Eradication of tuberculosis seems to be a long way off especially with the growing of drug resistance tuberculosis and HIV co-infection tuberculosis. The gaps in our knowledge and the limited sensitive and specific biomarkers especially for latent tuberculosis infection make it defensive. The fate of tuberculosis treatment ranged from cured to failure and there are many risk factors involved apart from the immune state and age. Therefore, this review focuses on the understanding of tuberculosis disease progression and the associated risk factors of the events in the disease progression. This article also highlights the diagnostic and predictive marker that may predict the disease progression. In addition, this review highlights the potential use of rifabutin in tuberculosis treatment regimen. It is hoped that this review could give an overview on future directions of research in tuberculosis.
Tuberculosis (TB) remains a very common disease in most of the low- and middle-income countries. As a result of high disease burden, TB control measures in these countries are usually concentrated on intensifying active disease case-finding and early treatment of infectious TB. On the contrary, in countries with low disease burden, the focus is on contact investigation to identify latently infected individuals and prophylactically treating them to prevent disease reactivation and transmission. These two strategies are deemed important for the effective TB control. Nonetheless, WHO cautions that targeted contact investigation and latent TB infection (LTBI) treatment should only be undertaken by countries that have the operational capacity/ resources and have achieved ≥ 85% treatment success rate of active TB. The screening of LTBI is further challenged by the lack of a “gold standard” test to identify and validate individuals with this condition. Tuberculin skin test (TST) is still the preferred investigation as it is cheap, widely available and validated in many trials. The sensitivity and specificity of the newer test—interferon gamma release assay (IGRA) for LTBI screening has been encouraging in low prevalence countries. However, the evidence supporting such usage remains uncertain in high burden settings. Diagnosis of LTBI should adhere to the strict criteria outlined in the guidelines to avoid misdiagnosing active TB as LTBI. The treatment of the latter involved only one or two anti-TB drugs. It has been demonstrated that in the properly conducted contact screening and LTBI treatment, chances of the emergence of multi-drug-resistant TB is very low.
Tuberculosis in children remains a public heath concern in Malaysia and other developing countries. Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extra pulmonary manifestation of TB. Tuberculous bacilli can reach the liver via hematogenous dissemination through hepatic artery, or by local spread from the gastrointestinal tract via portal vein [1].(Copied from article)
Emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) is one of the reasons why tuberculosis (TB) continues to cause great mortality and morbidity in less-developed countries. The development of rapid diagnostic methods targeting genetic mutations associated with resistance to the anti-tuberculous drugs is essential to fight this deadly pathogen. Isoniazid (INH) has been included in the multidrug regimens for the treatment of drug-susceptible TB for the decades. In the worldwide setting, isoniazid resistance was highly prevalent and was observed in one of every seven TB cases. Since katG315 mutation is highly prevalent, the common mutation in the enzyme essential for the activation of the INH concerned with the mechanism of drug resistance and associated with high level resistance to INH, katG315 mutation was necessary to be identified by molecular method as a molecular determinant of INH resistant Mycobacterium tuberculosis. The prevalence of katG315 mutation in various countries was discussed in this report and a new molecular method for the detection of the mutation was proposed.
Few studies have explored diagnosis delay by tuberculosis (TB) patients and its effects on the rate of infection among their close contacts. A cross-sectional study of the close contacts of 505 newly diagnosed TB patients was conducted in a TB referral centre in Sana'a, Yemen from 2008 to 2010. Only the close contacts of 89 new TB patients agreed to participate and completed the tuberculin skin test (TST). Of the 239 close contacts investigated, 133 (55.6%) had a positive TST result. Index patients were classified as long or short diagnosis delay (above or below the median). There was no significant difference in the number of infected close contacts between long and short delay index patients (Mann-Whitney U-test). A larger sample size, with more incentives for patients to participate and the use of other investigative tools could provide a better picture of the pattern of TB transmission among all contacts.
Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (Mtb), remains a major cause of human death worldwide. Innate immunity provides host defense against Mtb. Phagocytosis, characterized by recognition of Mtb by macrophages and dendritic cells (DCs), is the first step of the innate immune defense mechanism. The recognition of Mtb is mediated by pattern recognition receptors (PRRs), expressed on innate immune cells, including toll-like receptors (TLRs), complement receptors, nucleotide oligomerization domain like receptors, dendritic cell-specific intercellular adhesion molecule grabbing nonintegrin (DC-SIGN), mannose receptors, CD14 receptors, scavenger receptors, and FCγ receptors. Interaction of mycobacterial ligands with PRRs leads macrophages and DCs to secrete selected cytokines, which in turn induce interferon-γ- (IFNγ-) dominated immunity. IFNγ and other cytokines like tumor necrosis factor-α (TNFα) regulate mycobacterial growth, granuloma formation, and initiation of the adaptive immune response to Mtb and finally provide protection to the host. However, Mtb can evade destruction by antimicrobial defense mechanisms of the innate immune system as some components of the system may promote survival of the bacteria in these cells and facilitate pathogenesis. Thus, although innate immunity components generally play a protective role against Mtb, they may also facilitate Mtb survival. The involvement of selected PRRs and cytokines on these seemingly contradictory roles is discussed.
Gallbladder tuberculosis (GT) is an extremely rare condition. This is thought to be due to the protective property of bile against the infection. Clinical and radiological diagnosis of GT is difficult. We describe a case of GT who initially presented to us with jaundice, a right hypochondrial mass and computed tomographic findings suggestive of gallbladder empyema. Diagnosis was made from histopathological examination of the resected gallbladder which revealed epitheloid granulomas with caseating necrosis and presence of Langhan's giant cells. From a literature search and to the best of our knowledge, this is the first GT to be reported in South East Asia.
Two cases of tuberculosis of the thoracic spine with extrapleural extension of paravertebral abscesses, presenting radiologically as cold abscesses away from the spine in the PA chest radiograph, are presented. The radiographic features and response to antitubercular drugs are discussed.
Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.
The records of 141 consecutive patients with proven tuberculosis (TB) were reviewed to examine for changes in their serum proteins, erythrocyte sedimentation rate (ESR) and tuberculin skin test reactivity. Hypoalbuminaemia was present in 73% of patients and hyperglobulinaemia was seen in 92% of patients. ESR showed a negative correlation with the serum albumin level but a positive correlation with the serum globulin level. In the case of pulmonary TB, ESR was higher in patients with radiologically more extensive disease. Tuberculin reactivity was reduced in patients who were older, those with more severe hypoalbuminaemia and those with disseminated TB. KEYWORDS: Albumin, erythrocyte sedimentation rate, globulin, tuberculin reactivity, tuberculosis
Mycobacterium tuberculosis (MTB) is commonly used as a model to study pathogenicity and multiple drug resistance in bacteria. These MTB characteristics are highly dependent on the evolution and phylogeography of the bacterium. In this paper, we describe 15 new genomes of multidrug-resistant MTB (MDRTB) from Malaysia. The assessments and annotations on the genome assemblies suggest that strain differences are due to lineages and horizontal gene transfer during the course of evolution. The genomes show mutations listed in current drug resistance databases and global MTB collections. This genome data will augment existing information available for comparative genomic studies to understand MTB drug resistance mechanisms and evolution.
Molecular typing with IS6110 was applied to Mycobacterium tuberculosis isolates from all parts of Malaysia. The degree of clustering increased with patient age, suggesting that reactivation may contribute to clustering. Identical banding patterns were also obtained for isolates from widely separate regions. Therefore, the use of clustering as a measure of recent transmission must be treated with caution. Strains related to the Beijing family were common in Peninsular Malaysia but were less common in Sabah and Sarawak, while a distinct group of strains comprised nearly 40% of isolates from East Malaysia but such strains were rare in Peninsular Malaysia. Single-copy strains, common in South and Southeastern Asia, constituted nearly 20% of isolates from the peninsula but were virtually absent in East Malaysia. The marked geographical difference in the prevailing strains indicates not only a restricted dissemination of M. tuberculosis but also a considerable degree of stability in the banding patterns.
The most important targets for vaccine development are the proteins that are highly expressed by the microorganisms during infection in-vivo. A number of Mycobacterium tuberculosis (Mtb) proteins are also reported to be expressed in-vivo at different phases of infection. In the present study, we analyzed multiple published databases of gene expression profiles of Mtb in-vivo at different phases of infection in animals and humans and selected 38 proteins that are highly expressed in the active, latent and reactivation phases. We predicted T- and B-cell epitopes from the selected proteins using HLAPred for T-cell epitope prediction and BCEPred combined with ABCPred for B-cell epitope prediction. For each selected proteins, regions containing both T- and B-cell epitopes were identified which might be considered as important candidates for vaccine design against tuberculosis.
Scrotal tuberculosis (TB) is rare. Lack of awareness may lead to a misdiagnosis and/or delayed diagnosis of scrotal TB. Clinicians should have a high suspicion index for scrotal TB when facing a patient with a chronic scrotal lump. Since scrotal TB can be medically cured, biopsy of the scrotal lump for pathology study and/or urine polymerase chain reaction (PCR) analysis for M. tuberculosis should be performed first for rapid diagnostic purposes, and therefore unnecessary surgery may thereby be circumvented.
Matched MeSH terms: Tuberculosis, Male Genital/diagnosis*