Boxuan Feng

Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study

BACKGROUND Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. METHODS Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON [QFT]) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. FINDINGS 21,022 (90%) of 23,483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. INTERPRETATION On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. FUNDING The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.

Annual risk of tuberculosis infection in rural China: a population-based prospective study

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature. A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first years follow-up examination. The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second years follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age. In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China. Annual TB infection rate ∼1.5% in rural China, based on persistent positive results after IGRA conversion http://ow.ly/4n95Cw

Anal HPV/HIV co-infection among Men Who Have Sex with Men: a cross-sectional survey from three cities in China.

Anal human papillomavirus (HPV) infection, which is linked to anal warts and anal cancer, is common among men who have sex with men (MSM), especially among those HIV positives. MSM aged 18 years or older were recruited from mainland China. Blood and anal cytologic samples were collected for HIV-1 serological test and HPV genotyping. A total of 889 eligible participations were included. The genotyping results of HPV were available for 822 participants (92.46%), 65.32% of which were positive for the targeted 37 HPV types. Prevalence of infection with any type of HPV was higher among HIV-infected participants (82.69%) as compared to HIV-uninfected participants (62.81%) (p < 0.01). HPV06 (15.45%), HPV18(13.50%), HPV16 (11.44%), and HPV11 (10.71%) were the most frequent types identified in the study population. Ever had paid sex with man was found to be independent predictor for HPV positivity with an adjusted odds ratios (OR) of 2.34 (1.16–4.74). Anal HPV positivity was observed to be independently associated with HIV infection with an adjusted OR of 3.03 (1.76–5.21) in the study population. In conclusion, the prevalence of anal HPV infection was observed to be common among MSM from mainland China, and it was significantly associated with the status of HIV infection.

Anal Human Papillomavirus Genotyping among HIV-Positive Men Who Have Sex with Men in Xi'an, China.

Background Anal human papillomavirus (HPV) infection and its related diseases are relatively common in men who have sex with men (MSM), especially in those HIV positive. In China, molecular epidemiology of anal HPV infection among HIV-positive MSM has been sparsely studied. Methods A cross-sectional study was conducted among HIV-positive MSM in Xi’an, China between April and July 2014. Anal swabs were collected for HPV genotyping. Results A total of 195 HIV-positive MSM were included in this study. HPV genotyping showed that 99.0% (191/193) of participants were positive for at least one of the targeted 37 HPV genotypes. 183 (94.8%) of them were infected with multiple high-risk types and 154 (79.8%) of them with low-risk HPV types. HPV 18 was the most frequently identified high-risk type, followed by HPV 16 and HPV 51. As for low-risk types, HPV11, HPV 6 and HPV 81 were most commonly observe. High-risk HPV infection was found to be associated with the status of antiretroviral therapy (ART), the distribution of low-risk types was observed to be varied by CD4+ T cell level. Conclusion Almost all HIV-positive MSM were anal HPV infected in our study. It is highly recommended to consider regular active screening and preventive intervention of HPV infection among this high risk population.

Tuberculosis infection in rural labor migrants in Shenzhen, China: Emerging challenge to tuberculosis control during urbanization

During China’s urbanization process, rural labor migrants have been suggested to be one important bridge population to change urban-rural distribution on tuberculosis (TB) burden. Aiming to estimate the prevalence of TB infection and to track the active disease development in rural labor migrants, a prospective study was conducted in Shenzhen city, southern China. TB infection was detected using interferon-γ release assay (IGRA). Here we mainly report the characteristics of TB infection in the study population based on the baseline survey. A total of 4,422 eligible participants completed baseline survey in July 2013. QuantiFERON (QFT) positivity rates 17.87% (790/4,422) and was found to be consistent with the local TB epidemic of the areas where the participants immigrated from. Age, smoking, residence registered place, and present of BCG scars were found to be independently associated with QFT positivity. Additionally, evidence for interaction between smoking and age was observed (p for likelihood ratio test < 0.001). Our results suggested that the development of TB control strategy including latent TB infection management should pay more attention to the rural flowing population due to their high mobility and higher prevalence of TB infection.

Reversion of QuantiFERON-TB Gold In-Tube test in individuals with and without prophylactic treatment for latent tuberculosis infection: A systematic review and meta-analysis

OBJECTIVES Reversion of tuberculosis (TB) infection testing has been suggested to be associated with prophylactic treatment efficacy. However, evidences based on randomized controlled study were sparse. METHODS Studies on serial QuantiFERON-TB Gold In-Tube (QFT) test, among individuals with and without prophylactic treatment were identified in the databases of PubMed, MEDLINE and EMBASE up to 28 February 2018. The reversion rates were quantitatively summarized by means of meta-analysis using the random-effect model. RESULTS A total of 52 eligible studies were included in the meta-analysis on QFT test reversion rate among participants with (20 studies) and without (32 studies) prophylactic treatment. Summarized reversion rate was found to be 24.9% (95% confidence interval [CI]: 18.4-32.9%) and 25.3% (95% CI: 19.6-32.0%) for those completed or without treatment, respectively. When the analysis was restricted to the participants completed treatment, higher summarized rate of QFT reversion was found among those with longer course therapy (9INH vs. the other regimens), studies from Asia (vs. Europe and America), and individuals with immunosuppression disorders (vs. general populations). CONCLUSIONS Our results suggested that QFT reversion was frequently observed regardless of with or without prophylactic treatment. Serial QFT testing might be inappropriate for evaluating preventive treatment efficacy.

Serum level of IL-8 is associated with reversion of QuantiFERON-TB gold in-tube tests

BACKGROUND Frequent reversion has been commonly observed in serial QuantiFERON-TB Gold In-Tube (QFT) tests, which limited its accuracy in defining the status of Mycobacterium tuberculosis (MTB) infection. Serum cytokine profiles might provide additional information to clarify the infection status. METHOD Based on a population-based cohort study aiming to track MTB infection acquisition and disease development, serum profiles of 12 cytokines were determined by bead-based multiplex assays in parallel with QFT and tuberculin skin tests (TST) to explore potential relation between serum cytokines and MTB infection status. RESULTS Totally, 309 subjects got QFT conversion in one year (2013-2014) and 46.92% (145/309) of them got reversion in 2015. The study subjects were classified into three groups according to their QFT and TST results in 2015 (QFT persistence positive, QFT-/TST + and QFT-/TST-). The serum levels of MCP-1 and IL-8 were significantly different among the three groups. Furthermore, level of IL-8 was dramatically lower in QFT-/TST- group as compared to the other two groups, and no significant difference was observed for QFT-/TST + group as comparing with persistent positive group. CONCLUSION Our results suggested that the decreased serum level of IL-8 might be potential biomarker to identify QFT reversion caused by infection clearance.

Short-course Regimens of Rifapentine plus Isoniazid to Treat Latent Tuberculosis Infection in Older Chinese: a Randomised Controlled Study

Latent tuberculosis infection (LTBI) management is now a critical component of the World Health Organizations End TB Strategy. In this randomised controlled trial (Chinese Clinical Trial Registry identifier ChiCTR-IOR-15007202), two short-course regimens with rifapentine plus isoniazid (a 3-month once-weekly regimen and a 2-month twice-weekly regimen) were initially designed to be evaluated for rural residents aged 50–69 years with LTBI in China. Due to the increasingly rapid growth and unexpected high frequency of adverse effects, the treatments were terminated early (after 8 weeks for the once-weekly regimen and after 6 weeks for the twice-weekly regimen). In the modified intention-to-treat analysis on the completed doses, the cumulative rate of active disease during 2 years of follow-up was 1.21% (14 out of 1155) in the untreated controls, 0.78% (10 out of 1284) in the group that received the 8-week once-weekly regimen and 0.46% (six out of 1299) in the group that received the 6-week twice-weekly regimen. The risk of active disease was decreased, with an adjusted hazard ratio of 0.63 (95% CI 0.27–1.43) and 0.41 (95% CI 0.15–1.09) for the treatments, respectively. No significant difference was found in the occurrence of hepatotoxicity (1.02% (13 out of 1279) versus 1.17% (15 out of 1279); p=0.704). The short regimens tested must be used with caution among the elderly because of the high rates of adverse effects. Further work is necessary to test the ultrashort regimens in younger people with LTBI. A randomised controlled trial suggested that the short regimens tested for treatment of latent tuberculosis infection must be used with caution among the elderly because of the high rates of adverse effects http://ow.ly/AmmM30m7bYd

Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette–Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study

The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette–Guérin (BCG) booster vaccination in China was estimated using tuberculin skin testing (TST) and QuantiFERON-TB Gold assay (QFT) to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5–15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST (induration = 10 mm) and QFT positivity were 9.3% (264/2827) and 2.5% (71/2831), respectively. The rate of QFT indeterminate result was 2.2% (62/2831). The overall agreement between TST and QFT was low (concordance = 88.0%; ? coefficient = 0.125). Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26–2.31]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a twostep approach might be considered for TB infection testing among adolescents in China.