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1.  Case Management Reduces Drinking During Pregnancy among High Risk Women 
Estimate the efficacy of Case Management (CM) for women at high risk for bearing a child with Fetal Alcohol Spectrum Disorders (FASD).
Women were recruited from antenatal clinics and engaged in 18 months of CM.
A South African community with a subculture of heavy, regular, weekend, recreational drinking and high documented rates of FASD.
Forty-one women who were high risk for bearing a child with FASD.
Statistical analysis of trends in drinking and other risk factors.
At intake 87.8% were pregnant, most had previous alcohol-exposed pregnancies, most/all of their friends drink alcohol (67.5%), and 50.0% had stressful lives. CM was particularly valuable for pregnant women, as statistically significant reductions in alcohol risk were obtained for them in multiple variables: total drinks on weekends after six months of CM (p = .026) and estimated peak blood alcohol concentration (BAC) at six (p < .001) and 18 months (p < .001). For participants completing 18 months of CM, AUDIT scores improved significantly by 6-month follow-up (from 19.8 to 9.7, p = .000), and even though rising at 12 and 18 months, AUDIT scores indicate that problematic drinking remained statistically significantly lower than baseline throughout CM. Happiness scale scores correlated significantly with reduced drinking in most time periods.
An enduring change in drinking behavior is difficult in this social setting. Yet, CM provided by skilled and empathic case managers reduced maternal drinking at critical times, and therefore, alcohol exposure levels to the fetus.
PMCID: PMC3981106
fetal alcohol spectrum disorders (FASD); prevention; case management; alcohol abuse
2.  Prevalence of Virulence Genes Associated with Pathogenic Escherichia coli Strains Isolated from Domestically Harvested Rainwater during Low- and High-Rainfall Periods 
The possible health risks associated with the consumption of harvested rainwater remains one of the major obstacles hampering its large-scale implementation in water limited countries such as South Africa. Rainwater tank samples collected on eight occasions during the low- and high-rainfall periods (March to August 2012) in Kleinmond, South Africa, were monitored for the presence of virulence genes associated with Escherichia coli. The identity of presumptive E. coli isolates in rainwater samples collected from 10 domestic rainwater harvesting (DRWH) tanks throughout the sampling period was confirmed through universal 16S rRNA PCR with subsequent sequencing and phylogenetic analysis. Species-specific primers were also used to routinely screen for the virulent genes, aggR, stx, eae, and ipaH found in enteroaggregative E. coli (EAEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and enteroinvasive E. coli, respectively, in the rainwater samples. Of the 92 E. coli strains isolated from the rainwater using culture based techniques, 6% were presumptively positively identified as E. coli O157:H7 using 16S rRNA. Furthermore, virulent pathogenic E. coli genes were detected in 3% (EPEC and EHEC) and 16% (EAEC) of the 80 rainwater samples collected during the sampling period from the 10 DRWH tanks. This study thus contributes valuable information to the limited data available regarding the ongoing prevalence of virulent pathotypes of E. coli in harvested rainwater during a longitudinal study in a high-population-density, periurban setting.
PMCID: PMC3957612  PMID: 24375127
3.  Correction: Dietary Plasticity of Generalist and Specialist Ungulates in the Namibian Desert: A Stable Isotopes Approach 
PLoS ONE  2013;8(9):10.1371/annotation/89fe804f-20cc-40cc-99af-d42751676d36.
PMCID: PMC3782397  PMID: 24098621
4.  Dietary Plasticity of Generalist and Specialist Ungulates in the Namibian Desert: A Stable Isotopes Approach 
PLoS ONE  2013;8(8):e72190.
Desert ungulates live in adverse ecosystems that are particularly sensitive to degradation and global climate change. Here, we asked how two ungulate species with contrasting feeding habits, grazing gemsbok (Oryx g. gazella) and browsing springbok (Antidorcas marsupialis), respond to an increase in food availability during a pronounced rain period. We used a stable isotope approach to delineate the feeding habits of these two ungulates in the arid Kunene Region of Namibia. Our nineteen months field investigation included two time periods of drought when food availability for ungulates was lowest and an intermediate period with extreme, unusual rainfalls. We documented thirteen isotopically distinct food sources in the isotopic space of the study area. Our results indicated a relatively high dietary plasticity of gemsbok, which fed on a mixture of plants, including more than 30% of C3 plants during drought periods, but almost exclusively on C4 and CAM plant types when food was plentiful. During drought periods, the inferred gemsbok diets also consisted of up to 25% of Euphorbia damarana; an endemic CAM plant that is rich in toxic secondary plant compounds. In contrast, springbok were generalists, feeding on a higher proportion of C3 than C4/CAM plants, irrespective of environmental conditions. Our results illustrate two dietary strategies in gemsbok and springbok which enable them to survive and coexist in the hostile Kunene arid ecosystem.
PMCID: PMC3745446  PMID: 23977249
5.  HLA-A*7401–Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703 
The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade–infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401–restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401–restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703.
PMCID: PMC3738002  PMID: 21498667
6.  Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records 
Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research.
We describe development, implementation and evaluation of a bespoke de-identification algorithm used to create the register. It is designed to create dictionaries using patient identifiers (PIs) entered into dedicated source fields and then identify, match and mask them (with ZZZZZ) when they appear in medical texts. We deemed this approach would be effective, given high coverage of PI in the dedicated fields and the effectiveness of the masking combined with elements of a security model. We conducted two separate performance tests i) to test performance of the algorithm in masking individual true PIs entered in dedicated fields and then found in text (using 500 patient notes) and ii) to compare the performance of the CRIS pattern matching algorithm with a machine learning algorithm, called the MITRE Identification Scrubber Toolkit – MIST (using 70 patient notes – 50 notes to train, 20 notes to test on). We also report any incidences of potential breaches, defined by occurrences of 3 or more true or apparent PIs in the same patient’s notes (and in an additional set of longitudinal notes for 50 patients); and we consider the possibility of inferring information despite de-identification.
True PIs were masked with 98.8% precision and 97.6% recall. As anticipated, potential PIs did appear, owing to misspellings entered within the EHRs. We found one potential breach. In a separate performance test, with a different set of notes, CRIS yielded 100% precision and 88.5% recall, while MIST yielded a 95.1% and 78.1%, respectively. We discuss how we overcome the realistic possibility – albeit of low probability – of potential breaches through implementation of the security model.
CRIS is a de-identified psychiatric database sourced from EHRs, which protects patient anonymity and maximises data available for research. CRIS demonstrates the advantage of combining an effective de-identification algorithm with a carefully designed security model. The paper advances much needed discussion of EHR de-identification – particularly in relation to criteria to assess de-identification, and considering the contexts of de-identified research databases when assessing the risk of breaches of confidential patient information.
PMCID: PMC3751474  PMID: 23842533
De-identification; Anonymisation; Electronic health records; Psychiatric case register; Medical health records security; Medical information database security
7.  HIV Control through a Single Nucleotide on the HLA-B Locus 
Journal of Virology  2012;86(21):11493-11500.
Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and strong linkage disequilibrium between HLA class I alleles complicates the discrimination of individual HLA allelic effects from those of other HLA and non-HLA alleles on the same haplotype. Here, we exploit an experiment of nature involving two recently diverged HLA alleles, HLA-B*42:01 and HLA-B*42:02, which differ by only a single amino acid. Crucially, they occur primarily on identical HLA class I haplotypes and, as Bw6 alleles, do not act as NK cell ligands and are therefore largely unconfounded by other genetic factors. We show that in an outbred cohort (n = 2,093) of HIV C-clade-infected individuals, a single amino acid change at position 9 of the HLA-B molecule critically affects peptide binding and significantly alters the cytotoxic T lymphocyte (CTL) epitopes targeted, measured directly ex vivo by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay (P = 2 × 10−10) and functionally through CTL escape mutation (P = 2 × 10−8). HLA-B*42:01, which presents multiple Gag epitopes, is associated with a 0.52 log10 lower viral-load set point than HLA-B*42:02 (P = 0.02), which presents no p24 Gag epitopes. The magnitude of this effect from a single amino acid difference in the HLA-A*30:01/B*42/Cw*17:01 haplotype is equivalent to 75% of that of HLA-B*57:03, the most protective HLA class I allele in this population. This naturally controlled experiment represents perhaps the clearest demonstration of the direct impact of a particular HIV-specific CTL on disease control.
PMCID: PMC3486337  PMID: 22896606
8.  Where is the game? Wild meat products authentication in South Africa: a case study 
Wild animals’ meat is extensively consumed in South Africa, being obtained either from ranching, farming or hunting. To test the authenticity of the commercial labels of meat products in the local market, we obtained DNA sequence information from 146 samples (14 beef and 132 game labels) for barcoding cytochrome c oxidase subunit I and partial cytochrome b and mitochondrial fragments. The reliability of species assignments were evaluated using BLAST searches in GenBank, maximum likelihood phylogenetic analysis and the character-based method implemented in BLOG. The Kimura-2-parameter intra- and interspecific variation was evaluated for all matched species.
The combined application of similarity, phylogenetic and character-based methods proved successful in species identification. Game meat samples showed 76.5% substitution, no beef samples were substituted. The substitutions showed a variety of domestic species (cattle, horse, pig, lamb), common game species in the market (kudu, gemsbok, ostrich, impala, springbok), uncommon species in the market (giraffe, waterbuck, bushbuck, duiker, mountain zebra) and extra-continental species (kangaroo). The mountain zebra Equus zebra is an International Union for Conservation of Nature (IUCN) red listed species. We also detected Damaliscus pygargus, which is composed of two subspecies with one listed by IUCN as ‘near threatened’; however, these mitochondrial fragments were insufficient to distinguish between the subspecies. The genetic distance between African ungulate species often overlaps with within-species distance in cases of recent speciation events, and strong phylogeographic structure determines within-species distances that are similar to the commonly accepted distances between species.
The reliability of commercial labeling of game meat in South Africa is very poor. The extensive substitution of wild game has important implications for conservation and commerce, and for the consumers making decisions on the basis of health, religious beliefs or personal choices.
Distance would be a poor indicator for identification of African ungulates species. The efficiency of the character-based method is reliant upon availability of large reference data. The current higher availability of cytochrome b data would make this the marker of choice for African ungulates. The encountered problems of incomplete or erroneous information in databases are discussed.
PMCID: PMC3621286  PMID: 23452350
Biltong; conservation; Cytb; DNA barcoding; Food forensics; Meat; Species identification
9.  Co-Operative Additive Effects between HLA Alleles in Control of HIV-1 
PLoS ONE  2012;7(10):e47799.
HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles - irrespective of linkage disequilibrium - function co-operatively.
Methodology/Principal Findings
We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate ‘co-operative additive’ effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q<0.05 in each case). We developed a novel ‘sharing score’ to quantify the breadth of CD8+ T cell responses made by pairs of HLA alleles across the HIV proteome, and used this to demonstrate that successful viraemic suppression correlates with breadth of unique CD8+ T cell responses (p = 0.03).
These results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect.
PMCID: PMC3477121  PMID: 23094091
10.  Task shifting of antiretroviral treatment from doctors to primary-care nurses in South Africa (STRETCH): a pragmatic, parallel, cluster-randomised trial 
Lancet  2012;380(9845):889-898.
Robust evidence of the effectiveness of task shifting of antiretroviral therapy (ART) from doctors to other health workers is scarce. We aimed to assess the effects on mortality, viral suppression, and other health outcomes and quality indicators of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) programme, which provides educational outreach training of nurses to initiate and represcribe ART, and to decentralise care.
We undertook a pragmatic, parallel, cluster-randomised trial in South Africa between Jan 28, 2008, and June 30, 2010. We randomly assigned 31 primary-care ART clinics to implement the STRETCH programme (intervention group) or to continue with standard care (control group). The ratio of randomisation depended on how many clinics were in each of nine strata. Two cohorts were enrolled: eligible patients in cohort 1 were adults (aged ≥16 years) with CD4 counts of 350 cells per μL or less who were not receiving ART; those in cohort 2 were adults who had already received ART for at least 6 months and were being treated at enrolment. The primary outcome in cohort 1 was time to death (superiority analysis). The primary outcome in cohort 2 was the proportion with undetectable viral loads (<400 copies per mL) 12 months after enrolment (equivalence analysis, prespecified difference <6%). Patients and clinicians could not be masked to group assignment. The interim analysis was blind, but data analysts were not masked after the database was locked for final analysis. Analyses were done by intention to treat. This trial is registered, number ISRCTN46836853.
5390 patients in cohort 1 and 3029 in cohort 2 were in the intervention group, and 3862 in cohort 1 and 3202 in cohort 2 were in the control group. Median follow-up was 16·3 months (IQR 12·2–18·0) in cohort 1 and 18·0 months (18·0–18·0) in cohort 2. In cohort 1, 997 (20%) of 4943 patients analysed in the intervention group and 747 (19%) of 3862 in the control group with known vital status at the end of the trial had died. Time to death did not differ (hazard ratio [HR] 0·94, 95% CI 0·76–1·15). In a preplanned subgroup analysis of patients with baseline CD4 counts of 201–350 cells per μL, mortality was slightly lower in the intervention group than in the control group (0·73, 0·54–1.00; p=0·052), but it did not differ between groups in patients with baseline CD4 of 200 cells per μL or less (0·94, 0·76–1·15; p=0·577). In cohort 2, viral load suppression 12 months after enrolment was equivalent in intervention (2156 [71%] of 3029 patients) and control groups (2230 [70%] of 3202; risk difference 1·1%, 95% CI −2·4 to 4·6).
Expansion of primary-care nurses' roles to include ART initiation and represcription can be done safely, and improve health outcomes and quality of care, but might not reduce time to ART or mortality.
UK Medical Research Council, Development Cooperation Ireland, and Canadian International Development Agency.
PMCID: PMC3442223  PMID: 22901955
11.  Comparative Analysis of Mycobacterium tuberculosis pe and ppe Genes Reveals High Sequence Variation and an Apparent Absence of Selective Constraints 
PLoS ONE  2012;7(4):e30593.
Mycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of “classical” antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design.
PMCID: PMC3319526  PMID: 22496726
12.  Progression to AIDS in South Africa Is Associated with both Reverting and Compensatory Viral Mutations 
PLoS ONE  2011;6(4):e19018.
We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775). Immune responses were measured by γ-interferon ELISPOT assays. HLA-associated viral polymorphisms were determined using phylogenetically corrected techniques, and viral replication capacity (VRC) was measured by comparing the growth rate of gag-protease recombinant viruses against recombinant NL4-3 viruses. We report that in advanced disease (CD4 counts <100 cells/µl), T cell responses narrow, with a relative decline in Gag-directed responses (p<0.0001). This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of “immune relaxation”. The median VRC from patients with CD4 counts <100 cells/µl was higher than from patients with CD4 counts ≥500 cells/µl (91.15% versus 85.19%, p = 0.0004), potentially explaining the rise in viral load associated with disease progression. Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013). These data provide novel insights into the mechanisms of HIV disease progression in South Africa. Restoration of fitness correlates with loss of viral control in late disease, with evidence for both preserved and relaxed selection pressure across the HIV genome. Interventions that maintain viral fitness costs could potentially slow progression.
PMCID: PMC3081339  PMID: 21544209
13.  Integrated Gender-Based Violence and HIV Risk Reduction Intervention for South African Men: Results of a Quasi-Experimental Field Trial 
South Africa is in the midst of one of the world’s most devastating HIV/AIDS epidemics and there is a well documented association between violence against women and HIV transmission. Interventions that target men and integrate HIV prevention with gender-based violence prevention may demonstrate synergistic effects. A quasi-experimental field intervention trial was conducted with two communities randomly assigned to receive either: (a) a five session integrated intervention designed to simultaneously reduce gender-based violence (GBV) and HIV risk behaviors (N=242) or (b) a single 3-hour alcohol and HIV risk reduction session (N=233). Men were followed for 1, 3, and 6-months post intervention with 90% retention. Results indicated that the GBV/HIV intervention reduced negative attitudes toward women in the short term and reduced violence against women in longer term. Men in the GBV/HIV intervention also increased their talking with sex partners about condoms and were more likely to have been tested for HIV at the follow-ups. There were few differences between conditions on any HIV transmission risk reduction behavioral outcomes. Further research is needed to examine the potential synergistic effects of alcohol use, gender violence, and HIV prevention interventions.
PMCID: PMC3015088  PMID: 19353267
14.  Challenges Faced by People Living with HIV/AIDS in Cape Town, South Africa: Issues for Group Risk Reduction Interventions 
AIDS Research and Treatment  2010;2010:420270.
This paper presents the findings of an exploratory study to investigate the challenges faced by people living with HIV/AIDS (PLWHA) in communities in Cape Town, South Africa. The primary goal of the study was to gather data to inform the adaptation of a group risk reduction intervention to the South African context. Qualitative methods were used to examine the experiences of PLWHA. Eight focus group discussions (FGDs) were conducted with 83 HIV-positive participants and 14 key informants (KIs) involved in work with PLWHA were interviewed. Findings revealed that AIDS-related stigma was still pervasive in local communities. This was associated with the difficulty of disclosure of their status for fear of rejection. Also notable was the role of risky behaviours such as lack of condom use and that PLWHA considered their HIV/AIDS status as secondary to daily life stressors like poverty, unemployment, and gender-based violence. These findings have implications for the adaptation or development of behavioural risk reduction interventions for PLWHA.
PMCID: PMC3065817  PMID: 21490904
15.  Disclosure of HIV status to sex partners and sexual risk behaviours among HIV‐positive men and women, Cape Town, South Africa 
The HIV epidemic continues to amplify in southern Africa and there is a growing need for HIV prevention interventions among people who have tested HIV positive.
Anonymous surveys were completed by 413 HIV‐positive men and 641 HIV‐positive women sampled from HIV/AIDS services; 73% were <35 years old, 70% Black African, 70% unemployed, 75% unmarried, and 50% taking antiretroviral treatment.
Among the 903 (85%) participants who were currently sexually active, 378 (42%) had sex with a person to whom they had not disclosed their HIV status in the previous 3 months. Participants who had not disclosed their HIV status to their sex partners were considerably more likely to have multiple partners, HIV‐negative partners, partners of unknown HIV status and unprotected intercourse with non‐concordant sex partners. Not disclosing their HIV status to partners was also associated with having lost a job or a place to stay because of being HIV positive and feeling less able to disclose to partners.
HIV‐related stigma and discrimination are associated with not disclosing HIV status to sex partners, and non‐disclosure is closely associated with HIV transmission risk behaviours. Interventions are needed in South Africa to reduce the AIDS stigma and discrimination and to assist people with HIV to make effective decisions on disclosure.
PMCID: PMC2598581  PMID: 16790562
16.  [N,N-Bis(diphenyl­phosphino)propyl­amine-κ2 P,P′]dichloridoplatinum(II) 
The Pt(II) atom in the title compound, [PtCl2(C27H27NP2)], has a highly distorted square-planar geometry, as evidenced by the P—Pt—P bite angle [72.4 (1)°]. The strain in the complex is further illustrated by the distorted tetra­hedral angles of the P atoms, which range between 93.5 (1) and 122.2 (1)°. It is of inter­est to note that the N atom has to adopt an almost planar geometry with the two P atoms and the C atom attached to it [it is displaced by 0.093 (2) Å from the CP2 plane] in order to accommodate the steric bulk of the phenyl groups and the alkyl group of the ligand coordinated to the PtII centre. The mol­ecules pack in horizontal rows across the bc plane. C—H⋯Cl hydrogen bonds stabilize the crystal packing.
PMCID: PMC2980280  PMID: 21579949
17.  N,N-Bis(diphenyl­phosphino)ethyl­amine 
In the title compound, C26H25NP2, the diphenyl­phosphino groups are staggered relative to the PNP backbone, even though the ethyl substituent coordinated to the N atom is not sterically bulky. The N atom adapts an almost planar geometry with two P atoms and a C atom of the allyl group attached to it in order to accommodate the steric bulk of the phenyl groups and the alkyl group. The distortion of the trigonal-pyramidal geometry of the nitro­gen is further illustrated by the bond angles which range between 114.0 (1) and 123.7 (1)°. There are no classical inter­molecular inter­actions.
PMCID: PMC2972116  PMID: 21578811
18.  High Rates of Unprotected Sex occurring among HIV-Positive Individuals in a Daily Diary Study in South Africa: The Role of Alcohol Use 
To assess the prevalence of unprotected sex and examine the association between alcohol consumption before sex and unprotected sex among HIV+ individuals in Cape Town, South Africa.
For 42-days daily phone interviews assessed daily sexual behaviour and alcohol consumption. Logistic and Poisson GEE models were used to examine associations between alcohol consumption before sex and subsequent unprotected sex.
During the study which yielded 3,035 data points, the 58 HIV+ women and 24 HIV+ men drank an average of 6.13 drinks when they drank, and reported 4,927 sex events, of which 80.17% were unprotected. Over half (58%) of unprotected sex events were with HIV-negative or HIV-status-unknown partners. Extrapolating from the data using likelihood of infection per act estimates we calculated that an estimated 2.95 incident HIV-infections occurred during the study. Drinking alcohol before sex by the female, the male, or by both partners, increased the proportion and number of subsequent unprotected sex events. However, these associations held only when the quantity of alcohol consumed corresponded to moderate or higher risk drinking.
Among HIV-positives engaging in moderate or higher risk drinking prior to sex increases the likelihood and rate of unprotected sex. Prevention efforts need to address reducing alcohol-involved unprotected sex among HIV-positive persons.
PMCID: PMC2631279  PMID: 18769345
HIV seropositivity; alcohol drinking; prevention; condoms; sexual partners; prospective cohort study; South Africa
19.  Genetic variation in angiotensin-converting enzyme 2 gene is associated with extent of left ventricular hypertrophy in hypertrophic cardiomyopathy 
Human Genetics  2008;124(1):57-61.
Hypertrophic cardiomyopathy, a common, inherited cardiac muscle disease, is primarily caused by mutations in sarcomeric protein-encoding genes and is characterized by overgrowth of ventricular muscle that is highly variable in extent and location. This variability has been partially attributed to locus and allelic heterogeneity of the disease-causing gene, but other factors, including unknown genetic factors, also modulate the extent of hypertrophy that develops in response to the defective sarcomeric functioning. Components of the renin-angiotensin-aldosterone system are plausible candidate hypertrophy modifiers because of their role in controlling blood pressure and biological effects on cardiomyocyte hypertrophy.
PMCID: PMC2469277  PMID: 18560893
20.  Streamlining tasks and roles to expand treatment and care for HIV: randomised controlled trial protocol 
Trials  2008;9:21.
A major barrier to accessing free government-provided antiretroviral treatment (ART) in South Africa is the shortage of suitably skilled health professionals. Current South African guidelines recommend that only doctors should prescribe ART, even though most primary care is provided by nurses. We have developed an effective method of educational outreach to primary care nurses in South Africa. Evidence is needed as to whether primary care nurses, with suitable training and managerial support, can initiate and continue to prescribe and monitor ART in the majority of ART-eligible adults.
This is a protocol for a pragmatic cluster randomised trial to evaluate the effectiveness of a complex intervention based on and supporting nurse-led antiretroviral treatment (ART) for South African patients with HIV/AIDS, compared to current practice in which doctors are responsible for initiating ART and continuing prescribing. We will randomly allocate 31 primary care clinics in the Free State province to nurse-led or doctor-led ART. Two groups of patients aged 16 years and over will be included: a) 7400 registering with the programme with CD4 counts of ≤ 350 cells/mL (mainly to evaluate treatment initiation) and b) 4900 already receiving ART (to evaluate ongoing treatment and monitoring). The primary outcomes will be time to death (in the first group) and viral suppression (in the second group). Patients' survival, viral load and health status indicators will be measured at least 6-monthly for at least one year and up to 2 years, using an existing province-wide clinical database linked to the national death register.
Trial registration
Controlled Clinical Trials ISRCTN46836853
PMCID: PMC2377234  PMID: 18433494
21.  Effect of an IMCI intervention on quality of care across four districts in Cape Town, South Africa 
Archives of Disease in Childhood  2005;90(4):397-401.
Aims: To measure the change in quality of care provided to sick children as a result of the routine implementation of the IMCI intervention.
Methods: Structured observations of consultations with sick children, exit interviews with caregivers, and facility reviews were conducted both before and after IMCI intervention in four health districts in Cape Town. Interventions were case management training, orientation courses for supervisors and medical officers, and some reorganisation of management systems.
Results: Twenty one nurses in 21 clinics were observed before and after the IMCI intervention; 90 and 70 child observations were conducted before and after IMCI intervention respectively. There was a marked improvement in assessment of danger signs in sick children (7% before versus 72% after), assessment of co-morbidity (integrated score 5.2 versus 8.2), rational prescribing (62% versus 84%), and starting treatment in the clinic (40% versus 70%). However there was no change in the treatment of anaemia or the prescribing of vitamin A or counselling of caregivers. There was no change in the knowledge of caregivers regarding medication or when to return to the health facility. Facilities were well stocked and supervision regular both before and after IMCI.
Conclusion: This study has shown that under normal operating conditions and in a context of good facility infrastructure and management support, IMCI is associated with improvements in some important aspects of care
PMCID: PMC1720349  PMID: 15781932
22.  N,N-Bis(diphenyl­phosphino)-1,2-dimethyl­propyl­amine 
The diphenyl­phosphine groups in the title compound, C29H31NP2, are staggered relative to the PNP backbone. The N atom adopts an almost planar geometry with the two P atoms and the C atom attached to it, in order to accommodate the steric bulk of the phenyl groups and the alkyl group. Three C atoms of the 1,2-dimethylpropylamine group are disordered over two positions in a 9:1 ratio. The mol­ecules pack diagonally in the unit cell across the ac plane in a head-to-tail fashion.
PMCID: PMC2960458  PMID: 21201505
23.  Stigma and discrimination experiences of HIV-positive men who have sex with men in Cape Town, South Africa 
AIDS Care  2008;20(9):1105-1110.
Since the primary mode of HIV transmission in sub-Saharan Africa is heterosexual, research focusing on the sexual behaviour of men who have sex with men (MSM) is scant. Currently it is unknown how many people living with HIV in South Africa are MSM and there is even less known about the stigmatisation and discrimination of HIV-positive MSM. The current study examined the stigma and discrimination experiences of MSM living with HIV/AIDS in South Africa. Anonymous venue-based surveys were collected from 92 HIV-positive MSM and 330 HIV-positive men who only reported sex with women (MSW). Internalised stigma was high among all HIV-positive men who took part in the survey, with 56% of men reporting that they concealed their HIV status from others. HIV-positive MSM reported experiencing greater social isolation and discrimination resulting from being HIV-positive, including loss of housing or employment due to their HIV status, however these differences were not significant. Mental health interventions, as well as structural changes for protection against discrimination, are needed for HIV-positive South African MSM.
PMCID: PMC3320098  PMID: 18608067
South Africa; men who have sex with men (MSM); HIV-positive; AIDS-related stigma; discrimination

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