Clinical Characteristics Of Childhood Tuberculous Meningitis And Its Risk Factors

Childhood tuberculosis(TB)remains a serious worldwide public health threat.Compared with adulthood TB,childhood TB has a paucibacillary nature and is therefore known as non-infective disease.Because this,childhood TB is usually not included in the national anti-TB plan.Tuberculous meningitis(TBM)is the most severe form of TB,leading to a high rate of mortality.In children,mortality rates of 15%-29%were reported for TBM.Therefore,a better management of childhood TBM is required to improve the current situation of TB patients,especially the survival rate.To characterize the childhood TBM may improve the present situation in the management.In the study,we aimed to answer several scientific questions,as mentioned below.Chapter Ⅰ Epidemiological Trends in the Form of Childhood Tuberculosis in a Referral Tuberculosis Hospital in Shandong,ChinaObjective:In China,the prevalence of TB diseases and epidemiological trends in the TB forms among children is still unclear,a retrospective study was conducted aiming to assess it.Materials and Methods:Between Jan 2007 and Sep 2020,1577 consecutive childhood TB patients(aged≤15 years)were included in the study.Data,including demographic information and underlying diseases,were collected from medical records.Then,patients were categorized and reported according to the anatomical site of TB disease.To analyze the epidemiological trends in the proportion of each form of TB disease,A linear-by-linear association was used,and a P value<0.05 was considered to indicate a significant change occurred in the proportion of TB disease over the studied period.Results:During the fourteen-year study period,a total of 1577 children patients were enrolled,including 954 boys(60.5%)and 623 girls(39.5%),with a median age of 11.0 years.Among the studied patients,810(51.4%)patients have pulmonary TB,1137(72.1%)have extrapulmonary TB,372(23.6%)have both conditions and another 765(48.5%)extrapulmonary cases presented in isolated form.Pleural TB(29.0%)and tuberculous lymphadenitis(23.7%)were the most frequent two forms of childhood TB.In addition,during the past decade,the proportions of pulmonary TB,pleural TB,and tuberculous lymphadenitis showed an increasing trend(all P<0.05).However,no significant trends in the proportions of other forms of TB disease,such as extrapulmonary TB(P>0.05),TBM(P>0.05),endobronchial TB(P>0.05),and disseminated TB(P>0.05),were found.Conclusion:Our findings suggest that childhood TB is facing new challenges,and the policy should be adjusted timely to fit the real situation.Chapter Ⅱ Risk Factors for Poor Outcome in Childhood Tuberculous MeningitisObjective:TBM remains a serious disease for children and its risk factors of poor outcome remain unclear.Therefore,a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM.Materials and Methods:Between January 2006 and December 2019,consecutive children patients(≤15 years old)who had a diagnosis of TBM were included for the analysis.The demographic,clinical,laboratory,and radiographic data were collected from the electronic medical records retrospectively.Poor outcome was defined as death or transfer to a higher-level hospital.Patients were then divided into good and poor outcome groups.Subsequently,risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis.Results:A total of 149 children with TBM was enrolled,twenty-two patients suffered poor outcome,including 16 transfers to a higher-level hospital and 6 deaths,and the remaining 127 patients were classified as good outcome group.Further multivariate analysis revealed that coma(age-and sex-adjusted OR=6.425,95%CI:1.743,23.676;P<0.01)and CSF protein(>1188.3mg/L;age-and sex-adjusted OR=4.680,95%CI:1.469,14.902;P<0.01)were associated with the poor outcome of childhood TBM.Conclusions:Childhood TBM remains to have a high mortality rate in China.High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM.Hence,more attention is required to be paid to suspected patients with such characteristics,thus facilitating access to optimum treatment.Chapter Ⅲ Normal Cerebrospinal Fluid Protein and Associated Clinical Characteristics in Children with Tuberculous MeningitisObjective:Although abnormal CSF protein can be used to predict the outcome of TBM and diagnose TBM,normal CSF protein remains a concern in patients with TBM.This retrospective study aimed to assess the clinical characteristics associated with normal CSF protein,to resolve the dilemma of CSF protein in the management of childhood TBM.Materials and Methods:Between January 2006 and December 2019,consecutive child patients(≤15 years old,a diagnosis of TBM,and tested for CSF protein)were included for analysis.CSF protein was tested on a chemistry analyzer using the pyrogallol red-molybdate method.Abnormal CSF protein was defined as>450mg/L.Patient characteristics were collected from the electronic medical records.Then,characteristics associated with normal CSF protein were estimated in the study,using univariate and multivariate logistic regression analysis.Results:A total of 125 children who met the criteria were enrolled during the study period.Twenty-nine patients had a normal CSF protein and 96 had an abnormal CSF protein.Multivariate analysis(Hosmer-Lemeshow goodness-of-fit test:χ2=2.486,df=8,P=0.962)revealed that vomiting(age-and sex-adjusted OR=0.253,95%CI:0.091,0.701;P=0.008)and serum glucose(>5.08mmol/L;age-and sex-adjusted OR=0.119,95%CI:0.032,0.443;P=0.002)were associated with the normal CSF protein in childhood TBM.Conclusion:In suspected childhood TBM,patients without vomiting or having low serum glucose are easy to present with normal CSF protein.Hence,when interpreting the level of CSF protein in children with such characteristics,a careful clinical assessment is required.Chapter Ⅳ The Sensitivity of Diagnostic Criteria of Marais S,et al.in Confirmed Childhood Tuberculous MeningitisObjective:To establish the sensitivity of the diagnostic criteria published by Marais and co-workers in 2010 for childhood TBM,a retrospective study on children with confirmed TBM was conducted.Materials and Methods:Between January 2006 and December 2019,children consecutively diagnosed with TBM were recruited retrospectively at our center.TBM was defined in cases where any of the following criteria were met:the presence of acid-fast bacilli(AFB)in CSF microscopy,CSF nucleic acid amplification test(NAAT,+)or M.tuberculosis cultured from CSF.The demographic and clinical features of all enrolled patients were recorded including clinical characteristics,CSF findings,cerebral imaging features,and other evidence of TB.Results:A total of 30 children with confirmed diagnosis of TBM over a 14-year period were recruited.The mean age of patients was 7.0 years and 16(53.3%)were male.The estimated mean diagnostic score was 12.7±2.4.Twenty-three(76.7%;95%CI:59.1-88.2%)patients were classified as "Probable TBM"according to the Marais criteria and 7(23.3%;95%CI:11.8-40.9%)as "Possible TBM." Further statistical analysis revealed significant differences in CSF scores between Probable and Possible TBM groups.Other variables reported at a relatively low frequency,such as symptoms and imaging features,made little contribution to TBM diagnosis according to the Marais criteria.Conclusion:Childhood TBM could be effectively identified by the criteria defined by Marais et al.However,further revision is required to ensure that the system is more sensitive and easier to perform in practice.Chapter Ⅴ Cerebrospinal fluid findings of infant tuberculous meningitis:a scoping reviewObjective:Cerebrospinal fluid(CSF)examinations play an important role in the diagnosis of tuberculous meningitis(TBM).However,their yield in the diagnosis of infant TBM remains unclear.This scoping review aims to detail the role of CSF examination for the diagnosis of infant TBM.Materials and Methods:A comprehensive literature search of PubMed,EBSCO,Embase,Scopus,Web of Science,ClinicalTrials.gov,and Cochrane Central Register of Controlled Trials was performed to identify articles published prior to October 14th,2021.Articles describing the results of CSF exanimations among infant TBM were eligible for inclusion.Data extracted from each study included age,sex,CSF microbiological evidences(such as AFB smear,TB PCR,and TB culture),and routine CSF examinations(such as appearance,red blood cell count,white blood cell count,protein,and glucose).Results:A total of 98 cases were included in the final analysis.The yield of microbiological methods was listed as follows:CSF AFB smear,20.5%(9/44);CSF TB culture 47.5%(29/61);CSF TB PCR,65.0%(26/40);the combination of them,57.3%(47/82).According to Marais criteria,the positivities of CSF examinations were calculated as follows:WBC count(ref,50-500/μL),65.5%(55/84);lymphocyte predominance(ref,>0.5),75.4%(49/65);total protein(ref,>100 mg/dL),67.8%(59/87);glucose(ref,<2.2 mmol/L,or CSF/serum ratio<0.5),68.2%(58/85).Conclusions:Our data demonstrated that routine microbiological tools for infant TBM diagnosis have a sensitivity ranging from 20.5%to 65.0%,and most CSF features are non-specific and insufficient to predict a diagnosis of infant TBM.Therefore,further effort is required to develop new tools for infant TBM diagnosis.