Characterization of Rotavirus Strains Detected in Windhoek, Namibia during 1998-1999

Background. Namibia, located on the southwestern coast of southern Africa, is characterized by vast deserts, limited fresh water, and low population density. Mortality estimates among children <5 of age are 63 deaths per 1000 live-births, with diarrheal diseases contributing to 3% of these deaths. Data on the burden of rotavirus disease and circulating serotypes in Namibia are currently not available. Materials and methods. From May 1998 through December 1999, 815 stool specimens were collected from children <5 years of age who attended the Windhoek State Hospital, Windhoek, Namibia, for diarrhea. Specimens were screened for the presence of rotavirus antigens. Rotavirus-positive specimens were further analyzed to determine electropherotype, subgroup (SG) specificity, and G and P genotypes. Results. Rotavirus was detected in 113 (13.8%) of 815 specimens, with the majority of infections occurring in children <18 months of age. Strains bearing 1 long electropherotype, SGII, and G1P[8] or G1P[6] specificity predominated during the 20-month study period. In addition to the typical winter rotavirus season, a peak in rotavirus infection was also observed during the summer. Conclusions. Serotypes G1P[8], G1P[6], G1P[4], and G2P[4] were found throughout the study period, predominantly in children <18 months of age. The observed summer rotavirus peak coincided with increased rainfall in Namibia and an increase in the diversity of detected serotypes. During the October to December 1999 peak, 2 G9P[6] strains and 1 G8P[4] strain were identified. Expanded and updated information on prevalence of rotavirus infection, circulating serotypes, and burden of disease will be required to enable local government to make decisions on the implementation of rotavirus vaccination in Namibi

Why does the world need another rotavirus vaccine?

A “Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers” was held at the World Health Organization in Geneva, Switzerland on March 28–30, 2006. The purpose was to discuss, evaluate, and weigh the importance of additional rotavirus vaccine candidates following the successful international licensure of rotavirus vaccines by two major pharmaceutical companies (GlaxoSmithKline and Merck) that had been in development for many years. Both licensed vaccines are composed of live rotaviruses that are delivered orally as have been all candidate rotavirus vaccines evaluated in humans. Each is built on the experience gained with previous candidates whose development had either been discontinued or, in the case of the previously licensed rhesus rotavirus reassortant vaccine (Rotashield), was withdrawn by its manufacturer after the discovery of a rare association with intussusception. Although which alternative candidate vaccines should be supported for development and where this should be done are controversial topics, there was general agreement expressed at the Geneva meeting that further development of alternative candidates is a high priority. This development will help insure that the most safe, effective and economic vaccines are available to children in Third World nations where the vast majority of the >600,000 deaths due to rotavirus occur each year. This review is intended to provide the history and present status of rotavirus vaccines as well as a perspective on the future development of candidate vaccines as a means of promulgating plans suggested at the Geneva meeting

Effect of human rotavirus vaccine on severe diarrhea in African infants.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.

Emergence and Characterization of Serotype G9 Rotavirus Strains from Africa

Serotype G9 strains have been detected sporadically and in localized outbreaks in various African countries, including South Africa, Botswana, Malawi, Kenya, Cameroon, Nigeria, Ghana, Guinea-Bissau, Libya, and Mauritius. Serotype G9 strains were analyzed to investigate genogroup characteristics, including subgroup specificity, electropherotype, and P and G genotypes. In addition, the antigenic composition of the South African G9 strains was assessed. African G9 strains were associated with both DS-1-like characteristics and Wa-like characteristics, indicating the predisposition of G9 strains to frequently reassort. Despite these reassortment events, serotype G9 strains appear to maintain antigenic character in the outer capsid protein, as evident with the reaction of the South African G9 strains with the G9-specific monoclonal antibody F45:1. Phylogenetic analysis clustered African G9 strains geographically, regardless of genogroup characteristics, into 1 lineage (IIId). Two groups of G9 strains, originating in India and Japan, were identified in this lineage. Continuous surveillance of circulating rotavirus strains in Africa is vital to prepare for future vaccine implementation on a continent that clearly needs such preventative medicine

Rotavirus Strain Diversity in the Centre Coast of Tunisia from 2000 through 2003

An epidemiological survey investigating rotavirus infection in children was undertaken in the coastal region of Tunisia from January 2000 through September 2003. A total of 309 fecal specimens were screened by enzyme-linked immunosorbent assay and latex agglutination assay for the presence of group A rotavirus antigen. The detection rate was 26.2%. Rotavirus outbreaks showed a temperature-dependant pattern (P= .026) but no significant association with rainfall. Rotavirus strains isolated were analyzed by RNA polyacrylamide gel electrophoresis and were characterized antigenically by monoclonal antibodies to the VP6 subgroup. Eight RNA electropherotypes were identified, with 3 long and 5 short different RNA profiles. Among VP6 typeable strains, all isolates with a long electrophoretic pattern carried the subgroup II specificity, whereas those with a short profile belonged to subgroup I. In total, 48 rotavirus-positive samples were analyzed for G and P typing by reverse-transcription polymerase chain reaction. A total of 8 different G and P combinations were found: G1P[8] (35.7%), G1P[6] (21.4%), G2P[4] (4.8%), G3P[4] (4.8%), G4P[6] (4.8%), G8P[8] (4.8%), G3P[8] (2.3%), and G4P[8] (2.3%). Mixed infections were detected in 19.1% of stool samples. The emergence in Tunisia of unconventional types, such as G8VP7 specificity, highlights the need for a continual survey of the uncommon strains in North Afric

A physics-enabled flow restoration algorithm for sparse PIV and PTV measurements

The gaps and noise present in particle image velocimetry (PIV) and particle tracking velocimetry (PTV) measurements affect the accuracy of the data collected. Existing algorithms developed for the restoration of such data are only applicable to experimental measurements collected under well-prepared laboratory conditions (i.e. where the pattern of the velocity flow field is known), and the distribution, size and type of gaps and noise may be controlled by the laboratory set-up. However, in many cases, such as PIV and PTV measurements of arbitrarily turbid coastal waters, the arrangement of such conditions is not possible. When the size of gaps or the level of noise in these experimental measurements become too large, their successful restoration with existing algorithms becomes questionable. Here, we outline a new physics-enabled flow restoration algorithm (PEFRA), specially designed for the restoration of such velocity data. Implemented as a 'black box' algorithm, where no user-background in fluid dynamics is necessary, the physical structure of the flow in gappy or noisy data is able to be restored in accordance with its hydrodynamical basis. The use of this is not dependent on types of flow, types of gaps or noise in measurements. The algorithm will operate on any data time-series containing a sequence of velocity flow fields recorded by PIV or PTV. Tests with numerical flow fields established that this method is able to successfully restore corrupted PIV and PTV measurements with different levels of sparsity and noise. This assessment of the algorithm performance is extended with an example application to in situ submersible 3D-PTV measurements collected in the bottom boundary layer of the coastal ocean, where the naturally-occurring plankton and suspended sediments used as tracers causes an increase in the noise level that, without such denoising, will contaminate the measurements

Research Article (New England Journal of Medicine) Effect of human rotavirus vaccine on severe diarrhea in African infants

Background: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.Methods: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine — the pooled vaccine group — or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.Results: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus  gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus  gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.Conclusions: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.

Making the Most of Mealtimes (M3): protocol of a multi-centre cross-sectional study of food intake and its determinants in older adults living in long term care homes

Background: Older adults living in long term care (LTC) homes are nutritionally vulnerable, often consuming insufficient energy, macro-and micronutrients to sustain their health and function. Multiple factors are proposed to influence food intake, yet our understanding of these diverse factors and their interactions are limited. The purpose of this paper is to fully describe the protocol used to examine determinants of food and fluid intake among older adults participating in the Making the Most of Mealtimes (M3) study. Methods: A conceptual framework that considers multi-level influences on mealtime experience, meal quality and meal access was used to design this multi-site cross-sectional study. Data were collected from 639 participants residing in 32 LTC homes in four Canadian provinces by trained researchers. Food intake was assessed with three-days of weighed food intake (main plate items), as well as estimations of side dishes, beverages and snacks and compared to the Dietary Reference Intake. Resident-level measures included: nutritional status, nutritional risk; disease conditions, medication, and diet prescriptions; oral health exam, signs of swallowing difficulty and olfactory ability; observed eating behaviours, type and number of staff assisting with eating; and food and foodservice satisfaction. Function, cognition, depression and pain were assessed using interRAI LTCF with selected items completed by researchers with care staff. Care staff completed a standardized person-directed care questionnaire. Researchers assessed dining rooms for physical and psychosocial aspects that could influence food intake. Management from each site completed a questionnaire that described the home, menu development, food production, out-sourcing of food, staffing levels, and staff training. Hierarchical regression models, accounting for clustering within province, home and dining room will be used to determine factors independently associated with energy and protein intake, as proxies for intake. Proportions of residents at risk of inadequate diets will also be determined. Discussion: This rigorous and comprehensive data collection in a large and diverse sample will provide, for the first time, the opportunity to consider important modifiable factors associated with poor food intake of residents in LTC. Identification of factors that are independently associated with food intake will help to develop effective interventions that support food intake.Canadian Institutes of Health Research (CIHR) , The PI is an endowed research chair with the Schlegel-University of Waterloo Research Institute for Aging; half of her salary is provided by this non-profit organizatio

Duality Symmetries and G^{+++} Theories

We show that the non-linear realisations of all the very extended algebras G^{+++}, except the B and C series which we do not consider, contain fields corresponding to all possible duality symmetries of the on-shell degrees of freedom of these theories. This result also holds for G_2^{+++} and we argue that the non-linear realisation of this algebra accounts precisely for the form fields present in the corresponding supersymmetric theory. We also find a simple necessary condition for the roots to belong to a G^{+++} algebra.Comment: 35 pages. v2: 2 appendices added, other minor corrections. v3: tables corrected, other minor changes, one appendix added, refs. added. Version published in Class. Quant. Gra