Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens.

BACKGROUND: Prospective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting. METHODS: We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E), and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites, or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MLST) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams. RESULTS: Over 4 years (April 2017 to July 2021) 2660 isolates were sequenced. This included MDR gram-negative bacilli (n = 293 CPE, n = 1309 ESBL), MRSA (n = 620), and VRE (n = 433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the 3 target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In 1 hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy. CONCLUSIONS: Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.

Genomic Investigation Reveals Contaminated Detergent as the Source of an Extended-Spectrum-ß-Lactamase-Producing Klebsiella michiganensis Outbreak in a Neonatal Unit.

Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-ß-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.

Geographic Variations in Arthritis Prevalence, Health-Related Characteristics, and Management - United States, 2015.

PROBLEM/CONDITION: Doctor-diagnosed arthritis is a common chronic condition affecting an estimated 23% (54 million) of adults in the United States, greatly influencing quality of life and costing approximately $300 billion annually. The geographic variations in arthritis prevalence, health-related characteristics, and management among states and territories are unknown. Therefore, public health professionals need to understand arthritis in their areas to target dissemination of evidence-based interventions that reduce arthritis morbidity. REPORTING PERIOD: 2015. DESCRIPTION OF SYSTEM: The Behavioral Risk Factor Surveillance System is an annual, random-digit-dialed landline and cellular telephone survey of noninstitutionalized adults aged ≥18 years residing in the United States. Self-reported data are collected from the 50 states, the District of Columbia, Guam, and Puerto Rico. Unadjusted and age-standardized prevalences of arthritis, arthritis health-related characteristics, and arthritis management were calculated. County-level estimates were calculated using a validated statistical modeling method. RESULTS: In 2015, in the 50 states and the District of Columbia, median age-standardized prevalence of arthritis was 23.0% (range: 17.2%-33.6%). Modeled prevalence of arthritis varied considerably by county (range: 11.2%-42.7%). In 13 states that administered the arthritis management module, among adults with arthritis, the age-standardized median percentage of participation in a self-management education course was 14.5% (range: 9.1%-19.0%), being told by a health care provider to engage in physical activity or exercise was 58.5% (range: 52.3%-61.9%), and being told to lose weight to manage arthritis symptoms (if overweight or obese) was 44.5% (range: 35.1%-53.2%). Respondents with arthritis who lived in the quartile of states with the highest prevalences of arthritis had the highest percentages of negative health-related characteristics (i.e., arthritis-attributable activity limitations, arthritis-attributable severe joint pain, and arthritis-attributable social participation restriction; ≥14 physically unhealthy days during the past 30 days; ≥14 mentally unhealthy days during the past 30 days; obesity; and leisure-time physical inactivity) and the lowest percentage of leisure-time walking. INTERPRETATION: The prevalence, health-related characteristics, and management of arthritis varied substantially across states. The modeled prevalence of arthritis varied considerably by county. PUBLIC HEALTH ACTION: The findings highlight notable geographic variability in prevalence, health-related characteristics, and management of arthritis. Targeted use of evidence-based interventions that focus on physical activity and self-management education can reduce pain and improve function and quality of life for adults with arthritis and thus might reduce these geographic disparities.

Effect of population breast screening on breast cancer mortality to 2005 in England and Wales: A nested case-control study within a cohort of one million women.

Objectives To evaluate the effectiveness of the NHS breast screening programme (NHSBSP) on breast cancer mortality in England and Wales and to compare findings with a cohort analysis of the same underlying population. Methods A nested case-control study within a cohort of 959,738 women in England and Wales aged 49-64 who were eligible for routine NHSBSP screening during 1991-2005. Cases who died from breast cancer in 1991-2005 were matched to controls without breast cancer at the case diagnosis date and alive when the case died. Risk of breast cancer mortality associated with intention to screen (ITS) (7047 cases/28,188 controls) and screening attendance (4707 cases/9413 controls) was examined. Bias was minimised in accordance with currently advocated best practice. Odds ratios (ORs) were calculated using conditional logistic regression. Results were compared with findings from an incidence-based breast cancer mortality cohort analysis. Results ITS was associated with a 21% breast cancer mortality reduction (OR = 0.79, 95% confidence interval [CI]: 0.71-0.88, P < 0.001). Attendance ≤5 years before diagnosis was associated with a 47% reduction in breast cancer mortality after self-selection correction (OR = 0.53, 95% CI: 0.46-0.62, P < 0.001). Breast cancer mortality reduction associated with ITS was 21% in both the case-control and cohort analyses, but the impact of attendance was marginally greater in the case-control analysis (36% vs. 32%). Conclusions Case-control studies designed and analysed according to current best practice guidelines offer an effective means of evaluating population breast screening.

Reducing the socioeconomic gradient in uptake of the NHS bowel cancer screening Programme using a simplified supplementary information leaflet: a cluster-randomised trial.

BACKGROUND: Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the 'gist' of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP. METHODS: The trial was integrated within routine BCSP operations in November 2012. Using a cluster randomised controlled design all adults aged 59-74 years who were being routinely invited to complete the gFOBt were randomised based on day of invitation. The Index of Multiple Deprivation was used to create SES quintiles. The control group received the standard information booklet ('SI'). The intervention group received the SI booklet and the Gist leaflet ('SI + Gist') which had been designed to help people with lower literacy engage with the invitation. Blinding of hubs was not possible and invited subjects were not made aware of a comparator condition. The primary outcome was the gradient in uptake across IMD quintiles. RESULTS: In November 2012, 163,525 individuals were allocated to either the 'SI' intervention (n = 79,104) or the 'SI + Gist' group (n = 84,421). Overall uptake was similar between the intervention and control groups (SI: 57.3% and SI + Gist: 57.6%; OR = 1.02, 95% CI: 0.92-1.13, p = 0.77). Uptake was 42.0% (SI) vs. 43.0% (SI + Gist) in the most deprived quintile and 65.6% vs. 65.8% in the least deprived quintile (interaction p = 0.48). The SES gradient in uptake was similar between the study groups within age, gender, hub and screening round sub-groups. CONCLUSIONS: Providing supplementary simplified information in addition to the standard information booklet did not reduce the SES gradient in uptake in the NHS BCSP. The effectiveness of the Gist leaflet when used alone should be explored in future research. TRIAL REGISTRATION: ISRCTN74121020 , registered: 17/20/2012.

Effect of population breast screening on breast cancer mortality up to 2005 in England and Wales: an individual-level cohort study.

BACKGROUND: Population breast screening has been implemented in the UK for over 25 years, but the size of benefit attributable to such programmes remains controversial. We have conducted the first individual-based cohort evaluation of population breast screening in the UK, to estimate the impact of the NHS breast screening programme (NHSBSP) on breast cancer mortality. METHODS: We followed 988 090 women aged 49-64 years in 1991 resident in England and Wales, who because of the staggered implementation of the NHSBSP, included both invited subjects and an uninvited control group. Individual-level breast screening histories were linked to individual-level mortality and breast cancer incidence data from national registers. Risk of death from breast cancer was investigated by incidence-based mortality analyses in relation to intention to screen and first round attendance. Overdiagnosis of breast cancer following a single screening round was also investigated. RESULTS: Invitation to NHSBSP screening was associated with a reduction in breast cancer mortality in 1991-2005 of 21% (RR=0.79, 95% CI: 0.73-0.84, P<0·001) after adjustment for age, socioeconomic status and lead-time. Breast cancer deaths among first invitation attenders were 46% lower than among non-attenders (RR=0.54, 95% CI: 0.51-0·57, P<0.001) and 32% lower following adjustment for age, socioeconomic status and self-selection bias (RR=0.68, 95% CI: 0.63-0·73, P<0.001). There was little evidence of overdiagnosis associated with invitation to first screen. CONCLUSIONS: The results indicate a substantial, statistically significant reduction in breast cancer mortality between 1991 and 2005 associated with NHSBSP activity. This is important in public health terms.

Annual Incidence of Knee Symptoms and Four Knee Osteoarthritis Outcomes in the Johnston County Osteoarthritis Project.

OBJECTIVE: To estimate annual incidence rates (IRs) of knee symptoms and 4 knee osteoarthritis (OA) outcomes (radiographic, symptomatic, severe radiographic, and severe symptomatic), overall and stratified by sociodemographic characteristics and knee OA risk factors. METHODS: We analyzed baseline (1991-1997) and first followup (1999-2003) data (n = 1,518) from the Johnston County Osteoarthritis Project. Participants were African American and white adults, ages ≥45 years, living in Johnston County, North Carolina, US. Knee symptoms were pain, aching, or stiffness on most days in a knee. Radiographic OA was Kellgren/Lawrence grade ≤2 (severe radiographic ≥3) in at least 1 knee. Symptomatic OA was defined as symptoms in a radiographically affected knee; severe symptomatic OA was defined as severe symptoms and severe radiographic OA. RESULTS: The median followup time was 5.5 years. Average annual IRs were 6% for symptoms, 3% for radiographic OA, 2% for symptomatic OA, 2% for severe radiographic OA, and 0.8% for severe symptomatic OA. Across outcomes, IRs were highest among those with the following baseline characteristics: age ≥75 years, obese, a history of knee injury, or an annual household income ≤$15,000. CONCLUSION: The annual onset of knee symptoms and 4 OA outcomes in Johnston County was high. This may preview the future of knee OA in the US and underscores the urgency of clinical and public health collaborations that reduce risk factors for, and manage the impact of, these outcomes. Inexpensive, convenient, and proven strategies (e.g., physical activity, self-management education courses) complement clinical care and can reduce pain and improve quality of life for people with arthritis.

Pooled Open Blocks Shorten Wait Times for Nonelective Surgical Cases.

OBJECTIVE: Assess the impact of the implementation of a data-driven scheduling strategy that aimed to improve the access to care of nonelective surgical patients at Massachusetts General Hospital (MGH). BACKGROUND: Between July 2009 and June 2010, MGH experienced increasing throughput challenges in its perioperative environment: approximately 30% of the nonelective patients were waiting more than the prescribed amount of time to get to surgery, hampering access to care and aggravating the lack of inpatient beds. METHODS: This work describes the design and implementation of an "open block" strategy: operating room (OR) blocks were reserved for nonelective patients during regular working hours (prime time) and their management centralized. Discrete event simulation showed that 5 rooms would decrease the percentage of delayed patients from 30% to 2%, assuming that OR availability was the only reason for preoperative delay. RESULTS: Implementation began in January 2012. We compare metrics for June through December of 2012 against the same months of 2011. The average preoperative wait time of all nonelective surgical patients decreased by 25.5% (P < 0.001), even with a volume increase of 9%. The number of bed-days occupied by nonurgent patients before surgery declined by 13.3% whereas the volume increased by 4.5%. CONCLUSIONS: The large-scale application of an open-block strategy significantly improved the flow of nonelective patients at MGH when OR availability was a major reason for delay. Rigorous metrics were developed to evaluate its performance. Strong managerial leadership was crucial to enact the new practices and turn them into organizational change.

The calculation of targets for the cancer and adenoma detection rates for the NHS bowel screening programme.

OBJECTIVES: The NHS bowel screening programme offers people aged 60-69 screening by faecal occult blood (FOB) testing, with colonoscopy as the diagnostic test. This paper describes the calculation of targets for the purpose of monitoring screening performance in the programme. METHODS: Targets were calculated for the prevalent round of screening in people aged 60-69, and for the 'steady state' of the programme when people will be offered their first screen at age 60 and subsequent screens at ages 62-69. Targets for the cancer and adenoma detection rates per 1000 people screened and per 100 colonoscopies were calculated using information from the English bowel cancer screening pilot. RESULTS: For the prevalent round, prevalent screen and incident screens the calculated targets for the cancer detection rate are 2.3, 1.3 and 1.7 per 1000 people respectively. For the adenoma detection rate the targets are 6.7, 5.2 and 5.5 per 1000 respectively. Targets for the cancer detection rate per 100 colonoscopies are 11.3, 7.5 and 8.4 and those for the adenoma detection rate are 32.0, 30.4 and 32.5 respectively. CONCLUSIONS: The purpose of these targets is to ensure that the national bowel cancer screening programme is effective with a high quality of screening. The cancer detection and adenoma detection rates per 1000 people are those estimated to be necessary to achieve the expected mortality reduction. Rates per 100 colonoscopies (equivalent to the positive predictive value of referral to colonoscopy) are designed to maintain a high quality of screening by minimizing the number of false-positive referrals.

Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections.

Topical compounded Timentin(®) diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin(®) (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt(®) against P. aeruginosa and to determine the efficacy and stability of Timentin(®) aqueous stock concentrate solution. Timentin(®) stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or -20°C. The diluted Timentin(®)-Methopt(®) solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4°C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at -20°C and was also acceptable for shorter time periods (6-9 months) when stored at 4°C. The MIC for the diluted Timentin(®)-Methopt(®) solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24°C. The results of this study indicate that storage of the Timentin(®) stock solution at -20°C does not compromise efficacy for at least 12 months and that Timentin(®) diluted in Methopt(®) was stable for 28 days when stored at either 4 or 24°C.

Sexually transmitted infections and hepatitis in men with a history of incarceration.

BACKGROUND: Men entering correctional facilities have high rates of human immunodeficiency virus, sexually transmitted infections (STI), and hepatitis. Many prisons offer screening, treatment, and vaccination services; however, little is known about the rates of these infections in men after release to the community. METHODS: Young men were recruited from prisons in Mississippi, Rhode Island, and Wisconsin as part of a human immunodeficiency virus/STI/hepatitis intervention study. Participants were offered screening for Neisseria gonorrhoeae (GC), Chlamydia trachomatis, trichomoniasis, syphilis, hepatitis B (HBV) and C (HCV) 6 months after release. Logistic regression was performed to identify associations with prevalent infections. RESULTS: Of 248 eligible men, 178 (71.8%) participated. Their mean age was 22.5 years, and 92% reported multiple lifetime incarcerations. At 6-month postrelease, 79% reported unprotected vaginal or anal sex, and 26% tested positive for 1 or more infections (GC, 1%; C. trachomatis, 12%; trichomoniasis, 8%; syphilis, 0%; HCV, 6%; HBV, 1%). Of all, 55% were susceptible to HBV infection. Active STI (GC, C. trachomatis, or trichomoniasis) was associated with less education (odds ratios [OR], 2.25; P < 0.05). HCV infection was associated with injection drug use (OR, 69.70; P < 0.05) and being white (OR, 7.54; P < 0.05). HBV susceptibility was associated with older age (OR, 3.02; P < 0.05), more education (OR, 2.39; P < 0.05), or incarceration in Mississippi (OR, 6.69; P < 0.05) or Rhode Island (OR, 2.84; P < 0.05). CONCLUSIONS: Effective screening and prevention programs are needed for this population before and after release from custody to prevent acquisition and further transmission of these infections.

Feline bacterial urinary tract infections: An update on an evolving clinical problem.

Although feline urine is increasingly submitted for bacterial culture and susceptibility testing as part of a more general diagnostic work-up for a range of presentations in veterinary practice, bacterial urinary tract infections (UTIs) are relatively uncommon due to a variety of physical and immunological barriers to infection. Culture positive urine is most often obtained from older female cats and the clinical history may include hematuria, dysuria and pollakiuria, or the infection may be occult. Urinalysis usually reveals hematuria and pyuria, and Escherichia coli and Gram-positive cocci are cultured most frequently. Most feline UTIs can be successfully treated using oral amoxicillin or amoxicillin/clavulanic acid administered for at least 14days, but the prevalence of antimicrobial resistance amongst infecting bacterial species is a growing concern. There is currently no conclusive information on the safety and efficacy of alternative therapeutic agents for the treatment of feline UTIs.

Clonal complex Pseudomonas aeruginosa in horses.

Pseudomonas aeruginosa is associated with infectious endometritis in horses. Although infectious endometritis is often considered a venereal infection, there is relatively limited genotypic-based evidence to support this mode of transmission. The study sought to determine the relatedness between genital P. aeruginosa isolates collected from a limited geographical region using molecular strain typing. Enterobacterial repetitive intergenic consensus PCR typing was performed on 93 isolates collected between 2005 and 2009 from 2058 thoroughbred horses (including 18 stallions) at 66 studs. While P. aeruginosa was not detected in the stallions, 53/93 (57%) mares harbouring P. aeruginosa had clonally related strains, which included a single dominant genotype detected in 42 (45%) mares from 13 different studs. These novel findings suggest that most equine genital P. aeruginosa infections in this region may have been acquired from mechanisms other than direct horse to horse transmission. Instead, other potential acquisition pathways, as well as strain specific adaptation to the equine genital tract, should be investigated.

Occult bacterial lower urinary tract infections in cats-urinalysis and culture findings.

Bacterial urinary tract infections (UTIs) can be detected in feline urine submitted for urinalysis and culture as part of the diagnostic workup for a variety of conditions. Our aim was to investigate urinalysis and culture findings in urine specimens from cats with no history of lower urinary tract signs. Study inclusion criteria required cystocentesis specimens from cats with no history of lower urinary tract signs, inappropriate urination, or previous UTI (including pyelonephritis). Of 132 specimens, 38 were culture positive and 94 were culture negative. Culture positive urine specimens were more likely to come from older female cats (p=0.03, p<0.001, respectively) and they had higher pH (p=0.001), erythrocyte (p=0.013) and leukocyte counts (p=0.003) than culture negative urine specimens. Gram-negative infected specimens (n=15) had lower urine specific gravity and higher leukocyte counts than Gram-positive infected specimens (n=21; p=0.0012, p=0.005, respectively) and culture negative specimens (p=0.003, p<0.0001, respectively). Urine protein:creatinine ratio was higher in Gram-negative infected urine than in culture negative urine (p=0.013). Enterococcus faecalis was the most commonly isolated bacteria (19 of a total of 44 isolates; 43.2%) and E. coli phylogenetic group B2 was the most common Gram-negative isolate (14 of a total of 44 isolates; 31.8%). We conclude that feline bacterial urinary tract infections can occur in cats without lower urinary tract signs, particularly older females and that they are associated with high urine erythrocyte and leukocyte counts.

Clinical efficacy and palatability of pradofloxacin 2.5% oral suspension for the treatment of bacterial lower urinary tract infections in cats.

BACKGROUND: Pradofloxacin is a 3rd generation veterinary fluoroquinolone designed to restrict the emergence of antimicrobial resistance during therapy. HYPOTHESIS: Pradofloxacin 2.5% oral suspension is a safe, efficacious, and palatable treatment for bacterial urinary tract infections (UTI) in cats. ANIMALS: Seventy-eight cats presented with lower urinary tract signs and were positive on bacterial culture of urine. METHODS: Cats were allocated into 3 treatment groups depending on bacterial susceptibility results: pradofloxacin (n = 27), doxycycline (n = 23), or amoxicillin-clavulanic acid (n = 28). All antimicrobials were presented in palatable liquid form. Posttreatment urine specimens were collected after completion of the course of treatment and submitted for bacterial culture and sensitivity. Owners were questioned before and after treatment about their experiences with administering oral medication to their cats. RESULTS: Posttreatment urine culture was negative in all cats in the pradofloxacin group, but there were 3 treatment failures in each of the other groups. Owners' perceptions of the difficulty of administering oral medication to their cats was more positive posttreatment than pretreatment (P = .001; P < .001). There was no difference in palatability among the treatment groups (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: We conclude that pradofloxacin 2.5% oral suspension is a highly effective and safe antimicrobial treatment for bacterial lower urinary tract infection in cats, and that the palatable formulation optimizes owner compliance. These findings make pradofloxacin a useful addition to the veterinary formulary.

Prevalence of bacterial species in cats with clinical signs of lower urinary tract disease: recognition of Staphylococcus felis as a possible feline urinary tract pathogen.

This study investigated the prevalence of bacterial pathogens of the urinary tract in Australian cats. Urine was collected by cystocentesis and subjected to urinalysis, bacterial culture and susceptibility testing. A total of 126 isolates were obtained from 107 culture-positive cats. Escherichia coli was most commonly isolated (37.3% of isolates) with the majority of isolates showing susceptibility to the 14 antimicrobials tested. Just over a quarter of isolates (27.0%) were Enterococcus faecalis, which showed resistance to cephalosporins and clindamycin. Staphylococcus felis, a previously unreported feline urinary tract pathogen which was susceptible to all antimicrobial agents tested, comprised 19.8% of the isolates. S. felis was significantly associated with urine that had a higher specific gravity (p=0.011) and pH (p=0.006) and was more likely to contain crystals (p=0.002) than urine from which other bacterial species were isolated. This is the first published study that associates the isolation of S. felis with clinical signs of lower urinary tract disease in cats.

Undiagnosed HIV infection and couple HIV discordance among household members of HIV-infected people receiving antiretroviral therapy in Uganda.

INTRODUCTION: Systematic efforts to identify HIV-infected members and HIV-discordant couples in households of individuals taking antiretroviral therapy (ART) could theoretically reduce HIV transmission and improve ART adherence. METHODS: We enrolled HIV-infected clients of an AIDS support organization in a randomized evaluation of different ART monitoring regimens that offered home-based ART care to them and their clinically eligible household members. At baseline, counselors visited participants' homes and offered voluntary counseling and testing (VCT) to all household members. We assessed uptake, HIV prevalence, HIV discordance, and rate of ART eligibility. RESULTS: Of the 2373 household members, 2348 (99%) accepted VCT. HIV prevalence among household members was 7.5% and varied by age with 9.5% among children aged 0 to 5 years, 2.9% among persons aged 6 to 24 years, and 37.1% among adults aged 25 to 44 years. Of the household members with HIV, 74% had never been previously tested, and 39% of these were clinically eligible for ART. Of the 120 spouses of ART patients that were tested for HIV, 52 (43%) were HIV negative, and of these, 99% had not been previously tested. CONCLUSIONS: Provision of home-based VCT to household members of people initiating ART was well accepted and resulted in the detection of a large number of previously undiagnosed HIV infections and HIV-discordant relationships.

Depression and CD4 cell count among persons with HIV infection in Uganda.

Despite the importance of mental illness and the high prevalence of HIV in Africa, few studies have documented depressive symptoms among HIV-infected persons in Africa. We assessed factors associated with depression among HIV-infected adults undergoing anti-retroviral eligibility screening in Eastern Uganda. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Univariate and multiple regression analyses were conducted to identify socio-demographic characteristics and disease-related factors associated with depression. Among 1017 HIV-infected participants assessed for depression, 47% (476/1017) reported depressive symptoms (CES-D >/= 23). Adjusting for age, gender, education, and source of income, patients with CD4 counts <50 cells/microl were more likely to be depressed (odds ratio 2.34, 95% confidence interval, 1.39-3.93, P = 0.001). Women, participants >50 years, and those without an income source were more likely to be depressed. Depression was common among HIV-infected persons in rural Uganda and was associated with low CD4 cell counts. Appropriate screening and treatment for depression should be considered for comprehensive HIV care.

Identification of bla(CMY-7) and associated plasmid-mediated resistance genes in multidrug-resistant Escherichia coli isolated from dogs at a veterinary teaching hospital in Australia.

OBJECTIVES: To determine clonality and identify plasmid-mediated resistance genes in 11 multidrug-resistant Escherichia coli (MDREC) isolates associated with opportunistic infections in hospitalized dogs in Australia. METHODS: Phenotypic (MIC determinations, modified double-disc diffusion and isoelectric focusing) and genotypic methods (PFGE, plasmid analysis, PCR, sequencing, Southern hybridization, bacterial conjugation and transformation) were used to characterize, investigate the genetic relatedness of, and identify selected plasmid-mediated antimicrobial resistance genes, in the canine MDREC. RESULTS: Canine MDRECs were divided into two clonal groups (CG 1 and 2) with distinct restriction endonuclease digestion and plasmid profiles. All isolates possessed bla(CMY-7) on an approximately 93 kb plasmid. In CG 1 isolates, bla(TEM), catA1 and class 1 integron-associated dfrA17-aadA5 genes were located on an approximately 170 kb plasmid. In CG 2 isolates, a second approximately 93 kb plasmid contained bla(TEM) and unidentified class 1 integron genes, although a single CG 2 strain carried dfrA5. Antimicrobial susceptibility profiling of E. coli K12 transformed with CG 2 large plasmids confirmed that the bla(CMY-7)-carrying plasmid did not carry any other antimicrobial resistance genes, whereas the bla(TEM)/class 1 integron-carrying plasmid carried genes conferring resistance to tetracycline and streptomycin also. CONCLUSIONS: This is the first report on the detection of plasmid-mediated bla(CMY-7) in animal isolates in Australia. MDREC isolated from extraintestinal infections in dogs may be an important reservoir of plasmid-mediated resistance genes.