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Background Tuberculosis (TB) is global public health problem and up to 25% of TB cases present extrapulmonary involvement. The incidence of extrapulmonary tuberculosis (EPTB) is increased worldwide. Our study aimed to give an update on the epidemiology, current trends of EPTB from 2000 to 2017 and to predict future trajectories of EPTB up to 2030 in Monastir, Tunisia. Methods We performed an observational study from 2000 to 2017. Data were collected by the regional direction of primary health care. Incidence was estimated by the crude incidence rate (CIR). Poisson regression model was used to calculate the slope 'b' in order to describe trends and was performed to estimate incidence projection for 2030. Data were verified and analyzed using IBM SPSS Statistics version 22.0 software. Results During 18 years, 997 cases of TB were declared in Monastir. Almost 51% (n = 509) were EPTB. Sex ratio was 1.68. The main EPTB forms were lymph nodes in 234 (23.5%) cases, followed by pleural TB in 35 (3.5%) cases and bone and joints in 31 (3.1%) cases. CIR was 5.62/100,000 inhabitants (inh) for EPTB with a highest incidence in patients aged 60 years and above. A positive trend was showed for EPTB with a (b = 0.05; p Conclusions Despite the availability of a treatment and knowledge on prevention measures, EPTB remains a public health problem. Thus, investigating and identifying patients at higher risk is needed in order to improve its management. Key messages Updated epidemiology is important for healthcare experts to improve planning policies attributed to EPTB. Our results are a tool for decision-makers to assess the efficiency of TB control programs.

Background. Infants and toddlers often present with disseminated and lymph node tuberculosis, in which Mycobacterium tuberculosis (Mtb) is predominantly intracellular. Linezolid, used to treat tuberculosis in adults, has not been formally studied in infants. Infants clear linezolid 5 times faster than adults and achieve lower 0- to 24-hour area under the concentration-time curves (AUC0–24). Methods. To mimic intracellular disease, we infected human-derived THP-1 macrophages with Mtb and inoculated hollow fiber systems. We performed dose-effect and dose-scheduling studies in which we recapitulated the linezolid half-life of 3 hours encountered in infants. Repetitive sampling for linezolid pharmacokinetics, Mtb intracellular burden, viable monocyte count, and RNA sequencing reads were performed up to 28 days. Results. The linezolid extracellular half-life was 2.64 ± 0.38 hours, whereas intracellular half-life was 8.93 ± 1.30 hours (r2 = 0.89). Linezolid efficacy was linked to the AUC0–24 to minimum inhibitory concentration (MIC) ratio (r2 = 0.98). The exposure associated with maximal Mtb kill was an AUC0–24/MIC of 23.37 ± 1.16. We identified a 414-gene transcript on exposure to toxic linezolid doses. The largest number of genes mapped to ribosomal proteins, a signature hitherto not associated with linezolid toxicity. The second-largest number of differentially expressed genes mapped to mitochondrial enzyme inhibition. Linezolid AUC0–24 best explained the mitochondrial gene inhibition, with 50% inhibition at 94 mg × hour/L (highest r2 = 0.98). Conclusions. We identified the linezolid AUC0–24/MIC target for optimal efficacy against pediatric intracellular tuberculosis, and an AUC0–24 threshold associated with mitochondrial inhibition. These constitute a therapeutic window to be targeted for optimal linezolid doses in children with tuberculosis.

Background Lymph node tuberculosis (LNTB) represents the most common site of extrapulmonary tuberculosis. Among children, due to non-specific clinical features, the diagnosis is often delayed. We aimed to compare the clinical, therapeutic and evolutionary features of LNTB between adults and children. Methods We conducted a retrospective study including patients hospitalized for LNTB in the infectious diseases and pediatric department between 1993 and 2018. Children aged ≤18 years were included. Results Overall, we encountered 231 cases of LNTB. There were 40 children (17.3%) with a mean age of 11±4 years and 191 adults (82.7%) with a mean age of 42±16 years. As to gender, females were more affected (adults: 67% vs children: 70%), with no significant difference (p >0.05). A family history of tuberculosis was significantly more frequent among children (20% vs 6.3%; p=0.01). Raw milk consumption (38.2% vs 30%; p >0.05) and close contact with animals (29.8% vs 35%; p >0.05) were noted among both adults and children. Fever (53.4% vs 32.5%; p=0.01), night sweats (35.8% vs 10%; p=0.001), loss of appetite (38.2% vs 17.5%; p=0.01) and weight loss (35.1% vs 15%; p=0.01) were significantly more frequent among adults. Tuberculin skin test was positive in 75.8% of the cases among adults and in 86.2% of the cases among children (p >0.05). Multifocal tuberculosis was significantly more frequent among adults (23.8% vs 5.7%; p=0.01). Antitubercular therapy was prescribed for a mean duration of 10±4 months among adults and for 9±3 months among children, with no significant difference (p >0.05). Side effects of antitubercular drugs were more frequent among adults (33% vs 10.3%), with a significant difference (p=0.004). Comparison of the disease evolution showed no significant difference between adults and children, regarding recovery (94.8% vs 90%), relapse (5.2% vs 5%) and death (0.5% vs 2.5%). Conclusion The clinical presentation of LNTB among children was less common and misleading. A family history of tuberculosis and a high index of suspicion might shorten the diagnostic delay. Disclosures All Authors: No reported disclosures

Forty-three patients with miliary tuberculosis were evaluated for diagnostic usefulness of enzyme-linked immunospot (ELISPOT) assay. Among noninvasive rapid tests available within 3-5 days, ELISPOT had the highest sensitivity (93%), compared with acid-fast bacilli stain (sputum, 32% and bronchoalveolar lavage, 7%), Mycobacterium tuberculosis polymerase chain reaction (sputum, 53% and bronchoalveolar lavage, 36%), and tuberculin skin test (22%). In comparison with 44 patients with lymph node tuberculosis, the sensitivity of the ELISPOT assay in patients with miliary tuberculosis (93%) was as high as in those with lymph node tuberculosis (95%, P = .63), whereas the sensitivity of the tuberculin skin test was substantially lower in patients with miliary tuberculosis (22%) than in those with lymph node tuberculosis (73%, P < .001).

Host-pathogen interactions in tuberculosis should be studied at the disease site because Mycobacterium tuberculosis is predominately contained in local tissue lesions. Although M. tuberculosis infection involves different clinical forms of tuberculosis, such as pulmonary tuberculosis, pleural tuberculosis, and lymph node tuberculosis, most studies of human tuberculosis are performed using cells from the peripheral blood, which may not provide a proper reflection of the M. tuberculosis-specific immune responses induced at the local site of infection. A very low proportion of M. tuberculosis-specific effector T cells are found in the blood compared with the infected tissue, and thus there may be considerable differences in the cellular immune response and regulatory mechanisms induced in these diverse compartments. In this review, we discuss differences in the immune response at the local site of infection compared with the peripheral circulation. The cell types and immune reactions involved in granuloma formation and maintenance as well as the in situ technologies used to assess local tuberculosis pathogenesis are also described. We need to strengthen and improve the exploratory strategies used to dissect immunopathogenesis in human tuberculosis with the aim to accelerate the implementation of relevant research findings in clinical practice.

Peripheral tuberculous lymphadenitis accounts for ~10% of tuberculosis cases in the United States. Epidemiologic characteristics include a 1.4:1 female-to-male ratio, a peak age range of 30-40 years, and dominant foreign birth, especially East Asian. Patients present with a 1-2 month history of painless swelling of a single group of cervical lymph nodes. Definitive diagnosis is by culture or nucleic amplification of Mycobacterium tuberculosis; demonstration of acid fast bacilli and granulomatous inflammation may be helpful. Excisional biopsy has the highest sensitivity at 80%, but fine-needle aspiration is less invasive and may be useful, especially in immunocompromised hosts and in resource-limited settings. Antimycobacterial therapy remains the cornerstone of treatment, but response is slower than with pulmonary tuberculosis; persistent pain and swelling are common, and paradoxical upgrading reactions may occur in 20% of patients. The role of steroids is controversial. Initial excisional biopsy deserves consideration for both optimal diagnosis and management of the otherwise slow response to therapy.

We describe a 64-year-old woman with chronic sclerosing sialadenitis and dacryoadenitis, which developed during treatment for cervical lymph node tuberculosis. Anti-tuberculosis treatment did not improve the swelling in the lacrimal and submandibular glands, and a biopsy specimen of the lacrimal gland showed inflammation, with abundant lymphoid follicles with fibrosis and granuloma without caseous necrosis. Immunohistological examination of a repeat biopsy specimen showed abundant immunoglobulin (Ig) G4-positive plasma cell infiltration. Corticosteroid therapy improved the salivary gland swelling without reactivation of the tuberculosis. This case suggests that an abnormal immunological reaction to tuberculosis may be one of the etiological candidates for IgG4-related disease.

A case of lymphadenitis caused by Scedosporium apiospermum in a 25-year-old immunocompetent woman had been misdiagnosed as tuberculous lymphadenitis. Clinical response to itraconazole therapy was obtained in 6 months; to our knowledge, this is the first report of lymphadenitis caused by S. apiospermum in humans.

Sir, Tonsillar tuberculosis is a rare presentation of extrapulmonary tuberculosis. Although tuberculosis of the tonsils is nowadays an uncommon finding, tonsillar granulomas are occasionally seen by histopathologists, and can sometimes contain tuberculous organisms. Occasionally, tonsillar tuberculosis may precede the diagnosis of pulmonary tuberculosis.1 We present the case of a 40-year-old patient admitted for evaluation of hoarseness and difficulty in swallowing, firstly diagnosed as recurrent angina. He had also had chronic bilateral cervical lymphadenopathy for the last three years. All preceding investigations were normal. Clinical examination was …

When the body's defences are breached by infection, information about such an event is channelled through the lymphatic system to the lymphoid organs in which immune responses occur. The key participants in these responses are lymphocytes, which populate the lymph nodes, spleen, and mucosal lymphoid tissues. Together with other cells, they form an architecture and cell network that enables coordinated function. The lymph nodes, which are usually superficial, are easily accessible and therefore frequently sampled by clinicians. The findings on such samples are invaluable in the diagnosis, staging, treatment and prognosis of disease. From the 28 895 histology specimens submitted to the Histopathology unit in Harare, Zimbabwe in the period January 1988 to June 1990, we have selected and reviewed all lymphnode biopsy reports. The commonest diseases in the 2194 lymph node specimens submitted were: (a) non specific hyperplasia (33%); (b) tuberculous lymphadenitis (26.7%); (c) metastases (12.4%); (d) Kaposi's sarcoma (9%); (e) lymphomas (7%). The trends for nodal tuberculosis (including hyporeactive tuberculous lymphadenitis), Kaposi's sarcoma, florid follicular hyperplasia and lymphomas are discussed in the context of the increased incidence of HIV-related lymphoadenopathy.

Peripheral tuberculous lymphadenopathy is the commonest form of extrapulmonary tuberculosis. Sixty-seven patients with peripheral tuberculous lymphadenopathy who presented to general surgeons and underwent lymph node biopsy between 1979 and 1989 are reviewed. Fifty-four patients (81 per cent) were of Indian subcontinent ethnic origin and 13 (19 per cent) were of white ethnic origin. The sites most commonly afected were the cervical lymph nodes. Biopsy specimens obtained by open operation were sent for microbiological examination in all but 13 cases, of whom seven were patients of white ethnic origin. Tuberculous lymphadenopathy remains an important differential diagnosis of cervical lymphadenopathy and it is essential that peripheral lymph node biopsies are examined both histologically and microbiologically.

The lymph nodes from 10 cases of histiocytic necrotizing lymphadenitis (HNL), 3 cases of necrotizing lymphadenitis with follicular hyperplasia (NLFH), and 11 cases of various types of lymphadenitis (abscess-forming, tuberculous, Piringer-type, “viral”, and nonspecific lymphadenitides) were comparatively studied. The NLFH, clinically representing a milder form of collagen disease, showed necrotizing lesions similar to those of HNL but with follicular hyperplasia, more plasma cells, and scattered neutrophils; the latter features closely resemble those of some lymph nodes in systemic lupus erythematosus (SLE). Ultrastructurally, HNL and NLFH both showed coagul-ative necroses of individual lymphocytes, the macrophages with large cellular debris, prominent immunoblasts, and cytoplasmic inclusions such as frequent tubuloreticular structures (TRS) and “intracytoplasmic rodlets” (ICR). The necrotic modality in abscess-forming and tuberculous lymphadenitides was different and the macrophages contained smaller debris. The immunoblasts were less prominent in “viral” lymphadenitis and much less in the others. While TRS were present in may cases of other lymphadenitides as well, they were positive in a much smaller number of cells only; the ICR were found exclusively in HNL and NLFH. These findings suggest a relationship between HNL and NLFH; they may form a spectrum of hyperimmune reaction that includes fSLE as an extreme manifestation.