In vitro anthelmintic activity of nitazoxanide in comparison to praziquantel against Eurytrema coelomaticum / Atividade anti-helmíntica in vitro de nitazoxanida em comparação com praziquantel contra Eurytrema coelomaticum

ABSTRACT: Eurytrema coelomaticum are trematodes that parasitize cattle, buffaloes, goats, sheep, and camelids, and, accidentally, humans and cats. The affected animal usually has a subclinical pancreatic disease, but the damage caused to health and animal production is underestimated. Currently, praziquantel is the unique drug proven effective against this parasite, but no formulations containing this drug are available for ruminants in Brazilian market. The objective of the present study was to separately evaluate in vitro anthelmintic activity of praziquantel (PZQ) and nitazoxanide (NTZ) against E. coelomaticum by assessing motility after 3, 12, and, 15 hours of incubation and subsequent histopathological examination of the parasites. E. coelomaticum specimens were obtained from the pancreas of naturally infected cattle, collected from animals slaughtered in the city of Concordia-SC, Brazil. The specimens were incubated in plates with a culture medium (n = 60 per group), with 80µg/ml of PZQ (positive control group), or 61,5µg/ml of NTZ (treated group), or UNT (untreated control). After 12 hours of incubation all parasites of the NTZ and PZQ groups were motionless or dead, while in the negative control group, 91.67% (55/60) presented normal motility after 15 hours of incubation (P < 0.001). Histopathological examination showed severe damage in vitellogenic gland, intestine, parenchyma, integument, and testicle in both treated and positive control groups. It was concluded that PZQ and NTZ showed in vitro anthelmintic action against the parasite Eurytrema coelomaticum, as they caused significant lesions in the evaluated organs and reduced the parasite's motility.

RESUMO: Eurytrema coelomaticum são trematódeos que parasitam bovinos, bubalinos, caprinos, ovinos e camelídeos, e de forma acidental, humanos e felinos. O animal acometido geralmente apresenta doença pancreática subclínica, mas os danos causados à saúde e produção animal são subestimados. Atualmente, o praziquantel é o único medicamento comprovadamente eficaz contra este parasita, mas não há formulações contendo esse medicamento disponíveis para ruminantes no mercado brasileiro. O objetivo deste trabalho foi avaliar separadamente a atividade anti-helmíntica in vitro de praziquantel (PZQ) e nitazoxanida (NTZ) frente ao E. coelomaticum pela avaliação de motilidade após três, 12 e 15 horas de incubação e posterior exame histopatológico dos parasitos. Exemplares de E. coelomaticum foram obtidos do pâncreas de bovinos naturalmente infectados, coletados em animais abatidos na cidade de Concórdia, SC, Brasil. Incubados em placas com meio de cultura (n = 60 por grupo), adicionados de 80µg/ml de PZQ (grupo controle positivo) ou 61,5µg/ml de NTZ (grupo tratado) ou UNT (grupo controle sem tratamento). Em 12h de incubação todos os parasitos dos grupos NTZ e PZQ estavam imóveis ou mortos, enquanto no grupo controle negativo 91,67% (55/60) apresentaram motilidade normal após 15h de incubação (P < 0.001). Por exame histopatológico observou-se danos graves em glândula vitelogênica, intestino, parênquima, tegumento e testículo em ambos os grupos tratado e controle positivo. Concluiu-se que PZQ e NTZ apresentaram ação anti-helmíntica in vitro contra o parasito Eurytrema coelomaticum, pois causaram lesões significativas nos órgãos avaliados e diminuíram a motilidade do parasito.

In vitro anthelmintic activity of nitazoxanide in comparison to praziquantel against Eurytrema coelomaticum / Atividade anti-helmíntica in vitro de nitazoxanida em comparação com praziquantel contra Eurytrema coelomaticum

Eurytrema coelomaticum are trematodes that parasitize cattle, buffaloes, goats, sheep, and camelids, and, accidentally, humans and cats. The affected animal usually has a subclinical pancreatic disease, but the damage caused to health and animal production is underestimated. Currently, praziquantel is the unique drug proven effective against this parasite, but no formulations containing this drug are available for ruminants in Brazilian market. The objective of the present study was to separately evaluate in vitro anthelmintic activity of praziquantel (PZQ) and nitazoxanide (NTZ) against E. coelomaticum by assessing motility after 3, 12, and, 15 hours of incubation and subsequent histopathological examination of the parasites. E. coelomaticum specimens were obtained from the pancreas of naturally infected cattle, collected from animals slaughtered in the city of Concordia-SC, Brazil. The specimens were incubated in plates with a culture medium (n = 60 per group), with 80µg/ml of PZQ (positive control group), or 61,5µg/ml of NTZ (treated group), or UNT (untreated control). After 12 hours of incubation all parasites of the NTZ and PZQ groups were motionless or dead, while in the negative control group, 91.67% (55/60) presented normal motility after 15 hours of incubation (P < 0.001). Histopathological examination showed severe damage in vitellogenic gland, intestine, parenchyma, integument, and testicle in both treated and positive control groups. It was concluded that PZQ and NTZ showed in vitro anthelmintic action against the parasite Eurytrema coelomaticum, as they caused significant lesions in the evaluated organs and reduced the parasite's motility.

Eurytrema coelomaticum são trematódeos que parasitam bovinos, bubalinos, caprinos, ovinos e camelídeos, e de forma acidental, humanos e felinos. O animal acometido geralmente apresenta doença pancreática subclínica, mas os danos causados à saúde e produção animal são subestimados. Atualmente, o praziquantel é o único medicamento comprovadamente eficaz contra este parasita, mas não há formulações contendo esse medicamento disponíveis para ruminantes no mercado brasileiro. O objetivo deste trabalho foi avaliar separadamente a atividade anti-helmíntica in vitro de praziquantel (PZQ) e nitazoxanida (NTZ) frente ao E. coelomaticum pela avaliação de motilidade após três, 12 e 15 horas de incubação e posterior exame histopatológico dos parasitos. Exemplares de E. coelomaticum foram obtidos do pâncreas de bovinos naturalmente infectados, coletados em animais abatidos na cidade de Concórdia, SC, Brasil. Incubados em placas com meio de cultura (n = 60 por grupo), adicionados de 80µg/ml de PZQ (grupo controle positivo) ou 61,5µg/ml de NTZ (grupo tratado) ou UNT (grupo controle sem tratamento). Em 12h de incubação todos os parasitos dos grupos NTZ e PZQ estavam imóveis ou mortos, enquanto no grupo controle negativo 91,67% (55/60) apresentaram motilidade normal após 15h de incubação (P < 0.001). Por exame histopatológico observou-se danos graves em glândula vitelogênica, intestino, parênquima, tegumento e testículo em ambos os grupos tratado e controle positivo. Concluiu-se que PZQ e NTZ apresentaram ação anti-helmíntica in vitro contra o parasito Eurytrema coelomaticum, pois causaram lesões significativas nos órgãos avaliados e diminuíram a motilidade do parasito.

Eficacia y tolerabilidad de Nitazoxanida para parasitismo intestinal en escolares atendidos en el Centro de Salud de la Universidad del Quindío / Efficacy and tolerability of Nitazoxanide for intestinal parasitism in schoolchildren treated at the Health Center of the University of Quindío

Resumen Objetivo: Describir la efectividad del tratamiento antiparasitario intestinal brindado a niños de cuatro a nueve años atendidos en el centro de Salud de la Universidad del Quindío entre Julio de 2017 a marzo de 2018. Materiales y métodos: Estudio observacional prospectivo. Se extrajeron datos de historias clínicas de pacientes con rango de edad de 4 a 9 años, quienes consultaron en el Centro de Salud de la Universidad del Quindío y se diagnosticaron mediante coprológico con blastocistosis o giardiasis. Se seleccionaron las historias cuyo tratamiento fuese Nitazoxanida y tuviesen un coprológico control postratamiento. Se presentan estadísticas descriptivas; porcentaje de eficacia y tolerabilidad. Resultados: De 15 niños tratados con Nitazoxanida, respondieron al tratamiento 10, en quienes no se hallaron parásitos en el coprológico control. Con una eficacia del 83,3% (IC95% 60 - 100) en blastocistosis, 57,1% (IC95% 32 - 82%) en giardiasis. Conclusión: Se evidenciaron resultados porcentuales similares a los reportados en la literatura, siendo más eficaz en blastocisotisis que en giardiasis.

Abstract Objective: To describe the effectiveness of the intestinal antiparasitic treatment given to children ranging between 4 and 9 years old that were attended in the Health Center of the University of Quindío in the period of July 2017 and March 2018. Materials and methods: Prospective observational study. Data were extracted from medical records of patients with an age range of 4 to 9 years, who consulted at the Health Center of the University of Quindío and were diagnosed through coprological tests with Blastocystis and Giardiasis. The clinical records were selected by whose treatment was done with Nitazoxanide or Albendazole with coprological results of post-treatment check-up. Descriptive statistics are presented along with percentage of efficacy and tolerability. Results: From 15 children treated with Nitazoxanide, 10 responded to the treatment, who presented no parasites in the coprological check-up. The remaining population presented some type of parasitic infection (n = 5). With an efficiency of 83,3% (IC95% 32 - 82%) in blastocystis, and 57,1% (IC95% 32 - 82%) in giardiasis. Conclusion: Percentage results similar to those reported in the literature were evidenced, being more effective in blastocystis than in giardiasis.

Guía de manejo clínico del paciente con infección por SARS-CoV-2 / Guidelines for clinical management of SARS-Cov-2 infection

Resumen En infección por SARS-CoV-2 (COVID-19), las manifestaciones más comunes son las de vías aéreas superiores; en casos complicados se presenta neumonía intersticial bilateral, insuficiencia respiratoria aguda grave y falla orgánica múltiple que ameritan tratamiento hospitalario y soporte ventilatorio por puntas nasales o mascarilla, así como oxígeno con flujo a presión alta o intubación orotraqueal y ventilación mecánica. No hay antivirales específicos por lo que el manejo es sintomático, así como con antiplaquetarios (ácido acetilsalicílico, dipiridamol), heparina de bajo peso molecular ante hipercoagulabilidad (dímero D aumentado), dexametasona ante indicadores altos de inflamación. Previo consentimiento informado, experimentalmente se emplean antibióticos según los resultados microbiológicos, interferón beta 1b, favipiravir, tocilizumab, ivermectina e inmunoglobulina G. Cuando se presenta gastroenteritis se puede indicar nitazoxanida.

Abstract In SARS-CoV-2 infection (COVID-19), the most common manifestations involve the upper airways; in complicated cases, bilateral interstitial pneumonia, severe acute respiratory failure and multiple organ failure occur, which require hospital treatment and ventilatory support with nasal cannula or mask and high flow oxygen, or orotracheal intubation and mechanical ventilation. There are no specific antivirals, and thus management is symptomatic, as well as with antiplatelet drugs (acetylsalicylic acid, dipyridamole), low molecular weight heparin when there is hypercoagulability (increased D-dimer), dexamethasone when inflammation indicators are elevated; experimentally, under informed consent, antibiotics are used according to microbiological results, as well as interferon beta 1b, favipiravir, tocilizumab, ivermectin and immunoglobulin G. When gastroenteritis occurs, nitazoxanide can be indicated.

Guidelines for clinical management of SARS-CoV-2 infection.

In SARS-CoV-2 infection (COVID-19), the most common manifestations involve the upper airways; in complicated cases, bilateral interstitial pneumonia, severe acute respiratory failure and multiple organ failure occur, which require hospital treatment and ventilatory support with nasal cannula or mask and high flow oxygen, or orotracheal intubation and mechanical ventilation. There are no specific antivirals, and thus management is symptomatic, as well as with antiplatelet drugs (acetylsalicylic acid, dipyridamole), low molecular weight heparin when there is hypercoagulability (increased D-dimer), dexamethasone when inflammation indicators are elevated; experimentally, under informed consent, antibiotics are used according to microbiological results, as well as interferon beta 1b, favipiravir, tocilizumab, ivermectin and immunoglobulin G. When gastroenteritis occurs, nitazoxanide can be indicated.En infección por SARS-CoV-2 (COVID-19), las manifestaciones más comunes son las de vías aéreas superiores; en casos complicados se presenta neumonía intersticial bilateral, insuficiencia respiratoria aguda grave y falla orgánica múltiple que ameritan tratamiento hospitalario y soporte ventilatorio por puntas nasales o mascarilla, así como oxígeno con flujo a presión alta o intubación orotraqueal y ventilación mecánica. No hay antivirales específicos por lo que el manejo es sintomático, así como con antiplaquetarios (ácido acetilsalicílico, dipiridamol), heparina de bajo peso molecular ante hipercoagulabilidad (dímero D aumentado), dexametasona ante indicadores altos de inflamación. Previo consentimiento informado, experimentalmente se emplean antibióticos según los resultados microbiológicos, interferón beta 1b, favipiravir, tocilizumab, ivermectina e inmunoglobulina G. Cuando se presenta gastroenteritis se puede indicar nitazoxanida.

Uso de la nitazoxanida en el tratamiento de niños infectados con Giardia Lamblia / USE OF NITAZOXANIDE IN THE TREATMENT OF CHILDREN INFECTED WITH GIARDIA LAMBLIA

Introducción: La nitazoxanida es una nueva droga que ha mostrado ser útil contra diversos protozoarios intestinales in­cluyendo Giardia lamblia. Sin embargo, hay pocos trabajos al respecto a nivel nacional y regional. Se realizó un estudio para comprobar la utilidad terapéutica de la nitazoxanida en niños infectados con G. lamblia, habitantes de Ciudad Bolívar, estado Bolívar. Pacientes y métodos: Se diagnos­ticaron y seleccionaron 21 casos de niños parasitados con G. lamblia y fueron tratados con nitazoxanida, después se realizaron 3 controles post-tratamiento a los 7, 15 y 21 días mediante los métodos coproparasitólogicos de examen direc­to, Kato y sedimentación espontánea. Resultados: El por­centaje global de cura parasitológica fue de 37,5% (6/16) constituidos por 6 niños en quienes se erradicó el parásito posterior al tratamiento. De este análisis se excluyeron 5 niños de los 21 tratados debido a que no acudieron a uno o más controles post-tratamiento. Ninguno de los niños que recibie­ron el tratamiento con nitazoxanida presentó efectos adversos. Conclusión: En el grupo estudiado y debido a su bajo por­centaje de cura parasitológica, la nitazoxanida no parece ser la droga de elección y su uso debería reservarse en casos de falla terapéutica del metronidazol o cuando exista intolerancia a esta droga.

Introduction: Nitazoxanide is a new drug that has shown to be helpful against various intestinal protozoa including Giar­dia lamblia. However, there are few studies on the subject at national and regional scopes. A study was conducted to test the therapeutic utility of nitazoxanide in children infected with G. lamblia, citizens of Ciudad Bolívar, Bolívar state. Pa­tients and methods: Were diagnosed and selected 21 cases of children parasitized G. lamblia and they were treated with nitazoxanide, then 3 post-treatment controls at 7, 15 and 21 days using the methods of direct parasitological examina­tion, Kato and spontaneous sedimentation were performed. Results: The overall percentage of parasitological cure was 37.5 % (6/16) consisting of 6 children in whom posttreatment parasite was eradicated. From this analysis, 5 of the 21 trea­ted children were excluded because they did not attended one or more post- treatment controls. None of the children who received treatment with nitazoxanide presented adverse effects. Conclusion: In the group studied, and due to their low percentage of parasitological cure, nitazoxanide not ap­pear to be the drug of choice and should be reserved for use in cases of therapeutic failure or when there is intolerance to metronidazole.