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Background: Establishment of immune correlates of protection can provide a measurable criterion for assessing protection against infection or disease. For some vaccines, such as the measles vaccine, antibodies serve as the correlate of protection, but for others, such as human papillomavirus, the correlate of protection remains unknown. Merck & Co, Kenilworth, NJ, USA, in collaboration with multiple partners, developed a live recombinant vesicular stomatitis virus vaccine (rVSVΔG-ZEBOV-GP [ERVEBO]) containing the Zaire ebolavirus glycoprotein (GP) in place of the recombinant vesicular stomatitis virus GP to prevent Ebola virus disease. Seroresponse, defined as post-vaccination GP-ELISA of 200 ELISA units (EU) per mL or higher and two-times or more above baseline, was proposed; however, correlates of protection have not been determined. The objective of this post-hoc analysis was to infer possible correlates of protection for rVSVΔG-ZEBOV-GP., Methods: In this post-hoc analysis we included vaccinated participants with serology data from three phase 2/3 immunogenicity trials in Guinea, Sierra Leone, and Liberia (n=2199). Two of the trials were open-label, single-arm trials (one randomised [STRIVE], one non-randomised [FLW]); and one trial was randomised, placebo-controlled with two vaccine comparators (PREVAIL). Endpoints were total IgG antibody response (EU per mL) to rVSVΔG-ZEBOV-GP measured by GP-ELISA and neutralising antibody response to rVSVΔG-ZEBOV-GP measured by plaque reduction neutralisation test at days 14, 28, 180, and 365 after vaccination. Reverse cumulative distribution curves of the antibody concentrations were used to estimate statistical correlates of protection between 70% and 100% that might be applied to vaccine efficacy and effectiveness estimates., Findings: Although GP-ELISA and plaque reduction neutralisation tests showed similar response patterns, GP-ELISA provided a wider range of measurable titres and better differentiation for estimating correlates of protection compared with the plaque reduction neutralisation test. At day 14 after vaccination in the FLW trial, 1060 (100%) of 1060 participants had GP-ELISA levels at or above 68 EU per mL and 742 (70%) of 1060 had levels at or above 313 EU per mL. At day 28 after vaccination in the pooled population, 1953 (100%) of 1953 participants had levels at or above 73 EU per mL and 1368 (70%) of 1953 participants had levels at or above 735 EU per mL. GP-ELISA seroresponse 200 EU per mL or higher and two-times or more increase in antibody level from baseline occurred in 80% or higher of participants at each assessment and in 94% or higher of participants at any time after vaccination., Interpretation: Our results are consistent with previous work suggesting that seroresponse defined as GP-ELISA of 200 EU per mL or higher and two-times or more from baseline associated with vaccination might be the most appropriate dichotomous correlate of protection and falls within the seroprotective threshold range described herein., Funding: Merck Sharp & Dohme, Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Little information exists regarding Ebola vaccine rVSVΔG-ZEBOV-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 <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >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.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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, <25 cases per year have been reported in the United States since 2012.

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Invasive nontyphoidal Salmonella (NTS) infections in Africa cause an enormous burden of illness. These infections are often devastating, with mortality estimated at 20%, even with appropriate antimicrobial therapy. Two major groups-young children and HIV-infected adults-suffer the great majority of these infections. In children, younger age itself, as well as malaria, malnutrition, and HIV infection, are prominent risk factors. In adults, HIV infection is by far the most important risk factor. The most common serotypes in invasive infections are Salmonella enterica serotypes Typhimurium and Enteritidis. In recent years, a specific strain of Salmonella Typhimurium, multilocus sequence type 313, has caused epidemics of invasive disease. Little is known about risk factors for exposure to NTS, making the design of rational interventions to decrease exposure difficult. Antimicrobial therapy is critically important for treatment of invasive NTS infections. Thus, the emergence and spread of resistance to agents commonly used for treatment of invasive NTS infection, now including third-generation cephalosporins, is an ominous development. Already, many invasive NTS infections are essentially untreatable in many health care facilities in sub-Saharan Africa. Several candidate vaccines are in early development and, if safe and effective, could be promising. Interventions to prevent exposure to NTS (e.g., improved sanitation), to prevent the occurrence of disease if exposure does occur (e.g., vaccination, malaria control), and to prevent severe disease and death in those who become ill (e.g., preserving antimicrobial effectiveness) are all important in reducing the toll of invasive NTS disease in sub-Saharan Africa.

Introduction: Millions of U.S. residents become ill from foodborne pathogens each year. Most foodborne outbreaks occur among small groups of persons in a localized area. However, because many foods are distributed widely and rapidly, and because detection methods have improved, outbreaks that occur in multiple states and that even span the entire country are being recognized with increasing frequency., Methods: This report analyzes data from CDC's Foodborne Disease Outbreak Surveillance System to describe multistate foodborne outbreaks that occurred in the United States during 2010-2014., Results: During this 5-year period, 120 multistate foodborne disease outbreaks (with identified pathogen and food or common setting) were reported to CDC. These multistate outbreaks accounted for 3% (120 of 4,163) of all reported foodborne outbreaks, but were responsible for 11% (7,929 of 71,747) of illnesses, 34% (1,460 of 4,247) of hospitalizations, and 56% (66 of 118) of deaths associated with foodborne outbreaks. Salmonella (63 outbreaks), Shiga toxin-producing E. coli (34), and Listeria monocytogenes (12) were the leading pathogens. Fruits (17), vegetable row crops (15), beef (13), sprouts (10), and seeded vegetables (nine) were the most commonly implicated foods. Traceback investigations to identify the food origin were conducted for 87 outbreaks, of which 55 led to a product recall. Imported foods were linked to 18 multistate outbreaks., Conclusions: Multistate foodborne disease outbreaks account for a disproportionate number of outbreak-associated illnesses, hospitalizations, and deaths relative to their occurrence. Working together, food industries and public health departments and agencies can develop and implement more effective ways to identify and to trace contaminated foods linked to multistate outbreaks. Lessons learned during outbreak investigations can help improve food safety practices and regulations, and might prevent future outbreaks.

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 Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Shiga toxin-producing Escherichia coli (STEC) are an important cause of diarrhea and the major cause of postdiarrheal hemolytic uremic syndrome. Non-O157 STEC infections are being recognized with greater frequency because of changing laboratory practices., Methods: Foodborne Diseases Active Surveillance Network (FoodNet) site staff conducted active, population-based surveillance for laboratory-confirmed STEC infections. We assessed frequency and incidence of STEC infections by serogroup and examined and compared demographic factors, clinical characteristics, and frequency of international travel among patients., Results: During 2000-2010, FoodNet sites reported 2006 cases of non-O157 STEC infection and 5688 cases of O157 STEC infections. The number of reported non-O157 STEC infections increased from an incidence of 0.12 per 100,000 population in 2000 to 0.95 per 100,000 in 2010; while the rate of O157 STEC infections decreased from 2.17 to 0.95 per 100,000. Among non-O157 STEC, six serogroups were most commonly reported: O26 (26%), O103 (22%), O111 (19%), O121 (6%), O45 (5%), and O145 (4%). Non-O157 STEC infections were more common among Hispanics, and infections were less severe than those caused by O157 STEC, but this varied by serogroup. Fewer non-O157 STEC infections were associated with outbreaks (7% versus 20% for O157), while more were associated with international travel (14% versus 3% for O157)., Conclusions: Improved understanding of the epidemiologic features of non-O157 STEC infections can inform food safety and other prevention efforts. To detect both O157 and non-O157 STEC infections, clinical laboratories should routinely and simultaneously test all stool specimens submitted for diagnosis of acute community-acquired diarrhea for O157 STEC and for Shiga toxin and ensure that isolates are sent to a public health laboratory for serotyping and subtyping.

Salmonella species cause an estimated 1.2 million infections per year in the United States, making it one of the most commonly reported enteric pathogens. In addition, Salmonella is an important cause of travel-associated diarrhea and enteric fever, a systemic illness commonly associated with Salmonella serotypes Typhi and Paratyphi A. We reviewed cases of Salmonella infection reported to the Centers for Disease Control and Prevention's (CDC) Foodborne Diseases Active Surveillance Network (FoodNet), a sentinel surveillance network, from 2004 to 2008. We compared travelers with Salmonella infection to nontravelers with Salmonella infection with respect to demographics, clinical characteristics, and serotypes. Among 23,712 case-patients with known travel status, 11% had traveled internationally in the 7 days before illness. Travelers with Salmonella infection tended to be older (median age, 30 years) than nontravelers (median age, 24 years; p<0.0001), but were similar with respect to gender. The most common destinations reported were Mexico (38% of travel-associated infections), India (9%), Jamaica (7%), the Dominican Republic (4%), China (3%), and the Bahamas (2%). The proportions of travelers with Salmonella infection hospitalized and with invasive disease were inversely related to the income level of the destination (p<0.0001). The most commonly reported serotypes, regardless of travel status, were Enteritidis (19% of cases), Typhimurium (14%), Newport (9%), and Javiana (5%). Among infections caused by these four serotypes, 22%, 6%, 5%, and 4%, respectively, were associated with travel. A high index of clinical suspicion for Salmonella infection is appropriate when evaluating recent travelers, especially those who visited Africa, Asia, or Latin America.