To the best of our knowledge, this is the first report of risk factors and clinical phenotypes associated with the Beijing genotype in China. Many of the investigations performed in other countries are limited by sample size or loss of detailed epidemiological information [12, 13, 24, 25]. Using data for 3634 strains identified in the first national drug-resistance surveillance of China, our data describe the detailed population structure of both Beijing and non-Beijing genotype strains.
According to our study, the Beijing genotype is the most predominant genotype in China, and several factors have an influence on its distribution among the population. Of all the factors, the correlation between Beijing genotype with MDR and fluoroquinolone resistance might influence the overall risk factors for Beijing spoligotypes compared to other genotypes . In addition, a previous study in Vietnam indicated that the Beijing genotype is associated with young patients (aged less than 25 years), while research performed in other countries has suggested that infection with the Beijing genotype showed no association with a patient’s age . Consistent with results from Vietnam, we found that young age (less than 25 years) showed a strong association with infection by the Beijing genotype, suggesting that the Beijing genotype will tend to become dominant in the population in China, possibly because young people tend to engage in greater levels of social interaction. van Soolingen et al. hypothesized that BCG vaccination may be one of the selective forces implicated in the successful spread of the Beijing genotype . This hypothesis is supported by results from other studies . There is speculation that the Beijing genotype strains may have diverged from a common ancestor in the recent past. Although the exact date of their divergence cannot be calculated, it is thought that this evolutionary process has been completed in less than a century . Hence, one possible explanation for the low spread of the Beijing genotype in the older population is that older patients previously infected with the non-Beijing genotype are resistant to the recently-emerged Beijing genotype strain. Additionally, another possible explanation could be an increased ongoing transmission in the society of this form of TB, which would be reflected in a higher prevalence in the young. Further study is required to confirm the hypothesis.
In addition to age, infection with the Beijing genotype was associated with ethnicity. Compared with Han, people of both Uyghur and Zhuang ethnicities showed a lower than average risk of infection with the Beijing genotype. In a previous study we showed that the percentage of Uyghur patients infected with CAS1-DEHLI genotype strains was significantly higher than that of other ethnicities , and suggested that this may be due to the frequent exchange between Uyghur people and ethnicities from several neighboring Central Asian countries where the CAS1-DEHLI genotype is highly prevalent, since they share similar cultural traditions. Since the Zhuang ethnicity is mainly distributed in Guangxi Province in South China, the relatively low incidence of the Beijing genotype is consistent with the relatively low percentage of Beijing genotype strains in Southern China . In contrast to other ethnic minorities, Hui ethnicity is defined rather based on cultural or religious reasons instead of genetic one. Hence, the special traditions and ways of living in Hui ethnicity may be responsible for the high percentage of Beijing genotype. However, a larger study is needed to answer additional questions about the distribution of Beijing genotype and non-Beijing genotype strains among different ethnicities.
With respect to occupation, we found strong associations between urban people and infection with Beijing genotype strains. In China, rural people are usually living in rural area with less density of population, who depend on argricultural activities for their livelihoods, and therefore their mainly work condition is outside the building; whereas urban people tend to live in urban areas with more density of population and always work inside the crowd public environment, which contribute to Beijing infection of urban people. In addition, many studies have suggested that the Beijing genotype is associated with resistance to anti-tuberculosis drugs [18, 28–30]. Due to the unbalanced distribution of health care resources in China , misuse and overuse of antibiotics is more common in urban areas than in rural areas in China, and this may account for the higher prevalence of drug-resistant Beijing genotype strains among urban people.
In addition to demographic characteristics, patients infected with Beijing genotype strains presented different clinical profiles compared with those infected with non-Beijing genotype strains. Both hemoptysis and chest pain are common manifestations of pulmonary tuberculosis ; moreover, massive hemoptysis is a life-threatening condition with a poor treatment outcome in active tuberculosis patients . In this study, we observed that 25.1% and 32.4% of patients infected with Beijing strains had hemoptysis and chest pain, respectively, compared with 29.4% and 37.7%, respectively, of those infected with non-Beijing strains. These differences were statistically significant. That both symptoms have a lower occurrence in patients infected with the Beijing strain is reasonable as the two symptoms often occur together in the same patient. Our data indicate that chest symptoms occur more frequently in patients infected with non-Beijing strains. Our results are in agreement with a study performed in Singapore which demonstrated that there is a significantly higher frequency of cavitary disease in patients infected with non-Beijing genotype strains . Nevertheless, in studies on the CXR presentation of patients completed in Indonesia and in the Netherlands [12, 20], the authors did not find any significant difference between the two groups. While more attention has been given to the Beijing genotype than to other genotypes due to the association of its supposed higher virulence with relapse and treatment failure in humans [13, 20, 34–36], our findings suggest that patients infected with non-Beijing genotype strains may have more serious chest phenotypes.
Fever is a typical clinical symptom of tuberculosis patients, and recent findings have revealed that the frequency with which fever is observed is more frequently reported in non-Beijing genotype infected patients than in patients infected with the Beijing genotype . In contrast, we found that fevers occurred in a significantly higher proportion of patients infected with Beijing genotype strains in China than in those infected with non-Beijing genotype strains. Our results are in agreement with a cohort study by Parwati et al. which showed that more patients infected with Beijing genotype strains developed fever during treatment .