Abstracts
Identification of factors associated with Leishmania infection in dogs is essential for targeting visceral leishmaniasis control actions. Thus, the present study analyzed some of these factors in a population of dogs in a Brazilian municipality, along with the limitations of control strategies implemented there. The association between the exposure variables and occurrences of infection was analyzed through logistic regression models. The disease control interventions were treated qualitatively. Out of the 755 animals examined, 13.6% (103/755) were seropositive. Of these, 23.3% (24/103) were asymptomatic and 76.7% (79/103) presented at least one clinical sign possibly associated with visceral leishmaniasis. With weak associations, purebred, shorthaired, over 5 years of age, male and large dogs were more prone to infection. The latter two variables formed the final regression model and the association with dog size was statistically significant. The control strategies developed presented limitations and a great number of seronegative dogs was culled. The data presented contribute towards better understanding of the dynamics of infection in canine visceral leishmaniasis and indicate that actions aimed towards adequate implementation of Visceral Leishmaniasis control program in Brazilian endemic areas should be prioritized.
Leishmania infantum ; risk factors; serology
A identificação dos fatores associados à infecção por Leishmania em cães é essencial para o direcionamento das ações de controle da leishmaniose visceral. Desta forma, o presente estudo analisa alguns destes fatores em uma população de cães, bem como as limitações das estratégias de controle executadas em um município brasileiro. Por meio de modelos de regressão logística, analisou-se a associação entre as variáveis de exposição e a ocorrência de infecção. As ações de controle da doença foram analisadas qualitativamente. Dos 755 animais avaliados por meio de sorologia, 13,6% (103/755) foram soro-reagentes. Destes, 23,3% (24/103) eram assintomáticos e 76,7% (79/103) apresentaram pelo menos um sinal clínico possivelmente associado com a leishmaniose visceral. Com associações fracas, cães de raça pura, de pelo curto, com mais de cinco anos, machos e de grande porte foram mais propensos à infecção. As duas últimas variáveis compuseram o modelo final de regressão, sendo significativa a associação com o tamanho do cão. As estratégias de controle desenvolvidas apresentaram limitações e um número elevado de cães sorologicamente negativos foi submetido a eutanásia. Os dados apresentados contribuem para um melhor entendimento da dinâmica da infecção na leishmaniose visceral canina e indicam que ações visando a adequada execução do programa de controle da doença em áreas endêmicas brasileiras devem ser priorizadas.
Leishmania infantum ; fatores de risco; sorologia
American visceral leishmaniasis (AVL) is a zoonotic disease in which the
etiological agent is the protozoan Leishmania infantum (KUHLS et al., 2011Kuhls K, Alam MZ, Cupolillo E, Ferreira GEM, Mauricio IL, Oddone R,
et al. Comparative microsatellite typing of new world Leishmania infantum
reveals low heterogeneity among populations and its recent old world origin.
PLoS Negl Trop Dis 2011; 5(6): e1155 PMid:21666787 PMCid:PMC3110170.
http://dx.doi.org/10.1371/journal.pntd.0001155
http://dx.doi.org/10.1371/journal.pntd.0...
). Domestic dogs are the main
reservoir in urban areas of Brazil (BRAGA et al.,
1986Braga RR, Lainson R, Shaw JJ, Ryan L, Silveira FT. Leishmaniasis in
Brazil. XXII: Characterization of Leishmania from man, dogs and the sandfly
Lutzomyia longipalpis (Lutz & Neiva, 1912) isolated during an outbreak of
visceral leishmaniasis in Santarém, Pará State. Trans R Soc Trop Med Hyg 1986;
80(1): 143-145. http://dx.doi.org/10.1016/0035-9203(86)90214-2
http://dx.doi.org/10.1016/0035-9203(86)9...
; GAMA et al., 2004Gama MEA, Costa JML, Pereira JCR, Gomes CMC, Corbett CEP. Serum
cytokine profile in the subclinical form of visceral leishmaniasis. Braz J Med
Biol Res 2004; 37(1): 129-136. PMid:14689054.
http://dx.doi.org/10.1590/S0100-879X2004000100018
http://dx.doi.org/10.1590/S0100-879X2004...
) and the
infection is transmitted to humans through the bites of sandflies of the genus
Lutzomyia (REITHINGER et al., 2009). Epidemiological, environmental
and individual factors associated with canine visceral leishmaniasis (CVL) are not well
understood (RONDON et al., 2008Rondon FC, Bevilaqua CM, Franke CR, Barros RS, Oliveira FR,
Alcântara AC, et al. Cross-sectional serological study of canine
Leishmania infection in Fortaleza, Ceará state, Brazil. Vet Parasitol 2008;
155(1-2): 24-31. PMid:18565676.
http://dx.doi.org/10.1016/j.vetpar.2008.04.014
http://dx.doi.org/10.1016/j.vetpar.2008....
).
In the control program of visceral leishmaniasis in Brazil, action directed
towards the canine reservoir is restricted to cull seropositive animals, which are
identified by conducting sample surveys or censuses. In the Ministry of Health's
recommendations, there are no activities directly relating to investigation of potential
risk factors associated with the infection in dogs examined (BRASIL, 2006Brasil. Ministério do Saúde. Secretaria de Vigilância em
Saúde. Departamento de Vigilância Epidemiológica. Manual de
Vigilância e Controle da Leishmaniose Visceral. Brasília: Editora
Ministério da Saúde; 2006.). Given the relevance of such activities for better
comprehension of the dynamics of the disease and for defining better target control
measures (COURA-VITAL et al., 2011Coura-Vital W, Marques MJ, Veloso VM, Roatt BM, Aguiar-Soares RDO,
Reis LES, et al. Prevalence and factors associated with Leishmania infantum
infection of dogs from an urban area of Brazil as identified by molecular
methods. PLoS Negl Trop Dis 2011; 5(8): e1291. PMid:21858243 PMCid:PMC3156685.
http://dx.doi.org/10.1371/journal.pntd.0001291
http://dx.doi.org/10.1371/journal.pntd.0...
), the
importance of this kind of investigation in research and in the routine of the
healthcare service is clear.
The present study analyzed factors associated with infection by Leishmania in a population of dogs as well as the limitations of the VL control strategies implemented in a Brazilian municipality.
This cross-sectional study was conducted between March and October 2011. The area studied was the municipality of Divinópolis, which is located in the central-west region of the state of Minas Gerais, Brazil, with a population of approximately 223,000 inhabitants (IBGE, 2013).
Data collection was performed at the Health Surveillance Center of the municipal council (CREVISA). The diagnosis of VL was made in the Parasitology Laboratory of Universidade Federal de São João del Rei, Dona Lindu Central-West Campus. Initially, all animal blood samples were prepared and subjected to the Enzyme-Linked Immunosorbent Assay (ELISA). Those that tested positive or indeterminate were then tested using the Indirect Fluorescent Antibody Test (IFAT) technique. Both tests were performed in accordance with the Bio-Manguinhos/FIOCRUZ protocol.
A clinical-epidemiological data sheet that covered the exposure variables analyzed in this study (age, sex, breed, type of hair and size), as well as issues relating to the clinical signs presented by the animals and to how the dogs were put down, was developed by the study team together with the CREVISA professionals. The sheets were filled out by the veterinarians at the center, at the time of the consultation or after the neutering. The dogs were culled after authorization was given by the owners or by the citizens who had asked for the stray dogs to be caught. The decision was made and carried out by the veterinarians of CREVISA, based either on clinical signs or on the VL serological findings, and was conducted in accordance with the ethical principles for animal experimentation that have been adopted by the Brazilian College of Animal Experimentation.
Descriptive analyses on the population were carried out, together with evaluation of the most frequent clinical signs in the seropositive animals. Pearson's chi-square test was used to study the associations between the exposure variables and the outcome (positive in both diagnostic techniques or indeterminate result in the ELISA and positive in the IFAT). To describe the force of the associations, the prevalence ratio (PR) was calculated. Logistic regression models were also fitted, using non-automated procedures to select the variables that would form the final model. The age variable was dichotomized using a generalized additive model (HIN et al., 1999). Interaction terms were added to the model and were excluded if they were not statistically significant. Through the modeling, odds ratios and their respective confidence intervals (CI) were obtained for the selected variables. In the initial procedures for defining the inclusion of variables in modeling procedures, p values < 0.10 were considered significant. In all the other procedures, p values < 0.05 were used. To register the data and statistical analysis, Epi-Info version 3.4.2 and R version 2.9.2 were used, respectively.
The work at CREVISA was monitored throughout the study period. The completion of the sheets (mentioned above) was confirmed and the performance of control actions recommended by the Brazilian Ministry of Health was analyzed (BRASIL, 2006Brasil. Ministério do Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de Vigilância e Controle da Leishmaniose Visceral. Brasília: Editora Ministério da Saúde; 2006.). To record and analyze the observations, an empirical, qualitative approach was used (LUDKE; ANDRé, 1986Ludke M, André MEDA. Pesquisa em educação: abordagens qualitativas. São Paulo: EPU; 1986.). This study was submitted to the Animal Research Ethics Committee (CEPEA) of UFSJ and was approved, with protocol number 35/2010.
A total of 755 clinical-epidemiological records were analyzed. Two hundred and twelve dogs (28.08%) were seropositive and 32 (4.2%) had indeterminate results in the ELISA. In the IFAT, 57.8% (141/244) presented negative results and 42.2% (103/244) tested positive. Thus, the prevalence in the canine population studied was 13.6% (103/755).
Regarding the clinical signs of the disease in the seropositive dogs, 23.3% (24/103) were asymptomatic and 76.7% (79/103) presented at least one clinical sign possibly associated with VL. Lymphadenopathy, alopecia, weight loss, dermatitis and onychogryphosis were the most frequent (Table 1).
Clinical signs observed in 103 dogs seropositive for visceral leishmaniasis, which were evaluated between May and October 2011, in the municipality of Divinópolis, MG, Brazil.
There was a higher prevalence of infections in the following animals: a) of pure breeds (PR = 1.15, CI = 0.78 - 1.69; p = 0.55); b) with short hair (PR = 1.13, CI = 0.70 - 1.84; p = 0.71); and c) over five years of age, (PR = 1.27: CI = 0.84-1.92; p = 0.27). The final multivariate model was composed of gender and size. Although not statistically significant, male dogs had a higher prevalence of infection (OR = 1.47; CI = 0.98-2.06; p = 0.06). On the other hand, regarding the size of the animals, there was a statistically significant difference in positivity between small dogs and medium to large-sized dogs (OR = 1.71; CI = 1.14-2.59; in relation to small dogs, p < 0.001) (Table 2).
Factors associated with occurrences of visceral leishmaniasis in a population of 755 dogs evaluated between May and October 2011, in the municipality of Divinópolis, MG, Brazil.
Out of the 755 dogs examined, 303 were put down. In 299 cases, the dogs were put down regardless of the serological results (i.e. it was done before serological tests were performed) and only four dogs were culled based on positive serological tests. Therefore, 200 seronegative animals were euthanized using non-standardized clinical criteria as the justification.
The monitoring of the control activities performed in the municipality revealed that they were being done inadequately. The canine surveys outlined by the Brazilian Ministry of Health (BRASIL, 2006Brasil. Ministério do Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de Vigilância e Controle da Leishmaniose Visceral. Brasília: Editora Ministério da Saúde; 2006.) were not being developed. Thus, only dogs sent to CREVISA due to spontaneous requests from citizens were examined. Moreover, actions targeting priority areas and sandfly vector control initiatives were not being implemented.
Among the population analyzed, 23.3% were asymptomatic even though they were serologically positive. These data reinforce the importance of these dogs in the epidemiology of the disease and are coincident with those of Feitosa et al. (2000)Feitosa MM, Ikeda FA, Luvizotto, MCR, Perri SHV. Aspectos clínicos de cães com leishmaniose visceral no município de Araçatuba- São Paulo (Brasil). Clin Vet 2000; 28: 36-44., who reported that 20% to 40% of seropositive dogs presented no clinical signs.
Regarding the epidemiological associations studied, the results described are
consistent with what has been identified in the literature. Data from a recent
systematic review (BELO et al., 2013Belo VS, Struchiner CJ, Werneck GL, Barbosa DS, Oliveira RB,
Teixeira-Neto RG, et al. A systematic review and meta-analysis of the factors
associated with Leishmania infantum infection in dogs in Brazil. Vet Parasitol
2013; 195(1-2): 1-13. PMid:23561325.
http://dx.doi.org/10.1016/j.vetpar.2013.03.010
http://dx.doi.org/10.1016/j.vetpar.2013....
) showed that
the potential risk factors associated with Leishmania infection are
generally weak and non-significant. This pattern was confirmed in the present study,
since all the associations had small force and operated in the same direction as the
meta-analysis conducted in that review.
Concerning the potential mechanisms underlying the direction of the
associations observed in the present study and in the review cited above, maintenance of
positive findings in serological tests, even for long periods after the infection, may
be an important cause of higher prevalence in older dogs (SRIVASTAVA et al., 2011Srivastava P, Dayama A, Mehrotra S, Sundar S. Diagnosis of visceral
leishmaniasis. Trans R Soc Trop Med Hyg 2011; 105(1): 1-6. PMid:21074233
PMCid:PMC2999003.
http://dx.doi.org/10.1016/j.trstmh.2010.09.006
http://dx.doi.org/10.1016/j.trstmh.2010....
). Furthermore, according to Matos (2006)Matos MM, Filgueira KD, Amora SSA, Suassuna ACD, Ahid SMM, Alves ND.
Ocorrência da Leishmaniose Visceral em cães em Mossoró, Rio Grande do
Norte. Cienc Anim 2006; 16(1): 51-54., these animals are usually kept
outside the home, which increases the contact with the vector. Although it has been
suggested that the prevalence of infection in dogs has bimodal distribution, with one
peak among dogs under 3 years of age and another between the ages of 8 and 10 years
(MIRó et al., 2012Miró G, Checa R, Montoya A, Hernández L, Dado D, Gálvez R. Current
situation of Leishmania infantum infection in shelter dogs in northern Spain.
Parasit Vectors 2012; 5: 60. PMid:22452948 PMCid:PMC3348073.
http://dx.doi.org/10.1186/1756-3305-5-60
http://dx.doi.org/10.1186/1756-3305-5-60...
), this pattern was not
observed in the present study. Although Paltrinieri et
al. (2010)Paltrinieri S, Solano-Gallego L, Fondati A, Lubas G, Gradoni L,
Castagnaro M, et al. Guidelines for diagnosis and clinical classification of
leishmaniasis in dogs. J Am Vet Med Assoc 2010; 236(11): 1184-1191.
PMid:20513195. http://dx.doi.org/10.2460/javma.236.11.1184
http://dx.doi.org/10.2460/javma.236.11.1...
pointed out that some breeds are more prone to develop CVL,
neither the causes of higher positivity in purebreds nor the specific breeds that are
more likely to be infected have been clearly established in the literature (BELO et al., 2013Belo VS, Struchiner CJ, Werneck GL, Barbosa DS, Oliveira RB,
Teixeira-Neto RG, et al. A systematic review and meta-analysis of the factors
associated with Leishmania infantum infection in dogs in Brazil. Vet Parasitol
2013; 195(1-2): 1-13. PMid:23561325.
http://dx.doi.org/10.1016/j.vetpar.2013.03.010
http://dx.doi.org/10.1016/j.vetpar.2013....
). Regarding the higher prevalence
observed in shorthaired dogs, it has been hypothesized that shorter-length fur could
facilitate vector feeding, thereby increasing the chance that the dog might contract the
infection (MOREIRA-JUNIOR et al., 2003Moreira-Junior 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(4): 393-397.). It is
important to emphasize, however, that in the present study such associations were not
statistically significant, and the role of chance cannot be ruled out. On the other
hand, the association at the threshold of statistical significance between male gender
and CVL and the significantly higher prevalence in medium and large-sized dogs, even
after controlling for confounding by other study variables in logistic regression
models, indicate that these were possibly the most important variables in the population
analyzed. There is a possibility that the higher prevalence of infection in males can be
explained by the distinct risks of exposure in this group. Immunological factors
relating to gender and to the susceptibility to infection have also been discussed in
the literature (ZAFRA et al., 2008Zafra R, Jaber JR, Pérez-Ecija RA, Barragán A, Martínez-Moreno A,
Pérez J. High iNOS expression in macrophages in canine leishmaniasis is
associated with low intracellular parasite burden. Vet Immunol Immunopathol
2008; 123(3-4): 353-359. PMid:18406470.
http://dx.doi.org/10.1016/j.vetimm.2008.02.022
http://dx.doi.org/10.1016/j.vetimm.2008....
). The size of
the dog as a potential risk factor for CVL has been analyzed in few studies (BELO et al., 2013Belo VS, Struchiner CJ, Werneck GL, Barbosa DS, Oliveira RB,
Teixeira-Neto RG, et al. A systematic review and meta-analysis of the factors
associated with Leishmania infantum infection in dogs in Brazil. Vet Parasitol
2013; 195(1-2): 1-13. PMid:23561325.
http://dx.doi.org/10.1016/j.vetpar.2013.03.010
http://dx.doi.org/10.1016/j.vetpar.2013....
) and its importance needs to be
better evaluated in future investigations. According to Ferrer (1999)Ferrer L. Leishmaniasis. In: Kirk RW, Bonagura JD. Current
veterinary therapy: small animal practice. 3rd ed. Philadelphia: W.B. Saunders;
1999. p. 266-270., larger dogs are more susceptible to the insect vector because
they spend more time outside of the home. Furthermore, we hypothesize that the greater
body surface area of larger dogs could also be a facilitator for blood meals for
sandflies.
It is currently accepted that the scientific evidence available on the
efficiency of dog culling for reducing the incidence of zoonotic VL is poor and of low
quality (BOUZID et al., 2013Bouzid M, Hooper L, Hunter PR. The effectiveness of public health
interventions to reduce the health impact of climate change: a systematic review
of systematic reviews. PLoS One 2013; 8(4): e62041. PMid:23634220
PMCid:PMC3636259.
http://dx.doi.org/10.1371/journal.pone.0062041
http://dx.doi.org/10.1371/journal.pone.0...
). Factors such as
the existence of other reservoirs (QUINNELL; COURTENAY,
2009Quinnell RJ, Courtenay O. Transmission, reservoir hosts and control
of zoonotic visceral leishmaniasis. Parasitology 2009; 136(14): 1915-1934.
PMid:19835643. http://dx.doi.org/10.1017/S0031182009991156
http://dx.doi.org/10.1017/S0031182009991...
), the low sensitivity and specificity of diagnostic tests (SILVA et al., 2011Silva DA, Madeira MF, Teixeira AC, de Souza CM, Figueiredo FB.
Laboratory tests performed on Leishmania seroreactive dogs euthanized by the
leishmaniasis control program. Vet Parasitol 2011; 179(1-3): 257-261.
PMid:21349644. http://dx.doi.org/10.1016/j.vetpar.2011.01.048
http://dx.doi.org/10.1016/j.vetpar.2011....
) and the replacement of
eliminated dogs by susceptible puppies (NUNES et al.,
2008Nunes CM, Lima VM, Paula HB, 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(1-2): 19-23. PMid:18314275.
http://dx.doi.org/10.1016/j.vetpar.2008.01.005
http://dx.doi.org/10.1016/j.vetpar.2008....
) can negatively impact the effectiveness of the strategy. The data from
the present study relating to dog culling highlight the need for better evaluation of
this procedure in this municipality and also in the control program for visceral
leishmaniasis in Brazil. Although it is recommended that in areas with moderate or
severe transmission, dogs should be put down not only if they are seropositive, but also
if they have clinical signs indicative of VL (BRASIL,
2006Brasil. Ministério do Saúde. Secretaria de Vigilância em
Saúde. Departamento de Vigilância Epidemiológica. Manual de
Vigilância e Controle da Leishmaniose Visceral. Brasília: Editora
Ministério da Saúde; 2006.), there is no clear definition of what these symptoms would be. This
lack of definition may lead to application of non-standard and inadequate criteria,
similar to what was found in Divinopolis, where a large number of seronegative dogs was
inadvertently euthanized. Considering that owners' opposition and ethical issues
(COSTA, 2011Costa CHN. How effective is dog culling in controlling zoonotic
visceral leishmaniasis? A critical evaluation of the science, politics and
ethics behind this public health policy. Rev Soc Bras Med Trop, 2011; 44(2):
232-242. PMid:21468480.
http://dx.doi.org/10.1590/S0037-86822011005000014
http://dx.doi.org/10.1590/S0037-86822011...
) are also important reasons for
the apparent failure of control by means of dog culling, it cannot be considered
acceptable that vague and inconclusive criteria are used to identify dogs that are going
to be culled.
Although human cases of VL started to be identified in Divinopolis in 2007, it was found in 2011 (the application period of this study) that the disease control efforts had not followed the recommendations outlined by the Brazilian Ministry of Health. In accordance with the epidemiological pattern of the municipality, canine sampling surveys should have been conducted in areas without human cases and annual census surveys should have been conducted in areas with notified human cases. Because of this limitation, there were no random animal samples and the number of examinations, considering the population of the municipality, was low. Moreover, only variables relating to characteristics of the animals could be analyzed in this study.
Finally, we emphasize that our results contribute towards better understanding of the dynamics of CVL infection and should be taken into consideration in relation to improvement of VL control strategies in Brazil. The limitations identified in the actions undertaken in Divinopolis highlight not only that there is a need for these to be modified there, but also that the Ministry of Health should undertake supervision of greater thoroughness in endemic municipalities in Brazil, with the aim that its recommendations should be followed appropriately.
Acknowledgements
The authors wish to thank the staff at CREVISA for their essential cooperation in this study.
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Publication Dates
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Publication in this collection
Oct-Dec 2013
History
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Received
19 Mar 2013 -
Accepted
11 Oct 2013