Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam

Katoh, Shungo; Cuong, Ngo Chi; Hamaguchi, Sugihiro; Thuy, Pham Thanh; Duy, Cuong; Anh, Le Kim; Anh, Nguyen Thi Hien; Anh, Đặng Đức; Sando, Eiichiro; Suzuki, Motoi; Fujita, Hiromi; Yasunami, Michio; Yoshihara, K.; Yoshida, Lay‐Myint; Paris, Daniel; Ariyoshi, Koya

doi:10.1371/journal.pntd.0007928

Cited by 10 publications

(13 citation statements)

References 24 publications

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“…Between June 2012 and May 2014, we conducted a prospective observational study of undiagnosed febrile illness in the Infectious Disease Department of Bach Mai Hospital, which is the largest government referral medical center in Hanoi covering patients in northern Vietnam, as published previously [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Meningitis patients with Angiostrongylus cantonensis may present without eosinophilia in the cerebrospinal fluid in northern Vietnam

et al. 2020

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Background Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. Methodology/Principal findings Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. Conclusions The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF.

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Section: Methodsmentioning

confidence: 99%

Meningitis patients with Angiostrongylus cantonensis may present without eosinophilia in the cerebrospinal fluid in northern Vietnam

et al. 2020

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“…An underappreciated problem regarding the presence of eschars as a vital diagnostic clue is that their occurrence can vary broadly across different regions, and that pre-existing immunity can suppress eschar formation at the mite bite inoculation site [ 16 , 68 ]. Several studies in Vietnam revealed eschar prevalence across communities from 18.2% to 46.6% [ 8 , 37 ], while reports from other areas in Asia suggest eschar prevalence from 7%–97% among scrub typhus patients, depending on study site endemicity and study design [ 42 , 69 ]. It is important to realise that although the presence of an eschar is helpful, many scrub typhus patients may not have an eschar.…”

Section: Discussionmentioning

confidence: 99%

“…The similarities upon presentation of these two common causes of febrile illness complicate clinical management decisions at all health care levels of the country, from the primary health care centers to even the national tertiary hospital [ 37 ]. Non-specific symptoms such as high fever, headache, skin rash or myalgia are common to both scrub typhus and dengue, but different treatment strategies are required [ 38 – 41 ].…”

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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“…In contrast, murine typhus was more prevalent than scrub typhus (5% vs. 1%) among 397 patients with acute undifferentiated fever at the Bangkok Hospital for Tropical Diseases, Thailand [28]. A recent study from Vietnam reported that among 1127 non-malarial febrile patients, scrub typhus was the aetiology of fever in 33 cases (2.9%) [29]. However, the proportion of scrub typhus was possibly as high as 36% in a study of an agricultural area of Sabah, Malaysia [30].…”

Section: Travel-associated Rickettsiosismentioning

confidence: 96%

Rickettsiosis in Southeast Asia: Summary for International Travellers during the COVID-19 Pandemic

2022

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Rickettsiosis is an important cause of febrile illness among travellers visiting Southeast Asia (SEA). The true incidence of rickettsiosis is underestimated; however, murine typhus and scrub typhus are widely distributed across SEA. Among travellers visiting SEA, scrub typhus was mostly reported from Thailand, whereas murine typhus was frequently found in Indonesia. Although most cases are self-limited or present with mild symptoms, a few cases with severe clinical manifestations have been reported. Doxycycline remains the key treatment of rickettsiosis. Some travellers, such as backpackers, trekkers, or cave explorers, are at a higher risk for rickettsiosis than others. Therefore, in resource-limited conditions, empirical treatment should be considered in these travellers. The coronavirus disease 2019 (COVID-19) pandemic has contributed to difficulty in the diagnosis of rickettsiosis because of the clinical similarities between these diseases. In addition, physical distancing mandated by COVID-19 management guidelines limits accurate physical examination, resulting in misdiagnosis and delayed treatment of rickettsiosis. This review summarises the characteristics of murine typhus and scrub typhus, describes travel-associated rickettsiosis, and discusses the impact of the COVID-19 pandemic on rickettsiosis.

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Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam

Cited by 10 publications

References 24 publications

Meningitis patients with Angiostrongylus cantonensis may present without eosinophilia in the cerebrospinal fluid in northern Vietnam

Meningitis patients with Angiostrongylus cantonensis may present without eosinophilia in the cerebrospinal fluid in northern Vietnam

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

Rickettsiosis in Southeast Asia: Summary for International Travellers during the COVID-19 Pandemic

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