Modeling undetected poliovirus circulation following the 2022 outbreak in the United States.

BACKGROUND: New York State (NYS) reported a polio case (June 2022) and outbreak of imported type 2 circulating vaccine-derived poliovirus (cVDPV2) (last positive wastewater detection in February 2023), for which uncertainty remains about potential ongoing undetected transmission. RESEARCH DESIGN AND METHODS: Extending a prior deterministic model, we apply an established stochastic modeling approach to characterize the confidence about no circulation (CNC) of cVDPV2 as a function of time since the last detected signal of transmission (i.e. poliovirus positive acute flaccid myelitis case or wastewater sample). RESULTS: With the surveillance coverage for the NYS population majority and its focus on outbreak counties, modeling suggests a high CNC (95%) within 3-10 months of the last positive surveillance signal, depending on surveillance sensitivity and population mixing patterns. Uncertainty about surveillance sensitivity implies longer durations required to achieve higher CNC. CONCLUSIONS: In populations that maintain high overall immunization coverage with inactivated poliovirus vaccine (IPV), rare polio cases may occur in un(der)-vaccinated individuals. Modeling demonstrates the unlikeliness of type 2 outbreaks reestablishing endemic transmission or resulting in large absolute numbers of paralytic cases. Achieving and maintaining high immunization coverage with IPV remains the most effective measure to prevent outbreaks and shorten the duration of imported poliovirus transmission.

Mumps vaccine effectiveness of a 3rd dose of measles, mumps, rubella vaccine in school settings during a mumps outbreak -- Arkansas, 2016-2017.

Objectives: The largest mumps outbreak in the United States since 2006 occurred in Arkansas during the 2016-17 school year. An additional dose (third dose) of measles-mumps-rubella vaccine (MMR3) was offered to school children. We evaluated the vaccine effectiveness (VE) of MMR3 compared with two doses of MMR for preventing mumps among school-aged children during the outbreak. Study design: A generalized linear mixed effects model was used to estimate the incremental vaccine effectiveness (VE) of a third dose of MMR compared with two doses of MMR for preventing mumps. Methods: We obtained school enrollment, immunization status and mumps case status from school registries, Arkansas's immunization registry, and Arkansas's mumps surveillance system, respectively. We included students who previously received 2 doses of MMR in schools with ≥1 mumps case after the MMR3 clinic. We used a generalized linear mixed model to estimate VE of MMR3 compared with two doses of MMR. Results: Sixteen schools with 9272 students were included in the analysis. Incremental VE of MMR3 versus a two-dose MMR regimen was 52.7% (95% confidence interval [CI]: -3.6%‒78.4%) overall and in 8 schools with high mumps transmission it was 64.0% (95% CI: 1.2%‒86.9%). MMR3 VE was higher among middle compared with elementary school students (68.5% [95% CI: -30.2%‒92.4%] vs 37.6% [95% CI: -62.5%‒76.1%]); these differences were not statistically significant. Conclusion: Our findings suggest MMR3 provided additional protection from mumps compared with two MMR doses in elementary and middle school settings during a mumps outbreak.

Modeling poliovirus transmission and responses in New York State.

BACKGROUND: In July 2022, New York State (NYS) reported a case of paralytic polio in an unvaccinated young adult, and subsequent wastewater surveillance confirmed sustained local transmission of type 2 vaccine-derived poliovirus (VDPV2) in NYS with genetic linkage to the paralyzed patient. METHODS: We adapted an established poliovirus transmission and oral poliovirus vaccine (OPV) evolution model to characterize dynamics of poliovirus transmission in NYS, including consideration of the immunization activities performed as part of the declared state of emergency. RESULTS: Despite sustained transmission of imported VDPV2 in NYS involving potentially thousands of individuals (depending on seasonality, population structure and mixing assumptions) in 2022, the expected number of additional paralytic cases in years 2023 and beyond is small (less than 0.5). However, continued transmission and/or reintroduction of poliovirus into NYS and other populations remains a possible risk in communities that do not achieve and maintain high immunization coverage. CONCLUSION: In countries such as the US that use only inactivated poliovirus vaccine, even with high average immunization coverage, imported polioviruses may circulate and pose a small but non-zero risk of causing paralysis in non-immune individuals.

Six- and 12-month functional outcomes among patients with confirmed acute flaccid myelitis (AFM) with onset in 2018, United States.

PURPOSE: Acute flaccid myelitis (AFM), an uncommon but serious neurologic condition, primarily affects children, and can progress quickly to paralysis and respiratory failure. Data on long-term outcomes of patients with AFM are limited. This study reports on functional status through 12 months for AFM patients who became ill in 2018 in the United States. METHODS: Health departments collected information on outcomes at 6 and 12 months after onset of AFM using a standardized form that asked patients or their parents/guardians about functional status. Analyses were restricted to confirmed cases. RESULTS: Of the 238 confirmed AFM cases reported to CDC in 2018, 90 (38%) had assessments at 6 months, 82 (34%) at 12 months, and 49 (21%) at both 6 and 12 months. Among the 49 patients with data at both time points, the proportion of patients reporting significant or severe impairment at 6 months ranged from 2% to 59% depending on the outcome. Although proportions decreased by 12 months and ranged from 2% to 51%, most patients had some impairment at 12 months. No deaths were reported. CONCLUSION: Six- and 12-month outcomes in patients with onset of AFM in 2018 span a wide range of functionality, particularly of upper and lower extremities. Importantly, improvement appears to occur over time in some patients.

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged <18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers† within the New Vaccine Surveillance Network (NVSN) were summarized. This report provides a provisional description of EV-D68 detections during July-November in 2018, 2019 and 2020, and describes the demographic and clinical characteristics of these patients. In 2018, a total of 382 EV-D68 detections in respiratory specimens obtained from patients aged <18 years with ARI were reported by NVSN; the number decreased to six detections in 2019 and 30 in 2020. Among patients aged <18 years with EV-D68 in 2020, 22 (73%) were non-Hispanic Black (Black) persons. EV-D68 detections in 2020 were lower than anticipated based on the biennial circulation pattern observed since 2014. The circulation of EV-D68 in 2020 might have been limited by widespread COVID-19 mitigation measures; how these changes in behavior might influence the timing and levels of circulation in future years is unknown. Ongoing monitoring of EV-D68 detections is warranted for preparedness for EV-D68-associated ARI and AFM.

National Surveillance for Acute Flaccid Myelitis - United States, 2018-2020.

Acute flaccid myelitis (AFM), a recognized complication of certain viral infections, is a serious neurologic condition that predominantly affects previously healthy children and can progress rapidly, leading to respiratory insufficiency and permanent paralysis. After national AFM surveillance began in 2014, peaks in AFM cases were observed in the United States in 2014, 2016, and 2018 (1). On the basis of this biennial pattern, an increase in AFM was anticipated in 2020. To describe the epidemiology of confirmed AFM cases since 2018, demographic, clinical, and laboratory information collected as part of national AFM surveillance was reviewed. In 2018, a total of 238 confirmed AFM cases were reported to CDC, compared with 47 cases in 2019 and 32 in 2020. Enterovirus D68 (EV-D68) was detected in specimens from 37 cases reported in 2018, one case in 2019 and none in 2020. Compared with 2018, cases reported during 2019-2020 occurred in older children and were less frequently associated with upper limb involvement, febrile or respiratory prodromal illness, or cerebrospinal fluid (CSF) pleocytosis. These findings suggest that the etiologies of AFM in 2019 and 2020 differed from those in 2018. The absence of an increase in cases in 2020 reflects a deviation from the previously observed biennial pattern, and it is unclear when the next increase in AFM should be expected. Clinicians should continue to maintain vigilance and suspect AFM in any child with acute flaccid limb weakness, particularly in the setting of recent febrile or respiratory illness.

How adequate is measles surveillance in the United States? Investigations of measles-like illness, 2010-2017.

Given the availability of an effective and safe vaccine, the World Health Organization (WHO) declared that global measles eradication is achievable, and measles elimination goals have since been established as interim steps toward eradication. As part of a strategy to maintain elimination, the Pan American Health Organization (PAHO) and WHO stipulate a minimum annual reporting rate of discarded non-measles cases of ≥2 per 100,000 population, in order to ensure sensitive surveillance and adequate investigative effort. With its effective vaccination program, the United States in 2000 was among the first countries to verify elimination, although subsequently, it has not routinely reported discarded rates. We estimated MLI investigation rates among insured individuals during 2010-2017, using data from the MarketScan® databases. We defined "MLI investigations" as measles serologic testing within 5 days following diagnostic codes for measles-compatible symptoms and conditions. We provide a rationale for pre-specifying three subgroups for analysis: children aged ≤15 years; males aged 16-22 years excluding data from summer months; and males aged ≥23 years. MLI investigation rates ranged from 6.6─26.4 per 100,000, remaining stable over time except during the 2015 measles outbreaks when rates increased, particularly among young children. In addition to high vaccine uptake, measles elimination requires ongoing vigilance by clinicians and high-quality, case-based surveillance. Estimated rates of MLI investigations in this U.S. population suggesting that the quality of measles surveillance is sufficiently sensitive to detect endemic measles circulation if it were to be occurring.

Enterovirus D68-Associated Acute Flaccid Myelitis, United States, 2020.

Acute flaccid myelitis (AFM) is a serious neurologic condition that causes limb weakness or paralysis in previously healthy children. Since clusters of cases were first reported in 2014, nationwide surveillance has demonstrated sharp increases in AFM cases in the United States every 2 years, most occurring during late summer and early fall. Given this current biennial pattern, another peak AFM season is expected during fall 2020 in the United States. Scientific understanding of the etiology and the factors driving the biennial increases in AFM has advanced rapidly in the past few years, although areas of uncertainty remain. The Centers for Disease Control and Prevention and AFM partners are focused on answering key questions about AFM epidemiology and mechanisms of disease. This article summarizes the current understanding of AFM etiology and outlines priorities for surveillance and research as we prepare for a likely surge in cases in 2020.

Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015-2018.

Observed peaks of acute flaccid myelitis (AFM) cases have occurred biennially since 2014 in the United States. We aimed to determine if AFM etiology differed between peak and nonpeak years, considering that clinical features of AFM differ by virus etiology. We compared clinical and laboratory characteristics of AFM cases that occurred during peak (2016 and 2018, n = 366) and nonpeak (2015 and 2017, n = 50) years. AFM patients in peak years were younger (5.2 years) than those in nonpeak years (8.3 years). A higher percentage of patients in peak years than nonpeak years had pleocytosis (86% vs. 60%), upper extremity involvement (33% vs. 16%), and an illness preceding limb weakness (90% vs. 62%) and were positive for enterovirus or rhinovirus RNA (38% vs. 16%). Enterovirus D68 infection was associated with AFM only in peak years. Our findings suggest AFM etiology differs between peak and nonpeak years.

Acute Flaccid Myelitis in the United States: 2015-2017.

BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count >5 cells per mm3 in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age ≤21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition.

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.

Enterovirus D68-Associated Acute Respiratory Illness - New Vaccine Surveillance Network, United States, July-October, 2017 and 2018.

In the fall of 2014, an outbreak of enterovirus D68 (EV-D68)-associated acute respiratory illness (ARI) occurred in the United States (1,2); before 2014, EV-D68 was rarely reported to CDC (2,3). In the United States, reported EV-D68 detections typically peak during late summer and early fall (3). EV-D68 epidemiology is not fully understood because testing in clinical settings seldom has been available and detections are not notifiable to CDC. To better understand EV-D68 epidemiology, CDC recently established active, prospective EV-D68 surveillance among pediatric patients at seven U.S. medical centers through the New Vaccine Surveillance Network (NVSN) (4). This report details a preliminary characterization of EV-D68 testing and detections among emergency department (ED) and hospitalized patients with ARI at all NVSN sites during July 1-October 31, 2017, and the same period in 2018. Among patients with ARI who were tested, EV-D68 was detected in two patients (0.8%) in 2017 and 358 (13.9%) in 2018. Continued active, prospective surveillance of EV-D68-associated ARI is needed to better understand EV-D68 epidemiology in the United States.

Increase in Acute Flaccid Myelitis - United States, 2018.

In August 2018, CDC noted an increased number of reports of patients having symptoms clinically compatible with acute flaccid myelitis (AFM), a rare condition characterized by rapid onset of flaccid weakness in one or more limbs and spinal cord gray matter lesions, compared with August 2017. Since 2014, CDC has conducted surveillance for AFM using a standardized case definition (1,2). An Epi-X* notice was issued on August 23, 2018, to increase clinician awareness and provide guidance for case reporting.

Diffusion of Handwashing Knowledge and Water Treatment Practices From Mothers in an Antenatal Hygiene Promotion Program to Nonpregnant Friends and Relatives, Machinga District, Malawi.

Access to safe drinking water and improved hygiene are essential for preventing diarrheal diseases in low- and middle-income countries. Integrating water treatment and hygiene products into antenatal clinic care can motivate water treatment and handwashing among pregnant women. Free water hygiene kits (water storage containers, sodium hypochlorite water treatment solution, and soap) and refills of water treatment solution and soap were integrated into antenatal care and delivery services in Machinga District, Malawi, resulting in improved water treatment and hygiene practices in the home and increased maternal health service use. To determine whether water treatment and hygiene practices diffused from maternal health program participants to friends and relatives households in the same communities, we assessed the practices of 106 nonpregnant friends and relatives of these new mothers at baseline and 1-year follow-up. At follow-up, friends and relatives were more likely than at baseline to have water treatment products observable in the home (33.3% vs. 1.2%, p < 0.00001) and detectable free chlorine residual in their water, confirming water treatment (35.7% vs. 1.4%; p < 0.00001). Qualitative data from in-depth interviews also suggested that program participants helped motivate adoption of water treatment and hygiene behaviors among their friends and relatives.

Safe Water and Hygiene Integration with Human Immunodeficiency Virus and Antenatal Services: Leveraging Opportunities for Public Health Interventions and Improved Service Uptake.

Integrating public health interventions with antenatal clinic (ANC) visits may motivate women to attend ANC, thereby improving maternal and neonatal health, particularly for human immunodeficiency virus (HIV)-infected persons. In 2009, in an integrated ANC/Preventing Mother-to-Child Transmission program, we provided free hygiene kits (safe storage containers, WaterGuard water treatment solution, soap, and oral rehydration salts) to women at their first ANC visit and refills at subsequent visits. To increase fathers' participation, we required partners' presence for women to receive hygiene kits. We surveyed pregnant women at baseline and at 12-month follow-up to assess ANC service utilization, HIV counseling and testing (HCT), test drinking water for residual chlorine, and observe handwashing. We conducted in-depth interviews with pregnant women, partners, and health workers. We enrolled 106 participants; 97 (92%) were found at follow-up. During the program, 99% of pregnant women and their partners received HCT, and 99% mutually disclosed. Fifty-six percent of respondents had ≥ 4 ANC visits and 90% delivered at health facilities. From baseline to follow-up, the percentage of women who knew how to use WaterGuard (23% versus 80%, P < 0.0001), had residual chlorine in stored water (0% versus 73%, P < 0.0001), had confirmed WaterGuard use (0% versus 70%, P < 0.0003), and demonstrated proper handwashing technique (21% versus 64% P < 0.0001) increased. Program participants showed significant improvements in water treatment and hygiene, and high use of ANC services and HCT. This evaluation suggests that integration of hygiene kits, refills, and HIV testing during ANC is feasible and may help improve household hygiene and increase use of health services.

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

Estimating the attack rate of pregnancy-associated listeriosis during a large outbreak.

BACKGROUND: In 2011, a multistate outbreak of listeriosis linked to contaminated cantaloupes raised concerns that many pregnant women might have been exposed to Listeria monocytogenes. Listeriosis during pregnancy can cause fetal death, premature delivery, and neonatal sepsis and meningitis. Little information is available to guide healthcare providers who care for asymptomatic pregnant women with suspected L. monocytogenes exposure. METHODS: We tracked pregnancy-associated listeriosis cases using reportable diseases surveillance and enhanced surveillance for fetal death using vital records and inpatient fetal deaths data in Colorado. We surveyed 1,060 pregnant women about symptoms and exposures. We developed three methods to estimate how many pregnant women in Colorado ate the implicated cantaloupes, and we calculated attack rates. RESULTS: One laboratory-confirmed case of listeriosis was associated with pregnancy. The fetal death rate did not increase significantly compared to preoutbreak periods. Approximately 6,500-12,000 pregnant women in Colorado might have eaten the contaminated cantaloupes, an attack rate of ~1 per 10,000 exposed pregnant women. CONCLUSIONS: Despite many exposures, the risk of pregnancy-associated listeriosis was low. Our methods for estimating attack rates may help during future outbreaks and product recalls. Our findings offer relevant considerations for management of asymptomatic pregnant women with possible L. monocytogenes exposure.

Rapid assessment of cholera-related deaths, Artibonite Department, Haiti, 2010.

We evaluated a high (6%) cholera case-fatality rate in Haiti. Of 39 community decedents, only 23% consumed oral rehydration salts at home, and 59% did not seek care, whereas 54% of 48 health facility decedents died after overnight admission. Early in the cholera epidemic, care was inadequate or nonexistent.