Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model

Use of amplification refractory mutation system PCR assay as a simple and effective tool to detect HIV-1 drug resistance mutations

Access to genotyping assays to determine successful antiretroviral treatment (ART) is limited in resource-constrained settings by high cost, suggesting the need for a cost-effective and simplified method to identify HIV-1 drug resistance (HIVDR) mutations. In this study, an amplification refractory mutation system (ARMS)-PCR assay was developed and used to investigate the most frequent HIVDR mutations affecting first-line ART in settings where WHO ART guidelines are applied. Seventy-five HIV-positive (HIV(+)) samples from Cameroon were used to assess the performance of this assay. Sequencing of HIV-1 reverse transcriptase was simultaneously performed for comparison, and discordant samples were tested with a Trugene HIV-1 genotyping kit. The ARMS-PCR assay was able to detect M184V, T215Y/F, K103N, and Y181C mutations with sensitivities of 96.8%, 85.7%, 91.3%, and 70%, respectively, and specificities of 90.6%, 95%, 100%, 96.9%, respectively, compared with data on sequencing. The results indicated the highest positive predictive value for K103N (100%) and the highest negative predictive value for M184V (97.5%). ARMS-PCR's limits of detection for mutations M184V, T215Y/F, K103N, and Y181C were <75 copies/ml, 143 copies/ml, 143 copies/ml, and 836 copies/ml, respectively. ARMS-PCR efficiently identified mutations in individuals harboring different HIV-1 clades (CRF02_AG and non-CRF02_AG). In addition, this approach was more cost-effective than other genotyping assays. The high throughput, the cost-effectiveness, and the simplicity of the ARMS-PCR assay make it a suitable tool to monitor HIVDR patterns in resource-constrained settings with broad HIV-1 genetic diversity

HIV type 1 group M clades infecting subjects from rural villages in Equatorial rain forests of Cameroon

Not the final published versionThough the HIV-1 subtypes infecting patients living in urban and semi-urban areas in Cameroon have been reported, information on the subtypes infecting patients in rural villages is lacking. To begin to understand the diversity of the HIV-1 group M subtypes infecting persons living in rural villages in the equatorial rain forest regions of Cameroon, 49 plasma samples from 14 rural villages in four provinces of Cameroon were analyzed using heteroduplex mobility analysis (HMA), DNA sequencing, and phylogenetic tree analysis on the basis of env C2V5, gag, or pol regions. Sixty-one percent of the group M infections were clade A or CRF02_AG-like as subtyped by env and gag. Of the remaining group M infections, 12% were either A or CRF02_AG-like or CRF01_AE-like in recombination with other clades; 25% were infections that were entirely non-A or non-CRF02_AG-like; and 2% were CRF11_cpx. The HIV-1 group M clades identified included A, D, F (F2), G, and H. The CRF strains identified were CRF02_AG-like, CRF01_AE-like, and CRF11_cpx. Two new intersubtype recombinant infections, H/G and A/F2, were identified. This study suggests that the HIV-1 diversity in rural villages in the equatorial rain forest of Cameroon is at least as broad as has been observed in major cities of Cameroon and that multiple HIV-1 group M subtypes are infecting persons living in the countryside of Cameroon