Development of vaccines for Chagas disease (CRUZIVAX): stakeholders' preferences and potential impacts on healthcare.

A vaccine for Chagas disease does not currently exist. This study aims to inform the development of two vaccines for the prevention and treatment of Trypanosoma cruzi infection, and guide their pre-clinical phase up to clinical phase I. The three main objectives are: 1) to explore patients' and policy makers' preferences on the candidate vaccines in Argentina and Spain; 2) to investigate health-related quality of life of patients affected by Chagas disease; and 3) to assess the potential health provider savings associated with the vaccines, in terms of resource use and health care costs. Discrete choice experiments will be employed to estimate and characterize the theoretical demand for the vaccines and investigate patients' and policy makers' preferences. Health-related quality of life will be assessed using the EQ-5D-3L questionnaire. Resources use and costs associated with Chagas disease will be investigated using information from the databases of the Hospital Clínic of Barcelona.

Development of vaccines for Chagas disease (CRUZIVAX): stakeholders’ preferences and potential impacts on healthcare / Desarrollo de vacunas para la enfermedad de Chagas (CRUZIVAX): preferencias de las partes interesadas y posibles impactos en la asistencia sanitaria

A vaccine for Chagas disease does not currently exist. This study aims to inform the development of two vaccines for the prevention and treatment of Trypanosoma cruzi infection, and guide their pre-clinical phase up to clinical phase I. The three main objectives are: 1) to explore patients’ and policy makers’ preferences on the candidate vaccines in Argentina and Spain; 2) to investigate health-related quality of life of patients affected by Chagas disease; and 3) to assess the potential health provider savings associated with the vaccines, in terms of resource use and health care costs. Discrete choice experiments will be employed to estimate and characterize the theoretical demand for the vaccines and investigate patients’ and policy makers’ preferences. Health-related quality of life will be assessed using the EQ-5D-3L questionnaire. Resources use and costs associated with Chagas disease will be investigated using information from the databases of the Hospital Clínic of Barcelona. (AU)

No existen vacunas para la enfermedad de Chagas. Este trabajo pretende informar la fase preclínica de dos vacunas para la prevención y el tratamiento de la infección por Trypanosoma cruzi. Los objetivos principales son tres: 1) investigar las preferencias de los pacientes y de los responsables de políticas sanitarias en Argentina y España; 2) investigar la calidad de vida relacionada con la salud de los pacientes afectados por la enfermedad de Chagas; y 3) estimar los ahorros potenciales asociados con las vacunas para los proveedores de salud. Se usarán experimentos de elección discreta para estimar y caracterizar la demanda teórica de las vacunas e investigar las preferencias de los pacientes y de los responsables de las políticas sanitarias. La calidad de vida relacionada con la salud se evaluará mediante el cuestionario EQ-5D-3L. Se investigarán el uso de recursos y los costes asociados a la enfermedad de Chagas utilizando bases de datos del Hospital Clínic de Barcelona. (AU)

Long-term cardiology outcomes in children after early treatment for Chagas disease, an observational study.

BACKGROUND: Parasite persistence after acute infection with Trypanosoma cruzi is an important factor in the development of Chagas disease (CD) cardiomyopathy. Few studies have investigated the clinical effectiveness of CD treatment through the evaluation of cardiological events by long term follow-up of treated children. Cardiological evaluation in children is challenging since features that would be diagnosed as abnormal in an adult's ECG may be normal, age-related findings in a pediatric ECG trace. The objective was to evaluate cardiac involvement in patients with Chagas disease with a minimum follow-up of 6 years post-treatment. METHODOLOGY: A descriptive study of a cohort of pediatric patients with CD treated with benznidazole (Bz) or nifurtimox (Nf) was conducted. Children (N = 234) with at least 6 years post CD treatment followed at the Parasitology and Chagas Service, Buenos Aires Children's Hospital (Argentina) were enrolled. By convenience sampling, children who attended a clinical visit between August 2015 and November 2019 were also invited to participate for additional cardiovascular studies like 24-hour Holter monitoring and speckle-tracking 2D echocardiogram (STE). Benznidazole was prescribed in 171 patients and nifurtimox in 63 patients. Baseline parasitemia data was available for 168/234 patients. During the follow-up period, alterations in routine ECG were observed in 11/234 (4.7%, 95% CI [2-7.4%]) patients. In only four patients, with complete right bundle branch block (cRBBB) and left anterior fascicular block (LAFB), ECG alterations were considered probably related to CD. During follow-up, 129/130 (99%) treated patients achieved persistent negative parasitemia by qPCR. Also decrease in T.cruzi antibodies titers was observed in all patients and negative seroconversion occurred in 123/234 (52%) patients. CONCLUSIONS: A low incidence of cardiological lesions related to CD was observed in patients treated early for pediatric CD. This suggests a protective effect of parasiticidal treatment on the development of cardiological lesions and highlights the importance of early treatment of infected children. TRIAL REGISTRATION: ClinicalTrials.gov NCT04090489.

Different profiles and epidemiological scenarios: past, present and future.

The multiplicity of epidemiological scenarios shown by Chagas Disease, derived from multiple transmission routes of the aetiological agent, occurring on multiple geo-ecobiosocial settings determines the complexity of the disease and reveal the difficulties for its control. From the first description of the link between the parasite, the vector and its domestic habitat and the disease that Carlos Chagas made in 1909, the epidemiological scenarios of the American Trypanosomiasis has shown a dynamic increasing complexity. These scenarios changed with time and geography because of new understandings of the disease from multiple studies, because of policies change at the national and international levels and because human movements brought the parasite and vectors to new geographies. Paradigms that seemed solid at a time were broken down, and we learnt about the global dispersion of Trypanosoma cruzi infection, the multiplicity of transmission routes, that the infection can be cured, and that triatomines are not only a health threat in Latin America. We consider the multiple epidemiological scenarios through the different T. cruzi transmission routes, with or without the participation of a Triatominae vector. We then consider the scenario of regions with vectors without the parasite, to finish with the consideration of future prospects.

Different profiles and epidemiological scenarios: past, present and future

The multiplicity of epidemiological scenarios shown by Chagas Disease, derived from multiple transmission routes of the aetiological agent, occurring on multiple geo-ecobiosocial settings determines the complexity of the disease and reveal the difficulties for its control. From the first description of the link between the parasite, the vector and its domestic habitat and the disease that Carlos Chagas made in 1909, the epidemiological scenarios of the American Trypanosomiasis has shown a dynamic increasing complexity. These scenarios changed with time and geography because of new understandings of the disease from multiple studies, because of policies change at the national and international levels and because human movements brought the parasite and vectors to new geographies. Paradigms that seemed solid at a time were broken down, and we learnt about the global dispersion of Trypanosoma cruzi infection, the multiplicity of transmission routes, that the infection can be cured, and that triatomines are not only a health threat in Latin America. We consider the multiple epidemiological scenarios through the different T. cruzi transmission routes, with or without the participation of a Triatominae vector. We then consider the scenario of regions with vectors without the parasite, to finish with the consideration of future prospects.

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. 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.

Improved vector control of Triatoma infestans limited by emerging pyrethroid resistance across an urban-to-rural gradient in the Argentine Chaco.

BACKGROUND: The sustainable elimination of Triatoma infestans in the Gran Chaco region represents an enduring challenge. Following the limited effects of a routine pyrethroid insecticide spraying campaign conducted over 2011-2013 (first period) in Avia Terai, an endemic municipality with approximately 2300 houses, we implemented a rapid-impact intervention package to suppress house infestation across the urban-to-rural gradient over 2015-2019 (second period). Here, we assess their impacts and whether persisting infestations were associated with pyrethroid resistance. METHODS: The 2011-2013 campaign achieved a limited detection and spray coverage across settings (< 68%), more so during the surveillance phase. Following community mobilization and school-based interventions, the 2015-2019 program assessed baseline house infestation using a stratified sampling strategy; sprayed all rural houses with suspension concentrate beta-cypermethrin, and selectively sprayed infested and adjacent houses in urban and peri-urban settings; and monitored house infestation and performed selective treatments over the follow-up. RESULTS: Over the first period, house infestation returned to pre-intervention levels within 3-4 years. The adjusted relative odds of house infestation between 2011-2013 and 2015-2016 differed very little (adj. OR: 1.17, 95% CI 0.91-1.51). Over the second period, infestation decreased significantly between 0 and 1 year post-spraying (YPS) (adj. OR: 0.36, 95% CI 0.28-0.46), with heterogeneous effects across the gradient. Mean bug abundance also dropped between 0 and 1 YPS and thereafter remained stable in rural and peri-urban areas. Using multiple regression models, house infestation and bug abundance at 1 YPS were 3-4 times higher if the house had been infested before treatment, or was scored as high-risk or non-participating. No low-risk house was ever infested. Persistent foci over two successive surveys increased from 30.0 to 59.3% across the gradient. Infestation was more concentrated in peridomestic rather than domestic habitats. Discriminating-dose bioassays showed incipient or moderate pyrethroid resistance in 7% of 28 triatomine populations collected over 2015-2016 and in 83% of 52 post-spraying populations. CONCLUSIONS: The intervention package was substantially more effective than the routine insecticide spraying campaign, though the effects were lower than predicted due to unexpected incipient or moderate pyrethroid resistance. Increased awareness and diagnosis of vector control failures in the Gran Chaco, including appropriate remedial actions, are greatly needed.

Consenso Argentino de toxoplasmosis congénita 2020 / Argentine Consensus of congenital toxoplasmosis

Resumen La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del re cién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.

Abstract Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diag nosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.

[Argentine consensus of congenital toxoplasmosis]. / Consenso argentino de toxoplasmosis congénita 2020.

Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diagnosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.

La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del recién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.

Longitudinal follow up of serological response in children treated for Chagas disease.

BACKGROUND: Evaluation of therapeutic response in chronic Chagas disease is a major challenge, due to prolonged persistence of Trypanosoma cruzi-specific antibodies, lack of sensitivity of parasitological tests, and need for long-term follow-up to observe negative seroconversion of conventional serological tests (CS). The objective of this study was to evaluate F2/3-ELISA serology, a promising early biomarker of therapeutic response, and T.cruzi Polymerase chain reaction (PCR) for T. cruzi Deoxyribonucleic acid (DNA), for neonatal diagnosis and evaluation of parasitemia after treatment. METHODS: Prospective cohort study, with three-year clinical, serological and parasitological follow-up of pediatric Chagas disease patients treated with benznidazole. Serology was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA), Indirect hemagglutination (IHA) and F2/3-ELISA; Parasitemia by microhematocrit (MH) and PCR. RESULTS: A cohort of 107 pediatric patients treated with benznidazole was enrolled in the study. ELISA and IHA were initially reactive in 100% of patients, F2/3-ELISA serology was reactive in 80% (86/107) and 91% (97/107) had detectable parasitemia. Seventy-six (71%) patients completed at least 36 months of serological follow up after treatment. Although a similar decreasing linear trend was observed for all serological tests, F2/3-ELISA presented earlier, age dependent, negative seroconversion compared to CS. All patients reaching undetectable CS titers had previously seroreverted by F2/3-ELISA. All patients with persistently decreasing antibody titers had negative PCRs throughout the follow up period. No new cardiological lesions were observed during the 3 years follow-up period. CONCLUSIONS: The data reported here, using CS, F2/3 ELISA and PCR provide support for the efficacy of benznidazole in congenital Chagas diseases. These results provide support for scaling up of screening, diagnosis and access to benznidazole treatment. TRIAL REGISTRATION: ClinicalTrials.gov 0028/04 in the Research Council, Secretary of Health Buenos Aires city Goberment.

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Prevalencia de infección por Trypanosoma cruzi en escolares de Salta y Chaco, Argentina / Seroprevalencia of Trypanosoma cruzi infection in school-age children from localities in Salta and Chaco, Argentina / Prevalência de infecção por Trypanosoma cruzi em crianças em idade escolar de Salta e Chaco, na Argentina

El objetivo del trabajo consistió en identificar la seroprevalencia de la infección por Trypanosoma cruzi en niños en edad escolar en localidades de las provincias de Salta y Chaco. Se trabajó en 44 escuelas de la ciudad de Salta, en parajes de San Carlos; en 10 escuelas de La Unión y en 7 escuelas de Taco Pozo. El trabajo tiene un diseño de corte transversal. La toma de muestra se realizó por punción capilar con equipos Serokit, y la confirmación de los casos seropositivos o dudosos por punción venosa, y obtención de suero, para realizar HAI y ELISA. Los casos seropositivos confirmados fueron tratados con Benznidazol® durante 60 días en dosis de 5-7mg/kg/ día. Para el análisis estadístico se elaboraron tablas con frecuencias absolutas y relativas. Se analizaron 17.884 escolares y se detectaron159 seropositivos, siendo la mayor seroprevalencia en la localidad de La Unión y la menor en la ciudad de Salta. Se aplicó tratamiento a 93 niños (71,54 %) de la ciudad y en el ámbito rural se trataron todos los casos. La vía de infección vectorial fue la de mayor predominio en las madres (64,47%). Se concluye que aunque la seroprevalencia fue menor en la ciudad de Salta que en las zonas rurales, es necesario continuar con la vigilancia.

The aim of this work was to identify seroprevalence of Trypanosoma cruzi infection in school-age children who live in localities from Salta and Chaco. This work was conducted in the following schools: 44 located in Salta city, 10 in La Unión, 7 in Taco Pozo, and several in rural spots around San Carlos town. The design was cross-sectional and the samples were taken by capillary punction with Serokit equipment. Seropositive cases were confirmed by HAI and ELISA performed on serum obtained by venous punction. Confirmed seropositive cases were treated with Benznidazol® for 60 days in doses of 5-7 mg/kg/day. Tables with absolute and relative frequencies were made for statistical analysis. It resulted that the number of school-aged children analyzed was 17,884, 159 being seropositive. The highest seroprevalence was detected in La Unión and the lowest in Salta city. Treatment was given to 93 children (71.54%) from Salta city, while every child was treated in rural areas. Infections in mothers was vector-borne mainly (64.47%). It can be concluded that even though seroprevalence was lower in the city of Salta than in rural areas, it is important to continue monitoring for Chagas disease.

O objetivo do trabalho consistiu em identificar a soroprevalência da infecção por Trypanosoma cruzi em crianças em idade escolar em localidades das províncias de Salta e de Chaco. O trabalho foi realizado em 44 escolas da cidade de Salta, em paragens de San Carlos; em 10 escolas de La Unión e em 7 escolas de Taco Pozo. O mesmo tem um desenho de corte transversal. Tomada de amostra: foi realizada por punção capilar com equipamentos Serokit e a confirmação dos casos soropositivos ou duvidoso por punção venosa e obtenção de soro, para realizar HAI e ELISA. Os casos soropositivos confirmados foram tratados com Benznidazole® durante 60 dias em doses de 5-7 mg/kg/dia. Para a análise estatística foram preparadas tabelas com frequências absolutas e relativas. Analisaram-se 17.884 crianças detectando 159 soropositivos, sendo a maior soroprevalência na cidade de La Unión e a menor na cidade de Salta. Aplicou-se o tratamento a 93 crianças, (71,54%) da cidade e na área rural se trataram todos os casos. A via de infecção vetorial foi a de maior predominância nas mães (64,47%). Conclui-se que embora a soroprevalência tenha sido menor na cidade de Salta do que nas áreas rurais, é necessário continuar com a vigilância.

Sibilancias recurrentes: prevalencia y factores asociados en lactantes de Buenos Aires, Argentina / Recurrent wheezing: prevalence and associated factors in infants from Buenos Aires City, Argentina

Resumen: Introducción: Los episodios de obstrucción bronquial a temprana edad constituyen un problema frecuente en pediatría. El objetivo de este estudio, además de conocer la prevalencia de sibilancias recurrentes en lactantes de Buenos Aires, fue identificar los factores asociados. Métodos: Estudio de tipo transversal realizado durante 2011 y 2012, en el Hospital de Niños Ricardo Gutiérrez, Buenos Aires, como parte del Estudio Internacional de Sibilancias en Lactantes, mediante una encuesta validada para padres de lactantes de 12 a 15 meses. Se evaluó la prevalencia de sibilancias, fundamentalmente de tipo recurrentes (tres o más episodios) y los posibles factores asociados. El análisis estadístico se realizó por prueba de χ2, prueba de Fisher y análisis de regresión logística univariada y multivariada. El nivel de significación fue de 0.05. Resultados: De 1063 lactantes, el 58.9% (intervalo de confianza (IC) 95% 55.9-61.9) presentaron al menos un episodio de sibilancia y el 26.3% (IC 95% 23.8-29.9), tres o más episodios (sibilancias recurrentes). Los factores vinculados a padecer al menos un episodio de sibilancia fueron el sexo masculino (p = 0.001), seis o más resfríos en el primer año (p < 0.0001), edad del primer resfrío < 4 meses (p < 0.0001), neumonía (p < 0.0001), tabaquismo durante el embarazo (p = 0.01). Los factores relacionados con sibilancias recurrentes fueron seis o más resfríos en el primer año de vida (p < 0.0001), tener el primer episodio de sibilancia antes del cuarto mes de vida (p < 0.0001) y sibilancias nocturnas (p < 0.0001). Conclusiones: La prevalencia de sibilancias recurrentes en Buenos Aires es alta (26.3%). Algunos de los factores asociados serían prevenibles.

Abstract: Background: The episodes of bronchial obstruction at early age constitute a frequent problem in Pediatrics. The aim of this study was to evaluate the prevalence of recurrent wheezing in infants in Buenos Aires City, as well as to identify any associated factors. Methods: Cross-sectional study performed from 2011 to 2012 in the Children Hospital Ricardo Gutiérrez, Buenos Aires City, as part of the International Study of Wheezing in Infants. A validated questionnaire was applied to parents of infants aged between 12 and 15 months. The prevalence of wheezing, mostly the recurrent episodes (three or more), and their probable associated factors were evaluated. Data were statistically analyzed with χ2, Fisher's test, binary and logistics multiple regression analysis. The significance level was 0.05. Results: Over 1063 infants, 58.9% (confidence interval (CI) 95% 55.9-61.9) presented at least one episode of wheezing and 26.3% (CI95% 23.8-29.9) three or more episodes (recurrent wheezing). Risk factors associated to wheezing were male gender (p = 0.001), six or more episodes of cold during the first year of life (p < 0.0001), age at first cold < 4 months (p < 0.0001); pneumonia (p < 0.0001) and smoking during pregnancy (tobacco) (p = 0.01). For recurrent wheezing, risk factors we considered as six or more episodes of cold during the first year of life (p < 0.0001), early (< 4 month of age) onset wheezing (p < 0.0001) and nocturnal wheezing (p < 0.0001). Conclusions: The prevalence of recurrent wheezing among infants in Buenos Aires Ciy was high (26.3%). Some identified associated factors can be preventable.

Improving access to Chagas disease diagnosis and etiologic treatment in remote rural communities of the Argentine Chaco through strengthened primary health care and broad social participation.

BACKGROUND: Rural populations in the Gran Chaco region have large prevalence rates of Trypanosoma cruzi infection and very limited access to diagnosis and treatment. We implemented an innovative strategy to bridge these gaps in 13 rural villages of Pampa del Indio held under sustained vector surveillance and control. METHODOLOGY: The non-randomized treatment program included participatory workshops, capacity strengthening of local health personnel, serodiagnosis, qualitative and quantitative PCRs, a 60-day treatment course with benznidazole and follow-up. Parents and healthcare agents were instructed on drug administration and early detection and notification of adverse drug-related reactions (ADR). Healthcare agents monitored medication adherence and ADRs at village level. PRINCIPAL FINDINGS: The seroprevalence of T. cruzi infection was 24.1% among 395 residents up to 18 years of age examined. Serodiagnostic (70%) and treatment coverage (82%) largely exceeded local historical levels. Sixty-six (85%) of 78 eligible patients completed treatment with 97% medication adherence. ADRs occurred in 32% of patients, but most were mild and manageable. Four patients showing severe or moderate ADRs required treatment withdrawal. T. cruzi DNA was detected by qPCR in 47 (76%) patients before treatment, and persistently occurred in only one patient over 20-180 days posttreatment. CONCLUSIONS AND SIGNIFICANCE: Our results demonstrate that diagnosis and treatment of T. cruzi infection in remote, impoverished rural areas can be effectively addressed through strengthened primary healthcare attention and broad social participation with adequate external support. This strategy secured high treatment coverage and adherence; effectively managed ADRs, and provided early evidence of positive therapeutic responses.

[Recurrent wheezing: prevalence and associated factors in infants from Buenos Aires City, Argentina]. / Sibilancias recurrentes: prevalencia y factores asociados en lactantes de Buenos Aires, Argentina.

BACKGROUND: The episodes of bronchial obstruction at early age constitute a frequent problem in Pediatrics. The aim of this study was to evaluate the prevalence of recurrent wheezing in infants in Buenos Aires City, as well as to identify any associated factors. METHODS: Cross-sectional study performed from 2011 to 2012 in the Children Hospital Ricardo Gutiérrez, Buenos Aires City, as part of the International Study of Wheezing in Infants. A validated questionnaire was applied to parents of infants aged between 12 and 15 months. The prevalence of wheezing, mostly the recurrent episodes (three or more), and their probable associated factors were evaluated. Data were statistically analyzed with χ2, Fisher's test, binary and logistics multiple regression analysis. The significance level was 0.05. RESULTS: Over 1063 infants, 58.9% (confidence interval (CI) 95% 55.9-61.9) presented at least one episode of wheezing and 26.3% (CI95% 23.8-29.9) three or more episodes (recurrent wheezing). Risk factors associated to wheezing were male gender (p=0.001), six or more episodes of cold during the first year of life (p <0.0001), age at first cold <4 months (p <0.0001); pneumonia (p <0.0001) and smoking during pregnancy (tobacco) (p=0.01). For recurrent wheezing, risk factors we considered as six or more episodes of cold during the first year of life (p <0.0001), early (< 4 month of age) onset wheezing (p <0.0001) and nocturnal wheezing (p <0.0001). CONCLUSIONS: The prevalence of recurrent wheezing among infants in Buenos Aires Ciy was high (26.3%). Some identified associated factors can be preventable.

Abdominal Cystic Echinococcosis Treated with Albendazole. A Pediatric Cohort Study.

INTRODUCTION: Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. OBJECTIVE: To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. POPULATION AND METHODS: Patients (0-18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10-15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. RESULTS: A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. CONCLUSION: Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention.

Utilidad del strain bidimensional longitudinal por speckle tracking en pacientes con enfermedad de Chagas-Mazza sin cardiopatía demostrada / Usefulness of two-dimensional longitudinal strain by speckle tracking in patients with Chagas disease without evident heart disease / Utilidade de strain bidimensional longitudinal por speckle tracking em pacientes com doença de Chagas sem evidência de doença cardíaca

Introducción. La enfermedad de Chagas es una causa importante de insuficiencia cardíaca y su identificación precoz puede ayudar a identificar pacientes en riesgo de progresión de la enfermedad. El strain bidimensional longitudinal (Str2D) podría ser una herramienta útil para detectar disfunción ventricular izquierda incipiente. Objetivos. Analizar si el strain puede detectar alteraciones en pacientes asintomáticos y sin patología demostrable por los métodos convencionales en la enfermedad de Chagas. Materiales y métodos. Estudio transversal de 45 pacientes menores de 65 años de zona rural con enfermedad de Chagas, sin patología demostrada frente a 33 individuos sanos (controles). En todos realizamos serología por dos métodos, examen clínico, electrocardiograma y eco-Doppler cardíaco: diámetro diastólico del ventrículo izquierdo (DDVI), área auricular izquierda (AI), fracción de eyección del ventrículo izquierdo (Fey) por Simpson, excursión sistólica del plano del anillo tricuspídeo (TAPSE), E/A mitral (E/A), E/e', S tisular (S´) de ventrículo izquierdo (VI) y ventrículo derecho (VD), Str2D de cada segmento del VI y strain global. Estadística: variables cuantitativas de distribución normal se compararon mediante test de t y cualitativas con test de chi cuadrado. Variabilidad intra e interobservador por r de Pearson y coeficiente de correlación intraclase.Resultados. Edad, sexo y eco-Doppler convencional (DDVI, Fey, AI, TAPSE, E/A, E/e') no mostraron diferencias estadísticamente significativas. El strain global y el strain de los segmentos apicales del VI evidenciaron diferencias significativas entre pacientes con enfermedad de Chagas sin cardiopatía demostrada (SCD) y controles, aunque dichos valores se encuadran dentro de rangos considerados fisiológicos. Variabilidad intraobservador del strain global (r de Pearson: 0,93 y CCI: 0,93) e interobservador (coeficiente r de Pearson 0,89 y un CCI: 0,88). Conclusiones. Los hallazgos del estudio muestran reducción significativa del strain longitudinal global y distal, compatible con un daño miocárdico incipiente en los pacientes con serología positiva para enfermedad de Chagas sin cardiopatía demostrada, hipótesis de trabajo que sólo el tiempo y un prolijo seguimiento podrán confirmar.

Introduction. Chagas disease is a major cause of heart failure and early identification may help identify patients at risk for disease progression. The two-dimensional longitudinal strain (Str2D) could be a useful tool for detecting incipient left ventricular dysfunction. Objectives. Analyze whether longitudinal dimensional strain can detect abnormalities in asymptomatic patients without demonstrable pathology by conventional methods in Chagas disease. Materials and Methods. Cross-sectional study of 45 patients under age 65 years in an endemic rural area with Chagas disease without proven pathology (non evident cardiopathy: NEC) versus 33 control patients. In all patients study was made by two serologic methods, clinical examination, electrocardiogram and Doppler ultrasound of the heart: diastolic diameter of the left ventricle (LVDD), left atrial area (LAA), left ventricle ejection fraction (Fey) by Simpson, excursion of tricuspid ring (TAPSE), E/A mitral ratio (E/A), E/e' ratio, S tissue (S') of left ventricular (LV) and right ventricular (RV), Str2D of each segment LV and global strain. Statistics: Normal distribution quantitative variables were compared using t test and qualitative variables with chi square test. Intra- and inter-observer variability for r Pearson and intra-class correlation coefficient (ICC). Results. Age, sex and conventional Doppler echocardiography (LVDD, Fey, LAA, TAPSE, E/A, E/e') showed no statistically significant differences. Global strain and strain of the apical LV segments showed significant differences between patients with Chagas disease without proven disease and their controls, although these values fall within ranges considered physiological. Intraobserver variability of global strain (Pearson's r 0.93 and ICC: 0.93) and interobserver (Pearson coefficient r of 0.89 and an ICC: 0.88). Conclusions. In a group of asymptomatic patients with Chagas disease without apparent cardiac involvement (NEC stage), the Str2D was lower compared with healthy individuals, suggesting the existence of subtle myocardial damage in these patients. Hypotheses that only time can confirm and track.

Introdução. A doença de Chagas é uma das principais causas de insuficiência cardíaca e sua identificação precoce pode ajudar a identificar pacientes com risco de progressão da doença. Strain longitudinal bidimensional (Str2D) poderia ser uma ferramenta útil para a detecção de disfunção ventricular esquerda incipiente. Objetivos. Analise se strain longitudinal dimensional pode detectar anormalidades em pacientes assintomáticos, sem patologia demonstrável por métodos convencionais na doença de Chagas. Materiais e métodos. Estudo transversal de 45 pacientes com idade inferior a 65 anos em uma área rural endêmica de doença de Chagas sem comprovada patologia (cardiopatia não evidente: CNE) versus 33 pacientes do grupo controle. Em todos os pacientes do estudo foi feita por dois métodos sorológicos, exame clínico, eletrocardiograma e ultrasom Doppler do coração: diâmetro diastólico do ventrículo esquerdo (DDVE), área do átrio esquerdo (AE), fração de ejeção do ventrículo esquerdo (Fey) por Simpson, excursão de anel tricúspide (TAPSE), relação E/A mitral (E/A), E/e' ratio, S tecido (S') do ventrículo esquerdo (VE) e do ventrículo direito (VD), Str2D de cada segmento VI e strain geral. Estatística: variáveis quantitativas de distribuição normal foram comparadas pelo teste t e qualitativa com o teste qui-quadrado. Variabilidade intra e interobservador para r Pearson e coeficiente de correlação intraclasse (CCI). Resultados. Idade, sexo e ecocardiograma Doppler convencional (DDVI, Fey, AE, TAPSE, E/A, E/e') não mostraram diferenças estatisticamente significativas. Strain global e strain dos segmentos do VE apicais apresentaram diferenças significativas entre os pacientes com doença de Chagas sem doença comprovada e seus controles; embora estes valores caem dentro da faixa considerada fisiológica. Variabilidade intra-observador da strain global (r de Pearson: 0,93 e CCI: 0,93) e inter-observador (coeficiente r de Pearson 0,89 e um CCI: 0,88). Conclusões. Os resultados deste estudo poderiam mostrar uma lesão miocárdica incipiente em pacientes com sorologia positiva para doença de Chagas sem cardiopatia demonstrada. A hipótese de trabalho de que só o tempo e um longo seguimento irão confirmar.