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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 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 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.Item Nutritional anaemia and malaria in pre-school and school aged children(African Medicine Society and Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria, 2008) Anumudu, C.; Afolami, M.; Nwagwu, M.; Igwe, C.; Keshinro, O.Background: The most common cause of anemia is a deficiency of iron; but it may also be caused by deficiencies of folates, vitamin B12 and protein. Some anemias are not caused by nutritional factors, but by congenital factors and parasitic diseases such as malaria. This study attempted to estimate the prevalence of anemia among pre-school and school- aged children in two rural areas of Odogbolu Local government area, and to determine whether its cause was nutritional or could be attributed to malaria. Methods: A total of 177 children between the ages of 2 and 11 years were included in the study. Children were examined for malaria parasites by microscopy. The World Health Organization (WHO) age-adjusted cut-off for hemoglobin and hematocrit were used to classify anemia. An enzyme linked immunosorbent assay for serum ferritin was compared with standard methods of determining iron deficiency. Under- nutrition (stunting, wasting and underweight) was classified according to the National Centre for Health Statistics standards. Values below □ - 2SD were defined as mild-moderate under-nutrition, and those below □ -3SD as severe malnutrition. Results: Most of the children were anemic, 87.1%, having PCV values below the 32% cut-off and 95% with hemoglobin levels lower than the 11g/dl, although parasite prevalence and density were low. Malnutrition was patent; 36% of the children were stunted, 18.3% wasted and 44.2% underweight. Serum ferritin was more sensitive than PCV in detecting anemic children. Although anemia was higher in boys and preschoolers compared to girls and school aged children, the difference was significant only in preschoolers (P = .004). Anaemia was also significantly higher in Irawo village school than in Iloti (P = .0001) Conclusion: The anemia detected in this population may be due more to under-nutrition than to malaria.Item Specificities of antibodies to Plasmodium falciparum merozoite surface protein (MSP)-1 19(2002) Nwuba, R. I.; Adoro, S. A.; Anumudu, C. I.; Odaibo, A. B.; Omosun, Y.; Holder, A. A.; Nwagwu, M.In a survey of children living in South Western Nigeria, plasma levels of anti-MSP119 antibodies were not associated with patent parasitemia. Anti-MSP119 antibody titres correlated positively with age, indicating that development of antibodies to MSP119 may depend on long-term exposure to parasites. Using competitive ELISA, 82% of the samples inhibited the binding of processing-inhibitory monoclonal antibodies (mAb) 12.8 and 12.10 to immobilized recombinant MSP119. The binding of mAb 12.8 in the presence of 18% of these samples .was reduced to less than 10%. This suggest that these samples contain polyc1onal antibodies that have a similar binding specificity to that of mAb 12..S, which recognizes an epitope located in the first epidermal growth factor domain of MSP119. Our data provide useful leads for the design of an MSP119-based vaccine.Item Epidemiological factors that promote the development of severe malaria anaemia in children in Ibadan(Faculty of Medicine, Makerere University, 2007) Anumudu, C. I.; Okafor, C. M. F.; Ngwumohaike, V.; Afolabi, K. A.; Nwuba, R. I.; Nwagwu, M.Background: Effective control and management of severe malaria cases depends on a clear understanding of the local epidemiological factors and specific clinical manifestations of the disease in the different endemic regions. Objectives: To determine the prevalence of severe malaria and epidemiological factors that affect the development of malaria anaemia. Methods: A cross-sectional survey was carried out among children below 5 years of age, at the Adeoyo State Maternity Hospital, Ibadan, Nigeria. Questionnaires and case histories were taken from patients clinically diagnosed of malaria. Thus, 372 volunteers were recruited into the study from the 3131 paediatric cases that reported over the10-week period to the out-patient department (OPD) of the hospital. 229 (61.6%) of the recruited volunteers presented with fever (>37.5 oC) at consultation. These had malaria parasite and PCV tests done. Results: Clinical diagnosis was confirmed microscopically in 78% (290/372) for Plasmodium infection using thick film slides. Anaemia (PCV <28%) prevalence was 28.2%. Factors that contributed to the rapid progression of uncomplicated malaria to severe status included: age of the child, level of parasitaemia, careless response and attitude of parents or guardians to fever in the children; parents’ preoccupation with their jobs or other healthy children and unwillingness to use available health facilities. Conclusion: The study underscores the need for community involved partnership for malaria control especially through health education for the home management of malaria, especially among those experiencing some form of inequity in access to healthcare.Item Seasonal variations in antibody response to a Plasmodium falciparum recombinant circumsporozoite antigen in two villages in South Western Nigeria(Ibadan Biomedical Communications Group, 2006) Ozurumba, L. N.; Anumudu, C. I.; Nwagwu, M.An Enzyme Linked Immunosorbent Assay (ELISA), employing a recombinant peptide capture antigen (R32tet32) was used to detect antibodies against the circumsporozoite protein (CSP) of the malaria parasite, Plasmodium falciparum in 169 serum samples from 16 subjects from two villages, Afefu (FA) and Tobalogbo (TB), in Igbo-Ora Community of Oyo State, over a period of 12 months. The maximum and mean Ab response for FA was higher than for TB samples (0.511 AU±0.170, 0.124±0.045U and 0.250±0.070 AU, 0.090±0.019AU respectively), with the mean Ab being significantly different (t=2.313; P>0.05). Despite both villages (FA and TB) falling within the same rainfall data zone, the Ab response profile for FA showed a positive (seasonal) relationship with rainfall (r=+0.31, P>0.05) while that of TB was negatively correlated (r=-0.32; P>0.05). Habits and the environment could be prime contributing factors alongside the less controllable immunogenetic factors. Data obtained here would serve as baseline and we suggest other expanded sample size studies to include data on temperature and other climatic factors to help establish sub-populations at risk and better empower malariologists in planning and execution of control programmes.Item Variation in the relationship between anti-MSP-119 antibody response and age in children infected with Plasmodium falciparum during the dry and rainy seasons(Elsevier, 2005) Omosun, Y. O.; Anumudu, C. I.; Adoro, S.; Odaibo, A. B.; Sodeinde, O.; Holder, A. A.; Nwagwu, M.; Nwuba, R. I.Malaria remains a major parasitic disease in Africa, with 300–500 million new infections each year. There is therefore an urgent need for the development of new effective measures, including vaccines. Plasmodium falciparum merozoite surface protein-119 (MSP-119) is a prime candidate for a blood-stage malaria vaccine. Blood samples were collected from children aged 10 days to 15 years in the months of January–March (N=351) and October–November (N=369) corresponding to the dry and rainy seasons, respectively. P. falciparum infection was determined by microscopy and enzyme linked immunosorbent assay (ELISA) was used to determine the total IgG and IgG subclasses. There was a significant increase in the mean anti-MSP-119 antibody titre in the dry season (p < 0.05), compared to the rainy season. A significantly positive correlation between the anti-MSP-119 antibody titre and parasite density (p < 0.01, r = 0.138) was observed. In the rainy season, unlike in the dry season, P. falciparum positive children had higher anti-MSP-119 antibody titres than P. falciparum negative children and this difference was significant (p < 0.05). When all individuals were grouped together, the anti-MSP-119 antibody titre increased with age in both seasons (r = 0.186 and 0.002), this increase was more apparent in the dry season. However, when the study population was divided into P. falciparum positive and negative groups, it was observed that in the rainy season, there was a negative correlation between anti-MSP-119 titre and age in P. falciparum positive individuals, while those who were P. falciparum negative had a positive correlation between anti-MSP-119 titre and age. Analysis of anti-MSP-119 IgG subclass showed that IgG1 and IgG3 mean titres were highest in both the dry and rainy seasons with an increase in the mean antibody titres for IgG1, IgG2 and IgG3 in the rainy season. In the dry season there was a positive correlation between IgG1, IgG2, and IgG3 titres with age, while IgG4 was negative, whereas in the rainy season there was a positive correlation between IgG2 and IgG4 (non-cytophilic antibodies) with age and a negative correlation for IgG1 and IgG3 (cytophilic antibodies) with age. Seasonal differences in the level of MSP-119 IgG subclass titres were observed for P. falciparum negative and positive individuals. Only samples, which were positive for IgG2 and IgG4, showed positive correlation between parasitemia and total IgG. The incidence of P. falciparum infection, which increases during the rainy season, might be an important determinant of anti-MSP-119 antibody levels in children living in Igbo-Ora and the results point to the fact that non-cytophilic antibodies to MSP-119 in children might be associated with an increase in total IgG and parasitemia.