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International tuberculosis research and monitoring

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For years the Norwegian Institute of Public Health (NIPH) has been working closely with North West Russia to research and prevent tuberculosis. The NIPH has also been engaged in projects linked to monitoring of M. tuberculosis resistance, development of laboratory methods and epidemiology in countries such as Bangladesh, Brazil, China, Myanmar, Sudan, South Africa, Tanzania, Uganda and Vietnam.


Foto: CDC.

National reference laboratory for mycobacteria

The reference laboratory is based at the NIPH’s Department of Bacteriology and Infection Immunology. Since 1994 the laboratory has performed DNA fingerprint analyses of all Mycobacterium tuberculosis strains isolated in Norway. These efforts have gradually been expanded by co-operation with other countries. The main goal for the projects is to get better control over the global existence of tuberculosis.

The projects include collaboration to improve the quality of tuberculosis diagnosis, monitoring and prevention of resistance development, demonstration of infection sources and spread, infection control and research into diagnostic methods and epidemiological monitoring. The work also includes information and competence exchange with transfer of technology and methodology.

The laboratory at the NIPH has been engaged in projects linked to monitoring M. tuberculosis resistance and epidemiology in countries such as Myanmar, Bangladesh, Tanzania, Brazil, Vietnam, China, Uganda, Sudan and South Africa. Transfer by molecular epidemiological technology is time-consuming, but laboratories in some of these countries are establishing fingerprint methods with the help of the NIPH.

Bacteria strains from Arkhangelsk in North West Russia have been analysed at the NIPH, which acted as a reference laboratory for the Arkhangelsk region and helped to develop and improve the Russian laboratory. The collaboration ensured an improved diagnosis and treatment of tuberculosis patients there and has also led to many international publications, doctorates and master’s degrees.

General opinion suggests that the recent increase in tuberculosis incidence in Russia can be blamed on difficult social and economical conditions. However, studies at the NIPH show that the spread is also caused by the Beijing-type of M. tuberculosis which is well-established in North West Russia. This type is more contagious with a higher proportion of resistance than the other variants [1].

It is worrying that the proportion of resistant strains in the region has increased in the last few years and that the degree of new infections is rising while the genetic diversity in the bacteria population is sinking [2].

Genetic diversity

Studies at NIPH have helped to demonstrate that the genetic diversity in M. tuberculosis populations around the world is geographically limited and that different nations can be susceptible at different rates to different types of M. tuberculosis.
For example, the Central Asian (CAS) family of M. tuberculosis is widespread in Dar Es Salaam, Tanzania [3]. There is a great diversity of M. tuberculosis where 64% of the bacteria population differs from those earlier described from other countries. The finding indicates that the bacilli circulating in Dar Es Salaam are well-established and cannot be blamed on recent import of the disease. The Latin American Mediterranean (LAM) family is common in Rio de Janeiro, Brazil and much indicates that this bacteria type has developed independently of the Asian, African or European tuberculosis populations [4].

As in North West Russia, the tuberculosis situation in many Asian cities is dominated by the Beijing family [5]. Outside town areas in Bangladesh (Sunamganj-province) and in Yangon, Myanmar however, the NIPH work contributed to show that the East African Indian (EAI) family dominates. High proportions of resistant bacteria were also seen [6-8]. I Hanoi, Vietnam a great diversity of M. tuberculosis was visible despite dominance by EAI and Beijing types [9]. In Hanoi, resistance could not be related to a specific type of M. tuberculosis but the proportion of resistant bacteria was also high. When these findings are compared with other studies, the findings indicate that the global tuberculosis situation is a result of many independent epidemics. For example, the EAI family has circulated in Asian countries for a long time, whilst the Beijing family is a newcomer that is not yet well spread in isolated areas. The global spread of the diseases is not as extensive as earlier feared. Despite different areas struggling with completely separate epidemics, the findings indicate that the resistance problem has reached far, both in and out of urban areas, in many countries.

The situation in Norway

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In Norway the tuberculosis situation is complex and varied. Studies at NIPH have shown that immigrants to Norway infect others with tuberculosis to a small degree [10]. The majority of immigrants are infected before arrival and the incidence rate mirrors the incidence in their country of origin. Cases of resistant tuberculosis are mainly imported and can rarely be blamed on resistance development in Norway.

As a result of increasing immigration the incidence of tuberculosis has increased in Norway in the period 1994-2006. There has not been a corresponding increase in the proportion of newly infected patients within the country. This increase in incidence can be blamed on unique isolates, people who are infected outside the country or before 1994. The incidence of clustered bacteria isolates, that are considered to represent newly infected people, has been stable (Fig. 3). Although more immigrants are being diagnosed with tuberculosis in Norway, there has been a dramatic reduction in the cases of illness among non-immigrants. These findings indicate that the Norwegian programme against tuberculosis is working well. Immigrants and non-immigrants are exposed to completely different epidemics and the public health service is preventing spread of infection despite the challenge that imported tuberculosis represents.

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Since Norway is a small country with relatively few people with tuberculosis, it is possible to analyse all M. tuberculosis isolates with DNA-fingerprint analysis. Norway is therefore used as a good model to study the spread of infection of tuberculosis [11]. The finding can be used to evaluate control measures and give important input in the international debate about tuberculosis and immigration [12]. It is suggested, for example, that the findings from NIPH show that a nation can control its tuberculosis situation despite a large import from high-incidence countries [11, 12]. This emphasises the importance that control measures are established, financed and maintained locally in different countries and that one does not exclusively blame immigrants for the increasing spread experienced in many countries today. 

References

1. Toungoussova OS, Bjune G and Caugant DA. (2006) Epidemic of tuberculosis in the former Soviet Union: Social and biological reasons. Tuberculosis, 86(1): 1-10.
2. Baranov A. (2007) Current tuberculosis epidemic in the North Western federal region of Russia: drug resistance, molecular epidemiology and risk factor analysis (MSc. thesis). 
3. Eldholm V, et al. (2006) A first insight into the genetic diversity of Mycobacterium tuberculosis in Dar es Salaam, Tanzania, assessed by spoligotyping. BMC Microbiol. 6(1):76.
4. Lazzarini LCO, et al. (2007) Discovery of a Novel Mycobacterium tuberculosis Lineage That Is a Major Cause of Tuberculosis in Rio de Janeiro, Brazil. J. Clin. Microbiol. 45(12):3891-3902.
5. Brudey K et al (2006) Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiology, 6(1): 23.
6. Storla DG et al (2006) Heterogeneity of Mycobacterium tuberculosis isolates in Sunamganj District, Bangladesh. Scand. J. Infectious Diseases, 38(8):593-596.
7. Storla DG et al (2007) Drug resistance of Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Scand. J. Infectious Diseases, 39(2):142-145.
8. Phyu S et al (2003) Heterogeneity of Mycobacterium tuberculosis isolates in Yangon, Myanmar. J. Clin. Microbiol. 41(10): 4907-4908.
9. Trung P (2007) Distribution of Mycobacterium tuberculosis lineages overview in the North of Vietnam (MSc. Thesis).
10. Dahle UR et al (2007) Impact of Immigration on the Molecular Epidemiology of Mycobacterium tuberculosis in a Low-Incidence Country.  Am. J. Respir. Crit. Care Med., 176(9): 930-935.
11. Schwartzman K (2007) "Them" and "Us": The Two Worlds of Tuberculosis? Am. J. Respir. Crit. Care Med., 176(9): 840-842.
12. Mitchell S (2007) Don't blame immigrants for tuberculosis, in ScienceNow 1. Nov.2007