Tuberculosis in Newborns: The Lessons of the “Lübeck Disaster” (1929–1933)

PLoS Pathogens

Gregory J. Fox¹  Erwin Schurr¹  Marianna Orlova² 

[1] McGill International TB Centre, McGill University, Montreal, Quebec, Canada;Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, Quebec, Canada

关键词: Tuberculosis;    Mycobacterium tuberculosis;    Vaccines;    Prognosis;    Respiratory infections;    Infants;    Bovine tuberculosis;    Inoculation;   

DOI  :  10.1371/journal.ppat.1005271

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

In an accident later known as the Lübeck disaster, 251 neonates were orally given three doses of the new Bacille Calmette–Guérin (BCG) antituberculosis (TB) vaccine contaminated with Mycobacterium tuberculosis. A total of 173 infants developed clinical or radiological signs of TB but survived the infection, while 72 died from TB. While some blamed the accident on BCG itself by postulating reversion to full virulence, such a possibility was conclusively disproven. Rather, by combining clinical, microbiological, and epidemiological data, the chief public health investigator Dr. A. Moegling concluded that the BCG vaccine had been contaminated with variable amounts of fully virulent M. tuberculosis. Here, we summarize the conclusions drawn by Moegling and point out three lessons that can be learned. First, while mortality was high (approximately 29%), the majority of neonates inoculated with M. tuberculosis eventually overcame TB disease. This shows the high constitutional resistance of humans to the bacillus. Second, four semiquantitative levels of contamination were deduced by Moegling from the available data. While at low levels of M. tuberculosis there was a large spread of clinical phenotypes reflecting a good degree of innate resistance to TB, at the highest dose, the majority of neonates were highly susceptible to TB. This shows the dominating role of dose for innate resistance to TB. Third, two infants inoculated with the lowest dose nevertheless died of TB, and their median time from inoculation to death was substantially shorter than for those who died after inoculation with higher doses. This suggests that infants who developed disease after low dose inoculation are those who are most susceptible to the disease. We discuss some implications of these lessons for current study of genetic susceptibility to TB.

【 授权许可】

CC BY