Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

Vaccine development to prevent Staphylococcus aureus surgical-site infections.

BACKGROUND: Staphylococcus aureus surgical-site infections (SSIs) are a major cause of poor health outcomes, including mortality, across surgical specialties. Despite current advances as a result of preventive interventions, the disease burden of S. aureus SSI remains high, and increasing antibiotic resistance continues to be a concern. Prophylactic S. aureus vaccines may represent an opportunity to prevent SSI. METHODS: A review of SSI pathophysiology was undertaken in the context of evaluating new approaches to developing a prophylactic vaccine to prevent S. aureus SSI. RESULTS: A prophylactic vaccine ideally would provide protective immunity at the time of the surgical incision to prevent initiation and progression of infection. Although the pathogenicity of S. aureus is attributed to many virulence factors, previous attempts to develop S. aureus vaccines targeted only a single virulence mechanism. The field has now moved towards multiple-antigen vaccine strategies, and promising results have been observed in early-phase clinical studies that supported the recent initiation of an efficacy trial to prevent SSI. CONCLUSION: There is an unmet medical need for novel S. aureus SSI prevention measures. Advances in understanding of S. aureus SSI pathophysiology could lead to the development of effective and safe prophylactic multiple-antigen vaccines to prevent S. aureus SSI.

Evaluation of Gram-positive rod surveillance for early anthrax detection.

Since 2003, Connecticut laboratories have reported Gram-positive rod (GPR) isolates detected within 32 h of inoculation from blood or cerebrospinal fluid. The objectives were to rapidly identify inhalational anthrax and unusual Clostridium spp. infections, and to establish round-the-clock laboratory reporting of potential indicators of bioterrorism. From 2003 to 2006, Connecticut's GPR surveillance system identified 1134 isolates, including 657 Bacillus spp. (none B. anthracis) and 241 Clostridium spp. Reporting completeness and timeliness improved to 93% and 92%, respectively. Baseline rates of Bacillus spp., Clostridium spp. and other GPR findings have been established and are stable. Thus far, no cases of anthrax and no unusual clusters of Clostridium spp. have been detected by the GPR surveillance system. This system would probably have confirmed the inhalational anthrax case in Pennsylvania in 2006 3 days sooner than traditional reporting. Using audits and ongoing evaluation, the system has evolved into a highly functional 24/7 laboratory telephone reporting system with almost complete reporting.

The development of a staphylococcus aureus four antigen vaccine for use prior to elective orthopedic surgery.

Staphylococcus aureus (S. aureus) is a challenging bacterial pathogen which can cause a range of diseases, from mild skin infections, to more serious and invasive disease including deep or organ space surgical site infections, life-threatening bacteremia, and sepsis. S. aureus rapidly develops resistance to antibiotic treatments. Despite current infection control measures, the burden of disease remains high. The most advanced vaccine in clinical development is a 4 antigen S. aureus vaccine (SA4Ag) candidate that is being evaluated in a phase 2b/3 efficacy study in patients undergoing elective spinal fusion surgery (STaphylococcus aureus suRgical Inpatient Vaccine Efficacy [STRIVE]). SA4Ag has been shown in early phase clinical trials to be generally safe and well tolerated, and to induce high levels of bactericidal antibodies in healthy adults. In this review we discuss the design of SA4Ag, as well as the proposed clinical development plan supporting licensure of SA4Ag for the prevention of invasive disease caused by S. aureus in elective orthopedic surgical populations. We also explore the rationale for the generalizability of the results of the STRIVE efficacy study (patients undergoing elective open posterior multilevel instrumented spinal fusion surgery) to a broad elective orthopedic surgery population due to the common pathophysiology of invasive S. aureus disease and commonalties of patient and procedural risk factors for developing postoperative S. aureus surgical site infections.

Diabetes and depot medroxyprogesterone contraception in Navajo women.

BACKGROUND: Depot medroxyprogesterone acetate contraception is widely used in Navajo women, a high-risk population for diabetes mellitus. However, depot medroxyprogesterone may lead to weight gain and independently decrease insulin sensitivity. We studied the association between depot medroxyprogesterone and development of diabetes in Navajo women. METHODS: We studied Navajo women aged 18 to 50 years who had seen a health care provider at a Navajo Area Indian Health Service clinic at least once in 1998. Diabetic cases (n = 284) and nondiabetic controls (n = 570) were matched by age. Medical records were reviewed to determine contraception use before the diagnosis date of diabetes. RESULTS: Users of depot medroxyprogesterone were more likely to develop diabetes than patients who had used combination estrogen-progestin oral contraception only (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.8-7.9). The excess risk persisted after adjustment for body mass index (OR, 3.6; 95% CI, 1.6-7.9). Longer use was associated with greater risk of diabetes. Users of depot medroxyprogesterone were also more likely to develop diabetes than patients who had never used hormonal contraception, although excess risk was smaller (OR, 2.4; 95% CI, 1.4-3.6). CONCLUSIONS: Depot medroxyprogesterone contraception was associated with a greater risk of diabetes compared with combination oral contraceptive use only. Risk was associated with length of use and persisted after adjustment for body mass index. Additional research is needed for confirmation, but this risk should be considered in contraceptive choice for women at high risk for diabetes.

Training and experience of psychiatric residents in identifying domestic violence.

Of 221 psychiatric residents at four U.S. medical schools, 145 responded to a survey about their training and clinical experience in recognizing domestic violence and providing referrals and treatment. Only 28 percent reported receiving training in this area. Almost half reported that they asked about domestic violence in less than a quarter of their cases involving female patients. Fifty-nine percent of respondents did so "only when a problem was suspected." Eighty-seven percent had seen at least one case of domestic violence in the previous year. Those with training in recognizing domestic violence identified significantly more cases. Sixty-five percent of all residents surveyed were unable to list a local agency for referral.