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Background Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment. Methodology/Principal findings We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People’s Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites. Conclusions/Significance We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB. Trial registration The study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018., Author summary More than 500 million children worldwide receive a single oral dose of albendazole or mebendazole annually to reduce disease caused by intestinal worms (roundworm, whipworm and hookworm). However, it is unclear whether individuals respond differently to treatment. We re-analyzed 645 individual patient data from three standardized clinical trials with albendazole using a statistical method and explored how drug responses among individuals from study sites with different prior rounds of drug distribution. We found that individuals’ responses were worse when drug pressure and infection intensity were greater. Individual age and sex also affected the response, but these were often of negligible clinical significance and not consistent across worm species and study sites. We confirmed that albendazole is ineffective against whipworm on Pemba Island, but given the high intensity of infection at this study side, it remains unclear whether this treatment failure is explained by high drug pressure (and emerging anthelmintic resistance) or high infection intensity. Nevertheless, our results indicate that alternative treatment regimens are required to control intestinal worms in Pemba Island.

To estimate the prevalence of high cardiovascular risk (CVR), the proportion of people with high CVR who receive treatment and counseling, and to investigate the sociodemographic factors associated with this outcome, in Brazil.This was a cross-sectional study, using subsample data from the National Health Survey, collected via biochemical tests, in 2014-2015. Poisson regression was used.The proportion of high CVR in men was 11.2% (95%CI 9.6;12.9), and 10.4% (95%CI 9.2;11.8%) in women. In the group with high CVR, 68.8% (95%CI 63.7;73.4%) received counseling, 59.3% (95%CI 54.2;64.3%) received medication, and 55.6% (95%CI 50.4;60.7%) received both. In the multivariate analysis, receiving treatment and counseling was associated with being aged 50 years and over, and poor/very poor self-rated health (PR=1.26 - 95%CI 1.06;1.51).The proportion of people with high CVR who had received treatment and counseling was over 50%.Estimar a prevalência de risco cardiovascular (RCV) elevado, a proporção de pessoas com RCV elevado que recebem tratamento e aconselhamento, e investigar os fatores sociodemográficos associados ao desfecho, no Brasil.Estudo transversal, com dados de subamostra da Pesquisa Nacional de Saúde, coletados por exames bioquímicos, em 2014-2015. Empregou-se regressão de Poisson.A proporção de RCV elevado em homens foi de 11,2% (IC95% 9,6;12,9), e em mulheres, de 10,4% (IC95% 9,2;11,8%). No grupo com RCV elevado, 68,8% (IC95% 63,7;73,4%) receberam aconselhamento; 59,3% (IC95% 54,2;64,3%), medicamento; e 55,6% (IC95% 50,4;60,7%), ambos. Na análise multivariável, receber tratamento e aconselhamento mostrou associação com a idade de 50 anos e mais, e com autoavaliação de saúde ruim/muito ruim (RP=1,26 - IC95% 1,06;1,51).A proporção de pessoas com RCV elevado que receberam tratamento e aconselhamento foi superior a 50%.Estimar la prevalência de riesgo cardiovascular (RCV) elevado, la proporción de personas con RCV elevado que reciben tratamiento y asesoramiento, e investigar los factores sociodemográficos asociados al resultado, en Brasil.Estudio transversal, con datos de la submuestra de la Investigación Nacional de Salud, recolectados por exámenes bioquímicos, en 2014-2015. Se usó la regresión de Poisson.La proporción de RCV elevado en hombres fue del 11,2% (IC95% 9,6; 12,9) y en mujeres del 10,4% (IC95% 9,2;11,8%). En el grupo con RCV elevado, 68,8% (IC95% 63,7; 73,4%) recibió asesoramiento, 59,3% (IC95% 54,2;64,3%) medicamento y 55,6% (IC95% 50,4;60,7%) ambos. En el análisis multivariable, recebir tratamiento y asesoramiento se mostró asociado a la edad de 50 años y más, y a autoevaluación de salud mala/muy mala (RP=1,26 - IC95% 1,06;1,51).La proporción de personas con RCV elevado que recibió tratamiento y asesoramiento fue superior a 50%.

Objective To evaluate the effectiveness of two teaching strategies, both guided by the concept of dialogicity, on adolescents’ knowledge about schistosomiasis and adherence to diagnostic fecal testing. Methods Two teaching strategies related to schistosomiasis were developed, an educational video and group conversation, which were tested in two groups of students aged 10–15 years old. Before and after the intervention, a questionnaire was applied to assess participants' knowledge about schistosomiasis and, after the intervention, two fecal samples were requested from each participant. Comparisons were performed by paired t- and McNemar tests. Results Both strategies resulted in statistically significant improvements in knowledge between the pre- and post-tests. Students who watched the video had a higher return rate of fecal samples and percentage of correct questionnaire answers, mainly on questions about schistosomiasis infection. Conclusion Teaching strategies based on dialogue favored the construction of concepts about schistosomiasis that can influence the adoption of positives attitudes related to health. Practical implications Using teaching strategies based on the concept of dialogicity can favor the increase of knowledge of school age children about schistosomiasis and can influence behavioral change related to health.

to evaluate anthropometric and demographic indicators associated with high blood pressure in children aged 6 to 10 years in urban and rural areas of Minas Gerais.this is a cross-sectional study with 335 children. Anthropometric, demographic and blood pressure data were collected. The statistics analyzes were performed using the chi-square, t-student, Mann-Whitney and logistic regression tests, and the odds ratio was the association measure.the prevalence of high blood pressure was significantly higher among rural children. In the urban area, the chance of high blood pressure was higher in children who had a high body mass index (2.97 [1.13-7.67]) and in the rural area, in those who had increased waist circumference (35.4 [3.0-406.2]) and the age range of 9-10 years (4.29 [1.46-12.6]).elevated body mass index and waist circumference were important anthropometric indicators for high blood pressure, as well as age in children living in rural area. The evaluation of body mass index and waist circumference, in addition to nutritional assessments, represents an important action for the screening of high blood pressure in children from different territorial contexts.avaliar indicadores antropométricos e demográficos associados à pressão arterial elevada em crianças de 6 a 10 anos de idade de áreas urbana e rural de Minas Gerais.estudo transversal realizado com 335 crianças. Foram coletados dados antropométricos, demográficos e de pressão arterial. As análises foram realizadas por meio dos testes Qui-quadrado, t student, Mann-Whitney e regressão logística, com cálculo do odds ratio como medida de associação.a prevalência de pressão arterial elevada foi significativamente maior entre as crianças da área rural. Na área urbana, a chance de pressão arterial elevada foi maior nas crianças que possuíam o índice de massa corporal elevado (2,97 [1,13-7,67]) e, na área rural, naquelas que possuíam a circunferência da cintura aumentada (35,4 [3,0-406,2]) e faixa etária de 9-10 anos (4,29 [1,46-12,6]).o índice de massa corporal e a circunferência da cintura elevados foram importantes indicadores antropométricos para a pressão arterial elevada, assim como a idade em crianças residentes na área rural. A avaliação do índice de massa corporal e da circunferência da cintura, para além das avaliações nutricionais, representa importante ação para o rastreio de pressão arterial elevada em crianças de diferentes contextos territoriais.evaluar los indicadores antropométricos y demográficos asociados a la presión arterial elevada de niños entre 6 y 10 años de edad en zonas urbana y rurale de Minas Gerais.se trata de un estudio transversal realizado entre 335 niños. Se recopilaron datos antropométricos, demográficos y de presión arterial. Los análisis se realizaron con las pruebas de Chi-cuadrado, t de Student, Mann-Whitney y regresión logística, considerando el odds ratio como medida de asociación.la prevalencia de la presión arterial elevada era significativamente más alta entre los niños de las zonas rurales. En la zona urbana, la probabilidad era mayor en los niños con índice alto de masa corporal [2,97(1,13-7,67)] y en la zona rural, en los que tenían más perímetro de cintura [35,4(3,0-406,2)] y grupo de edad de 9-10 años [4,29(1,46-12,6)].el índice de masa corporal y la circunferencia de la cintura altos fueron indicadores antropométricos importantes para la presión arterial elevada, así como la edad en niños residentes de la zona rural. La evaluación del índice de masa corporal y del perímetro de la cintura, además de las evaluaciones nutricionales, son factores importantes para el sondeo de la hipertensión arterial en niños de diferentes contextos territoriales.

Praziquantel (PZQ) is an effective chemotherapy for schistosomiasis mansoni and a mainstay for its control and potential elimination. However, it does not prevent against reinfection, which can occur rapidly in areas with active transmission. A guide to ranking the risk factors for Schistosoma mansoni reinfection would greatly contribute to prioritizing resources and focusing prevention and control measures to prevent rapid reinfection. The objective of the current study was to explore the relationship among the socioeconomic, demographic, and epidemiological factors that can influence reinfection by S. mansoni one year after successful treatment with PZQ in school-aged children in Northeastern Minas Gerais state Brazil. Parasitological, socioeconomic, demographic, and water contact information were surveyed in 506 S. mansoni-infected individuals, aged 6 to 15 years, resident in these endemic areas. Eligible individuals were treated with PZQ until they were determined to be negative by the absence of S. mansoni eggs in the feces on two consecutive days of Kato-Katz fecal thick smear. These individuals were surveyed again 12 months from the date of successful treatment with PZQ. A classification and regression tree modeling (CART) was then used to explore the relationship between socioeconomic, demographic, and epidemiological variables and their reinfection status. The most important risk factor identified for S. mansoni reinfection was their “heavy” infection at baseline. Additional analyses, excluding heavy infection status, showed that lower socioeconomic status and a lower level of education of the household head were also most important risk factors for S. mansoni reinfection. Our results provide an important contribution toward the control and possible elimination of schistosomiasis by identifying three major risk factors that can be used for targeted treatment and monitoring of reinfection. We suggest that control measures that target heavily infected children in the most economically disadvantaged households would be most beneficial to maintain the success of mass chemotherapy campaigns.

Background Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. Methods An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. Principal findings and conclusions The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance. Trial registration ClinicalTrials.gov NCT03465488., Author summary During the last decade, the scale of deworming programs that aim to eliminate the morbidity caused by intestinal worms has increased to a level that is unprecedented in history. It is therefore of utmost importance to monitor any change in therapeutic efficacy that may arise from emerging drug resistance. Currently, a variety of novel methods have been described, but it remains unclear whether they can be used for monitoring drug efficacy. We applied different diagnostic methods to measure the efficacy of a commonly administered drug in deworming programs in 3 countries with different historical exposure to deworming programs. Compared to the standard diagnostic method, all diagnostic methods revealed good agreement in classifying the therapeutic efficacy according to World Health Organization guidelines, despite clear differences in diagnostic performance. We also noticed that the drug efficacy was lower in countries where drug pressure has been high. However, more research is necessary to identify factors that explain this variation in drug efficacy, including but not limited to the frequency in mutations in genes that are known to be linked with anthelmintic resistance.

Background Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs). Methodology We compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs. Principal findings All diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration. Conclusions/Significance Our results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program. Trial registration ClinicalTrials.gov NCT03465488, Author summary To control the burden caused by intestinal worms, the World Health Organization recommends large-scale deworming programs where anti-worm drugs are administered to at-risk populations. The decision to scale down drug distribution is based on the periodically assessment of prevalence and intensity of infections using a standard diagnostic method. Today, the scientific community strongly doubts whether this method can be used throughout the program. This is in particular when it fails to detect infections of low intensity, and hence may result in prematurely stopping the distribution of drugs. We compared the diagnostic performance of alternative diagnostic methods in three drug efficacy trials in two African and one Asian country. The diagnostic methods were based on demonstration of worm eggs or worm DNA in stool. We also checked the results with minimal diagnostic criteria which have been recently been proposed by the scientific community. Our results indicate that of all diagnostic methods based on demonstration of worm eggs, only the current standard method fulfills the diagnostic criteria for planning, monitoring and evaluation phases of deworming program. Furthermore, we showed that DNA-based methods could be considered in the phase that aims to seek confirmation for cessation of the deworming program.

Background Immunoepidemiologic studies have shown a relationship between IgE and IgG4 antibodies with age and with resistance and susceptibility to infection. It is believed that the IgE and IgG4 responses to soluble egg antigen (SEA) can be used for serological analysis of infection and post-treatment status. This study aimed to evaluate the association between Schistosoma mansoni infection and anti-SEA IgG4 and IgE reactivities, and determine whether these reactivities could be used as biomarkers of infection. Methods Between 2001 and 2009, a longitudinal study was performed in which parasitologic and blood specimens and socioeconomic and water-contact information were collected from 127 individuals. All patients positive for S. mansoni infection were treated. Results Schistosomiasis prevalence and the geometric mean of the egg count in 2001 were 59% and 61.05, respectively, decreasing to 26.8% and 8.78 in 2009. IgG4 anti-SEA reactivity in infected individuals was significantly higher than that in uninfected individuals at all time points. Analysis of receiver-operating characteristic (ROC) area showed that the IgG4 anti-SEA antibodies were able to predict infection by S. mansoni at each time point. Conclusion IgG4 anti-SEA reactivity can be used as a biomarker for immune monitoring of the presence of infection with S. mansoni in endemic areas.

The objective of the present paper was to compare accessibility and utilisation of schistosomiasis diagnostic and treatment services in a small village and the surrounding rural area in northern part of the state of Minas Gerais Brazil. The study included 1,228 individuals: 935 central village residents and 293 rural residents of Sao Pedro do Jequitinhonha. Schistosoma mansoni infection rates were significantly higher in the central village than in the rural area during a survey in 2007 (44.3% and 23.5%, respectively) and during the 2002 schistosomiasis case-finding campaign (33.1% and 26.5%, respectively) (p < 0.001). However, during the 2002-2006 period, only 23.7% of the villagers and 27% of the rural residents obtained tests on their own from health centres, hospitals and private clinics in various nearby towns. In 2007, 63% of the villagers and 70.5% of the rural residents reported never having received treatment for schistosomiasis. This paper reveals considerable variation in the accessibility and utilisation of schistosomiasis-related health services between the central village and the rural area. A combination of low utilisation rates between 2002-2006 and persistently high S. mansoni infection rates suggest that the schistosomiasis control program must be more rapidly incorporated into the primary health services.

We have been investigating whether human eosinophils play an important role in schistosomiasis mansoni morbidity. Our main focus has been on the activation-related cell surface markers (CD23/CD69/CD25/HLA-DR/CD28/CD80) and the detection of TNF-alpha, IL-4 and IL-5 in peripheral blood eosinophils from chronic Schistosoma mansoni-infected patients. Our studies compare both, intestinal (INT) and individuals with periportal fibrosis (FIB). Our major findings, point to distinct profile of activation-related surface markers on eosinophils as the hallmark of disease morbidity during chronic S. mansoni infection. Up-regulation of several activation-related markers was observed on eosinophils from FIB group, but not INT, which include early activation markers, such as CD69 and CD23. INT displayed a distinct profile, with up-regulation of molecules related to the late activation (CD25, HLA-DR, CD28 and CD80). These results suggest that some immunoregulatory events may take place controlling the early eosinophil activation in the INT group. Higher levels of eosinophil-derived cytokines were observed in FIB, regardless the antigen stimulation in vitro. A mixed cytokine pattern, characterized by positive correlation between TNF-alpha, IL-4 and IL-5 was observed in both INT and FIB. However, lack of correlation between the cytokine expression and the eosinophil activation status points out that even those FIB patients presenting minor increment on eosinophil activation displayed higher levels of cytokine-positive eosinophils. Indeed, the positive association between lymphocyte-derived IL-10 and the eosinophils cytokine profile was observed exclusively in INT further emphasize our hypothesis that immunoregulatory events take place controlling disease morbidity in human schistosomiasis. The impaired IL-10-driven immunoregulatory function may play an important role on the establishment of pathology in patients bearing periportal fibrosis.

Background Obtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research. Methodology/Principal Findings An informational video was produced to explain the work of the research team and the first planned hookworm vaccine trial, using a pedagogical method based on analogies. Seventy-two adults living in a rural community of Minas Gerais were administered a structured questionnaire that assessed their knowledge of hookworm, of research and of the planned hookworm vaccine trial, as well as their attitudes and perceptions about the researchers and participation in future vaccine trials. The questionnaire was administered before being shown the educational video and two months after and the results compared. After viewing the video, significant improvements in knowledge related to hookworm infection and its health impact were observed: using a composite score combining related questions for which correct answers were assigned a value of 1 and incorrect answers a value of 0, participants had a mean score of 0.76 post-video compared to 0.68 pre-video (p = 0.0001). Similar improvements were seen in understanding the purpose of vaccination and the possible adverse effects of an experimental vaccine. Although 100% of participants expressed a positive opinion of the researchers even before viewing the film and over 90% said that they would participate in a hookworm vaccine trial, an increase in the number who expressed fear of being vaccinated with a novel vaccine was seen after viewing the video (51.4% post-video versus 29.2% pre-video). Increases were also seen in the proportion who thought that participation in a vaccine trial would be inconvenient or disrupt their daily activities. Conclusions/Significance Even in rural, resource-limited populations, educational tools can be specially designed that significantly improve understanding and therefore the likelihood of obtaining truly informed consent for participation in clinical research. The observed changes in the knowledge and perceptions of the research participants about hookworm infection and the experimental hookworm vaccine demonstrate that the video intervention was successful in increasing understanding and that the subjects acquired knowledge pertinent to the planned research., Author Summary Conducting clinical trials of new vaccines in rural, resource-limited areas can be challenging since the people living in these areas often have high levels of illiteracy, little experience with clinical research, and limited access to routine health care. Especially difficult is obtaining informed consent for participation in this type of research and ensuring that potential participants adequately understand the potential risks and benefits of participation. The researchers have been preparing a remote field site in the northeastern part of the state of Minas Gerais, Brazil, for clinical trials of experimental hookworm vaccines. A special educational video was designed based on the method of analogies to introduce new scientific concepts related to the researchers' work and to improve knowledge of hookworm, a disease that is highly prevalent in their community. A questionnaire was administered both before and after the video was shown to a group of adults at the field site, which demonstrated the effectiveness of the video in disseminating knowledge about hookworm infection and about the vaccine being developed. Therefore, even in a rural, resource-limited area, educational tools can be specially designed that significantly improve understanding and therefore the likelihood of obtaining truly informed consent for participation in clinical research.

This study examines the relative contribution of age-specific total IgE levels, eosinophils and water contact behavior to the prevalence and intensity (geometric mean egg counts) of Schistosoma mansoni infection in the poor rural population of Virgem das Graças in northern Minas Gerais State. In bivariate analysis, age was strongly correlated with both prevalence and intensity of infection, while eosinophil levels with prevalence only (p