Over 3,000 yearly cases of Visceral Leishmaniasis (VL) are reported in Brazil. Brazilian Public Health System provides universal free access to antileishmania therapeutic options: Meglumine Antimoniate, Amphotericin B deoxycholate, and Liposomal Amphotericin B. Even though Amphotericin formulations have been advised for severe disease, this recommendation is mostly based on the opinion of experts and on analogy with studies conducted in other countries. Presently, there are two ongoing multicenter clinical trials comparing the efficacy and safety of the available therapeutic options. Some other issues require further clarification, such as severity markers and the approach to VL/AIDS coinfection. Brazil is facing the challenge of providing access to diagnosis and adequate treatment, in order to avoid VL-related deaths. 1. Introduction In the second decade of the 21st century, visceral leishmaniasis (VL) continues to challenge public health authorities around the world. The World Health Organization (WHO) estimates yearly incidence of 500,000 cases, with a case-fatality ratio of approximately 10% [1, 2]. This picture is especially worrisome for the six countries that harbor 90% of VL cases: India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil [1, 3]. Leishmania infantum chagasi is the agent of VL in Latin America. At least twelve Countries in the continent reported VL cases in the past decade. Brazil is by far the most affected country, with more than 3,000 reported cases per year and case-fatality ratio of 5.8% in the period from 2005 through 2009 [4]. Brazilian picture is worsened by the progressive territorial expansion and urbanization of LV. Up to the early 1980s, the disease was mainly restricted to rural areas in Northeastern Brazil [5]. In the turn of that decade, urban foci of VL were reported in major cities in that region. A southward expansion was also noticed, and the proportion of cases reported outside northeast region increased from 15% in 1998 to 44% in 2005 [6]. The changing epidemiology of visceral leishmaniasis posed new challenges for health protection of the residents of the affected areas. In the first place, there is the difficulty of prevention. Measures directed to the canine reservoirs (dog culling, vaccination) or to the vector (environmental intervention, insect repellents) are often impractical in large urban centers. Besides, they were not proved to be definitely effective [7, 8]. Another challenge concerns the management (including therapy) of VL cases. This is a relevant issue, since case-fatality ratio is
References
[1]
World Health Orgazination, “Leishmaniasis: epidemiology and access to medicines？an update based on the outcomes of WHO regional meetings, literature review and experts' opinion, Geneve (WHO),” 2012, http://www.who.int/leishmaniasis/resources/Leishmaniasis_worldwide_epidemiological_and_drug_access_update.pdf.
[2]
F. Chappuis, S. Sundar, A. Hailu et al., “Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?” Nature Reviews Microbiology, vol. 5, no. 11, pp. 873–882, 2007.
[3]
J. Alvar J, I. D. Vélez, C. Bern C et al., “Leishmaniasis worldwide and global estimates of its incidence,” PLoS One, vol. 7, no. 5, Article ID e35671, 2012.
[4]
D. M. Pelissari, M. P. Cechinel, M. L. Souza-Gomes, and F. E. Lima Junior, “Tratamento da leishmaniose visceral e tegumentar americana no Brasil,” Epidemiologia e Servi？os de Saúde, vol. 20, no. 1, pp. 107–110, 2011.
[5]
A. N. S. Maia-Elkhoury, W. A. Alves, M. L. De Sousa-Gomes, J. M. De Sena, and E. A. Luna, “Visceral leishmaniasis in Brazil: trends and challenges,” Cadernos de Saúde Publica, vol. 24, no. 12, pp. 2941–2947, 2008.
[6]
M. O. Harhay, P. L. Olliaro, D. L. Costa, and C. H. N. Costa, “Urban parasitology: visceral leishmaniasis in Brazil,” Trends in Parasitology, vol. 27, no. 9, pp. 403–409, 2011.
[7]
C. H. Costa, C. M. Tapety, and G. L. Werneck, “Controle da leishmaniose visceral em meio urbano: estudo de interven？？o randomizado fatorial,” Revista da Sociedade Brasileira de Medicina Tropical, vol. 40, no. 4, pp. 415–419, 2007.
[8]
G. A. S. Romero and M. Boelaert, “Control of visceral leishmaniasis in latin America—a systematic review,” PLoS Neglected Tropical Diseases, vol. 4, no. 1, Article ID e584, 2010.
[9]
Centro de vigilancia epidemiológica da secretaria de estado da saúde de s？o paulo, “Leishmaniose visceral Americana: dados estatísticos,” 2013, http://www.cve.saude.sp.gov.br/htm/zoo/leishv_dados.html.
[10]
G. Madalosso, C. M. Fortaleza, A. F. Ribeiro, L. L. Cruz, P. A. Nogueira, and J. A. Lindoso, “American visceral leishmaniasis: factors associated with lethality in the state of s？o paulo, Brazil,” Journal of Tropical Medicine, vol. 2012, Article ID 281572, 7 pages, 2012.
[11]
A. Kocyigit, S. Gur, M. S. Gurel, V. Bulut, and M. Ulukanligil, “Antimonial therapy induces circulating proinflammatory cytokines in patients with cutaneous leishmaniasis,” Infection and Immunity, vol. 70, no. 12, pp. 6589–6591, 2002.
[12]
M. I. Muniz-Junqueira and V. N. de Paula-Coelho, “Meglumine antimonate directly increases phagocytosis, superoxide anion and TNF-α production, but only via TNF-α it indirectly increases nitric oxide production by phagocytes of healthy individuals, in vitro,” International Immunopharmacology, vol. 8, no. 12, pp. 1633–1638, 2008.
[13]
R. R. de Saldanha, M. C. Martins-Papa, R. N. Sampaio, and M. I. Muniz-Junqueira, “Meglumine antimonate treatment enhances phagocytosis and TNF-α production by monocytes in human cutaneous leishmaniasis,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 106, no. 10, pp. 596–603, 2012.
[14]
S. Mondal, P. Bhattacharya, and N. Ali, “Current diagnosis and treatment of visceral leishmaniasis,” Expert Review of Anti-Infective Therapy, vol. 8, no. 8, pp. 919–944, 2010.
[15]
Y. M. Brustoloni, R. V. Cunha, L. Z. C？nsolo, A. L. L. Oliveira, M. E. C. Dorval, and E. T. Oshiro, “Treatment of visceral leishmaniasis in children in the central-west region of Brazil,” Infection, vol. 38, no. 4, pp. 261–267, 2010.
[16]
A. L. L. De Oliveira, Y. M. Brustoloni, T. D. Fernandes, M. E. C. Dorval, R. V. Da Cunha, and M. N. Bóia, “Severe adverse reactions to meglumine antimoniate in the treatment of visceral leishmaniasis: a report of 13 cases in the southwestern region of Brazil,” Tropical Doctor, vol. 39, no. 3, pp. 180–182, 2009.
[17]
Ministério Da Saúde, Secretaria De Vigilancia Em Saúde, Manual De Vigilancia E Controle Da Leishmaniose Visceral, Departamento De Vigilancia Epidemiológica, Brasília, Brazil, 2006.
[18]
G. F. Cota, M. R. de Sousa, T. O. Fereguetti, and A. Rabello, “Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison,” PLoS Neglected Tropical Diseases, vol. 7, no. 5, Article ID e2195, 2013.
[19]
H. W. Murray, “Progress in the treatment of a neglected infectious disease: visceral leishmaniasis,” Expert Review of Anti-Infective Therapy, vol. 2, no. 2, pp. 279–292, 2004.
[20]
W. R. Cuna, R. Velasquez, J. Riva, I. Guachalla, and C. Rodríguez, “Enhancement of a TH1 immune response in amphotericin B-treated mucocutaneous leishmaniasis,” Journal of Biomedicine and Biotechnology, vol. 2007, Article ID 96410, 4 pages, 2007.
[21]
S. Kumar and R. Chakrabarti, “Amphotericin B both inhibits and enhances T-cell proliferation: inhibitory effect is mediated through H2O2 production via cyclooxygenase pathway by macrophages,” Journal of Cellular Biochemistry, vol. 77, no. 3, pp. 361–371, 2000.
[22]
T. Ehrenfreund-Kleinman, A. J. Domb, C. L. Jaffe, A. Nasereddin, B. Leshem, and J. Golenser, “The effect of amphotericin B derivatives on Leishmania and immune functions,” Journal of Parasitology, vol. 91, no. 1, pp. 158–163, 2005.
[23]
S. Sundar and M. Chatterjee, “Visceral leishmaniasis—current therapeutic modalities,” Indian Journal of Medical Research, vol. 123, no. 3, pp. 345–352, 2006.
[24]
Ministério Da Saúde, Secretaria De Vigilancia Em Saúde, Leishmaniose Visceral : RecomenDa？？es Clínicas Para Redu？？o Da letalidade, Departamento De Vigilancia Epidemiológica, Brasília, Brazil, 2011.
[25]
Ministério Da Saúde, Secretaria De Vigilancia Em Saúde, Novo Protocolo de Tratamento Para a Leishmaniose Visceral, Departamento De Vigilancia Epidemiológica, Brasília, Brazil, 2013.
[26]
C. Cifani, S. Costantino, and M. Massi L Berrino, “Commercially available lipid formulations of amphotericin b: are they bioequivalent and therapeutically equivalent?” Acta Biomedica, vol. 83, no. 2, pp. 154–163, 2012.
[27]
A. H. Mohamed-Ahmed, S. Brocchini, and S. L. Croft, “Recent advances in development of amphotericin B formulations for the treatment of visceral leishmaniasis,” Current Opinion in Infectous Diseases, vol. 25, no. 6, pp. 695–702, 2012.
[28]
S. Sundar, J. Chakravarty, D. Agarwal, M. Rai, and H. W. Murray, “Single-dose liposomal amphotericin B for visceral leishmaniasis in India,” The New England Journal of Medicine, vol. 362, no. 6, pp. 504–512, 2010.
[29]
S. Sundar and J. Chakravarty, “Leishmaniasis: an update of current pharmacotherapy,” Expert Opinion in Pharmacotherapy, vol. 14, no. 1, pp. 53–63, 2013.
[30]
M. Balasegaram, K. Ritmeijer, M. A. Lima et al., “Liposomal amphotericin B as a treatment for human leishmaniasis,” Expert Opinion on Emerging Drugs, vol. 17, no. 4, pp. 493–510, 2012.
[31]
S？o Paulo (Estado), Secretaria de Estado da Saúde, Superintendência de Controle de Endemias—SUCEN e Coordenadoria de Controle de Doen？as, “Manual de Vigilancia e Controle da Leishmaniose Visceral Americana do Estado de S？o Paulo,” Secretaria de Saúde, S？o Paulo, Brazil, 2006.
[32]
V. Vanlerberghe, G. Diap, P. J. Guerin et al., “Drug policy for visceral leishmaniasis: a cost-effectiveness analysis,” Tropical Medicine and International Health, vol. 12, no. 2, pp. 274–283, 2007.
[33]
P. L. Olliaro, P. J. Guerin, S. Gerstl, A. A. Haaskjold, J. A. Rottingen, and S. Sundar, “Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980–2004,” Lancet Infectious Diseases, vol. 5, no. 12, pp. 763–774, 2005.
[34]
G. L. Werneck, M. S. A. Batista, J. R. B. Gomes, D. L. Costa, and C. H. N. Costa, “Prognostic factors for death from visceral leishmaniasis in Teresina, Brazil,” Infection, vol. 31, no. 3, pp. 174–177, 2003.
[35]
M. J. A. D. Q. Sampaio, N. V. Cavalcanti, J. G. B. Alves, M. J. C. F. Filho, and J. B. Correia, “Risk factors for death in children with visceral leishmaniasis,” PLoS Neglected Tropical Diseases, vol. 4, no. 11, Article ID e877, 2010.
[36]
V. E. M. de Araújo, M. H. F. Morais, I. A. Reis, A. Rabello, and M. Carneiro, “Early clinical manifestations associated with death from visceral leishmaniasis,” PLoS Neglected Tropical Diseases, vol. 6, no. 2, Article ID e1511, 2012.
[37]
A. Rabello, M. Orsini, and J. Disch, “Leishmania/HIV co-infection in Brazil: an appraisal,” Annals of Tropical Medicine and Parasitology, vol. 97, supplement 1, pp. 17–28, 2003.
[38]
J. Alvar, P. Aparicio, A. Aseffa et al., “The relationship between leishmaniasis and AIDS: the second 10 years,” Clinical Microbiology Reviews, vol. 21, no. 2, pp. 334–359, 2008.
[39]
M. L. Souza-Gomes, A. N. Maia-Elkhoury, D. M. Pelissari, F. E. Lima Junior, J. M. Sena, and M. P. Cechinel, “Coinfec？？o Leishmania-HIV no Brasil: aspectos epidemiológicos, clínicos e laboratoriais,” Epidemiologia e Servi？os de Saúde, vol. 20, no. 4, pp. 519–526, 2011.
[40]
J. N. Jarvis and D. N. Lockwood, “Clinical aspects of visceral leishmaniasis in HIV infection,” Current Opinion in Infectious Diseases, vol. 26, no. 1, pp. 1–9, 2013.
[41]
E. F. Daher, P. P. Fonseca, E. S. Gerhard, T. M. J. Silva Leit？o, and G. B. Silva Júnior, “Clinical and epidemiological features of visceral leishmaniasis and HIV co-infection in fifteen patients from Brazil,” Journal of Parasitology, vol. 95, no. 3, pp. 652–655, 2009.
[42]
G. F. Cota, M. R. de Sousa, and A. Rabello, “Predictors of visceral leishmaniasis relapse in HIV-infected patients: a systematic review,” PLoS Neglected Tropical Diseases, vol. 5, no. 6, Article ID e1153, 2011.
[43]
P. J. Flaer and M. Z. Younis, “The Brazilian experiment: HIV drugs for all,” Journal of Health Care Finance, vol. 36, no. 2, pp. 90–96, 2009.
[44]
J. van Griensven, M. Balasegaram, F. Meheus, J. Alvar, L. Lynen, and M. Boelaert, “Combination therapy for visceral leishmaniasis,” The Lancet Infectious Diseases, vol. 10, no. 3, pp. 184–194, 2010.
