JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data.

BACKGROUND: JYNNEOSTM vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited. METHODS: Effectiveness of a single dose of JYNNEOSTM vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022-August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEPL) and first (PEPF) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial. RESULTS: Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEPL was 7 days (range 1-16). Time to PEPL receipt was 7 days (range 0-14). Among 549 individuals, adjusted PEPL and PEPF effectiveness was 19 % (95 % Confidence Interval [CI], -54 % to 57 %) and -7% (95 % CI, -144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis. CONCLUSIONS: Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations.

Pfizer-BioNTech Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Long-term Care Facility Staff With and Without Prior Infection in New York City, January-June 2021.

BACKGROUND: Evidence is accumulating of coronavirus disease 2019 (COVID-19) vaccine effectiveness among persons with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated the effect against incident SARS-CoV-2 infection of (1) prior infection without vaccination, (2) vaccination (2 doses of Pfizer-BioNTech COVID-19 vaccine) without prior infection, and (3) vaccination after prior infection, all compared with unvaccinated persons without prior infection. We included long-term care facility staff in New York City aged <65 years with weekly SARS-CoV-2 testing from 21 January to 5 June 2021. Test results were obtained from state-mandated laboratory reporting. Vaccination status was obtained from the Citywide Immunization Registry. Cox proportional hazards models adjusted for confounding with inverse probability of treatment weights. RESULTS: Compared with unvaccinated persons without prior infection, incident SARS-CoV-2 infection risk was lower in all groups: 54.6% (95% confidence interval, 38.0%-66.8%) lower among unvaccinated, previously infected persons; 80.0% (67.6%-87.7%) lower among fully vaccinated persons without prior infection; and 82.4% (70.8%-89.3%) lower among persons fully vaccinated after prior infection. CONCLUSIONS: Two doses of Pfizer-BioNTech COVID-19 vaccine reduced SARS-CoV-2 infection risk by ≥80% and, for those with prior infection, increased protection from prior infection alone. These findings support recommendations that all eligible persons, regardless of prior infection, be vaccinated against COVID-19.

Measles infection in persons with secondary vaccine failure, New York City, 2018-19.

A large measles outbreak in New York City, which included cases among vaccinated persons and adults presumed to be immune, provided the opportunity to better understand vaccine failure and the potential impact on measles transmission. Immunoglobulin G (IgG) avidity can distinguish primary (low avidity IgG, indicating no evidence of prior immunity) versus secondary vaccine failure (high avidity IgG, indicating prior immune response and waning antibody). Measles IgG avidity was measured on samples from 62 persons: avidity was high in 53 (16 vaccinated and 37 with unknown vaccination history) and low in 9 (1 recently vaccinated and 8 with unknown vaccination history). Secondary transmission from 2 persons with high-avidity IgG results occurred. These findings illustrate that in settings of sustained measles elimination, measles infection and transmission can occur in persons with secondary vaccine failure, underscoring the need to maintain a high index of suspicion for measles during an outbreak despite prior or presumed prior vaccination.

SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years - United States, February 12-July 31, 2020.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).† These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

Trends in Hepatitis B Surveillance Among Pregnant Women in New York City, 1998-2015.

OBJECTIVE: Infants born to women with hepatitis B virus (HBV) infection are at high risk for chronic HBV infection and premature death. We examined epidemiologic trends among women with HBV infection who gave birth in New York City (NYC) to inform public health prevention activities. METHODS: We obtained data on HBV-infected women residing and giving birth in NYC during 1998-2015 from the NYC Perinatal HBV Prevention Program. We obtained citywide birth data from the NYC Office of Vital Statistics. We calculated the incidence of births to HBV-infected women per 100 000 live births and stratified by maternal race, birthplace, and age. We calculated annual percentage change (APC) in incidence of births to HBV-infected women by using joinpoint regression. RESULTS: Of 29 896 HBV-infected women included in the study, 28 195 (94.3%) were non-US-born, of whom 16 600 (58.9%) were born in China. Overall incidence of births to HBV-infected women per 100 000 live births increased from 1156 in 1998 to 1573 in 2006 (APC = 3.1%; P < .001) but declined to 1329 in 2015 (APC = -1.4%; P = .02). Incidence among US-born women declined from 1998 to 2015 (330 to 84; APC = -7.3%; P < .001) and among non-US-born women increased from 1998 to 2007 (1877 to 2864; APC = 3.6%; P < .001) but not thereafter. Incidence among women born in China increased from 1998 to 2006 (13 275 to 16 480; APC = 1.8%; P = .02) but decreased to 12 631 through 2015 (APC = -3.3%; P < .001). CONCLUSIONS: The incidence of births to HBV-infected women in NYC declined significantly among US-born women but not among non-US-born women, highlighting the need for successful vaccination programs worldwide.

Infectious Disease Hospitalizations, New York City, 2001-2014.

OBJECTIVE: Hospital discharge data are a means of monitoring infectious diseases in a population. We investigated rates of infectious disease hospitalizations in New York City. METHODS: We analyzed data for residents discharged from New York State hospitals with a principal diagnosis of an infectious disease during 2001-2014 by using the Statewide Planning and Research Cooperative System. We calculated annual age-adjusted hospitalization rates and the percentage of hospitalizations in which in-hospital death occurred. We examined diagnoses by site of infection or sepsis and by pathogen type. RESULTS: During 2001-2014, the mean annual age-adjusted rate of infectious disease hospitalizations in New York City was 1661.6 (95% CI, 1659.2-1663.9) per 100 000 population; the mean annual age-adjusted hospitalization rate decreased from 2001-2003 to 2012-2014 (rate ratio = 0.9; 95% CI, 0.9-0.9). The percentage of in-hospital death during 2001-2014 was 5.9%. The diagnoses with the highest mean annual age-adjusted hospitalization rates among all sites of infection and sepsis diagnoses were the lower respiratory tract, followed by sepsis. From 2001-2003 to 2012-2014, the mean annual age-adjusted hospitalization rate per 100 000 population for HIV decreased from 123.1 (95% CI, 121.7-124.5) to 40.0 (95% CI, 39.2-40.7) and for tuberculosis decreased from 10.2 (95% CI, 9.8-10.6) to 4.6 (95% CI, 4.4-4.9). CONCLUSIONS: Although hospital discharge data are subject to limitations, particularly for tracking sepsis, lower respiratory tract infections and sepsis are important causes of infectious disease hospitalizations in New York City. Hospitalizations for HIV infection and tuberculosis appear to be declining.

Consequences of Undervaccination - Measles Outbreak, New York City, 2018-2019.

BACKGROUND: Measles was declared eliminated in the United States in 2000, but the risk of outbreaks owing to international importations remains. An outbreak of measles in New York City began when one unvaccinated child returned home from Israel with measles; onset of rash occurred on September 30, 2018, 9 days after the child returned home. METHODS: We investigated suspected cases of measles by conducting interviews, reviewing medical and immunization records, identifying exposed persons, and performing diagnostic testing. Measles-mumps-rubella (MMR) vaccine (given as either MMR or measles-mumps-rubella-varicella vaccine and collectively referred to as MMR vaccine) uptake was monitored with the use of the Citywide Immunization Registry. The total direct cost to the New York City Department of Health and Mental Hygiene was calculated. RESULTS: A total of 649 cases of measles were confirmed, with onsets of rash occurring between September 30, 2018, and July 15, 2019. A majority of the patients (93.4%) were part of the Orthodox Jewish community, and 473 of the patients (72.9%) resided in the Williamsburg area of Brooklyn, New York. The median age was 3 years; 81.2% of the patients were 18 years of age or younger, and 85.8% of the patients with a known vaccination history were unvaccinated. Serious complications included pneumonia (in 37 patients [5.7%]) and hospitalization (in 49 patients [7.6%]); among the patients who were hospitalized, 20 (40.8%) were admitted to an intensive care unit. As a result of efforts to promote vaccination, the percentage of children in Williamsburg who received at least one dose of MMR vaccine increased from 79.5% to 91.1% among children 12 to 59 months of age. As of September 9, 2019, a total of 559 staff members at the Department of Health and Mental Hygiene (7% of the agency) had been involved in the measles response. The cost of the Department of Health and Mental Hygiene response was $8.4 million. CONCLUSIONS: Importation of measles and vaccination delays among young children led to an outbreak of measles in New York City. The outbreak response was resource intensive and caused serious illness, particularly among unvaccinated children.

National Update on Measles Cases and Outbreaks - United States, January 1-October 1, 2019.

During January 1-October 1, 2019, a total of 1,249 measles cases and 22 measles outbreaks were reported in the United States. This represents the most U.S. cases reported in a single year since 1992 (1), and the second highest number of reported outbreaks annually since measles was declared eliminated* in the United States in 2000 (2). Measles is an acute febrile rash illness with an attack rate of approximately 90% in susceptible household contacts (3). Domestic outbreaks can occur when travelers contract measles outside the United States and subsequently transmit infection to unvaccinated persons they expose in the United States. Among the 1,249 measles cases reported in 2019, 1,163 (93%) were associated with the 22 outbreaks, 1,107 (89%) were in patients who were unvaccinated or had an unknown vaccination status, and 119 (10%) measles patients were hospitalized. Closely related outbreaks in New York City (NYC) and New York State (NYS; excluding NYC), with ongoing transmission for nearly 1 year in large and close-knit Orthodox Jewish communities, accounted for 934 (75%) cases during 2019 and threatened the elimination status of measles in the United States. Robust responses in NYC and NYS were effective in controlling transmission before the 1-year mark; however, continued vigilance for additional cases within these communities is essential to determine whether elimination has been sustained. Collaboration between public health authorities and undervaccinated communities is important for preventing outbreaks and limiting transmission. The combination of maintenance of high national vaccination coverage with measles, mumps, and rubella vaccine (MMR) and rapid implementation of measles control measures remains the cornerstone for preventing widespread measles transmission (4).

Public Health Consequences of a 2013 Measles Outbreak in New York City.

Importance: Internationally imported cases of measles into the United States can lead to outbreaks requiring extensive and rapid control measures. Importation of measles from an unvaccinated adolescent in 2013 led to what has been the largest outbreak of measles in New York City, New York, since 1992. Objective: To describe the epidemiology and public health burden in terms of resources and cost of the 2013 measles outbreak in New York City. Design, Setting, and Participants: This epidemiologic assessment and cost analysis conducted between August 15, 2013, and August 5, 2014, examined all outbreak-associated cases of measles among persons residing in New York City in 2013. Exposures: Measles virus. Main Outcomes and Measures: Numbers of measles cases and contacts. Total personnel time and total direct cost to the New York City Department of Health and Mental Hygiene (DOHMH), calculated as the sum of inputs (supplies and materials, equipment, and logistics) and personnel time (salary and fringe benefits). Results: Between March 13, 2013, and June 9, 2013, 58 persons in New York City with a median age of 3 years (range, 0-32 years) were identified as having measles. Among these individuals, 45 (78%) were at least 12 months old and were unvaccinated owing to parental refusal or intentional delay. Only 28 individuals (48%) visited a medical health care professional who suspected measles and reported the case to the DOHMH at the initial clinical suspicion. Many case patients were not immediately placed into airborne isolation, resulting in exposures in 11 health care facilities. In total, 3351 exposed contacts were identified. Total direct costs to the New York City DOHMH were $394 448, and a total of 10 054 hours were consumed responding to and controlling the outbreak. Conclusions and Relevance: Vaccine refusals and delays appeared to have propagated a large outbreak following importation of measles into the United States. Prompt recognition of measles along with rapid implementation of airborne isolation of individuals suspected of measles infection in health care facilities and timely reporting to public health agencies may avoid large numbers of exposures. The response and containment of measles outbreaks are resource intensive.

Effectiveness of Measles Vaccination and Immune Globulin Post-Exposure Prophylaxis in an Outbreak Setting-New York City, 2013.

BACKGROUND: Measles, mumps, and rubella vaccine (MMR) or immune globulin (IG) are routinely used for measles post-exposure prophylaxis (PEP). However, current literature on the effectiveness of measles PEP is limited and variable. Here, we examined the effectiveness of MMR and IG PEP among children exposed to measles during an outbreak in New York City (NYC) in 2013. METHODS: Contacts were identified by the NYC Department of Health and Mental Hygiene between 13 March 2013 and 30 June 2013. Immunity to measles and receipt of PEP was determined for contacts. PEP effectiveness [(1 - relative risk of developing measles) × 100] was calculated for MMR, IG, and any PEP (MMR or IG) for nonimmune contacts aged <19 years. RESULTS: A total of 3409 contacts were identified, of which 208 (6.1%), 274 (8.0%), and 318 (9.3%) met the inclusion criteria for analysis of MMR, IG, and any PEP effectiveness, respectively. Of the contacts included, 44 received MMR PEP and 77 received IG PEP. Effectiveness of MMR PEP was 83.4% (95% confidence interval [CI], 34.4%, 95.8%). No contact who received IG PEP developed measles; effectiveness of IG PEP was 100% (approximated 95% CI, 56.2%, 99.8%). Effectiveness of receiving any PEP (MMR or IG) was 92.9% (95% CI, 56.2%, 99.8%). CONCLUSIONS: Contacts who received PEP were less likely to develop disease. Our findings support current recommendations for administration of PEP following exposure to measles. These results highlight the importance of a rapid public health outbreak response to limit measles transmission following case identification.

Mumps Outbreak Among a Highly Vaccinated University Community-New York City, January-April 2014.

Background: On 14 January 2014, a vaccinated student presented with parotitis. Mumps immunoglobulin M (IgM) testing was negative and reverse-transcription polymerase chain reaction (RT-PCR) testing was not performed, resulting in a missed diagnosis and the start of an outbreak at a New York City (NYC) university. Methods: Mumps case investigations included patient interviews, medical records review, and laboratory testing including mumps serology and RT-PCR. Case patients were considered linked to the outbreak if they attended or had epidemiologic linkage to the university. Epidemiologic, clinical, and laboratory data for outbreak cases residing in NYC were analyzed. Results: Fifty-six NYC residents with mumps were identified with onset between 12 January and 30 April 2014. Fifty-three cases (95%) were university students, 1 (2%) was a staff member, and 2 (4%) had epidemiologic links to the university. The median age was 20 years (range 18-37 years). All cases had parotitis. Three cases were hospitalized, including 1 of 2 cases with orchitis. Fifty-four (96%) cases had received ≥1 mumps-containing vaccine, 1 (2%) was unvaccinated due to religious exemption, and 1 (2%) had unknown vaccination status. Two of the 44 (5%) cases tested by serology were mumps IgM positive, and 27 of the 40 (68%) tested by RT-PCR were positive. Conclusions: Mumps outbreaks can occur in highly vaccinated populations. Mumps should be considered in patients with parotitis regardless of vaccination status. RT-PCR is the preferred testing method; providers should not rely on IgM testing alone. High vaccination coverage and control measures likely limited the extent of the outbreak.