Extensively Drug-Resistant Tuberculosis, China

Frequency of extensively drug-resistant tuberculosis in Pakistan increased from 1.5% in 2006 to 4.5% in 2009 (p<0.01). To understand the epidemiology, we genotyped selected strains by using spoligotyping, mycobacterial interspersed repetitive units–variable number of tandem repeats, and IS6110 restriction fragment length polymorphism analysis.

XDR TB has recently emerged as a global public health problem (2). It is defi ned as TB with resistance to at least isoniazid, rifampin, a fl uoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). XDR TB is a type of MDR TB that shows resistance to isoniazid and rifampin. Recent reports on current prevalence of XDR TB (3,4) indicate that China now has the second highest incidence of MDR TB worldwide. However, there is no information available on XDR TB in China.
To obtain information on XDR TB in China, we conducted a study at Shanghai Pulmonary Hospital. It is the only specialized hospital for TB in Shanghai and plays a major role in treating TB patients and providing state-of-the-art treatment. Most patients referred to this hospital have been previously treated or have recurrent TB. Therefore, higher rates of MDR TB and XDR TB are expected in this setting, which is not comparable to community or multicenter-based studies.
Among Our results indicate that 30.0% of MDR strains were XDR strains. Although our study was conducted in only 1 hospital, this prevalence of XDR strains indicates that XDR TB in China is a serious concern. A total of 78.3% of MDR isolates were resistant to ofl oxacin, which is higher than rates reported for South Korea (42.8%) (5) and Taiwan (16.6%) (6). Populationbased studies have reported lower frequencies of XDR strains among MDR strains; 9.9% for 14 qualifi ed reference laboratories (7), 5.3% for South Korea (8), and 23.9% for South Africa among patients co-infected with HIV and TB (9).
In our study, 2 factors may have contributed to high drug-resistance rates. First, fl uoroquinolones have been widely used for treatment of respiratory tract bacterial infections because of their effi cacy and mild adverse reactions. Second, we also prescribed fl uoroquinolones for treatment of patients with drugresistant TB and some patients with drug-sensitive TB who could not tolerate fi rst-line anti-TB drugs. More than 90% of patients with XDR TB had strains resistant to streptomycin, ethambutol, capreomycin, and amikacin, which was higher than rates reported in other studies (5,9,10). Currently, anti-TB medications in China for treatment of patients with XDR TB are scarce. This scarcity has resulted in poor treatment outcomes in patients with XDR TB.
One limitation of our study is that we investigated patients at only 1 specialized TB hospital in Shanghai. Therefore, data are not representative for the general population. A community-based multicenter study is needed to determine the true prevalence of XDR TB in China. Nevertheless, our study confi rms that the prevalence of MDR TB and XDR TB is high in some areas. It also emphasizes the need to increase TB prevention and therapy, educate society about TB, implement modern TB control strategies, and strengthen basic and clinical research to curb the spread of MDR TB and XDR TB.

Clade 2.3.2 Avian
Infl uenza Virus (H5N1), Qinghai Lake Region, China, 2009China, -2010 To the Editor: In 2005, a large population of wild migratory birds was infected with highly pathogenic avian infl uenza (HPAI) virus (H5N1) in the Qinghai Lake region of western People's Republic of China, resulting in the death of ≈10,000 birds (1,2). On the basis of phylogenetic analysis of the hemagglutinin (HA) gene, the virus was classifi ed as clade 2.2 according to the World Health Organization guidelines. Subsequently, viruses from this clade were found in Mongolia, Russia, Europe, and Africa along the migratory fl yways of birds (3,4). This unique distribution of the same clade of HPAI virus (H5N1) through different migratory routes indicates that migratory birds might play a global role in virus dissemination (3,4).
In 2006, viruses from the same clade were isolated in the Qinghai Lake region (3). Analysis of viral outbreaks along migratory fl yways demonstrated a similar outbreak pattern for the past 4 years (2006-2009) (5). During that period, clade 2.2 avian infl uenza virus (H5N1) was isolated in China, Mongolia, Russia, Germany, Egypt, and Nigeria; all viruses were closely related to the Qinghai Lake virus. Despite the broad distribution of clade 2.2 viruses in migratory fl yways, few isolates of clade 2.2 viruses in local domestic poultry were reported, especially in China (6). Outbreaks of these viruses were reported in poultry in Africa (7). The reason these viruses rarely cause outbreaks in poultry is unknown.
Phylogenetic analysis of HA sequences and an additional HA gene sequence from the 2009 Qinghai Lake subtype H5N1 virus isolate from a great crested grebe (from the National Avian Infl uenza Virus Reference Laboratory, Harbin, China) (GenBank accession no. CY063318) showed that HA genes from all 12 viruses clustered as clade 2.3.2 ( Figure); none clustered with clade 2.2 viruses. Additionally, the HA cleavage site in the new isolates is PQRERRRKRG, which is identical to that of clade 2.3.2 viruses. In clade 2.2, the cleavage site is PQRERRRKKRG.
A bootstrap (1,000×) maximum likelihood tree (8) also demonstrated that Qinghai 2009 and 2010 virus isolates are closely related to those isolated in Mongolia and Uvs Nuur Lake in 2009, as reported by Sharshov et al. (5). Qinghai Lake and Uvs Nuur Lake, which are found along the migratory fl yway in central Asia, are major lakes for bird migration and breeding. Many birds fl y from Qinghai Lake to Uvs Nuur Lake in the spring.
If one considers isolation date and bird species infected, viruses isolated in Mongolia and Russia and our isolates were likely transmitted between the 2 lake regions by bird migration. Moreover, HA sequences are closely related to viruses isolated from wild birds in Hong Kong and Japan during 2007-2008, which are the most recent isolates of clade 2.3.2 viruses before isolation of 2009 Qinghai Lake viruses. These results indicate that viruses in the Qinghai Lake region may be transmitted by wild birds along the migratory fl yway in eastern