Niclosamide attenuates lung vascular remodeling in experimental pulmonary arterial hypertension.

Despite advances in medical therapy, pulmonary arterial hypertension (PAH) remains an inexorably progressive and highly lethal disease. Signal transducer and activator of transcription (STAT)-3 is one of the main intracellular transcription factors implicated in PAH vascular remodeling. We hypothesized that niclosamide, a STAT3 inhibitor, would reduce vascular remodeling in an established pulmonary arterial hypertension model, thus enhancing cardiac function. Male Wistar rats were treated either with monocrotaline (60 mg/kg), to induce PAH, or saline (C group) by intraperitoneal injection. On day 14, PAH animals were randomly assigned to receive oral (1) saline (PAH-SAL); (2) niclosamide (75 mg/kg/day) (PAH-NICLO); (3) sildenafil (20 mg/kg/day) (PAH-SIL); or (4) niclosamide + sildenafil (PAH-NICLO + SIL), once daily for 14 days. On day 28, right ventricular systolic pressure was lower in all treated groups compared to PAH-SAL. Pulmonary vascular collagen content was lower in PAH-NICLO (37 ± 3%) and PAH-NICLO + SIL (37 ± 6%) compared to PAH-SAL (68 ± 4%), but not in PAH-SIL (52 ± 1%). CD-34, an endothelial cell marker, was higher, while vimentin, a mesenchymal cell marker, was lower in PAH-NICLO and PAH-NICLO + SIL compared to PAH-SAL, suggesting attenuation of endothelial-mesenchymal transition. Expression of STAT3 downstream targets such as transforming growth factor (TGF)-ß, hypoxia-inducible factor (HIF)-1, and provirus integration site for Moloney murine leukemia virus (PIM-1) in lung tissue was reduced in PAH-NICLO and PAH-NICLO + SIL compared to PAH-SAL. In conclusion, niclosamide, with or without sildenafil, mitigated vascular remodeling and improved right ventricle systolic pressure. This new role for a well-established drug may represent a promising therapy for PAH.

Systematic review of the effectiveness of selected drugs for preventive chemotherapy for Taenia solium taeniasis.

BACKGROUND: Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific evidence concerning the effectiveness and safety of different drugs in preventive chemotherapy for T. solium taeniasis in endemic populations. METHODS: A systematic review was conducted of controlled and uncontrolled studies, assessing the efficacy and adverse effects (among other outcomes) of albendazole, niclosamide and/or praziquantel for preventive chemotherapy of T. solium taeniasis. A comprehensive search was conducted for published and unpublished studies. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A meta-analysis of cure rate and relative reduction in prevalence was performed. The protocol for this review was registered on the International prospective register of systematic reviews (PROSPERO), number CRD42018112533. RESULTS: We identified 3555 records, of which we included 20 primary studies reported across 33 articles. Meta-analyses of drug and dose showed that a single dose of praziquantel 10mg/kg, albendazole 400mg per day for three consecutive days, or niclosamide 2g, resulted in better cure rates for T. solium taeniasis (99.5%, 96.4% and 84.3%, respectively) than praziquantel 5mg/kg or single dose albendazole 400mg (89.0% and 52.0%, respectively). These findings have a low certainty of evidence due to high risk of bias in individual studies and heterogeneity in combined estimates. In relation to side-effects, most studies reported either no or only mild and transient side-effects within the first three days following drug administration for all drugs and doses. CONCLUSION: Evidence indicated that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg were effective as taenicides and could be considered for use in mass drug administration programs for the control of T. solium taeniasis. Evidence was not found that any of these drugs caused severe side effects at the indicated doses, although the extent of the available evidence was limited.

The effect of Niclosamide in acetic acid induce colitis: an experimental study

Ulcerative colitis is an idiopathic chronic inflammatory disease of the colon for which a lot of treatment modalities are present. However, significant side effects are associated with them, and there is a need for a search for other tretment options. This study was aimed to assess the contribution of niclosamide in experimentally established colitis in rats. Animals were categorized into 5 groups; the control group undergoes no induction of UC, colitis group in which UC was induced, and animals receive no treatment, the niclosamide group that received niclosamide and sulfasalazine group that received sulfasalazine. Each group was composed of 10 animals. After the completion of a one-month period of the experiment animals were sacrificed and the following meausres were done: the weight of the colon, determination of the area of mucosal damage by mm2, histological scoring after hematoxylin and eosin stain together with MAC score and immunohistochemistry of IL-6, TNF-alpha, MPO, MDA, CD62, and ICAM1. The results of the current study revealed that Nicosamide was able to reduce the area of mucosal damage, colon weight, histological and Mac scores and immunohistochemical scores of inflammatory and oxidative markers, significantly when contrasted to a group of colitis (P< 0.05). It has been concluded that Niclosamide was proved to have a significant effect as an adjuvant mode of therapy for colitis through its, anti-inflamatory and anti-oxidant effects (AU)

An Alternative Treatment Against Acanthocephala ( Prosthenorchis elegans) in Captive Squirrel Monkeys ( Saimiri sciureus) in Mexico.

We provide the first report of Acanthocephala ( Prosthenorchis elegans) in Mexican non-human primates. There has been no known treatment against this parasite except for surgical removal, and this has been relatively ineffective because of the small juveniles. We report the presence of P. elegans in a captive breeding colony of squirrel monkeys ( Saimiri sciureus) in Mexico, and we describe a successful treatment protocol. Treatment involved 2 steps: oral administration of the drugs loperamide chlorhydrate (0.5 mg/0.9 kg/3 days) and niclosamide (0.2 mg/0.9 kg/3 days) followed by surgical removal of adult worms from the intestine. Fecal examination during treatment revealed live adults but no living juveniles and no eggs. Surgery after 1 wk of treatment revealed the presence of adults and an absence of juvenile parasites. All adults were physically extracted during the surgery. All subjects recovered from surgery within 1 wk.

Ring-screening to control endemic transmission of Taenia solium.

BACKGROUND: Taenia solium is a major cause of preventable epilepsy in developing nations. Screening and treatment of human intestinal stage infection (taeniasis) within high-risk foci may reduce transmission and prevent epilepsy by limiting human exposure to infective eggs. We piloted a ring-strategy that involves screening and treatment for taeniasis among households located nearby pigs heavily-infected with the larval stage (cysticercosis). These pigs mark areas of increased transmission and can be identified by tongue examination. METHODOLOGY: We selected two villages in northern Peru for a controlled prospective interventional cohort pilot study. In the intervention village (1,058 residents) we examined the tongues of all pigs every 4 months for nodules characteristic of cysticercosis. We then screened all residents living within 100-meters of any tongue-positive pig using enzyme-linked immunosorbent assay to detect Taenia antigens in stool. Residents with taeniasis were treated with niclosamide. In both the intervention and control (753 residents) we measured incidence of exposure by sampling the pig population every 4 months for serum antibodies against cysticercosis using enzyme-linked immunoelectrotransfer blot. PRINCIPAL FINDINGS: Baseline seroincidence among pigs born during the study was 22.6 cases per 100 pigs per-month (95% confidence interval [CI] 17.0-30.0) in the intervention and 18.1 (95% CI 12.7-25.9) in the control. After one year we observed a 41% reduction in seroincidence in the intervention village compared to baseline (incidence rate ratio 0.59, 95% CI 0.41-0.87) while the seroincidence in the control village remained unchanged. At study end, the prevalence of taeniasis was nearly 4 times lower in the intervention than in the control (prevalence ratio 0.28, 95% CI 0.08-0.91). CONCLUSIONS/SIGNIFICANCE: Ring-screening reduced transmission of T. solium in this pilot study and may provide an effective and practical approach for regions where resources are limited. However, this strategy requires validation in larger populations over a greater period of time.

Taeniasis and cysticercosis in housemaids working in affluent neighborhoods in Lima, Peru.

Taenia solium taeniasis/cysticercosis is endemic in most developing countries, where it is an important cause of epileptic seizures and other neurologic symptoms. In industrialized countries, cysticercosis results from travel or immigration of tapeworm carriers from endemic areas. In both endemic and nonendemic countries, housemaids commonly immigrate from cysticercosis-endemic areas and can transmit the infection if they carry the adult tapeworm. Between July 2001 and July 2002, 1,178 housemaids (961 of them work in the top five most affluent districts of Lima, a metropolis of 8 million inhabitants considered nonendemic for cysticercosis) were evaluated for serum antibodies to Taenia solium and stool microscopy for taeniasis and cysticercosis. The serosurvey revealed a prevalence of cysticercosis-specific antibodies of 14.6% (95% CI: 12.6-16.6%), and stool microscopy detected 12 T. solium tapeworm carriers, for a prevalence of taeniasis of 1.2% (95% CI: 0.6-1.8%). A nonrandom sample of 26 seropositive housemaids was examined by brain CT and 50% of them had brain lesions compatible with neurocysticercosis, mainly calcifications. From the families who used a tapeworm-carrier housemaid, cysticercosis antibodies were detected in 6 (23%) of 26 persons who agreed to participate. One seropositive member of the employer families was symptomatic for seizures and had brain calcifications. The prevalence of tapeworm infections in this housemaid group is similar to levels in endemic areas, constituting a source of neurocysticercosis infection.

Species identification after treatment for human taeniasis.

Identification of species of human tapeworms is crucial because the consequences of infection by Taenia solium and T saginata are very different. However, evacuation of species-identifiable tapeworms is uncommon and Taenia spp eggs are indistinguishable under the microscope. Treatment of taeniasis consists of niclosamide followed by a purgative. Recently, we adopted preniclosamide and postniclosamide electrolyte-polyethyleneglycol salt (EPS) purges to improve bowel cleaning. Retrospective comparison of traditional castor oil with EPS purge showed that recovery of the tapeworm scolex was significantly improved (20 of 68 vs none of 46, p=0.0001) in the EPS group. Furthermore, 42 of 68 (62%) individuals receiving EPS excreted identifiable gravid proglottids. EPS treatment helps the visual identification of Taenia spp.

Infección por dypilidium caninum en un lactante / A case of infection by dypilidium caninum in an infant

Dypilidium caninum es un cestode común en perros y gatos distribuido en todo el mundo. El ser humano, huesped accidental, adquiere la infección a través de las pulgas en asociación con las mascotas infectadas, siendo esta enfermedad más frecuente en niños. Presentamos el caso de una niña de un año y medio de edad, que durante siete meses eliminó proglótidas en las deposiciones, consultando en numerosas oportunidades siendo tratada con fármacos dirigidos a protozoos y nematelmintos. Finalmente, luego de la identificación del Dypilidium caninum se trató a la paciente con niclosamida, evolucionando satisfactoriamente

Anthelmintic efficacy of oxibendazole against some important nematodes in dogs and cats.

The anthelmintic efficacy and safety of the oxibendazole component in a combination oxibendazole-niclosamide paste were investigated in dogs and cats and in litters of pups with naturally acquired nematode infections. A single dose of 15 mg oxibendazole/kg body weight given to 70 dogs and to 29 cats reduced faecal worm egg counts (EPG) by 97.6% for Toxocara canis, 95.7% for Trichuris vulpis, 94.6% for Ancylostoma caninum, and 100% for Toxascaris leonina. In cats, 96.7% efficacy was demonstrated against Toxocara cati. In a second trial, 119 pups in 22 litters were treated with the same dosage at 2, 4, and 6 weeks of age. After treatment on two consecutive days, 95% of the pups did not shed T. canis eggs, compared with 85% after only a single treatment. Side effects were rare and only recorded in young animals. A 2-day treatment schedule is recommended for unweaned pups.

Mass chemotherapy for intestinal Taenia solium infection: effect on prevalence in humans and pigs.

Mass treatment of the human population with niclosamide was carried out in 2 villages in rural Guatemala where Taenia solium was endemic, to determine how this would affect the epidemiology of the parasite. Intestinal taeniasis was diagnosed by microscopy and coproantigen testing, and porcine cysticercosis by a specific Western blot. Before mass treatment, the prevalence of human taeniasis was 3.5%; 10 months after treatment it was 1%, a significant decrease (P < 10(-4)). All tapeworms that could be identified to the species level were T. solium. Similarly, the seroprevalence of antibodies to cysticercosis in pigs declined from 55% before treatment to 7% 10 months after treatment, once again a significant decrease (P < 10(-6)). These effects were seen in both villages. The possible use of mass chemotherapy as a tool in the control of T. solium is discussed.

Estudo de variáveis que podem influenciar na evoluçäo da esquistossomose mansônica: efeito da terapêutica específica e da interrupçäo da transmissäo / Study of variables that may influence in the evolution of the hepatosplenic form of Schistosomiasis mansoni: effect of specific therapy and interruption of the transmission

O desenvolvimento da forma hepatatoesplênica da esquistossomose mansônica, ainda näo foi completamente esclarecido. Geralmente säo invocadas a intensidade da carga parasitária, as reinfecçöes sucessivas ou periódicas, a resposta imunológica do hospedeiro, a raça e a terapêutica específica, como fatores marcantes para explicar a razäo pela qual, somente pequeno percentual dos parasitados desenvolve essa forma de doença. O presente trabalho faz parte do "Projeto sobre Esquistossomose na Chapada Diamantina - Bahia - Brasil", tendo como objetivo contribuir para o conhecimento do papel das variáveis intensidade de carga parasitária, reinfecçöes sucessivas, terapêutica específica e raça, no desenvolvimento da forma hepatoesplênica, por ser esta, a mais frequênte das formas graves da doença. Um programa de controle da esquistossomose foi desenvolvido em uma área hiperendêmica de esquistossomose, através do uso de moluscicida durante dez anos, com a ajuda da comunidade local. Exames clínicos e parasitológicos de fezes foram realizados antes, durante o período de interrupçäo da transmissäo e após o retorno da transmissäo da parasitose. Ao longo dos quinze anos de seguimento dessa populaçäo, algumas pessoas fizeram uso de medicaçäo anti-esquissomótica, por demanda espontânea e outras näo. A avaliaçäo parasitológica foi feita através os exames de fezes qualitativo e quantitativo, determinando a prevalência e a intensidade da carga parasitária, pelo número de ovos eliminados nas fezes e sua média geométrica. A avaliaçäo da evoluçäo clínica foi feita pela análise do tamanho do fígado e do baço, e pela classificaçäo das formas clínicas, comparando-se o exame inicial com os exames subsequentes. Os principais parâmetros clínicos de evoluçäo - hepatomegalia, esplenomegalia e forma hepatoesplênica - foram analisados em relaçäo à populaçäo geral e ao tratamento específico. Em cada uma dessas situaçöes, os dados foram analisados de acordo com a idade e a raça. O processamento e a análise dos dados foram feitos de acordo com o modelo estatístico mais apropriado para determinado caso, utilizando-se pacotes estatísticos adequados e considerando-se como significante o encontro de p menor que 0,05. Os resultados obtidos permitem confirmar que a intensidade da carga parasitária está diretamente relacionada com o desenvolvimento da forma hepatoesplênica e que o grupo racial negro apresenta maior resistência a desenvolver esta forma clínica da doença...

Efficacy of Niclosamide as a potential topical antipenetrant (TAP) against cercariae of Schistosoma mansoni in monkeys.

A 1% (W/V) formulation of Niclosamide (2', 5-Dichloro-4-nitrosalicylanilide) (TAP) was tested on Cebus apella monkeys as a topical prophylactic against schistosomiasis mansoni. Two experiments were conducted using the same formulation. In the first experiment, the TAP provided complete protection against schistosomiasis for 3 days. Of the 4 monkeys treated with TAP 7 days before exposure to Schistosoma mansoni cercariae, 2 were completely protected. The remaining 2 monkeys of the 7 day treatment group had a 78% or greater reduction in adult worm burdens when compared to the placebo treated monkeys. The second experiment was designed to determine the time between day 3 and 7 when the TAP no longer provided complete protection. However, all of the TAP treated monkeys in this experiment were completely protected, even the monkeys treated 7 days earlier. In both experiments, all monkeys used as infection controls and those receiving only the placebo became infected and showed typical experimental schistosomiasis. These results demonstrate that the TAP could provide fast acting, short-term protection to people who must enter cercariae infested water.

Taenia solium taeniasis and neurocysticercosis in a Mexican rural family.

A case of neurocysticercosis in a six-year-old Mexican boy and a case of Taenia solium taeniasis in his five-year-old brother are reported. Neurocysticercosis was suspected based on clinical findings and was confirmed by computed tomography scanning. A parasitologic examination with zinc-sulfate flotation and formalin-ether sedimentation techniques was carried out on the whole family, and revealed Taenia sp. eggs in three stool samples from the five-year-old boy. The entire family agreed to undergo chemotherapy with niclosamide, but only the child passing taeniid eggs eliminated T. solium. No additional taeniasis cases were found in an examination of 20% of the village population, using the same parasitologic techniques. The results of an ELISA using cysticercus antigens were negative for the boy with neurocysticercosis, for other family members, and for 24 village volunteers, but were positive for the T. solium tapeworm carrier. It was concluded that in this family, person-to-person transmission of the tapeworm occurred due to poor living conditions and hygiene.

Características clínicas de la infección por Hymenolepis nana en niños / Clinical characteristics of Hymenolepis nana infections in children

Con el objeto de evaluar las características clínicas, epidemiológicas y bioquímicas de esta infección en población infantil, se estudió a 55 niños infectados exclusivamente por Hymenolepis nana y que consultaron en forma consecutiva al Policlínico de Parasitología del Hospital Luis Calvo Mackenna. La edad promedio de ellos fue de 6 años 6 meses. A todos se les indicó una completa anamnesis, examen físico, examen coproparasitológico seriado de deposiciones, hemograma, carotinemia y proteinemia. Fueron tratados con niclosamida en dosis de 2g el 1- día y 1 g/día hasta completar 7 días de tratamiento, repitiéndose los controles y estudios ya enunciados al mes siguiente. Los síntomas más frecuentes resultaron dolor abdominal 74,5%, meteorismo 52,7%, diarrea crónica 49,1%, y falta de progreso ponderal en el 32,7%. El tratamiento fue efectivo sólo en el 74,5%de los niños. Las proteínas plasmáticas fueron normales en la totalidad de los casos infectados y un 20%presentó niveles de caroteno bajo 60 mg/dl las que se normalizaron una vez tratada la parasitosis. El 49%presentó eosinofilia que en promedio fue de 768 eosinófilos/ul. Los pacientes tratados subieron 1,4 kg en un lapso de 2 meses. Se destaca la importancia de la adecuada sospecha y tratamiento de esta parasitosis

A case report of a Hymenolepis diminuta infection in a child in St James Parish, Jamaica.

Hymenolepsis diminuta is a tapeworm which is an intestinal parasite of rats and mice. Rarely, through accidental ingestion of an infected arthropod, man can become the definitive host. This report documents, for the first time, that such infections occur in Jamaica, West Indies. The life cycle of the parasite and its treatment are also discussed.

A case report of a Hymenolepis diminuta infection in a child in St James Parish, Jamaica

Hymenolepis diminuta is a tapeworm which is an intestinal parasite of rats and mice. Rarely, through accidental ingestion of an infected arthropod, man can become the definitive host. This report documents, for the first time, that such infections occur in Jamaica, West Indies. The life cycle of the parasite and its treatment are also discussed. (AU)

[Epidemiology of diphyllobothriasis in the Valdivia river basin, Chile]. / Epidemiología de la difilobotriasis en la cuenca del Río Valdivia, Chile.

In the Valdivia (Chile) river basin 1,295 inhabitants of 6 riverside districts were examined between March and October 1987 and showed a 1.2% of prevalence by Diphyllobothrium in the districts of Riñihue and Las Huellas. Prevalence of 5.3% and 9.8% respectively were registered in dogs of the districts of Riñihue and Malihue. No cat or pig infection was observed in the different districts. The parasites recovered after the treatment were identified as Diphyllobothrium latum. Human infection by D. latum in the districts affected results from the consumption of smoked or insufficiently cooked fish. The investigation of 1,450 fish (4 exotic species and 11 autochthonous ones), caught in the Valdivia river basin in 1986 and 1987, showed the existence of plerocercoids of D. latum and/or Diphyllobothrium dendriticum in Salmo gairdneri and Salmo trutta among exotic fish and in some autochthonous species. Prevalence and mean intensity in the infection of fish as well as the degree of aggregation in the infrapopulations varied in the different districts. Some species of fish would act as intermediary hosts and others as paratenic hosts in the life cycles of Diphyllobothrium spp. in the Valdivia river basin. An improvement in the conditions of basic sanitation, in sanitary education and in the treatment of infected persons is proposed as a means for the control of diphyllobothriasis in the districts affected.