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A case of canine visceral leishmaniasis of unknown origin in Curitiba (state of Paraná, Brazil) treated successfully with miltefosine

Caso de leishmaniose visceral canina de origem desconhecida em Curitiba (Estado do Paraná, Brasil) tratado com sucesso com miltefosina

Abstract

There are no records of autochthonous cases of canine visceral leishmaniasis in the city of Curitiba, Paraná state, Brazil. In 2020, a male French bulldog (CW01), approximately 2 years old was taken by its owners to a private veterinarian clinic. The suspicion of CVL was confirmed by means of a serology test (ELISA/IFAT reagent), rapid chromatographic immunoassay (DPP®) (ELISA - Biomanguinhos®), parasitological culture and quantitative polymerase chain reaction (qPCR). The animal routinely frequented parks in Curitiba and was taken on several trips to the municipalities of Bombinhas and Balneário Camboriú (Santa Catarina) and to Matinhos (Paraná) where CVL had not previously been reported. Treatment was initiated orally with Milteforan™ which resulted in a significant reduction in the parasitic load. The suspicion of autochthony was investigated through entomological research. A total of 10 traps were installed, one at the animal’s home, seven in adjacent city blocks and two in a forest edge. No sandflies were trapped in the dog’s home and adjacent houses. The traps in the forest edge caught one Migonemyia migonei female and five Brumptomyia spp. females. This case serves as a warning of the possible introduction of CVL in the city of Curitiba.

Keywords:
Possible autochthonous transmission; Migonemyia migonei; Brumptomyia spp.; Leishmania infantum; visceral canine leishmaniasis

Resumo

Não há registros de casos autóctones de leishmaniose visceral canina (LVC) no município de Curitiba, Paraná, Brasil. Em 2020, um "bulldog" francês macho (CW01), com aproximadamente 2 anos de idade, foi levado por seus donos a uma clínica veterinária particular. A suspeita de LVC foi confirmada por meio de teste sorológico (reagente ELISA/IFAT), imunoensaio cromatográfico rápido (DPP®) (ELISA - Biomanguinhos®), cultura parasitológica e reação quantitativa em cadeia da polimerase (qPCR). O animal frequentava, rotineiramente, parques de Curitiba e foi levado em diversas viagens para Bombinhas e Balneário Camboriú (Santa Catarina) e para Matinhos (Paraná), onde a LVC não havia sido relatada anteriormente. O tratamento foi iniciado por via oral com Milteforan™ (Virbac) o que resultou em redução significativa da carga parasitária. A suspeita de autóctone foi investigada por meio de pesquisa entomológica. Foram instaladas 10 armadilhas, uma na casa do animal, sete em quarteirões adjacentes e duas na borda da mata. Nenhum inseto foi capturado na casa do proprietário do animal e nas casas adjacentes. As armadilhas na borda da mata capturaram uma fêmea de Migonemyia migonei e cinco Brumptomyia spp. fêmeas. Este caso serve de alerta para a possível introdução da LVC na cidade de Curitiba.

Palavras-chave:
Possível transmissão autóctone; Migonemyia migonei; Brumptomyia spp.; Leishmania infantum; leishmaniose visceral canina

Leishmaniasis is a parasitic disease caused by protozoan parasites of the genus Leishmania and transmitted by the bite of infected sandflies. The most severe form, visceral leishmaniasis (VL), has clinical features of severe evolution in humans (WHO, 2022World Health Organization - WHO. Leishmaniasis [online]. 2022 [cited 2022 Oct 10]. Available from: http://www.who.int/mediacentre/factsheets/fs375/en/#
http://www.who.int/mediacentre/factsheet...
), aggravated by the occurrence of a zoonotic cycle in South America and in the Mediterranean region (Werneck, 2014Werneck GL. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control. Rev Saude Publica 2014; 48(5): 851-855. http://dx.doi.org/10.1590/S0034-8910.2014048005615. PMid:25372177.
http://dx.doi.org/10.1590/S0034-8910.201...
). In this context, Leishmania infantum (syn = Leishmania chagasi) is the most important etiological agent involved, and domestic dogs (Canis familiaris) are the main reservoir in urban environments (Brasil, 2014Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Guia de vigilância em saúde. Brasília; 2014. 812 p.). Canine enzootic disease precedes the occurrence of human cases (Brasil, 2014Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Guia de vigilância em saúde. Brasília; 2014. 812 p.), and control of the zoonotic cycle is still the main challenge in disease control today (Werneck, 2014Werneck GL. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control. Rev Saude Publica 2014; 48(5): 851-855. http://dx.doi.org/10.1590/S0034-8910.2014048005615. PMid:25372177.
http://dx.doi.org/10.1590/S0034-8910.201...
).

An average of 3,500 new cases are recorded annually in Brazil, resulting in the death of approximately 250 humans. At first, the disease occurred mostly in small towns and rural areas in Brazil’s northeast region. However, in recent years, it has expanded rapidly to more populated urban areas, and an increasing number of cases have been reported in the north, center-west, southeast and even south of the country, which was free of the disease up to the 2000s (Brasil, 2022Brasil. Ministério da Saúde. Leishmaniose visceral [online]. Brasília; 2022 [cited 2022 Oct 10]. Available from: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/l/leishmaniose-visceral
https://www.gov.br/saude/pt-br/assuntos/...
).

Alternatives for treatment of the disease are limited and unsatisfactory. For over 60 years, human treatment involved the use of pentavalent antimonials (Chakravarty & Sundar, 2010Chakravarty J, Sundar S. Drug resistance in leishmaniasis. J Glob Infect Dis 2010; 2(2): 167-176. http://dx.doi.org/10.4103/0974-777X.62887. PMid:20606973.
http://dx.doi.org/10.4103/0974-777X.6288...
). Subsequently, new drugs were developed that still make up a small arsenal, which characterizes the disease as neglected. Current treatments are applied using three main drugs: pentavalent antimonials (drug of first choice), amphotericin B and miltefosine (Hefnawy et al., 2017Hefnawy A, Berg M, Dujardin G, Muylder G. Exploiting knowledge on Leishmania drug resistance to support the quest for new drugs. Trends Parasitol 2017; 33(3): 162-174. http://dx.doi.org/10.1016/j.pt.2016.11.003. PMid:27993477.
http://dx.doi.org/10.1016/j.pt.2016.11.0...
).

The treatment of canine visceral leishmaniasis with miltefosine started in Brazil in 2016 (Brasil, 2016Brasil. Ministério da Agricultura, Pecuária e Abastecimento. Nota técnica nº 11/2016. Brasília: Coordenação de Fiscalização de Produtos Veterinários; 2016.). However, failures have been reported in this treatment using solely miltefosine and in association with other drugs, in which the decrease in canine symptoms was not accompanied by parasite clearance (Andrade et al., 2011Andrade HM, Toledo VPCP, Pinheiro MB, Guimarães TMPD, Oliveira NC, Castro JA, et al. Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (= L. chagasi). Vet Parasitol 2011; 181(2-4): 83-90. http://dx.doi.org/10.1016/j.vetpar.2011.05.009. PMid:21641721.
http://dx.doi.org/10.1016/j.vetpar.2011....
). Thus, treatment is still not considered an effective measure because, in addition to the risk of parasite resistance (Gonçalves et al., 2021Gonçalves G, Campos MP, Gonçalves AS, Medeiros LCS, Figueiredo FB. Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol. Parasit Vectors 2021; 14(1): 599. http://dx.doi.org/10.1186/s13071-021-05100-x. PMid:34886876.
http://dx.doi.org/10.1186/s13071-021-051...
), relapses are frequent and dogs may be a source of infection by the invertebrate host even weeks after the end of treatment, despite clinical cure (Chappuis et al., 2007Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, et al. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control. Nat Rev Microbiol 2007; 5(11): 873-882. http://dx.doi.org/10.1038/nrmicro1748. PMid:17938629.
http://dx.doi.org/10.1038/nrmicro1748...
).

There are no records of autochthonous cases of canine visceral leishmaniasis in the city of Curitiba. However, studies such as those of Thomaz-Soccol et al. (2009)Thomaz-Soccol V, Castro EA, Navarro IT, Farias MR, de Souza LM, Carvalho Y, et al. Casos alóctones de leishmaniose visceral canina no Paraná, Brasil: implicações epidemiológicas. Rev Bras Parasitol Vet 2009; 18(3): 46-51. http://dx.doi.org/10.4322/rbpv.01803008. PMid:19772775.
http://dx.doi.org/10.4322/rbpv.01803008...
and Frehse et al. (2010)Frehse MS, Greca H Jr, Ullmann LS, Camossi L, Machado JG, Langoni H, et al. Surveillance of canine visceral leishmaniasis in a disease-free area. Rev Bras Parasitol Vet 2010; 19(1): 62-64. http://dx.doi.org/10.1590/S1984-29612010000100012. PMid:20385062.
http://dx.doi.org/10.1590/S1984-29612010...
observed positivity in dogs in this city, some of them allochthonous cases and some asymptomatic. These cases underscore the importance of epidemiological surveillance studies in the city, since domestic dogs are the main reservoir of the disease in urban environments, and once the vector is present, the transmission cycle can be established in new areas through the arrival of infected animals (Maia-Elkhoury et al., 2008Maia-Elkhoury ANS, Alves WA, Sousa-Gomes ML, Sena JM, Luna EA. Visceral leishmaniasis in Brazil: trends and challenges. Cad Saude Publica 2008; 24(12): 2941-2947. http://dx.doi.org/10.1590/S0102-311X2008001200024. PMid:19082286.
http://dx.doi.org/10.1590/S0102-311X2008...
). This article reports a case of canine visceral leishmaniasis of unknown origin, treated successfully with miltefosine, in Curitiba, state of Paraná, Brazil.

In January 2020, a male French bulldog (CW01), approximately 2 years old, non-neutered, exhibiting alopecia, skin desquamation and crusting, dermatitis, and lymphadenomegaly, was taken by its owners to a private veterinarian clinic. The staff veterinarian suspected canine visceral leishmaniasis (CVL) and ordered a blood count and serological tests.

After clinical and laboratory evaluation, it was found that the animal had normocytic and normochromic anemia, hyperproteinemia, but no biochemical alterations in liver and kidney functions. The suspicion of CVL was confirmed by means of a serology test (ELISA/IFAT reagent).

Following the recommendations of the Ministério da Saúde to confirm CVL, a new blood sample was collected and sent to the municipality’s official laboratory (LACEN-PR), where infection by L. infantum was confirmed in a rapid chromatographic immunoassay (DPP®) (ELISA - Biomanguinhos®).

As this case occurred in an area with no reports of transmission, other confirmatory tests such as parasitological culture and quantitative polymerase chain reaction (qPCR) were suggested and performed by the reference laboratory in Leishmaniasis (ICC-Fiocruz PR). For qPCR, intact skin fragments were collected using a 3 mm diameter punch, placed in a sterile flask free of RNase and DNase, and stored at -20 °C. For the parasitological culture, another fragment of skin, bone marrow and lymph node aspirates were collected. Samples were kept at 4 °C for 24 hours and then seeded in Novy-MacNeal-Nicole (NNN) medium and Schneider medium (supplemented with 10% SBF) and examined weekly for one month under an optical microscope to look for forms of promastigotes of the parasite. Infection was confirmed and the parasite was characterized as L. infantum using qPCR with species-specific primers. After DNA extraction, the sample was amplified using the TaqMan® system on the StepOne™ platform (Applied Biosystems®). The TaqMan® MGB probe (FAM-5’AAAAAAATGGGTGCAGAAAT-3’-NFQM-3GB) and PCR with primers LEISH-1 (5’-AACTTTCTGGCTCCGGGTAG-3’) and LEISH-2 (5’-ACCCCCAGTT TCCCGCC-3’) were designed to target conserved regions of L. infantum kDNA (Francino et al., 2006Francino O, Altet L, Sanchez-Robert E, Rodriguez A, Solano-Gallego L, Alberola J, et al. Advantages of real-time PCR assay for diagnosis and monitoring of canine leishmaniosis. Vet Parasitol 2006; 137(3-4): 214-221. http://dx.doi.org/10.1016/j.vetpar.2006.01.011. PMid:16473467.
http://dx.doi.org/10.1016/j.vetpar.2006....
). Samples were amplified on the StepOne™ platform (Applied Biosystems®). According to the stages suggested by Leishvet (Solano-Gallego et al., 2011Solano-Gallego L, Miró G, Koutinas A, Cardoso L, Pennisi MG, Ferrer L, et al. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit Vectors 2011; 4(1): 86. http://dx.doi.org/10.1186/1756-3305-4-86. PMid:21599936.
http://dx.doi.org/10.1186/1756-3305-4-86...
), this dog was in stage II (moderate disease), with a prognosis of good to moderate.

In describing the dog’s medical history, its owners stated that the animal routinely frequented parks in Curitiba and was taken on several trips to the municipalities of Bombinhas and Balneário Camboriú in the state of Santa Catarina and to Matinhos, a coastal town in the state of Paraná, where CVL had not previously been reported according to official data (Brasil, 2022Brasil. Ministério da Saúde. Leishmaniose visceral [online]. Brasília; 2022 [cited 2022 Oct 10]. Available from: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/l/leishmaniose-visceral
https://www.gov.br/saude/pt-br/assuntos/...
). The dog had never had a blood transfusion, and tests on the animal’s dam and sire could not be carried out.

The suspicion of CVL was confirmed by test results (T0, March 2020). A qPCR of the dog’s skin revealed a parasite load of ≤ 492 gEq, while DNA sequencing (Sanger method) confirmed that the growth of promastigote forms in parasite culture of skin and bone marrow was Leishmania infantum (MCAN/BR/19/CW01), with 100% homology.

Treatment was initiated orally with Milteforan™ (Virbac), following the manufacturer’s instructions of 2 mg/kg of body weight, once a day, for 28 consecutive days, as well as domperidone 0.5 mg/kg every 24 hours, orally, for 30 days. In addition, 10mg/kg of allopurinol was applied orally every 12 hours.

To control the parasite load and monitor for adverse effects, new tests were performed after 4 months of treatment (T1, July 2020). The qPCR revealed a significant reduction in the parasite load (0.1 gEq) of the animal, which was asymptomatic and showed no significant adverse effects. For follow-up, these tests were performed 1 year and 3 months after treatment (T2, October 2021) and 2 years after treatment (T3, August 2022), showing a low parasite load remained (0.1 gEq), without clinical signs. Upon the diagnosis of CVL, the lifelong use of an insect repellent dog collar was recommended to protect against sandflies.

The suspicion of autochthony was investigated through entomological research by the Paraná State Health Department (SESA) and the Curitiba Municipal Health Department (Surveillance and Zoonoses Unit), using CDC and Shannon light traps in the animal’s home and its surroundings for three consecutive days. A total of 10 traps were installed, one at the animal’s home, seven in adjacent city blocks and two in a forest edge located approximately 2.9 km from the home.

No sandflies were trapped in the dog’s home and adjacent houses. The traps in the forest edge caught one Migonemyia migonei female and five Brumptomyia spp. females, although the latter could not be identified to a specific level due to the similarity between the females that make up the genus.

This case serves as a warning of the possible introduction of CVL in the city of Curitiba. However, since the probable site of infection (PSI) of the case is unknown, the city is still considered to be free of transmission of this disease.

The patient in this report was taken to the municipality of Bombinhas (Santa Catarina, Brazil) on several occasions, and although there is no evidence of transmission of the disease in the aforementioned municipality, transmission is known to occur in other nearby locations, such as the capital Florianópolis (Steindel et al., 2013Steindel M, Menin A, Evangelista T, Stoco PH, Marlow MA, Fleith RC, et al. Outbreak of autochthonous canine visceral leishmaniasis in Santa Catarina, Brazil. Pesq Vet Bras 2013; 33(4): 490-496. http://dx.doi.org/10.1590/S0100-736X2013000400013.
http://dx.doi.org/10.1590/S0100-736X2013...
). Moreover, the dog was purchased from a kennel in the metropolitan region of Curitiba, but this information did not allow for identification of the kennel and the animal’s dam and sire, thus preventing the performance of tests. This is a troubling situation, because if the patient’s dam and/or sire are infected with the parasite, they can produce several generations of litters that are also positive, contributing to the spread of infected animals in an area initially not endemic for the disease.

Curitiba and its metropolitan area are located about 100 km from the region of Vale do Ribeira, which is widely known for the presence of sandflies. In this paper, we report for the first time the presence of Mi. migonei, mainly known for the transmission of cutaneous leishmaniasis (CL), in Curitiba, the capital of the state of Parana, which may be related to the registration of CL cases in and around Curitiba from 2001 to 2019 (Almeida et al., 2022Almeida TM, Romero I No, Consalter R, Brum FT, Rojas EAG, Costa-Ribeiro MCV. Predictive modeling of sand fly distribution incriminated in the transmission of Leishmania (Viannia) braziliensis and the incidence of Cutaneous Leishmaniasis in the state of Paraná, Brazil. Acta Trop 2022; 229: 106335. http://dx.doi.org/10.1016/j.actatropica.2022.106335. PMid:35101414.
http://dx.doi.org/10.1016/j.actatropica....
). However, this species has also previously been associated with the transmission of visceral leishmaniasis (Moya et al., 2015Moya SL, Giuliani MG, Manteca Acosta M, Salomón OD, Liotta DJ. First description of Migonemyia migonei (França) and Nyssomyia whitmani (Antunes & Coutinho) (Psychodidae: Phlebotominae) natural infected by Leishmania infantum in Argentina. Acta Trop 2015; 152: 181-184. http://dx.doi.org/10.1016/j.actatropica.2015.09.015. PMid:26409011.
http://dx.doi.org/10.1016/j.actatropica....
), making it of medical and veterinary importance in Leishmania spp. transmission. Additionally, Brumptomyia spp. have been reported to transmit L. braziliensis in northern Brazil (Araujo-Pereira et al., 2020Araujo-Pereira T, de Pita-Pereira D, Baia-Gomes SM, Boité M, Silva F, Pinto IS, et al. An overview of the sandfly fauna (Diptera: Psychodidae) followed by the detection of Leishmania DNA and blood meal identification in the state of Acre, Amazonian Brazil. Mem Inst Oswaldo Cruz 2020; 115(10): e200157. http://dx.doi.org/10.1590/0074-02760200157. PMid:33206821.
http://dx.doi.org/10.1590/0074-027602001...
), although previous studies described these species as non-anthropophilic (Rêgo et al., 2019Rêgo FD, Souza GD, Dornelles LFP, Andrade JD Fo. Ecology and molecular detection of Leishmania infantum Nicolle, 1908 (Kinetoplastida: Trypanosomatida) in wild-caught sand flies (Psychodidae: Phlebotominae) collected in Porto Alegre, Rio Grande do Sul: a new focus of visceral leishmaniasis in Brazil. J Med Entomol 2019; 56(2): 519-525. http://dx.doi.org/10.1093/jme/tjy175. PMid:30321358.
http://dx.doi.org/10.1093/jme/tjy175...
). This genus has also been reported in the states of São Paulo (Cutolo et al., 2013Cutolo AA, Galati EAB, Von Zuben CJ. Sandflies (Diptera, Psychodidae) from forest areas in Botucatu municipality, central western São Paulo State, Brazil. J Venom Anim Toxins Incl Trop Dis 2013; 19(1): 15. http://dx.doi.org/10.1186/1678-9199-19-15. PMid:23849624.
http://dx.doi.org/10.1186/1678-9199-19-1...
) and Paraná (Bianchi Galati et al., 2007Galati EAB, Santos DR, Silva AM. Brumptomyia angelae, a new species of Phlebotominae (Diptera, Psychodidae) of the Atlantic forest of the state of Paraná, Brazil. Mem Inst Oswaldo Cruz 2007; 102(6): 701-705. http://dx.doi.org/10.1590/S0074-02762007000600007. PMid:17923998.
http://dx.doi.org/10.1590/S0074-02762007...
), but has not been associated with the transmission of leishmaniasis. Published data report the presence of Lutzomyia neivai, Lu. fischeri and Lu. ayrozai, which are vectors of cutaneous leishmaniasis (CL), along the coast of Santa Catarina (Marcondes et al., 2005Marcondes CB, Conceição MBE, Portes MGT, Simão BP. Phlebotomine sandflies in a focus of dermal leishmaniasis in the eastern region of the Brazilian State of Santa Catarina: preliminary results (Diptera: Psychodidae). Rev Soc Bras Med Trop 2005; 38(4): 353-355. http://dx.doi.org/10.1590/S0037-86822005000400016. PMid:16082487.
http://dx.doi.org/10.1590/S0037-86822005...
). Species of the genus Lutzomyia have already been reported as naturally infected with L. infantum in endemic areas for visceral leishmaniasis, with indications of a possible participation of these species in disease transmission (Savani et al., 2009Savani ESMM, Nunes VLB, Galati EAB, Castilho TM, Zampieri RA, Floeter-Winter LM. The finding of Lutzomyia almerioi and Lutzomyia longipalpis naturally infected by Leishmania spp. in a cutaneous and canine visceral leishmaniases focus in Serra da Bodoquena, Brazil. Vet Parasitol 2009; 160(1-2): 18-24. http://dx.doi.org/10.1016/j.vetpar.2008.10.090. PMid:19062193.
http://dx.doi.org/10.1016/j.vetpar.2008....
; Falcão de Oliveira et al., 2017Falcão de Oliveira E, Oshiro ET, Fernandes WS, Murat PG, Medeiros MJ, Souza AI, et al. Experimental infection and transmission of Leishmania by Lutzomyia cruzi (Diptera: Psychodidae): Aspects of the ecology of parasite-vector interactions. PLoS Negl Trop Dis 2017; 11(2): e0005401. http://dx.doi.org/10.1371/journal.pntd.0005401. PMid:28234913.
http://dx.doi.org/10.1371/journal.pntd.0...
), alerting to the possible role of sand fly species not traditionally involved in the transmission of the parasite in the anthropozoonotic cycle of the disease.

Another interesting aspect of this case is the success of the treatment, which can be attributed to the fact that this was a young dog without comorbidity, with early diagnosis and correct treatment, which allowed rapid and continuous improvement of the patient’s clinical condition. It is worth noting that there is no parasitological cure for CVL, only clinical control; hence, a repellent collar must be worn throughout the animal’s lifetime and must be monitored continuously.

Since 2016, health authorities of the Zoonotic Disease Surveillance Unit and the Paraná State Health Department have carried out periodic CVL monitoring of dogs in the municipality. In addition, entomological surveys were carried out in 2018 and 2020, and over the years, awareness among veterinarians has been raised by an increase in notifications, with all cases investigated and followed up.

Canine visceral leishmaniasis is a complex disease that requires integrated actions for its control in animals and humans. In this report, we demonstrate the importance of interaction and communication among public agencies (LACEN - PR, Fiocruz PR, SESA, UVZ) and independent veterinarians for the diagnosis, treatment and control of this zoonotic disease.

Acknowledgements

This study was funded by Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) by the grant for productivity in research (309862/2015-9) and Professional Education Expansion Program (Proep) by the grant nº 442055/2019-6. This study also was supported by Instituto Carlos Chagas and Fundação Oswaldo Cruz (Fiocruz). The funders had no role in the decision to publish, or preparation of the manuscript.

  • How to cite: Gonçalves G, Campos MP, Tirado TC, Negrão DD, Silva GMP, Poleto APCM, et al. A case of canine visceral leishmaniasis of unknown origin in Curitiba (state of Paraná, Brazil) treated successfully with miltefosine. Braz J Vet Parasitol 2023; 32(2): e001123. https://doi.org/10.1590/S1984-29612023026

References

  • Almeida TM, Romero I No, Consalter R, Brum FT, Rojas EAG, Costa-Ribeiro MCV. Predictive modeling of sand fly distribution incriminated in the transmission of Leishmania (Viannia) braziliensis and the incidence of Cutaneous Leishmaniasis in the state of Paraná, Brazil. Acta Trop 2022; 229: 106335. http://dx.doi.org/10.1016/j.actatropica.2022.106335 PMid:35101414.
    » http://dx.doi.org/10.1016/j.actatropica.2022.106335
  • Andrade HM, Toledo VPCP, Pinheiro MB, Guimarães TMPD, Oliveira NC, Castro JA, et al. Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (= L. chagasi). Vet Parasitol 2011; 181(2-4): 83-90. http://dx.doi.org/10.1016/j.vetpar.2011.05.009 PMid:21641721.
    » http://dx.doi.org/10.1016/j.vetpar.2011.05.009
  • Araujo-Pereira T, de Pita-Pereira D, Baia-Gomes SM, Boité M, Silva F, Pinto IS, et al. An overview of the sandfly fauna (Diptera: Psychodidae) followed by the detection of Leishmania DNA and blood meal identification in the state of Acre, Amazonian Brazil. Mem Inst Oswaldo Cruz 2020; 115(10): e200157. http://dx.doi.org/10.1590/0074-02760200157 PMid:33206821.
    » http://dx.doi.org/10.1590/0074-02760200157
  • Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Guia de vigilância em saúde. Brasília; 2014. 812 p.
  • Brasil. Ministério da Agricultura, Pecuária e Abastecimento. Nota técnica nº 11/2016. Brasília: Coordenação de Fiscalização de Produtos Veterinários; 2016.
  • Brasil. Ministério da Saúde. Leishmaniose visceral [online]. Brasília; 2022 [cited 2022 Oct 10]. Available from: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/l/leishmaniose-visceral
    » https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/l/leishmaniose-visceral
  • Chakravarty J, Sundar S. Drug resistance in leishmaniasis. J Glob Infect Dis 2010; 2(2): 167-176. http://dx.doi.org/10.4103/0974-777X.62887 PMid:20606973.
    » http://dx.doi.org/10.4103/0974-777X.62887
  • Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, et al. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control. Nat Rev Microbiol 2007; 5(11): 873-882. http://dx.doi.org/10.1038/nrmicro1748 PMid:17938629.
    » http://dx.doi.org/10.1038/nrmicro1748
  • Cutolo AA, Galati EAB, Von Zuben CJ. Sandflies (Diptera, Psychodidae) from forest areas in Botucatu municipality, central western São Paulo State, Brazil. J Venom Anim Toxins Incl Trop Dis 2013; 19(1): 15. http://dx.doi.org/10.1186/1678-9199-19-15 PMid:23849624.
    » http://dx.doi.org/10.1186/1678-9199-19-15
  • Falcão de Oliveira E, Oshiro ET, Fernandes WS, Murat PG, Medeiros MJ, Souza AI, et al. Experimental infection and transmission of Leishmania by Lutzomyia cruzi (Diptera: Psychodidae): Aspects of the ecology of parasite-vector interactions. PLoS Negl Trop Dis 2017; 11(2): e0005401. http://dx.doi.org/10.1371/journal.pntd.0005401 PMid:28234913.
    » http://dx.doi.org/10.1371/journal.pntd.0005401
  • Francino O, Altet L, Sanchez-Robert E, Rodriguez A, Solano-Gallego L, Alberola J, et al. Advantages of real-time PCR assay for diagnosis and monitoring of canine leishmaniosis. Vet Parasitol 2006; 137(3-4): 214-221. http://dx.doi.org/10.1016/j.vetpar.2006.01.011 PMid:16473467.
    » http://dx.doi.org/10.1016/j.vetpar.2006.01.011
  • Frehse MS, Greca H Jr, Ullmann LS, Camossi L, Machado JG, Langoni H, et al. Surveillance of canine visceral leishmaniasis in a disease-free area. Rev Bras Parasitol Vet 2010; 19(1): 62-64. http://dx.doi.org/10.1590/S1984-29612010000100012 PMid:20385062.
    » http://dx.doi.org/10.1590/S1984-29612010000100012
  • Galati EAB, Santos DR, Silva AM. Brumptomyia angelae, a new species of Phlebotominae (Diptera, Psychodidae) of the Atlantic forest of the state of Paraná, Brazil. Mem Inst Oswaldo Cruz 2007; 102(6): 701-705. http://dx.doi.org/10.1590/S0074-02762007000600007 PMid:17923998.
    » http://dx.doi.org/10.1590/S0074-02762007000600007
  • Gonçalves G, Campos MP, Gonçalves AS, Medeiros LCS, Figueiredo FB. Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol. Parasit Vectors 2021; 14(1): 599. http://dx.doi.org/10.1186/s13071-021-05100-x PMid:34886876.
    » http://dx.doi.org/10.1186/s13071-021-05100-x
  • Hefnawy A, Berg M, Dujardin G, Muylder G. Exploiting knowledge on Leishmania drug resistance to support the quest for new drugs. Trends Parasitol 2017; 33(3): 162-174. http://dx.doi.org/10.1016/j.pt.2016.11.003 PMid:27993477.
    » http://dx.doi.org/10.1016/j.pt.2016.11.003
  • Maia-Elkhoury ANS, Alves WA, Sousa-Gomes ML, Sena JM, Luna EA. Visceral leishmaniasis in Brazil: trends and challenges. Cad Saude Publica 2008; 24(12): 2941-2947. http://dx.doi.org/10.1590/S0102-311X2008001200024 PMid:19082286.
    » http://dx.doi.org/10.1590/S0102-311X2008001200024
  • Marcondes CB, Conceição MBE, Portes MGT, Simão BP. Phlebotomine sandflies in a focus of dermal leishmaniasis in the eastern region of the Brazilian State of Santa Catarina: preliminary results (Diptera: Psychodidae). Rev Soc Bras Med Trop 2005; 38(4): 353-355. http://dx.doi.org/10.1590/S0037-86822005000400016 PMid:16082487.
    » http://dx.doi.org/10.1590/S0037-86822005000400016
  • Moya SL, Giuliani MG, Manteca Acosta M, Salomón OD, Liotta DJ. First description of Migonemyia migonei (França) and Nyssomyia whitmani (Antunes & Coutinho) (Psychodidae: Phlebotominae) natural infected by Leishmania infantum in Argentina. Acta Trop 2015; 152: 181-184. http://dx.doi.org/10.1016/j.actatropica.2015.09.015 PMid:26409011.
    » http://dx.doi.org/10.1016/j.actatropica.2015.09.015
  • Rêgo FD, Souza GD, Dornelles LFP, Andrade JD Fo. Ecology and molecular detection of Leishmania infantum Nicolle, 1908 (Kinetoplastida: Trypanosomatida) in wild-caught sand flies (Psychodidae: Phlebotominae) collected in Porto Alegre, Rio Grande do Sul: a new focus of visceral leishmaniasis in Brazil. J Med Entomol 2019; 56(2): 519-525. http://dx.doi.org/10.1093/jme/tjy175 PMid:30321358.
    » http://dx.doi.org/10.1093/jme/tjy175
  • Savani ESMM, Nunes VLB, Galati EAB, Castilho TM, Zampieri RA, Floeter-Winter LM. The finding of Lutzomyia almerioi and Lutzomyia longipalpis naturally infected by Leishmania spp. in a cutaneous and canine visceral leishmaniases focus in Serra da Bodoquena, Brazil. Vet Parasitol 2009; 160(1-2): 18-24. http://dx.doi.org/10.1016/j.vetpar.2008.10.090 PMid:19062193.
    » http://dx.doi.org/10.1016/j.vetpar.2008.10.090
  • Solano-Gallego L, Miró G, Koutinas A, Cardoso L, Pennisi MG, Ferrer L, et al. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit Vectors 2011; 4(1): 86. http://dx.doi.org/10.1186/1756-3305-4-86 PMid:21599936.
    » http://dx.doi.org/10.1186/1756-3305-4-86
  • Steindel M, Menin A, Evangelista T, Stoco PH, Marlow MA, Fleith RC, et al. Outbreak of autochthonous canine visceral leishmaniasis in Santa Catarina, Brazil. Pesq Vet Bras 2013; 33(4): 490-496. http://dx.doi.org/10.1590/S0100-736X2013000400013
    » http://dx.doi.org/10.1590/S0100-736X2013000400013
  • Thomaz-Soccol V, Castro EA, Navarro IT, Farias MR, de Souza LM, Carvalho Y, et al. Casos alóctones de leishmaniose visceral canina no Paraná, Brasil: implicações epidemiológicas. Rev Bras Parasitol Vet 2009; 18(3): 46-51. http://dx.doi.org/10.4322/rbpv.01803008 PMid:19772775.
    » http://dx.doi.org/10.4322/rbpv.01803008
  • Werneck GL. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control. Rev Saude Publica 2014; 48(5): 851-855. http://dx.doi.org/10.1590/S0034-8910.2014048005615 PMid:25372177.
    » http://dx.doi.org/10.1590/S0034-8910.2014048005615
  • World Health Organization - WHO. Leishmaniasis [online]. 2022 [cited 2022 Oct 10]. Available from: http://www.who.int/mediacentre/factsheets/fs375/en/#
    » http://www.who.int/mediacentre/factsheets/fs375/en/#

Publication Dates

  • Publication in this collection
    15 May 2023
  • Date of issue
    2023

History

  • Received
    23 Jan 2023
  • Accepted
    04 Apr 2023
Colégio Brasileiro de Parasitologia Veterinária FCAV/UNESP - Departamento de Patologia Veterinária, Via de acesso Prof. Paulo Donato Castellane s/n, Zona Rural, , 14884-900 Jaboticabal - SP, Brasil, Fone: (16) 3209-7100 RAMAL 7934 - Jaboticabal - SP - Brazil
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