the role of dogs as reservoirs of leishmania parasites, with emphasis on leishmania (leishmania)...
TRANSCRIPT
Review paper
The role of dogs as reservoirs of Leishmania parasites,
with emphasis on Leishmania (Leishmania) infantum and
Leishmania (Viannia) braziliensis
Filipe Dantas-Torres *
Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhaes, Fundacao Oswaldo Cruz, C.P. 7472,
Recife 50670-420, Pernambuco, Brazil
Received 24 March 2007; received in revised form 8 May 2007; accepted 5 July 2007
www.elsevier.com/locate/vetpar
Veterinary Parasitology 149 (2007) 139–146
Abstract
Leishmania parasites cause a group of diseases collectively known as leishmaniases. The primary hosts of Leishmania are
sylvatic mammals of several orders (Rodentia, Marsupialia, Carnivora, etc.). Under certain circumstances, particularly in
peridomestic and domestic transmission foci, synanthropic and domestic animals can act as source of infection for phlebotomine
sand fly vectors. Dogs have long been implicated as the main domestic reservoirs of Leishmania (Leishmania) infantum, the
aetiological agent of zoonotic visceral leishmaniasis, and there exists an increasing trend to regard dogs as the main domestic
reservoirs of Leishmania (Viannia) braziliensis, the most widespread aetiological agent of American tegumentary leishmaniasis.
However, insights derived from recent research indicate that not dogs but humans are probably the most important domestic
reservoirs of L. (V.) braziliensis. In the present article, the role of dogs as reservoirs of Leishmania parasites, with emphasis on L. (L.)
infantum and L. (V.) braziliensis, is reviewed.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Leishmaniasis; Reservoir; Leishmania; Dog; Epidemiology
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
2. What does define a reservoir of infection? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
3. Dogs as reservoir hosts of L. (L.) infantum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
4. Dogs as reservoir hosts of L. (V.) braziliensis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
5. Dogs as reservoir hosts of other Leishmania species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
6. General conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
7. Final comment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
* Tel.: +55 81 21012640; fax: +55 81 34532449.
E-mail address: [email protected].
0304-4017/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.vetpar.2007.07.007
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146140
1. Introduction
Leishmania (Kinetoplastida: Trypanosomatidae) are
protozoan parasites of great medical and veterinary
significance (Dantas-Torres, 2006b), which are trans-
mitted to a susceptible host by phlebotomine sand flies
(Diptera: Psychodidae) of the genera Phlebotomus and
Lutzomyia in the Old and New Worlds, respectively. The
genus Leishmania is divided into two subgenera,
Leishmania and Viannia, based on the pattern of
development of the parasites in the sand fly gut (Lainson
and Shaw, 1987). Of some 30 species of Leishmania
known at present, �20 are pathogenic for humans.
About 30 species of phlebotomine sand flies are proven
vectors (Ashford, 2000; Desjeux, 2004).
Leishmania parasites cause leishmaniases, a group
of diseases with diverse epidemiological and clinical
patterns (from self-healing skin ulcers to severe, life-
threatening visceral disease). With some exceptions,
the leishmaniases are zoonoses and the human
infection is incidental. Natural vertebrate hosts of
Leishmania parasites are mammals of the orders:
Edentata (e.g., armadillos, sloths), Carnivora (e.g.,
dogs, cats), Hyracoidea (e.g., hyraxes), Rodentia (e.g.,
rats, gerbils), Primates (e.g., humans, monkeys),
Marsupialia (e.g., opossums), and Perissodactyla
(e.g., horses) (Ashford, 1996; Saliba and Oumeish,
1999; Gramiccia and Gradoni, 2005). The primary
reservoir hosts of Leishmania are sylvatic mammals,
such as forest rodents and wild canids. With the
increasing process of domiciliation of the zoonotic
cycle of transmission of leishmaniases, synanthropic
and domestic animals have assumed an important
role as reservoirs of infection.
Dogs have been found naturally infected by different
species of Leishmania, such as Leishmania (Leishma-
nia) major (Elbihari et al., 1987), although their role as
reservoirs of some of these parasites is probably
negligible; that is, they are more likely to be victims
rather than reservoirs. In a recently published paper,
Gomes et al. (2007) emphasize the utility of PCR in
discriminating the species of Leishmania infecting
dogs, particularly in areas where both visceral and
cutaneous leishmaniasis are endemic. Indeed, PCR-
based methods have been proven to be powerful tools
for the detection – in different clinical specimens – and
discrimination of Leishmania species infecting a wide
range of vertebrate (Brandao-Filho et al., 2003; Oliveira
et al., 2005; Silva et al., 2005; Andrade et al., 2006) and
invertebrate hosts (e.g., phlebotomine sand flies, ticks)
(Coutinho et al., 2005; Parvizi et al., 2005). In the
aforementioned paper, Gomes et al. (2007) released the
following statement: ‘‘. . .domestic dogs are known to be
the main visceral leishmaniasis and cutaneous leish-
maniasis reservoirs’’. And this is an issue of ongoing
debate in the scientific literature.
As far it is known, the dog is not the main reservoir
host of the aetiological agents of zoonotic cutaneous
leishmaniasis (Ashford, 1996; Alvar et al., 2004;
Desjeux, 2004; Gramiccia and Gradoni, 2005); except
for Leishmania (Viannia) peruviana, the aetiological
agent of uta, a typical localized ulcerative cutaneous
leishmaniasis whose geographical distribution is
restricted to the Peruvian Andes. For some authors
(Llanos-Cuentas et al., 1999), dogs are believed to be
reservoir hosts of L. (V.) peruviana. But even in this
case, the incrimination is based on circumstantial
evidence; that is, the finding of dogs naturally infected
by L. (V.) peruviana and a relatively high dog blood
index (i.e., the proportion of blood meals taken from
dogs) among specimens of Lu. peruensis, a known
vector of L. (V.) peruviana (Llanos-Cuentas et al.,
1999). So, the status of dogs as reservoir hosts of L. (V.)
peruviana is still uncertain (Reithinger and Davies,
1999).
In this article, the role of dogs as reservoirs of
Leishmania parasites, with emphasis on Leishmania
(Leishmania) infantum [syn. Leishmania (Leishmania)
chagasi; Dantas-Torres, 2006a] and L. (V.) braziliensis,
is reviewed in the light of epidemiological and
experimental evidence as well as based on the author’s
personal experience.
2. What does define a reservoir of infection?
Many researchers have tried to define what the term
‘reservoir’ – treated here as synonymous with ‘reservoir
host’ and ‘reservoir of infection’ – actually means
(Ashford, 1996, 2003; Haydon et al., 2002; Silva et al.,
2005). On the contrary to what one might think, to
define what is a reservoir is not an easy task. In a
practical point of view, however, this term can be used
to define a host that fulfills some attributes that favor the
maintenance and dissemination of a given disease
agent. Although this definition is less elaborate than
some others (e.g., Ashford, 2003), it is the one used
here, as it provides a practical and applicable view of the
importance of reservoirs of infection for maintenance of
the transmission cycle of the pathogens they carry. It is
worthwhile to note that the importance of each animal
host as reservoir of a given disease agent can obviously
vary widely from region to region. Results from local
studies cannot be extrapolated to other regions, without
strong ecological evidence.
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146 141
Perhaps it would be opportune to mention here that
it is common to see in the scientific literature the
following statement: dogs are the main reservoirs of
visceral leishmaniasis. This should be avoided. Dogs
are not reservoirs of visceral leishmaniasis; that is,
they are reservoirs of the aetiological agent of visceral
leishmaniasis. When taking its blood meal from an
infected dog, a phlebotomine sand fly can become
infected by Leishmania parasites (and not by
leishmaniasis). In a subsequent blood meal, the
phlebotomine sand fly can transmit Leishmania
parasites to a naıve, susceptible human host. Note
that the vector transmits the parasite to the human
host, which can develop leishmaniasis or not,
depending on several factors related to the host
(e.g., age, nutritional status, genetics) and the parasite
(e.g., species, strain).
3. Dogs as reservoir hosts of L. (L.) infantum
Not only domestic dogs, but canids in general, fulfill
the required attributes to be efficient reservoirs of L. (L.)
infantum (Alvar et al., 2004; Dantas-Torres and
Brandao-Filho, 2006). Due to its close relationship
with humans, the domestic dog has long been
implicated as the main reservoir of L. (L.) infantum
in China, the Mediterranean basin and the Americas
(Ashford, 1996; Moreno and Alvar, 2002; Desjeux,
2004; Gramiccia and Gradoni, 2005; Lainson and
Rangel, 2005; Dantas-Torres and Brandao-Filho, 2006).
And there are some reasons for this:
� A
lthough some dog breeds – e.g., Ibizian hounds(Solano-Gallego et al., 2000) – appear to be more
resistant than others, dogs are often susceptible to L.
(L.) infantum infection (Moreno and Alvar, 2002).
� I
n areas where zoonotic visceral leishmaniasis isendemic, the prevalence of L. (L.) infantum infection
in dogs is often high, with a large proportion of
asymptomatic ones (Dantas-Torres et al., 2006).
� D
ogs may present an intense cutaneous parasitismby Leishmania amastigotes (intracellular forms),
increasing the possibility of transmission (Ashford,
1996; Dantas-Torres and Brandao-Filho, 2006).
� D
ogs are usually in or next to human houses, whichfavors the maintenance of the domestic transmission
cycle of L. (L.) infantum (Dantas-Torres and Brandao-
Filho, 2006).
� D
ogs can remain infected by L. (L.) infantum withoutdisplaying apparent clinical signs of visceral leish-
maniasis for years and even for their entire life
(Moreno and Alvar, 2002).
� T
he L. (L.) infantum zymodeme MON-1, which isresponsible for most of the cases of visceral
leishmaniasis around the Mediterranean basin, is
also the predominant zymodeme isolated from dogs
(Pratlong et al., 2004).
It has been proven that infected dogs are sources of
infection for phlebotomine sand flies of species Lu.
longipalpis (Deane and Deane, 1955) and P. perniciosus
(Molina et al., 1994), the main vectors of the
aetiological agent of zoonotic visceral leishmaniasis
in the New and Old Worlds, respectively. These
phlebotomine sand flies can easily adapt to the
peridomestic environment or human dwellings and
feed frequently on dogs (Colmenares et al., 1995;
Killick-Kendrick, 1999; Feliciangeli, 2004; Lainson
and Rangel, 2005).
There is sufficient epidemiological and experimental
evidence supporting dogs as the main reservoir hosts of
L. (L.) infantum for human infection. Therefore, it is
plausible to conclude that the domestic dog plays an
important role in the epidemiology of zoonotic visceral
leishmaniasis. So, why cannot dog-culling programs
control human visceral leishmaniasis? The definitive
answer for this question is still unknown. The possible
participation of other reservoir hosts, including asymp-
tomatic infected persons (Costa et al., 2002) and cats
(Maroli et al., 2007), in the transmission cycle of L. (L.)
infantum cannot be excluded. Other possible reasons for
the failure of dog-culling programs have been
extensively discussed elsewhere (Reithinger and
Davies, 1999; Courtenay et al., 2002; Moreira et al.,
2004; Dantas-Torres, 2006b,c; Dantas-Torres and
Brandao-Filho, 2006).
4. Dogs as reservoir hosts of L. (V.) braziliensis
There exists an increasing trend to regard dogs as the
main domestic reservoirs of L. (V.) braziliensis, the most
widespread aetiological agent of American tegumentary
leishmaniasis (Falqueto et al., 1991; Reithinger and
Davies, 1999; Davies et al., 2000; Reithinger et al.,
2000, 2003; Padilla et al., 2002; Gomes et al., 2007).
Attempts to control American tegumentary leishma-
niasis by treating (Sessa et al., 1994) or culling (Costa
et al., 2004) infected dogs have been proposed, although
there is little evidence to demonstrate its effectiveness
either in theory or in practice. There are many reports of
natural infection of dogs by L. (V.) braziliensis (Aguilar
et al., 1989; Reithinger and Davies, 1999; Madeira
et al., 2003, 2006; Ryan et al., 2003; Castro et al., 2007),
which is expected for the following reasons:
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146142
� D
ogs are susceptible to infection by L. (V.)braziliensis, as demonstrated by experimental studies
(Pirmez et al., 1988; Genaro et al., 1990).
� D
ogs appear to be relatively attractive for someproven or suspected vectors of L. (V.) braziliensis
(Campbell-Lendrum et al., 1999; Afonso et al., 2005).
� D
ogs are often present in areas where the perido-mestic and domestic transmission cycles of L. (V.)
braziliensis occur, which is obviously expected
because dogs are among the most popular domestic
animals around the world; that is, they are almost
invariably present anywhere where humans are.
Despite the relative attractiveness of dogs for some
vectors of L. (V.) braziliensis, some species such as
Lu. whitmani appear to be significantly more attracted
to humans than to dogs (Campbell-Lendrum et al.,
1999). Cases of natural infection by L. (V.) brazi-
liensis have been reported in dogs, but also in cats,
equines, rodents and opossums (Grimaldi and Tesh,
1993; Ashford, 1996; Gramiccia and Gradoni, 2005).
So, are domestic dogs the main reservoirs of L. (V.)
braziliensis?
It has been experimentally demonstrated that Lu.
whitmani can become infected by feeding on dogs
infected by L. (V.) braziliensis (Vexenat et al., 1986).
However, the results of this study cannot be extra-
polated, mainly because the phlebotomine sand flies
were fed artificially on lesions; that is, the insects were
allowed to feed directly on ulcerated lesions. In the
same study, 180 females of Lu. whitmani were allowed
to feed on non-ulcerated regions of an infected dog and
none of them became infected (Vexenat et al., 1986). In
a study carried out in Venezuela, Hernandez et al.
(2006) found Leishmania promastigotes (flagellate
forms) in only 0.88% (4 out of 455) of the dissected
specimens of Lu. youngi that were allowed to feed on
two dogs. It is also worthwhile to note that the
xenodiagnosis was performed with wild-caught phle-
botomine sand flies. As a consequence, the possibility
that the phlebotomine sand flies could have been
already infected (i.e., prior to feed on the dogs) cannot
be excluded, even though they were collected from an
area considered free of American tegumentary leish-
maniasis.
The results of a study recently carried out in
Colombia indicate that although dogs are susceptible to
L. (V.) braziliensis, their reservoir competence could be
low. Travi et al. (2006) tested the competence of two
naturally infected dogs to transmit L. (V.) braziliensis to
phlebotomine sand flies – both colonized and wild-
caught – of the following species: Lu. trapidoi, Lu.
gomezi, Lu. longipalpis, and Lu. youngi. Phlebotomine
sand flies were allowed to feed on the lesion borders, but
no infection was detected upon dissection of engorged
specimens. The results of this study should also be
interpreted with caution. The number of phlebotomine
sand flies fed on dogs per xenodiagnosis was relatively
low; that is, fewer than 50 per dog. Perhaps, this number
was insufficient to detect truly infective individuals
(Travi et al., 2006).
To incriminate an animal host as a reservoir of
Leishmania, the parasites isolated from the animals
must be indistinguishable from those of man. In a
study carried out in Argentina, Marco et al. (2005)
identified a Leishmania stock from a dog as L. (V.)
braziliensis. However, the zymodeme (KMS 3) found
in the dog was not expressed in any of the 15 isolates
from humans. Further studies, with a larger number of
stocks from humans, dogs and, if possible, vectors are
needed.
In areas where the human infection has been clearly
acquired under certain specific situations, such as
ecological tourism, road building, agricultural and
military activities (Brandao-Filho et al., 1999; Ashford,
2000; Desjeux, 2001, 2004; Andrade et al., 2005; Alvar
et al., 2006), the importance of dogs as reservoir hosts
of L. (V.) braziliensis is certainly negligible. In
peridomestic and domestic transmission foci (Camp-
bell-Lendrum et al., 2001; Yadon et al., 2003), dogs can
probably serve only as a minor source of infection for
phlebotomine sand flies. It is important to note that it is
not known whether the dog is an essential piece in the
peridomestic and domestic transmission of L. (V.)
braziliensis or not. Therefore, caution must be
exercised to avoid mistaken conclusions on the role
of dogs in the epidemiology of American tegumentary
leishmaniasis.
The natural (i.e., primary) reservoir hosts of L. (V.)
braziliensis are largely unknown or unproven. As its
cycle of transmission is primarily rural and often
associated with human penetration of forested or
wooded areas, it is suspected that sylvatic mammals
may be natural reservoir hosts of L. (V.) braziliensis
(Grimaldi and Tesh, 1993; Gramiccia and Gradoni,
2005). Results of a study conducted in northeastern
Brazil strongly indicate that, at least there, some small
rodents are involved in the maintenance of the parasite
in nature (Brandao-Filho et al., 2003).
Castro et al. (2007) have recently carried out a study
in Parana state, southern Brazil, to access the possible
role of dogs as reservoirs of L. (V.) braziliensis. Their
results also suggest that dogs are not good reservoirs of
this species of Leishmania.
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146 143
5. Dogs as reservoir hosts of other Leishmaniaspecies
Cases of natural infection of dogs by L. arabica
(Peters et al., 1986), L. (L.) major (Elbihari et al., 1987;
Morsy et al., 1987), Leishmania (Leishmania) tropica,
(Dereure et al., 1991; Guessous-Idrissi et al., 1997), L.
(V.) peruviana (Llanos-Cuentas et al., 1999), and
Leishmania (Leishmania) donovani (Dereure et al.,
2003) have been documented. Although dogs have been
found naturally infected by several species of Leish-
mania, their role as reservoir hosts of these parasites is
probably negligible. In some instance [e.g., L. (L.)
tropica in central to southwest Asia and L. (L.) donovani
in northeast India], the man is the sole source of
infection for the vector (Ashford, 2000). As previously
mentioned (see Section 1), there is only circumstantial
evidence about the role of dogs in the epidemiology of
uta. Thus, the status of the dog as a reservoir host of L.
(V.) peruviana is still uncertain.
6. General conclusions
The epidemiology of leishmaniasis involves a
dynamic network of highly complex interactions among
Leishmania parasites, phlebotomine sand fly vectors,
and susceptible hosts. These, in a given moment in their
life cycle, are linked by chance, by necessity, or both.
For most of the species of Leishmania, humans and
domestic dogs are merely accidental hosts, which are
unfortunate enough to be exposed to an infected female
phlebotomine sand fly. The increasing domestication of
the transmission cycle of some Leishmania species has
caused dramatic changes in the epidemiology of
leishmaniases, such as changes in transmission patterns
due to the adaptation of these parasites to new vectors
and hosts.
It is well known that the dog plays an important role
in the zoonotic cycle of transmission of L. (L.) infantum.
For L. (V.) braziliensis, however, the dog is most likely
to be an incidental host and its role in the zoonotic cycle
of transmission is probably negligible; except in
peridomestic and domestic transmission foci, where
not only dogs but domestic and synanthropic animals in
general are likely to have a role in the epidemiology of
American tegumentary leishmaniasis. Not necessarily
acting as reservoirs of infection, but attracting vectors to
human dwellings, for example.
For most Leishmania species, people are typical
incidental hosts, but in some cases can also act as
important reservoirs of infection (Ashford, 1996;
Desjeux, 2004). It has been suggested that some New
World leishmaniases could become anthroponoses
(Rotureau, 2006); that is, man is the sole source of
infection for the vector. Insights derived from recent
research strongly support this hypothesis. It is well
established now that American tegumentary leishma-
niasis patients may remain infected for several years,
even after treatment completion and clinical cure
(Schubach et al., 1998; Coutinho et al., 2002; Mendonca
et al., 2004). Leishmania DNA has also been detected in
blood of individuals with a positive leishmanin skin test
but no past or present history of leishmaniasis
(Coutinho et al., 2002). In Brazil, Ampuero et al.
(2005) carried out a matched case–control study to
identify risk factors for cutaneous leishmaniasis in
children under 5 years of age. The most important risk
factor was the presence of a family member with a
history of cutaneous leishmaniasis in the year prior to
the appearance of the disease in the child.
Based on the remarkable anthropophily (i.e.,
tendency towards human biting) of certain proven
vectors of L. (V.) braziliensis (Killick-Kendrick, 1990;
Campbell-Lendrum et al., 1999), the ability of
American tegumentary leishmaniasis patients to remain
infected for several years, and their infectivity to
laboratory-reared sand flies (Rojas and Scorza, 1989;
Vergel et al., 2006), one may obviously ask: are humans
the main domestic reservoirs of L. (V.) braziliensis? The
extensive available epidemiological and experimental
data supports this hypothesis, which, however, remains
to be proven. It is not known whether infected humans
can solely maintain the domestic transmission cycle
without the need of animals. Further studies aimed at
determining whether American tegumentary leishma-
niasis patients are infectious to phlebotomine sand flies,
prior and after treatment, are advocated.
7. Final comment
Considering the current scenery of the leishmaniases
around the world, it seems to be clear that the control of
these diseases is more complex than previously
supposed. The control of reservoirs, particularly dogs,
has been ethically rejected, mainly due its low impact
on the incidence of leishmaniases in humans. The
leishmaniases are intimately linked with poverty (Alvar
et al., 2006). The control of the leishmaniases is quite
complex but is possible with a strong commitment from
all parts involved. Future attempts to control the
leishmaniases must include measures not only to cut out
the transmission cycle but also to improve housing
conditions and environment sanitation as well as to
ensure water and food supply among the poorest. It is
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146144
also fundamental to emphasize the importance of
personal protective measures, such as the use of
insecticide-treated bed nets and curtains, and to provide
rapid diagnosis and treatment of the affected persons.
Acknowledgements
Thanks to the reviewers for their valuable comments
on a draft of this paper. The author is the recipient of a
PhD scholarship from the Coordenacao de Aper-
feicoamento de Pessoal de Nıvel Superior (CAPES).
References
Afonso, M.M., Gomes, A.C., Meneses, C.R., Rangel, E.F., 2005.
Studies on the feeding habits of Lutzomyia (N.) intermedia (Dip-
tera, Psychodidae), vector of cutaneous leishmaniasis in Brazil.
Cad. Saude Publica. 21, 1816–1820.
Aguilar, C.M., Rangel, E.F., Garcia, L., Fernandes, E., Momen, H.,
Grimaldi Filho, G., Vargas, Z., 1989. Zoonotic cutaneous leish-
maniasis due to Leishmania (Viannia) braziliensis associated with
domestic animals in Venezuela and Brazil. Mem. Inst. Oswaldo
Cruz 84, 19–28.
Alvar, J., Canavate, C., Molina, R., Moreno, J., Nieto, J., 2004. Canine
leishmaniasis. Adv. Parasitol. 57, 1–88.
Alvar, J., Yactayo, S., Bern, C., 2006. Leishmaniasis and poverty.
Trends Parasitol. 22, 552–557.
Ampuero, J., Urdaneta, M., Macedo, V.O., 2005. Factores de riesgo
para la transmision de leishmaniasis cutanea en ninos de 0 a 5 anos
en un area endemica de Leishmania (Viannia) braziliensis. Cad.
Saude Publica. 21, 161–170.
Andrade, M.S., Valenca, H.F., Silva, A.L., Almeida, F.A., Almeida,
E.L., Brito, M.E.F., Brandao-Filho, S.P., 2005. Sandfly fauna in a
military training area endemic for American tegumentary leish-
maniasis in the Atlantic Rain Forest region of Pernambuco, Brazil.
Cad. Saude Publica. 21, 1761–1767.
Andrade, H.M., Reis, A.B., dos Santos, S.L., Volpini, A.C., Marques,
M.J., Romanha, A.J., 2006. Use of PCR-RFLP to identify Leishma-
nia species in naturally infected dogs. Vet. Parasitol. 140, 231–238.
Ashford, R.W., 1996. Leishmaniasis reservoirs and their significance
in control. Clin. Dermatol. 14, 523–532.
Ashford, R.W., 2000. The leishmaniases as emerging and reemerging
zoonoses. Int. J. Parasitol. 30, 1269–1281.
Ashford, R.W., 2003. When is a reservoir not a reservoir? Emerg.
Infect. Dis. 9, 1495–1496.
Brandao-Filho, S.P., Campbell-Lendrum, D., Brito, M.E., Shaw, J.J.,
Davies, C.R., 1999. Epidemiological surveys confirm an increas-
ing burden of cutaneous leishmaniasis in northeast Brazil. Trans.
R. Soc. Trop. Med. Hyg. 93, 488–494.
Brandao-Filho, S.P., Brito, M.E.F., Carvalho, F.G., Ishikawa, E.A.,
Cupolillo, E., Floeter-Winter, L., Shaw, J.J., 2003. Wild and
synanthropic hosts of Leishmania (Viannia) braziliensis in the
endemic cutaneous leishmaniasis locality of Amaraji, Pernambuco
State, Brazil. Trans. R. Soc. Trop. Med. Hyg. 97, 291–296.
Campbell-Lendrum, D.H., Pinto, M.C., Brandao-Filho, S.P., de Souza,
A.A., Ready, P.D., Davies, C.R., 1999. Experimental comparison
of anthropophily between geographically dispersed populations of
Lutzomyia whitmani (Diptera: Psychodidae). Med. Vet. Entomol.
13, 299–309.
Campbell-Lendrum, D.H., Dujardin, J.P., Martinez, E., Feliciangeli,
M.D., Perez, J.E., Silans, L.N., Desjeux, P., 2001. Domestic and
peridomestic transmission of American cutaneous leishmaniasis:
changing epidemiological patterns present new control opportu-
nities. Mem. Inst. Oswaldo Cruz 96, 159–162.
Castro, E.A., Thomaz-Soccol, V., Augur, C., Luz, E., 2007. Leishma-
nia (Viannia) braziliensis: epidemiology of canine cutaneous
leishmaniasis in the state of Parana (Brazil). Exp. Parasitol.
117, 13–21.
Colmenares, M., Portus, M., Botet, J., Dobano, C., Gallego, M., Wolff,
M., Seguı, G., 1995. Identification of blood meals of Phlebotomus
perniciosus (Diptera: Psychodidae) in Spain by a competitive
enzyme-linked immunosorbent assay biotin/avidin method. J.
Med. Entomol. 32, 229–233.
Costa, C.H., Stewart, J.M., Gomes, R.B., Garcez, L.M., Ramos, P.K.,
Bozza, M., Satoskar, A., Dissanayake, S., Santos, R.S., Silva,
M.R., Shaw, J.J., David, J.R., Maguire, J.H., 2002. Asymptomatic
human carriers of Leishmania chagasi. Am. J. Trop. Med. Hyg. 66,
334–337.
Costa, C.M., Moutinho, F.F.B., Bruno, S.F., 2004. A experiencia do
municıpio de Paraty (Rio de Janeiro, Brasil) na prevencao e
controle da leishmaniose tegumentar americana. Parasitol. Lati-
noam. 59, 110–114.
Courtenay, O., Quinnell, R.J., Garcez, L.M., Shaw, J.J., Dye, C., 2002.
Infectiousness in a cohort of Brazilian dogs: why culling fails to
control visceral leishmaniasis in areas of high transmission. J.
Infect. Dis. 186, 1314–1320.
Coutinho, S.G., Pirmez, C., Da-Cruz, A.M., 2002. Parasitological
and immunological follow-up of American tegumentary leish-
maniasis patients. Trans. R. Soc. Trop. Med. Hyg. 96 (Suppl 1),
S173–S178.
Coutinho, M.T., Bueno, L.L., Sterzik, A., Fujiwara, R.T., Botelho,
J.R., Maria, M., Genaro, O., Linardi, P.M., 2005. Participation of
Rhipicephalus sanguineus (Acari: Ixodidae) in the epidemiology
of canine visceral leishmaniasis. Vet. Parasitol. 128, 149–155.
Dantas-Torres, F., 2006a. Leishmania infantum versus Leishmania
chagasi: do not forget the law of priority. Mem. Inst. Oswaldo
Cruz 101, 117–118.
Dantas-Torres, F., 2006b. Leishmune vaccine: the newest tool for
prevention and control of canine visceral leishmaniosis and its
potential as a transmission-blocking vaccine. Vet. Parasitol. 141,
1–8.
Dantas-Torres, F., 2006c. Presence of Leishmania amastigotes in
peritoneal fluid of a dog with leishmaniasis from Alagoas, north-
eastern Brazil. Rev. Inst. Med. Trop. Sao Paulo 48, 219–221.
Dantas-Torres, F., Brandao-Filho, S.P., 2006. Visceral leishmaniasis in
Brazil: revisiting paradigms of epidemiology and control. Rev.
Inst. Med. Trop. Sao Paulo 48, 151–156.
Dantas-Torres, F., Brito, M.E.F., Brandao-Filho, S.P., 2006. Seroepi-
demiological survey on canine leishmaniasis among dogs from an
urban area of Brazil. Vet. Parasitol. 140, 54–60.
Davies, C.R., Reithinger, R., Campbell-Lendrum, D., Feliciangeli, D.,
Borges, R., Rodriguez, N., 2000. The epidemiology and control of
leishmaniasis in Andean countries. Cad. Saude Publica. 16, 925–
950.
Deane, L.M., Deane, M.P., 1955. Observacoes preliminares da impor-
tancia comparativa do homem, do cao e da raposa (Lycalopex
vetulus) como reservatorios de Leishmania donovani, em area
endemica do calazar, no Ceara. Hospital (Rio J) 48, 79–98.
Dereure, J., Rioux, J.A., Gallego, M., Perieres, J., Pratlong, F.,
Mahjour, J., Saddiki, H., 1991. Leishmania tropica in Morocco:
infection in dogs. Trans. R. Soc. Trop. Med. Hyg. 85, 595.
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146 145
Dereure, J., El-Safi, S.H., Bucheton, B., Boni, M., Kheir, M.M.,
Davoust, B., Pratlong, F., Feugier, E., Lambert, M., Dessein,
A., Dedet, J.P., 2003. Visceral leishmaniasis in eastern Sudan:
parasite identification in humans and dogs; host–parasite relation-
ships. Microbes Infect. 5, 1103–1108.
Desjeux, P., 2001. The increase in risk factors for leishmaniasis
worldwide. Trans. R. Soc. Trop. Med. Hyg. 95, 239–243.
Desjeux, P., 2004. Leishmaniasis: current situation and new perspec-
tives. Comp. Immunol. Microbiol. Infect. Dis. 27, 305–318.
Elbihari, S., Cheema, A.H., el-Hassan, A.M., 1987. Leishmania
infecting man and wild animals in Saudi Arabia. 4. Canine
cutaneous leishmaniasis in the Eastern Province. Trans. R. Soc.
Trop. Med. Hyg. 81, 925–927.
Falqueto, A., Sessa, P.A., Varejao, J.B.M., Barros, G.C., Momen, H.,
Grimaldi Jr., G., 1991. Leishmaniasis due to Leishmania brazi-
liensis in Espırito Santo state, Brazil. Further evidence on the role
of dogs as a reservoir of infection for humans. Mem. Inst. Oswaldo
Cruz 86, 499–500.
Feliciangeli, M.D., 2004. Natural breeding places of phlebotomine
sandflies. Med. Vet. Entomol. 18, 71–80.
Genaro, O., Carvalho, M.D., Pinto, F.A., Dias, M., 1990. The course of
the experimental infections by Leishmania (Viannia) braziliensis
and Leishmania (Leishmania) amazonensis in dogs. Mem. Inst.
Oswaldo Cruz 85, S27.
Gomes, A.H., Ferreira, I.M., Lima, M.L., Cunha, E.A., Garcia, A.S.,
Araujo, M.F., Pereira-Chioccola, V.L., 2007. PCR identification of
Leishmania in diagnosis and control of canine leishmaniasis. Vet.
Parasitol. 144, 234–241.
Gramiccia, M., Gradoni, L., 2005. The current status of zoonotic
leishmaniases and approaches to disease control. Int. J. Parasitol.
35, 1169–1180.
Grimaldi, G., Tesh, R.B., 1993. Leishmaniasis in the New World:
current concepts and implications for future research. Clin. Micro-
biol. Rev. 6, 230–250.
Guessous-Idrissi, N., Berrag, B., Riyad, M., Sahibi, H., Bichichi, M.,
Rhalem, A., 1997. Short report: Leishmania tropica: etiologic
agent of a case of canine visceral leishmaniasis in northern
Morocco. Am. J. Trop. Med. Hyg. 57, 172–173.
Haydon, D.T., Cleaveland, S., Taylor, L.H., Laurenson, M.K., 2002.
Identifying reservoirs of infection: a conceptual and practical
challenge. Emerg. Infect. Dis. 8, 1468–1473.
Hernandez, D., Rojas, E., Scorza, J.V., Jorquera, A., 2006. Dog (Canis
familiaris) infectivity to Lutzomyia youngi in Trujillo, Venezuela.
Biomedica 26 (Suppl 1), 242–248.
Killick-Kendrick, R., 1990. Phlebotomine vectors of the leishma-
niases: a review. Med. Vet. Entomol. 4, 1–24.
Killick-Kendrick, R., 1999. The biology and control of phlebotomine
sand flies. Clin. Dermatol. 17, 279–289.
Lainson, R., Rangel, E.F., 2005. Lutzomyia longipalpis and the eco-
epidemiology of American visceral leishmaniasis, with particular
reference to Brazil: a review. Mem. Inst. Oswaldo Cruz 100, 811–
827.
Lainson, R., Shaw, J.J., 1987. Evolution, classification and geogra-
phical distribution. In: Peters, W., Killick-Kendrick, R. (Eds.),
The Leishmaniasis in Biology and Medicine, 1. Academic Press,
London, pp. 1–120.
Llanos-Cuentas, E.A., Roncal, N., Villaseca, P., Paz, L., Ogusuku, E.,
Perez, J.E., Caceres, A., Davies, C.R., 1999. Natural infections of
Leishmania peruviana in animals in the Peruvian Andes. Trans. R.
Soc. Trop. Med. Hyg. 93, 15–20.
Madeira, M.F., Uchoa, C.M., Leal, C.A., Macedo Silva, R.M., Duarte,
R., Magalhaes, C.M., Barrientos Serra, C.M., 2003. Leishmania
(Viannia) braziliensis em caes naturalmente infectados. Rev. Soc.
Bras. Med. Trop. 36, 551–555.
Madeira, M.F., Schubach, A., Schubach, T.M., Pacheco, R.S., Oli-
veira, F.S., Pereira, S.A., Figueiredo, F.B., Baptista, C., Marzochi,
M.C., 2006. Mixed infection with Leishmania (Viannia) brazi-
liensis and Leishmania (Leishmania) chagasi in a naturally
infected dog from Rio de Janeiro, Brazil. Trans. R. Soc. Trop.
Med. Hyg. 100, 442–445.
Marco, J.D., Barroso, P.A., Calvopina, M., Kumazawa, H., Furuya,
M., Korenaga, M., Cajal, S.P., Mora, M.C., Rea, M.M., Borda,
C.E., Basombrio, M.A., Taranto, N.J., Hashiguchi, Y., 2005.
Species assignation of Leishmania from human and canine
American tegumentary leishmaniasis cases by multilocus
enzyme electrophoresis in North Argentina. Am. J. Trop.
Med. Hyg. 72, 606–611.
Maroli, M., Pennisi, M.G., Di Muccio, T., Khoury, C., Gradoni, L.,
Gramiccia, M., 2007. Infection of sandflies by a cat naturally
infected with Leishmania infantum. Vet. Parasitol. 145, 357–360.
Mendonca, M.G., de Brito, M.E., Rodrigues, E.H., Bandeira, V.,
Jardim, M.L., Abath, F.G., 2004. Persistence of Leishmania
parasites in scars after clinical cure of American cutaneous
leishmaniasis: is there a sterile cure? J. Infect. Dis. 189, 1018–
1023.
Molina, R., Amela, C., Nieto, J., San-Andres, M., Gonzalez, F.,
Castillo, J.A., Lucientes, J., Alvar, J., 1994. Infectivity of dogs
naturally infected with Leishmania infantum to colonized Phle-
botomus perniciosus. Trans. R. Soc. Trop. Med. Hyg. 88, 491–493.
Moreira Jr., E.D., Mendes de Souza, V.M., Sreenivasan, M., Nasci-
mento, E.G., Pontes de Carvalho, L., 2004. Assessment of an
optimized dog-culling program in the dynamics of canine Leish-
mania transmission. Vet. Parasitol. 122, 245–252.
Moreno, J., Alvar, J., 2002. Canine leishmaniasis: epidemiological
risk and the experimental model. Trends Parasitol. 18, 399–405.
Morsy, T.A., Schnur, L.F., Feinsod, F.M., Salem, A.M., Wahba, M.M.,
el Said, S.M., 1987. Natural infections of Leishmania major in
domestic dogs from Alexandria, Egypt. Am. J. Trop. Med. Hyg.
37, 49–52.
Oliveira, F.S., Pirmez, C., Pires, M.Q., Brazil, R.P., Pacheco, R.S.,
2005. PCR-based diagnosis for detection of Leishmania in skin
and blood of rodents from an endemic area of cutaneous and
visceral leishmaniasis in Brazil. Vet. Parasitol. 129, 219–227.
Padilla, A.M., Marco, J.D., Diosque, P., Segura, M.A., Mora, M.C.,
Fernandez, M.M., Malchiodi, E.L., Basombrio, M.A., 2002.
Canine infection and the possible role of dogs in the transmission
of American tegumentary leishmaniosis in Salta, Argentina. Vet.
Parasitol. 110, 1–10.
Parvizi, P., Mauricio, I., Aransay, A.M., Miles, M.A., Ready, P.D.,
2005. First detection of Leishmania major in peridomestic Phle-
botomus papatasi from Isfahan province, Iran: comparison of
nested PCR of nuclear ITS ribosomal DNA and semi-nested
PCR of minicircle kinetoplast DNA. Acta Trop. 93, 75–83.
Peters, W., Elbihari, S., Evans, D.A., 1986. Leishmania infecting man
and wild animals in Saudi Arabia. 2. Leishmania arabica n. sp.
Trans. R. Soc. Trop. Med. Hyg. 80, 497–502.
Pirmez, C., Coutinho, S.G., Marzochi, M.C.A., Nunes, M.P., Grimaldi
Jr., G., 1988. Canine american cutaneous leishmaniasis: a clinical
and immunological study in dogs naturally infected with Leish-
mania braziliensis braziliensis in an endemic area of Rio de
Janeiro, Brazil. Am. J. Trop. Med. Hyg. 38, 52–58.
Pratlong, F., Rioux, J.A., Marty, P., Faraut-Gambarelli, F., Dereure, J.,
Lanotte, G., Dedet, J.P., 2004. Isoenzymatic analysis of 712 strains
of Leishmania infantum in the south of France and relationship of
F. Dantas-Torres / Veterinary Parasitology 149 (2007) 139–146146
enzymatic polymorphism to clinical and epidemiological features.
J. Clin. Microbiol. 42, 4077–4082.
Reithinger, R., Davies, C.R., 1999. Is the domestic dog (Canis
familiaris) a reservoir host of American cutaneous leishmaniasis?
A critical review of the current evidence. Am. J. Trop. Med. Hyg.
61, 530–541.
Reithinger, R., Lambson, B.E., Barker, D.C., Davies, C.R., 2000. Use
of PCR to detect Leishmania (Viannia) spp. in dog blood and bone
marrow. J. Clin. Microbiol. 38, 748–751.
Reithinger, R., Espinoza, J.C., Davies, C.R., 2003. The transmission
dynamics of canine American cutaneous leishmaniasis in Hua-
nuco, Peru. Am. J. Trop. Med. Hyg. 69, 473–480.
Rojas, E., Scorza, J.V., 1989. Xenodiagnostico con Lutzomyia youngi
en casos Venezolanos de leishmaniasis cutanea por Leishmania
braziliensis. Mem. Inst. Oswaldo Cruz 84, 29–34.
Rotureau, B., 2006. Are New World leishmaniases becoming
anthroponoses? Med. Hypotheses 67, 1235–1241.
Ryan, P.R., Arana, B.A., Ryan, J.R., Wirtz, R.A., Wortmann, G.W.,
Rizzo, N.R., 2003. The domestic dog, a potential reservoir for
Leishmania in the Peten region of Guatemala. Vet. Parasitol. 115,
1–7.
Saliba, E.K., Oumeish, Y.O., 1999. Reservoir hosts of cutaneous
leishmaniasis. Clin. Dermatol. 17, 275–277.
Schubach, A., Marzochi, M.C., Cuzzi-Maya, T., Oliveira, A.V.,
Araujo, M.L., Oliveira, A.L., Pacheco, R.S., Momen, H., Con-
ceicao-Silva, F., Coutinho, S.G., Marzochi, K.B., 1998. Cutaneous
scars in American tegumentary leishmaniasis patients: a site of
Leishmania (Viannia) braziliensis persistence and viability eleven
years after antimonial therapy and clinical cure. Am. J. Trop. Med.
Hyg. 58, 824–827.
Sessa, P.A., Falqueto, A., Varejao, J.B., 1994. Tentativa de controle da
leishmaniose tegumentar americana por meio do tratamento dos
caes doentes. Cad. Saude Publica. 10, 457–463.
Silva, E.S., Gontijo, C.M., Melo, M.N., 2005. Contribution of mole-
cular techniques to the epidemiology of neotropical Leishmania
species. Trends Parasitol. 21, 550–552.
Solano-Gallego, L., Llull, J., Ramos, G., Riera, C., Arboix, M.,
Alberola, J., Ferrer, L., 2000. The Ibizian hound presents a
predominantly cellular immune response against natural Leish-
mania infection. Vet. Parasitol. 90, 37–45.
Travi, B.L., Tabares, C.J., Cadena, H., 2006. Leishmania (Viannia)
braziliensis infection in two Colombian dogs: a note on infectivity
for sand flies and response to treatment. Biomedica 26 (Suppl 1),
249–253.
Vergel, C., Palacios, R., Cadena, H., Posso, C.J., Valderrama, L.,
Perez, M., Walker, J., Travi, B.L., Saravia, N.G., 2006. Evidence
for Leishmania (Viannia) parasites in the skin and blood of patients
before and after treatment. J. Infect. Dis. 194, 503–511.
Vexenat, J.A., Barreto, A.C., Rosa, A.C.O., 1986. Infeccao experi-
mental de Lutzomyia whitmani em caes infectados com Leish-
mania braziliensis braziliensis. Mem. Inst. Oswaldo Cruz 81,
125–126.
Yadon, Z.E., Rodrigues, L.C., Davies, C.R., Quigley, M.A., 2003.
Indoor and peridomestic transmission of American cutaneous
leishmaniasis in northwestern Argentina: a retrospective case–
control study. Am. J. Trop. Med. Hyg. 68, 519–526.