Visceral leishmaniasis in Northeast Brazil: What is the impact of HIV on this protozoan infection?


Autoři: Uiara Regina Silva de Lima aff001;  Luciano Vanolli aff002;  Elizabeth Coelho Moraes aff002;  Jorim Severino Ithamar aff003;  Conceição de Maria Pedrozo e Silva de Azevedo aff001
Působiště autorů: Post-graduation Program of Health Science, Federal University of Maranhão, São Luís, MA, Brazil aff001;  Medicine Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil aff002;  President Vargas Hospital, São Luís, MA, Brazil aff003;  Department of Medicine, Federal University of Maranhão, São Luís, MA, Brazil aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225875

Souhrn

Background

The aim of this study was to compare cases of Visceral Leishmaniasis (VL) with and without HIV in a state in northeastern Brazil.

Methodology

We performed a comparative study in the state’s referral hospital for infectious/parasitic diseases located in Northeast Brazil between January 2007 and July 2017. The data obtained using this protocol were analyzed with SPSS.

Principal findings

In total, 252 patients were evaluated, including 126 with coincident VL/HIV and 126 with VL alone. Both groups primarily consisted of male patients. The most commonly affected ages were 30–39 years in the coinfected group and 19–29 years in the VL group (p < 0.001). Fever and anorexia (p = 0.001), which were more common in those with VL alone, were frequently observed, while diarrhea, vomiting, bleeding and dyspnea were more common in patients with VL/HIV coinfection (p<0.005). According to the hemogram results, leukocyte levels were lower in the VL group (p < 0.0001). Additionally, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels differed between the groups, with higher levels in patients with VL (p < 0.001). On average, HIV was diagnosed 2.6 years before VL (p < 0.001), and VL relapse was observed only in the coinfection group (36.5% of cases). Fever (β = +0.17; p = 0.032) in the first VL/HIV episode was identified as a risk factor for relapse (R2 = 0.18). More deaths occurred in the VL/HIV group (11.1%) than in the VL group (2.4%).

Conclusion/Significance

VL/HIV was found to be prevalent among young adults, although the median patient age was higher in the VL/HIV group. The classic symptomatology of VL was more common in patients not coinfected with HIV; therefore, attention is needed in patients with HIV who present with any symptoms that suggest the presence of VL, especially in endemic areas. No cases of VL relapse occurred in patients without HIV, and death was more common in the VL/HIV co-infected group.

Klíčová slova:

Brazil – Co-infections – Fevers – HIV clinical manifestations – HIV diagnosis and management – HIV epidemiology – Kala-azar – Leishmaniasis


Zdroje

1. Boer MD, Davidson RN. Treatment options for visceral leishmaniasis. Rev Anti Infect Ther. 2006;4: 187–197. doi: 10.1586/14787210.4.2.187 16597201

2. Brasil.http://www2.datasus.gov.br/DATASUS/index.php?area=0203&id=29892192&VObj=http://tabnet.datasus.gov.br/cgi/deftohtm.exe?sinannet/cnv/leishv. Portal de Saúde DATASUS, 2019.

3. De la Loma A, Alvar J, Galiano EM, Blázquez J, Muñoz AA, Nájera R. Leishmaniasis or AIDS? Trans R Soc Trop Med Hyg. 1985;79: 421–422. doi: 10.1016/0035-9203(85)90400-6 4035745

4. Alvar J, Aparicio P, Aseffa A, Den Boer M, Canavate C, Dedet JP, et al. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev. 2008;21: 334–359. doi: 10.1128/CMR.00061-07 18400800

5. Nicodemo EL, Duarte MIS, Corbett CEP, Nicodemo AC, Mata VLR, Chebabo R, et al. Visceral leishmaniasis in AIDS patient. Rev Inst Med Trop S Paulo. 1990;32: 310–311. doi: 10.1590/s0036-46651990000400013 2101526

6. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de DST/Aids e Hepatites Virais. Boletim Epidemiológico—Aids e DST. Ano V—nº 1—até semana epidemiológica 26ª. Brasília. 2016. http://bvsms.saude.gov.br/bvs/publicacoes/manual_recomendacoes_diagnostico_leishmania_hiv.pdf. [In Portuguese]

7. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Boletim Epidemiológico–HIV Aids. Vol. 49 –nº 53. Julho 2017 a Junho de 2018. Brasília. 2018. http://www.aids.gov.br/pt-br/pub/2018/boletim-epidemiologico-hivaids-2018. [In Portuguese]

8. de Souza CC, de Mata LRF, Azevedo C, Gomes CRG, Cruz GEC, Toffano SE. Interiorização do HIV/Aids no Brasil: Um estudo epidemiológico. Revista Brasileira de Ciências da Saúde. 2012. Ano 11. Nº 35:25–30. [In Portuguese]

9. Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE. 2012;7: e35671. doi: 10.1371/journal.pone.0035671 22693548

10. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância das Doenças Transmissíveis. Manual de recomendações para diagnóstico, tratamento e acompanhamento de pacientes com a coinfecção leishmania-HIV. Brasília: 1. ed., rev. e ampl. 2015. http://bvsms.saude.gov.br/bvs/publicacoes/manual_recomendacoes_diagnostico_leishmania_hiv.pdf [In Portuguese]

11. Barbosa IR, Neto RDS, Souza PP, Silva RA, Lima SR, Cruz ID, et al. Aspectos da coinfecção Leishmaniose Visceral e HIV no nordeste do Brasil. Rev. Baiana de Saúde Pública. 2013;37: 672–687. [In Portuguese]

12. Brasil. http://portalms.saude.gov.br/artigos/955-saude-de-a-a-z/leishmaniose-visceral/14190-orientacoes-para-uso-racional-do-medicamento-anfotericina-b-lipossomal. Ministério da Saúde, 2014.

13. Brasil. Ministério da Saúde. Secretaria de vigilância em saúde. Departamento de vigilância epidemiológica. Manual de vigilância e controle da leishmaniose visceral. 2014. Brasília. 1 ed. 5º reimpressão. http://bvsms.saude.gov.br/bvs/publicacoes/manual_vigilancia_controle_leishmaniose_visceral_1edicao.pdf [In Portuguese]

14. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Leishmaniose visceral grave: normas e condutas. Brasília. Editora do Ministério da Saúde, 2006. [In Portuguese]

15. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/Aids e das Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para Manejo da Infecção pelo HIV em Adultos. 2018. Brasília. 1 ed. http://www.aids.gov.br/pt-br/pub/2013/protocolo-clinico-e-diretrizes-terapeuticas-para-manejo-da-infeccao-pelo-hiv-em-adultos. [In Portuguese]

16. Alvar J, Canavate C, Gutiérrez-Solar B, Jiménez M, Laguna F, López-Vélez R et al. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev. 1997;2: 334–359.

17. Cruz I, Nieto J, Moreno J, Cañavate C, Desjeux P, Alvar J et al. Leishmania/HIV co-infections in the second decade. Indian J Med Res. 2006;123:357–388. 16778317

18. Lindoso JA, Cota GF, da Cruz AM, Goto H, Maia-Elkhoury AN, Romero GA, et al. Visceral leishmaniasis and HIV coinfection in Latin America. PLoS Negl Trop Dis. 2014;8: e3136. doi: 10.1371/journal.pntd.0003136 25233461

19. Luz JGG, Naves DB, Carvalho AG, Meira GA, Dias JVL, Fontes CJF. Visceral leishmaniasis in a Brazilian endemic area: an overview of occurrence, HIV coinfection and lethality. Journal of the São Paulo institute of tropical medicine. 2018: 60: e12. doi: 10.1590/S1678-9946201860012 29538509

20. Secretaria Estadual de Saúde do Maranhão. Departamento de Controle de Zoonoses. Programa de Vigilância e Controle da Leishmaniose. Situação epidemiológica da Leishmaniose Visceral e Tegumentar, no estado do Maranhão, 2007 a 2017. Maranhão. Estado do Maranhão. 2017 [In Portuguese]

21. Alexandrino-de-Oliveira P, Santos-Oliveira JR, Dorval ME, Da-Costa FD, Pereira GR, Cunha RV, et al. HIV/AIDS- associated visceral leishmaniasis in patients from na endemic área in central-west Brazil. Memórias do Instituto Oswaldo Cruz. 2010;105: 692–697. doi: 10.1590/s0074-02762010000500016 20835619

22. Hurissa Z, Gebre-Silassie S, Hailu W, Tefera T, Lallo DG, Cuevas LE et al. Clinical characteristics and treatment outcome of patients with visceral leishmaniasis and HIV co-infection in northwest Ethiopia. Trop Med Int Health. 2010;15: 848–855. doi: 10.1111/j.1365-3156.2010.02550.x 20487426

23. Alencar J. E. Leishmaniose visceral no Novo Mundo. Publ. méd., Rio de Janeiro. 1956; 196: 71–85. [In Portuguese]

24. Badaró R.; Carvalho E. M.; Orge M. G. O.; Teixeira R.; Rocha H. Imunidade humoral e celular em indivíduos curados de leishmaniose visceral. Rev. Soc. bras. Med. trop. 1985; 18: 77–83. [In Portuguese]

25. Bradley F. J. Genetics of resistence to infection with special reference to leishmaniasis. Introduction, and genetics of susceptibility to Leishmania donovani. Trans. roy. Soc. Trop. Med. Hyg.,1982; 76: 134–46.

26. Cota GF, de Sousa MR, de Sousa MR, de Mendonça ALP, Patrocinio A, Assunção LS, et al. Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil. PLoS Negl Trop Dis. 2014;8: e2816. doi: 10.1371/journal.pntd.0002816 24743472

27. Furtado AS, Nunes FBBF, Santos AM, Caldas AJM. Análise espaço-temporal da leishmaniose visceral no estado do Maranhão. Brasil. Ciências & Saúde Coletiva. 2015;20: 3935–3942. doi: 10.1590/1413-812320152012.01672015 [In Portuguese] 26691816

28. Maia- Elkhoury NA, Alves WA, Sousa-Gomes ML, Sena JM, Luna EA. Visceral leishmaniases in Brazil: Trends and challenges. Cad Saude Pública. 2008;24: 2941–2947. doi: 10.1590/s0102-311x2008001200024 19082286

29. Távora LGF, Nogueira MB and Gomes ST. Visceral leishmaniasis/HIV co-infection in northeast Brazil: evaluation of outcome. Braz J Infect Dis. 2015;20: 286–299. doi: 10.1016/j.bjid.2015.07.004 26361839

30. Henn GA, Ramos Junior AN, Colares JK, Mendes LP, Silveira JG, Lima AA, et al. Is visceral leishmaniasis the same in HIV-coinfected adults? Braz J Infect Dis. 2018;22: 92–98. doi: 10.1016/j.bjid.2018.03.001 29601790

31. Viana GMC, Neto da Silva MAC, Garcia JVS, Guimarães HD, Arcos Junior GF, Santos AVA et al. Epidemiological profile of patients co-infected with visceral leishmaniasis and HIV/AIDS in Northeast, Brazil. Rev Soc Bras Med Trop. 2017;50: 613–620. doi: 10.1590/0037-8682-0494-2017 29160507

32. Sousa-Gomes ML, Romero GAS, Werneck GL. Visceral leishmaniasis and HIV/AIDS in Brazil: Are we aware enough?. PLoS Negl Trop Dis. 2017. 11:9. doi: e0005772 28945816

33. Pintado V, Martin-Rabadan P, Rivera ML, Moreno S, Bouza E. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine. 2001. 80;1: 54–73. doi: 10.1097/00005792-200101000-00006 11204503.

34. Graepp Fontoura I, Soeiro Barbosa D, Paes AMA, Santos FS, Santos Neto M, Fontoura VM, et al. Epidemiological, clinical and laboratory aspects of human visceral leishmaniasis (HVL) associated with human immunodeficiency vírus (HIV) coinfection: a systematic review. Parasitology. 2018; 1–17. doi: 10.1017/S003118201800080X 29806575

35. Lindoso JAL, Moreira CHV, Cunha MA, Queiroz IT. Visceral leishmaniasis and HIV coinfection: current perspectives. Dove Press journal: HIV/AIDS–Research and Palliative Care. 2018:10:193–201.

36. Grossman V, Herberman RB. T-cell homeostasis in HIV infection is neither failing nor blind: modified cell counts reflect an adaptive response of the host. Nat Med. 1997;3: 486–490. doi: 10.1038/nm0597-486 9142108

37. Varma N, Naseen S. Hematologic changes in visceral leishmaniasis/Kala Azar. Indian J Hematol Blood Transfus. 2010;26: 78–82. doi: 10.1007/s12288-010-0027-1 21886387

38. Mahajan R, Das P, Isaakidis P, Sunyoto T, Sagili KD, Lima MA, et al. Combination treatment for visceral leishmaniasis patients coinfected with human immunodeficiency virus in India. Clin Infect Dis. 2015;8: 1255–1262. doi: 10.1093/cid/civ530 26129756

39. Sinha PK, van Griensven J, Pandey K, Kumar N, Verma N, Mahajan R, et al. Lipossomal amphotericin B for visceral leishmaniasis in human immunodeficiency virus-coinfected patients: 2-year treatment outcomes in Bihar, India. Clin Infect Dis. 2015;53: e91–e98. doi: 10.1093/cid/cir521 21890763

40. Lima IP, ller MC, Holanda TA, Harhay M, Costa CH, Costa DL. Human immunodeficiency virus/Leishmania infantum in the first foci of urban American Visceral leishmaniasis: clinical presentation from 1994 to 2010. Rev Soc Bras Med Trop. 2013; 46: 156–160. doi: 10.1590/0037-8682-0033-2012 23666663

41. de Sousa GF, Biscione F, Greco DB and Rabelo A. Slow clinical improvement after treatment initiation in Leishmania/HIV coinfected patients. Rev Soc Bras Med Trop. 2012;45: 147–150. doi: 10.1590/s0037-86822012000200001 22534981

42. Bourgeois N, Lachaud L, Reynes J, Rouanet I, Mahamat A, Bastien P. Long term monitoring of visceral leishmaniasis in patients with AIDS. J Acquir Immune Defic Syndr. 2008;48: 13–19. e0005772. doi: 10.1097/QAI.0b013e318166af5d 18300698

43. Diro E, Lynen L, Mohammed R, Boelaert M, Hailu A, van Griensven J. High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia. PLoS Negl Trop Dis. 2014;8: e2875. doi: 10.1371/journal.pntd.0002875 24854196

44. Auyeung P, French MA. Hollingsworth PN. Immune restoration disease associated with Leishmania donovani infection following antiretroviral therapy for HIV infection. J Microbiol Immunol Infect. 2010;43:1:74–76. doi: 10.1016/S1684-1182(10)60011-4 20434127

45. Albuquerque LC, Mendonça IR, Cardoso PN, Baldaçara LR, Borges MR, Borges JD, et al. AIHIV/DS—related visceral leishmaniasis: a clinical and epidemiological descrition. Rev Soc Bras Med Trop. 2014;47: 38–46. doi: 10.1590/0037-8682-0180-2013 24603735

46. Meyerhoff A. US Food and drug administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clin Infect Dis. 1999;28: 42–8. doi: 10.1086/515085 10028069

47. Oliveira EN, Pimenta AM. Perfil epidemiológico das pessoas portadoras de leishmaniose visceral no município de Paracatu- MG no período de 2007 a 2010. Rev Min Enferm. 2014;18: 365–370. doi: 10.5935/1415-2762.20140028 [In Portuguese]


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2019 Číslo 12