This file contains supporting metadata for a study of human parvovirus 4 ('PARV4') in sou... more This file contains supporting metadata for a study of human parvovirus 4 ('PARV4') in southern Africa. We compiled data from three centres (Kimberley and Durban in South Africa, and Gaborone in Botswana), by recruiting adults and children with and without HIV infection (n=695). We sought evidence of previous or current PARV4 infection, using IgG and PCR respectively, and screened for coinfection with HBV and HCV. <br>Ethics approval for this study was granted by the University of KwaZulu-Natal Review Board, Oxford Research Ethics Committee, Massachusetts General Hospital Review Board, Harvard School of Public Health, Botswana Ministry of Health, Ethics Committee of the University of the Free State, and by site-specific research and development committees in the UK.
Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women i... more Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women in Botswana compared with norms for U.S.-born black infants
We examined associations between B and T cell phenotypic profiles and antibody responses to the p... more We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequen...
Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In su... more Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In sub-Saharan Africa, seroprevalence is high in the general population, but little is known about the transmission routes or the prevalence of coinfection with blood-borne viruses, HBV, HCV and HIV. Methods: To further explore the characteristics of PARV4 in this setting, with a particular focus on the prevalence and significance of coinfection, we screened a cohort of 695 individuals recruited from Durban and Kimberley (South Africa) and Gaborone (Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status. Results: Within these cohorts, 69% of subjects were HIV-positive. We identified no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive in 42%; seroprevalence was higher in adults (69%) compared to children (21%) (p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%) (p<0.0001), but there was no association wit...
Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live... more Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the World Health Organization recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants. We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in 4 African countries. Ninety-three % of HIV+ infants were receiving antiretroviral therapy prior to vaccination. Participants were followed for safety. Immune responses were measured 14 days after three doses of RV5, including serum anti-rotavirus neutralizing and IgA antibodies; IgA antibody in stool; and anti-rotavirus memory B- and T-cell Fluorospot. Shedding of RV5 in stool was monitored. 76 HIV+ and 126 HEU infants were enrolled from 2009-2013. No significant differences were found in adverse event rates, including grade 3 events, between RV5 and placebo recipients, for either HIV+ or HEU infants. The proportion of anti-rotavirus IgA responders (≥3-fold increase from baseline) after RV5 administration was 81% in both HIV+ and HEU infants, which was approximately 2.5-fold higher than in placebo recipients (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Neutralizing antibody responses to 3 of 5 serotypes were significantly higher after RV5 regardless of HIV status, and those of HIV+ infants were equal or greater than responses of HEU infants to all 5 serotypes. Only one HIV+ RV5 recipient had RV5 isolated from stool. RV5 was immunogenic in both HIV+ and HEU infants and no safety signals were observed.
The present work has demonstrated the ability of fine grained alumina containing small additions ... more The present work has demonstrated the ability of fine grained alumina containing small additions of copper oxide or nickel oxide to undergo superplastic tensile flow. The effect of small levels of porosity on superplastic behaviour has been examined using specimens subjected to HIP. This provides an effective way of controlling the density of ceramic materials while avoiding appreciable grain growth. Results showed that low density specimens tended to have higher superplastic elongations to failure than higher density specimens. In the latter case, long cracks developed during deformation and grew perpendicular to the tensile axis; this led to premature failure. The uniformly distributed pores in the lower density specimens provided sites for both crack initiation and crack arrest, leading to a large number of short cracks, and to higher failure strains. TEM observations gave evidence of significant dislocation activity in grain boundary regions of the deformed materials and this is tentatively interpreted in terms of the electronic contributions of the dopants to dislocation mobility.
Recent developments in the understanding of the mechanical behavior of ceramics assessed for supe... more Recent developments in the understanding of the mechanical behavior of ceramics assessed for superplastic deformation indicate that stoichiometric changes at interfaces and an associated “metallic” behaviour can account for the superplastic behaviour in the absence of a grain boundary glassy phase. Based on the experimental work carried out in Manchester and elsewhere, a “superplastic partition” is observed in ceramics which corresponds to a direct relationship with stoichiometric changes and a related “metallic” behaviour in ceramics. These changes in stoichiometry and the associated “metallic” behaviour can provide mechanisms for resistance to cavity nucleation and propagation, respectively. When this observation is linked with the Gifkins core-mantle concept and the findings of Mott, Cottrell and Gilman on insulator-metal transitions, this yields an improved appreciation of the superplastic partition in ceramics.
Tropical medicine & international health : TM & IH, Jan 25, 2016
Infants born to HIV-infected women receiving antiretroviral treatment (ART) can breastfeed throug... more Infants born to HIV-infected women receiving antiretroviral treatment (ART) can breastfeed through at least 6 months with very low risk of HIV acquisition. We aimed to identify demographic and cultural factors that may influence mothers' willingness to breastfeed for the recommended duration. We evaluated factors associated with early cessation of breastfeeding (i.e before 5 months post-partum) in a randomized clinical trial evaluating different ART regimens used for prevention of mother to child transmission during breastfeeding in Botswana. Univariate and multivariable Cox regression were used to describe predictors of early exclusive BF cessation. Among 677 women who started breastfeeding, the median time to breastfeeding cessation was 178 days (IQR 150-181) and 25.1% weaned early. In multivariable analysis, urban location (aHR=1.86 95%CI 1.27-2.73; p=0.002) salaried employment or being a student (aHR=2.78 95% CI 1.63-4.75); p<0.001), and infant hospitalization before wean...
Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity r... more Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of HIV coinfection. The factors driving different outcomes are not well understood, but there is increasing interest in an HLA Class I effect. We therefore studied the influence of HLA class I on HBV in an African HIV-positive cohort. We demonstrated that virologic markers of HBV disease activity (HBeAg status / HBV DNA level) are associated with HLA-A genotype. This finding supports the role of the CD8+ T cell response in HBV control, and potentially informs future therapeutic T cell vaccine strategies.
This file contains supporting metadata for a study of human parvovirus 4 ('PARV4') in sou... more This file contains supporting metadata for a study of human parvovirus 4 ('PARV4') in southern Africa. We compiled data from three centres (Kimberley and Durban in South Africa, and Gaborone in Botswana), by recruiting adults and children with and without HIV infection (n=695). We sought evidence of previous or current PARV4 infection, using IgG and PCR respectively, and screened for coinfection with HBV and HCV. <br>Ethics approval for this study was granted by the University of KwaZulu-Natal Review Board, Oxford Research Ethics Committee, Massachusetts General Hospital Review Board, Harvard School of Public Health, Botswana Ministry of Health, Ethics Committee of the University of the Free State, and by site-specific research and development committees in the UK.
Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women i... more Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women in Botswana compared with norms for U.S.-born black infants
We examined associations between B and T cell phenotypic profiles and antibody responses to the p... more We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequen...
Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In su... more Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In sub-Saharan Africa, seroprevalence is high in the general population, but little is known about the transmission routes or the prevalence of coinfection with blood-borne viruses, HBV, HCV and HIV. Methods: To further explore the characteristics of PARV4 in this setting, with a particular focus on the prevalence and significance of coinfection, we screened a cohort of 695 individuals recruited from Durban and Kimberley (South Africa) and Gaborone (Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status. Results: Within these cohorts, 69% of subjects were HIV-positive. We identified no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive in 42%; seroprevalence was higher in adults (69%) compared to children (21%) (p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%) (p<0.0001), but there was no association wit...
Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live... more Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the World Health Organization recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants. We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in 4 African countries. Ninety-three % of HIV+ infants were receiving antiretroviral therapy prior to vaccination. Participants were followed for safety. Immune responses were measured 14 days after three doses of RV5, including serum anti-rotavirus neutralizing and IgA antibodies; IgA antibody in stool; and anti-rotavirus memory B- and T-cell Fluorospot. Shedding of RV5 in stool was monitored. 76 HIV+ and 126 HEU infants were enrolled from 2009-2013. No significant differences were found in adverse event rates, including grade 3 events, between RV5 and placebo recipients, for either HIV+ or HEU infants. The proportion of anti-rotavirus IgA responders (≥3-fold increase from baseline) after RV5 administration was 81% in both HIV+ and HEU infants, which was approximately 2.5-fold higher than in placebo recipients (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Neutralizing antibody responses to 3 of 5 serotypes were significantly higher after RV5 regardless of HIV status, and those of HIV+ infants were equal or greater than responses of HEU infants to all 5 serotypes. Only one HIV+ RV5 recipient had RV5 isolated from stool. RV5 was immunogenic in both HIV+ and HEU infants and no safety signals were observed.
The present work has demonstrated the ability of fine grained alumina containing small additions ... more The present work has demonstrated the ability of fine grained alumina containing small additions of copper oxide or nickel oxide to undergo superplastic tensile flow. The effect of small levels of porosity on superplastic behaviour has been examined using specimens subjected to HIP. This provides an effective way of controlling the density of ceramic materials while avoiding appreciable grain growth. Results showed that low density specimens tended to have higher superplastic elongations to failure than higher density specimens. In the latter case, long cracks developed during deformation and grew perpendicular to the tensile axis; this led to premature failure. The uniformly distributed pores in the lower density specimens provided sites for both crack initiation and crack arrest, leading to a large number of short cracks, and to higher failure strains. TEM observations gave evidence of significant dislocation activity in grain boundary regions of the deformed materials and this is tentatively interpreted in terms of the electronic contributions of the dopants to dislocation mobility.
Recent developments in the understanding of the mechanical behavior of ceramics assessed for supe... more Recent developments in the understanding of the mechanical behavior of ceramics assessed for superplastic deformation indicate that stoichiometric changes at interfaces and an associated “metallic” behaviour can account for the superplastic behaviour in the absence of a grain boundary glassy phase. Based on the experimental work carried out in Manchester and elsewhere, a “superplastic partition” is observed in ceramics which corresponds to a direct relationship with stoichiometric changes and a related “metallic” behaviour in ceramics. These changes in stoichiometry and the associated “metallic” behaviour can provide mechanisms for resistance to cavity nucleation and propagation, respectively. When this observation is linked with the Gifkins core-mantle concept and the findings of Mott, Cottrell and Gilman on insulator-metal transitions, this yields an improved appreciation of the superplastic partition in ceramics.
Tropical medicine & international health : TM & IH, Jan 25, 2016
Infants born to HIV-infected women receiving antiretroviral treatment (ART) can breastfeed throug... more Infants born to HIV-infected women receiving antiretroviral treatment (ART) can breastfeed through at least 6 months with very low risk of HIV acquisition. We aimed to identify demographic and cultural factors that may influence mothers' willingness to breastfeed for the recommended duration. We evaluated factors associated with early cessation of breastfeeding (i.e before 5 months post-partum) in a randomized clinical trial evaluating different ART regimens used for prevention of mother to child transmission during breastfeeding in Botswana. Univariate and multivariable Cox regression were used to describe predictors of early exclusive BF cessation. Among 677 women who started breastfeeding, the median time to breastfeeding cessation was 178 days (IQR 150-181) and 25.1% weaned early. In multivariable analysis, urban location (aHR=1.86 95%CI 1.27-2.73; p=0.002) salaried employment or being a student (aHR=2.78 95% CI 1.63-4.75); p<0.001), and infant hospitalization before wean...
Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity r... more Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of HIV coinfection. The factors driving different outcomes are not well understood, but there is increasing interest in an HLA Class I effect. We therefore studied the influence of HLA class I on HBV in an African HIV-positive cohort. We demonstrated that virologic markers of HBV disease activity (HBeAg status / HBV DNA level) are associated with HLA-A genotype. This finding supports the role of the CD8+ T cell response in HBV control, and potentially informs future therapeutic T cell vaccine strategies.
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