A novel hybridization capture method for direct whole genome sequencing of clinical specimens to inform Legionnaires' disease investigations.

The unprecedented precision and resolution of whole genome sequencing (WGS) can provide definitive identification of infectious agents for epidemiological outbreak tracking. WGS approaches, however, are frequently impeded by low pathogen DNA recovery from available primary specimens or unculturable samples. A cost-effective hybrid capture assay for Legionella pneumophila WGS analysis directly on primary specimens was developed. DNA from a diverse range of sputum and autopsy specimens PCR-positive for L. pneumophila serogroup 1 (LPSG1) was enriched with this method, and WGS was performed. All tested specimens were determined to be enriched for Legionella reads (up to 209,000-fold), significantly improving the discriminatory power to compare relatedness when no clinical isolate was available. We found the WGS data from some enriched specimens to differ by less than five single-nucleotide polymorphisms (SNPs) when compared to the WGS data of a matched culture isolate. This testing and analysis retrospectively provided previously unconfirmed links to environmental sources for clinical specimens of sputum and autopsy lung tissue. The latter provided the additional information needed to identify the source of these culture-negative cases associated with the South Bronx 2015 Legionnaires' disease (LD) investigation in New York City. This new method provides a proof of concept for future direct clinical specimen hybrid capture enrichment combined with WGS and bioinformatic analysis during outbreak investigations.IMPORTANCELegionnaires' disease (LD) is a severe and potentially fatal type of pneumonia primarily caused by inhalation of Legionella-contaminated aerosols from man-made water or cooling systems. LD remains extremely underdiagnosed as it is an uncommon form of pneumonia and relies on clinicians including it in the differential and requesting specialized testing. Additionally, it is challenging to obtain clinical lower respiratory specimens from cases with LD, and when available, culture requires specialized media and growth conditions, which are not available in all microbiology laboratories. In the current study, a method for Legionella pneumophila using hybrid capture by RNA baiting was developed, which allowed us to generate sufficient genome resolution from L. pneumophila serogroup 1 PCR-positive clinical specimens. This new approach offers an additional tool for surveillance of future LD outbreaks where isolation of Legionella is not possible and may help solve previously unanswered questions from past LD investigations.

Delayed Recognition of Coronavirus Disease 2019 (COVID-19) in New York City: A Descriptive Analysis of COVID-19 Illness Prior to 29 February 2020.

BACKGROUND: On 30 January 2020, COVID-19 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. Almost a month later, on 29 February 2020, the first case in New York City (NYC) was diagnosed. METHODS: Three hundred sixty persons with COVID-19-like illness were reported to the NYC Department of Health and Mental Hygiene (DOHMH) before 29 February, but 37 of these tested negative and 237 were never tested for severe acute respiratory syndrome coronavirus 2. Records of 86 persons with confirmed COVID-19 and reported symptom onset prior to 29 February 2020 were reviewed by 4 physician-epidemiologists. Case-patients were classified as possible delayed recognition (PDR) of COVID-19 when upon medical review the reported onset date was believed to reflect the initial symptoms of COVID-19, or insufficient evidence to classify, when the onset could not be determined with confidence. Clinical and epidemiological factors collected by DOHMH and supplemented with emergency department records were analyzed. RESULTS: Thirty-nine PDR COVID-19 cases were identified. The majority had severe disease with 69% presenting to an emergency department within 2 weeks of symptom onset. The first PDR COVID-19 case had symptom onset on 28 January 2020. Only 7 of the 39 cases (18%) had traveled internationally within 14 days of onset (none to China). CONCLUSIONS: COVID-19 was in NYC before being classified as a PHEIC, and eluded surveillance for another month. The delay in recognition limited mitigation efforts; by the time city- and statewide mandates were enacted, 16 and 22 days later, there was already widespread community transmission.

Reduced Odds of Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection After Vaccination Among New York City Adults, July 2021-November 2021.

BACKGROUND: Belief that vaccination is not needed for individuals with prior infection contributes to coronavirus disease 2019 (COVID-19) vaccine hesitancy. Among individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before vaccines became available, we determined whether vaccinated individuals had reduced odds of reinfection. METHODS: We conducted a case-control study among adult New York City residents who tested positive for SARS-CoV-2 infection in 2020 and had not died or tested positive again >90 days after an initial positive test as of 1 July 2021. Case patients with reinfection during July 2021-November 2021 and controls with no reinfection were matched (1:3) on age, sex, timing of initial positive test in 2020, and neighborhood poverty level. Matched odds ratios (mORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. RESULTS: Of 349 827 eligible adults, 2583 were reinfected during July 2021-November 2021. Of 2401 with complete matching criteria data, 1102 (45.9%) were known to be symptomatic for COVID-19-like illness, and 96 (4.0%) were hospitalized. Unvaccinated individuals, compared with individuals fully vaccinated within the prior 90 days, had elevated odds of reinfection (mOR, 3.21; 95% CI, 2.70 to 3.82), of symptomatic reinfection (mOR, 2.97; 95% CI, 2.31 to 3.83), and of reinfection with hospitalization (mOR, 2.09; 95% CI, .91 to 4.79). CONCLUSIONS: Vaccination reduced odds of reinfections when the Delta variant predominated. Further studies should assess risk of severe outcomes among reinfected persons as new variants emerge, infection- and vaccine-induced immunity wanes, and booster doses are administered.

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.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Following the Largest Initial Epidemic Wave in the United States: Findings From New York City, 13 May to 21 July 2020.

BACKGROUND: New York City (NYC) was the US epicenter of the spring 2020 coronavirus disease 2019 (COVID-19) pandemic. We present the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and correlates of seropositivity immediately after the first wave. METHODS: From a serosurvey of adult NYC residents (13 May to 21 July 2020), we calculated the prevalence of SARS-CoV-2 antibodies stratified by participant demographics, symptom history, health status, and employment industry. We used multivariable regression models to assess associations between participant characteristics and seropositivity. RESULTS: The seroprevalence among 45 367 participants was 23.6% (95% confidence interval, 23.2%-24.0%). High seroprevalence (>30%) was observed among black and Hispanic individuals, people from high poverty neighborhoods, and people in healthcare or essential worker industry sectors. COVID-19 symptom history was associated with seropositivity (adjusted relative risk, 2.76; 95% confidence interval, 2.65-2.88). Other risk factors included sex, age, race/ethnicity, residential area, employment sector, working outside the home, contact with a COVID-19 case, obesity, and increasing numbers of household members. CONCLUSIONS: Based on a large serosurvey in a single US jurisdiction, we estimate that just under one-quarter of NYC adults were infected in the first few months of the COVID-19 epidemic. Given disparities in infection risk, effective interventions for at-risk groups are needed during ongoing transmission.

Coronavirus Disease 2019 (COVID-19) Outbreaks at 2 Construction Sites-New York City, October-November 2020.

During 23 October-16 November 2020, the New York City Department of Health and Mental Hygiene investigated coronavirus disease 2019 (COVID-19) outbreaks at 2 construction sites. Challenges in adhering to the New York State Department of Health "Interim COVID-19 Guidance for Construction" were reported. To minimize outbreaks, jurisdictions should increase tailored outreach to the construction industry, emphasizing infection prevention.

Lack of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Large Cohort of Previously Infected Persons.

BACKGROUND: Reports suggest that some persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack detectable immunoglobulin G (IgG) antibodies. We aimed to determine the proportion IgG seronegative and predictors for seronegativity among persons previously infected with SARS-CoV-2. METHODS: We analyzed serologic data collected from healthcare workers and first responders in New York City and the Detroit metropolitan area with a history of a positive SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) test result and who were tested for IgG antibodies to SARS-CoV-2 spike protein at least 2 weeks after symptom onset. RESULTS: Of 2547 persons with previously confirmed SARS-CoV-2 infection, 160 (6.3%) were seronegative. Of 2112 previously symptomatic persons, the proportion seronegative slightly increased from 14 to 90 days post symptom onset (P = .06). The proportion seronegative ranged from 0% among 79 persons previously hospitalized to 11.0% among 308 persons with asymptomatic infections. In a multivariable model, persons who took immunosuppressive medications were more likely to be seronegative (31.9%; 95% confidence interval [CI], 10.7%-64.7%), while participants of non-Hispanic Black race/ethnicity (vs non-Hispanic White; 2.7%; 95% CI, 1.5%-4.8%), with severe obesity (vs under/normal weight; 3.9%; 95% CI, 1.7%-8.6%), or with more symptoms were less likely to be seronegative. CONCLUSIONS: In our population with previous RT-PCR-confirmed infection, approximately 1 in 16 persons lacked IgG antibodies. Absence of antibodies varied independently by illness severity, race/ethnicity, obesity, and immunosuppressive drug therapy. The proportion seronegative remained relatively stable among persons tested up to 90 days post symptom onset.

Prevalence of SARS-CoV-2 Antibodies in First Responders and Public Safety Personnel, New York City, New York, USA, May-July 2020.

We conducted a serologic survey in public service agencies in New York City, New York, USA, during May-July 2020 to determine prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among first responders. Of 22,647 participants, 22.5% tested positive for SARS-CoV-2-specific antibodies. Seroprevalence for police and firefighters was similar to overall seroprevalence; seroprevalence was highest in correctional staff (39.2%) and emergency medical technicians (38.3%) and lowest in laboratory technicians (10.1%) and medicolegal death investigators (10.8%). Adjusted analyses demonstrated association between seropositivity and exposure to SARS-CoV-2-positive household members (adjusted odds ratio [aOR] 3.52 [95% CI 3.19-3.87]), non-Hispanic Black race or ethnicity (aOR 1.50 [95% CI 1.33-1.68]), and severe obesity (aOR 1.31 [95% CI 1.05-1.65]). Consistent glove use (aOR 1.19 [95% CI 1.06-1.33]) increased likelihood of seropositivity; use of other personal protective equipment had no association. Infection control measures, including vaccination, should be prioritized for frontline workers.

A fatal case report of antibody-dependent enhancement of dengue virus type 1 following remote Zika virus infection.

BACKGROUND: Dengue virus (DENV) is endemic in many parts of the world. Antibody dependent enhancement (ADE) in DENV infections occurs when a person with primary immunity is infected by a second, different DENV strain. Antibodies to Zika virus (ZIKV), which emerged in the Western Hemisphere in 2015, are cross reactive with DENV and theoretically could provoke ADE in a DENV naïve individual. CASE PRESENTATION: DENV infection was suspected in a child who had recently returned from a one-month stay in the Dominican Republic. The child presented with fever, vomiting, abdominal pain, and in hypovolemic shock. Volume and pressor resuscitation were unsuccessful, and the child died less than 24 h after hospitalization. Laboratory results suggested an early acute first DENV infection since serum, plasma, and spinal fluid had DENV1 detected by polymerase chain reaction (PCR), yet the serum lacked IgG antibodies to DENV nonstructural protein 1 (NS1) of all four DENV serotypes. This acute DENV infection occurred in the presence of a remote ZIKV infection as determined by antibodies to ZIKV NS1 envelope by multiplex microsphere immunoassay and an exceptionally high plaque reduction neutralization titer to ZIKV. ZIKV IgG avidity index was high, confirming a past infection. DENV1 RNA was detected in all ten organs and tissues examined by PCR. The severe and fatal complications reported here suggest that a remote ZIKV infection may provoke an exaggerated immune response leading to hypovolemic shock when primarily infected by DENV1. CONCLUSION: We report the first known patient in the United States with a rapidly progressive and fatal case of travel-associated DENV in which prior exposure to ZIKV likely played a role in triggering an ADE phenomenon. This association of prior ZIKV immunity and subsequent new dengue infection is a worrisome phenomenon and an important contribution to the body of knowledge on immunity to flaviviruses.

Carriage of Neisseria meningitidis in Men Who Have Sex With Men Presenting to Public Sexual Health Clinics, New York City.

BACKGROUND: We conducted a Neisseria meningitidis (Nm) carriage study among men who have sex with men (MSM) to explore possible sexual transmission. METHODS: We paired information on patient characteristics with oropharyngeal, rectal, and urethral Nm culture results to assess associations with Nm carriage among 706 MSM at New York City sexual health clinics. The Nm isolates were characterized by whole genome sequencing. RESULTS: Twenty-three percent (163 of 706) of MSM were Nm carriers. Oropharyngeal carriage was 22.6% (159 of 703), rectal 0.9% (6 of 695), and urethral 0.4% (3 of 696). Oropharyngeal carriage was associated with the following recent (past 30 days) exposures: 3 or more men kissed (adjusted relative risk [aRR], 1.38; 95% confidence interval [CI], 1.03-1.86), performing oral sex (aRR, 1.81; 95% CI, 1.04-3.18), and antibiotic use (aRR, 0.33; 95% CI, 0.19-0.57). Sixteen clonal complexes were identified; 27% belonged to invasive lineages. CONCLUSIONS: Our findings suggest that oral sex and the number of recent kissing partners contribute to Nm carriage in MSM.

Detection and Genetic Characterization of Community-Based SARS-CoV-2 Infections - New York City, March 2020.

To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1-20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness* increased, despite decreased influenza virus circulation.† The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1-20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)§ who had negative test results for influenza and, in some instances, other respiratory pathogens.¶ All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2-positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies.

Neonatal Conjunctivitis Caused by Neisseria meningitidis US Urethritis Clade, New York, USA, August 2017.

We characterized a case of neonatal conjunctivitis in New York, USA, caused by Neisseria meningitidis by using whole-genome sequencing. The case was a rare occurrence, and the isolate obtained belonged to an emerging clade (N. meningitidis US nongroupable urethritis) associated with an increase in cases of urethritis since 2015.

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.

Surveillance for Mosquitoborne Transmission of Zika Virus, New York City, NY, USA, 2016.

A large number of imported cases of Zika virus infection and the potential for transmission by Aedes albopictus mosquitoes prompted the New York City Department of Health and Mental Hygiene to conduct sentinel, enhanced passive, and syndromic surveillance for locally acquired mosquitoborne Zika virus infections in New York City, NY, USA, during June-October 2016. Suspected case-patients were those >5 years of age without a travel history or sexual exposure who had >3 compatible signs/symptoms (arthralgia, fever, conjunctivitis, or rash). We identified 15 suspected cases and tested urine samples for Zika virus by using real-time reverse transcription PCR; all results were negative. We identified 308 emergency department visits for Zika-like illness, 40,073 visits for fever, and 17 unique spatiotemporal clusters of visits for fever. We identified no evidence of local transmission. Our experience offers possible surveillance tools for jurisdictions concerned about local mosquitoborne Zika virus or other arboviral transmission.

Legionnaires' Disease Outbreak Caused by Endemic Strain of Legionella pneumophila, New York, New York, USA, 2015.

During the summer of 2015, New York, New York, USA, had one of the largest and deadliest outbreaks of Legionnaires' disease in the history of the United States. A total of 138 cases and 16 deaths were linked to a single cooling tower in the South Bronx. Analysis of environmental samples and clinical isolates showed that sporadic cases of legionellosis before, during, and after the outbreak could be traced to a slowly evolving, single-ancestor strain. Detection of an ostensibly virulent Legionella strain endemic to the Bronx community suggests potential risk for future cases of legionellosis in the area. The genetic homogeneity of the Legionella population in this area might complicate investigations and interpretations of future outbreaks of Legionnaires' disease.

Legionnaires' Disease Outbreaks and Cooling Towers, New York City, New York, USA.

The incidence of Legionnaires' disease in the United States has been increasing since 2000. Outbreaks and clusters are associated with decorative, recreational, domestic, and industrial water systems, with the largest outbreaks being caused by cooling towers. Since 2006, 6 community-associated Legionnaires' disease outbreaks have occurred in New York City, resulting in 213 cases and 18 deaths. Three outbreaks occurred in 2015, including the largest on record (138 cases). Three outbreaks were linked to cooling towers by molecular comparison of human and environmental Legionella isolates, and the sources for the other 3 outbreaks were undetermined. The evolution of investigation methods and lessons learned from these outbreaks prompted enactment of a new comprehensive law governing the operation and maintenance of New York City cooling towers. Ongoing surveillance and program evaluation will determine if enforcement of the new cooling tower law reduces Legionnaires' disease incidence in New York City.

Reportable Bacterial Infections among New York City-Born Infants, 2001-2009.

OBJECTIVE: To determine rates of reportable bacterial infections among infants in New York City and identify populations at risk and preventable causes of morbidity. STUDY DESIGN: This retrospective cohort study matched live births in New York City from 2001-2009 to reported cases of bacterial infections among infants less than 1 year of age. Characteristics recorded on birth certificates were compared between infants with bacterial enteric infection, bacterial nonenteric infection, and no reportable bacterial infection. Multinomial logistic regression and multivariable logistic regression were used to identify risk factors for infection. RESULTS: Bacterial infection was reported in 4.6 cases per 1000 live births. Of 4524 infants with a reportable infection, the majority (2880, 63%) had an enteric infection. Asian/Pacific Islanders in Brooklyn were the borough-level race/ethnic group with the highest enteric infection rate (8.5 per 1000 live births). Citywide, infants with enteric infections were disproportionately male, from higher poverty neighborhoods, born to foreign-born mothers, and enrolled in Special Supplemental Food Program for Women, Infants, and Children or Medicaid. In contrast, infants with nonenteric infections were more likely to have low birthweight and mothers characterized by US birth and black race or white Hispanic race/ethnicity. CONCLUSIONS: Distinct patterns of risk factors for enteric and nonenteric bacterial infections among infants were identified. The results suggest that infants born to Asian/Pacific Islander mothers residing in Brooklyn should be a focus of enteric disease prevention. More research is necessary to better understand what behaviors increase the risk of enteric disease in this population.

Suspected Female-to-Male Sexual Transmission of Zika Virus - New York City, 2016.

A routine investigation by the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) identified a nonpregnant woman in her twenties who reported she had engaged in a single event of condomless vaginal intercourse with a male partner the day she returned to NYC (day 0) from travel to an area with ongoing Zika virus transmission. She had headache and abdominal cramping while in the airport awaiting return to NYC. The following day (day 1) she developed fever, fatigue, a maculopapular rash, myalgia, arthralgia, back pain, swelling of the extremities, and numbness and tingling in her hands and feet. In addition, on day 1, the woman began menses that she described as heavier than usual. On day 3 she visited her primary care provider who obtained blood and urine specimens. Zika virus RNA was detected in both serum and urine by real-time reverse transcription-polymerase chain reaction (rRT-PCR) performed at the DOHMH Public Health Laboratory using a test based on an assay developed at CDC (1). The results of serum testing for anti-Zika virus immunoglobulin M (IgM) antibody performed by the New York State Department of Health Wadsworth Center laboratory was negative using the CDC Zika IgM antibody capture enzyme-linked immunosorbent assay (Zika MAC-ELISA) (2).

Risk Factors for Serogroup C Meningococcal Disease during Outbreak among Men who Have Sex with Men, New York City, New York, USA.

Risk factors for illness during a serogroup C meningococcal disease outbreak among men who have sex with men in New York City, New York, USA, in 2012-2013 included methamphetamine and cocaine use and sexually transmitted infections. Outbreak investigations should consider routinely capturing information regarding drug use and sex-related risk factors.

Community-Based Outbreak of Neisseria meningitidis Serogroup C Infection in Men who Have Sex with Men, New York City, New York, USA, 2010-2013.

In September 2012, the New York City Department of Health and Mental Hygiene identified an outbreak of Neisseria meningitidis serogroup C invasive meningococcal disease among men who have sex with men (MSM). Twenty-two case-patients and 7 deaths were identified during August 2010-February 2013. During this period, 7 cases in non-MSM were diagnosed. The slow-moving outbreak was linked to the use of websites and mobile phone applications that connect men with male sexual partners, which complicated the epidemiologic investigation and prevention efforts. We describe the outbreak and steps taken to interrupt transmission, including an innovative and wide-ranging outreach campaign that involved direct, internet-based, and media-based communications; free vaccination events; and engagement of community and government partners. We conclude by discussing the challenges of managing an outbreak affecting a discrete community of MSM and the benefits of using social networking technology to reach this at-risk population.