Molecular Epidemiology Study of Exogenous Reinfection in an Area with a Low Incidence of Tuberculosis

Abstract

In geographical areas with a low incidence of tuberculosis, recurrent tuberculosis is generally due to reactivation of the disease. However, the relative contribution of tuberculosis reinfection increases in parallel with the incidence of disease and is likely to depend on the epidemiological context: factors such as the spread of multidrug resistance, human immunodeficiency virus (HIV) infection, and immigration from developing countries could modify disease transmission in areas at low risk for tuberculosis. A molecular epidemiology study was performed in Lombardy, Northern Italy, where the incidence of tuberculosis is 17.5 cases per 100,000 persons. A total of 2,452 cases of culture-confirmed tuberculosis in 2,127 patients were studied. A group of 32 patients (1.5%), each of whom had two episodes of tuberculosis with cure as the outcome of the first episode and with more than 6 months between the two episodes, were studied by means of restriction fragment length polymorphism DNA fingerprinting analysis. For 5 of the 32 patients (16%), the DNA fingerprinting patterns of Mycobacterium tuberculosis strains responsible for the second episode did not match those of the corresponding isolates of the first episode, indicating exogenous reinfection. Two of these patients developed multidrugresistant tuberculosis during the second episode, and in three cases the isolates belonged to clusters of M. tuberculosis strains spreading in the community. A fourfold-increased risk for reinfection was observed in immigrant patients compared to Italian subjects. In contrast, a higher risk of relapse rather than reinfection was evidenced in HIV-positive subjects and in patients infected with multidrug-resistant tuberculosis. Episodes of tuberculosis reinfection in areas with a low incidence of tuberculosis are rare compared to those in high-incidence geographical regions. In populations that have immigrated from high-risk areas, reinfection may represent a considerable contributor to the rate of recurrent tuberculosis. This finding emphasizes the importance of containing the spread of epidemic strains in close communities, in order to prevent changes in global tuberculosis trends for developed countries.

Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis

“…However, active disease may also develop decades later either as a relapse of the initial infection or because of a secondary infection. Although most cases of tuberculosis were once believed to result from a endogenous reactivation acquired in the past, 4 recent studies indicate that onethird of tuberculosis cases are due to recent transmission by exogenous reinfection of multiple M. tuberculosis strains, [5][6][7][8][9] implicating that the exogenous reinfection significantly contributes to disease transmission. Therefore, novel immunotherapeutic approaches will be required to prevent reinfection as well as reactivation of M. tuberculosis in individuals with latent tuberculosis.…”

Analysis of a tuberculosis model with undetected and lost-sight cases

“…Exposed individuals who have been previously infected (in dormant stage) or recovered individuals may acquire new infection from another infectious individual due to low immunity of persons. Therefore, individuals in the latent stage of TB progress into active stage due to exogenous reinfection and recovered individual may progress to Latently infected class [45,47,48,49,52,5,22,29]. Studies confirmed that reinfection in areas with a low incidence of tuberculosis is possible, although less common than in high-incidence geographical regions, indicating that higher prevalence of M. tuberculosis represents the major risk for tuberculosis reinfection.…”

“…Some authors proposed mathematical models of TB including reinfection and assumed that the rate of reinfection is a multiple of the rate of first infection [45,47,48,49,52,5,22,29]. Exposed individuals who have been previously infected (in dormant stage) or recovered individuals may acquire new infection from another infectious individual due to low immunity of persons.…”

Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83

“…Hence, a Th1 response is probably required for 10,18,19 In contrast, a Th2 response is abundant during infection with M. tuberculosis, and thus a shift in the balance toward a Th1 response may be beneficial. 20,21 DNA vaccination can achieve such a shift particularly because of its own 'adjuvant' effect. 22 In our previous studies, the combined DNA vaccine encoding antigens 85B, MPT64 and MPT83 stimulated a strong Th1 response, induced strong anti-mycobacterial immunity in mice and offered significant prophylactic protection.…”