Current Research and Future Development in Leprosy and Tuberculosis control

INTRODUCTIONDuring recent years we have witnessed a burst of activity in leprosy research. By definition, leprosy is an infectious disease, the causative organism being cobacterium leprae. The leprosy bacillus is virtually non-toxic and may occur in large amounts in tissues with only moderate clinical symptoms. In fact, leprosy may to a great extent be regarded as an immunological disease since most symptoms arc due to immune reactions against antigens liberated from the leprosy bacilli. During recent years leprosy research has been centred, to a great extent, around studies of immunological phenomena since a better understanding of basic immunological mechanisms would provide a rational basis for improved treatment of patients with established disease, and for advancements in our understanding of the epidemiology of leprosy and its control

Anti-mycobacterial recall responses differentiate female patients with genital tuberculosis from patients with other gynecological problems

Background: Female Genital Tuberculosis (FGTB) is one form of extra pulmonary tuberculosis affecting the female reproductive organs, most commonly the fallopian tubes and the endometrium. It affects young women aged between 20 and 40 years of age and is an important cause of infertility. It often occurs as a secondary complication following pulmonary tuberculosis. Diagnosis depends mainly on clinical suspicion in countries where facilities for mycobacterial culture and histopathology are unavailable. Even in places where these facilities exist, diagnosis still remains difficult because of the lower sensitivity and specificity of the methods as well as the invasive procedure of acquiring biopsy specimens. Objective: To explore the immunological profiles of female genital tuberculosis (FGTB) patients in response to mycobacterial antigens. Methods: Twenty-five clinically suspected cases of FGTB and 12 control subjects who came to the Black Lion hospital for unrelated gynecological problems were included in the study. Peripheral blood samples were collected from each subject. Plasma was separated by centrifugation and PBMC were isolated over ficoll-hypaque and stimulated in vitro with mycobacterial antigens to examine their proliferative response as incorporation of tritiated thymidine using a β-counter. HIV status and total IgG-, IgA- and IgM- antibody levels were determined by ELISA tests.Results: In vitro recall responses to M. tuberculosis antigens (PPD and BCG sonicate) as well as plasma levels of IgGIgA- and IgM-antibodies to MPT59 showed statistically significant differences between the patients and the controls (

Major bleeding complications and persistence with oral anticoagulation in non-valvular atrial fibrillation:Contemporary findings in real-life Danish patients

Background The nonvitamin K antagonist oral anticoagulants have recently become available as an alternative to warfarin as stroke prophylaxis in atrial fibrillation, but data on real‐life patient experience, including bleeding risk, are lacking. Our objective was to compare major bleeding events and nonpersistence between the nonvitamin K antagonist oral anticoagulant apixaban and other nonvitamin K antagonist oral anticoagulants (dabigatran and rivaroxaban) and warfarin in a contemporary, nation‐wide cohort of patients with nonvalvular atrial fibrillation. Methods and Results Of 54 321 patients (median age, 73 years; 56% male; mean CHA 2 DS 2 ‐ VAS c score, 2.9), 7963, 6715, 15 413, and 24 230 patients initiated apixaban, rivaroxaban, dabigatran, and warfarin, respectively. Apixaban and rivaroxaban initiators were older, less often male, with higher HAS ‐ BLED and CHA 2 DS 2 ‐ VAS c scores compared with dabigatran and warfarin initiators. A total of 2418 patients (4.5%) experienced a major bleeding event over all available follow‐up. In this period, rivaroxaban (hazard ratio [ HR ] [95% CI], 1.49 [1.27–1.77]), dabigatran ( HR , 1.17 [1.00–1.38]), and warfarin ( HR , 1.23 [1.05–1.43]) users were significantly more likely to bleed than apixaban users. Findings were similar when restricted to the first 30 days after OAC initiation. Risk of nonpersistence was higher for dabigatran ( HR , 1.45 [1.33–1.59]) and warfarin initiators ( HR , 1.22 [1.12–1.33]), but not for rivaroxaban initiators ( HR , 1.07 [0.96–1.20]) compared with apixaban initiators. Conclusions In a real‐world cohort of nonvalvular atrial fibrillation patients, apixaban had a lower adjusted major bleeding risk compared with rivaroxaban, dabigatran, and warfarin. Apixaban had a lower risk of nonpersistence compared with dabigatran and warfarin and similar risk compared with rivaroxaban. </jats:sec

The Role of Properdin in Zymosan-and Escherichia coli-Induced Complement Activation

Properdin is well known as an enhancer of the alternative complement amplification loop when C3 is activated, whereas its role as a recognition molecule of exogenous pathogen-associated molecular patterns and initiator of complement activation is less understood. We therefore studied the role of properdin in activation of complement in normal human serum by zymosan and various Escherichia coli strains. In ELISA, microtiter plates coated with zymosan induced efficient complement activation with deposition of C4b and terminal complement complex on the solid phase. Virtually no deposition of C4b or terminal complement complex was observed with mannose-binding lectin (MBL)-deficient serum. Reconstitution with purified MBL showed distinct activation in both readouts. In ELISA, normal human serum-induced deposition of properdin by zymosan was abolished by the C3-inhibiting peptide compstatin. Flow cytometry was used to further explore whether properdin acts as an initial recognition molecule reacting directly with zymosan and three E. coli strains. Experiments reported by other authors were made with EGTA Mg 2+ buffer, permitting autoactivation of C3. We found inhibition by compstatin on these substrates, indicating that properdin deposition depended on initial C3b deposition followed by properdin in a second step. Properdin released from human polymorphonuclear cells stimulated with PMA did not bind to zymosan or E. coli, but when incubated in properdin-depleted serum this form of properdin bound efficiently to both substrates in a strictly C3-dependent manner, as the binding was abolished by compstatin. Collectively, these data indicate that properdin in serum as well as polymorphonuclear-released properdin is unable to bind and initiate direct alternative pathway activation on these substrates

Evidence for waning of latency in a cohort study of tuberculosis

<p>Abstract</p> <p>Background</p> <p>To investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age.</p> <p>Methods</p> <p>Cohort analysis of data for the separate ten year birth cohorts of 1876-1885 to 1959-1968 obtained from Statistics Norway and the National Tuberculosis Registry. These data were used to calculate the rates and the changes in the rates of bacillary (or active) tuberculosis. Data on bacillary tuberculosis for adult (20+) age groups were obtained from the National Tuberculosis Registry and Statistics Norway from 1946 to 1974. Most cases during this period arose due to reactivation of remote infection. Participants in this part of the analysis were all reported active tuberculosis cases in Norway from 1946 to 1974 as recorded in the National Tuberculosis Registry.</p> <p>Results</p> <p>Tuberculosis decreased at a relatively steady rate when following individual birth cohorts, but with a tendency of slower decline as time passed since infection. A mean estimate of this rate of decline was 57% in a 10 year period.</p> <p>Conclusions</p> <p>The risk of reactivation of latent tuberculosis decreases with age. This decline may reflect the rate at which latent tuberculosis is eliminated from a population with minimal transmission of tubercle bacilli. A model for risk of developing active tuberculosis as a function of time since infection shows that the rate at which tuberculosis can be eliminated from a society can be quite substantial if new infections are effectively prevented. The findings clearly indicate that preventative measures against transmission of tuberculosis will be the most effective. These results also suggest that the total population harbouring live tubercle bacilli and consequently the future projection for increased incidence of tuberculosis in the world is probably overestimated.</p