. et al. Epidemia de leishmaniose visceral no Estado do Piauí, Brasil, 1980-1986. Rev. Saúde públ, S. Paulo, 24: 1990.RESUMO: Analisou-se a epidemia de calazar ocorrida no Estado do Piauí, no período de 1980-1986. Os dados foram coletados pela SUCAM-Piauí, órgão do Ministério da Saúde para o controle de endemias, pela busca ativa na rede de assistência à saúde do Estado. A epidemia iniciou-se em municípios do centro e do norte, em 1980. No interior, ao contrário do período endêmico, quando predominou em áreas de maior altitude e clima semi-árido, a epidemia grassou nos vales de rios e em região mais úmida, de clima tropical. A capital do Piauí, Teresina, foi atingida em 1981, com pico epidêmico em 1984 e tendo sido responsável por mais de 60% dos 1.509 casos de todo o Estado. Foram feitas tentativas de controle pelo uso intensivo de inseticidas e eliminação de cães. Nas outras regiões do Piauí, borrifadas intensivamente para o controle da doença de Chagas e da malária, a epidemia foi pouco importante e cedeu espontaneamente. Nem a casuística e nem a população flebotomínica de Teresina apresentaram variações sazonais significativas, mas estiveram moderadamente correlacionadas entre si. Houve maior prevalência em menores de cinco anos, principalmente nos anos de maior incidência, e menor em maiores de 40 anos. A distribuição geográfica do processo epidêmico e a concomitância de seu início com seca prolongada acompanhada de emigração de pessoas e animais domésticos procedentes de regiões endêmicas para aquelas epidêmicas, sugerem que estes movimentos migratórios desencadearam a epidemia. O fato de o processo epidêmico ter cedido espontaneamente em áreas onde não se tentou o seu controle indica que não se pode atribuir apenas às medidas de controle o fim da epidemia. A partir da análise dos coeficientes de incidência específicos por faixa etária, é discutida a possiblilidade da progressiva redução na proporção de suscetíveis, determinada tanto por um grande número de infecções assintomáticas como pela ocorrência de imunidade duradoura, ter contribuído para a extinção da epidemia. DESCRITORES:

Abstract. In Brazil, programs based on elimination of infected dogs have not curtailed the spread of visceral leishmaniasis (VL), suggesting that other reservoirs of infection exist. Persons with active VL can infect the sand fly vector, but in endemic areas, persons with asymptomatic infections, whose infectivity to sand flies is unknown, are far more numerous. In this study, a polymerase chain reaction-based assay detected kinetoplast DNA of Leishmania chagasi in the blood of eight of 108 asymptomatic persons living with patients with recently diagnosed VL. These eight persons had low or unmeasurable levels of IgG antibodies to Leishmania, demonstrating the insensitivity of serology for subclinical infection. All eight persons had positive leishmanin skin test results, as did 70% of persons living in households of persons with active VL. Even if a small proportion of such asymptomatic persons are infective to sand flies, they represent a formidable reservoir of infection in endemic areas.

How effective is dog culling in controlling zoonotic visceral leishmaniasis? A critical evaluation of the science, politics and ethics behind this public health policyQuanto é efetivo o abate de cães para o controle do calazar zoonótico? Uma avaliação crítica da ciência, política e ética por trás desta política de saúde pública Carlos Henrique Nery Costa 1,2 ABSTRACT Introduction: Zoonotic kala-azar, a lethal disease caused by protozoa of the genus Leishmania is considered out of control in parts of the world, particularly in Brazil, where transmission has spread to cities throughout most of the territory and mortality presents an increasing trend. Although a highly debatable measure, the Brazilian government regularly culls seropositive dogs to control the disease. Since control is failing, critical analysis concerning the actions focused on the canine reservoir was conducted. Methods: In a review of the literature, a historical perspective focusing mainly on comparisons between the successful Chinese and Soviet strategies and the Brazilian approach is presented. In addition, analyses of the principal studies regarding the role of dogs as risk factors to humans and of the main intervention studies regarding the efficacy of the dog killing strategy were undertaken. Brazilian political reaction to a recently published systematic review that concluded that the dog culling program lacked efficiency and its effect on public policy were also reviewed. Results: No firm evidence of the risk conferred by the presence of dogs to humans was verified; on the contrary, a lack of scientific support for the policy of killing dogs was confirmed. A bias for distorting scientific data towards maintaining the policy of culling animals was observed. Conclusions: Since there is no evidence that dog culling diminishes visceral leishmaniasis transmission, it should be abandoned as a control measure. Ethical considerations have been raised regarding distorting scientific results and the killing of animals despite minimal or absent scientific evidence

American visceral leishmaniasis (AVL) is associated with the absence of lymphocyte proliferative responses and interleukin (IL)-2 and interferon-gamma (IFN-gamma) production upon stimulation with Leishmania antigen. In contrast, cure of AVL is associated with restoration of these T cell functions. In the present study, the ability of IL-12, a cytokine that acts on NK and T cells to restore cellular immune responses in AVL, was evaluated. Participants of the study included 12 patients with AVL and 7 subjects cured of AVL. The [3H]thymidine uptake and IFN-gamma production in cultures of peripheral blood mononuclear cells (from AVL patients) stimulated with Leishmania chagasi antigen were 882 +/- 1393 cpm and zero, respectively. Addition of IL-12 enhanced the proliferative response to 5097 +/- 6429 cpm (P < .001) and IFN-gamma production to 305 +/- 325 pg/mL (P < .01). IL-12 also restored cytotoxic activity against the K562 cell line. These results indicate that IL-12 has an important role in the regulation of the cellular immune response in human leishmaniasis.

Background:A possible strategy to reduce fatality rates of visceral leishmaniasis is to identify prognostic factors that can be easily assessed and used as an aid to clinical decision-making. Patients and Methods: A case-control study was developed in Teresina, Brazil, in which cases were patients who died during treatment (n = 12) and controls (n = 78) comprised a random sample of patients who were alive when treatment was finished. Results: Variables significantly associated with death were severe anemia, fever for more than 60 days, diarrhea and jaundice. The prognostic system had a sensitivity of 85.7% and a specificity of 92.5%. Conclusion: The prognostic model developed in this study had satisfactory performance and might be useful in developing countries, since it is simple and inexpensive. However, it is still preliminary and needs to be improved and validated using larger and more recent samples.

The failure of control programs for visceral leishmaniasis (VL) that depend on elimination of infected dogs suggests that other reservoir hosts may participate in the transmission cycle. To determine whether persons infected with Leishmania chagasi can infect the vector sand fly, laboratory-reared Lutzomyia longipalpis were allowed to feed on Brazilian subjects with active, cured, and asymptomatic VL and on asymptomatic residents of houses of persons with active VL. Of 3747 insects that had fed, 26 acquired infection from 11 of the 44 persons with active VL, but none acquired infection from the 137 asymptomatic persons. Among persons <4 years old with active VL, a history of diarrhea and higher peripheral blood neutrophil counts were independent predictors of infectivity. Further experiments using larger numbers of insects are necessary to evaluate the reservoir competence of persons with asymptomatic infections, who represent a large segment of the population of several Brazilian cities.

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Visceral leishmaniasis (VL) can be lethal if untreated; however, the majority of human infections with the etiological agents are asymptomatic. Using Illumina Bead Chip microarray technology, we investigated the patterns of gene expression in blood of active VL patients, asymptomatic infected individuals, patients under remission of VL and controls. Computational analyses based on differential gene expression, gene set enrichment, weighted gene co-expression networks and cell deconvolution generated data demonstrating discriminative transcriptional signatures. VL patients exhibited transcriptional profiles associated with pathways and gene modules reflecting activation of T lymphocytes via MHC class I and type I interferon signaling, as well as an overall down regulation of pathways and gene modules related to myeloid cells, mainly due to differences in the relative proportions of monocytes and neutrophils. Patients under remission of VL presented heterogeneous transcriptional profiles associated with activation of T lymphocytes via MHC class I, type I interferon signaling and cell cycle and, importantly, transcriptional activity correlated with activation of Notch signaling pathway and gene modules that reflected increased proportions of B cells after treatment of disease. Asymptomatic and uninfected individuals presented similar gene expression profiles, nevertheless, asymptomatic individuals exhibited particularities which suggest an efficient regulation of lymphocyte activation and a strong association with a type I interferon response. Of note, we validated a set of target genes by RT-qPCR and demonstrate the robustness of expression data acquired by microarray analysis. In conclusion, this study profiles the immune response during distinct states of infection of humans with Leishmania infantum with a novel strategy that indicates the molecular pathways that contribute to the progression of the disease, while also providing insights into transcriptional activity that can drive protective mechanisms.