Positive Tuberculosis Test Research Articles

Risk factors for and timing of presumptive recurrent TB.

<sec><title>INTRODUCTION</title>Understanding factors associated with increased risk for tuberculosis (TB) recurrence is essential in lowering the TB burden. We aimed to quantify the burden, risk factors, and timing of TB presumptive recurrence.</sec><sec><title>METHODS</title>We analyzed test results from 2013 to 2017 in the South African National Health Laboratory Service's database. We defined a person's TB episode to start with their first positive TB test. In the absence of treatment outcome data, we assumed the episode concluded 6 months later for rifampicin-susceptible TB (RS-TB) and 18 months later for rifampicin-resistant TB (RR-TB), provided that at least one negative smear or culture test was recorded within this period. We defined a presumptive recurrent TB episode to start with a positive TB test after the completion of a prior episode. We calculated recurrence measures stratified by various demographics and RR-TB status.</sec><sec><title>RESULTS</title>Of 574,316 people with RS-TB, 4.7% experienced at least one presumptive recurrent TB episode. Higher local TB notification rates, HIV coinfection, and males experienced higher recurrence rates. Most (89.4%) of the first RS-TB recurrences occurred within a year of the initial episode.</sec><sec><title>CONCLUSION</title>Our findings of when and among whom recurrent TB is more likely to occur can be used to assist early interventions and inform impact on patient care.</sec>.

The seroconversion history to SARS-CoV-2 in Indigenous people from Brazil - the interplay between exposure, vaccination, and tuberculosis.

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbyá. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARS-CoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVID-19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2.

Tuberculosis screening for patients on biologic Medications: A Single-Center experience and Society guideline Review, Monroe County, New York, 2018–2021

RationaleBiologic medications for immune-mediated inflammatory diseases may increase the risk of tuberculosis (TB) reactivation, but data on screening for TB in low TB prevalence areas are limited. ObjectiveTo assess the real-world practice patterns of TB screening among prescribers of biologic medications. MethodsWe conducted a retrospective observational study at a single, university-based healthcare facility in a low TB prevalence area. We enrolled adult patients prescribed a biologic medication between October 2018 and December 2021, and collected data on demographics, biologic medications and TB test results. For patients with positive TB tests, further data including prescriber specialty and response to positive tests were obtained. We reviewed pertinent major society guidelines/ consensus statements regarding TB screening among patients treated with biologic medications. Results4,085 patients were included. 3024 (74.0%) had at least one screening TB test and 42 were positive. Among patients treated with tumor necrosis factor-alpha (TNFα) inhibitors, 1779 of 2129 patients (83.6%) underwent TB testing and 25 (1.4%) were positive. Most with positive TB test results were prescribed biologic medication by gastroenterology (11 patients, 26%), dermatology (12, 29%), or rheumatology (15, 36%) providers. 32 (76%) patients had imaging and roughly half were treated for latent TB infection. Biologic medications were temporarily held for 27 patients (67%). Nine out of 13 society guidelines recommend TB screening for TNFα inhibitors but have differing recommendations for other biologic medications. ConclusionsSignificant practice pattern differences in TB screening for patients receiving biologic medications exist. Multiple society guidelines continue to recommend TB screening even for drugs with no known increased risk of TB reactivation.

Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding: A mixed-methods evaluation.

During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4≤200cells/μl. Adult participants with tuberculosis symptoms, recruited near-facility in Lesotho and South-Africa between 2021-2022, were offered HIV testing (capillary blood), Xpert MTB/RIF and Ultra, and MGIT culture (sputum). People living with HIV (PLHIV) were offered VISITECT (venous blood) and Alere tuberculosis-lipoarabinomannan (AlereLAM, urine) testing. AHD was defined as a CD4≤200cells/μl on VISITECT or a positive tuberculosis test. A CD4≤200cells/μl on VISITECT triggered Immy cryptococcal antigen (Immy CrAg, plasma) testing. Participants were referred with test results. To evaluate feasibility, we assessed i) acceptability and ii) intervention delivery of point-of-care diagnostics among study staff using questionnaires and group discussions, iii) process compliance, and iv) early effectiveness (12-week survival and treatment status) in PLHIV. Predictors for 12-week survival were assessed with logistic regression. Thematic content analysis and triangulation were performed. Among PLHIV (N = 676, 48.6% of 1392 participants), 7.8% were newly diagnosed, 81.8% on ART, and 10.4% knew their HIV status but were not on ART. Among 676 PLHIV, 41.7% had AHD, 29.9% a CD4≤200cells/μl and 20.6% a tuberculosis diagnosis. Among 200 PLHIV tested with Immy CrAg, 4.0% were positive. The procedures were acceptable for study staff, despite intervention delivery challenges related to supply and the long procedural duration (median: 73 minutes). At 12 weeks, among 276 PLHIV with AHD and 328 without, 3.3% and 0.9% had died, 84.8% and 92.1% were alive and 12.0% and 7.0% had an unknown status, respectively. Neither AHD nor tuberculosis status were associated with survival. Implementing AHD care package diagnostics was feasible during tuberculosis-case finding. AHD was prevalent, and not associated with survival, which is likely explained by the low specificity of VISITECT. Challenges with CD4 testing and preventive treatment uptake require addressing.

Genome-wide association analyses of common infections in a large practice-based biobank

IntroductionInfectious diseases are common causes of morbidity and mortality worldwide. Susceptibility to infection is highly heritable; however, little has been done to identify the genetic determinants underlying common infectious diseases. One GWAS was performed using 23andMe information about self-reported infections; we set out to confirm previous loci and identify new ones using medically diagnosed infections.MethodsWe used the electronic health record (EHR)-based biobank at Vanderbilt and diagnosis codes to identify cases of 12 infectious diseases in white patients: urinary tract infection, pneumonia, chronic sinus infections, otitis media, candidiasis, streptococcal pharyngitis, herpes zoster, herpes labialis, hepatitis B, infectious mononucleosis, tuberculosis (TB) or a positive TB test, and hepatitis C. We selected controls from patients with no diagnosis code for the candidate disease and matched by year of birth, sex, and calendar year at first and last EHR visits. We conducted GWAS using SAIGE and transcriptome-wide analysis (TWAS) using S-PrediXcan. We also conducted phenome-wide association study to understand associations between identified genetic variants and clinical phenotypes.ResultsWe replicated three 23andMe loci (p ≤ 0.05): herpes zoster and rs7047299-A (p = 2.6 × 10–3) and rs2808290-C (p = 9.6 × 10–3;); otitis media and rs114947103-C (p = 0.04). We also identified 2 novel regions (p ≤ 5 × 10–8): rs113235453-G for otitis media (p = 3.04 × 10–8), and rs10422015-T for candidiasis (p = 3.11 × 10–8). In TWAS, four gene-disease associations were significant: SLC30A9 for otitis media (p = 8.06 × 10–7); LRP3 and WDR88 for candidiasis (p = 3.91 × 10–7 and p = 1.95 × 10–6); and AAMDC for hepatitis B (p = 1.51 × 10–6).ConclusionWe conducted GWAS and TWAS for 12 infectious diseases and identified novel genetic contributors to the susceptibility of infectious diseases.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

1666. Yield of Tuberculosis Contact Tracing among Veterans after Outpatient Exposure

BackgroundTuberculosis contact tracing (TBCT) is essential to detecting transmission. High priority contacts for TBCT include children less than 5 and those with prolonged, close contact with a tuberculosis (TB) case. Other populations considered high priority include those with certain comorbidities. While data are limited, there is evidence for transmission in outpatient settings with short duration/casual contact. We describe the yield of TBCT among a high priority cohort after exposure in to active TB in VA clinics.MethodsBetween 2016-2019, VA Northern California performed 4 episodes of TBCT in the outpatient setting. In TBCT 1, the index case was an AFB smear positive healthcare worker (HCW) with 30-minute patient appointments. In TBCT 2-4, the index cases were patients, 2 of whom were AFB smear positive. TBCT included patients seen by the HCW (TBCT 1) and those with appointments one hour before or after the index patient in the same clinic (TBCT 2-4). Contacts were offered interferon-gamma release-assay (IGRA). Staff contacts were tested by purified protein derivative (PPD). Comorbidities, prevalent and new cases with positive TB testing were calculated and compared between different groups.ResultsFifty-one percent of veteran contacts had comorbidities placing them in a high priority group for TBCT. Among the 593 patients who had an IGRA during TBCT, 40 (6.7%) tested positive. Twenty-six (4.4%) had no known history of prior positive TB test of whom 6 reported a previous TB exposure history. Veterans exposed to the HCW did not have a higher prevalence of IGRA positivity or a new positive IGRA compared to TBCT 2-4 (5.5% vs 8.0%, p-value 0.22 and 3.4% vs. 5.3%, p-value 0.26). Among the 130 staff tested in TBCT 1-4, one (0.7%) converted during TBCT 1.ConclusionAfter extensive TBCT, the prevalence of latent TB among short duration/casual contacts of TB was 6.7%, similar to the baseline prevalence of latent TB of 6% in California. In this high priority population for TBCT, no difference was seen when there was face-to-face contact versus a shared waiting room with the index case. Staff conversion rate was extremely low. While decisions to perform TBCT in outpatient settings need to be individualized, the yield of TBCT in this population of veterans was low.Disclosures All Authors: No reported disclosures

Adenosine deaminase and lactate dehydrogenase levels in serum and cerebrospinal fluid of patients with tuberculous meningitis

Meningitis is an active inflammatory condition of CNS. However prompt and precise aetiological diagnosis remains a challenge. Often a thorough CSF examination may not give a precise diagnosis.There is considerable urgency in establishing correct diagnosis in patients with tuberculous meningitis because specific therapy is most effective when initiated early in course of illness, delay may cause irreversible brain damage.Diagnosis often rests on circumstantial evidence such as history, typical CSF findings and other evidence for presence of tuberculosis such as acid fast bacilli in sputum, positive tuberculosis test and suspicious Chest x-ray. Under present study the role of enzymes such as adenosine deaminase and lactate dehydrogenase has been evaluated in diagnosis of tuberculous meningitis. Result of the study suggest that adenosine deaminase level in CSF and serum may be a useful parameter along with other routine estimations. The enzyme activity is high in disease such as tuberculosis where cellular mediated immunity is stimulated.Estimation of lactate dehydrogenase levels may not be a specific parameter for tuberculous meningitis this requires further studies in patients of meningitis with different aetiological diagnosis.

Public Health Response to Tuberculosis Outbreak among Persons Experiencing Homelessness, Minneapolis, Minnesota, USA, 2017-2018.

Tuberculosis (TB) is a greater risk for populations experiencing homelessness. When a TB exposure occurs in a homeless shelter, evaluation of contacts is both urgent and challenging. In 2017, local public health workers initiated a response to a TB outbreak in homeless shelters in Minneapolis, Minnesota, USA. In this contact investigation, we incorporated multiple techniques to identify, evaluate, and manage patients, including the concentric-circle method to characterize amount of contact, identifying the most frequent sites of sporadic medical care, using electronic medical records, and engaging with medical providers treating this population. Of 298 contacts evaluated, 41 (14%) had latent TB infection and 2 had active TB disease. Our analysis indicated a significant relationship between duration of exposure and positive TB test result (p = 0.001). We encourage local public health departments to expand beyond traditional contact tracing techniques by leveraging partnerships and existing systems to reach contacts exposed in shelters.

Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections

Infectious diseases have a profound impact on our health and many studies suggest that host genetics play a major role in the pathogenesis of most of them. We perform 23 genome-wide association studies for common infections and infection-associated procedures, including chickenpox, shingles, cold sores, mononucleosis, mumps, hepatitis B, plantar warts, positive tuberculosis test results, strep throat, scarlet fever, pneumonia, bacterial meningitis, yeast infections, urinary tract infections, tonsillectomy, childhood ear infections, myringotomy, measles, hepatitis A, rheumatic fever, common colds, rubella and chronic sinus infection, in over 200,000 individuals of European ancestry. We detect 59 genome-wide significant (P < 5 × 10−8) associations in genes with key roles in immunity and embryonic development. We apply fine-mapping analysis to dissect associations in the human leukocyte antigen region, which suggests important roles of specific amino acid polymorphisms in the antigen-binding clefts. Our findings provide an important step toward dissecting the host genetic architecture of response to common infections.

A mode of error: Immunoglobulin binding protein (a subset of anti-citrullinated proteins) can cause false positive tuberculosis test results in rheumatoid arthritis

Citrullinated Immunoglobulin Binding Protein (BiP) is a newly described autoimmune target in rheumatoid arthritis (RA), one of many cyclic citrullinated peptides(CCP or ACPA). BiP is over-expressed in RA patients causing T cell expansion and increased interferon levels during incubation for the QuantiFERON-Gold tuberculosis test (QFT-G TB). The QFT-G TB has never been validated where interferon is increased by underlying disease, as for example RA.Of ACPA-positive RA patients (n = 126), we found a 13% false-positive TB test rate by QFT-G TB. Despite subsequent biologic therapy for 3 years of all 126 RA patients, none showed evidence of TB without INH. Most of the false-positive RA patients after treatment with biologic therapy reverted to a negative QFT-G test. False TB tests correlated with ACPA level (p < 0.02).Three healthy women without arthritis or TB exposure had negative QFT-G TB. In vitro, all three tested positive every time for TB correlating to the dose of BiP or anti-BiP added, at 2 ug/ml, 5 ug/ml, 10 ug/ml, and 20 ug/ml.BiP naturally found in the majority of ACPA-positive RA patients can result in a false positive QFT-G TB. Subsequent undertreatment of RA, if biologic therapy is withheld, and overtreatment of presumed latent TB may harm patients.

Pulmonary sarcoidosis and latent tuberculosis in a patient with psoriasis treated with adalimumab

Tumor necrosis factor (TNF) inhibitors are powerful biologic medications that have been used successfully in the treatment of a variety of inflammatory conditions, including psoriasis. Although TNF inhibitors are generally well tolerated, their use increases the risk of infections such as tuberculosis (TB), and paradoxically, they have been associated with development of sarcoidosis. We report the case of a 54-year old man with plaque psoriasis who developed a positive TB test and pulmonary sarcoidosis after 12 months of adalimumab treatment. After stopping adalimumab, his psoriasis worsened and he was started on ustekinumab and narrowband UVB, with improvement in symptoms. We provide a review of the literature and discuss treatment challenges.

Tuberculosis investigations associated with air travel: U. S. Centers for Disease Control and Prevention, January 2007–June 2008

Contact investigations conducted in the United States of persons with tuberculosis (TB) who traveled by air while infectious have increased. However, data about transmission risks of Mycobacterium tuberculosis on aircraft are limited. We analyzed data on index TB cases and passenger contacts from contact investigations initiated by the U.S. Centers for Disease Control and Prevention from January 2007 through June 2008. Contact investigations for 131 index cases met study inclusion criteria, including 4550 passenger contacts. U.S. health departments reported TB screening test results for 758 (22%) of assigned contacts; 182 (24%) had positive results. Of the 142 passenger contacts with positive TB test results with information about risk factors for prior TB infection, 130 (92%) had at least one risk factor and 12 (8%) had no risk factors. Positive TB test results were significantly associated with risk factors for prior TB infection (OR 23; p<0.001). No cases of TB disease among passenger contacts were reported. The risks of M. tuberculosis transmission during air travel remain difficult to quantify. Definitive assessment of transmission risks during flights and determination of the effectiveness of contact-tracing efforts will require comprehensive cohort studies.

Three air travel-related contact investigations associated with infectious tuberculosis, 2007–2008

The potential for transmission of Mycobacterium tuberculosis during air travel has garnered considerable attention in the media and among public health authorities due to high-profile cases of international travelers with infectious tuberculosis (TB). During 2007 and 2008, state and local health officials were asked to locate and conduct diagnostic follow-up for airline passengers considered contacts of three travelers, two with multidrug-resistant (MDR) TB and one considered highly contagious, who undertook air travel while infectious with TB disease. Public health departments in 21 states located and evaluated 79 (60%) of the 131 passenger contacts identified; 52 (40%) were lost to follow-up. Eight (10%) contacts had a history of TB disease or latent TB infection and were not retested. Sixteen (23%) of 71 contacts tested had positive TB test results suggesting latent TB infection, 15 of whom were from countries reporting estimated TB disease rates of greater than 200 cases/100,000 persons. Passenger contacts' positive test results may represent prior TB infection acquired in their countries of residence or may be a result of new TB infection resulting from exposure during air travel.

Lupus vulgaris: Isolation of Mycobacterium tuberculosis from the affected skin scraping and mucous membranes

In the second half of the last century skin tuberculosis has become a rarity. With the appearance of resistance to different kinds of pathogenes, HIV-immunodeficiency and decreasing standard of living, the incidence of skin tuberculosis increases. Lupus vulgaris is a chronic form of the secondary tuberculosis of the skin. This is a case report of a 66-year-old woman who presented with a growing, painless, brownish-red, slab-shaped, jelly, cutanesous mass, 2.5 centimeters in diameter, on the tip of her nose, reaching the mucous membrane of the nose. Apart from accelerated erythrocyte sedimentation rate (43/73) and a positive tuberculosis test (Mantoux 10 TU = 25x25 mm), all relevant findings were within reference values. Using Ziehl-Neelsen staining, no acido-resistent bacilli were found. The skin scraping sample, taken from the affected skin and the mucous membrane, was cultivated in Lowenstein medium base, and this resulted with cultivation of Mycobacterium tuberculosis. Using three-drug combination therapy for ten months, complete remission was achieved. Successful cultivation of pathogens represents an absolute diagnostic criterion. We present a case of a woman with lupus vulgaris, because there is a small number of cases documented around the world where the diagnosis was confirmed by culture of Mycobacterium tuberculosis.