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IMMUNITY STUDIES OF ROCKY MOUNTAIN SPOTTED FEVER

机译:岩石山斑热的免疫性研究

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摘要

From the results of the experiments presented it is evident that in guinea pigs an early administration of immune rabbit serum will suppress the infection; that is, if it is given within the period of incubation, the effect being proportionately greater the earlier the serum is administered. Almost no beneficial effect is observed when the serum is given after the onset of the disease. In the animals inoculated with 10 to 100 M.L.D. the incubation period is shorter than when 1 M.L.D. is injected; nevertheless 1 cc. of the immune serum saved the animals as late as 96 hours from the time of the introduction of the virus into the system. When administered within 24 hours in the case of 100 M.L.D. and within 48 hours in the case of 10 M.L.D., the serum completely neutralized the virus, and the animals escaped infection altogether. On the other hand, the same quantity of the serum only modified the infection into a non-fatal one when given a day or two later. In the animals which were inoculated with 1 M.L.D. the incubation period was a day or two longer, and the neutralizing effect of the serum was much more powerful. Here animals were saved as late as 5, 6, and 7 days and with a much smaller quantity of the serum (0.1 cc.). As to the usefulness of such an immune serum in human cases, the relative susceptibility of man and the guinea pig must first be considered. In a large number of experimental infections carried out with guinea pigs in the past 6 years almost never has a naturally refractory animal been encountered. The mortality is nearly 80 per cent with most strains, although as low as 50 per cent with some. The strain used in the present study caused death in nearly 80 per cent of the animals. Hence the susceptibility of guinea pigs is at least as great as that of man, in whom the mortality in the Bitter Root Valley is estimated to be about 70 per cent. The relative length of the incubation period in guinea pig and in man is another point which requires analysis. In guinea pigs it varies somewhat according to the number of passages, being as short as 3 days when 100 M.L.D. or more of an adapted virus are inoculated. On the other hand, when the infection is the result of 1 M.L.D. or the bite of an infected tick, the incubation period is much longer, being 5, 6, or 7 days in the former and 7 to 8½ days in the latter instance, as with the present strain. In man the infection is brought on by the bite of an infected tick, and the period of incubation varies from 3 to 10 days but is usually 7 days; i.e., it is about the same as in guinea pigs infected with 1 M.L.D. Hence we may regard the susceptibility of man and the guinea pig as nearly equal. The final point to be considered is the quantity of the immune serum that may be recommended for use in human cases. To prevent the infection in a guinea pig weighing 500 gm., 0.1 cc. of the serum was sufficient. This quantity protected the animal against 1 M.L.D. even as late as 5, 6, or 7 days. Calculated on this basis, 16 cc. of the serum would be required for a man weighing 80 kilos (about 160 pounds); that is, 16 cc. of an immune rabbit serum, administered before onset of the disease, should theoretically be sufficient to save a man of average weight against an infection brought about by the bite of an infected tick or by a laboratory accident. It would probably be best to administer the serum intravenously. The titer of the immune serum should be previously determined in guinea pigs, and 1 cc. should neutralize 100 M.L.D. completely and 0.1 and 0.01 cc. render the infection non-fatal. Such a serum is easily produced in rabbits (a rabbit weighing 2,500 gm. will yield 50 to 60 cc. of the serum) and probably will remain active a year or longer when kept at refrigerator temperature.
机译:从给出的实验结果可以明显看出,在豚鼠中尽早给予免疫兔血清可抑制感染。即,如果在温育期内给予,则越早给予血清,效果成比例地更大。在疾病发作后给予血清几乎没有观察到有益的作用。在接种了10至100 M.L.D.潜伏期比1 M.L.D.被注入;但是1 cc。自从将病毒引入系统以来,多达90%的免疫血清为动物挽救了生命。如果是100 M.L.D.,则在24小时内给药。在10 M.L.D.的情况下,在48小时内,血清完全中和了病毒,动物完全逃脱了感染。另一方面,当一两天后给予相同量的血清,感染只会变成非致命性感染。在接种了1 M.L.D.潜伏期要长一两天,血清的中和作用要强大得多。在这里,动物保存的时间最晚为5、6和7天,血清的含量要少得多(0.1 cc)。关于这种免疫血清在人类病例中的有用性,首先必须考虑人与豚鼠的相对易感性。在过去的6年中,使用豚鼠进行的大量实验感染中,几乎从未遇到过天然难治性动物。大多数菌株的死亡率接近80%,有些菌株的死亡率低至50%。本研究中使用的毒株导致近80%的动物死亡。因此,豚鼠的易感性至少与人的敏感性相同,据估计,人在苦根谷中的死亡率约为70%。豚鼠和人的潜伏期的相对长度是需要分析的另一点。在豚鼠中,根据传代次数的不同而有所不同,当100 M.L.D.时短至3天。接种了更多或多种适应病毒。另一方面,当感染是1 M.L.D.或被感染的the叮咬,潜伏期要长得多,与本菌株一样,前者的潜伏期为5、6或7天,后者为7至8½天。在人中,感染是由被感染的tick叮咬引起的,潜伏期从3天到10天不等,但通常为7天。即与感染1 M.L.D.的豚鼠大致相同因此,我们可以认为人与豚鼠的易感性几乎相等。要考虑的最后一点是可能建议用于人类病例的免疫血清的量。为防止重500克,0.1 cc的豚鼠感染。血清足够。此数量可保护动物免受1 M.L.D.即使是5、6或7天也是如此。在此基础上计算得出16毫升。一个体重80公斤(约160磅)的男人将需要50毫升的血清;即16 ​​cc。在疾病发作之前给予免疫兔血清,理论上应足以挽救一个中等体重的人,使其免受感染的tick叮咬或实验室事故引起的感染。静脉内施用血清可能是最好的。免疫血清的滴度应事先在豚鼠中测定,浓度为1 cc。应中和100 M.L.D.完全和0.1和0.01 cc。使感染不致命。这样的血清很容易在兔子中产生(重达2500 gm。的兔子将产生50至60 cc的血清),并且保持在冰箱温度下可能会保持一年或更长时间的活性。

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