Category Archives: Asia

Multi-Drug Resistant Tuberculosis in Former Soviet States

It has been known for some time that the former Soviet Union had a huge tuberculosis problem. The problem was so big that no one really knew how bad it was in the Soviet Union or is now in its successor states. Over the last couple months, three reports have appeared in Euro Surveillance  and Emerging Infectious Diseases that begin to quantitate the problem.

In  the first report, France sent out a warning to states accepting immigrants from the former Soviet Union. Over the last two complete years 2010 and 2011, France has experienced a surge in multi-drug resistant (MDR) tuberculosis.

MDR-TB in France 2006-2012 [1]
MDR-TB in France 2006-2012 [1]
XDR-TB by country of birth in France 2006-2012
XDR-TB in France 2006-2012 [1]
 When they examined the country of birth for these cases, almost all of the surge came from countries of the former Soviet Union (fig. 1) [1]. When they looked for more regionalism, they discovered that the majority of the increase came from the country of Georgia and the Russian Federation.[1] For the more worrisome extensively drug resistant (XDR) tuberculosis, the vast majority of the French cases have come from the former Soviet Union going back to 2008; 14 of 17 cases in 2012 came from Georgia (fig. 3) [1]. Genetic analysis of the MDR-TB and XDR-TB strains in France showed variation indicating that transmission did not occur in France but was brought into France by immigration [1].

A survey of MDR-TB in Uzbekistan yielded even more grim results. In the first national TB survey, 23% of all newly diagnosed cased of TB and 62% of previously treated cases were resistant to at least two antibiotics; only 3.8% of MDR-TB cases were co-infected with HIV [2].  The XDR-TB rate was 5.3% with no HIV co-infections [2].  Demographics analysis yielded three primary risk factors or groups: adults under age 45, institutionalization in prisons or previous anti-TB treatment centers, and not owning their own home [2].

The news out of Siberia is no better. A survey published last month showed MDR-TB rates in Siberia are over 25% of primary TB cases with a a mean age of 33 [3]. The two regions, Irkutsk and Yakutia had strains of different origins. The Irkutsk MDR-TB were primarily a common Beijing lineage. On the other hand, the more isolated community of Yakutia had the MDR-TB S256 strain that has been linked with a strain only found among Canadian aboriginal population [3]. The linkage between these the Siberian and Canadian strains have not yet been fully investigated. While these strains are related they are not identical so it is possible that these are a previously undetected ancient lineage that has developed antibiotic resistance in Russia. This was the first isolation of this strain in Russia. The Siberian strains had uncommon mutations in the resistance genes that would not have been picked up well by commercial tests. Zhdanova and co-authors stress the importance of investigating regional strains and developing tests that will adequately detect local strains.

MDR-TB rates from the former Soviet Union are higher than anywhere else in the world [5]. These surveys show that it is even worse than the WHO estimated in 2010. It is far worse than any survey coming out of South Africa, a country often mentioned as being a particular concern for MDR-TB. For comparison, the MDR-TB rate for the United States in 2011 was 1% for MDR-TB and far less than 1% for XDR-TB [4].  Given the vast size and population of the former Soviet Union, migration out of former Soviet states could jump-start a new white plague, strains of TB that even the best medical care will have difficulty keeping under control.

References:

  1. Bernard, C., Brossier, F., Sougakoff, W., Veziris, N., Frechet-Jachym, M., Metivier, N., et al. (2013). A surge of MDR and XDR tuberculosis in France among patients born in the Former Soviet Union. Euro Surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin, 18(33).
  2. Ulmasova, D. J., Uzakova, G., Tillyashayhov, M. N., Turaev, L., van Gemert, W., Hoffmann, H., et al. (2013). Multidrug-resistant tuberculosis in Uzbekistan: results of a nationwide survey, 2010 to 2011. Euro Surveilliance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin, 18(42).
  3. Zhdanova, S., Heysell, S. K., Ogarkov, O., Boyarinova, G., Alexeeva, G., Pholwat, S., et al. (2013). Primary Multidrug-Resistant Mycobacterium tuberculosis in 2 Regions, Eastern Siberia, Russian Federation. Emerging Infectious Diseases, 19(10), 1649–1652. doi:10.3201/eid1910.121108
  4. Centers for Disease Control and Prevention. (2013). Antibiotic Resistance Threats in the United States, 2013 (pp. 1–114). Department of Health and Human Services.
  5. World Health Organization. (2010)  Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 Global Report on Surveillance and Response.   http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf

Western Iranian Plague Foci Still Active, 2011-2012

In a letter in this month’s Emerging Infectious Diseases, an Iranian and French team of epidemiologists report that the old plague focus in western Iran bordering Kurdistan is still active. Between 1947 and 1966 there were nine human plague epidemics causing 156 human deaths.  The last recorded human case occurred in 1966 and in animals in 1978. No surveys for plague were conducted for the following 30 years. It is unlikely to be a coincidence that the Iranian Revolution also began in 1978.

During the summers of 2011 and 2012, the team captured and tested for the plague F1 antibody 98 rodents and counted their fleas, finding only one rodent with antibodies (1.08%). They also tested 117 sheepdogs finding 4 positive dogs or 3.42%.  In dogs, plague antibodies only last about six months suggesting that these sheepdogs must have had recent infections.  This is enough to suggest that the plague foci is still present in western Iran. Moreover, they believe the number of reservoir rodents and fleas per rodent (Xenopsylla species index 4.10) is “most favorable” circumstances for an epizootic. With plague antibodies found in the only area surveyed in 30 years, it is clear that surveillance needs to not only continue but expand extensively.

Reference:

Esamaeili S, Azadmanesh K, Naddaf SR, Rajerison M, Carniel E, & Mostafavi E (2013). Serologic survey of plague in animals, Western Iran. Emerging infectious diseases, 19 (9) PMID: 23968721

Asymptomatic Plague: Qinghai, China, 2005

Now that we know the Tibet-Qinghai plateau region is where Yersinia pestis originated and the region where subsequent pandemics arose, I think its time to look more closely at regional outbreaks and case studies.

In this region, the marmot (Marmota himalayana) is the primary reservoir for Yersinia pestis. This large communal burrowing rodent is hunted by local Tibetan tribesmen for both meat and pelts. Butchering marmots has long been considered a risk factor for contracting plague via their fleas, aerosols or skin abrasions. To investigate the exposure of marmot hunters to plague, Chinese epidemiologists collected serum from 120 Qinghai villagers, 68 male hunters and 52 female family members, along with 120 negative controls from the non-endemic area of Beijing. None of the villagers or controls reported having a fever within the last two years.

The results are eye-opening and illustrates the importance of occupational exposure. Over a third of the male villagers had an antibody response to Yersinia pestis. Only 2% of their female family members produced an antibody response. Wether two fever-free years are enough time to determine if they had symptomatic plague in the past is an open question. Their letter to Emerging Infectious Diseases does not provide much information on the test subject’s histories or oral reports.

Table 1: Plague antibody assays (Li et al, 2005)
Table 1: Plague antibody assays (Li et al, 2005)

The epidemiologists explained this high level of immune protection to the use of prophylactic antibiotics by marmot hunters. They suggest the presence of tetracycline or sulfamethaoxazole, common prophylactic antibiotics in Tibet, in  their system at the time of exposure would be enough to prevent a symptomatic infection while still giving them an immunizing dose of bacteria.

The use of prophylactic antibiotics is, of course, a double-edged sword. It is clearly preventing symptomatic infections and probably outbreaks. The Chinese epidemiologists credit  most outbreaks in Qinghai to marmot hunters who either a lack of prophylactic antibiotics or have ineffective antibiotics.  On the other hand, the use of antibiotics is possibly encouraging them to harvest the easier to catch, sicker marmots. The use of prophylactic antibiotics also promotes antibiotic resistance in Yersinia pestis.

Li, M., Song, Y., Li, B., Wang, Z., Yang, R, Jaing, L., and Yang, R. Asymptomatic Yersinia pestis, China. Emerging Infectious Disease, 2005, 11 (9): 1494-1496.