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.

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.

Zika virus outbreak on Yap Island, Federated States of Micronesia.

BACKGROUND: In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. METHODS: We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. RESULTS: We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. CONCLUSIONS: This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.

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.

West Nile virus in the Americas.

Since the first detection of West Nile virus in the Western Hemisphere in 1999, the virus has spread rapidly across the North American continent and as far south as Argentina. An unprecedented pattern of large annual epidemics of human neuroinvasive disease continues in North America, resulting in considerable public health impact. The high infection incidence in humans has resulted in non-mosquito transmission modes, such as through transfused blood and transplanted organs. West Nile virus incursion into Latin America and the Caribbean Islands has resulted in surprisingly low human, avian, and equine morbidity and mortality despite evidence that West Nile virus strains circulating in those regions are similar to those in North America.

West Nile virus neuroinvasive disease incidence in the United States, 2002-2006.

As the geographic range of reported human West Nile virus (WNV) disease has expanded across the United States, seasonal transmission and outbreaks have persisted over several years in many areas of the country. West Nile virus neuroinvasive disease (WNND) case reports from 2002 to 2006 were reviewed to determine which areas of the country have the highest reported cumulative incidence and whether those areas have had consistently high annual incidence. During the 5-year period examined, 9632 cases of WNND were reported nationwide. The cumulative incidence of WNND ranged from 0.2 to 32.2 per 100,000 population by state and from 0.1 to 241.2 per 100,000 population by county. States and counties with the highest cumulative incidence were primarily located in the northern Great Plains. States with consistently high annual incidence included South Dakota, North Dakota, Wyoming, New Mexico, Mississippi, Nebraska, Louisiana, and Colorado. All of these states, with the exception of New Mexico, were also among the states with the highest cumulative incidence. Counties with repeatedly high annual incidence were also primarily in the Great Plains and mid-South. The risk of WNND appears to be highest in areas where the primary WNV vectors are Culex tarsalis and Cx. quinquefasciatus mosquitoes.

Emerging infections and pregnancy: assessing the impact on the embryo or fetus.

The teratogenicity of several infections when acquired during pregnancy is well documented. However, for emerging infections (defined as those for which the incidence has risen in the past two decades or threatens to rise in the near future), the prenatal effects are often unknown, raising concern among women and their health care providers. Investigation of these effects is essential to ensure that pregnant women are appropriately assessed, advised, and treated, but such investigation is often challenging. The impact of emerging infections on the embryo or fetus is difficult to predict and varies depending on the agent and gestational timing of infection. Some women might be asymptomatic or have only mild or nonspecific symptoms, and thus, not be identified as infected, even when the embryo or fetus is severely affected. In addition, diagnosing congenital infection is often complicated. This article will discuss challenges to studying the teratogenicity of emerging infections, advantages, and disadvantages of different study designs, and examples of previous studies of the effects of emerging infections on the embryo or fetus.

Acute viscerotropic disease following vaccination against yellow fever.

Acute viscerotropic disease following yellow fever vaccination (YEL-AVD) is a rare but serious complication of vaccination with 17D yellow fever vaccine. This paper reviews the existing literature regarding YEL-AVD and discusses possible etiologic mechanisms. A greater understanding of this condition is essential to assuring safe and effective prevention of yellow fever and vaccination against other arboviral diseases for which 17D-based vaccines are being developed.

Fatal hemorrhagic fever caused by West Nile virus in the United States.

BACKGROUND: Most West Nile virus (WNV) infections in humans are asymptomatic; severe disease occurs in relatively few patients and typically manifests as encephalitis, meningitis, or acute flaccid paralysis. A few cases of life-threatening disease with diffuse hemorrhagic manifestations have been reported in Africa; however, this clinical presentation has not been documented for any of the >16,700 cases of WNV disease reported in the United States during 1999-2004. We describe a case of fulminant WNV infection in a 59-year-old Florida man who died following a brief illness that resembled hemorrhagic disease caused by Rickettsia reckettsii, dengue virus or yellow fever virus. METHODS: Traditional and contemporary diagnostic assays, including culture isolation, electron microscopic examination, reverse-transcriptase polymerase chain reaction amplification, and immunohistochemical stains, were used to confirm systemic WNV infection in the patient. RESULTS: WNV was isolated in a cell culture from a skin biopsy specimen obtained from the patient shortly prior to death. Electron microscopic examination identified the isolate as a flavivirus, and reverse-transcriptase polymerase chain reaction amplified specific WNV sequences from the isolate and patient tissue. Quantitative polymerase chain reaction identified approximately 1x10(7) viral copies/mL in the patient's serum. WNV antigens were detected by immunohistochemical stains in intravascular mononuclear cells and endothelium in skin, lung, liver, kidney, spleen, bone marrow, and central nervous system; no viral antigens were identified in neurons or glial cells of the central nervous system. CONCLUSIONS: Although hemorrhagic disease is a rare manifestation of WNV infection, the findings provided by this report may offer new insights regarding the clinical spectrum and pathogenesis of WNV disease in humans.

Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and corticosteroid therapy: eleven United States cases, 1996-2004.

During 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal. Stress-dose corticosteroid (SDS) therapy has recently been found to improve survival among patients with septic shock but benefit for the treatment of YEL-AVD patients in septic shock is unknown. We retrospectively reviewed medical records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3 of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%) survived. Altered mental status was documented on admission for 5 of the 11 patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and survived. The use of stress-dose steroids might be a factor that influenced the survival of these YEL-AVD patients and should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.

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.

Assessment of dengue risk in relief workers in Puerto Rico after Hurricane Georges, 1998.

Health risk assessment is important in the safe deployment of workers to tropical areas. We monitored dengue incidence in 204 of 222 North American relief workers visiting Puerto Rico after Hurricane Georges and during a dengue epidemic in 1998. We recorded information regarding participants' living conditions and any illness they experienced from arrival to 2 weeks after their departure. Virus isolation, polymerase chain reaction, and serological tests for anti-dengue immunoglobulin (Ig) M and IgG antibodies were used to diagnose dengue infection by means of departure and follow-up serum specimens. Among respondents, 82% (164 of 199) reported mosquito bites, 97% (156 of 161) reported having insect repellent available, and 41% (79 of 195) reported using repellent every day. Twelve participants reported a mild denguelike illness. No participants had laboratory evidence of dengue infection after 1.8 person-years of assessable exposure to areas with dengue transmission (upper 95% confidence limit of 1.67 cases per person-year). The risk of acquiring dengue among relief workers in this study appears low, possibly as a result of protective factors. Travelers to dengue-endemic areas should continue to be advised to protect themselves against mosquito bites.

Lyme disease trends--Dutchess County, New York, 1992-2000.

BACKGROUND: Lyme disease is a vector-borne infectious disease, accounting for more than 95% of all reported vector-borne illness in the United States. From 1992 2000, Dutchess County reported more cases of Lyme disease than any other county in the United States, consistently ranking among the top ten in incidence rates. We analyzed 1992-2000 Dutchess County Lyme disease surveillance data to characterize Lyme disease trends, identify high-risk populations, and examine the frequency of the characteristic lesion, erythema migrans. METHODS: A Lyme disease case was defined as a person with physician-diagnosed erythema migrans or at least one late manifestation of the disease, with laboratory confirmation. A surveillance database of cases reported in Dutchess County from 1992-2000 was obtained from the New York State Department of Health. Annual incidence rates by age, gender, race, ethnicity, and ZIP codes, and frequency of erythema migrans were calculated. RESULTS: From 1992 through 2000, a total of 9,548 cases of Lyme disease were reported by Dutchess County to the New York State Department of Health, for a crude mean annual incidence rate of 400 cases per 100,000 persons per year. The incidence rate peaked at 683/100,000 in 1996, and then declined from 1998 to 2000. A bimodal age distribution was seen, with the initial peak among children aged 5-9 years (617/100,000) and the second peak among adults aged 60-64 years (627/100,000). A male preponderance was clearly seen between the ages of 5-19 years, and beyond the age of 60 years. Highest incidence rates were reported in central Dutchess County. Onset of illness occurred most frequently in June, July, and August. Ninety-four percent of cases occurred among the predominantly white population, which had the highest incidence rate (431/100,000) among the races. Incidence rate for non-Hispanics was more than double that for Hispanics. Eighty-one percent of reported cases had erythema migrans. CONCLUSIONS: While some prevention programs could be broadly targeted to the entire Dutchess County population, other interventions might be most effective if they focused on the high-risk population groups and areas defined in this report. The high proportion of cases with erythema migrans suggests that early diagnosis and treatment should be effective in reducing late-stage complications of Lyme disease in Dutchess County. Surveillance data for other endemic counties and states can be similarly analyzed to enhance and monitor local prevention programs.

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.

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.