Browsing by Subject "Medicine and Health Sciences"

Now showing 1 - 4 of 4
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    Open Access
    Moving towards universal coverage in South Africa? Lessons from a voluntary government insurance scheme
    (2013) Govender, Veloshnee; Chersich, Matthew F; Harris, Bronwyn; Alaba, Olufunke; Ataguba, John E; Nxumalo, Nonhlanhla; Goudge, Jane
    BackgroundIn 2005, the South African government introduced a voluntary, subsidised health insurance scheme for civil servants. In light of the global emphasis on universal coverage, empirical evidence is needed to understand the relationship between new health financing strategies and health care access thereby improving global understanding of these issues.ObjectivesThis study analysed coverage of the South African government health insurance scheme, the population groups with low uptake, and the individual-level factors, as well as characteristics of the scheme, that influenced enrolment.MethodsMulti-stage random sampling was used to select 1,329 civil servants from the health and education sectors in four of South Africa's nine provinces. They were interviewed to determine factors associated with enrolment in the scheme. The analysis included both descriptive statistics and multivariate logistic regression.ResultsNotwithstanding the availability of a non-contributory option within the insurance scheme and access to privately-provided primary care, a considerable portion of socio-economically vulnerable groups remained uninsured (57.7% of the lowest salary category). Non-insurance was highest among men, black African or coloured ethnic groups, less educated and lower-income employees, and those living in informal-housing. The relatively poor uptake of the contributory and non-contributory insurance options was mostly attributed to insufficient information, perceived administrative challenges of taking up membership, and payment costs.ConclusionBarriers to enrolment include insufficient information, unaffordability of payments and perceived administrative complexity. Achieving universal coverage requires good physical access to service providers and appropriate benefit options within pre-payment health financing mechanisms.
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    Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
    (2013) Davis, Lea K; Yu, Dongmei; Keenan, Clare L; Gamazon, Eric R; Konkashbaev, Anuar I; Derks, Eske M; Neale, Benjamin M; Yang, Jian; Lee, S Hong; Evans, Patrick; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, Oscar J; Bloch, Michael H; Blom, Rianne M; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond; Cappi, Carolina; Cardona Silgado, Julio C; Cath, Danielle C; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Conti, David V; Cook, Edwin H; Coric, Vladimir; Cullen, Bernadette A; Deforce, Dieter
    The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
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    Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape
    (2017) Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N; Sheward, Daniel J; Joyce, M Gordon; Asokan, Mangai; Burton, Dennis R; Connors, Mark; Abdool Karim, Salim S; Mascola, John R; Robinson, James E; Ward, Andrew B; Kwong, Peter D; Morris, Lynn; Moore, Penny L
    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design.
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    Treatment guidelines and early loss from care for people living with HIV in Cape Town, South Africa: A retrospective cohort study
    (2017) Katz, Ingrid T; Kaplan, Richard; Fitzmaurice, Garrett; Leone, Dominick; Bangsberg, David R; Bekker, Linda‐Gail; Orrell, Catherine
    South Africa has undergone multiple expansions in antiretroviral therapy (ART) eligibility from an initial CD4+ threshold of ≤200 cells/μl to providing ART for all people living with HIV (PLWH) as of September 2016. We evaluated the association of programmatic changes in ART eligibility with loss from care, both prior to ART initiation and within the first 16 weeks of starting treatment, during a period of programmatic expansion to ART treatment at CD4+ ≤ 350 cells/μl.