RESUMO
The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.
L'Organisation mondiale de la Santé (OMS) vise à réduire le nombre de nouveaux cas de lèpre de 70% d'ici 2030, ce qui nécessite un meilleur diagnostic de la maladie. Dans le présent document, nous évoquons le développement de deux profils de produit cible établis par l'OMS à cette fin. Ces profils définissent des critères en matière d'utilisation, de conception, de performances, de configuration et de distribution du produit, en accordant une attention particulière à l'accessibilité et à l'abordabilité. Le premier profil de produit cible décrit les exigences pour les tests servant à confirmer le diagnostic de la lèpre chez les individus qui présentent des signes cliniques et des symptômes, afin d'orienter l'instauration d'un traitement à base de plusieurs médicaments. Le second profil de produit cible décrit les exigences pour les tests servant à détecter une infection à Mycobacterium leprae ou M. lepromatosis parmi les contacts asymptomatiques de patients lépreux, ce qui contribue à l'adoption de mesures prophylactiques et à la prévention. Nous avons eu recours à une modélisation statistique pour évaluer les exigences de sensibilité et de spécificité de ces tests diagnostiques. Cet article met en évidence les obstacles à l'atteinte d'un niveau élevé de spécificité en raison de l'endémicité variable de M. leprae, et à l'identification d'analytes cibles offrant de bons résultats chez les phénotypes lépreux. Nous concluons qu'un diagnostic reposant sur des caractéristiques de performance et de conception appropriées est essentiel pour détecter rapidement la maladie et intervenir en amont, et nous plaidons pour une prévention plutôt qu'une gestion de la lèpre.
La Organización Mundial de la Salud (OMS) pretende reducir los nuevos casos de lepra en un 70% para 2030, lo que requiere avances en el diagnóstico de la lepra. Aquí se analiza el desarrollo de dos perfiles de productos objetivo de la OMS para este tipo de diagnósticos. Estos perfiles definen los criterios de uso, diseño, rendimiento, configuración y distribución de los productos, centrándose en su accesibilidad y asequibilidad. El primer perfil de producto objetivo describe los requisitos de las pruebas para confirmar el diagnóstico de la lepra en personas con signos y síntomas clínicos, con el fin de orientar el inicio del tratamiento con múltiples fármacos. El segundo perfil de producto objetivo describe los requisitos de las pruebas para detectar la infección por Mycobacterium leprae o M. lepromatosis entre los contactos asintomáticos de los pacientes con lepra, para facilitar las intervenciones profilácticas y la prevención. Se utilizaron modelos estadísticos para evaluar los requisitos de sensibilidad y especificidad de estas pruebas diagnósticas. El artículo destaca las dificultades para lograr una alta especificidad, dada la diferente endemicidad de M. leprae, y para identificar analitos diana con un rendimiento sólido en todos los fenotipos de lepra. Concluimos que los diagnósticos con un diseño de producto y unas características de rendimiento adecuados son fundamentales para la detección precoz y la intervención preventiva, lo que favorece la transición del manejo de la lepra a la prevención.
Assuntos
Hanseníase , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Mycobacterium leprae/genética , Sensibilidade e Especificidade , Modelos Estatísticos , Diagnóstico PrecoceRESUMO
Bacteriocins are ribosomally-synthesized antimicrobial peptides, showing great potential as novel treatment options for multidrug-resistant pathogens. In this study, we designed a novel hybrid bacteriocin, Hybrid 1 (H1), by combing the N-terminal part and the C-terminal part of the related bacteriocins enterocin K1 (K1) and enterocin EJ97 (EJ97), respectively. Like the parental bacteriocins, H1 used the membrane-bound protease RseP as receptor, however, it differed from the others in the inhibition spectrum. Most notably, H1 showed a superior antimicrobial effect towards Staphylococcus haemolyticus-an important nosocomial pathogen. To avoid strain-dependency, we further evaluated H1 against 27 clinical and commensal S. haemolyticus strains, with H1 indeed showing high activity towards all strains. To curtail the rise of resistant mutants and further explore the potential of H1 as a therapeutic agent, we designed a bacteriocin-based formulation where H1 was used in combination with the broad-spectrum bacteriocins micrococcin P1 and garvicin KS. Unlike the individual bacteriocins, the three-component combination was highly effective against planktonic cells and completely eradicated biofilm-associated S. haemolyticus cells in vitro. Most importantly, the formulation efficiently prevented development of resistant mutants as well. These findings indicate the potential of a bacteriocins-based formulation as a treatment option for S. haemolyticus.
Assuntos
Bacteriocinas/farmacologia , Biofilmes/efeitos dos fármacos , Staphylococcus haemolyticus/fisiologia , Sequência de Aminoácidos , Anti-Infecciosos/farmacologia , Bacteriocinas/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Testes de Sensibilidade Microbiana , Modelos Biológicos , Mutação/genética , Staphylococcus haemolyticus/efeitos dos fármacos , Staphylococcus haemolyticus/genética , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Female Genital Tuberculosis (FGTB) causes infertility in a large number of females in developing countries. Presence of granuloma on histopathological examination of endometrial samples is diagnostic of FGTB. But immunohistochemical evaluation of endometrial aspirates has not been explored before. AIM: To evaluate the immunohistochemical delineation of immune cells in FGTB. METHODS: 1515 infertile women from 20 to 35 years were enrolled and underwent endometrial aspiration (EA), which was subjected to microbiological and histopathological examination along with PCR. Patients positive for conventional tests like granulomas, acid fast bacilli, mycobacterial culture on LJ medium or liquid (MGIT) culture were started on antitubercular therapy. Conventional test negative but PCR positive patients were posted for laparoscopy. Immunohistochemistry (IHC) for LCA, CD68, CD3, CD4, CD8, CD 20, CD138, IFN gamma and IL10 were evaluated. RESULT: 38/1515 (2.5%) subjects tested positive for conventional methods. PCR-TB was positive in 615/1515 samples (40.59%). On IHC, the number of CD45 (LCA) positive immune cells (p = 0.03) and IFN gamma (p = 0.002) and IL10 expression (p = 0.012) at 1 + level were higher in the PCR positive samples. Laparoscopy done in 418/463 patients and 89/418 (21.3%) showed definitive findings of tuberculosis. CD3, CD4, CD8, CD20, CD68 and CD138 showed no correlation with PCR and laparoscopy. CONCLUSION: Increased IFN gamma and IL 10 expressing immune cells in PCR positive EA suggests subclinical early changes, and can be useful as a research tool but have no role in diagnosing FGTB.
Assuntos
Infertilidade Feminina , Mycobacterium tuberculosis , Tuberculose dos Genitais Femininos , Antituberculosos/uso terapêutico , Biópsia , Endométrio , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Tuberculose dos Genitais Femininos/diagnóstico , Tuberculose dos Genitais Femininos/tratamento farmacológicoRESUMO
BACKGROUND: Non-healing plantar ulcers are one of the significant causes of disability in leprosy patients. Plantar ulcers often take months or years to heal, affecting the patient's quality of life. Presence of comorbid conditions in these patients can delay wound healing. The study aimed to evaluate the role of associated comorbid conditions as risk factors in ulcer healing. METHODOLOGY/PRINCIPAL FINDINGS: A total of 66 leprosy patients with plantar ulcers registered at LEPRA Society-Blue Peter Public Health and Research Center (BPHRC), Hyderabad, India from June 2018 to June 2019 were studied. Comprehensive clinical assessment was done, including screening for comorbid conditions and treated as per the recommended guidelines. About two-thirds of the participants were aged 50 and above, of which more than half were illiterates, and 93.5% were living below the poverty line. Majority of ulcers were seen on the forefoot; with the head of meta-tarsal bone 27 (41.6%) as the commonest site, followed by calcaneum 23 (38.3%) and great toe 10 (16.6%). Mean ulcer depth was 0.61 (0.57) cm, the area was 5.24 (6.73) cm2 and ulcer volume was 4.72 (14.33) cm3. Ulcer dimensions were significantly associated with low body mass index, hypertension and smoking. CONCLUSIONS/SIGNIFICANCE: Identifying the risk factors delaying wound healing and detailed assessment of ulcers are of profound importance to predict the outcome of plantar ulcers in leprosy patients. The study findings indicate the need for better policies by the leprosy control program for the comprehensive management of plantar ulcers.
Assuntos
Comorbidade , Úlcera do Pé/complicações , Hanseníase/complicações , Adulto , Idoso , Estudos Transversais , Feminino , Pé , Úlcera do Pé/epidemiologia , Humanos , Índia/epidemiologia , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Pobreza , Fatores de Risco , CicatrizaçãoRESUMO
Erythema nodosum leprosum (ENL), or type 2 lepra reaction, is a multi-system immune-mediated complication in patients with multibacillary leprosy, frequently associated with chronicity and recurrences. Management of ENL requires high doses of oral corticosteroids, which may not be universally effective and pose serious adverse effects. Thalidomide has proven to be a steroid-sparing agent and is useful in controlling the reactions. However, many centres do not employ it in outpatient settings due to adverse effects and teratogenicity risk. Hence, we studied the feasibility of treating ENLs and reported the therapeutic outcome.This is a five-year record-based analysis of ENL leprosy patients treated with thalidomide, includingdescriptive statistics of demographic variables. Clinical characteristics were stratified by treatment compliance status (yes/no). Incidence rates and rate ratios for recovery stratified by bacillary index, type of ENL presentation and MDT treatment status were calculated.Out of 102 ENL patients treated with thalidomide, 68 (66.7%) were compliant and improved. Among them, ENL recurrence was noted in 11(16.2%) patients. The commonest thalidomide side effect was pedal oedema (73.5%). Patients with bacillary index (BI) less than or equal to 4.0 had a 37% increase in the incidence of recovery. Patients with acute ENL were almost twice as likely to recover as those with chronic ENL. Also, the improvement was two and a half times greater among those who completed MDT as compared to those on MDT. The study showed that thalidomide treatment for patients with ENL is possible in outpatientclinics. We also successfully prevented pregnancies to a larger extent through counselling for contraception.We observed that early institution of thalidomide induces faster remission and prevents ENL recurrence.
Assuntos
Eritema Nodoso/tratamento farmacológico , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Adulto , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Antibiotic-resistant and biofilm-associated infections brought about by methicillin-resistant Staphylococcus aureus (MRSA) strains is a pressing issue both inside as well as outside nosocomial environments worldwide. Here, we show that a combination of two bacteriocins with distinct structural and functional characteristics, garvicin KS, and micrococcin P1, showed a synergetic antibacterial activity against biofilms produced in vitro by S. aureus, including several MRSA strains. In addition, this bacteriocin-based antimicrobial combination showed the ability to restore the sensitivity of the highly resilient MRSA strain ATCC 33591 to the ß-lactam antibiotic penicillin G. By using a combination of bacterial cell metabolic assays, confocal and scanning electron microscopy, we show that the combination between garvicin KS, micrococcin P1, and penicillin G potently inhibit cell viability within S. aureus biofilms by causing severe cell damage. Together these data indicate that bacteriocins can be valuable therapeutic tools in the fight against biofilm-associated MRSA infections.
Assuntos
Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Sinergismo Farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Confocal , Microscopia Eletrônica de Varredura , Penicilina G/farmacologiaRESUMO
Lymphatic filariasis (LF) is a parasitic infection, caused by three closely related nematodes, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. Previously, we have shown that lysate from B. malayi microfilariae induces the expression of interleukin (IL)-10 and programmed death-ligand (PD-L) 1 on monocytes, which lead to inhibition of CD4+ T-cell responses. In this study, we investigated associations of IL-10 and programmed cell death (PD)-1 pathway gene polymorphisms with clinical manifestation in LF. We evaluated the frequency of alleles and genotypes of IL-10 (rs3024496, rs1800872), IL-10RA (rs3135932), IL-10RB (rs2834167), PD-1 (rs2227982, rs10204525), PD-L1 (rs4143815), PD-L2 (rs7854413), and single-nucleotide polymorphisms (SNPs) in 103 patients with chronic pathology (CP), such as elephantiasis or hydrocele and 106 endemic normal (EN) individuals from a South Indian population living in an area endemic for LF. Deviations from the Hardy-Weinberg equilibrium were tested, and we found a significant difference between the frequency of polymorphisms in PD-L2 (rs7854413; P < 0.001) and IL-10RB (rs2834167; P = 0.012) between the CP and the EN group, whereas there were no significant differences found among IL-10, IL-10RA, PD-1, and PD-L1 SNPs. A multivariate analysis showed that the existence of a CC genotype in PD-L2 SNP rs7854413 is associated with a higher risk of developing CP (OR: 2.942; 95% confidence interval [CI]: 0.957-9.046; P = 0.06). Altogether, these data indicate that a genetically determined individual difference in a non-synonymous missense SNP of PD-L2 might influence the susceptibility to CP.
Assuntos
Filariose Linfática/genética , Predisposição Genética para Doença , Interações Hospedeiro-Parasita/genética , Polimorfismo de Nucleotídeo Único , Proteína 2 Ligante de Morte Celular Programada 1/genética , Adulto , Alelos , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Brugia/crescimento & desenvolvimento , Brugia/imunologia , Brugia Malayi/crescimento & desenvolvimento , Brugia Malayi/imunologia , Doença Crônica , Filariose Linfática/epidemiologia , Filariose Linfática/imunologia , Filariose Linfática/parasitologia , Feminino , Expressão Gênica , Frequência do Gene , Interações Hospedeiro-Parasita/imunologia , Humanos , Índia/epidemiologia , Interleucina-10 , Subunidade beta de Receptor de Interleucina-10/genética , Subunidade beta de Receptor de Interleucina-10/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Proteína 2 Ligante de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Wuchereria bancrofti/crescimento & desenvolvimento , Wuchereria bancrofti/imunologiaRESUMO
Leprosy is an infectious disease caused by Mycobacterium leprae and mainly affects skin, peripheral nerves, and eyes. Suitable tools for providing bacteriological evidence of leprosy are needed for early case detection and appropriate therapeutic management. Ideally these tools are applicable at all health care levels for the effective control of leprosy. This paper presents a systematic review analysis in order to investigate the performance of polymerase chain reaction (PCR) vis-à-vis slit skin smears (SSS) in various clinical settings and its potential usefulness as a routine lab test for leprosy diagnosis. Records of published journal articles were identified through PubMed database search. Twenty-seven articles were included for the analysis. The evidence from this review analysis suggests that PCR on skin biopsy is the ideal diagnostic test. Nevertheless, PCR on SSS samples also seems to be useful with its practical value for application, even at primary care levels. The review findings also indicated the necessity for improving the sensitivity of PCR and further research on specificity in ruling out other clinical conditions that may mimic leprosy. The M. leprae-specific repetitive element (RLEP) was the most frequently-used marker although its variable performance across the clinical sites and samples are a matter of concern. Undertaking further research studies with large sample numbers and uniform protocols studied simultaneously across multiple clinical sites is recommended to address these issues.
RESUMO
Objectivos: La lepra infantil es un buen indicador de transmisión comunitaria de la enfermedad y la necesidad de un diagnóstico precoz. La discapacidad de Grado 2 (G2D) en niños revela un retraso en el diagnóstico, a nivel de la atención sanitaria o en su reconocimiento y derivación por la familia. Este trabajo determina la proporción de G2D entre los nuevos casos de lepra diagnosticados en niños y adolescentes e identifica los factores asociados a su presencia.Métodos: Se llevó a cabo un análisis retrospectivo de las historias clínicas de niños y adolescentes ≤18 años diagnosticados durante 5 años, comprendidos entre abril de 2014 y septiembre de 2019, con especial atención a la presentación de G2D en el momento del diagnóstico.Resultados: Los niños y adolescentes constituían el 8.26% (327/3955) de todos los casos. De entre ellos, 58 (17.7%) presentaban G2D en el momento del diagnóstico. La G2D era más frecuente entre los del grupo de 1518 años y estaba significativamente relacionada con un retraso del diagnóstico, la presencia de convivientes, presentar lepra multibacilar, engrosamiento neural y neuritis.Conclusiones: Se informa de un elevado número de casos G2D entre los casos nuevos de lepra de niños y adolescentes, mucho mayor que la media nacional de los adultos. Con tan elevada proporción de casos G2D, el objetivo de cero discapacidades en niños en la India para el 2020 no se ha cumplido. Las actividades sanitarias dirigidas hacia una detección precoz en niños pueden reducir el retraso en el diagnóstico, y prevenir la aparición de discapacidades. (AU)
Objectives: Leprosy in children is a strong indicator of disease transmission in the community and the rapidity of case detection. Grade 2 disability (G2D) in children denotes a delay in diagnosis, which could be due to delay either at the health care level or in recognition and referral by the family. The current study determines the proportion of G2D among newly diagnosed leprosy-affected children and adolescents and identifies the associated factors.Methods: A 5-year retrospective analysis of records of children and adolescents aged ≤18 years newly diagnosed with leprosy between April 2014 and September 2019, was carried out with special reference to G2D presentation at the time of diagnosis.Results: Children and adolescents comprised 8.26% (327/3955) of all subjects. Among them, 58 (17.7%) had G2D at the time of diagnosis. G2D occurred more frequently among the 1518 years age group and was significantly associated with registration delay, presence of household contact cases, having multibacillary leprosy, nerve thickening and neuritis.Conclusions: We report a high rate of G2D among newly diagnosed leprosy cases in children and adolescents, much higher than the reported national average for adults. With such a high occurrence of G2D, the target of having zero disability in childhood cases is unlikely to be met in India in 2020. Early case detection activities with a child-focused approach may reduce the delay in diagnosis, preventing leprosy-associated disability in children. (AU)
Assuntos
Humanos , Criança , Adolescente , Hanseníase , Criança , Adolescente , Pessoas com Deficiência , Neurite (Inflamação) , Fatores de Risco , Índia , Estudos Retrospectivos , Estudos Transversais , Prontuários MédicosAssuntos
Quimioterapia Combinada/normas , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Paucibacilar/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/normas , Antibacterianos/uso terapêutico , Clofazimina/uso terapêutico , Guias como Assunto , Humanos , Organização Mundial da SaúdeRESUMO
We report whole-genome sequences of two clinical isolates of Mycobacterium tuberculosis isolated from patients in Odisha, India. The sequence analysis revealed that these isolates are of an ancestral type and might represent some of the "pristine" isolates in India that have not admixed with other lineages.
RESUMO
BACKGROUND: Monocytes and macrophages contribute to the dysfunction of immune responses in human filariasis. During patent infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive. AIM: To determine whether blood microfilariae directly act on blood monocytes and in vitro generated macrophages to induce a regulatory phenotype that interferes with innate and adaptive responses. METHODOLOGY AND PRINCIPAL FINDINGS: Monocytes and in vitro generated macrophages from filaria non-endemic normal donors were stimulated in vitro with Brugia malayi microfilarial (Mf) lysate. We could show that monocytes stimulated with Mf lysate develop a defined regulatory phenotype, characterised by expression of the immunoregulatory markers IL-10 and PD-L1. Significantly, this regulatory phenotype was recapitulated in monocytes from Wuchereria bancrofti asymptomatically infected patients but not patients with pathology or endemic normals. Monocytes from non-endemic donors stimulated with Mf lysate directly inhibited CD4+ T cell proliferation and cytokine production (IFN-γ, IL-13 and IL-10). IFN-γ responses were restored by neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate expressed high levels of IL-10 and had suppressed phagocytic abilities. Finally Mf lysate applied during the differentiation of macrophages in vitro interfered with macrophage abilities to respond to subsequent LPS stimulation in a selective manner. CONCLUSIONS AND SIGNIFICANCE: Conclusively, our study demonstrates that Mf lysate stimulation of monocytes from healthy donors in vitro induces a regulatory phenotype, characterized by expression of PD-L1 and IL-10. This phenotype is directly reflected in monocytes from filarial patients with asymptomatic infection but not patients with pathology or endemic normals. We suggest that suppression of T cell functions typically seen in lymphatic filariasis is caused by microfilaria-modulated monocytes in an IL-10-dependent manner. Together with suppression of macrophage innate responses, this may contribute to the overall down-regulation of immune responses observed in asymptomatically infected patients.
Assuntos
Brugia Malayi/imunologia , Filariose Linfática/imunologia , Interleucina-10/imunologia , Microfilárias/imunologia , Wuchereria bancrofti/imunologia , Imunidade Adaptativa/imunologia , Adolescente , Adulto , Idoso , Esclerose Lateral Amiotrófica , Animais , Linfócitos T CD4-Positivos/imunologia , Feminino , Humanos , Imunidade Inata/imunologia , Interleucina-13/genética , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Fenótipo , Adulto JovemRESUMO
Although the pathophysiological role of PE/PPE proteins of Mycobacterium tuberculosis is yet to be fully understood, recent evidence shows that these proteins play important roles in antigenic diversity, as well as in host-pathogen interactions and mycobacterial pathogenesis. Most of the PE/PPE proteins are highly expressed in pathogenic bacteria, pointing to their role in the pathogenesis of mycobacteria. Here, we provide an overview of our work in progress on a specific PPE protein, PPE2 (Rv0256c), which may inhibit nitric oxide (NO) production in activated macrophages. As NO and its by-products are considered to be toxic to bacilli, it is possible that the bacilli recruit Rv0256c in order to inhibit higher production of NO during infection.
Assuntos
Proteínas de Bactérias/fisiologia , Ativação de Macrófagos , Macrófagos/metabolismo , Macrófagos/microbiologia , Mycobacterium tuberculosis/patogenicidade , Óxido Nítrico/antagonistas & inibidores , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/fisiologia , Proteínas de Bactérias/genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Camundongos , Mycobacterium tuberculosis/imunologia , Óxido Nítrico/biossíntese , Tuberculose/etiologia , Tuberculose/microbiologia , Tuberculose/patologiaRESUMO
BACKGROUND: HupB is a 28 kDa cell-wall-associated protein co-expressed with the siderophores mycobactin and carboxymycobactin in iron-limited Mycobacterium tuberculosis. HupB is expressed in vivo and anti-HupB antibodies are present in the serum of TB patients. METHODS: The aims of this study were to evaluate the serodiagnostic potential of HupB and to correlate levels of anti-HupB antibodies with the serum iron status in TB patients, household contacts and normal healthy controls. RESULTS: TB patients from Hyderabad (India) showed high levels of anti-HupB antibodies compared with household contacts and normal healthy controls. Interestingly, the levels were maximal in extrapulmonary TB patients, with a two-fold higher titre than pulmonary TB patients. Serum iron levels, total iron-binding capacity (TIBC) and percent saturation of serum transferrin were low in subjects with active TB, whilst serum ferritin was notably high in pulmonary TB patients compared with normal controls. CONCLUSIONS: There is a strong negative correlation between serum iron levels and TIBC with the titre of anti-HupB antibodies in subjects with active TB. This study reflects the usefulness of screening for anti-HupB antibodies for diagnosis of pulmonary and extrapulmonary TB in this endemic region.