| BackgroundTalaromycosis marneffei(TSM)is an invasive fungal disease caused by Talaromyces marneffei infection.It is mainly prevalent in Southeast Asian countries and Southern China.It is one of the most common opportunistic infection among HIV/AIDS patients in Southeast Asian countries and South China.The onset of TSM was insidious,the clinical manifestations were atypical,and the specific serological indicators were lacking,therefore there was no effective early diagnosis method for TSM.The gold standard for diagnosis depends on etiology,including body fluids such as blood,bone marrow,and alveolar lavage fluid or tissue culture and histopathological examination found Talaromyces marneffei.But these diagnostic methods take a long time(cultivation takes 5 to 14 days),the positive rate is low(only 60%to 75%of blood or bone marrow cultures.are positive),and the pathological examination is invasive,many patients are difficult to accept,resulting in early difficult to diagnose.If patients can get effective antifungal treatment early,most of them can be cured.However,if the diagnosis is delayed or missed,the mortality rate of patients will increase greatly.Therefore,it is urgent to establish an early diagnosis method.The previous research of our research group found that the detection of galactomannan(GM)and the mannoprotein(Mp1p)of Talaromyces marneffei is of considerable value for the early diagnosis of TSM.Even though the specificity of GM is only about 85%,and the specificity of Mp1p is higher than 90%,but the sensitivity of those two indicators fluctuates between 50%and 70%.So it is still difficult to achieve high diagnostic efficiency solely by relying on these two indicators.In recent years,some domestic scholars have tried to use clinical indicators to construct a diagnostic model of AIDS combined with TSM,but the diagnostic efficiency is not satisfactory because the latest efficient and rapid diagnostic indicators are not included.This study intends to establish four diagnostic models of AIDS combined with TSM based on common clinical indicators,combined with two serological indicators of GM and Mp1p,and compare their efficacy,so as to explore the early diagnosis models suitable for clinical practice.ObjectiveTo establish four early diagnosis model of AIDS combined with TSM suitable for different situations,explore the best diagnosis model,and provide a new method for improving the diagnosis ability.MethodHIV/AIDS patients who were suspected of having opportunistic infections admitted to the Infectious Disease Center of the Eighth People’s Hospital Affiliated to Guangzhou Medical University from August 2018 to March 2020 and from April 2021 to April 2022 were enrolled.R(4.2.1)software was used for statistical analysis,t test,Wilcoxon test or chi-square test were used to compare the differences between TSM patients and non-TSM patients,and Lasso regression analysis was used for feature selection of difference indicators.Then,Logistic regression analysis was performed on the indicators selected by the Lasso regression to obtain the basic diagnostic model,and the corresponding score was established according to the proportion of the regression coefficient of each indicator.Mp1p,GM and Mp1p and GM indexes were respectively introduced into the basic diagnosis model to obtain Mp1p diagnosis model,GM diagnosis model,Mp1p and GM combined diagnosis model.Finally,the receiver operating characteristic curve(ROC)and the predictive calibration curve were used to verify the diagnostic performance of the four different models,and the quality of each model was compared using the red information criterion(AIC)and the Decision Curve Analysis(DCA).Results1.Comparison of clinical characteristics between TSM and non-TSM groupA total of 600 HIV/AIDS patients were enrolled in this study,including 300 patients in the TSM group and 300 patients in the non-TS module group.Compared with patients in the non-TSM group,the patients in the TSM group were younger and had lower white blood cell count,hemoglobin concentration and platelet count,the difference is statistically significant(P<0.01);The level of LDH,ADA,AST,BUN,TBIL and PCT were higher in TSM group than in non-TSM group,but the ALB level and the CD4+T cell count was lower,the difference is statistically significant(P<0.01);Compared with the non-TSM group,the positive rate of GM test and Mp1p detection in TSM group was higher,the difference is statistically significant(P<0.01).2.Establishment and validation of Basic diagnostic modelThere are 6 predictors in the basic diagnostic model,which are rash(16 points),liver or spleen or lymph node enlargement(21 points),CD4+T cell count<50/μl(21 points),ADA>20u/l(15 points),AST>3 × ULN(15 points),PLT<50.0×109/L(12 points).The red information criterion(AIC)of Basic diagnostic model was 374.35.When the cut-off value was 51.5,the area under the curve(AUC)was 0.879(95%CI:0.829-0.930),the sensitivity of the model was 82.4%(95%CI:74.7%-90.3%),and the specificity was 82.0%(95%%CI:74.0%-90.0%).3.Establishment and validation of Mp1p diagnostic modelThe Mp1p diagnostic model has 5 predictors,which are rash(12 points),liver or spleen or lymph node enlargement(20 points),CD4+T cell count<50/μl(20 points),ADA>20u/l(12 points),Mp1p positive(36 points).AIC of Mp1p+basic diagnostic model was 316.7.When the cutoff value was 50,the AUC was 0.907(95%CI:0.8620.951),the sensitivity of the model was 83.5%(95%CI:75.9%-91.1%),and the specificity was 85.4%(95%CI:78.1%)-92.7%).4.Establishment and validation of GM diagnostic modelThe GM diagnostic model has 5 predictors,which are rash(12 points),hepatosplenomegaly(19 points),CD4+T cell count<50/μl(22 points),ADA>20u/μl 1(12 points)and GM experiment positive(35 points).AIC of GM+basic diagnostic model was 298.95,When the cutoff value was 61.0,the AUC was 0.915(95%CI:0.8710.959),the sensitivity of the model was 75.8%(95%CI:67.0%-84.6%),and the specificity was 96.6%(95%CI:92.9%)-99%).5.Establishment and validation of Mp1p and GM combined diagnostic modelThe Mp1p and GM combined diagnostic model has 6 predictors,which are rash(9 points),hepatosplenomegaly lymphadenopathy(14 points),CD4+T cell count<50/μl(16 points),ADA>20u/l(10 points),GM test positive(24 points)and Mp1p positive(27 points).AIC of Mp1p+GM+basic diagnostic model:261.3.When the cutoff value was 44,the AUC was 0.925(95%CI:0.883-0.968),the sensitivity of the model was 80.2%(95%CI:72.0%-88.4%),and the specificity was 96.6%(95%CI:92.9%)-99%).6.Comparison of different diagnostic modelsAccording to the AIC of each model,the best fitting model is Mp1p and GM combined diagnostic model(AIC:261.3),followed by GM diagnostic model(AIC:298.95)and Mp1p diagnostic model(AIC:316.7),and the model with the worst fit was the basic diagnostic model(AIC:374.35).According to the DCA,the overall net benefit of MP1P combined with GM diagnostic model was higher than that of GM diagnostic model,MP1P diagnostic model and basic diagnostic model.ConclusionSuccessfully constructed and verified four diagnostic models of AIDS combined with TSM which was based on commonly used indicators,Mp1p and GM.The sensitivity and specificity of those four diagnostic models are high,and the diagnostic model included Mp1p and GM has the best performance. |
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