Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017.

OBJECTIVES: We aimed to provide population-based and whole-genome sequence (WGS) -based characterization of invasive pneumococcal disease isolates collected from multistate surveillance in the USA during 2017. METHODS: We obtained short-read WGS from 2881 isolates with associated bioinformatics pipeline strain feature predictions. For quality control, capsular serotypes and antimicrobial MICs were also obtained conventionally from 442 isolates. Annotated WGS were provided (inclusive of serotypes, MICs, multilocus sequence types, pilus type(s)) from 2723 isolates. For 158 isolates with suboptimal WGS, antimicrobial MICs were obtained conventionally. RESULTS: There were 127 isolates from children <5 years of age and 2754 isolates from those ≥5 years old in 2017. One of 43 different serotypes was predicted for 2877 of the 2881 isolates. Serotypes in the 13-valent conjugate vaccine together with 6C (PCV13+6C) accounted for 816 (28.3%) isolates, with PCV13 serotype 3 being the most common serotype overall. Non-PCV13-6C- serotypes accounted for 2065 (71.7%) isolates, comprising 96 (75.6%) isolates from children < 5 years old and 1969 (61.4%) isolates from those aged ≥5 years. Of 36 different categories of recently emerged serotype-switch variants, three showed marked increases relative to 2015-2016 in that the number from 2017 surpassed the number from 2015-2016 combined. Two of these included antimicrobial-resistant serotype 11A and 35B serotype-switch variants of the ST156 clonal complex. CONCLUSIONS: PCV13+6C strains are still identified in 2017 but non-PCV13-type strains impose a considerable burden. This well-annotated year 2017 WGS/strain data set will prove useful for a broad variety of analyses and improved our understanding of invasive pneumococcal disease-causing strains in the post-PCV13 era.

Lyme disease surveillance in the United States: Looking for ways to cut the Gordian knot.

Current surveillance methods have been useful to document geographic expansion of Lyme disease in the United States and to monitor the increasing incidence of this major public health problem. Nevertheless, these approaches are resource-intensive, generate results that are difficult to compare across jurisdictions, and measure less than the total burden of disease. By adopting more efficient methods, resources could be diverted instead to education of at-risk populations and new approaches to prevention. In this special issue of Zoonoses and Public Health, seven articles are presented that either evaluate traditional Lyme disease surveillance methods or explore alternatives that have the potential to be less costly, more reliable, and sustainable. Twenty-five years have passed since Lyme disease became a notifiable condition - it is time to reevaluate the purpose and goals of national surveillance.

Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA.

OBJECTIVES: Our objective was to evaluate and exploit a whole genome sequence (WGS) bioinformatics pipeline for predicting antimicrobial resistance and capsular serotypes from invasive group B streptococci (iGBS). METHODS: For 1975 iGBS recovered during 2015 from CDC's Active Bacterial Core surveillance, we compared pipeline predictions with broth dilution testing. Fifty-six isolates from earlier surveillance were included for testing ß-lactams. Conventional serotyping was compared to WGS-based assignments for 302 isolates. RESULTS: All 28 isolates with reduced susceptibility to ß-lactam antibiotics harboured one of 19 rare PBP2x types. Resistances to erythromycin/clindamycin (808/1975 isolates, 41.0%), erythromycin (235/1975, 11.9%) and lincosamide/streptogramin A/pleuromutilins (56/1975, 2.8%) were predicted by the presence of erm-methylase, mef and lsa determinants, respectively (41 of 56 lsa gene-positive isolates also contained lnu, erm and/or mef genes). Presence of both erm and lsa determinants (25 isolates) predicted non-susceptibility to quinupristin/dalfopristin. Most isolates (1680/1975, 85.1%) were tet gene-positive, although 41/1565 (2.6%) tetM-positive isolates were tetracycline-susceptible. All 53 fluoroquinolone-resistant isolates contained ParC and/or GyrA substitutions. Resistances to rifampin (eight isolates), trimethoprim, chloramphenicol and vancomycin (two isolates each) were predicted by the pipeline. Resistance to macrolides/lincosamides without pipeline prediction was rare and correlated to divergent resistance genes or rRNA A2062G substitution. A selection of 267 isolates assigned WGS-based serotypes were also conventionally serotyped. Of these, 246 (92.1%) were in agreement, with the remaining 21 (7.8%) conventionally non-serotypeable. For 32 of 1975 isolates (1.6%), WGS-based serotypes could not be assigned. CONCLUSION: The WGS-based assignment of iGBS resistance features and serotypes is an accurate substitute for phenotypic testing.

Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States.

Our whole genome sequence (WGS) pipeline was assessed for accurate prediction of antimicrobial phenotypes. For 2316 invasive pneumococcal isolates recovered during 2015 we compared WGS pipeline data to broth dilution testing (BDT) for 18 antimicrobials. For 11 antimicrobials categorical discrepancies were assigned when WGS-predicted MICs and BDT MICs predicted different categorizations for susceptibility, intermediate resistance or resistance, ranging from 0.9% (tetracycline) to 2.9% (amoxicillin). For ß-lactam antibiotics, the occurrence of at least four-fold differences in MIC ranged from 0.2% (meropenem) to 1.0% (penicillin), although phenotypic retesting resolved 25%-78% of these discrepancies. Non-susceptibility to penicillin, predicted by penicillin-binding protein types, was 2.7% (non-meningitis criteria) and 23.8% (meningitis criteria). Other common resistance determinants included mef (475 isolates), ermB (191 isolates), ermB + mef (48 isolates), tetM (261 isolates) and cat (51 isolates). Additional accessory resistance genes (tetS, tet32, aphA-3, sat4) were rarely detected (one to three isolates). Rare core genome mutations conferring erythromycin-resistance included a two-codon rplD insertion (rplD69-KG-70) and the 23S rRNA A2061G substitution (six isolates). Intermediate cotrimoxazole-resistance was associated with one or two codon insertions within folP (238 isolates) or the folA I100L substitution (38 isolates), whereas full cotrimoxazole-resistance was attributed to alterations in both genes (172 isolates). The two levofloxacin-resistant isolates contained parC and/or gyrA mutations. Of 11 remaining isolates with moderately elevated MICs to both ciprofloxacin and levofloxacin, seven contained parC or gyrA mutations. The two rifampin-resistant isolates contained rpoB mutations. WGS-based antimicrobial phenotype prediction was an informative alternative to BDT for invasive pneumococci.

Variant Influenza Associated with Live Animal Markets, Minnesota.

Variant influenza viruses are swine-origin influenza A viruses that cause illness in humans. Surveillance for variant influenza A viruses, including characterization of exposure settings, is important because of the potential emergence of novel influenza viruses with pandemic potential. In Minnesota, we have documented variant influenza A virus infections associated with swine exposure at live animal markets.

Heavy alcohol use as a risk factor for severe outcomes among adults hospitalized with laboratory-confirmed influenza, 2005-2012.

We examined heavy alcohol use as a risk factor for severe influenza (intensive care admission or death) among hospitalized adults. In <65- and ≥65-year-olds, heavy alcohol use increased disease severity [relative risk (RR) 1.34; 95 % confidence interval (CI): 1.04-1.74, and RR 2.47; 95 % CI: 1.69-3.60, respectively]. Influenza vaccination and early, empiric antiviral treatment should be emphasized in this population.

Haemophilus influenzae type b infection, vaccination, and H. influenzae carriage in children in Minnesota, 2008-2009.

An increase in invasive Haemophilus influenzae type b (Hib) cases occurred in Minnesota in 2008 after the recommended deferral of the 12-15 months Hib vaccine boosters during a US vaccine shortage. Five invasive Hib cases (one death) occurred in children; four had incomplete Hib vaccination (three refused/delayed); one was immunodeficient. Subsequently, we evaluated Hib carriage and vaccination. From 18 clinics near Hib cases, children (aged 4 weeks-60 months) were surveyed for pharyngeal Hib carriage. Records were compared for Hib, diphtheria-tetanus-acellular pertussis (DTaP), and pneumococcal (PCV-7) vaccination. Parents completed questionnaires on carriage risk factors and vaccination beliefs. In 1631 children (February-March 2009), no Hib carriage was detected; Hib vaccination was less likely to be completed than DTaP and PCV-7. Non-type b H. influenzae, detected in 245 (15%) children, was associated with: male sex, age 24-60 months, daycare attendance >15 h/week, a household smoker, and Asian/Pacific Islander race/ethnicity. In 2009, invasive Hib disease occurred in two children caused by the same strain that circulated in 2008. Hib remains a risk for vulnerable/unvaccinated children, although Hib carriage is not widespread in young children.

Clinical and laboratory characteristics of invasive infections due to methicillin-resistant Staphylococcus aureus isolates demonstrating a vancomycin MIC of 2 micrograms per milliliter: lack of effect of heteroresistant vancomycin-intermediate S. aureus phenotype.

We describe clinical and laboratory characteristics of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin MICs of 2 µg/ml and compare heteroresistant-intermediate S. aureus (hVISA) to non-hVISA. Health care-associated community-onset infections were the most common and resulted in frequent complications and relapses. hVISA-infected patients were more likely to have been hospitalized in the year prior to MRSA culture.

Risk factors for community-associated Staphylococcus aureus infections: results from parallel studies including methicillin-resistant and methicillin-sensitive S. aureus compared to uninfected controls.

Despite the increasing burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, the risk factors are not well understood. We conducted a hypothesis-generating study using three parallel case-control studies to identify risk factors for CA-MRSA and community-associated methicillin-susceptible S. aureus (CA-MSSA) infections. In the multivariate model, antimicrobial use in the 1-6 months prior to culture was associated with CA-MRSA infection compared to CA-MSSA [adjusted odds ratio (aOR) 1·7, P=0·07] cases. Antimicrobial use 1-6 months prior to culture (aOR 1·8, P=0·04), history of boils (aOR 1·6, P=0·03), and having a household member who was a smoker (aOR 1·3, P=0·05) were associated with CA-MRSA compared to uninfected community controls. The finding of an increased risk of CA-MRSA infection associated with prior antimicrobial use highlights the importance of careful antimicrobial stewardship.

Addressing emerging infections. The partnership between public health and primary care physicians.

In response to concerns about emerging infections, the Minnesota Department of Health, in conjunction with the Centers for Disease Control and Prevention, developed a model emerging infections program in 1995. The authors' experience with the program has demonstrated the key role clinicians have as partners with public health agencies in identifying and reporting disease cases, educating patients about infectious risks, and preventing emerging infections. This partnership is well illustrated by two examples from Minnesota: a recent outbreak of Neisseria meningitidis infection in a rural area and a laboratory surveillance study of invasive and drug-resistant Streptococcus pneumoniae infections in a metropolitan area.

Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. The New England Regional Toxoplasma Working Group.

BACKGROUND: Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. METHODS: In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. RESULTS: Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three). CONCLUSIONS: Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.

Varicella in pediatric renal transplant recipients.

As of November 1991, 8 of 83 children who had received renal transplants at Massachusetts General Hospital since January 1979 required admission for primary varicella. All 8 had cutaneous manifestations of disease, and 4 had evidence of visceral disease. Three of these 8 children received varicella zoster immune globulin (VZIG) after exposure to varicella; in the remaining children, exposure was not revealed until symptoms were present. All 8 children were treated with high-dose intravenous acyclovir. Two children died of complications of varicella infection, including 1 child who received VZIG on the day of exposure to varicella. Neither VZIG prophylaxis nor treatment with intravenous acyclovir offers complete protection against severe varicella infection to immunosuppressed children who have received organ transplants. A high priority should be given to the evaluation of alternative treatments, such as vaccination to the varicella virus, which could be administered to susceptible transplant candidates, preferably prior to transplantation.

Cancers-associated with HIV infection.

The spectrum of neoplastic disease seen in patients with the acquired immune deficiency syndrome (AIDS) is similar to that seen in several congenital and iatrogenic immunodeficiency states and provides a human model for studying neoplastic transformation in the immune compromised host. High grade lymphoid neoplasia, particularly of the central nervous system (CNS), as well as a virulent form of Kaposi's sarcoma (KS) and several types of squamous cell carcinomas, are appearing at an alarming rate in patients with AIDS. There is substantial serologic, pathologic and molecular evidence linking cytomegalovirus (CMV) to KS and Epstein-Barr virus (EBV) to squamous cell carcinoma and high-grade B-cell non-Hodgkin's lymphoma (NHL). The human T-cell lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) may be responsible for the permissive immune deficient state allowing for opportunistic neoplasia and the aggressive biologic behavior and atypical anatomic distribution these neoplasms exhibit. The clinical features as well as potential etiopathogenetic mechanisms of these malignancies are reviewed.