This study aimed to reconstruct the evolutionary history of Beijing strains of Mycobacterium tuberculosis and to test the hypothesis that evolution has influenced the ability of the Beijing strains within the different Beijing sublineages to spread and cause disease. A PCR-based method was used to analyze the genome structure of 40 different loci in 325 Beijing isolates collected from new and retreatment tuberculosis patients from an urban setting and 270 Beijing isolates collected from high-risk tuberculosis patients from a rural setting in the Western Cape, South Africa. The resulting data were subjected to phylogenetic analysis using the neighbor joining algorithm. Phylogenetic reconstructions were highly congruent with the "gold standard" phylogenetic tree based on synonymous single-nucleotide polymorphisms, thereby allowing a prediction of the order in which the evolutionary events had occurred. A total of seven independently evolving Beijing sublineages were identified. Analysis of epidemiological data in relation to the Beijing sublineage suggested an association between recent evolutionary change and frequency of occurrence in an urban population (P < 0.001) as well as in the rural population (P < 0.001). This concept was further supported by an association between more recently evolved Beijing strains and an increased ability to transmit and to cause disease (odds ratio, 5.82; 95% confidence interval, 3.13 to 10.82 [P < 0.001]). An association between Beijing sublineage and demographic and clinical parameters and drug resistance could not be demonstrated. From these data, we suggest that the pathogenic characteristics of Beijing strains are not conserved but rather that strains within individual lineages have evolved unique pathogenic characteristics.
Human-wildlife conflict (HWC) is a complex conservation issue and acknowledging the human dimensions of the problem is critical. Here we propose the Wildlife Tolerance Model (WTM), a novel theoretical framework to identify key drivers of tolerance to living with damage-causing wildlife. The WTM proposes an outer model, where the extent to which a person experiences a species determines perceptions of costs relative to benefits of living with a species. This in turn determines tolerance. A second component, the inner model predicts eleven variables that may further drive perceptions of costs and benefits. In the current paper we test the outer model while in a forthcoming publication we test the inner model using a case study of humanbaboon conflict in Cape Town, South Africa. Using Partial Least Squares Structural Equation Modeling we found support for the outer model. Experience explained 30% of variance in costs and benefits and 60% of tolerance was explained by perceptions of costs and benefits. Intangible costs and intangible benefits equally contributed to driving tolerance but tangible costs had no significant effect on tolerance. Separating two dimensions of experience, (i) exposure to a species explained costs more than benefits, and (ii) positive experiences explained intangible costs and benefits more than tangible costs while negative experiences equally explained costs and benefits. We discuss management implications of the findings and conclude that the WTM could be a useful diagnostic tool and theoretical framework to inform management interventions and policies to mitigate HWC.
Objectives
To evaluate the effect of early versus deferred antiretroviral therapy (ART) on neurodevelopment of infants from Cape Town participating in the CHER (Children with HIV Early Antiretroviral Therapy) trial.
Design
HIV-infected infants were randomised to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data.
Methods
Neurological examination and Griffiths Mental Development Scales (GMDS) were administered between 10–16 months of age, by testers blind to HIV status and randomised allocation. Mean quotients were compared using paired t-tests.
Results
64 infants on early ART and 26 on deferred ART (of potential 77 and 38 respectively on CHER trial) were assessed at median age 11 months (range 10-16). On the GMDS, all scores were lower in the deferred arm and the General Griffiths and Locomotor Scores were significantly lower: mean (standard deviation): 100.1 (13.8) vs 106.3 (10.6) p=0.02; and 88.9 (16.3) vs 97.7 (12.5), p<0.01, respectively. Children with HIV who received early ART performed as well as children without HIV except on the locomotor subscale. Both infected and uninfected mean GMDS scores were within the average range.
Conclusions
Infants initiated on early ART have significantly better Locomotor and General Scores on the GMDS at median age 11 months compared to infants on deferred ART, despite careful monitoring and ready access to ART in the latter.
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