Peripheral Exudative Hemorrhagic Chorioretinopathy (PEHCR): Diagnostic and Therapeutic Challenges.

Background and Objectives: Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a peripheral retinal vascular abnormality that is likely underreported. We review the differential diagnoses, etiology, and treatment options for PEHCR. Methods: We present a case of an asymptomatic 72-year-old female referred following left eye fundus photography finding of the peripheral lesion. Results: Fundus photography demonstrated a large temporal pigment epithelial detachment (PED) with adjacent fibrovascular membrane. Optical coherence tomography (OCT) confirmed the PED with trace subretinal fluid. Fluorescein angiography (FA) demonstrated early and late hypofluorescence of the PED with late leakage of the adjacent temporal fibrovascular membrane. Observation was elected, visual acuity remained unaffected, and the PED spontaneously resolved. Conclusions: Due to the peripheral location, patients often present as asymptomatic; however, vision loss can occur due to vitreous hemorrhage or extension of subretinal fluid, hemorrhage, or exudate to the macula. Commonly, these lesions are referred with concern for choroidal melanoma due to their large, dark, elevated presentation in the peripheral retina. Multimodal testing using B-scan, FA, and OCT is important in establishing the proper diagnosis. PEHCR lesions can often be observed without treatment, though intravitreal injection of anti-VEGF is increasingly used to prevent secondary causes of vision loss.

Safety and Side Effects of Rifampin versus Isoniazid in Children.

BACKGROUND: The treatment of latent infection with Mycobacterium tuberculosis is important in children because of their vulnerability to life-threatening forms of tuberculosis disease. The current standard treatment - 9 months of isoniazid - has been associated with poor adherence and toxic effects, which have hampered the effectiveness of the drug. In adults, treatment with 4 months of rifampin has been shown to be safer and to have higher completion rates than 9 months of isoniazid. METHODS: In this multicenter, open-label trial, we randomly assigned 844 children (<18 years of age) with latent M. tuberculosis infection to receive either 4 months of rifampin or 9 months of isoniazid. The primary outcome was adverse events of grade 1 to 5 that resulted in the permanent discontinuation of a trial drug. Secondary outcomes were treatment adherence, side-effect profile, and efficacy. Independent review panels whose members were unaware of trial-group assignments adjudicated all adverse events and progression to active tuberculosis. RESULTS: Of the children who underwent randomization, 829 were eligible for inclusion in the modified intention-to-treat analysis. A total of 360 of 422 children (85.3%) in the rifampin group completed per-protocol therapy, as compared with 311 of 407 (76.4%) in the isoniazid group (adjusted difference in the rates of treatment completion, 13.4 percentage points; 95% confidence interval [CI], 7.5 to 19.3). There were no significant between-group differences in the rates of adverse events, with fewer than 5% of the children in the combined groups with grade 1 or 2 adverse events that were deemed to be possibly related to a trial drug. Active tuberculosis, including 1 case with resistance to isoniazid, was diagnosed in 2 children in the isoniazid group during 542 person-years of follow-up, as compared with no cases in the rifampin group during 562 person-years (rate difference, -0.37 cases per 100 person-years; 95% CI, -0.88 to 0.14). CONCLUSIONS: Among children under the age of 18 years, treatment with 4 months of rifampin had similar rates of safety and efficacy but a better rate of adherence than 9 months of treatment with isoniazid. (Funded by the Canadian Institutes of Health Research and Conselho Nacional de Pesquisa; ClinicalTrials.gov number, NCT00170209 .).

Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults.

BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels. RESULTS: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events. CONCLUSIONS: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings.

BACKGROUND: Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen. OBJECTIVE: To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid. DESIGN: Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209). SETTING: High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). PARTICIPANTS: Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection. MEASUREMENTS: Health system costs per participant. RESULTS: A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population. LIMITATION: Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines. CONCLUSION: A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Universal Genotyping for Tuberculosis Prevention Programs: a 5-Year Comparison with On-Request Genotyping.

Prospective universal genotyping of tuberculosis (TB) isolates is used by many laboratories to detect clusters of cases and inform contact investigations. Prior to universal genotyping, most TB prevention programs genotyped isolates on request only, relying on requests from public health professionals whose knowledge of a patient's clinical, demographic, and epidemiological characteristics suggested potential transmission. To justify the switch from on-request to universal genotyping-particularly in the public health domain, with its limited resources and competing priorities-it is important to demonstrate the additional benefit provided by a universal genotyping program. We compared the clustering patterns revealed by retrospective 24-locus mycobacterial interspersed repetitive unit-variable-number tandem repeat genotyping of all culture-positive isolates over a 5-year period to the patterns previously established by our genotyping-on-request program in the low-incidence setting of British Columbia, Canada. We found that 23.8% of isolates were requested during the study period, and while requested isolates had increased odds of belonging to a genotype cluster (adjusted odds ratio, 2.3; 95% confidence interval, 1.5 to 3.3), only 54.6% clustered with the requested comparator strain. Universal genotyping revealed 94 clusters ranging in size from 2 to 53 isolates (mean = 5) and involving 432 individuals. On-request genotyping missed 54 (57.4%) of these clusters and 130 (30.1%) clustered individuals. Our results underscore that TB patient networks are complex, with unrecognized linkages between patients, and a prospective province-wide universal genotyping program provides an informative, bias-free tool to explore transmission to a degree not possible with on-request genotyping.

Whole-genome sequencing and social-network analysis of a tuberculosis outbreak.

BACKGROUND: An outbreak of tuberculosis occurred over a 3-year period in a medium-size community in British Columbia, Canada. The results of mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) genotyping suggested the outbreak was clonal. Traditional contact tracing did not identify a source. We used whole-genome sequencing and social-network analysis in an effort to describe the outbreak dynamics at a higher resolution. METHODS: We sequenced the complete genomes of 32 Mycobacterium tuberculosis outbreak isolates and 4 historical isolates (from the same region but sampled before the outbreak) with matching genotypes, using short-read sequencing. Epidemiologic and genomic data were overlaid on a social network constructed by means of interviews with patients to determine the origins and transmission dynamics of the outbreak. RESULTS: Whole-genome data revealed two genetically distinct lineages of M. tuberculosis with identical MIRU-VNTR genotypes, suggesting two concomitant outbreaks. Integration of social-network and phylogenetic analyses revealed several transmission events, including those involving "superspreaders." Both lineages descended from a common ancestor and had been detected in the community before the outbreak, suggesting a social, rather than genetic, trigger. Further epidemiologic investigation revealed that the onset of the outbreak coincided with a recorded increase in crack cocaine use in the community. CONCLUSIONS: Through integration of large-scale bacterial whole-genome sequencing and social-network analysis, we show that a socioenvironmental factor--most likely increased crack cocaine use--triggered the simultaneous expansion of two extant lineages of M. tuberculosis that was sustained by key members of a high-risk social network. Genotyping and contact tracing alone did not capture the true dynamics of the outbreak. (Funded by Genome British Columbia and others.).

Coats' Disease in a Patient With Cornelia de Lange Syndrome: Management With Laser and Bevacizumab.

Cornelia de Lange syndrome is a congenital disorder with multisystem abnormalities including multiple ocular findings. The authors report a case of Coats' disease in a patient with Cornelia de Lange syndrome who was successfully treated with laser and intravitreal bevacizumab. This case demonstrates the importance of fluorescein angiography in making the diagnosis and directing treatment and the efficacy of combined laser with intravitreal anti-vascular endothelial growth factor therapy for persistent vascular leakage associated with Coats' disease in Cornelia de Lange syndrome. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e45-e48.].

Long term follow-up of drug resistant and drug susceptible tuberculosis contacts in a Low incidence setting.

BACKGROUND: Studies examining the transmission of multidrug-resistant tuberculosis (MDR-TB) strains have yielded conflicting results. METHODS: We examined transmission of MDR-TB strains using contact tracing data from a low incidence setting. Contacts of MDR-TB cases diagnosed in British Columbia, Canada, from 1990-2008 were identified through a provincial tuberculosis (TB) registry. Tuberculin skin test (TST) results and TB disease incident rates were determined for contacts. For comparison, TB disease incident rates and TST results were measured in close contacts of isoniazid mono-resistant (HMR-TB) and drug susceptible TB (DS-TB) cases. RESULTS: Of 89 identified close contacts of MDR-TB patients, 5 patients (6%) developed TB disease and 42 (47%) were TST positive. The incidence rate of TB disease (3%, p = 0.31) and TST positivity (49%, p = 0.82) were similar in contacts of HMR-TB cases. Compared with MDR-TB contacts, DS-TB contacts had lower incidence rate of TB disease (2%, p = 0.04) and TST positivity (32%, p < 0.01). All MDR-TB contacts with culture positive TB diagnosed in follow-up were drug-susceptible; three of six HMR-TB contacts with culture positive TB were HMR-TB. Multivariate analysis demonstrated that contact with MDR-TB (adjusted OR 1.72; 95%CI 1.05-2.81) and HMR-TB (adjusted OR 1.99; 95%CI 1.48-2.67) was associated with TST positivity. In addition, adult age, male gender, BCG positivity, source case sputum smear positivity, foreign birth and fewer contacts per source case were significantly associated with TST positivity in the multivariate model. CONCLUSION: Contacts of MDR-TB and HMR-TB patients in a low incidence setting show high rates of TST positivity and TB disease but low rates of drug resistance.

Purtscher-Like Retinopathy with Cardioembolic Stroke: Case Report and Literature Review.

Purtscher-like retinopathy (PUR) is a rare condition characterized by sudden vision loss with associated retinal white patches thought to be due to precapillary arteriolar occlusion. We present a case of PUR associated with a cardioembolic stroke in a patient following temporary cessation of anticoagulant therapy for a surgical procedure. Our patient presented with multiple risk factors for PUR and classic signs and symptoms including multiple peripapillary white retinal lesions near arterioles and sudden unilateral decrease in visual acuity. Optical coherence tomography showed inner retinal hyperreflectivity and thinning consistent with inner retinal ischemia, and fluorescein angiography showed delayed retinal filling. Her complement C5 factor was elevated on laboratory testing. Brain magnetic resonance imaging showed acute/subacute left occipital lobe ischemia thought to be from a cardioembolic stroke. Shortly prior to visual symptoms, our patient's apixaban was held due to surgical drainage of a gluteal abscess. This case highlights the rare occurrence of PUR associated with cardioembolic stroke and the importance of cerebral imaging in a patient presenting with PUR of uncertain etiology.

Consideration of Nasal Contour in Endoscopic Forehead Rejuvenation.

Purpose: Preliminary studies have suggested an improvement in nasal aesthetics after endoscopic forehead lifting. We aimed to assess subjective and objective changes in nasal contour after minimally invasive forehead rejuvenation. Methods: We performed a retrospective review of patients who underwent endoscopic forehead lifting by four surgeons at a single surgery center from 2004 to 2018. All patients had subperiosteal blunt release of soft tissues overlying the radix. Changes in nasal contour were assessed on pre- and postoperative patient photos by four independent judges using the Global Aesthetic Improvement Scale. Objective changes in nasal length and length-to-base ratio were measured on patient photographs using ImageJ software. Measurements were further compared by demographic variables of age and gender. Results: In total, 326 patients met inclusion criteria. Summative judging results revealed 79.4% of patients with clinical improvement in nasal contour (11.1% very much improved, 25.6% much improved, and 42.6% improved), 20.1% with no change and 0.6% with worsening. There was a statistically significant increase in average nasal length (2.17 mm, p < 0.0001) and length-to-base ratio (0.03, p < 0.0001) postoperatively. Stratification of patients by age and gender did not reveal a significant difference in degree of nasal proportion change. Conclusions: There is a noteworthy subjective and quantitative improvement in nasal contour and length after endoscopic forehead lifting. This change restores ideal facial proportions and may serve as a useful counseling point when offering this surgery to patients.

CHOROIDAL NEOVASCULARIZATION AND CHORIORETINAL ATROPHY IN A PATIENT WITH MELANOMA-ASSOCIATED RETINOPATHY AFTER IPILIMUMAB/NIVOLUMAB COMBINATION THERAPY.

PURPOSE: To describe a case of choroidal neovascularization (CNV) and chorioretinal scarring in a patient with melanoma-associated retinopathy after ipilimumab/nivolumab combination immune therapy for malignant melanoma. METHODS: Retrospective case report with fundus photography, fluorescein angiography, optical coherence tomography, and electroretinography. RESULTS: A 65-year-old woman presented with symptoms of photopsia and visual field loss. She had previously undergone ipilimumab/nivolumab combination chemotherapy treatment for malignant melanoma 14 months earlier coinciding with the onset of her visual symptoms. Fundus photography showed bilateral atrophic chorioretinal lesions and peripheral retinal pigment epithelial changes. Fluorescein angiography revealed retinovascular leakage in both eyes with CNV in the right eye. Optical coherence tomography showed a pigment epithelial detachment with subretinal fluid and subretinal hyperreflective material consistent with occult CNV. Visual field testing showed generalized visual field loss in both eyes. Bloodwork discovered an elevated angiotensin-converting enzyme. Electroretinography revealed abnormal peripheral rod and cone function with impairment of the photoreceptor and inner nuclear layer. Serum Western blot was positive for 60 kDa antiretinal autoantibody. After a single bevacizumab injection in the right eye, CNV resolved and visual acuity improved from 20/50 before the injection to 20/25 3 months after the injection. Visual acuity in the left eye deteriorated for months to counting fingers but then improved to 20/100 on follow-up examinations. CONCLUSION: Ipilimumab and nivolumab have been associated with immune-related ocular adverse effects. We report a case of combination therapy presenting with chorioretinal scarring and subsequent CNV in a patient with melanoma-associated retinopathy, a rare yet important adverse effect.

Ocular Ischemic Syndrome With Congenital Absence of Internal Carotid Artery.

Purpose: This article describes a case of ocular ischemic syndrome (OIS) in a patient with a congenitally absent left internal carotid artery (ICA). Methods: Retrospective case report with anterior-segment and fundus photography, fluorescein angiography (FA), and computerized tomography angiography (CT-A). Results: A 31-year-old-man was found to have neovascularization of the iris (NVI) and angle of the left eye. FA showed capillary nonperfusion in the temporal periphery. He required intravitreal bevacizumab and triamcinolone injections and 2 panretinal photocoagulation treatments for persistent rubeosis and cystoid macular edema. Transient right-eye vision loss prompted CT-A, revealing an absent left ICA. Three years following presentation, FA continued to show delayed arteriovenous flow suggestive of OIS. He has required intravitreal bevacizumab injections every 12 weeks for persistent NVI. Conclusion: Congenitally absent left ICA with resultant cerebrovascular insufficiency is a rare cause of OIS, underscoring the pathophysiological principles of insufficient blood supply to the ophthalmic artery.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AFTER PREWORKOUT HAVOK INGESTION.

PURPOSE: To describe a case of transient, partial, central retinal artery occlusion with paracentral acute middle maculopathy optical coherence tomography presentation in a young healthy patient after ingestion of the synephrine-containing supplement, Havok. METHODS: Retrospective case report with fundus photography, fluorescein angiography, and optical coherence tomography. RESULTS: A 20-year-old man presented with severe acute vision loss in the right eye. Dilated examination demonstrated cherry red spot with surrounding edema in the macula. Optical coherence tomography showed hyperreflectivity in the middle retinal layer of the macula consistent with paracentral acute middle maculopathy. Fluorescein angiography showed delayed arteriovenous transit time consistent with a central retinal artery occlusion. Bloodwork to investigate a hypercoagulable state and vasculitis were negative. At 1-week follow-up, dilated examination demonstrated resolution of the cherry red spot. At 3 months, the patient's visual acuity was back to normal. Fluorescein angiography showed complete resolution of the retinal artery occlusion, but optical coherence tomography of the macula demonstrated mild, residual middle retina thinning consistent with chronic presentation of paracentral acute middle maculopathy. CONCLUSION: Because of synephrine's physiological and structural similarity to the vasoconstrictive compound ephedra, it is reasonable to suggest that there is potential health hazard in this performance-enhancing compound.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Fluoroquinolones for the treatment of pulmonary tuberculosis.

Tuberculosis (TB) continues to be a significant problem globally. Treatment includes a multiple drug regimen with isoniazid, rifampicin (rifampin), pyrazinamide and ethambutol. Often, one of these medications needs to be replaced as a result of adverse events or because Mycobacterium tuberculosis develops resistance against one these first-line agents. Fluoroquinolones, particularly the newer ones, possess good in vitro (levofloxacin, gatifloxacin, moxifloxacin) and in vivo (gatifloxacin and moxifloxacin) bactericidal activity against M. tuberculosis, making them attractive agents for the treatment of pulmonary TB. All relevant clinical trials, cohort studies and case reports investigating the clinical efficacy and tolerability of fluoroquinolones when used for the treatment of pulmonary TB were evaluated for this review. Specifically, efficacy and safety in the following indications were investigated: (i) first-line treatment of drug-sensitive pulmonary TB; (ii) first-line treatment for multi-drug resistant (MDR) TB; and (iii) treatment of patients with drug intolerance. Twenty-seven articles met our inclusion criteria; nine articles presented data from randomised, controlled or cohort studies. Seven studies used fluoroquinolones as first-line agents in drug-sensitive TB (1469 patients), 15 studies used fluoroquinolones to treat MDR-TB (1025 patients) and six studies (951 patients) investigated the use of fluoroquinolones in patients intolerant to other TB medications. In patients with susceptible M. tuberculosis strains, substitution with a fluoroquinolone did not have an effect on cure or radiological improvement at 8 weeks or failure at 12 months. Substitution of older fluoroquinolones into a regimen, especially ciprofloxacin, resulted in a higher rate of relapse and a longer time to sputum-culture conversions. The use of fluoroquinolones in patients with MDR-TB is supported by some trials where others show a lack of improvement in efficacy of a regimen. Our review of the literature does not support the use of older fluoroquinolones, especially ciprofloxacin, as substitute agents for drug-sensitive or drug-resistant TB. However, newer fluoroquinolones, such as moxifloxacin, may be a reasonable alternative based on results from one large clinical trial. Fluoroquinolones have an important role as substitute agents for those who are intolerant of first-line TB agents.

Mycobacterium kansasii.

The incidence of Mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of nontuberculous mycobacteria. In contrast to other common nontuberculous mycobacteria, M. kansasii is infrequently isolated from natural water sources or soil. The major reservoir appears to be tap water. Infection is likely acquired through the aerosol route, with low infectivity in regions of endemicity. Human-to-human transmission is thought not to occur. Clinical syndromes and radiological findings of M. kansasii infection are mostly indistinguishable from that of Mycobacterium tuberculosis, thus requiring microbiological confirmation. Disseminated disease is uncommon in HIV-negative patients and usually associated with severe immunosuppression. The majority of patients with M. kansasii pulmonary disease have underlying pulmonary comorbidities, such as smoking, chronic obstructive pulmonary disease, bronchiectasis, and prior or concurrent M. tuberculosis infection. Surveys in Great Britain, however, noted higher rates, with 8 to 9% of M. kansasii infections presenting with extrapulmonary disease. Common sites of extrapulmonary disease include the lymph nodes, skin, and musculoskeletal and genitourinary systems. The specificity of gamma interferon release assays (IGRAs) for M. tuberculosis may be reduced by M. kansasii infection, as M. kansasii encodes CFP-10 and ESAT-6, two antigens targeted by IGRAs. A study conducted to evaluate the therapy in rifampin-resistant disease found that patients with acquired rifampin resistance were treated with daily high-dose ethambutol, isoniazid, sulfamethoxazole, and pyridoxine combined with aminoglycoside therapy. Given the potential toxicities, particularly with aminoglycoside therapy, clarithromycin and/or moxifloxacin therapy could be considered as alternatives.

A systematic review on TST and IGRA tests used for diagnosis of LTBI in immigrants.

BACKGROUND: High immigration rates from tuberculosis (TB) endemic countries to low-incidence countries have caused new TB guidelines in these countries to reconsider latent TB infection (LTBI) screening in these immigrants. OBJECTIVES: We performed a systematic review with the primary outcome of evaluating the number of cases recommended LTBI treatment with the tuberculin skin test (TST) or interferon gamma release assay (IGRA). Secondary objectives were to examine prevalence of positive LTBI diagnostic tests stratified by age and incidence of TB in country of origin. METHODS: We performed a systematic search of seven electronic databases for studies assessing TST and/or IGRA performance in immigrant populations to low incidence countries. Demographics, LTBI diagnosis, longitudinal TB development, and test result data were the primary data extracted from the studies. Prevalence of positive test data was stratified by age and country of origin. Studies were evaluated using a modified SIGN checklist for diagnostic studies. Data was compared using Fisher's exact test or χ (2) test, where appropriate. RESULTS: Our literature search yielded 51 studies (n = 34 TST, n = 9 IGRA, n = 8 both). Recommendation of LTBI treatment was less common in those tested with an IGRA compared to TST (p < 0.0001), while long-term development of active TB appears higher in those with a positive IGRA. There was no difference in the sensitivity and specificity of the IGRA and TST for prevalent TB (p > 0.05). Prevalence of a positive test was significantly lower in those who were <18 years of age compared to those ≥18 years of age (p < 0.0001) and those from low TB incidence countries compared to high incidence countries (p < 0.0001) for both TST and IGRA. When comparing the two tests within the 2 subgroups: age and TB incidence in country of origin, the prevalence of positive results was significantly lower for the IGRA than the TST (p < 0.0001). LIMITATIONS: The number of available studies evaluating the IGRA and longitudinal active TB development in those tested limits this study. CONCLUSION: Prevalence of positive test results were significantly lower in immigrants who were tested with an IGRA, resulting in fewer immigrants being recommended for LTBI treatment compared to TST. Coupled with comparable performance for detecting prevalent TB cases, the IGRA appears to exhibit better specificity than the TST and may be preferred as the standard of care for detecting LTBI in immigrants moving to low TB incidence countries.

Latent tuberculosis infection screening in immigrants to low-incidence countries: a meta-analysis.

BACKGROUND: Immigration from regions with a high incidence of tuberculosis (TB) has slowed the decline of TB in low-incidence regions. Targeted screening of new immigrants and treatment for latent TB infection (LTBI) is needed to reinvigorate this decline. This meta-analysis compares LTBI diagnostic tests by positive test prevalence and proportion of positive tests by TB incidence. METHODS: A systematic literature search was performed and data extracted based on tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA) use in immigrants. For the eight studies performing tests concurrently, data were compared by positive tests and concordance, while other studies comparing individual tests were analyzed based on demographic factors. Data were analyzed via meta-analysis. RESULTS: Forty-five studies with a combined sample size of 93,249 individuals were included in the analyses, 2206 of which were from the eight concurrent studies. Odds of a positive TST were significantly higher than an IGRA (odds ratio 1.46; 95% confidence interval 1.07-2.01) and test agreement was moderate. Proportion of positive TST and IGRA tests increased with TB incidence, although not linearly. CONCLUSION: TST and IGRA data relating to immigrants are lacking, especially long-term follow-up and comparative data. Further data are urgently needed to determine TB risks after immigration, long-term TB development, and treatment outcomes.

Usefulness of Interferon-γ release assays in the diagnosis of erythema induratum.

BACKGROUND: Erythema induratum (EI) manifests as tender indurated nodules on the lower legs. It may be associated with concomitant active tuberculosis (TB) and is considered a hypersensitivity reaction to mycobacterial antigens. However, the results of Mycobacterium cultures are rarely positive, and the tuberculin skin test is of limited usefulness in populations exposed to bacille Calmette-Guérin (BCG). Interferon-γ release assays (IGRAs) are alternatives to the tuberculin skin test and have high specificity. We explored the use of IGRAs as an adjunct in the diagnosis of EI. We describe 5 patients with positive tuberculin skin test results and a history of vaccination against BCG or TB in whom IGRAs supported the diagnosis of EI. OBSERVATIONS: All patients were initially seen with tender nodules on the lower legs and a history of BCG vaccination or TB. Tuberculin skin test results were positive, and chest radiographic results were normal. The results of Mycobacterium cultures were negative in all patients, and biopsy specimens were compatible with EI. Interferon-γ release assays were performed in all patients and supported initiation of anti-TB treatment in 4 of 5 patients. Conclusion  Interferon-γ release assays may have value as an adjunct in the diagnosis of EI, particularly in the setting of prior BCG exposure.

A statistical method was used for the meta-analysis of tests for latent TB in the absence of a gold standard, combining random-effect and latent-class methods to estimate test accuracy.

OBJECTIVE: Because of the lack of a gold standard, the diagnostic performance of tests for the detection of latent tuberculosis infection (LTBI) is not known. However, statistical methods can be used to estimate the accuracy from the studies reporting the concordance among the tests. STUDY DESIGN AND SETTING: We developed a random-effect latent-class model to estimate performance characteristics of three LTBI diagnostic tests: tuberculin skin test (TST, at 10-mm cutoff), QuantiFERON-TB gold (QFG), and TSPOT-TB from the studies evaluating agreement among the tests. RESULTS: Nineteen studies were included. QFG had a sensitivity of 0.642 (95% confidence interval [CI]: 0.593-0.691) and specificity of 0.996 (95% CI: 0.989-1.000), TSPOT-TB had a sensitivity of 0.500 (95% CI: 0.334-0.666) and specificity of 0.906 (95% CI: 0.882-0.929), and TST had a sensitivity of 0.709 (95% CI: 0.658-0.761) and specificity of 0.683 (95% CI: 0.522-0.844). Results were not sensitive to the inclusion of any single study. When only the three studies that reported on TSPOT were removed, estimates for the other two tests varied minimally. CONCLUSIONS: Statistical methods can help estimate the accuracy of LTBI tests. Although the specificities were close to their reported values in the literature, the estimates for sensitivities were low; a finding that should be carefully evaluated.