Cases Of Tuberculosis Infection Research Articles

Costs of non-multidrug-resistant pulmonary tuberculosis and of preventive treatment in Germany – An update

BackgroundOnly 4076 new cases of tuberculosis (TB) were reported in Germany in 2022; of those 184 were multidrug-resistant TB (MDR-/RR-TB). MethodsBased on the current therapy guidelines of the German Central Committee against Tuberculosis and most recent renumeration data of the Statutory Health Insurances (SHI), this study estimates the mean in- and outpatient costs per adult infectious pulmonary non-MDR-TB patient, together with costs arising from Rifampicin (RIF)-based short-course options of tuberculosis preventive treatment (TPT) of their close contacts. ResultsFrom the insurance perspective, the mean inpatient cost (rounded) per adult case was 6138 EUR (SD±2810 EUR) for standard therapy; the cost of primary outpatient treatment only amounted to 1930 EUR and the cost of outpatient treatment post-hospital to 1093 EUR. The mean weighted cost was 6377 EUR (SD±2357 EUR), a drop of 27 % vs. 2019. This is mainly due to a decrease in hospitalizations of 5.6 %, and, given hospital treatment, by a 95 EUR decrease in the per-day reimbursement rate for TB patients who are hospitalized for at least 14 days. In contrast, the mean costs of TPT per person were 466 EUR (RIF solely over 4 months) and 423 EUR (RIF combined with Isoniazid over 3 months). ConclusionWhile costs for active non-MDR-TB treatment in Germany have clearly decreased thanks to increased engagement on the part of the private practice sector and lower reimbursement rates in hospital, the comparatively high costs of short-course TPT have surprisingly significant economic impact. This negative development can be countered through diligent selection of close contacts persons of infectious TB cases before using IGRA testing to detect latent TB, to minimize the number of those persons who are tested falsely determined to be at risk and needlessly undergo TPT.

The risk of tuberculosis infection in Saudi patients receiving adalimumab, etanercept, and tocilizumab therapy

BackgroundThe risk of infection including tuberculosis (TB) infection or reactivation during biological therapy with the current various clinical application is a major concern. This risk may be higher in countries endemic to TB. Our aim of this study is to determine the risk of TB infection in patients receiving 3 biological treatments, Adalimumab, Etanercept and Tocilizumab. MethodsA retrospective cohort study extending over 2 years follow-up for all patients receiving Adalimumab, Etanercept and Tocilizumab for various clinical indications in a tertiary care center in Saudi Arabia. ResultOver the period of 2015–2019, A total of 410 patients received Adalimumab, 271 received Etanercept and 58 patients received Tocilizumab. Rheumatoid arthritis was the most common indication for therapy in all groups and for Adalimumab the most common indication was inflammatory bowel disease, for Etanercept was psoriatic arthritis and for Tocilizumab was juvenile idiopathic arthritis. After a mean follow up period of 36 ± 8.9 months for patients receiving Adalimumab, 21.5 ± 8.4 months for patients receiving Etanercept and 21 ± 2.5 months for patients receiving Tocilizumab there were no reported cases of TB infection in all groups. Only one patient was diagnosed with latent TB 7 months later after starting Adalimumab and tow patients after starting Etanercept. The overall Interferon Gamma Release Assays (IGRA) positivity rate was 9.7%. There was significant association between IGRA positivity rate and patient age. The cutoff age in which IGRA positivity has significantly increased was 53.20 years. ConclusionIn our study, patients receiving Etanercept, Adalimumab and Tocilizumab had no increased risk of TB infection. Only 0.3% of patients treated with Adalimumab and 0.9% of patients treated with Etanercept converted to a positive IGRA during therapy.

Pooling sputum samples for the Xpert MTB/RIF assay: a practical screening strategy for highly infectious tuberculosis cases

The Xpert MTB/RIF test (Xpert) can help in the accurate screening of tuberculosis, however, its widespread use is limited by its high cost and lack of accessibility. Pooling of sputum samples for testing is a strategy to cut expenses and enhance population coverage but may result in a decrease in detection sensitivity due to the dilution of Mycobacterium tuberculosis (Mtb) by sample mixing. We investigated how the mixing ratio affected the detection performance of Xpert. We used frozen sputum samples that had been kept after individual Xpert assays of the sputa from Mtb-confirmed TB patients and non-TB patients. Our results showed that the overall sensitivity of the Xpert pooling assay remained higher than 80% when the mixing ratio was between 1/2 and 1/8. When the mixing ratio was raised to 1/16, the positive detection rate fell to 69.0%. For patients with either a high sputum Mtb smear score ≥ 2+, a time-to-positive culture ≤ 10 days, or an Xpert test indicating a high or medium abundance of bacteria, the pooling assay positivity rates were 93.3%, 96.8%, and 100% respectively, even at a 1/16 mixing ratio. For participants with cavities and cough, the pooling assay positivity rates were 86.2% and 90.0% at a 1/8 ratio, higher than for those without these signs. Our results show that the Xpert pooled assay has a high overall sensitivity, especially for highly infectious patients. This pooling strategy with lower reagent and labor costs could support TB screening in communities with limited resources, thereby facilitating reductions in the community transmission and incidence of TB worldwide.

IP-10 for the Diagnosis and Treatment Monitoring of Tuberculosis in Children.

To determine the utility of interferon-gamma-inducible protein 10 (IP-10) for identifying active tuberculosis (TB) and TB infection (TBI) in children in BCG-vaccinated populations, establish its diagnostic performance characteristics, and evaluate changes in IP-10 level during anti-TB chemotherapy. Concentrations of IP-10 and IFN-γ were measured in QuantiFERON-TB Gold (QFT) supernatants in children with suspected TB or due to recent TB contact. A total of 225 children were investigated: 33 with active TB, 48 with TBI, 83 TB contacts, 20 with suspected TB but other final diagnoses, and 41 controls. In 60 children, cytokine responses were evaluated at a follow-up visit after 2 months of anti-TB treatment. IP-10 expression was significantly higher in infected children (active TB and TBI cases) than in uninfected individuals. IP-10 proved effective in identifying TB infection at its optimal cut-off (>1084.5 pg/mL) but was incapable of differentiating between children with active TB and TBI. Combining IP-10 and IFN-γ increased the QFT sensitivity. IP-10 but not IFN-γ decreased significantly during anti-TB treatment in children with active TB (p = 0.003). IP-10 identifies TB infection and declines during anti-TB chemotherapy in children. Incorporating IP-10 into new immunodiagnostic assays could improve TB diagnosis and allow for treatment monitoring.

2143. Contact Investigation after Exposure to Active Pulmonary Tuberculosis in the Pediatric Cancer Center

Abstract Background The prevalence of tuberculosis (TB) in Korean children has decreased due to universal BCG vaccination and the national TB elimination project. However, exposure to TB in children has been consistently reported. There have been few reports of TB exposure in the pediatric hematology-oncology ward. Methods A mother of a pediatric cancer patient was diagnosed with active TB with a cavity. Contact investigation was performed on patients, their parents, and healthcare workers who were exposed to the index case. The criteria for close contact were exposure in the same space with the index patient for more than 8 hours continuously or a total of 40 hours in case of multiple exposures. The initial assessment was performed as soon as the index case was identified. The second evaluation was conducted 8–10 weeks after the initial exposure. Both tuberculin skin test (TST), TB Specific Interferon-Gamma (T-SPOT) tests, and chest radiography were used in immunocompromised pediatric patients. For immunocompetent adults, the QuantiFERON-TB Gold (QFT-G) test and chest radiography were performed. Results Total 23 patients and 29 parents were exposed. The median exposure duration of patients was 3 days (1–8 days). The initial evaluation did not detect TB infection in pediatric patients. However, at the second evaluation, five patients (17.4%) were diagnosed with latent TB infection (LTBI, three with positive TST and two with positive T-SPOT), and two patients (8.7 %) were diagnosed with active TB infection (lymphadenitis and pulmonary TB). Among the 29 parents, 11 individuals (37.9%) were diagnosed with LTBI at the initial evaluation, which was considered as preexisting LTBI before this exposure. No additional case of TB infection was identified in the second evaluation. Among exposed 24 healthcare workers, two (9.1%) were eventually confirmed as newly diagnosed LTBI. Conclusion TB exposure in pediatric hematology-oncology ward and outpatient chemotherapy clinic caused active TB or LTBI cases with an attack rate of 26% in children. The high LTBI rate, up to 38% among parents even before this exposure, needs further intervention such as routine LTBI evaluation and treatment for families of pediatric cancer patients to prevent a similar event. Disclosures Joon-sik Choi, MD, MS, Ministry of Trade, industry and Energy, Republic of Korea: Grant/Research Support Yae-Jean Kim, MD, PhD, Janssen: Grant/Research Support|Korean Society of Pediatric Infectious Diseases: Grant/Research Support|Ministry of Trade, Industry and Energy: Grant/Research Support|MSD: Grant/Research Support.

Tuberculosis Infection in Children and Adolescents.

The burden of tuberculosis (TB) in children and adolescents remains very significant. Several million children and adolescents are infected with TB each year worldwide following exposure to an infectious TB case and the risk of progression from TB infection to tuberculosis disease is higher in this group compared to adults. This review describes the risk factors for TB infection in children and adolescents. Following TB exposure, the risk of TB infection is determined by a combination of index case characteristics, contact features, and environmental determinants. We also present the recently recommended approaches to diagnose and treat TB infection as well as novel tests for infection. The tests for TB infection have limitations and diagnosis still relies on an indirect immunological assessment of cellular immune response to Mycobacterium tuberculosis antigens using immunodiagnostic testing. It is recommended that TB exposed children and adolescents and those living with HIV receive TB preventive treatment (TPT) to reduce the risk of progression to TB disease. Several TPT regimens of similar effectiveness and safety are now available and recommended by the World Health Organisation.

OPTIMAL CONTROL ANALYSIS OF A TUBERCULOSIS MODEL

In this paper, an optimal control theory was applied to the tuberculosis (TB) model governed by system of nonlinear ordinary differential equations. The aim is to investigate the impact of treatment failure on the TB epidemic. An optimal control strategy is proposed to minimize the disease effect and cost incurred due to treatment failure. The existence and uniqueness of optimal controls are proved. The characterization of optimal paths is analytically derived using Pontryagin’s Minimum Principle. The control-induced model is then fitted using TB infected cases reported from the year 2010–2019 in East Shewa zone Oromia regional state, Ethiopia. Different simulation cases were performed to compare with analytical results. The simulation results show that the combined effect of awareness via various mass media and continuous supervision during the treatment period helps to reduce treatment failure and hence reduced the TB epidemic in the community.

Mathematical modelling of the progression of active tuberculosis: Insights from fluorography data.

Little is known about the dynamics of the early stages of untreated active pulmonary tuberculosis: unknown are both the rates of progression and the model “scheme”. The “parallel” scheme assumes that infectiousness of tuberculosis cases is effectively predefined at the onset of the disease, and the “serial” scheme considers all cases to be non-infectious at the onset, with some of them later becoming infectious.Our aim was to estimate the progression of the early stages of pulmonary tuberculosis using data from a present-day population. We used the routine notification data from Moscow, Russia, 2013–2018 that contained the results and time of the last fluorographic screening preceding the detection of tuberculosis cases. This provided time limits on the duration of untreated tuberculosis.Parameters of TB progression under both models were estimated. By the goodness of fit to the data, we could prefer neither the “parallel”, nor the “serial” model, although the latter had a bit worse fit. On the other hand, the observed rise in the fraction of infectious tuberculosis cases with the time since the last screening was explained by the “serial” model in a more plausible way – as gradual progression of some cases to infectiousness. The “parallel” model explained it through less realistic quick removal of non-infectious cases and accumulation of the infectious ones.The results demonstrate the potential of using such detection data enriched with reassessments of the previous screenings.

The cascade of care in tuberculosis infection screening and management in newly arrived refugees in Aarhus, Denmark

BackgroundScreening for tuberculosis (TB) disease and infection is often a part of health screening programs offered to refugees, but the yield of screening varies and losses along the steps from screening to treatment completion was reported. MethodsA retrospective cohort study was performed investigating a newly arrived refugee population offered a systematic refugee health assessment in Aarhus, Denmark. Data was collected on screening, referral, diagnosis and treatment for TB disease and infection. ResultsAmong both adults and children IGRA positivity was associated with origin in a high TB incidence country and increasing age. The number needed to screen (NNS) to find one case of TB infection was 7 among adult refugees and 19 among children, while NNS for TB disease was 266 and 164 respectively. The proportion of the eligible population with a valid result was 78.1% for adults and 71.3% for children, while 43.1% and 50% of adults and children with presumed TB infection completed preventive treatment. DiscussionScreening for TB disease and infection among refugees in Aarhus had a high yield in terms of diagnosis, however significant losses were seen during screening, follow-up and preventive treatment completion.

Disease Surveillance Among U.S.-Bound Immigrants and Refugees - Electronic Disease Notification System, United States, 2014-2019.

Disease Surveillance Among U.S.-Bound Immigrants and Refugees - Electronic Disease Notification System, United States, 2014-2019.

Empowerment of Sto.Yohanes Maria Vianey Catholic Church Youth Naibonat of East Kupang, East Nusa Tenggara as A Supervision of Tuberculosis Ingestion

Tuberculosis (TB) is an infectious disease that causes death, and is the third leading cause of death in Indonesia. The increase in cases of tuberculosis infection is still a major health problem in Naibonat Village, Kupang Regency, East Nusa Tenggara Province. Treatment failure, among others, was caused by patient non-compliance in ingesting drugs. It is hoped that the presence of supervisors to swallow drugs for TB patients is expected to help reduce TB infection cases. In Indonesian, a person who supervisors to swallow drugs is called “PMO” or “Pengawas menelan obat (PMO)” . Church Youth is an educated / educated group that is expected to have the ability to function as PMO. The purpose of this activity is to carry out PMO training for STO. Yohanes Maria Vianey Naibonat church youth through the method of lectures, discussions and microscopic training. The level of knowledge was measured using a questionnaire in the pre-test and post-test training. Youth who have been trained will be directed to become PMO’s for their families and closest neighbors who suffer from TB as well as agents of change in changing healthy behavior to prevent TB infection. The results of the activity showed a change in the level of knowledge before and after training from72% enough category to be good 89%. It was concluded that empowering church youth as PMO is an effort to suppress the increase in TB cases. The provision of PMO training can increase level of knowledge about TB so that regular and scheduled training will increase the ability and understanding of the role of PMO in reducing the incidence of TB in the community.

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.

Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study

Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups. In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10-99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at ClinicalTrials.gov, NCT01622140. Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6-1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9-2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8-1·0) and 1·3 (1·2-1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (ptrend<0·0001). Test agreement was higher between the two IFN-γ release assays than between TST and either IFN-γ release assay, regardless of birthplace. κ agreement was particularly low between TST and IFN-γ release assays in non-US-born children younger than 5 years. Our findings support the preferential use of IFN-γ release assays for the diagnosis of latent tuberculosis in high-risk populations, especially in very young and older people born outside the USA. US Centers for Disease Control and Prevention.

The risk of tuberculosis infection in 410 Saudipatients receiving adalimumab therapy.

BACKGROUND: Adalimumab is a fully humanized monoclonal antibody inhibitor of tumor necrosis factor-a used to treat various autoimmune disorders. Adalimumab poses a risk for tuberculosis (TB) infection, especially in countries where TB is endemic.OBJECTIVE: Determine the rate of TB infection after adalimumab therapy in Saudi Arabia.DESIGN: Medical record review.SETTINGS: Tertiary care center in Riyadh.PATIENTS AND METHODS: Demographic and clinical data were retrieved from the electronic healthcare records of all patients who received adalimumab treatment from 2015 to 2019.MAIN OUTCOME MEASURES: Occurrence of TB after adalimumab therapy.SAMPLE SIZE: 410 patients (median ([QR] age, 37 [28], range 4–81 years), 40% malesRESULTS: Rheumatoid arthritis was the most frequent indication (n=153, 37%). The patients were followed for a mean of 36 (8.9) months. No case of TB infection or reactivation was observed. An inter-feron-gamma release assay (IGRA) was requested in 353/391 (90.3%) patients, prior to initiating therapy. The IGRA was positive in 26 cases (6.6%). The IGRA-positive patients received isoniazid prophylactically. Bacterial infectious complications of adalimumab therapy occurred in 12 (2.9%) patients. Urinary tract infection was the most frequent complication (culture requested in 48 patients, positive in 8).CONCLUSION: Adalimumab treatment was not associated with a risk of TB disease or TB reactivation in our cohort over the follow-up observation period. No TB reactivation occurred with adalimumab therapy when TB prophylaxis was used. The positive IGRA rate in patients on adalimumab treatment was low (7%).LIMITATIONS: Single center and one geographical area in Saudi Arabia.CONFLICT OF INTEREST: None.

Recent developments in the diagnosis and treatment of extrapulmonary non-tuberculous mycobacterial diseases.

Diseases due to pathogenic mycobacteria cause significant health and economic impact on humans worldwide. Although mycobacterial diseases primarily affect the lungs, the involvement of extrapulmonary organs has also gained ground, particularly among individuals with co-existing medical conditions. Besides Mycobacterium tuberculosis complex organisms, non-tuberculous mycobacteria (NTM) are also known to cause pulmonary and extrapulmonary diseases. Primary and disseminated extrapulmonary mycobacterial infections affect the brain, eye, mouth, tongue, lymph nodes of the neck, spine, bones, muscles, skin, pleura, pericardium, gastro-intestinal, peritoneum and genito-urinary system. The clinical presentation of extrapulmonary mycobacterial diseases, including systemic symptoms, of M. tuberculosis-infected cases and NTM-infected cases is similar. Moreover, extrapulmonary mycobacterial diseases are complicated by the involvement of diverse bacterial species as aetiological agents. Culture and molecular techniques are used to differentiate NTM from Mycobacterium tuberculosis and to classify sub-species of the pathogens. As sub-speciation and drug susceptibility profiling are critical factors in treating extrapulmonary NTM diseases, there are often significant delays in initiating treatment and customising the therapeutic regimen. Here, we summarise the clinical symptoms of NTM diseases in various extrapulmonary organs, and discuss the recent trends in diagnosing and treating these diseases. We also highlight the complications associated with the management of extrapulmonary NTM disease.

Diagnosis of latent tuberculosis infection among pediatric household contacts of Iranian tuberculosis cases using tuberculin skin test, IFN- \u03b3 release assay and IFN-\u03b3-induced protein-10

BackgroundAlthough the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran.MethodsWe conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active TB disease. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10(IP-10) concentrations were measured for all participants.ResultsA total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study. Significantly increased IP-10 levels were found in LTBI patients compared to healthy contacts. Accordingly, more than 50% of LTBI contacts and about 10% of healthy contacts were considered as IP-10-positive.ConclusionThis study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.

Effectiveness and outcomes of air travel-related TB incident follow-up: a systematic review.

The World Health Organization (WHO) recommends following up passengers after possible exposure to a case of infectious tuberculosis (TB) during air travel. This is time-consuming and difficult, and increasingly so with higher numbers each year of flights and passengers to and from countries with high TB endemicity. This paper systematically reviews the literature on contact tracing investigations after a plane exposure to active pulmonary TB. Evidence for in-flight transmission was assessed by reviewing the positive results of contacts without prior risk factors for latent TB.A search of Medline, EMBASE, BIOSIS, Cochrane Library and Database of Systematic Reviews was carried out, with no restrictions on study design, index case characteristics, duration of flight or publication date.In total, 22 papers were included, with 469 index cases and 15 889 contacts. Only 26.4% of all contacts identified completed screening after exposure. The yield of either a single positive tuberculin skin test (TST) or a TST conversion attributable to in-flight transmission was between 0.19% (95% CI 0.13%-0.27%) and 0.74% (95% CI 0.61%-0.88%) of all contacts identified (0.00%, 95% CI 0.00%-0.00% and 0.13%, 95% CI 0.00%-0.61% in random effects meta-analysis). The main limitation of this study was heterogeneity of reporting.The evidence behind the criteria for initiating investigations is weak and it has been widely demonstrated that active screening of contacts is labour-intensive and unlikely to be effective. Based on our findings, formal comprehensive contact tracing may be of limited utility following a plane exposure.

BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case.

The Bacille Calmette–Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23–0.73, p = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15–0.66, p = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13–4.53, p = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27–9.39, p = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case.

Tuberculosis Exposure and Conversion Rates Can Guide Deimplementation of Annual Tuberculosis Screening

Background: The CDC recently updated recommendations on tuberculosis (TB) screening in healthcare facilities, suggesting the discontinuation of annual TB screening. However, hospitals may opt to continue based on their local TB epidemiology. We assessed TB infection control parameters in our facility to guide the implementation of the new CDC recommendations. Methods:We retrieved data for patients with an International Classification of Disease, Tenth Revision (ICD-10) code for TB treated at the University of Iowa Hospitals and Clinics during 2016–2019. We supplemented our search with microbiology data: culture or PCR for Mycobacterium tuberculosis. Based on manual chart review, we adjudicated each patient as active TB, latent TB, previously treated TB, unclear history, or no TB. We further labeled active TB cases based on their risk of transmission (pulmonary or extrapulmonary cases that underwent an aerosol generating procedure). We then calculated the number of exposure events associated with those patients and tuberculin skin test (TST) conversion rates among the exposed. Results: During 2016–2019, we identified 197 patients based on ICD-10 codes. In total, 10 additional patients were detected by microbiology data review. Of these 207 patients, 48 (23.2%) had active TB: lung, n = 24 (50%); lymph node, n = 9 (19%); bone or spine, n = 5 (10%); eye, n = 3 (6%); disseminated, n = 2 (4%); pleura, n = 2 (4%); skin abscess, n = 2 (4%); and meningitis, n = 1 (2%). Of the 24 pulmonary patients, 6 (25%) had either a positive smear or a cavity on imaging. In total, 159 patients were excluded: no TB, n = 22 (14%); latent TB, n = 27 (17%); old or treated TB, n = 93 (58%); and unclear history, n = 9 (6%). Of the 48 cases with active TB, 31 (65%) were deemed potentially infectious. Also, 10 cases (32%) led to the exposure of 204 healthcare workers (HCWs). Baseline and postexposure TST were available for 179 HCWs (88%); 72 (35%) followed up in the employee health clinic within the 8–12 weeks after exposure. Of 161 HCWs with a negative TST at baseline, no conversions occurred. Of 18 HCWs with positive TST at baseline, no HCW developed symptoms during the observation period. Conclusions: Nearly one-third of infectious TB cases led to HCW exposures in a low-incidence setting. However, no TST conversions or active TB infections were seen. Exposure and conversion rates are useful indicators of TB infection control in healthcare facilities and may help guide implementation of the new CDC TB control recommendations.Funding: NoneDisclosures: None

Adherence to Isoniazid Preventive Therapy among Under-Five Children in Contact with Adult Bacteriologically Confirmed Pulmonary Tuberculosis Patients: A Mixed-Method Study.

Background The World Health Organization recommends that all children below the age of five who have household contact with an infectious tuberculosis case should receive isoniazid preventive treatment for at least six months after the active tuberculosis disease has been ruled out. This research aims to determine the adherence of children, eligible for isoniazid preventive treatment, to the treatment who had contact with pulmonary tuberculosis patients. Methods A mixed study design was used to prospectively assess the adherence to IPT among children under the age of 5 in contact with pulmonary TB patients through the quantitative study design and barriers of adherence in view of health care professionals and the family of children through a descriptive qualitative study. The study was conducted from July 2019 to December 2019 in Addis Ababa. Data were collected by a structured datasheet from the selected health center registration book. Data were entered into Epi Data software and analyzed by using SPSS version 20. Descriptive statistical methods were used to summarize the sociodemographic characteristics of the study participants. Result The ratio of the total number of pulmonary tuberculosis index cases recruited into the study to the number of child contacts aged less than 5 years was 1 : 1.32. The total isoniazid preventive treatment uptake in this study was 75.2%; one-fifth (21.3%) of the children who started IPT did not complete the full course of six-month isoniazid preventive treatment. Except for HIV not to be tested (P < 0.001), there was no significant association of the listed risk factors in default to complete the full six months of preventive treatment. Conclusion Enrolment of eligible children for isoniazid preventive treatment in the urban city Addis Ababa was still below the target of the World Health Organization End tuberculosis strategy by 2030. The treatment adherence rate also needs a great deal of effort to achieve the strategy. Child default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness-creating efforts by health extension workers will help to improve the outcomes.