Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina

Detalhes bibliográficos
Autor(a) principal: Pinto, Raquel de Medeiros
Data de Publicação: 2020
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade do Estado do Amazonas (UEA)
Texto Completo: https://ri.uea.edu.br/handle/riuea/2249
Resumo: In Brazil, Plasmodium falciparum resistance to several drugs, such as chloroquine, sulfadoxine- pyrimethamine, mefloquine, quinine and amodiaquine is reported. The monitoring of the sensitivity of Plasmodium to antimalarial drugs is of great importance for the therapeutic management and planning of malaria control policies. Currently, the World Health Organization (WHO) recommends Artemisinin-based combination therapy (ACT) as first-line for all cases of malaria in areas where P. falciparum predominates. In the present study, we analyzed a cohort of patients treated in a tertiary center of Manaus, with positive diagnosis of P. falciparum malaria by thick blood under treatment with artemisinin derivatives (artesunate, artesunate / mefloquine, artemether, artemether / mefloquine ) and followed over 35 days after treatment to evaluate the parasitic whitening profile. The variables evaluated were: date of service, gender, age, type of treatment, number of leukocytes, white blood cell count, sexual and asexual parasitaemia (D0) and day follow-up (D1-D7, D14, D21, D28 and D35). Survival analysis (AS) and logistic regression (LR) will be conducted to examine associations between parasitic and whitening treatment. For regression analysis, the outcome will be assessed parasitic whitening time in D3 and D4, while the survival analysis, the variable analyzed is the time to bleaching. Therefore the estimate of parasite clearance method provides a consistent, reliable and can be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds used in treatment. The results could form the basis for future studies related to genetic polymorphisms associated with decreased of parasite clearance time in the Americas
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spelling Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisininaPlasmidium falciparum parasitic clearance in response to artemisinin treatmentMaláriaArtemisininaPlasmodiumIn Brazil, Plasmodium falciparum resistance to several drugs, such as chloroquine, sulfadoxine- pyrimethamine, mefloquine, quinine and amodiaquine is reported. The monitoring of the sensitivity of Plasmodium to antimalarial drugs is of great importance for the therapeutic management and planning of malaria control policies. Currently, the World Health Organization (WHO) recommends Artemisinin-based combination therapy (ACT) as first-line for all cases of malaria in areas where P. falciparum predominates. In the present study, we analyzed a cohort of patients treated in a tertiary center of Manaus, with positive diagnosis of P. falciparum malaria by thick blood under treatment with artemisinin derivatives (artesunate, artesunate / mefloquine, artemether, artemether / mefloquine ) and followed over 35 days after treatment to evaluate the parasitic whitening profile. The variables evaluated were: date of service, gender, age, type of treatment, number of leukocytes, white blood cell count, sexual and asexual parasitaemia (D0) and day follow-up (D1-D7, D14, D21, D28 and D35). Survival analysis (AS) and logistic regression (LR) will be conducted to examine associations between parasitic and whitening treatment. For regression analysis, the outcome will be assessed parasitic whitening time in D3 and D4, while the survival analysis, the variable analyzed is the time to bleaching. Therefore the estimate of parasite clearance method provides a consistent, reliable and can be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds used in treatment. The results could form the basis for future studies related to genetic polymorphisms associated with decreased of parasite clearance time in the AmericasNo Brasil, a resistência do Plasmodium falciparum a várias drogas, como cloroquina, sulfadoxina- pirimetamina, mefloquina, quinina e amodiaquina é relatada. A vigilância da sensibilidade dos plasmódios a antimaláricos é de grande importância para a conduta terapêutica, bem como para o planejamento de políticas de controle da malária. Atualmente, a Organização Mundial da Saúde (OMS) preconiza a terapia combinada de artemisinina (ACT) como primeira escolha para todos os casos de malária em áreas onde o P. falciparum predomina. No presente estudo, foi analisada uma coorte de pacientes atendidos em uma unidade terciária de Manaus, com diagnóstico positivo para malária por P. falciparum através da gota espessa, sob tratamento com derivados da artemisinina (artesunato, artesunato/mefloquina, artemeter, artemeter/mefloquina) e acompanhados ao longo de 35 dias após o tratamento, visando avaliar o perfil de clareamento parasitário. As variáveis avaliadas foram: data do atendimento, sexo, idade, tipo de tratamento, número de leucócitos, leucometria, parasitemia sexuada e assexuada (D0) e nos dias de seguimento (D1-D7, D14, D21, D28 e D35). Análises de sobrevivência (AS) e regressão logística (RL) serão realizadas para verificar associações entre clareamento parasitário e tipo de tratamento. Para a análise de regressão, o desfecho avaliado será o tempo de clareamento parasitário em D3 e D4, enquanto para a análise de sobrevivência, a variável analisada será o tempo até o clareamento. Portanto a estimativa do clareamento parasitário nos fornece um método consistente, confiável e pode ser utilizado para detectar os primeiros sinais de resistência emergente para derivados de artemisinina e outros compostos utilizados no tratamento. Os resultados obtidos poderão servir de base para estudos futuros referentes aos polimorfismos genéticos associados à diminuição do tempo de clareamento do parasito nas AméricasUniversidade do Estado do AmazonasBrasilUEAPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIAWeber, Simone SchneiderMonteiro , Wuelton MarceloWeber, Simone SchneiderLacerda, Marcus Vinicius GuimarãesMonteiro, Welton MarceloPinto, Raquel de Medeiros2022-08-11T16:56:38Z2024-09-05T18:56:27Z2022-08-102022-08-11T16:56:38Z2020-04-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://ri.uea.edu.br/handle/riuea/2249por1. WHO. Global technical strategy for malaria 2016–2030. Geneva: World Health Organization; 2015. p. 1-32. 2. WHO. Guidelines for the Treatment of Malaria. Third Edition. Geneva: World Health Organization; 2015. p. 1-316. 3. Banek K, Webb EL, Smith SJ, Chandramohan D, Staedke SG. Adherence to treatment with artemether– lumefantrine or amodiaquine–artesunate for uncomplicated malaria in children in Sierra Leone: a randomized trial. Malar J. 2018; 17: 222. 4. WHO. Status report on artemisinin and ACT resistance. Geneva: World Health Organization; 2017. p. 1-11. 5. Ippolito MM, Johnson J, Mullin C, Mallow C, Morgan N, Wallender E, et al. The relative effects of artemether-lumefantrine and non-artemisinin antimalarials on gametocyte carriage and transmission of Plasmodium falciparum: a systematic review and meta-analysis. Clin Infect Dis. 2017; 65: 486-94. 6. Wampfler R, Mwingira F, Javati1 S, Robinson L, Betuela I, Siba P, et al. Strategies for detection of Plasmodium species gametocytes. PLoS One. 2013; 8: e76316. 7. Oliveira-Ferreira J, Lacerda MV, Brasil, P, Ladislau, JL, Tauil, PL, Daniel-Ribeiro, CT. Malaria in Brazil: an overview. Malar J. 2010; 9: 115. 8. Souza JM. Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil and its relevance to the treatment and control of malaria. Mem Inst Oswaldo Cruz. 1992; 87(3): 343-8. 9. Ladeia-Andrade S, de Melo GN, de Souza-Lima RC, Salla LC, Bastos MS, Rodrigues PT, et al. No clinical or molecular evidence of Plasmodium falciparum resistance to artesunate- mefloquine in northwestern Brazil. Am J Trop Med Hyg. 2016; 95: 148-54. 38 10. Dondorp AM, Smithuis FM, Woodrow C, Seidlein LV. How to contain artemisinin and multidrug-resistant falciparum malaria. Trends Parasitol. 2017; 33(5): 353-363. 11. Amato R, Lim P, Miotto O, Amaratunga C, Dek D, Pearson RD, et al. Genetic markers associated with dihydroartemisinin– piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype–phenotype association study. Lancet Infect Dis. 2017; 17: 164-73. 12. Dondorp AM. New genetic marker for piperaquine resistance in Plasmodium falciparum. Lancet Infect Dis. 2017; 17: 119-20. 13. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning, J. et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009; 361: 455–67. 14. MalERA. A research agenda for malaria eradication: basic science and enabling technologies. PLoS Med. 2011; 8: e1000399. 15. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, et al. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008; 359: 2619-20. 16. Musset L, Pelleau S, Girod R, Ardillon V, Carvalho L, Dusfour I, et al. Malaria on the Guiana Shield: a review of the situation in French Guiana. Mem Inst Oswaldo Cruz. 2014; 109: 525-33. 17. Tun KM, Imwong M, Lwin KM, Win AA, Hlaing TM, Hlaing T, et al. Spread of artemisinina-resistant Plasmodium falciparum in Myanmar: A cross-sectional survey of the K13 molecular marker. Lancet Infect Dis. 2015; 15: 415–21. 18. Rabinovich RN, Drakeley C, Djimde AA, Hall F, Hay SI, Hemingway J, et al. An updated research agenda for malaria elimination and eradication. PLoS Med. 2017; 14: e1002456. 39 19. Menard D, Dondorp A. Antimalarial Drug Resistance: A Threat to Malaria Elimination. Cold Spring Harb Perspect Med. 2017; 7: a025619. 20. Gomes LR, Lavigne A, Peterka CL, Brasil P, Menard D, Daniel-Ribeiro CT, et al. Absence of K13 polymorphism in Plasmodium falciparum parasites from Brazilian endemic areas. Antimicrob Agents Chemother. 2018; 62: 354-18. 21. Woitsh B, Wernsdorfer G, Prajakwong S, Rojanawatsirivet C, Kollaritsch H, Wernsdorfer WH. Comparative study of the in vitro sensitivity of Plasmodium falciparum to artemisinin in two border areas of Thailand. Wien Klin Wochenschr. 2004; 116: 35-40. 22. Wongsrichanalai C, Meshnick SR. Declining artesunate-mefloquine efficacy against falciparum Malaria on the Cambodia-Thailand border. Emerg Infect Dis. 2008; 14: 716-9. 23. Ferreira ID, Lopes D, Martinelli A, Ferreira C, do Rosario VE, Cravo P. In vitro assessment of artesunate, artemether and amodiaquine susceptibility and molecular analysis of putative resistance-associated mutations of Plasmodium falciparum from Sao Tome & Principe. Trop Med Int Health. 2007; 12: 353–62. 24. de Oliveira AM, Chavez J, de Leon GP, Durand S, Arrospide N, Roberts J, et al. Efficacy and effectiveness of mefloquine and artesunate combination therapy for uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon. Am J Trop Med Hyg. 2011; 85: 573-8. 25. Vreden SGS, Jitan JK, Bansie RD, Adhin MR. Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether. Mem Inst Oswaldo Cruz. 2013; 108: 968-73. 40 26. Vreden SGS, Bansie RD, Jitan JK, Adhin MR. Assessing parasite clearance during uncomplicated Plasmodium falciparum infection treated with artesunate monotherapy in Suriname. Infect Drug Resist. 2016;9:261-7. 27. Looareesuwan S, Wilairatana P, Chalermarent K, Rattanapong Y, Canfield CJ, Hutchinson. Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg. 1999; 60: 526-32. 28. Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, Barends M, et al. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS One. 2009; 4: e4551. 29. Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, et al. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis. 2006; 193: 1151-9. 30. Mohapatra MK, Dash LK, Bariha PK, Karua PC. Profile of mixed species (Plasmodium vivax and falciparum) malaria in adults. J Assoc Physicians India. 2012; 60: 20-4info:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade do Estado do Amazonas (UEA)instname:Universidade do Estado do Amazonas (UEA)instacron:UEA2024-09-25T21:18:10Zoai:ri.uea.edu.br:riuea/2249Repositório InstitucionalPUBhttps://ri.uea.edu.br/server/oai/requestbibliotecacentral@uea.edu.bropendoar:2024-09-25T21:18:10Repositório Institucional da Universidade do Estado do Amazonas (UEA) - Universidade do Estado do Amazonas (UEA)false
dc.title.none.fl_str_mv Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
Plasmidium falciparum parasitic clearance in response to artemisinin treatment
title Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
spellingShingle Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
Pinto, Raquel de Medeiros
Malária
Artemisinina
Plasmodium
title_short Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
title_full Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
title_fullStr Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
title_full_unstemmed Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
title_sort Clareamento parasitário de Plasmidium falciparum em resposta ao tratamento com artemisinina
author Pinto, Raquel de Medeiros
author_facet Pinto, Raquel de Medeiros
author_role author
dc.contributor.none.fl_str_mv Weber, Simone Schneider
Monteiro , Wuelton Marcelo
Weber, Simone Schneider
Lacerda, Marcus Vinicius Guimarães
Monteiro, Welton Marcelo
dc.contributor.author.fl_str_mv Pinto, Raquel de Medeiros
dc.subject.por.fl_str_mv Malária
Artemisinina
Plasmodium
topic Malária
Artemisinina
Plasmodium
description In Brazil, Plasmodium falciparum resistance to several drugs, such as chloroquine, sulfadoxine- pyrimethamine, mefloquine, quinine and amodiaquine is reported. The monitoring of the sensitivity of Plasmodium to antimalarial drugs is of great importance for the therapeutic management and planning of malaria control policies. Currently, the World Health Organization (WHO) recommends Artemisinin-based combination therapy (ACT) as first-line for all cases of malaria in areas where P. falciparum predominates. In the present study, we analyzed a cohort of patients treated in a tertiary center of Manaus, with positive diagnosis of P. falciparum malaria by thick blood under treatment with artemisinin derivatives (artesunate, artesunate / mefloquine, artemether, artemether / mefloquine ) and followed over 35 days after treatment to evaluate the parasitic whitening profile. The variables evaluated were: date of service, gender, age, type of treatment, number of leukocytes, white blood cell count, sexual and asexual parasitaemia (D0) and day follow-up (D1-D7, D14, D21, D28 and D35). Survival analysis (AS) and logistic regression (LR) will be conducted to examine associations between parasitic and whitening treatment. For regression analysis, the outcome will be assessed parasitic whitening time in D3 and D4, while the survival analysis, the variable analyzed is the time to bleaching. Therefore the estimate of parasite clearance method provides a consistent, reliable and can be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds used in treatment. The results could form the basis for future studies related to genetic polymorphisms associated with decreased of parasite clearance time in the Americas
publishDate 2020
dc.date.none.fl_str_mv 2020-04-02
2022-08-11T16:56:38Z
2022-08-10
2022-08-11T16:56:38Z
2024-09-05T18:56:27Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
dc.identifier.uri.fl_str_mv https://ri.uea.edu.br/handle/riuea/2249
url https://ri.uea.edu.br/handle/riuea/2249
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv 1. WHO. Global technical strategy for malaria 2016–2030. Geneva: World Health Organization; 2015. p. 1-32. 2. WHO. Guidelines for the Treatment of Malaria. Third Edition. Geneva: World Health Organization; 2015. p. 1-316. 3. Banek K, Webb EL, Smith SJ, Chandramohan D, Staedke SG. Adherence to treatment with artemether– lumefantrine or amodiaquine–artesunate for uncomplicated malaria in children in Sierra Leone: a randomized trial. Malar J. 2018; 17: 222. 4. WHO. Status report on artemisinin and ACT resistance. Geneva: World Health Organization; 2017. p. 1-11. 5. Ippolito MM, Johnson J, Mullin C, Mallow C, Morgan N, Wallender E, et al. The relative effects of artemether-lumefantrine and non-artemisinin antimalarials on gametocyte carriage and transmission of Plasmodium falciparum: a systematic review and meta-analysis. Clin Infect Dis. 2017; 65: 486-94. 6. Wampfler R, Mwingira F, Javati1 S, Robinson L, Betuela I, Siba P, et al. Strategies for detection of Plasmodium species gametocytes. PLoS One. 2013; 8: e76316. 7. Oliveira-Ferreira J, Lacerda MV, Brasil, P, Ladislau, JL, Tauil, PL, Daniel-Ribeiro, CT. Malaria in Brazil: an overview. Malar J. 2010; 9: 115. 8. Souza JM. Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil and its relevance to the treatment and control of malaria. Mem Inst Oswaldo Cruz. 1992; 87(3): 343-8. 9. Ladeia-Andrade S, de Melo GN, de Souza-Lima RC, Salla LC, Bastos MS, Rodrigues PT, et al. No clinical or molecular evidence of Plasmodium falciparum resistance to artesunate- mefloquine in northwestern Brazil. Am J Trop Med Hyg. 2016; 95: 148-54. 38 10. Dondorp AM, Smithuis FM, Woodrow C, Seidlein LV. How to contain artemisinin and multidrug-resistant falciparum malaria. Trends Parasitol. 2017; 33(5): 353-363. 11. Amato R, Lim P, Miotto O, Amaratunga C, Dek D, Pearson RD, et al. Genetic markers associated with dihydroartemisinin– piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype–phenotype association study. Lancet Infect Dis. 2017; 17: 164-73. 12. Dondorp AM. New genetic marker for piperaquine resistance in Plasmodium falciparum. Lancet Infect Dis. 2017; 17: 119-20. 13. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning, J. et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009; 361: 455–67. 14. MalERA. A research agenda for malaria eradication: basic science and enabling technologies. PLoS Med. 2011; 8: e1000399. 15. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, et al. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008; 359: 2619-20. 16. Musset L, Pelleau S, Girod R, Ardillon V, Carvalho L, Dusfour I, et al. Malaria on the Guiana Shield: a review of the situation in French Guiana. Mem Inst Oswaldo Cruz. 2014; 109: 525-33. 17. Tun KM, Imwong M, Lwin KM, Win AA, Hlaing TM, Hlaing T, et al. Spread of artemisinina-resistant Plasmodium falciparum in Myanmar: A cross-sectional survey of the K13 molecular marker. Lancet Infect Dis. 2015; 15: 415–21. 18. Rabinovich RN, Drakeley C, Djimde AA, Hall F, Hay SI, Hemingway J, et al. An updated research agenda for malaria elimination and eradication. PLoS Med. 2017; 14: e1002456. 39 19. Menard D, Dondorp A. Antimalarial Drug Resistance: A Threat to Malaria Elimination. Cold Spring Harb Perspect Med. 2017; 7: a025619. 20. Gomes LR, Lavigne A, Peterka CL, Brasil P, Menard D, Daniel-Ribeiro CT, et al. Absence of K13 polymorphism in Plasmodium falciparum parasites from Brazilian endemic areas. Antimicrob Agents Chemother. 2018; 62: 354-18. 21. Woitsh B, Wernsdorfer G, Prajakwong S, Rojanawatsirivet C, Kollaritsch H, Wernsdorfer WH. Comparative study of the in vitro sensitivity of Plasmodium falciparum to artemisinin in two border areas of Thailand. Wien Klin Wochenschr. 2004; 116: 35-40. 22. Wongsrichanalai C, Meshnick SR. Declining artesunate-mefloquine efficacy against falciparum Malaria on the Cambodia-Thailand border. Emerg Infect Dis. 2008; 14: 716-9. 23. Ferreira ID, Lopes D, Martinelli A, Ferreira C, do Rosario VE, Cravo P. In vitro assessment of artesunate, artemether and amodiaquine susceptibility and molecular analysis of putative resistance-associated mutations of Plasmodium falciparum from Sao Tome & Principe. Trop Med Int Health. 2007; 12: 353–62. 24. de Oliveira AM, Chavez J, de Leon GP, Durand S, Arrospide N, Roberts J, et al. Efficacy and effectiveness of mefloquine and artesunate combination therapy for uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon. Am J Trop Med Hyg. 2011; 85: 573-8. 25. Vreden SGS, Jitan JK, Bansie RD, Adhin MR. Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether. Mem Inst Oswaldo Cruz. 2013; 108: 968-73. 40 26. Vreden SGS, Bansie RD, Jitan JK, Adhin MR. Assessing parasite clearance during uncomplicated Plasmodium falciparum infection treated with artesunate monotherapy in Suriname. Infect Drug Resist. 2016;9:261-7. 27. Looareesuwan S, Wilairatana P, Chalermarent K, Rattanapong Y, Canfield CJ, Hutchinson. Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg. 1999; 60: 526-32. 28. Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, Barends M, et al. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS One. 2009; 4: e4551. 29. Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, et al. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis. 2006; 193: 1151-9. 30. Mohapatra MK, Dash LK, Bariha PK, Karua PC. Profile of mixed species (Plasmodium vivax and falciparum) malaria in adults. J Assoc Physicians India. 2012; 60: 20-4
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Brasil
UEA
PPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIA
publisher.none.fl_str_mv Universidade do Estado do Amazonas
Brasil
UEA
PPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIA
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