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Predictors of postinfectious inflammatory response syndrome in HIV-negative immunocompetent cryptococcal meningitis
  1. Jia Liu1,
  2. Chongliang Luo2,
  3. Min Li1,
  4. Yi-Jie Wang1,
  5. Xiaofeng Xu1,
  6. Lu Yang1,
  7. Bang-e Qin1,
  8. Yong Chen2,
  9. Ying Jiang1,
  10. Fuhua Peng1
  1. 1 Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
  2. 2 Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Pennsylvania, PA, USA
  1. Correspondence to Dr Ying Jiang, Third Affiliated Hospital of Sun Yat-Sen University Department of Neurology, Guangzhou, Guangdong 510630, China; jiangying722{at}

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Cryptococcal meningitis (CM) is an important opportunistic infection worldwide. After initiation of highly active antiretroviral therapy (HAART), about 10%–20% of patients with HIV–CM developed paradoxical cryptococcal immune reconstitution inflammatory syndrome (IRIS).1 2 Many retrospective studies have described risk factors for the development of HIV-related cryptococcal IRIS. A similar exuberant inflammatory response called postinfectious inflammatory response syndrome (PIIRS)1 3 is rarely noticed in previously healthy individuals. Early identification and treatment of PIIRS in patients with CM are very important. However, it is not clear which factors could predict the occurrence of CM-PIIRS. Therefore, in this study, we aimed to fill this research gap and to explore predictive indicators related to HIV-negative immunocompetent CM-PIIRS.


There were 113 previously healthy patients who were evaluated and treated for CM enrolled between January 2011 and December 2019 at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. The final diagnoses and reasons for exclusion of patients are shown in online supplemental figure S1). Demographic characteristics (age gender), clinical symptoms (headache, fever, vision and hearing impairment, mental status, nausea and vomiting) and treatment history, blood and cerebrospinal fluid (CSF) samples testing, modified Rankin Scale (mRS) scores and lumbar puncture were analysed online supplemental table S1).

Supplemental material


We used the random forests to select the useful predictor variables and to predict the development of PIIRS. The random forests were first fit in the training set (75%, n=84) using the selected variables and then were used to predict the PIIRS status of the testing set (25%, n=29). We demonstrate a parsimonious prediction rule by fitting a decision tree using all the patients and the most useful predictor variables. We further analysed the time from starting fungicidal therapy to the appearance of PIIRS or end of follow-up, and the association between the reduction rate of CSF …

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  • JL and CL contributed equally.

  • Contributors YJ, FP and YC contributed to the conception and design of this study. JL, ML, YW, XX and LY collected and organised the data. CL, JL, YJ and YC analysed the data. JL, YJ, CL, FP, YC and BQ drafted the manuscript. YJ, FP and YC reviewed the whole paper, figures and tables. All the authors read and approved the final manuscript. * YJ and FP contributed equally to this paper.

  • Funding This work was supported by the National Natural Science Foundation of China (81671182) and the Natural Science Foundation of Guangdong Province (2016A030313228), and Cultivation Project of the National Natural Science Foundation of China (2020GZRPYQN27). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.