Diagnosis of scrub typhus: recent advancements and challenges

Abstract

Scrub typhus is a mite-borne, acute febrile illness caused by the bacterium Orientia tsutsugamushi. It is a re-emerging infectious disease of the tsutsugamushi triangle. Scrub typhus is transmitted through bites of contaminated chiggers (larval stage). Diagnosis of scrub typhus is challenging as its symptoms mimic with other acute febrile illnesses. Several methods are effectual for diagnosis of scrub typhus that includes enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), immunochromatographic test (ICT), Weil-Felix, polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP). Weil-Felix test was initially used for the diagnosis of scrub typhus in underdeveloped countries but not preferred due to a lack of both specificity and sensitivity. Other immuno-based methods like IFA and ELISA are most outrank for detection of scrub typhus due to their higher sensitivity and specificity, but not vigorous to lay bare the infection at early stages and need the convalescent sampling for verification of positive samples. On another deed, PCR based methods becoming acceptable over era due to its dexterity of early-stage diagnosis with higher specificity and sensitivity but lack its applicability in circumstances of scrub typhus due to the variegated genetic makeup of Orientia tsutsugamushi among its serotypes. The present review focused on various detection methods along with their advantages and disadvantages used in the diagnosis of scrub typhus. A comparison between available methods of diagnosis with challenges in the detection of scrub typhus is also summarized.

Case report of atypical scrub typhus in pregnancy coexistent with HELLP syndrome mimicking pregnancy specific liver disease (P-sLD): A management dilemma

“…Table 2 describes the World Health Organization (WHO) diagnostic criteria for scrub typhus and scrub typhus infection criteria (STIC) [10,12,13]. As a direct method, real time polymerase chain reaction for the diagnosis of scrub typhus has more sensitivity and specificity compared to indirect methods used however cost is the limiting factor [12]. Eschar formation, 5-20 mm necrotic lesion at the site of bite or ulcer with regional lymphadenopathy is the single most important clue for the diagnosis but their presence can be highly variable (7-97%) [7].…”

“…There is evidence for the deposition of O. tsutsugamushi in endothelial cells which is supported by positive immunohistochemistry for its antigen. Almost 30% of the individuals go on to develop one organ dysfunction if untreated and the most common being AKI or acute hepatic failure (AHF) [7,[11][12][13][14][15].…”

The Orientia tsutsugamushi ScaB Autotransporter Protein Is Required for Adhesion and Invasion of Mammalian Cells

“…Scrub typhus is a re-emerging vector-borne disease prevalent in the Asia-Pacific region ( Kelly et al, 2009 ; Kala et al, 2020 ; Richards and Jiang, 2020 ). It is caused by an obligate intracellular Gram-negative bacterium, namely Orientia tsutsugamushi , which is transmitted to mammalian hosts, including rodents and humans, via Leptotrombidium mites at their larval stage ( Seong et al, 2001 ).…”

“…The clinical symptoms of scrub typhus are highly variable, ranging from mild to fatal infections. Approximately 1–2 weeks after being bitten by the infected vector, patients present with fever, headache, rash, nausea, lymphadenopathy, and eschar at the bite site ( Ponnusamy et al, 2018 ; Kala et al, 2020 ). Delayed treatment with appropriate antibiotics, such as tetracycline, chloramphenicol, and macrolides, often results in pneumonitis, meningitis, myocarditis, acute renal failure, and acute respiratory distress syndrome.…”

Leptospira interrogans Outer Membrane Protein-Based Nanohybrid Sensor for the Diagnosis of Leptospirosis

“…The emerging diagnostic methods, such as biosensors, are in demand because of their better performance in terms of onsite detection ability with less time and higher clinical sensitivity. An electrochemical DNA biosensor is becoming a need of ours due to its ability to lay bare the infection at the early stages with better sensitivity and accuracy [ 16 , 17 , 18 , 19 , 20 , 21 ]. It can create a point-of-care diagnostics facility even outside the laboratory settings and can be a replacement of the current diagnosis methods that require sophisticated instrument facilities and experts to carry out the tests [ 22 ].…”