Open Access Publications

Open Access HIV & TB PublicationsThe Victor Daitz Information Gateway provides financial support to HIV and TB researchers at the University of KwaZulu-Natal wishing to publish papers in Open Access journals. The list of Open Access articles below are papers published with the support of the Victor Daitz Information Gateway.

  • Mntlangula NM, Khuzwayo, N, & Taylor M

    Health SA Gesondheid, Vol 22, Issue , 12/2017

    HIV and AIDS, sexually transmitted infections (STIs) and tuberculosis (TB) are common co-infections in South Africa, and constitute major public health problems. Nurses have frequent contact with HIV positive and TB co-infected patients, their counselling behaviour being influenced by knowledge about counselling as well as their beliefs, attitudes and perceptions about barriers to counselling.

    The purpose of the survey was to assess the knowledge, attitude and beliefs of nurses about behavioural counselling for HIV and AIDS, STIs and TB (HAST) in three areas of the eThekwini Municipality.

    This was a quantitative descriptive cross sectional study, with stratified sampling being used to select 87 nurses from 24 PHC facilities who completed self-administered questionnaires. The most significant factors associated with the knowledge, attitude and beliefs of nurses about counselling behaviour were their age and level of education. Nurses were well informed about counselling behaviour (mean scores 4.1/5). However, the potential barriers to implementing effective counselling behaviour included their negative perceptions about counselling in HAST.

    There is an urgent need for further studies to explore barriers to counselling behaviour and how these can be addressed by the nurses and their managers.

  • Parboosing R, Chonco L, de la Mata FJ, Govender T, Maguire GE, Kruger HG

    International Journal of Nanomedicine, Vol 12, Issue , 01/2017

    Encapsidation, the process during which the genomic RNA of HIV is packaged into viral particles, is an attractive target for antiviral therapy. This study explores a novel nanotechnology-based strategy to inhibit HIV encapsidation by an RNA decoy mechanism. The design of the 16-mer oligoribonucleotide (RNA) decoy is based on the sequence of stem loop 3 (SL3) of the HIV packaging signal (Ψ). Recognition of the packaging signal is essential to the encapsidation process. It is theorized that the decoy RNA, by mimicking the packaging signal, will disrupt HIV packaging if efficiently delivered into lymphocytes by complexation with a carbosilane dendrimer. The aim of the study is to measure the uptake, toxicity, and antiviral activity of the dendrimer–RNA nanocomplex.

    A dendriplex was formed between cationic carbosilane dendrimers and the RNA decoy. Uptake of the fluorescein-labeled RNA into MT4 lymphocytes was determined by flow cytometry and confocal microscopy. The cytoprotective effect (50% effective concentration [EC50]) and the effect on HIV replication were determined in vitro by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and viral load measurements, respectively.
     

    Flow cytometry and confocal imaging demonstrated efficient transfection of lymphocytes. The dendriplex containing the Ψ decoy showed some activity (EC50 =3.20 µM, selectivity index =8.4). However, there was no significant suppression of HIV viral load.
     

    Oligoribonucleotide decoys containing SL3 of the packaging sequence are efficiently delivered into lymphocytes by carbosilane dendrimers where they exhibit a modest cytoprotective effect against HIV infection.

  • Chinta KC, Saini V, Glasgow JN, Mazorodze JH, Rahman MA, Reddy D, Lancaster JR Jr, Steyn AJ

    Nitric Oxide, Vol 59, Issue , 07/2016

    Mycobacterium tuberculosis (Mtb) is a facultative intracellular pathogen and the second largest contributor to global mortality caused by an infectious agent after HIV. In infected host cells, Mtb is faced with a harsh intracellular environment including hypoxia and the release of nitric oxide (NO) and carbon monoxide (CO) by immune cells. Hypoxia, NO and CO induce a state of in vitro dormancy where Mtb senses these gases via the DosS and DosT heme sensor kinase proteins, which in turn induce a set of ∼47 genes, known as the Mtb Dos dormancy regulon. On the contrary, both iNOS and HO-1, which produce NO and CO, respectively, have been shown to be important against mycobacterial disease progression. In this review, we discuss the impact of O2, NO and CO on Mtb physiology and in host responses to Mtb infection as well as the potential role of another major endogenous gas, hydrogen sulfide (H2S), in Mtb pathogenesis.

  • Cohen KA, El-Hay T, Wyres KL, Weissbrod O, Munsamy V, Yanover C, Aharonov R, Shaham O, Conway TC, Goldschmidt Y, Bishai WR, Pym AS

    EBioMedicine, Vol 9, Issue , 07/2016

    Mycobacterium tuberculosis (M. tuberculosis) is considered innately resistant to β-lactam antibiotics. However, there is evidence that susceptibility to β-lactam antibiotics in combination with β–lactamase inhibitors is variable among clinical isolates, and these may present therapeutic options for drug-resistant cases. Here we report our investigation of susceptibility to β-lactam/β–lactamase inhibitor combinations among clinical isolates of M. tuberculosis, and the use of comparative genomics to understand the observed heterogeneity in susceptibility. Eighty-nine South African clinical isolates of varying first and second-line drug susceptibility patterns and two reference strains of M. tuberculosis underwent minimum inhibitory concentration (MIC) determination to two β-lactams: amoxicillin and meropenem, both alone and in combination with clavulanate, a β–lactamase inhibitor. 41/91 (45%) of tested isolates were found to be hypersusceptible to amoxicillin/clavulanate relative to reference strains, including 14/24 (58%) of multiple drug-resistant (MDR) and 22/38 (58%) of extensively drug-resistant (XDR) isolates. Genome-wide polymorphisms identified using whole-genome sequencing were used in a phylogenetically-aware linear mixed model to identify polymorphisms associated with amoxicillin/clavulanate susceptibility. Susceptibility to amoxicillin/clavulanate was over-represented among isolates within a specific clade (LAM4), in particular among XDR strains. Twelve sets of polymorphisms were identified as putative markers of amoxicillin/clavulanate susceptibility, five of which were confined solely to LAM4. Within the LAM4 clade, ‘paradoxical hypersusceptibility’ to amoxicillin/clavulanate has evolved in parallel to first and second-line drug resistance. Given the high prevalence of LAM4 among XDR TB in South Africa, our data support an expanded role for β-lactam/β-lactamase inhibitor combinations for treatment of drug-resistant M. tuberculosis.

  • Dirk A Lamprecht, Peter M Finin, Mohammed A Rahman, Bridgette M Cumming, Shannon L Russell, Surendranadha R Jonnala, John H Adamson, Adrie JC Steyn

    Nature Communications, Vol 7, Issue , 08/2016

    The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received significant attention as a drug target, however its vulnerability may be affected by its flexibility in response to disruption. Here we determine the effect of the ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the value of the ETC as a drug target, by measuring Mtb’s respiration using extracellular flux technology. We find that Mtb’s ETC rapidly reroutes around inhibition by these drugs and increases total respiration to maintain ATP levels. Rerouting is possible because Mtb rapidly switches between terminal oxidases, and, unlike eukaryotes, is not susceptible to back pressure. Increased ETC activity potentiates clofazimine’s production of reactive oxygen species, causing rapid killing in vitro and in a macrophage model. Our results indicate that combination therapy targeting the ETC can be exploited to enhance killing of Mtb.

Pages