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Megan B Murray

Publications and source records attributed to Megan B Murray.

7 recordsLinked to original sources
PubMed2025

Should neighbours of tuberculosis (TB) cases be prioritised for active case finding in high TB-burden settings? A prospective molecular epidemiological study.

INTRODUCTION: In high tuberculosis (TB)-burden countries, considerable transmission of Mycobacterium tuberculosis (M. tb) likely occurs outside of households. We aimed to estimate the TB prevalence and incidence in households and neighbourhoods around known TB cases and to understand transmission patterns. METHODS: Household and neighbourhood contacts of pulmonary TB index cases from contiguous areas in Bandung, Indonesia, were screened and followed up for 12 months. Sputum samples underwent smear microscopy, M. tb culture, Xpert MTB/RIF, DNA isolation and whole-genome sequencing (WGS). Pairwise single-nucleotide polymorphism (SNP) distance ≤12 defined transmission for pairs with known epidemiological links, or SNP≤3 for pairs without epidemiological link. An SNP=12 cut-off was used to characterise transmission clusters. RESULTS: From 213 index cases, 514 household and 4141 neighbourhood contacts underwent TB screening: 19 household (3.70%, 95% CI 2.24 to 5.71) and 45 neighbourhood (1.09%, 95% CI 0.79 to 1.45) contacts were identified with TB, of whom 18 (3.50%, 95% CI 2.20 to 5.48) and 38 (0.92%, 95% CI 0.65 to 1.13) respectively, were bacteriologically confirmed. During follow-up, 11 household and 13 neighbourhood contacts were identified with TB (incidence per 100 000 person-years: 2286 (95% CI 1286 to 4148) and 350 (95% CI 190 to 563)), of whom 6 and 8, respectively, were bacteriologically confirmed (incidence per 100 000 person-years: 1247 (95% CI 560 to 2776) and 201 (95% CI 101 to 402)). A total of 223 patient M. tb isolates underwent WGS. Of 15 intra-household pairs, 8 (53.3%) were transmission pairs. Of 24 neighbour to index case pairs, 1 (4.2%) was a transmission pair. 11 of 19 transmission pairs shared no epidemiological link. We identified 25 M. tb genetic clusters from 205 mono-TB isolates overall. CONCLUSION: Neighbours have lower prevalence and incidence of TB than household contacts, but twice as many cases. Very few received M. tb from their index case, suggesting uncontrolled community-wide transmission. Whole population active case finding may be necessary in high TB-burden settings.

Humans↗
PubMed2006

Cost-effectiveness of alternative blood-screening strategies for West Nile Virus in the United States.

BACKGROUND: West Nile virus (WNV) is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist. METHODS AND FINDINGS: We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire) to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding USD 1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings. CONCLUSIONS: In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients is cost saving. In areas with low levels of infection, a status-quo strategy using a standard questionnaire is cost-effective.

Blood Donors↗
PubMed2004

Isoniazid resistance and the future of drug-resistant tuberculosis.

Bacterial chromosomal mutations that confer antibiotic resistance often have deleterious effects that impose costs on reproductive fitness. This observation has led to the generalization that in the absence of the selection pressure exerted through treatment, the frequency of resistance will decrease. This model implies that the prudent use of antibiotics will eventually result in a decline in the prevalence of drug resistance. Recent work, however, suggests that some resistance-conferring mutations may not significantly impair fitness and that others may be accompanied by compensatory mutations that restore the organisms' reproductive potential. Thus drug resistance, once introduced, may persist unless specific measures are implemented to target prevalent drug-resistant cases. Here we present ecological evidence to support the hypothesis that mutations at the 315 position of katG confer isoniazid resistance for Mycobacterium tuberculosis without diminishing virulence or transmissibility.

Bacterial Proteins↗
PubMed2003

Modeling bacterial evolution with comparative-genome-based marker systems: application to Mycobacterium tuberculosis evolution and pathogenesis.

The comparative-genomic sequencing of two Mycobacterium tuberculosis strains enabled us to identify single nucleotide polymorphism (SNP) markers for studies of evolution, pathogenesis, and epidemiology in clinical M. tuberculosis. Phylogenetic analysis using these "comparative-genome markers" (CGMs) produced a highly unusual phylogeny with a complete absence of secondary branches. To investigate CGM-based phylogenies, we devised computer models to simulate sequence evolution and calculate new phylogenies based on an SNP format. We found that CGMs represent a distinct class of phylogenetic markers that depend critically on the genetic distances between compared "reference strains." Properly distanced reference strains generate CGMs that accurately depict evolutionary relationships, distorted only by branch collapse. Improperly distanced reference strains generate CGMs that distort and reroot outgroups. Applying this understanding to the CGM-based phylogeny of M. tuberculosis, we found evidence to suggest that this species is highly clonal without detectable lateral gene exchange. We noted indications of evolutionary bottlenecks, including one at the level of the PHRI "C" strain previously associated with particular virulence characteristics. Our evidence also suggests that loss of IS6110 to fewer than seven elements per genome is uncommon. Finally, we present population-based evidence that KasA, an important component of mycolic acid biosynthesis, develops G312S polymorphisms under selective pressure.

Bacterial Proteins↗