Biomedical subjects

M W Guy

Publications and source records attributed to M W Guy.

18 recordsLinked to original sources

PubMed2001

A study of the pharmacokinetic profile of low-dose hepatitis B immune globulin in long-term liver transplant recipients for chronic hepatitis B infection.

Post-transplant protocols for hepatitis B (HBV) prophylaxis using high-dose intravenous hepatitis B immune globulin (10,000 IU) with or without lamivudine are commonly reported. Our centre has previously reported a low-dose intramuscular (i.m.) protocol and lamivudine with excellent results. There have been, however, no pharmacokinetic studies of i.m. hepatitis B immune globulin (HBIG) in this setting. The objective of this study was to determine the pharmacokinetic profile of i.m. HBIG in long-term post-liver-transplant recipients to determine a rational dosing protocol. Six stable liver transplant recipients receiving monthly i.m. HBIG injections for greater than one year were enrolled in this study. All patients had no detectable HBV DNA levels. HBIG titers (anti-HBs) were measured predose, then three times weekly for four weeks and then twice weekly until the serum HBIG titers were 100 IU/L or less. The pharmacokinetic parameters were calculated using noncompartment methods. The mean time to maximum concentration was 10.5 d (range 4-20 d) and the mean half-life was 20 d (range 13.5-23.5 d). Based on these pharmacokinetic parameters in stable long-term post-transplant patients, a rational dosing protocol was developed that allows for more appropriate utility of HBIG and improved patient convenience.

Area Under Curve↗

PubMed1992

Epidemiology of canine leishmaniasis: prevalence, incidence and basic reproduction number calculated from a cross-sectional serological survey on the island of Gozo, Malta.

Assessment of the resilience of canine leishmaniasis to control or, more ambitiously, the effort needed to eradicate infection, requires an estimate of the basic case reproduction number (R0). This paper applies the theoretical results of Hasibeder, Dye & Carpenter (1992) to data from a cross-sectional survey on the Maltese island of Gozo in which dogs of known age, sex and occupation (pet, guard etc) were subjected to three different serological tests for the presence of specific antibody (IFAT, DAT and ELISA). Difficulties in interpreting these test results, and hence of determining the proportion of dogs infected, present the main obstacle to estimating R0: estimates are critically dependent on the choice of threshold separating seropositives from seronegatives. The data do, however, allow a robust comparative analysis of risk which shows that the force of infection experienced by working dogs is about three times higher than that of pet dogs, a degree of non-homogeneous contact which actually has little effect on estimates of R0. We suggest a cautious point estimate of R0 congruent to 11, and comment briefly on its significance for leishmaniasis control.

Age Factors↗

PubMed1987

The life expectancy of phlebotomine sandflies: first field estimates from southern France.

1. A field study of Phlebotomus ariasi Tonnoir, the vector of Leishmania infantum Nicolle in southern France, addressed the following questions: Is it possible to estimate reliably the life expectancy of this sandfly; can spatial or temporal variation in the life expectancy be detected, and is such variation significant for disease transmission? 2. Life expectancy was estimated by examining follicular relics in the ovaries of more than ten thousand females caught in light traps at seven sites in the Cévennes and the Garrigues, throughout their active period in 1985 and 1986. Whilst the distinction between nulliparous and parous flies was easily made, assessments of the number of times a parous fly had laid eggs were unreliable. Best estimates of life expectancy were therefore calculated from the parous rate. 3. Large samples collected from one site in the Cévennes in both years gave very similar estimates of life expectancy. 4. There was also no significant difference between estimates obtained from the Cévennes and the Garrigues, despite their distinct vegetation and climates. Therefore, large regional differences in sandfly population size and the prevalence of canine leishmaniasis cannot be explained by a difference in adult survival rate. 5. With no systematic annual or regional variation, a useful mean life expectancy can be calculated from the data collected at all sites in both years. It is 1.54 (SE 0.04) ovarian cycles. However, this estimate is sensitive to the assumption that survival rate is a discrete rather than a continuous variable. 6. Local variation in the parous rate may be associated with the proximity of traps to P.ariasi emergence sites.

Age Factors↗

PubMed1985

Observations on early and late post-sporozoite tissue stages in primate malaria. III. Further attempts to find early forms and to correlate hypnozoites with growing exo-erythrocytic schizonts and parasitaemic relapses in Plasmodium cynomolgi bastianellii infections.

Rhesus monkeys were heavily infected with sporozoites of Plasmodium cynomolgi bastianellii in an attempt to demonstrate the site of invasion of sporozoites into tissue cells and their growth there. Further attempts were made to correlate the appearance and loss of hypnozoites with parasitaemic relapses. Hypnozoites were demonstrated and once again shown to decrease in numbers over 229 days during which time the infection showed parasitaemic relapses. Liver biopsies taken at two-day intervals for 12 days showed that hypnozoites decreased in numbers over-all and growing schizonts were demonstrated in the liver. At this time a parasite the size of a hypnozoite was seen with two nuclei and another was seen with an elongate, possibly dividing nucleus in one monkey. an attempt to find the location of the early intracellular exoerythrocytic forms in the liver at various times less than 40 hours after infection using smears and immunological staining with newly prepared anti-sera failed. Large numbers of sporozoites of P. knowlesi were also injected into a rhesus monkey the liver of which on the fifth day after infection showed no hypnozoites among 157 sections of growing schizonts and no parasites at all on the 42nd day after infection. In P. cynomolgi bastianellii infections parasites, mostly hypnozoites, were found in the liver up to 229 days after infection.

Animals↗

PubMed1984

Ecology of leishmaniasis in the south of France. 19. Determination of the hosts of Phlebotomus ariasi Tonnoir, 1921 in the Cévennes by bloodmeal analyses.

Engorged sandflies were collected using 58 CDC light traps set up nightly for 5 weeks at 12 stations in the commune of Roquedur, Gard, France, in the Cévennes focus of leishmaniasis. Of 782 engorged females, 593 were Phlebotomus ariasi, 3 were P. mascittii and 186 were not identified. Using the precipitin ring test and counter-current immuno-electrophoresis, the bloodmeals were tested with antisera to man, leporids, rodents, canids, mustelids, equids, suids, bovids, birds, lizards and amphibia. Of 530 identified bloodmeals, 2 were avian blood, 26 were mixed meals of mammalian blood and 25 were meals taken from unidentified mammals. Of the 477 other sandflies, 211 (44.2%) had fed on canids, 107 (22.4%) on man, 70 (14.7%) on bovids (presumed to be cattle at one station and goats elsewhere), 33 (6.9%) on leporids (probably mostly domesticated rabbits), 26 (5.5%) on mustelids (probably badgers), 17 (3.6%) on horses and 13 (2.7%) on rodents (probably brown rat). The proportions of feeds on different mammals varied according to their availability at each station. When both man and dog were equally available, the dog was preferred. The finding that, away from human habitation, P. ariasi commonly feeds on mustelids suggests the need for a reappraisal of animals of this family as possible reservoirs of leishmaniasis in the Cévennes.

Animals↗

PubMed1984

Ecology of leishmaniasis in the south of France. 20. Dispersal of Phlebotomus ariasi Tonnoir, 1921 as a factor in the spread of visceral leishmaniasis in the Cévennes.

The dispersal of Phlebotomus ariasi was studied in mark-release-recapture experiments in the summer of 1980 in a valley on the north-eastern slopes of the Oiselette range in the Cévennes mountains, in the commune of Roquedur, Gard, 50 km north of Montpellier, France. More than 5,000 specimens of P. ariasi were marked with fluorescent powders and released in 9 batches at 3 different places. Seven batches were engorged females and two were unengorged females and males. From 1-29 days after release, 497 marked sandflies (approximately 9%) were recaptured by active searches with UV lamps or in 58 CDC light traps set up in groups of 4 or 5 at 12 recapture stations. Females released engorged generally remained within 250 m of the release point for the first eight days while the bloodmeal was being digested after which there was a tendency to disperse to distances greater than 350 m presumably in a search for oviposition sites or another bloodmeal. The furthest distance to which a female released engorged was shown to move was 925 m; it was caught 12 days after release. Some of the females released unfed quickly moved away from release points, sometimes to distances of 1,000 m or more. One of these was caught 68.5 hrs after release at a station 2,200 m from the release point. Male sandflies tended to stay near the point of release and were not recaptured at distances greater than 600 m. There was no evidence that the movement of the sandflies was assisted by wind. Observations on the dispersal of female sandflies confirm that leishmaniasis can be more widely spread than generally assumed by the movements of the vector.

Animals↗

PubMed1983

Excreta disposal facilities and intestinal parasitism in urban Africa: preliminary studies in Botswana, Ghana and Zambia.

The relationships between intestinal parasitism and excreta disposal technologies in Gaborone (Botswana), Ndola (Zambia) and Kumasi (Ghana) were investigated. Parasitic prevalence and intensity rates amongst groups of urban residents having similar socio-economic status and housing, but different excreta disposal technologies, were compared. In Gaborone, there was no evidence of a difference in intestinal parasitism between those using aqua privies and having access to public taps and those in identical houses enjoying flush toilets, in-house water connections and showers. In Ndola, the group with sewered aqua privies had larger houses, cleaner toilets, better water supplies, longer residence and more people in paid employment than the groups using pit latrines or communal flush toilets. Despite this, the sewered aqua privy users were not found to be different from the other groups with regard to hookworm and protozoal infection but had significantly higher Ascaris infection rates. In Kumasi, despite the differences in toilet type--from squalid communal aqua privies, through often fouled bucket latrines to well-maintained flush toilet systems--and despite also the differences in water provision, no evidence was obtained of any differences in intestinal parasitism between the groups studied. These findings suggest that the provision of superior water and sanitation facilities to a small cluster of houses, or to houses scattered through an area, may not protect those families from infection if the over-all level of faecal contamination of the environment is high. The sample sizes and response rates achieved in this study were low and follow-up studies, employing the same methodology but with larger samples, are recommended.

Adolescent↗

PubMed1982

Observations on early and late post-sporozoite tissue stages in primate malaria. II. The hypnozoite of Plasmodium cynomolgi bastianellii from 3 to 105 days after infection, and detection of 36- to 40-hour pre-erythrocytic forms.

Confirmation of the existence of a persistent, uninucleate, dormant pre-erythrocytic stage, the hypnozoite, of the relapsing simian malaria parasite, Plasmodium cynomolgi bastianellii, has been obtained by means of experiments involving the intravenous injection into susceptible monkeys of 48 to 85 x 10(6) sporozoites derived from mosquitoes of a different species and source than employed previously. The development of these hypnozoites was traced from 3 days until 105 days after sporozoite inoculation, employing a sensitive immunofluorescence technique followed by restaining with Giemsa. From an average mean diameter of 4 micrometers at 3 and 5 days, uninucleate hypnozoites grow to 5 micrometers at 7 days, then persist with little change until at least 105 days after infection. Strong evidence for the viability of these persistent forms was obtained by treatment of a host monkey with primaquine, which eliminated all trace of hypnozoites present 2 weeks before. Examination of hepatic tissue from a monkey injected with sporozoites 36 and 40 hours earlier revealed rare uninucleate pre-erythrocytic forms of 2.5-micrometers diameter. These early forms were present in hepatocytes in a density only approximately 1/30th of that expected on the basis of numbers of pre-erythrocytic stages found in the same animal's liver 7 days after infection. Nevertheless, subinoculation experiments appeared to rule out the circulation as a vehicle for dissemination of any putative early intermediate hepatotropic forms from another site.

Animals↗

PubMed1982

Observations on early and late post-sporozoite tissue stages in primate malaria. I. Discovery of a new latent form of Plasmodium cynomolgi (the hypnozoite), and failure to detect hepatic forms within the first 24 hours after infection.

Previous work in this laboratory has demonstrated the ability of the immunofluorescence technique to detect pre-erythrocytic stages of the primate malaria parasite, Plasmodium cynomolgi bastianellii, in hepatic tissue obtained as early as 48 hours after sporozoite inoculation. In an attempt to visualize still earlier post-sporozoite stages, hepatic tissue obtained from a rhesus monkey infected with 12,000,000 sporozoites was examined at 2, 12, 24, and 48 hours after inoculation, employing antisera reactive with both invertebrate and vertebrate stages of the parasite. Tissue was also obtained at 7, 50, 102, and 105 days after sporozoite inoculation, and was examined for adequacy of the hepatic infection and for the presence of late exoerythrocytic schizonts. Although a new, previously unrecognized, uninucleate latent stage of 5 micrometer diameter (the "hypnozoite") was detected among large maturing schizonts in the 7-day and later biopsies, no intrahepatic parasites were found in tissue taken at 24 hours or earlier, despite the presence of up to 61 7-day schizonts and eight hypnozoites per 5 X 8 mm section. Pre-erythrocytic forms again were detected at 48 hours, although in far smaller numbers than expected on the basis of the density of parasites at 7 days after infection. The significance of these observations is discussed in the context of previous negative findings.

Animals↗

PubMed1980