SummaryBackgroundRecurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing—which is more accurate than conventional typing used to date—to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.MethodsWe assessed patients from the REMoxTB trial—a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.FindingsWe assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0–6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.InterpretationWhole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.FundingWellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.

Retention in HIV medical care has been recognized as critical for long-term favorable clinical outcomes among HIV-positive patients. However, relatively little is known about specific factors related to HIV medical care adherence among HIV-positive women in rural areas in the United States, where the epidemic is rapidly growing among minorities and women. The objective of the current study was to assess barriers and facilitators to HIV clinic visit adherence among HIV-positive women in the rural southeastern region of the United States. Forty HIV-positive women were recruited from four outpatient clinics providing services to HIV-positive patients residing in 23 predominately rural counties in Alabama. Four focus groups were conducted ranging from 5 to 16 participants each. Content analysis was used to analyze and interpret the data. Data coding and sorting was conducted using QRS NVivo 8 software. Participants were predominately African American (92.3%) ranging in age from 29 to 69 years (mean = 46.1 years). On average, participants reported living with HIV for 8.8 years. Factors that impacted participants' ability to maintain clinic visit appointments included personal, contextual, and community/environmental factors that included: patient/provider relationships, family support, access to transportation, organizational infrastructure of the health care facility visited and perceived HIV stigma within their communities. The current study highlights the myriad of retention-in-care barriers faced by HIV-positive women living in rural areas in the southeastern United States. Innovative multilevel interventions that address these factors are sorely needed to increase long-term retention-in-care among HIV-positive women residing in rural areas.

A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro, 98% (n ‫؍‬ 96) of sputum samples with a known number of bacilli (10 7 to 10 2 bacilli) could be enumerated within 0.5 log 10 . In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log 10 (95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml ؊1 sputum at day 0 (linear regression, P ‫؍‬ 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log 10 increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).

Multidrug resistance (MDR) represents a global threat to health. Here, we used whole genome sequencing to characterise Pseudomonas aeruginosa MDR clinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicates that: 1) these large plasmids comprise an emerging family present in different members of the Pseudomonas genus, and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the accessory genome of the megaplasmid family is highly flexible and diverse. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s.

During the transition to adulthood, many unhealthy behaviors are developed that in turn shape behaviors, health, and mortality in later life. However, research on unhealthy behaviors and risky transitions has mostly focused on one health problem at a time. In this article, we examine variation in health behavior trajectories, how trajectories cluster together, and how the likelihood of experiencing different behavior trajectories varies by sociodemographic characteristics. We use the National Longitudinal Study of Adolescent Health (Add Health) Waves I to IV to chart the most common health behavior trajectories over the transition to adulthood for cigarette smoking, alcohol consumption, obesity, and sedentary behavior. We find that health behavior trajectories cluster together in seven joint classes and that sociodemographic factors (including gender, parental education, and race-ethnicity) significantly predict membership in these joint trajectories.

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Despite the wide availability of effective treatments for HIV disease, many HIV-infected individuals are not in care, and HIV-infected women, particularly those residing in resource-poor areas, may have greater difficulty accessing HIV care than men. The purpose of this research was to explore perceived barriers to care experienced by HIV-infected women living in the Deep South region of the United States. Qualitative research methods were used to generate in-depth descriptions of women's experiences in accessing HIV care. Participants (N = 40) were recruited from 4 community-based HIV service organizations to participate in focus groups. Sessions lasted approximately 2 hours and were audio recorded. Verbatim transcripts, demographic data, and observational notes were subjected to content analysis strategies that coded the data into categories. Five categories of barriers to HIV care were identified as follows: personal, social, financial, geographic/transportation, and health system barriers. Implications of the findings for future research and practice are discussed in this study.

Coefficient of friction (COF) measurements and AFM of LLDPE films containing erucamide and behenamide indicated that COF reduction is not necessarily dependent on additive coverage of the film surface. A film containing 1010 ppm erucamide yielded a kinetic COF of 0.2 without complete surface coverage, whereas a 1080 ppm behenamide film exhibited a saturated surface and higher COF. AFM showed distinct differences in crystal formation between the surface-segregated additives, with erucamide exhibiting a plate-like structure.