The effect of niclofolan on desert sheep experimentally infected with immature Fasciola gigantica.

Eight desert sheep were each infected orally with 500 metacercariae of Fasciola gigantica and, after 4 weeks, four of the animals were given niclofolan orally at the recommended therapeutic dose rate of 7 mg/kg, the other four remaining as controls. One week later, the animals were slaughtered and the fasciocidal effect of the drug was evaluated on the basis of worm burden, haemogram, some plasma constituents, and gross and histopathological lesions of the liver, as indicators of efficacy. The treatment was found to be ineffective, the degree of infection remaining the same as in the untreated control group. The experiment was repeated using eight infected sheep: four were given the drug orally at a dose rate of 10.5 mg/kg, i.e., 1.5 times the recommended dose; and the same parameters were measured as described above. The drug failed to cure the infected sheep, and caused depression, anorexia and weakness. In a third experiment six sheep were infected as before and three were treated with niclofolan by deep i.m. injection at the recommended therapeutic dose of 2 mg/kg. A week later the animals were killed and examined as before. The drug was effective in treating the infection and produced no untoward effects except for transient signs of pain at the site of injection. It seems possible that the oral dose, unlike the i.m. dose, of niclofolan is not absorbed and/or metabolized sufficiently to prevent elimination of the infection.

Trematodiasis in Turkey: comparative efficacy of triclabendazole and niclofolan against natural infections of Fasciola hepatica and F. gigantica in sheep.

A new fasciolicide, triclabendazole, tested at single oral dose rates of 5 and 10 mg/kg body-weight, proved to be highly effective (greater than 99%) against chronic field infections of Fasciola hepatica and F. gigantica in sheep. The performance of the new drug compared favourably with niclofolan at the recommended dose. Neither product was effective against Dicrocoelium dendriticum and Paramphistomum spp.

Efficacy of triclabendazole against Fasciola hepatica in sheep and goats.

Triclabendazole (Fasinex), a new fasciolicide of the benzimidazole group, was tested in sheep and goats. A controlled test with 24 artificially-infected sheep revealed a 100% efficacy of triclabendazole at a dose of 10 mg kg-1 body weight against Fasciola hepatica aged 4 and 13 weeks, respectively. In naturally-acquired severe subacute to chronic fascioliasis in 66 sheep and 10 goats, the drug was highly effective in three trials when applied at 10 mg kg-1 in sheep and at 5 mg kg-1 in goats. Triclabendazole was well tolerated, whereas side effects occurred in one trial with niclofolan (Bilevon-M) (3 mg kg-1) which was used for comparison.

Pulmonary paragonimiasis in Cameroon.

Paragonimus africanus has been known to be endemic in the Bakossi area of Meme Division of Cameroon since it was first described in 1952. After a lapse of 25 years, exploratory work was undertaken in the area (but not in the same villages) to study the prevalence of the disease, to record the common presenting symptoms, to make a number of paraclinical examinations, to assess the beliefs and attitudes of the people towards the disease and the possible reasons for its persistent endemicity in that area and to carry out a therapeutic trial with Niclofolan (Bilevon). The disease was found to have a prevalence of 5% with a higher prevalence among those less than 20 years old. Boys were more affected than girls. The population did not appear to recognize the disease which they confused with tuberculosis. The disease was contracted by eating improperly cooked crabs, the intermediate host. The therapeutic trial with Bilevon given orally as a single dose was completely successful. This study showed that paragonimiasis must be considered seriously in the differential diagnosis of tuberculosis in this area and that a study on a much wider scale is required to establish the real extent of the disease.

Treatment of human fascioliasis with niclofolan.

We report a case of human Fasciola hepatica infection. For the first time evidence is presented of successful treatment of fascioliasis by oral administration of niclofolan, a biphenyl anthelmintic compound that is available for clinical testing in West Germany. Niclofolan therapy achieved elimination of eggs from the feces and normalization of eosinophil counts, liver enzymes and Fasciola titers, suggesting eradication of biliary flukes in our patient.

[Epidemiologic and clinical study of paragonimosis in Cameroon. Results of niclofolan treatment]. / Etude épidémiologique et clinique de la paragonimose au Cameroun. Résultats du traitement par le niclofolan.

Paragonimiasis does not occur only in the South West Province of Cameroon. Four foci exist in the country. They are the well known focus in the Mount Kupe area, the Mbam focus, the Nyong focus and the Ntem focus. All of them are located in the rainforest within the distribution area of Potadoma. This disease, characterized by the presence of eggs in sputum and feces, has often been confused with tuberculosis. In the villages where paragonimiasis is diagnosed by means of parasitological techniques circulating antibodies, revealed with a P. westermani antigen (ELISA), are often found in blood specimens taken from inhabitants. Teen agers suffer the most from the disease and females more often than males. Women and children are traditionally concerned with crabs fishing and they eat them after partly raw. Crabs of the genus Sudanautes contain the infective metacercariae. Paragonimiasis is enzootic and the civet cat V. civetta seems to be the main natural definitive host in Cameroon. Niclofolan given orally in a single dose of 2 mg/kg body weight showed a 100% cure rate. Side reactions are mild and transient.

Studies on the chemotherapy of human opisthorchiasis: II. Clinical trial of niclofolan.

A clinical trial of Niclofolan on human opisthorchiasis was carried out in 60 patients admitted to the Hospital for Tropical Diseases. Two dosage regimen, 2 mg and 3 mg per kg body weight repeated after a 72 hour interval was administered to 31 and 4 patients respectively. Comparative evaluation with the placebo group of 25 patients was made by the Stoll count on day 20, 40 and 60 after treatment. On day 60 percentage egg reduction of the treated and the placebo groups were similar. Mild and transient side effects such as nausea, anorexia, myalgia and arthralgia were recorded in all 3 groups but more severe in the higher dosage group. In this study, Niclofolan failed in reducing the egg production of Opisthorchis viverrini.

[Pathology of migrants: paragonimiasis (or pulmonary distomatosis)]. / Pathologie des migrants: la paragonimose (ou distomatose pulmonaire).

Three cases diagnosed and treated in Hmong Laotian refugees in Thailand are presented; one can expect to see more cases in western countries with the influx of south east Asian refugees. The symptoms are the ones of a chronic pulmonary tuberculosis. The origin of the patients must lead to a suspicion (mainly Laotian Hill tribes). Direct microscopic examination of th sputum reveals easily the eggs of the parasite. Radiologic signs are not specific. The Niclofolan (Bayer) is the ultimate progress in the treatment at a single dose of 2 mg per kilo body weight, its efficiency is much superior to the classic treatments (Emetin, Chloroquin, Bithionol), except in some pleural forms.

[Clinical trial of niclofolan (Bay 9015) in the treatment of human opisthorchiasis. Apropos of 51 cases]. / Essais de traitement des opistorchiases humaines par le niclofolan (Bay 9015). A propos de 51 cas.

51 refugees from South east Asia infected with Opisthorchis viverrini or Clonorchis sinensis were included in a therapeutic study with Niclofolan (Bay 9015) at a dose of 1 mg/kg body weight given three times at intervals of 48 hours. Clinical and biological tolerance was carefully controlled and in all cases proved to be very good or excellent particularly in several patients with various haemoglobinopathies or erythrocytal enzymopathies (G-6-PD deficiency). Of the total of 51 cases, 17 were cured. These comprised mainly those with light or moderate infections (less than 10,000 eggs/gram stool). Treatment was, however, not effective in the more severe infections, even when repeated after an interval of 30 days. Between day 30 and 60 after treatment, only a transitory reduction of eggs/gram stool was observed, these values increasing again after day 90. Niclofolan did not reveal to be the ideal treatment of opisthorchiasis. Nevertheless its excellent tolerance should be pointed out which justifies its tentative application in light infections and above all its use in the treatment of paragonimiasis against which it appears to be one of the best drugs available at present.

[The effectiveness of the drugs Dovenix and Bilevon(R)-Injection against liver fascioliasis (Fasciola hepatica, Linné 1758) in cattle]. / Ucinnost léku Dovenix a BilevonR-Injektion proti motolici jaterní (Fasciola hepatica, Linné 1758) u skotu.

Dovenix and Bilevon-injection (manufactured by SPECIA, France and BAYER, West Germany, respectively) were tested for their anthelmintic efficacy against Fasciola hepatica in cattle. The drugs proved highly effective against both adult and immature flukes. The faeces of the treated animals were negative for F. hepatica eggs when examined 91 days after the treatment. In experiments with rats Dovenix and Bilevon-injection were tolerated up to eight times and ten times higher doses than the normal therapeutic dose, respectively.

Single dose therapy of paragonimiasis with menichlopholan.

Menichlopholan, biphenyl compound, in a single dose of 2 mg/kg body weight, gave a 73%-90% cure rate in the treatment of pulmonary infections due to Paragonimus uterobilateralis at two centers in Nigeria. Ninety-five patients were followed up for 4 months, and 58 for 1 year. Side effects of the drug included sweating and body pains, but there was no significnat biochemical or hematological evidence of damage to the internal organs. The advantages of single dose therapy are likely to make menichlopholan the treatment of choice for paragonimiasis in Africa, and probably elsewhere.

[Committee on anthelmintics. Residual group]. / Geneesmiddelen-anthelmintica. Restgroep

A number of the older and a few recent anthelmintics are enumerated or briefly discussed. Moreover some attention is paid to anthelmintics, used for nematodes and trematodes which have a limited effect on cestodes.