Albert Z. Kapikian

Observations Questioning a Protective Role for Breast-feeding in Severe Rotavirus Diarrhea

ABSTRACT. To investigate whether breast‐feeding protects children against rotavirus diarrhea (RVD), we compared rates of breast‐feeding by age and enteric pathogens among 2 276 children with diarrhea 0‐4 years of age who attended a diarrhea hospital in Bangladesh. Infants 0‐5 months were less likely to be breast‐fed than children 6‐11 months of age suggesting that some protection against diarrhea with all agents was associated with early breast‐feeding. In every age group studied, breast‐feeding was more common among children with RVD than among children with non‐RYD whereas it was less common among children with cholera and shigellosis. Twenty percent of breast milks consumed by infants less than 1 year of age had high levels of neutralizing activity (>320) to the Wa strain of rotavirus but this activity did not appear to be protective since the 30 infants with RVD consumed milk which had titers that did not differ significantly from those consumed by 44 infants with diarrhea of other cause. Despite the prolonged breast‐feeding which is common in Bangladesh, the mean age of hospitalization with RYD is approximately the same as in countries where the duration of breastfeeding is quite short. None of these 3 independent observations support a protective role for breast‐feeding against rotavirus diarrhea after the first months of life.

Chapter 2 - Detection and Identification by Immune Electron Microscopy of Fastidious Agents Associated with Respiratory Illness, Acute Nonbacterial Gastroenteritis, and Hepatitis A

n Publisher Summaryn n This chapter discusses detection and identification by immune electron microscopy (IEM) of fastidious agents associated with respiratory illness, acute nonbacterial gastroenteritis, and hepatitis A. For Norwalk gastroenteritis and hepatitis A, the IEM technique enabled not only the definitive visualization and identification for the first time of virus-like particles from individuals with these diseases but also enabled researchers to demonstrate for the first time the serological association of an identifiable virus-like agent with each of these diseases. The chapter also explains that a mixture of tobacco mosaic virus (TMV) and anti-TMV rabbit serum resulted in aggregation of the virus particles, whereas by contrast, such aggregation did not occur when the virus reacted with a control normal rabbit serum. T. F. Anderson and W. M. Stanley demonstrated the electron-microscopic specificity of the reaction by observing the lack of such reactivity between TMV and rabbit antiserum to tomato bushy stunt virus; and between tomato bushy stunt virus and anti-TMV rabbit serum.n n

Rationale for the Development of a Rotavirus Vaccine for Infants and Young Children

Vaccinology is a relatively new term, but its very existence reflects the progress in vaccine development. The field of vaccinology embraces the breadth of biology ranging from molecular biologic initiatives to conven-tional, well-established techniques.

CHAPTER 11 – Rotavirus Vaccines

Publisher Summary nThis chapter describes the potential impact of a rotavirus vaccine. It also discusses current knowledge on rotaviruses applicable to vaccine development. Every year, about 1 million infants and young children die as a consequence of rotavirus diarrheal illness. While most of these deaths could be prevented by administration of oral rehydration therapy, this form of treatment is not yet widely implemented in the developing countries of the world. General environmental measures aimed at improving sanitation, water supply, and hygiene have been shown to reduce the occurrence of bacterial diarrhea, but, in contrast, such measures do not appear to influence the spread of rotavirus infection. The prevalence of rotavirus infection is similar in both developing and developed countries. An alternative approach to control rotavirus diarrhea is the development of a rotavirus vaccine. There is a general consensus that a live rotavirus vaccine should be administered orally. This is based on animal studies in which local intestinal antibody played a dominant role in the protection against rotavirus diarrhea.

CLINICAL TRIALS OF RHESUS ROTAVIRUS (REV-1) VACCINE IN YOUNG INFANTS

Live attenuated rhesus monkey rotavirus (RRV-1), cross-reactive with human serotype 3, was evaluated for irrmunogenicity and safety in 6 month-old children. A 1:10 diluted vaccine bulk (approximately 106/ml) given orally induced an antibody response in 21/24 (88%) of the children with high antibody titers. A febrile reaction (over 38°) on days 3 and 4 was seen in 60% of the children, and 20% of the vaccine recipients had some watery stools. It was concluded that the RRV-1 vaccine at the given dose was highly immunogenic but unacceptably reactogenic in the target population (Vesikari et al, J Infect Dis, in press).A second trial of the RRV-1 vaccine, diluted 1:100 from the bulk (approximately 105/ml) was initiated in December 1985 in 2 to 5 month-old children, who are likely to have transplacentally acquired rotavirus antibody. Preliminary analysis of 59 vaccinees indicated that about 15% had a febrile reaction (over 38°) on days 3 and 4. The study will continue as a placebo-controlled protection study over the current rotavirus season until June 1986.