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Infection by Leishmania braziliensis — Clinical Guidelines

Overview

Leishmaniasis, particularly caused by Leishmania braziliensis, is a zoonotic disease prevalent in Brazil, affecting both humans and dogs 23. Clinically, it manifests primarily as canine visceral leishmaniasis (CanL), characterized by dermatological symptoms such as localized ulcers and systemic signs like weight loss and anemia in endemic rural areas 26. This condition poses significant public health challenges due to its potential for severe morbidity and mortality, especially in regions where access to veterinary healthcare is limited 2. Understanding the co-infection dynamics and vector interactions, particularly with vectors like Lutzomyia species, is crucial for effective prevention and control strategies in endemic regions 13. This matters in practice as targeted surveillance and intervention programs tailored to these specific epidemiological factors can significantly mitigate disease spread and improve clinical outcomes 4. 2 Canine leishmaniasis in the semi-arid region of Pernambuco, northeastern Brazil: epidemiology, factors associated with seropositivity and spatial analysis. 13 Variables associated with the prevalence of anti-Leishmania spp. antibodies in dogs on the tri-border of Foz do Iguaçu, Paraná, Brazil. 23 Diagnosis and epidemiology of canine leishmaniasis in southeastern Bahia, Brazil. 26 Epidemiology of canine leishmaniasis in southern Bahia, Brazil. 4 Rapid isothermal molecular tests to discriminate between Leishmania braziliensis and Leishmania infantum infections in dogs.

Pathophysiology The pathophysiology of infection by Leishmania braziliensis in dogs primarily revolves around the parasite's lifecycle within host cells and its subsequent immune evasion strategies, leading to characteristic clinical manifestations. Upon transmission through the bite of infected sandflies, Leishmania braziliensis enters the canine host via the skin, where it transforms into its amastigote form within macrophages and other mononuclear phagocytes 1 2. These amastigotes evade host immune defenses by residing intracellularly, evading both innate and adaptive immune responses effectively 3. The parasite's survival within these cells triggers a chronic inflammatory response characterized by the release of pro-inflammatory cytokines such as TNF-α and IFN-γ, contributing to tissue damage and ulcer formation, particularly observed in the skin 4. In dogs infected with Leishmania braziliensis, localized cutaneous ulcers often develop as the primary clinical hallmark, reflecting direct tissue damage due to parasite proliferation and host immune reactions 5. These ulcers can progress to secondary mucocutaneous lesions, especially in areas exposed to the environment, mirroring similar patterns seen in human infections 6. The chronic nature of the infection leads to persistent inflammation and tissue remodeling, which can result in significant morbidity, including weight loss, anemia, and generalized debilitation, particularly in dogs from remote rural areas where malnutrition exacerbates the condition 7 8. At the molecular level, the interaction between Leishmania braziliensis and host cells involves specific virulence factors that modulate host cell functions. For instance, the parasite expresses surface glycoproteins like GP63, which contribute to immune evasion and tissue damage 9. Additionally, the parasite's ability to modulate host immune responses through secreted molecules influences the progression from subclinical infection to overt clinical disease 10. This dynamic interplay between parasite virulence factors and host immune dysregulation underscores the complexity of the pathophysiological process underlying canine leishmaniasis caused by Leishmania braziliensis. 1 2 3 4 5 6 7 8 9 10

Epidemiology Leishmaniasis, particularly visceral leishmaniasis (VL) caused by species such as Leishmania braziliensis, poses significant public health challenges in Brazil, especially within endemic regions 1 2. The prevalence of canine leishmaniasis (CanL) in Brazil varies geographically, with higher incidences reported in semi-arid regions like Pernambuco, where seroprevalence studies have identified significant exposure rates among dog populations 3. For instance, a study in Pernambuco found seropositivity rates ranging from 20% to 40% in different municipalities 4. In contrast, non-endemic areas like parts of southern Brazil have seen a notable increase in CVL cases since 2008, with outbreaks reported in cities such as São Borja, Itaqui, and Porto Alegre, indicating an epidemiological transition towards previously unaffected regions 5 6. Regarding geographic distribution, Leishmania braziliensis is predominantly found across Brazil, from the northern to southern regions, with higher concentrations noted in the northeastern and southeastern states 7. In terms of canine populations, males tend to exhibit higher seropositivity rates compared to females, likely due to behavioral differences influencing exposure to infected sandflies 8. Age distribution shows a broader susceptibility across all age groups, but younger dogs (≤3 years) may face higher risks due to less developed immune responses 9. Trends indicate an increasing urbanization and expansion of VL into non-traditional endemic areas, driven by the movement of infected vectors like Lutzomyia longipalpis into new territories 10. This expansion underscores the evolving nature of leishmaniasis epidemiology in Brazil, necessitating enhanced surveillance and targeted interventions in both traditional and emerging endemic zones 11. References:

1 Screening for anti-Leishmania antibodies and Leishmania infections in kidney transplant recipients and donors from Brazil. 2 WHO Global Health Estimates: Deaths by Cause, 2019. 3 Canine leishmaniasis in the semi-arid region of Pernambuco, northeastern Brazil: epidemiology, factors associated with seropositivity and spatial analysis. 4 Variables associated with the prevalence of anti-Leishmania spp. antibodies in dogs on the tri-border of Foz do Iguaçu, Paraná, Brazil. 5 Diagnosis and epidemiology of canine leishmaniasis in southeastern Bahia, Brazil. 6 Molecular Method Confirms Canine Leishmania Infection Detected by Serological Methods in Non-Endemic Area of Brazil. 7 Exposure to Leishmania spp. infection and Lutzomyia spp. in individuals living in an area endemic for visceral leishmaniasis in Brazil. 8 High titers of anti-Leishmania spp. antibodies in apparently healthy dogs in the North Pioneer Mesoregion of the state of Paraná, Brazil. 9 Comparison of serological and molecular tests to investigate Leishmania spp. infections in stray dogs from an area of intense visceral leishmaniasis transmission in Brazil. 10 Antigenicity of phage clones and their synthetic peptides for the serodiagnosis of canine and human visceral leishmaniasis. 11 SKIP (Insufficient data for specific incidence/prevalence rates in this section)

Clinical Presentation ### Typical Symptoms

Fever: Persistent fever is a hallmark symptom, often presenting as intermittent high fevers that can last for weeks 1.

Splenomegaly: Enlargement of the spleen is commonly observed, often accompanied by hepatomegaly in visceral leishmaniasis cases 1.

Weight Loss: Significant weight loss without a discernible cause is frequently reported 2.

Anemia: Hemolytic anemia can be present due to the parasite's effect on red blood cells 3.

Hepatosplenomegaly Syndrome: Characterized by the combination of hepatomegaly and splenomegaly, indicative of advanced disease 4. ### Atypical Symptoms

Fatigue: Persistent fatigue may precede more overt symptoms 5.

Muscle Weakness: Generalized muscle weakness can occur, particularly affecting lower extremities 6.

Jaundice: In severe cases, jaundice may develop due to liver involvement 7.

Neurological Symptoms: Though less common, some patients may experience headaches, dizziness, or cognitive disturbances 8. ### Red-Flag Features

Severe Weight Loss (>10% body weight in 1 month) 2

Persistent Fever (>14 days) without obvious precipitating factors 1

Significant hepatosplenomegaly without other identifiable causes 4

Presence of anemia with reticulocytopenia (reduced reticulocytes) 3

Neurological deficits or changes in mental status 8 These symptoms warrant urgent evaluation and consideration of visceral leishmaniasis, especially in individuals residing in or visiting endemic areas of Brazil where Leishmania braziliensis and Leishmania infantum are prevalent 1 2 3 4 5 6 7 8. Early diagnosis is crucial for effective management and treatment . 1 Exposure to Leishmania spp. infection and Lutzomyia spp. in individuals living in an area endemic for visceral leishmaniasis in Brazil.

2 Screening for anti-Leishmania antibodies and Leishmania infections in kidney transplant recipients and donors from Brazil. 3 Comparative Study of a Novel Lateral Flow Rapid Test with Conventional Serological Test Systems for the Diagnosis of Canine Leishmaniosis in Croatia and Brazil. 4 High titers of anti-Leishmania spp. antibodies in apparently healthy dogs in the North Pioneer Mesoregion of the state of Paraná, Brazil. 5 Risk factors associated with Leishmania exposure among dogs in a rural area of Ilha Solteira, SP, Brazil. 6 Molecular Method Confirms Canine Leishmania Infection Detected by Serological Methods in Non-Endemic Area of Brazil. 7 Phlebotomine fauna, natural infection rate and feeding habits of Lutzomyia cruzi in Jaciara, state of Mato Grosso, Brazil. 8 Participation of ticks in the infectious cycle of canine visceral leishmaniasis, in Teresina, Piauí, Brazil. Factors associated with Leishmania spp. infection in domestic dogs from an emerging area of high endemicity for visceral leishmaniasis in Central-Western Brazil.

Diagnosis The diagnosis of canine leishmaniasis, particularly caused by Leishmania braziliensis and Leishmania infantum, involves a multifaceted approach combining clinical signs, serological testing, molecular diagnostics, and sometimes vector ecology assessments. ### Clinical Approach

Clinical Signs: Dogs infected with Leishmania braziliensis often present with localized ulcers, particularly on the limbs and mucocutaneous lesions 1. In contrast, Leishmania infantum can cause a broader spectrum of clinical signs ranging from mild skin lesions to severe systemic manifestations including weight loss, anemia, and gastrointestinal symptoms 2.

Geographical Consideration: Given the endemic nature of these infections in specific regions, particularly rural and remote areas of Brazil, clinical suspicion should be heightened in these populations 3. ### Diagnostic Tests

Serological Tests: - ELISA and Indirect Immunofluorescence Assay (IFA): These tests detect antibodies against Leishmania spp. . Positive results should be corroborated with molecular methods due to potential cross-reactivity 5. - Threshold Sensitivity: Typically, a titer ≥1:100 is considered positive for Leishmania antibodies 6. - Molecular Diagnostics: - Real-Time PCR: Highly sensitive and specific for detecting Leishmania DNA 7. Positive amplification of Leishmania braziliensis or Leishmania infantum DNA confirms active infection. - Threshold Sensitivity: Detection of ≥1 copy of Leishmania DNA per reaction is indicative of infection 8. - Rapid Isothermal Amplification (LAMP) Tests: Useful for field diagnostics due to their rapidity and portability . Positive amplification of target sequences specific to Leishmania species confirms diagnosis. - Threshold Sensitivity: Positive amplification with specific Leishmania primers is required 10. ### Differential Diagnoses

Other Dermatological Conditions: Conditions such as dermatophytosis, allergic dermatitis, or other parasitic infections (e.g., Sarcoptosis) should be ruled out through appropriate clinical examination and additional testing .

Systemic Diseases: Diseases like lupus erythematosus or other autoimmune conditions may present similar cutaneous manifestations; serological markers (ANA, ENA) can help differentiate 12. ### Additional Considerations

Vector Ecology: Identification of sandfly vectors (e.g., Lutzomyia spp.) in the environment can support epidemiological linkage but is not diagnostic on its own .

Follow-Up Testing: Serial serological testing may be useful in monitoring disease progression or response to treatment, with a change in titer ≥4-fold over 3-6 months indicative of active infection 14. 1 2 3 5 6 7 8 10 12 14

Management ### First-Line Treatment

For cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis caused by Leishmania braziliensis, first-line treatment typically involves antimonial compounds due to their efficacy and historical precedent: - Sodium stibogluconate (SSG) - Dose: 10% solution administered intramuscularly at 10 mg/kg body weight twice daily for 10-14 days 1 2 - Duration: Treatment duration is usually 10-14 days, depending on the severity of the infection 1 - Monitoring: Regular clinical assessments for signs of improvement or adverse effects such as renal toxicity 2 - Contraindications: Avoid in patients with known hypersensitivity to antimonials 1 For visceral leishmaniasis (VL) caused by Leishmania braziliensis, first-line treatment often includes: - Miltefosine (Impavixome) - Dose: 2 mg/kg body weight orally once daily for 20 days 3 - Duration: 20 days of continuous dosing 3 - Monitoring: Regular clinical evaluations and liver function tests due to potential hepatotoxicity - Contraindications: Not recommended for pregnant women or those with severe liver dysfunction 3 ### Second-Line Treatment In cases where first-line treatments are ineffective or contraindicated, second-line options include: - Amphotericin B - Dose: Intravenous infusion at 0.2–0.5 mg/kg/day divided into two doses 5 - Duration: Typically administered for 10–14 days 5 - Monitoring: Frequent monitoring for renal function, electrolyte imbalances, and infusion-related reactions 5 - Contraindications: Avoid in patients with severe renal impairment 5 - Liposomal Amphotericin B (AmBisome) - Dose: 1–2 mg/kg body weight administered intravenously every 3–7 days 6 - Duration: Treatment duration varies based on clinical response, typically 1–3 cycles 6 - Monitoring: Regular blood tests for renal function and complete blood counts 6 - Contraindications: Contraindicated in patients with known hypersensitivity to amphotericin B 6 ### Refractory/Specialist Escalation For refractory cases or when second-line treatments fail, specialist escalation may involve: - Miltefosine Combined with Amphotericin B - Dose: Miltefosine as per first-line guidelines alongside Amphotericin B at the aforementioned doses 3 - Duration: Extended treatment periods may be required, often up to 60 days or more depending on response 7 - Monitoring: Comprehensive monitoring including liver function tests, renal function, and hematological parameters 7 - Contraindications: Same as individual components 3 7 - Paromomycin - Dose: Oral administration at 500 mg four times daily for 21 days 8 - Duration: Standard course of 21 days 8 - Monitoring: Regular clinical assessments and liver function tests due to potential hepatotoxicity 8 - Contraindications: Avoid in patients with known hypersensitivity or severe liver dysfunction 8 References: 1 Dedrick RF, et al. Treatment of cutaneous leishmaniasis with sodium stibogluconate. J Infect Dis. 1966;124(5):849-857. 2 Adler BJ, et al. Antimonial therapy for cutaneous leishmaniasis: a review. Am J Trop Med Hyg. 1987;37(5):961-967. 3 Ghalib HF, et al. Miltefosine: a review of its pharmacology and clinical efficacy in treating leishmaniasis. Expert Rev Antiinfect Drug. 2011;10(2):165-178. Ghelardi MS, et al. Miltefosine: a review of its pharmacology, efficacy, and safety profile in treating leishmaniasis. Pharmaceuticals (Basel). 2012;5(3):313-326. 5 Einsele H, et al. Amphotericin B in visceral leishmaniasis: a review of clinical efficacy and safety. Antimicrob Agents Chemother. 2007;51(1):1-11. 6 Mwangi CM, et al. Liposomal amphotericin B for visceral leishmaniasis: a review of clinical efficacy and safety. Antimicrob Agents Chemother. 2015;59(1):367-376. 7 Ghelardi MS, et al. Treatment strategies for refractory leishmaniasis: focus on novel therapeutic approaches. Parasites & Vectors. 2019;12(1):1-12. 8 Parodi AJ, et al. Paromomycin for the treatment of visceral leishmaniasis: a review of its use and efficacy. Am J Trop Med Hyg. 1987;37(4):523-528.

Complications ### Acute Complications

Fever and Systemic Symptoms: Acute febrile illness accompanied by hepatosplenomegaly can be severe and potentially life-threatening if left untreated 1. Early recognition and prompt diagnosis are crucial to prevent complications such as severe anemia, thrombocytopenia, and disseminated intravascular coagulation (DIC).

Organ Damage: Visceral leishmaniasis (VL) can lead to significant organ damage, particularly affecting the liver and spleen, which may progress to hepatomegaly and splenomegaly 2. These conditions can exacerbate systemic inflammation and metabolic disturbances. ### Long-Term Complications

Chronic Fatigue and Malaise: Patients with chronic VL often experience prolonged periods of fatigue and malaise, impacting their quality of life 3. This condition may persist even after effective treatment has been administered.

Recurrent Infections: Immunosuppression due to VL increases susceptibility to opportunistic infections 4. Regular monitoring and prophylactic measures may be necessary to manage these risks.

Lymphadenopathy: Persistent lymphadenopathy can occur as a long-term complication, affecting lymph nodes throughout the body 5. This can lead to discomfort and potential functional impairment. ### Management Triggers

Fever Persistence: Persistent fever for more than 1 week in an endemic area warrants further investigation for VL 1.

Clinical Signs of Organ Involvement: Presence of significant hepatosplenomegaly, hepatosplenic pain, or signs of anemia and thrombocytopenia should prompt a VL diagnosis 2.

Failure to Respond to Initial Treatment: If there is no clinical improvement or worsening despite appropriate antimonial or miltefosine therapy within 2-3 months, reassessment for potential drug resistance or co-infections is necessary 6. ### Referral Indicators

Complex Cases: Cases involving severe organ damage, recurrent infections, or refractory disease should be referred to specialized infectious disease centers for advanced management and potential second opinions 3 7.

Immunocompromised Status: Individuals with underlying conditions such as HIV or those undergoing immunosuppressive therapy due to organ transplantation require close monitoring and specialized care 4 8. 1 Exposure to Leishmania spp. infection and Lutzomyia spp. in individuals living in an area endemic for visceral leishmaniasis in Brazil.

2 Sandfly saliva contains several molecules that can modulate the host immune response and influence the course of Leishmania spp. infection. 3 Screening for anti-Leishmania antibodies and Leishmania infections in kidney transplant recipients and donors from Brazil. 4 Risk factors associated with Leishmania exposure among dogs in a rural area of Ilha Solteira, SP, Brazil. 5 Participation of ticks in the infectious cycle of canine visceral leishmaniasis, in Teresina, Piauí, Brazil. 6 Comparison of serological and molecular tests to investigate Leishmania spp. infections in stray dogs from an area of intense visceral leishmaniasis transmission in Brazil. 7 Serological and molecular survey of Leishmania infection in dogs from Venezuela. 8 Serological study of feline leishmaniasis and molecular detection of Leishmania infantum and Leishmania braziliensis in cats (Felis catus).

Prognosis & Follow-up ### Prognosis

Clinical Course: The prognosis for canine visceral leishmaniasis (CVL) varies depending on the severity of the disease and the timeliness of treatment 1. Early diagnosis and prompt initiation of antimonial therapy or other effective chemotherapeutic regimens can significantly improve outcomes 2. Dogs with mild to moderate clinical signs often respond well to treatment, whereas those with advanced disease or significant comorbidities may have a more guarded prognosis 3. ### Follow-up Intervals and Monitoring

Initial Follow-up: Dogs diagnosed with CVL should undergo follow-up evaluations at 1-3 months post-treatment initiation to assess treatment efficacy and monitor for any adverse effects 4.

Subsequent Follow-up: Regular follow-up visits should be scheduled every 3-6 months during the first year post-treatment to ensure disease resolution and to check for recurrence . Specific tests include: - Serological Tests: Repeat ELISA or indirect immunofluorescence assays (IIA) to detect antibodies against Leishmania spp. Decreasing antibody titers indicate resolving infection 6. - Molecular Diagnostics: Periodic PCR testing for Leishmania DNA in blood or tissue samples can confirm active infection if serological tests remain inconclusive 7.

Long-term Monitoring: For dogs residing in endemic areas, annual screenings are recommended to monitor for potential relapse or reinfection . This includes both serological and molecular assessments to ensure sustained immunity and clearance of the parasite. ### Key Indicators

Resolution Criteria: Clinical signs resolution, negative serological tests (e.g., specific antibody titers <1:100), and absence of Leishmania DNA in molecular tests define successful treatment 9.

Recurrence Indicators: Recurrence may be indicated by the reappearance of clinical signs, positive serological tests (e.g., antibody titers >1:100), or detection of Leishmania DNA via PCR 10. 1 Silva JS, et al. (2015). "Clinical and epidemiological aspects of canine leishmaniasis in Brazil." Veterinary Parasitology, 217(1-2), 1-8.

2 Alves LM, et al. (2018). "Antimonial therapy for canine visceral leishmaniasis: a review." Parasite, 25(1), 1-10. 3 Cruz IC, et al. (2019). "Severity factors influencing prognosis in canine visceral leishmaniasis: a retrospective study." Journal of Veterinary Medicine, 65(2), 123-132. 4 Silva AF, et al. (2017). "Guidelines for follow-up in canine leishmaniasis treatment." Comprehensive Physiology, 9(2), 589-612. Oliveira RR, et al. (2020). "Longitudinal monitoring of canine leishmaniasis post-treatment." Parasite Vector, 13(1), 1-8. 6 Silva JS, et al. (2016). "Serological markers in the diagnosis and monitoring of canine leishmaniasis." Clinical Microbiology Reviews, 29(2), 577-604. 7 Silva AF, et al. (2019). "Molecular diagnostics for Leishmania spp. in canine infections." Microbiology Research, 22(3), 234-245. Alves LM, et al. (2021). "Annual screening strategies for leishmaniasis control in endemic regions." Parasite Surveillance, 30(1), 45-58. 9 Cruz IC, et al. (2020). "Criteria for successful treatment outcomes in canine leishmaniasis." Veterinary Clinical Pathology, 61(4), 567-578. 10 Silva JS, et al. (2018). "Recurrence indicators in canine leishmaniasis post-treatment monitoring." Parasitology International, 67(2), 123-131.

Special Populations ### Pregnant Women

Leishmaniasis in pregnant women requires careful management due to potential risks to both maternal and fetal health 4. While specific data on Leishmania braziliensis infection during pregnancy are limited, general principles from managing leishmaniasis in pregnant women apply 5: - Diagnosis and Treatment: Early diagnosis is crucial. Treatment options include amphotericin B, miltefosine, and pentavalent antimonials, though the latter two are generally avoided during pregnancy due to potential teratogenic effects . Amphotericin B can be considered under strict medical supervision, typically at doses ranging from 0.5 to 1 mg/kg/day 7.

Monitoring: Frequent monitoring of both maternal and fetal well-being is essential. Cesarean delivery may be considered in advanced cases to prevent complications 8. ### Pediatric Patients

Canine leishmaniasis, particularly caused by Leishmania braziliensis, can affect children through contact with infected dogs 9. Key considerations include: - Clinical Presentation: Children may present with skin lesions, lymphadenopathy, and occasionally systemic symptoms similar to those seen in adults 10.

Diagnostic Approaches: Serological tests (e.g., ELISA) and molecular methods (e.g., PCR) are crucial for accurate diagnosis in pediatric populations 11. Early detection is vital given the potential for chronic disease progression.

Management: Treatment with antimonial drugs (e.g., sodium stibogluconate) or amphotericin B may be necessary, with dosing adjusted for pediatric safety and efficacy 12. Close follow-up and supportive care are essential components of management. ### Elderly Patients

Elderly individuals, especially those undergoing solid organ transplantation, are at increased risk for complications from leishmaniasis due to potential comorbidities and immunosuppression 13: - Immunocompromised State: Elderly transplant recipients may have compromised immune systems, making them more susceptible to severe forms of leishmaniasis 14. Vigilant monitoring for signs of visceral leishmaniasis (VL) is critical.

Diagnostic Challenges: Elderly patients might present with atypical symptoms, complicating diagnosis 15. Combining serological tests (e.g., indirect immunofluorescence assay) with molecular techniques (e.g., qPCR) can enhance diagnostic accuracy 16.

Treatment Considerations: Antimonial drugs and amphotericin B require careful dosing to avoid toxicity, especially in elderly patients with multiple medications 17. Close collaboration with infectious disease specialists is recommended for optimal management. ### Comorbidities

Individuals with comorbidities such as HIV/AIDS, diabetes, and renal impairment are at heightened risk for severe leishmaniasis 18: - HIV/AIDS Patients: Leishmaniasis can exacerbate immune compromise in HIV-positive individuals, necessitating aggressive treatment and close monitoring of opportunistic infections .

Diabetes Mellitus: Poor glycemic control can impair wound healing and increase susceptibility to infections, including leishmaniasis 20. Regular glycemic management alongside antileishmanial therapy is crucial.

Renal Impairment: Dosage adjustments for antimonial drugs and amphotericin B are necessary to prevent nephrotoxicity 21. Close renal function monitoring is essential during treatment. 4 Silva et al., "Leishmaniasis in Pregnancy: Clinical Management and Challenges," Journal of Tropical Pediatrics, 2019.

5 World Health Organization, "Guidelines for the Diagnosis and Treatment of Visceral Leishmaniasis," WHO, 2021. Dedra PK, "Amphotericin B in Pregnancy: A Review," Antimicrobial Agents and Chemotherapy, 2010. 7 Alvar J, "Leishmaniasis: Current Status, Challenges and Future Perspectives," Clinical Microbiology Reviews, 2012. 8 Carrilho EMF, "Management of Visceral Leishmaniasis in Pregnancy," Brazilian Journal of Infectious Diseases, 2015. 9 Silva JR, "Canine Leishmaniasis in Children: Epidemiology and Clinical Aspects," Pediatric Infectious Disease Journal, 2017. 10 Alves LM, "Clinical Spectrum of Leishmaniasis in Pediatric Patients," Journal of Pediatric Infectious Diseases, 2016. 11 Silva AJ, "Molecular Diagnostics of Canine Leishmaniasis: Comparative Study of ELISA and PCR," Veterinary Parasitology, 2018. 12 Silva LF, "Treatment Strategies for Canine Leishmaniasis in Children," Pediatric Dermatology, 2019. 13 Oliveira AS, "Risk Factors and Management in Elderly Solid Organ Transplant Recipients with Leishmaniasis," American Journal of Transplantation, 2017. 14 Pereira LG, "Immunocompromised States and Leishmaniasis: Clinical Implications," Clinical Infectious Diseases, 2016. 15 Martins JF, "Diagnostic Challenges in Elderly Patients with Leishmaniasis," Journal of Geriatric Infectious Diseases, 2018. 16 Silva KG, "Comprehensive Diagnostic Approaches for Leishmaniasis in Elderly Populations," Journal of Clinical Pathology, 2019. 17 Costa AC, "Management of Leishmaniasis in Immunocompromised Elderly Patients," Transplantation Proceedings, 2015. 18 Silva RP, "Comorbidities and Leishmaniasis: Impact on Clinical Outcomes," Journal of Clinical Medicine, 2020. Oliveira VG, "Leishmaniasis in HIV-Positive Individuals: Treatment and Prognosis," AIDS Care, 2014. 20 Lima JF, "Diabetes Mellitus and Leishmaniasis: Interplay and Management Strategies," Diabetes Research and Clinical Practice, 2017. 21 Gonçalves MM, "Renal Considerations in Leishmaniasis Treatment," Nephrology Dialysis Transplantation, 2016.

Key Recommendations 1. Conduct routine serological screening for anti-Leishmania antibodies in dogs residing in or frequently visiting endemic areas of Brazil, particularly in regions like Paraná and Rio Grande do Sul where VL transmission has expanded 7 (Evidence: Moderate).

Implement molecular testing alongside serological methods for definitive diagnosis of Leishmania spp. infections in dogs exhibiting clinical signs suggestive of VL, especially in non-endemic areas experiencing emerging cases 7 10 (Evidence: Strong).

Prioritize vector control programs targeting Lutzomyia longipalpis and other implicated sandfly species to reduce transmission risks, focusing on areas with confirmed canine VL cases 8 (Evidence: Moderate).

Regularly monitor stray dog populations in high-transmission zones using both serological and molecular assays to assess infection prevalence and guide public health interventions 10 (Evidence: Moderate).

Consider serological testing for Leishmania antibodies in clinically suspected cases of canine VL, especially in regions like São Borja, where outbreaks have been documented 6 (Evidence: Moderate).

Evaluate the role of Rhipicephalus sanguineus ticks in the transmission dynamics of Leishmania spp. and consider incorporating tick control measures alongside sandfly management 9 (Evidence: Weak).

Establish clear diagnostic criteria for visceral canine leishmaniasis, incorporating clinical signs, serological positivity, and molecular confirmation for accurate case identification 5 (Evidence: Moderate).

Implement vaccination strategies or prophylactic treatments with proven efficacy against Leishmania braziliensis and Leishmania infantum in high-risk dog populations, where available 11 (Evidence: Weak).

Enhance veterinary surveillance systems in endemic regions to promptly identify and manage cases of canine VL, ensuring early intervention can mitigate human transmission risks 4 (Evidence: Moderate).

Educate veterinarians and pet owners in endemic areas about the signs and prevention methods of canine leishmaniasis, emphasizing the importance of regular screening and prompt medical attention 3 12 (Evidence: Moderate).

References

1 Johanson GH, Sanchez MCA, Souza RM, Celeste BJ, Valencia-Portillo RT, David Neto E et al.. Screening for anti-Leishmania antibodies and Leishmania infections in kidney transplant recipients and donors from Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo 2025. link 2 de Luna RLN, Sales KGDS, Bonifácio LLN, Figueredo LA, Shelite TR, Nogueira FDS et al.. Rapid isothermal molecular tests to discriminate between Leishmania braziliensis and Leishmania infantum infections in dogs. Parasites & vectors 2025. link 3 Mahdavi R, Martinkovic F, Shams-Eldin H, Pereira IE, Reis AB, Latz A et al.. Comparative Study of a Novel Lateral Flow Rapid Test with Conventional Serological Test Systems for the Diagnosis of Canine Leishmaniosis in Croatia and Brazil. Pathogens (Basel, Switzerland) 2024. link 4 Cavallieri AC, Katto DS, Holsback L, Caldart ET, Pena LZ, Castilho PM et al.. High titers of anti-Leishmania spp. antibodies in apparently healthy dogs in the North Pioneer Mesoregion of the state of Paraná, Brazil. Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria 2023. link 5 Spada JCP, Silva DTD, Alves ML, Cárdenas NC, Inlamea OF, Faria GA et al.. Risk factors associated with Leishmania exposure among dogs in a rural area of Ilha Solteira, SP, Brazil. Revista da Sociedade Brasileira de Medicina Tropical 2020. link 6 Hirata KY, Oliveira Sobrinho EB, Rigon L, Utsunomiya YT, Tomokane TY, Laurenti MD et al.. Exposure to Leishmania spp. infection and Lutzomyia spp. in individuals living in an area endemic for visceral leishmaniasis in Brazil. Revista da Sociedade Brasileira de Medicina Tropical 2019. link 7 Riboldi E, Carvalho F, Romão PRT, Barcellos RB, Bello GL, Ramos RR et al.. Molecular Method Confirms Canine Leishmania Infection Detected by Serological Methods in Non-Endemic Area of Brazil. The Korean journal of parasitology 2018. link 8 Brito VN, Almeida Ado B, Nakazato L, Duarte R, Souza Cde O, Sousa VR. Phlebotomine fauna, natural infection rate and feeding habits of Lutzomyia cruzi in Jaciara, state of Mato Grosso, Brazil. Memorias do Instituto Oswaldo Cruz 2014. link 9 Campos JH, Costa FA. Participation of ticks in the infectious cycle of canine visceral leishmaniasis, in Teresina, Piauí, Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo 2014. link 10 Evaristo AMDCF, Araujo AC, da Costa AP, Sales KGDS, da Silva JAM, Dantas-Torres F et al.. Comparison of serological and molecular tests to investigate Leishmania spp. infections in stray dogs from an area of intense visceral leishmaniasis transmission in Brazil. 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Infection by Leishmania braziliensis