Cross reactivity of Dengue, Scrub typhus and Widal test among COVID-19 positive patients

Viral load generally rises in HIV-infected individuals with a concomitant infection, but falls markedly in some individuals with scrub typhus (ST), a common Asian rickettsial infection. ST infection appears to shift the viral population from CXCR4-using (X4) to CCR5-utilizing (R5) strains, and there is evidence of cross-reactivity between ST-specific antibodies and HIV-1. We examined the mechanism of ST suppression of HIV by measuring the effects of ST infection on X4 and R5 viruses in vivo and in vitro, and assessing the relative contributions of antibodies and chemokines to the inhibitory effect. In vivo, a single scrub typhus plasma infusion markedly reduced the subpopulation of HIV-1 viruses using the X4 co-receptor in all 8 recipients, and eliminated X4 viruses 6 patients. In vitro, the 14 ST sera tested all inhibited the replication of an X4 but not an R5 virus. This inhibitory effect was maintained if ST sera were depleted of chemokines but was lost upon removal of antibodies. Sera from ST-infected mice recognized a target that co-localized with X4 HIV gp120 in immunofluorescent experiments. These in vivo and in vitro data suggest that acute ST infection generates cross-reactive antibodies that produce potent suppression of CXCR4- but not CCR5-using HIV-1 viruses. ST suppression of HIV replication could reveal novel mechanisms that could be exploited for vaccination strategies, as well as aid in the development of fusion inhibitors and other new therapeutic regimens. This also appears to be the first instance where one pathogen is neutralized by antibody produced in response to infection by a completely unrelated organism.

Download Full-text

Relying on Widal test alone could lead to over diagnosis of typhoid fever: Findings from a records review of febrile patients at Damphu Hospital, Bhutan, 2011-2012

Bhutan Health Journal ◽

10.47811/bhj.57 ◽

2018 ◽

Vol 4 (1) ◽

pp. 50-54

Author(s):

Tej Nath Nepal ◽

Tshering Dorji ◽

Tsheten Tsheten ◽

Karma Tenzin ◽

Dorji Pelzom ◽

...

Keyword(s):

Typhoid Fever ◽

Scrub Typhus ◽

Correct Diagnosis ◽

High Sensitivity ◽

Salmonella Typhi ◽

Clinical Judgement ◽

Test Results ◽

Widal Test ◽

Duration Of Illness ◽

The Right

Introduction: The Widal test is widely used in hospitals in Bhutan for diagnosis of typhoid fever. The right test with high sensitivity and specificity supplements clinical judgement and contributes to correct diagnosis of disease. This study focuses on the contribution of the Widal test in the diagnosis of typhoid fever. Methods: Data was collected from records of patients who presented to Damphu hospital from March 2011 to June 2012 with clinical suspicion of typhoid fever. Blood samples were collected from patients and tested at Damphu Hospital, Tsirang and the Royal Centre for Disease Control, Thimphu. Seventy records were used for the study. Results: There was no growth of Salmonella typhi on blood cultures from patients who had tested positive in the Widal test. There were 20 (28.57%) samples which tested positive for scrub typhus; among these Widal test was positive in 10 (50%) samples. Thirty four out of 36 (94.44%) patients had duration of illness less than seven days and among them 26 (74.47%) had positive Widal test results. Conclusion: None of the samples that tested positive by Widal test gave a definite diagnosis of typhoid fever with blood culture. Clinical judgement may be more challenging because patients with other febrile illnesses like Scrub typhus also have positive Widal test result. We conclude that it is best not to rely on the Widal test alone for the diagnosis of typhoid fever and this test should be replaced by more accurate ones.

Download Full-text

Evaluation of a Commercially Available Recombinant-Protein Enzyme-Linked Immunosorbent Assay for Detection of Antibodies Produced in Scrub Typhus Rickettsial Infections

Journal of Clinical Microbiology ◽

10.1128/jcm.38.7.2701-2705.2000 ◽

2000 ◽

Vol 38 (7) ◽

pp. 2701-2705 ◽

Cited By ~ 15

Author(s):

Meagan V. Land ◽

Wei-Mei Ching ◽

Gregory A. Dasch ◽

Zhiwen Zhang ◽

Daryl J. Kelly ◽

...

Keyword(s):

Immunosorbent Assay ◽

Scrub Typhus ◽

Spotted Fever ◽

Cross Reactivity ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Whole Cell Lysate ◽

Immunodominant Antigen ◽

Rickettsial Infections ◽

Improved Performance

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 ofO. tsutsugamushi Karp or O. tsutsugamushiGilliam 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.

Download Full-text

Identification of Cross-Reactive Epitopes on the Conserved 47-Kilodalton Antigen of Orientia tsutsugamushi and Human Serine Protease

Infection and Immunity ◽

10.1128/iai.01298-08 ◽

2009 ◽

Vol 77 (6) ◽

pp. 2311-2319 ◽

Cited By ~ 16

Author(s):

Hua-Wei Chen ◽

Zhiwen Zhang ◽

Erin Huber ◽

Chien-Chung Chao ◽

Hui Wang ◽

...

Keyword(s):

Amino Acid ◽

Serine Protease ◽

Vaccine Candidate ◽

Scrub Typhus ◽

Cross Reactivity ◽

Orientia Tsutsugamushi ◽

Protein Sequence Analysis ◽

Protein Antigens ◽

Peptide Epitope ◽

C Terminus

ABSTRACT Orientia tsutsugamushi is the causative agent of scrub typhus. One of the protein antigens of this species, the conserved 47-kDa protein (HtrA), has been shown to induce an antibody response in patients and can provide protective immunity against live challenge by Orientia in mice. Pepscan experiments identified many peptide epitope clusters in different parts of this protein. The majority of the most reactive epitopes are located at the C terminus of the protein (from amino acid 333 to amino acid 430). Protein sequence analysis revealed that the 47-kDa protein contains a trypsin domain and has sequence homology to human serine protease HtrA1 (hHtrA1). As the 47-kDa protein is a potential vaccine candidate and its ability to induce autoimmunity is a concern, the reactivity of scrub typhus patient sera with purified recombinant 47-kDa and hHtrA1 proteins was tested. A significant percentage (>20%) of scrub typhus patient sera reacted strongly with recombinant hHTRA1 and two of the antigenic polypeptide epitopes in hHtrA1. These findings suggest that the safety of the full-length 47-kDa antigen as a vaccine candidate is a significant issue due to its cross-reactivity with a human protein, which may also contribute to autoimmune responses or enhanced pathology in some scrub typhus patients.

Download Full-text

Concomitant Clinical Sensitivity (CCS) and Cross-Reactivity

Allergy & Clinical Immunology International - Journal of the World Allergy Organization ◽

10.1027/0838-1925.15.1.18 ◽

2003 ◽

Vol 15 (01) ◽

pp. 018-029 ◽

Cited By ~ 1

Author(s):

Harris Steinman ◽

Steve Lee

Keyword(s):

Cross Reactivity ◽

Clinical Sensitivity

Download Full-text

Human Prothrombin Activation: Determination of Plasma and Serum Levels of Prothrombin Fragment 3 by Radioimmunoassay

10.1055/s-0038-1665668 ◽

1979 ◽

Author(s):

Daniel Walz ◽

Thomas Brown

Keyword(s):

Blood Clotting ◽

Factor Xa ◽

Heart Association ◽

Serum Levels ◽

Cross Reactivity ◽

Assay Procedure ◽

A Chain ◽

Prothrombin Activation ◽

Theoretical Amount

Human prothrombin activation is unique in that, in addition to the release of fragment 1.2 (FI.2) from the NH-terminus of prothrombin by factor Xa during the generation of thrombin, an additional 13 residue polypeptide, fragment 3 (F3), is autocatalytically removed from the amino-terminus of the thrombin A chain. We have developed a rapid radioimmunoassay for human F3 which incorporates short incubation times and the use of a preprecipitated second antibody; the assay can be performed in three hours. Specificity studies in buffer systems show prothrombin and prethrombin 1 cross-reacting at a level of 0.001; purified thrombin does not cross-react. In the presence of 5% BSA, prothrombin displays considerably less cross-reactivity. No immunoreactive material to F3 antibodies could be detected in 400 μL of plasma. Serum, obtained from whole blood clotting, contained measurable quantities of F3 (40-100 ng/mL). This amount in serum represents only 5-10% of the theoretical amount available should all of the fragment be hydrolytically cleaved during the conversion of prothrombin to thrombin. This assay procedure is currently being utilized to monitor the activation of purified human prothrombin in the absence and presence of selected plasma inhibitors. (Supported in part by NIH 05384-17 and the Michigan Heart Association).

Download Full-text