Forum: geographic spread and urbanization of visceral leishmaniasis in Brazil. Postscript: new challenges in the epidemiology of Leishmania chagasi infection

Fórum: expansão geográfica e urbanização da leishmaniose visceral no Brasil. Posfácio: novos desafios na epidemiologia da infecção por Leishmania chagasi

FÓRUM FORUM

Forum: geographic spread and urbanization of visceral leishmaniasis in Brazil. Postscript: new challenges in the epidemiology of Leishmania chagasi infection

Fórum: expansão geográfica e urbanização da leishmaniose visceral no Brasil. Posfácio: novos desafios na epidemiologia da infecção por Leishmania chagasi

Eliana L. T. Nascimento^I; Daniella R. Martins^II; Glória R. Monteiro^II; James D. Barbosa^II; Maria F. F. M. Ximenes^II; Bruna L. Maciel^II; Iraci Duarte^III; Selma M. B. Jerônimo^II

^ICentro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, Brasil

^IICentro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, Brasil

^IIIFundação Nacional de Saúde, Ministério da Saúde, Natal, Brasil

^{Correspondence}

Visceral leishmaniasis is a disease that reemerged in various locations in Brazil in the 1980s and spread to new areas, including the Southeast and Central-West of the country. Previously, visceral leishmaniasis was a disease that occurred in rural areas of the Northeast, mainly affecting children ¹. However, most cases of visceral leishmaniasis now come from periurban areas of cities in Northeast, Central-West, and Southeast Brazil ^2,3,4.

The articles in this Forum ^5,6,7,8 discuss key aspects related to the urbanization of visceral leishmaniasis in Brazil, including new approaches to deal with the disease and conditioning factors for the vector's capacity to transmit Leishmania. The complexity of vector and reservoir control is identified as a factor that hinders the management of visceral leishmaniasis in the country. The Forum proposes a new discussion and reassessment of current intervention measures. The latter focus on culling dogs infected with Leishmania and residual-action pesticide spraying, but these measures are normally implemented after human cases of visceral leishmaniasis have already been identified, often long after the occurrence of Leishmania infection, due mainly to its long incubation period ^9,10. Still, as commented in the article by Maia-Elkhoury et al. ⁵, the regularity of these intervention measures can have an impact with a reduction of up to 39% in Leishmania infection in humans, according to studies by the Brazilian Ministry of Health.

The peri-urbanization of visceral leishmaniasis in Belo Horizonte, presented by Oliveira et al. ⁶ as an example of this process in Brazil, was similar to that observed in the Northeast, with subsequent spread to other cities in the Southeast and Central-West. It is worrisome that these endemic areas have a high population density, thus placing the population at increased risk of infection.

Dogs have traditionally been considered the principal reservoirs of Leishmania chagasi in periurban areas ¹¹. Canine visceral leishmaniasis generally precedes human disease in these new areas ⁴. This was demonstrated in the visceral leishmaniasis epidemic in Araçatuba, São Paulo State ^12,13. Studies in the State of Rio Grande do Norte show a 32.6% Leishmania infection rate in dogs in an endemic area on the outskirts of the State capital Natal, with a 30% six-month seroconversion rate in these animals. Asymptomatic Leishmania infection in humans is also high, with 24.6% of individuals presenting anti-Leishmania antibodies and 38.6% of these showing a positive delayed hypersensitivity skin test to Leishmania antigens ¹⁴.

The high asymptomatic Leishmania infection rate in humans, as observed in Rio Grande do Norte, shows that visceral leishmaniasis is only the lesser component in the process, and that asymptomatic infection is more frequent. The role of asymptomatic Leishmania infection in humans and canines has still not been fully elucidated within the Leishmania transmission chain, and further studies are needed to better document and evaluate the impact of silent infection in maintaining the endemicity. This fact is a cause for concern, especially considering the endemization of visceral leishmaniasis in major peri-metropolitan areas of Brazil. Thus, studies are also needed to assess the role of asymptomatic Leishmania infection on blood and organ donations, since these procedures are currently widespread in cities that are endemic for visceral leishmaniasis and that present a high asymptomatic Leishmania infection rate. The development of post-transplantation visceral leishmaniasis has been documented in Europe, although the numbers are not high ¹⁵. The magnitude of asymptomatic Leishmania infection in Brazil may also result in a change in the epidemiological profile of visceral leishmaniasis. Given the panorama presented here, one can predict that more cases of visceral leishmaniasis associated with immune suppression will occur, involving greater severity and more complex treatment management, as observed in Europe ^16,17,18.

The control of dogs infected with Leishmania is difficult, as discussed in the article by Oliveira et al. ⁶. When dogs are culled, they are promptly replaced with others, and the act of culling is controversial and not always readily accepted by the population ¹⁹. It has been demonstrated in various places around the world ²⁰ that cypermethrin-impregnated dog collars are effective repellants against the visceral leishmaniasis vector, but the strategy is costly given that only a small portion of the population can afford this control method.

Lutzomyia longipalpis is the principal vector for L. chagasi in Brazil and elsewhere in Latin America ²¹. Rangel et al. ⁷ reviewed the conditioning factors for the vectorial competence of Lu. longipalpis in transmitting L. chagasi in Brazil and its adaptation to periurban areas. This vector has highly eclectic eating habits and adapts easily to peridomiciliary conditions ^22,23. Lu. longipalpis is most active from 7:00 to 11:00 PM ²², when most residents are normally inside or around their homes. These observations back the hypothesis that infections normally occur indoors or in the peridomicile. Meanwhile, we demonstrate that Leishmania infection in humans is found in all age brackets and equally in both sexes, although men develop visceral leishmaniasis more frequently than women ²⁴, thus reinforcing the hypothesis that Leishmania infection occurs in the domestic environment.

The adaptation of Leishmania vectors to periurban areas and their spread to new areas in Latin America expand the endemic leishmaniasis regions, with increased risk of infection. Leishmania infection is now found in northern Argentina and Paraguay ^25,26. Visceral leishmaniasis control measures in other countries have also been associated with vector control. The use of residual DDT in India to control malaria vectors resulted in a significant decrease in cases of visceral leishmaniasis ^27,28, indicating that effective vector control can be achieved. However, it is necessary to develop new insecticides and control the spraying areas with monitoring and evaluation of their efficacy, as discussed in the article by Costa ⁸.

Visceral leishmaniasis control also involves community education in risk areas, teaching measures to avoid producing areas that favor the development of phlebotomine sand files in backyards and in the vicinity of homes. The identification of spatial clusters of human and canine visceral leishmaniasis in Teresina, Piauí, led to the identification of focal areas at risk of Leishmania infection, thereby facilitating the definition of areas to undergo specific interventions ^29,30. However, the decentralization of epidemiological surveillance and visceral leishmaniasis control activities to the municipalities could be an additional complicating factor, due to deficiencies in infrastructure at the local level for dealing with the problem's complexity. On-going joint work between the Ministry of Health and the Brazilian scientific community can assist in the understanding and development of new strategies to deal with visceral leishmaniasis, including educational measures, especially considering that no anti-Leishmania vaccine will be available in the short term.

Contributors

All the authors contributed equally to the article.

Acknowledgements

The authors wish to thank Prof. Dulce Almeida (Department of Microbiology and Parasitology, Federal University in Rio Grande do Norte), for reviewing the manuscript.

Submitted on 06/Mar/2008

Final version resubmitted on 12/Jun/2008

Approved on 16/Jun/2008

• 1. Jeronimo SM, Souza AQ, Pearson RD. Leishmaniasis. In: Goldman L, Ausielo D, editors. Cecil Textbook of Medicine. Philadelphia: W. B. Saunders; 2004. p. 2082-8.
• 2. Costa CH, Pereira HF, Araujo MV. Epidemia de leishmaniose visceral no Estado do Piauí, Brasil, 1980-1986. Rev Saúde Pública 1990; 24:361-72.
• 3. Jeronimo SM, Oliveira RM, Mackay S, Costa RM, Sweet J, Nascimento ET, et al. An urban outbreak of visceral leishmaniasis in Natal, Brazil. Trans R Soc Trop Med Hyg 1994; 88:386-8.
• 4. Silva ES, Gontijo CM, Pacheco RS, Fiuza VO, Brazil RP. Visceral leishmaniasis in the Metropolitan Region of Belo Horizonte, State of Minas Gerais, Brazil. Mem Inst Oswaldo Cruz 2001; 96:285-91.
• 5. Maia-Elkhoury ANS, Alves WA, Sousa-Gomes ML, Sena JM, Luna EA. Visceral leishmaniasis in Brazil: trends and challenges. Cad Saúde Pública 2008; 24:2941-7.
• 6. Oliveira CDL, Morais MHF, Machado-Coelho GLL. Visceral leishmaniasis in large Brazilian cities: challenges for control. Cad Saúde Pública 2008; 24:2953-8.
• 7. Rangel EF, Vilela ML. Lutzomyia longipalpis (Diptera, Psychodidade, Phlebotominae) and urbanization of visceral leishmaniasis in Brazil. Cad Saúde Pública 2008; 24:2948-52.
• 8. Costa CHN. Characterization and speculations on the urbanization of visceral leishmaniasis in Brazil. Cad Saúde Pública 2008; 24:2959-63.
• 9. Evans TG, Teixeira MJ, McAuliffe IT, Vasconcelos I, Vasconcelos AW, Sousa AA, et al. Epidemiology of visceral leishmaniasis in northeast Brazil. J Infect Dis 1992; 166:1124-32.
• 10. Evans TG, Teixeira MJ, Sousa AQ, Pearson RD. Short report: extended follow-up of the natural history of persons infected with Leishmania chagasi Am J Trop Med Hyg 1995; 53:360-1.
• 11. Moreira Jr. ED, Souza VM, Sreenivasan M, Lopes NL, Barreto RB, Carvalho LP. Peridomestic risk factors for canine leishmaniasis in urban dwellings: new findings from a prospective study in Brazil. Am J Trop Med Hyg 2003; 69:393-7.
• 12. Andrade AM, Queiroz LH, Perri SHV, Nunes CM. Estudo descritivo da estrutura populacional canina da área urbana de Araçatuba, São Paulo, Brasil, no período de 1994 a 2004. Cad Saúde Pública 2008; 24:927-32.
• 13. Barão SC, Camargo-Neves VLF, Resende MR, Silva LJ. Human asymptomatic infection in visceral leishmaniasis: a seroprevalence study in an urban area of low endemicity. Preliminary results. Am J Trop Med Hyg 2007; 77:1051-3.
• 14. Duarte I, Queiroz JW, Pontes NN, Cabral A, Maciel BL, Araujo SF, et al. Changing natural history of Leishmania chagasi infection in Brazil: the magnitude of the asymptomatic infection and potential for cyclic epidemic of visceral leishmaniasis. Emerg Infect Dis; Submitted.
• 15. Antinori S, Cascio A, Parravicini C, Bianchi R, Corbellino M. Leishmaniasis among organ transplant recipients. Lancet Infect Dis 2008; 8:191-9.
• 16. Weisser M, Khanlari B, Terracciano L, Arber C, Gratwohl A, Bassetti S, et al. Visceral leishmaniasis: a threat to immunocompromised patients in non-endemic areas? Clin Microbiol Infect 2007; 13: 751-3.
• 17. Mannocci A, La Torre G, Chiaradia G, De Waure C, Mainelli MT, Cernigliaro A, et al. Epidemiology and direct medical costs of human leishmaniasis in Italy. J Prev Med Hyg 2007; 48:27-36.
• 18. Cruz I, Nieto J, Moreno J, Cañavate C, Desjeux P, Alvar J. Leishmania/HIV co-infections in the second decade. Indian J Med Res 2006; 123:357-88.
• 19. Nunes CM, Lima VM, Paula HN, Perri SH, Andrade AM, Dias FE, et al. Dog culling and replacement in an area endemic for visceral leishmaniasis in Brazil. Vet Parasitol 2008; 153:19-23.
• 20. Killick-Kendrick R, Killick-Kendrick M, Focheux C, Dereure J, Puech MP, Cadiergues MC. Protection of dogs from bites of phlebotomine sandflies by deltamethrin collars for control of canine leishmaniasis. Med Vet Entomol 1997; 11:105-11.
• 21. Lainson R, Rangel EF. Lutzomyia longipalpis and the eco-epidemiology of American visceral leishmaniasis, with particular reference to Brazil: a review. Mem Inst Oswaldo Cruz 2005; 100:811-27.
• 22. Ximenes MF, Castellón EG, Souza MF, Menezes AA, Queiroz JW, Silva VP, et al. Effect of abiotic factors on seasonal population dynamics of Lutzomyia longipalpis (Diptera: Psychodidae) in northeastern Brazil. J Med Entomol 2006; 43:990-5.
• 23. Ximenes MF, Silva VP, Queiroz PV, Rego MM, Cortez AM, Batista LM, et al. Phlebotomine (Diptera: Psychodidae) and leishmaniasis in Rio Grande do Norte State Brazil: anthropic environment responses. Neotrop Entomol 2007; 36:128-37.
• 24. Jeronimo SM, Duggal P, Braz RF, Cheng C, Monteiro GR, Nascimento ET, et al. An emerging peri-urban pattern of infection with Leishmania chagasi, the protozoan causing visceral leishmaniasis in northeast Brazil. Scand J Infect Dis 2004; 36:443-9.
• 25. Córdoba-Lanús E, De Grosso ML, Piñero JE, Valladares B, Salomón OD. Natural infection of Lutzomyia neivai with Leishmania spp. in northwestern Argentina. Acta Trop 2006; 98:1-5.
• 26. Salomon OD, Orellano PW. Lutzomyia longipalpis in Clorinda, Formosa province, an area of potential visceral leishmaniasis transmission in Argentina. Mem Inst Oswaldo Cruz 2005; 100:475-6.
• 27. Birley MH. An historical review of malaria, kala-azar and filariasis in Bangladesh in relation to the Flood Action Plan. Ann Trop Med Parasitol 1993; 87:319-34.
• 28. Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, et al. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2002; 2:494-501.
• 29. Werneck GL, Costa CH, Walker AM, David JR, Wand M, Maguire JH. The urban spread of visceral leishmaniasis: clues from spatial analysis. Epidemiology 2002; 13:364-7.
• 30. Werneck GL, Costa CH, Walker AM, David JR, Wand M, Maguire JH. Multilevel modeling of the incidence of visceral leishmaniasis in Teresina, Brazil. Epidemiol Infect 2007; 135:195-201.

Publication Dates

• Publication in this collection
  09 Dec 2008
• Date of issue
  Dec 2008

History

• Accepted
  16 June 2008
• Reviewed
  12 June 2008
• Received
  06 Mar 2008