Purified Protein Derivative Of Tuberculin Research Articles

Assessing the impact of various tuberculin PPD brands on bovine tuberculosis diagnosis

Although several brands of tuberculin purified protein derivatives (PPDs) are available for diagnosing bovine tuberculosis (bTB), comparative studies to determine their diagnostic accuracy are infrequent. In Ecuador we compared two different PPD brands for bTB diagnosis using skin testing and measuring skin thickness increase. Additionally, we evaluated four PPD brands, including those used for skin testing, in the Bovine Tuberculosis Interferon Gamma Test (IFN-γ test) measuring IFN-γ induction in whole blood. The study included 17 naturally tuberculosis-infected PPD and IFN-γ test positive bovines. Both the field and laboratory results showed significant differences in classifying the 17 bovines as bTB positive or negative. We hypothesize that several factors, such as the genetic background of the cows, sensitization to environmental mycobacteria, M. bovis strains involved in the bTB infection, and the manufacturing procedures of the PPDs, could have influenced the immune reaction toward the different tuberculin PPD brands. Our study emphasizes the necessity for comparative studies aimed at determining the diagnostic accuracy of PPD brands for bTB diagnosis as well as the development of standardized methods for PPD production and potency determination.

Efficacy and Safety Profile of Tuberculin Protein Purified Derivative Injection As Immunotherapy For the Treatment of Cutaneous and Anogenital Warts: A Review Article.

Various treatments available today for anogenital and cutaneous warts have limitations, including time-consuming, challenging to perform, and the risk of scarring. A new treatment using tuberculin purified protein derivative (PPD) has been developed, which is expected to generate cellular immunity against HPV. To assess the evidence for the efficacy and safety of PPD treatment for cutaneous and anogenital warts. A literature search was performed with the keyword-based search on digital libraries, including the National Library of Medicine, Cochrane Controlled Register of Trial, and Google Scholar, using the following terms: anogenital warts, condyloma acuminata, cutaneous warts, human papillomavirus, immunotherapy, and tuberculin purified protein derivative. Original studies on treating cutaneous or anogenital warts with PPD were included. The results were 47 clinical trials and 4 case reports. Most of the research was done in countries with common Mycobacterium tuberculosis infection. The treatment showed good efficacy. Comparative studies showed that the treatment has similar efficacy with other immunotherapies. No significant side effects were reported, with evidence of the safety use on the pregnant population. Based on good efficacy and safety, PPD can be considered an alternative therapy, especially in countries where tuberculosis is frequent.

Effectiveness and safety of tuberculin purified protein derivative for the treatment of anogenital warts in patients with human immunodeficiency virus

Individuals with human immunodeficiency virus (HIV) infection are prone to developing persistent and unremitting anogenital warts (AGWs). To address this health condition, immunotherapy using tuberculin purified protein derivative (PPD) has been proven to be a promising novel and safe treatment for AGWs in HIV patients. Therefore, this study involved a case of a 21-year-old man with stage I HIV infection, possessing CD4 counts 548 cells/uL and routinely receiving HIV antiretroviral. Patients presented with a condyloma acuminata type AGWs, supported by histopathological results, and tested positive for Human papillomavirus type 11. The treatment approach involved administering 15 tuberculin units of PPD weekly to the largest lesion for 5 weeks. The lesion started to respond two weeks following the first injection and showed a 50% decrease in size after five weeks. There was pain on the site of injection and sub-febrile for a short period. In conclusion, tuberculin PPD is safe and has the potential for the treatment of AGWs in HIV-positive patients for further development.

Intralesional injection of tuberculin purified protein derivative (PPD) versus measles, mumps, and rubella (MMR) vaccine in treatment of molluscum contagiosum: a comparative study

Molluscum contagiosum (MC) is a skin and mucous membrane infection caused by the molluscum virus (MCV). To evaluate safety and efficacy of intralesional injection of tuberculin purified protein derivative (PPD) antigen injection versus MMR (mumps, measles, rubella) antigen for the treatment of molluscum contagiosum (MC). A total of thirty clinically confirmed patients of molluscum were recruited for this trial. Patients who were divided into three groups (A, B and C). Each group consisted of (30) patients. Group (A) subjects received intralesional MMR injections, group (B) subjects received intralesional PPD injection and group (C) received intralesional saline injection. The results of the present study revealed complete clearance of the injected lesions in 12 patients (80%), partial response in 3 patients (20%) of group (A). In group (B), complete clearance of the treated warts was observed in 11 patients (73.3%) and partial response in 4 (26.7%) of patients. In group (C), the majority of patients 8 (53.3%) demonstrated no response while 7 (46.7%) patients showed only partial clearance. We established a good safety and efficacy profile for tuberculin PPD and MMR antigens in treatment of molluscum contagiosum.

Efficacy and Safety of Intralesional Immunotherapy with Tuberculin Purified Protein Derivative among Cutaneous Wart Patients.

Cutaneous warts are common skin problems caused by Human Papilloma Virus. Conventional therapies are mostly ablative and limited by recurrences and side effects. Immunotherapy using bacterial, fungal, and viral antigens is an emerging and safer technique to treat warts at local and distant sites. The objective of this study was to measure the efficacy and safety of intralesional immunotherapy with tuberculin purified protein derivative among cutaneous wart patients in the dermatology department of a tertiary care centre. A cross sectional, time series design, was conducted between October 2019 and September 2020 among 77 patients of cutaneous warts attending Dermatology out-patient department using convenience sampling. Percentage response was evaluated for patients treated with tuberculin purified protein derivative for eight weeks at an interval of two weeks into complete response (100% clearance), partial response (50-99% clearance), no response (0-49% clearance). Side effects were also recorded. Statistical Package for the Social Sciences version 20.0 was used for data analysis. Out of 77 patients, complete response (100%) was seen in 53.2% patients, partial response (50-99%) in 14.3% and no response (0-49%) was seen in 32.5%. Side effects noted were pain and erythema (19.50%), blisters (2.60%) and flu like symptoms (1.30%). Intralesional PPD is an effective and safer therapeutic option for the treatment of cutaneous warts.

Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis

Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. We obtained data from 13 studies out of 40 that were considered eligible (N=32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette-Guérin vaccine (BCG) status (15mm if BCG vaccinated and 5mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69-4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97-8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17-25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82-7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58-7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48-11.51 for QFT-GIT, when excluding the study, in which all 19TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23-2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98-3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p=0.68 for QFT-GIT). IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC_UU_00004/07].

Evaluation of the efficacy and safety of the intralesional purified protein derivative of tuberculin versus intralesional vitamin D3 for the management of recalcitrant warts

Introduction: Warts are caused by the human papillomavirus (HPV), which infects the epidermal cell layers leading to their hyperproliferation. The concept of immunotherapy has recently come to light. It acts by mounting delayed cell-mediated and humoral immunity against the HPV in the host. Objective: This study aimed to evaluate the efficacy and safety of the intralesional PPD versus intralesional vitamin D3 for the management of recalcitrant warts. Materials and Methods: This prospective randomized trial was conducted on patients between the ages of 12 and 65 years with two or more recalcitrant extragenital warts. The subjects were randomly divided into two groups, namely, group A (PPD) and group B (vitamin D3). In group A, a purified protein derivative (PPD) of tuberculin was employed without any prior pre-sensitization testing. Each patient in group I received 0.1–0.2 mL of antigen at the base of the largest wart. In group B, the patients received 0.1–0.2 mL in a similar manner. Results: In group A, 39 (78%) patients had complete clearance while, in group B, 38 (76%) had complete clearance in injected warts (p = 0.8). As far as distant warts were concerned, in group A, 35 (70%) had a complete response while, in group B, 29 (48%) had a complete response. There was a statistically significant difference between the two groups with a greater degree of clearance in distant warts with the tuberculin PPD (p = 0.04). Conclusion: Both the tuberculin PPD and vitamin D3 are reliable and safe management options for recalcitrant, treatment-resistant, and extensive warts.

Mass Casualty Incident Involving Rapid Acting Insulin

We report on an unusual prehospital incident involving the inadvertent administration of short-acting insulin among a group of high school students. Sixteen students iatrogenically received 10 units of insulin lispro intradermally instead of tuberculin purified protein derivative (PPD), resulting in several students experiencing symptomatic hypoglycemia. A mass casualty incident was declared and the local poison center consulted. An incident command system, with the support of on-scene EMS physicians, was established to track, treat, and transport the involved patients.

Successful treatment of giant anogenital condyloma accuminata with combined cryotherapy and intralesional tuberculin purified protein derivative: a case report

To show the effectiveness of combined cryotherapy and intralesional tuberculin purified protein derivative (PPD) in the treatment of giant condyloma accuminata. A 57-year-old female was presented with an extensive verrucous, ulcerated, cauliflower-like 10 × 5 cm mass of the perianal area with extension to labia majora. The mass had evolved progressively for 2 years and resulted in perianal discomfort, itching and bleeding. Histopathological examination ruled out the presence of malignancy and confirmed the diagnosis of condyloma accuminata.The lesions were treated by 6 sessions of combined cryotherapy (2 freeze thaw cycles 25 seconds each) and intralesional PPD with a dose of (0.3 ml each session) at two-week interval. The mass resolved completely after 3 months and the quality of life of the patient has improved dramatically. There was no recurrence within 1 year of follow-up. Although most case reports suggest surgical excision as the treatment of choice of giant condyloma accuminata, our case was successfully treated with a highly effective and safe combined modality of cryotherapy and intralesional PPD, with the advantage of preserving the normal anatomy and avoidance of post-surgical disfigurement. No conflict of interest to declare.

Successful treatment of giant anogenital condyloma accuminata with combined cryotherapy and intralesional tuberculin purified protein derivative: a case report

Successful treatment of giant anogenital condyloma accuminata with combined cryotherapy and intralesional tuberculin purified protein derivative: a case report

Peripheral tuberculin purified protein derivative specific T cell immunoreactivity dynamics in non-muscle invasive bladder cancer patients receiving bacillus Calmette-Guerin instillation treatment.

Intravesical bacillus Calmette-Guerin (BCG) instillation is recommended as an adjuvant therapy for intermediate-risk and high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBt) with nearly 70% reoccurrence. In the present study, we investigated the dynamics of peripheral purified protein derivative (PPD)-specific immune responses along the treatment. Intravesical BCG instillation caused a significant increase in peripheral PPD-specific IFN-γ release of NMIBC patients, when compared to those receiving chemo-drug instillation. Through a follow-up study, we detected rapid increase in PPD-specific IFN-γ, IL-2, and IL-17A producing CD4+ and CD8+ T cells in the induction phase. Interestingly, the frequencies of PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells decreased dramatically after induction treatment and were restored after BCG re-instillation, whereas IL-17A-producing T cells remained at the maintenance phase. However, we only observed that the percentages of peripheral CD8+ T cells were significantly higher in BCG responder patients than those in BCG refractory patients at the baseline with the potential of predicting the recurrence. A more dramatic increase in PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells after one and two dose BCG instillations was observed in refractory NMIBC patients. Therefore, regional BCG instillation induced transient peripheral PPD-specific T cell responses, which could be restored through repetitive BCG instillation. Higher proportions of peripheral CD8+ T cells at baseline were associated with better responses to BCG instillation for the prevention of recurrence of bladder cancer.

Intralesional Measles, Mumps, Rubella Vaccine versus Tuberculin Purified Protein Derivative Injections in the Treatment of Palmoplantar and Periungual Warts: A Double-Blind Randomized Controlled Trial

Background: Palmoplantar and periungual warts tend to be recalcitrant. Intralesional immunotherapy can provide high efficacy with additional benefit to distant warts. However, evidence on comparative effects between intralesional immunotherapy with measles, mumps, rubella vaccine (MMR) and tuberculin purified protein derivative (PPD) and roles of dermoscopy in predicting treatment outcomes in palmoplantar/periungual warts is limited. Objectives: The study aimed to compare efficacy and safety of intralesional MMR and PPD injections in treatment of palmoplantar/periungual warts and explore associations between dermoscopic findings and treatment outcomes. Methods: We conducted a double-blind randomized controlled trial involving 40 patients with palmoplantar/periungual warts who were equally assigned to receive MMR or PPD. Intralesional injection was done every 2 weeks until clearance or maximum of 5 treatments. Results: Complete resolution was higher in MMR than PPD group (90.0% vs. 80.0% in index lesion and 81.3% vs. 54.6% in distant lesions, respectively), although the differences were statistically nonsignificant. Dermoscopic findings were not significantly associated with complete resolution. Local swelling, i.e., the most common adverse event, occurred more frequently in PPD (40.0%) than MMR group (10.0%). Conclusion: This study suggests that intralesional immunotherapy with either MMR or PPD is efficacious in palmoplantar/periungual warts, with MMR showing a trend toward higher clearance and lower adverse events.

Interleukin-18 serum level before and after intralesional immunotherapy with tuberculin purified protein derivative in patients with cutaneous and genital warts.

Several studies demonstrated the efficacy of intralesional purified protein derivative (PPD) immunotherapy in warts eradication. Nevertheless, the precise induced immune mechanisms are undetermined. Injected PPD is hypothesized to induce a delayed hypersensitivity reaction associated with cytokines release. Interleukin (IL)-18 has a major role in defense against viral infection via inducing interferon-γ release from T-helper 1 and natural killer (NK) cells. Moreover, IL-18 triggers Fas ligand expression on cytotoxic T cells and NK cells enhancing their cytotoxicity against virally infected cells. The aim of this study was to assess the role of IL-18 in the response to intralesional PPD injection in patients with warts. The study included 25 patients with warts and 25 HCs. Patients underwent PPD skin test, and only patients with positive tests were included and received intralesional PPD injections starting 72 h after the test then every 2 weeks until wart clearance or a maximum of 3 sessions. Serum IL-18 level was measured via enzyme-linked immune-sorbent assay in patients (pre-treatment and 2 weeks after the last injection) and HCs. After 3 sessions of injection, six (24%) patients were designated responders, nine (36%) patients showed partial response, and 10 (40%) patients were designated non-responders. Serum IL-18 level, post-treatment, was significantly higher than pre-treatment level (p =0.025) and level in HCs (p =0.036). Furthermore, the post-treatment level was significantly higher in responders than non-responders (p= 0.025). IL-18 is probably implicated in the immune mechanisms induced by PPD injection that cause eradication of warts.

A Prospective Clinical Study for Safety and Efficacy of Intralesional Tuberculin Purified Protein Derivative in Treatment of Palmoplantar Verruca

Background: Multiple treatment options are available for verruca, however none is completely effective. Conventional modalities such as salicylic acid, cryotherapy have inconsistent treatment efficacies. Newer modalities such as immunotherapy, bleomycin and lasers have shown higher clearance rates of warts in recent studies. Immunotherapy is an innovative approach to treat warts which relies on the principle of enhancement of cell-mediated immunity. This study was done to evaluate the efficacy of immunotherapy with Tuberculin Purified Protein Derivative injection in palmoplantar verruca in our context.&#x0D; Materials and Methods: This is an open labelled, prospective interventional study. Patients with palmoplantar verruca enrolled in the study were injected with purified protein derivative intralesionally by an insulin syringe at a dose of 10 IU (0.1 mL) in the largest wart every 2 weeks until all lesions disappeared or for a maximum of six sessions. They were followed up for 3 months after final treatment session.&#x0D; Results: A total of 54 patients, 34 males and 20 females, were enrolled in the study. Commonest distribution of palmoplantar verruca was in plantar distribution (48.1%). Among them, 12 (22.2%) patients had periungual warts. Complete clearance of warts without any scarring was seen in 66.7% (36) patients with palmoplantar verruca at the end of 6th session whereas 33.3% (18) patients did not respond. Adverse effects noted were erythema, edema and pain at injection site.&#x0D; Conclusion: Intralesional injection of purified protein derivative is an effective and inexpensive treatment option for palmo-plantar verruca with good outcome.

In Vitro and In Vivo Antigen Presentation and Diagnosis Development of Recombinant Overlapping Peptides Corresponding to Mtb ESAT-6/CFP-10

Cellular immunity in Mycobacteria tuberculosis (Mtb) infection is important for the pathogenesis and final clearance of intracellular Mtb infection. In addition, it is valuable for the diagnosis of tuberculosis. In this pioneering work, we tested in vitro and in vivo antigen presentation and diagnostic application of a recombinant overlapping peptide-protein derived from two Mtb RD1 antigens ESAT-6 and CFP-10 (ROP-TB). The overlapping peptide sequence of ROP-TB is cleaved by the cathepsin S enzyme and covers the entire length of the two proteins. ROP-TB can be expressed and purified from E. coli. Once taken in by antigen-presenting cells, ROP-TB can be cleaved into a peptide pool by cathepsin S within the cells. We found that in dendritic cells, ROP-TB can be processed in 6 hours of co-culture, while the ESAT-6/CFP-10 fusion protein remained in the endosomal compartment. In Mtb-infected mice, ROP-TB stimulated stronger specific T cell responses than pooled synthetic peptides derived from ESAT-6 and CFP-10. With regard to the presentation of in vivo antigens, in a guinea pig model infected with Mtb, ROP-TB induced delayed type hypersensitivity (DTH) responses comparable to those of the tuberculin purified protein derivative (PPD) and ESAT-6/CFP-10 fusion protein. In Mycobacterium bovis (Bovine TB)-infected cattle, ROP-TB elicited DTH responses. Finally, in Mtb infected patients, ROP-TB stimulated cellular immune responses in majority of patients (16/18) of different HLA phenotypes while a single peptide derived from the same proteins did not elicit the immune responses in all patients. In summary, in vitro and in vivo data suggest that ROP-TB stimulates a strong cellular immune response irrespective of HLA phenotypes and is therefore suitable for use in vitro and in vivo diagnostics.

Freeze-Drying Improved the Stability of Tuberculin Purified Protein Derivative (PPD) in Mammals

Freeze-Drying Improved the Stability of Tuberculin Purified Protein Derivative (PPD) in Mammals

Combined intralesional injection of tuberculin purified protein derivative plus cryotherapy versus each alone in the treatment of multiple common warts.

Different modalities are used for treatment of common warts, but none of them had been proved the best in achieving complete cure. We aim to compare the effect of cryotherapy, intralesional injection of tuberculin purified protein derivative (PPD) and cryotherapy combined with intralesional injection of tuberculin PPD in the treatment of multiple common warts. This study is a randomized clinical trial in which the patients were randomly divided into three groups; group (A) included 25 patients subjected to cryotherapy, group (B) included 25 patients subjected to intralesional injection of tuberculin PPD and group (C) included 25 patients subjected to cryotherapy plus intralesional injection of tuberculin PPD. All the three groups showed a significant clinical improvement (p < 0.001) with statistically significant difference between cryotherapy group (A) and intralesional injection of tuberculin PPD group (B) (p < 0.001) and between cryotherapy group (A) and cryotherapy plus intralesional injection of tuberculin PPD group (C) (p < 0.001). However, there was no statistically significant difference between both intralesional injection of tuberculin PPD group alone (B) and cryotherapy plus intralesional injection of tuberculin PPD group (C) (p=0.213). In Conclusion the cryotherapy combined with intralesional injection of PPD and intralesional injection of PPD alone are better than cryotherapy alone in treatment of multiple common warts. However, better response could be reached in combination of both cryotherapy and intralesional PPD with less number of sessions.

Temporal trends and prediction of bovine tuberculosis: a time series analysis in the North-East of Iran.

Bovine tuberculosis (BTB) is a disease with high economic relevance. This study aimed to determine a fast alert surveillance system for bTB before the outbreak in the epidemic region of Iran. This cross-sectional study was conducted using the Auto-Regressive Integrated Moving Average (ARIMA) model for monthly bTB detections (reactors). These reactor cases result from the positive Tuberculin Purified Protein Derivative (PPD) test on cattle farms for the period between April 2007 and March 2019 in Razavi Khorasan province. Autocorrelation functions (ACF) and partial autocorrelation functions (PACF) plots were used to determine model parameters. The Akaike Information Criteria (AIC) were employed to select the best-fitted model. The root mean square error (RMSE) was applied for the evaluation of the models. Then, the best-fitted model was hired to predict the cases for 12 oncoming months. The data were analysed by STATA (ver. 14) software with a significant level at P≤0.05. ARIMA (3, 0, 3) 12 was introduced as a recommended fitted model according to white noise residual test (Q=22.87 and P=0.98), lower AIC (541.85), and more precise model RMSE (1.50). However, the forecast values were more than the observed values. The application and interpretation of ARIMA models are straightforward, and may be used as immediate tools for monitoring systems. However, we proposed an Auto-Regressive Integrated Moving Average with Exogenous Input (ARIMAX) model with some measurable exotic factors such as economic fluctuations, climate changes, and pulmonary tuberculosis to introduce a more precise and accurate model for the fast alert surveillance system.

Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol

IntroductionThe predictive utility for incident tuberculosis (TB) of the purified protein derivative tuberculin skin test and region of difference 1 (RD1)-based interferon-gamma release assays (IGRA) is comparable; and either is...

The diagnostic performance of novel skin-based in-vivo tests for tuberculosis infection compared with purified protein derivative tuberculin skin tests and blood-based in vitro interferon-γ release assays: a systematic review and meta-analysis

Novel skin-based tests for tuberculosis infection might present suitable alternatives to current tests; however, diagnostic performance of new tests compared with the purified protein derivative-tuberculin skin test (TST) or interferon-γ release assays (IGRA) needs systematic assessment. In this systematic review and meta-analysis, we searched English (Medline OVID), Chinese (Chinese Biomedical Literature Database and the China National Knowledge Infrastructure), and Russian (e-library) databases from the inception of each database to May 15, 2019, (with updated search of the Russian and English databases on Oct, 20 2020) using terms "ESAT6" OR "CFP10" AND "skin test" AND "Tuberculosis" OR "C-Tb" OR "Diaskintest". We included studies reporting on the performance of index tests alone or compared with a comparator. Inclusion criteria varied according to review objectives and performance outcome, but reporting of test cut-offs for positivity applied to study population was required from all studies. We used a hierarchy of reference standards for tuberculosis infection consistent with the 2020 WHO framework to evaluate diagnostic performance. Two authors independently reviewed the titles and abstracts for English and Chinese (LF and MK) and Russian studies (MK and VN). Study quality was assessed with QUADAS-2. Pooled random-effects estimates are presented when appropriate for total agreement proportion, sensitivity in microbiologically confirmed tuberculosis and specificity in cohorts with low risk of tuberculosis infection. This study is registered with PROSPERO, CRD42019135572. We identified 1466 original articles, of which 37 (2·5%) studies, including 10 915 individuals (7111 Diaskintest, 2744 C-Tb, 887 EC, 173 DPPD), were included in the qualitative analysis (29 [78%] studies of Diaskintest, five [15%] studies of C-Tb, two [5%] studies of EC-skintest, and one [3%] study of DPPD). 22 (1·5%) studies including 5810 individuals (3143 Diaskintest, 2129 C-Tb, 538 EC-skintest) were included in the quantitative analysis: 15 (68%) of Diaskintest, five (23%) of C-Tb, and two (9%) of EC-skintest. Tested sub-populations included individuals with HIV, children (0-18 years), and individuals exposed to tuberculosis. Studies were heterogeneous with moderate to high risk of bias. Nine head-to-head studies of index test versus TST and IGRA permitted direct comparisons and pooling. In a mixed cohort of people with and without tuberculosis, Diaskintest pooled agreement with IGRA was 87·16% (95% CI 79·47-92·24) and 55·45% (46·08-64·45) with TST-5 mm cut-off (TST5 mm). Diaskintest sensitivity was 91·18% (95% CI 81·72-95·98) compared with 88·24% (78·20-94·01) for TST5 mm, 89·66 (78·83-95·28) for IGRA QuantiFERON, and 90·91% (79·95-96·16) for TSPOT.TB. C-Tb agreement with IGRA in individuals with active tuberculosis was 79·80% (95% CI 76·10-83·07) compared with 78·92% (74·65-82·63) for TST5 mm/15 mm cut-off (TST5 mm/15 mm). TST5/15mm reflects threshold in cohorts that applied stratified cutoffs: 5 mm for HIV-infected, immunocompromised, or BCG-naive individuals, and 15mm for BCG-vaccinated immunocompetent individuals. C-Tb sensitivity was 74·52% (95% CI 70·39-78·25) compared with a sensitivity of 78·18% (67·75-85·94) for TST5 mm/15 mm, and 71·67% (63·44-78·68) for IGRA. Specificity was 97·85% (95% CI 93·96-99·25) for C-Tb versus 93·31% (90·22-95·48) for TST 15 mm cut-off and 99·15% (79·66-99·97) for IGRA. EC-skintest sensitivity was 86·06% (95% CI 82·39-89·07). Novel skin-based tests for tuberculosis infection appear to perform similarly to IGRA or TST; however, study quality varied. Evaluation of test performance, patient-important outcomes, and diagnostic use in current clinical algorithms will inform implementation in key populations. StopTB (New Diagnostics Working Group) and FIND. For the Chinese and Russian translations of the abstract see Supplementary Materials section.