Estimating risk determinants of HIV and TB in South Africa.

Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2009Where HIV/AIDS has had its greatest adverse impact is on TB. People with TB that are infected with HIV are at increased risk of dying from TB than HIV. TB is the leading cause of death in HIV individuals in South Africa. HIV is the driving factor that increases the risk of progression from latent TB to active TB. In South Africa no coherent analysis of the risk determinants of HIV and TB has been done at the national level this study seeks to mend that gab. This study is about estimating risk determinants of HIV and TB. This will be done using the national household survey conducted by Human Sciences Research Council in 2005. Since individuals from the same household and enumerator area more likely to be more alike in terms of risk of disease or correlated among each other, the GEEs will be used to correct for this potential intraclass correlation. Disease occurrence and distribution is highly heterogeneous at the population, household and the individual level. In recognition of this fact we propose to model this heterogeneity at community level through GLMMs and Bayesian hierarchical modelling approaches with enumerator area indicating the community e ect. The results showed that HIV is driven by sex, age, race, education, health and condom use at sexual debut. Factors associated with TB are HIV status, sex, education, income and health. Factors that are common to both diseases are sex, education and health. The results showed that ignoring the intraclass correlation can results to biased estimates. Inference drawn from GLMMs and Bayesian approach provides some degree of con dence in the results. The positive correlation found at an enumerator area level for both HIV and TB indicates that interventions should be aimed at an area level rather than at the individual level

Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine : results from a randomized, controlled, observer-blind study in adolescents and young adult

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.GlaxoSmithKline Biologicals SAhttps://www.tandfonline.com/journals/KHVIMedical Microbiolog

Determinants of knowledge of HIV status in South Africa: results from a population-based HIV survey

Abstract Background Over 30% of women and men in the South African national HIV household of 2005 indicated that they had previously been tested for HIV (of which 91% were aware of their test results). This paper seeks to describe the associations between socio-demographic, behavioural and social characteristics and knowledge of HIV status among a nationally representative population in South Africa. Methods A multistage probability sample involving 16395 male and female respondents, aged 15 years or older was selected. The sample was representative of the South African population by age, race, province and type of living area, e.g. urban formal, urban informal, etc. Respondents were interviewed on HIV knowledge, perceptions and behaviour and provided blood for research HIV testing. Bivariate and multivariate logistic regression was used to identify socio-demographic, social and behavioural factors associated with knowledge of HIV status. Results From the total sample 27.6% ever and 7.8% knew their HIV status in the past 12 months. In multivariate analyses being female, the age group 25 to 34 years old, other than African Black population group (White, Coloured, Asian), higher educational level, being employed, urban residence, awareness of a place nearby where one could be tested for HIV, impact of HIV on the household and having had two of more sexual partners in the past year were associated with knowledge of HIV status. Among HIV positive persons awareness of a place nearby where one could be tested for HIV and impact of HIV on the household were associated knowledge of HIV status, and among HIV negative persons HIV risk behaviour (multiple partners, no condom use), awareness of a place nearby where one could be tested for HIV, higher knowledge score on HIV and knowledge of serodiscordance were associated knowledge of HIV status. Conclusion Education about HIV/AIDS and access to HIV counselling and testing (HCT) in rural areas, in particular among the Black African population group needs to be improved, in order to enhance the uptake of HIV counselling and testing services, an essential step for the initiation of treatment.</p

Age lors du rapport sexuel initial : un déterminant des partenaires multiples chez la jeunesse de l&apos;Afrique du sud.

Age at sexual debut is an important determinant of HIV infection. The paper investigates the effects of age at sexual debut on sexual behaviour among South African youth. Among 2 875 respondents who ever had sexual intercourse, 39% had early sexual debut (sexual debut at age 16 years and below). Males (44.6%) were significantly more likely than females (35.1%) to report early sexual debut (odds ratio (OR)=1.45, p-value <0.001). Multiple sexual partners are significantly more common among those that had early sexual debut (10.4% vs. 4.8%) than those who had late sexual debut, (OR=2.29, p-value<0.001). Those aged 15 to 19 years were 1.4 times more likely to report multiple partners compared to those aged 20 to 24 years. Delaying sexual debut is a strategy many national programmes are promoting. The results of this study provide additional arguments to support such initiatives and show the need to strengthen intervention targeting youth.L&apos;âge lors du rapport sexuel initial est un déterminant de l&apos;infection du VIH. L&apos;article étudie les effets de l&apos;âge lors du rapport sexuel initial sur le comportement sexuel chez la jeunesse de l&apos;Afrique de sud. Parmi les 2875 répondants qui n&apos;ont jamais eu des rapports sexuels, 39% ont eu des rapports sexuels initiaux précoces (rapport sexuel initial à l&apos;âge de 16 ans ou au – dessous). Les mâles (44,6%) avaient beaucoup plus de possibilité que les femelles (35,1%) de signaler le rapport sexuel initial précoce (l&apos;indice de cote (IC) = 1,45, valeur – p < 0,001). Les partenaires sexuels multiples sont considérablement plus communs chez ceux qui ont eu des rapports sexuels initiaux précoces (10,4% contre 4,8%) que ceux qui ont eu des rapports sexuels tardifs (IC = 2,29, valeur – p < 0,001). Ceux qui ont 15 ans jusqu&apos;à 19 ans avaient 1,4 fois la possibilité de signaler d&apos;avoir des partenaires multiples par rapport à ceux qui ont entre 20 et 24 ans. Le rapport sexuel initial tardif est une stratégie que beaucoup de programmes nationaux encouragent. Les résultats de cette étude fournissent davantage des arguments qui soutiennent telles initiatives et montrent la nécessité de renforcer l&apos;intervention qui vise la jeunesse

Statistical Process Control Methods for Monitoring In-House Reference Standards

For certain types of medicine the biological strength or bioactivity of a drug is the main characteristic for release of products to the market. A pharmaceutical company may decide to use their own in-house reference standard to test the drug instead of using the expensive international reference standard. The company is then legally obliged to verify that the in-house reference standard remains stable over time with respect to the international one. This is a special problem within statistical process control (SPC) since the monitoring period is relatively short and bioassays are typically heterogenous. The objective of this article is to apply methods from SPC and dose-finding studies to different study designs and assess how well these methods perform in detecting a decline in bioactivity. The included methods are the exponentially weighted moving average (EWMA), Shewhart chart, and analysis of variance (ANOVA)-type contrasts (linear, Helmert, and reverse-Helmert). An optimal alpha-spending function was selected first to avoid inflating the familywise error rate. The normal alpha-spending function seemed to perform generally the best. Then from the results, the linear, reverse-Helmert, and the EWMA (lambda 0.6) performed better in later declines. Linear contrasts and the Shewhart chart performed better irrespective of the decline profile. Having more bioassay runs at the beginning of the stability study increased the probability of detecting a decline. If there is no prior information on the expected deterioration profile, linear contrasts or Shewhart chart should be preferred. Otherwise, reverse-Helmert or Helmert contrasts should be chosen for either early or late deterioration, respectively

Equivalence testing for similarity in bioassays using bioequivalence criteria on the relative bioactivity

\u3cp\u3eSimilarity in bioassays means that the test preparation behaves as a dilution of the standard preparation with respect to their biological effect. Thus, similarity must be investigated to confirm this biological property. Historically, this was typically conducted with traditional hypothesis testing, but this has received substantial criticism. Failing to reject similarity does not imply that the 2 preparations are similar. Also, rejecting similarity when bioassay variability is small might simply demonstrate a nonrelevant deviation in similarity. To remedy these concerns, equivalence testing has been proposed as an alternative to traditional hypothesis testing, and it has found its way in the official guidelines. However, similarity has been discussed mainly in terms of the parameters in the dose-response curves of the standard and test preparations, but the consequences of nonsimilarity on the relative bioactivity have never been investigated. This article provides a general equivalence approach to evaluate similarity that is directly related to bioequivalence on the relative bioactivity of the standard and test preparations. Bioequivalence on the relative bioactivity can only be guaranteed for positive (only nonblanks) and finite dose intervals. The approach is demonstrated on 4 case studies in which we also show how to calculate a sample size and how to investigate the power of equivalence on similarity.\u3c/p\u3

Bactericidal antibodies against hypervirulent Neisseria meningitidis C field strains following MenC-CRM or MenACWY-CRM priming and MenACWY-CRM booster in children

An increase in invasive meningococcal disease (IMD) incidence was observed in Tuscany in 2015/2016, mainly due to hypervirulent clonal complex (cc) 11 strains. In a post-hoc analysis, we assessed bactericidal activity of antibodies in sera from children primed with MenACWY-CRM or MenC-CRM conjugate vaccines and receiving a MenACWY-CRM booster dose against 5 meningococcal C (MenC) strains isolated from IMD cases. Sera collected from 90 infants/toddlers who participated in a phase III, open-label study (NCT00667602) and its extension (NCT01345721) were tested by serum bactericidal activity assay with human complement (hSBA). Children were primed with either MenACWY-CRM at 6–8 and 12 months of age (group 2_MenACWY; N = 30), MenACWY-CRM (group 1_MenACWY; N = 30), or MenC-CRM at 12 months of age (group 1_MenC; N = 30); all received MenACWY-CRM booster dose at 22–45 months of age. Four tested strains (FI001–FI004) were C:P1.5–1,10-8:F3-6:ST-11 (cc11) and 1 (FI005) was C:P1.7–4,14-6:F3-9:ST-1031 (cc334). Overall, immune responses tended to be higher against Fl002–FI004 than Fl001 and Fl005. Geometric mean titers were high in group 2_MenACWY (range: 94.8 [FI005]–588.1 [FI004]) and very high post-boosting with MenACWY-CRM in all groups (176.9 [FI005]–3911.0 [FI004]). Seroresponse rates tended to be higher in group 1_MenC (33.3% [FI005]–93.3% [FI004]) than in group 1_MenACWY (16.7% [FI005]–73.3% [FI004]). Irrespective of strains tested or the identity/number of priming doses, ≥96.7% of children had hSBA titers ≥1:8 post-MenACWY-CRM booster dose. MenACWY-CRM and MenC-CRM elicited bactericidal antibodies and immunological memory against hypervirulent cc11 and cc334 MenC strains responsible for IMD outbreaks