Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi
Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi
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DOI：
10.1016/s0140-6736(96)02166-6
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发表时间：
1996-07-06
期刊：
影响因子：
168.9
通讯作者：
Peto, R
中科院分区：
文献类型：
--
作者：
Fine, PEM;Ponnighaus, JM;Peto, R
背景重复接种卡介苗是许多国家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。在卡介苗中加入麻风分枝杆菌抗原可提高其抗麻风效果。在马拉维北方的卡隆加地区进行了一项双盲、随机、对照试验，以评估这两种方法，在那里，以前发现由常规卫生服务机构接种的单一卡介苗对麻风病的保护率超过50%，但对结核病没有保护作用。无卡介菌接种疤痕的患者被随机分为单独卡介菌接种组（27904例）和卡介菌接种加麻风杆菌灭活组（38251例）。有卡介苗疤痕的个体被随机分配安慰剂（23307），第二次卡介苗（23456），或卡介苗加杀死麻风杆菌（8102）。麻风病和结核病的发病病例在随后的5-9 years.Findings确定了139例麻风病，1995年5月，其中93例确诊，明确接种疫苗后的情况。在疤痕阳性个体中，第二次卡介苗接种比第一次卡介苗接种对麻风病有进一步的保护作用（约50%）。BCG组与安慰剂组在所有年龄段的所有确诊、明确接种后病例中的比率为0.51（95%CI 0.25-1.03，p=0.05）。这种益处在所有亚组中都是明显的，尽管最大的效果是在15岁以下接种疫苗的个体中（RR=0.40 [95% CI 0.15-1.01]，p=0.05）。添加杀死的麻风杆菌并不能提高初次接种卡介苗所提供的保护。在瘢痕阴性个体中，BCG+灭活麻风菌与BCG单独治疗的比率为1.06（0.62-1.82，p=0.82），而15岁以下接种者为0.37（0.11-1.24，p= 0.09）。在接受第二次卡介苗接种的疤痕阳性个体中，诊断为结核病的比率较高（1.43 [0.88-2.35]，p=0.15），并且没有证据表明任何试验疫苗有助于预防肺结核。如果第二次疫苗接种对麻风病的保护作用更大，但对结核病没有保护作用，那么第二次疫苗接种可明显增加对麻风病的保护作用，但对结核病没有任何保护作用。
Background 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.Methods 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.Findings 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.Interpretation 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.