Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Positive Culture and Prognosis in Patients With Sepsis: A Prospective Cohort Study.

PURPOSE: To analyze the prognostic role of positive cultures in patients with sepsis. METHODS: A prospective cohort study in a tertiary referral hospital in Medellín, Colombia. Adults older than 18 years of age with a bacterial infection diagnosis according to Centers for Disease Control criteria and sepsis (evidence of organ dysfunction) were included. A logistic regression model was used to determine the association between positive cultures and hospital mortality, and a Cox regression with a competing risk modeling approach was used to determine the association between positive cultures and hospital stay as well as secondary infections. RESULTS: Overall, 408 patients had positive cultures, of which 257 were blood culture, and 153 had negative cultures. Patients with positive cultures had a lower risk of mortality (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.27-0.68), but this association was not maintained after adjusting for confounding factors (OR, 0.56; 95% CI, 0.31-1.01). No association was found with the hospital stay (adjusted subhazard ratio [SHR], 1.06; 95% CI, 0.83-1.35). There was no association between positive cultures and the presence of secondary infections (adjusted SHR, 0.99; 95% CI, 0.58-1.71). CONCLUSION: Positive cultures are not associated with prognosis in patients with sepsis.

Follow-up results of isoniazid chemoprophylaxis during biological therapy in Colombia.

The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. The aim of this study was to present the follow-up results for isoniazid (INH) chemoprophylaxis in patients receiving different biological therapies. In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between 2 and 9 months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. A total of 221 patients, 122 females (55.2 %), with a mean age of 46.8 ± 11.3 years (16-74) were enrolled. LTBI was identified in 218 patients (98.7 %), all of whom received INH chemoprophylaxis. Seven patients (3.2 %) developed active tuberculosis, and 32 (17.2 %) patients developed intolerance or toxicity related to INH. Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivation in individuals with LTBI, but toxicity must be monitored during follow-up.

Tuberculous sternal osteomyelitis.

A 32-year-old female patient with systemic lupus erythematosus presented with 1 month of nocturnal subjective fevers, night sweats, poor appetite, malaise, 8-kg weight loss, and a 6-cm painful sternal mass. She had normal vital signs with a physical examination notable only for the presence of a fluctuating sternal mass. A computed tomographic scan of the thorax showed a 67 × 32 × 27-mm sternal mass associated with severe sternal osteomyelitis (Fig. 1); then a surgical drainage was performed, and abundant caseous material was removed, leaving a penrose drain (Fig. 2). Histologic examination of the bone tissue revealed extensive necrosis and granulomas with multinucleated giant cells. The bone, secretion, and soft tissue were negative for acid-fast bacillae on Ziehl-Neelsen stain; but culture grew Mycobacterioum tuberculosis, and she was started on 4 first-line antituberculosis medications, showing rapid symptomatic improvement, and was discharged 4 weeks after admission (Fig. 3).

[Effect of opportunistic infections on the frequency of leukocyte subpopulations from type-1 human immunodeficiency virus infected individuals]. / Efecto de las infecciones oportunistas sobre las subpoblaciones de leucocitos en individuos infectados con el virus de inmunodeficiencia humana tipo 1.

INTRODUCTION: The presence of opportunistic infections in patients with acquired immunodeficiency syndrome favors the progression of HIV-1 infection. Despite the key role that several leukocyte subpopulations exhibit during the anti-infectious response, few studies have focused on the role of these cells in HIV-1-infected patients with active opportunistic infections. OBJECTIVE: The quantity of several innate and adaptive cell subpopulations was evaluated in whole peripheral blood of HIV-1-infected patients, with and without a history of opportunistic infections. MATERIALS AND METHODS: The absolute number of each leukocyte subpopulation was evaluated by flow cytometry, and for each cell subpopulation, this number was correlated with viral load, CD4+ T cell count and the expression of activation markers on CD4+ and CD8+ T lymphocytes. RESULTS: Chronically HIV-1 infected patients exhibited a quantitative deficiency in several leukocyte subpopulations; this effect was more pronounced in individuals suffering an active opportunistic infection. This indicated that the coinfection by HIV-1 and opportunistic microorganisms potentiated the immunodeficiency by reducing significantly the frequency of different subpopulations of leukocytes. CONCLUSIONS: This finding underlines the importance of an early diagnose of HIV-1 infection, and the need for the rational use of antiretroviral medications to avoid the development of opportunistic infections. In addition, it points to the necessity of developing immunotherapy strategies for HIV-1-infected patients in order to re-establish the immune competence.

Tuberculous Lymphadenitis and Parotitis.

Tuberculous lymphadenitis is the most common extrapulmonary manifestation of disseminated tuberculosis (TB). It is considered to be the local manifestation of the systemic disease that has disseminated to local lymph nodes, but a high index of suspicion is needed for the diagnosis, because there are several infectious and noninfectious diseases that can mimic the same clinical picture. In recent years, different diagnostic methods have been introduced, including fine-needle aspiration cytology, which has emerged as a simple outpatient diagnostic procedure that replaced the complete excisional node biopsy, and a number of molecular methods which have greatly improved diagnostic accuracy. This chapter covers the most actual knowledge in terms of epidemiology, clinical manifestations, pathogenesis, and treatment and emphasizes current trends in diagnosis of tuberculous lymphadenitis. TB parotid gland involvement is extremely rare, even in countries in which TB is endemic. Because of the clinical similarity, parotid malignancy and other forms of parotid inflammatory disease always take priority over the rarely encountered TB parotitis when it comes to differential diagnosis. As a result, clinicians often fail to make a timely diagnosis of TB parotitis when facing a patient with a slowly growing parotid lump. This chapter highlights the most important features of this uncommon disease.

Rhinoschleroma.

A 39 year-old man came to our institution because of a five-year history of a progressive painful growing mass on his left nostril, which cause airway obstruction with ulceration. Because of a suspicion of malignancy, surgery (mass resection and subtotal nasal reconstruction) was performed. Histologic samples ruled out malignancy, and tissue cultures for fungus and mycobacteria were negative, but regular aerobic cultures were positive for Klebsiella rhinoscleromatis. The patient was given a six-month regimen of ciprofloxacin, and a dramatic improvement was observed.