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Ninety patients with advanced neoplastic diseases were inoculated intramuscularly with the Egypt 101 isolate of West Nile virus, as part of an experimental clinical evaluation of the antineoplastic effect of viruses. The Egypt 19 and Egypt 21 isolates of this same virus were inoculated into three and five patients respectively. This paper describes the clinical course and virology of the resulting infections. Reports concerning antineoplastic effects, serology, and histopathology have been, or will be, published elsewhere.
All three of the Egypt isolates of West Nile virus infected man, as indicated by the presence of virus in blood at three days or later following virus inoculation. No significant differences between the pathogenicity of the three isolates were apparent, but the trials of Egypt 19 and Egypt 21 were too few to warrant definite conclusions. Egypt 21 infection was followed by suggestive clinical evidences of diffuse encephalitis in one patient.
Virus was recovered from blood of 95 per cent of the patients inoculated with Egypt 101. Viremia persisted through day six in 73 per cent, and longer than day twelve in 10 per cent. Virus was not present in feces, urine, or throat washings. Virus was demonstrated in spinal fluid of three patients during infection with Egypt 101 virus. All three of these patients had clinical evidences of encephalitis. Two of the virus isolations from spinal fluid occurred during the period of viremia, but virus was present in spinal fluid of one patient five days after the blood had become virus free. Spinal fluid specimens from 11 other patients did not contain virus during infection with Egypt 101 or Egypt 21 viruses, even at the time of clinical encephalitis (five patients), or during viremia (six patients).
Eighty-nine per cent of patients inoculated with Egypt 101 virus had no clinical evidence of virus disease other than fever, and temperature elevation did not exceed 3°F. in 73 per cent. Eleven per cent of patients had definite or suggestive signs of diffuse encephalitis characterized by twitching and mental confusion and one of the patients also had flaccid paralysis of extremities. Neurologic impairment was transient and recovery was complete in all patients who did not rapidly succumb to their neoplastic disease.
There was a direct correlation between the duration of viremia and the severity of clinical illness. Patients with neoplastic disease of reticulo-endothelial cell origin had a striking predisposition to prolonged viremia and increased severity of clinical illness. Age and sex showed no significant correlation with either duration of viremia or severity of the clinical illness. There was marked individual variation in duration of viremia and severity of illness among patients who received identical inocula.
The distribution of virus in tissues obtained at autopsy was studied in 15 patients who died within four weeks after inoculation of virus. Virus was demonstrated in neoplastic tissue of various histopathologic types. The normal tissues most frequently containing virus were spleen, lymph nodes, liver, and lungs, suggesting distribution determined by reticulo-endothelial cells. Central nervous tissue was only occasionally found to contain virus and there was no consistent anatomical localization of virus within the central nervous system.
1 This work was supported in part by grants from The National Cancer Institute of the U.S. Public Health Service, The Damon Runyon Memorial Fund for Cancer Research, and The American Cancer Society.
2 The authors wish to acknowledge the assistance of Dr. Allyn P. Kidwell, Miss Marie Corazza, and Mr. David Mount for indispensable aid in various phases of this study, and their indebtedness to Drs. Joseph L. Melnick and John Paul for supplying stocks of these viruses.
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