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Evidence-based approaches to preventing child death require evidence; without data on common causes of child mortality, taking effective action to prevent these deaths is difficult at best. Minimally invasive tissue sampling (MITS) is a potentially powerful, but nascent, technique to obtain gold standard information on causes of death. The Gates Foundation committed to further establishing the methodology and obtain the highest quality information on the major causes of death for children under 5 years. In 2018, the MITS Surveillance Alliance was launched to implement, refine, and enhance the use of MITS across high mortality settings. The Alliance and its members have contributed to some remarkable opportunities to improve mortality surveillance, and we have only just begun to understand the possibilities on larger scales. This supplement showcases studies conducted by MITS Surveillance Alliance members and represents a significant contribution to the cause-of-death literature from high mortality settings., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The effect of malaria infection on the immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein (GP) vaccine (rVSVΔG-ZEBOV-GP) (ERVEBO) is unknown., Methods: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-2016 Ebola epidemic. In STRIVE's immunogenicity substudy, participants provided blood samples at baseline and at 1, 6, and 9-12 months. Anti-GP binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by polymerase chain reaction., Results: Overall, 506 participants enrolled in the immunogenicity substudy and had ≥1 postvaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73 (14.6%). All GP enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants showed seroresponse by GP-ELISA (≥2-fold rise and ≥200 ELISA units/mL), while 81.5% showed seroresponse by PRNT (≥4-fold rise) at ≥1 postvaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months., Conclusion: Asymptomatic adults with or without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP, persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

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].

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

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 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT., Conclusions: HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC., (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.)

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.)

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.)

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: Infants have increased risk for salmonellosis; but epidemiologic information is limited., Methods: We reviewed Foodborne Diseases Active Surveillance Network reports of laboratory-confirmed non-Typhi Salmonella infections in infants from 1996-2008. We calculated incidence, estimated relative risks, and assessed trends over the duration of the study period, using the first 3 years as reference., Results: Average annual incidence of salmonellosis per 100 000 infants was 177.8 (95% confidence interval [CI], 152.7-202.8) in blacks, 129.7 (95% CI, 94.8-164.7) in Asians, and 81.1 (95% CI, 70.2-92.0) in whites. Our analysis of ethnicity independent of race showed salmonellosis incidence of 86.7 (95% CI, 74.6-98.9) in Hispanics and 69.4 (95% CI, 54.8-84.1) in non-Hispanics. Salmonellosis was invasive more often in blacks (9.4%) and Asians (6.4%) than whites (3.6%, P <.001 and P = .01, respectively). Asian infants with salmonellosis were older (median, 31 weeks [range, 0-52]) than black (24 weeks [range, 0-52], P < .001) or white infants (23 weeks [range, 0-52], P < .001). Incidence of all salmonellosis remained stable for whites from 1996-1998 through 2008, but blacks had a sustained decrease, with relative risk of 0.48 (95% CI, .37-.63) in 2008 compared with 1996-1998. However, 2008 incidence remained highest among blacks (141.0 of 100 000 vs 113.5 of 100 000 among whites and 109.9 of 100 000 among Asians)., Conclusion: Black infants had a greater risk of salmonellosis and invasive disease than other racial groups, and despite the greatest decrease in incidence over the study period, they continued to have the highest incidence of salmonellosis. The decrease in salmonellosis in black infants suggests that future improvements may be possible for other population subgroups., (Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society 2013. This work is written by US Government employees and is in the public domain in the US.)

Background: Yersinia enterocolitica causes an estimated 116,716 illnesses annually in the United States. Black children have historically had the highest rates of infection, with incidence peaking in the winter., Methods: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts active surveillance for laboratory-confirmed Y. enterocolitica infections, defined as the isolation of Y. enterocolitica or unspeciated Yersinia from a human clinical specimen. We calculated the average annual crude incidence rate per 100,000 persons from 1996 through 2009 and described rates by age, race, and geographic site. To account for changes in the FoodNet catchment area, we used a negative binomial model to estimate statistical changes in incidence using the average annual incidence in 1996-1998 as the baseline., Results: From 1996 through 2009, 2085 Y. enterocolitica infections were reported to FoodNet. The average annual crude incidence was 0.5 per 100,000 persons and was highest in blacks (0.9 per 100,000 persons). Over time, the rate in blacks declined from 3.9 to 0.4 per 100,000 persons. Declines among other racial groups were not as pronounced. The largest decline occurred in black children <5 years old (from 41.5 per 100,000 persons in 1996 to 3.5 per 100,000 persons in 2009). From 2007 through 2009, the highest rate of infection was in Asian children (5.1 per 100,000 persons). Compared with 1996-1998, the incidence in 2009 was 66% (95% confidence interval, 51%-77%) lower among children <5 years old., Conclusions: Y. enterocolitica infections in FoodNet sites have significantly declined since 1996. These declines were greatest in young black children, the group that initially had the highest incidence, possibly as the result of educational efforts in Georgia.

Background: Cyclosporiasis is an enteric disease caused by the parasite Cyclospora cayetanensis. Since the mid-1990 s, the Centers for Disease Control and Prevention has been notified of cases through various reporting and surveillance mechanisms., Methods: We summarized data regarding laboratory-confirmed cases of Cyclospora infection reported during 1997-2009 via the Foodborne Diseases Active Surveillance Network (FoodNet), which gradually expanded to include 10 sites (Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Tennessee, and selected counties in California, Colorado, and New York) that represent approximately 15% of the US population. Since 2004, the number of sites has remained constant and data on the international travel history and outbreak status of cases have been collected., Results: A total of 370 cases were reported, 70.3% (260) of which were in residents of Connecticut (134 [36.2%]) and Georgia (126 [34.1%]), which on average during this 13-year period accounted for 29.0% of the total FoodNet population under surveillance. Positive stool specimens were collected in all months of the year, with a peak in June and July (208 cases [56.2%]). Approximately half (48.6%) of the 185 cases reported during 2004-2009 were associated with international travel, known outbreaks, or both., Conclusions: The reported cases were concentrated in time (spring and summer) and place (2 of 10 sites). The extent to which the geographic concentration reflects higher rates of testing, more sensitive testing methods, or higher exposure/infection rates is unknown. Clinicians should include Cyclospora infection in the differential diagnosis of prolonged or relapsing diarrheal illness and explicitly request stool examinations for this parasite.

Background: Approximately 40% of US travelers to less developed countries experience diarrheal illness. Using data from the Foodborne Diseases Active Surveillance Network (FoodNet), we describe travel-associated enteric infections during 2004-2009, characterizing the patients, pathogens, and destinations involved., Methods: FoodNet conducts active surveillance at 10 US sites for laboratory-confirmed infections with 9 pathogens transmitted commonly through food. Travel-associated infections are infections diagnosed in the United States but likely acquired abroad based on a pathogen-specific time window between return from international travel to diagnosis. We compare the demographic, clinical, and exposure-related characteristics of travelers with those of nontravelers and estimate the risk of travel-associated infections by destination, using US Department of Commerce data., Results: Of 64,039 enteric infections reported to FoodNet with information about travel, 8270 (13%) were travel associated. The pathogens identified most commonly in travelers were Campylobacter (42%), nontyphoidal Salmonella (32%), and Shigella (13%). The most common travel destinations were Mexico, India, Peru, Dominican Republic, and Jamaica. Most travel-associated infections occurred in travelers returning from Latin America and the Caribbean (LAC). Risk was greatest after travel to Africa (75.9 cases per 100,000 population), followed by Asia (22.7 cases per 100,000), and LAC (20.0 cases per 100,000)., Conclusions: The Latin America and Caribbean region accounts for most travel-associated enteric infections diagnosed in the United States, although travel to Africa carries the greatest risk. Although FoodNet surveillance does not cover enterotoxigenic Escherichia coli, a common travel-associated infection, this information about other key enteric pathogens can be used by travelers and clinicians in pre- and posttravel consultations.

Background: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices., Methods: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens., Results: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens., Conclusions: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.

Background: Listeriosis can cause severe disease, especially in fetuses, neonates, older adults, and persons with certain immunocompromising and chronic conditions. We summarize US population-based surveillance data for invasive listeriosis from 2004 through 2009., Methods: We analyzed Foodborne Diseases Active Surveillance Network (FoodNet) data for patients with Listeria monocytogenes isolated from normally sterile sites. We describe the epidemiology of listeriosis, estimate overall and specific incidence rates, and compare pregnancy-associated and nonpregnancy-associated listeriosis by age and ethnicity., Results: A total of 762 listeriosis cases were identified during the 6-year reporting period, including 126 pregnancy-associated cases (17%), 234 nonpregnancy-associated cases(31%) in patients aged <65 years, and 400 nonpregnancy-associated cases (53%) in patients aged ≥ 65 years. Eighteen percent of all cases were fatal. Meningitis was diagnosed in 44% of neonates. For 2004-2009, the overall annual incidence of listeriosis varied from 0.25 to 0.32 cases per 100,000 population. Among Hispanic women, the crude incidence of pregnancy-associated listeriosis increased from 5.09 to 12.37 cases per 100,000 for the periods of 2004-2006 and 2007-2009, respectively; among non-Hispanic women, pregnancy-associated listeriosis increased from 1.74 to 2.80 cases per 100,000 for the same periods. Incidence rates of nonpregnancy-associated listeriosis in patients aged ≥ 65 years were 4-5 times greater than overall rates annually., Conclusions: Overall listeriosis incidence did not change significantly from 2004 through 2009. Further targeted prevention is needed, including food safety education and messaging (eg, avoiding Mexican-style cheese during pregnancy). Effective prevention among pregnant women, especially Hispanics, and older adults would substantially affect overall rates.

Background: The Centers for Disease Control and Prevention monitors vibriosis through 2 surveillance systems: the nationwide Cholera and Other Vibrio Illness Surveillance (COVIS) system and the 10-state Foodborne Diseases Active Surveillance Network (FoodNet). COVIS conducts passive surveillance and FoodNet conducts active surveillance for laboratory-confirmed Vibrio infections., Methods: We summarized Vibrio infections (excluding toxigenic V. cholerae O1 and O139) reported to COVIS and FoodNet from 1996 through 2010. For each system, we calculated incidence rates using US Census Bureau population estimates for the surveillance area., Results: From 1996 to 2010, 7700 cases of vibriosis were reported to COVIS and 1519 to FoodNet. Annual incidence of reported vibriosis per 100,000 population increased from 1996 to 2010 in both systems, from 0.09 to 0.28 in COVIS and from 0.15 to 0.42 in FoodNet. The 3 commonly reported Vibrio species were V. parahaemolyticus, V. vulnificus, and V. alginolyticus; both surveillance systems showed that the incidence of each increased. In both systems, most hospitalizations and deaths were caused by V. vulnificus infection, and most patients were white men. The number of cases peaked in the summer months., Conclusions: Surveillance data from both COVIS and FoodNet indicate that the incidence of vibriosis increased from 1996 to 2010 overall and for each of the 3 most commonly reported species. Epidemiologic patterns were similar in both systems. Current prevention efforts have failed to prevent increasing rates of vibriosis; more effective efforts will be needed to decrease rates.

For decades, culture has been the mainstay of diagnostic testing for bacterial enteric pathogens. This paradigm is changing as clinical laboratories adopt culture-independent methods, such as antigen-based tests and nucleic acid-based assays. Public health surveillance for enteric infections addresses 4 interrelated but distinct objectives: case investigation for localized disease control; assessment of disease burden and trends to prioritize and assess impact of population-based control measures; outbreak detection; and microbiologic characterization to improve understanding of pathogens, their virulence mechanisms, and epidemiology. We summarize the challenges and opportunities that culture-independent tests present and suggest strategies, such as validation studies and development of culture-independent tests compatible with subtyping, that could be adopted to ensure that surveillance remains robust. Many of these approaches will require time and resources to implement, but they will be necessary to maintain a strong surveillance system. Public health practitioners must clearly explain the value of surveillance, especially how outbreak detection benefits the public, and collaborate with all stakeholders to develop solutions.

Background: Because classic pneumococcal serotyping methods cannot distinguish between serotypes 6A and 6C, the effects of pneumococcal vaccines against serotype 6C are unknown. Pneumococcal vaccines contain serotype 6B but not serotypes 6A and 6C., Methods: We used a phagocytic killing assay to estimate the immunogenicity of the 7-valent conjugate vaccine (PCV7) in children and the 23-valent polysaccharide vaccine (PPV23) in adults against serotypes 6A and 6C. We evaluated trends in invasive pneumococcal disease (IPD) caused by serotypes 6A and 6C in the United States, using active surveillance., Results: Serum specimens from PCV7-immunized children had median opsonization indices of 150 and < 20 for serotypes 6A and 6C, respectively. Similarly, only 52% of adults (25 of 48) vaccinated with PPV23 showed opsonic indices of > 20 against serotype 6C. During 1999--2006, the incidence of serotype 6A IPD decreased by 91% (from 4.9 to 0.46 cases per 100,000 persons; P < .05) among individuals aged < 5 years and by 58% (from 0.86 to 0.36 cases per 100,000 persons; P < .05) among those aged > or = 5 years. Although the incidence of 6C IPD showed no consistent trend (range, 0-0.6 cases per 100,000 persons) among individuals aged < 5 years, it increased from 0.25 to 0.62 cases per 100,000 persons (P < .05) among those aged > or = 5 years., Conclusions: PCV7 introduction has led to reductions in serotype 6A IPD but not serotype 6C IPD in the United States.