BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

The high-consequence pathogen Bacillus anthracis causes human anthrax and often results in lethal infections without the rapid administration of effective antimicrobial treatment. Antimicrobial resistance profiling is therefore critical to inform post-exposure prophylaxis and treatment decisions, especially during emergencies such as outbreaks or where intentional release is suspected. Whole-genome sequencing using a rapid long-read sequencer can uncover antimicrobial resistance patterns if genetic markers of resistance are known. To identify genomic markers associated with antimicrobial resistance, we isolated B. anthracis derived from the avirulent Sterne strain with elevated minimal inhibitory concentrations to clarithromycin. Mutants were characterized both phenotypically through broth microdilution susceptibility testing and observations during culturing, as well as genotypically with whole-genome sequencing. We identified two different in-frame insertions in the L22 ribosomal protein-encoding gene rplV, which were subsequently confirmed to be involved in clarithromycin resistance through the reversion of the mutant gene to the parent (drug-susceptible) sequence. Detection of the rplV insertions was possible with rapid long-read sequencing, with a time-to-answer within 3 h. The mutations associated with clarithromycin resistance described here will be used in conjunction with known genetic markers of resistance for other antimicrobials to strengthen the prediction of antimicrobial resistance in B. anthracis.IMPORTANCEThe disease anthrax, caused by the pathogen Bacillus anthracis, is extremely deadly if not treated quickly and appropriately. Clarithromycin is an antibiotic recommended for the treatment and post-exposure prophylaxis of anthrax by the Centers for Disease Control and Prevention; however, little is known about the ability of B. anthracis to develop resistance to clarithromycin or the mechanism of that resistance. The characterization of clarithromycin-resistant isolates presented here provides valuable information for researchers and clinicians in the event of a release of the resistant strain. Additionally, knowledge of the genetic basis of resistance provides a foundation for susceptibility prediction through rapid genome sequencing to inform timely treatment decisions.

Four Chlamydia psittaci isolates were recovered from clinical specimens from ill workers during a multistate outbreak at two chicken processing plants. Whole genome sequencing analyses revealed high similarity to C. psittaci genotype D. The isolates differed from each other by only two single nucleotide polymorphisms, indicating a common source.

Widespread release of Bacillus anthracis (anthrax) or Yersinia pestis (plague) would prompt a public health emergency. During an exposure event, high-quality whole genome sequencing (WGS) can identify genetic engineering, including the introduction of antimicrobial resistance (AMR) genes. Here, we developed rapid WGS laboratory and bioinformatics workflows using a long-read nanopore sequencer (MinION) for Y. pestis (6.5h) and B. anthracis (8.5h) and sequenced strains with different AMR profiles. Both salt-precipitation and silica-membrane extracted DNA were suitable for MinION WGS using both rapid and field library preparation methods. In replicate experiments, nanopore quality metrics were defined for genome assembly and mutation analysis. AMR markers were correctly detected and >99% coverage of chromosomes and plasmids was achieved using 100,000 raw sequencing reads. While chromosomes and large and small plasmids were accurately assembled, including novel multimeric forms of the Y. pestis virulence plasmid, pPCP1, MinION reads were error-prone, particularly in homopolymer regions. MinION sequencing holds promise as a practical, front-line strategy for on-site pathogen characterization to speed the public health response during a biothreat emergency.

OBJECTIVES: The study aim was to investigate multidrug-resistant (MDR) plasmids from a collection of 10 carbapenemase-producing Klebsiella pneumoniae clinical isolates identified within the same healthcare institution in Pakistan. Full characterization of the MDR plasmids including structure, typing characteristics, and AMR content as well as determination of their plasmid-based antimicrobial susceptibility profiles were carried out. METHODS: Plasmids were isolated from 10 clinical isolates of Klebsiella pneumoniae, and from a corresponding set of Escherichia coli transconjugants, then sequenced using Nanopore/Illumina technology to generate plasmid hybrid assemblies. Full characterization of MDR plasmids, including determination of next generation sequencing (NGS)-based AMR profiles, plasmid incompatibility groups, and types, was carried out. The structure of MDR plasmids was analyzed using the Galileo AMR platform. For E. coli transconjugants, the NGS-based AMR profiles were compared to NGS-predicted AMR phenotypes and conventional broth microdilution (BMD) antimicrobial susceptibility testing (AST) results. RESULTS: All carbapenemase-producing K. pneumoniae isolates (carrying either bla(NDM-1), or/and bla(OXA-48)) carried multiple AMR plasmids encoding 34 antimicrobial resistance genes (ARGs) conferring resistance to antimicrobials from 6 different classes. The plasmid incompatibility groups and types identified were: IncC (types 1 and 3), IncFIA (type 26) IncFIB, IncFII (types K1, K2, K7, and K9), IncHI1B, and IncL. None of the bla(NDM-1) and bla(ESBL)-plasmids identified in this study were previously described. Most bla(NDM-1-)plasmids shared identical AMR regions suggesting potential genetic material/plasmid exchange between K. pneumoniae isolates of this collection. The majority of NGS-based AMR profiles from the E. coli transconjugants correlated well with both NGS-based predicted and conventional AST results. CONCLUSION: This study highlights the complexity and diversity of the plasmid-based genetic background of carbapenemase-producing clinical isolates from Pakistan. This study emphasizes the need for characterization of MDR plasmids to determine their complete molecular background and monitor AMR through plasmid transmission between multi-resistant bacterial pathogens.

We developed and assessed the performance of a new multiplex real-time PCR assay for the detection of all Chlamydia species and simultaneous differentiation of Chlamydia psittaci and Chlamydia pneumoniae-two important human respiratory pathogens-in human clinical specimens. Next-generation sequencing was used to identify unique targets to design real-time PCR assays targeting all Chlamydia species, C. psittaci, and C. pneumoniae. To validate the assay, we used a panel of 49 culture isolates comprising seven C. psittaci genotypes, eight C. pneumoniae isolates, seven other Chlamydia species, and 22 near-neighbor bacterial and viral isolates, along with 22 specimens from external quality assessment (EQA) panels and 34 nasopharyngeal and oropharyngeal swabs and cerebrospinal fluid, stool, and sputum specimens previously identified as positive or negative for C. psittaci or C. pneumoniae. The assays were 100% specific, with limits of detection of 7.64- 9.02 fg/μL. The assay results matched with historical assay results for all specimens, except for one owing to the increased sensitivity of the new C. psittaci assay; the results of the EQA specimens were 100% accurate. This assay may improve the timely and accurate clinical diagnosis of Chlamydia infections and provide a greater understanding of the burden of disease caused by these agents.

During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3-17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3-August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non-fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.

Pregnant women with opioid use disorder (OUD) are at risk of overdose, infectious diseases, and inadequate prenatal care. Additional risks include adverse pregnancy and infant outcomes, such as preterm birth and neonatal abstinence syndrome. Management and treatment of OUD during pregnancy are associated with improved maternal and infant outcomes. Professional organizations, including the American College of Obstetricians and Gynecologists, recommend offering opioid agonist pharmacotherapy (i.e., methadone or buprenorphine) combined with behavioral therapy as standard treatment for pregnant women with OUD. Other medications and herbal supplements have also been used by pregnant women for OUD. Determining which OUD treatments optimize maternal and infant outcomes is challenging given the host of potential factors that affect these outcomes. The Centers for Disease Control and Prevention initiated the MATernaL and Infant NetworK to Understand Outcomes Associated with Treatment of Opioid Use Disorder during Pregnancy (MAT-LINK) to monitor more than 2000 mothers and their infants, using data collected from geographically diverse clinical sites. Information learned from MAT-LINK will inform the future management and treatment of pregnant women with OUD.

Human anthrax cases necessitate rapid response. We completed Bacillus anthracis nanopore whole-genome sequencing in our high-containment laboratory from a human anthrax isolate hours after receipt. The de novo assembled genome showed no evidence of known antimicrobial resistance genes or introduced plasmid(s). Same-day genomic characterization enhances public health emergency response.

Widespread release of Bacillus anthracis (anthrax) or Yersinia pestis (plague) would prompt a public health emergency. During an exposure event, high-quality whole genome sequencing (WGS) can identify genetic engineering, including the introduction of antimicrobial resistance (AMR) genes. Here, we developed rapid WGS laboratory and bioinformatics workflows using a long-read nanopore sequencer (MinION) for Y. pestis (6.5 h) and B. anthracis (8.5 h) and sequenced strains with different AMR profiles. Both salt-precipitation and silica-membrane extracted DNA were suitable for MinION WGS using both rapid and field library preparation methods. In replicate experiments, nanopore quality metrics were defined for genome assembly and mutation analysis. AMR markers were correctly detected and >99% coverage of chromosomes and plasmids was achieved using 100,000 raw sequencing reads. While chromosomes and large and small plasmids were accurately assembled, including novel multimeric forms of the Y. pestis virulence plasmid, pPCP1, MinION reads were error-prone, particularly in homopolymer regions. MinION sequencing holds promise as a practical, front-line strategy for on-site pathogen characterization to speed the public health response during a biothreat emergency.

BACKGROUND: High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized. METHODS: We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact. RESULTS: Baseline prevalence of any anal 9v HR-HPV type among men who have sex with men (MSM) and men who have sex with women (MSW) was 74% and 25% (P < .001), respectively. Among 299 MSM, abnormal cytology was detected in 161 (54%) MSM and was associated with the presence of any 9v HR-HPV (relative risk [RR], 1.8 [95% confidence interval {CI}, 1.3-2.6]; P < .001). Among 61 MSW, abnormal anal cytology was detected in 12 (20%) and was associated with the presence of any 9v HR-HPV (RR, 4.3 [95% CI, 1.6-11.5]; P < .001). CONCLUSIONS: Among men with HIV, the prevalence of the 7 HR-HPV types in the 9v vaccine was high and was associated with abnormal cytology. These findings indicate that men with HIV could benefit from prophylactic administration of the 9v HPV vaccine.

BACKGROUND: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16.5, 95% CI 14.2-19.2, p<0.0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4.4, 3.7-5.3, p<0.0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14.1, 11.1-17.9, p<0.0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12.9, 95% CI 6.7-24.8, p<0.0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2.3, 1.6-3.4, p<0.0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23.1, 9.4-57.0, p<0.0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3.6, 2.5-5.3, p<0.0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

OBJECTIVES: Adiponectin levels are inversely related to cardiovascular risk and are low in diabetics and obese persons. We examined the association between adiponectin concentration and HIV-associated lipodystrophy, which remains unclear. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) was a prospective cohort study of HIV-infected adults conducted in four US cities. Lean body and fat masses were assessed using dual-energy X-ray absorptiometry scans. Using baseline data from 2004 to 2006, we defined lipodystrophy using a sex-specific fat mass ratio and performed cross-sectional analyses of associated risks using multivariable logistic regression. RESULTS: Among 440 male participants (median age 42 years; 68% non-Hispanic white; 88% prescribed combination antiretroviral therapy; median CD4 lymphocyte count 468 cells/muL; 76% with viral load < 400 HIV-1 RNA copies/mL; 5% diabetic; median body mass index 25 kg/m(2) ), median concentrations of leptin and adiponectin were 3.04 ng/L [interquartile range (IQR) 1.77-5.43 ng/L] and 8005 mug/mL (IQR 4950-11 935 mug/mL), respectively. The prevalence of lipodystrophy was 14%. Lipodystrophy was significantly associated with increasing age [prevalence ratio (PR) 1.50; 95% confidence interval (CI) 1.10-2.06, per 10 years], adiponectin < 8005 mug/mL (PR 5.02; 95% CI 2.53-9.95), ever stavudine use (PR 2.26; 95% CI 1.36-3.75), CD4 cell count > 500 cells/muL (PR 2.59; 95% CI 1.46-4.61), viral load < 400 copies/mL (PR 3.98; 95% CI 1.25-12.6), highly sensitive C-reactive protein < 1.61 mg/L (PR 1.91; 95% CI 1.11-3.28) and smoking (PR 0.42; 95% CI 0.22-0.78). CONCLUSIONS: Among men in this HIV-infected cohort, the prevalence of lipodystrophy was similar to previous estimates for persons living with HIV, and was associated with lower adiponectin levels, potentially indicating increased cardiovascular disease risk.

INTRODUCTION: Studies among HIV-uninfected persons (mostly in their sixth decade of life) show that detectable coronary artery calcium (CAC) is independently associated with low bone mineral density (BMD), suggesting a possible common pathogenic mechanism. AIM: We assessed the relationship between CAC and BMD, which has not been well described among younger to middle-aged HIV-infected persons. METHODS: We studied participants with baseline CAC and BMD measures from a prospective cohort of HIV-infected persons enrolled in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) during 2004-2006. We used logistic regression to assess the association between detectable CAC (>0 Agatston score) and BMD (g/cm2, T-score), and adjusted for known traditional and HIV-related risk factors. RESULTS: Among 472 participants (76% male, 30% non-Hispanic black, median age 41 years, 71% with HIV RNA <400 copies/mL), the majority had no detectable CAC (82%), but had baseline osteopenia (53%) or osteoporosis (10%). In univariate analysis, participants with detectable CAC had lower femoral neck/total hip T-scores, lower femoral neck/total hip/lumbar spine BMD, and higher rates of osteopenia/osteoporosis. After adjustment for age, all associations were no longer significant; adjustment for traditional risk factors excluding age and HIV-related variables failed to attenuate these associations. CONCLUSIONS: We found aging attenuates the association between detectable CAC and BMD in this cohort. Aging remains an important contributor to non-AIDS-defining illnesses. These data reinforce the importance of developing screening and prevention strategies for ageing HIV-infected persons given their excess risk across a wide spectrum of end-organ complications.

Bacillus anthracis, the etiologic agent of anthrax, is characteristically susceptible to penicillin despite containing two chromosomal beta-lactamase genes. Few naturally occurring penicillin-resistant B. anthracis isolates have been reported. Here, we report the draft genome sequences for three penicillin-resistant B. anthracis strains, strain 32, UT308, and SK57.

Penicillin (PEN) is a low-cost option for anthrax treatment, but naturally occurring resistance has been reported. beta-Lactamase expression (bla1, bla2) in Bacillus anthracis is regulated by a sigma factor (SigP) and its cognate anti-sigma factor (RsiP). Mutations leading to truncation of RsiP were previously described as a basis for PEN resistance. Here, we analyze whole-genome sequencing (WGS) data and compare the chromosomal sigP-bla1 regions from 374 B. anthracis strains to determine the frequency of mutations, identify mutations associated with PEN resistance, and evaluate the usefulness of WGS for predicting PEN resistance. Few (3.5%) strains contained at least 1 of 11 different mutations in sigP, rsiP, or bla1. Nine of these mutations have not been previously associated with PEN resistance. Four strains showed PEN resistance (PEN-R) by conventional broth microdilution, including 1 strain with a novel frameshift in rsiP. One strain that carries the same rsiP frameshift mutation as that found previously in a PEN-R strain showed a PEN-susceptible (PEN-S) phenotype and exhibited decreased bla1 and bla2 transcription. An unexpectedly small colony size, a reduced growth rate, and undetectable beta-lactamase activity levels (culture supernatant and cell lysate) were observed in this PEN-S strain. Sequence analysis revealed mutations in genes associated with growth defects that may contribute to this phenotype. While B. anthracis rsiP mutations cannot be exclusively used to predict resistance, four of the five strains with rsiP mutations were PEN-R. Therefore, the B. anthracis sigP-bla1 region is a useful locus for WGS-based PEN resistance prediction, but phenotypic testing remains essential. IMPORTANCE Determination of antimicrobial susceptibility of B. anthracis is essential for the appropriate distribution of antimicrobial agents for postexposure prophylaxis (PEP) and treatment of anthrax. Analysis of WGS data allows for the rapid detection of mutations in antimicrobial resistance (AMR) genes in an isolate, but the presence of a mutation in an AMR gene does not always accurately predict resistance. As mutations in the anti-sigma factor RsiP have been previously associated with high-level penicillin resistance in a limited number of strains, we investigated WGS assemblies from 374 strains to determine the frequency of mutations and performed functional antimicrobial susceptibility testing. Of the five strains that contained mutations in rsiP, only four were PEN-R by functional antimicrobial susceptibility testing. We conclude that while sequence analysis of this region is useful for AMR prediction in B. anthracis, genetic analysis should not be used exclusively and phenotypic susceptibility testing remains essential.

Background: Nonavalent (9v) human papilloma virus vaccine targets high-risk (HR)-HPV types 16, 18, 31, 33, 45, 52, 58, and low-risk 6, 11. We examined prevalence, incidence, and clearance of anal and cervical HR-HPV in HIV-infected women. Methods: From 2004-2006, the SUN Study enrolled 167 women from four US cities. Anal and cervical specimens were collected annually for cytology and identification of 37 HPV types; 14 HR include: 9v 16, 18, 31, 33, 45, 52, 58; non-9v 35, 39, 51, 56, 59, 66, 68. Results: Baseline characteristics of 126 women included: median age 38 years; 57% non-Hispanic black; 67% HIV RNA < 400 copies/mL; 90% CD4 counts >/= 200 cells/mm3. HPV prevalence at anus and cervix was 90% and 83%; for 9v HR-HPV types, 67% and 51%; non-9v HR-HPV, 54% and 29%, respectively. 9v and non-9v HR-HPV incidence rates/100 person-years were similar (10.4 vs 9.5: 8.5 vs 8.3, respectively); 9v clearance rates were 42% and 61%; non-9v 46% and 59%, in anus and cervix, respectively. Conclusions: Anal HR-HPV prevalence was higher than cervical with lower clearance; incidence was similar. Although prevalence of non-9v HR-HPV was substantial, 9v HR-HPV types were generally more prevalent. These findings support use of nonavalent vaccine in HIV-infected women.

Coxiella burnetii is a human pathogen that causes the serious zoonotic disease Q fever. It is ubiquitous in the environment and due to its wide host range, long-range dispersal potential and classification as a bioterrorism agent, this microorganism is considered an HHS Select Agent. In the event of an outbreak or intentional release, laboratory strain typing methods can contribute to epidemiological investigations, law enforcement investigation and the public health response by providing critical information about the relatedness between C. burnetii isolates collected from different sources. Laboratory cultivation of C. burnetii is both time-consuming and challenging. Availability of strain collections is often limited and while several strain typing methods have been described over the years, a true gold-standard method is still elusive. Building upon epidemiological knowledge from limited, historical strain collections and typing data is essential to more accurately infer C. burnetii phylogeny. Harmonization of auspicious high-resolution laboratory typing techniques is critical to support epidemiological and law enforcement investigation. The single nucleotide polymorphism (SNP) -based genotyping approach offers simplicity, rapidity and robustness. Herein, we demonstrate SNPs identified within 16S rRNA gene sequences can differentiate C. burnetii strains. Using this method, 55 isolates were assigned to six groups based on six polymorphisms. These 16S rRNA SNP-based genotyping results were largely congruent with those obtained by analyzing restriction-endonuclease (RE)-digested DNA separated by SDS-PAGE and by the high-resolution approach based on SNPs within multispacer sequence typing (MST) loci. The SNPs identified within the 16S rRNA gene can be used as targets for the development of additional SNP-based genotyping assays for C. burnetii.

Background: The natural history of anal HPV infection among HIV-infected men is unknown. Methods: We collected anal swabs for cytology, HPV detection, and genotyping at annual visits from 2004-2012. We examined baseline prevalence, incidence and clearance of anal HPV infection at 48 months, and associated factors among HIV-infected men. Results: We examined 403 men who have sex with men (MSM) and 96 men who have sex with women (MSW) (median age 42 years for both, 87 vs. 91% were prescribed cART, median CD4 cell count was 454 vs. 379 cells/mm3, and 74 vs. 75% had undetectable viral load, respectively). For type 16, prevalence among MSM and MSW was 38% vs. 14% (p<0.001), and incidence was 24% vs. 6% (p=0.001), respectively. For type 18, prevalence was 24% vs. 8% (p<0.001), and incidence was 14% vs. 3% (p=0.009), respectively. Among MSM and MSW, clearance of prevalent HPV 16 and HPV 18 was 51% and 66% (p=0.682), and 69% and 60% (p=0.538), respectively. Condomless receptive anal sex was associated with persistent HPV 16 among all men (OR 2.37, p=0.014). Conclusions: MSM had higher prevalence and incidence of HPV than MSW, but similar clearance. Condomless anal sex may predict cancer risk among HIV-infected men.

Declining response rates may introduce bias into survey results and increase costs. Two national surveys, the National Immunization Survey (NIS) and the NIS-Teen, were used to study the impact of survey length, as stated by the interviewer, and inclusion of a topic of interest to respondents on response rates. The two studies included comparisons of the standard survey instruments to revised, condensed instruments. The NIS study also included variations of the standard survey with sections considered of interest for parental respondents, the Parental Concerns Module (PCM), which contained questions about parents' thoughts and beliefs about vaccinations. The outcomes of interest were differences in the response rates and resulting survey costs in each of the study conditions. The shortened instruments resulted in higher response rates compared to both the standard instruments and the instruments including the PCM and reduced the overall time needed to complete an interview. Based on these results, the NIS and NIS-Teen questionnaires were both shortened.

We report here the complete annotated genome sequence of the Burkholderia stabilis type strain ATCC BAA-67. There were three circular chromosomes with a combined size of 8,527,947 bp and G+C composition of 66.4%. These characteristics closely resemble the genomes of other sequenced members of the Burkholderia cepacia complex.

The duration of influenza virus shedding in HIV-infected adults is unknown and could affect quarantine and treatment recommendations. Participants were monitored for influenza-like illness (ILI), defined as fever and cough or sore throat, using weekly telephone audio computer-assisted self-interviews. Those with ILI were further evaluated at three HIV-specialty clinics. For those with influenza, we collected nasopharyngeal washes every three days after the date of confirmed influenza infection for 21-28 days; specimens underwent RT-PCR and viral culture. Duration of influenza virus shedding was the interval from the date of onset (day 0) of ILI to the date of last culture-positive specimen. Characteristics were compared between patients with and without influenza using Fisher's exact test. We used the Wilcoxon rank-sum test to examine factors that may have affected influenza virus shedding. From 10/2010 to 4/2011, we enrolled 961 participants in syndromic surveillance and diagnosed 20 patients with influenza whose characteristics were: median age 48 years (interquartile range [IQR]: 43-53), 60% male, 50% non-Hispanic black, 95% had been prescribed cART, 85% were virologically suppressed (HIV RNA <400 copies/mL), median CD4 cell count 317 cells/mm3 (IQR: 190-544), and median follow-up time 21 days (IQR: 19-22). Compared with persons without influenza, persons with influenza were more likely to be older, use injection drugs, have a lower median CD4 cell count, and were less likely to have had an influenza vaccination in the past 12 months. Median durations of shedding, PCR detection, and ILI symptoms were 3 (IQR: 0-5), 10 (IQR: 6-15), and 14 days (IQR: 12-26), respectively. Median days of shedding were similar among patients with and without any prior influenza vaccination (0 vs. 4, p=0.448), HIV viral suppression (2 vs. 6, p=0.053), and oseltamivir use (5 vs. 0, p=0.083). HIV-infected persons on cART in our study shed influenza virus for a similar duration as that reported for HIV-uninfected persons.

OBJECTIVES: Among virally suppressed HIV-infected persons, we examined the relationship between obesity and alterations in key clinical markers of immune activation and inflammation. These markers have also been associated with excess HIV-related cardiovascular disease and mortality. METHODS: We evaluated data from virally suppressed participants in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy, including inflammatory biomarkers (interleukin-6 and highly sensitive C-reactive protein), monocyte biomarkers [soluble CD163 (sCD163), sCD14], and monocyte immunophenotypes. We assessed associations with these immunologic measures and obesity, via logistic regression preadjustment and postadjustment for demographic and clinical factors, homeostatic model assessment of insulin resistance, and leptin levels. RESULTS: Among 452 evaluable participants, median (interquartile range) age was 41 (36-48) years, CD4 cell count was 475 (308-697) cells/mul, and 21% were obese (BMI ≥ 30 kg/m). In univariable models, obesity, smoking, and lower CD4 cell count were associated with higher measures of inflammation and monocyte activation. After adjustment, obesity remained independently associated with elevated levels (highest vs. lower two tertiles) of interleukin-6 [odds ratio (OR) 1.96; P = 0.02], highly sensitive C-reactive protein (OR 2.79; P < 0.001) and sCD163 (OR 1.94; P = 0.02), and elevated frequency of CD14CD16 (OR 1.77; P = 0.03) and CD14dimCD16 (OR 1.97; P = 0.01). Adjusting for homeostatic model assessment of insulin resistance and leptin modestly affected associations for obesity with inflammation and monocyte activation. CONCLUSION: Obesity was prevalent and independently associated with greater monocyte activation and systemic inflammation. Research is needed to determine how adipose tissue excess is functionally related to persistent immunologic abnormalities among HIV-infected persons with viral suppression.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4+ cell count 464 cells/mm3, 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

BACKGROUND: Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exist characterizing precursor abnormal anal cytology incidence. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in four U.S. cities. At baseline and annually thereafter, each completed a behavioral questionnaire, and providers collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline anal cytology, 37% developed abnormal cytology (incidence rate 13.9/100 person-years [p-y], 95% confidence interval [CI] 11.3 - 16.9) over a median 2.1 years of follow-up. Rates among men having sex with men, women, and men having sex with women, were 17.9 p-y (CI: 13.9 - 22.7), 9.4 p-y (CI: 5.6 - 14.9), 8.9 p-y (CI: 4.8 - 15.6), respectively. In multivariable analysis, number of persistent high-risk HPV (HR) types (adjusted hazards ratio [adjHR] 1.17, CI: 1.01 - 1.36), persistent HR-HPV types except 16 or 18 ([adjHR] 2.46, CI 1.31 - 4.60), and persistent types 16 or 18 (adjHR 3.90, CI: 1.78 - 8.54) remained associated with incident abnormalities. CONCLUSIONS: Abnormal anal cytology incidence was high and more likely to develop among persons with persistent HR-HPV.

The Veterans Aging Cohort Study (VACS) Index has previously been used to identify frail HIV-infected persons. However, data demonstrating the independent association between the VACS Index and baseline frailty status is lacking. Furthermore, the ability of the VACS Index to also reflect transitions in frailty status over time is unknown. We used data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) to determine independent association of baseline frailty status with the VACS Index. We also evaluated VACS Index changes with frailty status transitions over time. We included 303 participants (median age 48 years, 76% men, 57% non-Hispanic white, 91% with plasma HIV RNA <400 copies/ml, and median CD4(+) cell count 595 cells/ml) with baseline and follow-up frailty assessments and used the Fried's criteria to define frailty status. There were 184 (61%) nonfrail, 112 (37%) prefrail, and seven (2%) frail participants at baseline. Prefrail/frail participants had significantly higher median VACS Index scores compared with nonfrail participants (18 versus 10, p<0.001). In multivariable analysis, prefrailty/frailty was independently associated with a higher VACS Index score (odds ratio 1.025, p=0.019). After a median follow-up of 12 months, participants who remained prefrail/frail compared to those who remained nonfrail continued to have higher median VACS Index scores. The VACS Index score did not significantly change with transitions in frailty status over time. Our study highlights the potential utility of the VACS Index in frailty assessment within the clinical setting.

Vibrio navarrensis is an aquatic bacterium recently shown to be associated with human illness. We report the first genome sequences of three V. navarrensis strains obtained from clinical and environmental sources. Preliminary analyses of the sequences reveal that V. navarrensis contains genes commonly associated with virulence in other human pathogens.

BACKGROUND: We evaluated whether routine biannual sexually transmitted disease (STD) testing coupled with brief risk-reduction counseling reduces STD incidence and high-risk behaviors. METHODS: The SUN study is a prospective observational HIV cohort study conducted in 4 US cities. At enrollment and every 6 months thereafter, participants completed a behavioral survey and were screened for STDs, and if diagnosed, were treated. Medical providers conducted brief risk-reduction counseling with all patients. Among men who have sex with men (MSM), we examined trends in STD incidence and rates of self-reported risk behaviors before and after exposure to the risk-reduction intervention. The "preintervention" visit was the study visit that was at least 6 months after enrollment STD screening and treatment and at which the participant was first exposed to the intervention. The "postintervention" visit was 12 months later. RESULTS: Among 216 MSM with complete STD and behavioral data, median age was 44.5 years; 77% were non-Hispanic white; 83% were on highly active antiretroviral treatment; 84% had an HIV RNA level <400 copies/mL and the median CD4 (cluster of differentiation 4) count was 511 cells/mm. Twelve months after first exposure to the risk-reduction intervention, STD incidence declined from 8.8% to 4.2% (P = 0.041). Rates of unprotected receptive or insertive anal intercourse with HIV-positive partners increased (19% to 25%, P = 0.024), but did not change with HIV-negative partners or partners of unknown HIV status (24% to 22%, P = 0.590). CONCLUSIONS: STD incidence declined significantly among HIV-infected MSM after implementing frequent, routine STD testing coupled with risk-reduction counseling. These findings support adoption of routine STD screening and risk-reduction counseling for HIV-infected MSM.

In the combination antiretroviral therapy (cART) era, renal dysfunction remains common. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) (ClinicalTrials.gov number, NCT00146419) is a prospective observational cohort study of HIV-infected adults. At baseline, comprehensive data were collected, including cystatin C and measures of renal function. Univariate and multivariate regression analyses were performed to identify factors associated with baseline renal dysfunction [estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2) calculated using the simplified Modification of Diet in Renal Disease equation] and elevated cystatin C (>1.0 mg/liter) in a cross-sectional analysis. Among 670 subjects with complete data (mean age 41 years, mean CD4 cell count 530 cells/mm(3), 79% prescribed cART), the mean eGFR was 96.8 ml/min/1.73 m(2). Forty percent of subjects had renal dysfunction; 3.3% had chronic kidney disease (eGFR < 60 ml/min/1.73 m(2)). Elevated cystatin C was present in 18% of subjects. In multivariate analysis, renal dysfunction was associated with older age, non-Hispanic white race/ethnicity, higher body mass index (BMI), hypertension, higher cystatin C levels, and current prescription of ritonavir. Factors associated with elevated cystatin C included hepatitis C coinfection, hypertension, current smoking, older age, current tenofovir use, detectable plasma HIV RNA, and elevated microalbuminuria. The prevalence of chronic kidney disease (CKD) was low in this contemporary HIV cohort. However, mild to moderate renal dysfunction was common despite the widespread use of cART.

BACKGROUND: This study examined the effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. METHODS: Among the Study to Understand the Natural History of HIV/AIDS in the Era of Effective therapy (SUN) participants, we identified 25 individuals (cases) who were HLA-B5701-negative and who had ≥2 weeks without abacavir exposure at one visit and ≥2 weeks with abacavir exposure at the consecutive visit while maintaining viral suppression. We identified 43 individuals (controls) similarly unexposed and exposed to tenofovir. We assessed concentrations of prothrombin fragment F(1+2), D-dimer, high-sensitivity C-reactive protein, interleukin-8, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, P-selectin, serum amyloid A and serum amyloid P. We examined the median percentage change of these biomarkers from the unexposed to exposed state among cases and controls compared with the expected assay variability using a sign test, and compared changes among cases with controls using the Wilcoxon rank-sum test. RESULTS: Baseline characteristics were similar between cases and controls: median age 45 versus 46 years, 80% versus 81% male, 64% versus 63% non-Hispanic White and median CD4(+) T-cell count 538 versus 601 cells/mm(3), respectively. Mean exposure times were 65 and 15 weeks for abacavir and tenofovir, respectively. We observed no significant changes in biomarkers from the unexposed to exposed state among cases or controls compared with the expected assay variability. We found that no biomarkers were significantly increased among cases compared with controls; however, prothrombin fragment F(1+2) was significantly lower among controls (P=0.035). CONCLUSIONS: In virologically suppressed contemporary HIV-infected patients, abacavir exposure was not associated with increases in biomarkers associated with increased cardiovascular risk.