Quantitative determination of Epstein–Barr virus DNA in biological materials and EBV-related lung damage in HIV-infected patients


DOI: https://dx.doi.org/10.18565/epidem.2024.14.4.33-40

Shakhgildyan V.I., Yadrikhinskaya M.S., Domonova E.A., Orlovsky A.A., Kanestri V.G., 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) Lomonosov Moscow State University, Moscow, Russia
Objective. Evaluation of the frequency of detection of Epstein–Barr virus (EBV) DNA and its quantitative assessment in biological material samples using real-time PCR; description of the clinical and radiological picture of pulmonary pathology with high concentrations of EBV DNA in respiratory substrates and establishment of the relationship between the concentration of EBV DNA in biological materials and EBV-related lung damage in HIV-infected patients.
Materials and methods. The article presents the results of clinical follow-up and analysis of case histories of 5485 hospitalized HIV-infected patients, 1954 of whom had lung damage. Samples of whole blood (510), sputum (35), bronchoalveolar lavage fluid (BALF) (1026), pleural fluid (PF) (38), bronchial biopsy (BB) (133), lymph nodes (LN) (57) were examined by the RT-PCR method with the determination of EBV DNA, M. tuberculosis, Pn. jirovecii, Candida fungi, cytomegalovirus (CMV), human herpes virus 6a/b in qualitative and quantitative formats. The search for associations between the number of EBV DNA copies in biomaterials and EBV-related organ damage (in particular, lungs) was performed using ROC analysis.
Results. The frequency of EBV DNA detection in biomaterials exceeded 55%, the sensitivity was 84.6–100% with a specificity of 5.3–35.4%. Diagnostically significant concentrations of EBV DNA in blood leukocytes, EBV DNA concentrations in BALF, BB, PZ, LN samples with 95% and 99% probability confirming the EBV nature of pulmonary pathology, as well as low quantitative values of EBV DNA in biosamples with 95–99% probability excluding the EBV etiology of lung damage in patients with HIV infection were determined. EBV-related organ damage was detected in 379 patients. Clinical manifestations and radiographic data of 172 patients with EBV-related pulmonary pathology are described.
Conclusion. Quantitative determination of EBV DNA in biomaterials is of crucial importance for confirming the EBV nature of lung damage. Along with the «classical» pathogens of secondary diseases in HIV-infected patients, EBV can be the cause of severe organ pathology.

Literature


1. Кравченко А.В., Ладная Н.Н., Покровский В.В., Козырина Н.В., Юрин О.Г., Соколова Е.В. и др. Причины летальных исходов у лиц, инфицированных вирусом иммунодефицита человека. Эпидемиол. и инфекц. болезни. Актуал. вопр. 2023; 13(3): 56–63. DOI: 10.18565/epidem.2023.13.3.56-63


Kravchenko A.V., Ladnaia N.N., Pokrovsky V.V., Kozyrina N.V., Yurin O.G., Sokolova E.V. et al. [Causes of death in people infected with the human immunodeficiency virus]. Epidemiology and infectious diseases. Current items 2023; 13(3): 56–63. (In Russ.). DOI:10.18565/epidem.2023.13.3.56-63


2. 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): 109–17. DOI:10.22625/2072-6732-2019-11-3-109-117


Shakhgildyan V.I., Yandrinskaya 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 in HIV patients diagnosis]. Journal of Infectology 2019; 11(3): 109–17. (In Russ.). DOI: 10.22625/2072-6732-2019-11-3-109-117


3. Вознесенский С.Л., Самотолкина Е.С., Ермак Т.Н., Кожевникова Г.М., Климкова П.В., Корнева И.А. Опыт работы отделения интенсивной терапии для больных ВИЧ-инфекцией. Эпидемиол. и инфекц. болезни. Актуал. вопр. 2020; 10(3): 131–6. DOI: 10.18565/epidem.2020.10.3.131-6


Voznesensky S.L., Samotolkina E.S., Ermak T.N., Kozhevnikova G.M., Klimkova P.V., Korneva I.A. [Experience in the intensive care unit for patients with HIV-infection]. Epidemiology and infectious diseases. Current items 2020; 10(3): 131–6. (In Russ.). DOI: 10.18565/epidem.2020.10.3.131-6


4. Покровский В.В., ред. Лекции по ВИЧ-инфекции. 3-е изд., перераб. и доп. М: ГЭОТАР-Медиа, 2024. 720 с. DOI: 10.33029/9704-8268-1-LBI-2024-1-720


Pokrovsky V.V., ed., [Lectures on HIV infection]. 3rd ed., revised and add. Moscow: GEOTAR-Media, 2024. 720 p. (In Russ.). DOI: 10.33029/9704-8268-1-LBI-2024-1-720


5. Руженцова Т.А., Гарбузов А.А., Каниболоцкий А.А., Борисова О.Ю., Воропаева Е.А., Шушакова Е.К. и др. Герпесвирусные инфекции в формировании острой и хронической патологии: обоснование необходимости своевременной терапии. Инфекционные болезни 2023; 21(4): 64–70. DOI: 10.20953/1729-9225-2023-4-64-70


Ruzhentsova T.A., Garbuzov A.A., Kanibolotskiy A.A., Borisova O.Yu., Voropaeva E.A., Shushakova E.K. et al. [Herpesvirus infection in the formation of acute and chronic pathology: rationale for timely therapy]. Infectious Diseases 2023; 21(4): 64–70. (In Russ). DOI: 10.20953/1729-9225-2023-4-64-70


6. Ющук Н.Д., Венгеров Ю.Я., ред. Лекции по инфекционным болезням: руководство для врачей. В 2 т. 5-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2022. Т.2. 544 с.


Yushchuk N.D., Vengerov Yu.Ya., eds.. [Lectures on infectious diseases: a guide for doctors]. In 2 volumes. 5th ed., reprint. and add. Moscow: GEOTAR-Media, 2022. Vol.2. 544 p. (In Russ.).


7. Hoffmann Ch., Rockstroh J.K. (eds,). [HIV 2015/2016]. Hamburg: Medizin Fokus Velag, 2015. 756 p.


8. Шахгильдян В.И., Ядрихинская М.С, Орловский А.А., Яровая Е.Б. Клиническая, вирусологическая, иммунологическая характеристика госпитализированных больных ВИЧ-инфекцией. Тер. арх. 2018; 90(11): 18–23. DOI: 10.26442/terarkh2018901118-23


Shakhgildyan V.I., Yadrikhinskaya M.S., Orlovsky A.A., Yarovaya E.B. [Clinical, virological, immunological characteristics of hospitalized patients with HIV infection]. Therapeutic Archive 2018; 90(11): 18–23. (In Russ.). DOI: 10.26442/terarkh2018901118-23


9. Бартлетт Дж., Галлант Дж., Фам П. Клинические аспекты ВИЧ-инфекции. 2009–2010. М.: Р. Валент, 2010. 496 с.


Bartlett J., Gallant J., Pham P. [Clinical aspects of HIV infection. 2009–2010. Moscow: R. Valent, 2010. 496 p. (In Russ.).


10. Ющук Н.Д., ред. Вирусные болезни: учебное пособие. М.: ГЭОТАР-Медиа, 2016. 640 с.


Yushchuk N.D., ed. [Viral diseases: a ducational grant]. Moscow: GEOTAR-Media, 2016. 640 p. (In Russ.).


About the Autors


Vasily I. Shakhgildyan, MD, Senior Researcher, Department of Epidemiology and Prevention of AIDS, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance of Consumer Rights Protection and Human Well-Being, Moscow, Russia; vishakh@yandex.ru; http://orcid.org/0000-0002-8686-0487.
Marina S. Yadrikhinskaya, Resident Physician, Moscow City Center for AIDS Prevention and Treatment, Moscow, Russia; rusalo4ka_88@mail.ru; http://orcid.org/0000-0002-9649-8522.
Elvira A. Domonova, PhD, Head, Opportunistic and Papillomavirus Infections Research Group, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, Russia; elvira.domonova@pcr.ms; http://orcid.org/0000-0001-8262-3938.
Aleksey A. Orlovsky, Laboratory Researcher, Cardiovascular Disease Mortality Reduction Laboratory, National Medical Research Center of Cardiology, Ministry of Health of Russia, Moscow, Russia; leha-orl@yandex.by; http://orcid.org/0000-0002-0794-4683.
Veronika G. Kanestri, MD, Senior Researcher, Department of Epidemiology and Prevention of AIDS, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance of Consumer Rights Protection and Human Well-Being, Moscow, Russia; kanestri@yandex.ru; http://orcid.org/0000-0002-2234-7094
Elena B. Yarovaya, Ph.D. Phys.-Math., professor, Probability Theory Department, Faculty of Mechanics and Mathematics of Lomonosov Moscow State University, Moscow, Russia; yarovaya@mech.math.msu.su; http://orcid.org/0000-0002-6615-43157129


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