Mass Drug Administration of Triclabendazole for Fasciola Hepatica in Bolivia.

Human infection with Fasciola hepatica leads to obstruction of the common bile duct by adult worms and disease characterized by biliary colic, epigastric pain, and nausea. Recommended treatment is a single dose of triclabendazole (TCBZ) (10 mg/kg). Because in the 1990s the Bolivian Altiplano bordering Lake Titicaca was thought to have the highest prevalence of human fascioliasis worldwide, the Bolivian Ministry of Health instituted TCBZ mass drug administration (MDA). From 2008 to 2016 (excepting 2015), one dose of 250 mg was administered, usually in September/October, to each resident of highly endemic regions willing to participate. This is apparently the first reported use of MDA for Fasciola. The proportion of persons in key regions receiving TCBZ MDA was 87% in 2016. In 2017, we resurveyed key regions, and found that the MDA program had been dramatically successful. Whereas Fasciola prevalence was reported as 26.9% in Huacullani/Tiahuanaco and 12.6% in Batallas in 1999, there was 0.7% prevalence in Huacullani/Tiahuanaco and 1% in Batallas in 2017. However, lessons from schistosomiasis control efforts suggest that for sustained control of Fasciola infection, Fasciola MDA needs to be maintained and coupled with measures to control infection in the intermediary snail and in the animal hosts of F. hepatica.

Flukicide efficacy against Fasciola hepatica of Triclabendazole and Nitroxynil in cattle of the central valley of Chile.

On a farm with permanent history of fasciolasis a study was performed aimed to know the efficacy of triclabendazole (TCBZ) and then to contrast with that of nitroxynil. Thirty-nine cattle naturally infected with Fasciola hepatica were randomly allocated into 4 experimental groups: Group 1 (control) was left untreated. Group 2 was treated with of 12 mg/kg body weight (bw) of TCBZ by oral route. Group 3 treated with 24 mg/kg bw TCBZ orally. Group 4 was treated with 10 mg/kg bw of nitroxynil subcutaneously. The anthelmintic efficacy was calculated as the percentage of reduction in faecal egg count (FEC) at 14 and 28 d post-treatment. Results indicated that there were no significant differences in the percentage of FEC reduction between control group and the groups treated with 12 or 24 mg/kg of TCBZ. On the contrary, the treatment with nitroxinyl significantly reduced the FEC and decreased the percentage of positive animals. In conclusion, Fasciola hepatica is reported for first time as resistant to TCBZ in Chile, which highlights the need of rotating drugs and assessing the efficacy of the administered drug in order to avoid the selection of resistant worms.

Flukicide efficacy against Fasciola hepatica of Triclabendazole and Nitroxynil in cattle of the central valley of Chile / Avaliação da eficácia de triclabendazol e nitroxinil para o tratamento da infeção por Fasciola hepatica em bovinos do Vale Central do Chile

Abstract On a farm with permanent history of fasciolasis a study was performed aimed to know the efficacy of triclabendazole (TCBZ) and then to contrast with that of nitroxynil. Thirty-nine cattle naturally infected with Fasciola hepatica were randomly allocated into 4 experimental groups: Group 1 (control) was left untreated. Group 2 was treated with of 12 mg/kg body weight (bw) of TCBZ by oral route. Group 3 treated with 24 mg/kg bw TCBZ orally. Group 4 was treated with 10 mg/kg bw of nitroxynil subcutaneously. The anthelmintic efficacy was calculated as the percentage of reduction in faecal egg count (FEC) at 14 and 28 d post-treatment. Results indicated that there were no significant differences in the percentage of FEC reduction between control group and the groups treated with 12 or 24 mg/kg of TCBZ. On the contrary, the treatment with nitroxinyl significantly reduced the FEC and decreased the percentage of positive animals. In conclusion, Fasciola hepatica is reported for first time as resistant to TCBZ in Chile, which highlights the need of rotating drugs and assessing the efficacy of the administered drug in order to avoid the selection of resistant worms.

Resumo Em uma fazenda com histórico de fasciolose permanente, foi realizado um estudo com o objetivo de conhecer a eficácia do triclabendazol (TCBZ) e depois contrastar com o do nitroxinil. Trinta e nove bovinos naturalmente infectados com Fasciola hepatica foram distribuídos aleatoriamente em 4 grupos experimentais: Grupo 1 (controle), sem tratamento. O grupo 2 foi tratado com 12 mg/kg de peso vivo (PV) do TCBZ por via oral (VO). Grupo 3 tratado com 24 mg/kg de PV TCBZ por VO. O grupo 4 foi tratado com 10 mg /kg de PV Nitroxinil via subcutânea. A eficácia anti-helmíntica foi calculada comparando a percentagem de redução na contagem de ovos fecais (FEC) 14 e 28 dias pós tratamento. Não houve diferença significativa na porcentagem de redução FEC entre o grupo controle e os grupos tratados com 12 ou 24 mg/kg de TCBZ. Entretanto, o tratamento com nitroxinil reduziu significativamente o FEC e diminuiu a porcentagem de animais positivos. Em conclusão, a Fasciola hepatica é relatada pela primeira vez como resistente ao TCBZ no Chile, o que destaca a necessidade de realizar uma rotação em relação aos medicamentos anti-helmínticos e avaliar a eficácia do mesmo, a fim de evitar a seleção de vermes resistentes.

Mucocutaneous manifestations of helminth infections: Trematodes and cestodes.

In the 21st century, despite increased international travel for vacation, work, and medical missions and immigration into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. It has been estimated that 20% to 70% of international travelers suffer from some travel-related health problem. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on cutaneous diseases caused by helminth infections. Part I of the review focused on nematode infections; part II will focus on trematode and cestode infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.

Neurocysticercosis.

OBJECTIVE: Neurocysticercosis is the most common parasitosis of the central nervous system. Many forms, especially those inside the ventricles, carry a poor prognosis. Drug therapy is far from ideal. METHODS: We propose and comment on the use of the endoscope to remove cysts, treat hydrocephalus, and to perform membrane fenestration as a way to simplify treatment. RESULTS: Many patients, especially those with obstructive forms, benefit from the adjunctive use of neuroendoscopy. CONCLUSIONS: Neurocysticercosis treatment remains challenging and multimodal. Endoscopes can be helpful in this setting.

Neurocysticercosis.

Neurocysticercosis is the most common helminthic disease of the nervous system and currently represents a major public health problem in developing countries of Latin America, Asia, and Africa, as well as in industrialized nations with a high immigration rate of people from endemic areas. The disease occurs when humans become the intermediate host in the life cycle of Taenia solium by ingesting its eggs from contaminated food. Neurocysticercosis is pleomorphic in its presentation due to individual differences in the number, size, and location of the parasites, as well as differences in the severity of the host's immune reaction to the parasite. Epilepsy, focal neurological signs, and intracranial hypertension are the most common clinical manifestations of the disease. The diagnosis of neurocysticercosis is based on clinical data, neuroimaging abnormalities, and the results of immunological tests. Two drugs, albendazole and praziquantel, are cysticidal and destroy most intracranial parasites; however, surgery may be necessary in the management of some forms of the disease, particularly hydrocephalus and intraventricular cysts. Although the development of modern diagnostic tests and the introduction of potent cestocidal drugs have increased our ability to make the diagnosis of neurocysticercosis and improved prognosis, some patients still have a torpid clinical course despite prompt diagnosis and proper therapy.

Spinal cord schistosomiasis: a prospective study of 63 cases emphasizing clinical and therapeutic aspects.

A prospective study was conducted on 63 patients with schistosomal myeloradiculopathy admitted to a university hospital in Brazil. They were evaluated according to a protocol and treated with corticosteroid and praziquantel. The disease, in general, presented as a lower cord syndrome of acute progression characterized by motor, sensory and autonomic dysfunctions. The severity of the clinical picture was different among the patients, but the symptoms were quite constant. Cerebrospinal fluid examination showed an inflammatory pattern with or without eosinophils and/or IgG against schistosomal antigens. The most frequent alterations detected by imaging methods were enlargement of the medullary cone and of the roots of the cauda equina. Schistosome egg counts suggested a low parasite burden in 71.6% of the cases. Outcome was favorable in 38 (60.3%) patients and improvement usually started within the first 48 h after commencing on corticoid and was faster during the early period of treatment.

[Human diphyllobothriasis by Diphyllobothrium pacificum. A new case in Antofagasta, Chile]. / Difilobotriasis humana por Diphyllobothrium pacificum. Un nuevo caso en antofagasta, norte de Chile.

We report a 26 years old asymptomatic female that expelled spontaneously a 39 proglottid strobila. The taxonomic study of proglottids and eggs found in the stool examination concluded that the patient was infected by Diphyllobothrium pacificum. This infection was probably acquired by the ingestion of raw fish (Sciaena deliciosa) with lemon in a traditional plate called "cebiche". She was treated with a single dose of praziquantel in a dose of 10 mg/kg body weight. After 24 h of treatment there were no scolices on feces. The patient did not have anemia. All eight family members studied, did not have the infection. A follow up stool examination three months later remained negative.

Hymenolepis diminuta: praziquantel removal of adult tapeworms is followed by apoptotic down-regulation of mucosal mastocytosis.

The rat tapeworm, Hymenolepis diminuta, induces mastocytosis, hypertrophy of enteric smooth muscle, alteration of enteric myoelectric activity, and slowed enteric transit of the rat host's intestine. This report examines the resolution of both tapeworm-induced mastocytosis and tissue changes during the period following removal of the tapeworm with Praziquantel (PZQ). The dynamics of the mucosal mast cell (MMC) population following removal of the tapeworms was assessed by histochemical identification of MMC and morphometric techniques. As a possible mechanism of MMC population regulation, MMC apoptosis was examined over the same experimental period using the in situ nick end labeling of fragmented DNA (TUNEL). Shifts in MMC numbers were correlated with functional and morphological changes of the intestine following removal of the adult-stage tapeworm. Ileal tissues from rats infected 32 days with H. diminuta (the beginning of plateau phase of tapeworm-induced chronic mastocytosis) were harvested 1, 2, 3, and 4 weeks after the PZQ treatment. Control ilea were obtained either from rats which were never infected and never treated with PZQ or from rats infected with H. diminuta for 32 days but not treated with PZQ. In order to detect MMC and apoptosis, tissue sections of ileum were doubled stained sequentially with Astra blue for MMC granules followed by a modification of the TUNEL technique. No alteration in MMC numbers were observed in PZQ-treated animals until 3 weeks after the removal of the tapeworms. The decline of MMC occurred in the mucosa and submucosa. MMC numbers first approached uninfected control levels at 4 weeks posttreatment. Coincident with the decline in mucosal MMC numbers, the rate of MMC entering apoptosis also declined. Simultaneously, ileal smooth muscle layers, hypertrophied by infection, and mucosal structures began the process of involution and atrophy. Apoptosis of MMC in the submucosa and muscularis mucosa was not detected. In conclusion, H. diminuta-elicited mastocytosis and increased thickness of both mucosa and muscularis externa do not begin a decline toward control values until 3 weeks after the parasites are gone and normal intestinal motility is restored. These data are consistent with the lack of MMC mediation of altered motility, and the decline in the rate of MMC apoptosis at 3 weeks post-PZQ suggests that apoptosis may play an important role in the involution of tapeworm-induced mastocytosis.

Cysticercosis and epilepsy: a critical review.

Neurocysticercosis (NC) remains a major public health problem in developing and some developed countries. Currently, the best procedures for diagnosing NC are neuroimaging studies. Immunoserologic assays, such as enzyme-linked immunoelectrotransfer blot assay (EITB) or enzyme-linked immunosorbent assay (ELISA), detect antibodies against Taenia solium, or cysticercus. Consequently, they are useful in identifying a population at risk of contact with the parasite but do not necessarily indicate a systemic active infection. Most seropositive individuals are asymptomatic. No data from prospective studies concern the proportion of these individuals that will develop seizures or other neurologic symptoms. There is a discrepancy between the results of serologic assays and neuroimaging studies: >50% of those individuals with NC diagnosed by computed tomography (CT) scan test EITB negative. Pathophysiologic classification of NC into active, transitional, and inactive forms permits a good correlation between clinical manifestations and neuroimaging procedures and facilitates medical and surgical management and research. The most frequent clinical manifestations of NC are seizures. We assume that NC is the main cause of symptomatic epilepsy in developing countries; however, no case-control or cohort studies demonstrate this association. Most patients with NC with seizures have a good prognosis; nevertheless, further studies analyzing factors related to recurrence of seizures and possibilities of discontinuation of antiepileptic medications (AEDs) are needed. Regarding treatment of NC with antihelminthic drugs, no controlled clinical trials exist that establish specific indications, definitive doses, and duration of treatment. The most effective approach to taeniasis/cysticercosis infection is prevention. This should be a primary public health focus for developing countries. We critically review the available information regarding the epidemiology and diagnosis of human cysticercosis, the physiopathology and imaging correlation of the parasite in the central nervous system (CNS) of the host, the relation between seizures or epilepsy and NC, and the issues surrounding the treatment and prognosis of NC, including the use of antihelminthic therapy.

Fasciolasis hepática en ninos: manifestaciones clinicas poco frecuentes / Hepatic fascioliasis in children: uncommon clinical manifestations

La presente revisión tiene como objetivo identificar las características clínicas, epidemiológicas y la evolución de cuatro niños con Fasciola hepática con manifestaciones poco usuales, evaluados en el Servicio de Gastroenterología Pediátrica del Instituto de Salud del Niño, Lima-Perú, entre 1988 y 1992. El primer paciente fue una niña de 9 años de edad que tenía fiebre, edema de miembros inferiores, circulación colateral y hepatomegalia predominantemente del lóbulo derecho. El diagnóstico inicial fue un neoplasma hepático. El segundo caso fue un niño de 6 años de edad que tuvo hemorragia gastrointestinal alta y fiebre; el diagnóstico endoscópico demonstró hemobilia. El tercer caso fue un niño de 12 año de edad que presentó edema generalizado y fue diagnosticado como sindrome nefrótico pero este diagnóstico fue descartado. El cuarto paciente fue un niño de 9 años de edad que presentó ictericia, fiebre y hemorragia gastrointestinal alta. Se verificaron cirrosis y várices esofágicas. En los cuatro pacientes el diagnóstico se realizó mediante la identificación de los huevos del parásito en heces. Los tres primeros casos respondieron satisfactoriamente al tratamiento con bithionol, el cuarto paciente falleció debido a falla sistémica.

Quimioterapia de la cisticercosis. Resultados de 10 años o más después del seguimiento / Chemotherapy for cysticercosis. Results of 10 or more years after follow up

La quimioterapia de la neurocisticercosis nació lógicamente por el poco éxito de la cirugía, que generalmente es paliativa y no curativa. Praxicuantel es la única droga acerca de la cual se han publicado series de más de 100 casos y con seguimiento de más de dos años. Su uso se ha hecho universal. Razones éstas para escogerlo como tema de este escrito. Se pretende contribuir a determinar su valor terapéutico en el tratamiento de la neurocisticercosis por medio del monitoreo clínico y radiológico de 50 enfermos seguidos entre 10 (72 por ciento) y más de 10 años (28 por ciento). Se les había tratado con praxicuantel a la dosis de 50mg por kilogramo de peso, durante 15 días. El 26 por ciento recibió un tratamiento, el 58 por ciento dos tratamiento y el 22 por ciento tres o más. Se les estudió una vez más clínica y radiológicamente por tomografía axial computada de cráneo o resonancia magnética, las pruebas biológicas se hicienron únicamente en los casos sospechosos de actividad. Como resultados se registró 68 por ciento de curaciones clínicas o mejorías importantes. Se hace énfasis en 6 por ciento de los casos en donde el proceso de curación clínica fue aparente. Se confirma que neurociticercosis es un padecimiento crónico generalizado, en el que la evolución se hace por períodos de actividad, alternando con períodos de recesión. Se condena el uso de testigos y se sugiere para ulteriores investigaciones el que sigan amplias series de casos durante largos lapsos. Se insiste en que el mejor tratamiento de la enfermedad es la profilaxis

[The chemotherapy of cysticercosis. The results 10 years or more after follow-up]. / Quimioterapia de la cisticercosis. Resultados de 10 años ó más después del seguimiento.

Chemotherapy for neurocysticercosis was born logically because of the scant success of surgery, which is generally palliative, not curative. Prazicuantel is the only drug about which serious of more than 100 cases, and follow-up of more than 2 years, have been published. Its use has become universal, reason enough for this theme to be addressed. This paper pretends to contribute to the determination of its therapeutic value in the treatment of neurocysticercosis by means of the clinical and radiologic treatment of 50 sick persons followed up for from between 10 (72%) and more than 10 (28%) years. The patients had been treated with prazicuantel with a dose of 50 mg per kilo of body weight during 15 days; 26% received one treatment, 58% received two, and 22%, three or more treatments. The patients were studied once again clinically and radiologically with computed axial tomography of the cranium and magnetic resonance. Biological testing was done only if activity-suspected cases. The results showed a rate of 68% clinical cures or important improvement. Emphasis is made of the 6% of cases in which the clinical cure process was apparent. It was confirmed that neurocysticercosis is a generalized chronic ailment in which evolution is achieved by means of periods of activity alternating with periods of recession. The employment of witnesses is not advised, and it is suggested for later investigation that ample series of cases be followed-up over long periods of time. It is insisted upon that the best treatment for the illness is prophylaxis.

Humoral immune responses in patients with acute Schistosoma mansoni infection who were followed up for two years after treatment.

Eighteen patients with acute Schistosoma mansoni infection were followed up for 2 years after treatment with praziquantel or oxamniquine. Cure rates, clinical features, abdominal ultrasonographic findings, and specific humoral responses were determined at 2-, 6-, and 24-month follow-ups. Fourteen patients (77.8%) were considered parasitologically cured. Levels of IgA antibody to soluble egg antigen (SEA) and IgM antibody to keyhole limpet hemocyanin (KLH) became negative or decreased to the cutoff level for chronic infection 2 months after treatment, while levels of IgG antibody to KLH declined between 12 and 24 months after treatment. Levels of IgM and IgG antibodies to saline worm adult protein as well as IgM and IgG antibodies to SEA remained positive during the follow-up period. Discrete lymph node enlargement and hepatomegaly were still present in six of the eight cured children 2 years after treatment, while complete regression was observed in adults. In our group of patients, in addition to presenting with more intense clinical manifestations, children were cured less often and had slower abatement of symptomatology after treatment than adults.

Genotoxic activity of praziquantel.

Praziquantel is a synthetic drug with a remarkable activity against parasites, particularly treamatodes and cestodes. Initial genotoxicity tests used a spectrum of endpoints including tests in bacteria, yeasts, mammalian cells and Drosophila and each one gave negative results. Effects on reproductive cells of mice were negative as well. However, host mediated studies in mice and humans were contradictory and a comutagenic effect with several mutagens and carcinogens was found. Later studies, including monitoring in humans and pigs have shown that Praziquantel induces a greater frequency of hyperploid lymphocytes as well as structural chromosomal aberrations, but not in all the individuals treated. In vitro studies have demonstrated that Praziquantel can induce micronuclei in syrian hamster embryonic (SHE) cells and in lymphocytes of some individuals. The same was found about structural chromosomal aberrations. Fetal death and fetal resorption were found when Praziquantel was administered in high doses to pregnant rats between the 6th and 10th day of gestation. Due to its efficiency as a parasiticide, Praziquantel is in use in Latin-American, Asiatic, African and East-European countries where infections by trematodes and cestodes are frequent. However, the extensive use of Praziquantel in multiple reinfections, in non-infected and non-diagnosed individuals for prevention, in higher doses or repeated doses for cysticercosis treatment and in individuals exposed to environmental mutagens, in conjunction with new findings about its metabolism and genotoxic properties, make it necessary to further evaluate the potential of this drug not only to be mutagenic per se, but to contribute in the development of neoplasm.

[Tropical pyomyositis. A case report]. / Piomiosite tropicale. Descrizione di un caso.

Tropical pyomyositis is an infection of large muscle groups that can lead to sepsis and death. The most common etiologic agent is Staphylococcus aureus. It usually occurs in patients living in the tropics but is seen with increasing frequency in temperate climates, particularly in immunosuppressed patients, where it may be misdiagnosed and may cause severe morbidity and mortality. Diagnosis is based on the examination of pus from a muscle aspirate and treatment consists of surgical incision, drainage and appropriate antibiotic therapy. It is stressed to take into account pyomyositis in the differential diagnosis of immunocompromised patients with "cryptic" myalgia.

[Hepatic fascioliasis in children: uncommon clinical manifestations]. / Fasciolasis Hepática En Niños: manifestaciones clínicas pcop frecuentes.

The present review has the objective to identify clinical epidemiologic characteristics and evolution for four children with Fasciola hepatica evaluated at the Pediatric Gastroenterology Unit at the Children's Health Institute, Lima, Peru, between 1988 and 1992. The first patient was a 9-year old girl who had fever, leg edema, collateral circulation and hepatomegaly, predominantly at the right lobe. The second was a 6-year old by who had upper gastrointestinal hemorrhage and fever; endoscopic diagnosis demonstrated hemobilia. The third case was a 12-year old boy who presented generalized edema. The fourth patient was a 9-year old boy with jaundice, fever and upper gastrointestinal hemorrhage. Esophageal varices and cirrhosis were present. In the four patients the diagnosis was made by the identification of parasite eggs in the feces. The first three cases responded satisfactorily to treatment with bithionol; the fourth patient died because of systemic failure.

Esquistossomose aguda com comprometimento cerebral: relato de caso / Acute schistosomiasis with brain involvement: case report

É relatado um caso de esquistossomose na fase aguda com comprometimento cerebral precoce, síndrome piramidal nos membros inferiores, líquido cefalorraquidiano (LCR) normal e lesoes com padrao desmielinizante na ressonância magnética (RM) encefálica. O diagnóstico foi comprovado através da imunofluorescência indireta para esquistossomose no LCR. O envolvimento encefálico pelo Schistosoma mansoni é menos frequente do que o medular e a resposta ao tratamento com o praziquantel e a prednisolona foi eficaz neste caso. Sao poucos os relatos de neuroesquistossomose encefálica. Devido a esse fato sua fisiopatologia e terapêutica necessitam de melhores estudos. Os aspectos imunológicos e apresentaçao na RM foram enfatizados.

The immunopathology of human Schistosomiasis-III. Immunoglobulin isotype profiles and response to praziquantel.

Immunoglobulin (Ig) isotype (IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgD and IgE) levels were investigated, both pre- and post-treatment with praziquantel (PZQ), in 43 adults and children chronically infected with Schistosoma mansoni, by means of a two-site, isotype-specific immunoenzymometric assay. The patients were classified as responders (R) or non-responders (NR) on the basis of their circumoval precipitin test (COPT) results 12 months after treatment. In comparison with controls, pre-treatment R children showed significantly higher levels of IgG, IgG1, IgG4 (p < 0.001) and IgE (p < 0.01); and diminished IgG2 (p < 0.05), while NR children showed significantly elevated levels only of IgE (p < 0.05). Twelve months after therapy, R children maintained significantly lower levels of IgG2, but showed significantly decreased levels of IgG, IgG1, IgG4, and IgE, while the Ig isotype profile of NR children was unaltered. Adult R and NR showed similar isotype profiles before chemotherapy, with the exception of significantly elevated IgM levels in R. Twelve months after therapy, R adults showed significantly decreased levels of IgG, IgG1, and IgG4, while NR adults showed only diminished IgG4 levels. These results reveal different Ig isotype profiles in untreated adults and children chronically infected with S. mansoni. The results further show that the pre-treatment Ig isotype profile may be significantly modified after an effective R to chemotherapy, accounted for by down regulation of the IgG1 isotype in association with negative seroconversion of the COPT in R patients. The COPT reaction has been associated with the highly specific egg glycoprotein antigen omega 1, which shows a significant reduction in reactivity six months after treatment. IgG1 may thus play a main role in the response against the omega 1 antigen.