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As SARS-CoV-2, the virus that causes COVID-19, continues to circulate globally, high levels of vaccine- and infection-induced immunity and the availability of effective treatments and prevention tools have substantially reduced the risk for medically significant COVID-19 illness (severe acute illness and post-COVID-19 conditions) and associated hospitalization and death (1). These circumstances now allow public health efforts to minimize the individual and societal health impacts of COVID-19 by focusing on sustainable measures to further reduce medically significant illness as well as to minimize strain on the health care system, while reducing barriers to social, educational, and economic activity (2). Individual risk for medically significant COVID-19 depends on a person's risk for exposure to SARS-CoV-2 and their risk for developing severe illness if infected (3). Exposure risk can be mitigated through nonpharmaceutical interventions, including improving ventilation, use of masks or respirators indoors, and testing (4). The risk for medically significant illness increases with age, disability status, and underlying medical conditions but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments (3,5). CDC's public health recommendations change in response to evolving science, the availability of biomedical and public health tools, and changes in context, such as levels of immunity in the population and currently circulating variants. CDC recommends a strategic approach to minimizing the impact of COVID-19 on health and society that relies on vaccination and therapeutics to prevent severe illness; use of multicomponent prevention measures where feasible; and particular emphasis on protecting persons at high risk for severe illness. Efforts to expand access to vaccination and therapeutics, including the use of preexposure prophylaxis for persons who are immunocompromised, antiviral agents, and therapeutic monoclonal antibodies, should be intensified to reduce the risk for medically significant illness and death. Efforts to protect persons at high risk for severe illness must ensure that all persons have access to information to understand their individual risk, as well as efficient and equitable access to vaccination, therapeutics, testing, and other prevention measures. Current priorities for preventing medically significant illness should focus on ensuring that persons 1) understand their risk, 2) take steps to protect themselves and others through vaccines, therapeutics, and nonpharmaceutical interventions when needed, 3) receive testing and wear masks if they have been exposed, and 4) receive testing if they are symptomatic, and isolate for ≥5 days if they are infected.

The COVID-19 pandemic has disproportionately affected people with diabetes, who are at increased risk of severe COVID-19.* Increases in the number of type 1 diabetes diagnoses (1,2) and increased frequency and severity of diabetic ketoacidosis (DKA) at the time of diabetes diagnosis (3) have been reported in European pediatric populations during the COVID-19 pandemic. In adults, diabetes might be a long-term consequence of SARS-CoV-2 infection (4-7). To evaluate the risk for any new diabetes diagnosis (type 1, type 2, or other diabetes)30 days

The COVID-19 pandemic has highlighted and exacerbated long-standing inequities in the social determinants of health (1-3). Ensuring equitable access to effective COVID-19 therapies is essential to reducing health disparities. Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid) are oral antiviral agents effective at preventing hospitalization and death in patients with mild to moderate COVID-19 who are at high risk* for progression to severe COVID-19 when initiated within 5 days of symptom onset. These medications received Emergency Use Authorization from the Food and Drug Administration (FDA) in December 2021

To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.

ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by MerckCo., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries.We evaluated data from three Phase 2/3 clinical trials conducted in Liberia (PREVAIL), Guinea (FLW), and Sierra Leone (STRIVE) during the 2013-2016 West African EVD outbreak to assess immune responses using validated assays. We performed a post hoc analysis of the association of vaccine response with sex, age (18-50 yrs50 yrs), and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (200≥200 EU/mL), including individual study (PREVAIL, FLW, or STRIVE) data and pooled data from all 3 studies. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 28, 180, and 365 postvaccination.In the overall pooled population, in all subgroups, and in each trial independently, GP-ELISA and PRNT geometric mean titers increased from BL, generally peaking at Day 28 and persisting through Day 365. Immune responses were greater in women and participants with BL GP-ELISA ≥ 200 EU/mL, but did not differ across age groups.These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response through 12 months postvaccination in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in women and participants with pre-existing immunity are consistent with those described previously and for other vaccines. Trials were registered as follows: PREVAIL: ClinicalTrials.gov NCT02344407; FLW: Pan African Clinical Trials Registry PACTR201503001057193; STRIVE: ClinicalTrials.gov NCT02378753. Protocols V920-009, 011, and 018.

Urinary tract infections (UTIs) are common and may occur in foodborne Salmonella outbreaks. Using data from PulseNet, the U.S. national molecular subtyping network for foodborne disease surveillance, we analyzed the 9781 Salmonella isolates associated with the 110 outbreaks from 2004 to 2013 that included at least one urine isolate. Within each outbreak, we calculated standardized isolation dates, using these dates in a linear mixed model to estimate the difference in incubation period for infections yielding stool versus urine isolates. We estimate that the incubation period for Salmonella UTIs is on average 10.6 (95% confidence interval 6.0-15.2) days longer than for gastrointestinal illness, suggesting that outbreak investigators should interview UTI patients about a longer time period before illness onset to identify sources of infection.

Little information exists regarding Ebola vaccine rVSVΔGZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant 15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

The COVID-19 pandemic has exposed weaknesses in disease surveillance in nearly all countries. Early identification of COVID-19 cases and clusters for rapid containment was hampered by inadequate diagnostic capacity, insufficient contact tracing, fragmented data systems, incomplete data insights for public health responders, and suboptimal governance of all these elements. Once SARS-CoV-2 became widespread, interventions to control community transmission were undermined by weak surveillance of cases and insufficient national capacity to integrate data for timely adjustment of public health measures.1, 2 Although some countries had little or no reliable data, others did not share data consistently with their own populations and with WHO and other multilateral agencies. The emergence of SARS-CoV-2 variants has highlighted inadequate national pathogen genomic sequencing capacities in many countries and led to calls for expanded virus sequencing. However, sequencing without epidemiological and clinical surveillance data is insufficient to show whether new SARS-CoV-2 variants are more transmissible, more lethal, or more capable of evading immunity, including vaccine-induced immunity.

Urinary tract infections (UTIs) are common and may occur in foodborne

More than 85% of Covid-19 mortality in high income countries is among people 65 years of age or older. Recent disaggregated data from the UK and US show that minority communities have increased mortality among younger age groups and in South Africa initial data suggest that the majority of deaths from Covid-19 are under 65 years of age. These observations suggest significant potential for increased Covid-19 mortality among younger populations in Africa and South Asia and may impact age-based selection of high-risk groups eligible for a future vaccine.

The West Africa Ebola epidemic stimulated rapid implementation of Ebola vaccine trials in the 3 highly affected countries. In Sierra Leone, we studied the recombinant vesicular stomatitis virus Ebola vaccine (rVSV∆G-ZEBOV-GP) safety and efficacy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was a randomized, unblinded Phase 2/3 trial with phased vaccine introduction, no placebo, and concurrent evaluation of vaccine safety and efficacy. Healthcare and frontline response workers in 5 districts were randomized to immediate or deferred (18–24 weeks later) vaccination and followed for 6 months postvaccination. We enrolled 8651 participants from April through August 2015; 7998 were vaccinated. No participants developed Ebola virus disease so an efficacy assessment was not possible. Overall, 132 (1.5%) participants experienced serious adverse events (SAEs); none were vaccine-related. In a detailed safety substudy (N = 436), vaccinated participants reported significantly more systemic adverse events (AEs) within 7 days than unvaccinated participants including fever higher than 38°C (20.5% vs 3.9%), headache (71.2% vs 22.1%), fatigue (50.7% vs 10.4%), and joint pain (31.7% vs 6.5%); most AEs were mild to moderate severity and resolved within 5 days. During days 5-28, vaccinated participants more commonly reported joint pain (17.0% vs 4.8%) and rash (7.8% vs 1.7%) (P

The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE), a clinical trial of the investigational recombinant vesicular stomatitis virus–based Ebola virus vaccine (rVSV∆ZEBOV-GP; Merck), provided an opportunity to assess health conditions in a cohort of healthy Sierra Leonean adults before vaccination. Of the 8793 healthcare and frontline Ebola response workers screened for study enrollment, 7 (0.1%) self-reported human immunodeficiency virus infection or another significant immunodeficiency disorder and 11 of 3190 (0.3%) women 18–49 years old had a positive urine pregnancy test. Of the 440 participants included in a safety substudy, 124 (28.2%) reported at least 1 medical condition at baseline, most commonly drug hypersensitivity (11.6%), arthralgia (3.9%), arthropathy (2.7%), or gastric (3.0%) or peptic (2.7%) ulcer disease. We calculated the incidence per 100 person-years (PY) and 95% confidence intervals (CIs) of new medical conditions among the 4297 participants followed for 18–24 weeks from enrollment to scheduled vaccination. The most commonly reported conditions were headache (32.4 PY [95% CI, 29.7–35.3 PY]), pain (unspecified) (17.3 PY [95% CI, 15.4–19.4 PY]), arthralgia (9.3 PY [95% CI, 7.9–10.8 PY]), and abdominal pain (9.1 PY [95% CI, 7.7–10.7 PY]). Nasopharyngitis (7.0 PY [95% CI, 5.8–8.4 PY]) and malaria (1.9 PY [95% CI, 1.3–2.7 PY]) were the most commonly reported infectious conditions. Several cases of hypertension, diabetes mellitus, and cancer were also reported. Clinical Trials Registration ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

International regulatory standards ensure human subjects protection, data quality, and scientific integrity of clinical trials. Operationalizing regulatory standards during a large vaccine clinical trial—the Sierra Leone Trial to Introduce a Vaccine Against Ebola—in a resource-constrained setting during an epidemic required flexibility and creativity. We highlight areas that required special attention, such as developing standard operating procedures appropriate for the setting, obtaining space and supplies for the regulatory office, and creating a strategy to maintain both a dedicated central regulatory office and satellite regulatory sites for this trial with paper-based records. Clinical Trials Registration ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Studies estimating the human health impact of the foodborne disease often include estimates of the number of gastroenteritis hospitalisations. The aims of this study were to examine the degree to which hospital discharge data underreport hospitalisations due to bacterial gastroenteritis and to estimate the frequency of stool sample submission among patients presenting with gastroenteritis. Using linked laboratory and hospital discharge data from a healthcare organisation and its affiliated hospital, we examined the International Classification of Disease (ICD-9-CM) diagnosis codes assigned to hospitalised adults with culture-confirmedCampylobacter,Salmonella, orEscherichia coliO157 infections and determined the frequency of stool sample submission. Among 138 hospitalised patients with culture-confirmed infections, 43% ofCampylobacterpatients, 56% ofSalmonellapatients and 35% ofE. coliO157 patients had that pathogen-specific code listed on the discharge record. Among patients without their infection listed as a diagnosis, 65% were assigned a nonspecific gastroenteritis code. Submitting a specimen for culture ⩾3 days before discharge was significantly associated with having the pathogen-specific diagnosis listed. Of 6181 patients assigned a nonspecific gastroenteritis code, 69% had submitted a stool sample for bacterial culture. This study can be used to understand differences and adjust for the underreporting and underdiagnosed ofCampylobacter, SalmonellaandE. coliO157 in hospital discharge and surveillance data, respectively.

SUMMARYThe Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance forCampylobacterinfection. For 2010 through 2015, we compared patients withCampylobacter jejuniwith patients with infections caused by otherCampylobacterspecies.Campylobacter colipatients were more often >40 years of age (OR = 1·4), Asian (OR = 2·3), or Black (OR = 1·7), and more likely to live in an urban area (OR = 1·2), report international travel (OR = 1·5), and have infection in autumn or winter (OR = 1·2).Campylobacter upsaliensispatients were more likely female (OR = 1·6), Hispanic (OR = 1·6), have a blood isolate (OR = 2·8), and have an infection in autumn or winter (OR = 1·7).Campylobacter laripatients were more likely to be >40 years of age (OR = 2·9) and have an infection in autumn or winter (OR = 1·7).Campylobacter fetuspatients were more likely male (OR = 3·1), hospitalized (OR = 3·5), and have a blood isolate (OR = 44·1). International travel was associated with antimicrobial-resistantC. jejuni(OR = 12·5) andC. coli(OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however

SUMMARYVibrio alginolyticuscauses soft tissue and bloodstream infection; little systematically collected clinical and epidemiological information is available. In the USA,V. alginolyticusinfections are reported to the Cholera and OtherVibrioIllness Surveillance system. Using data from 1988 to 2012, we categorised infections using specimen source and exposure history, analysed case characteristics, and calculated incidence rates using US Census Bureau data. Most (96%) of the 1331V. alginolyticusinfections were from coastal states. Infections of the skin and ear were most frequent (87%); ear infections occurred more commonly in children, lower extremity infections more commonly in older adults. Most (86%) infections involved water activity. Reported incidence of infections increased 12-fold over the study period, although the extent of diagnostic or surveillance bias is unclear. Prevention efforts should target waterborne transmission in coastal areas and provider education to promote more rapid diagnosis and prevent complications.

Multidrug-resistant non-typhoidal Salmonella (NTS) infection has emerged as a prominent cause of invasive infections in Africa. We investigated the prevalence of ceftriaxone-resistant invasive NTS infections, conducted exploratory analysis of risk factors for resistance, and described antimicrobial use in western Kenya. We conducted a secondary analysis of existing laboratory, epidemiology, and clinical data from three independent projects, a malaria vaccine trial, a central nervous system (CNS) study, and the International Emerging Infections Program morbidity surveillance (surveillance program) during 2009-2014. We calculated odds ratios (OR) with 95% confidence intervals (CI) for ceftriaxone-resistant NTS infections compared with ceftriaxone-susceptible infections. We surveyed hospitals, pharmacies, and animal drug retailers about the availability and use of antimicrobials. In total, 286 invasive NTS infections were identified in the three projects; 43 NTS isolates were ceftriaxone- resistant. The absolute prevalence of ceftriaxone resistance varied among these methodologically diverse projects, with 18% (16/90) of isolates resistant to ceftriaxone in the vaccine trial, 89% (16/18) in the CNS study, and 6% (11/178) in the surveillance program. Invasive ceftriaxone-resistant infections increased over time. Most ceftriaxone-resistant isolates were co-resistant to multiple other antimicrobials. Having an HIV-positive mother (OR = 3.7; CI = 1.2-11.4) and taking trimethoprim-sulfamethoxazole for the current illness (OR = 9.6, CI = 1.2-78.9) were significantly associated with acquiring ceftriaxone-resistant invasive NTS infection. Ceftriaxone and other antibiotics were widely prescribed; multiple issues related to prescription practices and misuse were identified. In summary, ceftriaxone-resistant invasive NTS infection is increasing and limiting treatment options for serious infections. Efforts are ongoing to address the urgent need for improved microbiologic diagnostic capacity and an antimicrobial surveillance system in Kenya.

SUMMARYToxigenic strains ofVibrio choleraeserogroups O1 and O139 have caused cholera epidemics, but other serogroups – such as O75 or O141 – can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenicVibriospecies. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.

Background Enteric fever in the United States has been primarily associated with travel and with worrisome changes in global patterns of antimicrobial resistance. We present the first comprehensive report of National Typhoid and Paratyphoid Fever Surveillance System (NTPFS) data for a 5-year period (2008-2012). Methods We reviewed data on laboratory-confirmed cases reported to NTPFS, and related antimicrobial susceptibility results of Salmonella Typhi and Paratyphi A isolates sent for testing by participating public health laboratories to the Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System laboratory. Results During 2008-2012, 2341 enteric fever cases were reported, 80% typhoid and 20% paratyphoid A. The proportion caused by paratyphoid A increased from 16% (2008) to 22% (2012). Foreign travel within 30 days preceding illness onset was reported by 1961 (86%) patients (86% typhoid and 92% paratyphoid A). Travel to southern Asia was common (82% for typhoid, 97% for paratyphoid A). Among 1091 (58%) typhoid and 262 (56%) paratyphoid A isolates tested for antimicrobial susceptibility, the proportion resistant to nalidixic acid (NAL-R) increased from 2008 to 2012 (Typhi, 60% to 68%; Paratyphi A, 91% to 94%). Almost all NAL-R isolates were resistant or showed decreased susceptibility to ciprofloxacin. Resistance to at least ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug resistant [MDR]) was limited to Typhi isolates, primarily acquired in southern Asia (13%). Most MDR isolates were also NAL-R. Conclusions Enteric fever in the United States is primarily associated with travel to southern Asia, and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed.

Background The recent Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo highlights the sustained threat of EVD morbidity and mortality where healthcare and vaccine delivery are challenging. ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was developed by Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with multiple partners to prevent EVD and has been approved for human use in several countries. Methods We pooled data from three Phase 2/3 clinical trials conducted in Guinea (FLW), Sierra Leone (STRIVE), and Liberia (PREVAIL) during the 2013–2016 West African outbreak to assess immune responses using a validated assay in each of the three studies and performed a post hoc analysis by sex, age (18–50 yrs & >50 yrs) and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (< 200 & ≥200 EU/ml). The full analysis set (FAS) population included the primary immunogenicity populations (all vaccinated participants with serology data collected within an acceptable day range) from all three trials. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 14, 28, 180, and 365 postvaccination. Results In the overall population and in all subgroups, GP-ELISA and PRNT geometric mean titers increased from BL, with most peaking at Day 28 and persisting through Day 365. There were differences between males and females and between participants with BL GP-ELISA < 200 & ≥200 EU/ml. There did not appear to be a difference between age groups. Conclusion These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response up to 12 months in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in females and participants with preexisting immunity are consistent with those described in published literature for other vaccines. Disclosures Jakub Simon, MD, MS, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Stephen Kennedy, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Scientific Research Study Investigator) Barbara Mahon, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Sheri Dubey, MS, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Rebecca Grant-Klein, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Ken Liu, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Jonathan Hartzel, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Beth-Ann Coller, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Carolee Welebob, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Mary Hanson, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Rebecca Grais, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Scientific Research Study Investigator)

Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers ofSalmonellaserotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidalSalmonellaisolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study howSalmonellaserotype diversity varied within and among these populations in the USA during 1996–2016. We observed substantially higher serotype richness in children

Highlights • Phase 3 vaccine efficacy trial design during outbreaks and emergencies is challenging. • InterVax-Tool (vaxeval.com) is a structured decision-support tool for trial design. • Optimal design must include epidemiological, statistical, ethical, and logistical difficulties. • Navigating these issues in real-time requires tools to assist in decision-making. • Dynamic guidance, note taking, and tailored choices are key to good user engagement., Background Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions. Results Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations – grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural – inform each decision in the trial design process. Conclusions InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.

Guillain Barré syndrome (GBS), which is triggered by autoantibodies produced in response to antigenic stimuli such as certain infections and vaccinations, is the most common cause of acute flaccid paralysis worldwide. Campylobacter, the most common bacterial enteric infection in the USA, is reported to be the most commonly diagnosed antecedent of GBS, yet little information is available about the risk of post-Campylobacter GBS. Data collected through active, population-based surveillance in the Emerging Infections Program during the 2009–2010 novel Influenza A (H1N1) vaccination campaign allowed us to compare confirmed and probable GBS cases to non-cases to determine whether antecedent Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis) was more common among cases and to assess the risk of GBS following Campylobacter infection. We estimate that 8–12% of GBS cases in the USA are attributable to Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis), with 434–650 cases of post-diarrhoeal GBS annually and about 49 cases of GBS per 100 000 Campylobacter infections. These results provide updated estimates for post-Campylobacter GBS incidence in the USA and highlight an important benefit of effective measures to prevent Campylobacter infections.

The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE), an Ebola vaccine trial conducted during the 2014–2016 Ebola epidemic, coordinated with the Sierra Leone national response to identify Ebola cases among trial participants. The early symptoms of Ebola are similar to common vaccine reactions, so it was important to differentiate these to avoid unnecessary referral to an Ebola facility and an increased risk of Ebola exposure. STRIVE developed a modified version of the national case definition and case management algorithm to distinguish between symptoms associated with both Ebola and vaccination with the candidate Ebola vaccine (rVSV∆G-ZEBOV-GP) from those typically associated only with Ebola. For participants who presented ≤48 hours after vaccination, we used the more stringent modified case definition to trigger referral for Ebola evaluation. Participants whose symptoms did not meet case definitions could also be referred to an Ebola facility, based on clinical judgment. No Ebola cases were diagnosed among the 8651 STRIVE participants. Fifty participants were evaluated for Ebola, of whom 34 (68%) were tested after vaccination; 22 deceased participants, all of whom underwent postmortem Ebola testing, as required during the Ebola epidemic, and had negative test results, were excluded from analysis. Seven of 34 participants (21%) had symptom onset ≤48 hours after vaccination, of whom 3 met the modified case definition. The most common diagnosis among those evaluated for Ebola was malaria. STRIVE demonstrates the feasibility of conducting Ebola surveillance among persons vaccinated with rVSV-ZEBOV during an Ebola epidemic and introduces a modified case definition and case management algorithm to distinguish vaccine reactions from early symptoms of Ebola that may be useful for reducing unnecessary Ebola evaluations among persons vaccinated during Ebola outbreaks. Clinical Trials Registration ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Summary Background On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. Methods We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. Findings 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. Interpretation This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. Funding US Global Health Security.

Background Urinary tract infections (UTI) are common bacterial infections that may occur as a part of foodborne outbreaks. Salmonella, a less common cause of UTI, has been identified during foodborne outbreaks, but the epidemiology and pathogenesis are poorly understood. Methods PulseNet, the United States national molecular subtyping network for foodborne disease surveillance, was used to identify Salmonella isolates associated with outbreaks from 2004 to 2013 containing at least one urine and one stool isolate in which the duration was ≤1 year and a food vehicle was suspected or confirmed. We standardized isolation dates across outbreaks by calculating the mean date for stool isolation within an outbreak and subtracting this from the date of each stool/urine isolate in that outbreak. A linear-mixed model with random effect for stool/urine was used to estimate the difference in incubation periods between stool/urine isolates. We also surveyed patients from a 2012 Salmonella Cubana outbreak with many urinary isolates and associated with sprouts, to ask about diarrhea, UTI symptoms, diagnosis, and treatment. Descriptive statistics were calculated. Results Urine isolates had later isolation dates than stool isolates for 102 of the 110 outbreaks identified. The average difference between stool and urine isolates was 10.6 days (95% CI: 6.0, 15.2). Seven women from the Salmonella Cubana outbreak were reached. All women were diagnosed with either a UTI (6/7 = 86%) and/or kidney infection (2/7 = 29%) and were treated with antibiotics (7/7 = 100%). All six women completing the survey reported multiple signs and/or symptoms including frequency, urgency, dysuria, and hematuria with only two women reporting diarrhea prior to UTI. Conclusion Salmonella UTI seen during foodborne outbreaks are symptomatic foodborne infections not associated with diarrhea and appear to have a longer incubation period than Salmonella gastrointestinal (GI) illness. A 13- to 16-day incubation period for Salmonella UTI may be more appropriate, calculated by adding a 3- to 4-day GI illness incubation period plus delay in obtaining a stool isolate. Foodborne UTI investigation may need to change as the current method of obtaining a food history for the 6–72 hours prior to illness does not accurately reflect the incubation period for Salmonella UTI. Disclosures All authors: No reported disclosures.

Salmonella infections are a major cause of illness in the United States. The antimicrobial agents used to treat severe infections include ceftriaxone, ciprofloxacin, and ampicillin. Antimicrobial drug resistance has been associated with adverse clinical outcomes. To estimate the incidence of resistant culture-confirmed nontyphoidal Salmonella infections, we used Bayesian hierarchical models of 2004–2012 data from the Centers for Disease Control and Prevention National Antimicrobial Resistance Monitoring System and Laboratory-based Enteric Disease Surveillance. We based 3 mutually exclusive resistance categories on susceptibility testing: ceftriaxone and ampicillin resistant, ciprofloxacin nonsusceptible but ceftriaxone susceptible, and ampicillin resistant but ceftriaxone and ciprofloxacin susceptible. We estimated the overall incidence of resistant infections as 1.07/100,000 person-years for ampicillin-only resistance, 0.51/100,000 person-years for ceftriaxone and ampicillin resistance, and 0.35/100,000 person-years for ciprofloxacin nonsusceptibility, or ≈6,200 resistant culture-confirmed infections annually. These national estimates help define the magnitude of the resistance problem so that control measures can be appropriately targeted.

Background Nontyphoidal Salmonella (NTS), mainly serotypes Typhimurium and Enteritidis, cause invasive infections with high mortality in children in sub-Saharan Africa. Multidrug resistance is common, and resistance to third-generation cephalosporins has emerged. Methods We reviewed clinical features, outcomes, and antimicrobial resistance patterns in invasive NTS infections among children aged 6 weeks to 5 years participating in malaria vaccine studies in an area of high malaria and human immunodeficiency virus (HIV) transmission in Siaya, western Kenya. Blood culture was performed in hospitalized children and pediatric outpatients with prolonged fever. Results From July 2009 to December 2013, 1696 children aged 6 weeks to 17 months were enrolled into vaccine trials and followed for up to 53 months. We obtained 1692 blood cultures from 847 children. Of 134 bacterial pathogens isolated, 102 (76.1%) were Salmonella serogroup B or D. Invasive NTS disease occurred in 94 (5.5%) children, with an incidence of 1870, 4134, and 6510 episodes per 100 000 person-years overall, in infants, and in HIV-infected children, respectively. Malaria infection within the past 2 weeks occurred in 18.8% (3/16) of invasive NTS episodes in HIV-infected and 66.2% (53/80) in HIV-uninfected children. Case fatality rate was 3.1%. Salmonella group B resistant to ceftriaxone emerged in 2009 and 2010 (6.2% [2/32 isolates]), rising to 56.5% (13/23 isolates) in 2012 and 2013. Conclusions Incidence of invasive NTS disease was high in this area of high malaria and HIV transmission, especially in HIV-infected children. Rapidly emerging resistance against ceftriaxone requires urgent reevaluation of antibiotic recommendations and primary prevention of exposure to Salmonella.

The 2014A¢Â€Â“2015 Ebola virus disease (Ebola) epidemic is the largest in history and represents the first time Ebola has been diagnosed in the United States. On July 9, 2014, CDC activated its Emergency Operations Center and established an Ebola clinical consultation service to assist U.S. state and local public health officials and health care providers with the evaluation of suspected cases. CDC reviewed all 89 inquiries received by the consultation service during July 9, 2014A¢Â€Â“ January 4, 2015, about children (persons aged A¢Â‰Â¤18 years). Most (56 [63%]) children had no identifiable epidemiologic risk factors for Ebola; among the 33 (37%) who did have an epidemiologic risk factor, in every case this was travel from an Ebola-affected country. Thirty-two of these children met criteria for a person under investigation (PUI) because of clinical signs or symptoms. Fifteen PUIs had blood samples tested for Ebola virus RNA by reverse transcriptionA¢Â€Â“polymerase chain reaction; all tested negative. Febrile children who have recently traveled from an Ebola-affected country can be expected to have other common diagnoses, such as malaria and influenza, and in the absence of epidemiologic risk factors for Ebola, the likelihood of Ebola is extremely low. Delaying evaluation and treatment for these other more common illnesses might lead to poorer clinical outcomes. Additionally, many health care providers expressed concerns about whether and how parents should be allowed in the isolation room. While maintaining an appropriate level of vigilance for Ebola, public health officials and health care providers should ensure that pediatric PUIs receive timely triage, diagnosis, and treatment of other more common illnesses, and care reflecting best practices in supporting childrenA¢Â€Â™s psychosocial needs.

A growing segment of the population-adults aged ≥65 years-is more susceptible than younger adults to certain enteric (including foodborne) infections and experience more severe disease.Using data on laboratory-confirmed infections from the Foodborne Diseases Active Surveillance Network (FoodNet), we describe trends in the incidence of Campylobacter spp., Escherichia coli O157, Listeria monocytogenes, and nontyphoidal Salmonella infections in adults aged ≥65 years over time and by age group and sex. We used data from FoodNet and other sources to estimate the total number of illnesses, hospitalizations, and deaths in the United States caused by these infections each year using a statistical model to adjust for underdiagnosis (taking into account medical care-seeking, stool sample submission, laboratory practices, and test sensitivity).From 1996 to 2012, 4 pathogens caused 21,405 laboratory-confirmed infections among older adults residing in the FoodNet surveillance area; 49.3% were hospitalized, and 2.6% died. The average annual rate of infection was highest for Salmonella (12.8/100,000) and Campylobacter (12.1/100,000). Salmonella and Listeria led as causes of death. Among older adults, rates of laboratory-confirmed infection and the percentage of patients who were hospitalized and who died generally increased with age. A notable exception was the rate of Campylobacter infections, which decreased with increasing age. Adjusting for underdiagnosis, we estimated that these pathogens caused about 226,000 illnesses (≈600/100,000) annually among U.S. adults aged ≥65 years, resulting in ≈9700 hospitalizations and ≈500 deaths.Campylobacter, E. coli O157, Listeria, and Salmonella are major contributors to illness in older adults, highlighting the value of effective and targeted intervention.

The design and execution of rigorous, fast, and ethical vaccine efficacy trials can be challenging during epidemics of emerging pathogens, such as the 2014-2016 Ebola virus and 2015-2016 Zika virus epidemics. Response to an urgent public health crisis requires accelerated research even as emerging epidemics themselves change rapidly and are inherently less well understood than well-established diseases. As part of the World Health Organization Research and Development Blueprint, we designed a web-based interactive decision support system (InterVax-Tool) to help diverse stakeholders navigate the epidemiological, logistical, and ethical decisions involved in designing a vaccine efficacy trial during a public health emergency. In contrast to existing literature on trial design, InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of 1) the Primary Endpoint, (2) the Target Population, (3) Randomization, and (4) the Comparator. Guidance is provided on how each of fourteen key considerations–grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural–should be used to inform each decision in the trial design process. The tool is not intended to provide a black box decision framework for identifying an optimal trial design, but rather to facilitate transparent, collaborative and comprehensive discussion of the relevant decisions, while recording the decision process. The tool can also assist capacity building by providing a cross-disciplinary picture of trial design using concepts from epidemiology, study design, vaccinology, biostatistics, mathematical modeling and clinical research ethics. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.One Sentence SummaryAn interactive web-based decision support tool was developed to assist in the design of vaccine efficacy trials during emerging outbreaks.

Background Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results Among 249 HBAT-treated patients, 1 (

Background. In 2011, a multistate outbreak of listeriosis linked to contaminated cantaloupes raised concerns that many pregnant women might have been exposed toListeria 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 suspectedL. monocytogenesexposure.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 possibleL. monocytogenesexposure.

Response to sudden epidemic infectious disease emergencies can demand intensive and specialized training, as demonstrated in 2014 when Ebola virus disease (EVD) rapidly spread throughout West Africa. The medical community quickly became overwhelmed because of limited staff, supplies, and Ebola treatment units (ETUs). Because a mechanism to rapidly increase trained healthcare workers was needed, the US Centers for Disease Control and Prevention developed and implemented an introductory EVD safety training course to prepare US healthcare workers to work in West Africa ETUs. The goal was to teach principles and practices of safely providing patient care and was delivered through lectures, small-group breakout sessions, and practical exercises. During September 2014–March 2015, a total of 570 participants were trained during 16 course sessions. This course quickly increased the number of clinicians who could provide care in West Africa ETUs, showing the feasibility of rapidly developing and implementing training in response to a public health emergency.

Botulism had mortality rates >60% before the 1950s. We reviewed confirmed botulism cases in the USA during 1975-2009 including infant, foodborne, wound, and other/unknown acquisition categories, and calculated mortality ratios. We created a multivariate logistic regression model for non-infant cases (foodborne, wound, and other/unknown). Overall mortality was 3.0% with 109 botulism-related deaths among 3,618 botulism cases [18 (

Background Campylobacteriosis, a leading cause of foodborne illness in the United States, was not nationally notifiable until 2015. Data describing national patterns and trends are limited. We describe the epidemiology of Campylobacter infections in the United States during 2004-2012. Methods We summarized laboratory-confirmed campylobacteriosis data from the Nationally Notifiable Disease Surveillance System, National Outbreak Reporting System, National Antimicrobial Resistance Monitoring System, and Foodborne Diseases Active Surveillance Network. Results During 2004-2012, 303520 culture-confirmed campylobacteriosis cases were reported. Average annual incidence rate (IR) was 11.4 cases/100000 persons, with substantial variation by state (range, 3.1-47.6 cases/100000 persons). IRs among patients aged 0-4 years were more than double overall IRs. IRs were highest among males in all age groups. IRs in western states and rural counties were higher (16.2/100000 and 14.2/100000, respectively) than southern states and metropolitan counties (6.8/100000 and 11.0/100000, respectively). Annual IRs increased 21% from 10.5/100000 during 2004-2006 to 12.7/100000 during 2010-2012, with the greatest increases among persons aged >60 years (40%) and in southern states (32%). The annual median number of Campylobacter outbreaks increased from 28 in 2004-2006 to 56 in 2010-2012; in total, 347 were reported. Antimicrobial susceptibility testing of isolates from 4793 domestic and 1070 travel-associated infections revealed that, comparing 2004-2009 to 2010-2012, ciprofloxacin resistance increased among domestic infections (12.8% vs 16.1%). Conclusions During 2004-2012, incidence of campylobacteriosis, outbreaks, and clinically significant antimicrobial resistance increased. Marked demographic and geographic differences exist. Our findings underscore the importance of national surveillance and understanding of risk factors to guide and target control measures.

Cronobacter spp. are gram-negative bacteria mainly perceived to cause serious infections in infants (1). Cases are most common among newborns or young infants; estimated mortality rates are as high as 80% (2). Infections also occur in older children and adults (3). In adults, Cronobacter spp. cause septicemia, pneumonia, osteomyelitis, wound infections, and splenic abscesses (4). Little is known about reservoirs or routes of transmission other than ingestion of contaminated powdered infant formula (5–7). However, organisms have been isolated from other foods and environmental sources, and infections have occurred among persons who did not consume or handle formula (8,9). In the United States, the incidence of Cronobacter spp. infection is unknown, but evidence suggests it is low. In 1998, only 1 case was found among 10,660 hospitalized infants of low birth weight (10). In 2002, the Foodborne Diseases Active Surveillance Network (FoodNet) estimated an incidence of 1 case per 100,000 infants (11). However, these estimates might be unreliable because populations studied were small and the disease is rare. There is no national surveillance for Cronobacter spp. infections; such infections are reportable only for infants in Minnesota. To increase understanding of the public health effects and demographic distribution of Cronobacter spp. infections, we investigated incidence of laboratory-confirmed infection and characteristics of infected persons.