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Visceral leishmaniasis (VL) is a potentially fatal parasitic infection caused by Leishmania donovani in India. L. donovani is an obligate intracellular protozoan residing mostly in macrophages of the reticuloendothelial system throughout chronic infection. Monocytic phagocytes are critical in the pathogenesis of different forms of leishmaniasis. Subsets of monocytes are distinguished by their surface markers into CD14+CD16- classical monocytes, CD14+CD16+ intermediate monocytes, and CD16++CD14low non-classical monocyte subsets. During cutaneous leishmaniasis (CL), intermediate monocyte are reported to be a source of inflammatory cytokines IL-1β and TNF, and they express CCR2 attracting them to sites of inflammatory pathology. We examined monocyte subsets in the blood and bone marrow of patients with VL from an endemic site in Bihar, India, and found these contrasted with the roles of monocytes in CL. During VL, intermediate and non-classical CD16+ monocyte subsets expressed instead a non-inflammatory phenotype with low CCR2, high CX3CR1 and low microbicidal oxidant generation, making them more similar to patrolling monocytes than inflammatory cells. Bone marrow CD16+ monocyte subsets expressed a phenotype that might be more similar to the inflammatory subsets of CL, although our inability to obtain bone marrow from healthy donors in the endemic region hampered this interpretation Overall the data suggest that CD16+ intermediate monocyte subsets in VL patients express a phenotypes that contributes to an immunosuppressed pathologic immune state, but in contrast to CL, these do not mediate localized inflammatory responses.

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions.

BackgroundLeishmaniases are neglected tropical diseases that inflict great burden to poor areas of the globe. Intense research has aimed to identify parasite genetic signatures predictive of infection outcomes. Consistency of diagnostic tools based on these markers would greatly benefit from accurate understanding of Leishmania spp. population genetics. We explored two chromosomal loci to characterize a population of L. braziliensis causing human disease in Northeast Brazil.Methodology/principal findingsTwo temporally distinct samples of L. braziliensis were obtained from patients attending the leishmaniasis clinic at the village of Corte de Pedra: (2008-2011) primary sample, N = 120; (1999-2001) validation sample, N = 35. Parasites were genotyped by Sanger's sequencing of two 600 base pairs loci starting at nucleotide positions 3,074 and 425,451 of chromosomes 24 and 28, respectively. Genotypes based on haplotypes of biallelic positions in each locus were tested for several population genetic parameters as well as for geographic clustering within the region. Ample geographic overlap of genotypes at the two loci was observed as indicated by non-significant Cusick and Edward's comparisons. No linkage disequilibrium was detected among combinations of haplotypes for both parasite samples. Homozygous and heterozygous genotypes displayed Hardy-Weinberg equilibrium (HWE) at both loci in the two samples when straight observed and expected counts were compared by Chi-square (p>0.5). However, Bayesian statistics using one million Monte-Carlo randomizations disclosed a less robust HWE for chromosome 24 genotypes, particularly in the primary sample (p = 0.04). Fixation indices (Fst) were consistently lower than 0.05 among individuals of the two samples at both tested loci, and no intra-populational structuralization could be detected using STRUCTURE software.Conclusions/significanceThese findings suggest that L. braziliensis can maintain stable populations in foci of human leishmaniasis and are capable of robust genetic recombination possibly due to events of sexual reproduction during the parasite's lifecycle.

Abstract Yellow fever (YF) outbreaks continue, have expanded into new areas and threaten large populations in South America and Africa. Predicting where epidemics might occur must take into account local mosquito populations and specific YF virus strain, as well as ecoclimatic conditions, sociopolitical and demographic factors including population size, density, and mobility, and vaccine coverage. Populations of Aedes aegypti and Aedes albopictus from different regions vary in susceptibility to and capacity to transmit YF virus. YF virus cannot be eliminated today because the virus circulates in animal reservoirs, but human disease could be eliminated with wide use of the vaccine. WHO EYE (Eliminate Yellow Fever Epidemics) is a welcome plan to control YF, with strategies to be carried out from 2017 to 2026: to expand use of YF vaccine, to prevent international spread, and to contain outbreaks rapidly. YF vaccination is the mainstay in controlling YF outbreaks, but global supply is insufficient. Therefore, dose-sparing strategies have been proposed including fractional dosing and intradermal administration. Fractional dosing has been effectively used in outbreak control but currently does not satisfy International Health Regulations; special documentation is needed for international travel. Vector control is another facet in preventing YF outbreaks, and novel methods are being considered and proposed.

Leishmaniasis is a spectrum of diseases caused by Leishmania

Visceral leishmaniasis (VL) is a potentially fatal parasitic infection caused by Leishmania donovani in India. L. donovani is an obligate intracellular protozoan residing mostly in macrophages of the reticuloendothelial system throughout chronic infection. Monocytic phagocytes are critical in the pathogenesis of different forms of leishmaniasis. Subsets of monocytes are distinguished by their surface markers into CD14+CD16- classical monocytes, CD14+CD16+ intermediate monocytes, and CD16++CD14low non-classical monocyte subsets. During cutaneous leishmaniasis (CL), intermediate monocyte are reported to be a source of inflammatory cytokines IL-1β and TNF, and they express CCR2 attracting them to sites of inflammatory pathology. We examined monocyte subsets in the blood and bone marrow of patients with VL from an endemic site in Bihar, India, and found these contrasted with the roles of monocytes in CL. During VL, intermediate and non-classical CD16+ monocyte subsets expressed instead a non-inflammatory phenotype with low CCR2, high CX3CR1 and low microbicidal oxidant generation, making them more similar to patrolling monocytes than inflammatory cells. Bone marrow CD16+ monocyte subsets expressed a phenotype that might be more similar to the inflammatory subsets of CL, although our inability to obtain bone marrow from healthy donors in the endemic region hampered this interpretation Overall the data suggest that CD16+ intermediate monocyte subsets in VL patients express a phenotypes that contributes to an immunosuppressed pathologic immune state, but in contrast to CL, these do not mediate localized inflammatory responses. Author summary: The parasite Leishmania donovani causes the fatal systemic disease visceral leishmaniasis (VL) in endemic nations including India. The parasite is an obligate intracellular protozoan, residing mostly in monocytic cells in the bone marrow, blood and affected organs of infected human or other vertebrate hosts. Cells of the monocytic lineage can either provide a safe intracellular location in which the parasite survives, or they can be activated to kill intracellular parasites. We studied the contribution of monocyte subsets in the blood and bone marrow of patients from India with active visceral leishmaniasis, or control subjects without leishmaniasis. Our studies suggested that circulating monocytes of patients with VL are defective in their hability to kill intracellular parasites and to migrate toward sites of inflammation. These defects are most prominent in expanded subsets of monocytes expressing both the CD16 and CD14 receptors on their surface membranes. The immune defects underlying VL may be greatly influenced by subsets of blood monocytes that expand during disease. [ABSTRACT FROM AUTHOR]

Multiple organ dysfunction syndrome (MODS) is a serious event that can occur following infection or tissue injury, and is partly mediated by histones released in circulation. Here, the authors develop aptamers that neutralise histones involved in MODS, and demonstrate efficacy in human cells and in mouse models.

In this study, we generated a transgenic strain of Leishmania braziliensis, an etiological agent associated with a diversity of clinical manifestations of leishmaniasis ranging from localized cutaneous to mucocutaneous to disseminated disease. Transgenic parasites expressing reporter proteins are valuable tools for studies of parasite biology, host-pathogen interactions, and anti-parasitic drug development. To this end, we constructed an L. braziliensis line stably expressing the reporters eGFP and luciferase (eGFP-LUC L. braziliensis). The integration cassette co-expressing the two reporters was targeted to the ribosomal locus (SSU) of the parasite genome. Transgenic parasites were characterized for their infectivity and stability both in vitro and in vivo. Parasite maintenance in axenic long-term culture in the absence of selective drugs did not alter expression of the two reporters or infection of BALB/c mice, indicating stability of the integrated cassette. Infectivity of eGFP-LUC, L. braziliensis, both in vivo and in vitro was similar to that obtained with the parental wild type strain. The possibility of L. braziliensis tracking and quantification using fluorescence and luminescence broadens the scope of research involving this neglected species, despite its importance in terms of public health concerning the leishmaniasis burden.

BackgroundThe liver X receptors (LXRs) are a family of nuclear receptor transcription factors that are activated by oxysterols and have defined roles in both lipid metabolism and cholesterol regulation. LXRs also affect antimicrobial responses and have anti-inflammatory effects in macrophages. As mice lacking LXRs are more susceptible to infection by intracellular bacteria Listeria monocytogenes and Mycobacterium tuberculosis, we hypothesized that LXR might also influence macrophage responses to the intracellular protozoan parasite Leishmania chagasi/infantum, a causative agent of visceral leishmaniasis.Methods and findingsSurprisingly, both LXRα knock-out and LXRα/LXRβ double-knock-out (DKO) mice were markedly resistant to systemic L. chagasi/infantum infection compared to wild-type mice. Parasite loads in the livers and spleens of these animals were significantly lower than in wild-type mice 28 days after challenge. Bone marrow-derived macrophages from LXR-DKO mice infected with L. chagasi/infantum in vitro in the presence of IFN-γ were able to kill parasites more efficiently than wild-type macrophages. This enhanced killing by LXR-deficient macrophages correlated with higher levels of nitric oxide produced, as well as increased gene expression of IL-1β. Additionally, LXR ligands abrogated nitric oxide production in wild-type macrophages in response to infection.ConclusionsThese observations suggest that LXR-deficient mice and macrophages mount antimicrobial responses to Leishmania infection that are distinct from those mounted by wild-type mice and macrophages. Furthermore, comparison of these findings to other intracellular infection models suggests that LXR signaling pathways modulate host antimicrobial responses in a complex and pathogen-specific manner. The LXR pathway thus represents a potential therapeutic target for modulating immunity against Leishmania or other intracellular parasites.

Abstract Background The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. Symptomatic leishmaniasis causes considerable human morbidity in endemic regions. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment. MSP is a metalloprotease encoded by a tandem array of genes belonging to three msp gene classes, whose mRNAs are differentially expressed in different life stages of the parasite. Like other cells, Leishmania spp. release small membrane-bound vesicles called exosomes into their environment. The purpose of this study was to detect MSP proteins in exosomal vesicles of Leishmania spp. protozoa. Methods Using mass spectrometry data we determined the profile of MSP class proteins released in L. infantum exosomes derived from promastigotes in their avirulent procyclic (logarithmic) stage and virulent stationary and metacyclic stages. MSP protein isoforms belonging to each of the three msp gene classes could be identified by unique peptides. Results Metacyclic promastigote exosomes contained the highest, and logarithmic exosomes had the lowest abundance of total MSP. Among the MSP classes, MSPC class had the greatest variety of isoforms, but was least abundant in all exosomes. Nonetheless, all MSP classes were present at higher levels in exosomes released from stationary or metacyclic promastigotes than logarithmic promastigotes. Conclusions The data suggest the efficiency of exosome release may be more important than the identity of MSP isoform in determining the MSP content of Leishmania spp. exosomes.

Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change, and communication strategies. Because there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives.

Objective: To inform future interventions for advising travelers. Patients and Methods: We prospectively collected data on travelers seen at the Boston Area Travel Medicine Network, a Boston area research collaboration of 5 travel medicine clinics. Data from 15,440 travelers were collected from March 1, 2008, through July 31, 2010. We compared traveler and trip characteristics and differences in demographic characteristics and travel plans across the 5 clinics, including an analysis of pretravel preparations for certain high-risk destinations. Results: More than half of the 15,440 travelers were female (8730 [56.5]), and 72.4% (10,528 of 14,545) were white; the median age was 34 years, and 29.4% of travelers (3077 of 10,483) were seen less than 2 weeks before their departure date. Substantial variation in racial background, purpose of travel, and destination risk existed across the 5 clinics. For example, the proportion of travelers visiting friends and relatives ranged from 7.6% (184 of 2436) to 39.0% (1029 of 2639) (18.7% [2876 of 15,360] overall), and the percentage of travelers to areas with malaria risk ranged from 23.7% (333 of 1403) to 52.0% (1306 of 2512). Although most clinics were likely to have prescribed certain vaccines for high-risk destinations (eg, yellow fever for Ghana travel), there was wide variability in influenza vaccine use for China travel. Conclusion: Substantial differences in clinic populations can occur within a single metropolitan area, highlighting why individual physicians and travel clinics need to understand the specific needs of the travelers they serve in addition to general travel medicine.

Postmortem examination of 7 neonates with congenital Zika virus infection in Brazil revealed microcephaly, ventriculomegaly, dystrophic calcifications, and severe cortical neuronal depletion in all and arthrogryposis in 6. Other findings were leptomeningeal and brain parenchymal inflammation and pulmonary hypoplasia and lymphocytic infiltration in liver and lungs. Findings confirmed virus neurotropism and multiple organ infection.

Leishmaniasis is a global health problem with an estimated report of 2 million new cases every year and more than 1 billion people at risk of contracting this disease in endemic areas. The innate immune system plays a central role in controlling L. major infection by initiating a signaling cascade that results in production of pro-inflammatory cytokines and recruitment of both innate and adaptive immune cells. Upon infection with L. major, CXCL1 is produced locally and plays an important role in the recruitment of neutrophils to the site of infection. Herein, we report that L. major specifically targets murine CXCL1 for degradation. The degradation of CXCL1 is not dependent on host factors as L. major can directly degrade recombinant CXCL1 in a cell-free system. Using mass spectrometry, we discovered that the L. major protease cleaves at the C-terminal end of murine CXCL1. Finally, our data suggest that L. major metalloproteases are involved in the direct cleavage and degradation of CXCL1, and a synthetic peptide spanning the CXCL1 cleavage site can be used to inhibit L. major metalloprotease activity. In conclusion, our study has identified an immune evasion strategy employed by L. major to evade innate immune responses in mice, likely reservoirs in the endemic areas, and further highlights that targeting these L. major metalloproteases may be important in controlling infection within the reservoir population and transmittance of the disease.

Cutaneous leishmaniasis (CL) is a parasitic disease causing chronic, ulcerating skin lesions. Most humans infected with the causative Leishmania protozoa are asymptomatic. Leishmania spp. are usually introduced by sand flies into the dermis of mammalian hosts in the presence of bacteria from either the host skin, sand fly gut or both. We hypothesized that bacteria at the dermal inoculation site of Leishmania major will influence the severity of infection that ensues. A C57BL/6 mouse ear model of single or coinfection with Leishmania major, Staphylococcus aureus, or both showed that single pathogen infections caused localized lesions that peaked after 2-3 days for S. aureus and 3 weeks for L. major infection, but that coinfection produced lesions that were two-fold larger than single infection throughout 4 weeks after coinfection. Coinfection increased S. aureus burdens over 7 days, whereas L. major burdens (3, 7, 28 days) were the same in singly and coinfected ears. Inflammatory lesions throughout the first 4 weeks of coinfection had more neutrophils than did singly infected lesions, and the recruited neutrophils from early (day 1) lesions had similar phagocytic and NADPH oxidase capacities. However, most neutrophils were apoptotic, and transcription of immunomodulatory genes that promote efferocytosis was not upregulated, suggesting that the increased numbers of neutrophils may, in part, reflect defective clearance and resolution of the inflammatory response. In addition, the presence of more IL-17A-producing γδ and non-γδ T cells in early lesions (1-7 days), and L. major antigen-responsive Th17 cells after 28 days of coinfection, with a corresponding increase in IL-1β, may recruit more naïve neutrophils into the inflammatory site. Neutralization studies suggest that IL-17A contributed to an enhanced inflammatory response, whereas IL-1β has an important role in controlling bacterial replication. Taken together, these data suggest that coinfection of L. major infection with S. aureus exacerbates disease, both by promoting more inflammation and neutrophil recruitment and by increasing neutrophil apoptosis and delaying resolution of the inflammatory response. These data illustrate the profound impact that coinfecting microorganisms can exert on inflammatory lesion pathology and host adaptive immune responses.

BACKGROUND:Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). METHODS:We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. RESULTS:Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. CONCLUSION:We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.

Worldwide, an estimated 12 million people are infected with Leishmania spp. and an additional 350 million are at risk of infection. Leishmania are intracellular parasites that cause disease by suppressing macrophage microbicidal responses. Infection can remain asymptomatic or lead to a spectrum of diseases including cutaneous, mucocutaneous, and visceral leishmaniasis. Ultimately, the combination of both pathogen and host factors determines the outcome of infection. Leishmaniasis, as well as numerous other infectious diseases, exhibits sex-related differences that cannot be explained solely in terms of environmental exposure or healthcare access. Furthermore, transcriptomic evidence is revealing that biological sex is a variable impacting physiology, immune response, drug metabolism, and consequently, the progression of disease. Herein, we review the distribution, morbidity, and mortality among male and female leishmaniasis patients. Additionally, we discuss experimental findings and new avenues of research concerning sex-specific responses in cutaneous and visceral leishmaniasis. The limitations of current therapies and the emergence of drug-resistant parasites underscore the need for new treatments that could harness the host immune response. As such, understanding the mechanisms driving the differential immune response and disease outcome of males versus females is a necessary step in the development of safer and more effective treatments against leishmaniasis.

BackgroundAfter being eliminated during the 1950s, dengue reemerged in Brazil in the 1980s. Since then, incidence of the disease has increased, as serotypes move within and between cities. The co-circulation of multiple serotypes contributes to cycles of epidemic and interepidemic years, and a seasonal pattern of transmission is observed annually. Little is known regarding possible differences in the epidemiology of dengue under epidemic and interepidemic scenarios. This study addresses this gap and aims to assess the epidemiological characteristics and determinants of epidemic and interepidemic dengue transmission, utilizing data from the 5th largest city in Brazil (Fortaleza), at fine spatial and temporal scales.Methods/principal findingsLongitudinal models of monthly rates of confirmed dengue cases were used to estimate the differential contribution of contextual factors to dengue transmission in Fortaleza between 2011 and 2015. Models were stratified by annual climatological schedules and periods of interepidemic and epidemic transmission, controlling for social, economic, structural, entomological, and environmental factors. Results revealed distinct seasonal patterns between interepidemic and epidemic years, with persistent transmission after June in interepidemic years. Dengue was strongly associated with violence across strata, and with poverty and irregular garbage collection during periods of low transmission, but not with other indicators of public service provision or structural deprivation. Scrapyards and sites associated with tire storage were linked to incidence differentially between seasons, with the strongest associations during transitional precipitation periods. Hierarchical clustering analysis suggests that the dengue burden concentrates in the southern periphery of the city, particularly during periods of minimal transmission.Conclusions/significanceOur findings have direct programmatic implications. Vector control operations must be sustained after June even in non-epidemic years. More specifically, scrapyards and sites associated with tires (strongly associated with incidence during periods of minimal transmission), require sustained entomological surveillance, particularly during interepidemic intervals and in the urban periphery. Intersectoral collaborations that address urban violence are critical for facilitating the regular activities of vector control agents.

The role of NLRP12 in immunity to bacterial infection is controversial as varied and contrasting results have been published using C57BL/6 mice. Here the authors shed light on this issue, showing that unlike C57BL/6N mice, C57BL/6J mice have a missense point mutation in NLRP12 that is associated with defective neutrophil recruitment.

Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a ‘Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events.

From the discovery of Zika virus in Uganda in 1947 through 2007, when an outbreak occurred on Yap Island, Micronesia, only sporadic cases of human infection had been reported (1). [...]

Leishmania braziliensis is an intracellular parasite that resides mostly in macrophages. Both the parasite genome and the clinical disease manifestations show considerable polymorphism. Clinical syndromes caused by L. braziliensis include localized cutaneous (CL), mucosal (ML), and disseminated leishmaniasis (DL). Our prior studies showed that genetically distinct L. braziliensis clades associate with different clinical types. Herein, we hypothesized that: (1) L. braziliensis induces changes in macrophage gene expression that facilitates infection; (2) infection of macrophages with strains associated with CL (clade B), ML (clade C), or DL (clade A) will differentially affect host cell gene expression, reflecting their different pathogenic mechanisms; and (3) differences between the strains will be reflected by differences in macrophage gene expression after initial exposure to the parasite. Human monocyte derived macrophages were infected with L. braziliensis isolates from clades A, B, or C. Patterns of gene expression were compared using Affymetrix DNA microarrays. Many transcripts were significantly decreased by infection with all isolates. The most dramatically decreased transcripts encoded proteins involved in signaling pathways, apoptosis, or mitochondrial oxidative phosphorylation. Some transcripts encoding stress response proteins were up-regulated. Differences between L. braziliensis clades were observed in the magnitude of change, rather than the identity of transcripts. Isolates from subjects with metastatic disease (ML and DL) induced a greater magnitude of change than isolates from CL. We conclude that L. braziliensis enhances its intracellular survival by inhibiting macrophage pathways leading to microbicidal activity. Parasite strains destined for dissemination may exert a more profound suppression than less invasive L. braziliensis strains that remain near the cutaneous site of inoculation.

Visceral leishmaniasis (VL) caused by Leishmania infantum became a disease of urban areas in Brazil in the last 30 years and there has been an increase in asymptomatic L. infantum infection with these areas.A retrospective study of human VL was performed in the state of Rio Grande do Norte, Brazil, for the period of 1990-2014. The data were divided into five-time periods. For all VL cases, data on sex, age, nutritional status and childhood vaccination were collected. Geographic information system tools and statistical models were used to analyze the dispersion of human VL. The mean annual incidence of VL was 4.6 cases/100,000 inhabitants, with total 3,252 cases reported. The lethality rate was 6.4%. Over time the annual incidence of VL decreased in the 0-4 years (p40 years (p