Rotavirus Infection In Infants Research Articles

New drug and biological product approvals, 2006

FDA last year cleared for marketing 32 new molecular entities (NMEs) and new biological products. Some of the more notable new products are described below. A table listing the indications for NMEs and new biological products appears in the table on page 344. Nearly a third of the new agents that won FDA approval in 2006 are indicated for the treatment or prevention of infectious diseases, mostly those caused by viruses. These products include three vaccines from Merck: Gardasil, which was licensed in June for the prevention of cervical cancer and related conditions caused by human papillomavirus; RotaTeq, licensed in February to prevent rotavirus infection in infants and young children; and Zostavax, licensed in May for the prevention of shingles. Public health experts believe Gardasil could dramatically cut cervical cancer deaths if the vaccine comes into wide-spread use. But at an initial list price of $120 per dose, the three-shot series is financially out of reach in the developing world, where cervical cancer is a major cause of death among women. RotaTeq, with a list price of about $120 for a three-dose series, would likewise be too expensive for widespread use in the nations that are most severely affected by rotavirus infections.

Rotavirus Infection in Infants and Young Children

ABSTRACTRotaviruses are the major cause of severe gastroenteritis in infants and young children worldwide. The aim of the present study was to determine (1) the involvement of rotavirus in acute gastroenteritis (AGE) in children up to 3 years of age in geographical region of the study area, (2) the seasonal prevalence of rotavirus-related AGE and (3) the presence of asymptomatic rotavirus infection in children attending day care centers. A two-year retrospective study was carried out on 250 children with AGE aged 6 months to 3 years. Ninety children were hospitalized with pronounced disease symptoms, and 160 children with milder symptoms received ambulatory treatment. The investigation included 860 healthy children attending day care centers in Nis as well. A single stool sample was taken from each child for analysis. The samples were identified as rotavirus positive by antigen detection strategies, including latex agglutination (LA) tests. Out of 250 episodes of acute gastroenteritis 68 (27.20%) were associated with rotavirus antigen detection. Of 160 children with episodes of AGE treated ambulatory, rotavirus antigen was detected in 30 (18.75%). Of 90 children hospitalized with more severe AGE, higher percentage of rotavirus antigen-positive was recorded in 38 (42.22%). In the group of 860 healthy children attending day care centers in Nis, asymptomatic rotavirus infection was confirmed in 48 children (5.58%). The highest prevalence of rotavirus infection was observed in the period October-December (41.17%), and the lowest in the summer months July-September (14.71%). Rotaviruses are involved in a high percentage in the etiology of AGE in geographical region of the study area.

Human group C rotaviruses identified in Kenya

Rotavirus is associated with acute infantile gastro-enteritis in infants and young children worldwide. Rotavirus is associated with the high cases of morbidity and mortality and it is estimated that up to 650,000 deaths in young children occur annually in the less developed countries. Approximately a quarter of these deaths occur in African children yet minimal data exist on the circulating rotavirus strains in Africa. To characterise the circulating rotavirus strains in Kenya. A prospective study to investigate rotavirus infection in infants and young children with acute diarrhoea in different areas of Kenya. Between September 2001 and February 2002, 119 faecal specimens were collected from children aged between 1 and 60 months with acute infantile gastro-enteritis. Faecal samples were collected from clinics around Nairobi and its suburbs including Karen, Ngong, Ongata Rongai. Faecal samples were collected from 119 infants and young children with diarrhoea and were analysed by commercial ELISA and polyacrylamide gel electrophoresis (SDS-PAGE) to identify possible non-group A rotaviruses. Extraction of any potential rotavirus double-stranded RNA from faeces and characterisation by SDS-PAGE showed the presence of human group C rotaviruses. Examination of these samples with a commercial ELISA assay for the presence of group A rotavirus antigen showed that 13 specimens (11%) were positive. An analysis of all stool specimens was performed by polyacrylamide gel electrophoresis to identify possible non-group A rotaviruses. Extraction of any potential rotavirus double-stranded RNA from faeces and characterisation by SDS-PAGE showed the presence of human group C rotaviruses. This is the first report of group C rotaviruses in Kenya. Further studies are underway to continue the surveillance of rotavirus strains in Kenya; as this information will be useful in planning rotavirus vaccine trials in Africa.

Circulation of the novel G9 and G8 rotavirus strains in Nigeria in 1998/1999.

An epidemiological survey investigating the prevalence of rotavirus infection in infants and young children with acute diarrhoea was undertaken in Jos State, Nigeria, between January 1998 and April 1999. In total, 672 faecal specimens were collected from children aged between 1 and 60 months with acute infantile gastroenteritis. The 10-20% stool suspensions were examined by an ELISA for the presence of group A rotavirus antigen (Rotavirus IDEIA, Dako, UK). Only 116 specimens (17.3%) were positive for the group A rotavirus antigen detected by this ELISA. The rotavirus-positive specimens were analysed with monoclonal antibodies specific for rotavirus VP6 subgroup I and II, and for VP7 serotypes G1-G4, G8, and G9. Of the rotavirus strains that could be subgrouped, VP6 subgroup I and II strains circulated at similar levels. Amongst the strains that could be serotyped, VP7 G9 strains predominated occurring in 17 cases, with G3 (n = 10) and G1 (n = 9) strains occurring in lower numbers. Four G8 strains were detected and only one G2 and no G4 strains were identified. This report extends the description of the global distribution of G9 rotavirus strains.

VP6 subgroup and VP7 serotype of human rotavirus in Zaria, northern Nigeria.

A survey of rotavirus infection in infants and young children with acute diarrhoea was undertaken in Zaria, northern Nigeria during 1997 and 1998. In total, 375 faecal specimens were collected from children aged between 1 and 60 months and 122 specimens from age-matched control children without diarrhoea. Fourteen specimens were collected from neonates in the University Teaching Hospital. Rotavirus antigen was detected in 61 diarrhoeal and four control specimens; four neonates were shedding rotavirus. Polyacrylamide gel electrophoresis of the viral genome showed the presence of five strains of rotavirus with long RNA electropherotypes and one short pattern. The rotavirus VP6 subgroup was determined by monoclonal antibodies specific ELISA and showed that subgroup II strains predominated (72 vs. 9.8 per cent), while eight strains could not be subgrouped and three did not react at all. Examination of the VP7 serotype showed G1 and G3 strains circulating at similar levels (29 and 25 per cent), but no serotype G2 nor G4 strains were identified. G1/G3 'mosaic' virus strains circulated commonly (10 per cent).

Rotavirus serotypes: classification and importance in epidemiology, immunity, and vaccine development.

The development and implementation of safe and effective vaccines to prevent the enormous health burden of rotavirus-associated disease is a global public health goal. Human rotaviruses, the major aetiological agents of severe infantile diarrhoea worldwide, display surprisingly diverse and complex serotypic specificities. Ten VP7 serotypes and 7 VP4 serotypes have so far been detected. An increasing number of observations, obtained from analyses of (i) natural rotavirus infections in infants and young children, (ii) experimental rotavirus infections in laboratory animals, and (iii) extensive rotavirus vaccine field trials performed in different populations of various parts of the world, appears to support the concept that serotype-specific antibodies to rotaviruses play an important role in protection against rotavirus-associated illnesses. Thus, the first licensed rotavirus vaccine (RRV-based quadrivalent vaccine) was designed to cover the epidemiologically important VP7 serotype 1, 2, 3, and 4.

Passive immunity against rotavirus in infants.

Passive immunity against a variety of gastrointestinal infections, using orally administered human antibodies, has been tried in a number of clinical trials. Recently, antibodies from other species such as cows and chickens, which have shown efficacy in experimental animal systems, have also been tried in humans. This review summarizes published data on the use of immunoglobulin-containing preparations for prophylaxis and therapy against rotavirus infections in infants and children, and directions for their future use are suggested.

Rotavirus infection in infants as protection against subsequent infections: Velazquez FR, Matson DO, Calva JJ, Guerrero ML, Morrow AL, Carter-Campbell S, et al. N Engl J Med 1996;335:1022–8

Rotavirus infection in infants as protection against subsequent infections: Velazquez FR, Matson DO, Calva JJ, Guerrero ML, Morrow AL, Carter-Campbell S, et al. N Engl J Med 1996;335:1022–8

Rotavirus infection in infants as protection against subsequent infections.

Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.

Rotavirus gastroenteritis in infants aged 0–6 months in Melbourne, Australia: Implications for vaccination

The aim of this study was to determine the occurrence of rotavirus infection in infants under 6 months of age who were admitted to hospital in a developed country for treatment of gastroenteritis. Between April 1980 and April 1990, 595 such infants were admitted to the infectious diseases ward at the Royal Children's Hospital, Melbourne, Australia. Faecal specimens were collected within 6 h of admission and were tested for viral, bacterial and protozoal enteric pathogens. Rotaviruses of several serotypes were found in specimens from 15.1% of the infants, adenoviruses in 12.4% and other pathogens in 10.8%. Rotaviruses were found equally often in infants in each 1 month age group. No pathogens were able to be identified in 61.7% of cases. These results show that rotavirus is an important pathogen in infants under 6 months of age who are admitted to hospital with gastroenteritis. Rotavirus vaccination will need to be given during the first 1-3 months of life in developed countries, as is recommended for developing countries. The large group in whom no pathogens were isolated requires further consideration.

Preponderance of IgM from blood lymphocytes in response to infantile rotavirus gastroenteritis.

Immune responses triggered by acute rotavirus infection in infants are poorly defined. To obtain indirect evidence as to gut immune response to rotavirus, the solid phase enzyme linked immunoassay (ELISPOT) of immunoglobulin and specific antibody secreting cells among circulating blood lymphocytes was used. Seventeen well nourished patients from seven to 25 months of age were studied during the peak of rotavirus infection, and in convalescence. A transient but distinct immunoglobulin secreting cell response in IgM and IgG, but not in IgA, classes was found during the diarrhoeal phase. This response included a quantitatively prominent activation of specific antibody secreting cells against rotavirus in the IgM class, mean (95% confidence interval (CI)) 82 (32, 210)/10(6) cells v 8 (4, 17)/10(6) cells in convalescence, p = 0.01. The response in the IgA class was not significant. The results indicate that local immune mechanisms are activated in rotavirus diarrhoea. They further suggest that although IgA is the predominant immunoglobulin operative in the gastrointestinal tract, this may not be the case in infantile rotavirus enteritis.

A prospective study of rotavirus infection in infants and young children.

Diarrhea in neonates, followed as a cohort, and their families wasstudied prospectively. The families were followed for an average of 16.3 months. Stool and serum specimens were obtained at least every three months. Stool specimens were examined for viruses by electron microscopy and cultured for enteropathogens, and serum specimens were tested for antibodies to rotavirus and Norwalkvirus. During the study, 237episodes of gastroenteritis were observed in 104 infants and their 62 siblings. Rotavirus, detected 82 timesin 72 children, wasby far the most common enteropathogen. It was associated with gastrointestinal symptoms in 72% (with diarrhea in 65%). Rotavirus diarrhea occurred mostly in winter months and was significantly more frequently associated with respiratory symptoms than were diarrheas with other etiologies. Rotavirus infection was uncommon in the first six months of life, but by two years of age, 62% of the infants had had at least one infection. Neither breast feeding nor the presence of antibody to rotavirus in cord blood appeared to be protective.

Human rotavirus infection in infants and young children with intussusception

Human rotavirus was detected by electron microscopy in 11 of 30 infants and young children with intussusception (37% of subjects under study). Serologic complement fixation tests revealed evidence of infection with the rotavirus in 70% of the patients examined who eliminated the rotavirus in their stools. These results indicate that human rotavirus, in addition to adenovirus, may be an infectious agent causing intussusception in infants and young children.