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Yacoob Mahomed Coovadia Sharana Mahomed Melendhran Pillay Lise Werner Koleka Mlisana 《PloS one》2013,8(11)
Setting
The dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH. Increasing proportions of rifampicin mono-resistance resistance (RMR) have recently been reported from South Africa and other countries.Objective
This laboratory based study was conducted at NHLS TB Laboratory, Durban, which is the reference laboratory for culture and susceptibility testing in KwaZulu-Natal. We retrospectively determined, for the period 2007 to 2009, the proportion of RMR amongst Mycobacterium tuberculosis (MTB) isolates, that were tested for both RIF and INH, using the gold standard of culture based phenotypic drug susceptibility testing (DST). Gender and age were also analysed to identify possible risk factors for RMR.Design
MTB culture positive sputum samples from 16,748 patients were analysed for susceptibility to RIF and INH during the period 2007 to 2009. RMR was defined as MTB resistant to RIF and susceptible to INH. For the purposes of this study, only the first specimen from each patient was included in the analysis.Results
RMR was observed throughout the study period. The proportion of RMR varied from a low of 7.3% to a high of 10.0% [overall 8.8%]. Overall, males had a 42% increased odds of being RMR as compared to females. In comparison to the 50 plus age group, RMR was 37% more likely to occur in the 25–29 year age category.Conclusion
We report higher proportions of RMR ranging from 7.3% to 10% [overall 8.8%] than previously reported in the literature. To avoid misclassification of RMR, detected by the GeneXpert, as MDR-TB, culture based phenotypic DST must be performed on a second specimen, as recommended by the SA NDOH TB guidelines as well as WHO. We suggest that two sputum samples should be obtained at the first visit. The second sputum sample should be stored at 4°C. The latter sample is then readily available for performing additional DST (phenotypic or genotypic) for 2nd lines drugs, resulting in a decreased waiting period for DST results to become available. 相似文献33.
Proliferative capacity of epitope-specific CD8 T-cell responses is inversely related to viral load in chronic human immunodeficiency virus type 1 infection 下载免费PDF全文
Day CL Kiepiela P Leslie AJ van der Stok M Nair K Ismail N Honeyborne I Crawford H Coovadia HM Goulder PJ Walker BD Klenerman P 《Journal of virology》2007,81(1):434-438
The relationship between the function of human immunodeficiency virus (HIV)-specific CD8 T-cell responses and viral load has not been defined. In this study, we used a panel of major histocompatibility complex class I tetramers to examine responses to frequently targeted CD8 T-cell epitopes in a large cohort of antiretroviral-therapy-na?ve HIV type 1 clade C virus-infected persons in KwaZulu Natal, South Africa. In terms of effector functions of proliferation, cytokine production, and degranulation, only proliferation showed a significant correlation with viral load. This robust inverse relationship provides an important functional correlate of viral control relevant to both vaccine design and evaluation. 相似文献
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Christina F. Thobakgale Andrew Prendergast Hayley Crawford Nompumelelo Mkhwanazi Danni Ramduth Sharon Reddy Claudia Molina Zenele Mncube Alasdair Leslie Julia Prado Fundi Chonco Wendy Mphatshwe Gareth Tudor-Williams Prakash Jeena Natasha Blanckenberg Krista Dong Photini Kiepiela Hoosen Coovadia Thumbi Ndung'u Bruce D. Walker Philip J. R. Goulder 《Journal of virology》2015,89(15):8101
35.
Background
Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.Methods and Findings
A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6–24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB.Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons.Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).Conclusion
Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation. 相似文献36.
Phuti E. Makgotlho Marleen M. Kock Anwar Hoosen Ruth Lekalakala Shaheed Omar Michael Dove & Marthie M. Ehlers 《FEMS immunology and medical microbiology》2009,57(2):104-115
The aim of this study was to identify and characterize 97 methicillin-resistant Staphylococcus aureus (MRSA) isolates. Two conventional multiplex PCR assays, a real-time PCR assay and two PCR-based genotyping techniques including the spa - and hypervariable region (HVR)-typing methods were used to identify and characterize 97 MRSA strains isolated between April 2006 to September 2007 from the Steve Biko Academic Hospital. All MRSA isolates were positive for 16S rRNA gene, 99% were positive for the mec A gene and 4% positive for the Panton–Valentine leukocidin (PVL) gene. Staphylococcal cassette chromosome mec (SCC mec ) typing showed 67% of isolates were SCC mec II [health-care-associated MRSA (HA-MRSA)], 14% were SCC mec III (HA-MRSA) and 4% were SCC mec IVd [community-associated MRSA (CA-MRSA)]. These CA-MRSA isolates showed a prevalence of 100% for the PVL gene. Using spa typing, three distinct clusters could be identified while HVR typing revealed six different clusters. CA-MRSA isolates were clustered together using spa and HVR typing. This study showed the prevalence of the CA-MRSA strains, PVL genes, the SCC mec types and the clonality of the MRSA strains. The high prevalence of the PVL gene in CA-MRSA isolates already residing in intensive care units was alarming and indicated the emergence of new MRSA lineages with a particular fitness for community and hospital transmission. 相似文献
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Renaud Becquet Ruth Bland Valériane Leroy Nigel C. Rollins Didier K. Ekouevi Anna Coutsoudis Fran?ois Dabis Hoosen M. Coovadia Roger Salamon Marie-Louise Newell 《PloS one》2009,4(10)
Background
Both breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified.Methodology and Principal Findings
Pooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were achieved, but with longer duration (Vertical Transmission Study, VTS). 18-months HIV postnatal transmission (PT) was estimated by Kaplan-Meier in infants who were HIV negative, and assumed uninfected, at age >1 month. Censoring with (to assess impact of mode of breastfeeding) and without (to assess effect of breastfeeding duration) breastfeeding cessation considered as a competing event. Of 1195 breastfed infants, not HIV-infected perinatally, 38% DP and 83% VTS children were still breastfed at age 6 months. By age 3 months, 66% of VTS children were exclusively breastfed since birth and 55% of DP infants predominantly breastfed (breastmilk+water-based drinks). 18-month PT risk (95%CI) in VTS was double that in DP: 9% (7–11) and 5% (3–8), respectively (p = 0.03). However, once duration of breastfeeding was allowed for in a competing risk analysis assuming that all children would have been breastfed for 18-month, the estimated PT risk was 16% (8–28) in DP and 14% (10–18) in VTS (p = 0.32). 18-months PT risk was 3.9% (2.3–6.5) among infants breastfed for less than 6 months, and 8.7% (6.8–11.0) among children breastfed for more than 6 months; crude hazard ratio (HR): 2.1 (1.2–3.7), p = 0.02; adjusted HR 1.8 (0.9–3.4), p = 0.06. In individual analyses of PT rates for specific breastfeeding durations, risks among children exclusively breastfed were very similar to those in children predominantly breastfed for the same period. Children exposed to solid foods during the first 2 months of life were 2.9 (1.1–8.0) times more likely to be infected postnatally than children never exposed to solids this early (adjusted competing risk analysis, p = 0.04).Conclusions
Breastfeeding duration is a major determinant of postnatal HIV transmission. The PT risk did not differ between exclusively and predominantly breastfed children; the negative effect of mixed breastfeeding with solids on PT were confirmed. 相似文献38.
Haemophilus ducreyi is the causative bacterium of genital ulcers, which are collectively known as chancroid. Little is known about the cytotoxicity of H. ducreyi. The virulent strains are relatively resistant to phagocytosis and apoptosis by neutrophils. Therefore, experiments were designed to examine whether neutrophil degranulation caused by H. ducrey would provide insights into the virulence mechanisms through which cellular damage is affected by the organism. Clinical isolates of eight strains of H. ducreyi and the culture strain type CIP542 (Collection Institute Pasteur) were incubated with neutrophils harvested from human donor blood. The release by the organism of lysosomal enzymes from intracellular granules of neutrophils was indicative of degranulation. The results showed that H. ducreyi triggered the release of lysosomal enzymes from human neutrophils, and that the magnitude of the release was dependent both on the ratio of bacteria to neutrophils and the duration of incubation. In vitro experiments involving HeLa cells were designed to determine the manner in which H. ducreyi initiated the process of degranulation. The morphological changes associated with degranulation were visualized by confocal and transmission electron microscopy. This is the first report that describes degranulation of neutrophils induced by H. ducreyi which causes chancroid infection. 相似文献
39.
Mkwanazi NB Patel D Newell ML Rollins NC Coutsoudis A Coovadia HM Bland RM 《PloS one》2008,3(10):e3501
Background
Rapid testing of pregnant women aims to increase uptake of HIV testing and results and thus optimize care. We report on the acceptability of HIV counselling and testing, and uptake of results, before and after the introduction of rapid testing in this area.Methods and Principal Findings
HIV counsellors offered counselling and testing to women attending 8 antenatal clinics, prior to enrolment into a study examining infant feeding and postnatal HIV transmission. From August 2001 to April 2003, blood was sent for HIV ELISA testing in line with the Prevention of Mother-to-Child Transmission (PMTCT) programme in the district. From May 2003 to September 2004 women were offered a rapid HIV test as part of the PMTCT programme, but also continued to have ELISA testing for study purposes. Of 12,323 women counselled, 5,879 attended clinic prior to May 2003, and 6,444 after May 2003 when rapid testing was introduced; of whom 4,324 (74.6%) and 4,810 (74.6%) agreed to have an HIV test respectively. Of the 4,810 women who had a rapid HIV test, only 166 (3.4%) requested to receive their results on the same day as testing, the remainder opted to return for results at a later appointment. Women with secondary school education were less likely to agree to testing than those with no education (AOR 0.648, p<0.001), as were women aged 21–35 (AOR 0.762, p<0.001) and >35 years (AOR 0.756, p<0.01) compared to those <20 years.Conclusions
Contrary to other reports, few women who had rapid tests accepted their HIV results the same day. Finding strategies to increase the proportion of pregnant women knowing their HIV results is critical so that appropriate care can be given. 相似文献40.