Implementación de una estrategia de medicamentos en red: el caso de praziquantel / Implementation of a network drug strategy: the case of praziquantel

Resumen Las infecciones parasitarias provocan una enorme carga de enfermedad y constituyen un problema presente para la salud pública. Las enfermedades emergentes o reemergentes se ven influenciadas por fenómenos del mundo actual interconectado producto de la globalización, el desplazamiento de las personas, el comercio, la urbanización descoordinada y el cambio climático, contribuyendo en la transmisión de estas enfermedades. En el año 2021 hubo un aumento de la cantidad de pacientes que han requerido tratamiento para la difilobotriasis en la Región de los Ríos. Se revisan los aspectos relacionados con las redes integradas de servicios de salud para el acceso al tratamiento farmacológico a pacientes con diagnóstico de difilobotriasis, implementado por la Dirección de Servicio de Salud Valdivia, en colaboración con el hospital San José de Osorno, centros de atención primaria y centros privados de la Región de los Ríos.

Abstract Parasitic infections cause a huge burden of disease and are a current public health problem. The category of emerging or re-emerging disease is influenced by phenomena that occur in today's interconnected world because of globalization, the displacement of people, trade, uncoordinated urbanization and climate change, they have a very important influence on transmission of these diseases. In 2021 there was an increase in the number of patients who have required treatment for diphyllobothriasis in the Los Ríos Region. This article reviews aspects related to integrated Health Service networks to provide access to pharmacological treatments to patients diagnosed with diphyllobothriasis (tapeworm infection), implemented by the Valdivia Health Service Department, in collaboration with the San José de Osorno hospital, primary care centers and private centers in the Los Ríos Region.

Praziquantel-encapsulated niosomes against Schistosoma mansoni with reduced sensitivity to praziquantel / Niosomas encapsulados en prazicuantel contra Schistosoma mansoni con sensibilidad reducida al prazicuantel

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. Objective: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase. Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ- encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages. Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory- induced S. mansoni adult worms with reduced sensitivity to PZQ.

Introducción. El prazicuantel es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos y la falta de medidas preventivas eficaces aumentan su valor. La creciente prevalencia de la resistencia al prazicuantel bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia al prazicuantel mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni con sensibilidad reducida al fármaco durante la fase intramolusco. Materiales y métodos. Los caracoles que liberaban cercarias se trataron con prazicuantel en dosis de 200 mg/kg dos veces por semana, seguidas de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. La inducción exitosa de la sensibilidad reducida se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. El éxito en inducir una menor sensibilidad se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel. Resultados. El tratamiento oral con una dosis única de prazicuantel de 500 mg/kg en ratones infectados con cercarias con sensibilidad reducida al prazicuantel, reveló una reducción no significativa (35,1 %) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en prazicuantel inoculados por vía oral contra S. mansoni con sensibilidad reducida al prazicuantel, permitieron reestablecer con éxito la sensibilidad del patógeno al medicamento, como lo demostró la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a prazicuantel. La carga media total de gusanos fue de 1,33 ± 0,52, con una reducción estadísticamente significativa del 94,09 %, y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en el tejido del hígado y el intestino (97,68 % y 98,56 %, respectivamente), asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en prazicuantel restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni con sensibilidad reducida al prazicuantel inducida en el laboratorio.

In vivo effect of essential oil of Mentha x villosa and its active compound against Schistosoma mansoni (Sambon, 1907) / Efeito in vivo do óleo essencial de Mentha x villosa e seu composto ativo sobre Schistosoma mansoni (Sambon, 1907)

Abstract Schistosomiasis treatment is dependent on a single drug, praziquantel (PZQ). The development of resistance of PZQ has drawn the attention of many researchers to alternative drugs. One viable and promising treatment is the study of medicinal plants as a new approach to the experimental treatment for Schistosomiasis. The present work aimed to evaluate in vivo antischistosomal activity of effect of Mentha x villosa Oil Essential (Mv-EO) and rotundifolone (ROT) against Schistosoma mansoni. Thirty-day-old female Swiss webster mice (Mus musculus) weighing 50 grams were used. Mice were infected with 80 cercariae of S. mansoni (BH strain) and orally administered Mv-EO (50, 100 and 200 mg/Kg) and ROT (35.9, 70.9 and 141.9 mg/Kg) at 45-days post infection for 5 consecutive days. All mice were euthanized 60 days after infection. Praziquantel was the positive control in the experiment. Doses of 200 mg/kg (Mv-EO) and ROT (141.9 mg/Kg) resulted in a significant reduction in fluke burden (72.44% and 74.48%, respectively). There was also marked reduction in liver, intestinal and faecal and changed oogram pattern, compared to infected untreated mice. Considering the results obtained, further biological studies are required in order to elucidate the mechanism of schistosomicidal action on against adult S. mansoni.

Resumo O tratamento da esquistossomose é dependente de uma única droga, praziquantel (PZQ). O desenvolvimento da resistência de PZQ tem atraído atenção de muitos pesquisadores por medicamentos alternativos. Um tratamento viável e promissor é o estudo das plantas medicinais como uma nova abordagem para o tratamento experimental para esquistossomose. O presente trabalho objetivou avaliar a atividade esquistossomicida in vivo óleo essencial de Mentha x villosa (OE-Mv) e rotundifolona (ROT) contra Schistosoma mansoni. Foram utilizados camundongos Swiss webster (Mus musculus) fêmea de trinta dias de idade pesando 50 gramas. Os camundongos foram infectados com 80 cercárias de S. mansoni (cepa BH) e administrado por via oral OE-Mv (50, 100 e 200 mg/Kg) e ROT (35,9, 70,9 e 141,9 mg/Kg) apos 45 dias de infecção durante 5 dias consecutivos. Todos os animais foram eutanasiados 60 dias após a infecção. Praziquantel foi o controle positivo no experimento. O tratamento dos camundongos infectados com doses de 200 mg/kg (OE-Mv) e rotundifolona (141,9 mg/Kg) resultaram em redução significativa dos vermes (72.44% e 74.48%, respectivamente). Foi observado também redução no fígado, intestino e fecal e alteração no padrão do oograma, em comparação aos camundongos infectados e não tratados. Considerando os resultados obtidos, mais estudos biológicos são necessários a fim de elucidar o mecanismo de ação esquistossomicida contra adultos de S. mansoni.

Schistosomal myeloradiculopathy in a non-endemic area / Mielorradiculopatia esquistossomótica em região não endêmica

ABSTRACT Objective: To report a schistosomal myeloradiculopathy case in a non-endemic area. Case description: A previously healthy 11-year-old boy, stricken by an acute loss of strength on his lower limbs, followed by a loss of strength on his upper limbs and upper body, associated with altered sensitivity of the vesical globe formation. The patient's cerebrospinal fluid analysis showed eosinophilic meningitis, in addition to peripheral eosinophilia. The investigation resulted in a positive serology for Schistosoma mansoni. The treatment included steroids and praziquantel 60mg/kg, with a new dose after a month, as well as physical therapy for rehabilitation. The patient evolved with clinical improvement in the neurological exam, with a medullary section initially at C6, but now at T6. The patient is kept at prednisolone use (30mg/day) and longterm urinary catheter dependence. Comments: The schistosomiasis is endemic in many regions of Brazil; however, it has low incidence in the south of the country. Among its main manifestations, the schistosomal myeloradiculopathy is the most severe ectopic form of the disease, and should be suspected in patients with low back pain, strength and/or sensibility disorder of the lower limbs or urinary tract's disturbance. Early diagnosis and treatment should be done in order to reduce severe neurological sequelae. Treatment includes schistosomiasis drugs, corticosteroids and/or surgery.

RESUMO Objetivo: Relatar um caso de mielorradiculopatia esquistossomótica em área não endêmica. Descrição do caso: Paciente do sexo masculino, 11 anos, previamente hígido, com história aguda de paresia de membros inferiores, que evoluiu para membros superiores e tronco, associada à alteração de sensibilidade e formação de globo vesical. O exame do líquor demonstrava meningite eosinofílica, além de eosinofilia periférica. A investigação resultou em sorologia positiva para Schistosoma mansoni. O tratamento foi realizado com corticoterapia e praziquantel 60 mg/kg, com nova dose após um mês, além de fisioterapia para reabilitação. Evoluiu com melhora clínica no exame neurológico, com nível de secção medular que inicialmente correspondia a C6, encontrando-se atualmente em T6. Mantém uso de prednisolona 30 mg/dia e dependência de sonda vesical de demora. Comentários: A esquistossomose é uma doença endêmica em muitas regiões do Brasil, porém com pouca incidência no Sul do país. Dentre as principais manifestações, a mielorradiculopatia esquistossomótica é a forma ectópica mais grave e deve ser suspeitada na vigência de dor lombar, alteração de força e/ ou sensibilidade de membros inferiores e distúrbio urinário. O diagnóstico e o tratamento devem ser instituídos precocemente para diminuir o risco de sequelas neurológicas graves. O tratamento pode ser realizado com esquistossomicidas, corticosteroides e/ ou cirurgia.

Neurocisticercosis racemosa gigante resistente al tratamiento farmacológico convencional. Reporte de un caso clínico y revisión de la literatura / Giant Racemose Neurocysticercosis Resistant to Conventional Pharmacological Treatment. Case Report and Literature Review / Neurocisticercose racemosa gigante resistente ao tratamento farmacológico convencional. Relatório de um caso clínico e revisão da literatura

Resumen: La teniosis/cisticercosis es una enfermedad parasitaria causada por la infección del estado larvario de Taenia solium. La Organización Mundial de la Salud (OMS) considera esta patología un problema de salud pública, así como una infección olvidada. Las manifestaciones pueden variar según el tipo de presentación de la lesión, requiere manejo farmacológico en la mayoría de los casos e incluso puede llegar a requerir tratamiento quirúrgico, en algunas condiciones específicas. Se han reportado casos de resistencia del parásito al manejo con cisticidas, reportes en los cuales la ivermectina, antiparasitario de uso veterinario, se convierte en una importante opción de manejo. Para esta disertación, se presenta un caso de neurocisticercosis racemosa gigante, que requirió manejo quirúrgico en el cual se evidencia persistencia de las lesiones luego del tratamiento con cisticidas, el cual presentó mejoría con el manejo con albendazol de marca, en combinación con ivermectina.

Abstract: Taeniasis/cysticercosis is a parasitic disease caused by Taenia solium larval stage infection. The World Health Organization (WHO) considers this pathology a public health problem, as well as a neglected infectious disease. Its manifestations may vary according to the type of lesion, needs pharmacological management in most cases, and even requires surgical treatment in some specific conditions. Cases of parasite resistance to cysticides have been reported, in which ivermectin, an antiparasitic drug for veterinary use, has become an important treatment option. This paper presents a case of giant racemose neurocysticercosis that required surgical management because of persistent lesions after treatment with cysticides, which showed improvement with branded albendazole in combination with ivermectin.

Resumo: A teniose/cisticercose é uma doença parasitária causada pela infecção do estágio larval da Taenia solium. A Organização Mundial da Saúde (OMS) considera essa patologia um problema de saúde pública e uma infecção esquecida. As manifestações podem variar de acordo com o tipo de apresentação da lesão, que requer um tratamento farmacológico, na maioria dos casos, e pode até exigir tratamento cirúrgico, em alguns casos específicos. Foram relatados casos de resistência do parasita ao tratamento com cisticidas, relatórios nos quais a ivermectina, um antiparasitário para uso veterinário, torna-se uma importante opção de tratamento. Para esta dissertação, um caso de neurocisticercose racemose gigante é apresentado. Esse caso exigiu um tratamento cirúrgico, no qual a persistência das lesões após o tratamento com cisticidas foi evidente, mas mostrou melhoras após o tratamento com o albendazol e ivermectina.

Neobenedenia melleni (Monogenea: Capsalidae) in ornamental reef fish imported to Brazil / Neobenedenia melleni (Monogenea: Capsalidae) em peixes ornamentais de recife importados para o Brasil

Abstract The capsalid monogenean Neobenedenia melleni is known as a lethal pathogen for captured marine teleost ornamental fish, if left untreated. This study reports the occurrence of N. melleni parasitizing four species of ornamental reef fish imported into Brazil and maintained in quarantine: Arabian angelfish (Pomacanthus asfur ), yellowbar angelfish (Pomacanthus maculosus), regal angelfish (Pygoplites diacanthus), and bluecheek butterflyfish (Chaetodon semilarvatus). Ten days after the beginning of quarantine, some fish showed behavioral alterations, such as irritability, and corneal opacity, which were rapidly diagnosed to be caused by monogenean parasites by body surface scraping. The fish from the same batch were treated with two applications of 2 mg L-1 praziquantel each at an interval of four days. Seven days after the first treatment, the mucus surface of the fish was re-examined, which did not reveal the parasites presence being delivered for commercialization.

Resumo Neobenedenia melleni é conhecido como um parasito letal para peixes teleósteos ornamentais marinhos capturados se não tratado. Este estudo relata a ocorrência de N. melleni parasitando quatro espécies de peixes ornamentais importados para o Brazil: Arabian angelfish (Pomacanthus asfur), yellowbar angelfish (Pomacanthus maculosus), regal angelfish (Pygoplites diacanthus) e bluecheek butterflyfish ( Chaetodon semilarvatus). Dez dias depois do início da quarentena, foram observados irritabilidade e opacidade na córnea dos peixes que, foram diagnosticadas com N. melleni na superfície corporal. Todos os peixes foram tratados com duas aplicações de praziquantel 2 mg L-1 em intervalo de quatro dias. Sete dias após o início do tratamento, um novo exame parasitológico foi realizado o qual não revelou a presença dos parasitos, sendo liberados para comercialização.

Schistosomiasis mansoni in families of fishing workers of endemic area of Alagoas / Esquistosomiasis mansónica en familias de trabajadores de la pesca de área endémica de Alagoas / Esquistossomose mansônica em famílias de trabalhadores da pesca de área endêmica de Alagoas

Abstract Objective: To analyze the epidemiological and clinical aspects involved in the transmission and manifestation of schistosomiasis in a community of fishermen from the endemic area of Alagoas. Methods: Epidemiological, transversal, prospective, descriptive, quantitative study. The coproparasitological survey included 275 family units of fish workers and the epidemiological and clinical ones, those with a positive diagnosis for S. mansoni. Results: The prevalence of schistosomiasis was 13.9% (fishermen), 2.1% (shellfish) and 2.1% (family members). The occurrence of the infection varied according to gender, age, ethnicity and socioeconomic status. Exposure occurred near the home. Autochthonous and predominant low parasite burden, intestinal clinical presentation, abdominal pain and diarrhea were observed. There were no nutritional and pressure changes associated with parasitosis. Adherence to drug therapy and use of the schistosomicidal drug was feared. Conclusion: Fish workers are at high risk for contracting the disease with clinical hepatointestinal manifestation, which requires more intense health actions.

Resumen Objetivo: Analizar los aspectos epidemiológicos y clínicos involucrados en la transmisión y manifestación de la esquistosomiasis en una comunidad de pescadores de área endémica de Alagoas. Métodos: Estudio epidemiológico, transversal, prospectivo, descriptivo, cuantitativo. La encuesta coproparasitológica contempló 275 unidades familiares de los trabajadores de la pesca y el epidemiológico y clínico, aquellos con diagnóstico positivo para S. mansoni. Resultados: La prevalencia de la esquistosomiasis fue 13,9% (pescadores), 2,1% (marisqueras) y 2,1% (familiares). La ocurrencia de la infección varió según el género, edad, etnia y condición socioeconómica. La exposición ocurrió cerca del domicilio. Se observó autoctonía y predominio de carga parasitaria baja, presentación clínica intestinal, dolor abdominal y diarrea. No hubo alteraciones nutricionales y presión arterial asociadas a la parasitosis. Existia el temor de la adhesión a la terapia medicamentosa y al uso de la droga esquistomicida. Conclusión: Los trabajadores de la pesca presentan alto riesgo para contraer la enfermedad con manifestación clínica hepatointestinal, lo que requiere acciones de salud más intensas.

Resumo Objetivo: Analisar os aspectos epidemiológicos e clínicos envolvidos na transmissão e manifestação da esquistossomose em uma comunidade de pescadores de área endêmica de Alagoas. Métodos: Estudo epidemiológico, transversal, prospectivo, descritivo, quantitativo. O inquérito coproparasitólogico contemplou 275 unidades familiares de trabalhadores da pesca e o epidemiológico e clínico, àqueles com diagnóstico positivo para S. mansoni. Resultados: A prevalência da esquistossomose foi 13,9% (pescadores), 2,1% (marisqueiras) e 2,1% (familiares). A ocorrência da infecção variou conforme gênero, idade, etnia e condição socioeconômica. A exposição ocorreu próxima ao domicílio. Observou-se autoctonia e predominância de carga parasitária baixa, apresentação clínica intestinal, dor abdominal e diarreia. Não ocorreram alterações nutricionais e pressóricas associadas à parasitose. Houve receio na adesão à terapêutica medicamentosa e ao uso do fármaco esquistossomicida. Conclusão: Os trabalhadores da pesca apresentam alto risco para contrair a doença com manifestação clínica hepatointestinal, o que requer ações de saúde mais fortalecidas.

Echinochasmus caninus n. comb. (Trematoda: Echinostomatidae) Infection in Eleven Riparian People in Khammouane Province, Lao PDR

Adult specimens of Echinochasmus caninus n. comb. (Verma, 1935) (Trematoda: Echinostomatidae) (syn. Episthmium caninum Yamaguti, 1958) were recovered from 11 riparian people who resided along the Mekong River in Khammouane Province, Lao PDR. In fecal examinations done by the Kato-Katz technique, the cases revealed eggs of Opisthorchis viverrini/minute intestinal flukes, hookworms, and in 2 cases echinostome eggs. To recover the adult helminths, praziquantel 30–40 mg/kg and pyrantel pamoate 10–15 mg/kg in a single dose were given and purged with magnesium salts. Various species of trematodes (including O. viverrini and Haplorchis spp.), cestodes, and nematodes were recovered from their diarrheic stools. Among the trematodes, small echinostome flukes (n=42; av. 3.8 specimens per case) of 0.7–1.2 mm in length are subjected in this study. They are morphologically characterized by having 24 collar spines interrupted dorsally and anterior extension of vitellaria from the cirrus sac or genital pore level to the posterior end of the body. Particularly based on this extensive distribution of vitellaria, the specific diagnosis was made as Echinochasmus caninus. The cases were co-infected with various other helminth parasites; thus, clinical manifestations specific for this echinostome infection were difficult to determine. The present paper describes for the first time human E. caninus infections in Lao PDR. Our cases marked the 4–14th human infections with this echinostome around the world following the 3 previous cases reported from Thailand.

An Autochthonous Human Case of Fasciolopsiasis in Nepal

Fasciolopsiasis is rarely known as the parasitic disease in Nepal. Herein, we report a case of fasciolopsiasis in a 22-year-old man who was admitted in the hospital with abdominal pain, distension and loss of appetite for a month. He had previously diagnosed with acute viral hepatitis but, his abdominal pain was not resolving despite improvement in his liver function and general condition. During endoscopy an adult digenean worm was seen in the first part of the duodenum. After isolation, the worm was identified morphologically as Fasciolopsis buski. Microscogic examination of the patient’s stool revealed eggs with a morphology consistent with F. buski. Eggs were yellow-brown, ellipsoidal, unembmbryonated, operculated, filled with yolk cells, with thin shell and ranging 118–130 μm in length and 60–69 μm in width. The abdominal pain of the patient was resolved after treatment with praziquantel. By the present study, it was confirmed for the first time that fasciolopsiasis is indigenously transmitted in Nepal. Accordingly, the epidemiological studies in humans and reservoir host animals should be performed intensively in near future.

A Clonorchiasis Case of a Leopard Cat, Prionailurus bengalensis euptilurus, Diagnosed by Ultrasonography and Egg Detection in Republic of Korea

A clonorchiasis case in a captive leopard cat, Prionailurus bengalensis euptilurus, was confirmed by ultrasonographic findings and egg morphologies found in the bile juice sample in the Korea. The leopard cat was introduced from the wild habitat of Gyeongsangnam-do, to Cheongju Zoo in Cheongju-si, Chungcheongbuk-do, Korea in August 2014. Physical examinations were basically performed for quarantine and check-up health. The cat was comparatively good in health except anorexia. The cyst-like bile duct dilation and the increased echogenicity of gall bladder wall and hepatic parenchyma were observed by ultrasonography. Ultrasound-guided needle biopsy was conducted for collecting bile juice and the specimens were observed under light microscope. The numerous small trematode eggs were detected in the bile juice sample of the light microscopy. The eggs were 25–33 (28±3) μm by 18–22 (20±1) μm in size and showed typical characteristics of Clonorchis sinensis egg, i.e., a dominantly developed operculum, shoulder rim and dust-like wrinkles in surface. To treat the liver fluke infection, 20 mg/kg of praziquantel was orally administered only once to the case. Follow-up studies including fecal examinations were conducted during 2 years after treatment. But no more eggs were detected from the case. In the present study, we described the first clonorchiasis case of leopard cat, which was confirmed by ultrasonographic findings and egg morphologies from the bile juice sample in Korea.

In silico repositioning of new drugs against Schistosoma mansoni

Schistosomiasis is a neglected tropical disease caused by parasites of the genus Schistosoma. In Brazil only Schistosoma mansoni causes this disease. The World Health Organization estimated in 2012 approximately 249 million people at risk of acquiring this disease around the world. The main strategy to control this disease is praziquantel treatment of individuals living in endemic areas. The drug praziquantel is used on a large scale in the treatment of schistosomiasis and currently there are reported cases of resistance, indicating the need to discover new drugs. In silico drug repositioning is a time and cost reducing strategy in the search for anti-Schistosoma agents. This work used bioinformatic tools to identify potential schistosomicidal drugs. A list was compiled of S. mansoni potential targets that are part of essential processes in the database TDR and the targets that are part of the tegument were obtained in the scientific literature. The file with S. mansoni targets contained 1,376 targets, and of these only 61 targets associated with 399 drugs had homology with drug targets. After removal of duplicate drugs, drugs found in previous studies and after the analysis of the conservation of the binding site, only 28 S. mansoni targets associated with 102 drugs had 60% or more of the active site conserved. Some of the drugs had activity and are interesting to validate this study such as: artemether, lumefantrine, meloxicam. Among the drugs found 18 drugs were selected to be tested in prospective experimental assays according to the following criteria: low toxicity in vivo, off-patent status, and logP <5.0.

Praziquantel Treatment of Eosinophilic Gastritis Suspected to Be Due to Cerebral Sparganosis / 대한내과학회지

Eosinophilic gastritis is characterized by eosinophilic infiltration of the gastrointestinal tract, which is associated with abdominal pain, diarrhea, nausea, and vomiting. The possible etiologies of secondary eosinophilic gastritis, including drug reactions, parasitic infestation, and malignancy, must be evaluated. Herein we report the case of a 65-year-old North Korean defector who presented with nausea and vomiting for 1 year. Secondary (reactive) eosinophilic gastritis caused by cerebral sparganosis was suspected after a workup that included brain magnetic resonance imaging, cerebrospinal fluid tapping, and gastric mucosal biopsy. The patient showed dramatic clinical improvement with high-dose praziquantel treatment. Even though secondary (reactive) eosinophilic gastritis caused by parasites is very rare, this case shows the importance of considering parasitic infection in eosinophilic gastritis.

Albendazole and Praziquantel: Review and Safety Monitoring in Korea

Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for over 30 years. Worldwide, hundreds of millions tablets are administered to people and livestock every year. ADZ is poorly orally absorbed ( 75%) and uptake is enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not recommended for children < 2 years or for women in the first trimester of pregnancy. Serious adverse events occur following high dose and prolonged administration of these drugs for treatment of echinococcosis or neurocysticercosis, especially in patients with poor liver function. The adverse events may be induced by the drugs, or by the dead worms themselves. The Korea Institute of Drug Safety & Risk Management monitors drug-related adverse events in Korea, and its database included 256 probable or possible ADZ-associated events and 108 PZQT-associated events between 2006 and 2015. Such low incidence rates in Korea are due to the low single dose treatments of ADZ, and the short-term use of PZQT. The number of serious adverse events due to drug interaction induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and PZQT are generally safe drugs, but they must be used with caution in people with poor liver function or those being comedicated for gastroesophageal reflux disease.

Albendazole and Praziquantel: Review and Safety Monitoring in Korea

Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for over 30 years. Worldwide, hundreds of millions tablets are administered to people and livestock every year. ADZ is poorly orally absorbed ( 75%) and uptake is enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not recommended for children < 2 years or for women in the first trimester of pregnancy. Serious adverse events occur following high dose and prolonged administration of these drugs for treatment of echinococcosis or neurocysticercosis, especially in patients with poor liver function. The adverse events may be induced by the drugs, or by the dead worms themselves. The Korea Institute of Drug Safety & Risk Management monitors drug-related adverse events in Korea, and its database included 256 probable or possible ADZ-associated events and 108 PZQT-associated events between 2006 and 2015. Such low incidence rates in Korea are due to the low single dose treatments of ADZ, and the short-term use of PZQT. The number of serious adverse events due to drug interaction induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and PZQT are generally safe drugs, but they must be used with caution in people with poor liver function or those being comedicated for gastroesophageal reflux disease.

Impact of Single Dose Praziquantel Treatment on Schistosoma haematobium Infection among School Children in an Endemic Nigerian Community

Schistosomiasis is prevalent in Nigeria, and the foremost pathogen is Schistosoma haematobium, which affects about 29 million people. Single dose of the drug praziquantel is often recommended for treatment but the efficacy has not been documented in certain regions. Therefore, this study was designed to assess the impact of single dose praziquantel treatment on S. haematobium infection among school children in an endemic community of South-Western Nigeria. Urine samples were collected from 434 school children and 10 ml was filtered through Nucleopore filter paper before examination for egg outputs by microscopy. The prevalence was 24.9% at pre-treatment. There was no statistically significant difference for the prevalence of infection between males (14.7%) and females (10.2%), although the mean egg count for the females (9.87) was significantly more (P < 0.05) than the males (6.06). At 6 and 12 months post-treatment there was 74.4% and 86.4% reduction in the mean egg count, respectively. Interestingly, an increased prevalence of infection from 2.1% at 6 months to 7.7% at 12 months post-treatment was observed, nonetheless the mean egg count was reduced to 0.27 at 12th month from 1.98 at 6 months post-treatment. Resurgence in the prevalence rate between 6 and 12 months post-treatment with praziquantel is herein reported and the need for a follow-up treatment in endemic areas for adequate impact on schistosomiasis control is discussed.

Echinostoma ilocanum Infection in Two Residents of Savannakhet Province, Lao PDR

Adult specimens of Echinostoma ilocanum (Garrison, 1908) Odhner, 1911 (Trematoda: Echinostomatidae) were recovered from 2 riparian people who resided along the Mekong River in Savannakhet Province, Lao PDR. In fecal examinations done by the Kato-Katz technique, they revealed echinostome eggs together with eggs of Opisthorchis viverrini (and minute intestinal fluke eggs) and hookworms. To recover the adult flukes, they were treated with praziquantel 30–40 mg/kg in a single dose and purged with magnesium salts. A total of 658 adult fluke specimens were recovered from the 2 people; 456 from case 1 and 202 from case 2. Specimens from case 1 consisted of 335 echinostomes (301 E. ilocanum and 34 species undetermined), 120 O. viverrini, and 1 Haplorchis taichui, and those from case 2 consisted of 36 E. ilocanum, 134 O. viverrini, and 32 H. taichui. Thus, the number of E. ilocanum specimens was 337 in total (average per person, 168.5). From this study, it is suggested that foodborne intestinal flukes and liver flukes are highly prevalent along the Mekong River in Savannakhet Province. The present report describes for the first time human infections with E. ilocanum in Lao PDR.

A Case of Pulmonary Paragonimiasis with Chronic Abdominal Pain and Erythematous Rash in a 6-year-old Girl

Pleural paragonimiasis is uncommon in the pediatric population and therefore can be challenging to diagnose. This is a case of a 6-year-old girl with pleural effusion who had been having intermittent persistent epigastric pain and erythematous rash on the face, hands, and arms for 6 months. Exudative pleural effusion with prominent eosinophils and serum eosinophilia were observed. As patient showed high immunoglobulin M (IgM) titers against Mycoplasma pneumoniae , she was treated with antibiotics; however, the pleural effusion did not improve during hospitalization. Despite showing negative stool ova and cyst results, patient's serum and pleural effusion were positive for Paragonimus westermani-specific IgGs on enzyme-linked immunosorbent assay. Respiratory symptoms, pleural effusion, and skin symptoms improved after praziquantel treatment.

Diagnóstico de Inermicapsifer madagascariensis en dos niños / Diagnosis of Inermicapsifer madagascariensis in two children

Se presentan los casos de dos niños, hermanos, de los cuales se recibieron muestras de heces fecales en el laboratorio de microbiología del municipio Güines, provincia Mayabeque. Las muestras contenían minúsculos proglótides, que resultaron ser de Inermicapsifer madagascariensis. Luego del tratamiento con praziquantel 10 mg/kg en dosis única, orientado por el servicio de pediatría, se confirmó la expulsión de restos del parásito y la curación de dicha infección, tras resultados negativos por controles repetitivos de heces fecales durante seis meses. Se decide publicar estos raros casos diagnosticados y estimular estudios de campo que permitan completar el ciclo evolutivo de este parásito(AU)

We are presenting the cases of two sibling children, from whom samples of faeces were received in the microbiology laboratory of the Güines municipality, Mayabeque province. The samples contained tiny proglottids, which turned out to be from Inermicapsifer madagascariensis. After treatment with Praziquantel 10 mg/kg in a single dose, guided by the pediatric service, the expulsion of parasite remains and the cure of this infection were confirmed, after negative results due to repetitive controls of faecal stools for six months. It is decided to publish these rare diagnosed cases and stimulate field studies to complete the evolutionary cycle of this parasite(AU)

Ultrastructural alterations in Schistosoma mansoni juvenile and adult male worms after in vitro incubation with primaquine

BACKGROUND Praziquantel has been cited as the only drug for treating schistosomiasis. However, concerns over drug resistance have encouraged the search for novel drug leads. The antimalarial drug primaquine possesses interesting anti-schistosmal properties. OBJECTIVES This study is the first to document the potential role of primaquine as a schistosomicide and the ultrastructural changes induced by primaquine on juvenile or adult male worms of Schistosoma mansoni. METHODS Ultrastructural alterations in the tegumental surface of 21-day-old juvenile and adult male worms of S. mansoni were demonstrated following primaquine treatment at different concentrations (2, 5, 10, 15, and 20 µg/mL) and incubation periods (1, 3, 6, 24, and 48 h) in vitro, using both scanning and transmission electron microscopy. FINDINGS At low concentrations (2, 5, and 10 µg/mL) both juvenile and adult male worms were alive after 24 h of incubation, whereas contraction, paralysis, and death of all worms were observed after 24 h of drug exposure at 20 µg/mL. The tegument of juvenile and adult male worms treated with primaquine exhibited erosion, peeling, and sloughing. Furthermore, extensive damage of both tegumental and subtegumental layers included embedded spines, and shrinkage of muscles with vacuoles. The in vitro results confirmed that primaquine has dose-dependent effects with 20 µg/mL as the most effective concentration in a short incubation period. MAIN CONCLUSIONS The schistosomicidal activity of primaquine indicates that this drug possesses moderate in vitro activity against juvenile and adult male worms, since it caused high mortality and tegumental alterations. This study confirmed that the antimalarial drug primaquine possesses anti-schistosomal activity. Further investigation is needed to elucidate its mechanism of action.