Clinical Manifestations and Molecular Diagnosis of Scrub Typhus and Murine Typhus, Vietnam, 2015–2017

Trung, Nguyen Vu; Hoi, Le Thi; Dien, Vu Minh; Hương, Đặng Thị; Hoa, Tran Mai; Lien, Vu Ngoc; Luan, Phan Van; Lewycka, Sonia; Choisy, Marc; Bryant, Juliet E.; Nadjm, Behzad; Doorn, H. Rogier van; Richards, Allen L.; Kính, Nguyễn Văn

doi:10.3201/eid2504.180691

Cited by 18 publications

(27 citation statements)

References 36 publications

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“…In this study, only 33% of the patients were PCR þ ve. Given the relatively low sensitivity, other studies have demonstrated the value of performing PCR and serology for admission samples [21,22]. This study also examined the immune response following three different antibiotic treatments.…”

Section: Discussionmentioning

confidence: 99%

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

Phakhounthong

Mukaka

Dittrich

et al. 2020

Clinical Microbiology and Infection

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Objectives: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cutoffs ; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cutoff parameters for indirect immunofluorescence assay (IFA). Methods: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. Results: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to 3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36e204 days) and IgG was 177 days (interquartile range 134e355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cutoff reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%e85.2% sensitivity; 89.9%, 95% CI 62.5%e100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%e87.6% sensitivity; 99%, 95% CI 95%e100% specificity). Conclusions: This study suggests suitable diagnostic cutoffs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cutoffs in other geographically diverse locations.

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Section: Discussionmentioning

confidence: 99%

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

Phakhounthong

Mukaka

Dittrich

et al. 2020

Clinical Microbiology and Infection

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“…Although an antibody detection assay in the form of rapid tests is available and may be utilized as a point-of-care test, these tests are less sensitive during the early phase of the disease and may not be useful for providing information concerning options for early treatment. Besides, more recently, various versions of PCR with sensitivity ranging from 73 to 100% have been developed for scrub typhus early diagnosis [ 17 , 18 , 19 , 20 ]. Nevertheless, PCR is not a point-of-care test, especially for the resource-limited areas where endemic scrub typhus is a local healthcare concern.…”

Section: Introductionmentioning

confidence: 99%

GroEL Chaperonin-Based Assay for Early Diagnosis of Scrub Typhus

et al. 2022

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A point-of-care diagnostic for early and rapid diagnosis of scrub typhus caused by Orientia tsutsugamushi is required for prompt and proper treatment of patients presenting with undifferentiated febrile illnesses. In this study, an immunochromatographic antigen detection test kit (ICT AgTK) that targets the highly conserved O. tsutsugamushi 60 kDa GroEL chaperonin (heat shock protein 60) was developed. E. coli-derived recombinant GroEL expressed from DNA coding for the consensus sequence of 32 GroEL gene sequences extracted from the GenBank database was used to immunize rabbits and mice. Rabbit polyclonal antibodies (pAb) were used for preparing a gold-pAb conjugate, and the rGroEL-specific mouse monoclonal antibody was used as the antigen detection reagent at the ICT test line. In-house validation revealed that the ICT AgTK gave 85, 100 and 95% diagnostic sensitivity, specificity and accuracy, respectively, compared to the combined clinical features and standard IFA when tested on 40 frozen serum samples. The test kits correctly identified 10 scrub typhus samples out of 15 fresh plasma/buffy coat samples of patients with febrile illnesses. For independent laboratory validation, the ICT AgTK was sent to one provincial hospital. The ICT AgTK utilized by the hospital medical technologist correctly identified six scrub typhus samples out of 20 serum samples of patients with fever, as confirmed by specific IgM/IgG detection by IFA. The ICT AgTK is easy to perform with rapid turn-around time. It has the potential to be used as an important tool for on-site and early scrub typhus diagnosis by allowing testing of freshly collected samples (serum, plasma or buffy coat), especially in resource-limited healthcare settings.

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“…After approximately half a century of neglect, scrub typhus is beginning to receive more attention as an important cause of non-malarial febrile illness in Vietnam. Recent reports highlight scrub typhus as a disease of high clinical relevance and expanding (documentation of) distribution due to a notable recent increase in the number of diagnosed and reported cases [ 14 , 15 ]. In the 1960s, scrub typhus was considered a common disease among American veterans in Vietnam and an endemic disease in the midlands and mountainous forests of Vietnam, but after the discovery of Chloramphenicol the general interest in rickettsial diseases declined gradually with the availability of an effective antimicrobial [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…In Vietnam only a limited number of cases were registered after the 1970s, but the increasing reports of scrub typhus in recent years suggest a re-emerging trend of this rickettsial illness with documented geographical expansion and distribution within the population of Vietnam [ 8 , 15 , 18 ]. Results from various causes-of-fever studies in Southeast Asia have confirmed the importance of this easily treatable rickettsial disease [ 9 , 15 , 18 ]. Scrub typhus is a serious disease if untreated in elderly; the median mortality is 6% if untreated, and mortality increases with age (over 50 years old mortality >45%), while case fatality risks can reach 12–13% in South India or North Thailand [ 11 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Simple clinical and laboratory predictors to improve empirical treatment strategies in areas of high scrub typhus and dengue endemicity, central Vietnam

et al. 2022

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Background Dengue fever is highly endemic in Vietnam, but scrub typhus—although recognized as an endemic disease—remains underappreciated. These diseases together are likely to account for more than half of the acute undifferentiated fever burden in Vietnam. Scrub typhus (ST) is a bacterial disease requiring antimicrobial treatment, while dengue fever (DF) is of viral etiology and does not. The access to adequate diagnostics and the current understanding of empirical treatment strategies for both illnesses remain limited. In this study we aimed to contribute to the clinical decision process in the management of these two important etiologies of febrile illness in Vietnam. Methods Using retrospective data from 221 PCR-confirmed scrub typhus cases and 387 NS1 protein positive dengue fever patients admitted to five hospitals in Khanh Hoa province (central Vietnam), we defined predictive characteristics for both diseases that support simple clinical decision making with potential to inform decision algorithms in future. We developed models to discriminate scrub typhus from dengue fever using multivariable logistic regression (M-LR) and classification and regression trees (CART). Regression trees were developed for the entire data set initially and pruned, based on cross-validation. Regression models were developed in a training data set involving 60% of the total sample and validated in the complementary subsample. Probability cut points for the distinction between scrub typhus and dengue fever were chosen to maximise the sum of sensitivity and specificity. Results Using M-LR, following seven predictors were identified, that reliably differentiate ST from DF; eschar, regional lymphadenopathy, an occupation in nature, increased days of fever on admission, increased neutrophil count, decreased ratio of neutrophils/lymphocytes, and age over 40. Sensitivity and specificity of predictions based on these seven factors reached 93.7% and 99.5%, respectively. When excluding the “eschar” variable, the values dropped to 76.3% and 92.3%, respectively. The CART model generated one further variable; increased days of fever on admission, when eschar was included, the sensitivity and specificity was 95% and 96.9%, respectively. The model without eschar involved the following six variables; regional lymphadenopathy, increased days of fever on admission, increased neutrophil count, increased lymphocyte count, platelet count ≥ 47 G/L and age over 28 years as predictors of ST and provided a sensitivity of 77.4% and a specificity of 90.7%. Conclusions The generated algorithms contribute to differentiating scrub typhus from dengue fever using basic clinical and laboratory parameters, supporting clinical decision making in areas where dengue and scrub typhus are co-endemic in Vietnam.

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Clinical Manifestations and Molecular Diagnosis of Scrub Typhus and Murine Typhus, Vietnam, 2015–2017

Abstract: Scrub typhus was the predominant rickettsial disease diagnosed among hospitalized patients with acute undifferentiated fever in northern Vietnam.

Cited by 18 publications

References 36 publications

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

GroEL Chaperonin-Based Assay for Early Diagnosis of Scrub Typhus

Simple clinical and laboratory predictors to improve empirical treatment strategies in areas of high scrub typhus and dengue endemicity, central Vietnam

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