Canine Visceral Leishmaniasis (CVL) is a chronic and potentially fatal systemic disease caused by the digenetic protozoan Leishmania sp. Nicolle (1908) first reported dogs as the reservoir of human infection after he studied cases in Tunisia, where the human disease was clinically similar to the Indian kala-azar. He proposed the term Leishmania infantum as the etiological agent because the disease was diagnosed only in children under five years old. CVL is caused by Leishmania infantum, or its New World synonym Leishmania chagasi, in various regions of America, Europe, Asia and Africa (Deane, 1956; Desjeux, 2004). The prevalence of CVL is usually determined by seroepidemiological surveys using ELISA, Immunofluorescent (IFA), Direct Agglutination test (DAT), Western blotting and Immunochromatography. However, these serological techniques are limited by cross-reactivity with other parasitic diseases and have not been standardized (Ferreira et al. 2007). Early serological studies in Brazil showed lower prevalences: 1.9-3.9% in Ceará; 6.6-18.4% in Bahia. However, more recent studies have shown a dramatic increase in the seroprevalence of CVL: 21-26% in Fortaleza; 72-79% in Natal; 42% in Araçatuba; 73% (epizootia) in Mato Grosso. The infection is also highly prevalent in Mediterranean countries, e.g., 22% in Greece, 12-26% in Turkey and 22-30% in Italy; and in South America countries, e.g., 27.3% in Venezuela (Rondon et al. 2008). PCR studies in endemic areas have confirmed that many more dogs have the infection than actually develop symptomatic disease (Gomes et al. 2007). In fact, in a study in Spain, the prevalence of infection detected rose from 13-26% to 67% after PCR analysis (Solano-Gallego et al. 2001). In Greece, in a study of 73 clinically healthy hunting dogs, 63% were positive by PCR; in contrast, 12.3% tested positive when only serological tests were used (Leontides et al. 2002). Thus, it is much more common for dogs to be infected than actually to develop the disease. Studies in Brazil have indicated frequencies of asymptomatic seropositive animals such as 85.3% in Pernambuco; 32.4% in Minas Gerais; and 83.3% in Rio Grande do Norte (Queiroz et al. 2009). Findings from other countries are comparable, e.g., 30% in Spain (Fisa et al. 1999).
Two major concepts have arisen from epidemiological research in areas where CVL is endemic: 1) infection in the canine population is widespread, and the number of infected dogs is much higher than the number showing clinical illness; 2) infection spreads quickly and extensively among the dog population when environmental conditions for transmission are optimal. However, CVL must also be considered in nonendemic regions where the canine disease is often diagnosed, for instance in northern European countries such as Holland, Germany and the UK (Baneth et al. 2008). In Brazil, the year 1981 witnessed the beginning of urbanization of Human Visceral Leishmaniasis (HVL) in Teresina, Piauí. During the 1980s, epidemics occurred in other large Brazilian cities such as Natal, Belo Horizonte, Campo Grande, Aracaju, Araçatuba, Palmas, and more recently Fortaleza, Brasília (Federal District) and Piracicaba (Costa et al. 2008). In the city of Teresina, multilevel modeling of the disease outbreak has shown that low socioeconomic status (poverty) and increased vegetation amplify the association between canine infection and human disease (Werneck et al. 2007). In the city of Belo Horizonte, 84% of the human cases were correlated with canine infection, and almost 70% of all human and canine cases were detected at high altitudes (780-880m above sea level), where the density of the sand-fly vector Lutzomyia longipalpis is high (Margonari et al. 2006). In Europe, Acedo Sanchez et al. (1996) and Papadoupolou et al. (2005) described a related pattern in Spain and Greece, respectively. So what methods of intervention should be used for control of CVL? One approach used to reduce the incidence of HVL in Brazil is to cull infected dogs. However, killing infected dogs that are pets would be unacceptable--such dogs are considered part of the family--and its effectiveness in controlling infection is controversial (Moreira et al. 2004). In fact, the impact of dog-culling programs is low because replacement ensures a high turnover of dogs, and this has been shown to create a large new population of younger dogs susceptible to Leishmania infection. In addition, the lack of continuity, other visceral leishmaniasis reservoirs, persistence of false negative dogs and delay in culling the seropositive dogs must be also considered (Miró et al. 2008). The other proposed measure for controlling visceral leishmaniasis is vector control. However, it is expensive, operationally more complex, and requires more human resources and inputs. New control measures like deltamethrin-impregnated dog collars have proven to be effective for protecting dogs against a sand fly bite, but it is costly and difficult to monitor for use as public health control measures. Moreover, deltamethrin collars are an important measure for individual prevention since they act as an effective vector repellant (Oliveira et al. 2008). On the other hand, current treatment of CVL is still based on drugs that do not eliminate the infection and improve clinical signs only temporarily (Noli & Auxilia et al. 2005). An effective vaccine could prevent the disease in dogs and this might constitute a major strategy for controlling CVL. There are four classes of candidates (Miró et al. 2008): 1) Killed Leishmania vaccines consisting of inactivated promastigotes. 2) Three purified Leishmania fractions: (a) a glycoprotein GP63-enriched fraction, "fucose mannose ligand" (FML), from L. donovani, (commercial vaccine-Leishmune®); (b) a purified Leishmania antigen, the recombinant A2 (rA2) protein of L. donovani amastigotes; (c) purified ES antigen from L. infantum promastigotes (LiESAp). Immunization with rA2 antigen has enabled vaccinated and infected animals to be differentiated serologically, an important requirement for a canine visceral leishmaniasis (CVL) vaccine (commercial vaccine--Leish-Tec®). 3) A multisubunit recombinant Leishmania polyprotein known as Leish-111f. (4) DNA vaccines with protein antigens. Notwithstanding the efforts of researchers around the world to prevent CVL, control assays have not been practiced on a large scale in official programs. Future interdisciplinary studies among research institutes, particularly in Brazil, should be aimed at further improving the control of CVL and HVL.
Acknowledgments: The author thanks Dra. Marilene Michalick for contributing towards the manuscript revision.
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