Evaluation of effectiveness of mass screening for tuberculosis infection in children from 1 to 7 years old in Moscow

The objective: to evaluate effectiveness of mass screening for tuberculosis infection in children aged 1 to 7 years in different periods – before and after the use of tuberculosis recombinant allergen skin test (TRA) in primary health care as an additional diagnostic method.Subjects and Methods. The study was designed as continuous observational prospective-retrospective study. Two different periods were assessed: the first one was 2014-2016 when screening for tuberculosis infection was performed in all children from 1 to 17 years (inclusive) using Mantoux test with 2 TU PPD-L in pediatric primary health care, and then children suspected to have a positive reaction were referred to TB dispensary where they were examined with a skin test with TRA if necessary. The second period was from 2018 to 2020 when children of 1-7 years old were given Mantoux test and if tuberculosis infection was suspected, a skin test with TRA was done both in primary health care network and TB units. In the first 3 years, 1,864,137 children were examined and in the second 3 years, 2,078,800 children from 1 to 7 years old were examined.Results. Among children of 1-7 years old who were screened by two stages (initial Mantoux test, and then in those who had a positive reaction, the TRA test was used), only 10-12% of those referred to a phthisiologist were subject to dispensary follow-up. Thus, with the implementation of the new edict on screening for tuberculosis infection in children with two tests, this proportion has not changed compared to previous years, when screening was carried out only with one Mantoux test. The reason why almost 90% of the children who were referred to TB Dispensary were not subject to dispensary follow-up is the following: children who have had previous conversion of tuberculin tests, along with everyone else are again screened with Mantoux test despite being previously followed up by TB dispensary due to the primary infection.Recommendations:Currently, there is no division of Group VI into Subgroups A, B, C in the dispensary follow up grouping. Why should conversion of Mantoux test reaction from negative into positive not be considered an infection, and the increase in the reaction must be at least 6 mm.Since Order No. 124n of the Russian Ministry of Health allows testing with TRA in the primary health care in case of suspected infection, it is advisable to refer those who have already had this test to a phthisiologist.A child with conversion of Mantoux test should not be re-screened with Mantoux test but the TRA test should be used. If a positive reaction to the TRA test occurs for the first time, it should be considered as conversion of this test, and in this case the child should be examined by computed tomography (CT), and preventive therapy should be prescribed. If in subsequent years the TRA reaction increases by at least 6 mm after previous preventive therapy, the child should be re-referred for CT to rule out the development of active tuberculosis.

Clinical and Laboratory Profile of Patients With Anaphylaxis to Fire Ant Venom (Solenopsis Sp) Under Specific Subcutaneous Immunotherapy.

Anaphylaxis to fire ant venoms (Solenopsis sp) is a significant cause of systemic allergic reaction caused by Hymenoptera stings in children. There are only a few reports about the safety and efficacy of specific immunotherapy. We aim evaluate clinical characteristics, IgE and IgG4 specific responses of patients undergoing immunotherapy with a whole-body extract of Solenopsis sp after one year of the maintenance phase. Thirty-three patients were enrolled due to anaphylaxis by fire ant venom (Solenopsis sp) and underwent specific venom immunotherapy. They were assessed at baseline and one year after the beginning of the maintenance phase for skin test; specific IgE and IgG4 antibodies to fire ant venom; tryptase. All patients included presented a severe anaphylactic reaction. Although two patients (6.25%) presented a tryptase level higher than 11.4 ug/ml, systemic mastocytosis was ruled out. There was no relationship between the severity of the reaction with gender, tryptase level, atopy, previous reactions, concentration of the allergen in the skin test or specific IgE level. There was an increase of the specific IgG4/IgE ratio between the two time points. Reactions were local, with only two mild systemic reactions during the build-up phase. Twenty patients had accidental stings during immunotherapy, with 3 presenting only urticaria. This study is unprecedented in evaluating clinical and laboratory data in the fire ant immunotherapy. Our results show that after one year of the maintenance phase, patients did not develop any severe reaction with only a few mild reactions and presented a significant production of specific IgG4.

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 recommended to test for latent TB infection (LTBI). Despite associated high costs of IGRA, sites participating in LTBI screening in many high-income settings pragmatically favour IGRA due to its higher specificity and simpler logistics. A new RD1-based skin test, C-Tb, could offer an acceptable and as accurate, cheaper alternative to IGRA. Evaluating the impact of C-Tb on process and patient-related outcomes would provide important information to help guide its use in LTBI testing strategies.Methods and analysisThis is a pragmatic multicentre, open-label, non-inferiority, randomised controlled trial. The trial will assess the initiation of LTBI treatment following a positive result of the randomised test as the primary outcome. Participants will be randomised to receive the C-Tb test (intervention) or IGRA (usual care, control) for initiation of treatment. We will enrol 1530 participants in England aged≥16 years who are eligible for LTBI testing and treatment according to UK guidance. In the C-Tb arm, skin induration will be assessed 2–3 days after intradermal injection and measured in millimetres of induration. Results of IGRA will be obtained in line with standard practice. Behavioural studies will explore people’s experiences, perspectives and preferences of LTBI testing and treatment. Economic analysis will estimate cost-effectiveness of changes to the diagnostic algorithm for LTBI. The protocol was developed with Patient and Public Involvement (PPI), which will continue throughout the trial.Ethics and disseminationEthics approval has been obtained from The NHS Health Research Authority (269485). We will share results of the trial in peer-reviewed journals and conferences.Trial registration numberEudraCT 2019-002592-34; ISRCTN17936038.

Comparative Assessment of Platinum Salts and Taxane Group Hypersensitivity Reactions, The Role of Skin Tests in Diagnosis?

Purpose We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management. Materials and Method Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1–2 with the suspect drug. Results In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1–2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR ( p = 0.007, p = 0.001). A significant correlation was found between skin test positivity and early onset of symptoms ( p = 0.001 for PS, p = 0.015 for TX). In terms of symptoms witnessed in HSR, we observed the itching, urticaria, hypotension, syncope, and abdominal pain symptoms significantly more in the group with a positive skin test ( p < 0.024, p < 0.001, p < 0.001, p < 0.002, and p < 0.025, respectively). Conclusions We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.