Natural cytotoxicity receptor-dependent natural killer cytolytic activity directed at hepatitis C Virus (HCV) is associated with liver inflammation, African American race, IL28B genotype, and response to pegylated interferon/ribavirin therapy in chronic HCV infection.

BACKGROUND: Natural killer (NK) cells are implicated in the pathogenesis of hepatitis C virus (HCV) infection and outcome of interferon (IFN)-α based therapy, although mechanisms remain unclear. METHODS: To evaluate NK ability to control HCV infection, we analyzed healthy donor and HCV-infected donor NK-cell cytolytic activity directed at HCV-infected target cells. RESULTS: HCV-infected subjects' natural cytotoxicity receptor (NCR)-dependent NK-cell cytolytic activity directed at HCV-infected and uninfected Huh7.5 target cells was greater than that of cells from healthy donors, and this localized to the African American subset. However, IFN-α-enhanced NK cytolytic function was lower in HCV-infected subjects, again localized mainly to the African American subset. Additionally, whereas HCV-infected Huh7.5 cells were more readily targeted than uninfected cells, the selectivity of cytolytic activity for infected targets was lower during HCV infection and after IFN-α stimulation, and lower selectivity was in part attributable to greater NKp46 expression. Furthermore, cytolytic activity was associated with higher serum aspartate aminotransferase, rs12979860 IL28B genotype, and in vivo response to pegylated IFN/ribavirin therapy. CONCLUSIONS: These data indicate that during chronic HCV infection, race-associated increase in NCR expression and IL28B-associated cytolytic activity may participate in host response to IFN-α-containing HCV therapy.

Genetically associated CD16(+)56(-) natural killer cell interferon (IFN)-αR expression regulates signaling and is implicated in IFN-α-induced hepatitis C virus decline.

BACKGROUND: Natural killer (NK) cells likely contribute to outcome of acute hepatitis C virus (HCV) infection and interferon (IFN)-induced control of chronic HCV infection. We previously observed IFN-αR and NKp30 expression associated with IFN-α-dependent NK cell activity. METHODS: Here, we examined CD16(+)56(-), CD16(+)56(+), and CD16(-)56(+) NK cell subset IFN-αR and NKp30 expression in relation to magnitude of HCV genotype 1 decrease during pegylated IFN-α plus ribavirin therapy. RESULTS: We observed greater baseline IFN-αR and NKp30 expression on CD16(+)56(+) and CD16(-)56(+) NK subsets in HCV-infected patients than in healthy control subjects. Baseline CD16(+)56(-) NK IFN-αR expression was associated with IFN-α-induced pSTAT1, and both were associated with magnitude of HCV decrease during pegylated IFN-α plus ribavirin therapy. Baseline CD16(+)56(-) NK IFN-αR expression was associated with race and interleukin 28B genotype, negatively associated with aspartate aminotransferase-to platelet ratio index, and positively associated with increase in NKp30 expression after in vivo IFN-α exposure. Finally, in vitro IFN-α2a-activated NK cytolysis of HCV-infected target cells was in part dependent on NKp30, and CD16(+)56(-) NK cell IFN-αR expression correlated with cytolytic activity. CONCLUSIONS: IFN-αR expression on CD16(+)56(-) NK cells during chronic HCV infection may in part be genetically determined, and level of expression regulates IFN-α signaling, which in turn may contribute to control of HCV infection.

Baseline levels of soluble CD14 and CD16+56- natural killer cells are negatively associated with response to interferon/ribavirin therapy during HCV-HIV-1 coinfection.

Disease progression of human immunodeficiency virus type 1 (HIV-1) is associated with immune activation. Activation indices are higher during coinfection of hepatitis C virus (HCV) and HIV. The effect of immune activation on interferon α (IFN-α) therapy response is unknown. We evaluated soluble CD14 (sCD14) and natural killer (NK)-cell subsets at baseline, and during pegIFN-α2a/ribavirin therapy in HCV-HIV coinfection. The sCD14 level increased during therapy. Baseline sCD14 positively correlated with baseline HCV level and CD16(+)56(-) NK-cell frequency, and both sCD14 and CD16(+)56(-) NK cells correlated negatively with magnitude of HCV decline. IL28B genotype was associated with therapy response but not sCD14 or CD16(+)56(-) NK frequency. Markers of innate immune activation predict poor host response to IFN-α-based HCV therapy during HCV-HIV coinfection.

Deep learning for AI-based diagnosis of skin-related neglected tropical diseases: A pilot study.

BACKGROUND: Deep learning, which is a part of a broader concept of artificial intelligence (AI) and/or machine learning has achieved remarkable success in vision tasks. While there is growing interest in the use of this technology in diagnostic support for skin-related neglected tropical diseases (skin NTDs), there have been limited studies in this area and fewer focused on dark skin. In this study, we aimed to develop deep learning based AI models with clinical images we collected for five skin NTDs, namely, Buruli ulcer, leprosy, mycetoma, scabies, and yaws, to understand how diagnostic accuracy can or cannot be improved using different models and training patterns. METHODOLOGY: This study used photographs collected prospectively in Côte d'Ivoire and Ghana through our ongoing studies with use of digital health tools for clinical data documentation and for teledermatology. Our dataset included a total of 1,709 images from 506 patients. Two convolutional neural networks, ResNet-50 and VGG-16 models were adopted to examine the performance of different deep learning architectures and validate their feasibility in diagnosis of the targeted skin NTDs. PRINCIPAL FINDINGS: The two models were able to correctly predict over 70% of the diagnoses, and there was a consistent performance improvement with more training samples. The ResNet-50 model performed better than the VGG-16 model. A model trained with PCR confirmed cases of Buruli ulcer yielded 1-3% increase in prediction accuracy across all diseases, except, for mycetoma, over a model which training sets included unconfirmed cases. CONCLUSIONS: Our approach was to have the deep learning model distinguish between multiple pathologies simultaneously-which is close to real-world practice. The more images used for training, the more accurate the diagnosis became. The percentages of correct diagnosis increased with PCR-positive cases of Buruli ulcer. This demonstrated that it may be better to input images from the more accurately diagnosed cases in the training models also for achieving better accuracy in the generated AI models. However, the increase was marginal which may be an indication that the accuracy of clinical diagnosis alone is reliable to an extent for Buruli ulcer. Diagnostic tests also have their flaws, and they are not always reliable. One hope for AI is that it will objectively resolve this gap between diagnostic tests and clinical diagnoses with the addition of another tool. While there are still challenges to be overcome, there is a potential for AI to address the unmet needs where access to medical care is limited, like for those affected by skin NTDs.

An mHealth App (eSkinHealth) for Detecting and Managing Skin Diseases in Resource-Limited Settings: Mixed Methods Pilot Study.

BACKGROUND: In sub-Saharan Africa, the disease burden from skin diseases, including skin-related neglected tropical diseases (skin NTDs), is extremely high. These diseases often are overlooked due to limited access to health care stemming from, for example, remote geographical locations and a lack of experts. To address these gaps, we developed a mobile health app, eSkinHealth, which is a field-adapted platform to serve as a portable electronic patient chart and for teledermatology. OBJECTIVE: The purpose of the study is to evaluate the usability and effectiveness of the app in rural Côte d'Ivoire for diagnosing and managing skin NTDs and other skin diseases. METHODS: A 2-arm trial with local health care providers and patients with skin diseases was implemented over a 3-month period. The providers were assigned to an intervention receiving the eSkinHealth app or control with usual care. Four nurses and 8 community health care workers participated in each arm. The training was provided on the use of the app to the intervention arm only, while both arms were trained on skin diseases. For the usability study, we evaluated our approach with the System Usability Scale (SUS) and in-depth interviews. For the effectiveness study, our primary outcome was to evaluate the detection and management of 5 skin NTDs as our targeted diseases, namely, Buruli ulcer, leprosy, lymphatic filariasis, scabies, and yaws, using the eSkinHealth app. Procedures of our methods were reviewed and approved by the institutional review board of the Ministry of Health and by Tulane University. RESULTS: The mean age of our participants (providers) was 40.5 and 42.5 years for the intervention and control arms, respectively, and all were male (n=24). The average SUS scores taken from the intervention arm at baseline, the midpoint (6 weeks), and the end of study (12 weeks) were 72.3 (SD 11.5), 72.3 (SD 12.4), and 86.3 (SD 10.8), respectively. All participants interviewed, including 4 dermatologists and program managers, were satisfied with the app. Especially community health care workers felt empowered by being equipped with the tool. A total of 79 cases of skin NTDs were reported in the intervention arm as compared to 17 cases in the control arm (P=.002). Besides the skin NTDs, more skin diseases and conditions were reported from the control than from the intervention arm (P<.001). However, 100 cases (66%) were not given any particular diagnosis in the control arm and were documented only as a "dermatosis." In the intervention arm, 151 cases (72.9%) were diagnosed within the eSkinHealth platform, and the remaining were diagnosed on-site by dermatologists. CONCLUSIONS: The study provided evidence for the usability and effectiveness of the eSkinHealth app embedded into our surveillance approach to improve the detection and management of skin NTDs and other skin diseases in Côte d'Ivoire and, furthermore, is expected to contribute to knowledge on mobile health approaches in the control of skin diseases in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05300399; https://clinicaltrials.gov/ct2/show/NCT05300399.

Three-dimensional structure of a schistosome serpin revealing an unusual configuration of the helical subdomain.

Parasitic organisms are constantly challenged by the defence mechanisms of their respective hosts, which often depend on serine protease activities. Consequently, protease inhibitors such as those belonging to the serpin superfamily have emerged as protective elements that support the survival of the parasites. This report describes the crystal structure of ShSPI, a serpin from the trematode Schistosoma haematobium. The protein is exposed on the surface of invading cercaria as well as of adult worms, suggesting its involvement in the parasite-host interaction. While generally conforming to the well established serpin fold, the structure reveals several distinctive features, mostly concerning the helical subdomain of the protein. It is proposed that these peculiarities are related to the unique biological properties of a small serpin subfamily which is conserved among pathogenic schistosomes.

The Early Detection and Case Management of Skin Diseases With an mHealth App (eSkinHealth): Protocol for a Mixed Methods Pilot Study in Côte d'Ivoire.

BACKGROUND: There is a high prevalence of skin diseases sub-Saharan Africa, including skin neglected tropical diseases (NTDs) that could lead to lifelong disabilities and deformities if not diagnosed and treated early. To achieve early detection and early treatment of these skin diseases, we developed a mobile health app, eSkinHealth. OBJECTIVE: This paper outlines a protocol for evaluating the effect of our eSkinHealth app in the early detection and effective management of skin diseases in Côte d'Ivoire. METHODS: A mixed methods pilot trial will be conducted in Côte d'Ivoire and will consist of 3 phases: (1) the development and improvement of the eSkinHealth app, (2) a pilot trial to evaluate the usability of the eSkinHealth app for local medical staff in Côte d'Ivoire, and (3) a pilot trial to evaluate the effectiveness of early detection and case management of targeted skin NTDs (Buruli ulcer, leprosy, yaws, and lymphatic filariasis) with the eSkinHealth app in Côte d'Ivoire. The pilot study will be implemented as a 2-arm trial with local health care providers and patients with skin NTDs over a 3-month follow-up period. The local health care providers will be assigned to an intervention group receiving the eSkinHealth app to be used in their daily practices or a control group. Training will be provided on the use and implementation of the app and the diagnostic pipeline to the intervention group only, while both groups will receive training on skin diseases. Our primary outcome is to evaluate the early detection and effective management of skin diseases using the eSkinHealth app in Côte d'Ivoire by the number of cases diagnosed and managed. Additionally, we will evaluate the eSkinHealth app with validated questionnaires and in-depth interviews. Procedures of our methods have been reviewed and approved by the Institutional Review Board of the Ministry of Health, Côte d'Ivoire and by Tulane University in 2021. RESULTS: This study was funded in 2021. We started the enrollment of patients in February 2022, and data collection is currently underway. We expect the first results to be submitted for publication in 2023. CONCLUSIONS: Our eSkinHealth app is a field-adapted platform that could provide both direct diagnostic and management assistance to health workers in remote settings. The study will provide evidence for the usability and the effectiveness of the eSkinHealth app to improve the early detection and case management of skin NTDs in Côte d'Ivoire and, furthermore, is expected to contribute to knowledge on mobile health approaches in the control of skin NTDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05300399; https://clinicaltrials.gov/ct2/show/study/NCT05300399. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39867.

Cryptic population structure and transmission dynamics uncovered for Schistosoma mansoni populations by genetic analyses.

Patterns of diversity in pathogen genomes provide a window into the spatiotemporal spread of disease. In this study, we tested the hypothesis that Schistosoma mansoni parasites form genetic clusters that coincide with the communities of their human hosts. We also looked for genetic clustering of parasites at the sub-community level. Our data consists of 14 microsatellite DNA markers, typed from pooled DNA samples from [Formula: see text] infected individuals living in three Brazilian communities. We found a one-to-one correspondence between genetic clusters found by K-means cluster analysis and communities when [Formula: see text]. These clusters are also easily identified in a neighbor-joining tree and principal coordinates plots. K-means analysis with [Formula: see text] also reveals genetic clusters of parasites at the sub-community level. These sub-clusters also appear on the neighbor-joining tree and principal coordinates plots. A surprising finding is a genetic relationship between subgroups in widely separated human communities. This connection suggests the existence of common transmission sites that have wide influence. In summary, the genetic structure of S. mansoni in Brazil juxtaposes local isolation that is occasionally broken by long-range migration. Permanent eradication of schistosomes will require both local efforts and the identification of regional infection reservoirs.

Evidence for local transmission and maintenance of schistosomiasis in an urban neighbourhood in Northeast Brazil.

Schistosomiasis is a tropical neglected disease commonly associated with rural areas; however, urban schistosomiasis has been reported worldwide, and increasing urbanization is one of the most important demographic shifts of the 20th and now 21st centuries. The pattern of urbanization is not uniform so that within the same city the rates and sources of population increase vary. Here, we report on the parasite composition in one neighbourhood in the metropolitan area of Salvador, Bahia, Brazil. Using epidemiological data and population genetics, we find evidence for local transmission and maintenance of Schistosoma mansoni infection within an urban population and little contribution from rural-urban migration. Our findings provide direction for local mitigation strategies and to assist the public living in this neighbourhood to interrupt the local transmission cycle.

A Schistosoma mansoni tri- and tetramer microsatellite catalog for genetic population diversity and differentiation.

All Schistosoma mansoni tri- and tetranucleotide repeat microsatellites published as of December 2018 were identified. All 52 were evaluated for autosomal location, strength of amplification, scorability and behavior as single-copy loci by polyacrylamide and capillary gel electrophoresis. Of these, 27 were unique, autosomal, polymorphic, easily scored and single copy as assessed on pooled adult worm DNA from two different continental origins and adult worm clones. These microsatellites were distributed across all seven autosomal chromosomes. On laboratory strains their heterozygosity ranged from 0.22 to 0.77. Individual markers had 5-13 alleles, allelic richness of 2-10 and an effective allele number of 1.3-8.14. Those infected by Schistosoma mansoni carry many genetically distinct, sexually reproducing parasites, therefore, for an individual infection the complete allele frequency profile of their progeny consists of a pool of DNA from multiple diploid eggs. Using a set of 25 microsatellites, we calculated allele frequency profiles of eggs in fecal samples from people in two Brazilian communities separated by 6 km: Jenipapo (n = 80) and Volta do Rio (n = 38). There were no a priori characteristics that could predict the performance of markers in natural infections based on their performance with laboratory strains. Increasing marker number did not change accuracy for differentiation and diversity but did improve precision. Our data suggest that using a random set of 10-20 microsatellites appears to result in values that exhibit low standard deviations for diversity and differentiation indices. All identified microsatellites as well as PCR conditions, allele size, primer sequences and references for all tri- and tetramer microsatellites markers presented in this work are available at: https://sites.google.com/case.edu/cwru-and-fiocruz-wdrc/home.

The changing profile of schistosomiasis in a changing urban landscape.

Since 2007, most of humanity resides in urban areas, a trend which continues worldwide. Diseases usually associated with rural contexts are now emerging or newly recognised in cities. In the neighbourhood of São Bartolomeu in Salvador, Brazil, the prevalence of Schistosoma mansoni infection in 2011 was >20%. Following enrollment and treatment of a portion of the community, ~25% of the area underwent urban renewal. In 2015, we returned to enrol individuals who had previously participated and a cohort that had not taken part in 2011. Thus, infected individuals in one group experienced specific drug treatment plus improved living conditions and the second group only improved living conditions. Between 2011 and 2015 there were no organised treatment programs, but adequate sanitation increased from 69% to 92% coverage, household flooding decreased, and the presence of indoor toilets increased to 99% of households. Ownership of household appliances also increased significantly. The overall prevalence of schistosome infections was 6.2%. In 2015, the cohort first seen in 2011 had a higher prevalence (8.7%) than those first seen in 2015 (4.8%) and showed a few demographic differences. The 2011 cohort was older, more likely born in Salvador, less likely to have lived outside of Salvador, spent a greater percentage of their lifetime in Salvador, but more likely to have travelled. The population structure of the parasites from both cohorts underwent a marked change with similar increased component and infrapopulation differentiation and >10 fold decrease in effective population size. There was a 4-5 year shift in age-specific prevalence in 2015 for all compared with 2011. While praziquantel may have helped reduce prevalence, our evidence suggests that the structural changes and improvements in living conditions had the biggest impact on schistosomiasis in this community.

Population Structure and Dynamics of Helminthic Infection: Schistosomiasis.

While disease and outbreaks are mainly clonal for bacteria and other asexually reproducing organisms, sexual reproduction in schistosomes and other helminths usually results in unique individuals. For sexually reproducing organisms, the traits conserved in clones will instead be conserved in the group of organisms that tends to breed together, the population. While the same tools are applied to characterize DNA, how results are interpreted can be quite different at times (see another article in this collection, http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.AME-0002-2018). It is difficult to know what the real effect any control program has on the parasite population without assessing the health of this population, how they respond to the control measure, and how they recover, if they do. This review, part of the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases, concentrates on one approach using pooled samples to study schistosome populations and shows how this and other approaches have contributed to our understanding of this parasite family's biology and epidemiology. *This article is part of a curated collection.

Antibiotic Resistance in Enterobacteriaceae from Surface Waters in Urban Brazil Highlights the Risks of Poor Sanitation.

Surface waters are an unappreciated reservoir of antimicrobial resistance (AMR). Poor sanitation brings different species of environmental bacteria into contact, facilitating horizontal gene transfer. To investigate the role of surface waters as potential reservoirs of AMR, we studied the point prevalence of fecal contamination, AMR genes, and Enterobacteriaceae in an urban lake and rural river system in Northeast Brazil in comparison with a lake and sewer system in Northeast Ohio in the United States. Surface water samples were examined for evidence of human fecal contamination using microbial source tracking and screened for plasmid-mediated fluoroquinolone resistance and carbapenemase genes. Enterobacteriaceae were detected using selective agar followed by antimicrobial susceptibility testing and detection of AMR genes by microarray, and classified by repetitive sequence-based polymerase chain reaction and multilocus sequence typing. Concentrations of human fecal bacteria in the Brazilian urban lake and sewage in Northeast Ohio were similarly high. Filtered water samples from the Brazilian urban lake, however, showed the presence of bla OXA-48, bla KPC, bla VIM-2, qnrS, and aac(6')-lb-cr, whereas only bla VIM-2 was identified in raw sewage from Northeast Ohio. From the Brazilian urban lake, 85% of the Enterobacteriaceae (n = 40) cultured were resistant to at least one clinically important antibiotic, including ST131 Escherichia coli harboring the extended-spectrum beta-lactamase CTX-M. Although two isolates demonstrated polymyxin resistance, mcr-1/2 was not detected. Our findings indicate that surface waters in an urban Brazilian site can serve as an environmental reservoir of AMR and that improving wastewater treatment and sanitation generally may ameliorate AMR dissemination.

Genetic ancestry and income are associated with dengue hemorrhagic fever in a highly admixed population.

To test whether African ancestry is protective for severe dengue, we genotyped 49 hospitalized cases of dengue hemorrhagic fever (DHF) as well as 293 neighborhood cases of dengue fever and 294 asymptomatic controls in Salvador, Bahia, Brazil. Ancestry-informative markers and 282 unlinked SNPs not associated with the clinical presentation of dengue were used to estimate ancestry. After controlling for income, both self-defined Afro-Brazilian ethnicity and African ancestry were protective for DHF (P=0.02, OR=0.28 and P=0.02, OR=0.13, respectively). Income or an index of income indicators, however, was also independently associated with the diagnosis of DHF.

Population Genetics and Molecular Epidemiology of Eukaryotes.

Molecular epidemiology uses the distribution and organization of a pathogen's DNA to understand the distribution and determinants of disease. Since the biology of DNA for eukaryotic pathogens differs substantially from that of bacteria, the analytic approach to their molecular epidemiology can also differ. While many of the genotyping techniques presented earlier in this series, "Advances in Molecular Epidemiology of Infectious Diseases," can be applied to eukaryotes, the output must be interpreted in the light of how DNA is distributed from one generation to the next. In some cases, parasite populations can be evaluated in ways reminiscent of bacteria. They differ, however, when analyzed as sexually reproducing organisms, where all individuals are unique but the genetic composition of the population does not change unless a limited set of events occurs. It is these events (migration, mutation, nonrandom mating, selection, and genetic drift) that are of interest. At a given time, not all of them are likely to be equally important, so the list can easily be narrowed down to understand the driving forces behind the population as it is now and even what it will look like in the future. The main population characteristics measured to assess these events are differentiation and diversity, interpreted in the light of what is known about the population from observation. The population genetics of eukaryotes is important for planning and evaluation of control measures, surveillance, outbreak investigation, and monitoring of the development and spread of drug resistance. *This article is part of a curated collection.

Advances in Molecular Epidemiology of Infectious Diseases: Definitions, Approaches, and Scope of the Field.

Molecular epidemiology is a discipline that uses molecular microbiology tools to study the distribution and determinants of diseases in human populations and veterinary animals. Our understanding of epidemiology of infectious diseases has evolved with technological advancements made in molecular biology that refine our perception of the identity and dynamics of microorganisms. This review is an introduction to the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases that will discuss how these advancements have contributed to investigations of infectious disease outbreaks/epidemics, surveillance, transmission dynamics, risk factor identification, pathogenesis, and etiologic attribution of bacterial, viral, protozoan, and helminthic pathogens to a disease. Here we define "molecular epidemiology" and distinguish it from other disciplines that use many of the same molecular biology tools-taxonomy, phylogenetics, and molecular evolution of microorganisms. The Curated Collection will be spread throughout multiple issues of Microbiology Spectrum and will be divided into four general sections: (i) laboratory methods used to strain type microbial pathogens, (ii) methods used to analyze genotyping data, (iii) examples of molecular epidemiologic investigations of bacterial, viral, and parasitic diseases, and (iv) applications of molecular epidemiology to address new research questions in communicable and noncommunicable diseases. The major theme of this Curated Collection is to address the following question frequently asked by clinicians, clinical microbiologists, and public health professionals: what is the advantage or unique contribution of molecular epidemiology in solving infectious disease problems in the clinical and public health arenas? *This article is part of a curated collection.

The effect of sample size on estimates of genetic differentiation and effective population size for Schistosoma mansoni populations.

Eradication or local extinction of the human parasite Schistosoma mansoni is a goal for many control programs. Population genetic analyses are helping to evaluate and guide these efforts, yet what to sample, how to sample and how densely to sample is not well established. We determined the S. mansoni allele frequency profile of nearly all infected inhabitants in two small Brazilian communities and created sub-samples representing 5-50% of all detected human infections (infrapopulations). Samples were selected at random with replacement, and each size class was replicated 100 times. Mean pairwise differentiation for all infrapopulations (Di) and the variance effective population size (Ne) were calculated for each sample. Prior to community-wide treatment, the true mean Di was moderate (0.095-0.123) and Ne large (>30,000). Most samples of <50% of those infected produced estimates outside of 5% of the true value. For estimates within 10%, sample sizes of >15% of all infrapopulations were required. At the 3 year follow-up after treatment, the Di increased and Ne was reduced by >15 fold. At this time sampling of >30-45% was needed to achieve the same accuracy. Following a second treatment and 4 years from baseline, the Di further increased and Ne decreased with little change in the sampling effort required. Extensive sampling is required for accurate estimates of these important population parameters. Characteristics such as population census size, infection prevalence, the community's treatment history and the degree of infrapopulation differentiation should be taken into account. The intensity of infection was weakly correlated with the ability of a single infrapopulation to represent the component population (Dic), indicating a tendency toward random acquisition of parasite genotypes. This also suggests that targeted sampling from those most heavily infected will better represent the genetic diversity of the whole community than a random sample of infrapopulations.

Food Consumption as a Modifier of the Association between LEPR Gene Variants and Excess Body Weight in Children and Adolescents: A Study of the SCAALA Cohort.

No studies showing that food consumption is a modifier of the association of variants of the leptin receptor gene (LEPR) with body weight have involved a Brazilian population. The aim of this study was to evaluate the modifying effect of dietary intake on the association between the LEPR gene and excess weight. In this study, 1211 children and adolescents aged 4⁻11 years were assessed. Participants were genotyped for 112 single-nucleotide variants of the LEPR gene. Anthropometric measurements were performed, and dietary data were obtained. Logistic regressions were used to study the associations of interest. Of the participants, 13.4% were overweight/obese. The risk allele (G) of the rs1137100 variant was associated with excess weight in individuals with fat consumption below the median (odds ratio OR = 1.92; 95% confidence interval CI = 1.18⁻3.14), with daily frequency of consumption of drink/artificial juice (OR = 2.15; 95% CI = 1.26⁻3.68) and refined cereals (OR = 2.17; 95% CI = 1.31⁻3.62) above the median. The risk allele (G) of variant rs1177681 was also associated with excess weight (OR = 2.74; 95% CI = 1.65⁻4.57) in subjects with a daily frequency of refined cereal consumption above the median. The association between LEPR and excess weight can be modulated by the type and distribution of dietary fatty acids, sugary drinks, and refined cereals.

The relative influence of polyparasitism, environment, and host factors on schistosome infection.

Where prevalence of geohelminths and schistosomes is high, co-infections with multiple parasite species are common. Previous studies have shown that the presence of geohelminths either promotes or is a marker for greater prevalence and intensity of Schistosoma mansoni infections. Some of this apparent synergy may simply represent shared conditions for exposure, such as poor sanitation, and may not suggest a direct biologic interaction. We explored this question in a study of 13,279 school children in Jequié, Bahia, Brazil, with a survey of demographic characteristics and stool examinations. Cross-sectional analysis revealed a statistically significant increase in the prevalence and intensity of S. mansoni infection with increasing numbers of geohelminth species (OR 2.5, 95% CI 1.38-3.64). Less than 20% of the strength of this association was contributed by socioeconomic status or environmental conditions. Thus, polyparasitism itself, as well as intrinsic host factors, appears to produce greater susceptibility to additional helminth infections.