A computational structural analysis of functional attributes of hypodermin A and B proteins: A way forward for vaccine development.

Hypodermosis is a parasitic disease of cattle. The pathogenicity of the disease is attributed to Hypodermin proteins (Hypodermin A, Hypodermin B and Hypodermin C). Studies suggest that Hypodermin proteins may be defined as Serine proteases and collagenases. The structure of both proteases Hypodermin A and Hypodermin B were modeled using the Swiss-model server followed by its validation using Procheck, Errat and Verify-3D. Afterwards, both Hypodermin A and Hypodermin B were docked against collagen in order to study its interaction with respective Hypodermin proteins. The structure of both Hypodermin A and Hypodermin B showed more bent towards hydrophobic nature as more beta sheets were present in them. Both structures were also superimposed to check out similarities and differences present between them. Serine, Aspartic acid, Histidine, Glutamic acid and Lysine are found as interacting residues that are involved in hydrogen bonding with collagen. The interactions are found in the active domain region of Hypodermin proteins. The interacting residues were present in the active region of the hypodermin proteins thus validating the docking studies. This study may help in the drug development against hypodermosis with least side effects.

[Control of bovine hypodermosis in Switzerland; looking back]. / Die erfolgreiche Bekämpfung der Hypodermose in der Schweiz: Ein Blick zurück.

For many years, hypodermosis control - which started in the 1920's - was unsatisfactory, partly due to a lack of efficacy or a too high toxicity of the available products. An improved control became possible with the introduction (1957) of the organophosphate Metrifonate (Neguvon®, Bayer AG). Subsequent large-scale campaigns according to the Federal Ordinance on epizootic diseases (1967) quite reduced hypodermosis in Switzerland. However, due to a limited use of the product (only young and alpine-grazing cattle were allowed to be treated, administratively indicated maximum dose, side-effects) and its incomplete efficacy, a full control was not possible. The decision to maintain hypodermosis as a "notifiable" disease then allowed further epidemiological studies. In 2000/2001 a concerted action in close cooperation with the cantonal veterinarians allowed a consequent and systematic treatment of all cattle in all endemic areas by the large-scale use of Eprinomectin (Eprinex®, Merial Inc.) for dairy cattle and of Ivermectin (Merial Inc.) as microdose "off-label" for young cattle has led to a rapid and sustainable success.

Studies on the biology, chemotherapy and distribution of warble fly in Pakistan.

This paper presents data on the prevalence, biology and control of warble fly infestation (WFI) in cattle and goats in Pakistan. A questionnaire for obtaining information on biology and prevalence was circulated amongst field veterinary staff and livestock farmers in all five provinces (Punjab, Sindh, Balochistan, Khyber Pakhtunkhwa [KPK] and Gilgit-Baltistan) and in the Federally Administered Tribal Areas of the country. A total of 1,019 questionnaires were received (Punjab = 296, Sindh = 246, KPK = 318, Balochistan = 151, Gilgit-Baltistan = 8). Warble fly infestation was reported from each province and from the federally administered tribal areas, particularly from hilly, semi-hilly and sandy desert areas (the Cholistan desert, which adjoins the Rehim Yar Khan, Bahawalpur and Bahawalnagar districts, and the Nara area of Sanghar district). Warbles (nodules) started appearing on the backs of the infested animals from September through December and disappeared from October through March. The prevalence of WFI varied from 5% to 75%. It was highest in hilly areas and gradually decreased towards the plains. A map was developed of warble fly-infested areas. Four field trials were conducted to study the efficacy of different drugs indicated for the control of warble fly infestation. A total of 2,094 cattle and 3,876 goats were given five different injectables (avermectins); namely, Ivomec, Endectin, Euvectin, Dectomax and Promectin (ivermectin) during the first three weeks of September. A control group was given normal saline. All the medicines were found to be effective in controlling infestation.

Hidden antigens from third instar Hypoderma lineatum: impact of immunization on larval survival in artificial infestations.

Soluble fractions of Hypoderma lineatum third instar fat body, haemocytes and haemolymph were formulated with Quil A and used to immunize four groups of calves while a fifth group remained untreated. Calves received two subcutaneous injections of the soluble fractions, or adjuvant only delivered two weeks apart. Two weeks after the last injection the calves were exposed to 50 newly hatched larvae of H. lineatum which were placed on the skin and allowed to penetrate. Survival of larval stages was monitored by weekly palpation and collection of emergent third instars. Antibody responses to the immunogens were evaluated by immunoblots and following infestation antibody responses to first instar antigens were evaluated by an ELISA. Non-immunized calves and calves injected with adjuvant were all palpation positive for cattle grubs. In groups immunized with fat body, haemocyte and haemolymph components 100%, 33% and 33% were palpation positive for grubs respectively. First instar mortality, as reflected in palpable grubs, was high in the groups receiving injections with tissue components (99.3%, 95.1%, 95.8%, 83.9 and 80.4% mortality for those groups receiving fat body, haemocyte, haemolymph, adjuvant or control respectively). Second and third instar mortality was also higher in the immunized groups (100.0%, 91.7%, 91.7% for fat body, haemocyte, and haemolymph respectively) in comparison to the adjuvant only (14.0%) and unvaccinated (33.3%) groups. No viable flies emerged from pupae originating from larvae emergent from any of the immunized groups. Calves receiving the tissue extracts developed antibodies to several protein components following the second immunization which were still present 13 weeks post-infestation. Several proteins appeared to be common among the three tissue extracts and were recognized by antibodies from the immunized calves. All groups of calves became positive for antibodies to first instar antigens, although in some immunized calves the antibodies were transient.

A successful, sustainable and low cost control-programme for bovine hypodermosis in France.

Bovine hypodermosis affecting livestock performance and the leather industry was still widespread in France up to the nineties despite successive directives from the Ministry of Agriculture since 1941, encouraging livestock owners to treat, on a voluntary basis. In 1969 the French Ministry of Agriculture, asked the national Farmers' Animal Health Organisation (FAHO), to plan a durable hypodermosis control programme and a working group including all the partners in cattle production was set up, under the coordination of the national FAHO. Improved systems of hypodermosis control, including new treatment and surveillance methods were developed. Among the main benefits obtained from this original work, were (i) the identification of scientific data which allowed inexpensive and accurate immuno-surveillance procedures, and a highly effective low-cost treatment, Ivomec, administered at the micro dose rate (2 microg/kg), which is environmentally non-threatening, and (ii) the development of a new strategy to manage the control programmes progressively, on a regional basis, in two to three concentric zones over three successive years at a maximum. The current programme, coordinated at the National level since 1998, has been implemented in each region of France. The compulsory systemic winter treatments directed against the endo-parasitic stage, carried out by technicians and veterinarians involved the entire bovine population in controlled zones. As each zone reached a hypodermosis herd prevalence of under 5%, usually after two years, the treatments were suspended. However treatments of the infected farms and contiguous farms were maintained. An immuno-survey was carried out, each winter, to evaluate the prevalence of the disease and detect any residual foci or re-infestations. Since 2002, bovine hypodermosis in France is under control with immuno-surveillance maintained at a very low cost. In 2006 hypodermosis became a notifiable disease.

Field efficacy of minidosed eprinomectin against Hypoderma spp. in dairy cattle.

A chemoprophylactic field trial was conducted to assess the efficacy of pour-on eprinomectin applied at the approximate dose of 50 mcg/kg to dairy cattle with naturally occurring hypodermosis. Two-hundred-eleven cattle, selected from two herds with a high prevalence of Hypoderma spp. infestation, were divided in three groups: Group A (N = 71) was treated with pour-on eprinomectin at the recommended dosage of 500 mcg/kg, Group B (N = 64) at the lower dose of 50 mcg/kg, a third group (Group C, N = 76) served as untreated control group. Treatments were performed in November-December 2002 and the animals were examined for the presence of warbles in the following April and June. No larvae emerged in the treated groups, whereas a variable number of warbles (ranging from 1 to 28) were found in control animals. Adverse reactions were not observed in any animal, and only minor side effects were observed. A larger field trial carried out in the following year (1064 treated and 131 untreated control cattle) confirmed the chemoprophylactic efficacy of minidosed eprinomectin against Hypoderma spp. Administration of eprinomectin minidoses in dairy cattle is interesting because of the low costs involved and no need for milk withdrawal.

Durably controlling bovine hypodermosis.

Cattle hypodermosis, due to insect larvae, is widely spread over the northern hemisphere. Very efficient insecticides are available and their use in most countries are done on an individual level but never cover the whole cattle population of a country. Untreated animals remain the reservoir of the disease and annually re-infest the cattle population. The economic effects of this disease on animal production (meat, milk and the leather industry) but also on the general cattle health status, have led many European countries to launch organised control programs. The first example of definitive hypodermosis control goes back one hundred years ago when Danish farmers eradicated hypodermosis from the Danish islands by manual elimination of the warbles. Since then, more and more European countries have considered the feasibility and economic returns of such programs. The various factors which foster these programs are related to (i) biological factors, (parasite cattle specificity, synchronous biological cycles of both species of insects involved), (ii) the development of more and more efficient insecticides used only once a year by systemic application, with high efficiency at very low dosages against the first larval stage of Hypoderma spp., (iii) the development of acute techniques of detection of the disease for the monitoring of hypodermosis free countries and (iv) the durable successful results obtained in more and more European countries. Although the programs were imposed by different partners of the livestock channel production (farmers, dairy industry, leather industry) and have been engaged within the last 50 years in many European countries (Denmark, The Netherlands, Ireland, the United Kingdom, the Czech Republic, Germany, France and Switzerland) common features have emerged among these different eradication programs. They all need a preliminary statement of the economic impact of this pest and the farmers' awareness of the economic returns of such programs. The programs' efficacy depends: (i) on a good knowledge ofthe epidemiology of the parasites, (ii) on the simultaneous implementation of the control program on the whole national cattle population whatever the structure monitoring the treatments (veterinary services, farmers association), (iii) on a national Warble fly legislation making the treatments compulsory and (iv) on an acute epidemiological survey as soon as the status of a hypodermosis free country is reached and the treatments are suspended. The sanitary and financial returns of such programs are a benefit to all the partners of livestock production, to the quality of the environment and to the consumers.

[Hypoderma diana in roe deer in the Netherlands]. / Hypoderma diana horzels bij reeën in Nederland.

An infestation with Hypoderma diana in roe deer in the Netherlands is described. The condition of the infested deer was poor. Hypoderma diana is no threat for cattle.

[Bovine hypodermyiasis: a quasi sequential procedure for observation of live-stock for surveillance of recrudescence in eradicated zones]. / Hypodermose bovine: une procédure quasi séquentielle d'observation des cheptels pour la surveillance de la recrudescence en zone éradiquée.

A quasi-sequential sampling plan for observing cattle was undertaken in the framework of Hypoderma bovis epidemiological surveillance. This plan enabled us to test whether or not the prevalence of Hypoderma bovis is within a threshold p0 chosen for an eradication scheme or for qualifying a zone. The sampling cost was reduced but the estimation precision remained acceptable. The sensitivity of monthly controls with respect to the reference period (April, May, June, July) was studied from data observed over 6 consecutive years in Côtes d'Armor, France. The best ratio sensitivity/sampling cost was obtained with a unique counting plan in June where 48% (36 to 60%) of the herds found to be infested during the reference period were detected. The test procedure concerning the prevalence level was then adapted to take into account the sensitivity of the observation method. This is tantamount to reducing the threshold p0.

Effect of early treatment with ivermectin and doramectin on the dynamics of antibody response in cattle naturally infested by Hypoderma lineatum and H. bovis.

The field efficacy of two avermectins (ivermectin and doramectin) and the subsequent development of the antibody response were assessed in cows naturally infested with first-instar larvae (L-1) of Hypoderma sp. Twenty-eight Frisian cows were randomly divided into three groups while the first-instar larvae were still in migration: Group 1 (G-C) untreated control; Group 2 (G-Iv), treated with ivermectin injectable (0.2 mg kg-1 body weight) and Group 3 (G-Dor), which received doramectin injectable (0.2 mg kg-1 body weight). Serum antibody response was studied by an indirect ELISA test using, as antigen, the hypodermin C obtained from L-1 of H. lineatum. In treated animals no grubs were present on the back at any time during the trial, whereas a variable number of nodules were found in untreated animals. Both avermectins showed total efficacy against L-1 of Hypoderma sp., and there were no local or general reactions. In ivermectin-treated cattle serum antibody levels declined from one month p.t., while in those treated with doramectin they started to fall two weeks later, but no differences were found among both groups. On the other hand, G-C antibody levels progressively increased and remained high until December, when the first grubs became detectable on the back; after that, they began to decline. Early treatments against Hypoderma sp. have an influence on the results of ELISA, so they must be considered to determine the most suitable time for blood sampling.

Deer hypodermosis.

Hypodermyiasis is a common myiasis which affects a wide variety of deer species in many parts of the world. In this article a great review of the disease is made, treating the different species of flies that cause the myiasis in the different species of hosts. Biologies of deer and flies are also studied, with special dedication to the chronobiology of the life cycle of the parasite. Prevalence and intensity of parasitization in many parts of Europe are recorded like expression of the importance of hypodermyiasis in deer. Finally, some remarks about treatment and control are included.

Recombinant vaccine development: a novel approach to ectoparasite control. A review of development of a recombinant vaccine for hypodermosis based on hypodermin A.

Cattle grubs (Hypoderma lineatum and H. bovis) are obligate parasites of cattle for most of their one year life cycle. Previously exposed animals become resistant to productive reinfestation, presumably as a result of immune system involvement, suggesting potential control by vaccination. Research progress towards development and utilization of a recombinant subunit vaccine for hypodermosis is described.

Progress in the British hypodermosis eradication programme: the role of serological surveillance.

The British warble fly eradication programme has resulted in the numbers of infested cattle falling from an estimated four million in 1978 to zero in 1991. In 1982, when about 705 herds were infested the disease was made notifiable, and serological surveillance was begun in 1988. In spring 1991, 227,000 blood samples were tested by using the ELISA technique and no warbled animals were found. In addition no clinical cases were reported during 1991.