The relationship between the clinical course of tropical malaria and the structural features of the Plasmodium falciparum genome


DOI: https://dx.doi.org/10.18565/epidem.2020.10.1.67-74

Solovyev A.I., Uskov A.N., Gudkov R.V., Dementyeva N.V., Kapatsina V.A., Komarov A.G., Krutikova A.A., Kovalenko A.N., Laskin A.V., Rakin A.I.

1) S.M.Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; 2) Pediatric Research and Clinical Center for Infectious Diseases, Federal Biomedical Agency, Saint Petersburg, Russia; 3) Laboratory of Molecular Genetics, All-Russian Research Institute for Farm Animal Genetics and Breeding (Branch, L.K. Ernst Federal Research Center for Animal Husbandry), Saint Petersburg, Russia; 4) S.P. Botkin Clinical Infectious Diseases Hospital, Saint Petersburg, Russia
Objective. To study the genotypic characteristics of Plasmodium falciparum that causes tropical malaria complicated by hemolytic anemia.
Materials and methods. Two tropical malaria cases identified in Saint Petersburg hospitals in 2018 served as a material for clinical observations. In one case, the disease was severe and accompanied by the development of severe anemia; in the other case, it was uncomplicated. A polymerase chain reaction (PCR) assay was used for the investigation. The investigators used primers for the marker nucleotide sequences of the major virulence factor in P. falciparum (Plasmodium falciparum erythrocyte membrane protein 1 (PFEMP1)), encoding the structure of DBL1α, DBLß, CIDR1α domains.
Results. It was shown that in severe tropical malaria accompanied by the development of hemolytic anemia, the genetic markers of PFEMP1, which corresponded to the DBL1α and DBLß domains, were identified in the patient’s blood. In uncomplicated tropical malaria, these genetic markers were absent. It was suggested that there might be a relationship between the features of the P. falciparum genome and the clinical course of tropical malaria. The specific nucleotide sequences of the P. falciparum genome encoding the DBL1α and DBLß domains of PFEMP1 are early predictors for the severe course of the disease.
Conclusion. Detection of appropriate genetic markers in the blood of patients can be used in clinical practice to predict the development of tropical malaria.

Literature



  1. Баранова А.М. Малярия: диагностика, лечение и профилактика. Инфекционные болезни: Новости. Мнения. Обучение 2014; (1): 39–44.

    Baranova A.M. [Malaria: diagnosis, treatment and prophylaxis]. Infektsionnye bolezni: Novosti. Mneniya. Obucheniye 2014; (1): 39–44. (In Russ.).



  2. Бронштейн А.М., Малышев Н.А., Лобзин Ю.В. От колониальной и военной медицины к медицине тропической: дорога временных поражений и знаменитых побед. Эпидемиол. и инфекц. бол. 2015; (2): 43–8.

    Bronshteyn A.M., Malyshev N.A., Lobzin Yu.V. [From colonial and military medicine to tropical medicine: road of temporary defeats and famous victories]. Epidemiologiya i infektsionnye bolezni 2015; (2): 43–8. (In Russ.).



  3. Кондрашин А.В., Баранова А.М., Морозова Л.Ф., Степанова Е.Н. Тенденции в борьбе с малярией в мире. Мед. паразитол. и паразит. болезни 2011; (4): 3–7.

    Kondrashin A.V., Baranova A.M., Morozova L.F., Stepanova E.N. [Trends in malaria control in the world]. Meditsinskaya parazitologiya i parazitarnyye bolezni 2011; (4): 3–7. (In Russ.).



  4. World Health Organization. World malaria report 2018. https://www. who.int/malaria/publications/world-malaria-report-2018/report/en/

  5. Новак К.Е., Эсауленко Е.В., Дьячков А.Г. Эпидемиологические и клинико-лабораторные особенности течения завозных случаев малярии на территории Северо-Западного Федерального округа. Журнал инфектологии 2017; 9(1): 91–9. https://doi.org/10.22625/2072-6732-2017-9-1-91-99

    Novak K.E., Esaulenko E.V., Dyachkov A.G. [Epidemiological, clinical and laboratory features of imported malaria in the North-West federal district]. Zhurnal infektologii 2017; 9(1): 91–9. (In Russ.). https://doi.org/10.22625/ 2072-6732-2017-9-1-91-99



  6. Новак К.Е., Эсауленко Е.В., Лисица И.А. Завозной случай тропической малярии с летальным исходом в Санкт-Петербурге. Журнал инфектологии 2017; 9 (4): 139–43. https://doi.org/10.22625/2072-6732-2017-9-4-139-143

    Novak K.E., Esaulenko E.V., Lisitsa I.A. [Imported case of tropical malaria with a lethal outcome in Saint-Petersburg]. Zhurnal infektologii 2017; 9 (4): 139–43. (In Russ.). https://doi.org/10.22625/2072-6732-2017-9-4-139-143



  7. Angeletti D., Sandalova T., Wahlgren M., Achour A. Binding of Subdomains ½ of PfEMP1-DBL1α to Heparan Sulfateor Heparin Mediates Plasmodium falciparum Rosetting. PLoS ONE 2015; 10(3): e0118898. DOI: 10.1371/journal.

  8. Усков А.Н., Соловьев А.И., Кравцов В.Ю., Гудков Р.В., Коломоец Е.В., Левковский А.Е. Молекулярно-генетические механизмы вирулентности Plasmodium falciparum и патогенеза тропической малярии. Журнал инфектологии 2018; 10(3): 23–30. https://doi.org/10.22625/2072-6732-2018-10-3-23-29

    Uskov A.N., Solovev A.I., Kravtsov V.Y., Gudkov R.V., Kolomoyets E.V., Levkovskiy A.E. [Molecular-genetic mechanisms of Plasmodium falciparum virulence and tropical malaria pathogenesis]. Zhurnal infektologii 2018; 10(3): 23–30. (In Russ.). https://doi.org/10.22625/2072-6732-2018-10-3-23-29



  9. Лысенко А.Я., Кондрашин А.В., Ежов М.Н. Маляриология. 2-е изд. Копенгаген: Всемирная организация здравоохранения. Европейское региональное бюро, 2003. 510 с.

    Lysenko А.Ya., Kondrashin A.V., Ezhov M.N. [Malariology]. 2nd ed. Copenhagen: World Health Organization. Regional Office for Europe, 2003. 510 p. (In Russ.).



  10. Попович О.О., Мороз Л.В., Чабанов Ф.А., Вжецон Т.В., Слепова И.Г. Клинический случай тяжелого течения микст-малярии (Рl. falciparum, Рl. malariae) у пациента украинского происхождения. Актуальная инфектология 2017; 5(4): 189–94. DOI:10.22141/2312-413x.5.4.2017. 115733

    Popovych О.О., Moroz L.V., Chabanov F.A., Vzhetson T.V., Slepova I.G. [Clinical case of severe mixed species (Pl.falciparum, Pl. malariae) malaria in a patient of Ukrainian descent]. Aktualnaya infektologiya 2017; 5(4): 189–94. (In Russ.). DOI:10.22141/2312-413x.5.4.2017.115733



  11. Chen D.S., Barry A.E., Leliwa-Sytek A., Smith T.A., Peterson I., Brown S.M., Migot-Nabias F., Deloron P., Kortok M.M., Marsh K., Daily J.P., Ndiaye D., Sarr O., Mboup S., Day K.P. A Molecular Epidemiological Study of var Gene Diversity to Characterize the Reservoir of Plasmodium falciparum in Humans in Africa. PLoS One 2011; 6(2): e16629. DOI: 10.1371/journal.pone.0016629.

  12. Claessens A., Hamilton W.L., Kekre M., Otto T.D., Faizullabhoy A., Rayner J.C., Kwiatkowski D. Generation of Antigenic Diversity in Plasmodium falciparum by Structured Rearrangement of Var Genes During Mitosis. PLoS Genet 2014; 10(12): 6 e1004812. DOI:10.1371/journal.pgen.1004812

  13. Lalchhandama K. Plasmodium falciparum erythrocyte membrane protein 1. Wiki Journal of Medicine 2017; 4 (1): 4. DOI:10.15347/wjm/2017.004

  14. Fried M., Duffy P. Designing a VAR2CSA-based vaccine to prevent placental malaria. Vaccine 2015; 33(52): 7483–8. DOI:10.1016/j.vaccine. 2015.10.011.

  15. Gilbert D.N., Eliopoulos G.M., Chambers H.F., Saag M.S., Pavia A.T. (eds.). The Sanford Guide to Antimicrobial Therapy 2018. 48th ed. Perryville: Antimicrobial Therapy, 2018. 262 p.

  16. Clinton K.Y., Turner L., Jespersen J., Lowe E., Petersen B., Wang C., Petersen J., Lusingu J., Theander T., Lavstsen T., Higgins M. Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria. Cell Host. Microbe 2015; 17(1): 118–29. DOI: 10.1016/j.chom.2014.11.007

  17. World Health Organization. Guidelines for the treatment of malaria, 2015. https://www.who.int/malaria/publications/atoz/9789241549127/en/

  18. Kirchner S., Power B., Waters A. Recent advances in malaria genomics and epigenomics. Genome Med. 2016; 8(1): 92. DOI:10.1186/s13073-016-0343-7

  19. Лобан К.М., Полозок Е.С. Малярия. М.: Медицина, 1983. 224 с.

    Loban K.M., Polozok E.S. [Malaria]. Moscow: Meditsina, 1983. 224 p. (In Russ.).



  20. Коровина Н.А., Горяйнова А.Н., Ваджих А. Ф.А. Поражение почек у детей с тропической малярией. Детские инфекции 2010; 9(2): 28–31.

    Korovina N.A., Goryajnova A.N., Vadzhih A.F.A. [Kidney Lesions in Children with Tropical Malaria]. Detskiye infektsii 2010; 9(2): 28-31. (In Russ.).



  21. Nguansangiam S., Day N., Hien T.T., Mai N., Chaisri U., Riganti M., Dondorp A., Lee S., Phu N., Turner G., White N., Ferguson D., Pongponratn E. A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria. Trop. Med. Int. Heal. 2007; 12(9): 1037–50. DOI: full/10.1111/j.1365-3156.2007.01881.x

  22. Кондрашин А.В., Сабгайда Т.П., Сергиев В.П. Модуляция вирулентности Plasmodium falciparum как фактор саморегуляции паразитарной системы малярии. Медицинская паразитология и паразитарные болезни 2000; (2): 47–53.

    Kondrashin A.V., Sabgaĭda T.P., Sergiev V.P. [The modulation of Plasmodium falciparum virulence as a factor in the self-regulation of the malarial parasitic system]. Meditsinskaya parazitologiya i parazitarnyye bolezni 2000; (2): 47–53. (In Russ.).



  23. Беляков В.Д. Общие закономерности функционирования паразитарных систем (механизмы саморегуляции). Паразитология 1986; 20(4): 249-255.

    Beliakov V.D. [General regularities of functioning of parasitic systems (mechanisms of selfregulation)]. Parazitologiya 1986; 20 (4): 249–55. (In Russ.).




About the Autors


Alexey I. Solovyev, MD, Professor, Department of Biology, S.M. Kirov Military Medical  Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; e-mail: solopiter@gmail.com; ORCID: https://orcid.org/0000-0002-3731-1756
Prof. Aleksandr N. Uskov, MD, Deputy Director for Research, (Development and Coordination of National and International Projects), Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russia; e-mail: aouskov@gmail.com; ORCID: https://orcid.org/ 0000-0003-3185-516X
Roman V. Gudkov, Cand. Med. Sci., Lecturer, Department of Infectious Diseases (with Course of Medical Parasitology and Tropical Diseases), S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; e-mail: gudkoff@mail.ru; ORCID: https://orcid.org/0000-0001-5498-0479
Natalia V. Dementeva, Cand. Biol. Sci., Researcher, Laboratory of Molecular Genetics, All-Russian Research Institute of Farm Animal Genetics and Breeding (Branch, L.K. Ernst Federal Science Center for Animal Husbandry), Saint Petersburg, Russia; e-mail: dementevan@mail.ru
Vladimir A. Kapatsina, Head, Department, S.P. Botkin Clinical Infectious Diseases Hospital, Saint Petersburg, Russia; e-mail: ingashi@mail.ru; ORCID: https://orcid.org/0000-0002-8959-0873
Artem G. Komarov, Senior Laboratory Assistant, Department of Biology, S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; e-mail: qwer.xo@mail.ru
Anna A. Krutikova, Cand. Biol. Sci., Researcher, Laboratory of Molecular Genetics, All-Russian Research Institute of Farm Animal Genetics and Breeding (Branch, L.K. Ernst Federal Science Center for Animal Husbandry), Saint Petersburg, Russia; e-mail: anntim2575@mail.ru
Aleksandr N. Kovalenko, MD, Рrofessor, Department of Infectious Diseases (with Course of Medical Parasitology and Tropical Diseases), S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; e-mail: 9268754@mail.ru; ORCID: https://orcid.org/0000-0002-2976-8051
Aleksandr V. Laskin, Cand. Med. Sci., Lecturer, Department of Infectious Diseases (with Course of Medical Parasitology and Tropical Diseases), S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; e-mail: lar_vma@mail.ru
Aleksandr I. Rakin, Lecturer, Department of Biology, S.M. Kirov Military Medical  Academy, Ministry of Defense of the Russian Federation, Saint Petersburg, Russia; e-mail: rakinalex@gmail.com; ORCID: https://orcid.org/0000-0001-9085-1287


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