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Featured researches published by P.H. Holmes.


Parasite Immunology | 1995

Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta

M. J. Stear; Stephen Bishop; M. Doligalska; J.L. Duncan; P.H. Holmes; J. Irvine; L. McCririe; Quintin McKellar; E. Sinski; Max Murray

Following infection with Ostertagia circumcincta there was considerable variation in worm burdens, worm size and number of inhibited larvae even among sheep matched for age, sex, breed, farm of origin and history of parasite exposure. There was also substantial variation among sheep in the concentration of mast cells, globule leucocytes, eosinophils, IgA‐positive plasma cells and parasite‐specific IgA in the abomasal mucosa. With the exception of faecal egg counts over time, the parasitological and immunological traits were all continually distributed among animals and sheep did not fall into discrete high and low‐responder categories. The responses were correlated. Sheep with more mast cells also had more globule leucocytes, more eosinophils, more IgA plasma cells and greater amounts of parasite‐specific IgA in the abomasal mucosa. Female worm length was strongly and positively correlated with the number of eggs in utero. Faecal egg counts were associated with variation in worm number and with variation in the number of eggs in utero. The worm burden was negatively correlated with the number of globule leucocytes in the abomasal mucosa, suggesting that worm numbers are regulated by immediate hypersensitivity reactions. Decreased female worm length was associated with an increased local IgA response to fourth stage larvae. The number of inhibited larvae was positively associated with the size of the local IgA response and positively associated with the size of the worm burden. The results suggest that variation among mature sheep in faecal egg counts is due, at least in part, to variation in local IgA responses which regulate worm fecundity and to variation in local immediate hypersensitivity reactions which regulate worm burdens.


Nature | 1997

How hosts control worms

M. J. Stear; K. Bairden; J.L. Duncan; P.H. Holmes; Quintin McKellar; M. Park; S. Strain; Max Murray; S. C. Bishop; G. Gettinby

Nematodes are a major cause of disease and death in humans, domestic animals and wildlife. Understanding why some individuals suffer severely whereas others exposed to the same infection remain healthy may assist in the development of rational and sustainable strategies to control infection. Here, using a quantitative genetic analysis of the parasitic nematode population that had accumulated naturally in lambs, we find no apparent influence of host genetics on nematode numbers but an extremely strong influence on average worm length and fecundity. Our results indicate that in growing lambs the main manifestation of genetic resistance is the control of worm fecundity.


Veterinary Parasitology | 2001

Standardised tests in mice and cattle for the detection of drug resistance in tsetse-transmitted trypanosomes of African domestic cattle

Mark C Eisler; J. Brandt; B Bauer; Peter-Henning Clausen; V. Delespaux; P.H. Holmes; A Ilemobade; Noreen Machila; H Mbwambo; John J. McDermott; Dieter Mehlitz; Grace Murilla; Andrew S. Peregrine; I Sidibé; L. Sinyangwe; Stanny Geerts

Resistance to the drugs used to control African animal trypanosomosis is increasingly recognised as a constraint to livestock production in sub-Saharan Africa. The most commonly used tests for detection of trypanocidal drug resistance are tests using mice or ruminants, but these suffer from lack of standardisation and hence it may be difficult to compare the results of different investigators. Tests in mice are less expensive than tests in ruminants, but while tests in mice they may be useful as a general guide to resistance in a geographic area they should not be extrapolated to cattle on an individual trypanosome level. Moreover, the commonly used protocols are too laborious for their application to large number of trypanosome isolates on an area-wide basis. This paper presents guidelines for standardised testing of trypanocidal drugs in vivo, and introduces a simplified single-dose test for use in mice, which is convenient for use in areas with limited laboratory facilities. The single-dose test is appropriate for characterisation of geographic areas in terms of trypanocidal drug resistance using large numbers of trypanosome isolates, for making comparisons between areas, and for monitoring changes in trypanocidal drug resistance over time. Multiple-dose tests may be used to determine the degree of resistance of individual stabilates to be determined precisely in mice are also described, but for logistical reasons these will rarely be conducted on more than a few stabilates, and testing of a larger number of stabilates in the single-dose test will generally provide more useful information. Finally, we describe tests in cattle that may be used to determine the efficacy of recommended curative doses of trypanocidal drugs for the treatment of infection with individual trypanosome isolates, including Trypanosoma vivax, which is rarely infective for mice.


Parasitology | 1987

Pathophysiology of parasitic infections

P.H. Holmes

Parasites can have a wide range of pathophysiological effects on the host. This review describes those associated with some parasites of major importance in man and animals. Haemoprotozoan diseases such as trypanosomiasis and malaria are primarily associated with anaemia. Such anaemias have a complex aetiology involving various mechanisms responsible for red cell destruction as well as possible defects in red cell production. In addition to these haematological effects these diseases are associated with marked disturbances in heart function and the nervous, immune and urinary systems. The other major groups of parasitic diseases are those associated with the gastrointestinal tract. The most advanced studies have been conducted on the pathophysiology of gastrointestinal nematode parasites of sheep and have revealed significant effects on feed intake, gastrointestinal function, and protein and energy metabolism. Similar studies have yet to be conducted in other hosts and parasitic diseases. There is also a need to examine in greater detail the factors which can modulate pathophysiological responses by the host to parasitic infections.


Veterinary Parasitology | 1986

The effect of dietary protein on the pathophysiology of acute ovine haemonchosis

E.M. Abbott; J.J. Parkins; P.H. Holmes

An experiment was conducted to examine the effect of dietary protein on the pathophysiology of acute haemonchosis in Finn Dorset/Dorset Horn lambs. Erythrokinetic and metabolic studies using 51Cr-red cells, 59Fe-transferrin and 125I-albumin and digestive efficiency and nitrogen balance measurements were conducted between 19 and 39 days after infection. Identical radioisotopic and nutritional studies were conducted later on pair-fed control lambs. The results demonstrated that lambs on a low protein diet (88 g crude protein (CP) kg-1 dry matter (DM)) were less able to withstand the pathophysiological consequences of infection with 350 Haemonchus contortus larvae kg-1 body weight than lambs given a high protein (170 g CP kg-1 DM) diet, despite similar worm burdens. Erythrokinetic studies indicated that abomasal blood loss was similar in both groups of infected lambs, and circulating red cell volumes were reduced and plasma volumes were expanded to a similar degree in both groups. The majority of infected lambs in both dietary groups responded equally well to the gastric haemorrhage by increasing the rate of red cell production and their absorption of dietary iron was greater than in the control lambs. Albumin catabolism was increased in both groups of infected lambs, particularly in those given the low protein diet. Within each dietary group there were no differences in the digestibilities of the various proximate fractions of the experimental diets and no differences in the urinary or faecal nitrogen losses between infected lambs and their pair-fed controls. However, loss of appetite was a major feature of the disease, particularly in the lambs given the low protein diet and this feature appeared to be crucial in determining the ability of the infected sheep to withstand the pathophysiological effects of the parasite.


International Journal for Parasitology | 1987

Pathophysiology of nematode infections.

P.H. Holmes

Abstract Gastrointestinal nematodes are a major cause of reduced productivity in ruminants. An important feature of such infections is reduced feed intake, the aetiology of which remains uncertain. Alterations in gastrointestinal motility and digesta flow may be partially responsible for the inappetance as well as being associated with the occurrence of diarrhoea. However, digestion and absorption are, in general, not significantly impaired. The other distinctive feature of gastrointestinal parasitism is loss of proteins into the gastrointestinal tract and resultant changes in host metabolism account for much of the reduced protein and energy retention by infected animals. Mineral metabolism and water and electrolyte balance are also frequently disturbed. These pathophysiological effects may be modulated by a number of factors, including the nutritional and immunological status of the host. Details of the precise mechanisms involved in these interactions and several other aspects of the pathophysiology of nematode infections still require investigation.


Veterinary Parasitology | 1986

The effect of dietary protein on the pathogenesis of acute ovine haemonchosis

E.M. Abbott; J.J. Parkins; P.H. Holmes

Two experiments were conducted to examine the influence of dietary protein on parasite establishment and pathogenesis in Finn Dorset/Dorset Horn lambs infected with Haemonchus contortus. The lambs were introduced to high (169 g) or low (88 g crude protein (CP) kg-1 dry matter (DM)) protein diets at 3 months of age and infected 1 month later with 350 larvae kg-1 body weight (BW). Blood and faecal samples were collected for analysis and body weights recorded weekly. In the first experiment some of the infected lambs were killed 6 weeks after infection and the remainder 5 weeks later. In the second experiment all the infected lambs were killed 4 weeks after infection. The results showed that lambs on a low protein diet were less able to withstand the pathogenic effects of infection with 350 H. contortus larvae kg-1 BW than lambs given the higher protein diet. Thus mortality was greater in the low protein group and adverse clinical signs, such as inappetence, weight loss and oedema were observed more frequently. This group also had a more severe anaemia, hypoproteinaemia and hypoalbuminaemia than the high protein group. In contrast, faecal egg counts, total daily faecal egg output and worm burdens were similar in all groups of infected lambs, indicating that the diets did not influence parasite establishment.


Research in Veterinary Science | 1995

Influence of supplementation with dietary soyabean meal on resistance to haemonchosis in Hampshire Down lambs

D.S. Wallace; K. Bairden; J.L. Duncan; G. Fishwick; M. Gill; P.H. Holmes; Quintin McKellar; Max Murray; J.J. Parkins; M. J. Stear

The influence of dietary protein supplementation on resistance to haemonchosis was examined in Hampshire down lambs fed either a basal diet or a diet supplemented with soyabean. At seven months of age the lambs were challenged with an initial loading dose of Haemonchus contortus, followed by a trickle infection three times a week. Blood and faecal samples were collected three times a week and bodyweights were recorded weekly. After 10 weeks the lambs were slaughtered and their worm burdens and carcase composition determined. Although their mean worm burdens were similar, the lambs given the basal diet had higher faecal egg counts, lower packed red cell volumes and lower concentrations of total plasma protein and plasma albumin than the lambs given the supplemented diet. The dietary supplementation also improved the carcase composition of the lambs.


Veterinary Parasitology | 1985

Pathogenesis of trichostrongylosis

P.H. Holmes

Trichostrongylosis is a major cause of impaired productivity in ruminants. The pathogenesis of such infections is principally associated with inappetence and increased losses of proteins into the gastrointestinal tract. Resultant changes in host metabolism account for the poor productivity in infected animals, although the precise mechanisms require further investigation. Studies are also required to investigate in greater detail the interactions between trichostrongylosis and the nutritional and immunological status of the host.


Research in Veterinary Science | 1996

Influence of soyabean meal supplementation on the resistance of Scottish Blackface lambs to haemonchosis

D.S. Wallace; K. Bairden; J.L. Duncan; G. Fishwick; M. Gill; P.H. Holmes; Quintin McKellar; Max Murray; J.J. Parkins; M. J. Stear

Protein supplementation improves the resistance of sheep to haemonchosis. This experiment investigated the Scottish blackface breed to establish whether dietary protein supplementation is still beneficial in a genetically resistant breed. Lambs were given either a basal diet or a diet supplemented with soyabean meal to give an additional 80 g crude protein kg dry matter-1. The lambs were given an initial loading dose of Haemonchus contortus, followed by a trickle infection for 10 weeks. The weight gains of the lambs given the supplemented diet were greater and their carcases were leaner, irrespective of infection status. Infected animals on the basal diet were more anaemic and hypoalbuminaemic than animals receiving the supplemented diet, although there were no statistically significant differences in mean worm burdens or faecal egg counts.

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Ian Maudlin

University of Edinburgh

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