A descriptive analysis of an outbreak of measles and a multilevel mixed-effects analysis of factors associated with case isolation in healthcare settings, London (February-June 2016).

OBJECTIVES: We described the epidemiology and healthcare exposures during a measles outbreak in London and identified factors associated with isolation on arrival to healthcare premises. STUDY DESIGN: We conducted a cohort study including all confirmed measles cases in London residents from February 1, 2016, to June 30, 2016, and semistructured interviews with two infection prevention and control teams (IPCTs). METHODS: We described the outbreak and conducted a multilevel mixed-effects analysis to assess the relationship between sociodemographic and clinical factors and isolation on arrival to healthcare premises. We summarised the interviews. RESULTS: There were 182 cases, mostly aged 17-35 years (46%; 84). Excluding cases younger than one year, 76% (92/120) were unvaccinated, including two healthcare workers. The majority presented with rash (97%; 174), and 42% (70/166) required hospitalisation. Of the recorded cases, 93% of cases (164/178) had visited a healthcare setting during their infectious period (median number of visits = 2). In 33% (59/178) of the visits, the case was isolated on arrival; when not isolated, four healthcare exposures resulted in further transmission. Presenting to the hospital as opposed to a general practitioner (GP) was associated with higher odds of isolation (odds ratio = 2.23, 95% confidence interval = 1.1-4.4) when adjusted for age, gender and presenting with a cough. The IPCT identified measles training using standardised risk assessments by triage nurses in accident and emergency and intelligence regarding measles activity in the community as positive measures to prevent healthcare exposures. CONCLUSIONS: We recommend opportunistic immunisation of unvaccinated young adults by GPs and that occupational health departments ensure their staff are protected against measles. Raising measles awareness in healthcare settings via training or regular sharing of current measles surveillance activity from public health to the IPCT and GP may improve triage and isolation of cases on arrival to healthcare premises.

Expected background rates of latent TB infection in London inner city schools: lessons from a TB contact investigation exercise in a secondary school.

Following an extensive contact tracing exercise at a school in a London borough with one of highest tuberculosis (TB) rates in England, we estimated the background prevalence of latent TB infection to be significantly less than the widely accepted 10%. We screened 271 pupils aged 14-15 years in two groups: 96 pupils in group 1 had significant exposure (>8 h/week in the same room) to a case of infectious TB and 175 in group 2 who had minimal exposure. In group 1, 26% were diagnosed with latent or active TB, compared to 6.3% in group 2. Risk factors for TB infection (e.g. previous exposure or link to high-prevalence communities) were analysed using a cohort study design. In the univariable analysis only being in contact group 1 was statistically significantly associated with being a case (OR 5.25, 95%, P < 0.001). In the multivariable model contact group 1 remained significantly associated with being a case (adjusted OR 4.40, P = 0.001). We concluded that the 6.3% yield of TB infection in contact group 2 is either similar to or higher than the background prevalence rate of latent TB infection (LTBI) in this high TB prevalence London borough. Other parts of England with lower TB prevalence are likely to have even lower LTBI rates.

Matchout deuterium labelling of proteins for small-angle neutron scattering studies using prokaryotic and eukaryotic expression systems and high cell-density cultures.

Small-angle neutron scattering (SANS) is a powerful technique for the characterisation of macromolecular structures and interactions. Its main advantage over other solution state approaches is the ability to use D2O/H2O solvent contrast variation to selectively match out specific parts of a multi-component system. While proteins, nucleic acids, and lipids are readily distinguished in this way, it is not possible to locate different parts of a protein-protein system without the introduction of additional contrast by selective deuteration. Here, we describe new methods by which 'matchout labelled' proteins can be produced using Escherichia coli and Pichia pastoris expression systems in high cell-density cultures. The method is designed to produce protein that has a scattering length density that is very close to that of 100% D2O, providing clear contrast when used with hydrogenated partner proteins in a complex. This allows the production of a single sample system for which SANS measurements at different solvent contrasts can be used to distinguish and model the hydrogenated component, the deuterated component, and the whole complex. The approach, which has significant cost advantages, has been extensively tested for both types of expression system.

Evaluation of the impact of fetal fibronectin test implementation on hospital admissions for preterm labour in Ontario: a multiple baseline time-series design.

OBJECTIVE: To determine the impact of a health system-wide fetal fibronectin (fFN) testing programme on the rates of hospital admission for preterm labour (PTL). DESIGN: Multiple baseline time-series design. SETTING: Canadian province of Ontario. POPULATION: A retrospective population-based cohort of antepartum and delivered obstetrical admissions in all Ontario hospitals between 1 April 2002 and 31 March 2010. METHODS: International Classification of Diseases codes in a health system-wide hospital administrative database were used to identify the study population and define the outcome measure. An aggregate time series of monthly rates of hospital admissions for PTL was analysed using segmented regression models after aligning the fFN test implementation date for each institution. MAIN OUTCOME MEASURE: Rate of obstetrical hospital admission for PTL. RESULTS: Estimated rates of hospital admission for PTL following fFN implementation were lower than predicted had pre-implementation trends prevailed. The reduction in the rate was modest, but statistically significant, when estimated at 12 months following fFN implementation (-0.96 hospital admissions for PTL per 100 preterm births; 95% confidence interval [CI], -1.02 to -0.90, P = 0.04). The statistically significant reduction was sustained at 24 and 36 months following implementation. CONCLUSIONS: Using a robust quasi-experimental study design to overcome confounding as a result of underlying secular trends or concurrent interventions, we found evidence of a small but statistically significant reduction in the health system-level rate of hospital admissions for PTL following implementation of fFN testing in a large Canadian province.

Net Inflow: An Important Target on the Path to Aquifer Sustainability.

Aquifers supporting irrigated agriculture are a resource of global importance. Many of these systems, however, are experiencing significant pumping-induced stress that threatens their continued viability as a water source for irrigation. Reductions in pumping are often the only option to extend the lifespans of these aquifers and the agricultural production they support. The impact of reductions depends on a quantity known as "net inflow" or "capture." We use data from a network of wells in the western Kansas portions of the High Plains aquifer in the central United States to demonstrate the importance of net inflow, how it can be estimated in the field, how it might vary in response to pumping reductions, and why use of "net inflow" may be preferred over "capture" in certain contexts. Net inflow has remained approximately constant over much of western Kansas for at least the last 15 to 25 years, thereby allowing it to serve as a target for sustainability efforts. The percent pumping reduction required to reach net inflow (i.e., stabilize water levels for the near term [years to a few decades]) can vary greatly over this region, which has important implications for groundwater management. However, the reduction does appear practically achievable (less than 30%) in many areas. The field-determined net inflow can play an important role in calibration of regional groundwater models; failure to reproduce its magnitude and temporal variations should prompt further calibration. Although net inflow is a universally applicable concept, the reliability of field estimates is greatest in seasonally pumped aquifers.

Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children's Oncology Group Report.

Optimal therapy for posttransplant lymphoproliferative disease (PTLD) remains problematic. A phase II trial adding rituximab to a low-dose cyclophosphamide and prednisone regimen was conducted for pediatric patients with Epstein-Barr virus (EBV) (+), CD20 (+) PTLD. Fifty-five patients were enrolled. Toxicity was similar for cycles of therapy containing rituximab versus those without. The complete remission (CR) rate was 69% (95% confidence interval (CI); 57%-84%). Of 12 patients with radiographic evidence of persistent disease at the end of therapy, eight were in CR 28 weeks later without further PTLD therapy. There were 10 deaths, 3 due to infections while receiving therapy and 7 from PTLD. The 2-year event-free survival (alive with functioning original allograft and no PTLD) was 71% (95% CI: 57%-82%) and overall survival was 83% (95% CI: 69%-91%) with median follow-up of 4.8 years. Due to small numbers, we were unable to determine significance of tumor histology, stage of disease, allograft type or early response to treatment on outcome. These data suggest rituximab combined with low-dose chemotherapy is safe and effective in treating pediatric with EBV (+) PTLD following solid-organ transplantation.

Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group.

OBJECTIVE: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ function. 3+3 dose escalation was used for phase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. RESULTS: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. CONCLUSIONS: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.

Behavior problems in children at time of first recognized seizure and changes over the following 3 years.

OBJECTIVES: The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. METHODS: Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. RESULTS: Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. CONCLUSIONS: Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents' confidence in their ability to handle their children's behavior.

Do molecules matter more than morphology? Promises and pitfalls in parasites.

Systematics involves resolving both the taxonomy and phylogenetic placement of organisms. We review the advantages and disadvantages of the two kinds of information commonly used for such inferences--morphological and molecular data--as applied to the systematics of metazoan parasites generally, with special attention to the malaria parasites. The problems that potentially confound the use of morphology in parasites include challenges to consistent specimen preservation, plasticity of features depending on hosts or other environmental factors, and morphological convergence. Molecular characters such as DNA sequences present an alternative data source and are particularly useful when not all the parasite's life stages are present or when parasitaemia is low. Nonetheless, molecular data can bring challenges that include troublesome DNA isolation, paralogous gene copies, difficulty in developing molecular markers, and preferential amplification in mixed species infections. Given the differential benefits and shortcomings of both molecular and morphological characters, both should be implemented in parasite taxonomy and phylogenetics.

Comparative 16S rRNA gene surveys of granular sludge from three upflow anaerobic bioreactors treating purified terephthalic acid (PTA) wastewater.

The microbial communities from three upflow anaerobic bioreactors treating purified terephthalic acid (PTA) wastewater were characterized with 16S ribosomal RNA gene sequencing surveys. Universal bacterial and archaeal primers were used to compare the bioreactor communities to each other. A total of 1,733 bacterial sequences and 383 archaeal sequences were characterized. The high number of Syntrophus spp. and Pelotomaculum spp. found within these reactors indicates efficient removal of benzoate and terephthalate. Under anaerobic conditions benzoate can be degraded through syntrophic associations between these bacteria and hydrogen-scavenging microbes, such as Desulfovibrio spp. and hydrogenotrophic methanogens, which remove H(2) to force the thermodynamically unfavourable reactions to take place. The authors did not observe a relatively high percentage of hydrogenotrophic methanogens with the archaeal gene survey because of a high acetate flux (acetate is a main component in PTA wastewater and is the main degradation product of terephthalate/benzoate fermentation), and because of the presence of Desulfovibrio spp. (a sulfate reducer that scavenges hydrogen). The high acetate flux also explains the high percentage of acetoclastic methanogens from the genus Methanosaeta among the archaeal sequences. A group of uncultured bacteria (OD1) may be involved in the degradation of p-toluate (4-methyl benzoate), which is a component of PTA wastewater.

Effect of estradiol preceding and progesterone subsequent to ovulation on proportion of postpartum beef cows pregnant.

Two experiments were conducted to examine the effect of plasma concentrations of 17ß-estradiol (E2) preceding and progesterone (P4) subsequent to ovulation on proportions of beef cows pregnant following embryo transfer. Timing of ovulation (d 0) among postpartum cows was synchronized and cows that expressed estrus were removed from each study. In Experiment 1, plasma E2 concentration on d 0 was used to classify cows (n = 353) into Low, Medium, and High E2 groups. Pregnancy rate for cows with Low, Medium, or High E2 concentrations were different (P < 0.05). In Experiment 2, there were multiple administrations of PGF2α to evaluate the independent effects of Low or High E2 before ovulation and Low or Normal (no treatment) P4 after ovulation on proportions of cows pregnant. Treatment groups in Experiment 2, therefore, were: Low E2-Low P4 (LL; n = 71), Low E2-Normal P4 (LN; n = 69), High E2-Low P4 (HL; n = 74), and High E2-Normal P4 (HN; n = 73). Concentrations of P4 on d 7 subsequent to ovulation were less (P < 0.05) in cows of the HL compared to HN, and in LL compared to LN groups. Concentrations of E2 on d -2, 0, and change in E2 (d -2 to d 0) had a positive effect (P < 0.008) on pregnancy rates. In summary, relatively greater E2 concentrations preceding ovulation; and relatively greater P4 concentrations subsequent to ovulation combined with lesser E2 concentrations preceding ovulation had a positive effect on proportions of postpartum cows pregnant.

Pandemic (H1N1) 2009 virus outbreak in a school in London, April-May 2009: an observational study.

On 29 April 2009, an imported case of pandemic (H1N1) 2009 virus infection was detected in a London school. As further cases, pupils and staff members were identified, school closure and mass prophylaxis were implemented. An observational descriptive study was conducted to provide an insight into the clinical presentation and transmission dynamics in this setting. Between 15 April and 15 May 2009, 91 symptomatic cases were identified: 33 were confirmed positive for pandemic (H1N1) 2009 virus infection; 57 were tested negative; in one the results were unavailable. Transmission occurred first within the school, and subsequently outside. Attack rates were 2% in pupils (15% in the 11-12 years age group) and 17% in household contacts. The predominant symptoms were fever (97%), respiratory symptoms (91%), and sore throat (79%). Limited spread in the school may have been due to a combination of school closure and mass prophylaxis. However, transmission continued through household contacts to other schools.

Academic problems in children with seizures: relationships with neuropsychological functioning and family variables during the 3 years after onset.

OBJECTIVES: Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. METHODS: As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6-14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock-Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. RESULTS: The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement (r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement (P ≤ 0.006), with stronger relationships among younger children (ß = 0.25-0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety (P = 0.04; stronger for more anxious parents, ß = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology (P = 0.02; stronger for symptomatic/cryptogenic vs idiopathic, ß = 0.29). Gender and other family variables did not have significant moderating effects. CONCLUSIONS: Changes in neuropsychological function were associated with changes in academic achievement following onset of seizures, with risk factors being younger age at onset, lower caregiver education, high parental anxiety, and symptomatic/cryptogenic etiology. Academic performance should be closely monitored in children with early-onset seizures.

The relative importance of host characteristics and co-infection in generating variation in Heligmosomoides polygyrus fecundity.

We examined the relative importance of intrinsic host factors and microparasite co-infection in generating variation in Heligmosomoides polygyrus fecundity, a parameter that serves as a proxy for infectiousness. We undertook extensive trapping of Apodemus flavicollis, the yellow-necked mouse in the woodlands of the Italian Alps and recorded eggs in utero from the dominant nematode species H. polygyrus, and tested for the presence of five microparasite infections. The results showed that sex and breeding status interact, such that males in breeding condition harboured more fecund nematodes than other hosts; in particular, worms from breeding males had, on average, 52% more eggs in utero than worms from non-breeding males. In contrast, we found a weak relationship between intensity and body mass, and no relationship between intensity and sex or intensity and breeding condition. We did not find any evidence to support the hypothesis that co-infection with microparasites contributed to variation in worm fecundity in this system. The age-intensity profiles for mice singly-infected with H. polygyrus and those co-infected with the nematode and at least one microparasite were both convex and not statistically different from each other. We concluded that intrinsic differences between hosts, specifically with regard to sex and breeding condition, contribute relatively more to the variation in worm fecundity than parasite co-infection status.

Investigations and control measures following a non-travel-associated case of toxigenic Cornyebacterium diphtheriae, London, United Kingdom, December 2009-January 2010.

This article reports the investigation and control measures undertaken following the identification of a toxigenic strain of Cornyebacterium diphtheriae var gravis, designated ribotype Minsk , in a partially vaccinated teenager born in the United Kingdom with no recent history of travel or known contact with a case of diphtheria or a carrier. This case highlights the need for ongoing work to improve vaccine uptake rates to ensure children receive all scheduled vaccinations.

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Diet-induced adiposity alters the serum profile of inflammation in C57BL/6N mice as measured by antibody array.

Morbid obesity is considered a systemic inflammatory state. The objective of this project was to characterize the adipokine, cytokine and chemokine protein profile in serum from control, lean and obese mice. We hypothesized that chemokines and cytokines are altered by caloric restriction and diet-induced obesity as a function of changes in body composition. Six-week-old female C57BL/6N mice (n = 12 per group) were randomized to one of three diets: control (fed ad libitum); lean (30% calorie-restricted regimen relative to control) and diet-induced obese (DIO; high calorie diet, fed ad libitum). Body weight, body composition and food intake were monitored throughout the study. After 10 weeks on the diets, blood samples were collected, and adipokine/cytokine/chemokine serum profiles were measured by antibody array. Lean mice, relative to the control group, displayed increased concentrations of insulin-like growth factor (IGF) binding protein-3, -5 and -6 and adiponectin and decreased IGF-1. These mice also showed increased concentrations of interleukin (IL)-10, IL-12 p40/p70, eotaxin, monocyte chemoattractant protein-5 and SDF-1. In contrast, DIO mice displayed increased leptin, IL-6 and LPS-induced chemokine and decreased concentrations of all chemokines/cytokines measured relative to control mice. As such, these data indicate that DIO may lead to an inflammatory state characterized as a shift towards a T helper lymphocyte type 1-skewed responsiveness. The demonstration of differential adipokine, cytokine and chemokine protein profile in control, lean and DIO mice may have implications for immune responsiveness and risk of disease.

Multi-site, multi-country evaluation of analytical and operational performance of a low-mid volume chemiluminescent immunoassay analyzer.

BACKGROUND: A new automated immunoassay low-mid volume (< or = 250 immunoassays/day) chemiluminescent analyzer, Abbott Architect i1000sR, was evaluated by seven laboratories around the world (4 in Europe, one each in Canada, Japan, and the U.S.A.) to demonstrate equivalent performance for key operating characteristics (e.g., precision, turn around time, limit of detection, functional sensitivity, and linearity). METHODS: The laboratories followed standard protocols to assess precision, limit of detection (LoD), functional sensitivity, assay linearity, method comparison, and sample carryover. Turn around time for three stat assays (beta-hCG, BNP, and CK-MB) and the time required to complete workloads of 50 and 100 tests with a mixture of 75% routine tests and 25% stat tests was also evaluated. RESULTS: Total precision was typically < 5% CV for nine immunoassays. Analytical performance met design goals and demonstrated equivalency to package insert data for assays on market and in use for an existing high volume immunoassay system. Stat turn around times were consistent with the fixed analytical time of 15.6 minutes and met the expectations of the laboratories. Measured test throughput ranged from 47 - 54 tests per hour and demonstrated that the analyzer was fit for the intended purpose of supporting a laboratory that performs < or = 250 immunoassays per day. CONCLUSIONS: A multisite, international analyzer familiarization study is a practical means of confirming that a new instrument meets both a manufacturer's design specifications and users' real world expectations and provides a pragmatic test for the system. The experience of investigators at seven sites around the world indicates that a new fully automated chemiluminescent system is suitable for use.

Burden of multidrug-resistant tuberculosis in England: a focus on prevalent cases.

The incidence of multidrug-resistant tuberculosis (MDR-TB) is routinely reported by the Public Health England, UK, but prevalence better represents burden. To estimate MDR-TB prevalence, and identify the factors associated with acquired resistance and unsuccessful outcomes in people managed by the health services. We included notified MDR-TB cases prevalent between 2010 and 2014. Multivariable logistic regression was used to identify the factors associated with acquisition of resistance and unsuccessful outcomes. The social risk factors (SRFs) recorded were alcohol, drug misuse, homelessness and incarceration. Between 2010 and 2014, there were 2.3-3.1 times more prevalent than incident cases each year, with an increasing prevalence-to-incidence ratio over time; 86% of prevalent cases were foreign-born, and 15% had an SRF. Overall, 11% of MDR-TB cases acquired resistance, including 18% of those with SRFs and 22% of UK-born MDR-TB cases acquired resistance. Half of the cases completed treatment by 24 months; those with SRFs, extensive drug resistance or acquired resistance were less likely to complete treatment. The number of prevalent cases is higher than incident cases, and increases over time, so a focus on prevalent cases enables better planning for services to support patients. We recommend that additional support be provided for those at risk of acquiring resistance, including those with SRFs. .