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.

Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe -/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Potential effect of methanol leaf extracts from three Podocarpus species on experimental cryptosporidiosis

@#Cryptosporidiosis causes diarrhea in both immunocompetent and immunocompromised individuals, with acute manifestations occurring particularly in children and the elderly. Up till now, there is no curative therapy for cryptosporidiosis, so discovery of new classes of drugs are of great importance. This study aimed to examine the effect of methanol leaves extracts of the three Podocarpus species; P. macrophyllus (Thunb.), P. gracilior (Pilg.) and P. elongatus (Aiton) L’ Hér. ex Pers and their combination on Cryptosporidium parvum (C. parvum) in experimentally infected mice in comparison with the commercially used drug, Nitazoxanide. As well as spectrophotometric estimation of the total phenolic and flavonoid content of these extracts was done. Results revealed that treatment with these three Podocarpus extracts and their combination showed a significant reduction of the number of C. parvum oocyst shed in the stool of infected mice compared to infected control group and Nitazoxanideinfected treated group at P < 0.001. The combination of the three Podocarpus extracts was the most effective treatment showing the lowest number of oocysts shedding in comparison with other used extracts and Nitazoxanide. Histopathological inspection of sections from ilium and colon displayed signs of improvement after treatment with P. macrophyllus and P. gracilior extracts and more remarkable improvement when the three extracts were combined. It was concluded that the three Podocarpus species extracts used in this study had a promising anti-Cryptosporidium activity especially when they were combined.

Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide

ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women.

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.

Nitazoxanida para o tratamento de COVID-19 / Nitazoxanide for or COVID-19 treatment

CONTEXTO: A COVID-19 é uma pandemia de risco muito alto a nível global pela OMS. Até o momento não existem terapias específicas, embora diferentes tratamentos estejam em investigação. Mais recentemente, tem havido crescente interesse no uso da nitazoxanida no tratamento de COVID-19, dada sua atividade antiviral de amplo espectro. OBJETIVOS: Identificar, avaliar sistematicamente e sumarizar as melhores evidências científicas disponíveis sobre a eficácia e a segurança da nitazoxanida para COVID-19. MÉTODOS: Revisão sistemática rápida (rapid review methodology). RESULTADOS: Após o processo de seleção, foram avaliados cinco estudos clínicos em andamento. CONCLUSÃO: Cinco estudos com o objetivo de avaliar a eficácia e segurança da nitazoxanida no tratamento de COVID-19 estão em andamento. Devido à ausência de evidência sobre o uso deste medicamento para o tratamento de infecções por coronavírus que causem infecções respiratórias, não é possível recomendar seu uso como terapia para COVID-19.(AU)

Research on the synthesis of nitazoxanide / 国际药学研究杂志

Objective: To optimize the synthesis process of nitazoxanide. Methods: Acetylsalicylic acid was used as raw material and thionyl chloride as acyl chloride reagent to produce acetylsalicylic chloride. Then the prepared intermediate was reacted with 2-amino-5-nitrothiazole to obtain the target compound. The crude product was initially purified by a mixed solution of ethyl acetate and water, and then decolorized by activated carbon. Results: The structure of target compound was confirmed by MS, 1H NMR and 13C NMR. The total yield was 53.9%. The purity by HPLC was 99.83%, higher than the values of 92.8% to 99.5% in the literature, and the contents of two impurities were 0.09% and 0.08%, respectively. Conclusion: The optimized process is of low cost and simple postprocessing operation, and the quality of the final product meets the requirements of pharmaceutical production. Therefore it is suitable for industrial production.

Comparative Evaluation of Various Treatment Modalities in Treating Diarrhoea Patients at a Tertiary Care Teaching Hospital

Background: Diarrhoea is described as three or more loose orwatery stools a day. Infection commonly causes acuteDiarrhoea. Noninfectious etiologies are more common as theduration of Diarrhoea becomes chronic. Hence; under the lightof above mentioned data, we planned the present study assessand compare the efficacy of various treatment modalities in theTreating diarrhoea patients.Materials & Methods: A total of 160 patients with diarrhoeawere included in the present study. All the patients werebroadly divided into four study groups with 40 patients in eachgroup: group 1- patients who were given Nitazoxanide therapywhile group 2- included patients who were given metronidazoletherapy, group 3- patients who were given cefixime therapy,and group 4 – patients who were given norfloxacin therapy.Stool samples were obtained from patients of both the studygroups for assessing the effectiveness of treatment therapy.Both clinical and microbiological success was recorded. All theresults were recorded and analysed by SPSS software.Results: Clinical success was recorded in 95 percent of thepatients of group 1 and it was recorded in 97.5 percent ofthe patients of group 2. Microbiological and clinical successamong subjects of group 3 was 90 percent and 92.5 percentrespectively. Microbiological and clinical success amongsubjects of group 4 was 92.5 percent and 92.5 percentrespectively. Non-significant results were obtained whilecomparing the efficacy of both the antibiotics in treatingdiarrhoea patients.Conclusion: All the antibiotics can be used with equal efficacyin treating diarrhoea patients.

Introducing nitazoxanide as a promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in clinical isolates

OBJECTIVE@#To identify the frequencies (F) of ferredoxin and nitroreductase mutations on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazole-resistant giardiasis.@*METHODS@#Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran. DNAs were extracted and amplified by targeting ferredoxin and GlNR genes. The amplicons were directly sequenced to determine gene mutations.@*RESULTS@#The various amino acid substitutions (F: 20%, Haplotype diversity: 0.891, Tajima's D: -0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates. Only two haplotypes (F: 5%, HD: 0.345; Tajima's D: 0.77815) characterized in metronidazole-resistant isolates of GlNR, however, no point mutations was found in symptomatic isolates.@*CONCLUSIONS@#Non-synonymous mutations of ferredoxin oxidoreductase gene reduce translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression and its activity. This leads to decrease in metronidazole drug delivery into the cells. Mutations in these isolates may lead to their resistance to metronidazole. No to low synonymous mutations of GlNR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.

Introducing nitazoxanide as a promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in clinical isolates

Objective To identify the frequencies (F) of ferredoxin and nitroreductase mutations on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazole-resistant giardiasis. Methods Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran. DNAs were extracted and amplified by targeting ferredoxin and GlNR genes. The amplicons were directly sequenced to determine gene mutations. Results The various amino acid substitutions (F: 20%, Haplotype diversity: 0.891, Tajima's D: −0.440 13) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates. Only two haplotypes (F: 5%, HD: 0.345; Tajima's D: 0.778 15) characterized in metronidazole-resistant isolates of GlNR, however, no point mutations was found in symptomatic isolates. Conclusions Non-synonymous mutations of ferredoxin oxidoreductase gene reduce translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression and its activity. This leads to decrease in metronidazole drug delivery into the cells. Mutations in these isolates may lead to their resistance to metronidazole. No to low synonymous mutations of GlNR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.

Efficacy of nitazoxanide against toxocara canis: larval recovery and humoral immune response in experimentally infected mice / Eficácia da nitazoxanida contra Toxocara canis: recuperação larvária e resposta imune humoral em camundongos experimentalmente infectados

SUMMARYThe efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

RESUMOFoi investigada a eficácia da nitazoxanida (NTZ) na toxocaríase murina experimental e os resultados comparados com os obtidos usando mebendazol (MBZ). Sessenta camundongos BALB/c machos, com idade entre seis e oito semanas foram divididos em grupos de 10 cada, 50 foram infectados oralmente com 300 ovos larvados de T. canise agrupados a seguir: GI: camundongos infectados não tratados; GII: camundongos infectados tratados com MBZ (15 mg/kg/dia) 10 dias pós-infecção (dpi); GIII: camundongos infectados tratados com NTZ (20 mg/kg/dia) 10 dpi, GIV: camundongos infectados tratados com MBZ 60 dpi; GV: camundongos infectados tratados com NTZ 60 dpi; GVI: controle não infectado. Os camundongos foram sangrados via plexo retro orbitário em quatro ocasiões entre o 30º e 120º dpi. Os soros foram processados pela técnica de ELISA para detecção de anticorpos IgG anti- Toxocara.Aos 120 dpi, os animais foram sacrificados para a recuperação larvária do SNC, fígado, pulmões, rins, olhos e carcaça. Os resultados mostraram níveis similares de anticorpos IgG anti- Toxocaraentre os camundongos infectados mas não submetidos a tratamento e os grupos infectados e tratados com MBZ ou NTZ, aos 10 e 60 dpi. Os valores da recuperação larval foram similares nos grupos tratados com NTZ e MBZ 10 dpi. MBZ mostrou melhor eficácia aos 60 dpi, com redução de 72,6% da carga parasitária comparada com NTZ, que mostrou redução somente de 46,5%. Concluímos que a administração destes anti-helmínticos não modificou a resposta humoral na infecção experimental por T. canis. Não foi observada cura parasitológica com nenhuma das drogas; porém maior redução na carga parasitária foi obtida após o tratamento com MBZ.

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.

Voltammetric quantitation of nitazoxanide by glassy carbon electrode / 药物分析学报

The present study reports voltammetric reduction of nitazoxanide in Britton-Robinson (B-R) buffer by cyclic and square-wave voltammetry at glassy carbon electrode. A versatile fully validated voltammetric method for quantitative determination of nitazoxanide in pharmaceutical formulation has been proposed. A squrewave peak current was linear over the nitazoxanide concentration in the range of 20-140 mg/mL. The limit of detection (LOD) and limit of quantification (LOQ) was calculated to be 5.23μg/mL and 17.45μg/mL, respectively.

Validated stability indicating methods for determination of nitazoxanide in presence of its degradation products / 药物分析学报

Three sensitive,selective and reproducible stability-indicating methods are presented for determination of nitazoxanide (NTZ),a new anti-protozoal drug,in presence of its degradation products.Method A utilizes the first derivative of ratio spectra spectrophotometry by measurement of the amplitude at 364.4 nm using one of the degradation products as a divisor.Method B is a chemometric-assisted spectrophotometry,where principal component regression (PCR) and partial least squares (PLS) were applied.These two approaches were successfully applied to quantify NTZ in presence of degradation products using the information included in the absorption spectra in the range 260-360 nm.Method C is based on the separation of NTZ from its degradation products followed by densitometric measurement of the bands at 254 nm.The separation was carried out on silica gel 60F254,using chloroform-methanol-ammonia solution-glacial acetic acid (95∶5∶1∶1 by volume,pH=5.80) as a developing system.These methods are suitable as stability-indicating methods for the determination of NTZ in presence of its degradation products either in bulk powder or in pharmaceutical formulations.Statistical analysis of the results has been carried out revealing high accuracy and good precision.

The therapeutic effect of Nitazoxanide on the dogs infected with Giardia canis / 中国兽医学报

To observe the therapeutic effect of Nitazoxanide(NTZ) on dogs infected with Giardia canis trophozoites.Eight dogs were infected with Giardia canis trophozoites and divided into four groups rondomly,G1:2 dogs treated with Nitazoxanide at a single dose of 1 mg/kg body weight;G2:2 dogs treated with NTZ at a single dose of 2 mg/kg;G3:2 dogs treated with NTZ at a single dose of 41 mg/kg;G4:2 dogs treated without drugs as control.All groups were examined for Giardia canis cysts by Zinc Sulfate Flotation.Each group was subjected to collect stool per day and counted cysts.The results of G2 and G3 were negative after 1th day.G1 were negative after 4th days.The results indicated that NTZ at a dose of 2 mg/kg and 4 mg/kg in dogs had a faourable effect on the dogs infected with Giardia canis.