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Rate of Reinfection Tuberculosis after Successful Treatment Is Higher than Rate of New Tuberculosis

Suzanne Verver, Robin M. Warren, Nulda Beyers, Madalene Richardson, Gian D. van der Spuy, Martien W. Borgdorff, Donald A. Enarson, Marcel A. Behr and Paul D. van Helden

Desmond Tutu TB Center, Department of Pediatrics and Child Health, and MRC Center for Molecular and Cellular Biology, Department of Medical Biochemistry, Stellenbosch University, Cape Town, South Africa; KNCV Tuberculosis Foundation, The Hague; Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Amsterdam, The Netherlands; International Union against Tuberculosis and Lung Disease (IUATLD), Paris, France; and Division of Infectious Diseases, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada

Correspondence and requests for reprints should be addressed to Suzanne Verver, M.Sc., Ph.D., KNCV Tuberculosis Foundation, P.O. Box 146, 2501 CC The Hague, The Netherlands. E-mail: ververs{at}kncvtbc.nl

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: 612 of 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.

Key Words: incidence • molecular epidemiology • Mycobacterium tuberculosis • recurrence • survival analysis

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