Lancet. 1996 Jul 6;348(9019):17-24.
Repeat BCG vaccination is standard practice in many countries for prevention of tuberculosis and leprosy, but its effectiveness has not been evaluated. The addition of Mycobacterium leprae antigens to BCG might improve its effectiveness against leprosy. A double-blind, randomised, controlled trial to evaluate both these procedures was carried out in Karonga District, northern Malawi, where a single BCG vaccine administered by routine health services had previously been found to afford greater than 50% protection against leprosy, but no protection against tuberculosis.
Between 1986 and 1989, individuals lacking a BCG scar were randomly assigned BCG alone (27,904) or BCG plus killed M leprae (38,251). Individuals with a BCG scar were randomly allocated placebo (23,307), a second BCG (23,456), or BCG plus killed M leprae (8102). Incident cases of leprosy and tuberculosis were ascertained over the subsequent 5-9 years.
139 cases of leprosy were identified by May, 1995; 93 of these were diagnostically certain, definitely postvaccination cases. Among scar-positive individuals, a second BCG vaccination gave further protection against leprosy (about 50%) over a first BCG vaccination. The rate ratio for all diagnostically certain, definitely postvaccination cases, all ages, was 0.51 (95% CI 0.25-1.03, p = 0.05) for BCG versus placebo. This benefit was apparent in all subgroups, although the greatest effect was among individuals vaccinated below 15 years of age (RR = 0.40 [95% CI 0.15-1.01], p = 0.05). The addition of killed M leprae did not improve the protection afforded by a primary BCG vaccination. The rate ratio for BCG plus killed M leprae versus BCG alone among scar-negative individuals was 1.06 (0.62-1.82, p = 0.82) for all ages, though 0.37 (0.11-1.24, p = 0.09) for individuals vaccinated below 15 years of age. 376 cases of postvaccination pulmonary tuberculosis and 31 of glandular tuberculosis were ascertained by May, 1995. The rate of diagnostically certain tuberculosis was higher among scar-positive individuals who had received a second BCG (1.43 [0.88-2.35], p = 0.15) than among those who had received placebo and there was no evidence that any of the trial vaccines contributed to protection against pulmonary tuberculosis.
In a population in which a single BCG vaccination affords 50% or more protection against leprosy, but none against tuberculosis, a second vaccination can add appreciably to the protection against leprosy, without providing any protection against tuberculosis.
在许多国家，重复接种卡介苗是预防结核病和麻风病的标准做法，但其有效性尚未得到评估。在卡介苗中添加麻风杆菌抗原可能会提高其预防麻风病的有效性。在马拉维北部的卡龙加区进行了一项双盲、随机、对照试验，以评估这两种方法。此前发现，通过常规卫生服务接种一剂卡介苗可提供超过50%的麻风病防护，但对结核病无防护作用。
1986年至1989年期间，未接种卡介苗留下疤痕的个体被随机分配单独接种卡介苗（27904人）或接种卡介苗加灭活麻风杆菌（38251人）。有卡介苗接种疤痕的个体被随机分配接受安慰剂（23307人）、再次接种卡介苗（23456人）或接种卡介苗加灭活麻风杆菌（8102人）。在随后的5至9年中确定麻风病和结核病的发病病例。
到1995年5月，共确诊139例麻风病病例；其中93例诊断明确，肯定是接种疫苗后发病的病例。在有疤痕的个体中，再次接种卡介苗比首次接种卡介苗对麻风病提供了进一步的防护（约50%）。所有年龄组中，诊断明确、肯定是接种疫苗后发病的病例，接种卡介苗组与安慰剂组的发病率比为0.51（95%可信区间0.25 - 1.03，p = 0.05）。这种益处在所有亚组中都很明显，尽管最大效果出现在15岁以下接种疫苗的个体中（相对危险度 = 0.40 [95%可信区间0.15 - 1.01]，p = 0.05）。添加灭活麻风杆菌并没有提高初次接种卡介苗所提供的防护效果。所有年龄组中，无疤痕个体接种卡介苗加灭活麻风杆菌组与单独接种卡介苗组的发病率比为1.06（0.62 - 1.82，p = 0.82），而15岁以下接种疫苗的个体为0.37（0.11 - 1.24，p = 0.09）。到1995年5月，共确诊376例接种疫苗后发生的肺结核病例和31例腺结核病例。接受再次接种卡介苗的有疤痕个体中，诊断明确的结核病发病率（1.43 [0.88 - 2.35]，p = 0.15）高于接受安慰剂的个体，且没有证据表明任何一种试验疫苗有助于预防肺结核。
在一个群体中，单次接种卡介苗可提供50%或更高的麻风病防护，但对结核病无防护作用，再次接种可显著增加对麻风病的防护，而对结核病无防护作用。
