| Background: Scrub typhus(ST)is a natural focus disease caused by the organism Orientia tsutsugamushi that was transmitted to humans by the larva of trombiculid mites.It is estimated that there are 1 million new cases of ST infection each year and more than 1 billion people worldwide are at risk.“Tsutsugamushi triangle”,as the traditional endemic area of ST,covers from the Russian Far East in the north to Australia in the south and Pakistan in the west to Japan in the east.Recently,ST has shown a trend of geographic expansion in areas outside the “tsutsugamushi triangle”such as the United Arab Emirates in the Middle East,Kenya in East Africa,and Peru and Chile in South America.Generally,ST is associated with a broad range of symptoms,from mild diseases such as non-specific symptoms(i.e.,fever,headache,and myalgia),skin damage(i.e.,eschar,ulcer,and skin rash),and gastrointestinal symptoms(i.e.,nausea,vomit,and abdominal pain),to severe complications including pneumonitis,encephalitis,meningoencephalitis,acute kidney injury,acute respiratory distress syndrome,multiple organ failure,and shock,etc.If not appropriately treated,approximately 6% of ST patients would die.In addition,the mortality rate is higher in severe ST,and the case fatality rate is as high as 14% and 24% in complicated ST patients with encephalitis and multiple organ failure,respectively.In recent years,the annual incidence of ST has increased dramatically from 0.09 cases /100,000 population in 2006 to 1.60 cases/100,000 population in 2016 in China.Guangzhou City,as an important epidemic focus of ST,where the incidence of ST was on the rise,and the incidence of ST has increased dramatically to 7.52 cases/100,000 population in 2012.Therefore,it’s necessary to study epidemiological characteristics and clinical features of ST and the risk factors and prediction of severe ST in Guangzhou City,which is great significance for the early prevention,early detection,early diagnosis,and early treatment of ST.Objective:(1)To explore the epidemiologic trend and development pattern of ST in Guangzhou City,and to analyze high-incidence seasons,the hotspot regions,and the high-risk population of ST.(2)To explore the differences in clinical characteristics and laboratory indicators among patients with ST in different age groups,which will provide a basis for clinicians to apply an age-stratified approach to diagnosis and treatment of ST.(3)To explore the risk factors associated with disease severity in ST patients.Clinicians can carry out early clinical intervention and treatment for severe ST patients by assessing these influencing factors.(4)To conduct a prediction model for severe ST provides,which will provide a new approach to the risk management and the treatment optimization of patients with ST,as well as the use of medical resources.Methods: Based on the surveillance data of 5,835 cases of ST between 2012 to2018 in Guangzhou City,a descriptive study was applied to analyze the distribution and epidemic pattern of ST among time,spatial,and population.Based on the clinical data of 4,501 ST patients in 69 hospitals in Guangzhou City from 2012 to 2018,a descriptive study was applied for comparative analysis of clinical characteristics and laboratory indicators of ST with an age-stratified approach.A retrospective case study was applied to analyze the clinical characteristics and laboratory indicators that were associated with the occurrence of severe ST using univariate and multifactorial logistic regression models.A prediction model for severe ST was conducted by using boosted regression tree(BRT)machine learning model.Result: Between 2012 to 2018,a total of 5,835 cases of ST were legally reported from 11 districts in Guangzhou City,with an average annual incidence rate of 6.16cases/100,000 population.59.2% ST patients aged 40–69 years old,and more than half were farmers(51.2%).The average annual incidence of ST in each county area of Guangzhou City showed a high incidence outside and a low incidence inside,as a spatial pattern of "semicircular".From 2012 to 2018,a total of 4,501 hospitalized ST cases in 69 hospitals were included for analysis of clinical data.Severe complications were determined from 366 ST patients,with a disease severity rate of 8.1%(95% CI7.3%–8.9%),which did not differ across the studied years.Fifty-three of the severe cases died,with a case fatality rate of 1.2%(95% CI 0.9%–1.5%).Fever(98.2%),eschar(74.1%),anorexia(69.9%),headache(51.1%),and weakness(43.7%)were commonly observed in ST patients.The prominent sites of eschar were abdomen under umbilicus(31.5%)and upper limbs(25.2%).The most common laboratory abnormalities in ST patients were elevated levels of lactate dehydrogenase(92.0%),C reactive protein(86.0%),aspartate aminotransferase(83.7%),and alanine aminotransferase(76.0%),and decreased level of total protein(68.9%).Age-stratified analysis revealed pediatric patients(aged ≤14 years)had higher frequencies of lymphadenopathy,skin rash,enlarged tonsils,edema,hepatomegaly,and splenomegaly,etc.,accompanied by more abnormal changes in mean corpuscular volume,platelet count,and albumin,etc.,than adult patients(aged 15–59 years).The highest incidence of chest radiographic abnormality(28.4%)was observed in elderly patients(aged ≥60years),and higher incidence of edema,abdominal pain,hyponatremia,hypochloremia,and hypocalcemia,etc.,and lower incidence of hepatomegaly and splenomegaly were observed in elderly patients compared to adults.By multivariate logistic regression analysis in the general population,12 clinical manifestations were significantly related to severe disease,among which dyspnea had the most robust effect(adjusted OR 13.95,95% CI 9.94–19.58),followed by confusion(adjusted OR 7.18,95% CI 3.29–15.67),dysphoria(adjusted OR 6.76,95% CI 2.40–19.1),lethargy(adjusted OR 5.80,95% CI2.19–15.41),macroscopic hematuria(adjusted OR 5.32,95% CI 1.03–27.39),edema(adjusted OR 4.85,95% CI 3.25–7.24),icteric sclera(adjusted OR 4.67,95% CI 2.61–8.33),petechiae(adjusted OR 3.45,95% CI 1.05–11.38),coma(adjusted OR 2.90,95%CI 1.08–7.79),cerebral infarction(adjusted OR 2.33,95% CI 1.37–3.98),abdominal pain(adjusted OR 1.90,95% CI 1.32–2.73),and vomit(adjusted OR 1.45,95% CI 1.02–2.04).And 6 laboratory indicators were significantly related to severe disease,among which decreased platelet count was the most effective risk factor(adjusted OR 4.80,95% CI 3.39–6.82),followed by decreased albumin(adjusted OR3.78,95% CI 1.86–7.65),increased serum creatinine(adjusted OR 2.91,95% CI 2.12–4.00),increased total bilirubin(adjusted OR 2.62,95% CI 1.91–3.60),decreased hemoglobin(adjusted OR 2.19,95% CI 1.59–3.01),and increased neutrophil count(adjusted OR 2.03,95% CI 1.47–2.79).Edema,dyspnea,decreased platelet count,and decreased hemoglobin were significantly associated with severe disease observed across age groups by multivariate logistic regression analysis.A high effective prediction of severe disease was obtained based on boosted regression trees models,with an average AUC of 0.918 and an accuracy of 0.876 in the test dataset.The highest relative contribution in the prediction model was albumin(24.77%),followed by dyspnea(16.63%),platelet count(12.95%),serum creatinine(11.34%),total bilirubin(10.55%),neutrophil count(5.71%),total protein(5.59%),neutrophil percentage(5.40%),hemoglobin(4.25%),and age(2.79%).Conclusion: From 2012 to 2018,the surveillance data of ST in Guangzhou City and the medical records of inpatients with ST from 69 hospitals in Guangzhou City were included in our study.The epidemiological and clinical characteristics of ST patients were described,and the risk factors and the early predictors of severe ST patients were assessed.The incidence rate of ST has been at a high level from 2012 to2018 in Guangzhou City.The average annual incidence rate of ST in each county area,as a spatial pattern of “semicircular”,remains unchanged.Therefore,this spatial pattern needs to be constantly monitored in the future.Considering the remarkable age differences in clinical features and risk factors for severe disease of ST patients,it needs to take an age-based approach for the clinical diagnosis,treatment,and risk assessment for ST patients to reduce the occurrence of severe ST and death.In addition,a prediction model of severe ST patients,as a decision assistive technology,offers a new avenue for enhancing the clinicians’ early identification and risk management for severe ST patients. |
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