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Item Antibody specificities of children living in a malaria endemic area to inhibitory and blocking epitopes on MSP-119 of Plasmodium falciparum(Elsevier, 2009) Omosun, Y. O.; Adoro, S.; Anumudu, C. I.; Odaibo, A. B.; Uthiapibull, C.; Holder, A. A.; Nwagwu, M.; Nwuba, R. I.Merozoite surface protein-119 (MSP-119) specific antibodies which include processing inhibitory, blocking and neutral antibodies have been identified in individuals exposed to Plasmodium falciparum. Here we intend to look at the effect of single and multiple amino acid substitutions of MSP-119 on the recognition by polyclonal antibodies from children living in Igbo-Ora, Nigeria. This would provide us with information on the possibility of eliciting mainly processing inhibitory antibodies with a recombinant MSP-119 vaccine. Blood was collected from children in the rainy season and binding of anti-MSP-119 antibodies to modified mutants of MSP-119 was analysed by ELISA. The MSP-119 mutant proteins with single substitutions at positions 22 (Leu→Arg), 43 (Glu→Leu) and 53 (Asn→Arg) and the MSP-119 mutant protein with multiple substitutions at positions 27 + 31 + 34 + 43 (Glu→Tyr, Leu→Arg, Tyr→Ser, Glu→Leu); which had inhibitory epitopes; had the highest recognition. Children recognised both sets of mutants with different age groups having different recognition levels. The percentage of malaria positive individuals (32–80%) with antibodies that bound to the mutants MSP-119 containing epitopes that recognise only processing inhibitory and not blocking antibodies, were significantly different from those with antibodies that did not bind to these mutants (21–28%). The amino acid substitutions that abolished the binding of blocking antibodies without affecting the binding of inhibitory antibodies are of particular interest in the design of MSP-119 based malaria vaccines. Although these MSP-119 mutants have not been found in natural population, their recognition by polyclonal antibodies from humans naturally infected with malaria is very promising for the future use of MSP-119 mutants in the design of a malaria vaccine.Item Prevalence of HIV and Malaria parasites co-infection in pregnant mothers and their babies post delivery(International Institute for Science, Technology and Education, 2013) Adeoti, O. M.; Anumudu, C. I.; Nwuba, R. I.; Awobode, H. I.; Olaniyan, M. F.; Olayiwola, O.; Fagbade, O.Worsened perinatal outcomes and increased rates of maternal morbidity are consequences of co-infection of HIV and Plasmodium falciparum in pregnant-women. This study was designed to ascertain the proportion of co-infection of both diseases in pregnant mothers and babies born to HIV-infected mothers. A total of 149 pregnant mothers and 30 babies of HIV-infected mothers were engaged in a longitudinal study for 18 months in the endemic area of Saki and Ibadan. Only babies born to HIV infected mothers were enrolled and systematically followed-up for six months post delivery. Determine and Unigold rapid diagnostic tests kits were used for HIV test in mothers whereas HIV screening was conducted on the babies using polymerase chain reaction at six months post delivery. Giemsa stained thick blood smear was used to determine the presence of asexual stages of Plasmodium falciparum. Descriptive statistics was used to determine the percentage of infections status. Chi-square and student t-test was used to compare maternal data and babies six months after birth. The results showed that 85/149(57.0%) mothers and 11/30(36.7%) babies, had microscopically detectable malaria parasites whereas the seroprevalence were 64(33.0%) and 19(10.7%) for mothers and infants respectively. In mothers, 19(12.8%) had HIV alone, 51/149(34.2%) malaria only, 34/149 (22.8%) were co-Infected and 45/149(30.2%) had neither HIV nor malaria. In infants, 9/30 (30.0%), 10/30(33.3) had HIV only, 2/30(6.7%) had malaria only whereas 9/30(30.0%) had neither malaria nor HIV. Parasitemia ranged between 251.5 of cells/μL, in mothers and 205.7 of cells/μL, in babies born to HIV infected mothers.Item IgG Enzyme-linked Immunosorbent Assay (ELISA) for immunodiagnosis of Schistosoma haematobium infected subjects living in an endemic Nigerian village(Academic Journals, 2011-04) Oniya, M. O.; Omosun, Y. O.; Anumudu, C. I.; Nwuba, R. I.; Odaibo, A. B.Schistosoma haematobium infects school children in areas where the disease is endemic. This study was carried out to determine the reliability of IgG Enzyme-Linked Immunosorbent Assay (ELISA) as an immunodiagnostic tool, using whole antigen derived from Schistosoma eggs. Children of school going age living in Ipogun village, in south western Nigeria; a schistosomiasis endemic community; were used in this study. The sensitivity of the IgG ELISA in detecting positive cases was 68.0% and there was a significant correlation (P < 0.05) between IgG titres and the intensity of infection. However, the specificity was 59.3%, slightly lower than the sensitivity. Results from this study shows that IgG ELISA can be used as a diagnostic tool for determining S. haematobium infection, as it provides an evidence for the intensity of the infection in the infected individuals.Item Fine specificity of anti MSP 119 antibodies an multiplicity of Plasmodium falciparum merozoite protein 1 types in individuals in Nigeria with submicroscopic infection(Springer, 2010) Ngoundou-Landji, J.; Nwuba, R. I.; Anumudu, C. I.; Odaibo, A. B.; Matando Mayo, W. D.; Awobode, H. O.; Okafor, C. M.; Morenikeji, O. A.; Asinobi, A.; Nwagwu, M.; Holder, A. A.; Ntoumi, F.Background: The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study. Methods: Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured. Results: Plasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04). Conclusions: In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.Item Total immunoglobulin G and IgG1 subclass levels specific for the MSP-119 of Plasmodium falciparum are different in individuals with either processing-inhibitory, blocking or neutral antibodies(Faculty of Medicine, Makerere University, 2010) Omosun, Y. O.; Adoro, S.; Anumudu, C. I.; Odaibo, A.; Holder, A. A.; Nwagwu, M.; Nwuba, R. I.Background: Some MSP-119 specific antibodies that inhibit merozoite invasion also inhibit the secondary processing of MSP-1. However the binding of these inhibitory antibodies can be blocked by another group of antibodies, called blocking antibodies, which recognize adjacent or overlapping epitopes, but themselves have no effect on either MSP-1 processing or merozoite invasion. These antibodies have been reported to be present in individuals living in a malaria endemic area. Methods: Blood samples were obtained from children shown to have processing inhibitory, blocking, and neutral antibodies in a previous study. Enzyme linked immunosorbent assay (ELISA), was used to determine the total IgG, IgM and IgG subtypes. Results: There was a significant difference in anti-MSP-119 IgG, while there was no significant difference in the anti-MSP-119 IgM. Only anti MSP-119 IgG1, amongst the IgG subtypes was significantly different between the groups. Conclusion: This study shows that antibodies against MSP-1 are different not only in specificity and function but also in the amount of total IgG and IgG subtype produced.Item Cellular responses to modified Plasmodium falciparum MSP 119 antigens in individuals previously exposed to natural malaria infection(Springer, 2009) Okafor, C. M. F.; Anumudu, C. I.; Omosun, Y. O.; Uthaipibull, C.; Ayede, I.; Awobode, H. O.; Odaibo, A. B.; Langhorne, J.; Holder, A. A.; Nwuba, R. I.; Troye-Blomberg, M.Background: MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP119), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP119 had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP119 would affect critical T-cell responses to epitopes in this antigen. Methods: The cellular responses to wild-type MSP119 and a panel of modified MSP119 antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results: Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP119. A protein with four amino acid substitutions (Glu27→Tyr, Leu31→Arg, Tyr34→Ser and Glu43→Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins.Item Optimization of the T-cell proliferation assay in fascioliasis using a non-radioactive method, the Alamar Blue Assay(2009) Anumudu, C. I.; Molehin, A. J.; Nwuba, R. I.T-cell proliferation studies are traditionally carried out with radioactive reagents or fluorescent reagents that require measurement with advanced technology instrumentation. We attempted to calibrate the optimal conditions suitable for the use of a non-radioactive assay for the measurement of a T-cell proliferation assay in bovine fascioliasis, but applicable to the study of other infectious diseases in our developing 'country setting, Crude antigen extract was prepared from 15 adult Fasciola gigantica flukes: Cellular responses were detected by the proliferatjon of peripheral blood mononuclear cells (PBMC) in response to stimulation by serial dilutions of the crude antigen extract. The results showed that the antigen dilution 1:1,600 gave the highest PBMC proliferative response (Stimulation Index, S.I = 1.10± 0:2). Percentage reduced Alamar Blue was 27.3-71.6%. This suggests that the cell-mediated immune response in bovine immunity to Fasciola infection may be reliably measured in our setting with the Alamar Blue Assay.Item Cytokine profiles and antibody responses to Plasmodium falciparum malaria infection in individuals living in Ibadan, southwest Nigeria(Faculty of Medicine, Makerere University, 2009) Iriemenam, N. C.; Okafor, C. M.; Balogun, H. A.; Ayede, I.; Omosun, Y.; Persson, J. O.; Hagstedt, M.; Anumudu, C. I.; Nwuba, R. I.; Troye-Blomberg, M.; Berzins, K.Background: The ability of the host immune system to efficiently clear Plasmodium falciparum parasites during a malaria infection depends on the type of immune response mounted by the host. Study design: In a cross-sectional study, we investigated the cellular-and antibody responses in individuals with P. falciparum infection, in an attempt to identify immunological signs indicative of the development of natural immunity against malaria in Ibadan, Nigeria. Levels of IL-10, IL-12(p70), IFN-γ, and IgM, IgG and IgG1-4 subclasses in the serum of 36 symptomatic children with microscopically confirmed malaria parasitaemia and 54 asymptomatic controls were analysed by ELISA. Results: IFN-γ and IL-10 were significantly higher in the symptomatic children (p=0.009, p=0.025 respectively) than in the asymptomatic controls but no differences were seen for IL-12(p70). Estimated higher ratios of IFN-γ/IL-10 and IFN-γ/IL-12 were also observed in the symptomatic children while the asymptomatic controls had higher IL-12/IL-10 ratio. The mean concentration levels of anti-P. falciparum IgG1, IgG2, IgG3 antibodies were statistically significantly higher in the individuals >5 years of age than <5 years while anti-P. falciparum IgG3 antibodies were notably low in <5 years category. Children <5 years had higher IgM antibodies than IgG and the expression of IgG subclasses increased with age. Conclusion: Taken together, malaria infection is on a delicate balance of pro- and anti-inflammatory cytokines. The higher levels of IFN-γ seen in the symptomatic children (<6months) may be instrumental in immune-protection against malaria by limiting parasite replication. The observed variations in immunoglobulin subclass levels were age-dependent and exposure-relatedItem Antibody specificities of children living in a malaria endemic area to inhibitory and blocking epitopes on MSP-119 of Plasmodium falciparum(Elsevier, 2009) Omosun, Y. O.; Adoro, S.; Anumudu, C. I.; Odaibo, A. B.; Uthiapibull, C.; Holder, A. A.; Nwagwu, M.; Nwuba, R. I.Merozoite surface protein-119 (MSP-119) specific antibodies which include processing inhibitory, blocking and neutral antibodies have been identified in individuals exposed to Plasmodium falciparum. Here we intend to look at the effect of single and multiple amino acid substitutions of MSP-119 on the recognition by polyclonal antibodies from children living in Igbo-Ora, Nigeria. This would provide us with information on the possibility of eliciting mainly processing inhibitory antibodies with a recombinant MSP-119 vaccine. Blood was collected from children in the rainy season and binding of anti-MSP-119 antibodies to modified mutants of MSP-119 was analysed by ELISA. The MSP-119 mutant proteins with single substitutions at positions 22 (Leu→Arg), 43 (Glu→Leu) and 53 (Asn→Arg) and the MSP-119 mutant protein with multiple substitutions at positions 27 + 31 + 34 + 43 (Glu→Tyr, Leu→Arg, Tyr→Ser, Glu→Leu); which had inhibitory epitopes; had the highest recognition. Children recognised both sets of mutants with different age groups having different recognition levels. The percentage of malaria positive individuals (32–80%) with antibodies that bound to the mutants MSP-119 containing epitopes that recognise only processing inhibitory and not blocking antibodies, were significantly different from those with antibodies that did not bind to these mutants (21–28%). The amino acid substitutions that abolished the binding of blocking antibodies without affecting the binding of inhibitory antibodies are of particular interest in the design of MSP-119 based malaria vaccines. Although these MSP-119 mutants have not been found in natural population, their recognition by polyclonal antibodies from humans naturally infected with malaria is very promising for the future use of MSP-119 mutants in the design of a malaria vaccine.Item Epidemiology of malaria in children living at Igbo-Ora, South Western Nigeria(Faculty of Science Obafemi Awolowo University, Ile-Ife, Nigeria, 2008) Nwuba, R. I.; Omosun, Y. O.; Anumudu, C. I.; Adoro, S.; Odaibo, A. B.; Nwagwu, M.Malaria transmission is seasonal with higher transmission occurring in the rainy season. The burden of malaria falls mainly on children and causes anaemia and fever. Children of school going age are affected and this leads to absence from school. Blood samples were collected from children aged 10 days to 15 years in dry and rainy seasons. Parasite densities were determined by microscopy. Malaria prevalence was higher in the rainy season than in the dry season. In the dry season, 42.4% of the children studied were positive for P. falciparum. While at the end of the rainy season 48.4% of the children were malaria positive. The parasite prevalence was not significantly different between males and females. Parasite densities varied from 18 to 52174 parasites per 111 of blood. The most abundant group ranged from 1-100 (59%). There was a significant correlation between parasite density and age with the mean parasite density decreasing with age group. The study shows that malaria is more prevalent in the rainy season, and children in rural areas have high prevalence of asymptomatic parasitemia which might lead to symptomatic malaria. The results show that malaria immunity increases with age in both seasons.