Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil.
- 作者列表："Cubillos-Angulo JM","Arriaga MB","Melo MGM","Silva EC","Alvarado-Arnez LE","de Almeida AS","Moraes MO","Moreira ASR","Lapa E Silva JR","Fukutani KF","Sterling TR","Hawn TR","Kritski AL","Oliveira MM","Andrade BB
BACKGROUND:Host genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. METHODS:We examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. RESULTS:Among 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI=1.15-12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR=24.84; 95%CI=2.26-272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). CONCLUSIONS:Polymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.
背景: 宿主基因多态性在决定结核分枝杆菌 (Mtb) 感染易感性方面可能很重要，但其作用尚不完全清楚。微生物DNA的检测和I型干扰素 (IFN) 通路的激活调节巨噬细胞对Mtb感染的反应。 方法: 我们在巴西微生物学确诊的肺结核患者的密切接触者中检测了 7 个候选基因SNPs是否与结核菌素皮肤试验 (TST) 阳性相关。使用多变量logistic回归 (使用基因型和临床变量) 和遗传模型检测与TST阳性的独立相关性。 结果: 482 例TB指数病例的 145 名接触者中，296 名接触者TST阳性。多变量回归分析校正了与结核病风险增加相关的人群、年龄、家庭相关性、性别和临床变量，证明PYHIN1-IFI16-AIM2 的SNPs rs1101998 (校正OR [aOR]: 3.72; 95% CI = 1.15-12.0; p = 0.028) 和PYHIN1-IFI16-AIM2 rs1633256 (aOR = 24.84; 95% CI = 2.26-272.95; p = 0.009) 与隐性模型中TST阳性相关。此外，IRF7 多态性 (rs11246213) 与显性模型中TST阳性几率降低相关 (aOR: 0.50，95% CI: 0.26-0.93; p = 0.029)。 结论: 在巴西队列中，PYHIN1-IFI16-AIM2 rs1633256 、rs1101998 和IRF7 rs11246213 的多态性与Mtb感染易感性的改变相关。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.