Medline ® Abstracts for References 8-14

From 1924 onwards, mandatory tuberculin testing (von Pirquet's method) was introduced for student nurses on entry to the Ullevaal Hospital School of Nursing, Oslo. The chief physician of the hospital's Department IX, Olaf Scheel, was responsible for this measure. In 1927, his deputy Johannes Heimbeck showed that about half of the students were not infected at the time of entry, a conclusion that was in fundamental conflict with the prevailing view that nearly all tuberculous infection occurred in childhood. Virtually all tuberculin-negative student nurses, however, became infected during their 3-year training. These findings changed our understanding of the pathogenesis of tuberculosis. BCG vaccination had recently been introduced by Calmette. From 1927 onwards Heimbeck offered BCG vaccination to tuberculin-negative student nurses, while Scheel undertook a similar project among medical students. The two projects continued until respectively 1936 and 1939. Long-term follow-up of both groups demonstrated a protective effect of about 80% in those accepting vaccination. Calmette had given the vaccine per os to new-born babies. Heimbeck and Scheel pioneered giving the vaccine via injection and to adults. These projects have been criticised for being based on voluntary inclusion and not being conducted as randomised control trials. The results were so convincing, however, that they led to the launch of the Norwegian BCG programme shortly after World War II. Scheel and Heimbeck' efforts were also of great importance for the use of the BCG vaccine in other countries.

RATIONALE: In a high-tuberculosis (TB) incidence area of Cape Town, South Africa, there is a very high rate of unexplained recurrent TB. The incidence of new bacteriologically confirmed disease in the area is 313 per 100,000 individuals.

OBJECTIVE: To estimate the rate of recurrent TB attributable to reinfection after successful treatment.

METHODS: All patients with reported TB in the area between 1993 and 1998 were followed up to 2001 for disease needing retreatment (recurrences). Patients who were multi-drug-resistant or who had treatment failure, were transferred, or died during treatment were excluded. Analysis was restricted to patients for whom DNA fingerprinting of their Mycobacterium tuberculosis isolates was obtained. Reinfection TB was defined as a recurrent TB episode in which the strains of the separate episodes differed by more than four bands.

MEASUREMENTS AND MAIN RESULTS: 612of 897 (68%) patients had a DNA fingerprint available at enrollment. Median duration of follow-up was 5.2 years. Recurrent TB occurred in 108 of 612 (18%) patients, of whom 61 of 447 (14%) experienced recurrence after successful treatment, and 47 of 165 (28%) experience recurrence after default. Of the 108 patients with recurrent TB, 68 (63%) had a DNA fingerprint in the second episode. Among these patients, 24 of 31 (77%) recurrences after successful treatment and 4 of 37 (11%) recurrences after default were attributable to reinfection. The reinfection disease rate after successful treatment was estimated at 2.2 per 100 person-years.

CONCLUSIONS: The age-adjusted incidence rate of TB attributable to reinfection after successful treatment was four times that of new TB. People who had TB once are at a strongly increased risk of developing TB when reinfected.

BACKGROUND: Active tuberculosis is common among human immunodeficiency virus (HIV)-infected persons living in tuberculosis-endemic areas, but the hazard of subsequent tuberculosis disease has not been quantified in a single prospective cohort.

METHODS: Among HIV-infected, BCG-immunized adults with CD4 counts≥200 cells/μL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania, we compared the prospective risk of active tuberculosis between subjects who did and who did not report prior active tuberculosis. All subjects with a positive tuberculin skin test without prior active tuberculosis were offered isoniazid preventive treatment. Definite or probable tuberculosis was diagnosed during active follow-up using rigorous published criteria.

RESULTS: We diagnosed 52 cases of definite and 92 cases of definite/probable tuberculosis among 979 subjects during a median follow-up of 3.2 years. Among the 80 subjects who reported prior active tuberculosis, 11 (13.8%) subsequently developed definite tuberculosis and 17 (21.3%) developed definite/probable tuberculosis, compared with 41 (4.6%) and 75 (8.3%), respectively, of 899 subjects without prior active tuberculosis (definite tuberculosis risk ratio [RR], 3.01; 95% confidence interval [CI], 1.61-5.63, P<.001; definite/probable tuberculosis RR, 2.55; 95% CI, 1.59-4.09, P<.001). In a Cox regression model adjusting for age, CD4 count, and isoniazid receipt, subjects with prior active tuberculosis had substantially greater hazard of subsequent definite tuberculosis (hazard radio [HR], 3.69; 95% CI, 1.79-7.63, P<.001) and definite/probable tuberculosis (HR, 2.78; 95% CI, 1.58-4.87, P<.001).

CONCLUSIONS: Compared to subjects without prior tuberculosis, the hazard of active tuberculosis is increased 3-fold among HIV-infected adults with prior active tuberculosis. Clinical Trials Registration. NCT0052195.