J G Morris

Safety, infectivity, immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi, 541Ty and 543Ty, as live oral vaccines in humans.

Two Salmonella typhi mutants, 541Ty (Vi+) and 543Ty (Vi-), auxotrophic for p-aminobenzoate and adenine, were evaluated as live oral vaccines. 33 volunteers ingested single doses of 10(8), 10(9), or 10(10) vaccine organisms, while four others received two 2 X 10(9) organism doses 4 d apart. No adverse reactions were observed. Vaccine was recovered from coprocultures of 29 of 37 vaccinees (78%) and from duodenal string cultures of two; repeated blood cultures were negative. The humoral antibody response to S. typhi O, H, Vi, and lysate antigens in serum and intestinal fluid was meager. In contrast, all vaccinees manifested cell-mediated immune responses. After vaccination, 69% of vaccinees overall and 89% of recipients of doses greater than or equal to 10(9) responded to S. typhi particulate or purified O polysaccharide antigens in lymphocyte replication studies but not to antigens of other Salmonella or Escherichia coli. All individuals, postvaccination, demonstrated a significant plasma-dependent mononuclear cell inhibition of wild S. typhi.

Acute diarrhea in Baltimore children attending an outpatient clinic

Acute diarrheal illnesses in Baltimore children younger than 2 years of age attending an outpatient clinic were studied during a 12-month period. One in five acute care visits made to the clinic by children younger than 2 years was for diarrhea, and 5% of diarrhea cases required hospitalization. With the use of comprehensive methodology, a potential etiologic agent was identified in the stool of 105 (43%) of the 246 episodes of diarrhea in cases and in 43 (28%) of the 155 controls. Viral pathogens were found in 26% of episodes, and bacterial pathogens were found in 14%. Only rotavirus, enteric adenovirus and Salmonella were significantly associated with diarrhea. Cases were more likely to have measures of socioeconomic deprivation, such as household crowding, low maternal educational level and low birth weight, when compared to controls. Racial differences in morbidity from diarrheal illnesses were observed but could be attributed to these specific sociodemographic factors. Despite the low mortality caused by infantile gastroenteritis in the United States, it remains an important public health problem. However, even with intensive investigation the etiologies remain largely unknown.

Pediatric diarrhea: the challenge of prevention.

Conditions such as poverty, underdevelopment, and lack of education facilitate the widespread transmission of the pathogens that cause diarrheal disease, dysentery, and enteric fever in young children. Such infections produce high rates of morbidity, mortality, and adverse nutritional consequences in the first 2 years of life. Although rapid socioeconomic development has produced a precipitous decline in mortality due to diarrheal disease in the developed world, such a trend is not likely in developing countries unless alternative measures are pursued. Nonspecific interventions pursued have included oral rehydration therapy to prevent and treat dehydration, promotion of breast feeding, health education to teach maternal technology, and early realimentation to diminish the nutritional consequences of infant diarrhea. In addition, there is reason to be optimistic about the future development of various immunizing agents against the major enteric pathogens. Epidemiologic data support the conclusion that prior natural infection with enterotoxigenic E. coli, Shigella, rotavirus, and V. cholerae OL confers protective immunity. Among the divergent approaches being followed in the development of vaccines against rotavirus are: 1) use of animal rotavirus as possible attenuated strains; 2) attenuating human rotaviruses by passage in tissue culture; 3) development of hybrid reassortant strains by coinfecting tissue cultures with both an animal strain well adapted to tissue culture and a human strain and then selecting a hybrid virus that possesses the human virus neutralization antigen but grows to higher titre in tissue culture; 4) evaluation of rotaviruses isolated from asymptomatic infected neonates in nursery outbreaks for their safety, infectivity, and immunogenicity in older children; 5) cloning a DNA copy of the RNA genus responsible for the neutralization antigens of rotaviruses; and 6) preparation of a synthetic peptide of the critical epitope of the neutralization antigen.

Detection by Immune Electron Microscopy of 27-nm Viral Particles Associated with Community-Acquired Diarrhea in Children

Abstract The proportion of diarrheal illnesses of unknown origin that were associated with small round virus (SRV, 23-38 nm) particles among children <2 years old attending an outpatient clinic in Baltimore was determined. During a 9-month period, stool specimens from 188 patients with acute diarrhea and 108healthy age-matched control children were examined for enteric bacterial pathogens, protozoa, enteric adenovirus, and rotavirus. An enteropathogen was identified in 75 patients (40%) and in 21 controls (20%). A random sample of specimens without an identifiable pathogen wasthen examined for SRV particles by immune electron microscopy (IBM) using commercial human gamma globulin. Viruses of 26-30 nm diameter that were not enteroviruses were detected in specimens from 9 (12.5%) of the 7l patients and 1 (1.8%) of the 53 control subjects (P < .04). Of6 patients with available acute and convalescent sera, 4 demonstrated a significant immune response when tested by IBM. All patients experienced a mild, self-limited (1–3 days) illness. These findings suggest that SRV may be endemic in the Baltimore community and may result in clinically significant diarrheal illnesses.