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Biomedical subjects

P Prociv

Publications and source records attributed to P Prociv.

At least 19 recordsLinked to original sources

Giardia trophozoites in dog hookworm, Ancylostoma caninum: accident or hyperparasitism?

During the course of transmission electron microscopic studies of adult Ancylostoma caninum removed from a dog, several Giardia trophozoites were found in sections of the buccal cavity, oesophagus and intestine of several hookworms. Although the protozoa appeared viable, this unusual finding probably represents accidental uptake by, rather than an established infection of, the hookworm. It is feasible, however, that the trophozoites might have survived and even multiplied in this aberrant site.

Ancylostoma↗

Hemoglobin-degrading, aspartic proteases of blood-feeding parasites: substrate specificity revealed by homology models.

Blood-feeding parasites, including schistosomes, hookworms, and malaria parasites, employ aspartic proteases to make initial or early cleavages in ingested host hemoglobin. To better understand the substrate affinity of these aspartic proteases, sequences were aligned with and/or three-dimensional, molecular models were constructed of the cathepsin D-like aspartic proteases of schistosomes and hookworms and of plasmepsins of Plasmodium falciparum and Plasmodium vivax, using the structure of human cathepsin D bound to the inhibitor pepstatin as the template. The catalytic subsites S5 through S4' were determined for the modeled parasite proteases. Subsequently, the crystal structure of mouse renin complexed with the nonapeptidyl inhibitor t-butyl-CO-His-Pro-Phe-His-Leu [CHOHCH(2)]Leu-Tyr-Tyr-Ser- NH(2) (CH-66) was used to build homology models of the hemoglobin-degrading peptidases docked with a series of octapeptide substrates. The modeled octapeptides included representative sites in hemoglobin known to be cleaved by both Schistosoma japonicum cathepsin D and human cathepsin D, as well as sites cleaved by one but not the other of these enzymes. The peptidase-octapeptide substrate models revealed that differences in cleavage sites were generally attributable to the influence of a single amino acid change among the P5 to P4' residues that would either enhance or diminish the enzymatic affinity. The difference in cleavage sites appeared to be more profound than might be expected from sequence differences in the enzymes and hemoglobins. The findings support the notion that selective inhibitors of the hemoglobin-degrading peptidases of blood-feeding parasites at large could be developed as novel anti-parasitic agents.

Amino Acid Sequence↗

Immune responses in hookworm infections.

Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections.

Ancylostomatoidea↗

Gastrointestinal worm infections. The prevalence and treatment in Australia.

BACKGROUND: Intestinal worm (helminth) infections occur in a large proportion of the world's population, often constituting public health problems, and are occasionally encountered by practitioners in urban Australia. Prevalence levels in some remote Australian Aboriginal communities compare with those in developing countries. OBJECTIVE: To provide general practitioners with a brief outline of the most common human intestinal helminthiases, their usual clinical presentations and how they are diagnosed and managed. DISCUSSION: The pinworm, Enteroblus vermicularis, occurs in all populations, and is the most common species of nematode encountered in suburbia. Eradication is impossible, but its numbers can be kept low in those children who seem predisposed to heavy, symptomatic infections. The other nematodes are prevalent in some remote Australian Aboriginal communities, and are encountered occasionally in travellers from overseas. These infections are often asymptomatic, they cannot spread directly to other people and so do not pose any public health threat to the general community under suburban living conditions. The tapeworms are encountered even less frequently, except for Hymenolepis, the dwarf tapeworm, which is prevalent in some Aboriginal communities.

Animals↗

Host specificity in blood feeding parasites: a defining contribution by haemoglobin-degrading enzymes?

A hypothesis is presented that proposes that the compatibility between species-specific variants of haemoglobin-degrading proteases of blood-feeding parasites (e.g. hookworms, schistosomes, malarial parasites, etc.), and their natural substrates, i.e. haemoglobins from diverse species of mammals, has influenced to evolution of the host range of these parasites. Support for the hypothesis was drawn from molecular modelling studies of the three dimensional structure of an aspartic protease, Acasp, from the canine hookworm Ancylostoma caninum, and models of canine and human haemoglobins docked with the active site of Acasp. The molecular modelling suggested that Acasp, from a canine-specific hookworm, would have a higher substrate affinity for canine haemoglobin than for human haemoglobin.

Amino Acid Sequence↗

Neuro-angiostrongyliasis: unresolved issues.

Angiostrongylus cantonensis, the rat lungworm, probably evolved with its hosts, members of the genus Rattus and closely related species, in south-east Asia. Since its first discovery in rats in China and in a case of human infection in Taiwan, the parasite has been found to infect humans and other mammals across a wide and ever-increasing territory, which now encompasses much of south-east Asia, Melanesia, Polynesia and eastern Australia. It has also established a foothold in Africa, India, the Caribbean and south-eastern USA. This dispersal has been a direct result of human activity, and in some cases has been linked with the spread of the African giant land snail, Achatina fulica. However, this snail is not critical to the extension of the parasite's range, as numerous other indigenous molluscan species serve as adequate intermediate hosts; the importance of Achatina to the life cycle may have been over-emphasized. In Australia, the parasite is established along parts of the east coast, and the presence of an indigenous close relative, Angiostrongylus mackerrasae, suggests a long association of the parasite with its local rat hosts, a situation analogous to that of Angiostrongylus malaysiensis in south-east Asia. These three Angiostrongylus species share virtually the same life cycle, but only A. cantonensis has been confirmed to be a human pathogen.

Adult↗

Purification of a diagnostic, secreted cysteine protease-like protein from the hookworm Ancylostoma caninum.

The enteric infection of humans with the canine hookworm Ancylostoma caninum varies in its clinical presentation, ranging from asymptomatic to eosinophilic gastroenteritis requiring surgical intervention. Infections are not patent, but can be diagnosed immunologically by detecting antibodies to an immunodominant secreted hookworm protein termed Ac68. To characterise Ac68, we purified the native protein from A. caninum excretory/secretory products using size exclusion followed by anion exchange chromatography. The epitopes in the purified protein recognised by human infection sera were shown to be proteins and not carbohydrates. The N-terminal amino acid sequence of the purified Ac68 was determined and six of the 11 residues obtained were shared with a previously characterised cysteine protease of A. caninum, AcCP1.

Amino Acid Sequence↗

Persistent head lice following multiple treatments: evidence for insecticide resistance in Pediculus humanus capitis.

Viable head lice were found on the scalps of two family members following multiple topical insecticide treatments. The possibility of reinfestation had been reliably excluded. Persistent infestation could be diagnosed only after cutting the hair and combing repeatedly, which allowed visualization of juvenile (nymphal) and adult lice. Insecticide-resistant headlouse infestations are probably much more common than is generally realised and may persist unnoticed, so that more aggressive approaches will be needed to eradicate these ectoparasites from individuals and communities.

Animals↗

Parasitic meningitis.

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Angiostrongylus cantonensis↗

Health aspects of Antarctic tourism.

Increasing numbers of seaborne tourists are visiting Antarctica, with most coming from the United States (3503 in 1996-97), Germany (777), and Australia (680; cf. 356 in 1994-95 and 410 in 1995-96). The impression among travel medicine clinicians is that, each year, more prospective travelers seek advice about the health demands of this type of adventure, mostly relating to fitness for travel, exposure to extreme cold, hazards in ice and snow, and other potential health risks. This is a recent phenomenon. While a regular shipping service had been established between the Falklands and the subantarctic islands of South Georgia and the South Shetlands by 1924, the first documented tourists accompanied an Argentine expedition to the South Orkneys in 1933.1 Commercial airline flights over these islands and the Antarctic Peninsula began in 1956, from Chile, and recreational cruises to the Peninsula began in 1958. Tourist numbers subsequently grew slowly, for what was clearly an exclusive and very expensive undertaking, with few ships available for these hazardous voyages. From 1957 to 1993, 37,000 tourists visited by sea, most seeing only the Peninsula.2 The dramatic recent growth in numbers is a consequence of the collapse of the Soviet Union. The small fleet of ice-strengthened research vessels and working icebreakers, which was made redundant by withdrawal of central government support from isolated communities and military activities along the northern coast of Siberia (and from Antarctic research bases), now accounts for the bulk of charter-cruise tourism to Antarctica, at competitive prices. According to the International Association of Antarctica Tour Operators,3 7322 people traveled to Antarctica on commercially organized voyages in the 1996-97 season, and a record 10,000 shipborne visitors were expected for the 1997-98 season (November-March), traveling mainly from South America to the Peninsula on 15 ice-reinforced vessels, each carrying between 36 and 180 passengers. Most tours embark from Ushuaia in southern Argentina, or Punta Arenas in Chile, although occasional cruises leave from Australia, New Zealand, or even South Africa.

Adolescent↗

Cerebrospinal angiostrongyliasis in five captive tamarins (Sanguinus spp).

Four cotton-top tamarins (Sanguinus oedipus oedipus) and one emperor tamarin (S imperator subgrisescens) housed in a zoo became depressed, anorexic, paraparetic and eventually paralysed. The animals died within 5 days to 18 months of the appearance of clinical signs. Histological examination showed nonsuppurative and eosinophilic meningoencephalitis, and metastrongyle nematode larvae were found within subarachnoid spaces of all animals and within the spinal cord of one. Intact larvae with features consistent with Angiostrongylus cantonensis were recovered from the brain of one animal. This parasite is the classical cause of eosinophilic meningoencephalitis in many parts of the world and the diagnosis can be strongly suspected on clinical grounds. In endemic areas like south-east Queensland, protection of captive animals against infection with A cantonensis is a difficult balance between providing a stimulating, natural setting and eliminating potentially infectious definitive, intermediate and paratenic hosts. This is the first report of cerebrospinal angiostrongyliasis in tamarins and nonhuman primates in Australia.

Angiostrongylus cantonensis↗