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Biomedical subjects

Marc-Alain Widdowson

Publications and source records attributed to Marc-Alain Widdowson.

At least 19 recordsLinked to original sources

Will pediatricians adopt the new rotavirus vaccine?

OBJECTIVES: Our objective was to determine the following among US pediatricians: (1) perceptions regarding burden of rotavirus disease and need for a vaccine; (2) intentions for recommending a newly licensed rotavirus vaccine; (3) perceived barriers to implementation; and (4) factors associated with plans for vaccine adoption. PATIENTS AND METHODS: A network of 431 pediatricians was recruited from a random sample of American Academy of Pediatrics' members. The network was designed to be representative of the American Academy of Pediatrics with respect to region of the country, practice type, and practice setting. During January and February 2006, physicians were surveyed by Internet or mail. The survey contained a paragraph summarizing results of the new rotavirus vaccine trial. Respondents were asked about intentions to use the vaccine and anticipated barriers. RESULTS: The survey response rate was 71%. Of the respondents, 52% strongly agreed and 37% somewhat agreed with the need for a rotavirus vaccine. If recommended for routine use, 50% would strongly recommend and 34% would recommend but not strongly; 52% would begin to use within 6 months and 27% from 6 months to 1 year. The top 3 "definite" barriers to implementation included concerns about uniform coverage of vaccine by insurers, lack of adequate reimbursement, and parental reluctance because of withdrawal of previous rotavirus vaccine. In multivariate analysis, factors associated with very likely adoption of the vaccine included perception of a high burden of rotavirus disease and a high level of confidence in prelicensure studies of vaccine safety. The presence of physician concerns about safety of the new vaccine and the perception of parental concerns about vaccine safety in general were negatively associated with adoption. CONCLUSIONS: The majority of pediatricians reported willingness to implement the new rotavirus vaccine, most within 6 months. Major barriers to optimal implementation included provider concerns about reimbursement issues and parental acceptance of the vaccine.

Attitude of Health Personnel↗

Rotavirus vaccines: current prospects and future challenges.

Rotavirus is the most common cause of severe diarrhoea in children worldwide and diarrhoeal deaths in children in developing countries. Accelerated development and introduction of rotavirus vaccines into global immunisation programmes has been a high priority for many international agencies, including WHO and the Global Alliance for Vaccines and Immunizations. Vaccines have been developed that could prevent the enormous morbidity and mortality from rotavirus and their effect should be measurable within 2-3 years. Two live oral rotavirus vaccines have been licensed in many countries; one is derived from an attenuated human strain of rotavirus and the other combines five bovine-human reassortant strains. Each vaccine has proven highly effective in preventing severe rotavirus diarrhoea in children and safe from the possible complication of intussusception. In developed countries, these vaccines could substantially reduce the number and associated costs of child hospitalisations and clinical visits for acute diarrhoea. In developing countries, they could reduce deaths from diarrhoea and improve child survival through programmes for childhood immunisations and diarrhoeal disease control. Although many scientific, programmatic, and financial challenges face the global use of rotavirus vaccines, these vaccines-and new candidates in the pipeline-hold promise to make an immediate and measurable effect to improve child health and survival from this common burden affecting all children.

Child↗

Reevaluation of epidemiological criteria for identifying outbreaks of acute gastroenteritis due to norovirus: United States, 1998-2000.

BACKGROUND: Noroviruses are believed to be the most common etiologic agent of foodborne outbreaks of gastroenteritis, yet diagnostic tests for these agents are not readily available in the United States. In the absence of assays to detect norovirus, several clinical and epidemiologic profiles--the criteria of Kaplan et al. (vomiting in >50% of patients, mean incubation period of 24-48 h, mean duration of illness of 12-60 h, and no bacterial pathogen) and the ratios of fever to vomiting and diarrhea to vomiting--have been used to distinguish foodborne outbreaks of gastroenteritis caused by noroviruses from those caused by bacteria. METHODS: To examine how well clinical and epidemiological profiles discriminate between foodborne outbreaks of gastroenteritis due to noroviruses and those due to bacteria and to estimate the proportion of reported outbreaks that might be attributable to noroviruses, we reviewed subsets of the 4050 outbreaks reported from 1998 to 2000. RESULTS: The set of criteria of Kaplan et al. is highly specific (99%) and moderately sensitive (68%) in discriminating confirmed outbreaks due to bacteria from those due to norovirus and was the most useful diagnostic aid evaluated. Each individual component of the criteria, the fever-to-vomiting ratio, and the diarrhea-to-vomiting ratio were more sensitive, yet less specific, and therefore less useful, than the criteria of Kaplan et al. We estimated that, at a minimum, 28% of all the foodborne outbreaks reported to the Centers for Disease Control and Prevention may be attributed to norovirus on the basis of these criteria. CONCLUSION: Until norovirus diagnostic tests become widely available, the criteria of Kaplan et al. remain the most useful and discriminating diagnostic aid to identify foodborne outbreaks of gastroenteritis due to noroviruses.

Acute Disease↗

Risk of introduction of poliovirus into a Dutch Cape Verdian community during an outbreak of poliovirus in Cape Verde, 2000.

OBJECTIVE: To assess the risk of introduction of polio virus in a Cape Verdian community of Rotterdam, during the polio epidemic in Cape Verde in 2000. METHODS: All 225 insufficiently vaccinated 0-14-year-old Cape Verdian children (n=4188) and a random sample of 285 out of all 15-30-year-old Cape Verdians (n=5074) in Rotterdam were surveyed to assess travel behaviour and vaccination coverage. Faecal specimens were collected and sewage samples taken in neighbourhoods with a sizable Cape Verdian population for testing of polio virus. RESULTS: During the polio epidemic in Cape Verde, 10% of insufficiently vaccinated children aged 0-14 years and 17% of adults aged 15-30 years living in Rotterdam reported travelling to Cape Verde. 94.6% of Cape Verdians in Rotterdam aged 0-14 years were sufficiently vaccinated against polio, but 9 of 91 insufficiently vaccinated children had travelled to Cape Verde during the epidemic. Of those aged 15-30 years, 10% were not vaccinated against polio. In the faeces of 80 insufficiently vaccinated individuals aged 0-14 years and in 74 adults aged 15-30 years, no poliovirus was detected. Samples of sewage from six sites were negative for poliovirus. CONCLUSION: No evidence of poliovirus infection was found in the Cape Verde population in Rotterdam despite extensive travel to the Cape Verde during the outbreak.

Adolescent↗

Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000-2004.

Between July 2000 and June 2004, fecal specimens from 270 outbreaks of acute gastroenteritis were sent to the Centers for Disease Control and Prevention by local or state health departments for calicivirus testing. Of the 226 outbreaks that met the criteria for inclusion in the present study, caliciviruses were detected in 184 (81%) by reverse-transcription polymerase chain reaction and nucleotide sequencing. Nursing homes, retirement centers, and hospitals were the most frequently reported settings, and person-to-person contact was the most common mode of transmission, followed by foodborne spread. Overall, genogroup II norovirus (NoV) strains were the most abundant (79%), followed by genogroup I NoV strains (19%) and sapovirus (2%). Nucleotide-sequence analysis indicated a great diversity of NoV strains and implicated the emergence of one particular sequence variant in outbreaks occurring between July 2002 and June 2003. The public health impact of caliciviruses will not be fully appreciated, nor will interventions be completely evaluated, until methods to detect these viruses are more routinely used.

Acute Disease↗

Rotavirus antigenemia in patients with acute gastroenteritis.

Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July-August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool.

Antibodies, Viral↗

Detection of serum antibodies to bovine norovirus in veterinarians and the general population in the Netherlands.

The close genetic relationship of human and animal strains of norovirus has raised the possibility of transmission of noroviruses from animals to humans and may explain the emergence of certain norovirus strains. To assess if exposure to bovine noroviruses (NoV) might result in infection in humans, an enzyme immunoassay (EIA) was designed and validated in order to detect antibodies against bovine norovirus. This and two other EIAs were used to test sera from 210 veterinarians and 630 matched population controls for IgG and IgA antibodies to recombinant capsid protein of bovine NoV (rBoV), Norwalk virus (rNV), and Lordsdale virus (rLDV). Of 840 participants, IgG reactivity to rBoV was found in 185 (22%), to rNV in 638 (76%) and to rLDV in 760 (90%). IgG reactivity to rBoV was more common in veterinarians (58/210: 28%) than in controls (127/630: 20% [P = 0.03]). IgA reactivity to rBoV was similar in both veterinarians and controls. Cross-reactivity of IgA and IgG antibodies to rBoV and rNV was seen, but 26% of all specimens positive rBoV antibodies showed high IgG reactivity to rBoV but low reactivity to rNV, suggesting a specific response to bovine antigen. No evidence of overall cross-reactivity of antibodies to rBoV and rLDV was seen. Among veterinarians, youth spent on farm (Odds Ratio [OR] = 1.8) and membership of the bovine practitioners' society (OR = 2.7) were significantly associated with IgG seroreactivity to rBoV. These data indicate that bovine strains of NoV may infect humans though less frequently than human strains.

Adult↗

Norovirus and child care: challenges in outbreak control.

An infant with diarrhea attended a community playgroup. In the subsequent 48 hours, 6 of the 7 mothers and children reported gastroenteritis; fecal specimens from 5 persons tested positive for norovirus, with identical sequences. No breach of hygiene or contact with fecal matter was identified. Excluding the child with gastroenteritis from the playgroup could have prevented this outbreak.

Adult↗

Update on rotavirus vaccines.

Rotavirus was discovered in 1973, and 10 years later the first report of a rotavirus vaccine clinical trial appeared. This update reviews the epidemiology of rotavirus infections, assesses past and current vaccines and presents ideas for implementation of vaccination programs in developed and developing countries.

Animals↗

Norovirus and foodborne disease, United States, 1991-2000.

Efforts to prevent foodborne illness target bacterial pathogens, yet noroviruses (NoV) are suspected to be the most common cause of gastroenteritis. New molecular assays allow for better estimation of the role of NoV in foodborne illness. We analyzed 8,271 foodborne outbreaks reported to the Centers for Disease Control and Prevention from 1991 to 2000 and additional data from 6 states. The proportion of NoV-confirmed outbreaks increased from 1% in 1991 to 12% in 2000. However, from 1998 to 2000, 76% of NoV outbreaks were reported by only 11 states. In 2000, an estimated 50% of foodborne outbreaks in 6 states were attributable to NoV. NoV outbreaks were larger than bacterial outbreaks (median persons affected: 25 versus 15), and 10% of affected persons sought medical care; 1% were hospitalized. More widespread use of molecular assays will permit better estimates of the role of NoV illness and help direct efforts to control foodborne illness.

Animals↗

Norovirus transmission on cruise ship.

An outbreak of norovirus gastroenteritis affected passengers on two consecutive cruises of ship X and continued on 4 subsequent cruises despite a 1-week sanitization. We documented transmission by food and person-to-person contact; persistence of virus despite sanitization onboard, including introductions of new strains; and seeding of an outbreak on land.

Caliciviridae Infections↗

Rotavirus disease and its prevention.

PURPOSE OF REVIEW: Rotavirus infection is the foremost cause of severe gastroenteritis of young children worldwide. Efforts to develop safe and effective vaccines resulted in licensure of the first live oral vaccine, tetravalent, rhesus-based rotavirus vaccine (RRV-TV), which was incorporated into the US immunization schedule in 1998. Less than 1 year later, however, the vaccine was withdrawn when reports of cases of intussusception were linked to recent vaccination. This setback created significant hurdles as well as new opportunities for the development of the next generation of rotavirus vaccines. This review focuses on new information related to the clinical presentation and pathogenesis of rotavirus infection, the associated global disease burden, and the ongoing efforts to develop and introduce the next generation of rotavirus vaccines for widespread use. RECENT FINDINGS: Recent studies have confirmed that rotavirus infection is not confined only to the gut but can have extraintestinal manifestations, including viremia. Estimates of the global disease burden of rotavirus diarrhea have been refined and suggest that mortality has not declined, and that among hospitalized cases of diarrhea, the fraction associated with rotavirus has increased in many countries. In the United States, the estimated number of hospitalizations attributed to rotavirus has increased. Debate continues about the magnitude of the attributable risk of the association between RRV-TV and intussusception. Several new rotavirus vaccines are in late stages of development. One vaccine was licensed in Mexico in 2004 and a second has completed clinical trials in the United States and Europe and may be licensed within 2 to 3 years. SUMMARY: The tremendous burden of rotavirus diarrhea among children all over the world continues to drive the remarkable pace of vaccine development and the variety of approaches to creating rotavirus vaccines.

Child↗

Outbreaks of acute gastroenteritis on cruise ships and on land: identification of a predominant circulating strain of norovirus--United States, 2002.

In 2002, a sharp increase in outbreaks of norovirus-associated illness, both on cruise ships and on land, encouraged us to examine the molecular epidemiology of detected noroviruses, to identify a common strain or source. Of 14 laboratory-confirmed outbreaks on cruise ships, 12 (86%) were attributed to caliciviruses; among these 12, outbreak characteristics included continuation on successive cruises in 6 (50%), multiple modes of transmission in 7 (58%), and high (>10%) attack rates in 7 (58%). Eleven of the 12 calicivirus outbreaks were attributed to noroviruses, 7 (64%) of which were attributed to a previously unreported lineage, provisionally named "the Farmington Hills strain." From May 2002 to December 2002, 10 (45%) of 22 land-based outbreaks also were attributed to this strain. Nucleotide-sequence analysis provided insights into norovirus transmission, by documenting links among outbreaks, the introduction of strains onto ships, and viral persistence on board (despite cleaning). Control measures for outbreaks should address all routes of transmission. Better outbreak surveillance and collection of data on sequences will help to monitor norovirus strains and to identify common sources.

Acute Disease↗

SARS-associated coronavirus transmission, United States.

To better assess the risk for transmission of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Routine collection and testing of stool and sputum specimens of probable SARS case-patients may help the early detection of SARS-CoV infection.

Adolescent↗

Automated, laboratory-based system using the Internet for disease outbreak detection, the Netherlands.

Rapid detection of outbreaks is recognized as crucial for effective control measures and has particular relevance with the recently increased concern about bioterrorism. Automated analysis of electronically collected laboratory data can result in rapid detection of widespread outbreaks or outbreaks of pathogens with common signs and symptoms. In the Netherlands, an automated outbreak detection system for all types of pathogens has been developed within an existing electronic laboratory-based surveillance system called ISIS. Features include the use of a flexible algorithm for daily analysis of data and presentation of signals on the Internet for interpretation by health professionals. By 2006, the outbreak detection system will analyze laboratory-reported data on all pathogens and will cover 35% of the Dutch population.

Algorithms↗

Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands.

Increasing evidence suggests that hepatitis E virus (HEV) infection may occur in developed countries and that swine may act as a reservoir. We report a cluster of 2 confirmed cases and 1 presumptive case of hepatitis associated with HEV. The typed strain from 1 case was related to HEV strains found in North America and Europe, and it was also related to a cluster of swine HEV strains found in The Netherlands. Our findings indicate that locally acquired HEV infections in industrialized countries may be overlooked. Routine testing for HEV infection in patients with acute hepatitis in The Netherlands should be considered before a diagnosis of autoimmune hepatitis is reached and steroid therapy is initiated.

Acute Disease↗