Treatment Of Scrub Typhus Research Articles

Exploring the influencing factors of scrub typhus in Gannan region, China, based on spatial regression modelling and geographical detector

Scrub typhus is a significant public health issue with a wide distribution and is influenced by various determinants. However, in order to effectively eradicate scrub typhus, it is crucial to identify the specific factors that contribute to its incidence at a detailed level. Therefore, the objective of our study is to identify these influencing factors, examine the spatial variations in incidence, and analyze the interplay of two factors on scrub typhus incidence, so as to provide valuable experience for the prevention and treatment of scrub typhus in Gannan and to alleviate the economic burden of the local population.This study employed spatial autocorrelation analyses to examine the dependent variable and ordinary least squares model residuals. Additionally, spatial regression modelling and geographical detector were used to analyze the factors influencing the annual mean 14-year incidence of scrub typhus in the streets/townships of Gannan region from 2008 to 2021. The results of spatial1 autocorrelation analyses indicated the presence of spatial correlation. Among the global spatial regression models, the spatial lag model was found to be the best fitting model (log likelihood ratio = −319.3029, AIC = 666.6059). The results from the SLM analysis indicated that DEM, mean temperature, and mean wind speed were the primary factors influencing the occurrence of scrub typhus. For the local spatial regression models, the multiscale geographically weighted regression was determined to be the best fitting model (adjusted R2 = 0.443, AICc = 726.489). Further analysis using the MGWR model revealed that DEM had a greater impact in Xinfeng and Longnan, while the southern region was found to be more susceptible to scrub typhus due to mean wind speed. The geographical detector results revealed that the incidence of scrub typhus was primarily influenced by annual average normalized difference vegetation index. Additionally, the interaction between GDP and the percentage of grassland area had a significant impact on the incidence of scrub typhus (q = 0.357). This study illustrated the individual and interactive effects of natural environmental factors and socio-economic factors on the incidence of scrub typhus; and elucidated the specific factors affecting the incidence of scrub typhus in various streets/townships. The findings of this study can be used to develop effective interventions for the prevention and control of scrub typhus.

Monotherapy is Recommended in the Treatment of Scrub Typhus and Doxycycline Resistance is a Misconception

Monotherapy is Recommended in the Treatment of Scrub Typhus and Doxycycline Resistance is a Misconception

Scrub typhus Meningoencephalitis : Diagnostic dilemma

Background: Neurological involvement in the form of meningitis or meningoencephalitis, although well documented in scrub typhus, has not been extensively studied in the pediatric population. It is seldom considered in the differential diagnosis of meningitis in the Indian subcontinent. Case Presentation: We report a case of Scrub typhus meningitis in 13year old male child. The Cerebrospinal Fluid (CSF) revealed lymphocytic pleocytosis, raised proteins and a normal glucose level. Conclusion : Early diagnosis and prompt institution of doxycycline therapy may lead to early cure of scrub typhus even when features of meningitis supervene. However, Ceftriaxone which is commonly used to treat bacterial meningitis is suboptimal in the treatment of scrub typhus. Key words : Scrub typhus, Meningoencephalitis, CSF

An alarming surge of scrub typhus cases presenting as acute encephalitis in children.

Scrub typhus, which is prevalent in the Asia Pacific region is most feared owing to its life-threatening neurological complications. We present four cases of scrub typhus with acute encephalitis, including one with multiorgan failure and another serologically proven co-infection with Hepatitis C. Treatment of scrub typhus is not, however, so difficult, so its early diagnosis is paramount.

Epidemiological and clinical characteristics of scrub typhus in northern Fujian, China, from 2015 to 2019

BackgroundThis study aimed to analyze the epidemiological and clinical characteristics of scrub typhus in northern Fujian Province on the southeast coast of China.MethodsA retrospective analysis was performed on 303 patients with scrub typhus admitted to the First Hospital of Nanping City, Fujian Province, from January 2015 to December 2019. The epidemic characteristics were analyzed, such as the annual number of cases, age distribution, sex distribution, and seasonal distribution in each region. The patient's clinical manifestations, signs, complications, auxiliary examinations, and prognosis were analyzed.ResultsFrom 2015 to 2019, the age distribution of scrub typhus cases was mainly concentrated in 40–49 y (17.16%), 50–59 y (24.09%), and 60–69 y (26.73%). There were no sex differences among the patients. 68.98% of the cases were concentrated in rural areas, with farmers having the highest proportion. However, this study compared prognostic factors in the cured and uncured groups, and found significant differences in non-farmer occupation and diagnosis time ≥ 8 days. Scrub typhus showed two peaks north of Fujian; the prominent peak was from June to July, and the other slight rise was from October to November. The SDE plot showed that the cases were mainly concentrated in Yanping, Shunchang, Zhenghe, and Songxi counties. The number of cases in hilly and mountainous areas was higher than in plain areas. The main diagnostic methods in this area are based on specific eschar and epidemiology, while the positive rate of the Weil-Felix test is low.ConclusionsThe results of this study can guide primary care institutions to improve the level of diagnosis and treatment of scrub typhus and take effective public health intervention measures in endemic areas.

Association of scrub typhus with incidence of dementia: a nationwide population-based cohort study in Korea

BackgroundScrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data.MethodThis population-based cohort study enrolled patients aged 60–89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer’s disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity.ResultsDuring the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10–1.15, p < 0.001). The Kaplan–Meier curves for time to cumulative incidence of dementia showed that the dementia incidence in both groups increased over time, while individuals with a past history of scrub typhus had a higher incidence of dementia than the control group. Second, the risk of Alzheimer’s disease was significantly higher among patients with a history of scrub typhus (adjusted hazard ratio, 1.15; 95% confidence interval 1.13–1.18, p < 0.001).ConclusionIn conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer’s disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.

The diagnosis and treatment of scrub typhus should be emphasized in non-endemic areas: A retrospective case series study.

The morbidity of tsutsugamushi is increasing and is no longer limited to endemic areas. Delayed diagnosis and inappropriate treatment can cause severe complications and increase mortality rates. We conducted a retrospective case series of patients with scrub typhus at our institution to report our experience and discuss the diagnostic modalities. We encountered 21 cases of scrub typhus at our institution between 2014 and 2022. The average age of the patients was 52 years (range: 22-63 years), 11 (52%) were farmers, and 11 (52%) had clear outdoor activities. Twenty (95%) patients had an ineffective history of general antibiotic treatment. The classic presentation was repeated fever in 95% of patients. Seventeen patients (81%) had eschar mainly on the groin (35%) and armpit (35%). Common laboratory findings included eosinophilia (95%), elevated alanine aminotransferase (95%), elevated aspartate aminotransferase (86%), thrombocytopenia (76%), lower hemoglobin (71%), and neutrophilia (38%). Six (29%) patients received the treatment of tigecycline, 4 (19%) patients received the treatment of doxycycline, and 11 (52%) patients received the treatment of minocycline. After 3 days of specific treatment, the eosinophilic levels showed a recovery trend. Twenty (95%) patients fully recovered, and 1 (5%) died. Careful physical examination and medical history are important for the early diagnosis of scrub typhus; clinicians in non-endemic areas need to strengthen their understanding of scrub typhus.

Molecular-based study of scrub typhus in Kerala, South India from 2014 to 2021: a laboratory-based study.

The online version contains supplementary material available at 10.1007/s00580-023-03443-8.

Efficacy of Oral Doxycycline versus Intravenous Doxycycline for the Treatment of Uncomplicated Scrub Typhus in Children: A Prospective Interventional Study

Introduction: Orientia tsutsugamushi causes acute febrile illness known as scrub typhus, which is spread by the bite of the trombiculid mite. Doxycycline is the first-line treatment for clinically diagnosed cases of scrub typhus. If not diagnosed and treated early, it can lead to complications such as acute renal failure, meningoencephalitis, gastrointestinal bleeding, and multiple organ failure. However, there have been no trials comparing the effectiveness of oral and Intravenous (i.v.) doxycycline for scrub typhus treatment. Aim: To assess the efficacy of intravenous versus oral doxycycline in managing uncomplicated scrub typhus. Materials and Methods: This prospective interventional research was conducted in the Paediatrics Department at Maharajah’s Institute of Medical Sciences, Vizianagaram, India, from June 2021 to July 2022. Out of a total of 178 children diagnosed with scrub typhus during the study period, 102 children who received either oral or intravenous doxycycline as monotherapy were included. The primary outcome measures studied were the incidence of delayed defervescence and the time of defervescence. The t-test or Mann-Whitney test was applied for continuous data, and the Chi-square test or Fischer’s-exact test was used to compare dichotomous variables. Results: The mean age of children treated with oral doxycycline was 9.5±2.7 years and with i.v. doxycycline was 8.2±2.4 years. Among the 178 children diagnosed with scrub typhus, 102 (57.3%) children treated with doxycycline alone were included in the study. Out of these, 78 (76.4%) cases received oral doxycycline, while 28 (27.4%) cases received intravenous doxycycline. There was no statistically significant difference in the response rate between the two groups. The p-value for time to defervescence was 0.672, and the p-value for the incidence of delayed defervescence was 0.9845. Conclusion: Both oral and intravenous forms of doxycycline demonstrated similar efficacy in the treatment of scrub typhus. Nearly all children in both groups became afebrile within 72 hours after starting treatment.

Antibiotic Combination Therapy for Severe Scrub Typhus: Is It Necessary?

Scrub typhus can be adequately treated with doxycycline or azithromycin unless it is treated too late. Such cases present as severe scrub typhus, and their treatment remains a challenging problem. In this article, we briefly review the literature on the treatment of scrub typhus and the limitations of the combination of doxycycline and azithromycin. Several options are suggested for further study in the treatment of severe scrub typhus (such as encephalitis, myocarditis, and pneumonia), including dose escalation of doxycycline, the adjuvant use of steroids, the selective use of beta-lactam antibiotics, and the use of tigecycline.

Seroprevalence of Scrub Typhus in Patients Attending Dhulikhel Hospital, Kavre

Background Scrub typhus is a largely ignored tropical disease and a leading cause of undifferentiated febrile illness. It is caused by Orientia tsutsugamushi. Scrub Typhus is frequently observed in South Asian countries. However, clear epidemiological information of this disease is lacking in case of Nepal. Nepal has shown steady increase in cases of Scrub Typhus since 2015. The epidemiological data related to this disease would support the decision making and surveillance design for early outbreak detection and immediate responses including prevention and treatment of scrub typhus in Nepal.&#x0D; Objective To understand prevalence of Scrub Typhus in subjects who had visited outpatient department at Dhulikhel Hospital.&#x0D; Method In this study, we have studied antibody test data (n=784) for Scrub Typhus from 2019 to 2021. The tests were performed on serum samples of patients who had visited OPD at Dhulikhel Hospital with fever lasting more than 5 days. The kit used in analysis was Scrub Typhus Detect™ IgM ELISA Kit from InBios International.&#x0D; Result Out of the total subjects (n=784), 133 were positive (16.9%) for IgM antibody of Scrub Typhus. The positivity in female (18.6%) was higher than the male subjects (15.3%). The positivity rate was variable among the different age groups, with highest positivity for age group 0-14 years (25%). The seasonal variation was also observed among the seropositive cases.&#x0D; Conclusion Scrub Typhus being a neglected tropical disease has high prevalence. It can be postulated that female subjects and subjects of age group 0-14 years are vulnerable to the infection with Scrub Typhus. There is need to increase the surveillance of Scrub Typhus to add the knowledge for diagnosis and treatment.

Rickettsioses in Children - A Review.

Rickettsial diseases, caused by a variety of obligate intracellular, Gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma are considered some of the most covert emerging and re-emerging diseases. Scrub typhus, murine flea-borne typhus and Indian tick typhus are commonly being reported and during the last decade. Scrub typhus (ST) has emerged as a serious public health problem in India. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45% with multiple organ dysfunction, if the specific treatment is delayed. Early clinical suspicion, timely diagnosis followed by institution of specific antimicrobial therapy shortens the course of the disease, lowers the risk of complications and reduces morbidity and mortality due to rickettsial diseases. Still there is large gap in our knowledge of Rickettsioses and the vast variability and non-specific presentation of these have often made it difficult to diagnose clinically. The present review describes the epidemiology, clinical manifestations, diagnostic modalities and treatment of Scrub typhus which is a vastly underdiagnosed entity and clinicians should suspect and test for the disease more often.

Clinical and Laboratory Characteristics of Dengue-Orientia tsutsugamushi co-Infection from a Tertiary Care Center in South India.

BackgroundConcurrent infection with multiple pathogens is common in tropics, posing diagnostic and treatment challenges. Although co-infections of dengue, malaria, leptospirosis and typhoid in various combinations have been described, data on dengue and scrub typhus co-infection is distinctly limited.MethodologyThis study was a retrospective analysis of dengue and scrub typhus co-infection diagnosed between January 2010 and July 2014 at a tertiary care center. Clinical and laboratory features of these cases were compared with age and gender-matched patients with isolated dengue fever and isolated scrub typhus. Positive test for dengue non-structural 1 (NS1) antigen was considered diagnostic of dengue whereas scrub typhus was diagnosed by IgM scrub antibodies demonstrated by ELISA.ResultsThere were 6 cases of dengue-scrub co-infection during the review period which fitted clinical and laboratory profile with a mean age of 42.5 years. Fever, headache, and arthralgia were common. Normal hemoglobin, significant thrombocytopenia, transaminitis, and hypoalbuminemia were identified in these patients. Compared to patients with isolated dengue, those with co-infection had higher pulse rate, lower systolic blood pressure, normal leucocyte counts, higher levels of liver enzymes, greater prolongation of partial thromboplastin time (aPTT) and lower serum albumin. Co-infection was characterized by a lower nadir platelet count compared to scrub typhus, and lesser time to nadir platelet count and longer duration of hospital stay compared to either isolated dengue or scrub typhus.ConclusionDengue-scrub typhus co-infection may be under-diagnosed in tropics, particularly confounded during dengue epidemics. Normal leukocyte counts, early drop in platelets and hypoalbuminemia in dengue patients could be clues to concurrent scrub typhus infection. Prompt recognition and treatment of scrub typhus in such cases may reduce unnecessary hospital stay and cost.

Scrub typhus, myocarditis and a possible drug interaction

Scrub typhus, caused by O. Tsutsugamushi is a re-emerging disease which is being increasingly reported from different parts of India. This disease has a wide spectrum of presentation which can range from uncomplicated febrile illness to life-threatening sepsis with multi-organ dysfunction. Myocarditis has been described as one of the rare manifestations of this infection and very few cases have been reported. Myocarditis in scrub typhus is usually subclinical and therefore many times ignored. Here, we report of a case of scrub typhus presenting without the typical rash and eschar with features of myocarditis requiring treatment. We highlight a possible drug interaction between ivabradine and doxycycline which were used in this patient. We also highlight the possibility of other drug interactions between the various drugs used in the treatment of scrub typhus and its complications and stress the need to be vigilant when prescribing multiple drugs, especially in a disease with such a varied presentation and multiple complications that require the use of a number of drugs.

A Review of the Electrocardiography Changes and Clinical Manifestations of Scrub Typhus in a Single Center

Background/Aims: Most scrub typhus patients have normal electrocardiography (ECG) findings. Recently, however, several cases with ECG changes were reported. However, few studies have examined the ECG changes in scrub typhus. Methods: The ECG and demographic data of patients infected with Orientia tsutsugamushi seen at Dongsan Medical Center from January 2008 to June 2012 were reviewed retrospectively. Patients with pre-existing cardiac disease were excluded. The initial and follow-up ECG findings, demographic characteristics, and laboratory findings was examined. Results: The group in which the initial ECG showed an arrhythmia had a higher blood urea nitrogen (BUN) level than the normal and ischemic groups (median 26.0 vs. 15.0 vs. 15.5 mg/dL, p = 0.041). The group with a sustained abnormality in the follow-up ECG had higher BUN (median 17.0 vs. 15.0 mg/dL, p = 0.022) and creatinine (median 1.30 vs. 0.90 mg/dL, p = 0.026) levels than the normal ECG group. In addition, the group with a sustained abnormality in the follow-up ECG had a higher rate of intensive care unit (ICU) admission (30.8% vs. 5.3%, p = 0.015) and longer treatment period (average 9 vs. 6 days, p = 0.027) than the other groups. Conclusions: In our study, more than 30% of the patients with scrub typhus showed ECG abnormalities. Those with an arrhythmic ECG change on presentation had high BUN levels. The sustained ECG abnormality group had high BUN and creatinine levels, and an increased ICU admission rate and length of stay. We should pay attention to the ECG findings on presentation and during the treatment of scrub typhus.

Acute encephalitis syndrome following scrub typhus infection

Sir, We read the article titled “Acute encephalitis syndrome following scrub typhus infection” by Kar et al. with great interest.[1] The author reported six cases of acute encephalitis syndrome (AES) secondary to scrub typhus infection. We want to highlight certain issues regarding the management of these patients. According to the author, once the diagnosis of scrub typhus was established, patients were continued only on doxycycline 100 mg twice daily for a period of 7-10 days. For patients who showed inadequate response to doxycycline alone, azithromycin was “added.” We also agree that doxycycline is the first drug of choice for scrub typhus and, for doxycycline-resistant cases, azithromycin is a safe “alternative.”[2] But, we could not find any literature in which the combination of doxycycline and azithromycin was used for the treatment of poorly responsive scrub typhus. The Cochrane review 2010 found no difference between azithromycin and doxycycline for the treatment of scrub typhus.[3] A recent meta-analysis found macrolide antibiotics such as azithromycin to be highly effective against scrub typhus and concluded that they are appropriate “alternatives” in areas where doxycycline-resistant scrub typhus is prevalent.[4] The only study that evaluated combination therapy for scrub typhus used doxycycline and rifampicin.[5] But, unfortunately, this combination therapy was found to be ineffective against O. tsutsugamushi and rifampicin monotherapy was found to be more effective than doxycycline in the resistant strain. Therefore, we think that addition of azithromycin to doxycycline for patients who showed inadequate response to doxycycline alone was irrational. The author should have replaced doxycycline with azithromycin in those cases.

Acute respiratory distress syndrome following scrub typhus: A case report

To discuss a case of scrub typhus complicated with acute respiratory distress syndrome (ARDS) in a 67-year-old female. An overview of the prevalence and pathogenesis of the disorder, clinical diagnosis, and treatment are presented. Case report, diagnostic evidence, and scientific literature. If not properly treated, scrub typhus can cause serious complications, such as ARDS and septicemia. When left untreated, the mortality rate for scrub typhus will be increased. When there is a cause to believe that scrub typhus is present, doxycycline treatment leads to rapid symptom improvement. People might not be aware of the possibility of scrub typhus because it had been a more common disease in the past. Nurse practitioners (NPs) should take a detail history and be aware of common clinical manifestations to promote the early recognition and appropriate treatment of scrub typhus, which would prevent severe complications and reduce mortality. A resurgence of the disease could occur at any time among military troops serving in endemic regions.

Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

Scrub typhus is a public health concern for a population of over a billion humans, with an estimated incidence of one million cases/year in endemic areas. Although doxycycline remains the standard therapy, fluoroquinolones have been used successfully in a few patients. However, there is also clinical evidence that fluoroquinolones are ineffective in the treatment of scrub typhus. To clarify this matter, we determined the in vitro susceptibility of Orientia tsutsugamushi strain Kato to ciprofloxacin and ofloxacin and sequenced the quinolone resistance-determining region (QRDR) of the gyrA gene, the target of fluoroquinolones, of 18 fresh isolates from the Lao PDR. Orientia tsutsugamushi strain Kato was resistant to ciprofloxacin and ofloxacin in vitro (minimum inhibitory concentration = 8 μg/mL). All sequences obtained, including those from the two available genomes of O. tsutsugamushi (strains Boryong and Ikeda), had a Ser83Leu mutation in their QRDR domain that is known to be associated with fluoroquinolone resistance. These findings re-emphasise the usefulness of in silico analysis for the prediction of antibiotic resistance and suggest that fluoroquinolones should not be used in the treatment of scrub typhus.

In vitro Study on the Dose and Duration of Doxycycline Treatment against Orientia tsutsugamushi

Background :Doxycycline, azithromycin, and chloramphenicol have been used for the treatment of scrub typhus; however, the duration of treatment for this disease is still controversial. Most clinical studies on the treatment of scrub typhus focus on the effectiveness of antibiotics; few studies have focused on the duration of the treatment. There has been no in vitro evaluation of the optimal duration of treatment of scrub typhus. We performed an experiment to evaluate the regrowth of Orientia tsutsugamushi after exposure to doxycycline of various concentration and exposure time. Materials and Methods :O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi; thereafter, the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). Incubation in media containing 0.1 (the minimal inhibitory concentration of doxycycline against O. tsutsugamushi strain Boryong), 0.2, and 2 μg/mL doxycycline for 1, 3, 5, and 7 day was followed by incubation in antibiotic-free media for 5 day. Two inocula sizes were employed; low inoculum (45.18% of cells were infected) and high inoculum (87.21% of cells). Results : The incubation with 0.1 μg/mL doxycycline resulted in O. tsutsugamushi regrowth irrespective of doxycycline treatment duration. When the concentration of doxycycline was increased to 0.2 or 2 μg/mL, regrowth was observed in short duration treatments (1-5 day at 0.2 μg/mL; 1 day at 2 μg/mL). Higher inoculum size of O. tsutsugamushi increased regrowth (1 day at the low inoculum; 1-5 day at the high inoculum). Conclusions : The regrowth of O. tsutsugamushi after doxycycline treatment depends on the doxycycline dose; the higher the dose, the lower the relapse rate. If this result is extrapolated to humans, higher dose of doxycycline might be preferred to lower the relapse rate. The inoculum effect in O. tsutsugamushi infection needs further investigations.

Treatment of Scrub Typhus during Pregnancy : Review of Korean Patients

Treatment of Scrub Typhus during Pregnancy : Review of Korean Patients