Form Of Extrapulmonary Tuberculosis Research Articles

Culture proven extra pulmonary tuberculosis: drug susceptibility and genetic profile analysis

Tuberculosis is seen generally in the lungs. Besides, all organs in the body can be affected by tuberculosis. Diagnosis of extra pulmonary tuberculosis (EPTB) is more difficult than pulmonary tuberculosis (PTB). Although, the isolation of Mycobacterium tuberculosis is gold standard of diagnosis of EPTB, the rate of bacteriologic isolation is low especially in EPTB. If M. tuberculosis is detected, it gives some information about the epidemiological features of the disease and drug susceptibility. In this study, extra pulmonary samples isolated M. tuberculosis in mycobacteriology laboratory were evaluated between 2009-2016. The identification of the genotype of isolated bacteria and drug sensitivity tests were conducted. Spoligotyping was accomplished using a standard technique as described previously. During the study period, M. tuberculosis were cultured in 171 extra pulmonary samples of 165 patients (75 male, 90 female, mean age: 53.35 ± 19.92). Initial direct microscopically examination was revealed M. tuberculosis in 44 patients. There were more than one extra pulmonary organ involvement in six patients. The most common EPTB forms were lymph node TB in 60 patients, pleural tuberculosis in 32 patients and bone tuberculosis in 25 patients. Immunosuppression was detected in 44 (%26.6) patients. Among these, seven patients were infected with HIV. In 21 of 175 samples, drug resistance was detected. Rifampicin resistance in 7 samples, high level isoniazid resistance in 11 samples and rifampicin plus isoniazid resistance (multiply drug resistance) in 6 samples were demonstrated. One hundred thirty-five clinical isolates were cultured from tuberculosis patient's different samples, of which the genetic profile was determined by using Spoligotyping. The major Spoligotypes were T (n= 62; 45.9%), LAM7-TUR (ST41) (n= 11; 8.1%) and H1 (n= 9; 6%) genotypes. The most common EPTB form was lymph node tuberculosis in culture proven patients. In these patients group, multiply drug resistance rate was low (3.6%). Spoligotypes T (45.9%) was detected as most common genetic profile.

Abdominal tuberculosis: a surgical perplexity

Abdominal tuberculosis is one of the most challenging forms of extra pulmonary tuberculosis. The diagnosis of the disease itself poses the greatest challenge due to the variability of presentation. Clinical presentations in various forms with conflicting results on a multitude of haematological, immunological and radiological tests causes a lot of confusion in interpreting and correlating the symptoms to arrive at a diagnosis. This adds to the perplexity in surgical management of this complex disease especially in an era where AIDS has added to the problems. Having arrived at a diagnosis, chemotherapy is the mainstay of treatment. Surgery is indicated when the response to medical therapy is poor or complications supervene. Deciding the optimum procedure is again a major issue. Understanding the pathophysiology therefore is pivotal in making a value decision. The article briefly outlines the approach to this surgical perplexity.

Diminished TLR2-TLR9 mediated CD4+ T cell responses are associated with increased inflammation in intraocular tuberculosis

Intraocular tuberculosis (IOTB) is amongst the leading causes of uveitis in tropical countries. Despite reports on involvement of proinflammatory cytokines, studies on innate immune responses in disease pathogenesis are lacking. Reports from animal models and patients with pulmonary tuberculosis indicate that defects in toll like receptor (TLR)2 and TLR9 signalling predispose them to tuberculosis. In this context, we investigated the role of TLR2, TLR4 and TLR9 in generation of CD4+ T effector (Teff) cell responses during IOTB. Firstly, the cells in vitreous fluids showed lower expression of TLR2 and TLR9 in IOTB as compared to non-uveitis and non-TB uveitis groups. Next, peripheral CD4+ Teff cells of subjects with IOTB showed decreased proliferative responses and lower induction of Tregs following TLR2 and TLR9 stimulation. Further, TLR9 ligation resulted in increased IFN-γ and IL-17a but decreased expression of IL-10 and TGF-β. Lastly, lower expression of genes involved in TLR9 signalling after direct TLR9 ligation was observed in IOTB. Collectively, our results show that a subdued response to direct TLR2 and TLR9 stimulation in CD4+ T cells is associated with increased proinflammatory responses in IOTB. These findings reveal an important link between innate immune signalling and ensuing adaptive immune responses in IOTB with implications in other forms of extrapulmonary tuberculosis.

Splenic tuberculosis: a comprehensive review of literature.

Tuberculosis(TB) is one of the most common infections affecting the population in the developing countries. With the rising human immunodeficiency(HIV) infection its incidence is on a rise even in the developed countries. Pulmonary TB is the commonest form of infection, However, multiple extrapulmonary sites have also been reported. The spleen is thought to be a rare organ involved in this infection. Various presentations of the splenic TB have been reported in the literature. The definitive diagnosis of this is essentially formulated on the post-splenectomy specimen. A consensus statement based on the available case reports is lacking. The authors are providing an insight into this form of extrapulmonary TB after reviewing the available literature.

Panhypopituitarism- An unusual presenation of tuberculous meningitis

Pituitary gland involvement is a very rare entity of central nervous system tuberculosis. Tubercular meningitis (TBM) is a chronic meningitis on hypothalamic-pituitary axis which causes high morbidity and mortality hence it is the most dreaded form of extra pulmonary tuberculosis. Here we report a case of 24 year old female presenting with three months history of fever and headache along with altered sensorium since four days. There was also complain of secondary amenorrhea and generalised apathy. Neuroimaging revealed subependymal tuberculomas with meningitis and obstructive hydrocephalus. Cerebrospinal fluid (CSF) examination was also suggestive of tubercular meningitis. Endocrinological investigations showed multiple hormonal deficiencies manifesting as pituitary hypothyroidism, hypocortisolism, hypogonadotropic hypogonadism, and hypoprolactinemia. Anti-tuberculosis treatment was started, and it led to significant improvement in the general condition of the patient.

ASSESSING THE UTILITY OF GENEXPERT AS A DIAGNOSTIC TOOL IN THE DETECTION OF TUBERCULOSIS IN A NEUROLOGICAL TERTIARY CARE SETUP

Tuberculosis in the CNS(central nervous system) is the most dangerous form of extrapulmonaryTuberculosis and is still a formidable clinical challenge. Rapid diagnosis of Tuberculosis and detectionof Rifampicin resistance are essential for early disease management. The Xpert/Rif Assay is anautomated nucleic acid amplification test that can identify the Mycobacterium tuberculosis DNA andresistance to Rifampicin. In this experiment we used different pulmonary as well as extrapulmonarysamples from patients to assess the utility of genexpert as a diagnostic tool.

The Use of TB-Specific Antigen/Phytohemagglutinin Ratio for Diagnosis and Treatment Monitoring of Extrapulmonary Tuberculosis.

Extrapulmonary tuberculosis (EPTB) has become more common in recent years; however, the diagnosis of EPTB remains a challenge. In this study, we analyzed the performance of the ratio of TB-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) in T-SPOT.TB (T-SPOT) assay for diagnosis and treatment monitoring of EPTB. Between 2012 and 2017, 734 EPTB patients were diagnosed and recruited from Tongji hospital, and 1,137 suspected EPTB patients who had other diagnoses were recruited as non-EPTB controls. To validate the study, another small group of EPTB patients and non-EPTB controls were recruited from Sino-French New City Branch of Tongji Hospital. The positive rate of peripheral blood T-SPOT in EPTB and non-EPTB were 88.15 and 32.28%. In T-SPOT positive patients, the direct T-SPOT results had limited value in distinguishing these two conditions. A further calculation of the TBAg/PHA ratio of T-SPOT showed improved performance in each form of EPTB. If using 0.20 as the threshold value of the TBAg/PHA ratio, the pooled sensitivity and specificity were 70.79 and 91.55% in distinguishing EPTB from non-EPTB. The validation results showed a better performance of the TBAg/PHA ratio in distinguishing these two conditions, with a sensitivity and specificity of 81.82 and 97.56%, respectively. Comparing with directly using T-SPOT results, the TBAg/PHA ratio was less affected by immunosuppression. Furthermore, PHA value reflected immunosuppression and could help to judge the credibility of T-SPOT results in EPTB patients with different immune status. The TBAg/PHA ratio was significantly decreased during anti-tuberculosis (TB) treatment, which suggests that it can also be used to monitor therapeutic efficacy. These data provide new insights into the role of T-SPOT assay in TB disease, and the TBAg/PHA ratio might be a useful tool for diagnosis and treatment monitoring of EPTB.

Ocular tuberculosis: A case series

Ocular tuberculosis is a rare form of extra pulmonary tuberculosis. It represents 1-2% of all clinical forms. The aim of this work was to focus on diagnostic and therapeutic characteristics of ocular tuberculosis. We report a case series of 14 patients with ocular tuberculosis seen in an infectious diseases department between 2006 and 2015. The diagnosis was retained on clinical data and a positive tuberculin skin test or interferon-gamma release assay. The patient's mean age was 40.7±9years. The most common clinical presentation was uveitis (11 patients and 16 eyes). An extra ocular involvement was associated in three patients. The mean duration of antitubercular therapy was 10±2.5 months. Corticosteroid therapy was associated in 11 cases. The outcome was favorable in all cases. Two patients had maintained visual sequelae. Ocular tuberculosis is a rare disease but still remains a diagnostic problem. It should be considered in case of any chronic ocular symptoms, especially in endemic countries. Early management can improve the visual prognosis.

АБДОМИНАЛЬНЫЙ ТУБЕРКУЛЕЗ В РАБОТЕ ВРАЧА ОБЩЕЙ ПРАКТИКИ

Last years are marked by the increased number of cases of extra pulmonary localizations of tubercular process that are proved by the numerous publications. The diagnostics of these forms of tuberculosis is not easy because it requires a detailed examination of the patient. Cases of abdominal tuberculosis are among them. The article contains the data of modern medical literature on extra pulmonary forms of tuberculosis and information of clinical cases of posthumous diagnostics of tuberculosis of serous membranes of abdominal cavity and lungs.

Female genital tuberculosis cases with distinct clinical symptoms: Four case reports

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Genital TB (GTB) is a form of extrapulmonary TB that occurs more frequently in women, in whom it classically presents in association with menstrual irregularity, pregnancy loss and short and long-term sequelae especially infertility in infected women. Patients with GTB are usually young women diagnosed during workup for infertility. GTB is rare in postmenopausal women and responsible for only approximately 1% of postmenopausal bleeding. In this study, we aimed to evaluate the laboratory, clinical and demographic characteristics of female GTB cases. We presented four female GTB cases with distinct clinical symptoms. All patients have no history of TB, and no acid-fast bacilli were seen in smears prepared from the clinical materials of the patients. Histopathological examinations revealed granulomatous inflammation in all patients. In the light of the clinical features of these cases we aimed to emphasize that, female GTB must be taken into account in the patients with different clinical symptoms like postmenopausal bleeding, menometrorrhagia, infertility, and menstrual irregularities. We believe that these symptoms will be helpful for the diagnosis and treatment of female GTB.

Breast tuberculosis: clinical spectrum, diagnostic dilemmas and management

Background: Tuberculosis breast is a less known form of extrapulmonary tuberculosis. It poses diagnostic difficulties and confused with breast carcinoma and pyogenic abscess. Objective of the study was to determine the varied presentations of breast tuberculosis, diagnostic difficulties and surgical treatments.Methods: Study was conducted in Department of Surgery at Shri Guru Ram Rai Institute of Health and Medical Sciences, Dehradun, Uttarakhand, India. 651 patients with breast diseases over two years from September 2015- August 2017 were seen at the institution out of which 31 clinically diagnosed patients of breast tuberculosis, confirmed by laboratory work-up, were included in this study. Information regarding demographic details, clinical presentation, cytology, histopathology and management was noted.Results: All patients were females with mean age of 32.5years and out of them 15(48.38%) patients were having breast abscess, 10(32.25%) presented with lump breast and 6(19.35%) with lump with multiple draining sinuses and scars. 27(87.1%) patients had primary breast tuberculosis. Histopathology and TB-PCR reliably helped in diagnosing the disease.Conclusions: The presentation of breast TB is variable, and diagnosis is usually delayed. It should always be kept in mind as differential diagnosis of breast lump and pyogenic abscess. The disease can be diagnosed through pathological tests and a high suspicion. The definite treatment is adequate anti-tuberculosis chemotherapy and surgical excision or drainage especially in recurrent abscesses.

ИСПОЛЬЗОВАНИЕ УСКОРЕННЫХ МЕТОДОВ ВЫЯВЛЕНИЯ ВНЕЛЁГОЧНОГО ТУБЕРКУЛЁЗА С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ

Objective: To evaluate modern diagnostic methods in identifying extrapulmonary forms of tuberculosis (EPT) with drug resistance. Methods: To examine the time limits and identification of circumstances and diagnostics in EPT considered TB-06 registration forms for 2017, № 003/U (case history) of the 56 primary diagnosed patients registered for 2017-2018 in the National Center for Phthisiology. Results: The incidence of EPT in Kyrgyzstan in 2017 was 23.9 per 100 thousand of the population. According to TB-06 forms, extrapulmonary tuberculosis is only 1650 cases. 862 sowings were carried out, of which 503 were negative (58%). Positive results of sowings were 359 (42%). In 333 cases, a drug sensitivity test was performed: resistant forms were 192 (57.6%) and sensitive – 141 (42.4%) cases. Conclusion: From modern methods noted the high use of BactecMGIT and molecular genetic methods of research, which shortens the diagnosis time and promotes to the timely start of the treatment process. Keywords: Tuberculosis, extrapulmonary, bones and joints, urogenital, peripheral lymph nodes, abdominal, multiple drug resistance.

Pediatric cutaneous tuberculosis: Indian scenario

Burden of tuberculosis still persists in developing countries despite major advances in its treatment strategies. Cutaneous tuberculosis which is a form of extra-pulmonary tuberculosis is seen in a small but significant subset of patients visiting dermatology outpatient services. Cutaneous tuberculosis is characterized by a spectrum of multiple distinct clinical and histopathology presentations. A significant proportion of patients with cutaneous tuberculosis are seen in paediatric age group. Clinical features in children remain mostly the same as that in adults with cutaneous tuberculosis. However, systemic and lymph node involvement and incidence of disseminated disease is observed more commonly in paediatric age group . Awareness among clinicians of the clinical manifestations of cutaneous tuberculosis is of paramount importance for early diagnosis and management of cases with paediatric cutaneous tuberculosis. This would significantly prevent morbidity and complications of the disease . This review aims to discuss the epidemiology, clinical and histopathological features, diagnosis, differential diagnosis and treatment options in children with tuberculosis, especially in the Indian context.

Breast tuberculosis: a report of five cases

BackgroundBreast tuberculosis is a rare form of extrapulmonary tuberculosis with clinical and radiological misleading presentations. We report herein a retrospective study of clinicopathological features of five cases of breast tuberculosis collected at Hassan II University Hospital of Fès, Morocco, a country where tuberculosis is endemic.Case presentationThe mean age was 40.6 years (range of 21–59 years). Two patients presented with abscessed lesions, and three cases presented with breast lumps with a suspicion of malignancy on imaging techniques. The diagnosis has been made on histological specimens (3 biopsy specimens, 1 excisional biopsy, and 1 lumpectomy). All patients have been successfully treated after the completion of the standard antibiotherapy.ConclusionsOur current study shows that the breast is rarely affected by tuberculosis even in endemic area. The clinical presentation is often misleading, and the histopathological analysis constitutes a valuable diagnostic tool. The prognosis of breast tuberculosis is good after treatment by a standard antibiotherapy.

COMPARATIVE ANALYSIS OF M. TUBERCULOSIS DETECTION BY DIFFERENT HISTOLOGICAL METHODS IN LUNG TISSUE WITH PULMONARY TUBERCULOMA WITH DIFFERENT ACTIVITY OF SPECIFIC INFLAMMATION

Relevance. Modern histological diagnostics of tuberculosis with using of histobacterioscopy is based on the application of Ziehl-Neelsen method, fluorescent and immunohistochemical methods. And it is mainly used for extrapulmonary forms of tuberculosis. From a scientific and practical standpoint, it is advisable to use these methods in a combined.
 Objective. To conduct a comparative analysis of the detection of M. tuberculosis and their antigens by various histological methods in pulmonary tissue with tuberculoma at different activities of a specific inflammatory process.
 Materials and methods. The material for the study was 34 cases of resected parts of the lungs with tuberculoma, two groups were formed: the main group – 19 cases with a high degree of activity of specific inflammation; the comparison group – 15 cases with moderately or low activity. Ziehl-Neelsen staining, fluorescent and immunohistochemical methods were applied. The number of infected cells and extracellular bacilli was determined according to the working gradation: rarely (1-5), moderate (6-15), many (more than 16) bacteria in the field of view of the microscope. At the immunohistochemical examination it was determined the type and relative number of cells with clear positive results.
 Results. All methods of histological diagnosis revealed a free located MBT in the necrotic nucleus and capsule of tuberculoma, and in alveolar spaces at a distance. The greatest number of free located mycobacteria was detected with using fluorescent method and immunohistochemical examination. The Ziehl-Neelsen showed a significant predominance of observations of a moderate amount of infected alveolar macrophages in the main group and a small number of infected macrophages in a group with a moderately or low activity of the inflammatory process (p<0,01). At the progression of tuberculosis, a large number of macrophages with a positive staining to MBT antigens (p<0,001) was more often detected. Highest indicators of diagnostic standards are established for fluorescent and immunohistochemical methods.
 Conclusion. A combined histological study provided the most complete data on the presence, localization and distribution in the affected tissue of both whole structures MBTs and their antigens at the different activity of specific inflammation. Immunohistochemical study showed that the accumulation of MBT antigens is observed in different types of macrophages and monocytes cells.

HLA DRB1 polymorphism and risk of HIV/tuberculosis co-infection.

In the research data on the study of interconnection between polymorphism of HLA DRB1 genes and the risk of HIV infection and co-infection and HIV/tuberculosis are presented.The cohort of observation was HIV-infected individuals with different clinical stages aged from 24 to 58 years, average age being 38 years. 90 patients (89.2%) received HAART.There were 32 (31.4%) HIV-infected patients with manifestations of tuberculosis, 70 (68.6%) HIV patients without manifestations of tu­ber­culosis. Among the cohort of HIV-infected patients with manifestations of tuberculosis, pulmonary forms of tuberculosis was in 32 (100%), of which extrapulmonary forms of tuberculosis were in 12 (37.5%) patients. The majority of cases of tuberculosis occurred in HIV-infected patients in the IV clinical stage. Among HIV-infected patients, the following alleles of the HLA gene DRB1 *01 (10%) *04 (10%) *07 (13%), *11 (15%), *13 (13%), *15 (10%) occurred more often, HLA DRB1 *03 *08 *09 *10, *12, *14, *16, * 17, *18 were rarely found (1-7%). Similar distributions of DRB1 genes were noted among residents of the region with the dominance of HLA DRB1 *01 *04 *07 *11 *13 and *15. With the presence of alleles of the locus DRB1 *13, DRB1 *03 and DRB1 *08, the greatest probability of co-infection of tuberculosis was observed in HIV-infected patients. The risk of tuberculosis is by 2 times higher with a significant difference in HIV-infected patients with DRB1 *13 locus alleles, DRB1 *03 – by 4.4 times and DRB1 *08 – by 5.4 times. Significant chances of tuberculosis occurrence are higher – by 2.6 times in HIV-infected patients with DRB1 *13 locus alleles, DRB1 *03 – by 5.1 times and DRB1 *08 – by 6.4 times. Thus, the variability of the HLA DRB1 locus alleles may play a predisposing or protective role in the occurrence of tuberculosis in HIV-infected patients.

Characteristics and surgical outcomes of tuberculous meningitis and of tuberculous spondylitis in pediatric patients at Dr. Hasan Sadikin Hospital, Bandung: A single center experience

Abstract Introduction Tuberculous meningitis (TBM) and tuberculous spondylitis (TBS) are the form of extra-pulmonary tuberculosis. Material and method A retrospective cohort study was conducted among children with TBM (2009–2014) and TBS (2004–2014) who were treated in our center; Department of Child Health, Department Neurosurgery and Department Orthopedics. Results Of 123 children diagnosed with TBM (53) and TBS (70); based on modified British Medical Research Council: Stage I (3 cases), Stage IIa (3 cases), Stage IIb (23 cases), Stage III (24 cases). TBM developed hydrocephalus: 36 cases performed ventriculoperitoneal shunt and 17 cases external ventricular drainage. In TBM: 9.4% (5/53) had vegetative state and mortality rate was 20.8% (11/53). TBM Hospital discharge correlated with Glasgow coma scale preoperation (p Conclusions The surgical outcomes of both TBM and TBS still poor in many ways. Improving TB outcomes as implementation of the End TB Strategy program at 2030 remain our homework.

Extrapulmonary TB in Sohag Governorate: Study of 1,611 Cases

SESSION TITLE: Tuberculosis SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: To evaluate the clinical presentation and treatment outcomes in a retrospective& prospective study of extrapulmonary tuberculosis (EPTB) cases in Sohag Governorate. METHODS: 1611 cases of EPTB were included in the study. Data gathered included demographic data, site of disease, case category, treatment regimen, bacteriological, radiological, and histopathological status, and treatment outcome. RESULTS: There were 1611 patients for analysis. Approximately 51% of patients were aged between 20-39 years, and 35.8 % were male. 510 cases (31.7%%) lived in urban areas and 1101 (68.3%), in rural areas. New patients comprised 93.5% of cases. The most common form of EPTB was observed to be lymph node tuberculosis (39%);followed by pleural tuberculosis (22%), skeletal (19%), genitourinary (6.5%), and CNS (2.5%). EPTB was significantly higher in female compared with male (p<0.001). Among EPTB patients, treatment Completion was 77.7%%; remaining outcomes were 18.9% default, 0.7% failure, 1.4% death, 0.9 relapse and 0.7% transfer. Rate of defaulted from treatment was significantly higher in female compared with male,& in rural compared with urban areas (24.2%,vs 9.5% & 23.6%vs 8.8%, respectively, p<0.03). The proportion of completed treatment differ significantly between the urban & rural patients (87.1%, versus 73.4%, p<0.001). CONCLUSIONS: We conclude that EPTB is very common in early adulthood, female & rural areas in Sohag Governorate, where social conditions are poor. Lymph nodes the most common localization. Defaulted treatment was significantly higher in female patients & rural areas. The significant number of defaulted patients demands that measures be adapted for the treatment of these patients. CLINICAL IMPLICATIONS: EPT still remains as a significant morbidity and mortality reason in lower income populations and developing countries, so Early diagnosis and initiation of appropriate treatment are the keys for reducing morbidity and mortality in patients with EPT, particularly in the cases of older ages. DISCLOSURE: The following authors have nothing to disclose: Hamdy Mohammadien, Azza Mahmoud Ahmad, Ayman Mohmoud Abdel-Ghaffar No Product/Research Disclosure Information

Role of M Cells in Human Mucosal Immunity to Mycobacterium tuberculosis

BackgroundMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a bacterial pathogen that infects roughly one-third of the worldÕs population and causes 1–2 million deaths per year. The current paradigm is that phagocytosis of Mtb by patrolling alveolar macrophages initiates Mtb infection. While this model can account for pulmonary TB, it does not adequately explain the occurrence of extrapulmonary forms of TB that manifest in the absence of obvious lung involvement, such as tuberculous cervical lymphadenitis, also known as scrofula. We hypothesized that specialized epithelial cells called microfold cells (M cells) may be an alternate portal of entry for Mtb. Previously we demonstrated that Mtb is able to transcytose across an epithelial barrier in an M cell dependent manner and that M cell mediated transcytosis is vital for Mtb pathogenesis in a mouse model of tuberculosis.MethodsWe used an in vitro M-cell mediated translocation assay and a Mtb mutant lacking a key virulence factor, ESAT6. We used biochemistry and genetics to identify a novel receptor for ESAT6. We also developed a novel explanted human adenoid Mtb infection model to study mucosal immunity.ResultsWe now demonstrate that the Mtb virulence factor ESAT6 is necessary and sufficient to mediate binding and transcytosis by M cells in vitro and in vivo, and that uptake of Mtb by M cells requires a unique cell surface ESAT6 receptor. We developed a novel explanted human adenoid model of M cell biology and demonstrate rapid Mtb transcytosis by primary human tissue within 60–120 minutes. Using flow cytometry we find that Mtb is first ingested by M cells and then after transcytosis, by tissue resident antigen-presenting cells. Explanted adenoids from 10 independent donors display a wide range of Mtb uptake.ConclusionWe conclude that Mtb ESAT6 is necessary for Mtb uptake by M-cells and that binding and transcytosis require a host receptor. Because explanted adenoids display a wide range of Mtb uptake, M cell mediated transcytosis may confer differential susceptibility to scrofula and disseminated disease. These findings are significant as M cells could potentially serve as the basis for novel therapeutic targets against primary Mtb infection.Disclosures All authors: No reported disclosures.

Association of IFNG gene polymorphisms with pulmonary tuberculosis but not with spinal tuberculosis in a Chinese Han population

Spinal tuberculosis (STB) is an extrapulmonary form of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), which accounts for around 2% of all TB cases and can lead to spine degeneration. It is widely accepted that host genetic factors participate in the pathogenesis of active TB, but the factors controlling which TB form will manifest after Mtb infection remain unknown. We hypothesized that a genetic difference may exist between the development of STB and pulmonary tuberculosis (PTB). Here, three single nucleotide polymorphisms (SNPs) in the IFNG gene (rs2069718), IRGM gene (rs10065172), and MBL2 gene (rs11003125) were genotyped among 183 PTB patients, 177 STB patients, and 360 healthy controls from the Chinese Han population. We found that rs2069718 genotypes were significantly associated with PTB (TT, p = 0.007; CT, p = 0.008) but not STB, and the TT genotype (p = 0.046) of rs2069718 were less common in PTB than in STB. In contrast, neither PTB nor STB were found to be associated with rs10065172 and rs11003125. Overall, we found a difference in the rs2069718 genetic distribution between the STB and PTB patients in a Chinese Han population. The rs2069718 TT genotype was associated with a protective role in PTB but not STB development during active Mtb infection.