An unpassaged, safety-tested strain (CJN) of human rotavirus from a stool specimen of a hospitalized child was administered orally to 62 adult volunteers for determination of the dose required to produce infection with or without illness. Subjects ingested doses ranging from 9 X 10(-3) to 9 X 10(4) focus-forming units in buffered salt solution after consumption of 50 ml of 4% NaHCO3. The amount of virus in the inoculum required to cause infection (shedding of virus, seroconversion, or both) in study subjects was comparable to the minimum detectable in cultures of primary monkey kidney cells. Seventeen of 30 infected subjects became ill with doses equivalent to that required for infection. Although the preinoculation titers of serum neutralizing antibody to the challenge virus in study subjects ranged from less than 1:2 to 1:1,600, the concentration of serum antibody could not be correlated with protection from infection or illness in subjects given an infectious dose of virus.
Effects of preinoculation rotavirus antibody titers on the probability of infection and illness were evaluated in adults challenged orally with different doses of a virulent human rotavirus (CJN strain). Preinoculation titers considered were serum neutralizing antibody, serum rotavirus IgA, serum rotavirus IgG, jejunal neutralizing antibody, jejunal rotavirus IgA, and stool rotavirus IgA. Doses of virus of either 9 x 10(1) or 9 x 10(3) focus-forming units were administered to 19 subjects each. Twenty-six were infected; 15 experienced illness. The probability of either outcome was unrelated to dose. Stool rotavirus IgA titers could not be correlated to either infection or illness, but the mean titers of the other five antibodies were significantly or nearly significantly lower in subjects infected or ill, when compared with those negative for either outcome. When analyzed by stepwise logistic regression, only serum rotavirus IgG remained significantly (P = .005) related to the probability of infection, and only jejunal neutralizing antibody remained significantly (P = .01) related to the probability of illness.
A model was developed to examine the effects of disinfectants on the transmission of infectious rotavirus from a dried surface to humans. The initial experiments were designed to find a method of preserving rotavirus infectivity during drying. Culture-adapted human rotavirus (CJN strain) was dried at room temperature in different organic suspensions, including fecal matter, several laboratory media, and nonfat dry milk (NDM). Recoveries of infectious virus were then compared. Fecal matter provided little protection in this study relative to distilled water, but the other suspensions were quite protective, especially NDM, which consistently allowed recoveries of >50%. When 103 focus-forming units of unpassaged CJN virus were dried in NDM and administered to subjects who licked the dried material, 100% (8 of 8) became infected. The effect of Lysol brand disinfectant spray (LDS) was next examined. Although NDM provided some protection against inactivation by LDS, spraying under conditions recommended by the manufacturer consistently caused the CJN virus titer to decrease >5 loglo. Consumption of CJN virus (103 focus-forming units) sprayed with LDS caused no infection in 14 subjects, whereas 13 of 14 subjects who consumed the unsprayed virus became infected (P < 0.00001). The methods developed in this study could be used to test the effects of other disinfectants on the spread of infectious rotavirus from inanimate surfaces to humans.
A two-part study of echovirus-12 was done in volunteers. In the first part the human infectious dose of the virus was determined in 149 healthy adults with undetectable serum antibody, each of whom drank 0-330,000 plaque-forming units (pfu) of virus in 100 ml of nonchlorinated water. Infection was defined as fecal shedding of virus or significant (fourfold or greater) increases in serum antibody titer. The HID50 (i.e., the dose required for infection of 50% of the volunteers) was 919 pfu. Through statistical analysis of the data by probit transformation, a 1% human-infectious dose of 17 pfu was predicted. These results were used in the second portion of the study to determine the effect of previous infection on the infectious dose. Previously infected volunteers (those with neutralizing serum antibody) were given a dose of echovirus-12 (1,500 pfu) that had been found to infect 60% of persons with undetectable serum antibody. The presence of serum antibody caused no significant change in the percentage of volunteers infected by this dose. Furthermore, the concentration of serum antibody did not affect the rate of infection or the duration of viral shedding. These results indicate that previous infection with echovirus-12 does not provide lasting protection against reinfection.
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