The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations.

Animal contact is an established risk factor for nontyphoidal Salmonella infections and outbreaks. During 2015-2018, the U.S. Centers for Disease Control and Prevention (CDC) and other U.S. public health laboratories began implementing whole-genome sequencing (WGS) of Salmonella isolates. WGS was used to supplement the traditional methods of pulsed-field gel electrophoresis for isolate subtyping, outbreak detection, and antimicrobial susceptibility testing (AST) for the detection of resistance. We characterized the epidemiology and antimicrobial resistance (AMR) of multistate salmonellosis outbreaks linked to animal contact during this time period. An isolate was considered resistant if AST yielded a resistant (or intermediate, for ciprofloxacin) interpretation to any antimicrobial tested by the CDC or if WGS showed a resistance determinant in its genome for one of these agents. We identified 31 outbreaks linked to contact with poultry (n = 23), reptiles (n = 6), dairy calves (n = 1), and guinea pigs (n = 1). Of the 26 outbreaks with resistance data available, we identified antimicrobial resistance in at least one isolate from 20 outbreaks (77%). Of 1,309 isolates with resistance information, 247 (19%) were resistant to ≥1 antimicrobial, and 134 (10%) were multidrug-resistant to antimicrobials from ≥3 antimicrobial classes. The use of resistance data predicted from WGS increased the number of isolates with resistance information available fivefold compared with AST, and 28 of 43 total resistance patterns were identified exclusively by WGS; concordance was high (>99%) for resistance determined by AST and WGS. The use of predicted resistance from WGS enhanced the characterization of the resistance profiles of outbreaks linked to animal contact by providing resistance information for more isolates.

Retracing microbial emergence and spread is essential to understanding the evolution and dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal complex 1 (Lm-CC1) is the most prevalent clonal group associated with listeriosis, and is strongly associated with cattle and dairy products. Here we analysed 2,021 Lm-CC1 isolates collected from 40 countries, since the first Lm isolation to the present day, to define its evolutionary history and population dynamics. Our results suggest that Lm-CC1 spread worldwide from North America following the Industrial Revolution through two waves of expansion, coinciding with the transatlantic livestock trade in the second half of the 19th century and the rapid growth of cattle farming in the 20th century. Lm-CC1 then firmly established at a local level, with limited inter-country spread. This study provides an unprecedented insight into Lm-CC1 phylogeography and dynamics and can contribute to effective disease surveillance to reduce the burden of listeriosis.Competing Interest StatementThe authors have declared no competing interest.

INTRODUCTION: The gut microbiome is an integral partner in host health and plays a role in immune development, altered nutrition, and pathogen prevention. The mycobiome (fungal microbiome) is considered part of the rare biosphere but is still a critical component in health. Next generation sequencing has improved our understanding of fungi in the gut, but methodological challenges remain. Biases are introduced during DNA isolation, primer design and choice, polymerase selection, sequencing platform selection, and data analyses, as fungal reference databases are often incomplete or contain erroneous sequences. METHODS: Here, we compared the accuracy of taxonomic identifications and abundances from mycobiome analyses which vary among three commonly selected target gene regions (18S, ITS1, or ITS2) and the reference database (UNITE - ITS1, ITS2 and SILVA - 18S). We analyze multiple communities including individual fungal isolates, a mixed mock community created from five common fungal isolates found in weanling piglet feces, a purchased commercial fungal mock community, and piglet fecal samples. In addition, we calculated gene copy numbers for the 18S, ITS1, and ITS2 regions of each of the five isolates from the piglet fecal mock community to determine whether copy number affects abundance estimates. Finally, we determined the abundance of taxa from several iterations of our in-house fecal community to assess the effects of community composition on taxon abundance. RESULTS: Overall, no marker-database combination consistently outperformed the others. Internal transcribed space markers were slightly superior to 18S in the identification of species in tested communities, but Lichtheimia corymbifera, a common member of piglet gut communities, was not amplified by ITS1 and ITS2 primers. Thus, ITS based abundance estimates of taxa in piglet mock communities were skewed while 18S marker profiles were more accurate. Kazachstania slooffiae displayed the most stable copy numbers (83-85) while L. corymbifera displayed significant variability (90-144) across gene regions. DISCUSSION: This study underscores the importance of preliminary studies to assess primer combinations and database choice for the mycobiome sample of interest and raises questions regarding the validity of fungal abundance estimates.

The microbiome is an integral part of chicken health and can affect immunity, nutrient utilization, and performance. The role of bacterial microbiota members in host health is relatively well established, but less attention has been paid to fungal members of the gastrointestinal tract (GIT) community. However, human studies indicate that fungi play a critical role in health. Here, we described fungal communities, or mycobiomes, in both the lumen and mucosa of the chicken ileum and cecum from hatch through 14 days of age. We also assessed the effects of delayed access to feed immediately post-hatch (PH) on mycobiome composition, as PH feed delay is commonly associated with poor health performance. Chicken mycobiomes in each of the populations were distinct and changed over time. All mycobiomes were dominated by Gibberella, but Aspergillus, Cladosporium, Sarocladium, Meyerozyma, and Penicillium were also abundant. Relative abundances of some taxa differed significantly over time. In the cecal and ileal lumens, Penicillium was present in extremely low quantities or absent during days one and two and then increased over time. Meyerozyma and Wickerhamomyces also increased over time in luminal sites. In contrast, several highly abundant unclassified fungi decreased after days one and two, highlighting the need for improved understanding of fungal gut biology. Mycobiomes from chicks fed during the first 2 days PH versus those not fed during the first 2 days did not significantly differ, except during days one and two. Similarities observed among mycobiomes of fed and unfed chicks at later timepoints suggest that delays in PH feeding do not have long lasting effects on mycobiome composition. Together, these results provide a foundation for future mycobiome studies, and suggest that negative health and production impacts of delayed feeding are not likely related to the development of fungal populations in the GIT.

BACKGROUND: The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection. METHODS: We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm(3) or 500 cells per mm(3) and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination. FINDINGS: 226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18-68; IQR 32-43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm(3) (range 36-1659; IQR 500-885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1-8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 [IQR 6-21] for patients with HIV vs median rash burden score 6 [IQR 3-14] for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status. INTERPRETATION: Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact. FUNDING: US Centers for Disease Control and Prevention, International Society of Travel Medicine.

Human rabies is an acute, progressive encephalomyelitis that is nearly always fatal once symptoms begin. Several measures have been implemented to prevent human rabies in the United States, including vaccination of targeted domesticated and wild animals, avoidance of behaviors that might precipitate an exposure (e.g., provoking high-risk animals), awareness of the types of animal contact that require postexposure prophylaxis (PEP), and use of proper personal protective equipment when handling animals or laboratory specimens. PEP is widely available in the United States and highly effective if administered after an exposure occurs. A small subset of persons has a higher level of risk for being exposed to rabies virus than does the general U.S. population; these persons are recommended to receive preexposure prophylaxis (PrEP), a series of human rabies vaccine doses administered before an exposure occurs, in addition to PEP after an exposure. PrEP does not eliminate the need for PEP; however, it does simplify the rabies PEP schedule (i.e., eliminates the need for rabies immunoglobulin and decreases the number of vaccine doses required for PEP). As rabies epidemiology has evolved and vaccine safety and efficacy have improved, Advisory Committee on Immunization Practices (ACIP) recommendations to prevent human rabies have changed. During September 2019-November 2021, the ACIP Rabies Work Group considered updates to the 2008 ACIP recommendations by evaluating newly published data, reviewing frequently asked questions, and identifying barriers to adherence to previous ACIP rabies vaccination recommendations. Topics were presented and discussed during six ACIP meetings. The following modifications to PrEP are summarized in this report: 1) redefined risk categories; 2) fewer vaccine doses in the primary vaccination schedule; 3) flexible options for ensuring long-term protection, or immunogenicity; 4) less frequent or no antibody titer checks for some risk groups; 5) a new minimum rabies antibody titer (0.5 international units [IUs]) per mL); and 6) clinical guidance, including for ensuring effective vaccination of certain special populations.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). However, vaccination coverage among adults has been suboptimal, limiting further reduction in hepatitis B virus (HBV) infections in the United States. This Advisory Committee on Immunization Practices (ACIP) recommendation expands the indicated age range for universal HepB vaccination to now include adults aged 19-59 years. Removing the risk factor assessment previously recommended to determine vaccine eligibility in this adult age group (2) could increase vaccination coverage and decrease hepatitis B cases.

On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1).

If current population trends continue, the U.S. population will be a “majority minority” nation in 2044 according to a report by the Brookings Institution (Frey, 2014). Based on the United States Census Bureau projections, the non-Hispanic White population will decrease by 9.5% from 2016 (61.3%) to 2060 (44.3%; Vespa et al., 2020). In 2060, those who self-identify as White will make up 68.0% (44.3% self-identifying as non-Hispanic White) of the population; these percentages are 15.0% for Black people, 9.1% for Asian people, 1.4% for American Indian and Alaska Native people, 0.3% for Native Hawaiian and Other Pacific Islander people, and 6.2% for multiracial people (Vespa et al., 2020). Hispanic people will comprise 27.5% of the population (Vespa et al., 2020). These changing demographics have implications for the practice of public health and medicine, and the composition of the workforce. Foremost in responding to the needs of an increasingly diverse U.S. population is attaining a racially and ethnically diverse workforce at the organizational and systems levels. This diverse workforce, inclusive of interdisciplinary perspectives, would need to be culturally responsive and structurally competent to inform strategies for effective public health data and action (Hansen & Metzl, 2016). Coronado et al. (2020) contend “Public health agencies that employ a diverse workforce are better positioned to implement targeted approaches in communities where they are needed, create systems to support those needs, and supply a greater variety of effective solutions to help address health disparities” (p. 390). Intentional and progressive pedagogy is needed to ensure an educational pathway for currently underrepresented students to pursue careers in public health, medicine, and other health-related fields.

Retracing microbial emergence and spread is essential to understanding the evolution and 40 dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal 41 complex 1 (Lm-CC1) is the most prevalent clonal group associated with listeriosis, and is 42 strongly associated with cattle and dairy products. Here we analysed 2,021 Lm-CC1 43 isolates collected from 40 countries, since the first Lm isolation to the present day, to 44 define its evolutionary history and population dynamics. Our results suggest that Lm-CC1 45 spread worldwide from North America following the Industrial Revolution through two 46 waves of expansion, coinciding with the transatlantic livestock trade in the second half of 47 the 19th century and the rapid growth of cattle farming in the 20th century. Lm-CC1 then 48 firmly established at a local level, with limited inter-country spread. This study provides 49 an unprecedented insight into Lm-CC1 phylogeography and dynamics and can contribute 50 to effective disease surveillance to reduce the burden of listeriosis.

OBJECTIVE: To estimate the annual percentage of women of reproductive age with private insurance or Medicaid who had opioid prescription claims during 2013-2017 and describe trends over time. DESIGN: A secondary analysis of insurance claims data from IBM MarketScan® Commercial and Multi-State Medicaid Databases to assess outpatient pharmacy claims for prescription opioids among women aged 15-44 years during 2013-2017. PARTICIPANTS: Annual cohorts of 3.5-3.8 million women aged 15-44 years with private insurance and 0.9-2.1 million women enrolled in Medicaid. MAIN OUTCOME MEASURE: The percentage of women aged 15-44 years with outpatient pharmacy claims for opioid prescriptions. RESULTS: During 2013-2017, the proportion of women aged 15-44 years with private insurance who had claims for opioid prescriptions decreased by 22.1 percent, and among women enrolled in Medicaid, the proportion decreased by 31.5 -percent. CONCLUSIONS: Opioid prescription claims decreased from 2013 to 2017 among insured women of reproductive age. However, opioid prescription claims remained common and were more common among women enrolled in Medicaid than those with private insurance; additional strategies to improve awareness of the risks associated with opioid prescribing may be needed.

This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the rVSVΔG-ZEBOV-GP Ebola vaccine (Ervebo) in the United States. The vaccine contains rice-derived recombinant human serum albumin and live attenuated recombinant vesicular stomatitis virus (VSV) in which the gene encoding the glycoprotein of VSV was replaced with the gene encoding the glycoprotein of Ebola virus species Zaire ebolavirus. Persons with a history of severe allergic reaction (e.g., anaphylaxis) to rice protein should not receive Ervebo. This is the first and only vaccine currently licensed by the Food and Drug Administration for the prevention of Ebola virus disease (EVD). These guidelines will be updated based on availability of new data or as new vaccines are licensed to protect against EVD.ACIP recommends preexposure vaccination with Ervebo for adults aged ≥18 years in the U.S. population who are at highest risk for potential occupational exposure to Ebola virus species Zaire ebolavirus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff at biosafety level 4 facilities in the United States. Recommendations for use of Ervebo in additional populations at risk for exposure and other settings will be considered and discussed by ACIP in the future.

During the 2016-2017 Zika virus outbreak, preventing unintended pregnancy was recognized as a primary strategy to reduce adverse Zika-related pregnancy and birth outcomes. To increase awareness and uptake of contraceptive services provided through the Zika Contraception Access Network (Z-CAN) in Puerto Rico, a multi-strategy campaign called Ante La Duda, Pregunta (ALDP) was developed. The principal aim was to increase awareness of Z-CAN services, which included same-day access to the full range of reversible contraceptives at no cost to women living in Puerto Rico who choose to delay or avoid pregnancy during the 2016-2017 Zika virus outbreak. Using diverse strategies, ALDP increased exposure to and engagement with the campaign in order to raise awareness of Z-CAN services in Puerto Rico. The ALDP social marketing campaign played an important role in the overall Z-CAN effort. Of all the strategies utilized, Facebook appears to have reached the most people. While the importance of a social marketing campaign communicating to raise awareness and create demand has long been known, through the ALDP campaign efforts, it was shown that an effective campaign, built on formative research, can be developed and implemented rapidly in an emergency response situation without compromising on content, quality, or reach.

INTRODUCTION: Women and healthcare providers lack adequate information on medication safety during pregnancy. While resources describing fetal risk are available, information is provided in multiple locations, often with subjective assessments of available data. We developed a list of medications of greatest concern during pregnancy to help healthcare providers counsel reproductive-aged and pregnant women. METHODS: Prescription drug labels submitted to the U.S. Food and Drug Administration with information in the Teratogen Information System (TERIS) and/or Drugs in Pregnancy and Lactation by Briggs & Freeman were included (N = 1,186 medications; 766 from three data sources, 420 from two). We used two supervised learning methods ('support vector machine' and 'sentiment analysis') to create prediction models based on narrative descriptions of fetal risk. Two models were created per data source. Our final list included medications categorized as 'high' risk in at least four of six models (if three data sources) or three of four models (if two data sources). RESULTS: We classified 80 prescription medications as being of greatest concern during pregnancy; over half were antineoplastic agents (n = 24), angiotensin converting enzyme inhibitors (n = 10), angiotensin II receptor antagonists (n = 8), and anticonvulsants (n = 7). DISCUSSION: This evidence-based list could be a useful tool for healthcare providers counseling reproductive-aged and pregnant women about medication use during pregnancy. However, providers and patients may find it helpful to weigh the risks and benefits of any pharmacologic treatment for both pregnant women and the fetus when managing medical conditions before and during pregnancy.

The opioid crisis has impacted vulnerable populations, specifically pregnant and postpartum women, and infants prenatally exposed to substances, including infants with Neonatal Abstinence Syndrome. Lack of access to clinical and social services; potential stigma or discrimination; and lack of resources for provision of services, including screening and treatment, have impacted the health of these populations. In 2018, using a systems change approach, the Association of State and Territorial Health Officials (ASTHO) and the Centers for Disease Control and Prevention (CDC) convened an Opioid use disorder, Maternal outcomes, Neonatal abstinence syndrome Initiative Learning Community (OMNI LC) that included other federal agencies, national clinical and nonclinical organizations, and 12 state leadership groups. The purpose of the OMNI LC was to determine areas of focus and identify strategies and best practices for implementing systems change to improve maternal and infant outcomes associated with opioid use disorder (OUD) during the perinatal period. Activities included in-person convenings with policy goal action plan development, virtual learning sessions, intensive technical assistance (TA), and temporary field placements. The OMNI LC partnering agencies and state teams met bimonthly for the first year of the initiative. At the in-person convening, state teams identified barriers to developing and implementing systems change in activity-specific action plans within five areas of focus: financing and coverage; access to and coordination of quality services; provider training and awareness; ethical, legal, and social considerations; and data, monitoring, and evaluation. State teams also identified stakeholder partnerships as a necessary component of strategy development in all areas of focus. Four virtual learning sessions were conducted on the areas of focus identified by state teams, and ASTHO conducted three intensive TA opportunities, and five states were identified for temporary field placement. To successfully address the impact of the opioid crisis on pregnant and postpartum women and infants, states developed innovative strategies focused on increasing support, services, and resources. Moving forward, state teams will participate in two additional in-person meetings, continue to identify barriers to the work, refine and customize action plans, and set new goals, to effect broad-ranging systems change for these vulnerable populations.

Scientific evidence demonstrated a causal relationship between Zika virus infection during pregnancy and neurologic abnormalities and other congenital defects. The U.S. government's Zika Virus Disease Contingency Response Plan recognized the importance of preventing unintended pregnancy through access to high-quality family planning services as a primary strategy to reduce adverse Zika-related birth outcomes during the 2016-2017 Zika virus outbreak. The U.S.-affiliated Pacific Islands (USAPI) includes three U.S. territories: American Samoa, the Commonwealth of the Northern Mariana Islands, and Guam, and three independent countries in free association with the United States: the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau. Aedes spp. mosquitoes, the primary vector that transmits Zika virus, are common across the Pacific Islands, and in 2016, laboratory-confirmed cases of Zika virus infection in USAPI were reported. CDC conducted a rapid assessment by reviewing available reproductive health data and discussing access to contraception with family planning providers and program staff in all six USAPI jurisdictions between January and May 2017. In this report, we summarize findings from the assessment; discuss strategies developed by jurisdictions to respond to identified needs; and describe a training that was convened to provide technical assistance to USAPI. Similar rapid assessments may be used to identify training and technical assistance needs in other emergency preparedness and response efforts that pose a risk to pregnant women and their infants.

This cross-sectional study examines the national incidence rate of neonatal abstinence syndrome using data from the 2016 Healthcare Cost and Utilization Project Kids' Inpatient Database.

Recent public health emergencies have highlighted the unique vulnerabilities of pregnant women and infants to emerging health threats and the critical role of public health surveillance. Surveillance systems can collect critical data to measure the impact of a disease or disaster and can be used to inform clinical guidance and prevention strategies. These systems can also be tailored to collect data on vulnerable populations, such as pregnant women and their infants. Novel surveillance systems to assess risks and outcomes of pregnant women and infants have been established during public health emergencies but typically cease data collection once the public health response has ended, limiting our ability to collect data to understand longer-term outcomes. State-based birth defects surveillance systems are not available in all states, and no national surveillance system linking pregnancy exposure data to longitudinal outcomes for infants and children exists. In this report, we describe ongoing surveillance efforts to monitor congenital syphilis, Zika virus infection during pregnancy, and neonatal abstinence syndrome. We describe the need and rationale for an ongoing integrated surveillance system to monitor pregnant women and their infants and to detect emerging threats. We also discuss how data collected through this type of system can better position federal, state, and local health departments to more rapidly and comprehensively respond to the next public health emergency.

In response to the Zika virus outbreak in Puerto Rico (2015-2016), the Zika Contraception Access Network (Z-CAN) was established to provide same-day access to the full range of reversible contraception at no cost to women. Formative research was conducted to inform the development of a communication campaign about Z-CAN. Ten focus groups with women and men, aged 18 to 49 years, in Puerto Rico were conducted to collect data on contraception awareness, use, and decision making during the Zika outbreak, as well as culturally appropriate messaging and outreach strategies. Thematic analysis was conducted using the constant comparative method. Data showed that there was community awareness regarding Zika in Puerto Rico. However, it was not a motivating factor in contraception decision making; instead, economic factors were the major drivers. Most participants preferred to receive information on contraception, potential side effects, and where to access contraceptive services via Internet-based channels and health care providers. Based on these findings, the Ante La Duda, Pregunta [When in Doubt, Ask] campaign was launched to promote awareness of Z-CAN services among those who chose to prevent pregnancy during the Zika outbreak. Our results underscore the importance of conducting formative research to develop communication initiatives, while also demonstrating that it is feasible to perform these activities as part of an emergency response.

From 2004 to 2014, the incidence of neonatal abstinence syndrome (NAS) in the United States increased 433%, from 1.5 to 8.0 per 1,000 hospital births. The latest national data from 2014 indicate that one baby was born with signs of NAS every 15 minutes in the United States (1). NAS is a drug withdrawal syndrome that most commonly occurs among infants after in utero exposure to opioids, although other substances have also been associated with NAS. Prenatal opioid exposure has also been associated with poor fetal growth, preterm birth, stillbirth, and possible specific birth defects (2-5). NAS surveillance has often depended on hospital discharge data, which historically underestimate the incidence of NAS and are not available in real time, thus limiting states' ability to quickly direct public health resources (6,7). This evaluation focused on six states with state laws implementing required NAS case reporting for public health surveillance during 2013-2017 and reviews implementation of the laws, state officials' reports of data quality before and after laws were passed, and advantages and challenges of legally mandating NAS reporting for public health surveillance in the absence of a national case definition. Using standardized search terms in an online legal research database, laws in six states mandating reporting of NAS from medical facilities to state health departments (SHDs) or from SHDs to a state legislative body were identified. SHD officials in these six states completed a questionnaire followed by a semistructured telephone interview to clarify open-text responses from the questionnaire. Variability was found in the type and number of surveillance data elements reported and in how states used NAS surveillance data. Following implementation, five states with identified laws reported receiving NAS case reports within 30 days of diagnosis. Mandated NAS case reporting allowed SHDs to quantify the incidence of NAS in their states and to inform programs and services. This information might be useful to states considering implementing mandatory NAS surveillance.

BACKGROUND: Prevention of unintended pregnancy is a primary strategy to reduce adverse pregnancy and birth outcomes related to Zika virus infection. The Zika Contraception Access Network (Z-CAN) aimed to build a network of health-care providers offering client-centred contraceptive counselling and the full range of reversible contraception at no cost to women in Puerto Rico who chose to prevent pregnancy during the 2016-17 Zika virus outbreak. Here, we describe the Z-CAN programme design, implementation activities, and baseline characteristics of the first 21 124 participants. METHODS: Z-CAN was developed by establishing partnerships between federal agencies, territorial health agencies, private corporations, and domestic philanthropic and non-profit organisations in the continental USA and Puerto Rico. Private donations to the National Foundation for the Centers for Disease Control and Prevention (CDCF) secured a supply of reversible contraceptive methods (including long-acting reversible contraception), made available to non-sterilised women of reproductive age at no cost through provider reimbursements and infrastructure supported by the CDCF. To build capacity in contraception service provision, doctors and clinic staff from all public health regions and nearly all municipalities in Puerto Rico were recruited into the programme. All providers completed 1 day of comprehensive training in contraception knowledge, counselling, and initiation and management, including the insertion and removal of long-acting reversible contraceptives (LARCs). Z-CAN was announced through health-care providers, word of mouth, and a health education campaign. Descriptive characteristics of programme providers and participants were recorded, and we estimated the factors associated with choosing and receiving a LARC method. As part of a Z-CAN programme monitoring plan, participants were invited to complete a patient satisfaction survey about whether they had obtained free, same-day access to their chosen contraceptive method after receiving comprehensive counselling, their perception of the quality of care they had received, and their satisfaction with their chosen method and services. FINDINGS: Between May 4, 2016, and Aug 15, 2017, 153 providers in the Z-CAN programme provided services to 21 124 women. 20 110 (95%) women received same-day provision of a reversible contraceptive method. Whereas only 767 (4%) women had used a LARC method before Z-CAN, 14 259 (68%) chose and received a LARC method at their initial visit. Of the women who received a LARC method, 10 808 (76%) women had used no method or a least effective method of contraception (ie, condoms or withdrawal) before their Z-CAN visit. Of the 3489 women who participated in a patient satisfaction survey, 3068 (93%) of 3294 women were very satisfied with the services received, and 3216 (93%) of 3478 women reported receiving the method that they were most interested in after receiving counselling. 2382 (78%) of 3040 women rated their care as excellent or very good. INTERPRETATION: Z-CAN was designed as a short-term response for rapid implementation of reversible contraceptive services in a complex emergency setting in Puerto Rico and has served more than 21 000 women. This model could be replicated or adapted as part of future emergency preparedness and response efforts. FUNDING: National Foundation for the Centers for Disease Control and Prevention.

BACKGROUND: The originally recommended dosing schedule, 0, 2, 6months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2. METHODS: This multi-site, prospective study enrolled healthy 9-17year old girls (n=1321) on the day of or within 28days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age. RESULTS: Compared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants >/=15years old had no difference in post-dose 2 titers compared to <15year olds when dose 2 was substantially delayed. CONCLUSIONS: Prolonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV. ClinicalTrials.gov (NCT00524745).

To investigate the phenotypic evolution of West Nile virus (WNV) in California, we competed sixteen isolates made during 2007-08 against COAV997-5nt, a genetically marked clone from the founding 2003 California isolate COAV997-2003. Using in vivo fitness competitions in House Finches (HOFI) and Culex tarsalis mosquitoes, we found that the majority of WNV WN02 and SW03 genotype isolates exhibited elevated replicative fitness in both hosts compared to COAV997-5nt. Increased replicative capacity in HOFIs was not associated with increased mortality, indicating that these isolates had not gained avian virulence. One WN02 isolate from Coachella Valley, a region geographically close to the isolation of COAV997, showed neutral fitness in HOFIs and reduced fitness in Cx. tarsalis. Two isolates from Kern County and Sacramento/Yolo County out-competed COAV997-nt in HOFIs, but were transmitted less efficiently by Cx. tarsalis. Competition demonstrated neutral or increased fitness that appeared independent of both WN02 and SW03 genotypes.

Zika virus infection during pregnancy is a cause of microcephaly and other serious brain abnormalities. To support state and territory response to the threat of Zika, CDC's Interim Zika Response Plan outlined activities for vector control; clinical management of exposed pregnant women and infants; targeted communication about Zika virus transmission among women and men of reproductive age; and primary prevention of Zika-related adverse pregnancy and birth outcomes by prevention of unintended pregnancies through increased access to contraception.* The most highly effective,dagger reversible contraception includes intrauterine devices and implants, known as long-acting reversible contraception (LARC). On September 28, 2016, the Association of Maternal and Child Health Programs (AMCHP) and CDC facilitated a meeting in Atlanta, Georgia, of representatives from 15 states to identify state-led efforts to implement seven CDC-published strategies aimed at increasing access to contraception in the context of Zika virus. Qualitative data were collected from participating jurisdictions. The number of states reporting implementation of each strategy ranged from four to 11. Participants identified numerous challenges, particularly for strategies implemented less frequently. Examples of barriers were discussed and presented with corresponding approaches to address each barrier. Addressing these barriers could facilitate increased access to contraception, which might decrease the number of unintended pregnancies affected by Zika virus.

Our study sought to explore the actual and potential roles of patients, physicians, and pharmacists, as well as their shared challenges and opportunities, in improving the safety of medication use during pregnancy. We conducted virtual focus groups with 48 women and in-depth interviews with nine physicians and five pharmacists. Qualitative analysis revealed that all three groups of participants reported "playing it safe," the need for an engaged patient making informed decisions, challenges surrounding communication about pregnancy status, and a lack of patient-centric resources. Patients, physicians, and pharmacists are highly motivated to protect developing babies from potential harms of medication use during pregnancy while maintaining the patient's health. Strategic messaging could maximize the effectiveness of these interactions by helping physicians discuss the benefits and risks of medication use during pregnancy, pharmacists screen for pregnancy and counsel on medication safety, and patients using medications to share pregnancy intentions with their providers pre-pregnancy.

Objective To explore women's perceptions of the risks and benefits associated with medication use during pregnancy and to better understand how women make decisions related to medication use in pregnancy. Methods We conducted online focus groups with 48 women who used medication during pregnancy or while planning a pregnancy, and 12 in-depth follow-up interviews with a subset of these women. Results We found that women were aware of general risks associated with medication use but were often unable to articulate specific negative outcomes. Women were concerned most about medications' impact on fetal development but were also concerned about how either continuing or discontinuing medication during pregnancy could affect their own health. Women indicated that if the risk of a given medication were unknown, they would not take that medication during pregnancy. Conclusion This formative research found that women face difficult decisions about medication use during pregnancy and need specific information to help them make decisions. Enhanced communication between patients and their providers regarding medication use would help address this need. We suggest that public health practitioners develop messages to (1) encourage, remind, and prompt women to proactively talk with their healthcare providers about the risks of taking, not taking, stopping, or altering the dosage of a medication while trying to become pregnant and/or while pregnant; and (2) encourage all women of childbearing age to ask their healthcare providers about medication use.

CONTEXT: Opioid use and abuse have increased dramatically in recent years, particularly among women. OBJECTIVES: We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations. DATA SOURCES: We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies. STUDY SELECTION: We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process. DATA EXTRACTION: Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies. RESULTS: Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation. LIMITATIONS: Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement. CONCLUSIONS: Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age.

We modeled the potential cost-effectiveness of increasing access to contraception in Puerto Rico during a Zika virus outbreak. The intervention is projected to cost an additional $33.5 million in family planning services and is likely to be cost-saving for the healthcare system overall. It could reduce Zika virus-related costs by $65.2 million ($2.8 million from less Zika virus testing and monitoring and $62.3 million from avoided costs of Zika virus-associated microcephaly [ZAM]). The estimates are influenced by the contraception methods used, the frequency of ZAM, and the lifetime incremental cost of ZAM. Accounting for unwanted pregnancies that are prevented, irrespective of Zika virus infection, an additional $40.4 million in medical costs would be avoided through the intervention. Increasing contraceptive access for women who want to delay or avoid pregnancy in Puerto Rico during a Zika virus outbreak can substantially reduce the number of cases of ZAM and healthcare costs.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities. Since 2015, Zika virus has been spreading through much of the World Health Organization's Region of the Americas, including U.S. territories. Zika virus is spread through the bite of Aedes aegypti or Aedes albopictus mosquitoes, by sex with an infected partner, or from a pregnant woman to her fetus during pregnancy. CDC estimates that 41 states are in the potential range of Aedes aegypti or Aedes albopictus mosquitoes, and on July 29, 2016, the Florida Department of Health identified an area in one neighborhood of Miami where Zika virus infections in multiple persons are being spread by bites of local mosquitoes. These are the first known cases of local mosquito-borne Zika virus transmission in the continental United States.(dagger) CDC prevention efforts include mosquito surveillance and control, targeted education about Zika virus and condom use to prevent sexual transmission, and guidance for providers on contraceptive counseling to reduce unintended pregnancy. To estimate the prevalence of contraceptive use among nonpregnant and postpartum women at risk for unintended pregnancy and sexually active female high school students living in the 41 states where mosquito-borne transmission might be possible, CDC used 2011-2013 and 2015 survey data from four state-based surveillance systems: the Behavioral Risk Factor Surveillance System (BRFSS, 2011-2013), which surveys adult women; the Pregnancy Risk Assessment Monitoring System (PRAMS, 2013) and the Maternal and Infant Health Assessment (MIHA, 2013), which surveys women with a recent live birth; and the Youth Risk Behavior Survey (YRBS, 2015), which surveys students in grades 9-12. CDC defines an unintended pregnancy as one that is either unwanted (i.e., the pregnancy occurred when no children, or no more children, were desired) or mistimed (i.e., the pregnancy occurred earlier than desired). The proportion of women at risk for unintended pregnancy who used a highly effective reversible method, known as long-acting reversible contraception (LARC), ranged from 5.5% to 18.9% for BRFSS-surveyed women and 6.9% to 30.5% for PRAMS/MIHA-surveyed women. The proportion of women not using any contraception ranged from 12.3% to 34.3% (BRFSS) and from 3.5% to 15.3% (PRAMS/MIHA). YRBS data indicated that among sexually active female high school students, use of LARC at last intercourse ranged from 1.7% to 8.4%, and use of no contraception ranged from 7.3% to 22.8%. In the context of Zika preparedness, the full range of contraceptive methods approved by the Food and Drug Administration (FDA), including LARC, should be readily available and accessible for women who want to avoid or delay pregnancy. Given low rates of LARC use, states can implement strategies to remove barriers to the access and availability of LARC including high device costs, limited provider reimbursement, lack of training for providers serving women and adolescents on insertion and removal of LARC, provider lack of knowledge and misperceptions about LARC, limited availability of youth-friendly services that address adolescent confidentiality concerns, inadequate client-centered counseling, and low consumer awareness of the range of contraceptive methods available.