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3.
Int J Dermatol ; 58(12): 1477-1482, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31591706

RESUMO

BACKGROUND: Despite the numerous studies on the use of purified protein derivative (PPD), a protein extracted from Mycobacterium tuberculosis, in verruca vulgaris, there is no standardized regimen, and efficacy of single versus multiple injections has not been compared. METHODS: This is a randomized, open-label, superiority trial. Sixty-six patients with at least three warts in two different anatomic sites were randomized into two groups: a single injection (n = 29) and multiple injection (n = 29) groups. Patients were treated every 2 weeks until a maximum of six sessions. RESULTS: Multiple injections (79.3%) showed superior clearance rates compared to a single injection of PPD (58.6%) (P-value = 0.0236). Multiple injections also exhibited faster clearance at each time point (P = 0.048). Pain was statistically more significant in the multiple injection group (P = 0.0005). There was no statistically significant difference in incidence of adverse events (P = 0.1795). Amongst all cleared patients in both groups, there were no recurrences after 6 months. CONCLUSION: Multiple injections of warts with PPD cleared more patients with multiple common warts than the use of single injections at the end of 12 weeks and were faster in clearing patients at every time point. Single injection was better tolerated than multiple injections. Both treatments exhibited similar safety profiles and recurrence rates.


Assuntos
Imunoterapia/métodos , Tuberculina/administração & dosagem , Verrugas/terapia , Adulto , Esquema de Medicação , Feminino , Humanos , Injeções Intralesionais , Masculino , Recidiva , Resultado do Tratamento , Tuberculina/efeitos adversos
4.
J Med Primatol ; 48(6): 329-337, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31478213

RESUMO

BACKGROUND: As the widely used biomarker of whole-blood stimulation assays for tuberculosis diagnosis, the release of IFN-γ might be affected by multiple factors, such as immunosuppression and some infectious agents. Here, we evaluated additional cytokines as diagnostic biomarkers. METHODS: Forty-three cytokines were measured by Luminex xMAP technologies in 30 healthy and 10 naturally Mycobacterium tuberculosis (MTB)-infected rhesus monkeys pre- and post-stimulation by purified protein derivative (PPD). RESULTS: After stimulation, production of 23 and 38 cytokines was markedly increased in healthy and MTB-infected macaques, respectively. A comparison of the stimulation index (SI) between MTB infections and healthy macaques showed that the SIs of 32 cytokines in MTB-infected macaques were significantly higher than those in healthy macaques. Pooling the results, eight cytokines were suggested as ideal biomarkers for a whole-blood stimulation assay for MTB diagnosis. CONCLUSION: PPD could induce multiple cytokine responses in either healthy or MTB-infected monkeys, and eight cytokines had reliable predictive capacity as diagnostic biomarkers of MTB infection.


Assuntos
Citocinas/metabolismo , Macaca mulatta , Doenças dos Macacos/metabolismo , Mycobacterium tuberculosis/fisiologia , Tuberculina/administração & dosagem , Tuberculose/veterinária , Animais , Tuberculose/metabolismo
5.
Braz J Infect Dis ; 23(4): 246-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31421107

RESUMO

Accurate and rapid diagnostic tools are important aspects of managing tuberculosis (TB) cases appropriately. However, the sensitivity and specificity of diagnostic kits based on immune response such as the tuberculin skin test (TST) and interferon gamma release assay (IGRA) are still debated. Thus, the exploration and assessment of specific biomarker-targeted antibodies are needed for the development of an accurate and rapid diagnostic tool. The present study was conducted in patients with a respiratory problem suspected to be TB at Dr. Soetomo Hospital, Surabaya, Indonesia. Among 102 patients tested by GeneXpert and AFB, 59 serum samples were from cases retrospectively determined to have active TB. A total of 102 serum of healthy controls (HC) was also collected. The PPD antigen and the recombinant CFP-10 and ESAT-6 proteins were prepared. Antibody responses against these proteins were evaluated by ELISA. All samples were also screened for the possibility of Mycobacterium avium-intracellulare complex (MAC) infection using Capilla MaC kit. The results showed that TB patients had a significantly higher concentration of IgG antibody in response to PPD than the HC. In addition, the receiver operating characteristic (ROC) curve analysis showed that PPD was acceptable for diagnostic purposes with an AUC value of 0.835 (95% CI 0.770-0.900, p < 0.0001). However, ESAT-6 and CFP-10 had low AUCs, and 32 samples from both groups showed a low concentration of IgA antibody against all antigens. The MAC detection results also showed that the concentration of IgA in the HC group was the highest. The current results indicate that PPD is a better antigen for antibody-based detection of TB than ESAT-6 and CFP-10. Based on the MAC detection assay, 53 people in the HC group were probably infected with rapidly growing nontuberculous mycobacteria (NTM), although antibody response to PPD was low.


Assuntos
Formação de Anticorpos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculina/imunologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Teste Tuberculínico , Tuberculose Pulmonar/sangue , Adulto Jovem
6.
Tuberculosis (Edinb) ; 117: 36-44, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31378266

RESUMO

Plasminogen and plasmin are fundamental components of the fibrinolytic system that interact with microorganisms generating different immunopathological effects. The molecules of Mycobacterium tuberculosis interplaying with plasminogen have already been identified and characterized. In this work, we studied the effects of plasmin(ogen) bound toMycobacterium bovisCalmette-Guérin (BCG) on phagocytosis in THP1 macrophages as well as in granuloma formation and development on in vitrohuman granuloma model. For this purpose, BCG was coated with plasminogen and plasmin, obtained after activation of zymogen by tissue plasminogen activator. The results showed a significant reduction in the number of bacteria phagocytosed by macrophages in presence of plasminogen or plasmin on BCG surface. On the other hand, at 3 days BCG/plasminogen/plasmin induced an increase granuloma numbers with respect to those induced by uncoated bacteria. BCG/plasminogen/environments also showed a significant increase of IL-6 secretion. At 7 days, a reduced number of granulomas and an increased number of bacteria was observed with respect to uncoated BCG environment. Altogether, these results showed that plasmin(ogen) on the mycobacterial surface affects phagocytosis, granuloma development and the cytokine context, thus resulting in an increased number of bacteria in granulomas.


Assuntos
Fibrinolisina/metabolismo , Granuloma/microbiologia , Mycobacterium bovis/metabolismo , Fagocitose/fisiologia , Plasminogênio/metabolismo , Tuberculose/microbiologia , Células Cultivadas , Citocinas/biossíntese , Granuloma/imunologia , Humanos , Macrófagos/microbiologia , Mycobacterium bovis/isolamento & purificação , Tuberculina , Tuberculose/imunologia , Tuberculose/metabolismo
7.
Tuberculosis (Edinb) ; 117: 56-61, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31378269

RESUMO

Diagnostic tests based on cell-mediated immunity are used in programs for the control and eradication of bovine tuberculosis (bTB), which is mainly caused by Mycobacterium bovis. Additional serological assays could be performed as an ancillary method to detect an infected animal that fails to produce an immune response against the intradermal reaction (IDR), the official bTB test. In this study, we evaluated the effectiveness of an enzyme-linked immunosorbent assay (ELISA) that uses bovine PPD as a capture antigen as a complement to the IDR in herds with confirmed cases of bTB. The study was conducted in two stages. First, a panel of 200 serum samples was analyzed by ELISA. The sensitivity and specificity obtained were 60% and 99%, respectively. The subsequent stage consisted of evaluating 7,494 bovines from 14 selected dairy farms. The number of animals yielding a IDR negative/ELISA positive result were 200. A necropsy analysis of 33 of these IDR negative/ELISA positive animals revealed that 30 (91%) presented granulomatous lesions and positive M. bovis isolation. This finding confirmed bTB in most cases. Altogether, the results obtained in the present study suggest that the combined use of IDR and ELISA is an effective strategy to improve the control of bTB in endemic herds.


Assuntos
Ensaio de Imunoadsorção Enzimática/veterinária , Teste Tuberculínico/veterinária , Tuberculose Bovina/diagnóstico , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática/métodos , Reações Falso-Negativas , Mycobacterium bovis/imunologia , Sensibilidade e Especificidade , Tuberculina/imunologia , Teste Tuberculínico/métodos , Tuberculose Bovina/patologia
8.
J Med Microbiol ; 68(9): 1314-1319, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274404

RESUMO

Introduction. Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity.Aims. Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance.Methodology. Defined recombinant antigens that were unique to Mycobacterium tuberculosis (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and M. bovis bacille Calmette-Guérin (BCG) vaccine was evaluated.Results. The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB.Conclusion. Transdermal application of defined purified antigens might be a promising method for LTBI screening.


Assuntos
Hipersensibilidade Tardia/imunologia , Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/imunologia , Testes Cutâneos/métodos , Adesivo Transdérmico , Animais , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Feminino , Cobaias , Indicadores e Reagentes , Mycobacterium tuberculosis/isolamento & purificação , Testes Cutâneos/normas , Tuberculina/imunologia
9.
Dermatol Ther ; 32(5): e13034, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31355514

RESUMO

Intralesional (IL) vitamin D3 is an emerging treatment for cutaneous warts. However, its effectiveness and exact mechanism is not fully evaluated. We aimed to compare the efficacy and safety of IL purified protein derivative (PPD) and IL vitamin D3 in multiple warts and to investigate their systemic effect clinically and immunologically. Forty-five patients with multiple extragenital warts were treated with IL-PPD (22 patients) or IL vitamin D3 injection (23 patients) for a maximum of three sessions at 3 week intervals. Decrease in size and number of warts and adverse effects were evaluated. Serum interleukin-12 (IL-12) and interferon-gamma (IFN-γ) levels were measured before and 3 weeks after the last session. Higher clearance rates for all warts were observed with IL-PPD compared to IL vitamin D (59.1% vs. 21.7% complete clearance, p < .001). Significant increase was found in both serum IL-12 and IFN-γ after PPD treatment (p = .034 and p = .04, respectively), but only IFN-γ after vitamin D3 treatment (p = 0.02). Both IL vitamin D3 and PPD showed positive results in treatment of multiple warts. However, PPD showed higher clinical efficacy and more increase in both IL-12 and IFN-γ levels.


Assuntos
Colecalciferol/administração & dosagem , Dermatoses do Pé/tratamento farmacológico , Imunidade Celular , Células Th1/imunologia , Tuberculina/administração & dosagem , Verrugas/tratamento farmacológico , Adulto , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Dermatoses do Pé/sangue , Dermatoses do Pé/imunologia , Humanos , Injeções Intralesionais , Interferon gama/sangue , Interleucina-12/sangue , Masculino , Estudos Prospectivos , Resultado do Tratamento , Vitaminas/administração & dosagem , Verrugas/sangue , Verrugas/imunologia
10.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1122-1123: 73-77, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158650

RESUMO

Phenol is commonly used as an antimicrobial agent with an initial concentration of 0.35% (w/v) in injectable diluted tuberculin purified protein derivative (TPPD) solution. The anti-microbial action of phenol in TPPD is directly concentration dependent. Furthermore, high phenol content (>0.5%) may have a negative effect on the stability and clinical effectiveness of TPPD solution. Therefore, simple, rapid and reliable reversed phase liquid chromatographic (RPLC) and capillary zone electrophoretic (CZE) methods were firstly developed and validated for phenol quantification in Connaught tuberculin (CT68) PPD diluted preparations at 5 TU per test dose of 0.1 mL. In RPLC, the elution was carried out by 80% (v/v) ACN mixed with 20% (v/v) phosphate buffer containing 0.05% (v/v) triflouroacetic acid (pH 3.2) at 0.2 mL min-1 flow rate and 20.0 °C column temperature. In addition, phenol was separated from tuberculin (CT68) protein with a resolution of (R = 2.81) and was quantified within 3 min. In CZE, the migration of phenol was performed by 50 mmol L-1 borate buffer (pH 9.8) at -20 kV applied voltage and 25.0 °C capillary temperature. Furthermore, excellent linearity was achieved within 0.17-0.53% (w/v) for the phenol content with coefficients of determination (r2) higher than 0.9995. Moreover, the detection and quantification limits were found to be 0.046 & 0.153% and 0.051 & 0.171% (w/v) with RPLC and CZE respectively. Additionally, the intraday precision (RSD%, n = 9) was ranged between 0.18 and 0.39 and 0.33-54 with RPLC and CZE respectively. Moreover, the interday precision (RSD%, n = 27) was varied between 2.06 and 2.99 and 2.25-3.40 by RPLC and CZE, respectively. Furthermore, the obtained mean recoveries were ranged between 91.32 and 107.51% with RPLC and 90.71-108.92% with CZE. In addition, the effect of different storage temperatures at 4, 25 and 37 °C over storage periods of 2, 7, 14, 21 and 30 days was also studied on the TPPD product. The obtained results have revealed that the phenol content was effectively decreased about 37% of its original content after 30 days at storage temperatures of 25 and 37 °C. However, the phenol content did not change and was stable up to 21 days at storage temperature of 4 °C. Therefore, the simple and rapid proposed analytical methods could be used for a rapid expiry investigation of TPPD products based on phenol quantification, as a marker.


Assuntos
Cromatografia Líquida/métodos , Eletroforese Capilar/métodos , Fenóis/análise , Fenóis/química , Tuberculina/análise , Tuberculina/química , Limite de Detecção , Modelos Lineares , Estabilidade Proteica , Reprodutibilidade dos Testes
12.
Microb Pathog ; 134: 103574, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31170450

RESUMO

The present study was aimed to assess the prevalence and efficiency of techniques for the diagnosis of bovine tuberculosis (bTB) including enzyme-linked immunosorbent assay (ELISA), Gamma interferon assay (IFN-γ) and polymerase chain reaction (PCR) in comparison to skin tuberculin test and culture technique. A total of 2600 cross-breed dairy cattle in Menoufia and Daqahlia governorates were tested by the single intradermal tuberculin test where the disease prevalence was 1.8%. Serum and whole blood samples were collected from positive tuberculin reactors for ELISA and IFN-γ assay, respectively. After slaughtering of positive tuberculin reactors, the post-mortem examination was carried out and tissue samples were collected for the bacteriological examination and PCR. The percentage of visible lesions of tuberculin reactors was 78.7%, while non-visible lesions were 21.27%. Culture technique revealed that the percentage of bTB was 63.8%. The ELISA and IFN-γ assay using short-term culture filtrate (ST-CF) prepared antigen revealed higher sensitivity (72.3% and 82.9%) than the bovine purified protein derivative (PPD-B) antigen. Although prepared ST-CF antigen has great efficiency and eligibility for the diagnosis of bTB, PCR appeared to have a higher sensitivity (85.1%) than other diagnostic methods when dealing with post-mortem samples. Gamma interferon assay using ST-CF antigen is recommended for antemortem diagnosis of bTB in cattle.


Assuntos
Técnicas Bacteriológicas/métodos , Interferon gama/sangue , Mycobacterium bovis/isolamento & purificação , Tuberculose Bovina/diagnóstico , Animais , Bovinos , Técnicas de Cultura/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Mycobacterium bovis/imunologia , Reação em Cadeia da Polimerase/métodos , Prevalência , Sensibilidade e Especificidade , Tuberculina , Teste Tuberculínico/métodos , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia
13.
Indian J Dermatol Venereol Leprol ; 85(4): 355-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172979

RESUMO

Background: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. Aims: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. Methods: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. Results: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. Limitation: Unicentric trial. Conclusion: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.


Assuntos
Vacinas Bacterianas/uso terapêutico , Reação no Local da Injeção/etiologia , Tuberculina/uso terapêutico , Verrugas/terapia , Adolescente , Adulto , Vacinas Bacterianas/efeitos adversos , Método Duplo-Cego , Eritema/induzido quimicamente , Feminino , Seguimentos , Humanos , Hiperpigmentação/induzido quimicamente , Injeções Intradérmicas , Masculino , Dor/induzido quimicamente , Recidiva , Indução de Remissão , Úlcera Cutânea/induzido quimicamente , Tuberculina/efeitos adversos , Adulto Jovem
16.
PLoS One ; 14(4): e0214333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30946755

RESUMO

BACKGROUND: Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed. METHODS AND FINDINGS: We investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%. CONCLUSIONS: The analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.


Assuntos
Antígenos de Bactérias/imunologia , Ascite/metabolismo , Linfócitos T CD4-Positivos/imunologia , Interferon gama/biossíntese , Mycobacterium tuberculosis/imunologia , Peritônio/patologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Proteínas de Bactérias/imunologia , Bélgica/epidemiologia , Feminino , Humanos , Incidência , Lectinas/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Tuberculina/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia
17.
J Med Primatol ; 48(4): 218-225, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31012123

RESUMO

BACKGROUND: Nowadays, several test methods with different useful values are available for diagnosis of the tuberculosis (TB) in non-human primates (NHPs). Despite some limitations of tuberculin skin test (TST), it is still the most commonly used method for TB testing of NHPs. METHODS: During this investigation, TST was performed upon three groups of experimentally tuberculin sensitized and one group of non-sensitized vervet monkeys (Chlorocebus pygerythrus) by means of two types of old tuberculin (OT) and two types of purified protein derivative (PPD) tuberculin. RESULTS: The data obtained from this study revealed that PPD tuberculin prepared from both Mycobacterium tuberculosis and Mycobacterium bovis has more advantages over OT in tuberculin testing of the vervet monkeys. The potency of the PPD tuberculin prepared from M bovis was estimated almost twice as much of the M tuberculosis. CONCLUSIONS: Intrapalpebral injection of 0.1 mL of a concentration of ≥1 mg/mL of PPD tuberculin prepared from M bovis is the preferred method for TST of vervet monkeys.


Assuntos
Chlorocebus aethiops , Doenças dos Macacos/diagnóstico , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Teste Tuberculínico/veterinária , Tuberculina/imunologia , Tuberculose/veterinária , Animais , Feminino , Masculino , Teste Tuberculínico/métodos , Tuberculose/diagnóstico
18.
Drug Deliv Transl Res ; 9(4): 795-801, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30891708

RESUMO

BACKGROUND: The tuberculin skin test (TST) is a long-established screening method for tuberculosis. However, the Mantoux technique is often difficult to reliably perform, which affects testing results and safety, which causes local skin pain and pruritus. METHODS: In this study, dissolving microneedle-array patches (MNP) were used to deliver purified protein derivative (PPD) tuberculin into the skin. The skin reaction was compared between MNP delivery and conventional injection. RESULTS: The MNP penetrated the skin easily with a thumb press, and the microneedle dissolved into the skin completely after 1 h. The storage life of MNP loaded with PPD (MNP-PPD) was 7 weeks at atmospheric pressure and room temperature. Only 1/50 dosage of PPD (approximately 0.04 IU) was needed in MNP compared with conventional injection (2 IU) in terms of skin reactivity to TST. When TST was tested in volunteers, the redness and induration of the skin were 19.7 ± 5.6 mm in TB patients, 12.6 ± 4.4 mm in LTBI (latent TB infection) patients, and 5.8 ± 2.7 mm in BCG vaccination healthy volunteers and lasted approximately 26 ± 5.4 days. When applied with MNP-PPD, the redness and induration on the skin decreased significantly to 3.1 ± 0.7 mm in TB patients and 2.0 ± 0.5 mm in LTBI, and the duration time was only 8.5 ± 1.5 days. Moreover, despite the relatively mild skin reactivity in BCG vaccination healthy volunteers with conventional injection, there was no skin reactivity in BCG vaccination healthy volunteers with MNP-PPD. CONCLUSION: In addition to being minimally invasive, needle-free, and painless, no adverse effects were attributed to the new diagnostic method, which may be of value for the safe and effective clinical administration of TB screening. When applied with MNP-PPD, an area of redness and induration greater than 2.5 mm can identify a TB-positive patient.


Assuntos
Adesivo Transdérmico , Teste Tuberculínico/instrumentação , Tuberculina/administração & dosagem , Adolescente , Adulto , Vacina BCG , Feminino , Voluntários Saudáveis , Humanos , Masculino , Microinjeções , Pessoa de Meia-Idade , Agulhas , Pele/efeitos dos fármacos , Pele/metabolismo , Solubilidade , Teste Tuberculínico/métodos , Tuberculose , Adulto Jovem
20.
Res Vet Sci ; 122: 7-14, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30447501

RESUMO

Bovine tuberculosis (bTB) is an important animal and zoonotic disease, which causes severe economic losses. The main focus of this study was to assess the predictive power of previously identified biomarkers of bTB in infected animals that were negative to the tuberculin skin test (TST). We studied 16 animals with bTB, in which the disease was confirmed by necropsy, and 16 healthy animals. The level of expression of ten biomarkers (CXCL9, THBS1, MMP9, IL-22, CXCL10, IFNγ, IL-17, FYVE, CD14, IL-1R) was evaluated by RT-qPCR upon stimulation or not of peripheral blood mononuclear cells with PPDb (purified protein derivative of bovine tuberculin). In this assay, CXCL9, THBS1, MMP9, IL-22 and IFNγ changed their expression level depending on the bTB status. In addition, we evaluated different biomarker candidates simultaneously to infer the animal condition. By performing an analysis with classification trees, we found that the sturdiest combination was IL-22, IFNγ and IL-1R. On the other hand, CXCL10, IFNγ and IL-22's expression distinguished between bTB positive animals that were negative to TST (TST false negative animals) and the bTB negative groups. Thus, these biomarkers are promising candidates to be tested as an ancillary diagnostic assay. In addition, the expression of CXCL10 and IL-22 exhibited also significant differences between the bTB positive animals that were undetectable by IFNγ release assay (IGRA) and TST tests (TST and IGRA false negative animals) and the bTB negative groups. Therefore, CXCL10 and IL-22 constitute candidate biomarkers that could complement the two most widely used diagnostic tests.


Assuntos
Interferon gama/metabolismo , Teste Tuberculínico/veterinária , Tuberculose Bovina/diagnóstico , Animais , Biomarcadores/sangue , Bovinos , Reações Falso-Negativas , Leucócitos Mononucleares/metabolismo , Mycobacterium bovis , Tuberculina/imunologia
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