Although Phthirus pubis occurs in Europe, Asia, Africa, North America and Australia, and is found on negroes as well as whites, as herein recorded, further data are required relating to the geographical distribution of the species and the races of man it infests.

The crab-louse occurs less frequently on man than does Pediculus and appears to be parasitic chiefly on persons leading an active sexual life. It has, so far, only been twice recorded on another host than man, i.e. the dog.

Whilst the crab-louse is usually found confined to the pubic and perianal region, it frequently spreads upward upon the abdomen and breast, and may infest the axillae severely, or it may spread downward along the thighs. Generalized infestation is rare, in such cases only the hands and feet are spared, although the head and neck are as a rule also free from parasites. The crab-louse has occasionally been found localized upon the head in infants, being either confined entirely to the eyelids, the nits being encountered on the eyelashes, or occurring also upon the eyebrows and hairy portions of the scalp. In adults, the parasite occurs much more rarely in these situations; a case is recorded of an Arab in whom, in addition, the beard and moustache were infested. Such cases are rare in children, very rare indeed in adults.

Apparently the head is so rarely infested because it is less suitable as a habitat. As Waldeyer points out, the head is probably not a suitable habitat because the scalp-hairs are crowded close together and finer than on the pubis and in the axillae. The majority of the active stages are found clinging to two hairs on the regions of the body they most infest, and where the hairs are sparser than on the head. In these parts, the hairs are 2 mm. or more apart. The reach between the extended two hind leg-pairs of the adult insect is about 2 mm., these legs being the ones that are used for grasping the hair.

Whilst infestation usually takes place through coitus, there are many exceptions to the rule as proved by the occurrence of crab-lice on infants. The latter may become infested by their parents or other adults. The insect may pass from one infant to another through their sharing a cradle, or it may pass from soldier to soldier when crowding occurs in barracks or billets. Scratching of their persons by infested individuals no doubt aids in the spread of the parasite upon them and the dissemination of the insect further afield. Both the act of coitus and scratching promote the shedding of hairs, and these, when bearing nits or young larvae, may be of considerable importance in disseminating the parasite. Such hairs, and no doubt occasionally active stages of the louse, are shed on clothing, bedding, the seat of the privy, etc., and readily become entangled with the pubic or other hair of clean persons who may come in contact therewith. A detached louse promptly clings to any hair with which it comes in contact. Therefore, whilst Pthirus is commonly conveyed directly, it may also be acquired indirectly. It is a helpless creature when removed from the hair to which it clings continuously upon the body, where it moves about by shifting from hair to hair; it is therefore much more likely to be conveyed passively from host to host than is Pediculus.

Unless disturbed, the parasite remains confined throughout its life to a limited area upon the host's skin as I have demonstrated experimentally.

The females appear to preponderate over the males in number when upon the host, their relative proportion being about 3:2. In copulation, the male does not seize the female as in Pediculus; he seizes the hairs to which the female clings, using these as a support. Oviposition occurs as in Pediculus. A female that was raised experimentally, laid up to three eggs per day, laying a total of 26 eggs. The hatching period (on the leg) lasted 7–8 days. Like Pediculus, the crab-louse passes through three moults (there being as many larval stages) before it attains sexual maturity. When the adults are about 10 days old they exhibit to a well-marked degree the greenish coloration of the fat-body which is seen by transparency at the sides of the abdomen in the living insect. The life-cycle, from egg to egg, is completed in 22–27 days (on the leg).

Young unfed larvae usually die within ten hours of emergence. When removed from man, they survive longer at 16–20° C. than at 30° C. and die much more rapidly in a dry than in a moist atmosphere; none of the numerous lice of all stages that were tested were found to survive up to 42½ hours, when maintained under different conditions. Living on man a male survived 22 days, a female 17 days, but the insects can doubtless live longer.

The feeding habits of Pthirus recall those of Ixodidae in being practically continuous, and, like Boophilus, they stop feeding to moult upon the host. After moulting they promptly proceed to feed again, shifting but slightly to a fresh feeding ground. On emerging, the young larva clasps a single hair and feeds at its base, and after a day or more it may clasp two hairs as the later stages do usually. The habit of continuous feeding explains why the insects die so quickly when removed from the host.

Whilst a brief exposure to light renders the insects restless but does not cause them to wander away whilst feeding, a warm body brought within their sphere promptly produces great activity in Pthirus when it is removed from man.

The distribution of carbohydrates, lipids and enzymes in the daughter sporocyst and contained cercariae of Cercaria bucephalopsis haimaena Lacaze-Duthiers, 1854, is mapped and used as an indication of metabolism. It is concluded that host glucose, glycogen, fatty acids and neutral lipids are absorbed and pass through the syncytial tegument into the cellular sub-tegument. They are then either metabolized or passed into the body cavity and contained cercariae. Glucose seems to be either converted into glycogen and glycoproteins or metabolized anaerobically. The end products of anaerobic respiration are fatty acids and neutral lipids. These pass into the excretory system, which flushes them into the body cavity of the daughter sporocyst, from where they enter the body of the developing cercariae. In the cercariae they are deposited, together with host lipids, possibly as less toxic higher fatty acids or other stored lipids. The stored glycogen and lipids in the cercariae are probably utilized aerobically during the free-living existence. The transport of nutrients and excretory products across the cell membranes may be aided by alkaline phosphatase and esterase activity, as is the metabolism of carbohydrates and lipids. Acid mucopolysaccharide precursors appear to be synthesized in the dense cytoplasm of the mid-tegument of the daughter sporocyst and secreted into the host's visceral haemocoel. Acid phosphatase and esterase found in this region may be involved in the synthesis and also in the breakdown of complex incoming nutrients.

We are grateful to Professor E. W. Knight-Jones for laboratory facilities and to the Science Research Council for a grant to one of us (E. A. B.) which made the work possible.

The presence of antigenic carbohydrate epitopes shared by Biomphalaria glabrata as well as by the sporocysts and miracidia representing snail-pathogenic larval stages of Schistosoma mansoni was assayed by immunohistochemical staining of paraformaldehyde-fixed tissues. To this end, both polyclonal rabbit antiserum raised against soluble egg antigens (SEA) of S. mansoni and monoclonal antibodies recognizing the carbohydrate epitopes LDN [GalNAc(β1-4)GlcNAc(β1-)], F-LDN [Fuc(α1-3)GalNAc(β1-4)GlcNAc(β1-)], LDN-F [GalNAc(β1-4)[Fuc(α1-3)]GlcNAc(β1-)], LDN-DF [GalNAc(β1-4)[Fuc(α1-2)Fuc(α1-3)]GlcNAc(β1-)] and Lewis X [Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-)] were used. Intriguingly, anti-SEA serum as well as anti-F-LDN antibodies displayed significant binding in the foot region, anterior tissue and the hepatopancreas of uninfected snails, whereas the Lewis X epitope was only weakly detectable in the latter tissue. In contrast, increased binding of antibodies recognizing LDN, LDN-F and LDN-DF was observed in infected snail tissue, in particular in regions involved in sporocystogenesis, in addition to an enhanced binding of anti-SEA serum and antibodies reacting with F-LDN. A pronounced expression of most of these carbohydrate antigens was also observed at the surface of miracidia. Hence, the detection of shared carbohydrate determinants in uninfected snail tissue, sporocysts and miracidia may support the hypothesis of carbohydrate-based molecular mimicry as a survival strategy of S. mansoni.

Infection of ewes by Toxoplasma gondii may induce abortions, thus it has consequences for sheep production. Colima, Western State of Mexico, has favourable climatic conditions for transmission and both domestic and wild cats live there. The aim of this study was to determine the frequency of specific antibodies in sheep from the coast, a mountain, and a hill of Colima. Serum samples from 351 sheep were tested by a previously standardized indirect ELISA. The frequency of infection was estimated and the farm location and flock size, as well as the animals' age and sex were analysed as risk factors for toxoplasmosis. The frequency of antibodies depended on the altitude, being higher at sea level than at 1200 metres above sea level (OR=3·77, 95% CI=1·79–7·94, P<0·0001), and the size of the flock, being higher in the large ones (OR=2·23, 95% CI=1·35–3·71, P=0·002). Older animals were more frequently positive and with a stronger response than young ones (OR=1·77, 95% CI=1·07–2·93, P=0·016). No differences were observed between male and female sheep. In conclusion, toxoplasmosis is present in sheep of Colima with variations related to altitude, flock size and age.

Although Ixodes ricinus ticks are mainly associated with woodland, they are also present in open habitat such as pastures. The distribution of nymphal I. ricinus was monitored by drag sampling the vegetation in May–June 2003 on 61 grazed permanent pastures for cattle located in central France. After selecting explanatory variables from among a set of 155, tick abundance was modelled on the perimeter of the pasture using a negative binomial model that took into account data overdispersion. An abundant tree layer at the perimeter of the pasture associated with a high humidity before sampling greatly enhanced the average number of captured I. ricinus nymphs. The presence of apple or cherry trees around the pasture perimeter, the presence of trees or bushes at the pasture edge, woodland around the pasture and a high number of I. ricinus nymphs in the nearest woodland to the pasture were also favourable to nymph abundance in the pasture. The study highlighted that woodland vegetation associated with humidity and the presence of attractive foraging areas for tick hosts around the pasture played a key role in the abundance of I. ricinus. Finally, the results raised the question of whether and how transfer of ticks between woodland and grazed pastures occurs.

The range of interactions between blood-sucking arthropods and their hosts is enormous and their importance to man would be difficult to overestimate. From the tundra to the tropics man, and animals in which he has a vital nutritional or economic interest, represent to the blood-sucking arthropod a source of animal protein. By their activities in obtaining a blood meal the host may be subjected to minimal inconvenience, acute irritation, or suffer severely from blood loss or from the effects of toxins introduced during feeding. Superimposed upon these situations is an enormous variety of disease agents which may be transmitted to the host by the parasite during or after feeding.

The cercaria of Trichobilharzia ocellata finds and identifies its duck host with a seriesof different behavioural phases. Dispersal and selection of the water surface as microhabitat is achieved by an intermittent swimming behaviour, which is governed by the interplay of passive dropping with forward and backward swimming movements and includes a positive phototactic and a geonegative orientation. Then the cercariae tend to cling to the water surface in an energy-saving resting position. A movement towards the duck feet as the site of entry occurs when shadows evoke forward swimming movements, which are directed away from the source of light, i.e. normally downwards. Forward swimming movements are also stimulated by touch, but only in free-swimming cercariae and not when these are in the resting position. Attachments occur only when a substrate is touched during forward swimming movements. Attachments are stimulated by warm substrates (1 °C temperature difference triggers a nearly maximal response) and by chemical components of duck-foot skin, and the readiness to attach is increased when the forward swimming movement is started by shadow stimuli.

Samples of Peringia ulvae were collected and measured on eight occasions, over a period of two years from an isolated pool in the saltings of the River Tamar. Growth conditions in this pool are at a maximum. Spawning occurs in the autumn and the greatest number of small specimens are found in the sieve (1 mm. mesh) in February. Maximum growth takes place during April-July. After ten months of age,.uninfected snails which have reached a length of 5¾ mm. grow only 1–1¼ mm., and gradually die off from 17 months of age onwards. Infected snails display gigantism and variation and attain dimensions of 9–10 mm. They are probably no older than uninfected specimens measuring 6¾ mm. long.

The infection rate is high and shows certain seasonal fluctuations, no doubt linked with the migrations of the wading birds which are the principal final hosts of the trematodes.

An examination with light and electron microscopes has been made of the cell type which is considered by some authors to be a sporozoan parasite, Rhabdospora thelohani, and by others to be a tissue cell of fishes and amphibians.

The cell type was found in the minnow Phoxinus phoxinus in many tissue sites, including olfactory and pharygneal epithelia, kidney, eyes and brain. In some specimens it could not be found in any tissue.

The cell has a thick fibrous wall, a basal nucleus, an apical mitochondrial zone, a Golgi body, and from 8 to 50 characteristic refractile rodlets.

The rodlets give a negative reaction to the Feulgen test for nuclear material, but are positive to the periodic acid–Schiff stain, a test for polysaccharide. Glycogen does not appear to be present in the rodlets.

Under certain circumstances the rods rupture the cell wall and may protrude in the apical region of the cell.

The structures described are discussed with the evidence for and against a parasitic interpretation of the cell. It is concluded that Rhabdospora is a protozoan parasite, whose exact functional and taxonomic status is as yet unknown.

I am grateful to Professor G. E. H. Foxon and to Professor P. C. C. Garnham for their encouragement, advice, and helpful criticism of the manuscript. I am further indebted to the National Spastics Society for the use of the electron microscope housed in Guy&s Hospital Medical School, and to Mr I. D. Bradbrook for his assistance with the histological techniques.

The impact of immune sera, and peripheral blood cells (PBC) from mice immunized with Plasmodium berghei ookinetes; and of purified immunoglobulin or Fab fragments from anti-Pbs21 monoclonal antibody 13.1, upon establishment of oocyst infections in the mosquito was studied. Infections were initiated either from gametocyte-infected mice, or membrane feeders which contained either gametocytes or mature ookinetes. PBC from ookinete-immunized mice presented with non-immune serum failed to show any transmission-blocking activity. Anti-ookinete serum, intact anti-Pbs21 monoclonal antibody 13.1 or its Fab fragments, all inhibited oocyst formation significantly. When gametocyte-infected mice or gametocytes in membrane feeds were used, inhibition did not directly correlate with antibody concentration. In membrane feeders that contained ookinetes and antibody, concentration-dependent inhibition usually occurred. The efficacy of purified 13.1 IgG was dependent upon the ookinete concentration. The ookinete plasmalemma and cytoplasm were significantly disturbed after 12h in bloodmeals that contained antibody 13.1, but not in the isotype controls. These changes may have caused the observed failure of the ookinete to migrate as rapidly as the controls from the destructive environment of the bloodmeal.

Unisexual females, (80–100 days post-infection) were cultured in vitro and exposed to mature male worms from either mixed or single-sex infections. A comparison was made of the uptake of [3H]thymidine (used as a marker for DNA synthesis) by isolated unisexual females or by those females exposed to males derived from either mixed or unisexual infections during in vitro culture. All males were observed to be paired with females by approximately 18 h post-culture. At 24 h post-culture females paired with males from mixed infections had an elevated uptake of [3H]thymidine compared to females that had not paired and uptake was also significantly different (P ≥ 0–001) from females exposed to males from unisexual infections. By 48 h there was no significant difference between uptake in females paired with either type of male. The frequency of uptake in the paired females was approximately double that in unstimulated females while non-paired females in the presence of males had an increase of between 35 nd 45%. In a second experiment the effect of depriving a mature egg-laying female of the paired male was investigated. These females had a continual decrease in uptake of [3H]thymidine compared to mature females maintained with male partners. The uptake of [3H]thymidine was used as a marker for DNA synthesis and the effect of the male worm on DNA synthesis in the unisexual female is discussed in view of the above results.

1. The male rat is more susceptible to infections of Nematospiroides dubius than the female. As the rat grows older the resistance of the female rat to infection increases at a greater rate than that of the male.

2. The course of the infection is modified by the sex of the host.

3. More larvae penetrated the intestinal mucosa to encyst in the male than in the female. More larvae, however, formed cysts in the female than in the male rat by the fifth day.

4. The male harboured more adult worms than the female rat, although this difference was not significant in the immature animals.

5. The sex resistance of the rat to N. dubius infections was removed by bilateral gonadectomy. Castration decreased the susceptibility of the male rat, while spaying increased it in the female compared with the susceptibility in the respective normal hosts.

6. Subsequent replacement of the homologous sex hormone in the gonadectomized rat restores the sex resistance, and may even increase it (particularly in the immature animals). Oestradiol increased the resistance of the spayed female rat, while testosterone increased the susceptibility of the castrate male rat to infection.

7. Oestradiol implanted in castrate male rats increased the resistance of these hosts to a greater level than was shown in the normal male rat.

8. The rat shows a marked age resistance over which the sex resistance is superimposed.

9. The relationship between the sex of the host and its resistance to infection is discussed.

This work was done during the tenure of a Department of Scientific and Industrial Research Studentship. My thanks are due to Dr E. T. B. Francis for his helpful and critical supervision and to Professor I. Chester Jones, in whose department the work was done, for the facilities he provided.

Programmed cell death (PCD) has been observed in many unicellular eukaryotes; however, in very few cases have the pathways been described. Recently the early divergent amitochondrial eukaryote Giardia has been included in this group. In this paper we investigate the processes of PCD in Giardia. We performed a bioinformatics survey of Giardia genomes to identify genes associated with PCD alongside traditional methods for studying apoptosis and autophagy. Analysis of Giardia genomes failed to highlight any genes involved in apoptotic-like PCD; however, we were able to induce apoptotic-like morphological changes in response to oxidative stress (H2O2) and drugs (metronidazole). In addition we did not detect caspase activity in induced cells. Interestingly, we did observe changes resembling autophagy when cells were starved (staining with MDC) and genome analysis revealed some key genes associated with autophagy such as TOR, ATG1 and ATG 16. In organisms such as Trichomonas vaginalis, Entamoeba histolytica and Blastocystis similar observations have been made but no genes have been identified. We propose that Giardia possess a pathway of autophagy and a form of apoptosis very different from the classical known mechanism; this may represent an early form of programmed cell death.

Viviparous gyrodactylid monogeneans which are detached from their host may form an important source of infection in fish communities. This is particularly significant for these ectoparasites which have no specific free-living stage and where transmission usually occurs through transfer of adult parasites when fish come into close contact. In this study, in vitro survival of Gyrodactylus gasterostei was correlated with changes in tissue ultrastructure of parents and their embryos during detachment and following return to a host. At 10 °C, detached worms survived for up to 89 h (50% survival = 20 h) with mortality influenced by both age-independent and age-dependent factors. The gastrodermis of attached, fed parasites is syncytial and contains a variety of vesicles and feeding vacuoles. However, following detachment and starvation, degenerative changes occur within the gastrodermis, eventually leading to marked damage to the embryo/s. When starved worms reattached to a fish, they began browsing on host epithelial cells within 1 min and ultrastructural evidence for phagocytic activity in the gastrodermis was detected after 5 min. Putative waste vacuoles increased in abundance after 5–30 min on the new host, coinciding with the reappearance of electron-dense vesicles and possibly indicating completion of the first intracellular cycle of digestion. Parental feeding directly influenced the normal cyclical maturation and regression of the uterine lining between births. In extreme cases, starvation led to detached parasites (6·1%) aborting their embryos. However, even short periods off the host influenced development and survival of embryos, suggesting that temporary interruption of nutrient flow to the embryo can significantly affect gyrodactylid reproductive rates.

Partial (DNA) sequences were collected for 2 mitochondrial loci (Srrna and Lrrna, the rrnS and rrnL rRNA genes respectively) for Schistosoma indicum group species from 4 Southeast Asian countries. The samples included 7 populations, 4 of which were previously unstudied. In 11 cases the combination of locus and population was new. The aim of the study was to provide a phylogeny based on new independent data and multiple populations (earlier studies had mostly used a common set of field samples or laboratory lines) and to examine interrelationships and phylogeography within this species group. Paraphyly of the S. indicum group was confirmed, as was the basal position of Schistosoma incognitum in the Schistosoma phylogeny. Southeast Asian Schistosoma spindale and S. incognitum populations were shown to fall into their respective con-specific cohesive groupings. Estimated divergence times for these taxa were shown to be related to Pleistocene changes in sea level and the radiation of definitive host groups. A revised phylogeographical model is proposed in the light of these findings.

The effect of sainfoin (Onobrychis viciifolia) hay consumption on the pathophysiology and local cellular responses of growing lambs during infection with Trichostrongylus colubriformis was investigated. Thirty-two lambs, 16 weeks of age, were allocated to 1 of 4 treatment groups (n=8) that were offered either grass (G) or sainfoin (S) hay while concurrently either infected (+), or not (−) with 12 000 L3 T. colubriformis larvae per week for 6 weeks. Liveweight gains were affected by diet (P=0·002) and reduced by infection (P<0·005). Faecal egg count was reduced in S+ compared to G+from days 35 to 42 (P=0·001); however, total egg output, worm burdens at day 42 and worm fecundity were similar between diets (P>0·05). Feeding sainfoin appeared to enhance immune cell development with tissue eosinophils, mast cells and pan T cells present in greater concentrations in S+ than in G+ animals. However, further studies are required to determine if the enhanced immune cell development is a consequence of a greater nutrient supply or a direct influence of sainfoin metabolites on local inflammatory responses to the gastrointestinal nematode T. colubriformis.

Angiostrongylus vasorum, Crenosoma vulpis and Capillaria aerophila are the most common lungworms of domestic and wild canids. We investigated the short- and long-term lungworm prevalence changes in the Swiss fox population with a focus on A. vasorum. Between 2012 and 2017, lungs and hearts of 533 foxes from north-eastern Switzerland were necropsied and blood samples tested for circulating A. vasorum antigen. Angiostrongylus vasorum prevalence increased steadily from 21.5% in 2012 to 81.8% in 2017. In contrast, C. aerophila and C. vulpis prevalences fluctuated between 41.8 and 74.7%, and 3.6 and 14.9%, respectively. Based on 3955 blood samples collected between 1986 and 2017 from three geographic areas and during four time periods, antigen seropositivity increased from 2.4 to 62.0%. In north-eastern Switzerland, seropositivity was initially low (1.9 and 1.7% in the first two time periods) but increased in the following two decades to 22.2 and 62.0%, respectively. Our findings depict the spectacular expansion of A. vasorum in the past three decades. Regionally, the prevalence in foxes increased 4-fold within 6 years in some regions. This underpins the important role of foxes as reservoir hosts, likely explaining the increasing number of cases of canine angiostrongylosis in Switzerland. Our findings are representative of central Europe and may help anticipating future developments in areas where A. vasorum is present but (still) infrequent.

Hosts and parasites interact with each other in a variety of ways, and this diversity of interactions is reflected in the networks they form. To test for differences in interaction patterns of ecto- and endoparasites we analysed subnetworks formed by each kind of parasites and their host fish species in fish–parasite networks for 22 localities. We assessed the proportion of parasite species per host species, the relationship between parasite fauna composition and host taxonomy, connectance, nestedness and modularity of each subnetwork (n = 44). Furthermore, we evaluated the similarity in host species composition among modules in ecto- and endoparasite subnetworks. We found several differences between subnetworks of fish ecto- and endoparasites. The association with a higher number of host species observed among endoparasites resulted in higher connectance and nestedness, and lower values of modularity in their subnetworks than in those of ectoparasites. Taxonomically related host species tended to share ecto- or endoparasites with the same interaction intensity, but the species composition of hosts tended to differ between modules formed by ecto- and endoparasites. Our results suggest that different evolutionary and ecological processes are responsible for organizing the networks formed by ecto- and endoparasites and fish.

Parasitic helminths are ubiquitous in most host, including human, populations. Helminths often alter the likelihood of infection and disease progression of coinfecting microparasitic pathogens (viruses, bacteria, protozoa), and there is great interest in incorporating deworming into control programmes for many major diseases (e.g. HIV, tuberculosis, malaria). However, such calls are controversial; studies show the consequences of deworming for the severity and spread of pathogens to be highly variable. Hence, the benefits of deworming, although clear for reducing the morbidity due to helminth infection per se, are unclear regarding the outcome of coinfections and comorbidities. I develop a theoretical framework to explore how helminth coinfection with other pathogens affects host mortality and pathogen spread and evolution under different interspecific parasite interactions. In all cases the outcomes of coinfection are highly context-dependent, depending on the mechanism of helminth-pathogen interaction and the quantitative level of helminth infection, with the effects of deworming potentially switching from beneficial to detrimental depending on helminth burden. Such context-dependency may explain some of the variation in the benefits of deworming seen between studies, and highlights the need for obtaining a quantitative understanding of parasite interactions across realistic helminth infection ranges. However, despite this complexity, this framework reveals predictable patterns in the effects of helminths that may aid the development of more effective, integrated management strategies to combat pathogens in this coinfected world.

In this study, we characterized 8 new isolates obtained from healthy but congenitally infected calves using a BALB/c mouse model. Neospora caninum-infected mice survived without exhibiting any clinical signs of disease. Nevertheless, differences among isolates in parasite organ distribution, parasite burden and the severity of histopathological lesions were determined. Mice infected with the Nc-Spain 5H, Nc-Spain 7 and Nc-Spain 9 isolates showed higher parasite burdens and more severe brain lesions during the late phase of infection compared to mice infected with the Nc-Spain 2H, Nc-Spain 3H or Nc-Spain 6 isolates. Furthermore, differences in the immunoglobulin IgG1 and IgG2a isotype kinetics induced by these isolates were observed, with a more rapid IgG2a response seen in mice infected with the Nc-Spain 2H and Nc-Spain 3H isolates. These results confirm the intra-species variability of N. caninum pathogenicity.