Адъювантный и другие эффекты вакцины БЦЖ и ее влияние на эпидемиологию новой коронавирусной болезни COVID-19

Автор: Ивашкевич Я.В., Козачевская Л.Ю., Петяева А.В., Чурилов Л.П.

Статья в выпуске: 4 т.6, 2020 года.

Бесплатный доступ

Живая вакцина БЦЖ, вызывая комплексный ответ как врожденного, так и клеточного/гуморального адаптивного иммунитета, служит биологическим адъювантом. Она выступает триггером «тренированной» реакции иммунной системы, характеризующейся активацией моноцитов, макрофагов, естественных киллеров, а также лимфоидных клеток врожденных популяций. Это способствует скорейшей активации неантигенспецифических защитных программ организма в борьбе с рядом вирусных, грибковых, протозойных инфекций и неоплазией. Одной из таких инфекций может быть COVID-19. Патогенез развития острой интерстициальной пневмонии/респираторного дистресс-синдрома, вызванных COVID-19, характеризуется запуском избыточного системного действия медиаторов воспаления, в частности - цитокинов, при нарушении его фокальных барьеров. Гамма-интерферон, вырабатываемый лимфоцитами после вакцинации БЦЖ, модулирует активность ряда интерлейкинов, что, в свою очередь, может способствовать менее тяжелому течению COVID-19 за счет снижения активности ИЛ-12 и ИЛ-18-зависимых реакций. Между возбудителями микобактериозов и COVID-19 существует антигенный перекрест из-за гомологии белков. В отличие от многих адъювантов, неоднозначно влияние БЦЖ на разные аутоиммунные заболевания (провокация одних и протективное действие при других), как и на риск возникновения лимфом (БЦЖ его снижает, тогда как многие адъюванты повышают). Это, видимо, связано с назначением БЦЖ в очень ранний период, при незрелой иммунной системе и отражает симбионтный характер взаимодействия штамма БЦЖ и организма хозяина. Приведены по странам данные о связи исторической практики применения вакцинации БЦЖ и текущей заболеваемости новой коронавирусной инфекцией и смертности от нее. Рассмотрены в историческом ключе медико-социальные причины разной национальной политики органов здравоохранения в отношении применения вакцины БЦЖ.

Еще

Адъювант, аутоиммунитет, вакцинация бцж, острый респираторный дистресс-синдром, перекрестная антигенная специфичность, тренированный иммунитет, коронавирус, коронавирусная болезнь, цитокины

Короткий адрес: https://sciup.org/14117988

IDR: 14117988

Список литературы Адъювантный и другие эффекты вакцины БЦЖ и ее влияние на эпидемиологию новой коронавирусной болезни COVID-19

Авцын А.П. Адаптация и дизадаптация с позиции патолога // Клин. мед. 1974. № 5. С. 3-15.
Avtsyn AP. Adaptation and desadaptation from the viewpoint of pathologist. Klin. med. 1974;5:3-15. (in Russ).
Поземковска М., Чурилов Л.П. Илья Ильич Мечников и всемирное значение его наследия // Клин. патофизиол. 2016. Т. 22. № 3. С. 3-28.
Pozemkovska M, Churilov LP. Elie Metchnikoff and the global importance of his legacy. Clin. Pathophysiol. 2016;22(3):3-28. (in Russ).
Рябкова В.А., Чурилов Л.П., Шенфельд И. Гиперстимуляция иммунной системы как причина аутоиммунных заболеваний // Вестник РАМН. 2020. Т. 75. № 3. С. 204-213.
Ryabkova VA, Churilov LP. Shoenfeld Y. Hyperstimulation of the immune system as a cause of autoimmune diseases. Annals of the Russian Academy of Medical Sciences. 2020;75(3):204-213. (in Russ). DOI: 10.15690/vramn1276
Чурилов Л.П. Общая патофизиология с основами иммунопатологии. Изд-е 5-е, дополн., СПб.: ЭЛБИ-Спб, 2015.
Churilov LP. General Pathophysiology with the Fundamentals of Immunopathology. 5th ed., amended. ELBI-SPb Publisher: Saint Petersburg, 2015. (in Russ).
Abate G, Hamzabegovic F, Eickhoff CS, et al. BCG Vaccination Induces M. avium and M. abscessus Cross-Protective Immunity. Front Immunol. 2019;10:234. DOI: 10.3389/fimmu.2019.00234
Abbas AM, AbouBakr A, Bahaa N, et al. The effect of BCG vaccine in the era of COVID-19 pandemic. Scand J Immunol. 2020;e12947.
DOI: 10.1111/sji.12947
Ambrosch F, Krepler P, Wiedermann G. Zur Frage des Einflusses der BCG-Neugeborenen-Impfung auf die Leukämie-Häufigkeit. MMW Munch Med Wochenschr. 1978;120(8):243-246.
Angelidou A, Diray-Arce J, Conti MG, et al. BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny. Front Microbiol. 2020;11:332.
DOI: 10.3389/fmicb.2020.00332
Arts RJW, Moorlag SJCFM, Novakovic B, et al. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe. 2018;23(1):89-100.e5.
DOI: 10.1016/j.chom.2017.12.010
Asher R. The seven sins of medicine. Lancet. 1949;2(6574):358-360.
DOI: 10.1016/s0140-6736(49)90090-2
Ayoub BM. COVID-19 vaccination clinical trials should consider multiple doses of BCG. Pharmazie. 2020;75(4):159.
DOI: 10.1691/ph.2020.0444
Aziz AB, Dembinski JL, Jahan Y. Debate on Bacille Calmette-Guérin vaccination against COVID-19: Is it worth performing clinical trials? Biosaf Health. 2020;.
DOI: 10.1016/j.bsheal.2020.07.001
Bai JN, Bian YQ, Zhao BH. Construction of recombinant BCG bearing S1 glycoprotein of nephropathogenic IBV and study on its immunogenicity on chickens. Wei Sheng wu xue bao = Acta Microbiologica Sinica. 2007;47(2):324-328.
Barneoud P, Rivet JM, Vitiello S, et al. Brain norepinephrine levels after BCG stimulation of the immune system. Immunol Lett. 1988;18(3):201-4. 10.1016/0165-2478(88)90019-3. Erratum in: Immunol Lett 1988;19(4):351.
DOI: 10.1016/0165-2478(88)90019-3.Erratumin
Berg MR, Yu QG, Salvador CE, et al. Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19. Sci. Adv. 2020;6:eabc1463.
DOI: 10.1126/sciadv.abc1463
Berendsen ML, van Gijzel SW, Smits J, et al. BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa. BMJ Glob. Health. 2019;4:e001862.
Calmette A, Guerin C, Weill-Halle B, et al. Essai d'immunisation contre l'infection tuberculeuse. Bull Acad Med. (Paris);1924;91:787-796.
Caminati M, Furci F, Senna G, et al. BCG vaccination and COVID-19: Much ado about nothing? Med Hypotheses. 2020;144:110109.
DOI: 10.1016/j.mehy.2020.110109
Carroll MV, Lack N, Sim E, et al. Multiple routes of complement activation by Mycobacterium bovis BCG. Mol Immunol. 2009;46(16):3367-3378.
DOI: 10.1016/j.molimm.2009.07.015
Charoenlap S, Piromsopa K, Charoenlap C. Potential role of Bacillus Calmette-Guérin (BCG) vaccination in COVID-19 pandemic mortality: Epidemiological and Immunological aspects. Asian Pac J Allergy Immunol. 2020;.
DOI: 10.12932/AP-310520-0863
Checcucci E, Piramide F, Pecoraro A, et al. The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans. Panminerva Med. 2020;.
DOI: 10.23736/S0031-0808.20.03958-0
Ciliberto G, Mancini R, Paggi MG. Drug repurposing against COVID-19: focus on anticancer agents. J Exp Clin Cancer Res. 2020;39(1):86.
DOI: 10.1186/s13046-020-01590-2
Chopra KK, Arora VK, Singh S. COVID 19 and tuberculosis. Indian J Tuberc. 2020;67(2):149-151.
DOI: 10.1016/j.ijtb.2020.06.001
Covián C, Retamal-Díaz A, Bueno SM, et al. Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2? Front Immunol. 2020;11:970.
DOI: 10.3389/fimmu.2020.00970
Curtis N, Sparrow A, Ghebreyesus TA, et al. Considering BCG vaccination to reduce the impact of COVID-19. Lancet. 2020;395(10236):1545-1546.
DOI: 10.1016/S0140-6736(20)31025-4
Das G, Mukherjee N, Ghosh S. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020;11(9):1206-1209.
DOI: 10.1021/acschemneuro.0c00201
David P, Shoenfeld Y. Bacillus Calmette-Guerin (BCG) as a Protective Factor for COVID-19? Isr Med Assoc J. 2020;8(22):448-449.
Desouky E. BCG versus COVID-19: impact on urology. World J Urol. 2020;1-5.
DOI: 10.1007/s00345-020-03251-7
Ehrenfeld M, Tincani A, Andreoli L, et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597.
DOI: 10.1016/j.autrev.2020.102597
Faustman DL. Permanent reversal of diabetes in NOD mice. Science. 2007;317(5835):196.
DOI: 10.1126/science.317.5835.196a
Floc'h F, Werner GH. Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-guérin). Ann Immunol (Paris). 1976;127(2):173-186.
Freund J, McDermott K. Sensitization to horse serum by means of adjuvants. Proc Soc Exp Biol Med. 1942;49(4):548-553.
DOI: 10.3181/00379727-49-13625
Gheorghiu M. BCG-induced mucosal immune responses. Int J Immunopharmacol. 1994;16(5-6):435-444.
DOI: 10.1016/0192-0561(94)90033-7
Greenwood M. Professor Calmette's Statistical Study of BCG Vaccination. BMJ. 1928;1:793-795.
Gupta PK. New disease old vaccine: Is recombinant BCG vaccine an answer for COVID-19? Cell Immunol. 2020;356:104187.
DOI: 10.1016/j.cellimm.2020.104187
Jain VK, Iyengar K, Vaish A, et al. Differential mortality in COVID-19 patients from India and western countries. Diabetes Metab Syndr. 2020;14(5):1037-1041.
DOI: 10.1016/j.dsx.2020.06.067
Johnson S, Laloraya M. A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization. Cytokine and Growth Factor Reviews, 2020;preprint.
DOI: 10.1016/j.cytogfr.2020.06.014
Hanekom WA. The immune response to BCG vaccination of newborns. Ann N Y Acad Sci. 2005;1062:69-78.
DOI: 10.1196/annals.1358.010
Harandi AM. Systemic analysis of human vaccine adjuvants. Semin Immunol. 2018;39:30-34.
Hauer J, Fischer U, Auer F, Borkhardt A. Regional BCG vaccination policy in former East- and West Germany may impact on both severity of SARS-CoV-2 and incidence of childhood Leukemia. Leukemia. 2020;34:2217-2219.
DOI: 10.1038/s41375-020-0871-4
Hegarty PK, Sfakianos JP, Giannarini G, et al. COVID-19 and Bacillus Calmette-Guérin: What is the Link? Eur Urol Oncol. 2020;3(3):259-261.
DOI: 10.1016/j.euo.2020.04.001
Huszarik K, Wright B, Keller C, et al. Adjuvant immunotherapy increases beta cell regenerative factor Reg2 in the pancreas of diabetic mice. J Immunol. 2010;185(9):5120-5129.
DOI: 10.4049/jimmunol.1001596
Kantor IN. ¿BCG versus COVID-19? Medicina (B Aires). 2020;80(3):292-294.
Kinoshita M, Tanaka M. Impact of routine infant BCG vaccination in young generation on prevention of local COVID-19 spread in Japan. J Infect. 2020;S0163-4453(20)30547-8.
DOI: 10.1016/j.jinf.2020.08.013
Klein BY. Newborn BCG vaccination complemented by boosting correlates better with reduced juvenile diabetes in females, than vaccination alone. Vaccine. 2020;S0264-410X(20)31008-2.
DOI: 10.1016/j.vaccine.2020.07.066
Kleinnijenhuis J, Quintin J, Preijers P, et al. Netea, Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012;109:17537-17542.
Koti M, Morales A, Graham CH, et al. BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy. J Immunother Cancer. 2020;8(2):e001119.
DOI: 10.1136/jitc-2020-001119
Kowalewicz-Kulbat M, Locht C. BCG and protection against inflammatory and auto-immune diseases. Expert Rev Vaccines. 2017;16(7):1-10.
DOI: 10.1080/14760584.2017.1333906
Kumar J, Meena J. Demystifying BCG Vaccine and COVID-19 Relationship. Indian Pediatr. 2020;57(6):588-589.
DOI: 10.1007/s13312-020-1872-0
Lawton G. Trials of BCG vaccine will test for covid-19 protection. New Sci. 2020;246(3280):9.
DOI: 10.1016/S0262-4079(20)30836-8
Lee IF, van den Elzen P, Tan R, et al. NKT cells are required for complete Freund's adjuvant-mediated protection from autoimmune diabetes. J Immunol. 2011;187(6):2898-2904.
DOI: 10.4049/jimmunol.1002551
Lenfant L, Seisen T, Loriot Y, et al. Adjustments in the Use of Intravesical Instillations of Bacillus Calmette-Guérin for High-risk Non-muscle-invasive Bladder Cancer During the COVID-19 Pandemic. Eur Urol. 2020;78(1):1-3.
DOI: 10.1016/j.eururo.2020.04.039
Li X, Geng M, Peng Y, et al. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-108.
DOI: 10.1016/j.jpha.2020.03.001
Luca S, Mihaescu T. History of BCG Vaccine. Maedica (Bucharest). 2013;8(1):53-58.
Lyu J, Miao T, Dong J, et al. Reflection on lower rates of COVID-19 in children: Does childhood immunizations offer unexpected protection? Med Hypotheses. 2020;143:109842.
DOI: 10.1016/j.mehy.2020.109842
Macedo A, Febra C. Relation between BCG coverage rate and COVID-19 infection worldwide. Med Hypotheses. 2020;142:109816.
DOI: 10.1016/j.mehy.2020.109816
Marimuthu Y, Nagappa B, Sharma N, et al. COVID-19 and tuberculosis: A mathematical model based forecasting in Delhi, India. Indian J Tuberc. 2020;67(2):177-181.
DOI: 10.1016/j.ijtb.2020.05.006
Mastaglio S, Ruggeri A, Risitano AM, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020;215:108450.
DOI: 10.1016/j.clim.2020.108450
Matsumoto M, Seya T, Kikkawa S, et al. Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton. Int Immunopharmacol. 2001;1(8):1559-1569. 10.1016/s1567-5769(01)00071-6. Erratum in: Int Immunopharmacol 2002;2(5):731.
DOI: 10.1016/s1567-5769(01)00071-6.Erratumin
Miller A, Reandelar MJ, Fasciglione K, et al. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. MedRxiv. 2020;preprint.
DOI: 10.1101/2020.03.24.20042937
Miyasaka M. Is BCG vaccination causally related to reduced COVID-19 mortality? EMBO Mol Med. 2020;12(6):e12661.
DOI: 10.15252/emmm.202012661
Moorlag SJCFM, van Deuren RC, van Werkhoven CH, et al. Safety and COVID-19 Symptoms in Individuals Recently Vaccinated with BCG: a Retrospective Cohort Study. Cell Rep Med. 2020;1(5):100073.
DOI: 10.1016/j.xcrm.2020.100073
Morra ME, Kien ND, Elmaraezy A, et al. Early vaccination protects against childhood leukemia: a systematic review and meta-analysis. Sci Rep. 2017;7:15986.
Naserghandi A, Saffarpour R, Allameh SF. Exploring the causes of mild COVID-19 involvement in pediatric patients. New Microbes and New Infections. 2020;37:100741.
DOI: 10.1016/j.nmni.2020.100741
Netea MG, van Crevel R. BCG-induced protection: effects on innate immune memory. Semin Immunol. 2014;26(6):512-517.
DOI: 10.1016/j.smim.2014.09.006
Nuovo G, Tili E, Suster D, et al. Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine. Ann Diagn Pathol. 2020;48:151600.
DOI: 10.1016/j.anndiagpath.2020.151600
O'Connor E, Teh J, Kamat AM, et al. Bacillus Calmette Guérin (BCG) vaccination use in the fight against COVID-19 - what's old is new again? Future Oncol. 2020;16(19):1323-1325.
DOI: 10.2217/fon-2020-0381
O'Connor RA, Li X, Blumerman S, et al. Adjuvant immunotherapy of experimental autoimmune encephalomyelitis: immature myeloid cells expressing CXCL10 and CXCL16 attract CXCR3+CXCR6+ and myelin-specific T cells to the draining lymph nodes rather than the central nervous system. J Immunol. 2012;188(5):2093-2101.
DOI: 10.4049/jimmunol.1101118
O'Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20(6):335-337.
DOI: 10.1038/s41577-020-0337-y
Osama El-Gendy A, Saeed H, Ali AMA, et al. Bacillus Calmette-Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality. Vaccine. 2020;38(35):5564-5568.
DOI: 10.1016/j.vaccine.2020.06.083
Őzdemir C, Kucuksezer UC, Tamay ZU. Is BCG vaccination affecting the spread and severity of COVID-19? Allergy. 2020;75(7):1824-1827.
DOI: 10.1111/all.14344
Pan D, Sze S, Minhas JS, et al. The impact of ethnicity on clinical outcomes in COVID-19: A systematic review. EClinicalMedicine. 2020;23:100404.
DOI: 10.1016/j.eclinm.2020.100404
Petroff SA, Branch A, Steenken W. A Study of Bacillus Calmette-Guerin (B.C.G.). Am Rev Tuberc. 1929;19: 9-46.
Raghab Mohapatra P, Mishra B, Behera B. BCG vaccination induced protection from COVID-19. Indian Journal of Tuberculosis. 2020;preprint.
DOI: 10.1016/j.ijtb.2020.08.004
Riccò M, Gualerzi G, Ranzieri S, Bragazzi NL. Stop playing with data: there is no sound evidence that Bacille Calmette-Guérin may avoid SARS-CoV-2 infection (for now). Acta Biomed. 2020;91(2):207-213.
DOI: 10.23750/abm.v91i2.9700
Rosenthal SR, Crispen RG, Thorne MG, et al. BCG vaccination and leukemia mortality. J Am Med Assoc. 1972;222:1543-1544.
Sehrawat S, Rouse BT. Does the hygiene hypothesis apply to COVID-19 susceptibility? Microbes Infect. 2020;S1286-4579(20)30127-1.
DOI: 10.1016/j.micinf.2020.07.002
Semple PL, Watkins M, Davids V, et al. Induction of granulysin and perforin cytolytic mediator expression in 10-week-old infants vaccinated with BCG at birth. Clin Dev Immunol. 2011;2011:438463.
DOI: 10.1155/2011/438463
Sharma AR, Batra G, Kumar M, et al. BCG as a game-changer to prevent the infection and severity of COVID-19 pandemic? Allergol Immunopathol (Madrid). 2020:S0301-0546(20)30106-3.
DOI: 10.1016/j.aller.2020.05.002
Shoenfeld Y. Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev. 2020;19(6):102538.
DOI: 10.1016/j.autrev.2020.102538
Shoenfeld Y, Aron-Maor A, Tanai A, Ehrenfeld M. BCG and autoimmunity: another two-edged sword. J Autoimmun. 2001;16(3):235-240.
DOI: 10.1006/jaut.2000.0494
Shoenfeld Y, Isenberg DA. Mycobacteria and autoimmunity. Immunol. Today. 1988;9(6):178-182.
DOI: 10.1016/0167-5699(88)91294-7
Spix C, Eletr D, Blettner M, Kaatsch P. Temporal trends in the incidence rate of childhood cancer in Germany 1987-2004. Int J Cancer. 2008;122:1859-1867.
Ten Doesschate T, et al. Correction to: Two Randomized Controlled Trials of Bacillus Calmette-Guerin Vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: A structured summary of the study protocols for two randomised controlled Trials. Trials. 2020;21(1):555.
Van Rie A, Madhi SA, Heera JR, et al. Gamma interferon production in response to Mycobacterium bovis BCG and Mycobacterium tuberculosis antigens in infants born to human immunodeficiency virus-infected mothers. Clin Vaccine Immunol. 2006;13(2):246-252.
DOI: 10.1128/CVI.13.2.246-252.2006
Wardhana A, Datau EA, Sultana A, et al. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med. Indones. 2011;43:185-190.
Watad A, Quaresma M, Brown S, et al. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update. Lupus, 2017;26(7):675-681.
DOI: 10.1177/0961203316686406
Watad A, Bragazzi NL, Shoenfeld Y. Immunologist's Little Dirty Secret Finger: A Case Report of Polyautoimmunity Following an Accidental Self-injection of Complete Freund's Adjuvant. Isr Med Assoc J. 2020;22(6):393-394.
Wu J, Li X, Song W, et al. The roles and applications of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours. Autoimmun Rev. 2017;16(12):1270-1281.
DOI: 10.1016/j.autrev.2017.10.012
Yamamoto N, Bauer G. Apparent difference in fatalities between Central Europe and East Asia due to SARS-COV-2 and COVID-19: Four hypotheses for possible explanation. Med Hypotheses. 2020;144:110160.
DOI: 10.1016/j.mehy.2020.110160
Yamazaki-Nakashimada MA, Unzueta A, Berenise Gámez-González L, et al. BCG: a vaccine with multiple faces. Hum Vaccin Immunother. 2020;29:1-10.
DOI: 10.1080/21645515.2019.1706930
Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Front Med. 2020;14(2):117-125.
DOI: 10.1007/s11684-020-0773-x
Zwerling A, Behr MA, Verma A, et al. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices. PLoS Med. 2011;8(3):e1001012.
DOI: 10.1371/journal.pmed.1001012
URL: https://www.worldometers.info/coronavirus
URL: https://en.wikipedia.org/wiki/BCG_vaccine#Europe
URL:https://apps.who.int/immunization_monitoring/globalsummary/countres?countrycriteria%5Bcountry%5D%5B%5D=TJK
URL: https://www.whonamedit.com/synd.cfm/2816.html
URL: https://www.nobelprize.org/nomination/archive
Portrait of Jean Marie Camille Guerin with Leon Charles Albert Calmette // Wellcome Library, London. Wellcome Images. http://catalogue.wellcomelibrary.org/record=b1349948

Еще

Статья обзорная