Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand.

Coleman, Russell E.; Sangkasuwan, Vichai; Suwanabun, Nantavadee; Eamsila, Chirapa; Mungviriya, Siriporn; Devine, Peter L.; Richards, Allen L.; Rowland, Denise; Ching, Wei‐Mei; Sattabongkot, Jetsumon; Lerdthusnee, Kriangkrai

doi:10.4269/ajtmh.2002.67.497

Cited by 120 publications

(125 citation statements)

References 21 publications

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“…JEV infection was confirmed by the presence of specific IgM antibodies, using the AFRIMS JEV IgM capture ELISAs (2). Sera were screened for the presence of antibodies to the Chikungunya virus, using the hemagglutination inhibition method (4) at a 1:10 dilution, and for antibodies to Orientia tsutsugamushi (scrub typhus) and Rickettsia typhi (murine typhus), using indirect microimmunofluorescence (11) assays in which a fourfold (or greater) rise in titer defined acute infection (5).…”

Section: Methodsmentioning

confidence: 99%

Prospective Study To Determine Accuracy of Rapid Serological Assays for Diagnosis of Acute Dengue Virus Infection in Laos

Blacksell

Bell

Kelley

et al. 2007

Clin Vaccine Immunol

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), we recently evaluated eihgt commercially available immunochromatographic rapid diagnostic tests (RDTs) designed to detect dengue virus-specific immunoglobulin M (IgM) and/or IgG. We found that 6/8 RDTs had sensitivities of less than 50% (range, 6 to 65%), but specificities were generally high. Here, in conjuction with dengue virus serotyping by reverse transcriptase PCR and in the limited-resource setting of Laos, where dengue virus is endemic, we evaluated the same eight RDTs against a previously validated dengue IgM/IgG enzyme-linked immunosorbent assay for diagnosis of acute dengue virus infection. Paired serum samples were collected from 87 patients, of whom 38 had confirmed dengue virus infections (4 had primary infections, 33 had secondary infections, and 1 had an infection of indeterminate status). RDT sensitivity was low, with 7/8 RDTs having admission sample sensitivities of less than 20% (range, 4 to 26%). The majority (6/8) of the RDTs, demonstrated high specificity (>95%). Kappa statistic values ranged from 6 to 54% for the RDTs, demonstrating poor to moderate variation between three operators. No RDT adequately differentiated between primary and secondary dengue virus infections. The findings of this study suggest that currently available RDTs based on the detection of IgM antibodies for the diagnosis of acute dengue virus infections are unlikely to be useful for patient management.Dengue virus infection causes a wide spectrum of diseases, including dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Patients with dengue virus infection present with signs and symptoms similar to those of other acute tropical febrile illnesses, necessitating confirmatory laboratory diagnosis which is usually based on serology (13). Dengue hemorrhagic fever and DSS, which are more severe clinically, are thought to occur more commonly in those with a secondary infection (7), and early laboratory diagnosis could have prognostic value if accomplished prior to defervescence, the risk period for plasma leakage and shock. During the acute phase of infection, detection of dengue virusspecific immunoglobulin M (IgM) antibodies alone suggests primary infection, and the presence of both IgM and IgG antibodies suggests secondary or later infection. The development of rapid diagnostic tests (RDTs) using immunochromatographic or immunoblotting technologies has provided a mechanism for point-of-care serological testing.We recently compared the performance of eight RDTs for dengue by using a panel of reference sera from patients with and without dengue who had been characterized previously by gold standard methods (1). Performance characteristics of the dengue RDTs were poor, with only one RDT considered potentially clinically informative. Here we present the results of a complementary prospective study undertaken in the Lao People's Democratic Republic (Laos) to determine the diagnostic performance characteristics of the same eight RDTs and to determine the tests' suitability for acute dengue viru...

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Section: Methodsmentioning

confidence: 99%

Prospective Study To Determine Accuracy of Rapid Serological Assays for Diagnosis of Acute Dengue Virus Infection in Laos

Blacksell

Bell

Kelley

et al. 2007

Clin Vaccine Immunol

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“…The provisional diagnosis of scrub typhus is usually based on a single IgM titer on admission. An IgM titer of 1:400 is routinely accepted in some countries, including Thailand, as the cutoff value to diagnose scrub typhus (7,8). Therefore, we analyzed the PCR results from patients with different antibody titers on admission (Table 3; see also Table S4).…”

Section: Resultsmentioning

confidence: 99%

“…Although the clinical course of scrub typhus is usually mild and self-limiting, delaying the treatment in severe cases can lead to complications such as renal failure, myocarditis, meningoencephalitis, and death (2). Since scrub typhus is one of the most common causes of acute undifferentiated febrile illness (AUFI) in areas of endemicity (3, 4), an early, definite diagnosis is essential for providing appropriate treatment and gathering accurate epidemiological data.Scrub typhus diagnosis mainly relies on serologic tests, particularly the indirect immunofluorescence assay (IFA), whereby the illness is identified by a 4-fold increase in antibody titers in paired sera (5, 6) and/or a positive IgM titer in a single serum sample (7,8). However, these serologic tests require paired serum samples and good technician expertise, and even then they often return false negatives during the early phase of disease.…”

mentioning

confidence: 99%

“…Scrub typhus diagnosis mainly relies on serologic tests, particularly the indirect immunofluorescence assay (IFA), whereby the illness is identified by a 4-fold increase in antibody titers in paired sera (5,6) and/or a positive IgM titer in a single serum sample (7,8). However, these serologic tests require paired serum samples and good technician expertise, and even then they often return false negatives during the early phase of disease.…”

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confidence: 99%

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Use of Multiplex Real-Time PCR To Diagnose Scrub Typhus

et al. 2017

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Scrub typhus, caused by Orientia tsutsugamushi, is a common cause of acute undifferentiated febrile illness in the Asia-Pacific region. However, its nonspecific clinical manifestation often prevents early diagnosis. We propose the use of PCR and serologic tests as diagnostic tools. Here, we developed a multiplex real-time PCR assay using hydrolysis (TaqMan) probes targeting O. tsutsugamushi 47-kDa, groEL, and human interferon beta (IFN-␤ gene) genes to improve early diagnosis of scrub typhus. The amplification efficiency was higher than 94%, and the lower detection limit was 10 copies per reaction. We used a human gene as an internal DNA quality and quantity control. To determine the sensitivity of this PCR assay, we selected patients with confirmed scrub typhus who exhibited a clear 4-fold increase in the level of IgG and/or IgM. The PCR assay result was positive in 45 of 52 patients, indicating a sensitivity of 86.5% (95% confidence interval [CI]: 74.2 to 94.4). The PCR assessment was negative for all 136 non-scrub typhus patients, indicating a specificity of 100% (95% CI: 97.3 to 100). In addition, this test helped diagnose patients with inconclusive immunofluorescence assay (IFA) results and using single blood samples. In conclusion, the real-time PCR assay proposed here is sensitive and specific in diagnosing scrub typhus. Combining PCR and serologic tests will improve the diagnosis of scrub typhus among patients presenting with acute febrile illness.KEYWORDS Orientia tsutsugamushi, real-time PCR, scrub typhus S crub typhus is a mite-borne infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi. A characteristic feature of the disease is patients presenting nonspecific symptoms, including fever, headache, myalgia, cough, and abdominal pain, which cannot be differentiated from symptoms of other systemic infections. The presence of eschar can help diagnose this illness; however, it is found only in some patients (1). Although the clinical course of scrub typhus is usually mild and self-limiting, delaying the treatment in severe cases can lead to complications such as renal failure, myocarditis, meningoencephalitis, and death (2). Since scrub typhus is one of the most common causes of acute undifferentiated febrile illness (AUFI) in areas of endemicity (3, 4), an early, definite diagnosis is essential for providing appropriate treatment and gathering accurate epidemiological data.Scrub typhus diagnosis mainly relies on serologic tests, particularly the indirect immunofluorescence assay (IFA), whereby the illness is identified by a 4-fold increase in antibody titers in paired sera (5, 6) and/or a positive IgM titer in a single serum sample (7,8). However, these serologic tests require paired serum samples and good technician expertise, and even then they often return false negatives during the early phase of disease. In addition, reinfection by different O. tsutsugamushi strains is not uncommon in areas of endemicity and reinfected patients may sometimes

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“…ELISA testing for IgM has a good sensitivity and specificity of 90%. [20] Complications in scrub typhus develop after first week of illness due to increased blood load of O. tsutsugamushi. [21] Khandelwal et al has studied clinical and laboratory manifestation of scrub typhus in 183 children with fever and opined that scrub typhus should be considered in the differential diagnosis of acute febrile illness with hepatosplenomegaly, lymphadenopathy and gastro intestinal symptoms.…”

Section: Discussionmentioning

confidence: 99%

Scrub Typhus in Children at a Tertiary Care Hospital in Odisha: A Study on Clinical, Laboratory Profile, Complications and Its Outcome

Choudhury¹,

Rath²,

Sahu³

2016

AIMDR

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Background: To study the clinical profile, laboratory parameters, complications and outcome of scrub typhus in children. Methods: One hundred children with undiagnosed febrile illness admitted to our hospital from Aug 2014 to Nov 2014 were included in the study. All children were tested for scrub typhus using a commercial ELISA kit for specific IgM antibodies against Orientia tsutsugamushi. Results: Out of 100 children admitted to our hospital, only 50(50%) patients had positive IgM antibodies against O. tsutsugamushi. 30(60%) cases had fever of 5 to 10 days duration and 20(40%) cases had fever of more than 10 days duration. Vomiting with abdominal pain was reported in 20 (40%) cases, Lymphadenopathy in 18 (36%), hepatosplenomegaly in 35 (70%), generalized edema in 18 (36%) patients. Eschar was seen in 25(50%) patients. Most common abnormal laboratory parameters were raised SGOT, thrombocytopenia, raised bilirubin, raised CRP, leukocytosis and anemia. Most common complications were shock and electrolyte disturbances. Conclusion: In children Scrub typhus should be considered in the differential diagnosis of acute febrile illness associated with gastrointestinal symptoms, hepatosplenomegaly and lymphadenopathy .Prompt antibiotic treatment for scrub typhus should be given in cases with strong clinical suspicion to prevent morbidity and mortality.

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Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand.

Cited by 120 publications

References 21 publications

Prospective Study To Determine Accuracy of Rapid Serological Assays for Diagnosis of Acute Dengue Virus Infection in Laos

Prospective Study To Determine Accuracy of Rapid Serological Assays for Diagnosis of Acute Dengue Virus Infection in Laos

Use of Multiplex Real-Time PCR To Diagnose Scrub Typhus

Scrub Typhus in Children at a Tertiary Care Hospital in Odisha: A Study on Clinical, Laboratory Profile, Complications and Its Outcome

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