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Background and Aims: Louse-borne Bartonella quintana infection and flea-borne murine typhus are two potentially serious vector-borne diseases that have led to periodic outbreaks among people experiencing homelessness in the United States. Little is known about louse- and flea-borne disease awareness and prevention among staff who provide services to the population. We surveyed staff in seven US states to identify gaps in knowledge and prevention practices for these diseases., Methods and Results: Surveys were administered to 333 staff at 89 homeless shelters and outreach teams in California, Colorado, Georgia, Maryland, Minnesota, New York and Washington from August 2022 to April 2023. Most participants (>68%) agreed that body lice and fleas are a problem for people experiencing homelessness. About half were aware that diseases could be transmitted by these vectors; however, most could not accurately identify which diseases. Less than a quarter of staff could describe an appropriate protocol for managing body lice or fleas. Misconceptions included that clients must isolate or be denied services until they are medically cleared., Conclusions: Our findings reveal significant knowledge gaps among staff who provide services to people experiencing homelessness in the prevention and control of louse- and flea-borne diseases. This demonstrates an urgent need for staff training to both reduce disease and prevent unnecessary restrictions on services and housing., (© 2024 Wiley‐VCH GmbH. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jay Lucidarme, Stephen A. Clark, and Ray Borrow report performing contract research on behalf of the UK Health Security Agency (UKHSA) for GSK, Pfizer, and Sanofi. Muhamed-Kheir Taha reports performing contract research on behalf of the Institut Pasteur for GSK, Pfizer, and Sanofi. Shamez N. Ladhani reports performing contract research on behalf of the UKHSA and St. George’s University of London for GSK, Pfizer, Merck Sharp & Dohme, and Sanofi. Helen Campbell and Mary Ramsay report receipt of a recovery charge by the Immunisation and Vaccine Preventable Diseases Division at UKHSA for provision to vaccine manufacturers (GSK, Pfizer, and Sanofi) of postmarketing surveillance reports on meningococcal, Haemophilus influenzae, and pneumococcal infections, which are required by the U.K. Licensing Authority in compliance with their risk management strategy. Jennifer Zipprich reports that her spouse is employed by Pfizer. No other potential conflicts of interest were disclosed.

Background: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure., Methods: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively., Results: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay., Conclusion: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families., Impact: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We describe hepatitis C testing of 47 (2%) of 2,266 children diagnosed with perinatal hepatitis C who were exposed during 2018-2020 in 7 jurisdictions in the United States. Expected frequency of perinatal transmission is 5.8%, indicating only one third of the cases in this cohort were reported to public health authorities.

Flea-borne typhus (FBT), also referred to as murine typhus, is an acute febrile disease in humans caused by the bacteria Rickettsia typhi. Currently, cases of FBT are reported for public health surveillance purposes (i.e., to detect incidence and outbreaks) in a few U.S. states. In California, healthcare providers and testing laboratories are mandated to report to their respective local public health jurisdictions whenever R. typhi or antibodies reactive to R. typhi are detected in a patient, who then report cases to state health department. In this study, we characterize the epidemiology of flea-borne typhus cases in California from 2011 to 2019. A total of 881 cases were reported during this period, with most cases reported among residents of Los Angeles and Orange Counties (97%). Demographics, animal exposures, and clinical courses for case patients were summarized. Additionally, spatiotemporal cluster analyses pointed to five areas in southern California with persistent FBT transmission.

Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Sharon Balter reports serving on the executive committee of the California Association of Disease Controllers. No other potential conflicts of interest were disclosed.

Background: It is well established that pregnant persons with SARS-CoV-2 are at an increased risk for preterm birth, however, less is known about perinatal outcomes for neonates with intrauterine exposure to SARS-CoV-2., Methods: Characteristics of 50 SARS-CoV-2 positive neonates born to SARS-CoV-2 pregnant persons positive between May 22, 2020, and February 22, 2021, in Los Angeles County, CA, were assessed. Pattern of neonate SARS-CoV-2 test results and time to positive test was analyzed. Objective clinical severity criteria were applied to assess neonatal disease severity., Results: Median gestational age was 39 weeks with 8 (16%) neonates born preterm. Most (74%) were asymptomatic, while 13 (26%) were symptomatic from any cause. Four (8%) symptomatic neonates met criteria for severe disease, of which 2 (4%) were likely secondary to COVID-19. The other 2 with severe disease had more likely alternate diagnoses, and 1 of these neonates subsequently died at 7 months of life. Among 12 (24%) that were positive within 24 hours after birth, one was persistently positive and represented likely intrauterine transmission. Sixteen (32%) were admitted to the neonatal intensive care unit., Conclusion: In this case series of 50 SARS-CoV-2 positive mother-neonate pairs, we found that most neonates were asymptomatic regardless of when they tested positive during the 14 days after birth, that there was relatively low risk of COVID-19 associated severe disease, and that intrauterine transmission can occur in rare cases. Although short-term outcomes are mostly promising, more research is needed to study long-term consequences of SARS-CoV-2 infection in neonates born to positive pregnant persons., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases. † Among cases with available data, 44% occurred in cisgender women who were non-Hispanic Black or African American (Black), 25% who were non-Hispanic White (White), and 23% who were Hispanic or Latino (Hispanic). Among cisgender women with available data, 73% reported sexual activity or close intimate contact as the likely route of exposure, with mpox lesions most frequently reported on the legs, arms, and genitals. Twenty-three mpox cases were reported in persons who were pregnant or recently pregnant § ; all identified as cisgender women based on the mpox case report form. ¶ Four pregnant persons required hospitalization for mpox. Eleven pregnant persons received tecovirimat, and no adverse reactions were reported. Continued studies on mpox transmission risks in populations less commonly affected during the outbreak, including cisgender women and pregnant persons, are important to assess and understand the impact of mpox on sexual, reproductive, and overall health., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Multiple reports have described neonatal SARS-CoV-2 infection, including likely in utero transmission and early postnatal infection, but published estimates of neonatal infection range by geography and design type., Objectives: To describe maternal, pregnancy and neonatal characteristics among neonates born to people with SARS-CoV-2 infection during pregnancy by neonatal SARS-CoV-2 testing results., Methods: Using aggregated data from the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) describing infections from 20 January 2020 to 31 December 2020, we identified neonates who were (1) born to people who were SARS-CoV-2 positive by RT-PCR at any time during their pregnancy, and (2) tested for SARS-CoV-2 by RT-PCR during the birth hospitalisation., Results: Among 28,771 neonates born to people with SARS-CoV-2 infection during pregnancy, 3816 (13%) underwent PCR testing and 138 neonates (3.6%) were PCR positive. Ninety-four per cent of neonates testing positive were born to people with infection identified ≤14 days of delivery. Neonatal SARS-CoV-2 infection was more frequent among neonates born preterm (5.7%) compared to term (3.4%). Neonates testing positive were born to both symptomatic and asymptomatic pregnant people., Conclusions: Jurisdictions reported SARS-CoV-2 RT-PCR results for only 13% of neonates known to be born to people with SARS-CoV-2 infection during pregnancy. These results provide evidence of neonatal infection identified through multi-state systematic surveillance data collection and describe characteristics of neonates with SARS-CoV-2 infection. While perinatal SARS-CoV-2 infection was uncommon among tested neonates born to people with SARS-CoV-2 infection during pregnancy, nearly all cases of tested neonatal infection occurred in pregnant people infected around the time of delivery and was more frequent among neonates born preterm. These findings support the recommendation for neonatal SARS-CoV-2 RT-PCR testing, especially for people with acute infection around the time of delivery., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the second and third trimesters of pregnancy may impact fetal development via vertical transmission, complications of coronavirus disease 2019 (COVID-19), or placental injury. However, potential associations between prenatal SARS-CoV-2 infection and fetal loss are not well understood. This case series of thirteen second and third trimester fetal losses reported by local public health departments to California's state public health surveillance included maternal clinical and demographic characteristics as well as placental pathology, fetal autopsy reports, and coroner report. There was no evidence that maternal COVID-19 disease severity, placental injury, or SARS-CoV-2 vertical transmission contributed to pregnancy loss. However, this case series is a limited sample; more research is needed to identify factors of prenatal SARS-CoV-2 that may contribute to fetal death in the second and third trimesters., Competing Interests: None., (Copyright © 2022 The Chinese Medical Association, published by Wolters Kluwer Health, Inc.)

Background: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during 29 March 2020-5 March 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics., Results: Among 7950 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 25 years and older, healthcare occupation, prepregnancy obesity, chronic lung disease, chronic hypertension, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions., Conclusions: Older age and having underlying medical conditions were associated with increased risk of moderate-to-severe or critical COVID-19 illness among pregnant women. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and can inform targeted public health messaging., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Introduction: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a 5-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET)., Objectives: The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants., Methods: Mother-baby pairs are identified through prospective identification during pregnancy and/or identification of an infant with retrospective linking to maternal information. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting)., Results: Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing)., Discussion: SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has already demonstrated rapid adaptation to COVID-19. This innovative approach leverages existing data sources and rapidly collects data and informs clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.

Worksites with on-site operations have experienced coronavirus disease (COVID-19) outbreaks. We analyzed data for 698 nonresidential, nonhealthcare worksite COVID-19 outbreaks investigated in Los Angeles County, California, USA, during March 19, 2020‒September 30, 2020, by using North American Industry Classification System sectors and subsectors. Nearly 60% of these outbreaks occurred in 3 sectors: manufacturing (n = 184, 26.4%), retail trade (n = 137, 19.6%), and transportation and warehousing (n = 73, 10.5%). The largest number of outbreaks and largest number and highest incidence rate of outbreak-associated cases occurred in manufacturing. Furthermore, 7 of the 10 industry subsectors with the highest incidence rates were within manufacturing. Approximately 70% of outbreak-associated case-patients reported Hispanic ethnicity. Facilities employing more on-site staff had larger and longer outbreaks. Identification of highly affected industry sectors and subsectors is necessary for targeted public health planning, outreach, and response, including ensuring vaccine access, to reduce burden of COVID-19 in vulnerable workers.

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness and might be at risk for preterm birth (1-3). The full impact of infection with SARS-CoV-2, the virus that causes COVID-19, in pregnancy is unknown. Public health jurisdictions report information, including pregnancy status, on confirmed and probable COVID-19 cases to CDC through the National Notifiable Diseases Surveillance System.* Through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET), 16 jurisdictions collected supplementary information on pregnancy and infant outcomes among 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29-October 14, 2020. Among 3,912 live births with known gestational age, 12.9% were preterm (<37 weeks), higher than the reported 10.2% among the general U.S. population in 2019 (4). Among 610 infants (21.3%) with reported SARS-CoV-2 test results, perinatal infection was infrequent (2.6%) and occurred primarily among infants whose mother had SARS-CoV-2 infection identified within 1 week of delivery. Because the majority of pregnant women with COVID-19 reported thus far experienced infection in the third trimester, ongoing surveillance is needed to assess effects of infections in early pregnancy, as well the longer-term outcomes of exposed infants. These findings can inform neonatal testing recommendations, clinical practice, and public health action and can be used by health care providers to counsel pregnant women on the risks of SARS-CoV-2 infection, including preterm births. Pregnant women and their household members should follow recommended infection prevention measures, including wearing a mask, social distancing, and frequent handwashing when going out or interacting with others or if there is a person within the household who has had exposure to COVID-19. † ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes., Methods: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed., Results: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life., Conclusions: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The burden of arboviruses in the Americas is high and may result in long-term sequelae with infants disabled by Zika virus infection (ZIKV) and arthritis caused by infection with Chikungunya virus (CHIKV). We aimed to identify environmental drivers of arbovirus epidemics to predict where the next epidemics will occur and prioritize municipalities for vector control and eventual vaccination. We screened sera and urine samples (n = 10,459) from residents of 48 municipalities in the state of Rio de Janeiro for CHIKV, dengue virus (DENV), and ZIKV by molecular PCR diagnostics. Further, we assessed the spatial pattern of arbovirus incidence at the municipal and neighborhood scales and the timing of epidemics and major rainfall events. Lab-confirmed cases included 1,717 infections with ZIKV (43.8%) and 2,170 with CHIKV (55.4%) and only 29 (<1%) with DENV. ZIKV incidence was greater in neighborhoods with little access to municipal water infrastructure (r = -0.47, p = 1.2x10-8). CHIKV incidence was weakly correlated with urbanization (r = 0.2, p = 0.02). Rains began in October 2015 and were followed one month later by the largest wave of ZIKV epidemic. ZIKV cases markedly declined in February 2016, which coincided with the start of a CHIKV outbreak. Rainfall predicted ZIKV and CHIKV with a lead time of 3 weeks each time. The association between rainfall and epidemics reflects vector ecology as the larval stages of Aedes aegypti require pools of water to develop. The temporal dynamics of ZIKV and CHIKV may be explained by the shorter incubation period of the viruses in the mosquito vector; 2 days for CHIKV versus 10 days for ZIKV.

Primary Cytomegalovirus (CMV) infection is often not suspected as a cause of fever of unknown origin (FUO) in immune-competent adults. We present a case-series of symptomatic primary CMV infection in immunocompetent adults presenting as fever of unknown origin (FUO). All patients with CMV serology tested between November 2008 and June 2016 underwent chart review. Cases were defined as those between 18 and 65 years of age with documented fever and elevated serum anti-CMV IgM. Exclusion criteria were organ specific CMV disease, positive serum anti-EBV IgM, or presence of any immunocompromising condition. Sixteen patients (69% male, mean age 42.2 ± 11.7 years) met criteria. Mean duration of illness was 4.6 ± 3.3 weeks. Common symptoms other than fever included fatigue (94%), night sweats (81%), malaise (75%), myalgias (63%), and headache (56%). Eleven patients (68.8%) had contact with young children; six (35.3%) patients had children in daycare. Twelve (75%) patients had extensive testing and multiple visits or hospitalizations prior to consulting with an infectious disease specialist. Peripheral smear was done in twelve (75%) patients and all had atypical lymphocytes. Five patients (31.3%) had a leukocytosis. Peak serum transaminases were: AST 115.25 ± 50.5 IU/L and ALT 168.38 ± 92.0 IU/L. One patient had splenic infarcts. In addition, two cases of hydrops fetalis were attributed to primary CMV infection. In summary, primary CMV infection can present as FUO in immunocompetent adults. Contact with young children in daycare may be a risk factor. Heightened clinical suspicion will promote earlier diagnosis and avoid unnecessary testing.

Background: Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes., Methods: A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations., Results: 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397)., Conclusions: Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Current guidelines recommend screening eye examinations for infants with microcephaly or laboratory-confirmed Zika virus infection but not for all infants potentially exposed to Zika virus in utero., Objective: To evaluate eye findings in a cohort of infants whose mothers had polymerase chain reaction-confirmed Zika virus infection during pregnancy., Design, Setting, and Participants: In this descriptive case series performed from January 2 through October 30, 2016, infants were examined from birth to 1 year of age by a multidisciplinary medical team, including a pediatric ophthalmologist, from Fernandes Figueira Institute, a Ministry of Health referral center for high-risk pregnancies and infectious diseases in children in Rio de Janeiro, Brazil., Participants: Mother-infant pairs from Rio de Janeiro, Brazil, who presented with suspected Zika virus infection during pregnancy were referred to our institution and had serum, urine, amniotic fluid, or placenta samples tested by real-time polymerase chain reaction for Zika virus., Main Outcomes and Measures: Description of eye findings, presence of microcephaly or other central nervous system abnormalities, and timing of infection in infants with confirmed Zika virus during pregnancy. Eye abnormalities were correlated with central nervous system findings, microcephaly, and the timing of maternal infection., Results: Of the 112 with polymerase chain reaction-confirmed Zika virus infection in maternal specimens, 24 infants (21.4%) examined had eye abnormalities (median age at first eye examination, 31 days; range, 0-305 days). Ten infants (41.7%) with eye abnormalities did not have microcephaly, and 8 (33.3%) did not have any central nervous system findings. Fourteen infants with eye abnormalities (58.3%) were born to women infected in the first trimester, 8 (33.3%) in the second trimester, and 2 (8.3%) in the third trimester. Optic nerve and retinal abnormalities were the most frequent findings. Eye abnormalities were statistically associated with microcephaly (odds ratio [OR], 19.1; 95% CI, 6.0-61.0), other central nervous system abnormalities (OR, 4.3; 95% CI, 1.6-11.2), arthrogryposis (OR, 29.0; 95% CI, 3.3-255.8), and maternal trimester of infection (first trimester OR, 5.1; 95% CI, 1.9-13.2; second trimester OR, 0.5; 95% CI, 0.2-1.2; and third trimester OR, 0.3; 95% CI, 0.1-1.2)., Conclusions and Relevance: Eye abnormalities may be the only initial finding in congenital Zika virus infection. All infants with potential maternal Zika virus exposure at any time during pregnancy should undergo screening eye examinations regardless of the presence or absence of central nervous system abnormalities.

Background: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants., Methods: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes., Results: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester)., Conclusions: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

Background: Patients with primary sclerosing cholangitis (PSC) and colonic inflammatory bowel disease (IBD) demonstrate increased risk of colorectal cancer. Prior studies have yielded conflicting information on the relationship between ursodiol (UDCA) and the risk of colorectal cancer or dysplasia in this group., Aims: To examine the impact of UDCA on risk of colorectal cancer or dysplasia in adult PSC and IBD patients., Methods: A systematic review and meta-analysis of case-control and cohort studies was performed. Subgroup analysis compared the effects of "low-to-medium" (<25 mg/kg/day) versus "high" dose (≥ 25 mg/kg/day) UDCA exposures., Results: Inclusion and exclusion criteria, as well as all variables, were determined a priori. Seven papers, with 707 participants and greater than 5,751 person-years of follow-up time, met the criteria for final analysis. The overall pooled relative risk using a random effects model was not statistically significant (RR = 0.87, 95 % CI 0.51-1.49, p = 0.62). Subgroup analysis by UDCA dose category in a random effects model was not statistically significant (RR = 0.64, 95 % CI 0.38-1.07, p = 0.09), but suggested a possible trend in risk reduction at low-to-medium-dose exposures that may warrant further investigation., Conclusion: UDCA use was not associated with risk of colorectal cancer or dysplasia in adult PSC and IBD patients, but UDCA dose was a source of heterogeneity across studies. Subgroup analysis suggests a possible trend toward decreased colorectal cancer risk in low-to-medium-dose exposures. Additional study of UDCA treatments at low doses in PSC and IBD patients may be warranted.