Development and implementation of a strategy for early diagnosis and management of scrub typhus: an emerging public health threat.

Scrub typhus, caused by Orientia tsutsugamushi, is a re-emerging zoonotic disease in the tropics with considerable morbidity and mortality rates. This disease, which is mostly prevalent in rural areas, remains underdiagnosed and underreported because of the low index of suspicion and non-specific clinical presentation. Limited access to healthcare, diagnostics, and treatment in rural settings further makes it challenging to distinguish it from other febrile illnesses. While easily treatable, improper treatment leads to severe forms of the disease and even death. As there is no existing public health program to address scrub typhus in India, there is an urgent need to design a program and test its effectiveness for control and management of the disease. With this backdrop, this implementation research protocol has been developed for a trial in few of the endemic "pockets" of Odisha, an eastern Indian state that can be scalable to other endemic areas of the country, if found effective. The main goal of the proposed project is to include scrub typhus as a differential diagnosis of fever cases in every tier of the public health system, starting from the community level to the health system, for the early diagnosis among suspected cases and to ensure that individuals receive complete treatment. The current study aimed to describe the protocol of the proposed Scrub Typhus Control Program (STCP) in detail so that it can receive valuable views from peers which can further strengthen the attempt.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.

Central nervous system infections in the tropics.

PURPOSE OF REVIEW: Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. RECENT FINDINGS: In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. SUMMARY: A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.

Viral hepatitis-induced acute liver failure.

Viral hepatitis-induced acute liver failure (ALF) is a preventable cause for liver-related mortality worldwide. Viruses are the most common cause for ALF in developing nations in contrast to the west, where acetaminophen is largely responsible. Viruses may be hepatotropic or affect the liver secondary to a systemic infection. In tropical countries, infections such as leptospirosis, scrub typhus and malaria can mimic the symptoms of ALF. Differentiating these ALF mimics is crucial because they require etiology-specific therapy. Treatment of viral hepatitis-induced ALF is two-pronged and directed towards providing supportive care to prevent organ failures and antiviral drugs for some viruses. Liver transplantation (LT) is an effective modality for patients deteriorating despite adequate supportive care. Early referral and correct identification of patients who require a transplant are important. Liver support devices and plasma exchange have evolved into "bridging modalities" for LT. Preventive strategies such as hand hygiene, use of clean and potable water and inclusion of vaccines against viral hepatitis in the national program are simple yet very effective methods focusing on the preventive aspect of this disease.

Epidemiologic changes of a longitudinal surveillance study spanning 51 years of scrub typhus in mainland China.

Scrub typhus may be one of the world's most prevalent, neglected and serious, but easily treatable, febrile diseases. It has become a significant potential threat to public health in China. In this study we used national disease surveillance data to analyze the incidence and spatial-temporal distribution of scrub typhus in mainland China during 1952-1989 and 2006-2018. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of scrub typhus infection. Over the 51-year period, a total of 182,991 cases and 186 deaths were notified. The average annual incidence was 0.13 cases/100,000 population during 1952-1989. The incidence increased sharply from 0.09/100,000 population in 2006 to 1.93/100,000 population in 2018 and then exponentially increased after 2006. The incidence was significantly higher in females than males (χ2 = 426.32, P < 0.001). Farmers had a higher incidence of scrub typhus than non-farmers (χ2 = 684.58, P < 0.001). The majority of cases each year were reported between July and November with peak incidence occurring during October each year. The trend surface analysis showed that the incidence of scrub typhus increased gradually from north to south, and from east and west to the central area. The spatial autocorrelation analysis showed that a spatial positive correlation existed in the prevalence of scrub typhus on a national scale, which had the characteristic of aggregated distribution (I = 0.533, P < 0.05). LISA analysis showed hotspots (High-High) were primarily located in the southern and southwestern provinces of China with the geographical area expanding annually. These findings provide scientific evidence for the surveillance and control of scrub typhus which may contribute to targeted strategies and measures for the government.

Pattern of Fluid Overload and its Impact on Mortality Among Mechanically Ventilated Children: Secondary Analysis of the ReLiSCh Trial.

OBJECTIVES: To assess the pattern of fluid overload (FO) and its impact on mortality among mechanically ventilated children. METHODS: In this secondary analysis of an open-label randomized controlled trial (ReLiSCh trial, October 2020-September 2021), hemodynamically stable mechanically ventilated children (n = 100) admitted to a tertiary level pediatric intensive care unit (PICU) in North India were enrolled. The primary outcome was pattern of FO (FO% >10% and cumulative FO% from day 1-7); and secondary outcomes were pattern of FO among survivors and non-survivors, and prescription practices of maintenance fluid. RESULTS: The median (IQR) age was 3.5 (0.85-7.5) y and 57% were males. Common diagnoses were pneumonia (27%), scrub typhus (14%), Landry-Guillain-Barré syndrome (9%), dengue (8%), central nervous system infections (7%) and staphylococcal sepsis (6%). Common organ dysfunction included acute respiratory distress syndrome (ARDS) (41%), shock (38%), and acute kidney injury (AKI) (9%). The duration PICU stay was 11 (7-17) d and mortality was 12%. The FO% >10% was noted in 19% children; and there was significant increase in cumulative FO% from day 1-7 [1.2 (0.2-2.6)% to 8.5 (1.7-14.3)%, (p = 0.000)]. Among non-survivors, higher proportion had FO% >10% (66.7% vs. 12.5%, p 0.0001); and trend towards higher cumulative FO% on first seven days. From day 1-7, the percentage of maintenance fluid received increased from 60 (50-71)% to 70 (60-77)% (p = 0.691). CONCLUSIONS: One-fifth of mechanically ventilated children had FO% >10% and there was significant increase in cumulative FO% from day 1-7. Non-survivors had significantly higher degree of FO.

Macrolides versus other antibiotics in pediatric scrub typhus: A meta-analysis.

BACKGROUND: While Doxycycline is the recommended drug for treating scrub typhus, there is a growing trend of using Macrolides and Other antibiotics due to their perceived advantages. In this study, we compared the efficacy of Macrolides versus Other antibiotics in the treatment of pediatric scrub typhus. METHODS: Meta-analysis of randomized controlled trials (RCTs) with GRADE (Grading of Recommendations, Assessment, Development and Evaluation) application. Major databases were searched till 30th December 2022. Children of all age groups were included. Primary outcomes included mortality rate and time to defervescence (h). RESULTS: Of the 103 citations retrieved, 5 trials, including 383 children up to 15 years of age with probable and confirmed cases of scrub typhus, were included. None of the trials reported mortality rate. The pooled results from the trials found no significant difference between Azithromycin and Other antibiotics for any of the outcome measures. The certainty of evidence for the primary outcome was deemed to be of "very low certainty", while the certainty of evidence for the secondary outcomes ranged from "low to moderate certainty". CONCLUSIONS: The current meta-analysis revealed that there was no significant difference between Azithromycin and Other antibiotics (such as Doxycycline and Chloramphenicol) in the treatment of scrub typhus in children. However, it's important to note that the evidence generated for the primary outcome was of "very low certainty". PROSPERO REGISTRATION NUMBER: CRD42021276577.

Identification of novel variants for complicating cardiac disease in the scrub typhus infection using whole genome sequencing.

BACKGROUND/AIMS: Scrub typhus infection has been known to complicate cardiovascular diseases mainly attributing to high mortality. Genetic susceptibility loci for complicating cardiac diseases such as atrial fibrillation, heart failure, and ischemic heart disease identified by genomic study have been limited in scrub typhus infection. Therefore, we investigated the genetic novel variants predicting complicating cardiac diseases in patients with confirmed scrub typhus infection using whole genome sequencing. METHODS: We performed a prospective study for eight consecutive patients with scrub typhus infection. During follow-up, six cases were clinically diagnosed with complicating cardiac diseases and two controls without complicating cardiac diseases. The whole genomes of the all patients were sequenced, and the individual sequence variants were compared between accordcase and control patients. Variant genotypes were compared and identified as a single nucleotide polymorphism (SNP) of the different genotype distributions between six cases and two controls. RESULTS: The GG genotype in SNP (rs4977397) of solute carrier 24 family member 2 (SLC24A2) gene and non-TT genotype in SNP (rs2676750) of adenosine deaminase, RNA specific, B2 (ADARB2) gene were distinctively found in the case patients with complicated cardiac disease, compared with control patents in the scrub typhus infection. CONCLUSION: We suggest that the SNPs of SLC24A2 and ADARB2 might be genetic surrogate markers for complicating cardiac diseases in the scrub typhus infection. Our study show that early detection based on individual sequence variants might be feasible to predict complicating cardiac diseases in patients with scrub typhus infection, if further studies with more participants confirm these findings.

Cytokine and Chemokine Profiles in Acute Severe Fever with Thrombocytopenia Syndrome and Scrub Typhus in South Korea.

In East Asia, severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus, which are common endemic tick- and mite-mediated diseases sharing common clinical manifestations, are becoming public health concerns. However, there are limited data on the comparative immunopathogenesis between the two diseases. We compared the cytokine profiles of SFTS and scrub typhus to further elucidate immune responses that occur during the disease courses. We prospectively enrolled 44 patients with confirmed SFTS and 49 patients with scrub typhus from July 2015 to December 2020. In addition, 10 healthy volunteers were enrolled as healthy controls. A cytometric bead array was used to analyze plasma samples for 16 cytokines. A total of 68 plasma samples, including 31 (45.6%) from patients with SFTS and 37 (54.4%) from patients with scrub typhus, were available for cytokine measurement. There were three cytokine expression patterns: increased levels in both SFTS and scrub typhus (interleukin 6 [IL-6], IL-10, interferon gamma induced protein 10 [IP-10], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), highest levels in SFTS (interferon alpha [IFN-α], IFN-γ, granulocyte-CSF [G-CSF], monocyte chemotactic protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], and IL-8), and distinct levels in scrub typhus (IL-12p40, tumor necrosis factor alpha [TNFα], IL-1ß, regulated on activation and normally T-cell expressed and secreted [RANTES], IL-17A, and vascular endothelial growth factor [VEGF]). Although patients with acute SFTS and scrub typhus exhibited partly shared expression patterns of cytokines related to disease severity, the different profiles of cytokines and chemokines might contribute to higher mortality in SFTS than in scrub typhus. Discrete patterns of helper T cell-related cytokines and VEGF might reflect differences in CD4 T-cell responses and vascular damage between these diseases.

The burden, risk factors and unique etiologies of stroke in South-East Asia Region (SEAR).

The World Health Organization (WHO) South East Asia Region (SEAR) comprises 11 countries, which are one of the most culturally, topographically, and socially diverse areas worldwide, undergoing an epidemiological transition towards non-communicable diseases, including stroke and other cardiovascular diseases (CVDs). This region accounts for over 40% of the global stroke mortality. Few well-designed population-based epidemiological studies on stroke are available from SEAR countries, with considerable variations among them. Ischemic stroke, a common stroke subtype, has higher frequencies of intracerebral hemorrhage in many countries. Along with an aging population, the increased prevalence of risk factors such as hypertension, diabetes mellitus, tobacco and alcohol consumption, lack of physical activity, high ambient pollution, heat, and humidity contribute to the high burden of stroke in this region. SEAR's many unique and uncommon stroke etiologies include cerebral venous thrombosis, tuberculosis, dengue, scrub typhus, falciparum malaria, snake bite, scorpion sting, etc. Current data on stroke burden and risk factors is lacking, compelling an urgent need for high-quality hospital-level and population-level data in all SEAR countries. Strategies towards a consolidated approach for implementing improved stroke prevention measures, stroke surveillance, and established stroke systems of care are the path to bridging the gaps in stroke care.

[Epidemiological characteristics of tick-borne infectious diseases in Hubei Province, 2016-2021].

Objective: To understand the epidemiological characteristics of tick-borne infectious diseases (TBID) and the risk factors of severe illness and death in Hubei Province from 2016 to 2021. Methods: Based on the incidence data of fever with thrombocytopenia syndrome (SFTS), tsutsugamushi disease, typhus and other TBID reported during 2016-2021, the epidemiological analysis was conducted. Field investigation results of TBID in areas with high incidence in 2021, logistic regression analysis of population characteristics, epidemiological history and other factors were used to explore the risk factors of severe and fatal cases. In the field vector investigation, free ticks and surface ticks of the host animals in the cases' home and surrounding grassland were monitored and detected. Results: A total of 3 826 TBID cases were reported in Hubei from 2016 to 2021, of which 71.30% (2 728/3 826) were SFTS, 13.04% (499/3 826) were tsutsugamushi disease and 15.66% (599/3 826) were typhus. A total of 44 cases died in 6 years; the fatality rate was 1.15% (44/3 826). In the peak seasons of incidence from May to July, the cases in people engaged in agriculture related work accounted for 84.61% (3 237/3 826). The incidence rate in women was higher than that in men, and the cases aged ≥50 years accounted for 81.02% of the total (3 100/3 826), and the incidence rate increased with age (P<0.001). The TBID cases were distributed in 86 counties and districts in 16 prefectures (municipality). The incidence rates of different areas had significant differences (P<0.05), and there was a certain spatial-temporal clustering and expasion. Bovis microplus and Haemaphysalis longicornis were captured in the field, and the positive rates in host animals and grassland ticks were 10.94% (7/64) and 40.00% (2/5), respectively. Univariate logistic regression analysis results showed that age ≥50 years and leukocyte <2.0×109/L were risk factors for severe illness and death. Conclusions: The TBID reported in Hubei were mainly SFTS, tsutsugamushi disease and typhus. In order to reduce the incidence of TBID, it is necessary to strengthen the prevention and control in women aged ≥50 years and reduce field exposure and tick bites during the epidemic period.

Scrub typhus, a salient threat: Needs attention.

Scrub typhus (ST) infection is one of the most significant causes of acute undifferentiated febrile illness, and its prevalence has been increasing across the globe. Clinical suspicion and growing clinical understanding among healthcare professionals have resulted in the rapid diagnosis and effective management. Since ST has the potential to cause multiorgan failure and a higher mortality rate, it is critical to enhance surveillance, make rapid diagnosis, and administer antibiotics appropriately.

[Epidemiological characteristics of typhus in China, 1950-2021].

Objective: To analyze the epidemiological characteristics of typhus in China from 1950 to 2021, and discuss the challenges in typhus prevention and control in China and suggest future prevention and control strategies. Methods: Based on the reported data of typhus from 1950 to 2021 in China from the Infectious Disease History Database of China Public Health Science Data Center and the National Notifiable Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, we conducted a descriptive statistical analysis. Mann-Kendall test and circular distribution method were used to analyze the incidence, mortality and case fatality of typhus to reveal the temporal, spatial and population distributions and diagnosis of typhus in China. Results: From 1950 to 2021, a total of 452 965 typhus cases and 7 339 typhus deaths were reported in China, with the cases numbers exceeding 10 000 in 14 years of the 1950s, 1960s and 1980s, respectively. Since 1990s, the reported cases and incidence rate of typhus have decreased dramatically and the most cases were sporadic. However, the reported typhus cases in Anhui, Hubei, Hunan Provinces showed significant uptrends. Although typhus could occur all the year round, but the seasonality was observed with the incidence mainly in summer and autumn. For different provinces from the north to the south, the peaks of typhus' monthly incidence tended to shift to earlier dates. The male to female ratio of the cases was 1.01∶1 (18 529∶18 366). However, more cases occurred in women in recent years. The cases aged ≤9 years accounted for the highest proportion (18.9%), but the number of cases aged ≥50 years showed an upward trend. Most cases were farmers with the proportion increasing year by year. Moreover, the cases in students and scattered-living children also accounted for relatively higher proportions. The median of the interval between onset and diagnosis of typhus was 6 days. Most cases were clinically diagnosed, while the proportion of laboratory-confirmed cases was low and most laboratory cases were confirmed by Well-Felix reaction. Conclusions: Although the incidence and mortality of typhus in China has decreased significantly, the risk for local typhus outbreaks still exists. The prevention and control of typhus still face many challenges. It is indispensable to strengthen the pathogen detection and surveillance for typhus in China.

Co-infection of dengue, scrub typhus, and typhoid during dengue outbreak in Nepal, 2022: A case report.

In midst of the recent dengue outbreak in Nepal, in 2022, the risk of co-infection increases and may lead to fatal outcomes if the diagnosis of multiple infections is delayed. Thus, all available diagnostic approaches must be taken to decrease the burden of illness and lessen mortality.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Why are so many indigenous Pando people dying? Using observations from Chhattisgarh, India, to conduct structural assessment and identify solutions.

Health challenges of communities are often assessed using biomedical or individual risk-based frameworks which are often inadequate for understanding their full extent. We use observations from the global South to demonstrate the usefulness of structural assessment to evaluate a public health problem and spur action. Following newspaper reports of excessive deaths in the marginalised indigenous or Adivasi community of the Pando people in Northern Chhattisgarh in central India, we were asked by the state government's public health authorities to identify root causes of these deaths. In this rapidly evolving situation, we used a combination of public health, social medicine, and structural vulnerability frameworks to conduct biomedical investigation, social inquiry, and structural assessment. After biomedical investigations, we identified scrub typhus, a neglected tropical disease, as the most likely cause for some of the deaths which was unrecognised by the treating physicians. In the social inquiry, the community members identified the lack of Adivasi status certificates, education, and jobs as the three major social factors leading to these deaths. During the structural assessment of these deaths, we inductively identified the following ten structures- political, administrative, legal, economic, social, cultural, material, technical, biological, and environmental. We recommended improving the diagnosis and treatment of scrub typhus, making the hospitals more friendly for Adivasi people, and tracking the health status of the Adivasi communities as some of the measures. We suggest that a combination of biomedical, social,and structural assessments can be used to comprehensively evaluate a complex public health problem to spur action..

Clinical features and risk factors for death in acute undifferentiated fever: A prospective observational study in rural community hospitals in six states of India.

BACKGROUND: Acute undifferentiated fever (AUF) ranges from self-limiting illness to life-threatening infections, such as sepsis, malaria, dengue, leptospirosis and rickettsioses. Similar clinical presentation challenges the clinical management. This study describes risk factors for death in patients hospitalized with AUF in India. METHODS: Patients aged ≥5 y admitted with fever for 2-14 d without localizing signs were included in a prospective observational study at seven hospitals in India during 2011-2012. Predictors identified by univariate analysis were analyzed by multivariate logistic regression for survival analysis. RESULTS: Mortality was 2.4% (37/1521) and 46.9% (15/32) died within 2 d. History of heart disease (p=0.013), steroid use (p=0.011), altered consciousness (p<0.0001), bleeding (p<0.0001), oliguria (p=0.020) and breathlessness (p=0.015) were predictors of death, as were reduced Glasgow coma score (p=0.005), low urinary output (p=0.004), abnormal breathing (p=0.006), abdominal tenderness (p=0.023), leucocytosis (p<0.0001) and thrombocytopenia (p=0.001) at admission. Etiology was identified in 48.6% (18/37) of fatal cases. CONCLUSIONS: Bleeding, cerebral dysfunction, respiratory failure and oliguria at admission, suggestive of severe organ failure secondary to systemic infection, were predictors of death. Almost half of the patients who died, died shortly after admission, which, together with organ failure, suggests that delay in hospitalization and, consequently, delayed treatment, contribute to death from AUF.

Clinical profile and outcomes of Scrub typhus in pregnant women presenting to a tertiary care hospital of North India.

Scrub typhus, caused by Orientia tsutsugamushi, is a re-emerging endemic zoonosis in the Asia Pacific region. It is a febrile condition ranging in severity from mild to severe, with fatality rates as high as 30%. The present study aims towards analysing the clinical profile and pregnancy outcomes in 27 cases of scrub typhus admitted to a tertiary care centre in North India. The medical records of 27 pregnant women who had scrub typhus were analysed. The IgM ELISA was used to look for IgM antibodies to Orientia tsutsugamushi in the patient's serum sample. An optical density of more than or equal to 0.468 was considered as positive. Majority of the pregnant females delivered healthy and live babies. However, poor foetal outcomes were observed in four (14.8%) cases with intrauterine deaths occurring in two (7.4%) cases and still birth in one (3.7%) case, while one (3.7%) patient had spontaneous abortion. Maternal mortality was reported in one patient (3.7%) due to a delay in diagnosis. In endemic settings, a strong index of suspicion for scrub typhus is necessary in pregnant females presenting with fever. The key to reducing morbidity in both the mother and foetus is early diagnosis and treatment.Impact StatementWhat is already known on this subject? Scrub typhus is a febrile condition ranging in severity from mild to severe, with 30% mortality in untreated patients.What do the results of this study add? Majority of the pregnant females delivered healthy and live babies. However, poor foetal outcomes were observed in four (14.8%) cases with intrauterine deaths occurring in two (7.4%) cases and still birth in one (3.7%) case, while one (3.7%) patient had spontaneous abortion. Maternal mortality was reported in one patient (3.7%) due to a delay in diagnosis.What are the implications of these findings for clinical practice and/or further research? In endemic settings, a strong index of suspicion for scrub typhus is necessary for pregnant females presenting with fever. The key to reducing morbidity in both the mother and foetus is early diagnosis and treatment.

Treatment outcomes of oral doxycycline versus intravenous azithromycin in adults hospitalized with scrub typhus: A retrospective study using inverse probability treatment weighting (IPTW) propensity analysis.

OBJECTIVE: Only a few well-designed studies that have investigated the effectiveness of azithromycin in treating adult patients hospitalized with scrub typhus are currently available. The purpose of our study was to compare the effects of intravenous azithromycin administration with those of oral doxycycline, and to evaluate cardiovascular death associated with intravenous azithromycin in adult patients hospitalized with scrub typhus. METHODS: This retrospective study investigated Korean National Infectious Disease Cohort Collaborative-registered scrub typhus-infected patients who were hospitalized between January 1, 2013, and December 31, 2021, and who were ≥18 years old. The primary outcome was time to fever clearance and the secondary outcomes were treatment failure, relapse, scrub typhus-related death, or azithromycin-related cardiovascular death. To address any indication bias, inverse probability of treatment weighting (IPTW) analysis was performed. Times to fever clearance between the doxycycline and azithromycin groups were compared using log-rank tests and Kaplan-Meier curves. RESULTS: A total of 326 consecutive patients with laboratory-confirmed scrub typhus were included in this study of whom 109 were treated with azithromycin and 217 with doxycycline. Using IPTW, there were no statistically significant differences in the following end points between the azithromycin and doxycycline groups: median time to fever clearance (3 days vs. 3 days, P = 0.649), treatment failure (0.71% vs. 0.42%, P = 0.702), relapse (0.0% vs. 0.0%), and scrub typhus-related death (5.12% vs. 0.0%, P = 0.155). No azithromycin-related cardiovascular deaths occurred. In the sensitivity analyses, there were no significant changes in effect size. CONCLUSIONS: Our study showed that the therapeutic effects and safety of intravenous azithromycin are comparable to those of oral doxycycline administration in patients hospitalized with scrub typhus. A well-designed randomized controlled trial may help further evaluate the most adequate route of administration, dose and duration of treatment with azithromycin.

Epidemiological characteristics of tick-borne infectious diseases in Hubei Province, 2016-2021 / 中华流行病学杂志

Objective: To understand the epidemiological characteristics of tick-borne infectious diseases (TBID) and the risk factors of severe illness and death in Hubei Province from 2016 to 2021. Methods: Based on the incidence data of fever with thrombocytopenia syndrome (SFTS), tsutsugamushi disease, typhus and other TBID reported during 2016-2021, the epidemiological analysis was conducted. Field investigation results of TBID in areas with high incidence in 2021, logistic regression analysis of population characteristics, epidemiological history and other factors were used to explore the risk factors of severe and fatal cases. In the field vector investigation, free ticks and surface ticks of the host animals in the cases' home and surrounding grassland were monitored and detected. Results: A total of 3 826 TBID cases were reported in Hubei from 2016 to 2021, of which 71.30% (2 728/3 826) were SFTS, 13.04% (499/3 826) were tsutsugamushi disease and 15.66% (599/3 826) were typhus. A total of 44 cases died in 6 years; the fatality rate was 1.15% (44/3 826). In the peak seasons of incidence from May to July, the cases in people engaged in agriculture related work accounted for 84.61% (3 237/3 826). The incidence rate in women was higher than that in men, and the cases aged ≥50 years accounted for 81.02% of the total (3 100/3 826), and the incidence rate increased with age (P<0.001). The TBID cases were distributed in 86 counties and districts in 16 prefectures (municipality). The incidence rates of different areas had significant differences (P<0.05), and there was a certain spatial-temporal clustering and expasion. Bovis microplus and Haemaphysalis longicornis were captured in the field, and the positive rates in host animals and grassland ticks were 10.94% (7/64) and 40.00% (2/5), respectively. Univariate logistic regression analysis results showed that age ≥50 years and leukocyte <2.0×109/L were risk factors for severe illness and death. Conclusions: The TBID reported in Hubei were mainly SFTS, tsutsugamushi disease and typhus. In order to reduce the incidence of TBID, it is necessary to strengthen the prevention and control in women aged ≥50 years and reduce field exposure and tick bites during the epidemic period.