Biomedical subjects

Francisca Mutapi

Publications and source records attributed to Francisca Mutapi.

6 recordsLinked to original sources

PubMed2006

Immuno-epidemiology of human Schistosoma haematobium infection: preferential IgG3 antibody responsiveness to a recombinant antigen dependent on age and parasite burden.

BACKGROUND: Schistosomiasis is a major parasitic disease affecting over 200 million people in the developing world with a further 400 million people at risk of infection. The aim of this study was to identify a single antigen from adult Schistosoma haematobium worms and subsequently use this antigen to study the development of schistosome-acquired immunity in a human population. METHODS: The full-length cDNA sequence of a S. haematobium protein, a putative orthologue of the S. mansoni tegumental antigen Sm13, was obtained from a cDNA library of adult S. haematobium worms and named Sh13 following a small-scale expressed sequence tags (EST) project. The recombinant Sh13 protein expressed in E. coli, was used to investigate immuno-epidemiological patterns in 147 Zimbabweans (7-18 years old) exposed to S. haematobium. RESULTS: Sequence analysis of the full-length cDNA sequence of the S. haematobium protein Sh13, indicated that the protein has an N-terminal signal peptide and encodes an 85-amino acid mature protein with a highly conserved predicted transmembrane domain (86 % identity with the S. mansoni tegumental antigen Sm13). The recombinant Sh13 protein was used in ELISA assays to determine the reactivity of sera from the study participants. Antibody responses against Sh13 were predominantly IgG3 isotype compared to responses against crude worm antigens which were predominantly IgG1 and IgG4. The relationship between anti-Sh13 IgG3 levels and infection intensity varied significantly with host age. The youngest children (7-10 years old) had relatively low levels of both infection and anti-Sh13 IgG3. In older children (11-12 years old) rising infection levels were accompanied by a significant increase in anti-Sh13 IgG3 levels. Subsequently, infection intensity declined significantly in 13-18 year olds but levels of the antibody continued to rise. The changing relationship between infection intensity and anti-Sh13 IgG3 levels with host age is consistent with the profile of a protective immune response predicted from theoretical work. CONCLUSION: We have identified and characterised a novel S. haematobium antigen Sh13, a putative tegumental protein, and shown that it is recognised predominantly by IgG3 antibodies from people infected with/exposed to S. haematobium parasites. We have also shown that, the anti-Sh13 IgG3 response is maximal in older individuals with the lowest infection intensity, and that the age profile of the relationship between anti-Sh13 IgG3 and infection intensity is consistent with that predicted by theoretical work for a protective response stimulated by and directed against adult worms.

Adolescent↗

PubMed2005

Praziquantel treatment of individuals exposed to Schistosoma haematobium enhances serological recognition of defined parasite antigens.

BACKGROUND: Schistosomiasis is a major parasitic disease affecting >200 million people in the developing world, and 400 million people are at risk for infection. This study aimed to identify and compare proteins recognized by serum samples from schistosome-exposed individuals before and after curative praziquantel treatment. METHODS: Proteins recognized by pooled serum samples from Schistosoma haematobium-exposed Zimbabweans were determined by 2-dimensional Western blotting and identified by mass spectrometry. RESULTS: Serum samples recognized 71 spots, which resolved to 26 different characterized proteins. Eleven of these proteins have not previously been shown to be immunogenic in natural human infection or in experimental models of schistosomiasis, making them novel antigens in the parasite. Pretreatment serum samples recognized 59 spots, which resolved to 21 different identified proteins. Posttreatment serum samples recognized an additional 12 spots, which resolved to 8 different identified proteins. Of these 8 proteins, 3 had putative isoforms recognized before treatment, and 5 (calreticulin, tropomyosin 1, tropomyosin 2, paramyosin, and triose phosphate isomerase) did not. CONCLUSIONS: This study is the most comprehensive characterization of S. haematobium antigens to date and describes novel antigens in all schistosome species. Posttreatment results are consistent with praziquantel treatment inducing quantitative and qualitative changes in schistosome-specific antibody responses.

Adolescent↗

PubMed2005

Cluster analysis of schistosome-specific antibody responses partitions the population into distinct epidemiological groups.

Immuno-epidemiological studies in schistosomiasis continue to generate large amounts of immunology data, whose analysis requires sophisticated statistical approaches. Here cluster analysis, is used to explore the relationship between immune responses and observed epidemiological patterns of schistosome infection in two Zimbabwean communities. Analysis of cross-sectional antibody data (IgA, IgE, IgG1, IgG2, IgG3, IgG4 and IgM directed against Schistosoma haematobium soluble egg antigen (SEA)) showed that cluster analysis partitioned the data into distinct epidemiological groups based on all seven antibody isotypes (defined by age, infection intensity, treatment status and history of infection) confirming an already known partitioning based on IgA/IgG1 production. All treated participants (children) changed cluster membership following treatment from clusters where IgA was the predominant antibody to clusters where IgG1 predominated. There was a differential distribution of IgE and IgG4 between clusters consistent with the recently proposed balance between T-helper cells (Th) 1, Th2 and regulatory T cells. The analysis suggested that naturally acquired anti-schistosome responses associated with resistance to infection were different from drug-induced responses associated with resistance to re-infection. Furthermore, the analysis suggested that parasite-specific immune responses were dynamic. The analysis conducted on data from participants resident in the S. mansoni endemic area who were all children partitioned the data into two clusters, one with predominately pre-treatment data (cluster 1) and the other with post-treatment data (cluster 2). The antibody profiles of both clusters were most similar to the profile of people with a modified Th2 response. Following treatment 43% of the children in cluster 1 moved to cluster 2, which generally had higher levels of antibodies. A detailed study of factors determining which children moved between the clusters showed that it was mostly the older, infected children who moved to cluster 2. The results of the analysis are discussed in terms of current theories of the development of acquired immunity to schistosomiasis. The relative merits of cluster analysis as a statistical tool for analysing these data are also discussed.

Age Factors↗

PubMed2003

Chemotherapy-induced, age-related changes in antischistosome antibody responses.

Humoral responses directed against Schistosoma mansoni soluble egg antigen were studied in Zimbabwean children before and after treatment with either praziquantel (PZQ) or oxamniquine (OXAM). Treated children showed a significant increase in the proportion producing IgE and IgG3 and in mean levels of IgE, IgM, IgG3 six weeks post-treatment. At 18 weeks post-treatment, the proportion of treated children producing IgA, IgE, and IgG3 increased while the proportion producing IgG1 and IgG4 decreased. Mean levels of IgA, IgE, and IgG3 were higher than pre-treatment levels while levels of IgG1, IgG4 and IgM were lower. Statistical analyses showed that the magnitude of change in levels of IgE, IgM and IgG3 at 6 weeks post-treatment and of IgE, IgG3 and IgG4 at 18 weeks post-treatment was significantly greater in treated compared to untreated children, and there were no significant differences in immune responses between children treated with praziquantel and those treated with oxamniquine. The magnitude of change in IgE at 6 and 18 weeks, IgM at 6 weeks and IgG3 at 18 weeks post-treatment were significantly associated with age in treated but not in untreated children, with the change being greater in younger children. This suggests that treatment induced a change in the age-antibody relationship for these isotypes, and that the age-antibody relationship is not robust to chemotherapy. Pre-treatment infection levels were significantly associated (positive correlation) with the magnitude of change for IgE and IgG3 at 18 weeks post-treatment. Taken together, these results indicate that the age-antibody relationship observed in these children is due, at least in part, to cumulative host experience of parasite antigens and not host age alone.

Adolescent↗

PubMed2002

p values for pathogens: statistical inference from infectious-disease data.

Certain features of infectious-disease data-including the aggregated nature of the data, confounding variables, correlated variables, and non-linear relations-complicate the use of standard statistical procedures. Using data on a helminth infection, we review the use of three parametric tests (analysis of variance, linear regression, and logistic regression), address the complications arising from violation of the assumptions for these tests, and suggest methods of correction. We also compare the relative merits of parametric methods with equivalent non-parametric approaches, and illustrate the differences produced with results from a Kruskal-Wallis test and a t test. The value of using a resampling method-bootstrapping-is also shown. Finally, we discuss problems arising from use of a study design that requires data on the same attribute to be collected from the same individual over a period of time, and present three methods for overcoming this complication, showing that, in the example used, the mixed effect model and generalised estimating equation give similar results.

Analysis of Variance↗

PubMed2002

The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium.

The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection.

Adolescent↗