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LIVE POLIO IRUS VACCINES

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24<br />

Safety-Laboratory Evidence of Attenuation and Safety<br />

TABLE 10. NEUROVIRULENCE AND VIREMIA AFTER INTRAMUSCULAR INOCULATION OF MONKEYS WITH<br />

VIRULENT AND ATTENUATED <strong>POLIO</strong>V<strong>IRUS</strong>ES AND POLlOV<strong>IRUS</strong> ISOLATES FROM VACCINEES AND CONTACTS<br />

* Par. = paralysis.<br />

Wk. = weakness.<br />

t All 12 monkeys with viremia received Type 2 P, 2 vaccine virus.<br />

: 3 Polio-l.<br />

* * 2 Polio-2 and 19 Polio-3.<br />

shown in the last three columns of the table,<br />

viremia was present on days 2, 3, and 4, being<br />

a relatively common finding when a virulent<br />

strain was inoculated intramuscularly into<br />

monkeys.<br />

The attenuated strains yielded an entirely<br />

different picture. Of 64 monkeys in these tests,<br />

none developed disease, and only 5 showed<br />

lesions, all of these being mild. The pattern of<br />

viremia was also different. Of 36 animals<br />

studied on the second day, 12 were positive; all<br />

12 positives were Type 2. The chief importance<br />

of these data reside in the bottom two rows<br />

of the table-the data pertaining to the isolates.<br />

For the three d+T- isolates, 5 of 6 monkeys<br />

developed disease, and all 6 animals showed<br />

lesions in the spinal cord. For the 21 d+T+<br />

strains, 52 monkeys were used. Seventeen developed<br />

flagrant paralysis, 5 developed weakness,<br />

and 26 of the animals developed lesionsan<br />

attack rate of 50 per cent. As regards<br />

viremia, this was a common finding on the second<br />

day, when 33 of 50 animals were positive,<br />

but tapered off on the fourth day, when only<br />

7 out of 46 animals were positive.<br />

The data on the isolates are shown in greater<br />

detail in Table 11. In general, the pattern<br />

was the same for the different areas-for children<br />

fed during the winter in Houston and<br />

Cincinnati, or from children fed in warmer<br />

climates in Mexico. Paralysis occurred in many<br />

of the monkeys receiving strains with changed<br />

markers. However, a number of d+T+ Type 3<br />

isolates failed to paralyze the injected monkeys,<br />

although they did produce viremia and in this<br />

way differed from the d-T- Type 3 vaccine.<br />

Thus, genetic change as measured by reversion<br />

in the d-T- markers to d+T+ is not always<br />

associated with full intramuscular neurovirulence.<br />

Other factors, as yet unknown, are apparently<br />

also involved. This is further illustrated<br />

in the data in Table 12, which represents<br />

two families fed Type 3 vaccine virus in the<br />

Fox-Gelfand study in New Orleans. The vaccinated<br />

children in two families excreted a T-<br />

virus on the first day and a T± virus on the<br />

second day after the feeding, but later samples<br />

were d+T+. The d+T- specimens from the<br />

vaccinated children failed to produce lesions<br />

or disease in four monkeys although all four<br />

animals developed viremia on day 2, and three on<br />

day 4. In contrast, d+T+ specimens from three

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