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1.
Sci Rep ; 14(1): 5155, 2024 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431678

RESUMO

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.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Tuberculose , Animais , Feminino , Bovinos , Tuberculose Bovina/diagnóstico , Tuberculina , Teste Tuberculínico/veterinária
2.
mBio ; 15(3): e0340823, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38376260

RESUMO

Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores. In pneumonia patients, serum activin A levels were also raised, but in sarcoidosis patients, levels were lower. To determine whether blockade of the activin A signaling axis could play a functional role in TB, we harnessed a soluble activin type IIB receptor fused to human IgG1 Fc, ActRIIB-Fc, as a ligand trap in a murine TB model. The administration of ActRIIB-Fc to Mycobacterium tuberculosis-infected mice resulted in decreased bacterial loads and increased numbers of CD4 effector T cells and tissue-resident memory T cells in the lung. Increased frequencies of tissue-resident memory T cells corresponded with downregulated T-bet expression in lung CD4 and CD8 T cells. Altogether, the results suggest a disease-exacerbating role of ActRIIB signaling pathways. Serum activin A may be useful as a biomarker for diagnostic triage of active TB or monitoring of anti-tuberculosis therapy. IMPORTANCE: Tuberculosis remains the leading cause of death by a bacterial pathogen. The etiologic agent of tuberculosis, Mycobacterium tuberculosis, can remain dormant in the infected host for years before causing disease. Significant effort has been made to identify biomarkers that can discriminate between latently infected and actively diseased individuals. We found that serum levels of the cytokine activin A were associated with increased lung pathology and could discriminate between active tuberculosis and tuberculin skin-test-positive healthy controls. Activin A signals through the ActRIIB receptor, which can be blocked by administration of the ligand trap ActRIIB-Fc, a soluble activin type IIB receptor fused to human IgG1 Fc. In a murine model of tuberculosis, we found that ActRIIB-Fc treatment reduced mycobacterial loads. Strikingly, ActRIIB-Fc treatment significantly increased the number of tissue-resident memory T cells. These results suggest a role for ActRIIB signaling pathways in host responses to Mycobacterium tuberculosis and activin A as a biomarker of ongoing disease.


Assuntos
Mycobacterium tuberculosis , Pneumonia , Sarcoidose , Tuberculose , Humanos , Camundongos , Animais , Ligantes , Tuberculina , Ativinas , Imunoglobulina G , Biomarcadores
3.
BMC Vet Res ; 20(1): 65, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395846

RESUMO

BACKGROUND: Bovine tuberculosis (bTB) is a chronic disease that results from infection with any member of the Mycobacterium tuberculosis complex. Infected animals are typically diagnosed with tuberculin-based intradermal skin tests according to World Organization of Animal Health which are presently in use. However, tuberculin is not suitable for use in BCG-vaccinated animals due to a high rate of false-positive reactions. Peptide-based defined skin test (DST) antigens have been identified using antigens (ESAT-6, CFP-10 and Rv3615c) which are absent from BCG, but their performance in buffaloes remains unknown. To assess the comparative performance of DST with the tuberculin-based single intradermal test (SIT) and the single intradermal comparative cervical test (SICCT), we screened 543 female buffaloes from 49 organized dairy farms in two districts of Haryana state in India. RESULTS: We found that 37 (7%), 4 (1%) and 18 (3%) buffaloes were reactors with the SIT, SICCT and DST tests, respectively. Of the 37 SIT reactors, four were positive with SICCT and 12 were positive with the DST. The results show that none of the animals tested positive with all three tests, and 6 DST positive animals were SIT negative. Together, a total of 43 animals were reactors with SIT, DST, or both, and the two assays showed moderate agreement (Cohen's Kappa 0.41; 95% Confidence Interval (CI): 0.23, 0.59). In contrast, only slight agreement (Cohen's Kappa 0.18; 95% CI: 0.02, 0.34) was observed between SIT and SICCT. Using a Bayesian latent class model, we estimated test specificities of 96.5% (95% CI, 92-99%), 99.7% (95% CI: 98-100%) and 99.0% (95% CI: 97-100%) for SIT, SICCT and DST, respectively, but considerably lower sensitivities of 58% (95% CI: 35-87%), 9% (95% CI: 3-21%), and 34% (95% CI: 18-55%) albeit with broad and overlapping credible intervals. CONCLUSION: Taken together, our investigation suggests that DST has a test specificity comparable with SICCT, and sensitivity intermediate between SIT and SICCT for the identification of buffaloes suspected of tuberculosis. Our study highlights an urgent need for future well-powered trials with detailed necropsy, with immunological and microbiological profiling of reactor and non-reactor animals to better define the underlying factors for the large observed discrepancies in assay performance, particularly between SIT and SICCT.


Assuntos
Bison , Doenças dos Bovinos , Mycobacterium bovis , Tuberculose Bovina , Feminino , Animais , Bovinos , Tuberculose Bovina/diagnóstico , Búfalos , Tuberculina , Teorema de Bayes , Vacina BCG , Teste Tuberculínico/veterinária , Sensibilidade e Especificidade
4.
Prev Vet Med ; 224: 106129, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325115

RESUMO

In Ireland, the interferon-gamma (IFN-γ) assay is routinely used as an ancillary test interpreted in parallel with the single intradermal comparative tuberculin test (SICTT) to maximize the detection of bovine tuberculosis (bTB) infected animals. Up until 2018, a positive test result was recorded in the IFN-γ ELISA assay following whole blood stimulation with purified protein derivative (PPD)-bovine (B), PPD-avian (A) and nil sample (N), using the interpretation criteria, B-N > 50 optical density units (OD), B > 100 and B-A > 0. Following a review of available data, the threshold of the B-A component changed to B-A > 80. As predicting the impact of changing the cut-off thresholds for the IFN-γ test de novo is challenging, the aims of this study were to follow animals that initially tested negative using the new IFN-γ assay interpretation criteria and investigate their future risk of disclosure with bTB, with a focus on animals that otherwise would have been removed when using the older interpretation criteria (0 < B-A ≤ 80). Enrolled animals (n = 28,669 cattle from 527 herds) were followed up for two years (2019-2021), or to point of bTB detection or death. At the end of follow-up, 1151 (4.0%) of enrolled animals were bTB cases. The majority of these cases were diagnosed using SICTT (80.5%). The cumulative number of positive animals that would have been removed if the old cut-off (0 < B-A ≤ 80) was used amounted to 1680 cattle (5.9% of the enrolled cohort). Of these, 127 (7.5%) were diagnosed with bTB during follow-up. In contrast, 1024 of the 1151 cattle which subsequently tested positive during the study period following a negative IFN-γ test would not have been identified with the old or new IFN-γ cut-off criteria. Survival analysis showed that animals that would have been removed under the old interpretation criteria were at increased risk of a positive diagnosis with bTB during follow-up compared to other test negative animals. A newly developed risk prediction model (using a Cox proportional hazard model) showed that age, animal number of SICTT tests, number of inconclusive SICTT tests, B-A (IFN-γ assay), B-N (IFN-γ assay), animals from store herds and the percentage of the rest of the herd that were positive during the breakdown were statistically significantly associated with bTB detection. However, inclusion of the IFN-γ OD variables did not show added value in terms of prediction performance of the model.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Animais , Bovinos , Interferon gama , Irlanda/epidemiologia , Mycobacterium bovis/fisiologia , Tuberculina , Teste Tuberculínico/veterinária , Tuberculose Bovina/diagnóstico , Tuberculose Bovina/epidemiologia
5.
Res Vet Sci ; 168: 105159, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266351

RESUMO

Bovine tuberculosis (bTB) constitutes a global challenge for public and animal health with still some deficiencies regarding its diagnosis. This study aimed to estimate the accuracy of the single intradermal tuberculin test (SIT) and post-mortem inspection for different diagnostic objectives following WOAH guidelines. Tissue samples from 59 microbiological culture/PCR-positive and 58 microbiological culture/PCR-negative cattle were evaluated. The diagnostic sensitivity and specificity, the positive and negative probability indices as well as the positive and negative predictive values (PPV and NPV) of each technique were estimated for different pretest probabilities. The SIT with strict interpretation demonstrated moderate precision in confirming the absence of infection in populations historically free of bTB, with a 12.1% rate of false positives, but also detecting positive animals in the early stage of the eradication programs, with a 13.6% rate of false negatives. The diagnostic performance for ruling out bTB was notably high (NPV > 90%) in animals with a pre-test probability (PTP) below 42%. Post-mortem inspection constituted an interesting alternative tool to confirm suspected and positive cases for SIT, particularly in areas with bTB prevalence exceeding 19%, where implementing SIT and eradication measures may be impractical. In these areas, the likelihood that animals with tuberculosis-like lesions are affected by the disease surpasses 90%. Similarly, in herds with a PTP below 25%, the absence of bTB could be confidently ruled out with over 90% certainty. These findings highlight the effectiveness of SIT and post-mortem inspection as valuable techniques for current eradication programs and controlling bTB in high-prevalence areas where molecular techniques may not be feasible.


Assuntos
Doenças dos Bovinos , Mycobacterium bovis , Tuberculose Bovina , Bovinos , Animais , Tuberculose Bovina/epidemiologia , Teste Tuberculínico/veterinária , Teste Tuberculínico/métodos , Tuberculina , Testes Intradérmicos/veterinária , Fatores de Risco
6.
Eur J Clin Microbiol Infect Dis ; 43(3): 611-616, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38167987

RESUMO

Impaired T-cell responses to mitogens and high T-cell activation marker (TAM) expression on Mycobacterium tuberculosis-specific T-cells characterize immunopathology in patients with tuberculosis (TB). In a study of patients with TB (n = 60) and asymptomatic contacts (controls, n = 37), we found that TB patients had higher CD38+ T-cell proportions specific for M. tuberculosis protein (PPDMtb), yet total proportions of PPDMtb-specific T-cells were comparable. Notably, both activated (CD38+) and total IFN-γ+ T-cells from TB patients had lower mitogen (phytohemagglutinin, PHA)-induced responses. This impaired mitogen response improved the classification efficacy of the TAM-TB assay, especially employing the PPD/PHA-induced T-cell ratio.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mitógenos/farmacologia , Tuberculina , Linfócitos T , Antígenos de Bactérias
7.
Vet Microbiol ; 290: 110009, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280303

RESUMO

Mycobacterium microti is a member of the Mycobacterium tuberculosis complex that seldom causes disease in livestock and humans. This study evaluated the effects on immunodiagnosis and the pathological findings in goats after experimental exposure by different routes and doses to M. microti. In a first experiment goats were challenged orally (PO, n = 7) or intranasally (IN, n = 7) with 104 CFU. In a second experiment, the endobronchial route was assessed, with a low dose of 102 CFU (EB-LD, n = 7) and a high dose of 105 CFU (EB-HD, n = 7) as well as the subcutaneous route (SC, n = 5). Temperature, body weight, clinical signs and immunological responses were monitored. Pathological evaluation was carried out and samples were processed for mycobacterial detection. RESULTS: demonstrated the induction of a subclinical pulmonary infection in all the EB-HD challenged animals. Infection was also confirmed in one animal of the SC group, but not in the EB-LD, PO or IN groups. Two animals belonging to the EB-HD and SC groups, respectively, showed positive results to the single intradermal tuberculin test, and another two animals of the EB-HD and EB-LD groups showed doubtful (inconclusive) results, indicating that M. microti can induce mild responses to tuberculin skin testing. No positive results were observed when defined antigens absent in M. microti (ESAT-6 and CPF-10) were used. Our results indicate that animals exposed to M. microti can yield positive results to the skin tests currently performed in livestock tuberculosis eradication campaigns and reinforce the need to use specific antigens in antemortem tests to avoid interference with M. bovis/M. caprae diagnosis.


Assuntos
Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Animais , Teste Tuberculínico/veterinária , Tuberculina , Cabras , Tuberculose Pulmonar/veterinária
8.
Sci Rep ; 14(1): 288, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167543

RESUMO

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.


Assuntos
Vacina contra Sarampo-Caxumba-Rubéola , Molusco Contagioso , Tuberculina , Humanos , Injeções Intralesionais , Vacina contra Sarampo-Caxumba-Rubéola/uso terapêutico , Molusco Contagioso/tratamento farmacológico , Resultado do Tratamento
9.
Am J Otolaryngol ; 45(1): 104030, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37659223

RESUMO

BACKGROUND: Nontuberculous mycobacterial cervicofacial lymphadenitis (NTMCL) is an uncommon condition detected in young immunocompetent children who typically present with a nontender neck mass. Various tests have been proposed to assist in the work-up of suspected NTMCL, with varying diagnostic utility. This systematic review investigates the sensitivity of the various diagnostic methods used in the work-up of pediatric NTMCL. METHODS: A systematic review in accordance with PRISMA guidelines was performed using the Pubmed, EMBASE, and Web of Science databases. Searches were filtered for English language studies published prior to 05/10/22. Studies meeting criteria included studies featuring 15+ pediatric patients with confirmed or suspected NTMCL. Studies with any reported diagnostic methodology used in the workup of NTMCL were included. RESULTS: Of 836 abstracts/articles reviewed, 21 studies met inclusion criteria. Diagnostic methods included culture(n = 11 studies), PPD-Tb(Tuberculin)(n = 12), PPD-Scrofulaceum, -Avium, or -Kansasii(n = 6), staining techniques(n = 4), IGRA(n = 3), and ultrasound(n = 2). All studies had an overall low risk of bias. Among patients confirmed to have NTMCL based on PCR and/or culture, the most sensitive tests were PPD-A(0.94, 95 % CI 0.91 to 0.97; n = 210 patients) and PPD-S(0.75, 95 % CI 0.68 to 0.81; n = 171). Auramine and Ziehl-Neelsen staining techniques had moderately high sensitivity(0.85 and 0.60 respectively), though were limited by low patient numbers(n = 20). PPD-Tb(0.45, 95 % CI 0.39 to 0.50; n = 300) and IGRA(0.02; 95 % CI 0 to 0.06; n = 48) demonstrated poor sensitivity. Among patients suspected to have NTM lymphadenitis based on global assessment, the most sensitive tests included combined PPD-S + A + K(0.92, 95 % CI 0.86 to 0.98; n = 85), PCR(0.82, 95 % CI 0.75 to 0.88; n = 136), and PPD-A(0.72, 95 % CI 0.62 to 0.81; n = 84). Culture showed a sensitivity of 0.54(95 % CI 0.50 to 0.58; n = 494). PPD-K, PPD-S, IGRA, and staining techniques demonstrated lower sensitivity. CONCLUSIONS: This systematic review is the largest study investigating the sensitivity of the various diagnostic methods used in the work-up of pediatric NTMCL. Patients with clinical suspicion for NTMCL and a positive PPD-Tb should first have tuberculous lymphadenitis ruled out with IGRA. Patients with a positive PPD-Tb and negative IGRA and high clinical suspicion for NTMCL can undergo presumptive surgical intervention. Patients with a negative PPD-Tb can undergo NTM antigen skin testing if available, or if high clinical suspicion exists, surgical intervention to reduce tissue burden and elicit additional tissue data.


Assuntos
Linfadenite , Infecções por Mycobacterium não Tuberculosas , Tuberculose dos Linfonodos , Criança , Humanos , Tuberculina , Linfadenite/diagnóstico , Tuberculose dos Linfonodos/diagnóstico , Testes Cutâneos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/cirurgia
10.
Clin Imaging ; 105: 110024, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37989019

RESUMO

BACKGROUND: Chest radiographs (CXR) for tuberculosis (TB) screening in children are valuable in high-burden settings. However, less certain in low prevalence contexts. In the United States, positive PPD is sufficient to treat for "latent" TB, or TB infection in asymptomatic patients. OBJECTIVE: We sought to determine frequency of abnormal CXR findings after a positive purified protein derivative (PPD) test at a tertiary pediatric center in the United States. METHOD: A retrospective evaluation was conducted of patients (0-18 years) with a CXR after a positive PPD (e.g., known exposure, employment, migratory requirements or before immunosuppression) between 2011 and 2021. Clinical information, demographics, and reason for PPD were recorded from health record. CXRs were evaluated using initial report and by a pediatric radiologist with special interest in TB and 8 years of experience. RESULT: Of 485 patients, median [interquartile range (IQR)] age 8.5[3.3-14.4], abnormal CXRs were described in 5 (1%). Most common reasons for PPD included: close contact with someone with TB or with high risk for TB. Most patients 373 (76.9%) received treatment for latent TB, and 111 (22.9%) no treatment. One patient (0.2%) received treatment for active disease. Radiographic findings included isolated lymphadenopathy (n = 2), consolidation (n = 1), pleural fluid/thickening (n = 1) and a patient with lymphadenopathy and a calcified nodule (n = 1). CONCLUSION: In our experience, prevalence of chest radiographs findings for patients with positive PPD was very low. Moreover, no cases of severe disease were seen and those with abnormal findings would not merit treatment change under current WHO guidelines.


Assuntos
Linfadenopatia , Tuberculose Pulmonar , Tuberculose , Criança , Humanos , Adolescente , Estados Unidos/epidemiologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/epidemiologia , Tuberculina , Teste Tuberculínico , Estudos Retrospectivos , Tuberculose/diagnóstico por imagem , Tuberculose/epidemiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-38082919

RESUMO

Bovine tuberculosis (bTB), a chronic disease of cattle, is caused by the Mycobacterium bovis infection. Despite having a serious social and economic impact in the United Kingdom and Ireland, there is no antemortem gold standard diagnostic test. Tuberculin skin tests (CICT) are commonly used as a control measure with the interferon gamma (IFN-γ) assay being applied in certain circumstances. This paper utilizes data gathered describing tuberculin regression in reactors (test positive cattle) following the CICT at 72 ± 4 h post injection in herds with large bTB outbreaks. The work then applies machine learning techniques (Decision Trees, Bagging Trees and Random Forests, alongside several balancing approaches) to predict which cattle were likely to be truly infected with tuberculosis, enabling identification of atypical breakdowns that require extra investigation and providing a mechanism for quality assurance of the existing CICT bTB surveillance scheme. The analysis showed that Random Forests (RF) trained using SMOTE balancing had the joint best performance and accuracy (0.90). The importance of the two components of the interferon gamma assay within the RF model also indicated that varying the assay threshold for large outbreaks would be beneficial. Furthermore, the combined use of the RF and IFN- γ models could lead to the improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. An additional use of these models would be for quality assuring the current bTB surveillance based on CICT and post mortem inspection. Quality control is well recognized as an essential component of a disease surveillance/eradication programme.Clinical Relevance- Bovine tuberculosis remains a disease that is hard to control on a national level. The use of the machine learning model could lead to significant improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. Advanced modelling, such as this, has the potential to strengthen the efficacy of disease surveillance and the eradication strategy and can meaningfully contribute to animal disease national control plans.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Animais , Bovinos , Tuberculose Bovina/diagnóstico , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/microbiologia , Interferon gama , Tuberculina , Surtos de Doenças/prevenção & controle , Surtos de Doenças/veterinária
12.
Int J Mol Sci ; 24(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38068935

RESUMO

While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette-Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Animais , Cobaias , Proteínas Recombinantes de Fusão/genética , Tuberculina , Linfócitos T CD8-Positivos , Tuberculose/diagnóstico , Eritema , Antígenos de Bactérias
13.
BMC Infect Dis ; 23(1): 869, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38082230

RESUMO

BACKGROUND: Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. METHODS: The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov - Smirnov test and other statistical methods were used for statistical analysis, [Formula: see text] was obtained using the formula [Formula: see text] nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. RESULTS: Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P < 0.001) between these two types of educational institutions. Meanwhile, as for the age-wise distribution of latent infection among 17-20 years old freshmen, the LTBI rate exhibited 10.5%, 11.6%, 12.1% and 13.5%, respectively. Correlation between LTBI rate, the strong positive rate was statistically significant among different ages (χ2 = 34.559, P < 0.001). Over a follow-up period of 2 years, three students were diagnosed with active tuberculosis, one of which was resistant to rifampicin. All three students manifested a strong positive for PPD and declined preventive treatment during TB screening. CONCLUSIONS: The data indicates a high rate of LTBI amongst students in areas with a heavy TB burden, potentially leading to cross-regional TB transmission due to the migration of students. Education level might contribute to the limited uptake of TPT. Therefore, improving the implementation of TB preventive treatments is crucial in controlling and preventing TB across schools.


Assuntos
Tuberculose Latente , Tuberculose , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pequim/epidemiologia , Estudos Prospectivos , Tuberculina , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/prevenção & controle , China/epidemiologia
14.
Int J Mycobacteriol ; 12(4): 436-442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149540

RESUMO

Background: Tuberculosis (TB) remains a high burden disease in India. Nutrition plays a pivotal role in holistic recovery of the same. Methods: Patients with sputum positive pulmonary TB were consecutively recruited into the study aimed to observe the incidence of under nutrition and anergy purified protein derivative (PPD). Anthropometry and PPD testing were done at baseline. Patients were followed-up at 6 months, with PPD intradermal test repeated to study tuberculin conversion. Nutritional recovery, tuberculin conversion, and determination of persistent anergy were the outcomes of interest. Results: Of the 134 patients enrolled in the study, 43.2% were anergic to PPD at baseline. While 50.8% patients had normal body mass index (BMI), 14.2%, 9.7%, and 25.4% had chronic energy deficiency (CED) Grades I, II, and III, respectively. BMI at baseline showed a positive linear correlation with PPD response (r = 0.44, P < 0.001), and anergy was associated with CED (odds ratio - 3.25, P = 0.001). Forty-six patients completed follow-up and 19.6% showed anergy to PPD. At follow-up, 69.6% had normal BMI. Overall, there was an improvement in anthropometry and PPD reactivity in patients at 6 months, compared to baseline assessment. Conclusion: Anergy was significantly associated with CED at baseline in patients with TB. While most patients had an improvement in nutritional status and PPD reactivity, a small subset of patients had persistent anergy. Recovery from TB is multifactorial and its determinants include microbiological cure, nutritional status, and immunological recovery.


Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Tuberculina , Escarro , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/complicações , Tuberculose/epidemiologia , Teste Tuberculínico
15.
Proc Natl Acad Sci U S A ; 120(47): e2221186120, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37963250

RESUMO

Traditional understanding of the risk of progression from Mycobacterium tuberculosis (Mtb) infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a deterministic model of Mtb infection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB, informed by a rigorous evaluation of data from a systematic review of TB natural history. Using a Bayesian approach, we calibrated the model to data from historical cohorts that followed tuberculin-negative individuals to tuberculin conversion and TB, as well as data from cohorts that followed progression and regression between disease states, disease state prevalence ratios, disease duration, and mortality. We estimated incidence, pathways, and 10-y outcomes following Mtb infection for a simulated cohort. Then, 92.0% (95% uncertainty interval, UI, 91.4 to 92.5) of individuals self-cleared within 10 y of infection, while 7.9% (95% UI 7.4 to 8.5) progressed to TB. Of those, 68.6% (95% UI 65.4 to 72.0) developed infectious disease, and 33.2% (95% UI 29.9 to 36.4) progressed to clinical disease. While 98% of progression to minimal disease occurred within 2 y of infection, only 71% and 44% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model and 49.5% (95% UI 45.6 to 53.7) of those who developed infectious disease undulated between disease states. We identified heterogeneous pathways across disease states after Mtb infection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB.


Assuntos
Doenças Transmissíveis , Mycobacterium tuberculosis , Tuberculose , Humanos , Teorema de Bayes , Tuberculina , Tuberculose/microbiologia
16.
Ther Adv Respir Dis ; 17: 17534666231213638, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37993998

RESUMO

BACKGROUND: The tuberculin-purified protein derivative (PPD) test is commonly used as a screening tool for tuberculosis (TB). However, the traditional judgment standard of the PPD test is influenced by subjective factors, which can lead to less accurate and intuitive test results. OBJECTIVES: To evaluate the accuracy of ultrasonography as a novel auxiliary judgment method for the tuberculin-PPD test and its clinical application. DESIGN: This study was designed as a comparative study following the STROBE guidance. METHODS: From February to May 2022, 208 patients with active tuberculosis infection were enrolled. Manual judgment and ultrasonography were employed in a double-blind-utilized manner, and the PPD examination results were recorded. Kappa statistic was performed to measure the concordance between the two diagnostic methods. Fisher's exact test was used for the analyses of the PPD test results of all 208 active tuberculosis infection patients' PPD results. RESULTS: There was a significant difference between the two methods in the PPD result judgment (p < 0.001), particularly in the positive ratio of the PPD test results, (p < 0.05). Overall, 50 patients were determined as PPD positive based on manual judgment. However, only 24 patients' PPD test results were determined as positive via ultrasonography. The remaining 26 patients should have been classified as strong positive but were misclassified as positive. The misdiagnosis ratio was 52% (26/50). CONCLUSION: Ultrasonography has superior accuracy to traditional manual judgment. Moreover, it does not rely on sophisticated clinical experience or training and can reveal subtle changes of the skin corresponding to each PPD test result providing intuitive results. In conclusion, ultrasonography can be used as an auxiliary interpretive approach for PPD test and has a promising future for clinical application.


Assuntos
Tuberculina , Tuberculose , Humanos , Tuberculose/diagnóstico por imagem , Teste Tuberculínico , Ultrassonografia
17.
Arch Razi Inst ; 78(3): 815-821, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-38028850

RESUMO

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). The laboratory diagnosis of the disease includes various bacteriologic and immunologic methods. Despite the effectiveness of many of these methods in diagnosing active TB, their high cost and time-consuming nature have led researchers to adopt more accurate and rapid screening methods based on specific antigens for M. tuberculosis. The present study aimed to measure specific antibody serum levels against the early secretory antigenic target 6 kDa (ESAT-6) recombinant protein in healthy people and compare it to TB patients. The target population included 27 TB patients and 87 healthy individuals with no clinical TB symptoms. The healthy population was divided into two groups, including positive purified protein derivative (PPD) and negative PPD (35 and 52 people, respectively), using the Tuberculin skin test. The specific antibody level against the ESAT-6 recombinant antigen and the PPD protein was measured using an indirect Enzyme-Linked Immunosorbent Assay (ELISA) test. The results of the study showed that the majority of the healthy population with no symptoms of clinical TB and having negative skin test results did not have antibodies against the recombinant ESAT-6 (98%) and PPD (96%) antigens. On the other hand, there was a high level of the specific antibody of the ESAT-6 recombinant and PPD antigens in TB patients (77%). It is notable that in people with positive skin test results, the level of the antibody against the ESAT-6 recombinant antigen and PPD antigen was 94%. The results demonstrated that the ELISA method based on the measurement of antibodies against the ESAT-6 recombinant antigen can be a proper diagnostic method for rapid and accurate screening of healthy from infected people.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Proteínas de Bactérias , Tuberculina , Voluntários Saudáveis , Tuberculose/diagnóstico , Teste Tuberculínico
18.
Vet Rec ; 193(8): 311, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37861135
19.
Front Immunol ; 14: 1199092, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795082

RESUMO

Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by Mycobacterium bovis. Besides, the incidence of TB in humans due to M. bovis, and that in bovines (bovine TB, bTB) due to M. tuberculosis- indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bTB prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Mycobacterium tuberculosis Complex specific PCR positivity amongst the crossbred cattle. Further, ex vivo mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of M. bovis BCG, and M. tuberculosis H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), tank binding kinase-1 (TBK-1), and nitric oxide (NO) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1ß transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to bTB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.


Assuntos
Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculose Bovina , Tuberculose , Humanos , Animais , Bovinos , Leucócitos Mononucleares , Tuberculose/genética , Tuberculose/veterinária , Tuberculose/diagnóstico , Tuberculose Bovina/prevenção & controle , Tuberculina , Imunidade Inata
20.
PLoS One ; 18(10): e0292387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37796796

RESUMO

INTRODUCTION: The study aimed to evaluate the effectiveness of screening pediatric household contacts (under the age of 15 years) for tuberculosis (TB) in India through verbal screening, tuberculin skin testing, and chest radiography at intervals of 0, 3, 6, 9, and 12 months. The study also aimed to determine the proportion of contacts who tested positive for TB and to describe the challenges in implementing regular follow-up. Current National TB Elimination Programme (NTEP) guidelines only require verbal screening for contacts under 6 years old at TB treatment initiation. The study aimed to fill this knowledge gap and provide valuable insights for improving TB screening in pediatric household contacts in India. METHODS: The study was conducted in two districts of Karnataka, India from 2021 to 2022, and utilized a cohort study design to enroll contacts of index tuberculosis (TB) cases diagnosed under the National TB Elimination Programme (NTEP). Participants were followed up at regular intervals for one year to evaluate the effectiveness of TB screening in pediatric household contacts. RESULTS: In this study, 686 pediatric household contacts were enrolled and screened for tuberculosis (TB) using verbal symptom screening, tuberculin skin testing (TST), and chest radiography. Projected figures estimated that 0.8%, 42%, and 4% of contacts would test positive for symptomatic screening, TST, and chest radiography, respectively. TB cases were detected in 2.91% (1.84-4.38) of contacts, with females above 6 years of age having a 22% higher risk of contracting the infection than males above 6 to < 15 years. However, not all cases were subjected to TST and chest radiography. The primary reason for not investigating child contact for TB was their reported healthy or asymptomatic status. CONCLUSION: The implementation of regular screening intervals for tuberculin skin test (TST) and chest radiography, along with verbal screening, among pediatric household contacts under the age of 15 years seems to be beneficial for the National TB Elimination Programme (NTEP), despite the challenges faced during implementation. Innovative strategies should be explored by NTEP to ensure effective implementation.


Assuntos
Tuberculina , Tuberculose , Masculino , Feminino , Humanos , Criança , Adolescente , Estudos de Coortes , Características da Família , Índia/epidemiologia , Busca de Comunicante , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Teste Tuberculínico
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