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Biomedical subjects

M T Rogan

Publications and source records attributed to M T Rogan.

At least 19 recordsLinked to original sources

Canine echinococcosis in Turkana (north-western Kenya): a coproantigen survey in the previous hydatid-control area and an analysis of risk factors.

A study of Echinococcus granulosus infection in dogs, with risk-factor analysis, was carried out in the endemic area of northern Turkana district, Kenya, using necropsy on 42 strays and a coproantigen-ELISA survey of 161 owned animals. During the post-mortem examinations, 14 (33%) of the necropsied dogs were found infected with E. granulosus, with a mean burden of 540 worms (range=two to 4080 worms). The 26 necropsied dogs that came from the north-western Lokichoggio division--an area where, from 1983 to 1997, there had been a continuous programme of hydatid control--showed a similar prevalence of infection to the other dogs (34.6%) but a significantly lower mean burden, of 53 worms (range=two to 300). Forty-two (26%) of the animals tested for Echinococcus coproantigen were found positive. Although the dogs from the Lokichoggio division were more likely to be coproantigen-positive (29%) than those from the central Kakuma division (20%) or the north-eastern division (18%), the differences were not statistically significant. In questionnaire-based interviews, the owners of the dogs tested for coproantigens were asked about possible risk factors for canine infection with E. granulosus. Women were found to have twice the level of contact with dogs as men. The results of a univariate analysis of the dog-owners' responses revealed six factors that appeared to be significantly associated with a coproantigen-positive dog: non-restraint of the dog (P<0.001); dog fed on raw offal (P<0.001); the improper disposal of slaughter offal (P<0.001); the dog-owner's lack of knowledge about the transmission of echinococcosis (P=0.001); the dog not receiving anthelmintic treatment (P=0.003); and dog age < or =5 years (P=0.01). The results of a multivariate analysis confirmed that lack of dog restraint, access to raw offal, and young age of the dog (< or =5 years) each significantly increased the risk of coproantigen positivity (P, 0.005). Dogs that scavenged from cooking pots, were used to clean babies, had access to the inside of houses, and/or slept indoors appeared, however, to be at no increased risk of coproantigen positivity. The present results are discussed in relation both to older information on the epidemiology and role of human behaviour in the transmission of E. granulosus in Turkana, and the effects of the hydatid-control programme that ran continuously in the north-western division of Turkana between 1983 and 1997.

Animal Husbandry↗

Human cystic echinococcosis in two Mongolian communities in Hobukesar (China) and Bulgan (Mongolia).

In order to investigate the prevalence of human cystic echinococcosis (CE) in traditional Mongolian communities in western Mongolia and Xinjiang (northwest China), studies were carried out between 1995 and 2000, on two ethnically identical populations in Hobukesar (China) and Bulgan (Mongolia). The prevalence of human hepatic CE in the two communities was significantly different. In Hobukesar, human CE prevalence by ultrasound was 2.7% (49/1844), while in Bulgan it was 0.2% (4/1609) (P<0.001). Dog surveys showed that coproantigen-positive rates or dog necropsy positives were similar in both communities (35.0% in Hobukesar and 35.7% in Bulgan). Comparing possible risk factors, there appeared to be some significant differences between the two communities, which might contribute to the observed difference in CE prevalence. These included: the proportion of herdsman or farmers recorded; the proportions of dog ownership and livestock ownership; and the proportion of families practising home slaughter. The presence of a Russian dog-dosing programme up to the mid-1980s may explain the lower prevalence of human CE in the Bulgan population; no similar programme operated in the China-administered Hobukesar community.

Animals↗

Detection of antibodies to Staphylococcus aureus Toxic Shock Syndrome Toxin-1 using a competitive agglutination inhibition assay.

AIMS: To develop a competitive agglutination inhibition assay (CAIA) for the detection of anti-Toxic Shock Syndrome Toxin-1 (TSST-1) antibody in serum samples using a commercially available reverse passive agglutination assay (RPLA) kit. METHODS AND RESULTS: TSST-1 toxin and sera were incubated together, so that anti-toxin IgG would complex with the toxin. Latex particles sensitized with rabbit IgG anti-TSST-1 were added to test for un-complexed toxin. The sensitivity and specificity of the CAIA assay was determined relative to positive and negative ELISA results. The sensitivity (proportion of positive ELISA sera which tested positive by CAIA) was 66% whilst the specificity (proportion of ELISA negative sera which tested negative by CAIA) was 75%. Seven sera (14%) were negative by ELISA but positive for CAIA and 12 (18.8%) were positive for ELISA but negative for CAIA, suggesting some interference with the assays. Statistical analysis showed no significant difference between the methods in terms of the numbers of individuals testing positive (chi2, P = 0.04). CONCLUSIONS: The CAIA assay allowed detection of anti-TSST-1 within 18 h and was simple to read visually. SIGNIFICANCE AND IMPACT OF THE STUDY: The method is a useful test for individual serum samples and a preliminary investigation for medical screening of suspected toxic shock syndrome and is applicable in situations where antibody assays are not routinely used for anti-TSST-1 and also where sophisticated equipment (e.g. microtitre plate reader) is not available.

Animals↗

Echinococcosis: disease, detection and transmission.

Echinococcosis is one of the world's most geographically widespread parasitic zoonoses, with transmission occurring in tropical, temperate and arctic biomes. Most human infections are due to Echinococcus granulosus transmitted between domestic dogs and livestock, but this cosmopolitan species also cycles between wild carnivores (principally canids) and wild ungulates. The other species with significant zoonotic potential is E. multilocularis that occurs naturally in fox definitive hosts and small mammal intermediate hosts. These two species cause human cystic or alveolar echinococcosis respectively, which may be considered serious public health problems in several regions including developed countries. This review provides an introductory overview to the Supplement and summarises the biology and epidemiology of these two related cestodes with an emphasis on applied aspects relating to detection, diagnosis and surveillance in animal and human populations, and includes aspects of transmission ecology, and also considers aspects of community epidemiology and potential for control.

Animals↗

Rapid dot-ELISA for the detection of specific antigens in the cyst fluid from human cases of cystic echinococcosis.

A rapid dot-ELISA was developed for the detection of specific antigens in samples of cyst fluid from human cases of Echinococcus granulosus infection, permitting the confirmation of cystic echinococcosis (CE). Peroxidase-conjugated antibodies against antigen B (derived from the fluid in the cysts of sheep infected with E. granulosus) were used to test cyst-fluid samples from 22, surgically confirmed cases of human CE and 21 domestic animals (horses, sheep, buffalo, a cow and a camel) with CE. All of these samples were found to be strongly positive in the dot-ELISA, by direct reading with the naked eye. In contrast, fluid samples from seven, non-parasitic liver cysts of human origin were all negative, and a sample taken from the residual cavity left in a patient after previous CE surgery showed a weakly positive reaction. The antigen-detection assay, which can be completed within 10 min, may be a useful 'bedside' test for the differential diagnosis of cysts during surgery or percutaneous treatment for suspected CE.

Animals↗

In-vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production.

Murine hydatid cysts of Echinococcus granulosus were incubated in vitro in the presence of nitric oxide produced from S-nitroso-N-acetylpenicillamine (SNAP) or interferon-gamma activated peritoneal macrophages. In both situations, evidence of cyst damage and death was observed by microscopy in over 77% of cysts after 3 days, indicating that intact hydatid cysts could be susceptible to a Th1 driven macrophage attack. A crude extract of the laminated layer from cysts was found to be able to reduce the production of nitric oxide from activated macrophages in vitro and in vivo and this may have been due to phagocytosis of laminated layer fragments by the macrophages. The results indicate that, although cysts may be susceptible to the effects of nitric oxide, the laminated layer may be involved in downregulating nitric oxide production.

Animals↗

Apoptosis in human Jurkat T cells after culture with live Taenia crassiceps cysticerci in vitro.

This study examines the effects of Taenia crassiceps cysticerci on the viability of a human T lymphocyte cell line (Jurkat). Both budding and non-budding T. crassiceps metacestodes were cultured over 24 and 48 h in the presence of Jurkat cells. Cell viability decreased with increasing numbers of cysticerci, particularly budding cysticerci. Single cell gel electrophoresis (comet) analysis, which grades DNA damage, showed a significant increase in apoptosis at 24 and 48 h. The morphology of treated cells was determined using acridine orange with the classical morphology of apoptotic bodies seen to increase with increasing cysticerci numbers over time. These results indicate that parasite-induced apoptosis occurs during murine cysticercosis. Such a mechanism may be important in survival of other metacestode infections of medical or veterinary importance.

Acridine Orange↗

Helminth parasites of the wild rabbit Oryctolagus cuniculus near Malham Tarn, Yorkshire, UK.

Between 1992 and 1996, 95 rabbits from the immediate locality of Malham Tarn, North Yorkshire, UK were examined for the presence of helminth parasites. All the examinations took place in late September or October. Three species of nematodes, Graphidium strigosum, Passalurus ambiguus and Trichostrongylus retortaeformis and two species of cestodes, Taenia pisiformis and Cittotaenia pectinata were identified. There were no associations between helminth species richness and year of sampling, host weight or sex. A logistic model was fitted to the prevalence data from these helminths as was an over-dispersed Poisson model to the worm burden data. Graphidium strigosum was the most frequently identified species with an average prevalence of 78%. The mean prevalence and intensity of Graphidium infection were significantly effected by sampling year. The lower than normal rainfall recorded at the Tarn during the years 1995 and 1996 may have be one reason for this pattern. The worm burden of G. strigosum was significantly positively associated with rabbit body weight. The intensity of infection with P. ambiguus was significantly higher in female rabbits. There was a significant non-linear relationship between P. ambiguus worm burden and rabbit weight (P = 0.002) with worm burdens being highest in the 1000 g to 1499 g weight cohort. Trichostrongylus retortaeformis was only identified in 1994 and male rabbits harboured significantly higher worm burdens than females (48 vs. 7, P = 0.022). Over the five years, the average Taenia pisiformis prevalence was 31% and there was a significant positive association between worm burden and rabbit weight (P = 0.001). Cittotaenia pectinata had a prevalence of 37% over the whole study period with no interactions between prevalence or intensity and body weight, year of sampling or rabbit sex. All five helminths showed an overdispersed distribution with k values less than 1.

Animals↗

An extensive ultrasound and serologic study to investigate the prevalence of human cystic echinococcosis in northern Libya.

A prevalence study of abdominal cystic echinococcosis (CE) was undertaken in the northwest, north-central, and northeast regions of Libya. A total of 36 villages along the coast were included, in which 20,220 people were screened by portable ultrasound. Three hundred thirty-nine (1.7%) were diagnosed with CE. There was no significant difference between CE prevalence rates in the three regions of Libya (mean = 1.6%); however, intervillage rates were variable, ranging from 0% to 4.5%. The prevalence of CE increased significantly with age (P < 0.0001) and females were significantly more affected (2%) than males (1.3%) (P < 0.0001). Cases of CE were distributed among 3.2% of housewives, 2.6% of farmers, 2.3% of male civil servants, 1.3% of female students, and 1.1% of male students. Housewives (P < 0.0001) and students (P < 0.0001) were significantly more at risk for CE. A statistically significant proportion (62% [210 of 339]) of CE cases kept dogs (P < 0.0001). Of the ultrasound-positive CE cases 69% (233 of 339) were antibody seropositive by ELISA using Echinococcus granulosus hydatid cyst fluid antigen B. Blood samples (n = 10,096) collected onto filter papers were taken randomly from ultrasound-negative people who entered the study, of which 11.2% were found to be seropositive. Seropositivity increased with age (P < 0.0001), with females exhibiting higher seroprevalence than males for all age groups (P < 0.0001). Seroprevalence was distributed occupationally among 17.3% of female students, 11.2% of male students, 8.3% of housewives, 7.3% of farmers, and 6.4% of male civil servants. Housewives and students were more likely to be seropositive (P < 0.0001). Forty-seven percent (526) of the seroreactors kept dogs. All liver hydatid cysts detected by ultrasound during community screening were classified according to morphology and size into six types. Type I (17.5% of all cases) were small univesicular cysts less than 50 mm in diameter with no laminations or daughter cysts. Type II (34%) were univesicular cysts with only laminations. Type IIIa (8.5%) were univesicular cysts with the appearance of laminations and daughter cysts. Type IIIb (13%) were univesicular with laminations and less prominent daughter cysts. Type IV (5.6%) presented as a solid mass. Type V were degenerated calcified or partially calcified cysts (13.2%). Type VI presented as multiple cysts (8% of all cases). The CE cases that exhibited Types II, IIIa, IIIb, IV or VI cysts showed the highest seropositivity (86%, 96%, 95%, 100%, and 96%, respectively), while Types I and V were the least seroreactive (38% and 22%, respectively). Cases of CE occurred in 311 families, with 93% having only one member as a CE case while 7% of the families had two or more cases. However, 25% of the ultrasound-negative persons belonging to families with an index CE case were seropositive for antibodies to Echinococcus. These results confirm the importance of human CE in Libya. They also confirm the usefulness of ultrasound combined with serology as a mass screening approach for CE in north African communities.

Abdomen↗

T-cell activity associated with secondary infections and implanted cysts of Echinococcus granulosus in BALB/c mice.

Selected cytokine profiles of lymphocytes were assessed in BALB/c mice infected with protoscoleces of Echinococcus granulosus. Late stages of the infection (three months+) were characterized by more dominant Th2 activity with elevated IL-4 and IL-10 and reduced IFN-gamma output by Con-A and antigen stimulated splenocytes. Circumparasitic leucocytes produced mainly IL-10 by five months post infection. A peak in IFN-gamma production in the first month of infection may suggest Th1 or Th0 activity at this time and this may be correlated with initial protoscolex death. In addition, cytokine profiles from mice implanted with intact hydatid cysts were also assessed. At two weeks post implantation all cysts were still viable and cytokine production was characterized mainly by elevated IL-10 production. However, at four months post implantation, some of the cysts from two mice had been killed whilst all cysts in the remaining mouse remained viable. In the mice where dead cysts were present, elevated levels of IFN-gamma were detected from splenocytes and circumparasitic cells. Elevated IL-4 was also evident with the splenocytes. In the mouse with viable cysts IFN-gamma production was reduced Results indicate that IFN-gamma(Th1) activity may be correlated with killing of both protoscoleces and established cysts of E. granulosus.

Animals↗

Human cystic echinococcosis in a Uruguayan community: a sonographic, serologic, and epidemiologic study.

A prevalence and transmission study of human cystic echinococcosis (CE), due to infection with the dog tapeworm Echinococcus granulosus, was undertaken in the village of La Paloma in central Uruguay. The human population was registered and screened for CE by abdominal ultrasound scan as well as a number of serologic tests. Dogs were screened for E. granulosus infection by arecoline purgation as well as specific coproantigen testing. The total prevalence of human CE (new cases and those with a previous history) was 5.6% (64 of 1,149); 3.6% (40) of the cases were new ultrasound detected asymptomatic cases (mean age = 45 years). Age prevalence increased from 1.1% in the 4-6-year-old group to > 11% in the > 60-year-old group; the 20-29-year-old group had a significantly higher CE rate of 7.4%, compared with younger and older age groups, and there was no difference between sexes. A CE rate of 3.9% (20 of 514) was also recorded by ultrasound for new cases in the population residing outside the village. Most of the hydatid cysts were located in the liver presenting as either univesicular cysts or a solid mass, and of those 71% and 63%, respectively, with such cyst presentations were seropositive against E. granulosus cyst fluid antigens. Two of eight individuals who were filter paper blood spot seropositive, but ultrasound scan negative, were subsequently diagnosed respectively with pulmonary hydatidosis after radiography, and hepatic hydatidosis after computed tomography scan. Of 36 households with a CE patient, 32 were single cases while four households each harbored two CE cases. This did not represent a clustered distribution within families (23 of 117). Almost 20% of the dogs from La Paloma were found infected with E. granulosus after purge examination, with a mean worm number of 67 (range = 1-1,020). An additional eight dogs that were purge negative were Echinococcus coproantigen positive. The study showed that human CE is highly endemic in Uruguay, with one of the highest local prevalence rates in the world. Transmission appears to occur readily within well-developed towns, as well as on rural sheep ranches. Mass screening by ultrasound scanning with confirmatory serologic testing is an effective approach to case detection at the community level.

Adolescent↗

Fear conditioning induces associative long-term potentiation in the amygdala.

Long-term potentiation (LTP) is an experience-dependent form of neural plasticity believed to involve mechanisms that underlie memory formation. LTP has been studied most extensively in the hippocampus, but the relation between hippocampal LTP and memory has been difficult to establish. Here we explore the relation between LTP and memory in fear conditioning, an amygdala-dependent form of learning in which an innocuous conditioned stimulus (CS) elicits fear responses after being associatively paired with an aversive unconditioned stimulus (US). We have previously shown that LTP induction in pathways that transmit auditory CS information to the lateral nucleus of the amygdala (LA) increases auditory-evoked field potentials in this nucleus. Now we show that fear conditioning alters auditory CS-evoked responses in LA in the same way as LTP induction. The changes parallel the acquisition of CS-elicited fear behaviour, are enduring, and do not occur if the CS and US remain unpaired. LTP-like associative processes thus occur during fear conditioning, and these may underlie the long-term associative plasticity that constitutes memory of the conditioning experience.

Amygdala↗

Expression and immunological characterisation of Echinococcus granulosus recombinant antigen B for IgG4 subclass detection in human cystic echinococcosis.

A 165bp DNA fragment derived from the 12 kDa subunit of Echinococcus granulosus antigen B (AgB), a major hydatid cyst fluid antigen was cloned in the pMa1-c2 expression vector. A 52 kDa maltose binding-AgB fusion protein (rAgB.MBP) was produced and inclusion bodies containing the fusion protein were solubilised in urea and affinity purified on an amylose-Sepharose 6B column. The immunogenicity of the purified recombinant antigen for IgG4 antibody detection was tested with human serum using immunoblotting, ELISA and dot-ELISA assays and compared to native AgB. Both recombinant and native AgB preparations were highly reactive for human IgG4 antibodies in serum of cystic echinococcus (CE) patients. Recombinant AgB.MBP (rAgB.MBP) showed approximately 65% sensitivity in detection of IgG4 serum antibodies by ELISA from confirmed CE patients. Cross-reactivity (33%) occurred with alveolar echinococcosis (E. multilocularis) sera but recombinant AgB showed no seroreactivity with sera from other helminth infections tested (schistosomsis, onchocercsis, cysticercosis) or from uninfected individuals residing in CE endemic or non-endemic regions. The serologic sensitivity (63%) for IgG4 antibodies of a native AgB fraction enriched from human hydatid cyst fluid was similar to that for recombinant AgB (65%) though specificity was slightly lower (81%). A dot-ELISA for detection of total IgG, incorporating the rAgB.MBP resulted in 74% sensitivity and 88% specificity for human CE and 93% sensitivity and 65% specificity for native AgB. Recombinant AgB is a potential replacement for native antigens currently being used and could provide a better standardised E. granulosus specific test for clinical confirmation for CE especially for IgG4 antibody detection which appears to be predominantly associated with advanced disease.

Animals↗

AMPA receptor facilitation accelerates fear learning without altering the level of conditioned fear acquired.

Rats treated with the AMPA receptor-facilitating drug 1-(quinoxolin-6-ylcarbonyl)piperidine (BDP-12) during training acquired fear conditioning to a tone faster than vehicle-treated controls. The effect on acquisition was dependent on the dose given. BDP-12-treated rats and vehicle-treated controls reached the same level of conditioned fear and extinguished at the same rate. The dissociation of learning rate from these other normally covariant measures suggests that the drug had a specific and isolated effect on acquisition. Controls for drug effects on stimulus sensitivity, locomotor activity, generalized fearfulness, and other performance factors support this interpretation. The known action of BDP-12 on receptor dynamics suggests that its effect on acquisition may be attributed to specific modulation of an AMPA and NMDA receptor-dependent plasticity mechanism. The finding that the drug accelerates acquisition but does not affect the level of conditioned fear acquired parallels the effect of the drug on long-term potentiation (LTP) (increasing the rate but not the ceiling of potentiation) and suggests that common mechanisms may underlie fear conditioning and LTP.

Animals↗

IgG1 and IgG4 serum antibody responses in asymptomatic and clinically expressed cystic echinococcosis patients.

IgG1 and IgG4 subclass antibody responses were investigated in two clinically different groups of hepatic cystic echinococcosis (CE) patients. One group consisted of surgically proven CE cases (clinically expressed hospitalized cases) and a second group comprised asymptomatic CE patients (first time community detected cases) diagnosed by portable ultrasound and serology in four different endemic communities. Fifty eight sera from surgically proven CE patients and 133 sera from asymptomatic ultrasound diagnosed CE cases were screened by ELISA using purified human hydatid cyst fluid antigen B for total specific IgG, IgG1 and IgG4 antibodies. Fifty sera from healthy individuals from within endemic regions were used as control negatives. Compared to control negatives total IgG antibody levels were elevated in both surgically proven (85%) and asymptomatic CE cases (77%) but there was no significant difference between the two groups. IgG1 subclass antibody levels were also elevated in both surgically proven (55%) and asymptomatic cases (58%) compared to endemic controls and similarly the difference in this response was not significant between these two groups. In contrast the prevalence of IgG4 antibodies in surgically confirmed chronic CE patients was greater (71%) than the respective IgG1 antibody levels (55%). The greatest difference in specific antibody response, between advanced surgically confirmed CE patients and ultrasound detected asymptomatic CE cases, was observed for IgG4 antibody levels which were detected in 71% of symptomatic compared to only 23% of asymptomatic patients (P < 0.0001). These observations confirm that IgG4 is an important diagnostic parameter for clinically expressed cystic echinococcosis in humans and suggest that a switch from a predominant IgG1 response to IgG4 might occur in CE patients as the disease progresses.

Animals↗

A pilot, serological survey for cystic echinococcosis in north-western Mongolia.

The seroprevalence of cystic echinococcosis in north-western Mongolia was determined in a cross-sectional study of 334 semi-nomadic pastoralists in their summer grazing areas. Overall, 5.2% of the subjects were found to be strongly seropositive for antibodies to Echinococcus granulosus antigen B by ELISA. Only 10% of the adult subjects (aged > or = 15 years) had heard of the disease and only 5% recognized hydatid cysts in their livestock (in contrast to the neighbouring province in China, where 76% had seen and recognized cysts in the organs of slaughtered animals). The close association between Mongolian pastoralists, their dogs and livestock is likely to encourage ready transmission of the parasite in a region where home slaughter is practised and offal for various scavengers, including domestic dogs. Further information is needed to determine the prevalence of infection in other intermediate hosts and in dogs and the clinical importance of the disease in this remote region.

Adolescent↗