71 research outputs found
Anaemia in acute HIV-1 subtype C infection.
No full textBACKGROUND: 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
Establishing a cohort at high risk of HIV infection in South Africa: challenges and experiences of the CAPRISA 002 acute infection study.
No full textOBJECTIVES: To describe the baseline demographic data, clinical characteristics and HIV-incidence rates of a cohort at high risk for HIV infection in South Africa as well as the challenges experienced in establishing and maintaining the cohort. METHODOLOGY/PRINCIPLE FINDINGS: Between August 2004 and May 2005 a cohort of HIV-uninfected women was established for the CAPRISA 002 Acute Infection Study, a natural history study of HIV-1 subtype C infection. Volunteers were identified through peer-outreach. The cohort was followed monthly to determine HIV infection rates and clinical presentation of early HIV infection. Risk reduction counselling and male and female condoms were provided. After screening 775 individuals, a cohort of 245 uninfected high-risk women was established. HIV-prevalence at screening was 59.6% (95% CI: 55.9% to 62.8%) posing a challenge in accruing HIV-uninfected women. The majority of women (78.8%) were self-identified as sex-workers with a median of 2 clients per day. Most women (95%) reported more than one casual sexual partner in the previous 3 months (excluding clients) and 58.8% reported condom use in their last sexual encounter. Based on laboratory testing, 62.0% had a sexually transmitted infection at baseline. During 390 person-years of follow-up, 28 infections occurred yielding seroincidence rate of 7.2 (95% CI: 4.5 to 9.8) per 100 person-years. Despite the high mobility of this sex worker cohort retention rate after 2 years was 86.1%. High co-morbidity created challenges for ancillary care provision, both in terms of human and financial resources. CONCLUSIONS/SIGNIFICANCE: Challenges experienced were high baseline HIV-prevalence, lower than anticipated HIV-incidence and difficulties retaining participants. Despite challenges, we have successfully accrued this cohort of HIV-uninfected women with favourable retention, enabling us to study the natural history of HIV-1 during acute HIV-infection. Our experiences provide lessons for others establishing similar cohorts, which will be key for advancing the vaccine and prevention research agenda in resource-constrained settings
Evolution of HIV-1 subtype C immune responses during acute and chronic HIV infection
No full textThe aim of this study was to compare the magnitude and breadth of HIV-specific T cell responses to HIV Gag and Nef mounted during acute HIV infection with those that emerged during chronic infection and to investigate the association of these responses with subsequent HIV disease progression (CD4 counts and plasma viral loads)
Human immunodeficiency virus-specific gamma interferon enzyme-linked immunospot assay responses targeting specific regions of the proteome during primary subtype C infection are poor predictors of the course of viremia and set point.
No full textIt is unknown whether patterns of human immunodeficiency virus (HIV)-specific T-cell responses during acute infection may influence the viral set point and the course of disease. We wished to establish whether the magnitude and breadth of HIV type 1 (HIV-1)-specific T-cell responses at 3 months postinfection were correlated with the viral-load set point at 12 months and hypothesized that the magnitude and breadth of HIV-specific T-cell responses during primary infection would predict the set point. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay responses across the complete proteome were measured in 47 subtype C HIV-1-infected participants at a median of 12 weeks postinfection. When corrected for amino acid length and individuals responding to each region, the order of recognition was as follows: Nef > Gag > Pol > Rev > Vpr > Env > Vpu > Vif > Tat. Nef responses were significantly (P < 0.05) dominant, targeted six epitopic regions, and were unrelated to the course of viremia. There was no significant difference in the magnitude and breadth of responses for each protein region with disease progression, although there was a trend of increased breadth (mean, four to seven pools) in rapid progressors. Correlation of the magnitude and breadth of IFN-gamma responses with the viral set point at 12 months revealed almost zero association for each protein region. Taken together, these data demonstrate that the magnitude and breadth of IFN-gamma ELISPOT assay responses at 3 months postinfection are unrelated to the course of disease in the first year of infection and are not associated with, and have low predictive power for, the viral set point at 12 months
Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV-1 infection and associations with early disease progression.
No full textDeciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection
Adaptive changes in HIV-1 subtype c proteins during early infection and their effect on disease progression
No full textCHARACTERISING FACTORS PREDICTIVE OF INFECTION IN SEVERELY INJURED PATIENTS
No full textInfection after trauma complicates the patients clinical course. Infection leads to longer critical care and hospital stays, has been associated with increased mortality rates and places considerable cost pressures on health economies. The predictors of infection after severe injury are not known, and the effects on outcomes other than mortality are under-reported.
The overall objective of this research was to characterise factors predictive of infection in severely injured patients admitted to critical care. A prospective cohort study of 271 patients investigated admission factors predictive of the development of infection. A second study of 280 patients evaluated post-injury immune cell changes and the association with infection. Thirdly the relationship between early coagulopathy and infections was investigated in 158 patients. Finally a study of 385 patients examined the use of Tranexamic Acid (TXA) and its association with infection and other outcomes.
Infection was a significant burden for severely injured patients. Admission hypoperfusion was the only early characteristic associated with the development of infection, and a dose dependent relationship was observed between severity of shock and increased percentage of infection (p<0.01). Lymphopenia prolonged to day four post injury was strongly predictive infection (OR 0.10, CI 0.02-0.48, p<0.01). At 24 hours, the anticoagulant Protein C was lower in those with infection (Infection: 70.2 iu/dL vs. No infection: 83.3 iu/dL p=0.02), and increased fibrinolysis was also associated with infectious complications (Infection: 6156 μg/L vs. No infection: 3324 μg/L p=0.03). There was a trend to a beneficial relationship between TXA and infection, and it was independently associated with reduced organ failure (OR 0.27, CI: 0.10 – 0.73, p=0.01) and mortality (OR 0.16 CI 0.03 - 0.86, p=0.03).
In severely injured patients, admission shock, prolonged lymphopenia and early coagulation dysfunction post severe injury were independent predictors of infection. Timely modulation of these responses after trauma may help to reduce the burden of infection
Characterisation of HIV superinfection : genetic evolution and adaptive immune responses
No full textIn this thesis we aimed to determine the timing and frequency of intra-subtype C superinfection, and to determine if the reason for superinfection was a greater genetic distance within epitopes of the superinfecting virus compared to those of circulating strains from the same cohort
Microbiological evaluation of different reprocessing methods for cuffed and un-cuffed tracheostomy tubes in home-care and hospital setting
No full textBackground: Manufacturers’ recommendations on cleaning of tracheostomy tubes focus on general warning information and non-specific manual cleaning procedures. The aim of this experimental study was to evaluate different reprocessing methods and to determine the mechanical integrity and functionality of tracheostomy tubes following reprocessing.
Methods: Sixteen cuffed or un-cuffed tracheostomy tubes obtained from hospital in-patients were reprocessed using one of the following reprocessing methods: a) manual brushing and rinsing with tap water, b) manual brushing followed by disinfection with a glutaraldehyde solution, c) manual brushing followed machine-based cleaning in a dishwasher, and d) manual brushing followed by ultrasound cleaning in a commercially available ultrasound device. Microbial burden of the tubes before and after reprocessing was assessed by measurement of microbial colony-forming units per mL (CFU/mL) of rinsing fluid. After cleaning, tracheostomy tubes were investigated for loss of functionality.
Findings: Manual brushing and rinsing with tap water reduced microbial colonization in average by 102 CFU/mL, but with poor reproducibility and reliability. Complete microbial reduction was achieved only with additional chemical or machine-based thermal disinfection. Ultrasound sonification yielded no further microbial reduction after manual brushing.
Conclusion: Manual brushing alone will not result in complete eradication of microorganism colonising cuffed or un-cuffed tracheostomy tubes. However, manual cleaning followed by chemical or thermal disinfection may be regarded as safe and reproducible reprocessing method. If a machine-based reprocessing method is used for cuffed tubes, the cuffs’ ventilation hose must be secured in a safe position prior to thermal disinfection
Why do clinicians place indwelling urinary catheters with patients in acute medical care?
No full textBackground: Indwelling urinary catheters (IUCs) placed for short-term use in hospital frequently become long-term catheters, increasing the potential for infections, trauma and other complications. Current research has focused on the prompt removal of IUCs in place, with no published review of interventions to reduce the initial placement. Furthermore, little is known about why clinicians place IUCs in acute medical care. Without this knowledge, the effectiveness of strategies aimed at reducing IUC use is likely to be sub-optimal.Aim: To understand why clinicians decide to place IUCs in acute medical care. Methods: (1) A systematic review of interventions to minimise the initial placement of urinary catheters in acute care. (2) A qualitative study in the A&E department and acute medical wards of a 1200+ bed hospital. Clinicians who made the decision to place an IUC were asked to participate in a retrospective think aloud interview describing how they came to the decision, later participating in a semi-structured interview to discuss their wider experiences of making the decision to place an IUC. A purposive sample and thematic analysis were used. Results: (1) Eight (six uncontrolled) studies met the inclusion criteria for the systematic review, using a variety of interventions including clinician education and introduction of guidelines to reduce IUC use. Although seven demonstrated a reduction in the initial use of IUCs post-intervention (relative risk 0.19 – 0.86), the impact of individual interventions was unclear. Notably, each study provided a list of reasons considered to provide justifications for IUC use, with substantial variation between the lists. (2) 30 retrospective think aloud interviews and 20 semi-structured interviews were undertaken. Clinicians were influenced by cues taken from three groups; individual beliefs (e.g. on the clinical indication or IUC-associated risks), patient factors (e.g. age or gender) and organisational factors (e.g. resources or policy). Many spectrums of belief were found (e.g. varying opinions on using IUCs to protect skin from urinary incontinence). Conclusions: This work establishes that understanding of interventions to reduce the initial placement of IUCs is poor and there is a lack of agreement on when the benefits of IUC use outweigh the risks. Clinical reasoning in this area is frequently inconsistent and IUC placement decisions vary widely, indicating that there is considerable scope for a reduction in use
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