Betaine and I-LG may have a predictive value for ATB: A causal study in a large European population.

PURPOSE: To analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population. METHODS: In this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis. RESULTS: A total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB. CONCLUSION: Betaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies.

A community-based cross-sectional study of dietary composition and associated factors among tuberculosis patients in China.

To determine the dietary structure and its associated factors of tuberculosis (TB) patients in the community. This cross-sectional study analysed the dietary intake of 300 TB patients in two impoverished counties in China. Food intake was collected by using food frequency and two consecutive 24-h dietary review (24hdr) methods. The dietary composition and dietary structure of TB patients were compared with China's 2022 Dietary Reference Intake (DRIs) and the average reference value of dietary composition (ARC) in China in 2013. Binary logistic regression models were used to explore the factors associated with inadequate intake of animal food, insufficient protein and fat energy supply in patients with TB. The daily intake of various foods in TB patients was measured and the results were as follows: staple foods-median 372.12 g (interquartile range [IQR] 315.87 g); vegetables-median 200.00 g (IQR 205.55 g); fruits-median 20.22 g (IQR 36.82 g); animal foods-median 100.82 g (IQR 180.74 g); dairy products-median 0.00 g (IQR 0.00 g); nuts-median 17.10 g (IQR 29.75 g). The average daily intakes of vegetables, fruits, animal food, dairy products, soy and nuts were lower than those recommended by the DRIs (P < 0.01). Compared to women, men consumed more whole grains and mixed legumes, but less fruit. The dietary structures, including food and nutrient supply for energy, protein and fat, were significantly different in 300 patients compared with DRIs or ARC values. Inadequate rates of animal food intake were observed in 54.85% of men and 59.57% of women. Protein undersupply rates were 66.02% in men and 56.38% in women, while fat undersupply rates were 52.91% in men and 52.13% in women. The study revealed that being 18-49 years old, being the Han nationality, having less than 2 h of physical activity per day on average, and eating twice a day were risk factors for inadequate animal protein intake, protein energy deficiency and fat energy deficiency. TB patients from impoverished counties in China have inadequate intake of several food categories and insufficient protein and fat energy supply, correlating with multiple factors in socio-demographics, behavioral practices, and TB disease. To improve the nutritional status of TB patients, urgent public health actions, especially carrying out nutritional screening and evaluation once diagnosed, developing individualized nutritional support treatment plans, strengthening dietary nutritional health education and intervention, and advocating for enhanced nutritional support, should be taken.

Whole Genomic Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics of Mycobacterium tuberculosis in Guangxi, China.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health issue in China. Nevertheless, the prevalence and drug resistance characteristics of isolates vary in different regions and provinces. In this study, we investigated the population structure, transmission dynamics and drug-resistant profiles of Mtb in Guangxi, located on the border of China. Methods: From February 2016 to April 2017, 462 clinical M. tuberculosis isolates were selected from 5 locations in Guangxi. Drug-susceptibility testing was performed using 6 common anti-tuberculosis drugs. The genotypic drug resistance and transmission dynamics were analyzed by the whole genome sequence. Results: Our data showed that the Mtb in Guangxi has high genetic diversity including Lineage 1 to Lineage 4, and mostly belong to Lineage 2 and Lineage 4. Novelty, 9.6% of Lineage 2 isolates were proto-Beijing genotype (L2.1), which is rare in China. About 12.6% of isolates were phylogenetically clustered and formed into 28 transmission clusters. We observed that the isolates with the high resistant rate of isoniazid (INH, 21.2%), followed by rifampicin (RIF, 13.2%), and 6.7%, 12.1%, 6.7% and 1.9% isolates were resistant to ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and kanamycin (KAN), respectively. Among these, 6.5% and 3.3% of isolates belong to MDR-TB and Pre-XDR, respectively, with a high drug-resistant burden. Genetic analysis identified the most frequently encountered mutations of INH, RIF, EMB, SM, OFL and KAN were katG_Ser315Thr (62.2%), rpoB_Ser450Leu (42.6%), embB_Met306Vol (45.2%), rpsL_Lys43Arg (53.6%), gyrA_Asp94Gly (29.0%) and rrs_A1401G (66.7%), respectively. Additionally, we discovered that isolates from border cities are more likely to be drug-resistant than isolates from non-border cities. Conclusion: Our findings provide a deep analysis of the genomic population characteristics and drug-resistant of M. tuberculosis in Guangxi, which could contribute to developing effective TB prevention and control strategies.

Efficacy and Risk Factors of Interferon-Gamma Release Assays among HIV-Positive Individuals.

Latent tuberculosis is prevalent in HIV-infected people and has an impact on the progression of AIDS. The aim of this study is to match a more accurate IGRA method for the better detection of latent tuberculosis infection in HIV patients. All 2394 patients enrolled were tested using three IGRA methods. The positive rate consistency of pairwise comparison and risk factors were analyzed. Receiver operator characteristic (ROC) curve analysis was applied to evaluate the diagnostic value of T-SPOTTB. The positive rates of the three methods were statistically different (p < 0.001). The CD4+ T cell number statistically impacted the QuantiFERON and Wan Tai tests after the analysis with univariate logistic regression, while no statistical difference was observed in T-SPOT.TB. Additionally, there was a better sensitivity and specificity of T-SPOT.TB if the positive cut-off value of ESAT-6 and CFP-10 was 4.5 and 5.5, respectively. This study provides an insight into the IGRA methods and demonstrated that the positive response detected via QuantiFERON declined with decreased CD4+ T cells in the HIV-infected population; T-SPOT.TB functions independently of the CD4+ T cell level and Wan Tai was affected in some cases. This will be useful in the diagnosis of LTBI in the HIV-infected population, which will be a key step toward TB elimination in China.

Tuberculosis among Ambulatory People Living with HIV in Guangxi Province, China: A Longitudinal Study.

BACKGROUND: This study aims to determine the prevalence of TB among ambulatory people living with HIV in Guangxi Province, which experienced the biggest HIV epidemic in China. METHODS: We undertook a longitudinal study in five HIV/AIDS designated hospitals randomly selected from Guangxi Province; all newly diagnosed HIV/AIDS outpatients from 2019 to 2021 were screened for TB and interviewed with a questionnaire. RESULTS: A total of 4539 HIV/AIDS outpatients were enrolled, with 2886 (63.6%) men and 1653 (26.4%) women. The prevalence of TB/HIV coinfection was 0.8%, with a clear downward trend from 1.3% in 2019 to 0.4% in 2021 (p = 0.0011). The prevalence of LTBI was 24.3%, with no significant differences from 2019 to 2021. The percentages of AIDS, comorbidity, nine symptoms and abnormal chest X-ray of TB were higher than those of the other PLWH. CONCLUSION: The prevalence of TB among ambulatory people with HIV in Guangxi Province was 14 times higher than the general population, and the annual declined TB prevalence indicated the effectiveness of TB and HIV control and prevention over recent years. The findings proved that symptom screening was insufficient for TB diagnosis and highlighted the importance of systematic TB screening at every visit to a health facility.

Space-Time Distribution Characteristics of Tuberculosis and Its Socioeconomic Factors in Southern China from 2015 to 2019.

Purpose: Guangxi is a high prevalence area of tuberculosis (TB) in China, urgent needing of further TB reduction. Our purpose is to analyze the epidemiological characteristics of TB in Guangxi and analyze the relationship between socioeconomic factors and TB from the dimensions of time and space to provide evidence to effectively prevent and control TB. Patients and Methods: We performed a retrospective analysis of the epidemiology of TB. Moran's index (I) was used for spatial autocorrelation analysis, and space-time scanning was used to detect temporal, space, and space-time clusters of TB. A Bayesian space-time model was used to analyze related factors of the TB epidemic at the county level in Guangxi. Results: From 2015 to 2019, a total of 233,623 TB cases were reported in Guangxi. The majority of TB cases were in males; the reported incidence of TB was the highest in people aged ≥65 years. By occupation, farmers were the most frequently affected. The overall reported incidence of TB decreased by 4.95% during this period. Tuberculosis occurs all year round, but the annual reporting peak is usually from March to July. Spatial autocorrelation analysis showed that the reported incidence of TB in 2015-2019 was spatially clustered (Moran's I > 0, P < 0.05); Kulldorff's scan revealed that the space-time cluster (log-likelihood ratio = 2683.76, relative risk = 1.60, P < 0.001) was mainly concentrated in northern Guangxi. Using Bayesian space-time modeling, socioeconomic and healthcare factors are related to the high prevalence of TB. Conclusion: The prevalence of TB is influenced by a space-time interaction effect and is associated with socioeconomic and healthcare status. It is necessary to improve the economic development and health service in areas with a high TB prevalence.

Adolescent tuberculosis associated with tuberculosis exposure in classrooms and dorm rooms in Guangxi, China.

OBJECTIVE: Quantify tuberculosis (TB) risk attributable to dorm room exposure in addition to classroom exposure. METHODS: Adolescent school contact investigations were conducted for every reported index TB case, and similar contact investigations were conducted in selected community-control classes from November 2016 to October 2017 in Guangxi, China. RESULTS: A total of 6263 contacts of 112 index TB cases and 6130 classmates of 112 controls were investigated. There were 14, 12, and 2 new active TB cases detected among classmates/non-roommates of index cases, classmates/roommates of index cases, and control classmates, respectively. Compared with control contacts, the adjusted relative risk (95% confidence interval (CI)) and population attributable fraction (PAF) for being a classmate/non-roommate of the index case increased the risk of active TB diagnosis to 8.44 (95% CI: 1.31-54.48) and 44.1%. The adjusted RR and PAF for being a classmate/roommate of the index case was 29.37 (95% CI: 3.80, 227.11) and 41.4%. Being classmates/roommates significantly increased the risk of TB compared to a classmate/non-roommate of the index case (RR=3.48, 95% CI: 1.64, 7.40). CONCLUSION: The additional risk of TB due to exposure in the dorm room should be taken into account in planning of TB prevention and control in boarding schools.

Tuberculosis Transmission in Households and Classrooms of Adolescent Cases Compared to the Community in China.

The aim of this paper is to evaluate the link between the history of exposure to tuberculosis (TB) in the household and diagnosed TB cases at school, and to compare the detection rate of active TB among household contacts and classroom contacts of adolescent TB cases with the rates among contacts of healthy controls. From November 2016 to December 2017, a prospective matched case-control study was conducted using passively identified index adolescent student cases from the TB surveillance system and healthy controls (matched by county, school type, sex, age and ethnicity). Contacts in households and classrooms of index cases and of controls were investigated. Matched tabulation of 117 case-control pairs revealed exposure to TB in the household as a strong risk factor (odds ratio (OR) = 21.0, 95% confidence interval (CI): 3.4, 868.6). Forty-five (case detection rate 0.69%) and two (case detection rate 0.03%) new active TB cases were detected among 6512 and 6480 classroom contacts of the index cases and controls, respectively. Having an index case in the classroom significantly increased the risk of classmates contracting active TB (OR = 22.5, 95% CI: 5.9, 191.4). Our findings suggested that previous exposure to TB in the household could lead a child to catch TB at school, then spread TB to classmates.

[Advance in application of syndromic surveillance for detection of emerging infectious diseases and outbreak alerts].

Over the past decade, syndromic surveillance, as supplementation of disease surveillance, has provided possibility of early alert in a real-time way for detection of emerging infectious diseases and outbreaks of widespread infectious diseases, resulting in improvement in sensitivity of outbreak detection and public health alert capacity. This tool has been highly valued and widely used in the world, and effective implementation has been observed in China. Upon abundant literature search, the authors reviewed the progress and advance of syndromic surveillance in early alert of emerging infectious diseases and outbreaks, and analyzed the problem met in the current situation in China when implementing syndromic surveillance in local facilities, which are high cost, lack of medical information platform, lack of real-time digital alert system and lack of a comprehensive information exchange platform. The authors suggested that syndromic surveillance should be implemented considering the local situation and performed in a more effective way in the current situation. Syndromic surveillance has to be integrated into the conventional public health surveillance systems and advanced laboratory networks. Digital information system is urgently needed to achieve real-time alert.

Bacterial etiologies of five core syndromes: laboratory-based syndromic surveillance conducted in Guangxi, China.

BACKGROUND: Under the existing national surveillance system in China for selected infectious diseases, bacterial cultures are performed for only a small percentage of reported cases. We set up a laboratory-based syndromic surveillance system to elucidate bacterial etiologic spectrum and detect infection by rare etiologies (or serogroups) for five core syndromes in the given study area. METHODS: Patients presenting with one of five core syndromes at nine sentinel hospitals in Guagnxi, China were evaluated using laboratory-based syndrome surveillance to elucidate bacterial etiologies. We collected respiratory and stool specimens, as well as CSF, blood and other related samples for bacterial cultures and pulse field gel electrophoresis (PFGE) assays. RESULTS: From February 2009 to December 2011, 2,964 patients were enrolled in the study. Etiologies were identified in 320 (10.08%) patients. Streptococcus pneumonia (37 strains, 24.18%), Klebsiella pneumonia (34, 22.22%), Pseudomonas aeruginosa (19, 12.42%) and Haemophilus influenza (18, 11.76%) were the most frequent pathogens for fever and respiratory syndrome, while Salmonella (77, 81.05%) was most often seen in diarrhea syndrome cases. Salmonella paratyphi A (38, 86.36%) occurred in fever and rash syndrome, with Cryptococcus neoformans (20, 35.09%), Streptococcus pneumonia (5, 8.77%), Klebsiella pneumonia (5, 8.77%),streptococcus suis (3, 5.26%) and Neisseria meningitides group B (2, 3.51%) being the most frequently detected in encephalitis-meningitis syndrome. To date no pathogen was isolated from the specimens from fever and hemorrhage patients. CONCLUSIONS: In addition to common bacterial pathogens, opportunistic pathogens and fungal infections require more attention. Our study contributes to the strengthening of the existing national surveillance system and provides references for other regions that are similar to the study area.

[Comparative analysis of three diarrhea-household-surveys in Guangxi].

OBJECTIVE: To study the epidemiological characteristics and the effects of control measurements in Guangxi by comparing the results from diarrhea-household-surveys conducted in the three different periods of time and to develop control strategies. METHODS: Data on the incidence, health care seeking and treatment of diarrhea from three household surveys conducted in 1988, 1995 and 2007 was analyzed using SPSS (version 13.0). RESULTS: The incidence rates of diarrhea over the three periods of time were 0.562, 0.456 and 0.221 per person-year, respectively (P < 0.001). No significant difference was found in the incidence between males and females. The disease mainly attacked young age groups and those with lower educational levels. In recent years, longer durations of disease but less severe were observed in patients with diarrhea. The patients mainly visited first line health services with a health care seeking rate of 28.3%. Antibiotics were used by most of the patients (49.8% - 90.2%), while the rate of using oral rehydration salts (ORS) was only 1.4% - 11.5% but the use of traditional Chinese medicines has increased. Intake of untreated water, contaminated foods and contact with patients were important risk factors on diarrhea. CONCLUSION: The prevalence of diarrhea in Guangxi had declined and the health seeking rate was low in the past two decades. It is necessary to further regulate the treatment, in order to strengthen the health education programs to the general population, in order to improve the accessibility of health services and to increase both the health care seeking rate and effective diagnosis rate.

[Application of cluster randomization method on typhoid Vi vaccine trails].

OBJECTIVE: To describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation. METHODS: Simple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine. RESULTS: According to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced. CONCLUSION: Confounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; expanding the use of Vi polysaccharide vaccine in southeast China: a cluster-randomized trial.

BACKGROUND: One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. METHODS: The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. RESULTS: The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged < or = 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. CONCLUSION: The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

[Epidemiologic surveillance for bacterial meningitis in 140 000 children under 5 years of age in Nanning district, Guangxi province].

OBJECTIVE: To characterize the incidence, epidemiologic features, etiologic agents and sequelae of bacterial meningitis in children under 5 years of age in Nanning, Guangxi. METHODS: A population-based surveillance was conducted to evaluate children with signs and symptoms of meningitis. All hospitals, township health centers and village clinics in the surveillance area were structured to participate in the case referral and evaluation. Cerebrospinal fluid (CSF) and blood specimens were obtained and processed using standardized microbiologic methods. RESULTS: During the 26-month surveillance period, among the children under 5 years old, a total of 1272 cases who met the screening criteria of meningitis were studied. 265 of 1272 cases were identified as clinically diagnosed meningitis, with an incidence rate of 86.36 per 100 000 population. The annual incidence rate under the 38 cases of confirmed bacterial meningitis appeared to be 12.38/100 000. Staphylococcus species accounted for the largest proportion of laboratory-confirmed bacterial meningitis, followed by E. coli and S. pneumoniae. The highest attack rate occurred in neonates < 1 month, followed by children aged 1 - 12 months in the confirmed patients. Meningitis caused by Sp and Hi mainly occurred in children aged 1 - 12 months. All cases of meningitis due to Hi and Sp were children aged 1 - 24 months. 13.16% and 0.00% of the cases survived with complications and sequelae, and the case-fatality rate was 18.42%. 40 bacterial isolates were identified from 1193 blood cultures and 23 from 1211 cerebrospinal fluid samples, but no Neisseria meningitidis was found. CONCLUSION: Meningitis due to Hi was first confirmed in Guangxi with the incidence of 0.98 per 100 000 population. The annual incidence rate of confirmed bacterial meningitis was 12.38 per 100 000, which was considered an important public health problem in children. Staphylococci was the predominant pathogen in confirmed bacterial meningitis.