Cases Of Tuberculosis Disease Research Articles

Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life: a South African birth cohort study

Paediatric tuberculosis leads to more than 200 000 deaths annually. We aimed to investigate the incidence of Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life in the Drakenstein Child Health Study (DCHS), a South African cohort in a community with high tuberculosis and HIV incidence. In this prospective birth cohort study, we enrolled pregnant women aged 18 years or older who were between 20 and 28 weeks' of gestation in a peri-urban setting outside of Cape Town, South Africa. We followed up their children for tuberculosis until age 10 years. To measure M tuberculosis infection tuberculin skin tests were administered to children at age 6 months, 12 months, and then annually in children with a negative test, and at the time of a lower respiratory tract infection. Tuberculin skin test conversion was defined by an induration reaction of 10 mm or more. To measure tuberculosis disease, active surveillance was done throughout follow-up. Each episode of presumed tuberculosis disease was investigated using sputum induction, tested with Xpert MTB/RIF and liquid culture for M tuberculosis. Survival analyses were performed and multivariable Cox regression was used to measure factors associated with M tuberculosis infection or disease. Between March 5, 2012, and March 31, 2015, 1137 women and their 1143 children (248 [21·7%] of 1143 children were HIV-exposed, two [0·2%] children with HIV) were included in the analysis. Children were followed up for 8870 person-years (median follow-up 9·1 years [IQR 8·2-10·2]). The annual risk of tuberculin conversion during follow-up was 6·6 infections per 100 person-years (95% CI 5·8-7·3) but ranged from 4-9 infections per 100 person-years over the follow-up period. 98 children developed tuberculosis (1105 cases per 100 000 person-years; 95% CI 906-1347). The cumulative hazard of tuberculin conversion was 36% (95% CI 32-41) at age 8 years and the cumulative hazard of tuberculosis disease was 10% (8-12) at age 10 years. Preventive treatment was associated with a reduction in tuberculosis disease among children who had tuberculin conversion (adjusted hazard ratio 0·23 [95% CI 0·12-0·47]). Most cases of tuberculosis disease (78 [79%; 95% CI 69-86] of 98 children) occurred among children who had tuberculin skin test conversion but were not administered preventive treatment. In this prospective South African birth cohort, M tuberculosis transmission was consistently high throughout the first decade of life leading to approximately 10% of children developing tuberculosis disease. A multipronged approach to decrease paediatric tuberculosis is needed that combines preventive treatment for children at risk, reducing community M tuberculosis transmission, and active case finding. Bill & Melinda Gates Foundation, Medical Research Council South Africa, and National Research Foundation South Africa.

Cardiac Tuberculosis: A Case Series from Ethiopia, Italy, and Uganda and a Literature Review.

Extrapulmonary tuberculosis (TB) is estimated to account for up to 20% of active cases of TB disease, but its prevalence is difficult to ascertain because of the difficulty of diagnosis. Involvement of the heart is uncommon, with constrictive pericarditis being the most common cardiac manifestation. Diagnostic research for cardiac disease is frequently lacking, resulting in a high mortality rate. In addition to direct cardiac involvement, instances of cardiac events during antitubercular therapy are described. This case series describes five cases of TB affecting the heart (cardiac TB) from Italy and high-burden, low-income countries (Ethiopia and Uganda), including a case of Loeffler syndrome manifesting as myocarditis in a patient receiving antitubercular therapy. Our study emphasizes how cardiac TB, rare but important in high-burden areas, is a leading cause of pericardial effusion or pericarditis. Timely diagnosis and a comprehensive approach, including imaging and microbiological tools, are crucial. Implementing high-sensitivity methods and investigating alternative samples, such as detection of tuberculosis lipoarabinomannan or use of the GeneXpert assay with stool, is recommended in TB control programs.

Quantitative interferon-gamma releasing assay in predicting tuberculosis in South Korean military: a retrospective cohort study

ObjectiveThe interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. MethodsThe analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. ResultsFrom 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1–147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1–205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 – 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2–3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3. DiscussionElevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.

Prior Screening for Latent Tuberculosis Among Patients Diagnosed With Tuberculosis Disease: Missed Opportunities?

California has the largest number of tuberculosis (TB) disease cases in the United States. This study in a large California health system assessed missed opportunities for latent tuberculosis (LTBI) screening among patients with TB disease. Kaiser Permanente Southern California patients who were ≥18 years old with membership for ≥24 months during the study period from 1 January 2008 to 31 December 2019 were included. Prior LTBI test (tuberculin skin test or interferon-γ release assay) or diagnosis code prior to TB disease diagnosis was assessed among patients with observed TB disease (confirmed by polymerase chain reaction and/or culture). In the absence of current treatment practices, more patients screened for LTBI may have developed TB disease. We estimated hypothetical TB disease cases prevented by multiplying LTBI progression rates by the number of LTBI-positive patients prescribed treatment. A total of 1289 patients with observed TB disease were identified; 148 patients were LTBI positive and 84 were LTBI negative. Patients not prescreened for LTBI made up 82.0% of observed TB disease cases (1057/1289). Adding the hypothetical maximum estimate for prevented cases decreased the percentage of patients who were not prescreened for LTBI to 61.7% [1057/(1289 + 424)]. One-fifth of patients were screened for LTBI prior to their active TB diagnosis. Assuming the upper bound of cases prevented through current screening, almost 62% of TB disease patients were never screened for LTBI. Future work to elucidate gaps in LTBI screening practices and to identify opportunities to improve screening guidelines is needed.

Tuberculosis Infection and Disease Among Pregnant People Living in Sweden With Origin in Tuberculosis-Endemic Countries.

Pregnancy has been associated with elevated incidence of tuberculosis (TB) disease. Since 2014, people living in Sweden with origin in TB-endemic countries have been offered screening for TB infection in antenatal care (ANC) using Quantiferon-TB assays. We assessed factors associated with TB infection in this population and determined the incidence of TB disease during pregnancy and postpartum periods with regard to ANC Quantiferon-TB results. Quantiferon-TB results obtained during ANC in Sweden, 2014-2018, were linked to data from national registers (Pregnancy Register, Patient Register and Tuberculosis Register). Factors associated with TB infection (defined as Quantiferon-TB ≥0.35 IU/mL) were identified using logistic regression analysis. Incidence of TB disease was determined with regard to pregnancy, postpartum and subsequent periods, and ANC Quantiferon-TB results. Among 7638 screened individuals, 1424 (18.6%) had TB infection. Tuberculosis infection was independently associated with higher age at immigration (adjusted odds ratio, 1.04 [95% confidence interval, 1.03-1.05]; P < .001), and was more common among people originating from Africa compared to other world regions (845/3088 [27.4%] vs 579/4550 [12.7%]; P < .001). In total, 16 participants were diagnosed with TB disease (10 during pregnancy, 4 at <6 months after delivery, 2 at >6 months after delivery); among these, all diagnosed during pregnancy/postpartum had positive ANC Quantiferon-TB results (constituting 14/1424 [1%] of people with TB infection). Among pregnant people screened in Swedish ANC, TB infection was associated with higher age and African origin. All cases of TB disease reported in persons with TB infection at ANC screening occurred during pregnancy or postpartum.

Understanding the biology, morbidity and social contexts of adolescent tuberculosis: a prospective observational cohort study protocol (Teen TB)

IntroductionA considerable burden of the tuberculosis (TB) epidemic is found in adolescents. The reasons for increased susceptibility to TB infection and higher incidence of TB disease in adolescence, compared with...

COVID-19 and global childhood tuberculosis notifications

Globally, an estimated 1·2 million cases of tuberculosis disease each year occur in children younger than 15 years, and around 67 million children have tuberculosis infection, putting them at the risk of developing tuberculosis disease.1 Tuberculosis in childhood was historically neglected in surveillance efforts, with national tuberculosis programmes focusing primarily on cases of microscopically smear-positive tuberculosis, which is more common among older adolescents or adults. The diagnosis of tuberculosis in children is made challenging by low suspicion among health-care providers, reliance on sputum microscopy, which has very low sensitivity (ranging from 1–14%), children's difficulty in producing sputum, or disease with low bacillary load.

Contribution of Reinfection to Annual Rate of Tuberculosis Infection (ARI) and Incidence of Tuberculosis Disease.

Modeling studies have concluded that 60-80% of tuberculosis (TB) infections result from reinfection of previously infected persons. The annual rate of infection (ARI), a standard measure of the risk of TB infection in a community, may not accurately reflect the true risk of infection among previously infected persons. We constructed a model of infection and reinfection with Mycobacterium tuberculosis to explore the predictive accuracy of ARI and its effect on disease incidence. We created a deterministic simulation of the progression from TB infection to disease and simulated the prevalence of TB infection at the beginning and end of a theoretical year of infection. We considered 10 disease prevalence scenarios ranging from 100/100 000 to 1000/100 000 in simulations where TB exposure probability was homogeneous across the whole simulated population or heterogeneously stratified into high-risk and low-risk groups. ARI values, rates of progression from infection to disease, and the effect of multiple reinfections were obtained from published studies. With homogeneous exposure risk, observed ARI values produced expected numbers of infections. However, when heterogeneous risk was introduced, observed ARI was seen to underestimate true ARI by 25-58%. Of the cases of TB disease that occurred, 36% were among previously infected persons when prevalence was 100/100 000, increasing to 79% of cases when prevalence was 1000/100 000. Measured ARI underestimates true ARI as a result of heterogeneous population mixing. The true force of infection in a community may be greater than previously appreciated. Hyperendemic communities likely contribute disproportionally to the global TB disease burden.

Tuberculosis, focussed tools and the right schools: estimated impact and cost of a targeted student screening programme for tuberculosis infection.

The World Health Organization (WHO) recommends targeted screening for latent tuberculosis infection (LTBI) among high-risk populations. Recent studies that evaluate targeted school-based programmes in low burden settings are scarce. To evaluate a school screening programme for recently arrived migrant students from moderate and high tuberculosis (TB) burden countries and estimate (1) the number of cases of active TB that were prevented and (2) the cost per case of active TB prevented. Students were screened with tuberculin skin tests (TST) at schools with a high migrant population intake. Those with positive results were referred for specialist evaluation. Outcomes were retrospectively assessed using 5 years of prospectively collected data. Cost data were collected. Main outcomes measured were the number of children were diagnosed with LTBI who completed treatment, and programme costs. Of 4728 student screened, 295 (6.2%) were diagnosed with LTBI. Of these, 273 (92.5%) were offered preventive therapy, 242 (82.0%) commenced and 204 (69.2%) completed therapy. The number needed to screen (NNS) was 23 per completed course of preventive treatment for LTBI. Assuming a 10% lifetime risk of reactivation, the NNS was 386 per case of TB disease notification avoided. The cost of screening was A$23 932 per case of TB disease avoided. This TB strategy is supported by the high rate of TB infection in the student group, the treatment uptake and completion rates. Cost-benefit is linked with lifetime risk of TB reactivation. Targeted school screening programmes represent an important opportunity for TB control in low-burden settings.

Analisis Akses Informasi Kesehatan Dalam Memperoleh Pelayanan Kesehatan TB Paru Di Puskesmas Ngoresan, Jebres, Kota Surakarta

Background: Incidence case of Tuberculosis (TB) still ranks first in the classification of infectious diseases at several health centers in Surakarta for the last 4 years. Meanwhile, in the last 4 years, efforts have been made to improve pulmonary TB health services, starting from case detection, access to services and treatment. The health centers that have the highest cases of pulmonary TB disease in Surakarta over the last 5 years include the Ngoresan Health Center (2018), Sangkrah Health Center (2017), Pajang Health Center (2016) and Banyuanyar Health Center (2015). Objectives: This study aims to analyze access of health information related to health services obtained by patients with pulmonary TB at Ngoresan Health Center, Jebres, Surakarta City. Methods: This research method uses a cross-sectional research design by filling out questionnaires on a research sample of 30 respondents. Result: Factors related to access of health information to obtaining Pulmonary TB Health Services at Ngoresan Health Center, Jebres Surakarta City are availability of health information, communication with health workers, transportation, family support and knowledge. Conclusion: the availability of health information, communication with health workers, transportation, family support and knowledge are affected by access of health information to obtaining pulmonary TB health services at Ngoresan Health Center, Jebres, Surakarta City.

Latent tuberculosis infection: Misperceptions among non-U.S.–born-populations from countries where tuberculosis is common

ABSTRACT The Centers for Disease Control and Prevention works to eliminate tuberculosis (TB) disease by finding and treating cases of TB disease and expanding latent tuberculosis infection (LTBI) testing and treatment to prevent TB disease. Approximately 70% of reported TB cases in the United States occur among non-U.S.–born persons. We conducted 15 focus groups with U.S. residents born in the six most common countries of birth among non-U.S.–born TB patients: Mexico, the Philippines, India, Vietnam, China and Guatemala. Participants reacted to 39 messages on LTBI and TB disease risk factors, the Bacille Calmette-Guérin (BCG) vaccine, and LTBI testing and treatment. There was low awareness of LTBI, the TB blood test, and how the TB blood test is not affected by prior BCG vaccination. Several participants thought TB disease is contracted by sharing kitchenware. Some felt negatively targeted when presented with information about countries where TB disease is more common than the U.S. Findings highlight the need for communication aimed at increasing LTBI testing and treatment to include messages framed in ways that will be resonant and actionable to populations at risk. Focus groups revealed LTBI misconceptions which highlight areas for targeted education to decrease TB stigma and increase LTBI testing and treatment.

ВОЗМОЖНЫЕ ПРИЧИНЫ ФОРМИРОВАНИЯ РЕЦИДИВОВ ТУБЕРКУЛЕЗА У ДЕТЕЙ В СОВРЕМЕННЫХ УСЛОВИЯХ: КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ

The epidemiological situation of tuberculosis (TB) has been improving steadily in recent years however, in the structure of TB patients, there is a high proportion of patients with multidrugresistant/extensively drug-resistant (XDR) pathogens and people with HIV and TB co-infection. As a result, cases of TB disease in children with many risk factors for unfavorable outcome of therapy are recorded, leading to subsequent relapse. the aim of the work was to analyze possible causes of formation and structure of clinical forms of recurrence of TB in children. A retrospective analysis of outpatient cards and medical records of children of residents of the Leningrad region, who had a TB relapse, was carried out. It has been established that in Leningrad Oblast, there were 3 cases of recidivism of TB among children registered from 2011 to 2020. The main risk factor for the development of primary TB was the lack of immunization against TB due to perinatal contact with an HIV-infected mother. The provoking factors of TB relapse were the occurrence of exogenous superinfection of TB, the presence of HIV infection in the child, the presence of large residual changes after primary TB, close contact with a TB patient with an XDR of the causative agent.

Pulmonary tuberculosis and management of contact patients in a Department of Nephrology and Kidney Transplantation

ObjectivesTo describe the investigation, follow-up, management, and outcomes in a cohort of chronic kidney disease (CKD) and kidney transplant recipients (KTR) exposed to a case of pulmonary tuberculosis (TB). MethodsContacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with evidence of latent TB infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. ResultsA total of 130 patients with CKD and 180 KTR were identified as contacts and followed-up over a 2-year period. Few vulnerable high-priority contacts received anti-TB treatment, including the two (100%) highly exposed patients in circle 1, 11/78 (14.1%) CKD patients and 4/142 (2.8%) KTR in circle 2, and 10/52 (19.2%) CKD patients and 2/36 (5.6%) KTR in circle 3; all had a positive interferon-gamma release assay result. No incident cases of TB disease occurred. ConclusionsThese findings suggest that latent TB treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2, with a negative interferon-gamma release assay and in countries with low prevalence of TB.

State-level prevalence estimates of latent tuberculosis infection in the United States by medical risk factors, demographic characteristics and nativity.

Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity. We created a mathematical model using all incident TB disease cases during 2013-2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015. We estimated that 2.7% (CI: 2.6%-2.8%) of the U.S. population, or 8.6 (CI: 8.3-8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%-1.1%) and among non-US-born persons was 13.9% (CI: 13.5%-14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45-64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%). Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.

Predictors of unsuccessful tuberculosis treatment outcomes in children from a prospective cohort study in Pakistan.

BackgroundEvery year, about 239 000 children die from tuberculosis (TB), despite availability of highly effective regimens. Few studies have evaluated predictors for poor treatment outcomes in children treated for TB.MethodsWe assessed predictors of unsuccessful TB treatment outcomes in a prospective cohort of children diagnosed by an intensified TB patient-finding intervention at four facilities in Pakistan between 2014 and 2016. A case of TB disease was determined through either bacteriologic confirmation of disease or a clinical diagnosis. To estimate characteristics predictive of experiencing an unsuccessful treatment outcome, we used a multi-level model with a modified Poisson approach, accounting for clustering at the facility level. We report estimated relative risks (RR) and 95% confidence intervals (CI).ResultsDuring the study period, 1404 children less than 15 years old were initiated on treatment for drug-susceptible TB. In total, 709 (50.5%) were 0-4, 406 (28.9%) were 5-9 years, and 289 (20.6%) were 10-14 years old; 614 (43.7%) were female; and of the 1377 children assessed for malnourishment, 1161 (84.3%) were malnourished. A total of 1322 (94.2%) children experienced a successful treatment outcome, 14 (1.0%) children transferred out to a different facility, and 68 (4.8%) children experienced an unsuccessful treatment outcome: 14 (1.0%) died, 20 (1.4%) failed treatment, and 34 (2.4%) were lost to follow-up. After adjustment for age group, sex, and malnutrition status, we identified increased risk of unsuccessful treatment outcome in children presenting with fever (RR = 2.56, 95% CI = 1.02-6.44; P = 0.05) or an abdominal examination suggestive of TB disease (RR = 2.34, 95% CI = 1.20-4.58; P = 0.01), and a decreased risk in children who initiated treatment at a rural facility (RR = 0.05, 95% CI = 0.00-0.74; P = 0.03).ConclusionsMore than 94% of children experienced successful treatment outcomes. We identified individual-, facility-, and clinical-factors predictive of experiencing unsuccessful treatment outcomes. Children with fevers and abdominal findings suggestive of TB disease should be tested for TB and followed closely throughout treatment to ensure necessary support for successful completion of treatment.

Distribution of molecular strains of Mycobacterium tuberculosis in an intermediate burden Asia Pacific city.

Hong Kong is an intermediate tuberculosis (TB) burden city in Asia Pacific with slow decline of case notification in the last decade. By 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats genotyping, we examined 534 Mycobacterium tuberculosis isolates collected from culture-positive hospitalised TB patients in a 1.7 million population geographic region in the city. Overall, 286 (75%) were classified as Beijing genotype, of which 216 (76%) and 59 (21%) belonged to modern and ancient sub-lineage, respectively. Only two cases were genetically clustered while spatial clustering was absent. Male gender, permanent residency in Hong Kong and born in Hong Kong or Mainland China were associated with Beijing genotype. The high prevalence of Beijing modern lineage was similar to that in East Asia, which reflected the pattern resulting from population migration. The paucity of clustering suggested that reactivation accounted for most of the TB disease cases, which was and echoed by observation that half were 60 years old or above, and the presence of co-morbid medical conditions. The predominance of reactivation TB cases in intermediate burden localities implies that the detection and control of latent TB infection would be the major challenge in achieving TB elimination.

Recent Advances in Effective Management of Patients with Multidrug-ResistantTuberculosis (MDR-TB)

Tuberculosis (TB) is a major infectious disease worldwide. Most active TB disease cases in humans are caused by Mycobacterium tuberculosis [1]. Some cases in Africa are caused by Mycobacterium africanum while Mycobacterium bovis (bovine bacillus) can also cause TB in individuals who consume unpasteurized milk [1,2]. The global burden of TB is still enormous. According to the World Health Organization (WHO), an estimated 10 million new active TB diseases cases and 1.451 million deaths occurred in 2018, making TB as one of the top 10 killers and the leading cause of death from a single infectious agent [3]. Near 87% of TB cases occurred in 30 high TB burden countries and two-third of all cases in only eight (India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa) countries [3]. Most active TB disease cases in high TB burden countries occur as a result of recent infection/reinfection while in low TB incidence countries, they usually arise as a result of reactivation of latent infection, acquired few to several years earlier [2,4,5].

Interferon-γ Release Assays for Tuberculosis Infection Diagnosis in Refugees

New guidelines support using interferon-γ release assays (IGRAs) in children ≥2 years for diagnosis of latent tuberculosis infection (LTBI). However, lack of experience in young children and concern that IGRAs are less sensitive than tuberculin skin tests (TSTs) limit their use. Our aim was to identify active tuberculosis (TB) cases among high risk children <5 years and tested for LTBI with an IGRA. . Retrospective review of domestic TB screening data from California's Refugee Health Electronic Information System for children <5 years old who resettled in California between October, 2013 and December, 2016. Children were crossmatched with the California TB registry to identify cases of TB disease between October 2013 and December 2018. A total of 3371 children <5 years were identified; the majority were born in countries with high TB incidence (>150 cases per 100 000). Half received IGRAs (n = 1878; 56%), a quarter received TSTs (n = 811; 24%); 1.4% of children were IGRA-positive (n = 26) and 13% were TST-positive (n = 106). Twenty-two IGRA results were indeterminate (1.2%). Sixteen children had both tests; 9 were discrepant (positive TST with negative IGRA). No cases of TB disease were identified during 10 797 person-years of follow-up. IGRA positivity was less than TST positivity in high risk children <5 years old. Despite fewer LTBI diagnoses in the IGRA-tested population, no cases of TB disease among children who tested negative were identified, suggesting IGRA is valuable tool for identifying LTBI in this population.

IL-33/ST2 Axis as a Well-Known Endogenous Defense Against Tuberculosis

Tuberculosis (TB) infection is caused by an intracellular bacterium, Mycobacterium tuberculosis (Mtb). The disease is among the most important infectious diseases, which has dedicated most cases of morbidity and mortality to itself worldwide. The global report of World Health Organization (WHO) in 2019 shows that from 10.7 million infected people in 2018, 1.6 million died. Although the BCG vaccine has been used for about a hundred years, it is only effective in children, but is not able to produce a protective and reliable immunity against adult pulmonary TB. Hence, using an alternative vaccine with high more efficacy than BCG seems to be urgent. The IL-33/ST2 axis forms of IL-33 and ST2, and both of them are the members of IL-1 family. IL-33 is secreted as an alarm in response to cell damages and cellular stress, and ST2 causes stimulation of MyD88/NF-κB signaling pathway, which is needed for the proper response of infected cells to Mtb and other intracellular pathogens. In Th2 cells, NF-κB enters into the nucleus, and acts as a transcription factor. Finally, cytokines such as IL-4, IL-5, and IL-10 are produced which are effective in the prevention of tissue damage. Based on various information, it is recommended that IL-33 can be as a novel therapeutic candidate in post-exposure cases of TB disease.

Modeling the Impact of Recommendations for Primary Care-Based Screening for Latent Tuberculosis Infection in California.

Targeted testing and treatment of persons with latent tuberculosis infection (LTBI) is a critical component of the US tuberculosis (TB) elimination strategy. In January 2016, the California Department of Public Health issued a tool and user guide for TB risk assessment (California tool) and guidance for LTBI testing, and in September 2016, the US Preventive Services Task Force (USPSTF) issued recommendations for LTBI testing in primary care settings. We estimated the epidemiologic effect of adherence to both recommendations in California. We used an individual-based Markov micro-simulation model to estimate the number of cases of TB disease expected through 2026 with baseline LTBI strategies compared with implementation of the USPSTF or California tool guidance. We estimated the risk of LTBI by age and country of origin, the probability of being in a targeted population, and the probability of presenting for primary care based on available data. We assumed 100% adherence to testing guidance but imperfect adherence to treatment. Implementation of USPSTF and California tool guidance would result in nearly identical numbers of tests administered and cases of TB disease prevented. Perfect adherence to either recommendation would result in approximately 7000 cases of TB disease averted (40% reduction compared with baseline) by 2026. Almost all of this decline would be driven by a reduction in the number of cases among non-US-born persons. By focusing on the non-US-born population, adherence to LTBI testing strategies recommended by the USPSTF and the California tool could substantially reduce the burden of TB disease in California in the next decade.