Resistance to benzimidazole and macrocyclic lactone anthelmintics in cattle nematodes in Argentina.

In April 2003, persistent scouring and ill-thrift that was reported in calves form an intensive beef rearing operation in central Argentina despite treatments with benzimidazole and ivermectin. In order to conduct a controlled faecal egg count reduction test on this herd, 40 calves 5-8-months-old were selected on the basis that they had a nematode eggs per gram (epg) of faeces count greater than 150. Animals were divided into four groups (1-4) of 10 calves. Calves of groups 1-3 were treated, respectively, with subcutaneous injection of ivermectin (200 mcg/kg), ricobendazole (4 mg/kg) and levamisole (7.5 mg/kg), while calves of group 4 remained as untreated controls. The egg count reductions carried out 10 days later were lower than 15% in calves treated with ivermectin and ricobendazole, but 100% in animals receiving levamisole. Pooled post-treatment faecal cultures showed larval percentages of 92 and 95 for Haemonchus and 8 and 5 for Cooperia in the faeces of calves treated with ivermectin and ricobendazole, respectively. This is the first reported case of Haemonchus parasiting cattle showing simultaneous resistance to avermectins and benzimidazole type anthelmintics.

Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents.

The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K) to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquine, and praziquantel) were evaluated in infected female Swiss albino mice. These schistosomal isolates had been maintained in the laboratory without further drug pressure for 20 to 30 generations. Multiple dosage regimens were used for each drug against each isolate of S. mansoni to generate ED50 (effective dose 50%) values. Results demonstrated that the K isolate is resistant to niridazole, the MPR-1 isolate to oxamniquine, and the MAP isolate to both hycanthone and oxamniquine. The BH isolate was susceptible to all drugs and was used as the reference isolate. All isolates were susceptible to parziquantel. The significance of the difference in response of the MPR-1 and MAP isolates is discussed. These results confirm the resistance of these isolates of S. mansoni to three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs.

Efficacy of alternating therapy with oxamniquine and praziquantel to treat Schistosoma mansoni in children following failure of first treatment.

Two hundred children infected with Schistosoma mansoni were treated with either 20 mg/kg oxamniquine or 60 mg/kg praziquantel. Cure rates (about 85%) were similar as was the percentage reduction (80%) in egg counts in uncured children. Treatment with the alternative drug of children not cured with the first treatment resulted in negative stools in 11 of 12 cases examined one month after the second round of therapy. In order to minimize the risk of the development of drug resistance, our data suggest that infected patients be treated with one drug, and therapeutic failures with another. Evidence from experiments in mice with isolates obtained after failures of one treatment in children suggests that therapeutic failure does not necessarily indicate the presence of drug-resistant schistosomes. The value of using mice to assess drug resistance in schistosomes is questioned.

Rate of action of schistosomicides in mice infected with Schistosoma mansoni.

Mice infected with adult Schistosoma mansoni were dosed with a single oral dose of 125 or 250 mg/kg oltipraz, 50 or 100 mg/kg oxamniquine, or 200 or 400 mg/kg praziquantel. The mortality rate of worms and oogram changes were determined between 1 and 16 weeks after dosing. The time required between dosing and postmortem to obtain maximum effectiveness was 1 week for praziquantel, 2 weeks for oxamniquine and 8 weeks for oltipraz. Changes in oograms persisted throughout most of the experiment, although relapse has been observed at the 4th week on.

Drug resistance in schistosomiasis: a review.

Drug resistance associated with the treatment of human schistosomiasis appears to be an emerging problem requiring more attention from the scientific community than the subject currently receives. Drug-resistant strains of Schistosoma mansoni have been isolated by various investigators as a result of laboratory experimentation or from a combination of field and laboratory studies. Review of this data appears to indicate that the lack of susceptibility observed for some of the isolated strains cannot be ascribed solely to previous administration of antischistosome drugs and thus further studies are required to elucidate this phenomena. Strains of S. mansoni have now been identified from Brazil which are resistant to oxamniquine, hycanthone and niridazole; from Puerto Rico which are resistant to hycanthone and oxamniquine; and from Kenya which are resistant to niridazole and probably oxamniquine. Strains derived by in vitro selection and resistant to oxamniquine and possibly to oltipraz are also available. All of these strains are currently maintained in the laboratory in snails and mice, thus providing for the first time an opportunity for indepth comparative studies. Preliminary data indicates that S. haematobium strains resistant to metrifonate may be occurring in Kenya. This problem could poise great difficulty in the eventual development of antischistosomal agents. Biomphalaria glabrata from Puerto Rico and Brazil were found to be susceptible to drug-resistant S. mansoni from each country.

The biology of NippostrongyLus brasiliensis in SPF rats.

When maintained under SPF (specific pathogen free) conditions, Wistar rats had low and variable counts of adult Nippostrongylus brasiliensis. Worm counts were increased if rats were kept in solid rather than wire-bottom cages, if rats were maintained under non-SPF conditions, or if SPF rats were orally inoculated with gut contents from non-SPF rats. It is concluded that gut flora in SPF wistar rats directly or indirectly affects the numbers of larvae establishing as adult worms.