High Risk Of Tuberculosis Infection Research Articles

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Using Electronic Health Record Data to Measure the Latent Tuberculosis Infection Care Cascade in Safety-Net Primary Care Clinics

Prevention of tuberculosis disease through diagnosis and treatment of latent tuberculosis infection is critical for achieving tuberculosis elimination in the U.S. Diagnosis and treatment of latent tuberculosis infection in safety-net primary care settings that serve patients at risk for tuberculosis may increase uptake of this prevention effort and accelerate progress toward elimination. Optimizing tuberculosis prevention in these settings requires measuring the latent tuberculosis infection care cascade (testing, diagnosis, and treatment) and identifying gaps to develop solutions to overcome barriers. We used electronic health record data to describe the latent tuberculosis infection care cascade and identify gaps among a network of safety-net primary care clinics. Electronic health record data for patients seen in the OCHIN Clinical Network, the largest network of safety-net clinics in the U.S., between 2012 and 2019 were extracted. electronic health record data were used to measure the latent tuberculosis infection care cascade: patients who met tuberculosis screening criteria on the basis of current recommendations were tested for tuberculosis infection, diagnosed with latent tuberculosis infection, and prescribed treatment for latent tuberculosis infection. Outcomes were stratified by diagnostic test and treatment regimen. Among 1.9 million patients in the analytic cohort, 43.5% met tuberculosis screening criteria, but only 21.4% were tested for latent tuberculosis infection; less than half (40.4%) were tested using an interferon-gamma release assay. Among those with a valid result, 10.5% were diagnosed with latent tuberculosis infection, 29.1% of those were prescribed latent tuberculosis infection treatment, and only 33.6% were prescribed a recommended rifamycin-based regimen. Electronic health record data can be used to measure the latent tuberculosis infection care cascade. A large proportion of patients in this safety-net clinical network are at high risk for tuberculosis infection. Addressing identified gaps in latent tuberculosis infection testing and treatment may have a direct impact on improving tuberculosis prevention in primary care clinics and accelerate progress toward elimination.

The prevalence and risk factors for tuberculosis among healthcare workers in Yogyakarta, Indonesia.

Healthcare workers (HCWs) are at risk of contracting TB, particularly when in high tuberculosis (TB) burden settings. Routine surveillance data and evidence are limited on the burden of TB amongst HCWs in Indonesia. We aimed to measure the prevalence of TB infection (TBI) and disease among HCWs in four healthcare facilities in Yogyakarta province in Indonesia, and explore risk factors for TBI. A cross-sectional TB screening study targeted all HCWs from four pre-selected facilities (1 hospital, 3 primary care) in Yogyakarta, Indonesia. Voluntary screening included symptom assessment, Chest X-ray (CXR), Xpert MTB/RIF (if indicated) and tuberculin skin test (TST). Analyses were descriptive and included multivariable logistic regression. Of 792 HCWs, 681 consented (86%) to the screening; 59% (n = 401) were female, 62% were medical staff (n = 421), 77% worked in the one participating hospital (n = 524), and the median time working in the health sector was 13 years (IQR: 6-25 years). Nearly half had provided services for people with TB (46%, n = 316) and 9% reported ever having TB (n = 60). Among participants with presumptive TB (15%, n = 99/662), none were diagnosed microbiologically or clinically with active TB disease. TBI was detected in 25% (95% CI: 22-30; n = 112/441) of eligible HCWs with a TST result. A significant association was found between TB infection and being male (adjusted Odds Ratio (aOR) 2.02 (95%CI: 1.29-3.17)), currently working in the participating hospital compared to primary care (aOR 3.15 (95%CI: 1.75-5.66)), and older age (1.05 OR increase per year of life between 19-73 years (95%CI: 1.02-1.06)). This study supports prioritisation of HCWs as a high-risk group for TB infection and disease, and the need for comprehensive prevention and control programs in Indonesia. Further, it identifies characteristics of HCWs in Yogyakarta at higher risk of TBI, who could be prioritised in screening programs if universal coverage of prevention and control measures cannot be achieved.

Risk And Prevalence of Latent Tuberculosis Infection Among Healthcare Workers of Tertiary Care Hospital in Karachi Pakistan

More than 10 million people fall sick due to TB annually; Pakistan ranks 5th for highest tuberculosis (TB) burden globally. Latent tuberculosis infection (LTBI) is asymptomatic TB infection that can reactivate later on, causing transmission and disease. Health care workers dealing with positive Mycobacterium Tuberculosis (MTB) samples and patients are at high risk of TB infection. In this study, we investigated the frequency of LTBI in health care workers as well as a comparative group of patients suspected to have LTBI by their physicians. A total of 77 healthy healthcare workers (including phlebotomists, medical technologists, nurses, doctors, and faculty members working closely with TB samples or patients) and 104 patients diagnosed with TB were recruited in our study after institutional ethical approval. 3ml of whole blood was collected from study participants and was dispensed into three specific QFT tubes. (NIL, TB, Mitogen). Samples were investigated for interferon specifically released against TB according to the manufacturer’s protocol by using QuantiFERON TB Gold assay kit. Out of 77 healthcare workers, 16.8% (n=13) were positive for LTBI; these included microbiologists, technicians, phlebotomists, and housekeeping staff. However, none of the doctors and medical technologists tested positive. On the other hand, out of 104 patients, 23.1 % (n=24) were found to be positive, 10.5% (n=11) were indeterminate and 65.3% (n=68) were negative for LTB. The one-tail chi-square test revealed 35.14% risk to the highly exposed HCWs with the overall estimated risk of 42.54%. This study reports a high prevalence of LTBI in HCWs. Among the HCWs, microbiologists and technicians were the most affected. Housekeeping staff was also found to have LTBI. This study also found a higher risk for LTBI in technicians, medical technologists, microbiologists, and phlebotomist as compared to doctors and interns. This highlights the importance of regular screening of all HCWs, including housekeeping staff, in order to control and prevent the spread of this disease.

Preventive Treatment for Household Contacts of Drug-Susceptible Tuberculosis Patients.

People who live in the household of someone with infectious pulmonary tuberculosis are at a high risk of tuberculosis infection and subsequent progression to tuberculosis disease. These individuals are prioritized for contact investigation and tuberculosis preventive treatment (TPT). The treatment of TB infection is critical to prevent the progression of infection to disease and is prioritized in household contacts. Despite the availability of TPT, uptake in household contacts is poor. Multiple barriers prevent the optimal implementation of these policies. This manuscript lays out potential next steps for closing the policy-to-implementation gap in household contacts of all ages.

Predisposing Factors of Tuberculosis Infection in Systemic Lupus Erythematosus Patients: A Single-Center Case-Control Study.

Introduction: Indonesia has the second-highest tuberculosis cases in the world, according to the global WHO tuberculosis report, amounting to approximately 10% of the world's tuberculosis cases. Systemic lupus erythematosus (SLE) patients are at an increased risk for tuberculosis infection. This research aims to analyze the association between corticosteroid pulse dose, corticosteroid cumulative dose, SLE disease duration, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and lupus nephritis status with the development of tuberculosis in SLE patients.Methods: This research was a matched case-control study to identify risk factors of tuberculosis infection in SLE patients. Data were taken from medical records of Cipto Mangunkusumo National General Hospital, a national tertiary hospital. Inclusion criteria were patients who meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria of SLE in the period of 2012-2016 or patients who meet the SLICC 2012 SLE criteria and developed tuberculosis between 2012 and 2016. Statistical analyses used were bivariate analysis and correlation analysis. All statistical analyses were conducted using SPSS software (IBM Corp., Armonk, NY). All statistical analyses were defined as statistically significant when the p-value was less than 0.05.Results: A total of 48 SLE patients were included from medical records consisting of 24 SLE patients with tuberculosis infection and controls of 24 SLE patients without tuberculosis infection. In this study, it was observed that the presence of lupus nephritis (p = 0.001), administration of pulse corticosteroids (p = 0.048), high corticosteroid cumulative dose (p = 0.001), and high SLEDAI score (p = 0.003) were associated with tuberculosis infection. Correlation analysis showed that all of these variables had a weak positive correlation with tuberculosis infection in SLE patients.Conclusion: SLE patients with lupus nephritis, administration of pulse corticosteroids, high cumulative corticosteroid dose, and high SLEDAI score have a higher risk of tuberculosis infection. Clinicians and patients should be aware of these risk factors in SLE patients to prevent tuberculosis infection. Corticosteroid pulse dose should be avoided in SLE patients and if it is needed, tuberculosis prophylaxis may be considered.

Variability of interferon-γ release assays in people at high risk of tuberculosis infection or progression to tuberculosis disease living in the United States

ObjectivesInterferon-γ release assays, including T-SPOT.TB (TSPOT) and QuantiFERON Gold In-Tube (QFT), are important diagnostic tools for tuberculosis infection, but little work has been done to study the performance of these tests in populations prioritized for tuberculosis testing in the United States, especially those other than health care personnel. MethodsParticipants were enrolled as part of a large, prospective cohort of people at high risk of tuberculosis infection or progression to tuberculosis disease. All participants were administered a tuberculin skin test, TSPOT, and QFT test. A subset of participants had their QFT (n = 919) and TSPOT (n = 885) tests repeated when they returned to get their tuberculin skin test read 2 to 3 days later (repeat study). A total of 531 participants had a TSPOT performed twice on the same sample taken at the same time (split study). ResultsThe QFT repeat test interpretations were discordant (one test positive and the other negative) for 6.4% of participants (59 of 919), and the TSPOT tests were discordant for 60 of 885 participants in the repeat study (6.8%) and 41 of 531 participants in the split study (7.7%). There was a high degree of variability in the quantitative test results for both QFT and TSPOT, and discordance was not associated with both test results being near the established cut-offs. Furthermore, the proportion of discordance was similar when comparing participants in both the TSPOT repeat and TSPOT split studies. DiscussionBoth QFT and TSPOT were 6% to 8% discordant. The results should be interpreted with caution, particularly when seeing a conversion or reversion in serial testing.

Comparing the Risk of M. Tuberculosis Infection among Men and Women in an African City

Background: Despite the well-known male bias in tuberculosis disease, the underlying reasons remained elusive. We examined whether male predominance in tuberculosis disease is result of higher risk of tuberculosis infection or not. If so, whether it is due to higher likelihood of exposure or higher susceptibility to infection among men. Methods: A household contact study and a prospective cohort study conducted in Kampala, Uganda, from 2013 to 2017 were used to estimate and compare prevalence and annual risk of tuberculosis infection among men and women. In household contact study, index tuberculosis cases and healthy index controls were asked to list their household contacts and extra-household contacts. All contacts were tested with tuberculin skin test to detect tuberculosis infection. In prospective cohort study, individuals with tuberculin skin test (TST) < 5 mm were enrolled and retested with the skin test at one year to detect new infection. Poisson regression with robust standard errors was used to estimate prevalence ratio and relative risk of tuberculous infection between men and women. Results: In household contact study, 123 index tuberculosis cases and 124 index controls listed 382 household contacts of tuberculosis cases, 624 extra-household contacts of tuberculosis cases, and 1044 contacts of controls. Of 1681 enrolled participants in cohort study, 1213 (72%) were retested with TST at one year. There was no sex difference in prevalence of tuberculosis infection among household contacts of tuberculosis cases, but men had a higher prevalence of tuberculosis infection among extra-household contacts of tuberculosis cases (prevalence ratio 1.25, 95% CI 1.06 – 1.48) and contacts of controls (prevalence ratio 1.53, 95% CI 1.30 – 1.81). Similarly, in cohort study, there was no sex difference in annual risk of tuberculosis infection when participant reported knowing tuberculosis cases, but men had a higher annual risk of tuberculosis infection when participants no known contact with tuberculosis (relative risk 1.94, 95% CI: 1.34, 2.80). Conclusion: Men have higher risk of acquiring tuberculous infection than women. Men and women may have the same susceptibility to tuberculosis infection given known exposure to tuberculosis cases. The observed difference in rate of infection may be partially explained by higher rates of exposure to undetected, infectious tuberculosis cases among men.

The seroconversion rate of QuantiFERON-TB gold in-tube test in psoriatic patients receiving anti-interleukin-23 monoclonal antibodies

Background: Biologic therapies have become the gold standard for the treatment of moderate-to-severe psoriasis and psoriatic arthritis. However, concerns for opportunistic infections exist, especially for tuberculosis (TB) in endemic areas. Previously, tumor necrosis factor inhibitors were reported to carry higher risks of latent TB infection (LTBI) reactivation or new active TB, followed by anti-interleukin (IL)-12/23 and IL-17 agents in Taiwan. Objectives: The objective of the study is to provide real-world clinical rate of seroconversion of serial QuantiFERON-TB gold in-tube (QFT-GIT) tests, for detection of LTBI and newly-acquired TB, in psoriasis patients while receiving IL-23 inhibitors in an intermediate TB burden country. Methods: The local risk management plan required regular monitoring of TB while receiving biologics for psoriasis. This retrospective cohort evaluated consecutive psoriasis patients who received guselkumab or risankizumab between 2015 and 2021 in a tertiary referral center in Taiwan. Results: A total of 144 patients were included, with negative baseline QFT-GIT in 88% and positive in 13%. After receiving at least 6 months of anti-IL-23 drugs, persistently seropositive was found in 15 patients (10%), persistently seronegative in 125 patients (87%), seroconversion in 1 patient (0.6%), and seroreversion in 3 patients (1.9%). The seroconversion rate was 1% (1/127) in individuals under anti-IL-23 medications for at least 12 months. No case of LTBI reactivation was identified. Conclusion: In psoriasis patients under anti-IL-23 therapy, serial interferon-gamma release assays demonstrated a low seroconversion rate (<1%). Anti-IL-23 agents may be a favorable choice for psoriasis patients with a higher risk of TB infection and LTBI reactivation or those who reside in endemic regions.

The Research Progress in Immunotherapy of Tuberculosis.

Tuberculosis (TB) is a serious public health problem worldwide. The combination of various anti-TB drugs is mainly used to treat TB in clinical practice. Despite the availability of effective antibiotics, effective treatment regimens still require long-term use of multiple drugs, leading to toxicity, low patient compliance, and the development of drug resistance. It has been confirmed that immune recognition, immune response, and immune regulation of Mycobacterium tuberculosis (Mtb) determine the occurrence, development, and outcome of diseases after Mtb infection. The research and development of TB-specific immunotherapy agents can effectively regulate the anti-TB immune response and provide a new approach toward the combined treatment of TB, thereby preventing and intervening in populations at high risk of TB infection. These immunotherapy agents will promote satisfactory progress in anti-TB treatment, achieving the goal of “ultra-short course chemotherapy.” This review highlights the research progress in immunotherapy of TB, including immunoreactive substances, tuberculosis therapeutic vaccines, chemical agents, and cellular therapy.

Comparing Tuberculin Anergy Skin Test Reactions and Lymphoblastic Transformation in Medical Student

Background: Tuberculin Skin Test (TST) reaction is an accepted screening test for diagnosing acute and latent Tuberculosis (TB) infection among at-risk populations. It is performed with a standard Protein Purified Derivative (PPD) solution. The skin reaction of PPD is unreliable to distinguish natural infection from the Bacillus Calmette Guerin (BCG) effect. The present survey aimed to determine the prevalence of Tuberculin Anergy (TA) reactions among medical students. Accordingly, we evaluated its sensitivity, specificity, and efficiency by applying the Recall Panel Antigen Test (RPAT) and the Lymphoblastic Transformation Test (LTT). Methods: The participants were sequentially enrolled in this study according to the designed protocol. The current study was conducted on healthy medical students before registering for the hospital training course. All research subjects were healthy, having a cicatrix of Bacillus Calmette Guerin (BCG) vaccination on the arm, and at a young age (20-24 years). Results: In total, 180 medical students met the inclusion criteria of the study. The study subjects’ Mean±SD age was 22±3.07 years (male=89, female=91). Moreover, 75 (42%) subjects presented a TA reaction in the first step of TST screening. Furthermore, 13 (64%) individuals presented a negative result of the RPAT. The sensitivity and specificity of the TST reactions, compared with the LTT were 100% and 94.4 %, respectively. Conclusion: Significant TA reactions were found among medical students with positive cicatrix post-vaccinated. The obtained data suggested that the BCG protection for individuals may be decreased as time expired. Consequently, the medical students will especially be at high risk for TB infection during the clinical training course. The collected data highlighted the patient-safety from the viewpoint of forensic medicine.

Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis

BackgroundPolycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD.MethodsA nationwide population-based cohort study was performed using Taiwan’s National Health Insurance Research Database. We used patients’ hospitalization files for the entire analysis during 2000–2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection.ResultsA total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51–2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46–4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29–2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69–4.30).ConclusionsTaken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

The risk of pulmonary tuberculosis after traumatic brain injury

After traumatic brain injury (TBI), an inflammatory response in the brain might affect the immune system. The risk of pulmonary infection reportedly increases in patients with TBI. We aimed to evaluate the risk of tuberculosis (TB) in patients with TBI in Taiwan. All participants were selected from the intensive care unit (ICU). Patients with TBI were defined as patients in ICU with intracranial injury, and comparison cohort were patients in ICU without TBI diagnosis. There was a significant difference in TB risk between the patients with TBI and the comparison cohort according to age and the Charlson’s comorbidity index (CCI) score. Thus, we divided patients based on CCI into three groups for further analysis: mild (CCI = 0), moderate (CCI = 1/2), severe (CCI > 2). Mild-CCI group had a lower TB incidence rate (0.74%) and longer time to TB development (median: 2.43) than the other two groups. Moderate-CCI group had 1.52-fold increased risk of TB infection (p < 0.0001) compared with mild-CCI group. In the severe-CCI group, patients aged ≥ 80 years had 1.91-fold risk of TB compared with mild-CCI group (p = 0.0481). Severe-CCI group had significantly higher mortality than the mild-CCI group (p = 0.0366). Patients with TBI and more comorbidities had higher risk of TB infection with higher mortality rate.

Prevalence of Latent Tuberculosis Infection Among Non-US-Born Persons by Country of Birth-United States, 2012-2017.

Most tuberculosis (TB) disease in the United States (US) is attributed to reactivation of remotely acquired latent TB infection (LTBI) in non-US-born persons who were likely infected with Mycobacterium tuberculosis in their countries of birth. Information on LTBI prevalence by country of birth could help guide local providers and health departments to scale up the LTBI screening and preventive treatment needed to advance progress toward TB elimination. A total of 13 805 non-US-born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON Gold In-Tube test, and T-SPOT.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CrIs) for each country or world region of birth. Among the study population, the estimated LTBI prevalence was 31% (95% CrI, 26%-35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42% to 55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8% to 13%. LTBI prevalence in persons born outside the US varies widely by country. These estimates can help target community outreach efforts to the highest-risk groups.

Analysis and predication of tuberculosis registration rates in Henan Province, China: an exponential smoothing model study

BackgroundThe World Health Organization End TB Strategy meant that compared with 2015 baseline, the reduction in pulmonary tuberculosis (PTB) incidence should be 20 and 50% in 2020 and 2025, respectively. The case number of PTB in China accounted for 9% of the global total in 2018, which ranked the second high in the world. From 2007 to 2019, 854 672 active PTB cases were registered and treated in Henan Province, China. This study was to assess whether the WHO milestones could be achieved in Henan Province.MethodsThe active PTB numbers in Henan Province from 2007 to 2019, registered in Chinese Tuberculosis Information Management System were analyzed to predict the active PTB registration rates in 2020 and 2025, which is conductive to early response measures to ensure the achievement of the WHO milestones. The time series model was created by monthly active PTB registration rates from 2007 to 2016, and the optimal model was verified by data from 2017 to 2019. The Ljung-Box Q statistic was used to evaluate the model. The statistically significant level is α = 0.05. Monthly active PTB registration rates and 95% confidence interval (CI) from 2020 to 2025 were predicted.ResultsHigh active PTB registration rates in March, April, May and June showed the seasonal variations. The exponential smoothing winter’s multiplication model was selected as the best-fitting model. The predicted values were approximately consistent with the observed ones from 2017 to 2019. The annual active PTB registration rates were predicted as 49.1 (95% CI: 36.2–62.0) per 100 000 population and 34.4 (95% CI: 18.6–50.2) per 100 000 population in 2020 and 2025, respectively. Compared with the active PTB registration rate in 2015, the reduction will reach 23.7% (95% CI, 3.2–44.1%) and 46.8% (95% CI, 21.4–72.1%) in 2020 and 2025, respectively.ConclusionsThe high active PTB registration rates in spring and early summer indicate that high risk of tuberculosis infection in late autumn and winter in Henan Province. Without regard to the CI, the first milestone of WHO End TB Strategy in 2020 will be achieved. However, the second milestone in 2025 will not be easily achieved unless there are early response measures in Henan Province, China.

Association of gene polymorphisms and environmental factors in tuberculosis patients and their household contacts.

Tuberculosis (TB) is an important public health problem in China and environmental and genetic factors have an impact on its occurrence and development. We explored the relationship between environmental factors, genetic susceptibility genes and gene-environment interactions and the incidence of TB, as well as their high-risk combination, which can provide a scientific basis for prevention of the disease. The 242 individuals, which included 82 TB patients, 67 family genetically related patients and 93 healthy controls, all of whom were of the Han population in Guangdong Province. The basic information of subjects was collected, including general conditions, behaviour habits, family environmental factors and blood samples. Two single nucleotides with potential functions (interleukin-10 [IL-10] rs1800896, interferon-γ [IFN-γ] rs2430561) were screened by bioinformatics tools and identified by polymerase chain reaction-restriction fragment length polymorphism. We found that gender, education, TB exposure history, fitness activities, residential areas and indoor hygiene conditions were all associated with the occurrence of TB. In the dominant model, AG+GG of IL-10 and AA of IFN-γ are high-risk genotypes. Multifactor dimensionality reduction (MDR) analysis of TB-prone families shows that a combination of male sex, IL-10 AA and AG genotypes and smoking history are elements of high risk for TB infection (prediction accuracy 62.45%, cross-validation consistency 10/10). The MDR analysis of the TB patients group and the healthy control group showed that the combination of low education level, history of TB exposure, and IFN-γ AA genotype represented a higher risk of TB infection (prediction accuracy 80.34%, cross-validation consistency 10/10). The occurrence of TB in TB-prone families in the Han population of Guangdong Province is related to environmental factors as well as cytokines IL-10 and IFN-γ. We also found high-risk combinations of genes and environmental factors, providing clues for the timely detection of high-risk groups.

The Prevalence and Demographic Risk Factors for Latent Tuberculosis Infection (LTBI) Among Healthcare Workers in Semarang, Indonesia.

PurposeTo determine the prevalence and demographic risk factors for latent tuberculosis infection (LTBI) among healthcare workers in Semarang, Indonesia.MethodsA cross-sectional study involving 195 healthcare workers from 34 primary health centers was conducted from August to October 2019. The relationship between independent variables and dependent variables was analyzed using a multivariable logistic regression analysis.ResultsThe prevalence of LTBI among healthcare workers in this study was 23.6%. Comorbidities were the only risk factor for LTBI identified among other risk factors (OR=3.39, 95% CI: 0.99–11.62, p=0.04). Other demographic factors such as age (OR=0.93, 95% CI: 0.45–1.92, p=0.839), gender (OR=0.79, 95% CI: 0.23–2.72, p=0.708, smoking habits (OR=2.54, 95% CI: 0.52–12.38, p=0.247), and length of work (OR=1.43, 95% CI: 0.70–2.91, p=0.331) were not significant risk factors for LTBI.ConclusionHealthcare workers suffering from comorbidity have a high risk for tuberculosis infection, and should not work in areas where they would be exposed to patients with tuberculosis. Healthcare workers need to apply occupational safety standards during contact with TB patients or specimens to minimize the disease transmission.

Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a multisystem disease that affects the joints and various organs, resulting in compromised quality of life and increased mortality. A wide spectrum of treatment options is available for RA. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are the first-line of treatment for RA, whereas tumor necrosis factor α inhibitors are commonly used as a second-line biological disease-modifying antirheumatic drug following inadequate response to csDMARDs. However, remission remains difficult to achieve. No single agent is effective for all patients. It is important to consider patients' comorbidities, perspectives, and preferences when selecting treatment.Interleukin 6 (IL-6) plays a prominent role in the pathophysiology of RA and is an important therapeutic target for RA. Tocilizumab and sarilumab are approved IL-6 inhibitors, which have demonstrated good efficacy and tolerability as combination therapy or monotherapy in RA patients with inadequate response to csDMARDs or tumor necrosis factor α inhibitors. Apart from alleviating joint symptoms, inducing remission, and reducing structural damage, tocilizumab and sarilumab exhibit additional advantages in alleviating extra-articular symptoms, such as fatigue and morning stiffness, and have positive effect on anemia and glucose metabolism. Additionally, evidence showed that certain patient subgroups, such as those with comorbidities including anemia and diabetes mellitus, those with early RA, those with high baseline IL-6 levels, those at high risk of tuberculosis infection, or those intolerant to methotrexate monotherapy, may benefit from IL-6 inhibition. Given these advantages, tocilizumab and sarilumab can be considered earlier as a rational choice for treating RA in suitable patients. Future clinical investigations will help refine the use of these agents.

Contact evaluation and isoniazid preventive therapy among close and household contacts of tuberculosis patients in Lima, Peru: an analysis of routine data

Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19years. Of 191 eligible contacts <5years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19years old), and, only for those 5-19years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.

Transmissibility and potential for disease progression of drug resistant Mycobacterium tuberculosis: prospective cohort study

ObjectiveTo measure the association between phenotypic drug resistance and the risk of tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis.Setting106 district health centers in Lima, Peru...