Prospective study of pregnancy and newborn outcomes in mothers with West nile illness during pregnancy.

BACKGROUND: A previous case report of West Nile virus (WNV) illness during pregnancy suggested that WNV could be a cause of congenital defects. We performed a prospective, longitudinal cohort study of pregnant women with WNV illness to increase our knowledge of the effects of WNV illness during pregnancy. METHODS: Participants were enrolled in 2005 to 2008 from pregnant women with serologically confirmed WNV illness reported to the Centers for Disease Control and Prevention. Comparison was made to WNV-uninfected women, matched on maternal age and enrollment month. Pregnancy and newborn data were collected; cord blood WNV serology was obtained. Pediatric exams and the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) were performed. RESULTS: Twenty-eight WNV-infected mothers and 25 WNV-uninfected mothers participated. Maternal demographics were similar except for a higher rate of planned pregnancies, education, and household income in the WNV-uninfected mothers. There were no differences in pregnancy and delivery characteristics except that infected mothers had a higher incidence of febrile illnesses and used more medications. Birth weight, length, head circumference, and rate of congenital malformations were similar in babies born to WNV-infected and -uninfected mothers. Follow-up physical exams were generally normal. The Bayley-III assessments, available for 17 children born to mothers with WNV illness, showed performance at or above age level across domains. CONCLUSION: The risk for adverse pregnancy and newborn outcomes in women experiencing WNV illness in pregnancy appears to be low, but future studies with larger numbers are needed to rule out a small risk. Birth Defects Research (Part A) 106:716-723, 2016. © 2016 Wiley Periodicals, Inc.

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.

Aetiology, epidemiology and clinical characteristics of acute moderate-to-severe diarrhoea in children under 5 years of age hospitalized in a referral paediatric hospital in Rabat, Morocco.

The objective of the study was to describe the aetiology, epidemiology and clinical characteristics of the principal causes of acute infectious diarrhoea requiring hospitalization among children under 5 years of age in Rabat, Morocco. A prospective study was conducted from March 2011 to March 2012, designed to describe the main pathogens causing diarrhoea in hospitalized children >2 months and less than 5 years of age. Among the 122 children included in the study, enteroaggregative Escherichia coli (EAEC) and rotavirus were the main aetiological causes of diarrhoea detected. Twelve (9.8 %) children were referred to an intensive care unit, while two, presenting infection by EAEC, and EAEC plus Shigella sonnei, developed a haemolytic uraemic syndrome. Additionally, six (4.9 %) deaths occurred, with EAEC being isolated in four of these cases. Diarrhoeagenic E. coli and rotavirus play a significant role as the two main causes of severe diarrhoea, while other pathogens, such as norovirus and parasites, seem to have a minimal contribution. Surveillance and prevention programmes to facilitate early recognition and improved management of potentially life-threatening diarrhoea episodes are needed.

Developmental outcomes in young children born to mothers with West Nile illness during pregnancy.

BACKGROUND: West Nile virus (WNV) infection is associated with acute morbidity and mortality in adults and children. Information on the effects of maternal WNV illness during pregnancy on early childhood development is limited. This study was designed to examine the relationship between maternal WNV illness during pregnancy and birth and developmental outcomes at age 3 years. METHODS: Mother-child participants were identified using a national surveillance registry for women with WNV illness during pregnancy. Maternal and infant health data and relevant family characteristics were obtained through medical record reviews and maternal questionnaires. All infants received ophthalmologic examinations. Child development was evaluated at age 3 years using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). RESULTS: As a group, the children's (N = 11) birth weight, head circumference, and infant ophthalmologic examination results were within age expectations; one child was born preterm (gestational age 36 weeks). Mean (SD) age at the time of Bayley-III testing was 36.7 (3.8) months. The group's mean performance on the Bayley-III was at or above age level in all domains, but one child showed a mild delay in the Adaptive domain. The variability observed in this sample (1/53 [1.9%] Domain scores < -2.0 SDs) was consistent with expectations based upon the distribution of Bayley-III Domain scores in the general population. CONCLUSION: Maternal WNV infection does not appear to be associated with global developmental delays in young children. These results are preliminary, however, and require confirmation in future research.

The epidemiology and aetiology of infections in children admitted with clinical severe pneumonia to a university hospital in Rabat, Morocco.

OBJECTIVES: Scarce and limited epidemiological, clinical and microbiological data are available regarding paediatric respiratory tract infections in the Kingdom of Morocco, a middle-income country in northwestern Africa. The results of hospital-based surveillance aiming at describing the aetiology and epidemiology of respiratory distress among children <5 years of age are presented. METHODS: Children admitted to the Hôpital d'Enfants de Rabat, Morocco, and meeting the World Health Organization clinical criteria for severe pneumonia were recruited over a period of 14 months and were thoroughly investigated to ascertain a definitive diagnosis. RESULTS: In total, 700 children were recruited for the study. Most frequent clinical diagnoses included wheezing-related conditions (bronchitis/asthma, 46%; bronchiolitis, 15%), while typical bacterial pneumonia was infrequent (only 19% of the cases). Invasive bacterial disease detected by classical microbiology or molecular methods was also uncommon, affecting only 3.5% of the patients, and with an overall low detection of pneumococcal or Haemophilus influenzae type b disease. Conversely, coverage of respiratory viral detection in the nasopharynx was almost universal among cases (92%), with the three most frequent viruses detected being rhinovirus (53%), respiratory syncytial virus (18%) and adenovirus (17%). The overall case fatality rate (CFR) among recruited patients with a known outcome was 4.1% (28/690). CONCLUSIONS: In Morocco, the epidemiological profile of paediatric acute respiratory infections is markedly shifted towards wheezing-related diseases and thus resembles that of high-income countries. However, the high associated CFRs found in this study call for an improvement in preventive and clinical management strategies.

A survey of US travelers to Asia to assess compliance with recommendations for the use of Japanese encephalitis vaccine.

BACKGROUND: Japanese encephalitis (JE) vaccine is recommended for travelers to Asia whose itineraries increase their risk of exposure to JE virus. The numbers of travelers with such itineraries and the proportion of those who receive JE vaccine are unknown. We performed a survey to estimate the proportion of US travelers to Asia who receive JE vaccine according to the Advisory Committee on Immunization Practices (ACIP) recommendations. METHODS: We surveyed US residents ≥ 18 years old departing on 38 flights to Asia selected through a stratified random sample of all direct flights to JE-endemic countries from three US airports. We asked participants about planned itineraries and activities, sources of travel health information, JE vaccination status, and potential barriers to vaccination. Participants planning to spend ≥ 30 days in Asia or at least half of their time in rural areas were defined as "higher JE risk" travelers for whom vaccination should have been considered. RESULTS: Of 2,341 eligible travelers contacted, 1,691(72%) completed the survey. Among these 1,691 participants, 415 (25%) described itineraries for which JE vaccination should have been considered. Of these 415 higher JE risk travelers, only 47 (11%) reported receiving ≥ 1 dose of JE vaccine. Of the 164 unvaccinated higher JE risk travelers who visited a health care provider before their trip, 113 (69%) indicated that they had never heard of JE vaccine or their health care provider had not offered or recommended JE vaccine. CONCLUSIONS: A quarter of surveyed US travelers to Asia reported planned itineraries for which JE vaccination should have been considered. However, few of these at-risk travelers received JE vaccine.

Pandemic influenza A(H1N1) outbreak among a group of medical students who traveled to the Dominican Republic.

BACKGROUND: From the beginning of the influenza pandemic until the time the outbreak described here was detected, 77,201 cases of pandemic influenza A(H1N1) with 332 deaths had been reported worldwide, mostly in the United States and Mexico. All of the cases reported in Spain until then had a recent history of travel to Mexico, the Dominican Republic, or Chile. We describe an outbreak of influenza among medical students who traveled from Spain to the Dominican Republic in June 2009. METHODS: We collected diagnostic samples and clinical histories from consenting medical students who had traveled to the Dominican Republic and from their household contacts after their return to Spain. RESULTS: Of 113 students on the trip, 62 (55%) developed symptoms; 39 (45%) of 86 students tested had laboratory evidence of influenza A(H1N1) infection. Most students developed symptoms either just before departure from the Dominican Republic or within days of returning to Spain. The estimated secondary attack rate of influenza-like illness among residential contacts of ill students after return to Spain was 2.1%. CONCLUSIONS: The attack rate of influenza A(H1N1) can vary widely depending on the circumstances of exposure. We report a high attack rate among a group of traveling medical students but a much lower secondary attack rate among their contacts after return from the trip. These findings may aid the development of recommendations to prevent influenza.

Hospitalizations due to rotavirus gastroenteritis in Catalonia, Spain, 2003-2008.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children in Spain and worldwide. We evaluated hospitalizations due to community and hospital-acquired rotavirus gastroenteritis (RVGE) and estimated related costs in children under 5 years old in Catalonia, Spain. RESULTS: We analyzed hospital discharge data from the Catalan Health Services regarding hospital admissions coded as infectious gastroenteritis in children under 5 for the period 2003-2008. In order to estimate admission incidence, we used population estimates for each study year published by the Statistic Institut of Catalonia (Idescat). The costs associated with hospital admissions due to rotavirus diarrhea were estimated for the same years. A decision tree model was used to estimate the threshold cost of rotavirus vaccine to achieve cost savings from the healthcare system perspective in Catalonia. From 2003 through 2008, 10655 children under 5 years old were admitted with infectious gastroenteritis (IGE). Twenty-two percent of these admissions were coded as RVGE, yielding an estimated average annual incidence of 104 RVGE hospitalizations per 100000 children in Catalonia. Eighty seven percent of admissions for RVGE occurred during December through March. The mean hospital stay was 3.7 days, 0.6 days longer than for other IGE. An additional 892 cases of presumed nosocomial RVGE were detected, yielding an incidence of 2.5 cases per 1000 child admissions. Total rotavirus hospitalization costs due to community acquired RVGE for the years 2003 and 2008 were 431,593 and 809,224 €, respectively. According to the estimated incidence and hospitalization costs, immunization would result in health system cost savings if the cost of the vaccine was 1.93 € or less. At a vaccine cost of 187 € the incremental cost per hospitalization prevented is 195,388 € (CI 95% 159,300; 238,400). CONCLUSIONS: The burden of hospitalizations attributable to rotavirus appeared to be lower in Catalonia than in other regions of Spain and Europe. The relatively low incidence of hospitalization due to rotavirus makes rotavirus vaccination less cost-effective in Catalonia than in other areas with higher rotavirus disease burden.

Persistence of yellow fever vaccine RNA in urine.

To evaluate possible persistence of 17D yellow fever vaccine, we tested urine samples from 44 healthy recipients of yellow fever vaccine at varying times up to one year after vaccination. Urine samples from two vaccine recipients had detectable yellow fever virus RNA. The time since vaccination was reported as 21 days for one sample and 198 days for the other sample. These results suggest that yellow fever vaccine virus might persist for at least 6 months after vaccination in some people.

Is it time for a new yellow fever vaccine?

An inexpensive live attenuated vaccine (the 17D vaccine) against yellow fever has been effectively used to prevent yellow fever for more than 70 years. Interest in developing new inactivated vaccines has been spurred by recognition of rare but serious, sometimes fatal adverse events following live virus vaccination. A safer inactivated yellow fever vaccine could be useful for vaccinating people at higher risk of adverse events from the live vaccine, but could also have broader global health utility by lowering the risk-benefit threshold for assuring high levels of yellow fever vaccine coverage. If ongoing trials demonstrate favorable immunogenicity and safety compared to the current vaccine, the practical global health utility of an inactivated vaccine is likely to be determined mostly by cost.

Looking the other way: preventing vector-borne disease among travelers to the United States.

Millions of travelers visit the United States every year during warm months when risk of vector-borne disease is highest. The epidemiology and geographic distribution of the principal vector-borne diseases in the United States are reviewed and recommendations for visitors to reduce their risk of disease are described. Travel advice should focus on preventing Lyme disease, anaplasmosis and babesiosis in the northeast and north central States, West Nile virus disease in western plains States, and Rocky Mountain spotted fever and tularemia in the southeast; other diseases and itineraries requiring particular attention are described. All travelers to the United States should be advised to practice personal protection against arthropod bites, including appropriate use of insect repellents, especially when visiting rural and suburban areas during the warm months.

Twins: prevalence, problems, and preterm births.

The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in 2006. Aside from determining chorionicity, first-trimester screening and second-trimester ultrasound scanning should ascertain whether there are structural or chromosomal abnormalities. Compared with singleton births, genetic amniocentesis-related loss at <24 weeks of gestation for twin births is higher (0.9% vs 2.9%, respectively). Selective termination for an anomalous fetus is an option, although the pregnancy loss rate is 7% at experienced centers. For singleton and twin births for African American and white women, approximately 50% of preterm births are indicated; approximately one-third of these births are spontaneous, and 10% of the births occur after preterm premature rupture of membranes. From 1989-2000, the rate of preterm twin births increased, for African American and white women alike, although the perinatal mortality rate has actually decreased. As with singleton births, tocolytics should be used judiciously and only for a limited time (<48 hours) in twin births. Administration of antenatal corticosteroids is an evidence-based recommendation.

Household-based sero-epidemiologic survey after a yellow fever epidemic, Sudan, 2005.

From September through early December 2005, an outbreak of yellow fever (YF) occurred in South Kordofan, Sudan, resulting in a mass YF vaccination campaign. In late December 2005, we conducted a serosurvey to assess YF vaccine coverage and to better define the epidemiology of the outbreak in an index village. Of 552 persons enrolled, 95% reported recent YF vaccination, and 25% reported febrile illness during the outbreak period: 13% reported YF-like illness, 4% reported severe YF-like illness, and 12% reported chikungunya-like illness. Of 87 persons who provided blood samples, all had positive YF serologic results, including three who had never been vaccinated. There was also serologic evidence of recent or prior chikungunya virus, dengue virus, West Nile virus, and Sindbis virus infections. These results indicate that YF virus and chikungunya virus contributed to the outbreak. The high prevalence of YF antibody among vaccinees indicates that vaccination was effectively implemented in this remotely located population.

Relationship between maternal methadone dose at delivery and neonatal abstinence syndrome.

OBJECTIVE: To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS). STUDY DESIGN: We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score>24 during the prior 24 hours. RESULTS: A total of 330 women treated with methadone and their 388 offspring were included. Average methadone dose at delivery was 117+/-50 mg/d (range, 20-340 mg/d). Overall, 68% of infants were treated for NAS. Of infants exposed to methadone doses160 mg/d, treatment for NAS was initiated for 68%, 63%, 70%, and 73% of neonates, respectively (P=.48). The rate of maternal illicit opiate abuse at delivery was 26%, 28%, 19%, and 11%, respectively (P=.04). CONCLUSION: No correlation was found between maternal methadone dose and rate of NAS. However, higher doses of methadone were associated with decreased illicit opiate abuse at delivery.

Recurrent shoulder dystocia: a review.

OBJECTIVE: The goals of this review were to determine the incidence of recurrent shoulder dystocia and the incidence of brachial plexus injury in such cases. MATERIALS AND METHODS: A search of PubMed was conducted between 1980 and March 2009. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: The search yielded 191 publications, of which 9 provided complete data; these were used to calculate the incidence of recurrent shoulder dystocia. The rate of shoulder dystocia in the prior pregnancies was 1.64% (31,311/1,911,014). Among 10,591 known subsequent vaginal births, the rate of recurrent shoulder dystocia was 12% (OR, 8.25; 95% CI, 7.77, 8.76). Brachial plexus injury occurred significantly more often during recurrent shoulder dystocia than during the first shoulder dystocia (4% vs. 1%; OR, 3.59; 95% CI, 2.44, 5.29; or 45/1000 vs. 13/1000 births). CONCLUSION: About 12% of parturients with a history of shoulder dystocia have a recurrent dystocia in the subsequent pregnancy, a risk of about 1 in 8. Brachial plexus injury occurs in 19/1000 vaginal births during the first episode of shoulder dystocia, and in 45/1000 vaginal births after recurrent dystocia. TARGET AUDIENCE: Obstetricians & Gynecologist, Family Physicians. LEARNING OBJECTIVES: After completion of this educational activity, the reader will be able to compare the risk of primary versus recurrent shoulder dystocia. Formulate counseling and treatment strategies for pregnant women who have had a prior pregnancy complicated by shoulder dystocia. Assess the strength of the evidence suggesting the risk of recurrent shoulder dystocia.

Shoulder dystocia: comparison of the ACOG practice bulletin with another national guideline.

Our objective was to compare national guidelines regarding shoulder dystocia. Along with the American College of Obstetricians and Gynecologists (ACOG) practice bulletin on shoulder dystocia, guidelines from England, Canada, Australia, and New Zealand were reviewed. The Royal College of Obstetricians and Gynaecologists (RCOG) guideline agrees with the ACOG definition of shoulder dystocia, but there are variances in the management of suspected macrosomia and resolution of impacted shoulders. How recommendations are categorized differ also. Only 53% (20 of 38) of eligible references are cited by both publications. The two national guidelines on shoulder dystocia have differences and disagreements with each other, raising concerns about how the literature is synthesized and which is more comprehensive.

Zika virus outside Africa.

Zika virus (ZIKV) is a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses. In 2007 ZIKV caused an outbreak of relatively mild disease characterized by rash, arthralgia, and conjunctivitis on Yap Island in the southwestern Pacific Ocean. This was the first time that ZIKV was detected outside of Africa and Asia. The history, transmission dynamics, virology, and clinical manifestations of ZIKV disease are discussed, along with the possibility for diagnostic confusion between ZIKV illness and dengue.The emergence of ZIKV outside of its previously known geographic range should prompt awareness of the potential for ZIKV to spread to other Pacific islands and the Americas.

Viscerotropic disease following yellow fever vaccination in Peru.

Five suspected cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) clustered in space and time following a vaccination campaign in Ica, Peru in 2007. All five people received the same lot of 17DD live attenuated yellow fever vaccine before their illness; four of the five died of confirmed YEL-AVD. The surviving case was classified as probable YEL-AVD. Intensive investigation yielded no abnormalities of the implicated vaccine lot and no common risk factors. This is the first described space-time cluster of yellow fever viscerotropic disease involving more than two cases. Mass yellow fever vaccination should be avoided in areas that present extremely low risk of yellow fever.