Lindsay Kim

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

SUMMARY Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand.

Incremental Cost-Effectiveness of 13-valent Pneumococcal Conjugate Vaccine for Adults Age 50 Years and Older in the United States

ABSTRACTBACKGROUNDRecently released results from a randomized controlled trial have shown that 13-valent pneumococcal conjugate vaccine (PCV13) is efficacious against vaccine-type nonbacteremic pneumonia in adults.OBJECTIVEWe examined the incremental cost-effectiveness of adding PCV13 to the Advisory Committee on Immunization Practices (ACIP) adult immunization schedule.METHODSWe used a probabilistic model following cohorts of 50-, 60-, or 65-year-olds. We used separate vaccination coverage and disease incidence data for healthy and high-risk adults. Incremental cost-effectiveness ratios were determined for each potential vaccination strategy.RESULTSIn the base case scenario, our model indicated that adding PCV13 at age 65 or replacing 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 with PCV13 provided more value for money than adding PCV13 at ages 50 or 60. After projections of six additional years of herd protection from the childhood immunization program were incorporated, we found adding PCV13 dominated replacing PPSV23. For a cohort of 65-year-olds in 2013, the cost of adding PCV13 at age 65 to the schedule was

Prevention of Antibiotic-Nonsusceptible Invasive Pneumococcal Disease With the 13-Valent Pneumococcal Conjugate Vaccine

62,065 per quality-adjusted life year (QALY) gained, which rose to

Response to Emergence of Middle East Respiratory Syndrome Coronavirus, Abu Dhabi, United Arab Emirates, 2013–2014

272,621 after 6 years of projected herd protection.CONCLUSIONThe addition of one dose of PCV13 for adults appears to have a cost-effectiveness ratio comparable to other vaccination interventions in the short run, though anticipated herd protection from the childhood immunization program may dramatically increase the cost per QALY after only a few years.

Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE

BACKGROUND Antibiotic-nonsusceptible invasive pneumococcal disease (IPD) decreased substantially after the US introduction of the pediatric 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. However, rates of antibiotic-nonsusceptible non-PCV7-type IPD increased during 2004-2009. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7. We assessed the impact of PCV13 on antibiotic-nonsusceptible IPD rates. METHODS We defined IPD as pneumococcal isolation from a normally sterile site in a resident from 10 US surveillance sites. Antibiotic-nonsusceptible isolates were those intermediate or resistant to ≥1 antibiotic classes according to 2012 Clinical and Laboratory Standards Institute breakpoints. We examined rates of antibiotic nonsusceptibility and estimated cases prevented between observed cases of antibiotic-nonsusceptible IPD and cases that would have occurred if PCV13 had not been introduced. RESULTS From 2009 to 2013, rates of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not in PCV7 decreased from 6.5 to 0.5 per 100 000 in children aged <5 years and from 4.4 to 1.4 per 100 000 in adults aged ≥65 years. During 2010-2013, we estimated that 1636 and 1327 cases of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not PCV7 were prevented among children aged <5 years (-97% difference) and among adults aged ≥65 years (-64% difference), respectively. Although we observed small increases in antibiotic-nonsusceptible IPD caused by non-PCV13 serotypes, no non-PCV13 serotype dominated among antibiotic-nonsusceptible strains. CONCLUSIONS After PCV13 introduction, antibiotic-nonsusceptible IPD decreased in multiple age groups. Continued surveillance is needed to monitor trends of nonvaccine serotypes. Pneumococcal conjugate vaccines are important tools in the approach to combat antibiotic resistance.

Cohort profile: the China Ageing REespiratory infections Study (CARES), a prospective cohort study in older adults in Eastern China

We found that this virus may be detected in mildly ill and asymptomatic case-patients.

Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008-2010.

Since the emergence of Middle East respiratory syndrome coronavirus (MERS‐CoV) in 2012, there have been a number of clusters of human‐to‐human transmission. These cases of human‐to‐human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. In this study, we sequenced whole MERS‐CoV genomes directly from respiratory samples collected from 23 confirmed MERS cases in the United Arab Emirates (UAE). These samples included cases from three nosocomial and three household clusters. The sequences were analysed for changes and relatedness with regard to the collected epidemiological data and other available MERS‐CoV genomic data. Sequence analysis supports the epidemiological data within the clusters, and further, suggests that these clusters emerged independently. To understand how and when these clusters emerged, respiratory samples were taken from dromedary camels, a known host of MERS‐CoV, in the same geographic regions as the human clusters. Middle East respiratory syndrome coronavirus genomes from six virus‐positive animals were sequenced, and these genomes were nearly identical to those found in human patients from corresponding regions. These data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS‐CoV diversity results from multiple zoonotic introductions.

Respiratory syncytial virus testing capabilities and practices among National Respiratory and Enteric Virus Surveillance System laboratories, United States, 2016

Purpose This study was established to provide direct evidence on the incidence of laboratory-confirmed influenza virus and respiratory syncytial virus (RSV) infections in older adults in two cities in Jiangsu Province, China, and the potential impact of acute respiratory infections on frailty. Participants The cohort was enrolled in Suzhou and Yancheng, two cities in Jiangsu Province in Eastern China. Between November 2015 and March 2016, we enrolled 1532 adults who were 60–89 years of age, and collected blood samples along with baseline data on demographics, general health, chronic diseases, functional status and cognitive function through face-to-face interviews using a standardised questionnaire. Participants are being followed weekly throughout the year to identify acute respiratory illnesses. We schedule home visits to ill participants to collect mid-turbinate nasal and oropharyngeal swabs for laboratory testing and detailed symptom information for the acute illness. Regular follow-up including face-to-face interviews and further blood draws will take place every 6–12 months. Findings to date As of 3 September 2016, we had identified 339 qualifying acute respiratory illness events and 1463 (95%) participants remained in the study. Laboratory testing is ongoing. Future plans We plan to conduct laboratory testing to estimate the incidence of influenza virus and RSV infections in older adults. We plan to investigate the impact of these infections on frailty and functional status to determine the association of pre-existing immune status with protection against influenza and RSV infection in unvaccinated older adults, and to assess the exposure to avian influenza viruses in this population.

Serologic Follow-up of Middle East Respiratory Syndrome Coronavirus Cases and Contacts—Abu Dhabi, United Arab Emirates

Background Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. Methods A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008–31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. Results Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). Conclusions The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment.

Simplified Pneumococcal Vaccination Schedules for Adults Age 50 and Over Lead to Worse Health

BACKGROUND Laboratory tests to detect respiratory syncytial virus (RSV) vary in sensitivity and specificity. Diagnostic testing practices can impact RSV disease diagnosis and burden estimates. OBJECTIVES We surveyed a sample of laboratories that participated in the National Respiratory and Enteric Virus Surveillance System (NREVSS) in 2015-2016 to understand RSV testing, diagnostic capabilities, and practices. STUDY DESIGN We distributed surveys in fall 2016 to NREVSS laboratories using an internet survey platform. We conducted a descriptive analysis of survey responses and stratified results by self-identified childrens hospital laboratories (CHL, i.e. laboratories affiliated with or in a childrens hospital) or general hospital laboratories (GHL, i.e. laboratories that performed analysis on specimens from only adults or adults and children). RESULTS We sampled 367 (82.5%) of 445 eligible NREVSS laboratories with a 35.7% response rate; 11.5% (n = 15) were CHLs. All CHLs had PCR-based assay capability to test for RSV compared to 48.7% of GHLs (p < 0.001), and it was the most frequent method used by CHLs (n = 9, 75.0%). GHLs used rapid antigen detection tests most frequently (n = 65, 60.2%) to detect RSV compared to CHLs (p = 0.02, n = 3, 25.0%). Almost half (n = 41, 48.2%) of GHLs reported specimen submission from adults ≥50 years for RADTs. CONCLUSIONS Laboratory testing and diagnostic capabilities differed by whether laboratories self-identified as a CHL or GHL. Many GHLs reported use of RADTs in adults ≥50 years, a less sensitive diagnostic method for this population compared to PCR-based assays. RADT use in adults might miss RSV cases and affect diagnoses and disease burden estimates.