 12.9 +/- 7.1%) in ST. The unique changes in the T-cell subsets in the peripheral blood samples from the patients with ST support the importance of the cellular immune responses to the natural infection of ST in humans.

Adult↗
PubMed2000

Evaluation of a commercially available recombinant-protein enzyme-linked immunosorbent assay for detection of antibodies produced in scrub typhus rickettsial infections.

The 56-kDa major outer membrane protein antigen of Orientia tsutsugamuchi is the immunodominant antigen in human scrub typhus (ST) infections. An enzyme-linked immunosorbent assay (ELISA) using a recombinant 56-kDa protein (r56) to detect specific immunoglobulin M (IgM) produced in ST infections was developed, and its performance was evaluated using sera from patients with active ST (n = 59), spotted fever (SF) (n = 31), and murine typhus (MT) (n = 6) and from those without rickettsial infection (n = 52). The r56 ELISA was compared to an ELISA using native whole cell lysate of O. tsutsugamushi Karp or O. tsutsugamushi Gilliam as antigens. The performance of the assays using r56 was similar to that of those using native antigens. Using indirect immunoperoxidase (IIP) as the reference test, sensitivities were 86, 88, and 88% while specificities were 84, 90, and 87% in the three assays. Furthermore, cross-reactivity in confirmed cases of SF and MT was low (5.4, 2.7, and 2.7% respectively). The additional use of IgG in the r56 ELISA gave improved performance (sensitivity, 80%; specificity, 96%; cross-reactivity in SF and MT, 2.7%). The detection of high levels of IgG in some IgM-negative patients illustrates the importance of including a test for IgG in the detection of secondary or reactivated infections, since many of these patients were from regions in Thailand where these infections are endemic.

Antibodies, Bacterial↗
PubMed2002

Acute scrub typhus in Northern Thailand: EKG changes.

The electrocardiographic (EKG) manifestations of scrub typhus were prospectively evaluated in 29 adult patients who acquired Orientia tsutsugamushi infection in Chiang Rai, Northern Thailand. EKGs were normal in 22 of the 29 patients (76%); minor non-specific changes were found in the other 7 patients; ie ST segment/T wave changes (10%), U waves (7%), and premature ventricular contractions (4%). These results suggest that EKG changes in scrub typhus acquired in areas of diminished antibiotic susceptibility are similar to those observed in O. tsutsugamushi infection acquired elsewhere.

Acute Disease↗
PubMed1977

Electrocardiographic changes in scrub typhus patients.

Ninety-eight cases of scrub typhus were examined electrocardiographically. Various findings beyond the normal range were as follows: In the febrile stage, sinus arrhythmia with some beats below 60 per minute, flat or low T waves in the left precordial leads, sinus tachycardia, ST segment elevation of 4-l mm in V2, prominent u waves measuring 1 mm or more in amplitude, tall and peaked T waves in V2-4, incomplete right bundle branch block, T wave inversion in V3-4, first degree A-V block, Q-Tc interval prolongation, notched T waves in V3, AV junctional escapes, prominent Ta waves or depression of PR segments in V2, and right axis deviation; in the convalescent stage, sinus arrhythmia with some beats below 60 per minute, prominent u waves measuring 1 mm or more in amplitude, tall and peaked T waves in V2-4, flat or low T waves in the left precordial leads, incomplete right bundle branch block, sinus tachycardia, first degree A-V block, Q-Tc interval prolongation, T wave inversion in V3-4, ST segment elevation of 4 mm in amplitude in V2, ventricular premature contractions, atrial premature contractions, and right axis deviation. In comparison with the electrocardiographic findings in 101 asymptomatic normal subjects, flat T waves in the precordial leads, tall and peaked T waves in V2-4 in both acute and convalescent stages, and sinus arrhythmia with some beats below 60 per minute in the convalescent stage were more frequent in cases. Electrocardiographic abnormalities were present most commonly in the acute illness, and our findings support the impression that, with few exceptions, prompt treatment of scrub typhus with antibiotics prevents the serious cardiac complications seen prior to the antibiotic era.

Adult↗
PubMed1999

Meningoencephalitis, myocarditis and disseminated intravascular coagulation in a patient with scrub typhus.

A 21-year-old male soldier was admitted due to a sore throat, headache, generalized lymphadenopathy and persistent fever for 12 days. Despite empirical antibiotic treatment for four days at a clinic prior to admission, he continued to have persistent abdominal pain over his right upper quadrant region and progressive jaundice was followed by shock. After admission, he developed an episode of clonic seizures and became delirious and agitated. An electrocardiogram showed first degree atrioventricular (AV) block and non-specific ST-T wave changes. Hematological studies revealed thrombocytopenia, hypofibrinogenemia, abnormal partial thromboplastin time (PTT) and a positive test for D-dimer. The cerebrospinal fluid analysis showed pleocytosis with white cells of 84/mm3 with a lymphocyte predominance, protein of 97 mg/dL and glucose of 79 mg/dL. Indirect immunofluorescence assay showed a fourfold rise in antibodies to Orientia tsutsugamushi in paired serum with IgM antibody titer of 1:640. The patient had a favorable response after parenteral chloramphenicol in addition to oral tetracycline. Early ricognition of scrub typhus and early prescription of anti-rickettsial agents prevent complications of central nervous system involvement and further deterioration of cardiac and hematological function.

Adult↗