Laboratory diagnosis of bacterial meningitis by direct detection, serotyping and Next Generation Sequencing: How 10 years of testing in New York State has evolved to improve laboratory diagnosis and public health.

Since 2005, the Wadsworth Center (WC) has provided molecular testing on cerebrospinal fluid (CSF) and whole blood specimens in close collaboration with epidemiologists in New York State and New York City. In this study, we analyzed 10 years of data to demonstrate the significant value of utilizing molecular methods to assess patient specimens for etiologic agents of bacterial meningitis. A comprehensive molecular testing algorithm to detect and serotype/serogroup bacterial agents known to cause bacterial meningitis (Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus agalactiae) has evolved, and retrospective specimen testing has been essential for each improvement. Over a ten-year span from 2010 to 2019 the WC received 831 specimens from 634 patients with suspected bacterial meningitis. Real-time PCR was positive for at least one of the agents in 223 (27%) specimens from 183 patients (29%). Of the 223 positives, 146 (66%) were further characterized by real-time PCR into serogroup/serotype. Additionally, examination of 131 paired specimens of CSF and whole blood from the same patients found better detection in CSF, but whole blood is a useful alternative for diagnosis when CSF is not available. For specimens initially PCR-negative, 16S rDNA Sanger sequencing was requested by the submitter for 146 cases resulting in the identification of bacterial agents in an additional 24 (16%) specimens. In a retrospective study, Next Generation Sequencing (NGS) was evaluated for the detection of pathogens in 53 previously tested PCR-negative CSF specimens and identified bacteria in 14 (26%) specimens. This molecular testing algorithm has provided clinicians a diagnosis when culture is negative with the potential to guide therapy. It has also aided public health in determining when antibiotic prophylaxis was needed, augmented surveillance data to yield a fuller picture of community prevalence, and highlighted gaps in the spectrum of agents that cause bacterial meningitis.

Candida auris Colonization After Discharge to a Community Setting: New York City, 2017-2019.

BACKGROUND: Patients colonized with multidrug-resistant Candida auris and discharged to a community setting can subsequently seek care in a different healthcare facility and might be a source of nosocomial transmission of C auris. METHODS: We designed a case management pilot program for a cohort of New York City residents who had a history of positive C auris culture identified during clinical or screening activities in healthcare settings and discharged to a community setting during 2017-2019. Approximately every 3 months, case managers coordinated C auris colonization assessments, which included swabs of groin, axilla, and body sites yielding C auris previously. Patients eligible to become serially negative were those with ≥2 C auris colonization assessments after initial C auris identification. Clinical characteristics of serially negative and positive patients were compared. RESULTS: The cohort included 75 patients. Overall, 45 patients were eligible to become serially negative and had 552 person-months of follow-up. Of these 45 patients, 28 patients were serially negative (62%; rate 5.1/100 person-months), 8 were serially positive, and 9 could not be classified as either. There were no clinical characteristics that were significantly different between serially negative and positive patients. The median time from initial C auris identification to being serially negative at assessments was 8.6 months (interquartile range, 5.7-10.8 months). CONCLUSIONS: A majority of patients, assessed at least twice after C auris identification, no longer had C auris detectable on serial colonization assessments.

Sex Difference in Meningococcal Disease Mortality, New York City, 2008-2016.

Background: The case fatality rate (CFR) from invasive meningococcal disease (IMD) in New York City (NYC) is greater than national figures, with higher rates among females than males across all age groups. Methods: We conducted a retrospective cohort study among 151 persons aged ≥15 years diagnosed with IMD in NYC during 2008-2016 identified through communicable disease surveillance. We examined demographic, clinical, and community-level associations with death to confirm the elevated risk of mortality among female IMD patients after adjusting for confounders and to determine factors associated with female IMD mortality. Relative risks of death were estimated using multivariable log-linear Poisson regression with a robust error variance. Results: Females had a higher CFR (n = 23/62; 37%) following IMD than males (n = 17/89; 19%) (adjusted relative risk [aRR], 2.1; 95% confidence interval [CI], 1.2-3.8). Controlling for demographic and clinical factors, there was a significant interaction between sex and fatal outcomes related to meningitis: the relative risk of death for females with meningitis was 13.7 (95% CI, 3.2-58.1) compared with males. In the model restricted to females, altered mental status (aRR, 7.5; 95% CI, 2.9-19.6) was significantly associated with an increased risk of death. Conclusions: Female mortality from IMD was significantly increased compared with males, controlling for other predictors of mortality. Sex-based differences in recognition and treatment need to be evaluated in cases of meningococcal disease. Our study highlights the importance of analyzing routine surveillance data to identify and address disparities in disease incidence and outcomes.

Notes from the Field: Increase in Reported Hepatitis A Infections Among Men Who Have Sex with Men - New York City, January-August 2017.

Since 2011, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has typically been notified of three or fewer cases of hepatitis A virus (HAV) infection each year among men who have sex with men (MSM) who reported no travel to countries where HAV is endemic. This year, DOHMH noted an increase in HAV infections among MSM with onsets in January-March 2017, and notified other public health jurisdictions via Epi-X, CDC's communication exchange network. As a result, 51 patients with HAV infection involving MSM were linked to the increase in NYC.

Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012-2015.

BACKGROUND: Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well described. METHODS: All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described. Annualized incidence rates among MSM and non-MSM were compared through calculation of the relative risk and 95% confidence intervals. Isolates from meningococcal disease cases among MSM were characterized using standard microbiological methods and whole-genome sequencing. RESULTS: Seventy-four cases of meningococcal disease were reported among MSM and 453 among non-MSM. Annualized incidence of meningococcal disease among MSM was 0.56 cases per 100000 population, compared to 0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1-5.1). Among the 64 MSM with known status, 38 (59%) were infected with human immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6) the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were serogroup C sequence type 11. CONCLUSIONS: MSM are at increased risk for meningococcal disease, although the incidence of disease remains low. HIV infection may be an important factor for this increased risk. Routine vaccination of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in accordance with Advisory Committee on Immunization Practices recommendations should be encouraged.

Notes from the Field: Fungal Bloodstream Infections Associated with a Compounded Intravenous Medication at an Outpatient Oncology Clinic - New York City, 2016.

On May 24, 2016, the New York City Department of Health and Mental Hygiene notified CDC of two cases of Exophiala dermatitidis bloodstream infections among patients with malignancies who had received care from a single physician at an outpatient oncology facility (clinic A). Review of January 1-May 31, 2016 microbiology records identified E. dermatitidis bloodstream infections in two additional patients who also had received care at clinic A. All four patients had implanted vascular access ports and had received intravenous (IV) medications, including a compounded IV flush solution containing saline, heparin, vancomycin, and ceftazidime, compounded and administered at clinic A.

Delayed recognition of fatal invasive meningococcal disease in adults.

INTRODUCTION: Invasive meningococcal disease can be difficult to detect early in its course when patients may appear well and the severity of their illness is obscured by non-specific complaints. CASE PRESENTATION: We report five cases of meningococcal sepsis in adult patients who presented to an emergency department early in the course of their disease, but whose severity of illness was not recognized. CONCLUSION: Suspicion of meningococcal sepsis should be heightened in the setting of hypotension, tachycardia, elevated shock index, leukopaenia with left shift, thrombocytopaenia and hypokalaemia, prompting early sepsis care.

Direct molecular testing to assess the incidence of meningococcal and other bacterial causes of meningitis among persons reported with unspecified bacterial meningitis.

Confirmed and probable cases of invasive Neisseria meningitidis (Nm) infection are reportable in New York City. We conducted a study to identify Nm among culture-negative reports of bacterial and viral meningitis. During the study period, 262 reports of suspected meningitis were eligible. Cerebrospinal fluid (CSF) specimens from 138 patients were obtained for testing. No Nm cases were detected. Results from real-time polymerase chain reaction and 16S on CSF specimens were concordant with hospital microbiology findings in 80%; however, other pathogenic organisms were detected in 14 culture-negative specimens. New York City's surveillance system appears to be effective at capturing cases of Nm meningitis. Nucleic acid testing is useful for detecting the presence of bacterial DNA when antibiotic therapy precedes lumbar puncture or bacterial cultures are negative. It remains unanswered whether culture-negative cases of Nm bacteremia are being missed by reportable disease surveillance.

A cluster of methicillin-susceptible Staphylococcus aureus infections at a rheumatology practice, New York City, 2011.

A cluster of 5 methicillin-susceptible Staphylococcus aureus infections occurred after administration of methylprednisolone acetate injections in a rheumatology practice. A site visit was conducted to inspect examination rooms, observe techniques, and review charts. The investigation revealed a pervasive lack of aseptic technique that led to multiple opportunities for medication contamination.

Functional capacity is a better predictor of coronary heart disease than depression or abnormal sleep duration in Black and White Americans.

OBJECTIVE: To assess whether functional capacity is a better predictor of coronary heart disease (CHD) than depression or abnormal sleep duration. METHODS: Adult civilians in the USA (n=29,818, mean age 48 ± 18 years, range 18-85 years) were recruited by a cross-sectional household interview survey using multistage area probability sampling. Data on chronic conditions, estimated habitual sleep duration, functional capacity, depressed moods, and sociodemographic characteristics were obtained. RESULTS: Thirty-five percent of participants reported reduced functional capacity. The CHD rates among White and Black Americans were 5.2% and 4%, respectively. Individuals with CHD were more likely to report extreme sleep durations (short sleep [≤ 5h] or long sleep [≥ 9 h]; odds ratio [OR] 1.65, 95% confidence interval [CI] 1.38-1.97; P<0.0001), less likely to be functionally active (anchored by the ability to walk one-quarter of a mile without assistance [OR 6.27, 95% CI 5.64-6.98; P<0.0001]) and more likely to be depressed (OR 1.78, 95% CI 1.60-1.99; P<0.0001) than their counterparts. On multivariate regression analysis adjusting for sociodemographic factors and health characteristics, only functional capacity remained an independent predictor of CHD (OR 1.81, 95% CI 1.42-2.31; P<0.0001). CONCLUSION: Functional capacity was an independent predictor of CHD in the study population, whereas depression and sleep duration were not independent predictors.

Epidemiology and burden of hepatitis A, malaria, and typhoid in New York City associated with travel: implications for public health policy.

We examined New York City Department of Health and Mental Hygiene surveillance data on hepatitis A, malaria, and typhoid to determine the proportion of these diseases related to travel and their geographic distribution. We found that 61% of hepatitis A cases, 100% of malaria cases, and 78% of typhoid cases were travel related and that cases clustered in specific populations and neighborhoods at which public health interventions could be targeted. High-risk groups include Hispanics (for hepatitis A), West Africans living in the Bronx (for malaria), and South Asians (for typhoid).