[Exogenous re-infection in tuberculosis]

Patients infected by tuberculosis (TB) had been thought to never experience exogenous re-infection. However, exogenous re-infection in HIV-positive patients is well known. Thanks to the introduction of histopathological examination, analysis of similarities in drug-resistance patterns and epidemiological surveys of genetic phage typing for TB infection, we have begun to understand that even people with a normal immune system can experience re-infection. Recent advances in the techniques of restriction fragment length polymorphism (RFLP) and spoligotyping allow determination of similarities in tubercle bacilli, revealing a high ratio of exogenous re-infection. In this mini-symposium, Dr. Kazunari Tsuyuguchi reported cases of nosocomial multidrug-resistant tuberculosis (MDRTB) infection, as exogenous re-infection, at 3 tuberculosis hospitals in the Osaka area. Although the virulence of MDRTB as a variant strain has generally been regarded as weaker than that of drug-sensitive strains, he reported even non-Beijing strain MDRTB, which displays strong virulence, could possess possible infectiosity with a 42% ratio of clustering formation and 2 of 8 patients with MDRTB exhibiting exogenous re-infection, as analyzed by RFLP. Dr. Hideo Ogata reported the actual condition of exogenous re-infection, having cited a large number of reports at home and abroad. In his report he indicated that even among hosts without serious hypoimmunity, re-infection rate is high in high-prevalence countries. Conversely, endogenous TB reactivation is high in low-prevalence countries. As Japan has become a low-prevalence country, endogenous reactivation might be seen in TB wards. Dr. Katsuhiro Kuwabara reported on his study about exogenous re-infection of Mycobacterium avium, which represented resident flora in the environment, using IS1245 RFLP analysis. He demonstrated that re-infection and multiple infections were frequently observed in M. avium infection. Dr. Tomoshige Matsumoto finally added that about 90% of patients with recurrence in the Osaka area exhibit endogenous reactivation, as found using molecular epidemiologic analysis of bacterial strains from initially treated and retreated patients. Compared with reports from other countries, the ratio of exogenous re-infection in Japan is lower than elsewhere. Thanks to the public health service about TB, sources of TB infection are not present, so patients with TB do not experience exogenous re-infection, he concluded. He also discussed the variable number of tandem repeats (VNTR)-typing method that has been taking the place of the IS6110 RFLP. In this mini-symposium referring to molecular epidemiological analyses and reports from Japan and overseas, we showed that depending on factors involving hosts, parasites and the density of TB re-exposure, the possibility of universal exogenous nosocomial re-infection exists. Each presenter alerted us to the fact that as exogenous re-infection occurs mainly in TB inpatient wards, prevention of TB infection is crucial for inpatients and medical staff in Japan as a low-prevalence country. (1) Exogenous re-infection by multidrug-resistant tuberculosis: Kazunari TSUYUGUCHI, Shiomi YOSHIDA, Katsuhiro SUZUKI, Masaji OKADA, Mitsunori SAKATANI (NHO Kinki-chuo Chest Medical Center) We describe three recurrent cases of multidrug-resistant (MDR) tuberculosis (TB) nosocomially re-infected with MDRTB strain during treatment for drug-sensitive TB. The first and the second patients, both of whom were middle-aged heavy smoker men, were associated with the outbreak caused by non-Beijing MDRTB strain. The third patient was a immunocompetent young man and the isolated strain was Beijing MDRTB strain. All the patients were HIV-seronegative. We conclude that exogenous re-infection by MDRTB can occur on various situations. These results underscore the importance of placing MDRTB patients separately from drug-sensitive TB patients. (2) Reviews of the exogenous re-infection in tuberculosis: Hideo OGATA (Fukujuji Hospital, JATA) In Japan, they have thought that a tubercular relapse is based on endogenous reactivation in almost all cases. However, there are many studies which prove exogenous re-infection using tuberculin test or drug susceptibility test. The technique of developed strain typing contributed exogenous re-infection to clarifying greatly in a real proof and its frequency in recent years. (3) Multiple and repeated polyclonal infections in patients with Mycobacterium avium lung diseases: Katsuhiro KUWABARA (NHO Nishi-Niigata Chuo National Hospital) The routes of transmission and environmental reservoirs of Mycobacterium avium infections have been unclear. IS1245 based RFLP analysis showed genetic diversity of Mycobacterium avium clinical isolates and the relation between clinical subtype and polyclonal infection. Our study demonstrates that polyclonal infections are common in Mycobacterium avium lung diseases, especially nodular bronchiectasis type. In addition, not only simultaneous polyclonal infections but also repeated polyclonal infections were observed in some patients. The knowledge of polyclonal infection will lead to better understanding of Mycobacteriuim avium pathogenesis and epidemiology. SPECIAL COMMENTARIES: Consideration of exogenous re-infection of tuberculosis in Osaka. Japan, by using molecular epidemiologic tools: Tomoshige MATSUMOTO (Osaka Prefectural Medical Center for Respiratory and Allergic Diseases) By using IS6110 RFLP, we showed that 9.5% of TB recurrence was caused by re-infection in the middle-eastern area of Osaka Prefecture, Japan. The molecular typing tools are now being applicable not only to epidemiological but also to clinical fields by an introduction of PCR-based method, such as Variable Numbers of Tandem Repeats (VNTR) typing. We showed some examples about usefulness of the clinical application of molecular epidemiology, using VNTR.