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1.
Parasit Vectors ; 17(1): 172, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566124

RESUMO

BACKGROUND: Antigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA. METHODS: We report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland-Altman (BA) analysis and Lin's concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA. RESULTS: The TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin's CCC: 0.69, 0.92, and 0.96, respectively, all P < 0.001). In pigs infected with T. hydatigena, almost all paired log-OD differences were within the LoA in the BA analysis, whereas the concordance of log-ODs between assays was low at baseline (Lin's CCC: 0.24) but increased on days 28 and 90 PI (Lins' CCC: 0.88 and 0.98, P < 0.001). CONCLUSIONS/SIGNIFICANCE: The TsW8/TsW5 Ag-ELISA recognizes antigens in pigs with T. solium cysticercosis and is highly concordant with the B158/B60 Ag-ELISA. However, its diagnostic use is hampered by cross-reactions with T. hydatigena, as in other mAb-based Ag-ELISAs.


Assuntos
Cisticercose , Cistos , Doenças dos Suínos , Taenia solium , Taenia , Animais , Humanos , Suínos , Cysticercus , Anticorpos Monoclonais , Doenças dos Suínos/diagnóstico , Cisticercose/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Antígenos , Antígenos de Helmintos , Anticorpos Anti-Helmínticos
2.
PLOS Glob Public Health ; 4(4): e0002996, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635669

RESUMO

In order to understand the impacts in the post-disaster scenario of the 2017 El Niño events in the Piura region-Peru, we examined post-traumatic stress disorder (PTSD), food insecurity (FI), and social capital (SC) across three-time points in mothers in highly affected areas. In the Piura, Castilla, and Catacaos districts, we studied mothers combining mixed-method assessments at three (June-July 2017), eight and 12 months after the flooding. Each outcome was measured with the PTSD-Checklist-Civilian (PCL-C), the Household-Food-Insecurity-Access-Scale (HFIAS), the Adapted-Social-Capital-Assessment-Tool (SASCAT) surveys. In-depth interviews at the first evaluation were also conducted. At the first evaluation, 38.1% (n = 21) of 179 mothers reported PTSD; eight months and one year after the flooding, it dropped to 1.9% and virtually zero, respectively. Severe FI also declined over time, from 90.0% three months after the flooding to 31.8% eight months after, to 13.1% one year after. Conversely, high-cognitive SC was increased three months after the flooding (42.1%) and much greater levels at eight and 12 months after (86.7% and 77.7%, respectively). High levels of PTSD and severe FI three months after the flooding consistently decreased to nearly zero one-year post-disaster. High levels of high-cognitive SC may have helped mothers to recover from PTSD and FI in Piura.

3.
Front Public Health ; 12: 1332319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584932

RESUMO

Background: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrheal morbidity and mortality in children, although the data on disease burden, epidemiology, and impact on health at the community level are limited. Methods: In a longitudinal birth cohort study of 345 children followed until 24 months of age in Lima, Peru, we measured ETEC burden in diarrheal and non-diarrheal samples using quantitative PCR (LT, STh, and STp toxin genes), studied epidemiology and measured anthropometry in children. Results: About 70% of children suffered from one or more ETEC diarrhea episodes. Overall, the ETEC incidence rate (IR) was 73 per 100 child-years. ETEC infections began early after birth causing 10% (8.9-11.1) ETEC-attributable diarrheal burden at the population level (PAF) in neonates and most of the infections (58%) were attributed to ST-ETEC [PAF 7.9% (1.9-13.5)] and LT + ST-ETEC (29%) of which all the episodes were associated with diarrhea. ETEC infections increased with age, peaking at 17% PAF (4.6-27.7%; p = 0.026) at 21 to 24 months. ST-ETEC was the most prevalent type (IR 32.1) with frequent serial infections in a child. The common colonization factors in ETEC diarrhea cases were CFA/I, CS12, CS21, CS3, and CS6, while in asymptomatic ETEC cases were CS12, CS6 and CS21. Only few (5.7%) children had repeated infections with the same combination of ETEC toxin(s) and CFs, suggested genotype-specific immunity from each infection. For an average ETEC diarrhea episode of 5 days, reductions of 0.060 weight-for-length z-score (0.007 to 0.114; p = 0.027) and 0.061 weight-for-age z-score (0.015 to 0.108; p = 0.009) were noted in the following 30 days. Conclusion: This study showed that ETEC is a significant pathogen in Peruvian children who experience serial infections with multiple age-specific pathotypes, resulting in transitory growth impairment.


Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Recém-Nascido , Humanos , Escherichia coli Enterotoxigênica/genética , Peru/epidemiologia , Estudos de Coortes , Diarreia/epidemiologia , Enterotoxinas/genética , Infecções por Escherichia coli/epidemiologia
4.
Gut Microbes ; 16(1): 2309681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38300753

RESUMO

Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children's incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children's risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children's risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children's incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.


Assuntos
Aleitamento Materno , Microbioma Gastrointestinal , Criança , Feminino , Humanos , Adolescente , Lactente , Recém-Nascido , Estudos Prospectivos , Peru/epidemiologia , Escherichia coli , Antibacterianos/farmacologia
5.
Brain Pathol ; 34(5): e13237, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38212958

RESUMO

Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with Taenia solium oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, p < 0.0001), higher spheroids count (45.2 vs. 0.2, p = 0.0001), and increased inflammation (72.0% vs. 21.4%, p = 0.003). In this rat model, anthelmintic treatment destroyed brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.


Assuntos
Anti-Helmínticos , Encéfalo , Neurocisticercose , Taenia solium , Animais , Neurocisticercose/tratamento farmacológico , Neurocisticercose/patologia , Ratos , Anti-Helmínticos/uso terapêutico , Encéfalo/patologia , Encéfalo/parasitologia , Albendazol/uso terapêutico , Albendazol/farmacologia , Praziquantel/uso terapêutico , Modelos Animais de Doenças , Masculino , Feminino , Benzimidazóis
6.
Front Cell Neurosci ; 17: 1183322, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37323586

RESUMO

Neurocysticercosis (NCC) is the most common parasitic disease affecting the nervous system and is a leading cause of acquired epilepsy worldwide, as well as cognitive impairment, especially affecting memory. The aim of this study was to evaluate the effect of NCC on spatial working memory and its correlation with hippocampal neuronal density, in a rat model of NCC. This experimental study was conducted on female (n = 60) and male (n = 73) Holtzman rats. NCC was induced by intracranial inoculation of T. solium oncospheres in 14 day-old-rats. Spatial working memory was assessed using the T-maze test at 3, 6, 9, and 12 months post-inoculation, and sensorimotor evaluation was performed at 12 months post-inoculation. Hippocampal neuronal density was evaluated by immunostaining of NeuN-positive cells of the CA1 region. Of the rats inoculated with T. solium oncospheres, 87.2% (82/94) developed NCC. The study showed a significant decline in spatial working memory over a 1-year follow-up period in rats experimentally infected with NCC. Males showed an early decline that started at 3 months, while females demonstrated it at 9 months. Additionally, a decrease in neuronal density was observed in the hippocampus of NCC-infected rats, with a more significant reduction in rats with cysts in the hippocampus than in rats with cysts in other brain areas and control rats. This rat model of NCC provides valuable support for the relationship between neurocysticercosis and spatial working memory deficits. Further investigations are required to determine the mechanisms involved in cognitive impairment and establish the basis for future treatments.

7.
J Clin Microbiol ; 61(7): e0028223, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37367233

RESUMO

Coproantigen detection by enzyme-linked immunosorbent assay (coAg ELISA) is a vital tool for detecting and treating cases of Taenia solium taeniasis. However, the assay's procedures require costly materials and sophisticated equipment, which are typically inaccessible in rural settings where the disease is endemic. To overcome these barriers, we developed and evaluated a field-applicable coAg ELISA. The field coAg ELISA was developed and evaluated across four phases using known positive and negative stool samples collected from northern Peru. Phase I focused on field assay development, phase II on a small-scale performance evaluation, phase III on a large-scale evaluation, and phase IV on the use and reliability of a colorimetric scale card. All samples were processed using the field and standard assay procedures and compared using signal-to-noise ratios, correlation tests, performance characteristics, and agreement statistics where appropriate. The field coAg ELISA using reagents stored at -20°C and commercially available water and milk powder, and relying on spontaneous separation of the supernatant, had performance comparable to the standard assay. The field coAg ELISA was strongly correlated with the standard in both the small- and large-scale laboratory evaluation (r = 0.99 and r = 0.98, respectively). Finally, the field assay had an almost perfect agreement between independent readers (kappa = 0.975) and between each reader and the spectrophotometer. The field coAg ELISA demonstrated performance comparable to the standard, providing a low-cost alternative to the standard assay for identifying cases of intestinal taeniasis in a low-resource setting.


Assuntos
Cisticercose , Taenia solium , Teníase , Humanos , Animais , Peru , Reprodutibilidade dos Testes , Antígenos de Helmintos , Teníase/diagnóstico , Teníase/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Fezes/química , Cisticercose/diagnóstico , Cisticercose/epidemiologia
8.
Trop Med Int Health ; 28(2): 107-115, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36573344

RESUMO

OBJECTIVE: We aimed (1) to evaluate the agreement between two methods (equation and bio-impedance analysis [BIA]) to estimate skeletal muscle mass (SMM), and (2) to assess if SMM was associated with all-cause mortality risk in individuals across different geographical sites in Peru. METHODS: We used data from the CRONICAS Cohort Study (2010-2018), a population-based longitudinal study in Peru to assess cardiopulmonary risk factors from different geographical settings. SMM was computed as a function of weight, height, sex and age (Lee equation) and by BIA. All-cause mortality was retrieved from national vital records. Cox proportional-hazard models were developed and results presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: At baseline, 3216 subjects, 51.5% women, mean age 55.7 years, were analysed. The mean SMM was 23.1 kg (standard deviation [SD]: 6.0) by Lee equation, and 22.7 (SD: 5.6) by BIA. Correlation between SMM estimations was strong (Pearson's ρ coefficient = 0.89, p < 0.001); whereas Bland-Altman analysis showed a small mean difference. Mean follow-up was 7.0 (SD: 1.0) years, and there were 172 deaths. In the multivariable model, each additional kg in SMM was associated with a 19% reduction in mortality risk (HR = 0.81; 95% CI: 0.75-0.88) using the Lee equation, but such estimate was not significant when using BIA (HR = 0.98; 95% CI: 0.94-1.03). Compared to the lowest tertile, subjects at the highest SMM tertile had a 56% reduction in risk of mortality using the Lee equation, but there was no such association when using BIA estimations. CONCLUSION: There is a strong correlation and agreement between SMM estimates obtained by the Lee equation and BIA. However, an association between SMM and all-cause mortality exists only when the Lee equation is used. Our findings call for appropriate use of approaches to estimate SMM, and there should be a focus on muscle mass in promoting healthier ageing.


Assuntos
Composição Corporal , Músculo Esquelético , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Composição Corporal/fisiologia , Músculo Esquelético/fisiologia , Estudos de Coortes , Estudos Longitudinais , Impedância Elétrica
9.
Rev Peru Med Exp Salud Publica ; 39(3): 328-335, 2022.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-36478166

RESUMO

OBJECTIVE.: To explore the feasibility of developing a sheep model of neurocysticercosis (NCC) by intracranial infection with T. solium oncospheres. MATERIALS AND METHODS.: We carried out an experimental infection model of NCC in sheep. Approximately 10 T. solium oncospheres previously cultured for 30 days were inoculated intracranially into ten sheep. The oncospheres, in 0.1 mL of physiological saline, were injected into the parietal lobe through an 18-gauge needle. RESULTS.: After three months, granulomas were found in two sheep. In a third sheep we identified a 5 mm diameter cyst in the right lateral ventricle and histological evaluation confirmed that the cyst corresponded to a T. solium larva. Immunohistochemistry with monoclonal antibodies directed against membrane components and excretory/secretory antigens of the T. solium cyst was also used to confirm the etiology of the found granulomas. One of them showed reactivity to the monoclonal antibodies used, thus confirming that it was a cysticercus. CONCLUSION.: This experiment is the proof of concept that it is possible to infect sheep with cysticercosis by intracranial inoculation.


OBJETIVO: . Explorar la viabilidad de desarrollar un modelo de neurocisticercosis (NCC) de oveja mediante infección intracraneal de oncosferas de T. solium. MATERIALES Y MÉTODOS.: Se realizó un modelo de infección experimental de NCC en ovejas. Se inocularon aproximadamente 10 posoncósferas de T. solium cultivadas previamente por 30 días por vía intracraneal en diez ovejas. Las oncósferas, en 0,1 mL de solución salina fisiológica, se inyectaron en el lóbulo parietal a través de una aguja de calibre 18. RESULTADOS.: Después de tres meses, en dos ovejas se encontraron granulomas y en una tercera identificó un quiste de 5 mm de diámetro en el ventrículo lateral derecho y la evaluación histológica confirmó que el quiste corresponde a una larva de T. solium. También se utilizó inmunohistoquímica con anticuerpos monoclonales dirigidos contra componentes de membrana y antígenos excretorios/secretorios del quiste de T. solium para confirmar la etiología de los granulomas encontrados. Uno de ellos mostro reactividad ante los anticuerpos monoclonales utilizados, confirmando así que se trató de un cisticerco. CONCLUSIÓN.: Este experimento es la prueba de concepto de que es posible infectar ovejas con cisticercosis por inoculación intracraneal.


Assuntos
Encéfalo , Cistos , Animais , Ovinos , Anticorpos Monoclonais
11.
Tuberculosis (Edinb) ; 137: 102273, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403561

RESUMO

Tuberculosis phenotypic detection assays are commonly used in low-resource countries. Therefore, reliable detection methods are crucial for early diagnosis and treatment. The microscopic observation drug susceptibility (MODS) assay is a culture-based test to detect Mycobacterium tuberculosis and characterize drug resistance in 7-10 days directly from sputum. The use of MODS is limited by the availability of supplies necessary for preparing the enriched culture. In this study, we evaluated three dry culture media that are easier to produce and cheaper than the standard one used in MODS [1]: an unsterilized powder-based mixed (Boldú et al., 2007) [2], a sterile-lyophilized medium, and (Sengstake et al., 2017) [3] an irradiated powder-based mixed. Mycobacterial growth and drug susceptibility were evaluated for rifampin, isoniazid, and pyrazinamide (PZA). The alternative cultures were evaluated using 282 sputum samples with positive acid-fast smears. No significant differences were observed in the positivity test rates. The positivity time showed high correlations (Rho) of 0.925, 0.889, and 0.866 between each of the three alternative media and the standard. Susceptibility testing for MDR and PZA showed an excellent concordance of 1 compared to the reference test. These results demonstrate that dry culture media are appropriate and advantageous for use in MODS in low-resource settings.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Análise Custo-Benefício , Meios de Cultura , Testes de Sensibilidade Microbiana , Pós/farmacologia , Pós/uso terapêutico , Sensibilidade e Especificidade , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
12.
Rev. peru. med. exp. salud publica ; 39(3): 328-335, jul.-sep. 2022. graf
Artigo em Espanhol | LILACS | ID: biblio-1410000

RESUMO

RESUMEN Objetivo . Explorar la viabilidad de desarrollar un modelo de neurocisticercosis (NCC) de oveja mediante infección intracraneal de oncosferas de T. solium. Materiales y métodos. Se realizó un modelo de infección experimental de NCC en ovejas. Se inocularon aproximadamente 10 posoncósferas de T. solium cultivadas previamente por 30 días por vía intracraneal en diez ovejas. Las oncósferas, en 0,1 mL de solución salina fisiológica, se inyectaron en el lóbulo parietal a través de una aguja de calibre 18. Resultados. Después de tres meses, en dos ovejas se encontraron granulomas y en una tercera identificó un quiste de 5 mm de diámetro en el ventrículo lateral derecho y la evaluación histológica confirmó que el quiste corresponde a una larva de T. solium. También se utilizó inmunohistoquímica con anticuerpos monoclonales dirigidos contra componentes de membrana y antígenos excretorios/secretorios del quiste de T. solium para confirmar la etiología de los granulomas encontrados. Uno de ellos mostro reactividad ante los anticuerpos monoclonales utilizados, confirmando así que se trató de un cisticerco. Conclusión. Este experimento es la prueba de concepto de que es posible infectar ovejas con cisticercosis por inoculación intracraneal.


ABSTRACT Objective. To explore the feasibility of developing a sheep model of neurocysticercosis (NCC) by intracranial infection with T. solium oncospheres. Materials and methods. We carried out an experimental infection model of NCC in sheep. Approximately 10 T. solium oncospheres previously cultured for 30 days were inoculated intracranially into ten sheep. The oncospheres, in 0.1 mL of physiological saline, were injected into the parietal lobe through an 18-gauge needle. Results. After three months, granulomas were found in two sheep. In a third sheep we identified a 5 mm diameter cyst in the right lateral ventricle and histological evaluation confirmed that the cyst corresponded to a T. solium larva. Immunohistochemistry with monoclonal antibodies directed against membrane components and excretory/secretory antigens of the T. solium cyst was also used to confirm the etiology of the found granulomas. One of them showed reactivity to the monoclonal antibodies used, thus confirming that it was a cysticercus. Conclusion. This experiment is the proof of concept that it is possible to infect sheep with cysticercosis by intracranial inoculation.


Assuntos
Animais , Encéfalo , Cisticercose , Ovinos , Ventrículos Laterais , Cistos , Epilepsia , Granuloma
13.
Am J Trop Med Hyg ; 107(4): 881-892, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-35970283

RESUMO

Chemical and microbiological drinking water contaminants pose risks to child health but are not often evaluated concurrently. At two consecutive visits to 96 households in Piura, Peru, we collected drinking water samples, administered health and exposure questionnaires, and collected infant stool samples. Standard methods were used to quantify heavy metals/metalloids, pesticides, and Escherichia coli concentrations in water samples. Stool samples were assayed for bacterial, viral, and parasitic enteropathogens. The primary drinking water source was indoor piped water for 70 of 96 households (73%); 36 households (38%) stored drinking water from the primary source in containers in the home. We found high prevalence of chemical and microbiological contaminants in household drinking water samples: arsenic was detected in 50% of 96 samples, ≥ 1 pesticide was detected in 65% of 92 samples, and E. coli was detected in 37% of 319 samples. Drinking water samples that had been stored in containers had higher odds of E. coli detection (adjusted odds ratio [aOR]: 4.50; 95% CI: 2.04-9.95) and pesticide detection (OR: 6.55; 95% CI: 2.05-21.0) compared with samples collected directly from a tap. Most infants (68%) had ≥ 1 enteropathogen detected in their stool. Higher odds of enteropathogen infection at the second visit were observed among infants from households where pesticides were detected in drinking water at the first visit (aOR: 2.93; 95% CI: 1.13-7.61). Results show concurrent risks of exposure to microbiological and chemical contaminants in drinking water in a low-income setting, despite high access to piped drinking water.


Assuntos
Arsênio , Água Potável , Metais Pesados , Praguicidas , Coorte de Nascimento , Criança , Água Potável/microbiologia , Escherichia coli , Humanos , Lactente , Peru/epidemiologia , Prevalência , Abastecimento de Água
14.
PLoS Negl Trop Dis ; 16(6): e0010449, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35653367

RESUMO

BACKGROUND: Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group. METHODS/PRINCIPAL FINDINGS: Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups. CONCLUSION/SIGNIFICANCE: Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment.


Assuntos
Cistos do Sistema Nervoso Central , Neurocisticercose , Doenças dos Suínos , Taenia solium , Animais , Cysticercus , Neurocisticercose/tratamento farmacológico , Suínos , Doenças dos Suínos/parasitologia
15.
Comput Struct Biotechnol J ; 20: 1821-1828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35521552

RESUMO

Genetic and omics analyses frequently require independent observations, which is not guaranteed in real datasets. When relatedness cannot be accounted for, solutions involve removing related individuals (or observations) and, consequently, a reduction of available data. We developed a network-based relatedness-pruning method that minimizes dataset reduction while removing unwanted relationships in a dataset. It uses node degree centrality metric to identify highly connected nodes (or individuals) and implements heuristics that approximate the minimal reduction of a dataset to allow its application to complex datasets. When compared with two other popular population genetics methodologies (PLINK and KING), NAToRA shows the best combination of removing all relatives while keeping the largest possible number of individuals in all datasets tested and also, with similar effects on the allele frequency spectrum and Principal Component Analysis than PLINK and KING. NAToRA is freely available, both as a standalone tool that can be easily incorporated as part of a pipeline, and as a graphical web tool that allows visualization of the relatedness networks. NAToRA also accepts a variety of relationship metrics as input, which facilitates its use. We also release a genealogies simulator software used for different tests performed in this study.

16.
Infect Genet Evol ; 102: 105291, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35490957

RESUMO

Rickettsial diseases have seen a re-emergence in the Americas in the last few decades, with concerning morbidity, mortality and economic implications that result from loss of productivity, income, curbs in liberal trade agreements, and reduction in agricultural practices. The aim of this study is to determine the socioecological determinants and seroprevalence for Rickettsia typhi and Rickettsia rickettsii among residents of Teabo, a rural community of Yucatán, Mexico. Sociodemographic data and serum samples were obtained from 180 consenting participants. Antibody titers for R. typhi and R. rickettsii were determined by indirect immunofluorescence assay (IFA). Participants also submitted tick samples collected from their residential area. We conducted logistic regression models to evaluate the association between exposure variables and seroprevalence. Rhipicephalus sanguineus s.l. (37%; n = 65), and Amblyomma cajennense Fabricius (17%; n = 29) were the predominant tick species in peri-domestic areas. Out of the 180 participants, there was significantly higher seroprevalence of R. typhi (n = 77; 46%) compared to R. rickettsii [n = 27, 15%, (p < 0.05)]. Pearson's chi-square test of independence revealed significant differences in R. rickettsii seroprevalence by gender (X2 [n = 175, df = 4, (p < 0.001)] = 180.26), level of education, (X2 [n = 180, df = 4, (p < 0.001)] = 44.0), and by tick species found in residential area, (X2 [n = 180, df = 4, (p = 0.050)] = 9.48). After adjusting for other variables in a logistic regression model, for each unit increase in the number of dogs present in the residential area, there was a 27% increase in the odds of human seroprevalence for R. typhi IgG (AOR = 1.27, 95% CI: 1.01-1.63). Compared to study participants living in residential areas with a 'low' height of vegetation, those living in residential areas with a 'medium' height of vegetation had 2.5 times greater odds of human seroprevalence for R. typhi IgG (AOR = 2.51, 95% CI: 1.19-5.40). Potentially modifiable existing factors in the peri-domestic area may constitute a high-risk source of seroprevalence for rickettsial antibodies among residents of the rural community of Teabo, Yucatán, Mexico.


Assuntos
Doenças do Cão , Rhipicephalus sanguineus , Rickettsia , Animais , Doenças do Cão/microbiologia , Cães , Humanos , Imunoglobulina G , México/epidemiologia , Rhipicephalus sanguineus/microbiologia , População Rural , Estudos Soroepidemiológicos
17.
Clin Transl Sci ; 15(6): 1400-1405, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35266293

RESUMO

PDE4B (phosphodiesterase-4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, PDE4B variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. PDE4B allele rs6683977.G, associated with genomic regions of Native American origin in US-Hispanics (admixed among Native Americans, Europeans, and Africans), increases ALL relapse risk, contributing to an association between Native American ancestry and ALL relapse that disappeared with an extra-phase of chemotherapy. This result insinuates that indigenous populations along the Americas may have high frequencies of rs6683977.G, but this has never been corroborated. We studied ancestry and PDE4B diversity in 951 healthy individuals from nine Latin American populations. In non-admixed Native American populations rs6683977.G has frequencies greater than 90%, is in linkage disequilibrium with other ALL relapse associated and regulatory variants in PDE4B-intron-7, conforming haplotypes showing their highest worldwide frequencies in Native Americans (>0.82). Our findings inform the discussion on the pertinence of an extra-phase of chemotherapy in Native American populations, and exemplifies how knowledge generated in US-Hispanics is relevant for their even more neglected and vulnerable Native American ancestors along the American continent.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Neoplasias , Farmacogenética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Genética Populacional , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Recidiva , Indígena Americano ou Nativo do Alasca
18.
Antibiotics (Basel) ; 11(2)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35203794

RESUMO

Poultry farming represents Peru's primary food animal production industry, where antimicrobial growth promoters are still commonly used, exerting selective pressure on intestinal microbial populations. Consumption and direct animal-to-human transmission have been reported, and farmworkers are at high risk of colonization with resistant bacteria. We conducted a cross-sectional survey among 54 farmworkers to understand their current antimicrobial resistance (AMR) awareness in Ica, Peru. To gain insight into the potential work-related risk of exposure to bacteria, we also measured the AMR rates in Escherichia coli isolated among 50 broiler chickens. Farmworkers were unaware of antimicrobial resistance (31.5%) or antibiotic resistance (16.7%) terms. Almost two-thirds (61%) consumed antibiotics during the previous month, and only 42.6% received a prescription from a healthcare professional. A total of 107 E. coli chicken isolates were obtained, showing a high frequency of multidrug-resistant (89.7%) and extended-spectrum beta-lactamase (ESBL) production (71.9%). Among ESBL-producer isolates, 84.4% carried the blaCTX-M gene. Results identified gaps in knowledge that reflect the need for interventions to increase antimicrobial awareness among poultry farmworkers. The high AMR rates among E. coli isolates highlight the need to reduce antimicrobial use in poultry farms. Our findings reveal a critical need for effective policy development and antimicrobial stewardship interventions in poultry production in Ica, Peru.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35224529

RESUMO

BACKGROUND: Limited information exists about the incidence of first-ever stroke at the population level, particularly in low- and middle-income countries (LMIC). Longitudinal data from the CRONICAS Cohort Study includes both altitude and urbanization and allows a detailed assessment of stroke incidence in resource constrained settings. The aim of this study was to estimate the incidence and explore risk factors of first-ever stroke at the population level in Peru. METHODS: Stroke was defined using a standardised approach based on information from cohort participants or family members. This information was adjudicated centrally by trained physicians using common definitions. Time of follow-up was calculated as the difference between date of enrolment and the reported date of the stroke event. Unstandardised and age-standardised, first-ever stroke incidence rate and 95% confidence intervals (95% CI) were calculated. Generalized linear models, assuming Poisson distribution and link log, were utilized to determine potential factors to develop stroke. FINDINGS: 3,601 individuals were originally enrolled in the cohort and 2,471 provided data for the longitudinal analysis. The median time of follow-up was 7.0 (range: 1 - 9) years, accruing a total of 17,308 person-years. During followup, there were 25 incident cases of stroke, resulting in an age-standardised incidence of stroke of 98.8 (95% CI: 63.8 - 154.0) per 100,000 person-years. After adjustment by age and sex, stroke incidence was higher among people with hypertension (incidence risk ratio (IRR) = 5.18; 95% CI: 1.89 - 14.16), but lower among people living at high altitude (IRR = 0.09; 95% CI: 0.01 - 0.63). INTERPRETATION: Our results indicate a high incidence of first-ever strokes in Peruvian general population. These results are consistent with the estimates found in previous LMIC reports. Our study also found a contributing role of hypertension, increasing the risk of having a first-ever stroke. This work further advances the field of stroke epidemiology by identifying high altitude as a factor related to lower incidence of stroke in a longitudinal study. However, this information needs to be considered with cautions because of the study limitations.


DISCLAIMER: This translation in Spanish was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. ANTECEDENTES: Existe información limitada sobre la incidencia del accidente cerebrovascular (ACV) a nivel poblacional, especialmente en los países de ingresos bajos y medios (PIBM). Los datos longitudinales del estudio de cohorte CRONICAS incluyen tanto la altitud como la urbanización y permiten una evaluación detallada de la incidencia de ACV en entornos con recursos limitados. El objetivo de este estudio fue estimar la incidencia y explorar los factores de riesgo del primer ACV a nivel poblacional en Perú. MÉTODOS: El accidente cerebrovascular se definió utilizando un método estandarizado basado en la información de los participantes de la cohorte o de familiares. Esta información fue adjudicada centralmente por médicos entrenados usando definiciones estándar. El tiempo de seguimiento se calculó como la diferencia entre la fecha de enrolamiento y la fecha reportada del evento de ACV. Se calculó la tasa de incidencia del primer ACV no estandarizada y estandarizada por edad y los intervalos de confianza al 95% (IC 95%). Se utilizaron modelos lineales generalizados, asumiendo la distribución de Poisson y el link log, para determinar los factores potenciales para desarrollar un accidente cerebrovascular. RESULTADOS: 3.601 individuos se reclutaron originalmente en la cohorte y 2.471 proporcionaron datos para el análisis longitudinal. La mediana del tiempo de seguimiento fue de 7,0 (rango 1 - 9) años, haciendo un total de 17 308 personas-año. Durante el seguimiento, se produjeron 25 casos incidentes de ACV, lo que dio lugar a una incidencia estandarizada por edad de 98,8 (IC 95%: 63,8-154,0) por 100.000 personas-año. Tras el ajuste por edad y sexo, la incidencia de ACV fue mayor entre las personas con hipertensión (riesgo relativo (RR) = 5,18; IC 95%: 1,89 ­ 14,16), pero menor entre las que vivían a nivel de altura (RR = 0,09; 95% CI: 0,01 ­ 0,63). INTERPRETACIÓN: Los resultados indican una alta incidencia de ACV en la población general. Estos resultados son consistentes con las estimaciones encontradas en informes anteriores de PIBM. En consonancia con la literatura publicada, nuestro estudio también encontró un papel contribuyente de la hipertensión, aumentando el riesgo de tener un primer ACV. Nuestro estudio supone un avance en el campo de la epidemiología del ACV al identificar la altitud como un factor relacionado con una menor incidencia en un estudio longitudinal. Sin embargo, esta información debe de tomarse con precaución debido a las limitaciones del estudio.

20.
Trop Med Infect Dis ; 7(1)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35051124

RESUMO

Trypanosoma cruzi infection leads to Chagas disease (CD), a neglected tropical infection of significant public health importance in South and Central America and other, non-endemic, countries. Pregnant women and their children are of particular importance to screen as T. cruzi can be transmitted vertically. The objective of this study was to screen for T. cruzi infection among pregnant women from endemic areas seen at the Hospital General de Mexico for prenatal care, so that they and their children may be quickly connected to CD treatment. Pregnant women were recruited through the hospital prenatal clinic and screened for T. cruzi infection using a series of serological and molecular tests. Of 150 screened patients, mean age 26.8 (SD 6.4), 30 (20.0%) were positive by at least one diagnostic test. Of these, only nine (6%) were positive as determined by PCR. Diagnosis of chronic CD is difficult in endemic places like Mexico due to the limitations of current commercially available diagnostic tests. Further evaluation of diagnostic performance of various assays could improve current CD diagnostic algorithms and proper care management in these regions. Genetic variability in the parasite may also play a role in the differing assay performances seen in this study, and this may be a valuable avenue of further research.

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