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1.
PLoS Negl Trop Dis ; 17(4): e0011206, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37011128

RESUMO

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.


Assuntos
Leishmaniose Visceral , Animais , Humanos , Leishmaniose Visceral/epidemiologia , Estudos Retrospectivos , Brasil/epidemiologia , Teorema de Bayes , Cidades , Doenças Negligenciadas
2.
Am J Trop Med Hyg ; 104(4): 1404-1411, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591939

RESUMO

In Brazil, schistosomiasis continues to be an important health issue. The aim of this study was to identify factors associated with Schistosoma mansoni infestation. A cross-sectional study was performed to assess factors associated with S. mansoni endemicity in a municipality in Northeast Brazil with a history of reporting schistosomiasis. Participants were divided into four groups: 1) new S. mansoni cases (n = 44), 2) past history of S. mansoni treatment (n = 78), 3) immediate neighbors (n = 158), and 4) nearby controls (n = 35). Multiple comparisons analysis was performed. Subjects had a mean of 6.6 ± 3.9 years of education, and no difference was observed regarding family income (one-way analysis of variance, P = 0.215). A total of 95.9% of the individuals had rudimentary cesspit as sanitary wastewater. The mean body mass index was 28.3 ± 5.1, with 41.0% and 24.1% overweight and obesity, respectively. Of note, 28.9% of adults had hypertension. Hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin were higher in the recent S. mansoni treated group (Wilks' lambda, P < 0.001). Male gender was more prevalent in new S. mansoni cases (likelihood ratio, P < 0.001), close proximity to water collections was a risk for S. mansoni infestation (likelihood ratio, P < 0.001), and a better hematological status was observed in individuals recently treated with praziquantel. This study indicates the need to maintain surveillance for S. mansoni in low-transmission areas and the need to establish community-based interventions to control transmission.


Assuntos
Fezes/parasitologia , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/transmissão , Animais , Brasil/epidemiologia , Estudos Transversais , Feminino , Água Doce/parasitologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/etiologia
3.
Am J Trop Med Hyg ; 98(1): 142-145, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29165220

RESUMO

Leishmania infantum causes visceral leishmaniasis (VL) in Brazil. We previously observed that VL is more common in males than females living in endemic neighborhoods, despite similar exposure. Using a larger sample, we document that VL is more common in males than females, but only after puberty. BALB/c and C57BL/6 mouse models confirmed that there is a biological basis for male susceptibility to symptomatic VL, showing higher parasite burdens in males than females. Female C57BL/6 mice generated more antigen-induced cytokines associated with curative responses (interferon-γ, interleukin [IL]-1ß). Males expressed higher levels of IL-10 and tumor necrosis factor, which are linked to exacerbated disease. Different parasite lines entered or survived at a higher rate in macrophages of male- than female-origin. These results suggest that males are inherently more susceptible to L. infantum than females and that mice are a valid model to study this sex-dependent difference.


Assuntos
Leishmania infantum , Leishmaniose Visceral/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-1beta/sangue , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fatores Sexuais , África do Sul/epidemiologia , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
4.
Ann Hum Genet ; 81(1): 41-48, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28054334

RESUMO

Genetic risk factors contribute to asymptomatic versus symptomatic visceral leishmaniasis (VL) outcomes following infection with Leishmania infantum. We therefore carried out a family-based (n = 918 post-quality control fully genotyped and phenotyped individuals) candidate gene study for symptomatic VL or asymptomatic delayed-type hypersensitivity (DTH) skin test phenotypes in highly endemic neighborhoods of northeast Brazil. A total of 248 SNPs were genotyped in 42 genes selected as candidates on the basis of prior genetic, immunological, and transcriptional profiling studies. The most significant association with the VL phenotype was with SNP rs6785358 (P = 5.7e-04; pcorrected = 0.026) 3.8 kb upstream of TGFBR2, the gene encoding the type 2 receptor for transforming growth factor beta (TGFß). A second inhibitory member of the TGBß superfamily signaling pathway, SMAD7, was associated with the DTH phenotype (SNP rs7238442: P = 0.001; pcorrected = 0.051). The most significant association for the DTH phenotype was with SNP rs10800309 (P = -8.4e-06; pcorrected = 3.9e-04) situated 3.1 kb upstream of FCGR2A, the gene encoding the low-affinity IIa receptor for the Fc fragment of IgG. Overall, our results imply a role for IgG-mediated inflammation in determining DTH associated with asymptomatic infection and contribute to growing evidence that the TGFß pathway is important in the immunopathogenesis of VL.


Assuntos
Leishmania infantum , Leishmaniose Visceral/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de IgG/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Adolescente , Infecções Assintomáticas , Brasil , Criança , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Leishmaniose Visceral/parasitologia , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Receptor do Fator de Crescimento Transformador beta Tipo II
5.
Infect Genet Evol ; 43: 1-5, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27155051

RESUMO

Infection with the protozoan Leishmania infantum can lead to asymptomatic infection and protective immunity, or to the progressive and potentially fatal disease visceral leishmaniasis (VL). Published studies show host genetic background determines in part whether infected individuals will develop a symptomatic or asymptomatic outcome. The purpose of the current study was to fine map chromosome regions previously linked with risk for symptomatic (chromosome 9) or asymptomatic (chromosomes 15 and 19) manifestations of L. infantum infection. We conducted a family-based genetic study of VL and asymptomatic infection (detected by a DTH skin test) with a final post quality control sample of 961 individuals with full genotype and phenotype information from highly endemic neighborhoods of northeast Brazil. A total of 5485 SNPs under the linkage peaks on chromosomes 9, 15 and 19 were genotyped. No strong SNP associations were observed for the DTH phenotype. The most significant associations with the VL phenotype were with SNP rs1470217 (p=5.9e-05; pcorrected=0.057) on chromosome 9, and with SNP rs8107014 (p=1.4e-05; pcorrected=0.013) on chromosome 19. SNP rs1470217 is situated in a 180kb intergenic region between TMEM215 (Transmembrane protein 215) and APTX (Aprataxin). SNP rs8107014 lies in the intron between exons 26 and 27 of a 34 exon transcript (ENST00000204005) of LTBP4, (Latent transforming growth factor-beta-binding protein 4a). The latter supports growing evidence that the transforming growth factor-beta pathway is important in the immunopathogenesis of VL.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 9/genética , Leishmaniose Visceral/genética , Polimorfismo de Nucleotídeo Único , Brasil , Proteínas de Ligação a DNA/genética , Feminino , Ligação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Leishmania infantum/fisiologia , Masculino , Proteínas Nucleares/genética , Linhagem , Fenótipo , Locos de Características Quantitativas
6.
Drug Dev Res ; 72(6): 451-462, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25821334

RESUMO

Visceral leishmaniasis [VL] represents a major public health problem in many areas of the world. This review focuses on the impact of periurbanization on the epidemiology and treatment of VL, using Brazil as an example. VL continues to be mostly a disease of poverty with impact on families. However, the disease has expanded in Latin America, with foci reported as far south as Argentina. There is an increasing overlap of Leishmania infantum chagasi and HIV infections and other immunosuppressive conditions, resulting in VL emerging as an opportunistic infection. This new setting poses new challenges for VL disease control and patient management.

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