Browsing by Author "Karim, Salim S Abdool"

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    Open Access
    Anaemia in acute HIV-1 subtype C infection
    (Public Library of Science, 2008) Mlisana, Koleka; Auld, Sara C; Grobler, Anneke; Loggerenberg, Francois van; Williamson, Carolyn; Iriogbe, Itua; Sobieszczyk, Magdalena E; Karim, Salim S Abdool; Team, for the CAPRISA Acute Infection Study
    BACKGROUND: The high prevalence of anaemia and the increased morbidity and mortality associated with anaemia during AIDS has been well described yet there has been little information about anaemia and changes in haemoglobin levels during acute and early HIV-1 infection. METHODS: HIV-negative women (n = 245) were enrolled into an observational cohort as part of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) Acute Infection Study. Acute infection was diagnosed following a positive HIV RNA PCR in the absence of antibodies, or detection of HIV-1 antibodies within 3 months of a previously negative antibody test. Haemotologic parameters were assessed before infection and at regular intervals in the first twelve months of HIV infection. RESULTS: Fifty-seven participants with acute HIV infection were identified at a median of 14.5 days post-infection (range 10-81) and were enrolled in the CAPRISA Acute Infection cohort at a median of 41 days post-infection (range 15-104). Mean haemoglobin prior to HIV-1 infection was 12.7 g/dL, with a mean decline of 0.46 g/dL following infection. The prevalence of anaemia increased from 25.0% prior to HIV-1 infection to 52.6% at 3 months post-infection, 61.1% at 6 months post-infection, and 51.4% at 12 months post-infection. CONCLUSIONS: Haematologic derangements and anaemia with a trend towards iron deficiency are common with acute HIV-1 subtype C infection in this small cohort. The negative impact of anaemia concurrent with established HIV infection upon morbidity and mortality has been well documented but the prognostic potential and long-term effects of anaemia during acute HIV-1 infection remain unknown.
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    An assessment of the management of sexually transmitted diseases (STDs) in a rural district health ward of Northern Kwazulu
    (1997) McCoy, David; Karim, Salim S Abdool
    This study is an assessment of the quality of sexually transmitted disease (STD) management and control in a rural district of South Africa. A semi-structured questionnaire was administered to 5 nurses from public sector primary health care clinics, 5 doctors from the public district hospital, 5 private general practitioners, 6 traditional healers and 7 STD patients. A patient simulation exercise involving 6 nurses and 6 general practitioners was also conducted. Using routine data collection forms, the spectrum of STD syndromes and the contact tracing rate were assessed. The private sector treated nearly a third of the STDs even though they charge about ten times the price of the public sector services. In general, the clinical skills of all providers were poor. While hypothetical patient histories produced reasonable responses on STD management during the interviews, the patient simulation results showed that health service providers provided STD management that was much poorer than the questionnaires indicated. The private general practitioners did not practice syndromic STD management and often did not use laboratory tests appropriately resulting in incorrect diagnosis and inappropriate treatment for STDs. All health service providers did not counsel, promote condoms or encourage contact notification adequately. All health service providers were keen to participate in continuing medical education that better equip them to manage STDs. Any attempts at improving the quality of care in the district must therefore include private general practitioners as an important and central component of STD policy and planning. Interviews with traditional healers and patients showed the importance of using non-biomedical constructs of health and illness in developing health promotion strategies. There is an urgent need to improve STD management at district level in an attempt to meet the first milestone of ensuring that a patient presenting with an STD to a health service is correctly managed. This can be done through the design of simple quality assurance methods as demonstrated in this paper.
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    Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection
    (Public Library of Science, 2009) Moore, Penny L; Ranchobe, Nthabeleng; Lambson, Bronwen E; Gray, Elin S; Cave, Eleanor; Abrahams, Melissa-Rose; Bandawe, Gama; Mlisana, Koleka; Karim, Salim S Abdool; Williamson, Carolyn
    Author Summary Most HIV-1 infected individuals develop neutralizing antibodies against their own virus, termed an autologous neutralizing response. It is known that this response exerts pressure on the envelope of HIV, the target of such antibodies, resulting in neutralization escape. Here we have identified the targets of these antibodies and the precise genetic basis of neutralization escape in 4 individuals infected with HIV-1 subtype C. We show that V1V2 is commonly involved in escape, and that the C3 region is also a target in some cases. The latter observation confirms this region is exposed in subtype C, unlike subtype B. We show that neutralization escape is conferred by a few amino acid mutations, some of which are outside the antibody target site. Moreover, escape from these limited specificities even within a single individual occurs via a variety of different pathways involving substitutions, indels and glycan shifts. The finding in 2 individuals that an anti-C3 response developed first, followed by an anti-V1V2 response, suggests there may be specific regions of envelope particularly vulnerable to antibody neutralization. Overall, we propose a mechanistic explanation for how HIV-1 epitopes drive sequential waves of neutralization escape in early subtype C infection.
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    Randomized cross-sectional study to compare HIV-1 specific antibody and cytokine concentrations in female genital secretions obtained by menstrual cup and cervicovaginal lavage
    (Public Library of Science, 2015) Archary, Derseree; Liebenberg, Lenine J; Werner, Lise; Tulsi, Sahil; Majola, Nelisile; Naicker, Nivashnee; Dlamini, Sarah; Hope, Thomas J; Samsunder, Natasha; Karim, Salim S Abdool
    Introduction Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods. METHODS: Forty HIV-infected, antiretroviral therapy-naïve women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital fluid collected using the MC with subsequent CVL, or by CVL alone. Qualitative data, which assessed levels of comfort and acceptability of MC using a 5-point Likert scale, was collected. Luminex multiplex assays were used to measure HIV-specific IgG against multiple gene products and 48 cytokines. RESULTS: The majority (94%) of participants indicated that insertion, wearing and removal of the MC was comfortable. Nineteen MCs with 18 matching, subsequent CVLs and 20 randomized CVLs were available for analysis. Mucosal IgG responses against four HIV-antigens were detected in 99% of MCs compared to only 80% of randomized CVLs (p = 0.029). Higher specific antibody activity and total antibodies were observed in MCs compared to CVL (all p<0.001). In MCs, 42/48 (88%) cytokines were in the detectable range in all participants compared to 27/48 (54%) in CVL (p<0.001). Concentrations of 22/41 cytokines (53.7%) were significantly higher in fluid collected by MC. Both total IgG (r = 0.63; p = 0.005) and cytokine concentrations (r = 0.90; p<0.001) correlated strongly between MC and corresponding post-MC CVL. CONCLUSIONS: MC sampling improves the detection of mucosal cytokines and antibodies, particularly those present at low concentrations. MC may therefore represent an ideal tool to assess immunological parameters in genital secretions, without interfering with concurrent collection of conventional CVL samples.
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    Utilizing nucleic acid amplification to identify acute HIV infection
    (2007) Karim, Salim S Abdool; Mlisana, Koleka; Kharsany, Ayesha B M; Williamson, Carolyn; Baxter, Cheryl; Karim, Quarraisha Abdool
    Two case reports have recently been published describing possible immune reconstitution inflammatory syndrome (IRIS) to Strongyloides infection [1,2]; however, there is debate as to whether the presentations may alternatively be caused by Strongyloides hyperinfection [3]. We report, we believe for the first time, a case that fulfils the criteria for Strongyloides IRIS with no evidence of hyperinfection syndrome.
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    Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes
    (Public Library of Science, 2013) Wibmer, Constantinos Kurt; Bhiman, Jinal N; Gray, Elin S; Tumba, Nancy; Karim, Salim S Abdool; Williamson, Carolyn; Morris, Lynn; Moore, Penny L
    Identifying the targets of broadly neutralizing antibodies to HIV-1 and understanding how these antibodies develop remain important goals in the quest to rationally develop an HIV-1 vaccine. We previously identified a participant in the CAPRISA Acute Infection Cohort (CAP257) whose plasma neutralized 84% of heterologous viruses. In this study we showed that breadth in CAP257 was largely due to the sequential, transient appearance of three distinct broadly neutralizing antibody specificities spanning the first 4.5 years of infection. The first specificity targeted an epitope in the V2 region of gp120 that was also recognized by strain-specific antibodies 7 weeks earlier. Specificity for the autologous virus was determined largely by a rare N167 antigenic variant of V2, with viral escape to the more common D167 immunotype coinciding with the development of the first wave of broadly neutralizing antibodies. Escape from these broadly neutralizing V2 antibodies through deletion of the glycan at N160 was associated with exposure of an epitope in the CD4 binding site that became the target for a second wave of broadly neutralizing antibodies. Neutralization by these CD4 binding site antibodies was almost entirely dependent on the glycan at position N276. Early viral escape mutations in the CD4 binding site drove an increase in wave two neutralization breadth, as this second wave of heterologous neutralization matured to recognize multiple immunotypes within this site. The third wave targeted a quaternary epitope that did not overlap any of the four known sites of vulnerability on the HIV-1 envelope and remains undefined. Altogether this study showed that the human immune system is capable of generating multiple broadly neutralizing antibodies in response to a constantly evolving viral population that exposes new targets as a consequence of escape from earlier neutralizing antibodies.