Biomedical subjects

Thea K Fischer

Publications and source records attributed to Thea K Fischer.

17 recordsLinked to original sources

PubMed2006

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↗

PubMed2006

Community cohort study of rotavirus and other enteropathogens: are routine vaccinations associated with sex-differential incidence rates?

OBJECTIVE: Community studies in West Africa have demonstrated that routine vaccinations may have non-targeted effects, the female-male mortality ratio being reduced after administration of BCG and increased after diphtheria-tetanus-pertussis (DTP). We examined whether immunisation status was associated with infection with rotavirus and other enteropathogens. METHODS: We recruited 200 children shortly after birth and followed them until 2 years of age with weekly morbidity interviews and stool sampling. Vaccination status for each child was classified according to the most recent vaccination as documented by vaccination card. MAIN OUTCOME MEASURES: The female-male incidence rate ratios (IRR) of infection with an enteropathogen and of enteropathogen-associated diarrhoea were estimated for children according to whether they had received BCG or DTP as their last vaccination. RESULTS: For children who received BCG as their last vaccine, the adjusted female-male IRRs for primary rotavirus-infection and diarrhoea were 1.05 (95% CI: 0.21-5.28) and 0.0 (95% CI: 0-3.02), respectively. For children who received DTP as their last vaccine, the adjusted female-male IRRs were 1.93 (0.89-4.21) and 1.92 (0.70-5.32), respectively, for rotavirus-associated infection and diarrhoea. Restricted to the rotavirus season, the female-male IRRs for rotavirus infection and diarrhoea were 2.56 (1.17-5.63) and 2.63 (0.94-7.34), respectively. The female-male IRR for rotavirus-associated diarrhoea differed significantly among BCG and DTP recipients (p=0.02). Infections with enteropathogens not associated with diarrhoea were associated with lower female-male IRRs after BCG of 0.82 (0.55-1.23) and higher female-male IRRs after DTP vaccination of 1.32 (1.03-1.70) for primary infection (p=0.05). Though there were few infections with other diarrhoea-causing enteropathogens, these were also associated with a lower female-male IRR after BCG of 0.62 (0.26-1.52) and a higher female-male IRR after DTP vaccination of 1.51 (1.04-2.20) for all infection. CONCLUSION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with lower risk for girls, whereas, DTP is associated with higher risk for girls relative to boys.

BCG Vaccine↗

PubMed2006

Community cohort study of Cryptosporidium parvum infections: sex-differential incidences associated with BCG and diphtheria-tetanus-pertussis vaccinations.

OBJECTIVE: Community studies in West Africa have suggested that routine vaccinations may have sex-differential non-targeted effects, the female-male mortality ratios being increased after receiving diphtheria-tetanus-pertussis (DTP) vaccination and reduced after administration of BCG or measles vaccine (MV). Using an existing data set, we examined whether vaccinations were associated with gender-differential incidences of Cryptosporidium parvum infection. METHODS: Two hundred children had been recruited shortly after birth and followed until 2 years of age or until follow-up was interrupted by a war. We performed weekly morbidity interviews and collected stool specimens, irrespective of whether the children had diarrhoea. Vaccination status for each child was classified according to the most recent vaccination with BCG, DTP, or MV. FINDINGS: The female-male incidence rate ratio (IRR) for Cryptosporidium infection among children who had received BCG as their last vaccine was 0.0 (95% CI: 0-3.49). However, among those who had received DTP as their last vaccine, the female-male IRR was 6.25 (2.06-18.9) for Cryptosporidium infection and 3.60 (0.91-14.2) for Cryptosporidium-associated diarrhoea. The female-male IRRs for Cryptosporidium infection differed significantly among BCG and DTP recipients (p=0.01). Among children who had received measles as their last routine vaccine, the female-male IRR was 1.57 (0.60-4.11) for Cryptosporidium infection and 0.98 (0.28-3.52) for Cryptosporidium-associated diarrhoea. The female-male IRRs for Cryptosporidium infection differed among DTP and MV recipients (p=0.02). For girls, early DTP vaccination compared with late or no DTP vaccination was associated with increased incidence rate of Cryptosporidium infection (IRR=4.23 (1.04-17.2)). For girls, the incidence rate decreased when they received MV. INTERPRETATION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with a low risk for girls relative to boys, whereas DTP is associated with a high female-male IRR of C. parvum infection.

Animals↗

PubMed2006

The burden of rotavirus diarrhea in Khanh Hoa Province, Vietnam: baseline assessment for a rotavirus vaccine trial.

BACKGROUND: In Vietnam, rotavirus is seen as a priority disease because studies have demonstrated that >50% of children hospitalized for treatment of diarrhea have rotavirus as the pathogen. To anticipate the availability of new vaccines, we have examined our field area in Nha Trang, Khanh Hoa Province, Vietnam, as a potential site to conduct a field trial of a future rotavirus vaccine. METHODS: Data from a population census, incidence rates of diarrhea from a previous cholera vaccine trial and hospitalization rates from computerized records collected from the 2 main hospitals in the province were reviewed to estimate the burden of rotavirus-related diarrhea that might be expected during a field trial of a rotavirus vaccine. RESULTS: For a birth cohort of approximately 5000 children, we would expect approximately 2500 clinic visits and 650-850 hospitalizations for treatment of diarrhea, of which approximately 375-425 would be attributable to rotavirus. For the Vietnamese birth cohort of 1,639,000 children, these numbers translate into approximately 820,000 clinic visits, 122,000-140,000 hospitalizations and 2900-5400 deaths annually attributable to rotavirus-related diarrhea. CONCLUSIONS: Vietnam is an early adaptor of new vaccines, has high national coverage rates (>85%) for childhood immunization and receives international donor support for the introduction of new vaccines. We found the epidemiologic features of rotavirus in rural Vietnam to be more similar to those of rotavirus in a developed country than to those of rotavirus in India or Bangladesh.

Child, Preschool↗

PubMed2006

Diarrhea- and rotavirus-associated hospitalizations among children less than 5 years of age: United States, 1997 and 2000.

OBJECTIVE: A new rotavirus vaccine may be licensed in the United States in early 2006. Estimates of the burden of severe rotavirus disease, particularly hospitalizations, will help evaluate the potential benefits of a national rotavirus immunization program. DESIGN: The Kids' Inpatient Database, a robust sample of 10% of the uncomplicated births and 80% of other pediatric discharges was used to estimate the number and rate of diarrhea- and rotavirus-associated hospitalizations among US children <5 years of age in 1997 and 2000. RESULTS: In 1997 and 2000, diarrhea was coded in 13% of all childhood hospitalizations, for an estimated cumulative incidence of 1 diarrhea hospitalization per 23 to 27 children by age 5. Most diarrhea-associated hospitalizations (62%) were coded as unspecified etiology, and 35% as viral. Rotavirus was the most common pathogen recorded for 18% and 19% of diarrhea-associated hospitalizations in 1997 and 2000, respectively. Diarrhea-associated hospitalizations coded as unspecified or viral exhibited a marked winter peak similar to that of hospitalizations coded as rotavirus, suggesting that the rotavirus-specific code captures a fraction of all rotavirus hospitalizations. Using indirect methods, we estimated that rotavirus was associated with 51142-60155 and 46839-56820 hospitalizations in 1997 and 2000, respectively. By these estimates, rotavirus is associated with 4% to 5% of all childhood hospitalizations, and 1 in 67 to 1 in 85 children will be hospitalized with rotavirus by 5 years of age. CONCLUSIONS: Diarrhea is an important cause of hospitalization in US children, and rotavirus is the most important etiology. Disease burden estimates have remained stable during the past decade. An effective rotavirus vaccine will likely reduce substantially the burden of severe rotavirus disease, estimated to account for 4% to 5% of all hospitalizations and approximately 30% of hospitalizations for watery diarrhea among children <5 years of age.

Child, Preschool↗

PubMed2005

Health care costs of diarrheal disease and estimates of the cost-effectiveness of rotavirus vaccination in Vietnam.

BACKGROUND: Rotavirus disease causes a significant health and economic burden worldwide. Several rotavirus vaccines may soon be available for use. A country's decision to introduce these vaccines will depend on its rotavirus disease burden, on the cost of the vaccine, and on the results of an economic assessment of the cost and effectiveness of a rotavirus vaccination program. METHODS: Data on medical and nonmedical direct costs and indirect costs were established in Khanh Hoa Province, Vietnam, and extrapolated to national estimates on the basis of the birth cohort in 2004. The main outcome measures were economic burden and cost-effectiveness ratio (United States dollars per disability-adjusted life-year averted and dollars per life saved) of vaccination. RESULTS: The disease burden is equivalent to an economic burden of an estimated 3.1 million US dollars in medical direct costs, 685,000 US dollars in nonmedical direct costs, and 1.5 million US dollars in indirect costs. From a societal perspective, treatment of rotavirus disease costs an estimated 5.3 million US dollars per year. From the health care system perspective, universal vaccination of infants at a cost of < or = 7.26 US dollars/vaccine dose would be a cost-effective public health intervention, according to the World Bank cost-effectiveness standard for low-income countries (140 US dollars/disability-adjusted life-year). CONCLUSIONS: Vaccination can effectively reduce the disease burden and health care costs of rotavirus-specific diarrhea in Vietnam.

Child, Preschool↗

PubMed2005

Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs.

The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.

Animals↗

PubMed2005

Epidemiological profile and burden of rotavirus diarrhea in Vietnam: 5 years of sentinel hospital surveillance, 1998-2003.

For 5 years, we have conducted sentinel surveillance for rotavirus at 6 hospitals in 4 cities in Vietnam. Stool samples obtained from >10,000 children <5 years old who were admitted to the hospital with diarrhea have been screened for rotavirus. Overall, 55% of samples were positive, and there was little variability in rates of detection of rotavirus between sites (44%-62%). In Vietnam, the characteristics of rotavirus infection more closely resemble those seen in developed countries, rather than those seen in developing countries: children become infected at an older age, the percentage of stool samples in which rotavirus is detected is extremely high, and the rotavirus strains appear to be the common types, with fewer mixed infections occurring. It is estimated that 5300-6800 children <5 years old die of rotavirus infection each year in Vietnam, representing 8%-11% of all deaths in this age group (cumulative risk per child by age 5 years, 1 in 200 to 1 in 285). Additional studies are ongoing to document the economic cost of the disease and to assess the burden of both fatal cases and milder cases of disease. Study outcomes will provide information for future testing and potential use of a rotavirus vaccine.

Child, Preschool↗

PubMed2005

Rotavirus vaccines: targeting the developing world.

For the past 2 decades, rotavirus infection, the most common cause of severe diarrhea in children, has been a priority target for vaccine development. This decision to develop rotavirus vaccines is predicated on the great burden associated with fatal rotavirus disease (i.e., 440,000 deaths/year), the firm scientific basis for developing live oral vaccines, the belief that increased investment in development at this time could speed the introduction of vaccines in developing countries, and the appreciation that implementation of a vaccine program should result in a measurable decrease in the number of hospitalizations and deaths associated with rotavirus disease within 2-3 years. RotaShield (Wyeth-Ayerst), the first rotavirus vaccine licensed in the United States, was withdrawn after 9 months because of a rare association of the vaccine with the development of intussusception. In the developing world, this vaccine could still have had a measurable effect, because the benefits of preventing deaths due to rotavirus disease would have been substantially greater than the rare risk of intussusception. Two live oral vaccines being prepared by GlaxoSmithKline and Merck have completed large-scale clinical trials. The GlaxoSmithKline vaccine has been licensed in Mexico and the Dominican Republic, and the Merck vaccine could be licensed in the United States within 1 year; several other candidate vaccines are in earlier stages of testing. However, many challenges remain before any of these vaccines can be incorporated into childhood immunization programs in the developing world. First, vaccine efficacy, which has already been demonstrated in children in industrialized and middle-income countries, needs to be proven in poor developing countries in Africa and Asia. The safety of vaccines with regard to the associated risk of intussusception must be demonstrated as well. Novel financing strategies will be needed to ensure that new vaccines are affordable and available in the developing world. Decision makers and parents in developing countries need to know about this disease that has little name recognition and is rarely diagnosed. Finally, for the global effort toward the prevention of rotavirus disease to be successful, special efforts will be required in India, China, and Indonesia, because one-third of all deaths due to rotavirus disease occur in these countries, and because these countries depend almost entirely on vaccines manufactured domestically.

Administration, Oral↗

PubMed2005

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↗

PubMed2005

A national survey of severe influenza-associated complications among children and adults, 2003-2004.

This report summarizes findings of a national survey conducted among infectious diseases consultants to assess complications associated with influenza during the 2003-2004 influenza season. The survey identified severe complications, including secondary infection with Staphylococcus aureus and deaths among children and adults, as well as perceived shortages in rapid diagnostic tests and influenza vaccine.

Adolescent↗

PubMed2004

Rotavirus vaccines and the prevention of hospital-acquired diarrhea in children.

Rotavirus, the major cause of severe acute dehydrating gastroenteritis in children less than 5 years of age, is responsible for an estimated 20-50% of all hospitalizations for diarrhea and approximately 440,000 deaths annually, primarily in the developing world. Rotavirus vaccines are considered the most promising means for disease prevention. While the prime rationale for developing rotavirus vaccines has been the enormous burden of rotavirus infection leading to severe and fatal disease, a secondary benefit may be the prevention of nosocomial rotavirus diarrhea. We have reviewed the burden of intra-hospital-acquired rotavirus infections from several countries and found that in the United States alone, as many as 25% of rotavirus hospitalizations or approximately 16,000-18,000 hospitalizations each year might be due to rotavirus infections acquired within hospitals. To countries with low rotavirus-associated mortality, prevention of these infections and the resulting economic savings therefore represent an important secondary goal. Several rotavirus vaccines are in development, and two candidates are currently being tested in large-scale safety and efficacy trials. Development of safe and effective rotavirus vaccines will protect children worldwide against the severe consequences of rotavirus infections including prolonged hospitalizations for nosocomially acquired infections.

Child, Preschool↗

PubMed2003

Cohort study of Guinean children: incidence, pathogenicity, conferred protection, and attributable risk for enteropathogens during the first 2 years of life.

We recruited 200 children shortly after birth and collected stool specimens weekly, irrespective of whether the children had diarrhea, until up to 2 years of age. All children were recruited during the first year of the study and were monitored for a median of 18.4 months. To measure pathogenicity, the odds ratio for diarrhea, adjusted for age, sex, and coinfections with other enteropathogens, was determined by logistic regression. Standard estimation of the population attributable risk indicated that rotavirus, enterotoxigenic Escherichia coli that produced only the heat-stable toxin ST, Isospora spp., Cryptosporidium parvum, Shiga toxin (Stx)-producing E. coli (STEC), and Shigella spp. or enteroinvasive E. coli were the most important contributors to diarrhea in this population. Stx2- but not Stx1-producing STEC strains were pathogenic. Enteroaggregative E. coli, diffusely adherent E. coli, and attaching-and-effacing E. coli strains, which were the most commonly isolated microorganisms, were not associated with diarrhea. For most of the microorganisms, primary infections did not confer protection against reinfection with the same organism, but some conferred protection against diarrhea from reinfection.

Age Factors↗

PubMed2002

Enterotoxigenic Escherichia coli infections and diarrhea in a cohort of young children in Guinea-Bissau.

In an effort to describe the natural history of enterotoxigenic Escherichia coli (ETEC) infection and diarrhea, 200 children in Guinea-Bissau, West Africa, were followed up from birth until up to age 2 years with weekly stool specimen collection, regardless of whether the children had diarrhea. ETEC isolates were tested for the presence of the porcine and human heat-stable toxins (STp and STh), the heat-labile toxin (LT), and 18 of 21 known colonization factors (CFs). The rate of primary infections increased substantially after age 3 or 6 months (depending on the type of ETEC causing the infection). The pathogenicity of STh-containing ETEC was substantially higher than that of STp-containing ETEC, and STp and STh were associated with separate sets of CFs. Small epidemics were observed, mainly caused by STh-containing ETEC. The difference in epidemic propensity, CF association, and pathogenicity suggests that STh- and STp-containing ETEC represent 2 different groups of human ETEC. Vaccines should primarily target STh-containing ETEC.

Cohort Studies↗

PubMed2002

Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau, west Africa.

To study the natural history of rotavirus infection and to determine the protection it confers against reinfection and diarrhea, 200 newborns in Guinea-Bissau were prospectively followed for up to 2 years. Rotavirus was detected in stool specimens collected weekly. By age 2 years, the incidence of primary rotavirus infection was 74%. In the first 3 months of life, 17% of the infections were diarrhea associated, compared with 60% at 9-11 months; after age 18 months, all infections were asymptomatic. A primary infection conferred 52% (95% confidence interval [CI], 16% to 73%) and 70% (95% CI, 29% to 87%) protection against subsequent rotavirus infection and rotavirus diarrhea, respectively. The protection was 66% (95% CI, 24% to 85%) against reinfection within the same epidemic, compared with 34% (95% CI, -29% to 67%) against reinfection in any subsequent epidemic. The high level of protection against symptomatic rotavirus infection provides an important incentive for development of a rotavirus vaccine.

Cohort Studies↗

PubMed2002

Rotavirus particles can survive storage in ambient tropical temperatures for more than 2 months.

Typing and in vitro cultivation of rotavirus-positive human stool samples stored unintentionally at ambient tropical temperatures for 2 1/2 months showed that rotavirus is stable and may still be infectious in vitro. This indicates that stool specimen collection for rotavirus studies can be performed in areas and settings where reliable cold storage is not available. The retained infectivity of rotavirus particles underscores the need for safe systems for disposal of feces, in particular in developing countries where rotavirus is a major cause of childhood mortality.

Feces↗

PubMedDate not supplied

Rotavirus typing methods and algorithms.

Vaccination is the current strategy for control and prevention of severe rotavirus infections, a major cause of acute, dehydrating diarrhoea in young children worldwide. Public health interventions aimed at improving water, food and sanitation are unlikely adequately to control the disease. The development of vaccines against severe rotavirus diarrhoea is based upon homotypic or heterotypic protection provided against either a single common G serotype (monovalent vaccines) or against multiple serotypes (multivalent vaccines). Rotavirus strain surveillance has a high priority in disease control programmes worldwide. The continued identification of the most common G and P serotypes for inclusion in vaccines is an important priority. And subsequent to the introduction of a vaccine candidate, not only monitoring of circulating strains is recommended, but also surveillance of potential reassortment of animal rotavirus genes from the vaccine into human rotavirus strains is critical. Conventional methods used in the characterisation of rotavirus strains, such as enzyme immunoassay serotyping and reverse-transcription PCR-based genotyping often fail to identify uncommon and newly appearing strains. The application of newer molecular approaches, including sequencing and oligonucleotide microarray hybridisation, may be required to characterise such strains. The present paper presents a brief overview of the variety of standard methods available, followed by suggestions for a systematic approach for routine rotavirus strain surveillance as well as for characterisation of incompletely typed rotavirus strains. Improved detection and characterisation of incompletely typed strains will help to develop a comprehensive strain surveillance that may be required for tailoring effective rotavirus vaccines.

Algorithms↗