Global Distribution of Canine Visceral Leishmaniasis and the Role of the Dog in the Epidemiology of the Disease.

Visceral leishmaniasis is a disease caused by protozoa of the species Leishmania (Leishmania) infantum (syn = Leishmania chagasi) and Leishmania (Leishmania) donovani, which are transmitted by hematophagous insects of the genera Lutzomyia and Phlebotomus. The domestic dog (Canis familiaris) is considered the main urban reservoir of the parasite due to the high parasite load on its skin, serving as a source of infection for sandfly vectors and, consequently, perpetuating the disease in the urban environment. Some factors are considered important in the perpetuation and spread of canine visceral leishmaniasis (CVL) in urban areas, such as stray dogs, with their errant behavior, and houses that have backyards with trees, shade, and organic materials, creating an attractive environment for sandfly vectors. CVL is found in approximately 50 countries, with the number of infected dogs reaching millions. However, due to the difficulty of controlling and diagnosing the disease, the number of infected animals could be even greater. In the four continents endemic for CVL, there are reports of disease expansion in endemic countries such as Brazil, Italy, Morocco, and Tunisia, as well as in areas where CVL is not endemic, for example, Uruguay. Socio-environmental factors, such as migration, drought, deforestation, and global warming, have been pointed out as reasons for the expansion into areas where it had been absent. Thus, the objective of this review is to address (i) the distribution of CVL in endemic areas, (ii) the role of the dog in the visceral leishmaniasis epidemiology and the factors that influence dog infection and the spread of the disease, and (iii) the challenges faced in the control of CVL.

New Approaches to the Prevention of Visceral Leishmaniasis: A Review of Recent Patents of Potential Candidates for a Chimeric Protein Vaccine.

The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.

A Review of Major Patents on Potential Malaria Vaccine Targets.

Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite's complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite's replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite's life cycle.

Vaccine approaches applied to controlling dog ticks.

Ticks are considered the most important vectors in veterinary medicine with a profound impact on animal health worldwide, as well as being key vectors of diseases affecting household pets. The leading strategy applied to dog tick control is the continued use of acaricides. However, this approach is not sustainable due to surging tick resistance, growing public concern over pesticide residues in food and in the environment, and the rising costs associated with their development. In contrast, tick vaccines are a cost-effective and environmentally friendly alternative against tick-borne diseases by controlling vector infestations and reducing pathogen transmission. These premises have encouraged researchers to develop an effective vaccine against ticks, with several proteins having been characterized and used in native, synthetic, and recombinant forms as antigens in immunizations. The growing interaction between domestic pets and people underscores the importance of developing new tick control measures that require effective screening platforms applied to vaccine development. However, as reviewed in this paper, very little progress has been made in controlling ectoparasite infestations in pets using the vaccine approach. The control of tick infestations and pathogen transmission could be obtained through immunization programs aimed at reducing the tick population and interfering in the pathogenic transmission that affects human and animal health on a global scale.

Budgetary impact of diagnostic tests for visceral leishmaniasis in Brazil / Impacto orçamentário dos testes diagnósticos para leishmaniose visceral no Brasil

O estudo teve como objetivo estimar os custos financeiros da incorporação e/ou substituição dos testes diagnósticos para a leishmaniose visceral (LV) humana no Brasil. A análise foi realizada na perspectiva do Sistema Único de Saúde (SUS) ao longo de três anos. Foram avaliados seis testes diagnósticos: reação de imunofluorescência indireta (RIFI), teste rápido IT LEISH, exame parasitológico de aspirado de medula óssea, teste de aglutinação direta DAT-LPC padronizado pelo Laboratório de Pesquisas Clínicas do Instituto René Rachou, Fundação Oswaldo Cruz, teste rápido Kalazar Detect e reação em cadeia da polimerase (PCR). Os parâmetros utilizados foram o número de casos suspeitos de LV notificados ao Ministério da Saúde em 2014 e o custo direto dos testes diagnósticos. Os custos do diagnóstico de casos suspeitos de LV ao longo de três anos usando o RIFI e DAT-LPC foram estimados em USD 280.979,91 e USD 121.371,48, respectivamente. De acordo com a análise, comparado ao uso do RIFI, a incorporação do DAT-LPC pelo SUS resultaria numa economia de USD 159.608,43. Com relação ao impacto dos testes rápidos, o uso do IT LEISH resultou em economia de USD 21.708,72 ao longo de três anos. Comparado ao exame parasitológico, o diagnóstico com PCR resultou em economia de USD 3.125.068,92 ao longo de três anos. Neste estudo, a substituição do RIFI pelo DAT-LPC mostrou ser financeiramente vantajosa. Além disso, a substituição do teste rápido Kalazar Detect com o IT LEISH em 2015 foi economicamente apropriada, e a substituição do exame parasitológico pela PCR está economicamente indicada.

Aplicabilidade de testes sorológicos para diagnóstico da forma mucosa da leishmaniose tegumentar

A leishmaniose mucosa (LM) é a forma de acometimento mucoso tardio que afeta entre 3 a 5% dos pacientes com histórico de leishmaniose cutânea (LC) causada pela Leishmania (Viannia) braziliensis. A LM é caracterizada pelo surgimento de lesões e ulcerações em mucosas dos tratos respiratório e digestivo superiores, provocando deformidades estruturais e estigmatizantes nestes pacientes. O diagnóstico da LM por critérios clínico-epidemiológicos é insuficiente, devido à sua similaridade com doenças que podem acometer mucosas. Entretanto, os exames laboratoriais com desempenho suficiente, custo e operacionalidade acessíveis são escassos. Além disso, a produção do antígeno, que era usado na Intradermorreação de Montenegro (IDRM), exame complementar mais utilizado nos últimos anos, foi interrompida no Brasil em 2015. Nesse contexto, a aplicabilidade dos testes sorológicos, desenvolvidos e registrados na Agência Nacional de Vigilância Sanitária (ANVISA) para o diagnóstico da leishmaniose visceral (LV), foi avaliada para o diagnóstico da LM. Por meio de uma pesquisa na plataforma eletrônica pública da ANVISA, realizada em setembro de 2016, foram identificados seis testes sorológicos para o diagnóstico da LV e com registro ativo no Brasil. Desses, Leishmania ELISA IgG+IgM da Vircell S.L., Ridascreen® Leishmania Ab da R-Biopharm AG., IFI Leishmaniose Humana ­ BioManguinhos, IT-LEISH® da Bio-Rad Laboratories, Inc. foram avaliados nesse estudo. Além destes, foi avaliado também o protótipo de kit do teste de aglutinação direta aprimorado no Instituto René Rachou (DAT-LPC). Análise de desempenho dos testes foi realizada em 40 amostras de soro de pacientes com diagnóstico de LM, confirmados por critérios clínico-epidemiológicos, e prova terapêutica, ou laboratoriais, preconizados pelo Ministério da Saúde, e 20 amostras de soro de pacientes com suspeita de LM, mas que tiveram confirmação de outra etiologia, atendidos no Centro de Referência em Leishmaniose do Instituto René Rachou, no período de 2009 a 2016. A acurácia diagnóstica foi moderada, destacando os testes Ridascreen®Leishmania Ab (86,2%) e Leishmania ELISA IgG+IgM (73,3%). A IFI Leishmaniose Humana apresentou a curaria de 66,7%, enquanto IT-LEISH® e DAT-LPC demonstraram a menor acurácia (38,3%), apesar de alta especificidade (100% e 95%, respectivamente). Após determinação de novos pontos de corte, para os testes Leishmania ELISA IgG+IgM e Ridascreen®Leishmania Ab, houve melhora da acurácia de 73,3% para 88% (p=0,04) e de 86,2% para 89% (p =0,64), respectivamente. Os testes Leishmania ELISA IgG+IgM e Ridascreen®Leishmania Ab apresentaram maior sororreativade e sensibilidade com amostras de pacientes com a forma clínica moderada/grave em comparação às amostras de pacientes com a forma leve da LM. Os resultados obtidos nesse estudo indicam diferenças significativas na aplicabilidade dos testes sorológicos, desenvolvidos e registrado na ANVISA para o diagnóstico da LV, quando aplicado para o diagnóstico da LM, o que deve orientar o planejamento de novos estudos.