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Biomedical subjects

P Hagan

Publications and source records attributed to P Hagan.

At least 19 recordsLinked to original sources
PubMed2002

Detection of the parasitic dinoflagellate Hematodinium in the Norway lobster Nephrops norvegicus by ELISA.

Norway lobsters Nephrops norvegicus from the coastal waters of Scotland are seasonally infected by a parasitic dinoflagellate of the genus Hematodinium. An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of the parasite in the haemolymph of N. norvegicus. The ELISA is simple to perform with a detection limit of 5 x 10(4) parasites ml(-1) haemolymph. The ELISA is currently being used to study the prevalence and seasonality of Hematodinium infection in N. norvegicus and other crustacean hosts.

Animals↗
PubMed2001

Acidic vesicles of Schistosoma mansoni.

The fluorescent probe LysoTracker Red was used to examine for the presence of acidic vesicles in cercariae and schistosomula of Schistosoma mansoni. Acidic vesicles were widely distributed throughout the body of freshly transformed schistosomula and 24-h-old schistosomula but were absent from cercariae. The vesicles of freshly transformed schistosomula were undetectable after incubation with drugs that affect the functionality of acidic vesicles including monensin, ouabain, primaquine, and amiloride. In 24-h transformed schistosomula, the same effect was observed with monensin but not with ouabain, primaquine or amiloride. Praziquantel also affected the acidic vesicles of the schistosomula. We suggest that these acidic vesicles could be large lysosome-like organelles.

Animals↗
PubMed2001

Cytokine responses to mitogen and Schistosoma haematobium antigens are different in children with distinct infection histories.

Prevalence of Schistosoma haematobium infection in children from two neighbouring villages in Zimbabwe was 77.1% and 40.3%, respectively. The age-intensity data indicated peak intensities of infection at a lower age in the high prevalence village. This study investigated whether the difference in infection histories was reflected in a difference in cytokine profiles between children resident in these two villages. Blood samples were taken to assay for cytokine secretion 1 year after treatment for schistosomiasis. They were cultured with phytohaemagglutinin (PHA), schistosome egg antigens (SEA) or cultured without stimulant and tested for the presence of interleukin (IL)-4, IL-5, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma. Blood samples from children from the low prevalence village were more likely to produce IL-4 (P < 0.0001) and produced higher levels of IFN-gamma (P < 0.02) and GM-CSF (P < 0.03) when cultured with PHA for 24 h. Residence in the high prevalence village was associated with production of IL-10 (P < 0.006) and GM-CSF (P < 0.04) in response to culture with SEA and IL-5 (P < 0.02) with PHA for 48 h. The interaction between age and village was not significant for these results; however, there was a significant interaction between age and village for IL-5 detected in blood samples cultured with PHA for 24 h (P < 0.01). These results concur with previous observations that major patterns of cytokine production can be related to immunosuppression, but also indicate an underlying pattern which reflects the importance of history of infection to the immune response.

Adolescent↗
PubMed2001

T cell clones from Schistosoma haematobium infected and exposed individuals lacking distinct cytokine profiles for Th1/Th2 polarisation.

T cell clones were derived from peripheral blood mononuclear cells of Schistosoma haematobium infected and uninfected individuals living in an endemic area. The clones were stimulated with S. haematobium worm and egg antigens and purified protein derivative. Attempts were made to classify the T cell clones according to production of the cytokines IL-4, IL-5 and IFN-gamma. All the T cell clones derived were observed to produce cytokines used as markers for the classification of Th1/Th2 subsets. However, the 'signature' cytokines marking each subset were produced at different levels. The classification depended on the dominating cytokine type, which was having either Th0/1 or Th0/2 subsets. The results indicated that no distinct cytokine profiles for polarisation of Th1/Th2 subsets were detected in these S. haematobium infected humans. The balance in the profiles of cytokines marking each subset were related to infection and re-infection status after treatment with praziquantel. In the present study, as judged by the changes in infection status with time, the T cell responses appeared to be less stable and more dynamic, suggesting that small quantitative changes in the balance of the cytokines response could result in either susceptibility or resistant to S. haematobium infection.

Animals↗
PubMed2001

The impact of repeated treatment with praziquantel of schistosomiasis in children under six years of age living in an endemic area for Schistosoma haematobium infection.

Praziquantel was given every eight weeks for two years to children aged under six years of age, living in a Schistosoma haematobium endemic area. Infection with S. haematobium and haematuria were examined in urine and antibody profiles (IgA, IgE, IgM, IgG1, IgG2, IgG3, and IgG4) against S. haematobium adult worm and egg antigens were determined from sera collected before each treatment. Chemotherapy reduced infection prevalence and mean intensity from 51.8% and 110 eggs per 10 ml urine, respectively, before starting re-treatment programme to very low levels thereafter. Praziquantel is not accumulated after periodic administration in children. Immunoglobulin levels change during the course of treatment with a shift towards 'protective' mechanisms. The significant changes noted in some individuals were the drop in 'blocking' IgG2 and IgG4 whereas the 'protecting' IgA and IgG1 levels increased. The antibody profiles in the rest of the children remained generally unchanged throughout the study and no haematuria was observed after the second treatment. The removal of worms before production of large number of eggs, prevented the children from developing morbidity.

Animals↗
PubMed2000

Exposure, infection and immune responses to Schistosoma haematobium in young children.

Behavioural, parasitological and immunological data were obtained from 48 children up to 6 years old, resident in a Schistosoma haematobium endemic area in Zimbabwe. The children averaged more than 1 contact with infective water bodies every 3 days and all showed immunological evidence of exposure (an anti-cercarial and/or anti-egg antibody response). IgM was the dominant isotype and appeared in the youngest children, followed by IgA, IgE and IgG3. However, only 38 children showed evidence of infection (an anti-egg response or eggs in urine) and only 14 were excreting eggs. The best estimates from these data are that less than 1 in 100 contacts results in infection and less than 1 in 1000 result in egg output. This suggests that there may be substantial attrition of invading cercaria even in naïve individuals.

Animals↗
PubMed2000

Anti-schistosome antibody responses in children coinfected with malaria.

People residing in schistosome endemic areas are often infected with other parasites. The interaction of the parasites in the host has important implications in the development of acquired immunity to schistosomiasis, and schistosome immuno-epidemiology. An analysis of specific anti-schistosome egg responses in children coinfected with schistosomiasis and malaria shows that malaria positive children produce significantly more anti-schistosome IgE and IgG3 than schistosome infected children who are negative for malaria.

Adolescent↗
PubMed2000

Dissociation of interleukin-4 and interleukin-5 production following treatment for Schistosoma haematobium infection in humans.

Infection with Schistosoma haematobium, the causative agent of urinary schistosomiasis is characterized by high levels of specific immunoglobulin (Ig) E and eosinophilia. The primary cytokines driving production of IgE and eosinophilia are IL-4 and IL-5, respectively. In this study, IL-4 and IL-5 production in children from a schistosome endemic area of Zimbabwe were investigated. Blood samples were taken, stimulated in vitro with either mitogen or schistosome antigens and assayed for IL-4 and IL-5 production. These samples produced either IL-4 or IL-5 but rarely both cytokines when blood was cultured in vitro for 24 or 48 h. After 72 h culture in vitro, both cytokines were detected in most samples. These data imply that while IL-4 and IL-5 are both produced by schistosome infected people, they are not necessarily coproduced.

Adolescent↗
PubMed1999

Seeking the ghost of worms past.

The mechanisms of protective immunity to parasite infections in humans are still elusive. Here, Woolhouse and Hagan discuss new evidence suggesting that the extremely slow development of acquired immunity to human schistosomes may depend on exposure to antigens from these worms after they die.

Adult↗
PubMed1999

A comparison of re-infection rates with Schistosoma haematobium following chemotherapy in areas with high and low levels of infection.

Two groups of children (6-15 years) from a Schistosoma haematobium endemic area were followed for 9 months after praziquantel treatment. Seventy-three children came from an area of high infection while 67 children came from an area of low infection. Pre-treatment infection prevalence in the high infection area (76.6%) was significantly higher than that in low infection area (36.3%). Levels of anti-SEA immunoglobulin (Ig)A and IgM were significantly higher and levels of IgG3 significantly lower in children from the low infection area. Nine months after treatment, infection prevalence was significantly higher in the high infection area (29.0%) (where re-infection rates were higher) than in the low infection area (12.9%). Children from the high infection area were six times more likely to get re-infected than those from the low infection area, while younger children were 30 times more likely to get re-infected than older children. These results are discussed in relation to differences in transmission and the development of acquired immunity. Pre-treatment levels of IgM and the difference between IgE and IgG4 were positively associated with re-infection in the high infection area. These results are discussed in relation to the interpretation of simple correlations between infection and some antibody levels and the inference of causal relationships between observed epidemiological and immunological patterns.

Adolescent↗
PubMed1999

Ultrastructural localization of Sm15 and Sm25, two major tegumental adult worm antigens of Schistosoma mansoni.

Sm15 and Sm25 are two of the principal tegumental antigens recognized by antibodies from mice protectively vaccinated with adult worm tegumental membranes and may therefore be potential vaccine candidate antigens. Using antibodies affinity purified from anti-tegumental membrane anti-sera, and antibodies raised against the recombinant antigens, Sm15 and Sm25 were shown to be located specifically in the tegument of adult worms being distributed throughout the syncitium but not associated with the outer membrane.

Animals↗
PubMed1998

Changes in specific anti-egg antibody levels following treatment with praziquantel for Schistosoma haematobium infection in children.

Fifty-seven children 6-15 years old resident in a Schistosoma haematobium endemic area in eastern Zimbabwe were treated with praziquantel at 40 mg/kg body weight. Levels of IgA, IgE, IgG1, IgG2, IgG3, IgG4, and IgM antibodies against soluble egg antigen (SEA) were assayed by ELISA before treatment and at 18 and 36 weeks following treatment. Prevalence of infection (as determined by urine egg counts) was 65% before treatment, all children were confirmed egg negative six weeks after treatment, and reinfection prevalence was 4% at 18 weeks and 21% at 36 weeks after treatment. At 18 weeks after treatment, there was a massive increase in IgG1 levels and significant increases in IgE and IgG4 levels and significant decreases in IgA and IgG2 levels. Similar patterns occurred at 36 weeks after treatment. Egg positive children showed a more marked increase in IgG1 and (for older children) a more marked decrease in IgG2 levels. There were no other effects of age or sex. IgA and IgG1 levels fell significantly between 18 and 36 weeks following treatment but not to pretreatment levels. The results show that specific anti-egg antibody responses are highly sensitive to the effects of praziquantel treatment. A possible consequence is that the susceptibility of children to infection with S. haematobium is altered by chemotherapy; this requires further investigation.

Adolescent↗
PubMed1998

Failure to transilluminate the stomach is not an absolute contraindication to PEG insertion.

Percutaneous endoscopic gastrostomy (PEG) tubes are now a well established method of enteral feeding. With the introduction of nurse endoscopists it has been possible to site PEG tubes with only one member of medical staff being present. Furthermore transillumination of the stomach is considered by many to be essential prior to gastric puncture. We present a series of 62 consecutive PEG tube sitings performed by the same nurse endoscopist/doctor team without transillumination of the stomach prior to gastric puncture. Sixty of the 62 patients (97%) had successful PEG tube insertion. There were no immediate complications. There were two failures, neither of which related to the technique. It is concluded that failure of transillumination is not an absolute contraindication to PEG tube insertion.

Adolescent↗