Systematic review and meta-analysis of the pharmacokinetics of benznidazole in the treatment of Chagas disease

Chagas disease is a neglected parasitic illness affecting approximately 8 million people, predominantly in Latin America. Benznidazole is the drug of choice for treatment, although its availability has been limited. A paucity of knowledge of the pharmacokinetic properties of this drug has contributed to its limited availability in several jurisdictions. The objective of this study was to conduct a systematic literature review and a Bayesian meta-analysis of pharmacokinetic studies to improve estimates of the basic pharmacokinetic properties of benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO (Scientific Electronic Library Online) databases was conducted. Eligible studies reported patient-level data from single-100-mg-dose pharmacokinetic evaluations of benznidazole in adults or otherwise provided data relevant to the estimation of pharmacokinetic parameters which could be derived from such studies. A Bayesian hierarchical model was used for analysis. Secondary data (i.e., data from studies that did not include patient-level, single-100-mg-dose data) were used for the generation of empirical priors for the Bayesian analysis. The systematic search identified nine studies for inclusion. Nine pharmacokinetic parameters were estimated, including the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (Cmax), the time to Cmax, the elimination rate constant (kel), the absorption rate constant (Ka), the absorption and elimination half-lives, the apparent oral clearance, and the apparent oral volume of distribution. The results showed consistency across studies. AUC and Cmax were 51.31 mg · h/liter (95% credible interval [CrI], 45.01, 60.28 mg · h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter), respectively. Ka and kel were 1.16 h-1 (95% CrI, 0.59, 1.76 h-1) and 0.052 h-1 (95% CrI, 0.045, 0.059 h-1), respectively, with the corresponding absorption and elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI, 11.79, 15.42 h), respectively. The oral clearance and volume of distribution were 2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58, 42.17 liters), respectively. A Bayesian meta-analysis was used to improve the estimates of the standard pharmacokinetic parameters of benznidazole. These data can inform clinicians and policy makers as access to this drug increases.Fil: Wiens, Matthew O.. University of British Columbia; CanadáFil: Kanters, Steve. Precision Global Health;Fil: Mills, Edward. Mc Master University; CanadáFil: Peregrina Lucano, Alejandro A.. Universidad de Guadalajara; MéxicoFil: Gold, Silvia. Fundación Mundo Sano; ArgentinaFil: Ayers, Dieter. Precision Global Health;Fil: Ferrero, Luis. Fundación Mundo Sano; ArgentinaFil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin

The importance of early diagnosis for the survival of HIV positive patients

En la Argentina, el diagnóstico del HIV se realiza por solicitud voluntaria de los individuos o a través de la detección de sintomatología asociada a la infección. Sin embargo, debido a la elevada proporción de sujetos portadores que desconocen su estado serológico son necesarias nuevas estrategias. En el presente artículo mostramos cómo un modelo matemático predice el impacto de la expansión de la prueba diagnóstica del HIV en la Argentina. El modelo se basa en matrices de Markov y utiliza probabilidades de transición dependientes de parámetros obtenidos de estudios de cohortes nacionales e internacionales. Las predicciones incluyen tiempo en estadios clínicos y tratamiento, conteo de CD4, carga viral, estadío de infección, edad, tasas de mortalidad y proporción de infección desconocida a nivel poblacional. Las simulaciones se desarrollaron para la situación actual y para un escenario hipotético con diagnóstico más temprano. Mostramos predicciones que sugieren que el diagnóstico realizado antes de la progresión a sida incrementaría la expectativa de vida en unos 10.7 años. También, mostramos cómo la reducción del tiempo al diagnóstico hasta 5 años o menos desde la infección reduciría la tasa de mortalidad en el primer año de HAART de 7.6% a 2.1%, la proporción de infección no reconocida de 43.2% a 23.8% y la proporción de individuos con infección desconocida y que requieren tratamiento de 12% a 0.2%. Basados en estas predicciones resaltamos la importancia de implementar políticas de salud destinadas a detectar la infección por HIV en estadios tempranos en la Argentina.In Argentina, HIV diagnosis is reached by voluntary testing or symptom-based case findings. However, because of the high proportion of infected individuals unaware of their serologic status new strategies are required. In this article we show how a mathematic model predicts the impact of expanding HIV testing in Argentina. The model is based on time-dependent Markov matrixes and applies parameters-dependent transition-probabilities obtained from both national and international cohort studies. Outputs include time on clinical stages and therapy regime, CD4-count, viral-load, infection-state and age; mortality rates and proportion of unidentified infection at a population-level. Simulations were performed for current testing strategy and for a theoretical scenario with earlier diagnosis. We show how our prediction suggests that diagnosis before onset of symptoms would increase life expectancy by 10.7 years. Also, we show how a reduction of time to diagnosis to 5 or less years from infection would reduce mortality rates in the first year of HAART from 7.6% to 2.1%, the proportion of unrecognized infection from 43.2% to 23.8% and the proportion of individuals with unaware infection needing treatment from 12% to 0.2%. Based on this prediction we stress the importance of implementing health policies aimed at detecting HIV infection in early stages in Argentina.Fil: Dilernia, Dario Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mónaco, Daniela Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: César, Carina. Fundación Huésped; ArgentinaFil: Cahn, Pedro. Fundación Huésped; ArgentinaFil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Identification of human intestinal parasites affecting an asymptomatic peri-urban Argentinian population using multi-parallel quantitative real-time polymerase chain reaction

Background: In resource-limited countries, stool microscopy is the diagnostic test of choice for intestinal parasites (soil-transmitted helminths and/or intestinal protozoa). However, sensitivity and specificity is low. Improved diagnosis of intestinal parasites is especially important for accurate measurements of prevalence and intensity of infections in endemic areas. Methods: The study was carried out in Orán, Argentina. A total of 99 stool samples from a local surveillance campaign were analyzed by concentration microscopy and McMaster egg counting technique compared to the analysis by multi-parallel quantitative real-time polymerase chain reaction (qPCR). This study compared the performance of qPCR assay and stool microscopy for 8 common intestinal parasites that infect humans including the helminths Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, and the protozoa Giardia lamblia, Cryptosporidium parvum/hominis, and Entamoeba histolytica, and investigated the prevalence of polyparasitism in an endemic area. Results: qPCR showed higher detection rates for all parasites as compared to stool microscopy except T. trichiura. Species-specific primers and probes were able to distinguish between A. duodenale (19.1 %) and N. americanus (36.4 %) infections. There were 48.6 % of subjects co-infected with both hookworms, and a significant increase in hookworm DNA for A. duodenale versus N. americanus (119.6 fg/μL: 0.63 fg/μL, P∈<∈0.001) respectively. qPCR outperformed microscopy by the largest margin in G. lamblia infections (63.6 % versus 8.1 %, P∈<∈0.05). Polyparasitism was detected more often by qPCR compared to microscopy (64.7 % versus 24.2 %, P∈<∈0.05). Conclusions: Multi-parallel qPCR is a quantitative molecular diagnostic method for common intestinal parasites in an endemic area that has improved diagnostic accuracy compared to stool microscopy. This first time use of multi-parallel qPCR in Argentina has demonstrated the high prevalence of intestinal parasites in a peri-urban area. These results will contribute to more accurate epidemiological survey, refined treatment strategies on a public scale, and better health outcomes in endemic settings.Fil: Cimino, Rubén Oscar. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jeun, Rebecca. Baylor College Of Medicine; Estados UnidosFil: Juarez, Marisa. Universidad Nacional de Salta; ArgentinaFil: Cajal, Pamela S.. Universidad Nacional de Salta; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Echazú, Adriana. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bryan, Patricia E.. Baylor College Of Medicine; Estados UnidosFil: Nasser, Julio Rubén. Universidad Nacional de Salta; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mejia, Rojelio. Baylor College Of Medicine; Estados Unidos. Universidad Nacional de Salta; Argentin

Effect of Poor Access to Water and Sanitation As Risk Factors for Soil-Transmitted Helminth Infection: Selectiveness by the Infective Route

Background: Soil-transmitted helminth (STH) infections are a public health problem in resource-limited settings worldwide. Chronic STH infection impairs optimum learning and productivity, contributing to the perpetuation of the poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal recommendation for its control; along with water, sanitation and hygiene (WASH) interventions. The impact of joint WASH interventions on STH infections has been reported; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH. The aim of this study is to assess the association of lacking access to water and sanitation with STH infections, taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home. Methods and Findings: Cross-sectional study, conducted in Salta province, Argentina. During a deworming program that enrolled 6957 individuals; 771 were randomly selected for stool/serum sampling for parasitological and serological diagnosis of STH. Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators (hookworms and Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and Trichuris trichiura). After controlling for potential confounders, unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6–5.9). Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested (aOR = 2.2; 95% CI: 1.3–3.7). Conclusions: Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species. Interventions aimed to improve water and sanitation access should be highlighted in the recommendations for the control of STH.Fil: Echazú, Adriana. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonanno, Daniela. Ministerio de Salud de la Nación. Dirección Nacional de Prevención de Enfermedades y Riesgos; ArgentinaFil: Juarez, Marisa. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Fundación Mundo Sano; ArgentinaFil: Cajal, Silvana P.. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Heredia, Viviana. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Caropresi, Silvia. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Cimino, Rubén Oscar. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caro, Nicolas. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paredes, Gladys. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Estimation of HIV-testing rates to maximize early diagnosis-derived benefits at the individual and population level

In HIV infection, initiation of treatment is associated with improved clinical outcom and reduced rate of sexual transmission. However, difficulty in detecting infection in early stages impairs those benefits. We determined the minimum testing rate that maximizes benefits derived from early diagnosis.Fil: Dilernia, Dario Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;Fil: Mónaco, Daniela Celeste. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;Fil: Cesar, Carina. Fundación Huésped; Argentina;Fil: Krolewiecki, Alejandro Javier. Fundación Huésped; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Patologia Experimental; Argentina;Fil: Friedman, Samuel R.. National Development and Research Institutes; Estados Unidos de América;Fil: Cahn, Pedro. Fundación Huésped; Argentina;Fil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina

Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection

Background:The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference ("gold") standard.Methods:The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests).Results:According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2-96.9), followed by IVD-ELISA (92.3%, 87.7-96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9-100), followed by IVD-ELISA (97.4%, 95.5-99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity.Conclusions:NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials.Fil: Bisoffi, Zeno. Sacro Cuore Hospital; ItaliaFil: Buonfrate, Dora. Sacro Cuore Hospital; ItaliaFil: Sequi, Marco. Istituto Di Ricerche Farmacologiche Mario Negri; ItaliaFil: Mejia, Rojelio. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Albonico, Marco. Sacro Cuore Hospital; ItaliaFil: Gobbo, Maria. Sacro Cuore Hospital; ItaliaFil: Bonafini, Stefania. Sacro Cuore Hospital; ItaliaFil: Angheben, Andrea. Sacro Cuore Hospital; ItaliaFil: Requena-Mendez, Ana. Universidad de Barcelona; EspañaFil: Muñoz, José. Universidad de Barcelona; EspañaFil: Nutman, Thomas B.. National Institute Of Allergy And Infectious Diseases; Estados Unido

Clinical diagnosis of COVID-19. A multivariate logistic regression analysis of symptoms of COVID-19 at presentation

Introduction The objective of this cross-sectional study was to describe the main symptoms associated with COVID-19, and their diagnostic characteristics, to aid in the clinical diagnosis. Methods An analysis of all patients diagnosed by RT-PCR for SARS-CoV-2 between April and May 2020 in Argentina was conducted. The data includes clinical and demographic information from all subjects at the time of presentation (n=67318, where 12% were positive for SARS-CoV-2). The study population was divided into four age groups: pediatric (0-17 years), young adults (18-44 years), adults (45-64 years), and elderly (65-103 years). Multivariate logistic regression was used to measure the association of all symptoms and to create a diagnostic model based on symptoms.Results Symptoms associated with COVID-19 were anosmia, dysgeusia, headache, low-grade fever,odynophagia, and malaise. However, the presentation of these symptoms was different between thedifferent age groups. In turn, at the time of presentation, the symptoms associated with respiratoryproblems (chest pain, abdominal pain, and dyspnea) had a negative association with COVID-19 or did not present statistical relevance. On the other hand, the model based on 16 symptoms, age and sex, presented a sensitivity of 80% and a specificity of 46%.Conclusions There were significant differences between the different age groups. Additionally, therewere interactions between different symptoms that were highly associated with COVID-19. Finally, our findings showed that a regression model based on multiple factors (age, sex, interaction between symptoms) can be used as an accessory diagnostic method or a rapid screening of suspected COVID-19 cases.Fil: Fleitas, Pedro Emanuel. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paz, Jorge Augusto. Universidad Nacional de Salta. Facultad de Ciencias Económicas, Jurídicas y Sociales. Instituto de Estudios Laborales y del Desarrollo Económico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Simoy, Mario Ignacio. Universidad Nacional de Salta. Facultad de Cs.exactas. Departamento de Física. Instituto de Energias No Convencionales; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto Multidisciplinario sobre Ecosistemas y Desarrollo Sustentable. Grupo de Ecología Matemática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energía no Convencional. Grupo Vinculado al INENCO - Instituto de Investigaciones y Políticas del Ambiente Constituido | Universidad Nacional de Salta. Facultad de Cienicas Exactas. Departamento de Física. Instituto de Investigaciones en Energía no Convencional. Grupo Vinculado al INENCO - Instituto de Investigaciones y Políticas del Ambiente Constituido; ArgentinaFil: Vargas, Carlos. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aparicio, Juan Pablo. Universidad Nacional de Salta. Facultad de Cs.exactas. Departamento de Física. Instituto de Energias No Convencionales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Mini-FLOTAC, Kato-Katz and McMaster: three methods, one goal; highlights from north Argentina

Background: Copro-parasitological diagnosis is still a challenge in management of helminth infections at individualand community levels in resource-limited settings.The aim of our study was to compare the performance of three quantitative techniques: Kato-Katz, McMaster andMini-FLOTAC methids. The study was carried out in Oran, Northern Argentina.Methods: 200 schoolchildren were enrolled to provide a single stool sample, which was tested for helminthinfections with Kato-Katz, McMaster and Mini-FLOTAC methods. The Mini-FLOTAC was performed with two flotationsolutions (FS2 saturated saline and FS7 zinc sulphate). Preparation and reading time for each of the three methodswas calculated both when processing single and multiple samples.Results: Out of 193 schoolchildren examined, 40% were positive for any helminth infection by any method; themost prevalent was Hymenolepis nana (23%) followed by Ascaris lumbricoides (17%) and a third group of lessprevalent helminths: Enterobius vermicularis, Trichuris trichiura and hookworms (11% all together). Mini-FLOTAC FS2was more sensitive than FS7 for H. nana (93% vs 78%) and for other helminths (85% vs 80%), whereas FS7 was moresensitive for A. lumbricoides (87% vs 61%). Kato-Katz method was more sensitive than McMaster method for A.lumbricoides (84% vs 48%) and for other helminths (48% vs 43%) except for H. nana (49% vs 61%). As for eggcounts, Mini-FLOTAC FS2 reported 904 eggs per gram of faeces (EPG) for H. nana (vs 457 with McMaster and 111with Kato-Katz) and 1177 EPG for A. lumbricoides (vs 1315 with Kato-Katz and 995 with McMaster); FS2 detected thehighest EPG for both H.nana and A.lumbricoides (904 vs 568 and 1177 vs 643 respectively), the differences werenot statistically significant. The technique feasibility was calculated: Kato-Katz mean time was 48 minutes/sample,Mini-FLOTAC 13 minutes/sample and McMaster 7 minutes/sample. However, especially for Kato-Katz and Mini-FLOTAC,the mean time (min/sample) decreased significantly when processing multiple samples.Conclusions: Mini-FLOTAC is a promising technique for helminth diagnosis, it is more sensitive than Kato-Katz andMcMaster for H. nana and as sensitive as Kato-Katz and more sensitive than McMaster for A. lumbricoides identification.Egg counts differences although relevant, did not reach statistical significance.Fil: Barda, Beatrice. San Raffaele Hospital; ItaliaFil: Cajal, Pamela. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Villagran, Eliana. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Cimino, Ruben. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Juarez, Marisa. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Rinaldi, Laura. Universidad de Napoles Federico III; ItaliaFil: Cringoli, Giuseppe. Universidad de Napoles Federico III; ItaliaFil: Burioni, Roberto. San Raffaele Hospital; ItaliaFil: Albonico, Marco. Ivo de Carneri Foundation; Itali

Detecting albendazole metabolites in serum and urine: a first step in developing an indicator of MDA compliance in humans

The neglected tropical diseases (NTDs) are a group of pathogens affecting individuals in the poorest regions of the world. Among them, Soil Transmitted Helminth (STH) infections directly impact nutritional status, educational development, individual productivity, and physical and mental development in human populations. Currently, these infections are controlled through mass drug administration (MDA) programs using albendazole (ABZ) or mebendazole. However, not all programs have demonstrated expected impact on prevalence or intensity of infections. These failures may be related to poor programmatic coverage, suboptimal adherence or the exposure of parasites to sub-therapeutic drug concentrations due to poor drug dissolution, insufficient gastrointestinal absorption and/or systemic availability of the active ingredient. Accordingly, improved knowledge of the basic pharmaco-kinetics of ABZ in treated people is critical. As part of the DeWorm3 project, we sought to characterize the serum disposition kinetics and pattern of urinary excretion of ABZ and its main metabolites (ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2)) in non-infected human volunteers. In addition, we sought to determine the duration and optimal timepoint where ABZ and/or its metabolites can be measured in urine as an indirect assessment of an individual?s adherence to treatment. Consecutive venous blood and urine samples were collected from eight (8) healthy volunteers between 2 and 72 h (serum) and 4 and 72 h (urine) for HPLC analysis of ABZ/metabolites following administration of a single postprandial oral dose of ABZ (400 mg Glaxo SmithKline).The ABZSO metabolite was the main analyte recovered either in serum and urine samples from ABZ-treated human. ABZSO serum concentrations reached its peak concentration (Cmax= 1.20 ± 0.44 μg/mL) at 4.75 h post-treatment. In urine ABZSO Cmax value was 3.24 ± 1.51 μg/mL, reached at 6.50 h post ABZ administration. The urinary AUC value, resulted higher (2.3 fold) compared to that measured in serum. The overall, PK-based information reported here demonstrates that the measurement of ABZSO concentrations both in serum and urine could be useful to confirm compliance to ABZ treatment and an objective measurement of program coverage.Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Juarez, Marisa del Valle. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Banal, Juan Pablo. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Walson, Judd. Natural History Museum; Reino UnidoFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina66° Annual Meeting of American Society of Tropical Medicine and HygieneBaltimoreEstados UnidosAmerican Society of Tropical Medicine and Hygien

Role of DNA-detection–based tools for monitoring the soil-transmitted helminth treatment response in drug-efficacy trials

[EN] More than 1 billion people have been reported to be infected with at least one soil-transmitted helminth (STH) worldwide, according to the last published report of the World Health Organization (WHO) [1]. WHO guidelines for STH control mainly encompass periodic administration of benzimidazoles (albendazole or mebendazole) to at-risk people of the endemic areas [1]. However, extended use of benzimidazoles could entail a great selection pressure for parasitic-resistant strains. In veterinary medicine, anthelmintic resistance in gastrointestinal nematodes has been developed in response to their excessive use, and it is currently considered a serious threat to livestock health and welfare [2, 3]. In humans, the estimated efficacy of albendazole and mebendazole against Trichuris trichiura has been observed to significantly decrease over time [4]. This observed decrement in drug efficacy could be due to the development of anthelmintic resistance (among other reasons such as drug quality and administration, the increasing of drug-efficacy studies, improvements in sensitivity of diagnostic tools after treatment, etc) after years of mass drug-administration campaigns, which is one of the major oncerns in STH controlSIThe Stopping Transmission Of intestinal Parasites (STOP) project is part of the EDCTP2 programme supported by the European Union (grant number RIA2017NCT-1845 — STOP). JG is personally supported by Ramon Areces Foundation, Spain; MMV by the Spanish ‘Ramo´n y Cajal’ Programme, Ministry of Economy and Competitiveness (RYC-2015-18368); and SK is supported by DELTAS Africa Initiative grant # DEL- 15-011 to THRiVE-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip