Русский
Novel approaches to etiological diagnosis of central nervous system lesions in patients with HIV
DOI: https://dx.doi.org/10.18565/epidem.2023.13.1.46-54
Shakhgildyan V.I., Yadrikhinskaya M.S., Domonova E.A., Orlovsky А.А., Tishkevich O.A., Yarovaya E.B.
1) Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; 2) Moscow City Center for AIDS Prevention and Control, Moscow, Russia; 3) M.V. Lomonosov Moscow State University, Moscow, Russia; 4) Clinical Infectious Diseases Hospital Two, Moscow, Russia
Subjects and methods. Clinical observations were conducted in 5485 inpatients with HIV infection and their case histories were analyzed. Of these, 3333 patients had Stage 4B AIDS; 1310 patients had CNS lesions. The patients underwent contrast-enhanced brain MRI and diagnostic lumbar puncture. A total of 1667 CSF samples were studied using real time RT-PCR with the qualitative or quantitative determination of secondary disease pathogen DNA and HIV RNA. The reagent kits made by the Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, were used. The authors applied Statistica version 10.0 and SPSS version 20 statistical software packages, R was a programming language. Associations were examined by making a contingency table analysis using Pearson’s χ2 test. The significance level for the tested statistical hypotheses was taken equal to 0.05.
Results. The paper presents the quantitative measures of blood and CSF HIV RNA. Statistically significant associations were found between the blood and CSF HIV RNA levels. CNS lesions as encephalitis, meningoencephalitis, or meningitis were diagnosed in 1310 patients with HIV infection (23.8% of the total number of inpatients, 39.3% of those having Stage 4B AIDS, and 62.7% among the deceased). Among the patients with CNS lesions, there was a significant proportion (53.7%) of cases having encephalitis of unclear etiology. The presence of CSF neuroinfection pathogen DNA and HIV RNA were shown to have a high diagnostic sensitivity and the etiological role of the pathogen could be excluded in the absence of CSF. The qualitative detection of the DNAs of T. gondii, M. tuberculosis, C. neoformans, and human polyomavirus 2 (JCPyV) was shown to have a high diagnostic specificity. On the contrary, the fact of detecting the DNAs of cytomegalovirus, Epstein-Barr virus, human herpes virus type 6 (HHV-6 A/B type), fungi of the genus Candida, and HIV RNA was insufficient to confirm the etiological role of these pathogens in brain lesions. A wide CSF concentration range of these pathogens was established.in HIV-infected patients.
Conclusion. The absence of neuroinfection pathogen DNA and HIV RNA in the CSF excludes the corresponding etiology of brain damage. Detection of CSF T. gondii, M. tuberculosis, C. neoformans, or JCPyV DNAs confirms the nature of encephalitis. Quantitative determination should be used when examining CSF for EBV, CMV, HHV-6A/B, and Candida fungi DNAs and HIV RNA,
Literature
1. Покровский В.В., ред. ВИЧ-инфекция и СПИД: национальное руководство. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2021. 512 с. Pokrovsky V.V., ed. [HIV infection and AIDS: national guidelines]. 2nd ed., reprint. and add. Moscow: GEOTAR-Media, 2021. 512 p. (In Russ.). 2. Ладная Н.Н., Покровский В.В., Соколова Е.В., Чекрыжова Л.Г., Киржанова В.В. Распространение инфекции, вызываемой вирусом иммунодефицита человека, на территориях Российской Федерации в 2021 г. Эпидемиол. инфекц. болезни. Актуал. вопр. 2022; 12(3): 12–8. DOI: https://dx.doi.org/10.18565/epidem.2022.12.3.12-8 Ladnaia N.N., Pokrovsky V.V., Sokolova E.V., Chekryzhova D.G., Kirzhanova V.V. [Prevalence of human immune deficiency virus infection in the territories of the Russian Federation in 2021]. Epidemiology and infectious diseases. Current items 2022; 12(3): 12–8 (In Russ.). DOI: https://dx.doi.org/10.18565/epidem.2022.12.3.12-8 3. Перегудова А.Б., Ермак Т.Н., Шахгильдян В.И., Шипулина О.Ю., Гончаров Д.Б. Церебральный токсоплазмоз в структуре поражения центральной нервной системы у больных ВИЧ-инфекцией. Эпидемиол. инфекц. болезни. Актуал. вопр. 2013; (1): 26–30. Peregudova A.B., Ermak T.N., Shakhgildyan V.I., Shipulina О.Y., Goncharov D.B. [Cerebral toxoplasmosis in the structure of central nervous system lesions in patients with HIV infection]. Epidemiоlоgy and infectious diseases. Сurrent items 2013; (1): 26–30. (In Russ.). 4. Langford T.D., Letendre S.L., Larrea G.J., Masliah E. Changing patterns in the neuropathogenesis of HIV during the HAART era. Brain Pathology. 2003; 13(2): 195–210. DOI: 10.1111/j.1750-3639.20,03.tb00019. 5. Jellinger K., Setinek U., Drlicek M., Böhm G., Steurer A., Lintner F. et al. Neuropathology and general autopsy findings in AIDS during the last 15 years. Acta Neuropathol. 2000; 100: 213–20. https://doi.org/10.1007/s004010000245 6. Беляков Н.А., Рассохин В.В. Коморбидные состояния при ВИЧ-инфекции. Часть 1. Основы проблемы. СПб.: Балтийский медицинский образовательный центр, 2018. 184 с. Belyakov N.A., Rassokhin V.V. [Comorbid conditions in HIV infection. Part 1. The basics of the problem]. St. Petersburg: Baltic Medical Educational Center, 2018. 184 p. (In Russ.). 7. Макаров А.Ю., Чикова Р.С., Улюкин И.М., Помников В.Г. Неврологические синдромы при ВИЧ-инфекции. Неврологический журнал 2004; (5): 45–52. Makarov A.Yu., Chikova R.S., Ulyukin I.M., Pomnikov V.G. [Neurological syndromes in HIV infection]. Neurological Journal 2004; (5): 45–52. (In Russ.). 8. Tauber S.C., Staszewski O,. Prinz M., Wies J., Nolte K., Bunkowski А. et al.. HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair. HIV Med. 2016; 17(2): 143–51. doi:10.1111/hiv.12288 9. Masliah E., DeTeresa R.M., Mallory M.E., Hansen L.A. Changes in pathological findings at autopsy in AIDS cases for the last 15 years. AIDS 2000; 14: 69– 74. 10. Вознесенский С.Л., Шахгильдян В.И., Петрова Е.В., Кожевникова Г.М., Ермак Т.Н., Тишкевич О.А. и др. Энцефалиты неясной этиологии у больных ВИЧ-инфекцией: клиническая и патологоанатомическая расшифровка. Терапевтический архив 2021; 93(11): 1278–82. https://doi.org/10.2644/00403660.2021.11.201197 Voznesenskiy S.L., Shakhgildyan V.I., Petrova E.V., Kozhevnikova G.M., Ermak T.N., Tishkevich O.A. et al. [Unspecified Encephalitis in HIV-Infected Patients: Clinical and Post Mortem Evaluation]. Therapeutic archive 2021; 93(11): 1278–82. (In Russ.). https://doi.org/10.2644/00403660.2021.11. 201197 11. Кравченко А.В., Ладная Н.Н., Козырина Н.В., Покровский В.В., Юрин О.Г., Соколова Е.В., Дементьева Л.А. Причины летальных исходов среди лиц, инфицированных ВИЧ, в Российской Федерации в 2008–2018 гг. Эпидемиол. инфекц. болезни. Актуал. вопр. 2020; 10(3): 63–9. DOI: https://dx.doi.org/10.18565/epidem.2020.10.3.63-9 Kravchenko A.V., Ladnaia N.N., Kozyrina N.V., Pokrovsky V.V., Yurin O.G., Sokolova E.V. et al. [Causes of deaths among people infected with HIV in the Russian Federation in 2008–2018]. Epidemiоlоgy and infectious diseases. Сurrent items 2020; 10(3): 63–9. (In Russ.). DOI: https://dx.doi.org/10.18565/epidem.2020.10.3.63-9 12. Шахгильдян В.И., Соколова Е.А., Юрин О.Г., Ладная Н.Н., Канестри В.Г. Определение случая СПИДа и причины летальных исходов у больных ВИЧ-инфекцией. Эпидемиол. инфекц. болезни. Актуал. вопр. 2020; 10(3): 70–8. DOI: https://dx.doi.org/10.18565/epidem.2020.10.3.70-8 Shakhgildyan V.I., Sokolova E.A., Yurin O.G., Ladnaia N.N., Kanestri V.G. [Case definition of AIDS and causes of death in patients with HIV infection]. Epidemiоlоgy and infectious diseases. Сurrent items 2020; 10(3): 70–8. (In Russ.). DOI: https://dx.doi.org/10.18565/epidem.2020.10.3.70-8 13. Акимкин В.Г., Творогова М.Г. (ред.). Лабораторная диагностика инфекционных болезней. М., 2020. 480 с. Akimkin V.G., Tvorogova M.G. (eds.). [Laboratory diagnosis of infections diseases]. Moscow, 2020. 480 p. (In Russ.). 14. Шахгильдян В.И., Ядрихинская М.С., Орловский А.А., Шипулина О.Ю., Домонова Э.А., Тишкевич О.А. и др. Концентрация ДНК ЦМВ в биологических материалах – ключ к диагностике цитомегаловирусной пневмонии у больных ВИЧ-инфекцией. Журнал инфектологии 2019; 11(3, приложение 1): 109–17. https://doi.org/10.22625/2072-6732-2019-11-3S1 Shakhgildyan V.I., Yandrikhinskaya M.S., Orlovsky А.А., Shipulina О.Y., Domonova E.A., Tishkevich О.А. et al. [Quantity of CMV DNA in biological samples – a key to CMV pneumonia diagnosis in HIV patients]. Journal Infectology 2019; 11(3, Suppl. 1): 109–17. (In Russ.). https://doi.org/ 10.22625/2072-6732-2019-11-3S1
About the Autors
Vasily I. Shakhgildyan, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; vishakh@yandex.ru; http://orcid.org/0000-0002-8686-0487.
Marina S. Yadrikhinskaya, Resident, Moscow City Center for AIDS Prevention and Control, Moscow City Healthcare Department, Moscow, Russia; rusalo4ka_88@mail.ru; http://orcid.org/0000-0002-9649-8522.
Elvira A. Domonova, Cand. Biol. Sci. Head, Scientific Group for Development of New Methods for Diagnosing Opportunistic and Papillomavirus Infections, Department for Molecular Diagnosis and Epidemiology, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; elvira.domonova@pcr.ms; http://orcid.org/0000-0001-8262-3938.
Aleksey A. Orlovsky, Laboratory Researcher, Laboratory for Monitoring Programs for Reduction of Mortality from Cardiovascular Diseases, National Medical Research Center of Cardiology, Ministry of Health of Russia, Moscow, Russia; leha-orl@yandex.by; http://orcid.org/0000-0002-0794-4683.
Oleg A. Tishkevich, Pathologist, Clinical Infectious Diseases Hospital Two, Moscow City Healthcare Department, Moscow, Russia; tishol@mail.ru; https://orcid.org/0000-0002-0789-7709.
Elena B. Yarovaya, Phys. Math. D., Professor, Department of Probability Theory, Faculty of Mechanics and Mathematics, M.V. Lomonosov Moscow State University, Moscow, Russia; yarovaya@mech.math.msu.su; http://orcid.org/0000-0002-6615-43157129
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