Razón linfocito/proteína C reactiva disminuida como factor pronóstico de mortalidad en pacientes con neumonía por SARS-CoV-2

Objetivo: Determinar que la razón linfocito/proteína C reactiva disminuida es factor pronóstico de mortalidad en pacientes con neumonía por SARS-CoV-2 en la unidad principal de cuidados intensivos del Hospital Regional Docente de Trujillo. Material y métodos: El presente estudio tuvo un diseño analítico, observacional, de cohorte retrospectivo y longitudinal realizado en 93 pacientes con neumonía por SARS-CoV-2. Se obtuvo los datos de distribución de frecuencias de variables cualitativas y las medidas de centralización y dispersión de variables cuantitativas. Además, se empleó la prueba Chi Cuadrado (X2 ), por tanto, las asociaciones se consideraron significativas si el valor de p era menor a 0,05. Finalmente, se calculó, entre las variables cualitativas, el riesgo relativo de la razón L/PCR respecto al riesgo de mortalidad en neumonía por SARS-CoV-2. Después se llevó a cabo el análisis multivariado con regresión logística para las variables intervinientes que resultaron significativas en el análisis bivariado. Resultados: De los 93 pacientes incluidos en el estudio, se pudo evidenciar que 41 fallecieron (44,1%), y de dichos pacientes, un 53,7% fueron de una edad menor o igual a 60 años y un 78% fueron varones. Sumado a ello, se encontró que, la edad mayor a 60 años, el recuento normal de linfocitos y los valores disminuidos del Índice L/PCR demostraron ser un factor de riesgo de mortalidad en los pacientes con neumonía por SARS-CoV-2. Conclusiones: La razón L/PCR disminuida fue factor pronóstico de mortalidad en pacientes con neumonía por SARS-CoV-2 del Hospital Regional Docente de Trujillo.Aim: To determine that the decreased lymphocyte/C-reactive protein (L/CRP) ratio was a prognostic factor for mortality in patients with SARS-CoV-2 pneumonia at the Trujillo Regional Teaching Hospital. Material and methods: The present study had an analytical, observational, retrospective and longitudinal cohort design carried out in 93 patients with SARS CoV-2 pneumonia. The frequency distribution data of qualitative variables and the measures of centralization and dispersion of quantitative variables were obtained. In addition, the Chi Square (X2) test was used, therefore, the associations were considered significant if the p value was less than 0.05. Finally, among the qualitative variables, the relative risk of the L/CRP ratio with respect to the risk of mortality in SARS-CoV-2 pneumonia was calculated. Afterwards, the multivariate analysis was carried out with logistic regression for the intervening variables that were significant in the bivariate analysis. Results: Of the 93 patients included in the study, it was possible to show that 41 died (44.1%), and of these patients, 53.7% were less than or equal to 60 years of age and 78% were male. Added to this, it was found that age over 60 years, normal lymphocyte count and decreased values of the L/CRP Index proved to be a risk factor for mortality in patients with SARS-CoV-2 pneumonia. Conclusions: The decreased L/CRP ratio was a prognostic factor for mortality in patients with SARS-CoV-2 pneumonia at the Trujillo Regional Teaching Hospital.Tesi

Human infectiousness and parasite load in chronic patients seropositive for Trypanosoma cruzi in a rural area of the Argentine Chaco

A key parameter in the transmission of vector-borne infections, including Chagas disease, is the ability of the different host species to transmit the parasite to the vector (infectiousness). Here, we determined infectiousness to the vector of Trypanosoma cruzi-seropositive humans examined by artificial xenodiagnosis (XD), established its relationship with T. cruzi DNA levels (a surrogate of intensity of parasitemia) quantified by real-time PCR (qPCR), and assessed whether infectiousness was associated with the body mass index (BMI), age, ethnic background and parasite genotype. XD was performed to 117 T. cruzi-seropositive residents from Pampa del Indio and parasite load was quantified in 81 of them. Using optical microscopy (OM) 33.6% of the seropositive people tested were infectious and this fraction nearly doubled (66.0%) when XD triatomines were examined by kDNA-PCR. The mean infectiousness (defined as the percentage of all infected triatomines detected by OM at any time point among the total number of insects examined by OM 30 days post-feeding) was 5.2%, and the mean parasite load was 0.51 parasite equivalents per ml. Infectiousness to the vector was associated negatively with age and BMI, and positively with the detection of parasitemia by kDNA-PCR, and parasite load by qPCR in bivariate analysis. Patients with a positive XD by OM exhibited a significantly higher mean parasite load. Using multiple regression, infectiousness was associated with parasite load (positively) and with the household presence of T. infestans and Qom ethnic group (negatively); no significant association was observed with age or its interaction with ethnicity. We did not find significant associations between identified DTUs and infectiousness or parasite load. Infectiousness was aggregated: 18% of the people examined by XD generated 80% of the infected triatomines. Detecting and treating the super-infectious fraction of the infected human would disproportionally impact on domestic transmission risks. Nonetheless, treatment of all eligible infected people who meet the inclusion criteria regardless of their parasitemia should be ensured to improve their prognosis.Fil: Macchiaverna, Natalia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Enriquez, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Sartor, Paula Andrea. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gurtler, Ricardo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Cardinal, Marta Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Interplay between productive traits, the social rank, and the cow’s stability in the order of entrance to the milking parlour

The aim of this study was to investigate whether social rank (SR) and stability in the order of entrance to the milking parlour are associated with production traits. The study was conducted on a dairy farm where cows (n = 215) were managed in three groups according to lactation stage (group 1: 78 cows, 0–100 days in milk (DIM); group 2: 65 cows, 101–200 DIM and group 3: 72 cows, >200 DIM). SR was calculated from observations made from agonistic behaviour performed at the water troughs and feed bunks of each pen (n = 3). The animals were classified into three levels of dominance based on at least five clear interactions, resulting in: 61 dominant, 75 intermediate and 69 subordinate cows based on SR. Stability in the order of entry was estimated as the standard deviation of the entry position. SR was weakly correlated with milk yield, urea and protein content in milk. The results showed that stable cows had higher milk production and entered the milking parlour after the non-stable animals. Stability in the order of entry to the milking parlour was not affected by SR. Overall, the use of milking facilities appears to be associated with production traits rather than SR

New human isolates of Trypanosoma cruzi confirm the predominance of hybrid lineages in domestic transmission cycle of the Argentinean Chaco

Trypanosoma cruzi, the etiological agent of Chagas disease, was initially classified into 6 Discrete Typing Units (DTUs). The hybrid DTUs TcV and TcVI are the most frequent in domestic transmission cycles throughout the Southern Cone countries of South America. Here, we genotyped parasite isolates from human residents in Pampa del Indio municipality, Chaco, to further characterize the structure of T. cruzi populations, and to assess the degree of overlapping between the domestic and sylvatic transmission cycles. Artificial xenodiagnostic tests were performed to blood samples from 125 T. cruzi-seropositive people (age range, 3–70 years) who represented 14.3% of all seropositive residents identified. Parasites were obtained from feces of T. cruzi-infected Triatoma infestans examined 30 or 60 days after blood-feeding, and grown in vitro. The cultured parasites were genotyped by means of two PCR-based protocols. DTUs were determined from 39 (31%) patients residing in 28 dwellings. The only DTUs identified were TcV (92%) and TcVI (8–36%). Households with more than one parasite isolate consistently displayed the same DTU. Further sequencing of a fragment of the TcMK gene from selected samples argue against the occurrence of mixed TcV-TcVI infections in the study population. Sequencing data revealed an unexpected degree of genetic variability within TcV including two apparently robust subgroups of isolates. Our results for human residents confirm the predominance of hybrid lineages (TcV and to a much lesser extent TcVI) and the absence of sylvatic genotypes (TcI and TcIII) in (peri)domestic transmission cycles in the Argentinean Chaco area.Fil: Macchiaverna, Natalia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Enriquez, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Gurtler, Ricardo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Cardinal, Marta Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Treatment of dogs with fluralaner reduced pyrethroid-resistant Triatoma infestans abundance, Trypanosoma cruzi infection and human-triatomine contact in the Argentine Chaco

Background: Triatomine elimination efforts and the interruption of domestic transmission of Trypanosoma cruzi are hampered by pyrethroid resistance. Fluralaner, a long-lasting ectoparasiticide administered to dogs, substantially reduced site infestation and abundance of pyrethroid-resistant Triatoma infestans Klug (Heteroptera: Reduviidae) in an ongoing 10-month trial in Castelli (Chaco Province, Argentina). We assessed the effects of fluralaner on vector infection with T. cruzi and blood meal sources stratified by ecotope and quantified its medium-term effects on site infestation and triatomine abundance. Methods: We conducted a placebo-controlled, before-and-after efficacy trial of fluralaner in 28 infested sites over a 22-month period. All dogs received either an oral dose of fluralaner (treated group) or placebo (control group) at 0 month post-treatment [MPT]. Placebo-treated dogs were rescue-treated with fluralaner at 1 MPT, as were all eligible dogs at 7 MPT. Site-level infestation and abundance were periodically assessed by timed manual searches with a dislodging aerosol. Vector infection was mainly determined by kDNA-PCR and blood meal sources were determined by enzyme-linked immunosorbent assay. Results: In fluralaner-treated households, site infestation dropped from 100% at 0 MPT to 18–19% over the period 6–22 MPT while mean abundance plummeted from 5.5 to 0.6 triatomines per unit effort. In control households, infestation dropped similarly post-treatment. The overall prevalence of T. cruzi infection steadily decreased from 13.8% at 0–1 MPT (baseline) to 6.4% and subsequently 2.3% thereafter, while in domiciles, kitchens and storerooms it dropped from 17.4% to 4.7% and subsequently 3.3% thereafter. Most infected triatomines occurred in domiciles and had fed on humans. Infected-bug abundance plummeted after fluralaner treatment and remained marginal or nil thereafter. The human blood index of triatomines collected in domiciles, kitchens and storerooms highly significantly fell from 42.9% at baseline to 5.3–9.1% over the period 6–10 MPT, increasing to 36.8% at 22 MPT. Dog blood meals occurred before fluralaner administration only. The cat blood index increased from 9.9% at baseline to 57.9–72.7% over the period 6–10 MPT and dropped to 5.3% at 22 MPT, whereas chicken blood meals rose from 39.6% to 63.2–88.6%. Conclusion: Fluralaner severely impacted infestation- and transmission-related indices over nearly 2 years, causing evident effects at 1 MPT, and deserves larger efficacy trials.Fil: Gurtler, Ricardo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Laiño, Mariano Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Alvedro, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Enriquez, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Macchiaverna, Natalia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Gaspe, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Cardinal, Marta Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Incorporating a fresh mixed annual ryegrass and berseem clover forage into the winter diet of dairy cows resulted in reduced milk yield, but reduced nitrogen excretion and reduced methane yield

The winter diet of dairy cows in Mediterranean climate regions is usually a total mixed ration with a base of conserved summer crops such as corn silage and alfalfa hay. However, there is increased labor and financial cost related to this kind of feeding, which could be reduced if fresh forages were used in place of some of the conserved forage in the cow diet. The objective of our study was to evaluate the effect of including fresh mixed annual ryegrass and berseem clover into the diet of dairy cows on milk, nitrogen utilization, and methane emission. Twenty-four lactating dairy cows were split into two groups and offered either a diet similar to that usually offered to the cows (CON) or one where a mixture of fresh annual ryegrass and berseem clover was used to partially substitute the corn silage and alfalfa hay in the diet (MIX). Milk yield was recorded automatically, and methane emissions were estimated using the SF6 tracer technique. The MIX diet had lower crude protein concentration (148 vs. 170 g/kg DM) but higher DM digestibility (81.6 vs. 78.6%) than the CON diet. Compared to the cows offered the CON diet, milk yield was reduced when cows were fed the MIX diet (36.4 vs. 31.9 kg/d), but methane emissions (381 vs. 332 g/d) and nitrogen excretion were also reduced (238 vs. 180 g/d). Nitrogen use efficiency was unaffected (30.8%). In addition, milk from cows fed the MIX diet had a fatty acid profile considered to be more beneficial to human health than that of the milk from cows fed the CON diet. Increasing the protein concentration in the MIX diet, either by direct supplementation or increasing the proportion of legume in the mixed herbage, could overcome the reduction on milk and positively affect methane emission and N use efficiency

Long-term impact of a ten-year intervention program on human and canine Trypanosoma cruzi infection in the Argentine Chaco

Background Interruption of domestic vector-borne transmission of Trypanosoma cruzi is still an unmet goal in several American countries. In 2007 we launched a long-term intervention program aimed to suppress house infestation with the main domestic vector in southern South America (Triatoma infestans) and domestic transmission in Pampa del Indio, a resource-constrained, hyperendemic municipality with 1446 rural houses inhabited by Creole and indigenous people, in the Argentine Chaco ecoregion. Here, we assessed whether the 10-year insecticide-based program combined with community mobilization blocked vector-borne domestic transmission of T. cruzi to humans and dogs. Methods We carried out two municipality-wide, cross-sectional serosurveys of humans and dogs (considered sentinel animals) during 2016–2017 to compare with baseline data. We used a risk-stratified random sampling design to select 273 study houses; 410 people from 180 households and 492 dogs from 151 houses were examined for antibodies to T. cruzi using at least two serological methods. Results The seroprevalence of T. cruzi in children aged <16 years was 2.5% in 2017 (i.e., 4- to 11-fold lower than before interventions). The mean annual force of child infection (λ) sharply decreased from 2.18 to 0.34 per 100 person-years in 2017. One of 102 children born after interventions was seropositive for T. cruzi; he had lifetime residence in an apparently uninfested house, no outside travel history, and his mother was T. cruzi-seropositive. No incident case was detected among 114 seronegative people of all ages re-examined serologically. Dog seroprevalence was 3.05%. Among native dogs, λ in 2016 (1.21 per 100 dog-years) was 5 times lower than at program onset. Six native adult dogs born after interventions and with stable lifetime residence were T. cruzi-seropositive: three had exposure to T. infestans at their houses and one was an incident case. Conclusions These results support the interruption of vector-borne transmission of T. cruzi to humans in rural Pampa del Indio. Congenital transmission was the most likely source of the only seropositive child born after interventions. Residual transmission to dogs was likely related to transient infestations and other transmission routes. Sustained vector control supplemented with human chemotherapy can lead to a substantial reduction of Chagas disease transmission in the Argentine Chaco.Fil: Cardinal, Marta Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; ArgentinaFil: Enriquez, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; ArgentinaFil: Macchiaverna, Natalia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; ArgentinaFil: Argibay, Hernán Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; ArgentinaFil: Fernandez, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; Argentina. Washington State University; Estados UnidosFil: Alvedro, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; ArgentinaFil: Gaspe, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; ArgentinaFil: Gurtler, Ricardo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; Argentin

Over-dispersed Trypanosoma cruzi parasite load in sylvatic and domestic mammals and humans from northeastern Argentina

Background: The distribution of parasite load across hosts may modify the transmission dynamics of infectious diseases. Chagas disease is caused by a multi-host protozoan, Trypanosoma cruzi, but the association between host parasitemia and infectiousness to the vector has not been studied in sylvatic mammalian hosts. We quantified T. cruzi parasite load in sylvatic mammals, modeled the association of the parasite load with infectiousness to the vector and compared these results with previous ones for local domestic hosts. Methods: The bloodstream parasite load in each of 28 naturally infected sylvatic mammals from six species captured in northern Argentina was assessed by quantitative PCR, and its association with infectiousness to the triatomine Triatoma infestans was evaluated, as determined by natural or artificial xenodiagnosis. These results were compared with our previous results for 88 humans, 70 dogs and 13 cats, and the degree of parasite over-dispersion was quantified and non-linear models fitted to data on host infectiousness and bloodstream parasite load. Results: The parasite loads of Didelphis albiventris (white-eared opossum) and Dasypus novemcinctus (nine-banded armadillo) were directly and significantly associated with infectiousness of the host and were up to 190-fold higher than those in domestic hosts. Parasite load was aggregated across host species, as measured by the negative binomial parameter, k, and found to be substantially higher in white-eared opossums, cats, dogs and nine-banded armadillos (range: k = 0.3–0.5) than in humans (k = 5.1). The distribution of bloodstream parasite load closely followed the “80–20 rule” in every host species examined. However, the 20% of human hosts, domestic mammals or sylvatic mammals exhibiting the highest parasite load accounted for 49, 25 and 33% of the infected triatomines, respectively. Conclusions: Our results support the use of bloodstream parasite load as a proxy of reservoir host competence and individual transmissibility. The over-dispersed distribution of T. cruzi bloodstream load implies the existence of a fraction of highly infectious hosts that could be targeted to improve vector-borne transmission control efforts toward interruption transmission. Combined strategies that decrease the parasitemia and/or host–vector contact with these hosts would disproportionally contribute to T. cruzi transmission control.Fil: Enriquez, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Orozco, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Macchiaverna, Natalia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Alvarado Otegui, Julián Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Argibay, Hernán Darío. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Washington State University; Estados UnidosFil: Gurtler, Ricardo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Cardinal, Marta Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Background: Chagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure. Methods: Following a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples. Results: Pilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres. Conclusions: We show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. Graphical abstract: We show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.Fil: Murphy, Niamh. University of London; Reino UnidoFil: Cardinal, Marta Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Eco-Epidemiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Bhattacharyya, Tapan. University of London; Reino UnidoFil: Enriquez, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Macchiaverna, Natalia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Alvedro, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Freilij, Héctor. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Martinez de Salazar, Pablo. Barcelona Institute For Global Health; EspañaFil: Molina, Israel. Barcelona Institute For Global Health; EspañaFil: Mertens, Pascal. No especifíca;Fil: Gilleman, Quentin. No especifíca;Fil: Gurtler, Ricardo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Miles, Michael A.. University of London; Reino Unid

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

BACKGROUND In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES The authors aimed to determine the role of the calcineurin splicing variant CnA beta 1 in the context of cardiac hypertrophy and its mechanism of action. METHODS Transgenic mice overexpressing CnAb1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnA beta 1 (CnA beta 1(Delta i12) mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. RESULTS In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnA beta 1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAb1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnA beta 1. CnA beta 1(Delta i12) mice show increased cardiac hypertrophy and declined contractility. CONCLUSIONS The metabolic reprogramming induced by CnAb1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches. (J Am Coll Cardiol 2018; 71: 654-67) (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).This work was supported by grants from the European Union (CardioNeT-ITN-289600 and CardioNext-608027 to Dr. Lara-Pezzi; Meet-ITN-317433 to Dr. Enriquez; UE0/MCA1108 to Dr. Acin-Perez), from the Spanish Ministry of Economy and Competitiveness (SAF2015-65722-R and SAF2012-31451 to Dr. Lara-Pezzi; SAF2015-71521-REDC, BFU2013-50448, and SAF2012-32776 to Dr. Enriquez; RyC-2011-07826 to Dr. Acin-Perez; BIO2012-37926 and BIO2015-67580-P to Dr. Vazquez), from the Spanish Carlos III Institute of Health (CPII14/00027 to Dr. Lara-Pezzi; RD12/0042/066 to Drs. Garcia-Pavia and Lara-Pezzi), from the Regional Government of Madrid (2010-BMD-2321 ``Fibroteam´´ to Dr. Lara-Pezzi; 2011-BMD-2402 ``Mitolab´´ to Dr. Enriquez) and the FIS-ISCIII (PRB2-IPT13/0001 and RD12/0042/0056-RIC-RETICS to Dr. Vazquez). This work was also supported by the Plan Estatal de IthornDthornI 2013-2016-European Regional Development Fund (FEDER) ``A way of making Europe,´´ Spain. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Drs. Vazquez and Garcia-Pavia have served as consultants for VL39. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Padron-Barthe, Villalba-Orero, and Gomez-Salinero contributed equally to this work and are joint first authors. Robyn Shaw, MD, PhD, served as Guest Editor for this paper.S