Leishmanioses: avanços científicos no controlo, diagnóstico e epidemiologia moleculares no contexto dos países de língua oficial Portuguesa

  • Isabel Maurício UEI Parasitologia Médica, Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, IHMT-NOVA, Lisboa, Portugal
Palavras-chave: Leishmaniose, diagnóstico, vacinas, fármacos, epidemiologia molecular, medicina de precisão

Resumo

As leishmanioses são doenças tropicais negligenciadas causadas por parasitas protozoários do género Leishmania. Embora as estratégias e esforços de controle tenham contribuído para a redução da sua prevalência e impacto, até 1 milhão de casos ainda ocorrem por ano, e a leishmaniose visceral ainda mata até 90 000 pessoas anualmente. Alguns importantes avanços no controle da leishmaniose são apresentados e discutidos nesta revisão, com foco nos países de língua portuguesa. Compara-se a situação epidemiológica da leishmaniose humana em Portugal e no Brasil e analisam-se casos notificados noutros países. Os métodos de diagnóstico são revistos de forma breve ​​ e genómica e sistemas de aprendizagem de máquina (“machine learning”) são discutidos juntamente com a necessidade de algoritmos validados. O desenvolvimento de medicamentos e vacinas é discutido, incluindo o potencial para vacinas terapêuticas e de RNA. O advento da epidemiologia genómica é analisado, inclusivamente na redefinição da taxonomia de Leishmania, assim como o uso de ferramentas moleculares para identificação de potenciais reservatórios. Por fim, aborda-se os primeiros passos no desenvolvimento da medicina de precisão. Em conclusão, embora tenha havido avanços importantes no controle da leishmaniose, ainda permanecem desafios significativos, que podem ser efetivamente superados com o aumento do investimento e um maior compromisso político.

Downloads

Não há dados estatísticos.

Biografia Autor

Isabel Maurício, UEI Parasitologia Médica, Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, IHMT-NOVA, Lisboa, Portugal

 

 

Referências

WHO. Leishmaniasis [Internet]. [cited 2023 Jul 24]. Available from: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis

Espinosa OA, Serrano MG, Camargo EP, Teixeira MMG, Shaw JJ. An appraisal of the taxonomy and nomenclature of trypanosomatids presently classified as Leishmania and Endotrypanum. Parasitology. 2018 Apr 1;145(4):430–42

Maurício IL. Leishmania taxonomy. The Leishmaniases: Old Neglected Tropical Diseases. 2018

Maurício IL, Stothard JR, Miles MA. The strange case of Leishmania chagasi. Parasitol Today. 2000;16(5)

Leblois R, Kuhls K, François O, Schönian G, Wirth T. Guns, germs and dogs: On the origin of Leishmania chagasi. Infect Genet Evol. 2011 Jul;11(5):1091–5.

Castro LS, França A de O, Ferreira E de C, Hans Filho G, Higa Júnior MG, Gontijo CMF, et al. Leishmania infantum as a causative agent of cutaneous leishmaniasis in the state of Mato Grosso do Sul, Brazil. Rev Inst Med Trop Sao Paulo. 2016;58:23

Campino L, Bajanca R, Franca I, Pratlong F, Dedet J, Fiadeiro T. [Cutaneous leishmaniosis in Portugal due to Leishmania infantum MON-1]. Acta Med Port. 2005;18(6):475–7

Cecílio P, Cordeiro-da-Silva A, Oliveira F. Sand flies: Basic information on the vectors of leishmaniasis and their interactions with Leishmania parasites. Commun Biol. 2022 Dec 1;5(1)

ECDC. Surveillance, prevention and control of leishmaniases in the European Union and its neighbouring countries Surveillance, prevention and control of leishmaniases in the European Union and its neighbouring countries ii. 2022

Doenças de Declaração Obrigatória — Transparência [Internet]. [cited 2023 Jul 26]. Available from: https://transparencia.sns.gov.pt/explore/dataset/doencas-de-declaracao-obrigatoria/table/?disjunctive.regiao_de_saude_de_notificacao&disjunctive.residencia_nut_iii&disjunctive.doenca_de_declaracao_obrigatoria&disjunctive.sexo&disjunctive.grupo_etario&sort

PAHO. Leishmaniasis: Epidemiological Report for the Americas. No.11 (December 2022). Leishmaniases Epidemiol Rep Am No11 (December 2022). 2022 Dec 8;11

Almeida M, Maia C, Cristóvão JM, Morgado C, Barbosa I, Ibars RF, et al. Seroprevalence and Risk Factors Associated with Leishmania Infection in Dogs from Portugal. Microorganisms. 2022 Nov 1;10(11)

Marzochi MC de A, Barbosa DS, Belo VS, Araújo GR de, Silva AF da, Pimentel MI, et al. Visceral leishmaniasis in Brazil: scenarios and challenges for the surveillance and control. J Trop Pathol. 2023;52(1):1–10

Jimenez M, Puente S, Gutierrez-Solar B, Martinez P, Alvar J. Visceral leishmaniasis in Angola due to Leishmania (Leishmania) infantum. Am J Trop Med Hyg. 1994;50(6):687–92

Vilhena H, Granada S, Oliveira AC, Schallig HD, Nachum-Biala Y, Cardoso L, et al. Serological and molecular survey of Leishmania infection in dogs from Luanda, Angola. Parasit Vectors. 2014 Mar 24;7(1):114

Pedro JM, Nhamba LA, Rodriguez VME. Presentation of two clinical cases of Leishmaniasis in Angola. Rev Angolana Ciências da Saúde. 2022;3(2):17–21

Cortes S, Pereira A, Vasconcelos J, Paixão JP, Quivinja J, Afonso JDM, et al. PO 8505 LEISHMANIASIS IN ANGOLA – AN EMERGING DISEASE? BMJ Glob Heal. 2019 Apr 1;4(Suppl 3):A47.3-A48

Huambo: Sobe para 38 casos de suspeita de leishmaniose | Portal de Angola [Internet]. [cited 2023 Jul 19]. Available from: https://www.portaldeangola.com/2017/03/13/huambo-sobe-para-38-casos-de-suspeita-de-leishmaniose/

Sabbatani S, Calzado AI, Ferro A, Goudiaby AML, Borghi V, Zanchetta GP, et al. Atypical leishmaniasis in an HIV-2-seropositive patient from Guinea-Bissau - PubMed. AIDS. 1991;5(7):899–901

Chevalier B, Carmoi T, Sagui E, Carrette P, Petit D, De Mauleon P, et al. Report of the first cases of cutaneous leishmaniasis in East Timor. Clin Infect Dis. 2000;30(5):840

dos Santos MML, Amaral S, Harmen SP, Joseph HM, Fernandes JL, Counahan ML. The prevalence of common skin infections in four districts in Timor-Leste: A cross sectional survey. BMC Infect Dis. 2010 Mar 10;10(1):1–6

East Timor: Weekly Epidemiological Bulletin Week 21/2000 - Timor-Leste | ReliefWeb [Internet]. [cited 2023 Jul 19]. Available from: https://reliefweb.int/report/timor-leste/east-timor-weekly-epidemiological-bulletin-week-212000

Kumari D, Perveen S, Sharma R, Singh K. Advancement in leishmaniasis diagnosis and therapeutics: An update. Eur J Pharmacol. 2021 Nov 5;910

Gow I, Smith NC, Stark D, Ellis J. Laboratory diagnostics for human Leishmania infections: a polymerase chain reaction-focussed review of detection and identification methods. Parasites Vectors 2022 151. 2022 Nov 5;15(1):1–24

Taslimi Y, Sadeghipour P, Habibzadeh S, Mashayekhi V, Mortazavi H, Müller I, et al. A novel non-invasive diagnostic sampling technique for cutaneous leishmaniasis. PLoS Negl Trop Dis. 2017 Jul 13;11(7)

Nakkash-Chmaisse H, Makki R, Nahhas G, Knio K, Nuwayri-Salti N. Detection of Leishmania parasites in the blood of patients with isolated cutaneous leishmaniasis. Int J Infect Dis. 2011 Jul;15(7)

Ates SC, Bagirova M, Allahverdiyev AM, Kocazeybek B, Kosan E. Utility of the microculture method for Leishmania detection in non-invasive samples obtained from a blood bank. Acta Trop. 2013 Oct;128(1):54–60

Ladopoulos T, Ntais P, Tsirigotakis N, Dokianakis E, Antoniou M. The proliferation potential of promastigotes of the main Leishmania species of the old world in NNN culture medium prepared using blood of four different mammals. Exp Parasitol. 2015 Oct 1;157:124–7

Paixão-Marques MDS, Alves-Martin MF, Guiraldi LM, Dos Santos WJ, De Lemos FA, Sánchez GP, et al. First isolation of Leishmania infantum by blood culture in bovines from endemic area for canine visceral leishmaniasis. Parasitology. 2019 Jun 1;146(7):911–3

Bowdre JH, Campbell JL, Walker DH, Tart DE. American mucocutaneous leishmaniasis. Culture of a Leishmania species from peripheral blood leukocytes. Am J Clin Pathol. 1981;75(3):435–8

Prina E, Roux E, Mattei D, Milon G. Leishmania DNA is rapidly degraded following parasite death: an analysis by microscopy and real-time PCR. Microbes Infect. 2007 Sep 1;9(11):1307–15

De Pascali AM, Todeschini R, Baiocchi S, Ortalli M, Attard L, Ibarra-Meneses AV, et al. Test combination to detect latent Leishmania infection: A prevalence study in a newly endemic area for L. infantum, northeastern Italy. PLoS Negl Trop Dis. 2022;16(8):e0010676

Castillo-Castañeda A, Patiño LH, Muñoz M, Ayala MS, Segura M, Bautista J, et al. Amplicon-based next-generation sequencing reveals the co-existence of multiple Leishmania species in patients with visceral leishmaniasis. Int J Infect Dis. 2022 Feb 1;115:35–8

Laffitte MCN, Leprohon P, Légaré D, Ouellette M. Deep-sequencing revealing mutation dynamics in the miltefosine transporter gene in Leishmania infantum selected for miltefosine resistance. Parasitol Res. 2016 Oct 1;115(10):3699–703

Cloots K, Singh OP, Singh AK, Kushwaha AK, Malaviya P, Kansal S, et al. Diagnosis of Visceral Leishmaniasis in an Elimination Setting: A Validation Study of the Diagnostic Algorithm in India. Diagnostics (Basel, Switzerland). 2022 Mar 1;12(3).

Pereira A, Maia C. Leishmania infection in cats and feline leishmaniosis: An updated review with a proposal of a diagnosis algorithm and prevention guidelines. Curr Res Parasitol vector-borne Dis. 2021 Jan 1;1

Zare M, Akbarialiabad H, Parsaei H, Asgari Q, Alinejad A, Bahreini MS, et al. A machine learning-based system for detecting leishmaniasis in microscopic images. BMC Infect Dis. 2022 Dec 1;22(1)

Coelho ML, França T, Fontoura Mateus NL, da Costa Lima Junior MS, Cena C, do Nascimento Ramos CA. Canine visceral leishmaniasis diagnosis by UV spectroscopy of blood serum and machine learning algorithms. Photodiagnosis Photodyn Ther. 2023 Jun 1;42:103575

Robles-Loaiza AA, Pinos-Tamayo EA, Mendes B, Teixeira C, Alves C, Gomes P, et al. Peptides to Tackle Leishmaniasis: Current Status and Future Directions. Int J Mol Sci. 2021 May 1;22(9)

Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, et al. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med. 2002 Nov 28;347(22):1739–46

Ware JAM, O’Connell EM, Brown T, Wetzler L, Talaat KR, Nutman TB, et al. Efficacy and Tolerability of Miltefosine in the Treatment of Cutaneous Leishmaniasis. Clin Infect Dis. 2021 Oct 1;73(7):E2457–562

PAHO. Guideline for the Treatment of Leishmaniasis in the Americas. Second Edi. PAHO, WHO; 2022. 136 p

Pinart M, Rueda JR, Romero GAS, Pinzón-Flórez CE, Osorio-Arango K, Silveira Maia-Elkhoury AN, et al. Interventions for American cutaneous and mucocutaneous leishmaniasis. Cochrane database Syst Rev. 2020 Aug 27;8(8)

Afonso RC, Yien RMK, de Siqueira LB de O, Simas NK, dos Santos Matos AP, Ricci-Júnior E. Promising natural products for the treatment of cutaneous leishmaniasis: A review of in vitro and in vivo studies. Exp Parasitol. 2023 Aug 1;251

Volpedo G, Huston RH, Holcomb EA, Pacheco-Fernandez T, Gannavaram S, Bhattacharya P, et al. From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection. Expert Rev Vaccines. 2021;20(11):1431–46

Aguiar-Soares RD de O, Roatt BM, Mathias FAS, Reis LES, Cardoso JM de O, de Brito RCF, et al. Phase I and II Clinical Trial Comparing the LBSap, Leishmune®, and Leish-Tec® Vaccines against Canine Visceral Leishmaniasis. Vaccines 2020, Vol 8, Page 690. 2020 Nov 17;8(4):690

Comunicado recolhimento Leish-Tec 22/maio/2023 / RECOLHIMENTO LEISH-TEC / Ceva no Brasil / Notícias / Ceva Brasil [Internet]. [cited 2023 Jul 26]. Available from: https://www.ceva.com.br/Noticias/Ceva-no-Brasil/RECOLHIMENTO-LEISH-TEC/Comunicado-recolhimento-Leish-Tec-22-maio-2023

Mapa suspende fabricação e venda e determina o recolhimento de lotes de vacina contra Leishmaniose — Ministério da Agricultura e Pecuária [Internet]. [cited 2023 Jul 26]. Available from: https://www.gov.br/agricultura/pt-br/assuntos/noticias/mapa-suspende-fabricacao-e-venda-e-determina-o-recolhimento-de-lotes-de-vacina-contra-leishmaniose-apos-fiscalizacao

Velez R, Domenech E, Rodríguez-Cortés A, Barrios D, Tebar S, Fernández-Arévalo A, et al. Evaluation of canine leishmaniosis vaccine CaniLeish® under field conditions in native dog populations from an endemic Mediterranean area-A randomized controlled trial. Acta Trop. 2020 May 1;205

Velez R, Gállego M. Commercially approved vaccines for canine leishmaniosis: a review of available data on their safety and efficacy. Trop Med Int Health. 2020 May 1;25(5):540–57

Fonseca BN. Comparação entre as vacinas Letifend® e CaniLeish® relativamente aos seus efeitos secundários em cães domésticos: um estudo retrospetivo. Universidade de Lisboa; 2020

Neoleish: Pending EC decision | European Medicines Agency [Internet]. [cited 2023 Jul 26]. Available from: https://www.ema.europa.eu/en/medicines/veterinary/summaries-opinion/neoleish

Pandey SC, Kumar A, Samant M. Genetically modified live attenuated vaccine: A potential strategy to combat visceral leishmaniasis. Parasite Immunol. 2020 Sep 1;42(9)

Zhang WW, Karmakar S, Gannavaram S, Dey R, Lypaczewski P, Ismail N, et al. A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing. Nat Commun 2020 111. 2020 Jul 10;11(1):1–14

Volpedo G, Pacheco-Fernandez T, Holcomb EA, Zhang WW, Lypaczewski P, Cox B, et al. Centrin-deficient Leishmania mexicana confers protection against New World cutaneous leishmaniasis. NPJ vaccines. 2022 Dec 1;7(1)

Karmakar S, Volpedo G, Zhang WW, Lypaczewski P, Ismail N, Oliveira F, et al. Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis. npj Vaccines 2022 71. 2022 Dec 3;7(1):1–9

Duthie MS, Machado BAS, Badaró R, Kaye PM, Reed SG. Leishmaniasis Vaccines: Applications of RNA Technology and Targeted Clinical Trial Designs. Pathog (Basel, Switzerland). 2022 Nov 1;11(11)

Kaye PM, Mohan S, Mantel C, Malhame M, Revill P, Le Rutte E, et al. Overcoming roadblocks in the development of vaccines for leishmaniasis. Expert Rev Vaccines. 2021;20(11):1419–30

Nascimento LFM, Miranda DFH, Moura LD, Pinho FA, Werneck GL, Khouri R, et al. Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs. Vaccine X. 2019 Apr 9;4

Domagalska MA, Dujardin JC. Next-Generation Molecular Surveillance of TriTryp Diseases. Trends Parasitol. 2020 Apr 1;36(4):356–67

Franssen SU, Durrant C, Stark O, Moser B, Downing T, Imamura H, et al. Global genome diversity of the Leishmania donovani complex. Elife. 2020 Mar 25;9

Lau R, Mukkala AN, Kariyawasam R, Clarke S, Valencia BM, Llanos-Cuentas A, et al. Comparison of Whole Genome Sequencing versus Standard Molecular Diagnostics for Species Identification in the Leishmania Viannia Subgenus. Am J Trop Med Hyg. 2021 Sep 1;105(3):660–9

Sereno D. Leishmania ( Mundinia) spp.: from description to emergence as new human and animal Leishmania pathogens. New microbes new Infect. 2019 Jul 1;30.

Becvar T, Vojtkova B, Siriyasatien P, Votypka J, Modry D, Jahn P, et al. Experimental transmission of Leishmania (Mundinia) parasites by biting midges (Diptera: Ceratopogonidae). PLoS Pathog. 2021 Jun 1;17(6)

Santos RL, de Oliveira AR. Leishmaniasis in non-human primates: Clinical and pathological manifestations and potential as reservoirs. J Med Primatol. 2020 Feb 1;49(1):34–9

Azami-conesa I, Gómez-muñoz MT, Martínez-díaz RA. A systematic review (1990–2021) of wild animals infected with zoonotic leishmania. Microorganisms. 2021 May 1;9(5)

Blackwell JM, Fakiola M, Castellucci LC. Human genetics of leishmania infections. Hum Genet. 2020 Jun 1;139(6–7):813–9

Castellucci LC, Almeida L, Cherlin S, Fakiola M, Francis RW, Carvalho EM, et al. A Genome-wide Association Study Identifies SERPINB10, CRLF3, STX7, LAMP3, IFNG-AS1, and KRT80 As Risk Loci Contributing to Cutaneous Leishmaniasis in Brazil. Clin Infect Dis. 2021 May 15;72(10):E515–25

Oliveira IBN, Borges CL, Gomes RS, Ribeiro-Dias F. Single nucleotide polymorphisms in genes involved in immune responses and outcome of tegumentary leishmaniasis. Acta Trop. 2022 Nov 1;235

Grace CA, Sousa Carvalho KS, Sousa Lima MI, Silva VC, Reis-Cunha JL, Brune MJ, et al. Parasite Genotype Is a Major Predictor of Mortality from Visceral Leishmaniasis. MBio. 2022 Dec 1;13(6)

Zijlstra EE. Precision Medicine in Control of Visceral Leishmaniasis Caused by L. donovani. Front Cell Infect Microbiol. 2021 Nov 9;11

Publicado
2024-01-31
Como Citar
1.
Maurício I. Leishmanioses: avanços científicos no controlo, diagnóstico e epidemiologia moleculares no contexto dos países de língua oficial Portuguesa. ihmt [Internet]. 31Jan.2024 [citado 28Fev.2024];22(2):66-4. Available from: https://anaisihmt.com/index.php/ihmt/article/view/458