Background The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae, is largely unknown in regions lacking blood culture surveillance. New serologic markers have proven accurate in diagnosing enteric fever, but whether they could be used to reliably estimate population-level incidence is unknown.Methods We collected longitudinal blood samples from blood culture-confirmed enteric fever cases enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to Hemolysin E (HlyE) and S. Typhi lipopolysaccharide (LPS). We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titers and decay rate to estimate population-level incidence rates from cross-sectional serosurveys.Findings The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children <5 years ranged between 58.5 per 100 person-years (95% CI: 42.1 - 81.4) in Dhaka, Bangladesh to 6.6 (95% CI: 4.3-9.9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates.Interpretation The approach described here has the potential to expand the geographic scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographic regions and time.Funding This work was supported by the Bill and Melinda Gates Foundation (INV-000572).Evidence before this study Previous studies have identified serologic responses to two antigens (Hemolysin E [HlyE] and Salmonella lipopolysaccharide [LPS]) as promising diagnostic markers of acute typhoidal Salmonella infection. We reviewed the evidence for seroepidemiology tools for enteric fever available as of November 01, 2021, by searching the National Library of Medicine article database and medRxiv for preprint publications, published in English, using the terms “enteric fever”, “typhoid fever”, “Salmonella Typhi”, “Salmonella Paratyphi”, “typhoidal Salmonella”, “Hemolysin E”, “Salmonella lipopolysaccharide”, “seroconversion”, “serosurveillance”, “seroepidemiology”, “seroprevalence” and “seropositivity.” We found no studies using HlyE or LPS as markers to measure the incidence or prevalence of enteric fever in a population. Anti-Vi IgG responses were used as a marker of population seroprevalence in cross-sectional studies conducted in South Africa, Fiji, and Nepal, but were not used to calculate population-based incidence estimates.Added value of this study We developed and validated a method to estimate typhoidal Salmonella incidence in cross-sectional population samples using antibody responses measured from dried blood spots. First, using longitudinal dried blood spots collected from over 1400 blood culture-confirmed cases in four countries, we modeled the longitudinal dynamics of antibody responses for up to two years following infection, accounting for heterogeneity in antibody responses and age-dependence. We found that longitudinal antibody responses were highly consistent across four countries on two continents and did not differ by clinical severity. We then used these antibody kinetic parameters to estimate incidence in population-based samples in six communities across the four countries, where concomitant population-based incidence was measured using blood cultures. Seroincidence estimates were much higher than blood-culture-based case estimates across all six sites, suggestive of a high incidence of asymptomatic or unrecognized infections. Still, the rank order of seroincidence and culture-based incidence rates were the same, with the highest rates in Bangladesh and lowest in Ghana.Implications of all the available evidence Many a -risk low- and middle-income countries lack data on typhoid incidence needed to inform and evaluate vaccine introduction. Even in countries where incidence estimates are available, data are typically geographically and temporally sparse due to the resources necessary to initiate and sustain blood culture surveillance. We found that typhoidal Salmonella infection incidence can be estimated from community-based serosurveys using dried blood spots, representing an efficient and scalable approach for generating the typhoid burden data needed to inform typhoid control programs in resource-constrained settings.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by th eBill and Melinda Gates Foundation (grant INV-000572)Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Institutional Review Boards in the United States (Centers for Disease Control and Prevention; Stanford University Institutional Review Board), Bangladesh (Bangladesh Institute of Child Health Ethical Review Committee), Nepal (Nepal Health Research Council Ethical Review Board), Pakistan (AKU Ethic Review Committee and Pakistan National Bioethics Committee), Korea (International Vaccine Institute IRB), Belgium (Institute of Tropical Medicine Antwerp Institutional Review Board) and Ghana (Komfo Anokye Teaching Hospital, Committee on Human Research, Publication and Ethics) approved the study forms and protocols.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information.

BACKGROUND: The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae (Salmonella enterica serovars Typhi and Paratyphi), is largely unknown in regions without blood culture surveillance. The aim of this study was to evaluate whether new diagnostic serological markers for typhoidal Salmonella can reliably estimate population-level incidence. METHODS: We collected longitudinal blood samples from patients with blood culture-confirmed enteric fever enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana between 2016 and 2021 and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to hemolysin E and S Typhi lipopolysaccharide. We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titres and decay rate to estimate population-level incidence rates from cross-sectional serosurveys. FINDINGS: The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children younger than 5 years ranged between 58·5 per 100 person-years (95% CI 42·1-81·4) in Dhaka, Bangladesh, to 6·6 per 100 person-years (4·3-9·9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates. INTERPRETATION: The approach described here has the potential to expand the geographical scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographical regions and time. FUNDING: Bill & Melinda Gates Foundation. TRANSLATIONS: For the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section.

BACKGROUND: Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used CDC's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and non-pregnant women of childbearing age. METHODS: Pertussis cases in women aged 18-44 years with cough onset between 1/1/2012-12/31/2017 were identified in 7 EPS states. Surveillance data were collected through patient and provider interview and immunization registries. Bridged-race, intercensal population data and live birth estimates were used as denominators. RESULTS: 1,582 pertussis cases were identified among women aged 18-44 years; 5.1% (76/1499) of patients with known pregnancy status were pregnant at cough onset. Of pregnant patients with complete information, 81.7% (49/60) reported onset during the second or third trimester. The median age of pregnant and non-pregnant patients was 29.0 and 33.0 years, respectively. Most pregnant and non-pregnant patients were white (78.3% vs. 86.4%, p=0.09) and non-Hispanic (72.6% vs. 77.3%, p=0.35). Average annual pertussis incidence was 5.7/100,000 among pregnant and 7.3/100,000 among non-pregnant women. Compared to non-pregnant patients, more pregnant patients reported whoop (41.9% vs. 31.3%), post-tussive vomiting (58.1% vs. 47.9%) and apnea (37.3% vs. 29.0%); however, differences were not statistically significant (p>0.05 for all). A similar proportion of pregnant and non-pregnant patients reported ever having received Tdap (31.6% vs. 32.7%, p=0.84). CONCLUSIONS: Our analysis suggests that pertussis incidence and clinical characteristics of disease are similar among pregnant and non-pregnant women. Continued monitoring is important to further define pertussis epidemiology in pregnant women.

Characteristics of vaccine-associated rash illness (VARI) and confirmed measles cases were compared during a measles outbreak. Although some clinical differences were noted, having a measles exposure and identification of the vaccine strain were helpful for public health decision-making. Rapid, vaccine strain-specific diagnostic assays will more efficiently distinguish VARI from measles.

From September 2015 to March 2018, CDC confirmed four cases of cutaneous diphtheria caused by toxin-producing Corynebacterium diphtheriae in patients from Minnesota (two), Washington (one), and New Mexico (one). All patients had recently returned to the United States after travel to countries where diphtheria is endemic. C. diphtheriae infection was not clinically suspected in any of the patients; treating institutions detected the organism through matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) testing of wound-derived coryneform isolates. MALDI-TOF is a rapid screening platform that uses mass spectrometry to identify bacterial pathogens. State public health laboratories confirmed C. diphtheriae through culture and sent isolates to CDC's Pertussis and Diphtheria Laboratory for biotyping, polymerase chain reaction (PCR) testing, and toxin production testing. All isolates were identified as toxin-producing C. diphtheriae. The recommended public health response for cutaneous diphtheria is similar to that for respiratory diphtheria and includes treating the index patient with antibiotics, identifying close contacts and observing them for development of diphtheria, providing chemoprophylaxis to close contacts, testing patients and close contacts for C. diphtheriae carriage in the nose and throat, and providing diphtheria toxoid-containing vaccine to incompletely immunized patients and close contacts. This report summarizes the patient clinical information and response efforts conducted by the Minnesota, Washington, and New Mexico state health departments and CDC and emphasizes that health care providers should consider cutaneous diphtheria as a diagnosis in travelers with wound infections who have returned from countries with endemic diphtheria.

During September 14–October 1, 2018, the Minnesota Department of Health (MDH) was notified of six children hospitalized in the Minneapolis-St. Paul region with symptoms consistent with acute flaccid myelitis (AFM). A confirmed case of AFM is defined as acute onset of flaccid limb weakness with magnetic resonance image indicating spinal cord lesions largely restricted to gray matter and spanning one or more vertebral segments (1). All six cases were confirmed by CDC. After a cluster of three cases occurred in 2014, an average of fewer than one AFM case per year had been reported to MDH.

We thank Dr. Kenyon for his letter [1] in response to our recent study modeling the impact of human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) on the incidence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis among men who have sex with men (MSM) [2]. His letter questioned our model’s lack of inclusion of antimicrobial resistance (AMR) for NG, which may have led to overestimating the benefits of PrEP-specific biannual NG screening and treatment. | | Resistant NG is a critical epidemiological issue. Reduced susceptibility to macrolides and cephalosporins has been rising, although it is still relatively rare in the United States: 2.5% for azithromycin, 0.8% cefixime, and 0.1% for ceftriaxone in the US general population, and approximately twice those levels for MSM [3]. On this basis, the Centers for Disease Control and Prevention (CDC) currently continues to recommend dual therapy with azithromycin and ceftriaxone [4].

Background: In 2012, >48000 pertussis cases were reported in the United States. Many cases occurred in vaccinated persons, showing that pertussis vaccination does not prevent all pertussis cases. However, pertussis vaccination may have an impact on disease severity. Methods: We analyzed data on probable and confirmed pertussis cases reported through Enhanced Pertussis Surveillance (Emerging Infections Program Network) between 2010 and 2012. Surveillance data were collected through physician and patient interview and vaccine registries. We assessed whether having received an age-appropriate number of pertussis vaccines (AAV) (for persons aged ≥3 months) was associated with reduced odds of posttussive vomiting, a marker of more clinically significant illness, or of severe pertussis (seizure, encephalopathy, pneumonia, and/or hospitalization). Adjusted odds ratios were calculated using multivariable logistic regression. Results: Among 9801 pertussis patients aged ≥3 months, 77.6% were AAV. AAV status was associated with a 60% reduction in odds of severe disease in children aged 7 months-6 years in multivariable logistic regression and a 30% reduction in odds of posttussive vomiting in persons aged 19 months-64 years. Conclusions: Serious pertussis symptoms and complications are less common among AAV pertussis patients, demonstrating that the positive impact of pertussis vaccination extends beyond decreasing risk of disease.

On April 10, 2017, the Minnesota Department of Health (MDH) was notified about a suspected measles case. The patient was a hospitalized child aged 25 months who was evaluated for fever and rash, with onset on April 8. The child had no history of receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles. On April 11, MDH received a report of a second hospitalized, unvaccinated child, aged 34 months, with an acute febrile rash illness with onset on April 10. The second patient's sibling, aged 19 months, who had also not received MMR vaccine, had similar symptoms, with rash onset on March 30. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing of nasopharyngeal swab or throat specimens performed at MDH confirmed measles in the first two patients on April 11, and in the third patient on April 13; subsequent genotyping identified genotype B3 virus in all three patients, who attended the same child care center. MDH instituted outbreak investigation and response activities in collaboration with local health departments, health care facilities, child care facilities, and schools in affected settings. Because the outbreak occurred in a community with low MMR vaccination coverage, measles spread rapidly, resulting in thousands of exposures in child care centers, schools, and health care facilities. By May 31, 2017, a total of 65 confirmed measles cases had been reported to MDH (Figure 1); transmission is ongoing.

BACKGROUND: In the United States, infants have the highest reported pertussis incidence and death rates. Improved understanding of infant risk factors is needed to optimize prevention strategies. METHODS: We prospectively enrolled infants ≤4 months of age with incident-confirmed pertussis from 4 sites during 2002-2005 (preceding pertussis-antigen-containing vaccination recommendations for adolescents/adults); each case-patient was age- and site-matched with 2 control subjects. Caregivers completed structured interviews. Infants and their contacts ≥11 years of age were offered serologic testing for IgG; being seropositive was defined as ≥94 anti-pertussis toxin IgG enzyme-linked immunosorbent assay units/mL. RESULTS: Enrolled subjects (115 case-patients; 230 control subjects) had 4,396 contacts during incubation periods; 83 (72%) case-patients had ≥1 contact with prolonged (≥5 days) new cough in primary or secondary households. In multivariable analysis, the odds for pertussis were higher for infants with primary/secondary household contacts who had a prolonged new cough, compared with infants who did not. These contacts included mother (adjusted matched odds ratio [aMOR] 43.8; 95% confidence interval [CI], 6.45-298.0) and ≥1 nonmother contact (aMOR, 20.1; 95% CI, 6.48-62.7). Infants receiving breast milk with 0-1 formula feedings daily had decreased pertussis odds (aMOR, 0.27; 95% CI, 0.08-0.89), compared with those receiving more formula. Of 41 tested case-patients, 37 (90%) were seropositive. CONCLUSIONS: Pertussis in infants was associated with prolonged new cough (≥5 days) in infants' household contacts. Findings suggest breastfeeding protects against pertussis, and warrants recommendation with pertussis prevention strategies, which currently include pertussis vaccination of pregnant mothers and infants' close contacts.

Self-reported epilepsy may be influenced by culture, knowledge, and beliefs. We screened 6420 residents of the District of Columbia (DC) for epilepsy to investigate whether socio-demographics were associated with whether they reported their diagnosis as epilepsy or as seizure disorder. Lifetime and active prevalence rates were 0.54% and 0.21%, respectively for 'epilepsy' and 1.30% and 0.70%, respectively for 'seizure disorder'. Seizure disorder was reported significantly more often than epilepsy among blacks, females, respondents≥50years, those with lower level education, respondents who lived alone and in low income neighborhoods, and those who resided in DC for at least five years. Clinicians should assure that patients and caregivers understand that epilepsy is synonymous with seizure disorder and other culturally appropriate terms, in order to optimize compliance with treatment, disease management instructions, and utilization of other resources targeted at persons with epilepsy. Furthermore, education and awareness campaigns aimed at improving access-to-care, reducing stigma, and increasing awareness of adverse events, such as SUDEP, should include a more diverse definition of epilepsy in their messages.

During 2014-2016, CDC, working with U.S. and international partners, mounted a concerted response to end the unprecedented epidemic of Ebola virus disease (Ebola) in West Africa. CDC's response, which was the largest in the agency's history, was directed simultaneously at controlling the epidemic in West Africa and strengthening preparedness for Ebola in the United States. Although experience in responding to approximately 20 Ebola outbreaks since 1976 had provided CDC and other international responders an understanding of the disease and how to stop its spread, the epidemic in West Africa presented new and formidable challenges. The initial response was slow and complicated for several reasons, including wide geographic spread of cases, poor public health and societal infrastructure, sociodemographic factors, local unfamiliarity with Ebola, and distrust of government and health care workers. In the United States, widespread public alarm erupted after Ebola cases were diagnosed in Dallas, Texas, and New York City, New York. CDC, in collaboration with its U.S. and international counterparts, applied proven public health strategies as well as innovative new approaches to help control the Ebola epidemic in West Africa and strengthen public health readiness in the United States. Lessons learned include the recognition that West African and other countries need effective systems to detect and stop infectious disease threats, the need for stronger international surge capacity for times when countries are overwhelmed by an outbreak, and the importance of improving infection prevention and control in health care settings. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

BACKGROUND: Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. METHODS: Three sizes of graphite nanoplates [20 mum lateral (Gr20), 5 mum lateral (Gr5), and <2 mum lateral (Gr1)] ranging from 8-25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 mug/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. RESULTS: All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m(2). At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently elevated in Gr5 and Gr20, relative to Gr1. CONCLUSIONS: Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates > 5 mum laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1-2 mum graphite nanoplate.

BACKGROUND: Nonstandardized specimen-transport logistics, lack of laboratory personnel to transport specimens, lack of standard specimen containers, and long turnaround time (TAT) hindered access to quality laboratory services. The objective of the Becton, Dickinson, and Company (BD)-US President's Emergency Plan for AIDS Relief (PEPFAR) Public-Private Partnership (PPP) was to support country-specific programs to develop integrated laboratory systems, services, and quality improvement strategies, with an emphasis on strengthening the specimen-referral system (SRS). METHODS: In 2007, through the Centers for Disease Control and Prevention (CDC), the Ethiopian Public Health Institute (EPHI) joined with the BD-PEPFAR PPP to strengthen laboratory systems. A joint planning and assessment committee identified gaps in the SRS for prioritization and intervention and piloted the system in Addis Ababa and Amhara Region. RESULTS: The PPP established standardized, streamlined specimen logistics, using the Ethiopian Postal Service Enterprise to support a laboratory network in which 554 facilities referred specimens to 160 laboratories. The PPP supported procuring 400 standard specimen containers and the training of 586 laboratory personnel and 81 postal workers. The average TAT was reduced from 7 days (range, 2-14 days) to 2 days (range, 1-3 days) in Addis Ababa and from 10 days (range, 6-21 days) to 5 days (range, 2-6 days) in Amhara Region. CONCLUSIONS: This study highlights the feasibility and untapped potential of PPPs to strengthen laboratory systems. This planned and structured approach to improving specimen referral enhanced access to quality laboratory services.

BACKGROUND: Pertussis is poorly controlled, with the highest rates of morbidity and mortality among infants. Although the source of infant pertussis is often unknown, when identified, mothers have historically been the most common reservoir of transmission. Despite high vaccination coverage, disease incidence has been increasing. We examined whether infant source of infection (SOI) has changed in the United States in light of the changing epidemiology. METHODS: Cases <1 year old were identified at Enhanced Pertussis Surveillance sites between January 1, 2006 to December 31, 2013. SOI was collected during patient interview and was defined as a suspected pertussis case in contact with the infant case 7 to 20 days before infant cough onset. RESULTS: A total of 1306 infant cases were identified; 24.2% were <2 months old. An SOI was identified for 569 cases. Infants 0 to 1 months old were more likely to have an SOI identified than 2- to 11-month-olds (54.1% vs 40.2%, respectively; P < .0001). More than 66% of SOIs were immediate family members, most commonly siblings (35.5%), mothers (20.6%), and fathers (10.0%); mothers predominated until the transition to siblings beginning in 2008. Overall, the SOI median age was 14 years (range: 0-74 years); median age for sibling SOIs was 8 years. CONCLUSIONS: In contrast to previous studies, our data suggest that the most common source of transmission to infants is now siblings. While continued monitoring of SOIs will optimize pertussis prevention strategies, recommendations for vaccination during pregnancy should directly increase protection of infants, regardless of SOI.

In June, 2014, the Minnesota Department of Health (MDH) was notified of a suspected varicella case in a child aged 2 years. The patient had a generalized rash with relative sparing of the trunk and was hospitalized overnight for treatment of dehydration. The child's mother, who was near the end of a pregnancy, also had a generalized rash, which included the perineal area. Identifying the cause of the rash was important to determine whether administration of varicella zoster immune globulin was indicated to prevent neonatal varicella. Enterovirus was detected in specimens from the woman and child by reverse transcriptase-polymerase chain reaction (RT-PCR) testing performed at MDH; partial genome sequencing by CDC showed that both patients were infected with coxsackievirus A6 (CVA6), one of the members of the genus Enterovirus that causes hand, foot, and mouth disease (HFMD).

The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.

INTRODUCTION: Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. METHODS: The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m3, five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. RESULTS: No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution by day 7. CONCLUSIONS: In summary, acute repeated exposure to COREXIT EC9500A did not alter pulmonary function, lung injury/inflammation, systemic immune responses, or vascular tone, but did cause transient chronotropic effects on cardiac function.

Processing and synthesis of purified nanomaterials of diverse composition, size, and properties is an evolving process. Studies have demonstrated that some nanomaterials have potential toxic effects and have led to toxicity research focusing on nanotoxicology. About two million workers will be employed in the field of nanotechnology over the next 10 years. The unknown effects of nanomaterials create a need for research and development of techniques to identify possible toxicity. Through a cooperative effort between National Institute for Occupational Safety and Health and IBM to address possible occupational exposures, silicon-based nanowires (SiNWs) were obtained for our study. These SiNWs are anisotropic filamentary crystals of silicon, synthesized by the vapor–liquid–solid method and used in bio-sensors, gas sensors, and field effect transistors. Reactive oxygen species (ROS) can be generated when organisms are exposed to a material causing cellular responses, such as lipid peroxidation, H2O2 production, and DNA damage. SiNWs were assessed using three different in vitro environments (H2O2, RAW 264.7 cells, and rat alveolar macrophages) for ROS generation and possible toxicity identification. We used electron spin resonance, analysis of lipid peroxidation, measurement of H2O2 production, and the comet assay to assess generation of ROS from SiNW and define possible mechanisms. Our results demonstrate that SiNWs do not appear to be significant generators of free radicals.

BACKGROUND: A recent increase in B. pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the U.S. Determining whether pertactin-deficient (PRN-) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed. METHODS: We retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis. RESULTS: Among 753 isolates, 640 (85%) were PRN-. The age distribution differed between cases caused by PRN- B. pertussis and cases caused by B. pertussis producing pertactin (PRN+) (p-value= 0.01). The proportion reporting individual pertussis symptoms was similar between the two groups, except a higher proportion of PRN+ case-patients reported apnea (p-value=0.005). 22 case-patients were hospitalized; 6% in the PRN+ group compared to 3% in the PRN- group (p-value=0.11). Cases having received at least one pertussis vaccine dose had a higher odds of having PRN- B. pertussis as compared to unvaccinated cases (adjusted OR=2.2; 95% CI= 1.3-4.0). When restricted to cases-patients at least 1 year of age and those age-appropriately vaccinated the adjusted OR increased to 2.7 (95% CI=1.2-6.1). CONCLUSIONS: The significant association between vaccination and isolate pertactin produciton suggests the likelihood of having reported disease caused by PRN- compared to PRN+ strains is greater in vaccinated persons. Additional studies are needed to assess whether vaccine effectiveness is diminished against PRN- strains.

Since Ebola virus was first identified in 1976, no previous Ebola outbreak has been as large or persistent as the current epidemic, and none has spread beyond East and Central Africa. To date, more than 1000 people, including numerous health care workers, have been killed by Ebola virus disease (EVD) in 2014, and the number of cases in the current outbreak now exceeds the number from all previous outbreaks combined. Indirect effects include disruption of standard medical care, including for common and deadly conditions such as malaria, and substantial economic losses, insecurity, and social disruption in countries that were already struggling to recover from decades of war.

Measles is readily spread to susceptible individuals, but is no longer endemic in the United States. In March 2011, measles was confirmed in a Minnesota child without travel abroad. This was the first identified case-patient of an outbreak. An investigation was initiated to determine the source, prevent transmission, and examine measles-mumps-rubella (MMR) vaccine coverage in the affected community. Investigation and response included case-patient follow-up, post-exposure prophylaxis, voluntary isolation and quarantine, and early MMR vaccine for non-immune shelter residents >6 months and <12 months of age. Vaccine coverage was assessed by using immunization information system records. Outreach to the affected community included education and support from public health, health care, and community and spiritual leaders. Twenty-one measles cases were identified. The median age was 12 months (range, 4 months to 51 years) and 14 (67%) were hospitalized (range of stay, 2-7 days). The source was a 30-month-old US-born child of Somali descent infected while visiting Kenya. Measles spread in several settings, and over 3000 individuals were exposed. Sixteen case-patients were unvaccinated; 9 of the 16 were age-eligible: 7 of the 9 had safety concerns and 6 were of Somali descent. MMR vaccine coverage among Somali children declined significantly from 2004 through 2010 starting at 91.1% in 2004 and reaching 54.0% in 2010 (chi2 for linear trend 553.79; P < .001). This was the largest measles outbreak in Minnesota in 20 years, and aggressive response likely prevented additional transmission. Measles outbreaks can occur if undervaccinated subpopulations exist. Misunderstandings about vaccine safety must be effectively addressed.

A catastrophic confluence of factors contributed to the rapid spread of cholera in Haiti following its introduction in late 2010. The outbreak is now the largest in modern history to affect a single country1; cases from Haiti comprised nearly half of the cholera cases reported worldwide in 2012.2 Although cases of cholera related to this outbreak have occurred in the Dominican Republic, the United States,3 and possibly in Cuba and other countries,4,5 spread in these other countries has been nil or limited. The factors responsible for rapid spread in Haiti include: long-standing water and sanitary inadequacies in Haiti; the further disruptions to water and sanitary systems imposed by the earthquake; above average rainfall; high water and ambient temperatures; and insufficient capacity of the government infrastructure to respond to the crisis. | | In 2008, before the earthquake, 63% of Haitians had access to improved sources of drinking water, and only 17% of the population had access to improved sanitation.6 To address these inadequacies, in January 2012 the Pan American Health Organization (PAHO), the United States Centers for Disease Control and Prevention (CDC), and the United Nations Children's Fund (UNICEF) put forward a call to action for international partners to support the governments of Haiti and the Dominican Republic with their long-term vision to strengthen water, sanitation, and hygiene (WASH) conditions in their respective countries.7 The same group supported the development of national plans for the elimination of cholera transmission on the Island of Hispaniola. In Haiti, the National Plan outlined a 10-year strategy to strengthen and sustain broad efforts for prevention and control of cholera infection, including water and sanitation infrastructure, surveillance, health promotion, and treatment measures.8 Plans in the Dominican Republic focused on bridging gaps in WASH access, and improving surveillance, health communication, and treatment. Partners were asked to assist the National governments to finance and implement these plans.

Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 mug/m(3) ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 mug/m(3)) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 mug Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.

OBJECTIVE: To assess the risk of pertussis by time since vaccination in children in Minnesota and Oregon who received 5 doses of acellular pertussis vaccines (DTaP). METHODS: These cohort analyses included Minnesota and Oregon children born between 1998 and 2003 who had 5 DTaP doses recorded in state Immunization Information Systems. Immunization records and statewide pertussis surveillance data were combined. Incidence rates and risk ratios for pertussis were calculated for the 6 years after receipt of the fifth DTaP dose. RESULTS: The cohorts included 224 378 Minnesota children and 179 011 from Oregon; 458 and 89 pertussis cases were identified in Minnesota and Oregon, respectively. Pertussis incidence rates rose each year of follow-up: 15.6/100 000 (95% confidence interval [CI]: 11.1-21.4) at year 1 to 138.4/100 000 (CI: 113.3-166.9) at year 6 (Minnesota); 6.2/100 000 (CI: 3.3-10.6) in year 1 to 24.4/100 000 (CI: 15.0-37.8) in year 6 (Oregon). Risk ratios increased from 1.9 (CI: 1.3-2.9) in year 2 to 8.9 (CI: 6.0-13.0) in year 6 (Minnesota) and from 1.3 (CI: 0.6-2.8) in year 2 to 4.0 (CI: 1.9-8.4) in year 6 (Oregon). CONCLUSIONS: This evaluation reports steady increase in risk of pertussis in the years after completion of the 5-dose DTaP series. This rise is likely attributable in part to waning immunity from DTaP vaccines. Continuing to monitor disease burden and vaccine effectiveness in fully vaccinated children in coming years will be important to assess ongoing risk as additional cohorts vaccinated solely with acellular pertussis vaccines are introduced.

We investigated social and demographic factors as they relate to prevalence and incidence of epilepsy in Washington, DC, a culturally diverse area. Probability-based sampling was used to select 20,000 households to complete a mailed epilepsy screening survey on all household members. Screened individuals with a history of epilepsy were sent a detailed case survey about seizures and treatment. Prevalence and incidence of epilepsy were estimated using weighted data. Lifetime prevalence was 1.53% overall; 0.77% in Whites, 2.13% in Blacks, and 3.4% in those with less than a high school diploma. Prevalence of active epilepsy was 0.79% and followed similar subgroup comparisons as lifetime prevalence. Age-adjusted lifetime and active epilepsy from multivariate analyses demonstrated significantly higher rates for Blacks compared to Whites and for those not completing high school compared to those that attended graduate school. The incidence of epilepsy was 71 per 100,000 persons. Adults with active epilepsy were significantly less likely to live alone than those without epilepsy. Residents of DC for <4 years had the lowest prevalence and incidence of all subgroups indicating a possible healthy mover effect. This is the first study to provide estimates and profiles of the epilepsy population in DC which can help better target resources to improve the health and outcomes of people with epilepsy and their families.

The Phase 2 drug metabolism of busulfan yields a glutathione conjugate that undergoes a beta-elimination reaction. The elimination product is an electrophilic metabolite that is a dehydroalanine-containing tripeptide, gamma-glutamyldehydroalanylglycine (EdAG). In the process, glutathione lacks thiol-related redox properties and gains a radical scavenging dehydroalanine group. EdAG scavenged hydroxyl radical generated in the Fenton reaction in a concentration-dependent manner was monitored by electron paramagnetic resonance (EPR) spectroscopy. The apparent rate of hydroxyl radical scavenging was in the same range as published values for known antioxidants, including N-acyl dehydroalanines. A captodatively stabilized carbon-centered radical intermediate was spin trapped in the reaction of EdAG with hydroxyl radical. The proposed structure of a stable product in the Fenton reaction with EdAG was consistent with that of a gamma-glutamylserylglycyl dimer. Observation of the hydroxyl trapping properties of EdAG suggests that the busulfan metabolite EdAG may contribute to or mitigate redox-related cytotoxicity associated with the therapeutic use of busulfan, and reaffirms indicators that support a role in free radical biology for dehydroalanine-containing peptides and proteins.

This report reviews U.S. guidelines for the identification of persons exposed to rubella during air travel. In response to an individual with rubella who traveled on multiple flights, CDC conducted an airline contact investigation that was expanded beyond customary protocol to assess if current operating procedures are adequate. Of 250 potentially exposed airline passengers, 215 (86%) were contacted and none developed a rubella-like rash, arguing against the need to notify passengers beyond the standard protocol in most cases.