Antiparasitic and immunomodulating effects of nitazoxanide, ivermectin and selenium on Cryptosporidium infection in diabetic mice / Efeitos antiparasitários e imunomodulantes da nitazoxanida, ivermectina e selênio sobre a infecção por Cryptosporidium em camundongos diabéticos

Abstract The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

Resumo O presente trabalho tem como objetivo investigar os efeitos anti-parasitários e imunomodulantes da nitazoxanida (NTZ) e ivermectina (IVC), isoladas ou em associação, e do selênio (SE), associado à NTZ ou à IVC, sobre a infecção por Cryptosporidium em camundongos diabéticos. Os resultados revelaram que a terapia combinada com NTZ e IVC resultou em maior redução de oocistos fecais, enquanto a NTZ isolada mostrou a menor redução de oocistos fecais (63%). Além disso, a associação do SE com a NTZ ou IVC resultou em redução do número de oocistos fecais de 63% para 71% e de 82% para 84%, respectivamente. Todos os tratamentos, com exceção da monoterapia com NTZ, mostraram uma melhora significativa nos índices relacionados à histopatologia intestinal. Os resultados da imuno-histoquímica mostraram reversão da razão celular CD4/CD8 T normal nos camundongos infectados não tratados, no entanto, após a terapia, houve retorno à razão celular CD4/CD8 T normal. O tratamento combinado (NTZ+ IVC) demonstrou o mais alto nível de expressão celular CD4 T. Em conclusão, a terapia combinada com NTZ e IVC mostrou efeitos anti-parasitários e imunoestimuladores notáveis, especificamente para a população CD4, que parecem ser promissores para o controle da criptosporidiose em indivíduos diabéticos.

Criptosporidiosis intestinal en niños con HIV/SIDA / Intestinal cryptosporidiosis in HIV infected children

El Cryptosporidium parvum, protozoo parásito intracelular, infecta el epitelio gastrointestinal produciendo diarrea autolimitada en individuos inmunocompetentes pero potencialmente grave en pacientes inmunocomprometidos, especialmente en aquellos con Sida. En este trabajo se evaluó, durante un lap-so de 6 años, la incidencia de infección intestinal por C. parvum en una población pediátrica con HIV/Sida analizando las características clínicas e inmunológicas de la coinfección. Todos los pacientes iniciaron o continuaron el tratamiento antirretroviral de alta eficacia HAART durante el período de estudio, mientras que la infección intestinal fue tratada con azitromicina. La incidencia de criptosporidiosis fue de 13.7%. 33 de los 240 niños en seguimiento presentaron diarrea crónica de más de 14 días de evolución o recurrente, sin complicaciones hidroelectrolíticas. Los pacientes evaluados presentaron niveles porcentuales variables de células T CD4+ en sangre periférica, y la presencia del parásito no estuvo en relación con el compromiso inmunitario. Al momento del cuadro entérico 31 de los 33 pacientes tuvieron niveles plasmáticos de carga viral que superaban el límite de detección. Se observó eosinofilia leve o moderada en el 23% de los pacientes y la coinfección con otros parásitos fue detectada en 11 niños. No se obtuvieron diferencias significativas al relacionar el número de episodios intestinales con los estadios clínico-inmunológicos de los pacientes. La correcta implementación del HAART con la subsecuente restauración de la función inmune se relacionaría con la ausencia de cuadros diarreicos agudos y de las complicaciones hidroelectrolíticas derivadas de la coinfección con C. parvum.

Cryptosporydium parvum is an intracellular parasite that infects gastrointestinal epithelium and produces diarrhea that is self-limited in immunocompetent persons but potentially life-threatening in immunocompromised, especially those with the acquired immunodeficiency syndrome (AIDS). C. parvum enteric infection's incidence in a pediatric HIV/AIDS cohort, during a 6 years period, was studied. Clinical and immunologic characteristics of the dual infection were also recorded. Highly active antiretroviral therapy (HAART) was started or continued by all the patients during follow-up. Azithromicyn was used as antiparasitic drug. Cryptosporidiosis incidence was 13.7%; 33 out 240 children showed chronic diarrhea lasting 14 days at least, or recurrent, without dehydration and electrolytic disturbance. Peripheral blood T CD4+ percentage levels of the patients were variable and without relationship with C. parvum presence. Viral load levels in 31 out 33 patients were over cut-off at the enteric episode time. Mild or moderate eosinophilia were recorded in 23% of the patients and other intestinal parasites were present in 11 children. When the number of enteric episodes were compared with the clinical and immunological patient's status, not significant differences were recorded. HAART is the best treatment to improve immune function in HIV patients avoiding potentially fatal complications that accompany acute diarrhea during concomitant infection with C. parvum.

AIDS-associated diarrhea and wasting in northeast Brazil is associated with subtherapeutic plasma levels of antiretroviral medications and with both bovine and human subtypes of Cryptosporidium parvum

Advanced HIV infection is frequently complicated by diarrhea, disruption of bowel structure and function, and malnutrition. Resulting malabsorption of or pharmacokinetic changes in antiretroviral agents might lead to subtherapeutic drug dosing and treatment failure in individual patients, and could require dose adjustment and/or dietary supplements during periods of diarrheal illness. We determined the plasma levels of antiretroviral medications in patients that had already been started on medication by their physicians in an urban infectious diseases hospital in northeast Brazil. We also obtained blood samples from patients hospitalized for diarrhea or AIDS-associated wasting, and we found reduced stavudine and didanosine levels in comparison with outpatients without diarrhea or wasting who had been treated at the same hospital clinic. There was a predominance of the protozoal pathogens Cryptosporidium and Isospora belli, typical opportunistic pathogens of AIDS-infected humans, in the stool samples of inpatients with diarrhea. We conclude that severe diarrhea and wasting in this population is associated with both protozoal pathogens and subtherapeutic levels of antiretroviral medications

Cyclospora cayetanensis in sputum and stool samples

We report the observation of acid-fast Cyclospora cayetanensis oocysts in a sputum sample. The patient, a 60 year-old, HIV negative man, was successfully treated for pulmonary tuberculosis during 1997. On February 1998, he was admitted to our center due to loss of weight, cough with purulent expectoration, dysphonia and a radiological picture of pulmonary fibrosis. Bacilloscopic study of sputum (negative for acid-fast bacilli) stained with Ziehl-Neelsen technique showed large (8-10 µm) spherical, acid-fast Cyclospora cayetanensis oocysts. No other pathogens were isolated on cultures from this sample or from laryngeal biopsy. Serial parasitologic studies showed C. cayetanensis and also eggs of Trichuris trichiura, Ascaris lumbricoides and Hymenolepis nana and of Entamoeba coli cysts. The patient lives in the outskirts of Buenos Aires in a brick-made house with potable water and works as builder of sewers. He travelled in several occasions to the rural area of province of Tucumán which has poor sanitary conditions. C. cayetanensis is an emergent agent of diarrhea and as far as we know this is the first time the parasite is observed in respiratory samples.

Coccidial infection in immunosuppressed mice: prophylaxis and treatment with dehydroepiandrosterone

Cryptosporidiosis and toxoplasmosis are diseases caused by opportunistic coccidial parasites that can lead to life-threatening infection in immunocompromised patients. We evaluated dehydroepiandrosterone as prophylaxis and therapy in immunosuppressed mice infected with Cryptosporidium parvum and avirulent Toxoplasma gondii. Mice were infected with either Cryptosporidium oocysts or Toxoplasma cysts. Assessment was by mortality rates, parasitic counts and electron microscopic studies. Mortality rates were significantly reduced in all treated groups. A significant reduction in the cryptosporidial oocyst count in stool and intestinal villi and in Toxoplasma cysts in the brains of infected mice was observed in all the groups. The effect of the drug was greater when given prior to infection

Diarreas parasitarias no amebianas / Non amoebian parasitary diarrheas

Se analiza un conjunto de infecciones parasitarias que se traducen por diarreas agudas altas, hipersecretoras, de evolución más arrastrada que las bacterianas; de curso inicialmente febril y que comprometen el estado general debido a alteraciones hidroelectrolíticas y trastornos de la absorción intestinal. Estos cuadros, producidos por protozoos esporulados (Isospora belli, Sarcocystis hominis, Cryptosporidium, Cyclosporidium y Mycrosporidium), afecta de preferencia los pacientes inmunodeprimidos y no tienen tratamiento reconocidamente eficaces. En los sujetos no inmunodeprimidos son autolimitados

Tratamento da criptosporidíase em pacientes com AIDS, por meio da paromomicina / Treatment of cryptosporidiasis with paramomycin in AIDS patients

The authors treated with paromomycin 25 patients, with AIDS and cryptosporidiosis. The drug was given orally in a doses of 500 mg qid, for a period of 14 days. Tolerance was good, with just two cases of mild side-effects. Clinical improvement was obtained in 19 (76 per cent) patients. Parasitological cure, however, occurred only in a low percentage (25 per cent). In some cases where initial success was observed, recrudescence occurred after some weeks or few months, but with retreatment again clinical improvement was obtained. Even if it does not lead to frequent parasite eradication, the good clinical results and tolerance permit us to consider paromomycin one of the few drugs effective for the treatment of cryptosporidial diarrhea in AIDS patients. Studies with maintainance therapy are indicated.

Prevalencia de Cryptosporidium en muestras de materia fecal llevadas a diez laboratorios del Area Metropolitana de Bucaramanga, Colombia

Con la técnica de Kinyoun para Cryptosporodium se estudiaron 1988 muestras de materia fecal llevadas para estudio a diez laboratorios del área metropolitana de Bucaramanga, Colombia. Correspondían a 103 lactantes, 113 preescolares, 201 escolares, 1162 adultos jóvenes, 322 adultos mayores y 87 ancianos; 55.48 por ciento eran mujeres y el 97.94 por ciento vivían en zona urbana. Un 13.93 por ciento pertenecían a personas con diarrea. Se encontraron tres muestras positivas, todas en menores de dos años y con diarrea: 2.91 por ciento de los lactantes y el 4.69 por cientode los lactantes con diarrea. Con esto se confirma la presencia del parásito en el Nororiente colombiano, con una prevalencia similar a la encontrada en otras partes del país

Empleo de la espiramicina en el tratamiento de la diarrea de terneros infectados con cryptosporidium parvum / Use of spiramycin in the treatment of calf diarrhea produced by crytosporidium parvum

Se realizó un estudio para evaluar la eficiencia de la espiramicina en el tratamiento de la diarrea causada por infecciones naturales de cryptosporidium parvum. Para ello se emplearon 48 terneros diarreicos, de los cuales 30 estaban infectados y 18 eran negativos al protozoo. Los infectados se distribuyeron en dos grupos: Grupo 1=20 terneros fueron tratados con espiramicina (20 mg/kg i.m., 2 aplic. cad 36 horas) y Grupo 2=10 terneros sometidos al tratamiento habitual de la lechería correspondiente. La mitad de los 18 negativos al protozoo fueron tratados con espiramicina (Grupo 3) y los 9 restantes (Grupo 4), recibieron el tratamiento convencional. La eficiencia del tratamiento se midió a través de la evolución de la diarrea y monitoreo de la presencia de ooquistes mediante observación de frotis de excrementos teñidos con Ziehl-Neelsen modificado, a los 2, 5 y 8 días post tratamiento (p.t). Se observaron diferencias significativas a los 2 y 5 días p.t. entre los 20 terneros tratados con espiramicina (Grupo 1) versus aquéllos que recibieron el tratamiento convencional (Grupo 2; p< 0,05). No hubo diferencia en el número de terneros diarreicos negativos a C. parvum del Grupo 3 y 4 (p> 0,05). La proporción de terneros que eliminaban ooquistes fue más baja en aquéllos tratados con espiramicina que los que recibieron el tratamiento convencional (p< 0,05). Se concluye que la espiramicina aunque no fue totalmente efectiva, ella demostró un mejor efecto que los tratamientos habituales para controlar en forma oportuna la diarrea del ternero causada por C. parvum

Updates on AIDS crytosporidiosis: a review

Cryptosporidio en un parásito que se caracteriza entre otras enfermedades por la formación de diarreas crónicas acuosos. El curso de la enfermedad depende mayormente del estado inmunológico del paciente. Las diarreas pueden causar hasta un 80% de mortalidad en pacientes inmunosuprimidos como de SIDA. Aunque hasta el momento no existe ningún tipo de terapia efectiva, resultados prometedores se le han atribuido al uso de Espiromicina, Eritromicina, Somatostatina y sus análogos, y a Zidovudina

Cryptosporidium sp. coccidio parasito de interes médico: situación en la V Región: Chile / Cryptosporidium sp. coccidio: parasite of medical interest: situation in the fifth region - Chile

La cryptosporidiosis es una infección parasitaría cuyo agente causal, el Cryptosporidium sp. provoca diarrea autolimitadas en pacientes inmunocompetentes. En la actualidad, es uno de los parásitos oportunistas de mayor relevancia debido a sus implicancias en pacientes inmunodeficientes, en los que puede determinar la muerte solo o asociado a otros agentes. La finalidad del presente artículo es proporcionar una revisión bibliográfica, con el objeto de dar antecedentes a los clínicos de la existencia de este parásito oportunista, causante de síndromes diarreicos, y por otra parte informar los avances obtenidos por nuestra Cátedra en las investigaciones pertinentes realizadas en al V Región