Most infections with pandemic Vibrio cholerae are thought to result in subclinical disease and are not captured by surveillance. Previous estimates of the ratio of infections to clinical cases have varied widely (2 to 100 infections per case). Understanding cholera epidemiology and immunity relies on the ability to translate between numbers of clinical cases and the underlying number of infections in the population. We estimated the infection incidence during the first months of an outbreak in a cholera-naive population using a Bayesian vibriocidal antibody titer decay model combining measurements from a representative serosurvey and clinical surveillance data. 3,880 suspected cases were reported in Grande Saline, Haiti, between 20 October 2010 and 6 April 2011 (clinical attack rate 18.4%). We found that more than 52.6% (95% Credible Interval (CrI) 49.4-55.7) of the population ≥2 years showed serologic evidence of infection, with a lower infection rate among children aged 2-4 years (35.5%; 95%CrI 24.2-51.6) compared with people ≥5 years (53.1%; 95%CrI 49.4-56.4). This estimated infection rate, nearly three times the clinical attack rate, with underdetection mainly seen in those ≥5 years, has likely impacted subsequent outbreak dynamics. Our findings show how seroincidence estimates improve understanding of links between cholera burden, transmission dynamics and immunity.

BACKGROUND: A petroleum leak into the Joint Base Pearl Harbor-Hickam water system on Oahu, Hawaii in November 2021 contaminated the drinking water of approximately 93,000 users, causing many to relocate for months. Perceptions of health and wellbeing were captured using the Centers for Disease Control/Agency for Toxic Substances and Disease Registry (CDC/ATSDR) Assessment of Chemical Exposures (ACE) cross-sectional survey in collaboration with the Hawaii Department of Health (HDOH). METHODS: Responses from the ACE online survey of community members, businesses, schools, health care and veterinary care organizations during the contamination event, containing quantitative questions and qualitative information from an open text field, were analyzed. Separately, a qualitative key informant questionnaire was administered to community establishments. Thematic content analysis was used to analyze and identify prominent themes from the ACE open text field and the key informant responses that were triangulated by the quantitative data when the themes aligned. RESULTS: Six major themes of disruption, communication, trust, stress, support, and ongoing needs were identified. Burdensome logistics from obtaining alternate water, negative financial impacts from relocation or losing business, distrust of information, perceived lack of support from response entities and uncertainty of long-term health impact caused significant disruption, stress and mental health. Individuals reported needing water, shelter, and mental health care while establishments wanted financial reimbursement and a resolution. CONCLUSIONS: The findings show that environmental disasters have significant disruptive and mental health impacts from stress. Identified themes can inform and improve emergency response and communication strategies and increase trust with community members during and after large chemical exposure events.

BACKGROUND: Limited research exists on suicide among children aged 5 to 9 years. The objective of this study was to examine characteristics of suicide in children younger than 10 years. METHODS: Data are from the National Fatality Review-Case Reporting System (NFR-CRS) for years 2006 through 2021 for children aged 6 to 9 years who died by suicide. No suicide deaths were reported in NFR-CRS for children aged ≤ 5 years. Descriptive analyses by demographics and circumstances were conducted. A thematic analysis of prevention recommendations made by child death review teams was performed. RESULTS: From 2006 to 2021, NFR-CRS identified 78 suicide decedents aged 6 to 9 years. The largest share were aged 9 years (72%), male (74%), non-Hispanic Black (42%), and died by hanging (86%) at home (91%). School-related problems (39%), history of child maltreatment (36%), history of mental health services (30%), argument with parents (23%), and familial discord (19%) were common circumstances. Key suicide prevention themes included education for caregivers and school staff, improved behavioral health services, and implementation of school policies and programs. CONCLUSIONS: Results provide a more complete picture of suicide among younger children, improving understanding of their unique characteristics. It is recommended that program planners consider both age-appropriateness and the impacts of social (eg, racism) and structural inequities in their approaches to prevention, encompassing both community and school-based strategies. For pediatricians, results emphasize the importance of lethal means counseling, safety planning, and educating parents and caregivers on the distinct warning signs of suicide for younger children.

In 2020 the U.S. Federal Committee on Statistical Methodology (FCSM) released 'A Framework for Data Quality', organized by 11 dimensions of data quality grouped among three domains of quality (utility, objectivity, integrity). This paper addresses the use of the FCSM Framework for data quality assessments of blended data. The FCSM Framework applies to all types of data, however best practices for implementation have not been documented. We applied the FCSM Framework for three health-research related case studies. For each case study, assessments of data quality dimensions were performed to identify threats to quality, possible mitigations of those threats, and trade-offs among them. From these assessments the authors concluded: 1) data quality assessments are more complex in practice than anticipated and expert guidance and documentation are important; 2) each dimension may not be equally important for different data uses; 3) data quality assessments can be subjective and having a quantitative tool could help explain the results, however, quantitative assessments may be closely tied to the intended use of the dataset; 4) there are common trade-offs and mitigations for some threats to quality among dimensions. This paper is one of the first to apply the FCSM Framework to specific use-cases and illustrates a process for similar data uses. © 2024 - IOS Press. All rights reserved.

This report updates the previously published summary of recommendations for vaccinating health-care personnel (HCP) in the United States (CDC. Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices [ACIP] and the Hospital Infection Control Practices Advisory Committee [HICPAC]. MMWR 1997;46[No. RR-18]). This report was reviewed by and includes input from the Healthcare (formerly Hospital) Infection Control Practices Advisory Committee. These updated recommendations can assist hospital administrators, infection-control practitioners, employee health clinicians, and HCP in optimizing infection prevention and control programs. The recommendations for vaccinating HCP are presented by disease in two categories: 1) those diseases for which vaccination or documentation of immunity is recommended because of risks to HCP in their work settings for acquiring disease or transmitting to patients and 2) those for which vaccination might be indicated in certain circumstances. Background information for each vaccine-preventable disease and specific recommendations for use of each vaccine are presented. Certain infection-control measures that relate to vaccination also are included in this report. In addition, ACIP recommendations for the remaining vaccines that are recommended for certain or all adults are summarized, as are considerations for catch-up and travel vaccinations and for work restrictions. This report summarizes all current ACIP recommendations for vaccination of HCP and does not contain any new recommendations or policies. The recommendations provided in this report apply, but are not limited, to HCP in acute-care hospitals; long-term-care facilities (e.g., nursing homes and skilled nursing facilities); physician's offices; rehabilitation centers; urgent care centers, and outpatient clinics as well as to persons who provide home health care and emergency medical services.

In the United States, unintentional injury is the fourth leading cause of death among infants (i.e., children aged <1 year) and is the top cause of death among children and adolescents aged 1-17 years; firearms are a leading injury method. Unsecured firearms (e.g., unlocked and loaded) are associated with risk for unintentional childhood firearm injury death. Data recorded during 2003-2021 by the National Violent Death Reporting System (NVDRS) from 49 states, the District of Columbia, and Puerto Rico were used to characterize unintentional firearm injury deaths of U.S. infants, children, and adolescents aged 0-17 years (referred to as children in this report). NVDRS identified 1,262 unintentional firearm injury deaths among children aged 0-17 years: the largest percentage (33%) of these deaths were among children aged 11-15 years, followed by 29% among those aged 0-5 years, 24% among those aged 16-17 years, and 14% among persons aged 6-10 years. Overall, 83% of unintentional firearm injury deaths occurred among boys. The majority (85%) of victims were fatally injured at a house or apartment, including 56% in their own home. Approximately one half (53%) of fatal unintentional firearm injuries to children were inflicted by others; 38% were self-inflicted. In 9% of incidents, it was unknown whether the injury was self- or other-inflicted. Approximately two thirds (67%) of shooters were playing with or showing the firearm to others when it discharged. Overall, firearms used in unintentional injury deaths were often stored loaded (74%) and unlocked (76%) and were most commonly accessed from nightstands and other sleeping areas (30%). Unintentional firearm injury deaths of children are preventable. Secured firearm storage practices (e.g., storing firearms locked, unloaded, and separate from ammunition) have been identified as protective factors against child firearm injuries and deaths, underscoring the importance of policymakers, health care professionals (e.g., pediatricians), and others partnering with parents, caregivers, and firearm owners to promote secure firearm storage.

BACKGROUND: In 2021, a large petroleum leak contaminated a water source that supplied drinking water to military and civilians in Oahu, Hawaii. METHODS: We conducted an Assessment of Chemical Exposures (ACE) survey and supplemented that information with complementary data sources: (1) poison center caller records; (2) emergency department visit data; and (3) a key informant questionnaire. RESULTS: Among 2,289 survey participants, 86% reported ≥1 new or worsening symptom, 75% of which lasted ≥30 days, and 37% sought medical care. Most (n = 1,653, 72%) reported new mental health symptoms. Among equally observable symptoms across age groups, proportions of children ≤2 years experiencing vomiting, runny nose, skin rashes, and coughing (33, 46, 56, and 35%, respectively) were higher than other age groups. Poison center calls increased the first 2 weeks after the contamination, while emergency department visits increased in early December 2021. Key informant interviews revealed themes of lack of support, mental health symptoms, and long-term health impact concerns. DISCUSSION: This event led to widespread exposure to petroleum products and negatively affected thousands of people. Follow-up health surveys or interventions should give special consideration to longer-term physical and mental health, especially children due to their unique sensitivity to environmental exposures.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

We conducted a case-control study to identify risk and protective factors during a cholera outbreak in Jijiga, Ethiopia, in June 2017. A case-patient was defined as anyone > 5 years old with at least three loose stools in 24 hours who was admitted to a cholera treatment center in Jijiga on or after June 16, 2017. Two controls were matched to each case by type of residency (rural or urban) and age group. We enrolled 55 case-patients and 102 controls from June 16 to June 23, 2017. Identified risk factors for cholera were male sex, eating cold food, and eating food outside the home. Eating hot food was protective, as was reported handwashing after defecation; no other reported water, sanitation, and hygiene factors were associated with cholera risk. Recommendations included continuing messaging about safe food handling practices at home, the dangers of consuming meals prepared away from home, and the importance of hand hygiene practices.

BACKGROUND: Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them. METHODS: For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers. FINDINGS: Globally, 14·3 million (95% uncertainty interval [UI] 12·5-16·3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44·6% (42·2-47·0) decline from 25·9 million (22·0-29·9) in 1990. Age-standardised incidence rates declined by 54·9% (53·4-56·5), from 439·2 (376·7-507·7) per 100 000 person-years in 1990, to 197·8 (172·0-226·2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76·3% (71·8-80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54-1·53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135·9 thousand (76·9-218·9) deaths from typhoid and paratyphoid fever globally in 2017, a 41·0% (33·6-48·3) decline from 230·5 thousand (131·2-372·6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9·8 million (5·6-15·8) DALYs in 2017, down 43·0% (35·5-50·6) from 17·2 million (9·9-27·8) DALYs in 1990. INTERPRETATION: Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease. FUNDING: Bill & Melinda Gates Foundation.

PURPOSE OF REVIEW: This review describes the basic epidemiologic, clinical, and microbiologic aspects of cholera, highlights new developments within these areas, and presents strategies for applying currently available tools and knowledge more effectively. RECENT FINDINGS: From 1990 to 2016, the reported global burden of cholera fluctuated between 74,000 and 595,000 cases per year; however, modeling estimates suggest the real burden is between 1.3 and 4.0 million cases and 95,000 deaths yearly. In 2018, the World Health Assembly endorsed a new initiative to reduce cholera deaths by 90% and eliminate local cholera transmission in 20 countries by 2030. New tools, including localized GIS mapping, climate modeling, whole genome sequencing, oral vaccines, rapid diagnostic tests, and new applications of water, sanitation, and hygiene interventions, could support this goal. Challenges include a high proportion of fragile states among cholera-endemic countries, urbanization, climate change, and the need for cholera treatment guidelines for pregnant women and malnourished children. SUMMARY: Reducing cholera morbidity and mortality depends on real-time surveillance, outbreak detection and response; timely access to appropriate case management and cholera vaccines; and provision of safe water, sanitation, and hygiene.

BACKGROUND: Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2-59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya. METHODS: VIDA was a prospective case-control study (May 2015-July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD). We defined inappropriate antibiotic use as prescription or use of antibiotics when not indicated by World Health Organization (WHO) guidelines. We used logistic regression to assess factors associated with antibiotic prescription for MSD cases who had no indication for an antibiotic, at each site. RESULTS: VIDA enrolled 4840 cases. Among 1757 (36.3%) who had no apparent indication for antibiotic treatment, 1358 (77.3%) were prescribed antibiotics. In The Gambia, children who presented with a cough (adjusted odds ratio [aOR]: 2.05; 95% confidence interval [95% CI]: 1.21-3.48) were more likely to be prescribed an antibiotic. In Mali, those who presented with dry mouth (aOR: 3.16; 95% CI: 1.02-9.73) were more likely to be prescribed antibiotics. In Kenya, those who presented with a cough (aOR: 2.18; 95% CI: 1.01-4.70), decreased skin turgor (aOR: 2.06; 95% CI: 1.02-4.16), and were very thirsty (aOR: 4.15; 95% CI: 1.78-9.68) were more likely to be prescribed antibiotics. CONCLUSIONS: Antibiotic prescription was associated with signs and symptoms inconsistent with WHO guidelines, suggesting the need for antibiotic stewardship and clinician awareness of diarrhea case-management recommendations in these settings.

BACKGROUND: Pediatric exposures to unsafe sources of water, unsafely managed sanitation, and animals are prevalent in low- and middle-income countries. In the Vaccine Impact on Diarrhea in Africa case-control study, we examined associations between these risk factors and moderate-to-severe diarrhea (MSD) in children <5 years old in The Gambia, Kenya, and Mali. METHODS: We enrolled children <5 years old seeking care for MSD at health centers; age-, sex-, and community-matched controls were enrolled at home. Conditional logistic regression models, adjusted for a priori confounders, were used to evaluate associations between MSD and survey-based assessments of water, sanitation, and animals living in the compound. RESULTS: From 2015 to 2018, 4840 cases and 6213 controls were enrolled. In pan-site analyses, children with drinking water sources below "safely managed" (onsite, continuously accessible sources of good water quality) had 1.5-2.0-fold higher odds of MSD (95% confidence intervals [CIs] ranging from 1.0 to 2.5), driven by rural site results (The Gambia and Kenya). In the urban site (Mali), children whose drinking water source was less available (several hours/day vs all the time) had higher odds of MSD (matched odds ratio [mOR]: 1.4, 95% CI: 1.1, 1.7). Associations between MSD and sanitation were site-specific. Goats were associated with slightly increased odds of MSD in pan-site analyses, whereas associations with cows and fowl varied by site. CONCLUSIONS: Poorer types and availability of drinking water sources were consistently associated with MSD, whereas the impacts of sanitation and household animals were context-specific. The association between MSD and access to safely managed drinking water sources post-rotavirus introduction calls for transformational changes in drinking water services to prevent acute child morbidity from MSD.

BACKGROUND: The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. METHODS: In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. RESULTS: Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12-2.17), as well as cows (RR, 1.61; 95% CI, 1.16-2.24) and sheep (RR, 1.48; 95% CI, 1.11-1.96) living in the compound, were associated with Shiga toxin-producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15-1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. CONCLUSIONS: Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children.

BACKGROUND: Giardia has been associated with reduced risk of diarrhea in children in low-resource settings, but the mechanism underlying this association is unknown. To assess whether Giardia may shape colonization or infection with other enteric pathogens and impact associations with diarrhea, we examined Giardia and enteric pathogen codetection among children <5 years old in Kenya, The Gambia, and Mali as part of the Vaccine Impact on Diarrhea in Africa study. METHODS: We tested for Giardia and other enteric pathogens using enzyme-linked immunosorbent assays and real-time polymerase chain reaction (PCR) on stool, respectively. We evaluated associations between Giardia and enteric pathogen detection using multivariable logistic regression models separately for children with moderate-to-severe diarrhea (MSD, cases) and free of diarrhea (controls). RESULTS: Among 11 039 enrolled children, Giardia detection was more common among controls (35%) than cases (28%, P < .001). Campylobacter coli/jejuni detection was associated with Giardia in controls in The Gambia (adjusted odds ratio [aOR] [95% confidence interval {CI}]: 1.51 [1.22‒1.86]) and cases across all sites (1.16 [1.00‒1.33]). Among controls, the odds of astrovirus (1.43 [1.05‒1.93]) and Cryptosporidium spp. (1.24 [1.06‒1.46]) detection were higher among children with Giardia. Among cases, the odds of rotavirus detection were lower in children with Giardia in Mali (.45 [.30‒.66]) and Kenya (.31 [.17‒.56]). CONCLUSIONS: Giardia was prevalent in children <5 years old and was associated with detection of other enteric pathogens, with differing associations in cases versus controls and by site. Giardia may affect colonization or infection by certain enteric pathogens associated with MSD, suggesting an indirect mechanism of clinical impact.

BACKGROUND: To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin-producing E. coli (STEC) positive children with moderate-to-severe diarrhea (MSD) in Mali, The Gambia, and Kenya. METHODS: Between May 2015 and July 2018, children aged 0-59 months with medically attended MSD and matched controls without diarrhea were enrolled. Stools were tested conventionally using culture and multiplex polymerase chain reaction (PCR), and by quantitative PCR (qPCR). We assessed DEC detection by site, age, clinical characteristics, and enteric coinfection. RESULTS: Among 4840 children with MSD and 6213 matched controls enrolled, 4836 cases and 1 control per case were tested using qPCR. Of the DEC detected with TAC, 61.1% were EAEC, 25.3% atypical EPEC (aEPEC), 22.4% typical EPEC (tEPEC), and 7.2% STEC. Detection was higher in controls than in MSD cases for EAEC (63.9% vs 58.3%, P < .01), aEPEC (27.3% vs 23.3%, P < .01), and STEC (9.3% vs 5.1%, P < .01). EAEC and tEPEC were more frequent in children aged <23 months, aEPEC was similar across age strata, and STEC increased with age. No association between nutritional status at follow-up and DEC pathotypes was found. DEC coinfection with Shigella/enteroinvasive E. coli was more common among cases (P < .01). CONCLUSIONS: No significant association was detected between EAEC, tEPEC, aEPEC, or STEC and MSD using either conventional assay or TAC. Genomic analysis may provide a better definition of the virulence factors associated with diarrheal disease.

BACKGROUND: To address a paucity of data from sub-Saharan Africa, we examined the prevalence, severity, and seasonality of norovirus genogroup II (NVII) among children <5 years old in The Gambia, Kenya, and Mali following rotavirus vaccine introduction. METHODS: Population-based surveillance was conducted to capture medically-attended moderate-to-severe diarrhea (MSD) cases, defined as a child 0-59 months old passing ≥3 loose stools in a 24-hour period with ≥1 of the following: sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization within 7 days of diarrhea onset. Diarrhea-free matched controls randomly selected from a censused population were enrolled at home. Stools from cases and controls were tested for enteropathogens, including norovirus and rotavirus, by TaqMan quantitative polymerase chain reaction (PCR) and conventional reverse transcription PCR. We used multiple logistic regression to derive adjusted attributable fractions (AFe) for each pathogen causing MSD, which takes into consideration the prevalence in both cases and controls, for each site and age. A pathogen was considered etiologic if AFe was ≥0.5. In further analyses focusing on the predominant NVII strains, we compared rotavirus and NVII severity using a 20-point modified Vesikari score and examined seasonal fluctuations. RESULTS: From May 2015 to July 2018, we enrolled 4840 MSD cases and 6213 controls. NVI was attributed to only 1 MSD episode. NVII was attributed to 185 (3.8%) of all MSD episodes and was the sole attributable pathogen in 139 (2.9%); peaking (36.0%) at age 6-8 months with majority (61.2%) aged 6-11 months. MSD cases whose episodes were attributed to NVII alone compared with rotavirus alone were younger (median age, 8 vs 12 months, P < .0001) and had less severe illness (median Vesikari severity score, 9 vs 11, P = .0003) but equally likely to be dehydrated. NVII occurred year-round at all study sites. CONCLUSIONS: Infants aged 6-11 months bear the greatest burden of norovirus disease, with NVII predominating. An early infant vaccine schedule and rigorous adherence to guidelines recommended for management of dehydrating diarrhea may offer substantial benefit in these African settings.

The occurrence and antimicrobial resistance (AMR) of typhoid fever in the WHO Eastern Mediterranean Region (EMR) are poorly characterized. Robust surveillance data are needed to inform strategies for typhoid control and prevention in the region. We conducted a systematic review of typhoid fever occurrence, complications, and AMR patterns in EMR countries. We identified 70 studies published from 1990 to 2021, including a total of 44,541 cases with blood culture confirmed typhoid fever in 12 EMR countries, with 48 (69%) studies and 42,008 cases from Pakistan. Among 56 studies with AMR data, fluroquinolone (68% of 13,013 tested isolates), and multidrug resistance (40% of 15,765 tested isolates) were common. Forty (57%) of the 56 studies were from Pakistan, and all reports of extensively drug resistant Salmonella Typhi (48% of 9,578 tested isolates) were from studies in Pakistan. Our findings support the need for continued efforts to strengthen surveillance and laboratory capacity for blood-culture detection of typhoid fever in the region, including data from an ongoing collaboration among CDC, the American University of Beirut, and the WHO EMR office.

A high burden of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) bacteremia has been reported from urban informal settlements in sub-Saharan Africa, yet little is known about the introduction of these strains to the region. Understanding regional differences in the predominant strains of S. Typhi can provide insight into the genomic epidemiology. We genetically characterized 310 S. Typhi isolates from typhoid fever surveillance conducted over a 12-year period (2007-2019) in Kibera, an urban informal settlement in Nairobi, Kenya, to assess the circulating strains, their antimicrobial resistance attributes, and how they relate to global S. Typhi isolates. Whole genome multi-locus sequence typing (wgMLST) identified 4 clades, with up to 303 pairwise allelic differences. The identified genotypes correlated with wgMLST clades. The predominant clade contained 290 (93.5%) isolates with a median of 14 allele differences (range 0-52) and consisted entirely of genotypes 4.3.1.1 and 4.3.1.2. Resistance determinants were identified exclusively in the predominant clade. Determinants associated with resistance to aminoglycosides were observed in 245 isolates (79.0%), sulphonamide in 243 isolates (78.4%), trimethoprim in 247 isolates (79.7%), tetracycline in 224 isolates (72.3%), chloramphenicol in 247 isolates (79.6%), β-lactams in 239 isolates (77.1%) and quinolones in 62 isolates (20.0%). Multidrug resistance (MDR) determinants (defined as determinants conferring resistance to ampicillin, chloramphenicol and cotrimoxazole) were found in 235 (75.8%) isolates. The prevalence of MDR associated genes was similar throughout the study period (2007-2012: 203, 76.3% vs 2013-2019: 32, 72.7%; Fisher's Exact Test: P = 0.5478, while the proportion of isolates harboring quinolone resistance determinants increased (2007-2012: 42, 15.8% and 2013-2019: 20, 45.5%; Fisher's Exact Test: P<0.0001) following a decline in S. Typhi in Kibera. Some isolates (49, 15.8%) harbored both MDR and quinolone resistance determinants. There were no determinants associated with resistance to cephalosporins or azithromycin detected among the isolates sequenced in this study. Plasmid markers were only identified in the main clade including IncHI1A and IncHI1B(R27) in 226 (72.9%) isolates, and IncQ1 in 238 (76.8%) isolates. Molecular clock analysis of global typhoid isolates and isolates from Kibera suggests that genotype 4.3.1 has been introduced multiple times in Kibera. Several genomes from Kibera formed a clade with genomes from Kenya, Malawi, South Africa, and Tanzania. The most recent common ancestor (MRCA) for these isolates was from around 1997. Another isolate from Kibera grouped with several isolates from Uganda, sharing a common ancestor from around 2009. In summary, S. Typhi in Kibera belong to four wgMLST clades one of which is frequently associated with MDR genes and this poses a challenge in treatment and control.

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.

Cases of extensively drug-resistant (XDR) typhoid fever have been reported in the United States among patients who did not travel internationally. Clinicians should consider if and where the patient traveled when selecting empiric treatment for typhoid fever. XDR typhoid fever should be treated with a carbapenem, azithromycin, or both.

Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1-4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.

BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Out of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar amongst both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone but African isolates were susceptible to these antibiotics. CONCLUSION: Our data confirms that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multi-drug resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.

BACKGROUND: Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. METHODS: We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. RESULTS: 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0-50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). CONCLUSIONS: Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Typhoid fever transmission occurs through ingestion of food or water contaminated with Salmonella Typhi, and case-control studies are often conducted to identify outbreak sources and transmission vehicles. However, there is no current summary of the associations among water, sanitation, and hygiene (WASH); and food exposures and typhoid from case-control studies. We conducted a systematic review and meta-analysis of case-control studies to evaluate the associations among typhoid fever and predicted WASH or food exposure risk factors (13), and protective factors (7). Overall, 19 manuscripts describing 22 case-control studies were included. Two studies were characterized as having low risk of bias, one as medium risk, and 19 as high risk. In total, nine of 13 predicted risk factors were associated with increased odds of typhoid (odds ratio [OR] = 1.4-2.4, I (2) = 30.5-74.8%.), whereas five of seven predicted protective factors were associated with lower odds of typhoid (OR = 0.52-0.73, I (2) = 38.7-84.3%). In five types of sensitivity analyses, two (8%) of 26 summary associations changed significance from the original analysis. Results highlight the following: the importance of household hygiene transmission pathways, the need for further research around appropriate food interventions and the risk of consuming specific foods and beverages outside the home, and the absence of any observed association between sanitation exposures and typhoid fever. We recommend that typhoid interventions focus on interrupting household transmission routes and that future studies provide more detailed information about WASH and food exposures to inform better targeted interventions.

In Zambia limited access to adequate water and sanitation is a key developmental challenge, particularly for rapidly expanding peri-urban areas. During 20162017, a cross-sectional household survey was conducted among 12,500 households representing ~60,000 individuals to assess the burden of household diarrheal and respiratory disease and to measure water, sanitation, and hygiene (WASH) characteristics in Lusaka, Zambia. We found that socio-economic factors, including having an additional household member, having children <5 years old in the household, living in a rental home, and higher annual household expenditure were associated with diarrhea and respiratory illness. We also found an increased risk for diarrhea associated with a number of WASH-related factorssuch as not covering all water storage containers, not using soap for handwashing, having an unimproved sanitation facility, and utilizing a heavily shared toilet (18 people). Detectable free chlorine residual in household stored water and more hours of water availability per day were associated with reduced odds of waterborne illness. In all, 75% of household stored water was contaminated with E. coli and households consuming less water (<20 L/day per person) for all purposes had lower odds of diarrhea than households consuming more waterthese findings highlight the need for enhanced WASH services within densely populated peri-urban areas and the importance of achieving universal access to safely managed water and sanitation services.

On October 6, 2017, the Zambia Ministry of Health declared a cholera outbreak in Lusaka. By December, 1,462 cases and 38 deaths had occurred (case fatality rate, 2.6%). We conducted a case-control study to identify risk factors and inform interventions. A case was any person with acute watery diarrhea (>/= 3 loose stools in 24 hours) admitted to a cholera treatment center in Lusaka from December 16 to 21, 2017. Controls were neighbors without diarrhea during the same time period. Up to two controls were matched to each case by age-group (1-4, 5-17, and >/= 18 years) and neighborhood. Surveyors interviewed cases and controls, tested free chlorine residual (FCR) in stored water, and observed the presence of soap in the home. Conditional logistic regression was used to generate matched odds ratios (mORs) based on subdistricts and age-groups with 95% CIs. We enrolled 82 cases and 132 controls. Stored water in 71% of case homes had an FCR > 0.2 mg/L. In multivariable analyses, those who drank borehole water (mOR = 2.4, CI: 1.1-5.6), had close contact with a cholera case (mOR = 6.2, CI: 2.5-15), and were male (mOR = 2.5, CI: 1.4-5.0) had higher odds of being a cholera case than their matched controls. The use of groundwater for drinking, contact with a cholera case, and male gender were associated with cholera. Based on these findings, we recommended health education about household water chlorination and hygiene in the home. Emergency responses included providing chlorinated water through emergency tanks and maintaining adequate FCR levels through close monitoring of water sources.

Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.

During September 5–6, 2018, a total of 52 patients in Harare, Zimbabwe, were hospitalized with suspected cholera, an acute bacterial infection characterized by watery diarrhea. Rapid diagnostic testing was positive for Vibrio cholerae O1, and on September 6, Zimbabwe’s Ministry of Health and Child Care (MOHCC) declared an outbreak of cholera. From September 4, 2018, (date of the first reported cases) through March 12, 2019, a total of 10,730 cases and 69 (0.64%) deaths were reported nationally from nine of Zimbabwe’s 10 provinces (Figure). Most cases (94%) were reported from Harare Province, the country’s largest province, with a population of approximately 2 million.