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Title: Serological assessment of treatment outcome in patients with schistosomiasis by enzyme linked immunoabsorbent assay
Author: Bligh, William John
ISNI:       0000 0001 3467 9662
Awarding Body: University of Portsmouth
Current Institution: University of Portsmouth
Date of Award: 2008
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This study was the development of an assay, a blood test, to provide a more discriminatory way of identifying patients, whose treatment for schistosomiasis has failed. The. aim was to improve post-treatment follow-up of infection with either Schistosoma mansoni or Schistosoma haematobium. The objective was to use cationic egg fraction 6 (CEF6) antigen in an enzyme linked immunoabsorbent assay (ELISA) as the antibody capture antigen and compare it with the soluble egg antigen (SEA) ELISA and microscopy, the two most widely used standard diagnostic tests for this infection. Another objective was to use the results from this new assay and correlate Total IgG schistosome antibody levels with treatment outcomes. Blood from 63 patients whose clinical material was positive for schistosome eggs were tested to establish assay sensitivity, 79.4% and specificity, 98.2%. Patients with suitable clinical indicators and exposure history, but who were egg negative (n=132), were tested to show that the index assay could distinguish uninfected patients from infected ones. Multiple sera obtained over approximately 12 months or more, from individual patients who have been treated for infection were tested. With the results from the SEA and CEF6 assays a timeline of optical densities was used to assess treatment success and failure. Optical densities and therefore antibody levels on sera post-treatment were found to be significantly different to those at initial diagnosis. It is proposed that a negative sloping timeline correlates with treatment success, but, a positive sloping timeline indicates that the treatment has failed. Analysis by logistic regression was used to determine a probability of outcome for all patients in the study. The same mUltiple sera were tested for IgG subclasses in the CEF6 and SEA ELlSAs. With respect to the determination of treatment outcomes, results from each of these assays generally paralleled the results of the Total IgG assay and consequently added little helpful information.Possible confounders such as, age, gender and type of infecting species, are shown not to influence treatment outcomes. The conclusion was that the total CEF6 antibody timeline is a useful indicator of treatment success or failure when the patient was infected with S. mansoni. If infected with S. haematobium, the timeline shows that there is very little difference in the rate of decline of Total IgG CEF6 antibodies and the rate of decline in Total IgG SEA antibodies. When there was treatment failure, the positive sloping Total IgG CEF6 antibody timeline was only a more useful tool than the Total IgG SEA timeline when there was an infection with S. mansoni. The proportion of patients showing treatcnent failure (15.4%) was higher than has been reported in travellers. This was because in this study, the majority (68%) of the patients were egg negative. Also, it was found that the burden of infection, although crudely measured, does not affect tr~atment outcomes. Serological speciation was performed on the sera of egg negative patients so that confounding issues could be addressed. On the basis of serological speciation, and microscopy, the ratio (2.4:1) of S. haematobium to S. mansoni has shifted from previous reports for patients attending the study centre, the Hospital for Tropical Diseases. Again, this is probably as a consequence of there being many patients who are egg negative. This is the first investigation of its type, to include ,egg negative patients in a treatment outcome study.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available