Association of Socioeconomic Status and Oral Cancer Mortality in Brazil: Temporal Trends and Spatial Distribution.

OBJECTIVE: The objective of this observational study was to evaluate the relationship between the oral cancer mortality rate and socioeconomic indicators throughout the Brazilian territory, between 2010 and 2019. METHOD: The variables used in this study were oral cancer mortality rates from the Mortality Information System (SIM) and population data from the Brazilian Institute of Geography and Statistics (IBGE) to calculate oral cancer mortality rates, along with the Human Development Index (HDI) and Social Vulnerability Index (SVI). The analysis was performed in tertile stratifications (Microsoft Excel 16.0), while temporal trends were examined by segmented linear regression (JoinPoint 4.9.0). RESULTS: High mortality rates were observed in more developed regions (South and Southeast), whereas temporal analysis showed significant increasing trends in the North (annual percentage changes [APC] = +3.9%; p < 0.05) and Northeast (APC = +2.4%; p < 0.05) regions. The greater HDI (APC = +1.7%; p < 0.05) and SVI (APC = +2.2%; p < 0.05) tertiles had the lowest annual percentage increase, showing an inverse relationship between the temporal trend of mortality and socioeconomic indicators. CONCLUSION: Despite the higher number of oral cancer deaths in regions with higher social indices, increasing temporal trends are more accentuated in regions with lower socioeconomic levels.

Magnitude of visceral leishmaniasis and HIV coinfection and association with social determinants of health in the Northeast region of Brazil: a retrospective, spatiotemporal model (2010-2018).

The Northeast region of Brazil (NRB) includes the states with the highest prevalence of visceral leishmaniasis (VL), as well as those with significant increases in HIV cases. This study aims to analyze the spatiotemporal patterns of VL-HIV coinfection and its association with the social determinants of health (SDH) in the NRB. Time trend analysis and Bayesian spatial statistical inferences, Moran's autocorrelation, and retrospective space-time scanning were performed. Spatial regression modelling was used to build an explanatory model for the occurrence of VL-HIV coinfection within NRB. A total of 1550 cases of VL-HIV coinfection were confirmed. We observed a higher prevalence among males (1232; 83%), individuals aged from 20 to 59 years (850; 54.8%), non-white skin color (1,422; 91.7%), and with low education (550; 35.48%). NRB showed an increasing and significant trend in the detection rate of coinfection (APC, 5.3; 95% CI, 1.4 to 9.4). The states of Maranhão and Piauí comprised the high-risk cluster. The SDH that most correlated with the occurrence of coinfection were poor housing, low income, and low education. VL-HIV is dispersed in the NRB but chiefly affects states with greater social vulnerability. Taken together, these findings reinforce the necessity to implement surveillance strategies that will contribute to the reduction of cases in these populations.

Association between chemosensory dysfunctions and inflammatory biomarkers in patients with SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: There is evidence that chemosensory dysfunctions, including smell and taste disorders, are common findings in patients with SARS-CoV-2 infection. However, the underlying biological mechanisms and the role of inflammatory markers are still poorly understood. AIM: To investigate the inflammatory biomarkers levels in patients with COVID-19 presenting chemosensory dysfunctions. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic literature search was performed from January 1, 2020, to May 12, 2022. Observational studies that provided data on hematological, biochemical, infection-related indices and cellular immunity, and coagulation function in patients with COVID-19 experiencing smell and/or taste disorders were considered eligible. Effect sizes were reported as standardized mean difference (SMD) with 95% confidence intervals (CI). A negative effect size indicated that the inflammatory biomarker levels were lower among patients with chemosensory dysfunctions. RESULTS: Eleven studies were included. Patients with chemosensory disturbances had lower levels of leukocytes (SMD - 0.18, 95% CI - 0.35 to - 0.01, p = 0.04), lactate dehydrogenase (SMD - 0.45, 95% CI - 0.82 to - 0.09, p = 0.01), IL-6 (SMD - 0.25, 95% CI - 0.44 to - 0.06, p < 0.01), and C-reactive protein (SMD - 0.33, 95% CI - 0.58 to - 0.08, p < 0.01) than patients without chemosensory disturbances. CONCLUSION: Patients with SARS-CoV-2 infection who have olfactory and gustatory disorders have a lower inflammatory response than patients who do not have chemosensory alterations. The presence of these symptoms may indicate a more favorable clinical course for COVID-19.

Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages.

Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

Leishmania infantum (syn. L. chagasi) parasites affect the release of soluble CD14 by infected macrophages.

Functionally, cluster of differentiation 14 (CD14) is a co-receptor of the complex formed by lipopolysaccharide (LPS) and LPS-binding protein expressed on the membrane of a variety of cells. However, CD14 can be shed from the cell membrane into the circulation as soluble CD14 (sCD14) upon cell activation. Previously, our group reported that elevated sCD14 serum levels were associated with the clinical and laboratory findings in the context of visceral leishmaniasis (VL), but not in the context of LPS stimulation or bacterial infection. In the present study, we investigated the secretion dynamics of sCD14 in the context of Leishmania infantum (syn. L. chagasi) in vitro infection. Macrophages from treated VL patients and delayed-type hypersensitivity positive (DTH+) subjects were infected with L. infantum (syn. L. chagasi) promastigotes, and the infection index was evaluated (number of amastigotes per 100 infected macrophages). Additionally, the levels of sCD14, Inteleukin (IL)10, IL-6 and tumour necrosis factor alpha (TNF-α) were measured in the culture supernatants using the Luminex assay. Interestingly, the release of sCD14 was inversely correlated with the L. infantum (syn. L. chagasi) infection index. Of note, the release of sCD14 was upregulated and downregulated in the context of infected macrophages from DTH+ subjects and treated VL patients, respectively. Additionally, we also observed that the levels of sCD14 in the culture supernatants were positively correlated with the levels of TNF-α, IL-6 and IL-10. Therefore, our data suggest that macrophages from treated VL patients and DTH+ subjects respond differently to L. infantum (syn. L. chagasi) infection in the context of the release of sCD14; therefore, the release of sCD14 may be associated with the outcome of VL.

Influence of Testosterone in Neglected Tropical Diseases: Clinical Aspects in Leprosy and In Vitro Experiments in Leishmaniasis.

Neglected tropical diseases encompass a group of chronic and debilitating infectious diseases that primarily affect marginalized populations. Among these diseases, leprosy and leishmaniasis are endemic in numerous countries and can result in severe and disfiguring manifestations. Although there have been reports indicating a higher incidence of leprosy and leishmaniasis in males, the underlying factors contributing to this observation remain unclear. Therefore, the objective of this study was to examine both clinical and experimental evidence regarding the role of testosterone in leprosy and leishmaniasis. A prospective clinical study was conducted to compare the clinical forms of leprosy and assess circulating testosterone levels. Additionally, the impact of testosterone on Leishmania amazonensis-infected macrophages was evaluated in vitro. The findings demonstrated that serum testosterone levels were higher in women with leprosy than in the control group, irrespective of the multi- or pauci-bacillary form of the disease. However, no differences in testosterone levels were observed in men when comparing leprosy patients and controls. Interestingly, increasing doses of testosterone in macrophages infected with L. amazonensis resulted in a higher proportion of infected cells, decreased CD40 expression on the cell surface, elevated expression of SOCS1, and decreased expression of IRF5. These findings provide biological evidence to support the influence of testosterone on intracellular infections, though the interpretation of clinical evidence remains limited.

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly.

Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case-control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.

Levels of inflammatory markers are differentially expressed in sickle cell anemia and sickle cell trait.

Although sickle cell anemia (SCA) is related to inflammation, the profile of inflammatory markers in sickle cell trait (SCT) is poorly studied. This is a cross-sectional study of inflammatory biomarkers carried out involving adults with SCA in steady state, SCT and controls. The SCA group had higher levels of lactato dehydrogenase, IL-1ß, IL-6, IL-10, and tumor necrosis factor alpha than the others, while the SCT group had similar levels to control group. In addition, SCA group had lower IL-8/IL-10 and soluble triggering receptor expressed on myeloid cells-1/IL-10 ratios. These findings indicate that individuals with SCT do not have a chronic inflammatory profile and reinforce that cytokines are involved in the maintenance of the inflammatory state in SCA.

Association between interleukin 10 (IL-10) polymorphisms and leishmaniasis progression: a systematic review and meta-analysis.

Interleukin 10 (IL-10) is associated with the progression of leishmaniasis because it inhibits the leishmanicidal action of macrophages and the production of mediators such as IFN-γ and nitric oxide. Studies have shown that specific polymorphisms are associated with the regulatory role of IL-10 and the development of more relevant clinical forms of leishamaniasis. We performed a systematic review and meta-analysis to determine whether single nucleotide polymorphisms (SNPs) of IL-10 influence the progression of leishmaniasis. The selected articles were read in full and only those consistent with the eligibility criteria were included in our study. Seven studies were eligible according to the inclusion criteria and were included in the present systematic review, but only five were subjected to statistical analysis. The pooled odds ratios showed no significant association between the rs1800871 SNP and the progression of leishmaniasis in all genotype models, including the dominant, recessive, homozygote, heterozygote, and allelic models. Regarding the association between rs1800896 SNP and the progression of leishmaniasis, the pooled odds ratios showed no association under all genotype models. Hence, IL-10 SNPs did not show significant association and were not considered a risk factor for the progression of leishmaniasis.

TREM-1 Expression on the Surface of Neutrophils in Patients With Visceral Leishmaniasis Is Associated With Immunopathogenesis.

Visceral leishmaniasis (VL) is a systemic chronic and potentially fatal disease for humans. Mechanisms related to the dysregulation of the inflammatory response may be involved in both the pathogenesis and prognosis of VL. Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) is a receptor constitutively expressed on neutrophils and monocyte subsets. The protein serves to regulate and amplify inflammatory responses. This study aimed to evaluate the expression profile of TREM-1 on the surface of neutrophils from patients with VL at varying time points during leishmanicidal treatment. For this purpose, neutrophils were isolated from the peripheral blood of patients with VL at different stages of treatment, which include 0, 7, and 30 days after treatment. Surface TREM-1 expression was assessed by immunophenotyping neutrophil populations. In addition, the association of TREM-1 expression on the surface of neutrophils with clinical and laboratory parameters and serum levels of inflammatory mediators was also evaluated. Results demonstrate a lower surface expression of TREM-1 in VL patients in the absence of treatment. However, increased levels of TREM-1 expression were observed 7 and 30 days after the start of treatment, with levels similar to those of healthy controls. TREM-1 expression was directly correlated with lymphocyte and erythrocyte count and indirectly correlated with spleen and liver size. Furthermore, elevated levels of TREM-1 expression were also correlated with lower serum levels of interleukin (IL)-22. Taken together, these results suggest that infection by Leishmania infantum leads to depressed TREM-1 expression on the neutrophil surface and may contribute to the inflammatory imbalance that characterizes active VL disease.

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments.

This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.

Spatial and spatiotemporal dynamics of visceral leishmaniasis in an endemic North-eastern region of Brazil.

Visceral Leishmaniasis (VL) is a neglected disease with increasing incidence in Brazil, particularly in the North-eastern. The aim of this study was to analyze the spatial and spatiotemporal dynamics of VL in an endemic region of North-eastern Brazil, between 2009 and 2017. Using spatial analysis techniques, an ecological and time series study was made regarding VL cases in Sergipe filed as notifiable disease events. With data from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística, IBGE), a digital population and cartographic baseline was established. Segmented linear regression was used to examine the temporal trends. The statistical analysis methods of Global and Local Moran' I, local Bayesian empirical methodology and spatial-temporal scanning were used to produce thematic maps. High instances were found among adults, males, urban residents, non-Whites and persons with low levels of education. A decrease in the recovery rate and an increase in the proportion of urban cases and lethality was found. A heterogeneous VL distribution with spatiotemporal agglomeration on the seaside of the state was seen in Sergipe. To better manage the disease, new research is encouraged together with development of public health strategies. Further, improving health care networks, especially primary care, is suggested as this approach has a key role in health promotion, prevention and monitoring of the most prevalent diseases.

Coronavirus disease and basic sanitation: too early to be worried?

INTRODUCTION: Considering that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in feces, this study aimed to verify a possible relationship between basic sanitation indices and coronavirus disease (COVID-19) numbers/rates. METHODS: Data of COVID-19 cases registered in Brazil until May 28, 2020, and independent variables associated with basic sanitation were analyzed. RESULTS: A significant correlation between the number of cases and sewage treatment index/population density was observed. In addition, COVID-19 incidence and mortality rates were significantly associated with the total water service index and lethality rate was significantly associated with the sewage treatment index. CONCLUSIONS: Precarious basic sanitation infrastructure may potentially increase the SARS-CoV-2 transmission in Brazil.

Quality of life and metamemory in higher education students during the COVID-19 pandemic / Qualidade de vida e metamemória em estudantes do nível superior durante a pandemia da COVID-19

ABSTRACT Purpose: to analyze the quality of life and metamemory and verify their predictors in students during the COVID-19 pandemic. Methods: a cross-sectional survey carried out through online collection with the application of an initial questionnaire to characterize the sample, the WHOQOL-brief to investigate the quality of life, and the Metamemory Questionnaire in Adults (short version) - MIAr to evaluate metamemory in a group of undergraduate and postgraduate students. Data were analyzed using descriptive and inferential statistics. Multiple linear regression was performed to verify the predictor variables. A significance level of 5% (p ≤ 0.05) was considered. Results: 977 university students participated in the study, the majority (70.73%) of whom were females and with an income range below three minimum wages (63.56%). For quality of life, income range, being in the risk group for COVID-19, and age were predictors for both the undergraduate and postgraduate groups. In contrast, on an excellent metamemory, the predictors were male gender and age. Conclusion: for students, during the COVID-19 pandemic, the main predictor of quality of life was having a higher income bracket, and the main predictor of metamemory was being a male.

RESUMO Objetivo: analisar a qualidade de vida e a metamemória e verificar seus preditores em estudantes durante a pandemia da COVID-19. Métodos: trata-se de uma pesquisa transversal realizada por meio de coleta online com a aplicação de um questionário inicial para caracterizar a amostra, do WHOQOL-bref para investigar a qualidade de vida e do Questionário de Metamemória em Adultos (versão reduzida) - MIAr para avaliar a metamemória, em um grupo de estudantes de graduação e outro de pós-graduação. Os dados foram analisados por meio de estatística descritiva e inferencial. Realizou-se a regressão linear múltipla para verificar as variáveis preditoras. Foi considerado o nível de significância de 5% (p≤0,05). Resultados: participaram do estudo 977 universitários, sendo a maioria (70,73%) do gênero feminino e com faixa de renda menor que três salários-mínimos (63,56%). Para a qualidade de vida, tanto para o grupo de graduandos quanto de pós-graduandos, a faixa de renda, o grupo de risco para COVID-19 e a idade foram preditores, enquanto para uma boa metamemória os preditores foram o gênero masculino e a idade. Conclusão: para os estudantes, durante a pandemia da COVID-19, o principal preditor da qualidade de vida foi possuir maior faixa de renda e o da metamemória foi ser do gênero masculino.

Seroprevalence of anti-Toxoplasma gondii antibodies in dogs from rural area of Nossa Senhora da Glória, Sergipe, Brazil / Soroprevalência de anticorpos anti-Toxoplasma gondii em cães de área rural de Nossa Senhora da Glória, Sergipe, Brasil

Toxoplasma gondii is a protozoan parasite with worldwide distribution. Dogs are considered sentinel animals, useful for the detection of environmental infections and outbreaks of disease through serological surveys. Considering this, we aimed to assess the seroprevalence of toxoplasmosis in dogs from rural areas of the hinterland of the state of Sergipe, Northeastern Brazil. A total of 77 blood samples were collected from dogs and analyzed by the Indirect Hemagglutination test for the detection of anti-T. gondii antibodies Samples were considered positive when titers greater than or equal to 1:16 were observed. In addition, an epidemiological questionnaire designed to identify characteristics of the animal was performed to owners regarding sex, breed, age, sterilization, access to areas outside the house, environmental hygiene, contact with other animals and dog food. A total of 49.3% of dogs (n = 38) were positive for anti-T. gondii antibodies, most with high titers (44.7%). A higher relative frequency of seropositivity was observed in male dogs, not sterilized, mixed breed, which were fed exclusively on homemade food and had access to the street and contact with other animals. Taken together, our data reinforce the importance of developing health education actions within the scope of public health aimed at preventing this zoonosis.

Toxoplasma gondii é um protozoário com distribuição mundial. Os cães são considerados animais sentinela, úteis para a detecção de infecções ambientais e surtos da doença por meio de levantamentos sorológicos. Portanto, o presente estudo teve como objetivo determinar a soroprevalência da toxoplasmose em cães da zona rural da região rural do Alto Sertão Sergipano, Brasil. Um total de 77 amostras de sangue de cães foram coletadas no município de Nossa Senhora da Glória, Sergipe e submetidas ao teste de Hemaglutinação Indireta para detecção de anticorpos anti-T. gondii, considerando títulos maiores ou iguais a 1:16 como positivos. Além disso, foi aplicado um questionário epidemiológico aos proprietários solicitando informações sobre sexo, raça, idade, esterilização, acesso às ruas, limpeza do ambiente, contato com outros animais e ração, além de dados do proprietário, como renda familiar e nível de educação. 49,3% dos cães (38/77) apresentaram anticorpos anti-T. gondii, a maioria com títulos elevados (44,7%). Foi observado maior frequência relativa de soropositividade em cães macho, não esterilizados, sem raça definida, que se alimentam exclusivamente de comida caseira e tem acesso a rua e contato com outros animais. Os dados obtidos reforçam a importância do desenvolvimento de ações de educação em saúde no âmbito da saúde pública voltadas à prevenção dessa zoonose.

Primary school educational intervention r egarding schistosomiasis in a riverside community, northeastern Brazil

Schistosomiasis is still a serious public health concern in Brazil and Sergipe State presents the highest prevalence rate of the disease. Brazil implemented the Schistosomiasis Control Program (PCE) with several strategies to control the disease, including health education actions in endemic areas. Herein, we assessed the impact of an educational intervention on knowledge concerning schistosomiasis in students from a riverside village of Sergipe, Northeastern Brazil. The study was carried out in 3 phases. 1) A questionnaire was applied to assess the students' knowledge about the biological, clinical, and epidemiological aspects of schistosomiasis mansoni (pre-test). 2) Next, an educational intervention was conducted. Pamphlets about schistosomiasis were distributed to the entire school community, who were then invited to a lecture. 3) A post-test was performed using the questionnaire to assess acquired knowledge. 151 elementary school students were interviewed. 2.6% of the pre-test students and 4.3% of the post-test group had already been diagnosed with schistosomiasis. In the pre-test, only 24.5% knew the cause of the disease and 48.3% the transmission sites. In the post-test, 74.3% (OR= 8.9; p-value<0.0001) knew the etiology and 77.1% the possible transmission sites (OR= 3.6; p-value<0.0001). There was also significant improvement in knowledge regarding signs, symptoms and prophylactic measures. Most students were unaware of the risk of reinfection by Schistosoma mansoni after treatment. The educational intervention proved quite effective in increasing information on schistosomiasis. These results reinforce the importance of health education as an auxiliary tool in the control of schistosomiasis.

Coronavirus disease and basic sanitation: too early to be worried?

Abstract INTRODUCTION: Considering that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in feces, this study aimed to verify a possible relationship between basic sanitation indices and coronavirus disease (COVID-19) numbers/rates. METHODS: Data of COVID-19 cases registered in Brazil until May 28, 2020, and independent variables associated with basic sanitation were analyzed. RESULTS: A significant correlation between the number of cases and sewage treatment index/population density was observed. In addition, COVID-19 incidence and mortality rates were significantly associated with the total water service index and lethality rate was significantly associated with the sewage treatment index. CONCLUSIONS: Precarious basic sanitation infrastructure may potentially increase the SARS-CoV-2 transmission in Brazil.

Soluble CD40 Ligand in Sera of Subjects Exposed to Leishmania infantum Infection Reduces the Parasite Load in Macrophages.

BACKGROUND: While CD40L is typically a membrane glycoprotein expressed on activated T cells and platelets that binds and activates CD40 on the surface on antigen presenting cells, a soluble derivative (sCD40L) that appears to retain its biological activity after cleavage from cell membrane also exists. We recently reported that sCD40L is associated with clinical resolution of visceral leishmaniasis and protection against the disease. In the present study we investigated if this sCD40L is functional and exerts anti-parasitic effect in L. infantum-infected macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Macrophages from normal human donors were infected with L. infantum promastigotes and incubated with either sera from subjects exposed to L. infantum infection, monoclonal antibodies against human CD40L, or an isotype control antibody. We then evaluated infection by counting the number of infected cells and the number of parasites in each cell. We also measured a variety of immune modulatory cytokines in these macrophage culture supernatants by Luminex assay. The addition of sCD40L, either recombinant or from infected individuals' serum, decreased both the number of infected macrophages and number of intracellular parasites. Moreover, this treatment increased the production of IL-12, IL-23, IL-27, IL-15, and IL1ß such that negative correlations between the levels of these cytokines with both the infection ratio and number of intracellular parasites were observed. CONCLUSIONS/SIGNIFICANCE: sCD40L from sera of subjects exposed to L. infantum is functional and improves both the control of parasite and production of inflamatory cytokines of infected macrophages. Although the mechanisms involved in parasite killing are still unclear and require further exploration, these findings indicate a protective role of sCD40L in visceral leishmaniasis.