Cancer Drugs Remain Hot Targets.

Estimates of future growth in the oncology market, a predicted increase of 11% per year in sales, and the need to expand drug-development pipelines to sustain profits have been driving up the value of corporate mergers, such as Pfizer's purchase of Medivation for $14 billion.

The economic effects of whole-herd versus selective anthelmintic treatment strategies in dairy cows.

Current control practices against gastrointestinal nematodes in dairy cows rely strongly on anthelmintic use. To reduce the development of anthelmintic resistance or disposition of drug residues in the environment, novel control approaches are currently proposed that target anthelmintic treatment to individual animals instead of the whole herd. However, such selective treatment strategies come with additional costs for labor and diagnostics and, so far, no studies have addressed whether they could be economically sustainable. The objectives of this study were to (1) investigate the economic effects at farm level of whole-herd versus more selective anthelmintic treatment strategies in adult dairy cows, and (2) determine how these economic effects depend on level of infection and herd size. A Monte Carlo simulation, fed by current epidemiological and economical knowledge, was used to estimate the expected economic effects and possible variation of different control strategies under Belgian conditions. Four treatment strategies were compared with a baseline situation in which no treatments were applied: whole herd at calving (S1), selective at calving with (S2) or without (S3) treatment of the first-calf cows, and whole-herd when animals are moved from grazing to the barn in the fall (housing treatment, S4). The benefit per lactation for an average dairy herd varied between -$2 and $131 (average $64) for S1, between -$2 and $127 (average $62) for S2, between -$17 and $104 (average $43) for S3, and between -$41 and $72 (average $15) for S4. The farmer's risk associated with any treatment strategy, as indicated by the width of the 95% credible intervals of economic benefit of anthelmintic treatment, decreased with increasing level of exposure, as assessed by bulk tank milk ELISA. The order of the different strategies when sorted by expected benefit was robust to changes in economic input parameters. We conclude that, on average, strategies applying anthelmintic treatment at calving outperform a strategy applying treatment at housing. Within the strategies that applied treatment at calving, more selective treatment strategies can be economically sustainable. However, given the large variation in possible benefits within each treatment strategy, decision support systems are needed to account for the multitude of cow, epidemiological, and economic factors that determine the economics of nematode control and select the optimal treatment strategy for a specific farm.

In a survey, marked inconsistency in how oncologists judged value of high-cost cancer drugs in relation to gains in survival.

Amid calls for physicians to become better stewards of the nation's health care resources, it is important to gain insight into how physicians think about the cost-effectiveness of new treatments. Expensive new cancer treatments that can extend life raise questions about whether physicians are prepared to make "value for money" trade-offs when treating patients. We asked oncologists in the United States and Canada how much benefit, in additional months of life expectancy, a new drug would need to provide to justify its cost and warrant its use in an individual patient. The majority of oncologists agreed that a new cancer treatment that might add a year to a patient's life would be worthwhile if the cost was less than $100,000. But when given a hypothetical case of an individual patient to review, the oncologists also endorsed a hypothetical drug whose cost might be as high as $250,000 per life-year gained. The results show that oncologists are not consistent in deciding how many months an expensive new therapy should extend a person's life before the cost of therapy is justified. Moreover, the benefit that oncologists demand from new treatments in terms of length of survival does not necessarily increase according to the price of the treatment. The findings suggest that policy makers should find ways to improve how physicians are educated on the use of cost-effectiveness information and to influence physician decision making through clinical guidelines that incorporate cost-effectiveness information.

Serine/threonine phosphatases in socioeconomically important parasitic nematodes--prospects as novel drug targets?

Little is known about the fundamental biology of parasitic nematodes (=roundworms) that cause serious diseases, affecting literally billions of animals and humans worldwide. Unlocking the biology of these neglected pathogens using modern technologies will yield crucial and profound knowledge of their molecular biology, and could lead to new treatment and control strategies. Supported by studies in the free-living nematode, Caenorhabditis elegans, some recent investigations have provided improved insights into selected protein phosphatases (PPs) of economically important parasitic nematodes (Strongylida). In the present article, we review this progress and assess the potential of serine/threonine phosphatase (STP) genes and/or their products as targets for new nematocidal drugs. Current information indicates that some small molecules, known to specifically inhibit PPs, might be developed as nematocides. For instance, some cantharidin analogues are known to display exquisite PP-inhibitor activity, which indicates that some of them could be designed and tailored to specifically inhibit selected STPs of nematodes. This information provides prospects for the discovery of an entirely novel class of nematocides, which is of paramount importance, given the serious problems linked to anthelmintic resistance in parasitic nematode populations of livestock, and has the potential to lead to significant biotechnological outcomes.

Coverage and costs of a school deworming programme in 2007 targeting all primary schools in Lao PDR.

Infections with soil-transmitted helminths (STHs) are among the commonest infections in Lao PDR. Recent investigation in this country showed that intestinal helminths currently infect the majority of school-aged children. The Lao Government has addressed the problem by organizing regular anthelminthic chemotherapy with mebendazole 500mg for school and pre-school children in conjunction with health education activities incorporated into the national school curriculum. The school deworming campaign in Lao PDR reached a national coverage rate of 95% at a cost of US$0.124/head for two rounds of deworming per year. The programme operates under the umbrella of the national school health programme. After 1 year (two rounds of deworming) the intervention reduced the prevalence of Ascaris lumbricoides from 60% to 20% and of Trichuris trichiura from 42% to 31%. Although infection was not eliminated by the deworming interventions, over 90% of those children who remain infected had a 'light' infection. The virtual absence of high and moderate intensity infection demonstrates the effectiveness of periodical deworming in reducing morbidity due to STHs. We expect that additional rounds of deworming will further reduce the STH prevalence in Lao PDR.

Prevalence of common gastrointestinal nematode parasites in scavenging pigs of different ages and sexes in eastern centre province, Burkina Faso.

The range and infestation intensities of gastrointestinal parasitic nematode species depend on the type of swine production system. The present study focused mainly on nematodes of veterinary importance in scavenging pigs in Burkina Faso, and aimed at determining the prevalence of gastro-intestinal nematode parasites by means of faecal egg per gram (EPG) counts. Between November 2001 and October 2002, faecal samples from 383 pigs of different sexes and ages (< 5 months, 5-12 months and > 12 months) were collected from the rectum and examined for gastrointestinal nematodes parasites using the Mc Master method. Of the 383 pigs examined, 91% were infected by one or more parasites. Ascaris suum (40%; 100-1 400 EPG) was the most prevalent parasite followed by Strongyloides ransomi (21%; 100-4200 EPG), Oesophagostomum spp. (18%; 100-1000 EPG), Hyostrongylus rubidus (11%; 100-1 800 EPG), Globocephalus spp. (10%; 100-400 EPG) and Trichuris suis (1 %; 100-200 EPG). The prevalence was significantly higher in female pigs (n = 239) than in males. In addition, females excreted significantly (P < 0.05) more eggs in their faeces than males, except in the case of Globocephalus spp. The age of the animal had no effect on the prevalence of A. suum whereas there were significant differences in age categories concerning S. ransomi, H. rubidus, Oesophagostumum spp. and Globocephalus spp. Unexpectedly, the high prevalence of these common parasites was not accompanied by elevated EPG values, which suggests the existence of moderate infestations. The present work indicates that the common nematode infestations in pigs do not necessarily need a systematic herd anthelmintic treatment, as only a small number of worms is required to induce immunity. A further study is needed to formulate appropriate and cost-effective strategies for the control of gastro-intestinal nematode parasites in pigs in Burkina Faso.

Efficacy of albendazole against the whipworm trichuris trichiura--a randomised, controlled trial.

OBJECTIVES AND DESIGN: To test the efficacy of albendazole against the whipworm Trichuris trichiura for school-based deworming in the south-western Cape, South Africa. Children infected with Trichuris were randomised to 3 doses of albendazole (400, 800 or 1200 mg), each repeated 4 times. The boy/girl ratio was 1. A group not infected with worms was treated with placebo, creating a negative control. SUBJECTS AND SETTING: Pupils at a primary school serving a wine-producing area approximately 90 km east of Cape Town. OUTCOME MEASURES: Trichuris cure rates and reduction in the number of eggs/g in faeces, as well as the infection dynamics of Trichuris and Ascaris during treatment with placebo. RESULTS: Albendazole treatment was associated with Trichuris cure rates of 23% (400 mg), 56% (800 mg) and 67% (1200 mg) after the final treatment. The corresponding reductions in the number of eggs/g of faeces were 96.8%, 99.3% and 99.7%. Environmental pollution by human faeces was confirmed because worm egg-negative children in the placebo group became egg-positive while the study was in progress. CONCLUSION: The 400 mg stat dose had a low Trichuris cure rate. To repeat the dose on 2 or 3 days would increase cost, reduce compliance and complicate management. Albendazole cannot be used in deworming programmes in South Africa because it is a Schedule 4 prescription medicine. De-scheduling is needed urgently, particularly because of high efficacy against hookworm in KwaZulu-Natal and neighbouring countries.

The cost-effectiveness of ivermectin vs. albendazole in the presumptive treatment of strongyloidiasis in immigrants to the United States.

The presumptive treatment of parasitosis among immigrants with albendazole has been shown to save both money and lives, primarily via a reduction in the burden of Strongyloides stercoralis. Ivermectin is more effective than albendazole, but is also more expensive. This coupled with confusion surrounding the cost-effectiveness of guiding therapy based on eosinophil counts has led to disparate practices. We used the newly arrived year 2000 immigrant population as a hypothetical cohort in a decision analysis model to examine the cost-effectiveness of various interventions to reduce parasitosis among immigrants. When the prevalence of S. stercoralis is greater than 2%, the incremental cost-effectiveness ratios of all presumptive treatment strategies were similar. Ivermectin is associated with an incremental cost-effectiveness ratio of 1700 dollars per QALY gained for treatment with 12 mg ivermectin relative to 5 days of albendazole when the prevalence is 10%. Any presumptive treatment strategy is cost-effective when compared with most common medical interventions.

Effects of anthelmintic treatment and feed supplementation on grazing Tuli weaner steers naturally infected with gastrointestinal nematodes.

A study was carried out to determine the epidemiology of gastrointestinal nematodes in indigenous Tuli cattle and the effect of dietary protein supplementation and anthelmintic treatment on productivity in young growing cattle. Forty steers with an average age of 18 months were divided into 4 groups; 1) fenbendazole (slow release bolus) and cottonseed meal (FCSM group), 2) fenbendazole (FBZ group), 3) cottonseed meal (CSM group) and 4) control (no cottonseed meal and no fenbendazole) (control group). Performance parameters measured included worm eggs per gram of faeces (EPG), packed cell volume (PCV), albumin and live-weight gain. Results showed that faecal worm egg counts were lower and PCV was higher in the FCSM and FBZ groups than in the CSM and control groups (P < 0.01). Weight gains were higher in the CSM and FCSM groups than in the FBZ and control groups (P < 0.05). The cost benefits of anthelmintic treatment and dietary supplementation were apparent in this study. The improved growth performance of the FCSM, FBZ and CSM groups reflected a financial gain over the controls on termination of the study. The dominant genera of gastrointestinal nematodes on faecal culture, pasture larval counts and necropsy were Cooperia and Haemonchus. The incidences of Trichostrongylus, Oesophagostomum and Bunostomum were low.

Relative cost-effectiveness of treatment of feedlot calves with ivermectin versus treatment with a combination of fenbendazole, permethrin, and fenthion.

OBJECTIVE: To compare growth performance, animal health characteristics, and carcass characteristics of feedlot calves treated with ivermectin topically with that of feedlot calves treated with a combination of fenbendazole orally and permethrin and fenthion topically. DESIGN: Clinical trial. ANIMALS: 14,184 British crossbred steer calves (mean weight, 286 kg [630 lb]) in 30 pens at a commercial feedlot in Nebraska. PROCEDURE: On arrival at the feedlot, calves were randomly assigned to be treated with ivermectin topically or with a combination of fenbendazole orally and permethrin and fenthion topically (control). At the time of assignment to treatment groups, fecal samples were collected from 5% of the calves. Growth performance, carcass characteristics, and health information were recorded. RESULTS: Geometric mean fecal egg counts at the time of arrival at the feedlot were not significantly different between groups. Final weight, weight gain, average daily gain, and the dry matter intake-to-gain ratio were significantly improved for calves in the ivermectin group. The percentage of carcasses classified as quality grade choice was higher for the ivermectin group than the control group; however, the percentage of carcasses classified as yield grade 1 and the dressing percentage were higher for the control group than for the ivermectin group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of ivermectin to feedlot calves is relatively more cost-effective than administration of a combination of fenbendazole orally and permethrin and fenthion topically.

Comparative cost-effectiveness of ivermectin versus topical organophosphate in feedlot yearlings.

A replicated-pen field trial was performed under commercial feedlot conditions in western Canada to determine the cost-effectiveness of administering ivermectin to yearling beef cattle upon entry to the feedlot after the grazing season, and to establish the level of trichostrongylid gastrointestinal parasite infection in this population, as estimated by fecal egg counts. Six thousand eight hundred and eighty-three, mixed breed, yearling steers were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: Ivermectin, which received topical ivermectin (0.5%) at the rate of 1.0 mL/10 kg body weight; or Fenthion, which received topical fenthion (20%) at the rate of 12 mL/295 kg body weight. There were 15 pens in each experimental group. Final weight, weight gain, average daily gain, and dry matter intake to gain ratio were significantly (P < 0.05) improved in the Ivermectin group as compared with the Fenthion group. There were no significant (P > or = 0.05) differences in initial weight, days on feed, or daily dry matter intake between the experimental groups. The geometric mean fecal egg counts at the time of allocation were 14.7 eggs/5 g and 16.6 eggs/5 g for the Ivermectin and Fenthion groups, respectively (P > or = 0.05). There were no significant (P > or = 0.05) differences in morbidity or mortality between the experimental groups. In the economic analysis, the significant improvements in feedlot performance in the Ivermectin group resulted in a net economic advantage of $4.20 CDN per animal.

Economic evaluation of three anthelmintic strategies for lamb flocks affected by benzimidazole-resistant nematodes.

OBJECTIVE: To compare the profitability of three anthelmintic strategies in growing lambs in flocks with nematodes resistant to benzimidazole anthelmintics. METHOD: A partial-budgeting analysis was carried out by means of a stochastic simulation model, which allows inputs to be described as distributions rather than as fixed values, and hence permits variation between farms to be considered in the analysis. RESULTS: The results show that control of nematode parasites by use of an effective anthelmintic provides the highest net returns, yielding a margin over ineffectively treated lambs of A$114 per 100 lambs on average. Suppressive treatment based on the administration of two controlled-release capsules and monthly with moxidectin resulted in an average loss of A$131 per 100 lambs in comparison with animals treated with an ineffective anthelmintic. Analysis of the results from capsule-treated lambs did not take into account the unmeasured benefits associated with less contamination of pastures. Sensitivity analysis using a stochastic model indicates that apart from the effect of treatment on weight gain variation in carcase price greatly influences the profitability of all the parasite control programs examined. CONCLUSION: The results suggest that it is economically important for farmers to adjust their strategy in the presence of anthelmintic resistance. But as a result of uncertainty in the factors influencing economic return, the expected economic benefit is likely to vary substantially.

A cost-effectiveness analysis of anthelminthic intervention for community control of soil-transmitted helminth infection: levamisole and Ascaris lumbricoides.

A study to compare effects of mass, targeted, and selective chemotherapy with levamisole as an intervention for the control of Ascaris lumbricoides was carried out in 3 communities in rural Oyo State, Nigeria. Selective treatment was applied in 1 village by treating the most heavily infected 20% of the inhabitants, targeted treatment in the second village involved children aged 2-15 yr, whereas mass treatment was offered to all inhabitants in the third village, excluding infants under 1 yr and pregnant women. Intensity (eggs per gram,) of A. lumbricoides infection was determined immediately before and 3 mo after the period of intervention as a means of assessing the relative efficacy of the treatment regimes. During the field study, information on resource use was also collected for a retrospective cost analysis of the 3 strategies Resources used included manpower, materials, drugs, and transport. The results of the parasitological evaluation on the effect of treatment on egg intensity were then combined with the cost analysis to provide an overall measure of the cost-effectiveness of mass, targeted, and selective interventions. The results were expressed in terms of the cost per 1,000 egg reduction in intensity and the cost per person treated. The results showed the mass and targeted approach to be considerably more cost effective than the selective approach.

Anthelmintic sales in the highveld region of Eastern Transvaal.

Throughout a survey from 1991 to 1993 in the Highveld region of Eastern Transvaal, levamisole sales dominated in the sheep anthelmintic market. The macrocyclic lactone sales dominated in the cattle anthelmintic market, but were superseded by those of levamisole in 1993. The salicylanilides enjoyed the second highest demand in the sheep anthelmintic market. Anthelmintics were purchased throughout the year, but sales peaked in summer and autumn. When it rained in winter, sales increased during winter and peaked in spring. Eastern Transvaal Co-operative (OTK) sold 2,64 therapeutic doses per sheep during the driest year and 3,54 per sheep during the wettest year in the Highveld region. Only 24-29% of the cattle in the region could be treated with the anthelmintics sold by OTK for cattle. Total sales are estimated at double these figures.

Control of Ascaris infection by chemotherapy: which is the most cost-effective option?

Cost-effectiveness analysis is used to predict the optimal design of mass chemotherapy strategies in controlling Ascaris lumbricoides infection. The question of who to treat, how many to treat, and how often to treat are addressed using a population dynamic model of helminth transmission that assesses effectiveness in terms of disease reduction, combined with cost data from an actual control programme. Child-targeted treatment can be more cost-effective than population treatment in reducing the number of disease cases. The model also implies that, in the circumstances described here, enhancing coverage is a more cost-effective approach than increasing frequency of treatment.