RESUMO
[This corrects the article DOI: 10.1016/j.eclinm.2021.100959.].
RESUMO
BACKGROUND: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. METHODS: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. FINDINGS: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. INTERPRETATION: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. FUNDING: This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.
RESUMO
BACKGROUND: On an absolute basis, Argentina is the country with the largest affected population with Chagas Disease (ChD). This constitutes a significant public health issue. As a consequence of Argentina's migratory patterns, there has been a significant increase of affected population in urban centers. An innovative project for early diagnosis and timely treatment of ChD was designed for Municipal Primary Care Facilities of La Plata City, a non- endemic area, in line with a proposal from the Pan-American Health Organization. The project was a public -private intervention. The objectives of this study were to demonstrate the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD; to design and implement a tailor made program and to innovate in a public-private association. METHODS: The healthcare barriers for early diagnosis and timely treatment for the population with ChD of La Plata were analyzed. The four dimensions described by Peters et al. (Ann N Y Acad Sci 1136:161-71, 2008) were used. The baseline was measured during a previous pilot project and the same items were evaluated at the end of 2017. The model from Damschroder et al. (Implement Sci 4:50, 2009) was used during the implementation process. RESULTS: With all the information gathered during this investigation, a "patient-centered" model was designed. During the program, 17,894 people were serologically tested for ChD, 1,394 were positive and 1,035 were treated. Additionally, 3,750 children from 46 public schools were evaluated for risk factors of ChD. CONCLUSIONS: This project showed the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD. Tailor made programs and public-private associations should be considered for vulnerable populations in emerging economies in order to enhance efforts and obtain better results. This program may be replicated in other countries of Latin America were Chagas is a main public health issue and, with the corresponding adaptations, for other neglected diseases as well.
Assuntos
Doença de Chagas/diagnóstico , Atenção Primária à Saúde/métodos , Saúde Pública/métodos , Parcerias Público-Privadas , Adolescente , Adulto , Argentina/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/terapia , Criança , Diagnóstico Precoce , Estudos de Viabilidade , Feminino , Implementação de Plano de Saúde , Humanos , Masculino , Projetos Piloto , Fatores de Risco , Instituições Acadêmicas , Tempo para o Tratamento , População Urbana , Adulto JovemRESUMO
[ABSTRACT]. This study evaluated and compared follow-up and adverse drug reaction (ADR) reporting for Chagas disease (CD) patients treated with benznidazole (BZN) by two health teams with different levels of experience, using medical records for 204 patients participating in the first year of a scaled-up public health program for CD case detection and treatment conducted at all 46 primary health care centers in La Plata district, Buenos Aires, Argentina, in 2014. Both teams were experienced in CD patient management and trained in BZN administration, and included senior physicians, but one team had no experience in administering BZN while the other team had three years of experience due to their participation in the program’s pilot project. Patients with positive serology for CD were treated with 5 mg/kg/day of BZN for 60 days. Patients’ median age was 35 years and 84.3% were female. There was a statistically significant difference in the number of ADRs reported by the experienced versus the inexperienced health teams (18 versus 44 respectively; P < 0.001). Health team experience in administering BZN to CD patients, and treatment duration, were significantly associated with reporting of ADRs (adjusted odds ratios (aORs) 0.340 (95% confidence interval (CI): 0.177–0.652) and 0.967 (CI: 0.942–0.993) respectively). ADR reporting increased with patient age, occurring at the highest frequency (42.9%) in people 50+ years old. All treatment discontinuations (nine) occurred in patients followed up by the inexperienced health team. Level of experience in BZN administration to CD patients was significantly and inversely associated with frequency of ADR reports: inexperienced health team members tended to report more.
[RESUMEN]. El presente estudio evaluó y comparó el seguimiento y la notificación de reacciones adversas medicamentosas (RAM) en pacientes con enfermedad de Chagas tratados con benznidazol por dos equipos de salud con diferentes niveles de experiencia, mediante el uso de los expedientes médicos de 204 pacientes que participaron en el primer año de un programa de salud pública ampliado para la detección de casos de enfermedad de Chagas y su tratamiento, realizado en los 46 centros de atención primaria de salud del distrito de La Plata (Buenos Aires) en el 2014. Ambos equipos tenían experiencia en la atención de pacientes con enfermedad de Chagas, estaban capacitados en la administración de benznidazol e incluían médicos experimentados, pero uno de los equipos nunca había usado benznidazol, mientras que el otro tenía tres años de experiencia por su participación en el proyecto piloto del programa. Los pacientes con pruebas serológicas positivas para la enfermedad de Chagas recibieron 5 mg/kg/día de benznidazol durante 60 días. La mediana de edad de los pacientes era de 35 años y 84,3% eran mujeres. Hubo una diferencia estadísticamente significativa entre el número de reacciones adversas medicamentosas notificadas por el equipo de salud experimentado y el equipo sin experiencia (18 y 44, respectivamente; P<0.001). Tanto la experiencia de los equipos de salud en la administración de benznidazol a los pacientes con enfermedad de Chagas como la duración del tratamiento se asociaron significativamente con la notificación de reacciones adversas medicamentosas (razones de posibilidades ajustadas, 0,340; intervalo de confianza de 95% [IC]: 0,177–0,652; y 0,967, IC: 0,942–0,993, respectivamente). La notificación de reacciones adversas medicamentosas aumentó a mayor edad de los pacientes; la frecuencia máxima (42,9%) se observó en las personas mayores de 50 años. Todas las interrupciones del tratamiento (nueve) fueron en pacientes atendidos por el equipo de salud sin experiencia. El nivel de experiencia en la administración de benznidazol a los pacientes con enfermedad de Chagas mostró una asociación significativa e inversa con la frecuencia de notificación de reacciones adversas medicamentosas: los miembros del equipo de salud sin experiencia tendieron a notificar más reacciones.
[RESUMO]. Neste estudo foram analisados e comparados dados notificados de reação adversa medicamentosa e de acompanhamento de pacientes com doença de Chagas tratados com benznidazol (BZN) por dois grupos de profissionais da saúde com níveis de experiencia distintos. Os dados foram obtidos dos prontuários médicos de 204 pacientes que participaram do primeiro ano de um programa expandido de saúde pública para detecção de casos e tratamento da doença de Chagas implantado nas 46 unidades básicas de saúde do distrito de La Plata em Buenos Aires, Argentina, em 2014. Ambos os grupos eram formados por médicos mais graduados e profissionais com experiencia na conduta de pacientes com doença de Chagas e capacitados em administrar BZN, porém um dos grupos era inexperiente em administrar BZN enquanto o outro contava com experiência de três anos por ter participado do projeto-piloto do programa. Os pacientes com sorologia positiva para doença de Chagas foram tratados com 5 mg/kg/dia de BZN por 60 dias. A mediana de idade foi 35 anos e 84,3% dos pacientes eram do sexo feminino. Verificou-se uma diferença estatisticamente significativa no número de reações adversas medicamentosas notificadas pelo grupo experiente em relação ao grupo inexperiente (18 vs. 44, respectivamente; P < 0.001). Ter experiência em administrar BZN aos pacientes com doença de Chagas e a duração do tratamento foram fatores significativamente associados à notificação de reação adversa medicamentosa (razão de chances ajustada [aOR] 0,340, intervalo de confiança de 95% [IC 95%] 0,177–0,652 e aOR 0,967, IC 95% 0,942–0,993, respectivamente). A notificação de reação adversa medicamentosa aumentou de acordo com a idade do paciente, ocorrendo com maior frequência (42,9%) nos pacientes acima de 50 anos. Os 9 casos de interrupção do tratamento ocorreram em pacientes acompanhados pelo grupo inexperiente. O nível da experiência em administrar BZN aos pacientes com doença de Chagas teve uma associação significativa e inversa com a frequência de notificação de reação adversa medicamentosa: os integrantes do grupo inexperiente tenderam a notificar mais.
Assuntos
Doença de Chagas , Atenção Primária à Saúde , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Saúde Pública , Argentina , América Latina , Doença de Chagas , América Latina , Atenção Primária à Saúde , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Saúde Pública , Doença de Chagas , Atenção Primária à SaúdeRESUMO
This study evaluated and compared follow-up and adverse drug reaction (ADR) reporting for Chagas disease (CD) patients treated with benznidazole (BZN) by two health teams with different levels of experience, using medical records for 204 patients participating in the first year of a scaled-up public health program for CD case detection and treatment conducted at all 46 primary health care centers in La Plata district, Buenos Aires, Argentina, in 2014. Both teams were experienced in CD patient management and trained in BZN administration, and included senior physicians, but one team had no experience in administering BZN while the other team had three years of experience due to their participation in the program's pilot project. Patients with positive serology for CD were treated with 5 mg/kg/day of BZN for 60 days. Patients' median age was 35 years and 84.3% were female. There was a statistically significant difference in the number of ADRs reported by the experienced versus the inexperienced health teams (18 versus 44 respectively; P < 0.001). Health team experience in administering BZN to CD patients, and treatment duration, were significantly associated with reporting of ADRs (adjusted odds ratios (aORs) 0.340 (95% confidence interval (CI): 0.177-0.652) and 0.967 (CI: 0.942-0.993) respectively). ADR reporting increased with patient age, occurring at the highest frequency (42.9%) in people 50+ years old. All treatment discontinuations (nine) occurred in patients followed up by the inexperienced health team. Level of experience in BZN administration to CD patients was significantly and inversely associated with frequency of ADR reports: inexperienced health team members tended to report more.
El presente estudio evaluó y comparó el seguimiento y la notificación de reacciones adversas medicamentosas (RAM) en pacientes con enfermedad de Chagas tratados con benznidazol por dos equipos de salud con diferentes niveles de experiencia, mediante el uso de los expedientes médicos de 204 pacientes que participaron en el primer año de un programa de salud pública ampliado para la detección de casos de enfermedad de Chagas y su tratamiento, realizado en los 46 centros de atención primaria de salud del distrito de La Plata (Buenos Aires) en el 2014. Ambos equipos tenían experiencia en la atención de pacientes con enfermedad de Chagas, estaban capacitados en la administración de benznidazol e incluían médicos experimentados, pero uno de los equipos nunca había usado benznidazol, mientras que el otro tenía tres años de experiencia por su participación en el proyecto piloto del programa. Los pacientes con pruebas serológicas positivas para la enfermedad de Chagas recibieron 5 mg/kg/día de benznidazol durante 60 días. La mediana de edad de los pacientes era de 35 años y 84,3% eran mujeres. Hubo una diferencia estadísticamente significativa entre el número de reacciones adversas medicamentosas notificadas por el equipo de salud experimentado y el equipo sin experiencia (18 y 44, respectivamente; P<0.001). Tanto la experiencia de los equipos de salud en la administración de benznidazol a los pacientes con enfermedad de Chagas como la duración del tratamiento se asociaron significativamente con la notificación de reacciones adversas medicamentosas (razones de posibilidades ajustadas, 0,340; intervalo de confianza de 95% [IC]: 0,1770,652; y 0,967, IC: 0,9420,993, respectivamente). La notificación de reacciones adversas medicamentosas aumentó a mayor edad de los pacientes; la frecuencia máxima (42,9%) se observó en las personas mayores de 50 años. Todas las interrupciones del tratamiento (nueve) fueron en pacientes atendidos por el equipo de salud sin experiencia. El nivel de experiencia en la administración de benznidazol a los pacientes con enfermedad de Chagas mostró una asociación significativa e inversa con la frecuencia de notificación de reacciones adversas medicamentosas: los miembros del equipo de salud sin experiencia tendieron a notificar más reacciones.
Neste estudo foram analisados e comparados dados notificados de reação adversa medicamentosa e de acompanhamento de pacientes com doença de Chagas tratados com benznidazol (BZN) por dois grupos de profissionais da saúde com níveis de experiência distintos. Os dados foram obtidos dos prontuários médicos de 204 pacientes que participaram do primeiro ano de um programa expandido de saúde pública para detecção de casos e tratamento da doença de Chagas implantado nas 46 unidades básicas de saúde do distrito de La Plata em Buenos Aires, Argentina, em 2014. Ambos os grupos eram formados por médicos mais graduados e profissionais com experiência na conduta de pacientes com doença de Chagas e capacitados em administrar BZN, porém um dos grupos era inexperiente em administrar BZN enquanto o outro contava com experiência de três anos por ter participado do projeto-piloto do programa. Os pacientes com sorologia positiva para doença de Chagas foram tratados com 5 mg/kg/dia de BZN por 60 dias. A mediana de idade foi 35 anos e 84,3% dos pacientes eram do sexo feminino. Verificou-se uma diferença estatisticamente significativa no número de reações adversas medicamentosas notificadas pelo grupo experiente em relação ao grupo inexperiente (18 vs. 44, respectivamente; P < 0.001). Ter experiência em administrar BZN aos pacientes com doença de Chagas e a duração do tratamento foram fatores significativamente associados à notificação de reação adversa medicamentosa (razão de chances ajustada [aOR] 0,340, intervalo de confiança de 95% [IC 95%] 0,1770,652 e aOR 0,967, IC 95% 0,9420,993, respectivamente). A notificação de reação adversa medicamentosa aumentou de acordo com a idade do paciente, ocorrendo com maior frequência (42,9%) nos pacientes acima de 50 anos. Os 9 casos de interrupção do tratamento ocorreram em pacientes acompanhados pelo grupo inexperiente. O nível da experiência em administrar BZN aos pacientes com doença de Chagas teve uma associação significativa e inversa com a frequência de notificação de reação adversa medicamentosa: os integrantes do grupo inexperiente tenderam a notificar mais.
RESUMO
ABSTRACT This study evaluated and compared follow-up and adverse drug reaction (ADR) reporting for Chagas disease (CD) patients treated with benznidazole (BZN) by two health teams with different levels of experience, using medical records for 204 patients participating in the first year of a scaled-up public health program for CD case detection and treatment conducted at all 46 primary health care centers in La Plata district, Buenos Aires, Argentina, in 2014. Both teams were experienced in CD patient management and trained in BZN administration, and included senior physicians, but one team had no experience in administering BZN while the other team had three years of experience due to their participation in the program's pilot project. Patients with positive serology for CD were treated with 5 mg/kg/day of BZN for 60 days. Patients' median age was 35 years and 84.3% were female. There was a statistically significant difference in the number of ADRs reported by the experienced versus the inexperienced health teams (18 versus 44 respectively; P < 0.001). Health team experience in administering BZN to CD patients, and treatment duration, were significantly associated with reporting of ADRs (adjusted odds ratios (aORs) 0.340 (95% confidence interval (CI): 0.177-0.652) and 0.967 (CI: 0.942-0.993) respectively). ADR reporting increased with patient age, occurring at the highest frequency (42.9%) in people 50+ years old. All treatment discontinuations (nine) occurred in patients followed up by the inexperienced health team. Level of experience in BZN administration to CD patients was significantly and inversely associated with frequency of ADR reports: inexperienced health team members tended to report more.
RESUMEN El presente estudio evaluó y comparó el seguimiento y la notificación de reacciones adversas medicamentosas (RAM) en pacientes con enfermedad de Chagas tratados con benznidazol por dos equipos de salud con diferentes niveles de experiencia, mediante el uso de los expedientes médicos de 204 pacientes que participaron en el primer año de un programa de salud pública ampliado para la detección de casos de enfermedad de Chagas y su tratamiento, realizado en los 46 centros de atención primaria de salud del distrito de La Plata (Buenos Aires) en el 2014. Ambos equipos tenían experiencia en la atención de pacientes con enfermedad de Chagas, estaban capacitados en la administración de benznidazol e incluían médicos experimentados, pero uno de los equipos nunca había usado benznidazol, mientras que el otro tenía tres años de experiencia por su participación en el proyecto piloto del programa. Los pacientes con pruebas serológicas positivas para la enfermedad de Chagas recibieron 5 mg/kg/día de benznidazol durante 60 días. La mediana de edad de los pacientes era de 35 años y 84,3% eran mujeres. Hubo una diferencia estadísticamente significativa entre el número de reacciones adversas medicamentosas notificadas por el equipo de salud experimentado y el equipo sin experiencia (18 y 44, respectivamente; P<0.001). Tanto la experiencia de los equipos de salud en la administración de benznidazol a los pacientes con enfermedad de Chagas como la duración del tratamiento se asociaron significativamente con la notificación de reacciones adversas medicamentosas (razones de posibilidades ajustadas, 0,340; intervalo de confianza de 95% [IC]: 0,177-0,652; y 0,967, IC: 0,942-0,993, respectivamente). La notificación de reacciones adversas medicamentosas aumentó a mayor edad de los pacientes; la frecuencia máxima (42,9%) se observó en las personas mayores de 50 años. Todas las interrupciones del tratamiento (nueve) fueron en pacientes atendidos por el equipo de salud sin experiencia. El nivel de experiencia en la administración de benznidazol a los pacientes con enfermedad de Chagas mostró una asociación significativa e inversa con la frecuencia de notificación de reacciones adversas medicamentosas: los miembros del equipo de salud sin experiencia tendieron a notificar más reacciones.
RESUMO Neste estudo foram analisados e comparados dados notificados de reação adversa medicamentosa e de acompanhamento de pacientes com doença de Chagas tratados com benznidazol (BZN) por dois grupos de profissionais da saúde com níveis de experiência distintos. Os dados foram obtidos dos prontuários médicos de 204 pacientes que participaram do primeiro ano de um programa expandido de saúde pública para detecção de casos e tratamento da doença de Chagas implantado nas 46 unidades básicas de saúde do distrito de La Plata em Buenos Aires, Argentina, em 2014. Ambos os grupos eram formados por médicos mais graduados e profissionais com experiência na conduta de pacientes com doença de Chagas e capacitados em administrar BZN, porém um dos grupos era inexperiente em administrar BZN enquanto o outro contava com experiência de três anos por ter participado do projeto-piloto do programa. Os pacientes com sorologia positiva para doença de Chagas foram tratados com 5 mg/kg/dia de BZN por 60 dias. A mediana de idade foi 35 anos e 84,3% dos pacientes eram do sexo feminino. Verificou-se uma diferença estatisticamente significativa no número de reações adversas medicamentosas notificadas pelo grupo experiente em relação ao grupo inexperiente (18 vs. 44, respectivamente; P < 0.001). Ter experiência em administrar BZN aos pacientes com doença de Chagas e a duração do tratamento foram fatores significativamente associados à notificação de reação adversa medicamentosa (razão de chances ajustada [aOR] 0,340, intervalo de confiança de 95% [IC 95%] 0,177-0,652 e aOR 0,967, IC 95% 0,942-0,993, respectivamente). A notificação de reação adversa medicamentosa aumentou de acordo com a idade do paciente, ocorrendo com maior frequência (42,9%) nos pacientes acima de 50 anos. Os 9 casos de interrupção do tratamento ocorreram em pacientes acompanhados pelo grupo inexperiente. O nível da experiência em administrar BZN aos pacientes com doença de Chagas teve uma associação significativa e inversa com a frequência de notificação de reação adversa medicamentosa: os integrantes do grupo inexperiente tenderam a notificar mais.
Assuntos
Humanos , Atenção Primária à Saúde/organização & administração , Doença de Chagas/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Argentina , Saúde PúblicaRESUMO
BACKGROUND: Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm. METHODOLOGY: Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed. PRINCIPAL FINDINGS: STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009). CONCLUSIONS: Hookworm' infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis.
Assuntos
Albendazol/uso terapêutico , Ancylostomatoidea , Infecções por Uncinaria/tratamento farmacológico , Ivermectina/uso terapêutico , Strongyloides stercoralis , Estrongiloidíase/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Helmínticos/uso terapêutico , Argentina/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Solo/parasitologia , Adulto JovemAssuntos
Antiprotozoários/administração & dosagem , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/administração & dosagem , Doença de Chagas/diagnóstico , Doença de Chagas/parasitologia , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Humanos , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/fisiologia , Organização Mundial da SaúdeRESUMO
Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included.