Tuberculosis (TB) is a disease associated with inequality, and wise investment of economic resources is considered critical to its control. Panama has recently secured its status as an upper-middle-income country with robust economic growth. However, the prioritisation of resources for TB control remains a major challenge. In this article, we highlight areas that urgently require action to effectively reduce TB burden to minimal levels. Our conclusions suggest the need for fund allocation and a multidisciplinary approach to ensure prompt laboratory diagnosis, treatment assurance and workforce reinforcement, complemented by applied and operational research, development and innovation. PMID:24670562
Tarajia, M; Goodridge, A
Anatomy and mortuary technical staff faces an ever existing risk of contracting an infectious disease, such as Mycobacterium tuberculosis (MTB), when exposed to human remains. The transfer and handling of a corpse expels air from the lungs of the diseased and this aerosolizes the bacilli. It is for this reason that personal protective equipment and work space precautions such as ultraviolet germicidal irradiation is a necessity. In this study, the authors explore the viability of MTB before and after embalming. Briefly, lung tissue samples, both apical and hilar, were obtained from 20 cadavers whose death certificate indicated MTB as cause of death. The first sample was taken before embalming and second set 3 weeks after embalming. Tissue was deposited into sterile specimen containers and transported for analysis which included Mycobacterium growth indicator tube cultures and polymerase chain reaction. Results demonstrated that both the apical and the perihilar sample tested positive prior to embalming, 36 days after death. After three weeks post-embalming none tested positive. The results demonstrated that MTB can remain viable after death for up to 36 days. This viability extends beyond the documented cases and highlights the need for precautionary measures and standard operating procedures in accordance with occupational health and safety guidelines. PMID:24343882
Correia, J C; Steyl, J L; De Villiers, H C
Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB. PMID:24226751
Müller, Romy; Roberts, Charlotte A; Brown, Terence A
Although tuberculosis remains a substantial global threat, the mechanisms that enable mycobacterial persistence and replication within the human host are ill defined. This study represents the first genome-wide expression analysis of Mycobacterium tuberculosis from clinical lung samples, which has enabled the identifi- cation of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal informa- tion from our DNA
Helmy Rachman; Michael Strong; Timo Ulrichs; Leander Grode; Johannes Schuchhardt; Hans Mollenkopf; George A. Kosmiadi; David Eisenberg; Stefan H. E. Kaufmann
BackgroundDefaulting from treatment remains a challenge for most tuberculosis control programmes. It may increase the risk of drug resistance, relapse, death, and prolonged infectiousness. The aim of this study was to determine factors predicting treatment adherence among smear-positive pulmonary tuberculosis patients.Methods and FindingsA cohort of smear-positive tuberculosis patients diagnosed and registered in Hossana Hospital in southern Ethiopia from 1 September
Estifanos Biru Shargie; Bernt Lindtjørn
Background. Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. Methods. A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. Results. Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0–16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. Conclusions. ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.
Girardi, Enrico; Palmieri, Fabrizio; Angeletti, Claudio; Vanacore, Paola; Matteelli, Alberto; Gori, Andrea; Carbonara, Sergio; Ippolito, Giuseppe
Background In Ethiopia where tuberculosis epidemic remains high, studies that describe hotspots of the disease are unavailable. This study tried to detect the spatial distribution and clustering of smear-positive tuberculosis cases in Dabat, Ethiopia. Methods and Findings A population-based cross sectional study conducted in the Dabat Health and Demographic Surveillance System site from October 2010 to September 2011 identified smear-positive tuberculosis cases. Trained field workers collected demographic and location data from each study participant through house-to-house visits. A spatial scan statistic was used to identify purely spatial and space–time clusters of tuberculosis among permanent residents. Two significant (p<0.001) spatial and space-time clusters were identified in the study district. Conclusion Tuberculosis is concentrated in certain geographic locations in Dabat, Ethiopia. This kind of clustering can be common in the country, so the National Tuberculosis Control Program can be more effective by identifying such clusters and targeting interventions.
Tadesse, Takele; Demissie, Meaza; Berhane, Yemane; Kebede, Yigzaw; Abebe, Markos
Background Orbital tuberculosis (OTb) is rare and may be regarded as a manifestation of extrapulmonary tuberculosis. We report an interesting case series of six patients with varied presentations of orbital and adnexal tuberculosis in a South Indian patient population. Results A retrospective, interventional case series of six patients diagnosed with orbital and adnexal tuberculosis on the basis of clinical, radiological and histopathological evaluations between 2010 and 2013 was performed. Among the six patients with histopathologically proven OTb, five were women. The varied presentations included tubercular dacryoadenitis (two cases), classical periostitis (two cases), OTb with bone involvement (one case) and ocular adnexal tuberculosis (one case). Systemic involvement was seen in one case. All cases were treated with a regimen of antitubercular therapy (ATT). Conclusions OTb, though rare, should form a part of the differential diagnosis of orbital lesions in a high tuberculosis (TB) endemic country like ours. Biopsy still remains the mainstay of diagnosis.
BACKGROUND\\/OBJECTIVES: Healthcare facilities remain a potential risk environment where transmission of Mycobacterium tuberculosis disease (TB) will occur. As Mtb cases decrease in the United States, more emphasis is being placed on latent tuberculosis infection. The Veterans Health Administration (VHA) is a national healthcare system with over 4 million patients seen during the last year, for which approximately 600,000 inpatient admissions
S. Kralovic; L. Simbartl; G. Roselle
Background Tuberculosis remains a deadly infectious disease, affecting millions of people worldwide. Ethiopia ranks seventh among the twenty two high tuberculosis burden countries. The aim of this study was to determine the prevalence of smear positive pulmonary tuberculosis and its associated risk factors in Goba and Robe hospitals of Bale zone. Methods A cross-sectional study was conducted on tuberculosis suspected patients from February-May 2012. Sputum samples were examined for acid fast bacilli using Ziehl-Neelsen staining and interview was conducted for each patient. Descriptive statistics, binary logistic and multivariable logistic regression analyses were employed to identify factors associated with pulmonary tuberculosis infection. Result The prevalence of smear positive tuberculosis was 9.2%. Age >36 (AOR?=?3.54, 95% CI?=?1. 3–9.82), marital status (AOR?=?8.40, 95% CI?=?3.02-23.20), family size (AOR?=?4. 10, 95% CI?=?1.60-10.80), contact with active tuberculosis patient (AOR?=?5. 90; 95% CI?=?2. 30–15.30), smoking cigarette regularly (AOR?=?3. 90; 95% CI?=?1. 20–12.40), and human immunodeficiency virus sero-status (AOR?=?11. 70; 95% CI?=?4. 30–31.70) were significantly associated with smear positive pulmonary tuberculosis. Conclusion The prevalence of smear positive pulmonary tuberculosis was high in the study area. Age, marital status, family size, history of contact with active tuberculosis patient, smoking cigarettes, and HIV sero-status were among the risk factors significantly associated with acquiring tuberculosis. Hence, strict pulmonary tuberculosis screening of HIV patients and intensification of health education to avoid risk factors identified are recommended.
Tuberculosis remains a major health problem worldwide. The disease is caused by Mycobacteriumtuberculosis whose preferred habitat is the host macrophage. The immune response against tuberculosis is mediated by different subsets of T cells including both conventional CD4 and CD8 T cells as well as unconventional CD1 restricted and ?? T cells. The CD1 restricted T cells are particularly remarkable because they recognise the glycolipids abundant in the mycobacterial cell wall. Although a vaccine, M.bovis BCG, is available which protects toddlers against miliary tuberculosis, it is ineffective in preventing pulmonary tuberculosis in adults. Therefore, a novel vaccine is urgently required. Knowledge about the functioning of different T cell populations during infection and disease provides the basis for rational vaccine design. We have constructed a recombinant BCG vaccine which, compared with wild-type BCG, induces superior protection not only against laboratory strains but also against clinical isolates of M. tuberculosis.
Background In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown. Methods We estimated annual tuberculosis incidence stratified by HIV status during 2006–2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998–2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population. Results Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998–2004 then remained relatively stable until 2007. During 2007–2012, tuberculosis incidence declined by 28–44% among adults with HIV and by 11–26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839–1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231–238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV. Conclusions Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues.
Yuen, Courtney M.; Weyenga, Herman O.; Kim, Andrea A.; Malika, Timothy; Muttai, Hellen; Katana, Abraham; Nganga, Lucy; Cain, Kevin P.; De Cock, Kevin M.
Spinal tuberculosis is a destructive form of tuberculosis. It accounts for approximately half of all cases of musculoskeletal tuberculosis. Spinal tuberculosis is more common in children and young adults. The incidence of spinal tuberculosis is increasing in developed nations. Genetic susceptibility to spinal tuberculosis has recently been demonstrated. Characteristically, there is destruction of the intervertebral disk space and the adjacent vertebral bodies, collapse of the spinal elements, and anterior wedging leading to kyphosis and gibbus formation. The thoracic region of vertebral column is most frequently affected. Formation of a ‘cold’ abscess around the lesion is another characteristic feature. The incidence of multi-level noncontiguous vertebral tuberculosis occurs more frequently than previously recognized. Common clinical manifestations include constitutional symptoms, back pain, spinal tenderness, paraplegia, and spinal deformities. For the diagnosis of spinal tuberculosis magnetic resonance imaging is more sensitive imaging technique than x-ray and more specific than computed tomography. Magnetic resonance imaging frequently demonstrates involvement of the vertebral bodies on either side of the disk, disk destruction, cold abscess, vertebral collapse, and presence of vertebral column deformities. Neuroimaging-guided needle biopsy from the affected site in the center of the vertebral body is the gold standard technique for early histopathological diagnosis. Antituberculous treatment remains the cornerstone of treatment. Surgery may be required in selected cases, e.g. large abscess formation, severe kyphosis, an evolving neurological deficit, or lack of response to medical treatment. With early diagnosis and early treatment, prognosis is generally good.
Garg, Ravindra Kumar; Somvanshi, Dilip Singh
Cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide. Mycobacterium tuberculosis, Mycobacterrium bovis, and the Bacille Calmette-Guérin vaccine can cause tuberculosis involving the skin. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a multitude of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Further, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. The authors report a case that illustrates the challenges faced by dermatologists when considering a diagnosis of cutaneous tuberculosis.
Frankel, Amylynne; Penrose, Carolin
Although tuberculosis remains a substantial global threat, the mechanisms that enable mycobacterial persistence and replication within the human host are ill defined. This study represents the first genome-wide expression analysis of Mycobacterium tuberculosis from clinical lung samples, which has enabled the identification of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal information from our DNA array analyses, we analyzed the differentially expressed genes within the context of computationally inferred protein networks. Protein networks were constructed using functional linkages established by the Rosetta stone, phylogenetic profile, conserved gene neighbor, and operon computational methods. This combined approach revealed that during pulmonary tuberculosis, M. tuberculosis actively transcribes a number of genes involved in active fortification and evasion from host defense systems. These genes may provide targets for novel intervention strategies. PMID:16428773
Rachman, Helmy; Strong, Michael; Ulrichs, Timo; Grode, Leander; Schuchhardt, Johannes; Mollenkopf, Hans; Kosmiadi, George A; Eisenberg, David; Kaufmann, Stefan H E
Background Tuberculosis is a serious global health problem. Its paradigms are shifting through time, especially in rapidly developing countries such as China. Health providers in China are at the forefront of the battle against tuberculosis; however, there are few empirical studies on health providers' perspectives on the challenges they face in tuberculosis control at the county level in China. This study was conducted among health providers to explore their experiences with tuberculosis control in order to identify bottlenecks and emerging challenges in controlling tuberculosis in rural China. Methods A qualitative approach was used. Semi-structured, in-depth interviews were conducted with 17 health providers working in various positions within the health system of one rural county (ZJG) of China. Data were analyzed based on thematic content analysis using MAXQDA 10 qualitative data analysis software. Results Health providers reported several problems in tuberculosis control in ZJG county. Migrant workers and the elderly were repeatedly documented as the main obstacles in effective tuberculosis control in the county. At a personal level, doctors showed their frustration with the lack of new drugs for treating tuberculosis patients, and their opinions varied regarding incentives for referring patients. Conclusion The results suggest that several problems still remain for controlling tuberculosis in rural China. Tuberculosis control efforts need to make reaching the most vulnerable populations a priority and encourage local health providers to adopt innovative practices in the local context based on national guidelines to achieve the best results. Considerable changes in China's National Tuberculosis Control Program are needed to tackle these emerging challenges faced by health workers at the county level.
Lu, Hui; You, Hua; Fan, Hong; Huang, Lifang; Wang, Qungang; Shen, Hongbing; Wang, Jianming
Background: To examine the effects of a community program on tuberculosis incidence, prevalence, and transmission requiring users of public facilities to carry cards certifying their compliance with a tuberculosis screening, prophylaxis, and treatment program. Community knowledge of tuberculosis and costs and benefits of the program are described.Setting: A West Coast “skid row” community with historically high rates of tuberculosis, homelessness,
Neal J Rendleman
There are 9 million cases of active tuberculosis reported annually; however, an estimated one-third of the world's population is infected with Mycobacterium tuberculosis and remains asymptomatic. Of these latent individuals, only 5-10% will develop active tuberculosis disease in their lifetime. CD4(+) T cells, as well as the cytokines IL-12, IFN-?, and TNF, are critical in the control of Mycobacterium tuberculosis infection, but the host factors that determine why some individuals are protected from infection while others go on to develop disease are unclear. Genetic factors of the host and of the pathogen itself may be associated with an increased risk of patients developing active tuberculosis. This review aims to summarize what we know about the immune response in tuberculosis, in human disease, and in a range of experimental models, all of which are essential to advancing our mechanistic knowledge base of the host-pathogen interactions that influence disease outcome. PMID:23516984
O'Garra, Anne; Redford, Paul S; McNab, Finlay W; Bloom, Chloe I; Wilkinson, Robert J; Berry, Matthew P R
Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower in poorly-controlled DM patients than that in well-controlled DM patients and healthy subjects. Thus, these clinical data suggest that the high incidence of tuberculosis in DM patients is due to the impaired production of Th1-related cytokines. However, direct evidences to prove this possibility remain to be obtained. In 1980, Saiki and co-workers reported that host defense and delayed-type hypersensitivity response to M. tuberculosis was hampered in a mouse DM model established by injecting streptozotocin (Infect Immun. 1980; 28: 127-131). We followed their investigation with the similar observations. Interestingly, levels of IFN-gamma and IL-12 in serum, lung, liver and spleen after infection were significantly reduced in DM mice when compared with those in control mice. Considered collectively, these results strongly suggest that the reduced production of Th1-related cytokines leads to the susceptibility of DM to mycobacterial infection. However, it remains to be understood how DM hampers the synthesis of Th1-related cytokines. In our preliminary study, the production of these cytokines by PBMC from DM patients and healthy subjects was not affected under a high glucose condition. Thus, it is not likely that the increased level of glucose directly suppresses the cell-mediated immune responses. Further investigations are needed to make these points clear. 2. A study of gastrectomy cases in pulmonary tuberculosis patients: Takenori YAGI (Division of Thoracic Disease, National Chiba-Higashi Hospital). Patients who have undergone gastric resection are considered at increased risk of developing pulmonary tuberculosis. I have investigated the role played by gastrectomy in giving rise to pulmonary tuberculosis. Of 654 pulmonary tuberculosis patients admitted to National Chiba-Higashi Hospital from January 1999 to December 2001, 55 patients (31-84 years old, mean 63.5 +/- 12.5 years, 48 males and 7 females) had the history of gastric resection. The incidence of gastrectomy among patients with pulmonary tuberculosis was 8.4 percent. The mean age of gastric resection
A 19-year-old Filipino man was admitted to our hospital because of persisting fever and back pain. He had recognized his symptoms 6 months previously, but a definite diagnosis was not made. Image testing demonstrated a compressed fracture of the thoracic vertebrae accompanied with a perivertebral abscess. A biopsy specimen revealed granuloma compatible with tuberculosis (TB). Anti-TB drugs were initiated, and his clinical symptoms steadily improved. However, he developed neuropathic symptoms due to exacerbation of the abscess two months after starting the anti-TB drugs. An immediate laminectomy was performed resulting in symptom relief; however severe kyphosis remained. Polymerase chain reaction testing of the abscess collected during the operation was positive for Mycobacterium tuberculosis, confirming the diagnosis of spinal TB. The diagnosis of spinal TB has been a challenge world-wide. Clinicians should be aware of the demographic background as well as the clinical and laboratory features of spinal tuberculosis, facilitating earlier diagnosis. PMID:24665589
Morioka, Hiroshi; Yanagisawa, Naoki; Sekiya, Noritaka; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi
Tuberculosis is a chronic specific granulomatous disease and a major cause of death in developing countries. The clinical presentation of tuberculosis lesions of oral cavity varies widely, including ulceration, diffuse inflammatory lesions, granulomas and fissures. Oral lesions usually appear as secondary to primary tuberculosis infection elsewhere, although primary infection of the oral mucosa by Mycobacterium tuberculosis has been described. We report a case of tuberculosis of gingiva, manifesting as gingival enlargement. Diagnosis was based on histopathological examination, complete blood count, X-ray chest and immunological investigations with detection of antibodies against Mycobacterium tuberculosis. Anti-tuberculous therapy was carried out for over six months. This case report emphasizes the need for dentists to include tuberculosis in the differential diagnosis of various types of gingival enlargements.
Jain, Sanjeev; Vipin, Bharti; Khurana, Pankaj
Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is the most successful pathogen of mankind and remains a major threat to global health as the leading cause of death due to a bacterial pathogen. Yet 90–95% of those who are infected with MTB remain otherwise healthy. These people are classified as “latently infected,” but remain a reservoir from which active TB cases will continue to develop (“reactivation tuberculosis”). Latent infection is defined by the absence of clinical symptoms of TB in addition to a delayed hypersensitivity reaction to the purified protein derivative of MTB used in tuberculin skin test or a T-cell response to MTB-specific antigens. In the absence of reliable control measures for tuberculosis, understanding latent MTB infection and subsequent reactivation is a research priority. This review aims to summarize the recent findings in human and non-human primate models of tuberculosis that have led to new concepts of latent tuberculosis.
Gideon, Hannah P.
Hepatobiliary tuberculosis is a rare manifestation of Mycobacterium tuberculosis infection and is usually secondary to tuberculosis of the lungs or gastrointestinal tract. Diagnosis is difficult pre-operatively in local (focal and tubular) forms because of its rarity and presentation in the form of non-specific symptoms and signs and lack of any defined criteria on imaging studies. Histopathological examination is necessary for definite diagnosis but in cases where there is suspicion of hepatobiliary tuberculosis, with PCR assay diagnosis it is possible pre-operatively. Recommended treatment is with conventional antituberculous drugs and surgical intervention in tuberculous abscess or granulomas. The disease is usually associated with good prognosis under complete antituberculous treatment. The author encountered 4 cases of hepatobiliary tuberculosis over 5 years. The aim of this article is to present current knowledge of hepatobiliary tuberculosis and to comprehensively review all the available literature.
Background Although it is established that opioid and Mycobacterium tuberculosis are both public health problems, the mechanisms by which they affect lung functions remain elusive. Methodology/Principal Findings We report here that mice subjected to chronic morphine administration and M. tuberculosis infection exhibited significant apoptosis in the lung in wild type mice as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Morphine and M. tuberculosis significantly induced the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, deficiency in TLR9 significantly inhibited the morphine and M. tuberculosis induced apoptosis in the lung. In addition, chronic morphine treatment and M. tuberculosis infection enhanced the levels of cytokines (TNF-?, IL-1?, and IL-6) in wild type mice, but not in TLR9 knockout (KO) mice. The bacterial load was much lower in TLR9 KO mice compared with that in wild type mice following morphine and M. tuberculosis treatment. Morphine alone did not alter the bacterial load in either wild type or TLR9 KO mice. Moreover, administration of morphine and M. tuberculosis decreased the levels of phosphorylation of Akt and GSK3? in the wild type mice, but not in TLR9 KO mice, suggesting an involvement of Akt/GSK3? in morphine and M. tuberculosis-mediated TLR9 signaling. Furthermore, administration of morphine and M. tuberculosis caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type mice, but not in TLR9 KO mice, indicating a role of Bcl-2 family in TLR9-mediated apoptosis in the lung following morphine and M. tuberculosis administration. Conclusions/Significance These data reveal a role for TLR9 in the immune response to opioids during M. tuberculosis infection.
Sun, Xiuli; Fan, Xionglin; LeSage, Gene; Li, Hui; Li, Yi; Zhang, Yi; Zhang, Xiumei; Zhang, Ying; Yin, Deling
Although the resurgence of tuberculosis in the early 1990s has largely been controlled, the risk of contracting this disease remains high in homeless persons, recent immigrants and persons infected with the human immunodeficiency virus (HIV). Purified protein derivative testing should be targeted at these groups and at persons with known or suspected exposure to active tuberculosis. Most patients with latent tuberculosis are treated with isoniazid administered daily for nine months. In patients with active tuberculosis, the initial regimen should include four drugs for at least two months, with subsequent therapy determined by mycobacterial sensitivities and clinical response. To avoid harmful drug interactions, regimens that do not contain rifampin may be employed in HIV-infected patients who are taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. To maximize compliance and minimize the emergence of mycobacterial drug resistance, family physicians should consider using directly observed therapy in all patients with tuberculosis. PMID:10821149
Jerant, A F; Bannon, M; Rittenhouse, S
The purpose of the study is to highlight the varied presentation of tuberculosis (TB) simulating a brain tumour. Headache and seizures are becoming frequent presenting complaints without any history of tuberculosis. The study comprises 1200 patients of both sexes with ages ranging from ten to sixty years. CT scan and MRI brain control with and without contrast medium were the investigations performed in these cases. In some patients Electroencephalography (EEG), cerebral angiography (DSA) and spectroscopy were also performed. The final diagnosis of tuberculosis was made on the basis of craniotomy, stereotactic and burr hole biopsies with histopathology in most of the cases. Forty per cent of the patients were followed up for eight months. They were put on anti-tuberculosis treatment with symptomatic and anti-epileptic drugs. The incidence was 544 and 757 per 100,000 in Africa and Indo Pakistan respectively. The male to female ratio was 1:1. Tuberculosis, especially with CNS involvement, is not only common in immunosuppressed patients in our setting, but TB has been and remains an important public health problem. TB may involve the CNS either as meningitis or as parenchymal granulomas or abscesses. Patients with brain TB usually present with fever, multiple cranial nerve involvement and occasional behavioural changes. CSF findings remain non specific in most cases. The most common sites are the cerebral hemisphere and basal ganglion in adults and the cerebellum in children. Tuberculosis has unique findings on brain CT and MRI. Cortical and subcortical locations are typical whereas the brain stem is a less common site. Tuberculosis lesions are usually solitary but multiple in 10% to 35% of cases. In spite of all these facts some cases of brain TB still need aggressive neurointervention to reach the final diagnosis of brain TB. Tuberculosis in the CNS may manifest in many different ways. So one should always include tuberculosis in the differential diagnosis in the etiology of delayed onset epilepsy and acute on chronic headache. In case of a discrepancy between clinical manifestations and CT/MRI findings, one can always anticipate tuberculous lesion in the brain. PMID:24059657
Chaudhry, U R; Farooq, M; Rauf, F; Bhatti, S K
Tuberculosis is an immense health problem in the developing world, and it remains a health care challenge in the developed world. It can affect virtually any organ system in the body. Diagnosis of tuberculosis is often difficult. Many patients with tuberculosis present with nonspecific symptoms, negative purified protein derivative skin test result, and negative findings on culture specimens. Cross-sectional imaging with ultrasound, multidetector computed tomography, and magnetic resonance imaging plays an important role in the diagnosis of tuberculosis. Tuberculosis demonstrates a variety of radiologic features depending on the organ involved and can mimic a number of other disease entities. Cross-sectional imaging alone is insufficient in reaching a conclusive diagnosis. Tuberculosis is a great mimicker as its radiologic manifestations can simulate numerous other diseases across the body systems. However, recognition and understanding of the common and uncommon radiologic manifestations of tuberculosis should alert considering tuberculosis in the high-risk population and correct clinical setting to enable appropriate treatment. PMID:24929261
Prapruttam, Duangkamon; Hedgire, Sandeep S; Mani, Sunithi Elizabeth; Chandramohan, Anuradha; Shyamkumar, N K; Harisinghani, Mukesh
There has been a renewed interest in the pathogenesis of bovine tuberculosis in many countries, in an attempt to understand better its transmission, to improve diagnosis and assess the potential of vaccination. This paper, which overviews current knowledge of aspects of the pathogenesis of bovine tuberculosis, draws from studies of field cases and experimental infections and highlights deficiencies in current understanding. The pathogenesis of bovine tuberculosis has not received the same level of attention as with human tuberculosis, and in many instances, the processes involved in bovine tuberculosis have been drawn from studies of human tuberculosis or from small animal models of infection. This paper however, considers the successful emulation of naturally acquired tuberculosis using experimental cattle models and identifies the complex and integrated nature of microbiological, immunological and pathological events involved. Current understanding of the initiation of infection, immune responses, and subsequent pathology, which can vary significantly in individual animals are discussed. Whilst there are aspects of M. bovis that still remain elusive to scientific investigation, further studies on the pathogenesis of bovine tuberculosis are advocated as necessary to provide a better scientific basis on which to review control and eradication strategies, which are currently less than effective in many regions. PMID:11463227
Neill, S D; Bryson, D G; Pollock, J M
Background.? The interleukin 10 (IL-10) family comprises cytokines structurally related to IL-10 that share signaling receptors that have conserved signaling cascades. The immunopathogenesis of immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) infection and tuberculosis remains incompletely understood. We hypothesized that a deficiency of IL-10 and its homologs may contribute to the immunopathology of IRIS in these patients. Methods.?We performed a case-control analysis involving patients with HIV infection and tuberculosis who had IRIS at clinical presentation (tuberculosis-IRIS) and similar patients with HIV infection and tuberculosis who did not develop tuberculosis-IRIS (non-IRIS). Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 hours. Messenger RNA was analyzed by quantitative reverse transcription polymerase chain reaction analysis. Cytokine concentrations in serum were also determined. Results.?Cultures of PBMCs stimulated with M. tuberculosis for 24 hours yielded higher IL-10 and interleukin 22 (IL-22) transcript levels for tuberculosis-IRIS patients, compared with non-IRIS patients. Analysis of corresponding serum samples showed significantly higher concentrations of IL-10 and IL-22 in tuberculosis-IRIS patients, compared with non-IRIS patients. Conclusions.?IL-10 and IL-22 were differentially induced in PBMCs from tuberculosis-IRIS patients after in vitro stimulation, and higher concentrations of their corresponding proteins were detected in serum (in vivo). The higher levels of IL-10 observed in this study may represent a compensatory antiinflammatory response during tuberculosis-IRIS. The elevated levels of IL-22 suggest an association between this cytokine and immunopathology during tuberculosis-IRIS.
Tadokera, Rebecca; Wilkinson, Katalin A.; Meintjes, Graeme A.; Skolimowska, Keira H.; Matthews, Kerryn; Seldon, Ronnett; Rangaka, Molebogeng X.; Maartens, Gary; Wilkinson, Robert J.
Infection with Mycobacterium tuberculosis remains a major cause of morbidity and mortality all over the world. Since the effectiveness of the only available tuberculosis vaccine, Mycobacterium bovis bacillus Calmette- Guerin (BCG), is suboptimal, there is a strong demand to develop new tuberculosis vaccines. As tuberculosis is an airborne disease, the intranasal route of vaccination might be preferable. Live influenza virus
Sabine Sereinig; Marina Stukova; Natalia Zabolotnyh; Boris Ferko; Christian Kittel; Julia Romanova; Tatiana Vinogradova; Hermann Katinger; Oleg Kiselev; Andrej Egorov
Australia has one of the lowest incidence of tuberculosis in the world. The crude annual notification rate for tuberculosis (TB) has remained stable at between 5 and 6 per 100,000 population since 1991. In 1999, there were a total of 1,159 TB notifications in Australia of which 1,117 were new TB cases, and 42 were relapsed cases. The corresponding annual
Paul Roche; Angela Merianos; John Carnie; Amanda Christensen; Justin Waring; Anastasios Konstantinos; Vicki Krause; Mark Hurwitz; Ivan Bastian
Background Transmission of Mycobacterium tuberculosis (M. tuberculosis) complex could be possible between farmers and their cattle in Ethiopia. Methodology/Principal Findings A study was conducted in mixed type multi-purposes cattle raising region of Ethiopia on 287 households (146 households with case of pulmonary tuberculosis (TB) and 141 free of TB) and 287 herds consisting of 2,033 cattle belonging to these households to evaluate transmission of TB between cattle and farmers. Interview, bacteriological examinations and molecular typing were used for human subjects while comparative intradermal tuberculin (CIDT) test, post mortem and bacteriological examinations, and molecular typing were used for animal studies. Herd prevalence of CIDT reactors was 9.4% and was higher (p<0.01) in herds owned by households with TB than in herds owned by TB free households. Animal prevalence was 1.8% and also higher (p<0.01) in cattle owned by households with TB case than in those owned by TB free households. All mycobacteria (141) isolated from farmers were M. tuberculosis, while only five of the 16 isolates from cattle were members of the M. tuberculosis complex (MTC) while the remaining 11 were members of non-tuberculosis mycobacteria (NTM). Further speciation of the five MTC isolates showed that three of the isolates were M. bovis (strain SB1176), while the remaining two were M. tuberculosis strains (SIT149 and SIT53). Pathology scoring method described by “Vordermeier et al. (2002)” was applied and the average severity of pathology in two cattle infected with M. bovis, in 11 infected with NTM and two infected with M. tuberculosis were 5.5, 2.1 and 0.5, respectively. Conclusions/Significance The results showed that transmission of TB from farmers to cattle by the airborne route sensitizes the cows but rarely leads to TB. Similarly, low transmission of M. bovis between farmers and their cattle was found, suggesting requirement of ingestion of contaminated milk from cows with tuberculous mastitis.
Ameni, Gobena; Tadesse, Konjit; Hailu, Elena; Deresse, Yohannes; Medhin, Girmay; Aseffa, Abraham; Hewinson, Glyn; Vordermeier, Martin; Berg, Stefan
Transmission of Mycobacterium tuberculosis (Mtb) continues uninterrupted. Pre-exposure vaccination remains a central focus of tuberculosis research but 25 years of follow up is needed to determine whether a novel childhood vaccination regime protects from adult disease, or like BCG assists Mtb dissemination by preventing childhood illness but not infective adult pulmonary tuberculosis. Therefore, different strategies to interrupt the life cycle of Mtb need to be explored. This personal perspective discusses alternative approaches that may be delivered in a shorter time frame.
Elkington, Paul T
Background.?Changes in the phenotype and function of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4+ and CD8+ T-cell subsets in response to stage of infection may allow discrimination between active tuberculosis and latent tuberculosis infection. Methods.?A prospective comparison of M. tuberculosis-specific cellular immunity in subjects with active tuberculosis and latent tuberculosis infection, with and without human immunodeficiency virus (HIV) coinfection. Polychromatic flow cytometry was used to measure CD4+ and CD8+ T-cell subset phenotype and secretion of interferon ? (IFN-?), interleukin 2 (IL-2), and tumor necrosis factor ? (TNF-?). Results.?Frequencies of CD4+ and CD8+ cells secreting IFN-?-only, TNF-?-only and dual IFN-?/TNF-? were greater in active tuberculosis vs latent tuberculosis infection. All M. tuberculosis-specific CD4+ subsets, with the exception of IL-2-only cells, switched from central to effector memory phenotype in active tuberculosis vs latent tuberculosis infection, accompanied by a reduction in IL-7 receptor ? (CD127) expression. The frequency of PPD-specific CD4+ TNF-?-only-secreting T cells with an effector phenotype accurately distinguished active tuberculosis from latent tuberculosis infection with an area under the curve of 0.99, substantially more discriminatory than measurement of function alone. Conclusions.?Combined measurement of T-cell phenotype and function defines a highly discriminatory biomarker of tuberculosis disease activity. Unlocking the diagnostic and monitoring potential of this combined approach now requires validation in large-scale prospective studies.
Pollock, Katrina M.; Whitworth, Hilary S.; Montamat-Sicotte, Damien J.; Grass, Lisa; Cooke, Graham S.; Kapembwa, Moses S.; Kon, Onn M.; Sampson, Robert D.; Taylor, Graham P.; Lalvani, Ajit
Background Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship. Methodology/Principal Findings We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9250-8160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. Conclusions/Significance Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen.
Minnikin, David E.; Besra, Gurdyal S.; Lee, Oona Y-C.; Gernaey, Angela M.; Galili, Ehud; Eshed, Vered; Greenblatt, Charles L.; Lemma, Eshetu; Bar-Gal, Gila Kahila; Spigelman, Mark
DNA fingerprinting of Mycobacterium tuberculosis by IS6110 restriction fragment length polymorphism analysis requires substantial high-quality DNA. We demonstrated that, despite extraction treatments that might be expected to inactivate this organism, M. tuberculosis remained viable during this process. These data suggest that the extraction of M. tuberculosis DNA should be performed within containment until complete. The standard method employed for DNA
Wendy Somerville; Louise Thibert; Kevin Schwartzman; Marcel A. Behr
Tuberculosis remains a public health problem in Turkey. Rapid detection of Mycobacterium tuberculosis plays a key role in control of infection. In this article, the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) was evaluated for detection of M. tuberculosis in urine samples. The performance of the MTD was very good and appropriate for routine laboratory diagnosis.
Sener, Asli Gamze; Kurultay, Nukhet; Afsar, Ilhan
Background While the overall population prevalence of tuberculosis in Quebec has been declining for many years, tuberculosis is still disproportionately more prevalent among the immigrant and Inuit communities. As such, the aim of this study was to forecast the incidence of tuberculosis in the Province of Quebec over time in order to examine the possible impact of future preventative and treatment programs geared to reducing such disparities. Methods A compartmental differential equation based on a Susceptible Exposed Latent Infectious Recovered (SELIR) model was simulated using the Euler method using Visual Basic for Applications in Excel. Demographic parameters were obtained from census data for the Province of Quebec and the model was fitted to past epidemiological data to extrapolate future values over the period 2015 to 2030. Results The trend of declining tuberculosis rates will continue in the general population, falling by 42% by 2030. The incidence among immigrants will decrease but never vanish, and may increase in the future. Among the Inuit, the incidence is expected to increase, reaching a maximum and then stabilizing, although if re-infection is taken into account it may continue to increase. Tuberculosis among non-indigenous Canadian born persons will continue to decline, with the disease almost eradicated in that group in the mid 21st century. Conclusions While the incidence of tuberculosis in the Province of Quebec is expected to decrease overall, certain populations will remain at risk.
Background Tuberculosis continues to be one of the leading causes of death worldwide and in the American region. Although multidrug-resistant tuberculosis (MDR-TB) remains a threat to TB control in Panama, few studies have focused in typing MDR-TB strains. The aim of our study was to characterize MDR Mycobacterium tuberculosis clinical isolates using PCR-based genetic markers. Methods From 2002 to 2004, a total of 231 Mycobacterium tuberculosis isolates from TB cases country-wide were screened for antibiotic resistance, and MDR-TB isolates were further genotyped by double repetitive element PCR (DRE-PCR), (GTG)5-PCR and spoligotyping. Results A total of 37 isolates (0.85%) were resistant to both isoniazid (INH) and rifampicin (RIF). Among these 37 isolates, only two (5.4%) were resistant to all five drugs tested. Dual genotyping using DRE-PCR and (GTG)5-PCR of MDR Mycobacterium tuberculosis isolates revealed eight clusters comprising 82.9% of the MDR-TB strain collection, and six isolates (17.1%) showed unique fingerprints. The spoligotyping of MDR-TB clinical isolates identified 68% as members of the 42 (LAM9) family genotype. Conclusion Our findings suggest that MDR Mycobacterium tuberculosis is highly clustered in Panama’s metropolitan area corresponding to Panama City and Colon City, and our study reveals the genotype distribution across the country.
BACKGROUND AND PURPOSE: Tuberculosis of the calvaria is a rare entity, and only anecdotal reports describing its imaging features have been previously published in the literature. We report the role of conventional radiography and CT findings on in the evaluation of calvarial tuberculosis in 42 cases. METHODS: Forty-two cases of pathologically verified calvarial tuberculosis were analyzed retrospectively by using conventional
Abhijit A. Raut; Arpit M. Nagar; Datta Muzumdar; Ashish J. Chawla; Ranjeet S. Narlawar; Sudhir Fattepurkar; Veena L. Bhatgadde
Tuberculosis remains a global threat to public health. Considerable efforts have been made to combat this disease. However,\\u000a the emergence ofMycobacterium tuberculosis (Mtb) strains resistant to the major anti-tuberculosis drugs especially multidrug resistant (MDR) strains poses a deadly\\u000a threat to control programs. The present study aims to identify the most common mutations within multidrug-resistantM. tuberculosis Moroccan isolates in order to
Radia Sabouni; Moussa Kourout; Imane Chaoui; Annemarie Jordaan; Mohammed Akrim; Thomas C. Victor; Karim Maltouf Filali; Mohammed El Mzibri; Ouafae Lahlou; Rajae El Aouad
Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.
Kaufmann, Stefan H.E.; Cole, Stewart T.; Mizrahi, Valerie; Rubin, Eric; Nathan, Carl
Extra-pulmonary tuberculosis constitutes 15-20% of total tuberculosis (TB) case load in immuno-competent patients. Affliction of the skeletal system is rare with still rarer presentation of sternal osteomyelitis even in endemic countries. A patient with primary sternal TB presenting with multiple cutaneous sinuses over the anterior chest wall is being reported. A high element of suspicion is needed more so in resource limited setting for early diagnosis and treatment. PMID:24349840
Sachdeva, R; Sachdeva, S; Arora, S
Background Breast tuberculosis is an uncommon disease even in countries where the incidence of tuberculosis is high. Case Report This is a case series concerning 4 postmenopausal breast tuberculosis cases encountered in Moulay Youssef Hospital between January 2007 and December 2010. Breast tuberculosis represents 0.25% of all hospitalized tuberculosis patients in our department. The mean age of our patients was 62.5 ± 5.8 years. Clinical findings were heterogeneous; 1 case was multifocal tuberculosis, and another case was coexistent tuberculosis and malignancy of the breast. Mammography and ultrasonography findings were suspicious for malignancy in all 4 cases. Fine needle aspiration was negative in 3 cases. The diagnosis was made in all patients by histological examination of biopsy specimens, which revealed typical tuberculous lesions. Anti-tuberculosis therapy formed the mainstay of treatment. Conclusion The clinical and radiological features of mammary tuberculosis can be very confusing and easily mistaken for breast cancer. Symptoms suggestive of tuberculosis warrant a biopsy to exclude possible cancer.
Bouti, Khalid; Soualhi, Mouna; Marc, Karima; Zahraoui, Rachida; Benamor, Jouda; Bourkadi, Jamal Eddine; Iraqi, Ghali
Background Tuberculosis (TB) is an infectious, granulomatous disease caused by acid-fast bacilli of the genus Mycobacterium. The disease affects practically all species of vertebrates. Although mammalian tuberculosis has been nearly controlled in many developed countries, it is still a serious problem in humans and domestic animals including pigs in developing countries. In Ethiopia, the prevalence of TB in pigs is not known. Therefore, this study was designed to estimate the prevalence of TB in pigs in central Ethiopia and to characterize the causative agents using molecular techniques. Results The estimated prevalence of TB was 5.8% (49/841). Age and origin of pigs were significantly associated (P<0.001) with the prevalence. In contrast, an association of sex, floor type and water source with the prevalence could not be shown. Culture positivity was confirmed in 30.6% (15/49) of the tuberculous-like lesions. Of the 15 isolates, 12 were acid fast positive while five of the latter were confirmed by multiplex PCR as members of the M. tuberculosis complex. Speciation of the five isolates further confirmed that they were M. tuberculosis, belonging to SIT1088 (two isolates) and SIT1195 (one isolate). The remaining two isolates belong to an identical spoligotype, the pattern of which was not found in the spoligotype database (SpolDB4). Conclusions The isolation of M. tuberculosis from pigs suggests a possible risk of transmission between humans and pigs. Hence, establishing feasible control methods is required.
Background & objectives: Extensively drug resistant tuberculosis (XDR-TB) has become a new threat for the control of TB in many countries including India. Its prevalence is not known in India as there is no nation-wide surveillance. However, there have been some reports from various hospitals in the country. Methods: We have reviewed the studies/information available in the public domain and found data from 10 tertiary care centres in 9 cities in India. Results: A total of 598 isolates of XDR Mycobacterium tuberculosis have been reported in the studies included. However, the reliability of microbiological methods used in these studies was not checked and thus the XDR-TB data remained invalidated in reference laboratories. Interpretation & conclusions: Systematic surveillance and containment interventions are urgently needed.
Michael, Joy Sarojini; John, T. Jacob
Against a background of rising tuberculosis (TB) rates, increasing incidence of TB and human immunodeficiency virus (HIV) co-infection, coupled with the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), the need for effective TB infection control has never been more vital (World Health Organization (WHO), 2009). TB infection control has been defined as 'a combination of measures aimed at minimizing the risk of TB transmission within populations' (WHO, 2009: p.ix). Health professionals are frequently confused about appropriate infection control measures when caring for patients affected by infectious respiratory tuberculosis (Mohandas and Cunniffe, 2009). This article aims to address the key infection control measures required to optimize patient care and reduce the risk of TB transmission within hospital and community settings. PMID:22067583
Tuberculosis (popularly known as "TB") is a disease caused by the bacteria Mycobacterium tuberculosis . It mainly infects the lungs, although it also ... and Symptoms In older infants and children, latent tuberculosis infection (LTBI), which is the first infection with ...
Background There is a lack of information on the clinical characteristics of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB in the Jiangxi Province of China; furthermore, data have not been reported on the utility of mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analyses in genotyping Mycobacterium tuberculosis strains isolated from this region. The aim of this study was to analyse the clinical features of patients with MDR and XDR TB from Jiangxi Province and to evaluate the discriminatory power of the 15-loci MIRU-VNTR method. Methods A retrospective study was conducted on patients diagnosed with MDR and XDR TB at the Jiangxi Chest Hospital from July 2010 to June 2011. The RD105 deletion-targeted multiplex PCR (DTM-PCR) and the 15-loci MIRU-VNTR method were used to determine the genetic background of the identified MDR and XDR M. tuberculosis clinical isolates. Results Of 804?M. tuberculosis clinical isolates, 159 (159/804, 19.8%) of the isolates were identified as MDR with first-line drug susceptibility testing. Of the 123 available MDR isolates, 13 (13/123, 10.6%) were XDR. The RD105 deletion-targeted multiplex PCR method identified 85 (85/110, 77.3%) MDR and 12 (12/13, 92.3%) XDR isolates as the Beijing genotype. MIRU-VNTR cluster analysis demonstrated that 101 MDR and 13 XDR strains had unique genotype patterns; the remaining 9 MDR strains were in 4 clusters, namely 1 cluster with 3 strains and 3 clusters with 2 strains, resulting in a low clustering rate (4.06%). The Hunter-Gaston discriminatory index (HGDI) of the 15-loci MIRU-VNTR method was as high as 0.992. In addition, clinical surveys showed that 87 (87/110, 79.1%) MDR TB patients and 10 (10/13, 76.9%) XDR TB patients had been previously treated. Diabetes mellitus was the most common comorbidity in both MDR TB (16/110, 14.5%) and XDR TB (2/13, 15.4%) patients. Conclusions Based on our preliminary data, the MDR and XDR M. tuberculosis clinical isolates identified at the Jiangxi Chest Hospital were genetically diverse and clustered at a low frequency. The 15-loci MIRU-VNTR method showed high discriminatory power and may be used as a first-line genotyping tool in investigating the molecular epidemiology of M. tuberculosis in Jiangxi, China. Decisive measures are urgently needed to effectively prevent and manage MDR and XDR tuberculosis in this province.
BACKGROUND: Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health
Saidi Egwaga; Abdallah Mkopi; Nyagosya Range; Vera Haag-Arbenz; Amuri Baraka; Penny Grewal; Frank Cobelens; Hassan Mshinda; Fred Lwilla; Frank van Leth
Background Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. Methods Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). Results Seventy participants were randomized to standard (n?=?37, 53%) or intensive (n?=?33, 47%) diagnostics. At 8 weeks, 100% (n?=?22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p?=?0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p?=?0.04). Conclusions Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.
(See the Editorial Commentary by Vernon and Villarino, on pages 792–3.) Background.?The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable. Methods.?We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study. Results.?We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0–26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6–87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14–.30). Conclusions.?Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models.
Noubary, Farzad; Walensky, Rochelle P.; Cerda, Rodrigo; Losina, Elena; Horsburgh, C. Robert
Background. Unknown proportions of tuberculosis cases remain undiagnosed and untreated as result of several factors which further increases the number of tuberculosis cases per index case. Objective. To identify factors associated with patient's delay in initiating treatment of tuberculosis. Methods. Cross-sectional study was employed from January to April, 2013, in Bahir Dar Ethiopia. A total of 360 patients were included. Data were collected from tuberculosis patients using a semistructured questionnaire. Data were entered and analyzed using SPSS version 16 windows. Multivariate logistic regression analysis was used to identify factors associated with patient delay. Results. Of all patients, 211 (62%) sought medical care after the WHO recommended period (21 days). The median patient delays of smear positive, smear negative, and extrapulmonary patients were 27 (IQR:?10–59), 30 (IQR:?9–65), and 31 (IQR:?10–150) days, respectively, with statistically significant variations among them (ANOVA: F = 5.96; P < 0.003). Place of residence and educational status were the predictors of patient delay. Conclusion. Around two-thirds of all patients and more than half of smear positive tuberculosis patients were delayed in seeking medical care within the recommended period. Provision of DOTS service in the vicinity and health education on TB may reduce patient delay and its consequences.
Gebeyehu, Endalew; Abeje, Gedefaw
Tuberculosis remains a leading cause of human mortality. The emergence of strains of Mycobacterium tuberculosis, the causative agent, that are resistant to the major frontline antitubercular drugs increases the urgency for the development of new therapeutic agents. Sequencing of the M. tuberculosis genome revealed the existence of twenty cytochrome P450 enzymes, some of which are potential candidates for drug targeting. The recent burst of studies reporting microarray-based gene essentiality and transcriptome analyses under in vitro, ex vivo and in vivo conditions highlight the importance of selected P450 isoforms for M. tuberculosis viability and pathogenicity. Current knowledge of the structural and biochemical properties of the M. tuberculosis P450 enzymes and their putative redox partners is reviewed, with an emphasis on findings related to their physiological function(s) as well as their potential as drug targets.
Ouellet, Hugues; Johnston, Jonathan B.; Ortiz de Montellano, Paul R.
Tuberculosis remains a leading cause of human mortality. The emergence of strains of Mycobacterium tuberculosis, the causative agent, that are resistant to the major frontline antitubercular drugs increases the urgency for the development of new therapeutic agents. Sequencing of the M. tuberculosis genome revealed the existence of 20 cytochrome P450 enzymes, some of which are potential candidates for drug targeting. The recent burst of studies reporting microarray-based gene essentiality and transcriptome analyses under in vitro, ex vivo and in vivo conditions highlight the importance of selected P450 isoforms for M. tuberculosis viability and pathogenicity. Current knowledge of the structural and biochemical properties of the M. tuberculosis P450 enzymes and their putative redox partners is reviewed, with an emphasis on findings related to their physiological function(s) as well as their potential as drug targets. PMID:19635450
Ouellet, Hugues; Johnston, Jonathan B; Ortiz de Montellano, Paul R
Background Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics. Methodology Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias. Principal Findings A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates – higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis. Conclusion Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.
Win, Wah; Chee, Cynthia Bin-Eng; Hsu, Li Yang; Mak, Estelle; Earnest, Arul; Ong, Marcus Eng-Hock; Cutter, Jeffery; Wang, Yee Tang
Summary Background: Despite the fact that joint tuberculosis is one of the most common forms of extrapulmonary tuberculosis, it is a disease entity that is very rare in Poland (less than 100 cases a year in the last 10 years). The symptoms are non-specific, and thus the disease is rarely taken into account in preliminary differential diagnosis. Case Report: A 68-year-old female patient was admitted to the Internal Diseases Clinic due to oedema and pain of the right shoulder joint. The pain has been increasing for about 8 months. Physical examination revealed increased circumference and elevated temperature of the right shoulder joint. Limb function was retained. The full range of radiological and laboratory diagnostic examinations was performed, including the biopsy of the affected tissue which revealed the presence of Mycobacterium tuberculosis in the bacterial culture. Clinical improvement was obtained after introduction of TB drugs. Conclusions: Radiological diagnostic methods (X-ray, CT scans, MRI scans) provide high precision monitoring of articular lesions. However, the decisive diagnosis requires additional laboratory tests as well as histopathological and bacteriological assays.
Ostrowska, Monika; Gietka, Jan; Nesteruk, Tomasz; Piliszek, Agnieszka; Walecki, Jerzy
Tuberculosis (TB) is one of the major health problems that our country is facing today. Despite active interventions by our government, control of TB still remains to be achieved. The emergence and exponential growth of the human immunodeficiency virus and drug-resistant strains threaten to further complicate the TB situation in our country. Even in this era of advanced chemotherapy, many lives are lost every day in our country. Tuberculosis of the urinary tract, despite being one of the commonest forms of extra-pulmonary TB, is generally overlooked. Most patients present with vague lower urinary symptoms typical of urinary tract infection. In this article, we shall highlight the various issues related to the surgical management of renal and ureteral tuberculosis.
Krishnamoorthy, Sriram; Gopalakrishnan, Ganesh
Tuberculosis is increasing in prevalence in many countries and is now the leading infectious cause of death world wide, being responsible for three million deaths annually. Infection with HIV, likewise increasing in prevalence, has emerged as the most important predisposing factor for developing overt tuberculosis in people co-infected with Mycobacterium tuberculosis. Owing to the widespread geographical overlap of these two infections, it is estimated that in 1999, HIV related tuberculosis will reach one million cases and will cause 30% of the expected 2.5 million AIDS related deaths. Tuberculosis in HIV infected individuals may have unusual clinical features and can cause diagnostic difficulties. Despite the effectiveness of modern short course treatment, the mortality of HIV related tuberculosis during and after treatment remains high, and this may be due to other HIV related infections. The "cursed duet" of infection with both HIV and M tuberculosis is generating a threat to human health of unparalleled proportions which, if not taken seriously by health workers and decision makers, could become totally unmanageable.???Keywords: HIV; AIDS; tuberculosis
Zumla, A.; Malon, P.; Henderson, J.; Grange, J.
Background Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. Methods We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. Results Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007). Conclusions The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated.
Cortes, Claudia P.; Wehbe, Firas H.; McGowan, Catherine C.; Shepherd, Bryan E.; Duda, Stephany N.; Jenkins, Cathy A.; Gonzalez, Elsa; Carriquiry, Gabriela; Schechter, Mauro; Padgett, Denis; Cesar, Carina; Madero, Juan Sierra; Pape, Jean W.; Masys, Daniel R.; Sterling, Timothy R.
Background Treatment of recent tuberculosis infection in children <2 years old is essential because of high risk of progression to disease, but diagnosis is hindered by the inaccuracy of the tuberculin skin test (TST). More accurate T cell-based tests for infection could enhance diagnosis by optimizing TST interpretation. Methods 979 child tuberculosis contacts in Istanbul underwent TST and enzyme-linked immunospot (ELISpot) testing. Using ELISpot results as a reference standard, we assessed the effect of age and BCG-vaccination on sensitivity and specificity of TST, and computed optimal TST cut-off points (OCPs) using receiver operator characteristic curves. Results Using a ?10mm TST cut-off point, sensitivity of TST was 66% in children <2y, lower than in older children (p=0.006). Specificity was 75% in BCG-vaccinated children, compared with 92% in unvaccinated children (p=0.001). OCPs improved TST specificity in children with 1 BCG scar with little loss of sensitivity. Despite use of OCPs, sensitivity of TST remained <70% in children <2y, specificity remained <87% in BCG-vaccinated children >2y and overall accuracy was low in children with >1 BCG scar. Conclusions Negative TST results cannot exclude tuberculosis infection in child tuberculosis contacts <2 years old, supporting use of preventive therapy regardless of TST results in this age group. In children >2 years old, accuracy of TST can be improved by adjustment of cut-off points in BCG-vaccinated children but remains poor in children with >1 BCG scar. This methodology can define optimal TST cut-off points for diagnosis of tuberculosis infection tailored to target populations.
Bakir, Mustafa; Dosanjh, Davinder P S; Deeks, Jonathan J; Soysal, Ahmet; Millington, Kerry A; Efe, Serpil; Aslan, Yasemin; Polat, Dilek; Kodalli, Nihat; Yagci, Aysegul; Barlan, Isil; Bahceciler, Nerin; Demiralp, Emel E; Lalvani, Ajit
Tuberculosis has staged a global comeback and forms a dangerous combination with AIDS. The abdomen is one of the common sites of extrapulmonary involvement. Patients with abdominal tuberculosis have a wide range and spectrum of symptoms and signs; the disease is therefore a great mimic. Diagnosis, mainly radiological and supported by endoscopy, is difficult to make and laparotomy is required in a large number of patient. Management involves judicious combination of antitubercular therapy and surgery which may be required to treat complications such as intestinal obstruction and perforation. The disease, though potentially curable, carries a significant morbidity and mortality. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13
Kapoor, V. K.
The case discussed is that of a previously healthy 48-year-old female who presented with a week long history of epigastric pain and continuing weight loss. A series of investigations and supporting literature alluded to a diagnosis of oesophageal tuberculosis (TB), and antituberculous medication was commenced accordingly. An accompanying discussion considers the incidence, differential diagnoses, pathogenesis, clinical features, investigations and aspects of management of oesophageal TB.
Bonthala, Latha; Wood, Eleanor
Background one of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued. Method a systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and ClinicalTrial.gov websites. Results 100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed. Conclusions Several vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050.
Mycobacterium tuberculosis remains one of the most pernicious of human pathogens. Current vaccines are ineffective and drugs, although efficacious, require prolonged treatment with constant medical oversight. Overcoming these problems requires a greater appreciation of M. tuberculosis in the context of its host. Upon infection of either macrophages in culture or animal models, the bacterium re-aligns its metabolism in response to the new environments it encounters. Understanding these environments, and the stresses that they place on M. tuberculosis, should provide insights invaluable for the development of new chemo- and immuno-therapeutic strategies.
Russell, David G.; VanderVen, Brian C.; Lee, Wonsik; Abramovitch, Robert B.; Kim, Mijeong; Homolka, Susanne; Niemann, Stefan; Rohde, Kyle H.
Tuberculosis has a high prevalence in Tunisia, but pulmonary embolism is rarely reported in Mycobacterium tuberculosis infection. We describe 3 cases of pulmonary embolism associated with severe pulmonary tuberculosis. Pulmonary embolism occurred within 2 to 13 days of pulmonary tuberculosis diagnosis. Clinical, bacteriological, and radiological evolutions were noted within 6 months for pulmonary tuberculosis, but controlling the international normalized ratio was difficult in 2 cases, and low-molecular-weight heparin was prescribed for 6 months in one case. The association between tuberculosis and pulmonary embolism is rare, but it should be systematically investigated, particularly in those with severe pulmonary or disseminated tuberculosis. PMID:24771743
Kwas, Hamida; Habibech, Sonia; Zendah, Ines; Elmjendel, Imen; Ghedira, Habib
Japanese Ministry of Health, Labour and Welfare issued new criteria for admission and discharge of tuberculosis patients in 2007. The criteria for admission are extended for the patients of the risk of Mycobacterium tuberculosis transmission and of the possible risk of treatment failure. The criteria for discharge are consisted of the 3 factors, (1) symptoms (cough, fever, etc.) are free after the standard chemotherapy of more than 2 weeks, (2) three different sputum smears are negative for acid-fast bacilli after the standard chemotherapy of more than 2 weeks, (3) patients are estimated to adhere to the chemotherapy after discharge and understand the infection control of M. tuberculosis. Although the criteria were simple, the goal was to treat tuberculosis patients successfully and improve treatment outcomes. For the effective operation of these criteria, the network of primary care facilities for early diagnosis and treatment after discharge, tuberculosis treatment facilities for hospitalization and local government including health care center is important. Four speakers proposed the problems and revealed their own resolutions. Three speakers from tuberculosis treatment facilities were positive for the shortening of hospitalization length by modifying the discharging criteria, however 1 speaker from the Tokyo Metropolitan Government emphasized that the regional medical system should be established for the treatment of discharged tuberculosis patient. 1. Reconsideration of admission and discharge criteria for tuberculosis patients: Kazunari TSUYUGUCHI (Department of Infectious Diseases, Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center) According to the present guideline in Japan, three consecutive negative sputum results for smear or culture are required for discharge of tuberculosis (TB) patients, making their duration of hospitalization extremely long. On the other hand, most of the TB ward in Japan consists of big rooms without air conditioning which carries a potential risk of nosocomial transmission and reinfection. In order to establish effective TB control, suspected or confirmed TB patient should be isolated in a single room equipped with the capacity for airborne infection isolation during hospitalization, as long as sputum smear or culture remains positive. It is reasonable to discharge patients to home before sputum conversion if effective chemotherapy is provided and all household members have been previously exposed. Rapid drug sensitivity testing will be helpful in assuring the effectiveness of chemotherapy for prompt discharge and detecting multidrug-resistance immediately. 2. Reconsideration of admission and discharge criteria for tuberculosis patient in Japan : Taku NAKAGAWA, Kenji OGAWA (Department of Pulmonary Medicine, National Hospital Organization Higashi Nagoya National Hospital) Admission criteria for tuberculosis patient are based on the positive result of sputum AFB smear test in principle. But admission criteria should be applied flexibly depending on the extent and severity of illness, socioeconomic background of the patient, and adherence to treatment in cooperation with the public health center. The Japanese Tuberculosis Society published "Guidelines for Admission and Discharge of Tuberculosis Patient" in January 2005. This guideline was consistent with the notice from Ministry of Health, Labour and Welfare. Improvement of management of patients with tuberculosis is most important, but bacteriological conversion is not necessary to release isolation from the hospital. The patients treated with standard regimen over two weeks and having improvement of clinical symptoms may be able to go home back in the absence of compromised person. As a result of putting this guideline into practice, there were no problems about infectiousness for tuberculosis. But the modified notice from Ministry of Health, Labour and Welfare based on bacteriological conversion was made public in September 2007. This modified notice brought in a prolonged period of hospi
Masuyama, Hidenori; Igari, Hidetoshi
Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics. PMID:22496353
McNerney, Ruth; Maeurer, Markus; Abubakar, Ibrahim; Marais, Ben; McHugh, Timothy D; Ford, Nathan; Weyer, Karin; Lawn, Steve; Grobusch, Martin P; Memish, Ziad; Squire, S Bertel; Pantaleo, Giuseppe; Chakaya, Jeremiah; Casenghi, Martina; Migliori, Giovanni-Batista; Mwaba, Peter; Zijenah, Lynn; Hoelscher, Michael; Cox, Helen; Swaminathan, Soumya; Kim, Peter S; Schito, Marco; Harari, Alexandre; Bates, Matthew; Schwank, Samana; O'Grady, Justin; Pletschette, Michel; Ditui, Lucica; Atun, Rifat; Zumla, Alimuddin
Summary: Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field.
Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K.
BackgroundA significant body of evidence accumulated over the last century suggests a link between hypoxic microenvironments within the infected host and the latent phase of tuberculosis. Studies to test this correlation have identified the M. tuberculosis initial hypoxic response, controlled by the two-component response regulator DosR. The initial hypoxic response is completely blocked in a dosR deletion mutant.Methodology\\/Principal FindingsWe show
Tige R. Rustad; Maria I. Harrell; Reiling Liao; David R. Sherman; Jürg Bähler
We present a case of a 38-year-old-man who presented with 1-week history of developing weakness of peripheral and cranial nerves. His MRI scan of the brain showed a large cavitating lesion at the brainstem and two further lesions of the right cerebral cortex and his CT chest showed features of old tuberculosis (TB). The identification of acid-fast bacilli was confirmed by analysis of bronchoalveolar lavage taken during bronchoscopy. He was started on anti-TB medications and repeat MRI 3 months later confirmed shrinkage of the cavitating lesion. PMID:23868024
Demetriou, George A
INTRODUCTION: Tuberculosis remains a major public health problem worldwide. In recent years, increasing efforts have been dedicated to assessing the health-related quality of life experienced by people infected with tuberculosis. The objectives of this study were to better understand the impact of tuberculosis and its treatment on people's quality of life, and to review quality of life instruments used in
Na Guo; Fawziah Marra; Carlo A Marra
Background Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV). Methods The study population comprised prospective cohorts of children who were undergoing evaluation for suspected tuberculosis in South Africa (655 children), Malawi (701 children), and Kenya (1599 children). Patients were assigned to groups according to whether the diagnosis was culture-confirmed tuberculosis, culture-negative tuberculosis, diseases other than tuberculosis, or latent tuberculosis infection. Diagnostic signatures distinguishing tuberculosis from other diseases and from latent tuberculosis infection were identified from genomewide analysis of RNA expression in host blood. Results We identified a 51-transcript signature distinguishing tuberculosis from other diseases in the South African and Malawian children (the discovery cohort). In the Kenyan children (the validation cohort), a risk score based on the signature for tuberculosis and for diseases other than tuberculosis showed a sensitivity of 82.9% (95% confidence interval [CI], 68.6 to 94.3) and a specificity of 83.6% (95% CI, 74.6 to 92.7) for the diagnosis of culture-confirmed tuberculosis. Among patients with cultures negative for Mycobacterium tuberculosis who were treated for tuberculosis (those with highly probable, probable, or possible cases of tuberculosis), the estimated sensitivity was 62.5 to 82.3%, 42.1 to 80.8%, and 35.3 to 79.6%, respectively, for different estimates of actual tuberculosis in the groups. In comparison, the sensitivity of the Xpert MTB/RIF assay for molecular detection of M. tuberculosis DNA in cases of culture-confirmed tuberculosis was 54.3% (95% CI, 37.1 to 68.6), and the sensitivity in highly probable, probable, or possible cases was an estimated 25.0 to 35.7%, 5.3 to 13.3%, and 0%, respectively; the specificity of the assay was 100%. Conclusions RNA expression signatures provided data that helped distinguish tuberculosis from other diseases in African children with and those without HIV infection. (Funded by the European Union Action for Diseases of Poverty Program and others). PMID:24785206
Anderson, Suzanne T; Kaforou, Myrsini; Brent, Andrew J; Wright, Victoria J; Banwell, Claire M; Chagaluka, George; Crampin, Amelia C; Dockrell, Hazel M; French, Neil; Hamilton, Melissa S; Hibberd, Martin L; Kern, Florian; Langford, Paul R; Ling, Ling; Mlotha, Rachel; Ottenhoff, Tom H M; Pienaar, Sandy; Pillay, Vashini; Scott, J Anthony G; Twahir, Hemed; Wilkinson, Robert J; Coin, Lachlan J; Heyderman, Robert S; Levin, Michael; Eley, Brian
It has been well established that the host genetic background is an important modulator of tuberculosis susceptibility. The NRAMP1 (alias SLC11A1) gene has been associated with tuberculosis susceptibility in several ethnic groups. Here we studied the association and linkage of NRAMP1 with tuberculosis in 116 nuclear families, comprising 211 affected offspring, from Casablanca, Morocco. All enrolled tuberculosis cases were culture-positive. No evidence was found of linkage or association of NRAMP1 with tuberculosis. These findings suggest heterogeneity in the genetic control of tuberculosis susceptibility. PMID:12797705
El Baghdadi, J; Remus, N; Benslimane, A; El Annaz, H; Chentoufi, M; Abel, L; Schurr, E
Although the development of novel drugs and combination regimens for tuberculosis has accelerated in recent years, the pipeline remains thin and major challenges remain to be addressed in efficiently evaluating newer drugs to improve treatment outcomes, shorten duration of therapy and tackle drug resistance. PMID:22378254
Zumla, Alimuddin; Hafner, Richard; Lienhardt, Christian; Hoelscher, Michael; Nunn, Andrew
BackgroundElucidation of the basic mechanistic and biochemical principles underlying siderophore mediated iron uptake in mycobacteria is crucial for targeting this principal survival strategy vis-à-vis virulence determinants of the pathogen. Although, an understanding of siderophore biosynthesis is known, the mechanism of their secretion and uptake still remains elusive.Methodology\\/Principal FindingsHere, we demonstrate an interplay among three iron regulated Mycobacterium tuberculosis (M.tb) proteins,
Aisha Farhana; Sandeep Kumar; Shailendra S. Rathore; Prahlad C. Ghosh; Nasreen Z. Ehtesham; Anil K. Tyagi; Seyed E. Hasnain; Dana Davis
Background Tuberculosis is one of the world’s leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1intCD11b+ cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. Methodology/Principal Findings We compared the bacterial burden, lung pathology and Gr1intCD11b+ myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1+ cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1+CD11b+ cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1hi and Gr1int populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1int populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1hi and Gr1int cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4+ T to Gr1+ cells increased. Our results illustrate a yet unrecognized interplay between Gr1+ cells and CD4+ T cells in tuberculosis.
Obregon-Henao, Andres; Henao-Tamayo, Marcela; Orme, Ian M.; Ordway, Diane J.
Background This study was set out to investigate the magnitude, patterns and molecular characterization of drug-resistant Mycobacterium tuberculosis strains at a tertiary referral hospital in Bangladesh. Methods Pulmonary tuberculosis (TB) patients admitted at National Institute of Diseases of the Chest and Hospital from February 2002 to September 2005 with or without previous history of TB and/or other complications were randomly interviewed. Among 265 participants enrolled, M. tuberculosis isolates from 189 patients were finally tested for susceptibility to rifampicin (RMP), isoniazid (INH), ethambutol (ETM) and streptomycin (STM). Genotyping of M. tuberculosis was done using deletion analysis and spoligotyping. Results Eighty-eight percent (n?=?167) of the patients had history of previous anti-TB treatment while the remaining 12% were new TB cases. Of the 189 isolates, 9% were fully susceptible to the first line anti-TB drugs and 73.5% were multi-drug resistant TB. Other susceptibility results showed 79.4%, 77.2%, 76.7% and 78.8% resistance to INH, RMP, ETM and STM respectively. Multi-drug resistance was significantly higher among the 130 (78%) patients with previous history of anti-tuberculosis treatment (95% confidence interval, p?=?0.001). Among the 189 analyzed isolates, 69% were classified as “modern” M. tuberculosis strains (i.e. TbD1- strains, lacking the M. tuberculosis-deletion region TbD1), whereas the remaining 31% were found to belong to the “ancestal” TbD1+ M. tuberculosis lineages. One hundred and five different spoligotype patterns were identified in which 16 clusters contained 100 strains and 89 strains had unique pattern. Strains with a spoligotype characteristic for the “Beijing” cluster were predominant (19%) and most of these strains (75%) were multi-drug resistant (MDR). Conclusions A high level of drug resistance observed among the re-treatment patients poses a threat of transmission of resistant strains to susceptible persons in the community. Proper counseling of patients and attention towards the completion of the anti-TB treatment is needed.
Banu, Sayera; Mahmud, Asif Mujtaba; Rahman, Md. Toufiq; Hossain, Arman; Uddin, Mohammad Khaja Mafij; Ahmed, Tahmeed; Khatun, Razia; Akhanda, Wahiduzzaman; Brosch, Roland
BACKGROUND: Delay in diagnosis of pulmonary tuberculosis results in increasing severity, mortality and transmission. Various investigators have reported about delays in diagnosis of tuberculosis. We aimed at summarizing the data on these delays in diagnosis of tuberculosis. METHODS: A systematic review of literature was carried out. Literature search was done in Medline and EMBASE from 1990 to 2008. We used
Chandrashekhar T Sreeramareddy; Kishore V Panduru; Joris Menten; J Van den Ende
BACKGROUND: The prevalence of pulmonary tuberculosis among college students in Shaanxi is high. Although tuberculosis leaves much psychological and social impact on patients, little is known about its impact on college students. The objective of this study is to explore the experiences and psychological process of college students with pulmonary tuberculosis in Shaanxi, China. METHODS: 17 college students with pulmonary
Shao-Ru Zhang; Hong Yan; Jin-Jing Zhang; Tian-Hua Zhang; Xiao-Hong Li; Yin-Ping Zhang
BACKGROUND--In a previous retrospective study of tuberculosis in south London among Asian immigrants from the Indian subcontinent Hindu Asians were found to have a significantly increased risk for tuberculosis compared with Muslims. This finding has been further investigated by examining the role of socioeconomic and lifestyle variables, including diet, as risk factors for tuberculosis in Asian immigrants from the Indian
D P Strachan; K J Powell; A Thaker; F J Millard; J D Maxwell
Two similar mycobacteria, Mycobacteria tuberculosis H37Ra and Mycobacteria smegmatis are rapidly detected and identified within samples containing a complex background of respiratory effluents using Single Particle Aerosol Mass Spectrometry (SPAMS). M. tuberculosis H37Ra (TBa), an avirulent strain, is used as a surrogate for virulent tuberculosis (TBv); M. smegmatis (MSm) is utilized as a near neighbor confounder for TBa. Bovine lung
K L Adams; P T Steele; M J Bogan; N M Sadler; S Martin; A N Martin; M Frank
BACKGROUND: Delay in the diagnosis of tuberculosis may worsen the disease, increase the risk of death and enhance tuberculosis transmission in the community. This study aims to determine the length of delay between the onset of symptoms and patients first visit to health care (patient delay), and the length of delay between health care visit and the diagnosis of tuberculosis
Meaza Demissie; Bernt Lindtjorn; Yemane Berhane
Mycobacterium tuberculosis remains a major cause of morbidity and mortality worldwide. Studies have reported human pathogens to have geographically structured population genetics, some of which have been linked to ancient human migrations. However, no study has addressed the potential evolutionary consequences of such longstanding human-pathogen associations. Here, we demonstrate that the global population structure of M. tuberculosis is defined by
Sebastien Gagneux; Kathryn Deriemer; Tran van; Midori Kato-Maeda; Bouke C. de Jong; Sujatha Narayanan; Mark Nicol; Stefan Niemann; Kristin Kremer; M. Cristina Gutierrez; Markus Hilty; Philip C. Hopewell; Peter M. Small
The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world.
Forrellad, Marina A.; Klepp, Laura I.; Gioffre, Andrea; Sabio y Garcia, Julia; Morbidoni, Hector R.; Santangelo, Maria de la Paz; Cataldi, Angel A.; Bigi, Fabiana
Mycobacterium tuberculosis, the human pathogen that causes tuberculosis, warrants enormous attention due to the emergence of multi drug resistant and extremely drug resistant strains. RNA polymerase (RNAP), the key enzyme in gene regulation, is an attractive target for anti-TB drugs. Understanding the structure-function relationship of M. tuberculosis RNAP and the mechanism of gene regulation by RNAP in conjunction with different ? factors and transcriptional regulators would provide significant information for anti-tuberculosis drug development targeting RNAP. Studies with M. tuberculosis RNAP remain tedious because of the extremely slow-growing nature of the bacteria and requirement of special laboratory facility. Here, we have developed and optimized recombinant methods to prepare M. tuberculosis RNAP core and RNAP holo enzymes assembled in vivo in Escherichia coli. These methods yield high amounts of transcriptionally active enzymes, free of E. coli RNAP contamination. The recombinant M. tuberculosis RNAP is used to develop a highly sensitive fluorescence based in vitro transcription assay that could be easily adopted in a high-throughput format to screen RNAP inhibitors. These recombinant methods would be useful to set a platform for M. tuberculosis RNAP targeted anti TB drug development, to analyse the structure/function of M. tuberculosis RNAP and to analyse the interactions among promoter DNA, RNAP, ? factors, and transcription regulators of M. tuberculosis in vitro, avoiding the hazard of handling of pathogenic bacteria. PMID:24832563
Banerjee, Rajdeep; Rudra, Paulami; Prajapati, Ranjit Kumar; Sengupta, Shreya; Mukhopadhyay, Jayanta
Female genital tuberculosis remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome. Genital tuberculosis (TB) is commonly asymptomatic and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools such as computed tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpinography has been considered as the standard screening test for evaluation of tubal infertility and as a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and the "leopard skin tube". Part II will describe adverse effects of tuberculosis on structure of endometrium and radiological specific findings, such as "T-shaped" tuberculosis uterus, "pseudo-unicornuate "uterus, "collar-stud abscess" and "dwarfed" uterus with lymphatic intravasation and occluded tubes which have not been encountered in the majority of non-tuberculosis cases. PMID:24696765
Ahmadi, Firoozeh; Zafarani, Fatemeh; Shahrzad, Gholam Shahrzad
Female genital tuberculosis remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome. Genital tuberculosis (TB) is commonly asymptomatic and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools such as computed tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpinography has been considered as the standard screening test for evaluation of tubal infertility and as a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and the "leopard skin tube". Part II will describe adverse effects of tuberculosis on structure of endometrium and radiological specific findings, such as "T-shaped" tuberculosis uterus, "pseudo-unicornuate "uterus, "collar-stud abscess" and "dwarfed" uterus with lymphatic intravasation and occluded tubes which have not been encountered in the majority of non-tuberculosis cases.
Ahmadi, Firoozeh; Zafarani, Fatemeh; Shahrzad, Gholam Shahrzad
Background Isoniazid resistance is an obstacle to the treatment of tuberculosis disease and latent tuberculosis infection in children. We aim to summarize the literature describing the risk of isoniazid-resistant tuberculosis among children with tuberculosis disease. Methods We did a systematic review of published reports of children with tuberculosis disease who had isolates tested for susceptibility to isoniazid. We searched PubMed, Embase and LILACS online databasesuptoJanuary 12, 2012. Results Our search identified 3,403 citations, of which 95 studies met inclusion criteria. These studies evaluated 8,351 children with tuberculosis disease for resistance to isoniazid. The median proportion of children found to have isoniazid-resistant strains was 8%; the distribution was right-skewed (25th percentile: 0% and 75th percentile: 18%). Conclusions High proportions of isoniazid resistance among pediatric tuberculosis patients have been reported in many settings suggesting that diagnostics detecting only rifampin resistance are insufficient to guide appropriate treatment in this population. Many children are likely receiving sub-standard tuberculosis treatment with empirical isoniazid-based regimens, and treating latent tuberculosis infection with isoniazid may not be effective in large numbers of children. Work is needed urgently to identify effective regimens for the treatment of children sick with or exposed to isoniazid-resistant tuberculosis and to better understand the scope of this problem.
Yuen, Courtney M.; Tolman, Arielle W.; Cohen, Ted; Parr, Jonathan B.; Keshavjee, Salmaan; Becerra, Mercedes C.
... Laws Publications & Products Fact Sheets General Fact sheets - Spanish TB - General Information The Difference Between Latent TB ... HIV Coinfection Patient Education Series English Only English/Spanish English/Tagalog Tuberculosis - Get the Facts Tuberculosis - La ...
... Laws Publications & Products Fact Sheets General Fact sheets - Spanish TB - General Information The Difference Between Latent TB ... HIV Coinfection Patient Education Series English Only English/Spanish English/Tagalog Tuberculosis - Get the Facts Tuberculosis - La ...
There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupational disease among health care workers, presenting the current Peruvian law related. PMID:22858771
Tuberculosis of parotid is a rare clinical entity, and cases of bilateral tubercular parotitis are even rarer. We present a case of bilateral primary parotid tuberculosis in a 49-year-old female. The patient received anti-tuberculosis treatment for six months, resulting in complete resolution of the disease. We also review the theories related to the pathogenesis of tubercular parotitis, and propose a novel hypothesis about greater involvement of parotid gland as compared to other salivary glands in primary tuberculosis.
Thakur, JS; Thakur, A; Mohindroo, NK; Mohindroo, S; Sharma, DR
Background Tuberculosis remains a high burden for Human society despite considerable investments in its control. Unique features in the history of infection and transmission dynamics of tuberculosis pose serious limitations on the direct interpretation of surveillance data and call for models that incorporate latent processes and simulate specific interventions. Methods A transmission model was adjusted to the dataset of active tuberculosis cases reported in Portugal between 2002 and 2009. We estimated key transmission parameters from the data (i.e. time to diagnosis, treatment length, default proportion, proportion of pulmonary TB cases). Using the adjusted model to the Portuguese case, we estimated the total burden of tuberculosis in Portugal. We further performed sensitivity analysis to heterogeneities in susceptibility to infection and exposure intensity. Results We calculated a mean time to diagnose of 2.81 months and treatment length of 8.80 months in Portugal. The proportion defaulting treatment was calculated as 0.04 and the proportion of pulmonary cases as 0.75. Using these values, we estimated a TB burden of 1.6 million infected persons, corresponding to more than 15% of the Portuguese population. We further described the sensitivity of these estimates to heterogeneity. Conclusions We showed that the model reproduces well the observed dynamics of the Portuguese data, thus demonstrating its adequacy for devising control strategies for TB and predicting the effects of interventions.
Two cases of isolated colonic tuberculosis are reported, and recent literature on this field is reviewed. Isolated colonic tuberculosis is defined as a tuberculosis which exists in the colon except for ileocaecum, without focus in any other organ. The morphological changes are tuberculous granulation primarily located to the submucosa layer of the colon with smooth surfaces of both mucous and
Y. A. Wang; W. Y. Yu
Tuberculosis is a diffusive infectious disease whose typical behaviour differentiates it from other infectious diseases spread by human-to-human transmission (flu, chicken pox, cholera, etc.) that follow a classic epidemic pattern. Indeed, in the presence of a known source of Koch bacilli that is capable of spreading the bacteria by air, not all exposed individuals inhale the bacteria, not all those who inhale them absorb them, not all those who absorb the bacteria are unable to eliminate them, not all who are able to eliminate them do so using delayed hypersensitivity, not all those who react with delayed hypersensitivity suffer lasting tissue damage (among other things, minor), not all who suffer tissue damage have anatomical sequelae, and not all those who have anatomical sequelae, however minimal, become carriers of bacilli in the latent period. The vast majority (90-95%) of the latter - which are in any case a portion, not the totality of those exposed - remain asymptomatic throughout their lives and never develop active tuberculosis. Based on these biological characteristics and the legal concepts of "epidemic" and "disease," it becomes highly problematic, if not impossible, to assert both that tuberculosis can cause events of sufficient magnitude to be associated with the crime of "epidemic," and that the mere diagnosis of a latent tuberculosis infection is sufficient to assume the presence of an illness legally prosecutable in criminal proceedings or a disability prosecutable in civil proceedings. Furthermore, clinically apparent tuberculosis is a temporarily-and in some cases permanently-disabling condition, and in certain work environments, even with the difficulties caused by the lack of available effective diagnostic tools and the insidious behaviour of the disease in the early stages, targeted monitoring to identify other persons who may become ill is appropriate. PMID:24804006
Vetrugno, G; De-Giorgio, F; D'Alessandro, F; Scafetta, I; Berloco, F; Buonsenso, D; Abbate, F; Scalise, G; Pascali, V L; Valentini, P
Tuberculosis is a diffusive infectious disease whose typical behaviour differentiates it from other infectious diseases spread by human-to-human transmission (flu, chicken pox, cholera, etc.) that follow a classic epidemic pattern. Indeed, in the presence of a known source of Koch bacilli that is capable of spreading the bacteria by air, not all exposed individuals inhale the bacteria, not all those who inhale them absorb them, not all those who absorb the bacteria are unable to eliminate them, not all who are able to eliminate them do so using delayed hypersensitivity, not all those who react with delayed hypersensitivity suffer lasting tissue damage (among other things, minor), not all who suffer tissue damage have anatomical sequelae, and not all those who have anatomical sequelae, however minimal, become carriers of bacilli in the latent period. The vast majority (90–95%) of the latter – which are in any case a portion, not the totality of those exposed – remain asymptomatic throughout their lives and never develop active tuberculosis. Based on these biological characteristics and the legal concepts of “epidemic” and “disease,” it becomes highly problematic, if not impossible, to assert both that tuberculosis can cause events of sufficient magnitude to be associated with the crime of “epidemic,” and that the mere diagnosis of a latent tuberculosis infection is sufficient to assume the presence of an illness legally prosecutable in criminal proceedings or a disability prosecutable in civil proceedings. Furthermore, clinically apparent tuberculosis is a temporarily—and in some cases permanently—disabling condition, and in certain work environments, even with the difficulties caused by the lack of available effective diagnostic tools and the insidious behaviour of the disease in the early stages, targeted monitoring to identify other persons who may become ill is appropriate.
Vetrugno, G.; De-Giorgio, F.; D'Alessandro, F.; Scafetta, I.; Berloco, F.; Buonsenso, D.; Abbate, F.; Scalise, G.; Pascali, V.L.; Valentini, P
Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis that accounts for 1% to 2% of cases. Childhood skin tuberculosis represents 18% to 82% of all cutaneous tuberculosis cases. Scrofuloderma and lupus vulgaris are the two most common clinical forms in children. An increase in the number of tuberculids, especially lichen scrofulosorum, has been observed in the last several years. Cutaneous tuberculosis in children can be severe and have a protracted course. Multiplicity of lesions and multifocal disseminated involvement in scrofuloderma and lupus vulgaris is common. Scrofuloderma progressing to gummatous lesions (scrofulous gumma) is mostly described in children. Morbidities and deformities are more severe in children. PMID:23173930
Sethuraman, Gomathy; Ramesh, Venkatesh
Tuberculosis remains a disease with an enormous impact on public health worldwide. With the continuously increasing epidemic of drug-resistant tuberculosis, new drugs are desperately needed. However, even for the treatment of drug-sensitive tuberculosis, new drugs are required to shorten the treatment duration and thereby prevent development of drug resistance. Within the past ten years, major advances in tuberculosis drug research have been made, leading to a considerable number of antimycobacterial compounds which are now in the pipeline. Here we discuss a number of these novel promising tuberculosis drugs, as well as the discovery of two new potential drug targets for the development of novel effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein kinase G pathways. Protein kinase G is secreted by mycobacteria and is responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is responsible for activating the phosphatase, calcineurin, and thereby preventing phagosome-lysosome fusion within the macrophage. Blocking these two pathways may lead to rapid killing of mycobacteria.
Janssen, Saskia; Jayachandran, Rajesh; Khathi, Lulama; Zinsstag, Jakob; Grobusch, Martin P; Pieters, Jean
Two amateur paleontologists kept their eyes to the ground in Oregon on one of their recent hikes and discovered what are believed to be the first remains of a marine reptile called the plesiosaur to be unearthed in the Pacific Northwest. This radio broadcast reports on the discovery and what it could mean to the understanding of dinosaurs in the area. The clip is 5 minutes and 6 seconds in length.
Background The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis control programme activities within a strengthened health system. Discussion HIV and tuberculosis share many similarities in terms of their disease burden and the recommended stratagems for their control. HIV and tuberculosis programmes implement similar sorts of control activities, e.g. case finding and treatment, which depend for success on generic health system issues, including vital registration, drug procurement and supply, laboratory network, human resources, and financing. However, the current health system approach to HIV and tuberculosis control often involves separate specialised services. Despite some recent progress, collaboration between the programmes remains inadequate, progress in obtaining synergies has been slow, and results remain far below those needed to achieve universal access to key interventions. A fundamental re-think of the current strategic approach involves promoting integrated delivery of HIV and tuberculosis programme activities as part of strengthened general health services: epidemiological surveillance, programme monitoring and evaluation, community awareness of health-seeking behavior, risk behaviour modification, infection control, treatment scale-up (first-line treatment regimens), drug-resistance surveillance, containing and countering drug-resistance (second-line treatment regimens), research and development, global advocacy and global partnership. Health agencies should review policies and progress in HIV and tuberculosis epidemic control, learn mutual lessons for policy development and scaling up interventions, and identify ways of joint planning and joint funding of integrated delivery as part of strengthened health systems. Summary As both a danger and an opportunity, the global financial crisis may entail disaster or recovery for global health sector efforts for HIV and tuberculosis epidemic control. Review of policies and progress in control paves the way for identification of synergies between the two programmes, within strengthened health services. The silver lining in the global economic crisis could be better control of the HIV and tuberculosis epidemics, better overall health system performance and outcomes, and better value for money.
Background Tuberculosis remains a major public health problem in sub-Saharan Africa. District hospitals (DHs) play a central role in district-based health systems, and their relation with vertical programmes is very important. Studies on the impact of vertical programmes on DHs are rare. This study aims to fill this gap. Its purpose is to analyse the interaction between the National Tuberculosis Control Programme (NTCP) and DHs in Cameroon, especially its effects on the human resources, routine health information system (HIS) and technical capacity at the hospital level. Methods We used a multiple case study methodology. From the Adamaoua Region, we selected two DHs, one public and one faith-based. We collected qualitative and quantitative data through document reviews, semi-structured interviews with district and regional staff, and observations in the two DHs. Results The NTCP trained and supervised staff, designed and provided tuberculosis data collection and reporting tools, and provided anti-tuberculosis drugs, reagents and microscopes to DHs. However, these interventions were limited to the hospital units designated as Tuberculosis Diagnostic and Treatment Centres and to staff dedicated to tuberculosis control activities. The NTCP installed a parallel HIS that bypassed the District Health Services. The DH that performs well in terms of general hospital care and that is well managed was successful in tuberculosis control. Based on the available resources, the two hospitals adapt the organisation of tuberculosis control to their settings. The management teams in charge of the District Health Services are not involved in tuberculosis control. In our study, we identified several opportunities to strengthen the local health system that have been missed by the NTCP and the health system managers. Conclusion Well-managed DHs perform better in terms of tuberculosis control than DHs that are not well managed. The analysis of the effects of the NTCP on the human resources, HIS and technical capacity of DHs indicates that the NTCP supports, rather than strengthens, the local health system. Moreover, there is potential for this support to be enhanced. Positive synergies between the NTCP and district health systems can be achieved if opportunities to strengthen the district health system are seized. The question remains, however, of why managers do not take advantage of the opportunities to strengthen the health system.
... gov . Tuberculosis (TB) Share Compartir Factsheet ( PDF - 672k) Spanish Tuberculosis in Hispanics/Latinos Tuberculosis (TB) is a ... Laws Publications & Products Fact Sheets General Fact sheets - Spanish TB - General Information The Difference Between Latent TB ...
Background South Africa endorses the global policy shift from primarily client-initiated voluntary counselling and testing (VCT) to routine\\/provider-initiated\\u000a testing and counselling (PITC). The reason for this policy shift has been to facilitate uptake of HIV testing amongst at-risk\\u000a populations in high-prevalence settings. Despite ostensible implementation of routine\\/PITC, uptake amongst tuberculosis (TB)\\u000a patients in this country remains a challenge. This study presents
N Gladys Kigozi; J Christo Heunis; Edwin Wouters; Henriëtte S van den Berg
Following primary tuberculosis (TB) infection, only approximately 10% of individuals develop active T.B. Most people are assumed to mount an effective immune response to the initial infection that limits proliferation of the bacilli and leads to long-lasting partial immunity both to further infection and to reactivation of latent bacilli remaining from the original infection. Infected individuals may develop active TB
Zhilan Feng; Carlos Castillo-Chavez; Angel F. Capurro
Seven outbreaks involving increasing numbers of banded mongoose troops and high death rates have been documented. We identified a Mycobacterium tuberculosis complex pathogen, M. mungi sp. nov., as the causative agent among banded mongooses that live near humans in Chobe District, Botswana. Host spectrum and transmission dynamics remain unknown.
Laver, Pete N.; Michel, Anita L.; Williams, Mark; van Helden, Paul D.; Warren, Robin M.; Gey van Pittius, Nicolaas C.
Seven outbreaks involving increasing numbers of banded mongoose troops and high death rates have been documented. We identified a Mycobacterium tuberculosis complex pathogen, M. mungi sp. nov., as the causative agent among banded mongooses that live near humans in Chobe District, Botswana. Host spectrum and transmission dynamics remain unknown. PMID:20678329
Alexander, Kathleen A; Laver, Pete N; Michel, Anita L; Williams, Mark; van Helden, Paul D; Warren, Robin M; Gey van Pittius, Nicolaas C
CD8+ T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis (Mtb), Salmonella species, and Listeria monocytogenes, yet the repertoire and dominance pattern of human CD8 antigens for these pathogens remains poorly characterized. Tuberculosis (TB), the disease caused by Mtb infection, remains one of the leading causes of infectious morbidity and mortality worldwide and is
Deborah A Lewinsohn; Ervina Winata; Gwendolyn M Swarbrick; Katie E Tanner; Matthew S Cook; Megan D Null; Meghan E Cansler; Alessandro Sette; John Sidney; David M Lewinsohn
Background Tuberculosis (TB) remains a global public health problem whose effects have major impact in developing countries like Uganda. This study aimed at investigating genotypic characteristics and drug resistance profiles of Mycobacterium tuberculosis isolated from suspected TB patients. Furthermore, risk factors and economic burdens that could affect the current control strategies were studied. Methods TB suspected patients were examined in a cross-sectional study at the Mubende regional referral hospital between February and July 2011. A questionnaire was administered to each patient to obtain information associated with TB prevalence. Isolates of M. tuberculosis recovered during sampling were examined for drug resistance to first line anti-TB drugs using the BACTEC-MGIT960TMsystem. All isolates were further characterized using deletion analysis, spoligotyping and MIRU-VNTR analysis. Data were analyzed using different software; MIRU-VNTR plus, SITVITWEB, BioNumerics and multivariable regression models. Results M. tuberculosis was isolated from 74 out of 344 patients, 48 of these were co-infected with HIV. Results from the questionnaire showed that previously treated TB, co-infection with HIV, cigarette smoking, and overcrowding were risk factors associated with TB, while high medical related transport bills were identified as an economic burden. Out of the 67 isolates that gave interpretable results, 23 different spoligopatterns were detected, nine of which were novel patterns. T2 with the sub types Uganda-I and Uganda-II was the most predominant lineage detected. Antibiotic resistance was detected in 19% and multidrug resistance was detected in 3% of the isolates. Conclusion The study detected M. tuberculosis from 21% of examined TB patients, 62% of whom were also HIV positive. There is a heterogeneous pool of genotypes that circulate in this area, with the T2 lineage being the most predominant. High medical related transport bills and drug resistance could undermine the usefulness of the current TB strategic interventions.
Muwonge, Adrian; Malama, Sydney; Johansen, Tone B.; Kankya, Clovice; Biffa, Demelash; Ssengooba, Willy; Godfroid, Jacques; Dj?nne, Berit; Skjerve, Eystein
Background: Poor treatment adherence to tuberculosis treatment is a problem among rural patients in Ethiopia. We aimed to decentralize directly observed treatment of tuberculosis at village level using volunteer Community Health Workers (CHWs) in order to improve treatment adherence. However, we need to determine their training needs and willingness to supervise treatment of patients with tuberculosis in their respective villages.
Mengiste M Mesfin; Tesfay W Tasew; Israel G Tareke; Madeley RJ Richard
Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease.
Jaganath, Devan; Mupere, Ezekiel
Tuberculosis is the second leading cause of infectious deaths globally. Many effective conventional antimycobacterial drugs have been available, however, emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has overshadowed the effectiveness of the current first and second line drugs. Further, currently available agents are complicated by serious side effects, drug interactions and long-term administration. This has prompted urgent research efforts in the discovery and development of new anti-tuberculosis agent(s). Several families of compounds are currently being explored for the treatment of tuberculosis. This review article presents an account of the existing chemotherapeutics and highlights the therapeutic potential of emerging molecules that are at different stages of development for the management of tuberculosis disease.
Shakya, Neeraj; Garg, Gaurav; Agrawal, Babita; Kumar, Rakesh
Background Mycobacterium tuberculosis DNA topoisomerase I is an attractive target for discovery of novel TB drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product. It shares a common transesterification domain with other type IA DNA topoisomerases. There is, however, no homology between the C-terminal DNA binding domains of Escherichia coli and M. tuberculosis DNA topoisomerase I proteins. Results A new protocol for expression and purification of recombinant M. tuberculosis DNA topoisomerase I (MtTOP) has been developed to produce enzyme of much higher specific activity than previously characterized recombinant enzyme. MtTOP was found to be less efficient than E. coli DNA topoisomerase I (EcTOP) in removal of remaining negative supercoils from partially relaxed DNA. DNA cleavage by MtTOP was characterized for the first time. Comparison of DNA cleavage site selectivity with EcTOP showed differences in cleavage site preferences, but the preferred sites of both enzymes have a C nucleotide in the -4 position. Conclusion Recombinant M. tuberculosis DNA topoisomerase I can be expressed as a soluble protein and purified in high yield from E. coli host with a new protocol. Analysis of DNA cleavage with M. tuberculosis DNA substrate showed that the preferred DNA cleavage sites have a C nucleotide in the -4 position.
Annamalai, Thirunavukkarasu; Dani, Neil; Cheng, Bokun; Tse-Dinh, Yuk-Ching
Tuberculosis (TB) is an important cause of mortality and morbidity all over the world and is particularly relevant in developing countries like India where the disease is endemic. Female reproductive system is very vulnerable to this infection and clinical presentation of this disease in female reproductive tract is protean in nature and in a large majority of patients could be completely silent. This disease is an important cause of infertility, menstrual irregularity, pregnancy loss, and in association with pregnancy, morbidity to both the mother and child increases. Some of the effects of TB infection on female genital tract could be remote in nature due to infection elsewhere. Medicines used to treat TB infection can also have adverse effects on contraception and other areas of female reproductive health. HIV coinfection and multidrug-resistant tuberculosis (MDR-TB) and increased population migration from developed to developing countries have now added a whole new dimension to this infection. Though new, finer diagnostic tools of detection of TB are increasingly available in the form of bacterial cultures and polymerase chain reaction (PCR) based diagnostics, suspicion by clinicians remains the main tool for diagnosis of the condition. Hence, doctors need to be properly trained to become "Tuberculosis Minded". PMID:22120860
Ghosh, K; Ghosh, K; Chowdhury, J R
Isolated tuberculosis of the coccyx is extremely rare. A 35-year-old man presented with a 3-month history of coccygeal and gluteal pain. Computed tomography and magnetic resonance imaging revealed osseous destruction and a large enhancing mass involving the coccyx with anterior and posterior extension. Pathologic examination of the surgical specimen revealed necrosis, chronic granulomatous inflammation, and multinucleated giant cells consistent with tuberculosis. This case highlights the importance of considering tuberculosis as a diagnosis even though unusual sites are involved.
Kim, Do Un; Ju, Chang IL
Isolated pancreatic tuberculosis (TB) remains a rarity despite the high incidence of tuberculosis in many of the African and Asian countries. Presentation as discrete pancreatic mass often masquerades as pancreatic neoplasm and diagnosis may require histology. Extra-hepatic portal hypertension due to splenic vein thrombosis complicating pancreatic TB has been reported in the literature. We report here a case of isolated pancreatic TB with pancreatic head mass mimicking neoplasm with extra-hepatic portal hypertension. The possibility of TB should be considered in the list of differential diagnoses of pancreatic mass and an endoscopic, ultrasound-guided biopsy might help to clinch the diagnosis of this potentially curable disease.
Zacharia, George S.; Antony, Rajany; Kolassery, Sandesh; Ramachandran, Thazhath M.
Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto.
We report a case of granulomatous mastitis caused by Mycobacterium tuberculosis in an immunocompetent woman with chronic inflammatory lesions of the breast. It was diagnosed by detection of mycobacteria DNA using polymerase chain reaction technique targeting IS6110 insertion element of M. tuberculosis complex in a paraffin-embedded histological specimen. The primary breast tuberculosis is rare, even in countries where the incidence and prevalence of pulmonary and extra pulmonary tuberculosis are high. It should be suspected in female patients with chronic granulomatous mastitis with no apparent cause. The cornerstone of treatment is antituberculous chemotherapy, and surgery is rarely required. PMID:23715305
Cuervo, Sonia Isabel; Bonilla, Diego Andrés; Murcia, Martha Isabel; Hernández, Johana; Gómez, Julio César
Para-H2 may constitute the only other superfluid besides helium. The superfluid transition temperature is predicted to be around 2 K, well below freezing of H2 at 13.8 K. Numerous attempts to supercool macroscopic H2 samples proved to be unsuccessful. Our approach includes formation of H2 clusters in a pulsed cryogenic nozzle beam expansion of a neat pH2 gas as well as X% of pH2 diluted in He and interrogation via Coherent Anti-Stokes Raman Scattering. At X = 2 -- 100 % the frequency of the vibrational Q1(0) line in clusters remains constant at about ? = 4149.7 cm-1 very similar to 4149.6 cm-1 as in solid pH2 and lower than in liquid pH2 at 18 K (4151.9 cm-1). The rotational S0(0) transition show some characteristic crystal field splitting having magnitude of about 6 cm-1. The splitting pattern is different from that in the hcp solid, suggesting different structure in solid pH2 clusters. At X <= 2 %, the frequency of the Q1(0) line increases to about 4150.5 cm-1, which is consistent with that expected in the supercooled liquid. The S0(0) transition in these clusters, consisting of about 5 x 10^4 molecules, appears as a single line at the same frequency as in liquid pH2. The temperature of these supercooled clusters is estimated to be less than about 1 K. Possible superfluidity of the clusters is discussed.
Kuyanov-Prozument, Kirill; Vilesov, Andrey
Risk factors for post-transplant tuberculosis.BackgroundPost-transplant tuberculosis (post-TxTB) occurs in 12 to 20% of patients in India and results in the death of 20 to 25% of those patients. Prospective studies on post-TxTB are few.MethodsRenal allograft recipients were studied prospectively for 3.1 (0 to 13.9) median (range) years for incidence, manifestations, risk factors, and prognosis for post-TxTB. Kaplan-Meier analysis was used
George Tharayil John; Viswanathan Shankar; Abi Mookanottle Abraham; Uma Mukundan; Paulose Punnakuzhathil Thomas; Chakko Korula Jacob
Endobronchial tuberculosis (EBTB) is defined as tuberculous infection of the tracheobronchial tree. Common symptoms are cough, haemoptysis, sputum production, wheezing, chest pain and fever in active disease and dyspnoea and wheezing in the fibrous stage. This form of tuberculosis is difficult to diagnose because the lesion is not evident in the chest radiograph, frequently delaying treatment. Computed tomography is very useful in evaluating bronchial lesions such as stenosis or obstruction. The most important goal of treatment in active EBTB is eradication of tubercle bacilli. The second most important goal is prevention of bronchial stenosis. Corticosteroid therapy for the prevention of bronchial stenosis in EBTB remains controversial. However, the healing time of ulcerous lesions was shorter and bronchial stenosis was less severe, in patients treated with aerosol therapy, consisting of streptomycin 100 mg, a corticosteroid (dexamethasone 0.5 mg) and naphazoline 0.1 mg administered twice-daily along with conventional oral therapy. In inactive disease, treatment to restore full patency is appropriate. As steroids or other medications are unable to reverse stenosis from fibrous disease, airway patency must be restored mechanically by surgery or endobronchial intervention. Effectiveness and complications remain important issues with the mechanical techniques as use and evaluation continue. Corticosteroid therapy for prevention of bronchial stenosis in EBTB remains controversial. Our observations suggest that progression of bronchial stenosis can be prevented in patients who are treated with aerosol therapy with corticosteroids. PMID:15212597
Both origin and evolution of tuberculosis and its pathogens (Mycobacterium tuberculosis complex) are not fully understood. The paleopathological investigation of human remains offers a unique insight into the molecular evolution and spread including correlative data of the environment. The molecular analysis of material from Egypt (3000–500 BC), Sudan (200–600 AD), Hungary (600–1700 AD), Latvia (1200–1600 AD), and South Germany (1400–1800 AD) urprisingly revealed constantly high frequencies of tuberculosis in all different time periods excluding significant environmental influence on tuberculosis spread. The typing of various mycobacteria strains provides evidence for ancestral M. tuberculosis strains in Pre- to early Egyptian dynastic material (3500–2650 BC), while typical M. africanum signatures were detected in a Middle Kingdom tomb (2050–1650 BC). Samples from the New Kingdom to Late Period (1500–500 BC) indicated modern M. tuberculosis strains. No evidence was seen for M. bovis in Egyptian material while M. bovis signatures were first identified in Siberian biomaterial dating 2000 years before present. These results contraindicates the theory that M. tuberculosis evolved from M. bovis during early domestication in the region of the “Fertile Crescent,” but supports the scenario that M. tuberculosis probably derived from an ancestral progenitor strain. The environmental influence of this evolutionary scenario deserves continuing intense evaluation.
Nerlich, Andreas G.; Losch, Sandra
Background Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a facultative intracellular pathogen that can persist within the host. The bacteria are thought to be in a state of reduced replication and metabolism as part of the chronic lung infection. Many in vitro studies have dissected the hypothesized environment within the infected lung, defining the bacterial response to pH, starvation and hypoxia. While these experiments have afforded great insight, the picture remains incomplete. The only way to study the combined effects of these environmental factors and the mycobacterial response is to study the bacterial response in vivo. Methodology/Principal Findings We used the guinea pig model of tuberculosis to examine the bacterial proteome during the early and chronic stages of disease. Lungs were harvested thirty and ninety days after aerosol challenge with Mtb, and analyzed by liquid chromatography-mass spectrometry. To date, in vivo proteomics of the tubercle bacillus has not been described and this work has generated the first large-scale shotgun proteomic data set, comprising over 500 unique protein identifications. Cell wall and cell wall processes, and intermediary metabolism and respiration were the two major functional classes of proteins represented in the infected lung. These classes of proteins displayed the greatest heterogeneity indicating important biological processes for establishment of a productive bacterial infection and its persistence. Proteins necessary for adaptation throughout infection, such as nitrate/nitrite reduction were found at both time points. The PE-PPE protein class, while not well characterized, represented the third most abundant category and showed the most consistent expression during the infection. Conclusions/Significance Cumulatively, the results of this work may provide the basis for rational drug design – identifying numerous Mtb proteins, from essential kinases to products involved in metal regulation and cell wall remodeling, all present throughout the course of infection.
Kruh, Nicole A.; Troudt, Jolynn; Izzo, Angelo; Prenni, Jessica; Dobos, Karen M.
Background: Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, yet no new drugs have been developed in the last 40 years. Objective: The exceedingly lengthy TB chemotherapy and the increasing emergence of drug resistance complicated by HIV co-infection call for the development of new TB drugs. These problems are further compounded by a poor understanding of the biology of persister bacteria. Methods: New molecular tools have offered insights into potential new drug targets, particularly the enzymes of the shikimate pathway, which is the focus of this review. Results/conclusion: Shikimate pathway enzymes, especially shikimate kinase, may offer attractive targets for new TB drug and vaccine development. PMID:23484927
Kapnick, Senta M; Zhang, Ying
BackgroundAnti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China.Methodology\\/Principal FindingsIn a population-based prospective
Penghui Shang; Yinyin Xia; Feiying Liu; Xiaomeng Wang; Yanli Yuan; Daiyu Hu; Dehua Tu; Yixin Chen; Peiyuan Deng; Shiming Cheng; Lin Zhou; Yu Ma; Lizhen Zhu; Weiwei Gao; Hongyuan Wang; Dafang Chen; Li Yang; Pingping He; Shanshan Wu; Shaowen Tang; Xiaozhen Lv; Zheng Shu; Yuan Zhang; Zhirong Yang; Yan Chen; Na Li; Feng Sun; Xiaoting Li; Yingjian He; Paul Garner; Siyan Zhan
Early diagnosis of active tuberculosis remains an elusive challenge. In addition, one third of the world’s population is latently infected with Mycobacterium tuberculosis (Mtb) and up to 10% of infected individuals develop tuberculosis (TB) in their lifetime. In this investigation, the incidence of urinary tuberculosis among renal patients was studied. Three hundreds urine samples were processed for detection of Mtb by Ziehl-Neelsen (ZN) smear examination, Lowenstein Jensen (LJ) medium, radiometric BACTEC460 system as well as polymerase chain reaction (PCR) followed by DNA Enzyme Immunoassay (DEIA) test. Out of 300 urine samples, 2 were positive by both ZN smears and LJ medium with incidence rate of 0.66 %, 3 positive samples by BACTEC460 culture system with incidence of 1%. PCR assay gave more positive results than smear and culture examination (i.e. 8 positive samples with incidence rate of 2.6%). The specificities were 25% for both ZN smears and LJ medium, 37.5% for BACTEC460 culture system, and 100% for PCR test, while sensitivities of all assays were 100%. Thus PCR is a rapid and sensitive method for the early diagnosis of urinary tuberculosis.
Ghaleb, Khaled; Afifi, Magdy; El-Gohary, Mohamad
The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, infects one-third of the world population. TB remains the leading cause of mortality due to a single bacterial pathogen. The worldwide increase in incidence of M. tuberculosis has been attributed to the high proliferation rates of multi and extensively drug-resistant strains, and to co-infection with the human immunodeficiency virus. There is thus a continuous requirement for studies on mycobacterial metabolism to identify promising targets for the development of new agents to combat TB. Singular characteristics of this pathogen, such as functional and structural features of enzymes involved in fundamental metabolic pathways, can be evaluated to identify possible targets for drug development. Enzymes involved in the pyrimidine salvage pathway might be attractive targets for rational drug design against TB, since this pathway is vital for all bacterial cells, and is composed of enzymes considerably different from those present in humans. Moreover, the enzymes of the pyrimidine salvage pathway might have an important role in the mycobacterial latent state, since M. tuberculosis has to recycle bases and/or nucleosides to survive in the hostile environment imposed by the host. The present review describes the enzymes of M. tuberculosis pyrimidine salvage pathway as attractive targets for the development of new antimycobacterial agents. Enzyme functional and structural data have been included to provide a broader knowledge on which to base the search for compounds with selective biological activity. PMID:21366534
Villela, A D; Sánchez-Quitian, Z A; Ducati, R G; Santos, D S; Basso, L A
BACKGROUND: Although chest radiographs usually provide adequate information for the diagnosis of active pulmonary tuberculosis, minimal exudative tuberculosis can be overlooked on standard chest radiographs. The aim of the present study was to assess the findings of active pulmonary tuberculosis on high resolution computed tomographic (HRCT) scans, and to evaluate their possible use in determining disease activity. METHODS: Thirty two patients with newly diagnosed active pulmonary tuberculosis and 34 patients with inactive pulmonary tuberculosis were examined. The diagnosis of active pulmonary tuberculosis was based on positive acid fast bacilli in sputum and bronchial washing smears or cultures and/or changes on serial radiographs obtained during treatment. RESULTS: With HRCT scanning centrilobular lesions (n = 29), "tree-in-bud" appearance (n = 23), and macronodules 5-8 mm in diameter (n = 22) were most commonly seen in cases of active pulmonary tuberculosis. HRCT scans showed fibrotic lesions (n = 34), distortion of bronchovascular structures (n = 32), emphysema (n = 28), and bronchiectasis (n = 24) in patients with inactive tuberculosis. CONCLUSIONS: Centrilobular densities in and around the small airways and "tree-in-bud" appearances were the most characteristic CT features of disease activity. HRCT scanning clearly differentiated old fibrotic lesions from new active lesions and demonstrated early bronchogenic spread. These findings may be of value in decisions on treatment. Images
Hatipoglu, O. N.; Osma, E.; Manisali, M.; Ucan, E. S.; Balci, P.; Akkoclu, A.; Akpinar, O.; Karlikaya, C.; Yuksel, C.
Background The Philippines has an extremely high rate of tuberculosis but little is known about M. tuberculosis genotypes and transmission dynamics in this country. The aim of this study was to determine the proportion of household contacts who develop active TB due to direct transmission from an index case in that household. Methods Mycobacterium tuberculosis isolates from household contacts of tuberculosis patients in the Philippines were characterized using restriction-fragment-length polymorphism analysis, spoligotyping, and mycobacterial interspersed repetitive units – variable number tandem repeats typing (12-loci) to determine their utility in elucidating transmission in an area of high tuberculosis prevalence. Drug susceptibility patterns for these isolates were also determined. Results Spoligotyping and MIRU-VNTR typing results matched in 10 (62.5%) of 16 index patient-household contact pairs while IS6110 fingerprints matched in only six (37.5%) pairs. Only 3/16 (18.8%) index patient-household contact pairs had identical drug susceptibility results. Conclusions Strain typing of M. tuberculosis isolates from household contacts in the Philippines indicates that transmission of strains does not necessarily occur directly from the index patient living in close proximity in the same household but rather that community-based transmission also frequently occurs. Accurate susceptibility testing of all isolates is necessary to insure optimal care of both the index patients and any culture-positive household contacts.
Tuberculosis in the elderly remains a health burden in Japan. Most of the elderly aged more than 70 years in Japan had become infected with Mycobacterium tuberculosis in their youth, and the elderly represent a population at a special high risk for developing tuberculosis owing to comorbidity and age-related immunosuppression. The characteristics of tuberculosis in the elderly are different from young patients. To reduce active tuberculosis in the elderly, treatment of latent tuberculosis infection for compromised host could be strengthened, however its impact might be limited. Elderly tuberculosis patients have not only clinical problems but also socioeconomic problems. Major problems of elderly tuberculosis patients are concurrent diseases, bed ridden states, necessity of nursing care, undernourished, poor adherence, and poor performance status of patients. With this symposium, we focused on the issue of tuberculosis in the elderly in Japan. The speakers were invited from various areas, including tuberculosis surveillance center, public health center and national hospital organization medical center. (1) Current trend of elderly TB: Masako OHMORI (Tuberculosis Surveillance Center, Research Institute of Tuberculosis, JATA) Although the tuberculosis (TB) incidence rate in Japan reached 19.4 per 100,000 in 2008, the rates among the elderly (65 + yrs) were high, e.g., 29.5 of those aged 64-74 years, 64.2 of those aged 75-84 years and 97.3 of those aged 85 years and over. The proportion of those aged 65 years and over increased from 36.8% in 1987 to 56.7% in 2008. Regarding the delay of case detection among elderly TB patients, the patient's delay tended to be shorter but the doctor's delay was longer. Although most TB patients including elderly TB patients were detected upon visiting a medical institution with some symptoms, in the case of elderly TB more patients were detected as outpatients or inpatients for a disease other than TB. Among TB patients aged 65 years and over, 26.4% died within one year. (2) The issues of elderly tuberculosis--An outbreak of pulmonary tuberculosis at nursing home for the elderly: Michiaki OKUMURA (Public Health Division, Public Health and Welfare Bureau, City of Osaka) I experienced a mass outbreak of pulmonary tuberculosis with 8 patients (including the source of infection) and 6 latent tuberculosis infections. Five patients (including the source) of the 8, I underwent restriction fragment length polymorphism (RFLP) analysis of isolated from the sputum. Five patients showed an identical RFLP pattern. These results showed that the infection had arisen from one source. The disease of 4 patients (aged 74-103) seemed to be caused by exogenous reinfections. The elderly tend to have some complications and to be malnutrition. These factors may be risk factors of tuberculosis reinfection for elderly. (3) The community DOTS in the elderly: Yoko HASHIMOTO (Wakayama Prefecture Gobo Health Center) In Wakayama prefecture, we have established a standard assessment list of adherence for tuberculosis patients. To identify predictors of default in the elderly, we investigated assessment lists of tuberculosis patients registered in Gobo Health Center from 2004 to 2007. Factors associated with default were concurrent diseases, side effects, disability and no family support. We have developed a liaison critical pathway for tuberculosis in Gobo Health Center and Tanabe Health Center since 2007. Introducing the path, we could strengthen community medical cooperation and build a network to support adherence. Health center staff should expand the community DOTS in the elderly with establishing an effective community collaboration. (4) The clinical issue of tuberculosis in the elderly: Takeshi KAWASAKI (Department of Respirology, Graduate School of Medicine, Chiba University, Department of Thoracic Disease, National Hospital Organization Chiba-East National Hospital) To identify the clinical issue of TB in the elderly, 139 cases were studied. There were 63 elderly cases in the 139. In the elderly TB patients, ther
Toyota, Makoto; Sasaki, Yuka
Primary tuberculosis of the nose is very rare. We report a case of a 35-year-old woman who presented with bilateral nasal obstruction and epistaxis of 3 months' duration but who was otherwise healthy. She was diagnosed with primary nasal septal tuberculosis and was treated with antituberculosis DOTS (directly observed treatment, short course) therapy for 6 months with complete recovery. Given the resurgence of tuberculosis in recent times, it is important that clinicians remain aware of this rare and treatable clinical entity. PMID:21792783
Lerra, Sandeep; Nazir, Tanvir; Mir Qadri, Sajjad; Kirmani, Masod
The need to isolated health providers with critical knowledge in tuberculosis (TB) case management prompted the development of "Tuberculosis Case Management" CD-ROM. Features include "Learning Center,""Examination Room," and "Library." The combination of audio, video, and graphics allows participants to practice acquired skills in a simulated…
Knebel, Elisa; Kolodner, Jennifer
Mycobacterium tuberculosis, responsible for 2 million deaths per year, can cause both primary disease and latent infections in humans. The factors responsible for control of M. tuberculosis include T cells, macrophages, and cytokines such as IFN-g and TNF. Formation of a granuloma, which consists of a spherical collection of macrophages and lymphocytes, is essential to the process of controlling infection
JoAnne L. Flynn
Objectives: This study was designed to review previous studies and analyse the current knowledge and controversies related to seasonal variability of tuberculosis (TB) to examine whether TB has an annual seasonal pattern. Study Design and Methods: Systematic review of peer reviewed studies identified through literature searches using online databases belonging to PubMed and the Cochrane library with key words “Tuberculosis, Seasonal influence” and “Tuberculosis, Seasonal variation”. The search was restricted to articles published in English. The references of the identified papers for further relevant publications were also reviewed. Results: Twelve studies conducted between the period 1971 and 2006 from 11 countries/regions around the world (South Western Cameroon, South Africa, India, Hong Kong, Japan, Kuwait, Spain, UK, Ireland, Russia, and Mongolia) were reviewed. A seasonal pattern of tuberculosis with a mostly predominant peak is seen during the spring and summer seasons in all of the countries (except South Western Cameroon and Russia). Conclusions: The observation of seasonality leads to assume that the risk of transmission of M. tuberculosis does appear to be the greatest during winter months. Vitamin D level variability, indoor activities, seasonal change in immune function, and delays in the diagnosis and treatment of tuberculosis are potential stimuli of seasonal tuberculosis disease. Additionally, seasonal variation in food availability and food intake, age, and sex are important factors which can play a role in the tuberculosis notification variability. Prospective studies regarding this topic and other related subjects are highly recommended.
Tuberculosis is a major cause of death around the world, with most of the 1.5 million deaths per year attributable to the disease occurring in developing countries. This disease is caused by Mycobacterium tuberculosis, an acid-fast bacillus that is transmitted primarily via the respiratory route. Infection occurs in the lungs, but the organism can seed any organ via hematogenous spread.
JOANNE L. FLYNN; JOHN CHAN
Background.?Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts. Methods.?Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995–August 2009. Parametric survival models identified factors associated with tuberculosis occurrence. Results.?Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131–333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk. Conclusions.?Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm3 or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.
Lau, Bryan; Zhang, Jinbing; Freeman, Aimee; Bosch, Ronald J.; Brooks, John T.; Deeks, Steven G.; French, Audrey; Gange, Stephen; Gebo, Kelly A.; John Gill, M.; Horberg, Michael A.; Jacobson, Lisa P.; Kirk, Gregory D.; Kitahata, Mari M.; Klein, Marina B.; Martin, Jeffrey N.; Rodriguez, Benigno; Silverberg, Michael J.; Willig, James H.; Eron, Joseph J.; Goedert, James J.; Hogg, Robert S.; Justice, Amy C.; McKaig, Rosemary G.; Napravnik, Sonia; Thorne, Jennifer; Moore, Richard D.
Background DNA microarrays can detect tuberculosis and its multi-drug resistant form in M. tuberculosis isolates and sputum specimens with high sensitivity and specificity. However, no performance data currently exists for its use in spinal tuberculosis specimens. This study was aimed to assess the performance of the CapitalBio™ DNA microarray in the detection of isoniazid (INH) and rifampicin (RMP) resistance in spinal tuberculosis compared with the BACT/MGIT 960 system. Methods From March 2009 to December 2011, 153 consecutive patients from Southwest Hospital, Chongqing with clinically and pathologically diagnosed spinal tuberculosis were enrolled into this study. Specimens collected during surgery from the tuberculosis patients were subjected to M. tuberculosis species identification and drug-resistance detection by the CapitalBio™ DNA microarray, and results were compared with those obtained from the absolute concentration drug susceptibility testing. Results The CapitalBio™ DNA microarray achieved 93.55% sensitivity for the correct M. tuberculosis species identification of the 93 specimens that tested positive for spinal tuberculosis through culture. In addition, twenty-seven additional patients (45.0%) were detected by the DNA microarray to be positive for M. tuberculosis among sixty spinal tuberculosis patients who were culture negative. Moreover, the DNA microarray had a sensitivity of 88.9% and a specificity of 90.7% for RMP resistance, and the microarray had a sensitivity of 80.0% and a specificity of 91.0% for INH resistance. The mean turn-around time of M. tuberculosis species identification and drug resistance detection using the DNA microarray was 5.8 (range, 4–9) hours. Conclusions The CapitalBio™ DNA microarray is a feasible and accurate tool for the species identification of M. tuberculosis and for directly detecting RMP and INH resistance from spinal tuberculosis specimens in fewer than 9 hours.
53. INTERIOR VIEW LOOKING NORTH NORTHEAST SHOWING THE REMAINS OF A WOODEN SETTLING BOX IN THE BACKGROUND RIGHT. AMALGAMATING PANS IN THE FOREGROUND. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA
7. VIEW OF VESSEL FROM PORT BON, SHOWING REMAINS OF MAIN CABIN. AFT CABIN STILL STANDS ON STERN IN BACKGROUND - Motorized Sailing Vessel "Fox", Beached on East Bank ofBayou Lafourche, Larose, Lafourche Parish, LA
Mycobacterium tuberculosis (MTB), the agent of human tuberculosis remains a leading cause of mortality globally. Its resurgence during the last two decades is a reflection of its opportunistic relationship with HIV. The challenges associated with the disease are enormous and often debilitating. The role of clinical and research laboratories is central and significant in this regard as prompt and adequate diagnosis are key factors in the management and control of the disease. PMID:19143160
Ani, A E
Background & objectives: Accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of the patients, and to reduce its spread. Clinical presentation of Mycobacterium tuberculosis complex (MTBC) and non tuberculous mycobacteria (NTM) may or may not be the same, but the treatment regimen is always different for both the infections. Differentiation between MTBC and NTM by routine laboratory methods is time consuming and cumbersome. This study was aimed to evaluate an immunochromatographic test (ICT), based on mouse monoclonal anti-MPT64, for simple and rapid discrimination between MTBC and NTM in clinical isolates from extra-pulmonary tuberculosis cases. Methods: A total of 800 clinical samples were collected from patients suspected to have extra-pulmonary tuberculosis. Preliminary diagnosis has been done by direct Ziehl–Neelsen (ZN) staining followed by culture in BACTEC system. A total of 150 clinical isolates, which were found positive in BD 460 TB system during September 2009 to September 2010 were selected for the screening by ICT test. p-nitro-?-acetylamino- ?-hydroxy propiophenone (NAP) test was performed for differentiation of MTBC and NTM. M. tuberculosis complex was further confirmed by IS6110 PCR of BACTEC culture positive isolates, this served as the reference method for MTBC identification and comparative evaluation of the ICT kit. Results: Of the 150 BACTEC culture positive isolates tested by ICT kit, 101 (67.3%) were found positive for MTBC and remaining 49 (32.7%) were considered as NTM. These results were further confirmed by IS6110 PCR that served as the reference method for detection of MTBC. H37Rv reference strain was taken as a control for ICT test and IS6110 PCR. The reference strain showed the presence of MPT64 antigen band in the ICT test. Similar bands were formed in 101 of 102 MTBC isolates tested, proving 99.1 per cent sensitivity and no bands were detected in 48 (100%) NTM isolates tested, proving 100 per cent specificity of the ICT kit. Interpretation & conclusions: Our findings show that ICT test can be used on direct culture positive specimens. It does not require any special equipment, is simple and less time consuming. It can easily discriminate between MTBC and NTM and thus can help in appropriate management of tuberculosis.
Maurya, Anand Kumar; Nag, Vijaya Lakshmi; Kant, Surya; Kushwaha, Ram Aawadh Singh; Kumar, Manoj; Mishra, Vikas; Rahman, W.; Dhole, Tapan N.
In many parts of the world, the diagnosis of tuberculosis (TB) has rapidly shifted to molecular detection and sequencing formats. The collection and transport of Mycobacterium tuberculosis specimens thus remains a challenging problem where TB is common and the infrastructure required for ensuring sample integrity is lacking. PrimeStore(®) Molecular Transport Medium (MTM) addresses this problem, rapidly inactivating/killing M. tuberculosis while preserving genomic DNA even at elevated temperatures for subsequent downstream molecular analysis. PMID:24902564
Daum, L T; Choi, Y; Worthy, S A; Rodriguez, J D; Chambers, J P; Fischer, G W
Mycobacterium tuberculosis is an obligate human intracellular pathogen which remains a major killer worldwide. A remarkable feature of M. tuberculosis infection is the ability of the pathogen to persist within the host for decades despite an impressive onslaught of stresses. In this review we seek to outline the host inflicted stresses experienced by Mycobacterium tuberculosis, the bacterial strategies used to withstand these stresses, and how this information should guide our efforts to combat this global pathogen.
Stallings, Christina L.; Glickman, Michael S.
Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios (HRs) ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis.
Engels, E.A.; Shen, M.; Chapman, R.S.; Pfeiffer, R.M.; Yu, Y.Y.; He, X.Z.; Lan, Q. [NCI, Rockville, MD (USA). Infectious and Immunoepidemiology Branch
Reported Tuberculosis in the United States, 2011 presents summary data for tuberculosis (TB) cases verified and counted in 2011. Reports of verified cases of tuberculosis (RVCT) are submitted to the Division of Tuberculosis Elimination (DTBE), Centers for...
Reported Tuberculosis in the United States, 2010 presents summary data for tuberculosis (TB) cases verified and counted in 2010. Reports of verified cases of tuberculosis (RVCT) are submitted to the Division of Tuberculosis Elimination (DTBE), Centers for...
Reported Tuberculosis in the United States, 2012 presents summary data for tuberculosis (TB) cases verified and counted in 2012. Reports of verified cases of tuberculosis (RVCT) are submitted to the Division of Tuberculosis Elimination (DTBE), Centers for...
Background Interleukin (IL)–32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. Methods and Findings In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR) agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor ? and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-? (IFN?); endogenous IFN? is, in turn, dependent on M. tuberculosis–induced IL-18 via caspase-1. Conclusions In conclusion, IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFN?.
Netea, Mihai G; Azam, Tania; Lewis, Eli C; Joosten, Leo A. B; Wang, Maorong; Langenberg, Dennis; Meng, Xianzhong; Chan, Edward D; Yoon, Do-Young; Ottenhoff, Tom; Kim, Soo-Hyun; Dinarello, Charles A
Background Defaulting from treatment remains a challenge for most tuberculosis control programmes. It may increase the risk of drug resistance, relapse, death, and prolonged infectiousness. The aim of this study was to determine factors predicting treatment adherence among smear-positive pulmonary tuberculosis patients. Methods and Findings A cohort of smear-positive tuberculosis patients diagnosed and registered in Hossana Hospital in southern Ethiopia from 1 September 2002 to 30 April 2004 were prospectively included. Using a structured questionnaire, potential predictor factors for defaulting from treatment were recorded at the beginning of treatment, and patients were followed up until the end of treatment. Default incidence rate was calculated and compared among preregistered risk factors. Of the 404 patients registered for treatment, 81 (20%) defaulted from treatment. A total of 91% (74 of 81) of treatment interruptions occurred during the continuation phase of treatment. On a Cox regression model, distance from home to treatment centre (hazard ratio [HR] = 2.97; p < 0.001), age > 25 y (HR = 1.71; p = 0.02), and necessity to use public transport to get to a treatment centre (HR = 1.59; p = 0.06) were found to be independently associated with defaulting from treatment. Conclusions Defaulting due to treatment noncompletion in this study setting is high, and the main determinants appear to be factors related to physical access to a treatment centre. The continuation phase of treatment is the most crucial time for treatment interruption, and future interventions should take this factor into consideration.
Background Emergence of drug resistant varieties of tuberculosis is posing a major threat to global tuberculosis eradication programmes.\\u000a Although several approaches have been explored to counter resistance, there has been limited success due to a lack of understanding\\u000a of how resistance emerges in bacteria upon drug treatment. A systems level analysis of the proteins involved is essential\\u000a to gain insights into
Karthik Raman; Nagasuma Chandra
Background The Mtb72f subunit vaccine for tuberculosis, currently in clinical trials, is hoped to provide improved protection compared to the current BCG vaccine. It is not clear, however, whether Mtb72f would be equally protective in the different human populations suffering from a high burden of tuberculosis. Previous work by Hebert and colleagues demonstrated that the PPE18 protein of Mtb72f had significant variability in a sample of clinical M. tuberculosis isolates. However, whether this variation might impact the efficacy of Mtb72f in the context of the microbial and host immune system interactions remained to be determined. The present study assesses Mtb72f's predicted efficacy in people with different DRB1 genotypes to predict whether the vaccine will protect against diverse clinical strains of M. tuberculosis in a diverse host population. Results We evaluated the binding of epitopes in the vaccine to different alleles of the human DRB1 Class II MHC protein using freely available epitope prediction programs and compared protein sequences from clinical isolates to the sequences included in the Mtb72f vaccine. This analysis predicted that the Mtb72f vaccine would be less effective for several DRB1 genotypes, due either to limited vaccine epitope binding to the DRB1 proteins or to binding primarily by unconserved PPE18 epitopes. Furthermore, we found that these less-protective DRB1 alleles are found at a very high frequency in several populations with a high burden of tuberculosis. Conclusion Although the Mtb72f vaccine candidate has shown promise in animal and clinical trials thus far, it may not be optimally effective in some genotypic backgrounds. Due to variation in both M. tuberculosis protein sequences and epitope-binding capabilities of different HLA alleles, certain human populations with a high burden of tuberculosis may not be optimally protected by the Mtb72f vaccine. The efficacy of the Mtb72f vaccine should be further examined in these particular populations to determine whether additional protective measures might be necessary for these regions.
BACKGROUND: Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where on-going tuberculosis transmission is occurring
Patrick K Moonan; Manuel Bayona; Teresa N Quitugua; Joseph Oppong; Denise Dunbar; Kenneth C Jost Jr; Gerry Burgess; Karan P Singh; Stephen E Weis
BackgroundTuberculosis is a leading cause of death in people living with HIV (PLWH). We conducted a meta analysis to assess the effect of tuberculosis on mortality in people living with HIV.MethodsMeta-analysis of cohort studies assessing the effect of tuberculosis on mortality in PLWH. To identify eligible studies we systematically searched electronic databases (until December 2008), performed manual searches of citations
Masja Straetemans; Ana L. Bierrenbach; Nico Nagelkerke; Philippe Glaziou; Marieke J. van der Werf; Madhukar Pai
Introduction There has been an increasing number of tuberculosis cases worldwide, but tuberculosis of the breast remains rare. In rare cases this is seen with a cutaneous manifestation of erythema nodosum. Case presentation We report the case of a 33-year-old Chinese woman with tuberculosis of the left breast accompanied by erythema nodosum on the anterior aspect of both lower legs. Due to her poor clinical response to conventional therapy, and the histopathological findings of fine needle aspiration cytology, there were strong indications of tuberculosis. Her clinical diagnosis was confirmed by molecular detection of Mycobacterium tuberculosis complex by polymerase chain reaction. The diagnosis was further confirmed by a second polymerase chain reaction test of erythema nodosum which tested positive for Mycobacterium tuberculosis complex. She received anti-tuberculous therapy for 18 months, and finally underwent residual lumpectomy. During her follow-up examination after 12 months, no evidence of either residual or recurrent disease was present. Conclusion Histopathological features and a high index of clinical suspicion are necessary to confirm a diagnosis of tuberculosis of the breast. Anti-tuberculous therapy with or without simple surgical intervention is the core treatment.
Background Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection.
Fox, Gregory J.; Sy, Dinh Ngoc; Nhung, Nguyen Viet; Yu, Bing; Ellis, Magda K.; Van Hung, Nguyen; Cuong, Nguyen Kim; Thi Lien, Luu; Marks, Guy B.; Saunders, Bernadette M.; Britton, Warwick J.
BACKGROUND: The identification and differentiation of strains of Mycobacterium tuberculosis by DNA fingerprinting has provided a better understanding of the epidemiology and tracing the transmission of tuberculosis. We set out to determine if there was a relationship between the risk of belonging to a group of tuberculosis patients with identical mycobacterial DNA fingerprint patterns and the HIV sero-status of the
Benon B Asiimwe; Moses L Joloba; Solomon Ghebremichael; Tuija Koivula; David P Kateete; Fred A Katabazi; Alexander Pennhag; Ramona Petersson; Gunilla Kallenius
Tuberculosis is a re-emerging disease and is a major problem in both developing and developed countries today. An estimated one third of the world's population is infected and almost two million people die from the disease each year. Bone lesions occur in 3–5% of active tuberculosis cases and can be used to diagnose the disease in ancient skeletal remains. A
K. L. Holloway; R. J. Henneberg; M. de Barros Lopes; M. Henneberg
The book deals with a disease which mainly occurs in economically under-developed countries, however even the affluent societies are not completely free from the disease. All aspects of tuberculosis of the spine including pathogenesis, clinical and radiol...
S. M. Tuli
Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is not very frequent and particularly difficult to diagnose. It incidence ranges between 1.5 and 4% of all extrapulmonary tuberculosis, according to bibliography. The clinic presentations depend on the arrival via of the bacillus to the skin, the patient's immune state and the environment. We show a cutaneous tuberculosis on a child with chronic dermatologic lesions, with torpid evolution, without response to treatments; the skinbiopsy showed caseous granulomas. The aim is to show a patient with an infrequent clinic presentation of this disease, to emphasize the importance of an early recognition and treatment, avoiding the appearance of complications and sequels. PMID:24862824
Bisero, Elsa; Luque, Graciela; Melillo, Karina; Favier, María Inés; Zapata, Alejandra; Cuello, María Soledad
Understanding the genetic diversity of Mycobacterium tuberculosis is needed for a better understanding of the epidemiology of TB and could have implications for the development of new diagnostics, drugs, and vaccines. M. tuberculosis isolates were characterized using spoligotyping and were compared with the SpoIDB4 database of the Pasteur Institute of Guadeloupe. A total of 53 different patterns were identified among 192 isolates examined. 169 of the isolates were classified into one of the 33 shared SITs, whereas the remaining 23 corresponded to 20 orphan patterns. 54% of the isolates were ascribed to the T family, a family which has not been well defined to date. Other prominent families were CAS, Haarlem, LAM, Beijing, and Unknown comprising 26%, 13%, 2.6%, 0.5%, and 2.1%, respectively. Among HIV-positive patients, 10 patterns were observed among 25 isolates. The T (38.5%), H (26.9%), and CAS (23.1%) families were the most common among HIV-positive individuals. The diversity of the M. tuberculosis strains found in this study is very high, and there was no difference in the distribution of families in HIV-positive and HIV-negative TB patients except the H family. Tuberculosis transmission in Addis Ababa is due to only the modern M. tuberculosis families (CAS, LAM, T, Beijing, Haarlem, and U).
Mihret, Adane; Bekele, Yonas; Loxton, Andre G.; Jordan, Annemie M.; Yamuah, Lawrence; Aseffa, Abraham; Howe, Rawleigh; Walzl, Gerhard
We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment. We discuss current screening methods and their limitations, the approach after positive screening and the timing to resume anti-TNF? treatment after TB infection. We shortly mention the immune reconstitution inflammatory syndrome (IRIS), described in a few cases after the stop of anti-TNFalpha while treating the tuberculosis infection. We conclude with some remaining questions concerning tuberculosis in IBD patients. PMID:24295645
Debeuckelaere, Celine; De Munter, Paul; Van Bleyenbergh, Pascal; De Wever, Walter; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Severine
Background Functional characterization of genes in important pathogenic bacteria such as Mycobacterium tuberculosis is imperative. Rv2135c, which was originally annotated as conserved hypothetical, has been found to be associated with membrane protein fractions of H37Rv strain. The gene appears to contain histidine phosphatase motif common to both cofactor-dependent phosphoglycerate mutases and acid phosphatases in the histidine phosphatase superfamily. The functions of many of the members of this superfamily are annotated based only on similarity to known proteins using automatic annotation systems, which can be erroneous. In addition, the motif at the N-terminal of Rv2135c is ‘RHA’ unlike ‘RHG’ found in most members of histidine phosphatase superfamily. These necessitate the need for its experimental characterization. The crystal structure of Rv0489, another member of the histidine phosphatase superfamily in M. tuberculosis, has been previously reported. However, its biochemical characteristics remain unknown. In this study, Rv2135c and Rv0489 from M. tuberculosis were cloned and expressed in Escherichia coli with 6 histidine residues tagged at the C terminal. Results Characterization of the purified recombinant proteins revealed that Rv0489 possesses phosphoglycerate mutase activity while Rv2135c does not. However Rv2135c has an acid phosphatase activity with optimal pH of 5.8. Kinetic parameters of Rv2135c and Rv0489 are studied, confirming that Rv0489 is a cofactor dependent phosphoglycerate mutase of M. tuberculosis. Additional characterization showed that Rv2135c exists as a tetramer while Rv0489 as a dimer in solution. Conclusion Most of the proteins orthologous to Rv2135c in other bacteria are annotated as phosphoglycerate mutases or hypothetical proteins. It is possible that they are actually phosphatases. Experimental characterization of a sufficiently large number of bacterial histidine phosphatases will increase the accuracy of the automatic annotation systems towards a better understanding of this important group of enzymes.
Background Despite great efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant. Methodology To understand the nature of CD4+ T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4+ T cells from healthy individuals (HD), two distinct populations with latent infection (with low or high IFN-? levels, LTBL/LTBH) and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4+ T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion. Principal Findings Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4+ T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF), which belongs to the TNF family, and a proliferation-inducing ligand (APRIL) were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4+ T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic.
Liu, Kai; Zhang, Yan; Hu, Shizong; Yu, Yang; Yang, Qianting; Jin, Dongdong; Chen, Xinchun; Jin, Qi; Liu, Haiying
Background Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea. Methods New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed. Results The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ?3 previous TB episodes, ?1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ?35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ?50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history. Conclusions Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes. Trial registration ClinicalTrials.gov ID: NCT00341601
Background Pneumonectomy remains the ultimate curative treatment modality for destroyed lung caused by tuberculosis despite multiple risks involved in the procedure. We retrospectively evaluated patients who underwent pneumonectomy for treatment of sequelae of pulmonary tuberculosis to determine the risk factors of early and long-term outcomes. Materials and Methods Between January 1980 and December 2008, pneumonectomy or pleuropneumonectomy was performed in 73 consecutive patients with destroyed lung caused by tuberculosis. There were 48 patients with empyema (12 with bronchopleural fistula [BPF]), 11 with aspergilloma and 7 with multidrug resistant tuberculosis. Results There were 5 operative mortalities (6.8%). One patient had intraoperative uncontrolled arrhythmia, one had a postoperative cardiac arrest, and three had postoperative respiratory failure. A total of 29 patients (39.7%) suffered from postoperative complications. Twelve patients (16.7%) were found to have postpneumonectomy empyema (PPE), 4 patients had wound infections (5.6%), and 7 patients required re-exploration due to postoperative bleeding (9.7%). The prevalence of PPE increased in patients with preoperative empyema (p=0.019). There were five patients with postoperative BPF, four of which occurred in right-side operation. The only risk factor for BPF was the right-side operation (p=0.023). The 5- and 10-year survival rates were 88.9% and 76.2%, respectively. The risk factors for late deaths were old age (?50 years, p=0.02) and low predicted postoperative forced expiratory volume in one second (FEV1) (<1.2 L, p=0.02). Conclusion Although PPE increases in patients with preoperative empyema and postoperative BPF increases in right-side operation, the mortality rates and long-term survival rates were found to be satisfactory. However, the follow-up care for patients with low predicted postoperative FEV1 should continue for prevention and early detection of pulmonary complication related to impaired pulmonary function.
Byun, Chun Sung; Narm, Kyoung Sik; Lee, Jin Gu; Hong, Daejin; Lee, Chang Young
Responsible for nearly two million deaths each year, the infectious disease tuberculosis remains a serious global health challenge. The emergence of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis confounds control efforts, and new drugs with novel molecular targets are desperately needed. Here we describe lead compounds, the indoleamides, with potent activity against both drug-susceptible and drug-resistant strains of M. tuberculosis by targeting the mycolic acid transporter MmpL3. We identify a single mutation in mmpL3 which confers high resistance to the indoleamide class while remaining susceptible to currently used first- and second-line tuberculosis drugs, indicating a lack of cross-resistance. Importantly, an indoleamide derivative exhibits dose-dependent anti-mycobacterial activity when orally administered to M. tuberculosis-infected mice. The bioavailability of the indoleamides, combined with their ability to kill tubercle bacilli, indicates great potential for translational developments of this structure class for the treatment of drug-resistant tuberculosis.
Lun, Shichun; Guo, Haidan; Onajole, Oluseye K.; Pieroni, Marco; Gunosewoyo, Hendra; Chen, Gang; Tipparaju, Suresh K.; Ammerman, Nicole C.; Kozikowski, Alan P.; Bishai, William R.
Balloonborne aerosol particle counter measurements are used in studying the stratospheric sulfate layer at Laramie, Wyoming, during 1978 and 1979, a 2-year volcanically quiescent period in which the layer appears to have been in a near equilibrium background state. Subtracting the background aerosol concentration from data obtained during an earlier volcanically active period indicates that the actual decay rate of volcanic aerosol is over 30% faster than one would obtain without this correction. At background, the aerosol size distribution is found to remain remarkably constant between the tropopause and an altitude of approx.25 km, with a sudden transition to a distribution dominated by smaller particles above this altitude. The observations, in some respects, compare favorably with equilibrium one-dimensional stratospheric aerosol models and thus to some extent support the concept of relatively inert tropospheric sulfurous gases, such as carbonyl sulfide and carbon disulfide, as the main background stratospheric aerosol sulfur source. Models which incorporate sulfur chemistry are apparently not able to predict the observed variation of particle size with altitude. The 2-year background period is not long enough in itself to establish long-term trends. The eruption of Mt. St. Helens in May 1980 has considerably disrupted the background stratospheric aerosol which will probably not recover for several years. A comparison of the 1978--79 observations with Junge's original measurements made some 20 years earlier, also during a period void of volcanic perturbations, does not preclude a long-term increase in the background stratospheric aerosol level.
Hofmann, D.J.; Rosen, J.M.
Despite efforts to generate new vaccines and antibiotics for tuberculosis, the disease remains a public health problem worldwide. The zebrafish Danio rerio has emerged as a useful model to investigate mycobacterial pathogenesis and treatment. Infection of zebrafish with Mycobacterium marinum, the closest relative of the Mycobacterium tuberculosis complex, recapitulates many aspects of human tuberculosis. The zebrafish model affords optical transparency, abundant genetic tools and in vivo imaging of the progression of infection. Here, we review how the zebrafish–M. marinum system has been deployed to make novel observations about the role of innate immunity, the tuberculous granuloma, and crucial host and bacterial genes. Finally, we assess how these findings relate to human disease and provide a framework for novel strategies to treat tuberculosis.
Cronan, Mark R.; Tobin, David M.
Tuberculosis, in its various forms, remains an important cause of morbidity and mortality in developing countries in immunodeficitary patients. The indicatives of epidemiology of tuberculosis show that Romania presents a fresh outbreak of the disease in the last few years. The purpose of this paper is to present from the various forms of extrapulmonary tuberculosis, the intestinal tipe which have a high incidence. The authors describe theirs preliminary experience of intraoperative small and large bowel emergencies resections in a short period (1 year) of three young patients (between 30 and 40 years old) with history of pulmonary tuberculosis. The pathology was complex (bowel obstructions, peritonitis) and so were the surgical operations (resections, devirations). The patients showed short and long term good results. PMID:12731239
Ciurea, M; Ion, D; Ionescu, S; Tica, M R
Endobronchial tuberculosis (EBTB), of which the incidence has been increasing in recent years, is a special type of pulmonary tuberculosis. The endobronchial tuberculose focuses often injure the tracheobronchial wall and lead to tracheobronchial stenosis. The tracheobronchial stenosis may cause intractable tuberculosis and make patients become chronic infection sources of tuberculosis, or may even cause pulmonary complications and result in death. The etiological confirmation of Mycobacterium tuberculosis is most substantial for diagnosis. However, because the positive rate of acid-fast bacillus staining for sputum smears is low and the clinical and radiological findings are usually nondistinctive, the diagnosis of EBTB is often mistaken and delayed. For early diagnosis, a high index of awareness of this disease is required and the bronchoscopy should be performed as soon as possible in suspected patients. The eradication of Mycobacterium tuberculosis and the prevention of tracheobronchial stenosis are two most substantial treatment goals. To get treatment goals, the diagnosis must be established early and aggressive treatments must be performed before the disease progresses too far. PMID:21499709
Xue, Q; Wang, N; Xue, X; Wang, J
Characteristic features of a migratory process of tuberculosis patients in the Republic of Moldova were subjected to study. Two tendencies have been revealed: growth of a number of the arriving subjects and deterioration of the structure of pulmonary tuberculosis among them. Patients who arrived from the places of confinement where morbidity persists on a high level constitute a particular hazard concerning tuberculosis dissemination. Certain organization measures have been taken. The epidemiologic situation for tuberculosis in the penitentiary-labour establishments at the republican Ministry of Internal Affairs was subjected to a comprehensive analysis with subsequent discussion of the results at a meeting of the staff of the Ministry of Public Health; instruction and plan of measures to be taken have been compiled by both ministries; a permanent board has been instituted for rendering help to medical workers of the penitentiary establishments; all law-protective organs have been involved in tuberculosis control; a specialized institution has been set up with a hospital for 200 beds intended for skilled examination and treatment of patients. As a result, the index of tuberculosis morbidity in the republican penitentiary-labour establishments reduced by more than half to promote an improvement of the epidemiologic situation in the republic. PMID:1409515
Degtiarev, V P; Evtodiev, V S; Bylich, F G
The plasma membrane of Mycobacterium tuberculosis is likely to contain proteins that could serve as novel drug targets, diagnostic probes or even components of a vaccine against tuberculosis. With this in mind, we have undertaken proteome analysis of the membrane of M. tuberculosis H37Rv. Isolated membrane vesicles were extracted with either a detergent (Triton X114) or an alkaline buffer (carbonate) following two of the protocols recommended for membrane protein enrichment. Proteins were resolved by 2D-GE using immobilized pH gradient (IPG) strips, and identified by peptide mass mapping utilizing the M. tuberculosis genome database. The two extraction procedures yielded patterns with minimal overlap. Only two proteins, both HSPs, showed a common presence. MALDI–MS analysis of 61 spots led to the identification of 32 proteins, 17 of which were new to the M. tuberculosis proteome database. We classified 19 of the identified proteins as ‘membrane-associated’; 14 of these were further classified as ‘membrane-bound’, three of which were lipoproteins. The remaining proteins included four heat-shock proteins and several enzymes involved in energy or lipid metabolism. Extraction with Triton X114 was found to be more effective than carbonate for detecting ‘putative’ M. tuberculosis membrane proteins. The protocol was also found to be suitable for comparing BCG and M. tuberculosis membranes, identifying ESAT-6 as being expressed selectively in M. tuberculosis. While this study demonstrates for the first time some of the membrane proteins of M. tuberculosis, it also underscores the problems associated with proteomic analysis of a complex membrane such as that of a mycobacterium.
Arora, Shalini; Kosalai, K.; Namane, Abdelkader; Pym, Alex S.; Cole, Stewart T.
Mycobacterium tuberculosis is an important human pathogen, and yet diagnosis remains challenging. Little research has focused on the impact of M. tuberculosis on the gut microbiota, despite the significant immunological and homeostatic functions of the gastrointestinal tract. To determine the effect of M. tuberculosis infection on the gut microbiota, we followed mice from M. tuberculosis aerosol infection until death, using 16S rRNA sequencing. We saw a rapid change in the gut microbiota in response to infection, with all mice showing a loss and then recovery of microbial community diversity, and found that pre-infection samples clustered separately from post-infection samples, using ecological beta-diversity measures. The effect on the fecal microbiota was observed as rapidly as six days following lung infection. Analysis of additional mice infected by a different M. tuberculosis strain corroborated these results, together demonstrating that the mouse gut microbiota significantly changes with M. tuberculosis infection.
Gupta, Shashank; Guo, Haidan; Fraser, Claire; Bishai, William
Mycobacterium tuberculosis is an important human pathogen, and yet diagnosis remains challenging. Little research has focused on the impact of M. tuberculosis on the gut microbiota, despite the significant immunological and homeostatic functions of the gastrointestinal tract. To determine the effect of M. tuberculosis infection on the gut microbiota, we followed mice from M. tuberculosis aerosol infection until death, using 16S rRNA sequencing. We saw a rapid change in the gut microbiota in response to infection, with all mice showing a loss and then recovery of microbial community diversity, and found that pre-infection samples clustered separately from post-infection samples, using ecological beta-diversity measures. The effect on the fecal microbiota was observed as rapidly as six days following lung infection. Analysis of additional mice infected by a different M. tuberculosis strain corroborated these results, together demonstrating that the mouse gut microbiota significantly changes with M. tuberculosis infection. PMID:24819223
Winglee, Kathryn; Eloe-Fadrosh, Emiley; Gupta, Shashank; Guo, Haidan; Fraser, Claire; Bishai, William
The pathogenesis of intraocular tuberculosis remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. Using a recently developed model of ocular tuberculosis following aerosol infection of guinea pigs with Mycobacterium tuberculosis, we studied the microbiological, histological, and clinical features of intraocular tuberculosis infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after aerosol delivery of ?200 bacilli to guinea pig lungs. Choroidal tuberculous granulomas showed reduced oxygen tension, as evidenced by staining with the hypoxia-specific probe pimonidazole, and expression of vascular endothelial growth factor (VEGF) was detected in the retinal pigment epithelium (RPE) and photoreceptors. Fundoscopic examination of M. tuberculosis-infected guinea pig eyes revealed altered vascular architecture and chorioretinal hemorrhage by Day 56 after infection. This model may be useful in further elucidating the pathogenesis of ocular tuberculosis, as well as in developing tools for diagnosis and assessment of antituberculosis treatment responses in the eye. PMID:22162767
Thayil, Seema M; Albini, Thomas A; Nazari, Hossein; Moshfeghi, Andrew A; Parel, Jean-Marie A; Rao, Narsing A; Karakousis, Petros C
Background: The homeless are at very high risk of suffering tuberculosis (TB). The aims of this study were to determine the prevalence and risk factors for tuberculosis infection and disease among the homeless in Barcelona and to evaluate the roles of case finding and contact investigation. Methods: Observational prevalence study carried out between 1997 and 1998. Participants: 447 homeless patients
J. Solsona; J. A. Caylà; J. Nadal; M. Bedia; C. Mata; J. Brau; J. Maldonado; C. Milà; J. Alcaide; N. Altet; H. Galdós-Tangüis
Background: Six to eight million people are infected with tuberculosis (TB) annually throughout the world, out of which 2 to 3 million die. BCG vaccination and its efficacy are always used in tuberculosis control planning. There are different rates of BCG vaccination efficacy in the world from 0 to 80%. BCG vaccine has different efficacy in endemic and non-endemic areas.
Masoomeh Alimagham; Saeid Aminiafshar; Siamak Farahmand; Parviz Vahdani; Mostafa Alavi; Kamran Sharafi
BACKGROUND: Species identification of isolates belonging to the Mycobacterium tuberculosis complex (MTC) seems to be important for the appropriate treatment of patients, since M. bovis is naturally resistant to a first line anti-tuberculosis (TB) drug, pyrazinamide, while most of the other MTC members are susceptible to this antimicrobial agent. A simple and low-cost differentiation method was needed in higher TB
Chie Nakajima; Zeaur Rahim; Yukari Fukushima; Isamu Sugawara; Adri GM van der Zanden; Aki Tamaru; Yasuhiko Suzuki
BACKGROUND: DOTS as a strategy was introduced to the tuberculosis control programme in Southern region of Ethiopia in 1996. The impact of the programme on treatment outcomes and the trend in the service coverage for tuberculosis has not been assessed ever since. The aim of the study was to assess trends in the expansion of DOTS and treatment outcomes for
Estifanos B Shargie; Bernt Lindtjørn
BackgroundGiven the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of
Marcela Parra; Steven C. Derrick; Amy Yang; JinHua Tian; Kristopher Kolibab; Miranda Oakley; Liyanage P. Perera; William R. Jacobs; Sanjai Kumar; Sheldon L. Morris
BACKGROUND: Delayed diagnosis and treatment of tuberculosis (TB) results in severe disease and a higher mortality. It also leads to an increased period of infectivity in the community. The objective of this study was to determine the length of delays, and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment.
Solomon Yimer; Gunnar Bjune; Getu Alene
BACKGROUND: The clinical, radiological and microbiological features of culture-confirmed childhood tuberculosis diagnosed at two referral hospitals are described. METHODS: Cultures of Mycobacterium tuberculosis from children less than 13 years of age at Tygerberg and Red Cross Children's Hospitals, Cape Town, South Africa, were collected from March 2003 through February 2005. Folder review and chest radiography were performed and drug susceptibility
H Simon Schaaf; Ben J Marais; Andrew Whitelaw; Anneke C Hesseling; Brian Eley; Gregory D Hussey; Peter R Donald
Tuberculosis Getting Healthy, Staying Healthy U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases Tuberculosis Getting Healthy, Staying Healthy U.S. DEPARTMENT OF HEALTH ...
Background: Routinely collected data from tuberculosis surveillance system can be used to investigate and monitor the irregularities and abrupt changes of the disease incidence. We aimed at using a Hidden Markov Model in order to detect the abnormal states of pulmonary tuberculosis in Iran. Methods: Data for this study were the weekly number of newly diagnosed cases with sputum smear-positive pulmonary tuberculosis reported between April 2005 and March 2011 throughout Iran. In order to detect the unusual states of the disease, two Hidden Markov Models were applied to the data with and without seasonal trends as baselines. Consequently, the best model was selected and compared with the results of Serfling epidemic threshold which is typically used in the surveillance of infectious diseases. Results: Both adjusted R-squared and Bayesian Information Criterion (BIC) reflected better goodness-of-fit for the model with seasonal trends (0.72 and ?1336.66, respectively) than the model without seasonality (0.56 and ?1386.75). Moreover, according to the Serfling epidemic threshold, higher values of sensitivity and specificity suggest a higher validity for the seasonal model (0.87 and 0.94, respectively) than model without seasonality (0.73 and 0.68, respectively). Conclusion: A two-state Hidden Markov Model along with a seasonal trend as a function of the model parameters provides an effective warning system for the surveillance of tuberculosis.
Rafei, A; Pasha, E; Jamshidi Orak, R
We present a case of multifocal tuberculosis of contralateral costo-transverse joints. Even in countries where tuberculosis\\u000a is common, extrapulmonary multifocal infection is uncommon. Furthermore, a bilateral, symmetric distribution is distinctly\\u000a unusual. The index of suspicion for tuberculosis should increase when the patient is from a country where tuberculosis is\\u000a endemic or when a history of AIDS is present.
S. M. Levine; E. B. Marianacci; S. V. Kattapuram
Background Successful treatment of tuberculosis (TB) involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi. Methods A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945) defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied. Results Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned treatment within first and second months (intensive phase) of treatment respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7% (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0), alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16-4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1.56; 95% CI 1.25-1.94) and male gender (OR 1.43; 95% CI 1.15-1.78) were independently associated with default. Conclusion The rate of defaulting was highest during initial two months, the intensive phase of treatment. Multiple factors were attributed by defaulting patients as cause for abandoning treatment whereas several were independently associated with default. Enhanced patient pre-treatment counseling and education about TB is recommended.
Background Mycobacterium tuberculosis kills approximately 2 million people each year and presents an urgent need to identify new targets and new antitubercular drugs. Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M. tuberculosis genome contains two putative TS enzymes, a conventional ThyA and a flavin-based ThyX. In M. tuberculosis, both TS enzymes have been implicated as essential for growth, either based on drug-resistance studies or genome-wide mutagenesis screens. To facilitate future small molecule inhibitors against these proteins, a detailed enzymatic characterization was necessary. Methodology/Principal Findings After cloning, overexpression, and purification, the thymidylate-synthesizing ability of ThyA and ThyX gene products were directly confirmed by HPLC analysis of reaction products and substrate saturation kinetics were established. 5-Fluoro-2?-deoxyuridine 5?-monophosphate (FdUMP) was a potent inhibitor of both ThyA and ThyX, offering important clues to double-targeting strategies. In contrast, the folate-based 1843U89 was a potent inhibitor of ThyA but not ThyX suggesting that it should be possible to find ThyX-specific antifolates. A turnover-dependent kinetic assay, combined with the active-site titration approach of Ackermann and Potter, revealed that both M. tuberculosis enzymes had very low kcat values. One possible explanation for the low catalytic activity of M. tuberculosis ThyX is that its true biological substrates remain to be identified. Alternatively, this slow-growing pathogen, with low demands for TMP, may have evolved to down-regulate TS activities by altering the turnover rate of individual enzyme molecules, perhaps to preserve total protein quantities for other purposes. In many organisms, TS is often used as a part of larger complexes of macromolecules that control replication and DNA repair. Conclusions/Significance Thus, the present enzymatic characterization of ThyA and ThyX from M. tuberculosis provides a framework for future development of cell-active inhibitors and the biological roles of these TS enzymes in M. tuberculosis.
Hunter, Joshua H.; Gujjar, Ramesh; Pang, Cullen K. T.; Rathod, Pradipsinh K.
Tuberculosis (TB) remains a worldwide scourge and its incidence appears to be increasing due to various factors, such as the spread of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). The insidious onset and non-specific constitutional symptoms of genitourinary tuberculosis (GUTB) often lead to delayed diagnosis and rapid progression to a non-functioning kidney. Due to hematogenous dissemination of TB, there is a potential risk of involvement of the contralateral kidney too. Imaging plays an important role in the making of a timely diagnosis and in the planning of treatment, and thus helps to avoid complications such as renal failure. Imaging of GUTB still remains a challenge, mainly on account of the dearth of literature, especially related to the use of the newer modalities such as magnetic resonance imaging (MRI). This two-part article is a comprehensive review of the epidemiology, pathophysiology, and imaging findings in renal TB. Various imaging features of GUTB are outlined, from the pathognomonic lobar calcification on plain film, to finer early changes such as loss of calyceal sharpness and papillary necrosis on intravenous urography (IVU); to uneven caliectasis and urothelial thickening, in the absence of renal pelvic dilatation, as well as the hitherto unreported ‘lobar caseation’ on ultrasonography (USG). Well-known complications of GUTB such as sinus tracts, fistulae and amyloidosis are described, along with the relatively less well-known complications such as tuberculous interstitial nephritis (TIN), which may remain hidden because of its ‘culture negative’ nature and thus lead to renal failure. The second part of the article reviews the computed tomography (CT) and MRI features of GUTB and touches upon future imaging techniques along with imaging of TB in transplant recipients and in immunocompromised patients.
Merchant, Suleman; Bharati, Alpa; Merchant, Neesha
Background: Tuberculosis, a communicable disease with significant morbidity and mortality, is the leading cause of death in the world from bacterial infectious disease. Because of its public health importance, there is need for rapid and definitive method of detecting the causative organism. Several approaches have been attempted, but the molecular methods, especially Polymerase Chain Reaction assays are the most promising for rapid detection of Mycobacterium tuberculosis complex from clinical samples. Aim: This study was aimed at using Polymerase Chain Reaction for detection of Mycobacterium tuberculosis complex from clinical samples using universal sample processing methodology. Subjects and Methods: Two hundred clinical samples sent to Tuberculosis laboratories in Ibadan and Osogbo, Nigeria, were enrolled in this study. The samples were processed by universal sample processing methodology for PCR; smear microscopy was carried out on sputum samples by Ziehl Nelseen staining technique; and cultured on Middlebrook agar medium containing oleic acid albumin dextrose complex supplement after decontamination of samples. Results: Ninety six (48%) samples were detected positive for M. tuberculosis complex by polymerase chain reaction using the combination of boiling and vortexing and microscopy detected 72 (36%) samples positive for acid fast bacilli. Using culture method as gold standard, it was found that polymerase chain reaction assay was more sensitive (75.5%) and specific (94.8%) than microscopy (sensitivity of 48.5% and specificity of 85.7%) in detecting M. tuberculosis complex from clinical samples. There was significant difference in detecting M. tuberculosis from clinical samples when compared to microscopy (p<0.05). Conclusion: The study recommends that direct molecular detection of M. tuberculosis complex is sensitive and specific and polymerase chain reaction method should be used as an adjunct to other methods of laboratory diagnosis of tuberculosis.
Alli, Oyebode A. T.; Ogbolu, Olusoga D.; Alaka, Olubunmi O.
The first section of this report on childhood tuberculosis in developed and developing countries discusses the epidemiology of tuberculosis in children. Information is presented on: (1) sources and prevalence of infection; (2) risks, frequency, and types of tuberculosis; (3) mortality rates; and (4) the relation of poverty and AIDS to…
Chaulet, Pierre; And Others
Lifeguards run the risk of workplace infection by tuberculosis-carrying swimmers. Even if they work in ventilated, sunlit areas (which reduces risk), they can contract tuberculosis when performing respiratory resuscitation. Without appropriate precautions, lifeguards may be unnecessarily exposed. A tuberculosis infection control plan is needed in…
The incidence of tuberculosis among Alaskan children under 15 was more than twice the national rate, with Alaska Native children showing a much higher incidence. Children with household exposure to adults with active tuberculosis had a high risk of infection. About 22 percent of pediatric tuberculosis cases were identified through school…
Gessner, Bradford D.
Tuberculosis has plagued humankind since prehistoric times, as is evident from characteristic lesions on human skeletons dating back to the Neolithic period. The disease in man is due predominantly to infection with either Mycobacterium tuberculosis or Mycobacterium bovis, both members of the M. tuberculosis (MTB) complex. A number of studies have shown that when conditions permit, surviving mycobacterial DNA may be amplified from bone by PCR. Such ancient DNA (aDNA) analyses are subject to stringent tests of authenticity and, when feasible, are invariably limited by DNA fragmentation. Using PCRs based on single-nucleotide polymorphic loci and regions of difference (RDs) in the MTB complex, a study was made of five Iron Age individuals with spinal lesions recovered from the cemetery of Aymyrlyg, South Siberia. A sensitive screening PCR for MTB complex mycobacteria was positive in four out of the five cases. Genotyping evidence indicated that all four cases were due to infection with M. bovis rather than M. tuberculosis and the data were consistent with the proposed phylogenetic model of the MTB complex. This is believed to be the first report of M. bovis causing Pott's disease in archaeological human remains. The study shows that genotyping of ancestral strains of MTB complex mycobacteria from contexts of known date provides information which allows the phylogeny of the model to be tested. Moreover, it shows that loss of DNA from RD4, which defines classic M. bovis, had already occurred from the genome over 2000 years before the present. PMID:17379733
Taylor, G Michael; Murphy, Eileen; Hopkins, Richard; Rutland, Paul; Chistov, Yuri
Background Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis. Methods Plasma from humans with latent tuberculosis (TB) infection (n?=?23), active TB disease (n?=?40), and uninfected controls (n?=?9) were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins). Results When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (??=?0.72 log10), whole cell lysate (??=?0.82 log10), and secreted proteins (??=?0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (??=?1.4 to 2.6) to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (??=?–1.53, p?=?0.004). Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (??=?0.55 log10, p?=?0.008), foreign-born (??=?0.61 log10, p?=?0.004), or HIV-seronegative (??=?0.60 log10, p?=?0.04). Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (??=?1.12, p<0.001) and foreign-born (??=?0.87, p?=?0.01). Conclusions/Significance Humans with active TB disease produce antibodies to the surface of M. tuberculosis with low avidity and with a low IgG/IgM ratio. Highly-avid IgG antibodies to the M. tuberculosis surface may be an appropriate target for future TB vaccines.
Perley, Casey C.; Frahm, Marc; Click, Eva M.; Dobos, Karen M.; Ferrari, Guido; Stout, Jason E.; Frothingham, Richard
Tuberculosis is a major health threat in many regions of the world. Opportunistic infections in immunocompromised HIV/AIDS patients and multi-drug-resistant bacterial strains have exacerbated the problem, while diagnosing tuberculosis still remains a challenge. When left undiagnosed and thus untreated, mortality rates of patients with tuberculosis are high. Standard diagnostics still rely on methods developed in the last century. They are slow and often unreliable. In an effort to reduce the burden of the disease, this paper presents our automated approach for detecting tuberculosis in conventional posteroanterior chest radiographs. We first extract the lung region using a graph cut segmentation method. For this lung region, we compute a set of texture and shape features, which enable the X-rays to be classified as normal or abnormal using a binary classifier. We measure the performance of our system on two datasets: a set collected by the tuberculosis control program of our local county's health department in the United States, and a set collected by Shenzhen Hospital, China. The proposed computer-aided diagnostic system for TB screening, which is ready for field deployment, achieves a performance that approaches the performance of human experts. We achieve an area under the ROC curve (AUC) of 87% (78.3% accuracy) for the first set, and an AUC of 90% (84% accuracy) for the second set. For the first set, we compare our system performance with the performance of radiologists. When trying not to miss any positive cases, radiologists achieve an accuracy of about 82% on this set, and their false positive rate is about half of our system's rate. PMID:24108713
Jaeger, Stefan; Karargyris, Alexandros; Candemir, Sema; Folio, Les; Siegelman, Jenifer; Callaghan, Fiona; Zhiyun Xue; Palaniappan, Kannappan; Singh, Rahul K; Antani, Sameer; Thoma, George; Yi-Xiang Wang; Pu-Xuan Lu; McDonald, Clement J
Mycobacterium tuberculosiscomplex DNA has been detected in two ancient, North American human bone samples, dating from the Pre-Columbian period. Using polymerase chain reaction (PCR) and DNA sequence analysis, diagnostic portions of the IS6110genomic element ofMycobacterium tuberculosishave been confirmed in a Canadian ossuary sample dating to the 15th centuryADas well as from a Middle Mississippian burial dating to the early 11th
Mark Braun; Della Collins Cook; Susan Pfeiffer
Background The acid-fast bacillus Mycobacterium tuberculosis (MTB) is often the first manifestation of AIDS in HIV infected patients. This study was conducted to better understand the mechanism underlying MTB-specific pathogenicity early in HIV infection. Methods MTB-specific T Helper 1 (TH1) cells were studied in HIV negative (n=114) and chronically HIV infected (n=68) Tanzanian subjects usinEarly Secreted Antigenic Target 6 (ESAT6) protein or Tuberculin (PPD) by Interferon gamma (IFN?) ELISPOT and intracellular cytokine staining. In a longitudinal study the effect of acute HIV infection on MTB-specific TH1 cells was determined by polychromatic flow cytometric analysis in 5 subjects with latent MTB infection, who became infected with HIV. Results In Tuberculosis (TB) asymptomatic subjects, chronic HIV infection was associated with a decreased frequency of responders with detectable MTB-specific TH1 cells (p-value = 0.0003) that was not observed in subjects with active TB. Acute HIV infection induced a rapid depletion of MTB-specific TH1 cells in 4 subjects who remained TB asymptomatic, but were stable in subjects who remained HIV negative (p<0.01). Conclusions Together these data suggest a mechanism of rapid MTB-specific TH1 cell depletion that may contribute to the early onset of TB in latently MTB infected individuals who become HIV infected.
Geldmacher, Christof; Schuetz, Alexandra; Ngwenyama, Njabulo; Casazza, Joseph P.; Sanga, Erica; Saathoff, Elmar; Boehme, Catharina; Geis, Steffen; Maboko, Leonard; Singh, Mahavir; Minja, Fred; Meyerhans, Andreas; Koup, Richard A.; Hoelscher, Michael
An 81-year-old woman was admitted to our hospital for hyponatremia and impaired consciousness after unsuccessful antibiotic treatment for pneumonia-like symptoms by a previous doctor. A chest X-ray film revealed unilateral infiltration. Mycobacterium tuberculosis was detected on a sputum smear and pulmonary tuberculosis was diagnosed. Based on the diagnostic criteria, we believed that her hyponatremia a consequence of syndrome of inappropriate antidiuretic hormone secretion (SIADH) as a complication of pulmonary tuberculosis. Sodium loading and water restriction quickly improved her serum sodium level and impaired consciousness. Anti-tuberculosis therapy reduced the abnormal shadows noted on chest X-ray films, and the sputum smear became negative for Mycobacterium tuberculosis. Her serum sodium level remained normal after the discontinuation of sodium loading. Previous reports have associated SIADH with severe types of tuberculosis such as miliary tuberculosis, tuberculosis meningitis, and pulmonary tuberculosis with massive bacterial excretion. However, this complication can also occur in mild tuberculosis, as in this case, thus SIADH should also be considered in mild cases of tuberculosis. PMID:21894778
Minami, Takahiro; Wakamatsu, Kentarou; Kumazoe, Hiroyuki; Nagata, Nobuhiko; Kajiki, Akira; Kitahara, Yoshinari
The Singapore Tuberculosis Elimination Programme (STEP) was launched in 1997 because the incidence of the disease had remained between 49 and 56 per 100,000 resident population for the preceding 10 years. STEP involves the following key interventions: directly observed therapy (DOT) in public primary health care clinics; monitoring of treatment progress and outcome for all cases by means of a National Treatment Surveillance Registry; and preventive therapy for recently infected close contacts of infectious tuberculosis cases. Among other activities are the revamping of the National Tuberculosis Notification Registry, the discontinuation of BCG revaccination for schoolchildren, the tightening up of defaulter tracing, and the education of the medical community and the public. Future plans include an outreach programme for specific groups of patients who are unable to attend their nearest public primary care clinics for DOT, the detention of infectious recalcitrant defaulters for treatment under the Infectious Diseases Act, the molecular fingerprinting of tuberculosis isolates, and targeted screening of high-risk groups. The incidence of tuberculosis fell from 57 per 100,000 population in 1998 to 48 per 100,000 in 1999 and continued to decline to 44 per 100,000 in 2001. With political will and commitment and the support of the medical community and the public it is hoped that STEP will achieve further progress towards the elimination of tuberculosis in Singapore.
Chee, Cynthia B. E.; James, Lyn
Mycobacterium tuberculosis (M. tuberculosis) infects all organs in the body; however, lung infection is the primary lesion. The total number of infections is decreasing, but the percentage of infections in older people is rising. Because this disease is due to infection with M. tuberculosis, the diagnosis requires the presence of M. tuberculosis. Chest X-ray and CT are very powerful tools to suggest the presence of M. tuberculosis infection. Pathological examination of the tissues also shows the typical findings of M. tuberculosis infection; however, the presence of the bacterium was not proven in certain cases of M. tuberculosis infection, and especially in cases of latent infection. Recently, the whole-blood interferon--gamma test (QuantiFERON-TB, QFT) became more popular than the tuberculin skin test. It is reported that the specificity and sensitivity of QFT are similar to or better than the tuberculin skin test. However, it should be noted that QFT positive does not automatically lead to a diagnosis of active M. tuberculosis infection and that QFT is one of the supplementary tests in the diagnosis of M. tuberculosis infection. Currently, massive infection with M. tuberculosis is increasing. The precise responsible linkage in massive infection with M. tuberculosis needs DNA polymorphism analysis using variable numbers of tandem repeats (VNTR) or restricted fragment length polymorphism (RFLP). PMID:23198540
Koyama, Sekiya; Sakaguchi, Nobuki; Hotta, Jyunnichi
The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective “protective immunity” against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis. Newly diagnosed tuberculosis patients (n?=?23), their close household contacts (n?=?80), and community controls (n?=?46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up. Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes. These data suggest tuberculosis may be associated with decreased T-cell survival (perhaps due to apoptosis) while inhibition of apoptosis in monocytes could lead to a relative increase in these cells: a situation predicted to favour Mtb.
Rakotosamimanana, Niaina; Doherty, T. Mark; Andriamihantasoa, Lova H.; Richard, Vincent; Gicquel, Brigitte; Soares, Jean-Louis; Zumla, Alimuddin; Razanamparany, Voahangy Rasolofo
Rationale: Tuberculosis remains a major cause of morbidity and mortality in the developing world. A better understanding of the mechanisms of disease protection could allow novel strategies to disease management and control. Objectives: To identify human genomic loci with evidence of linkage to tuberculosis susceptibility and, within these loci, to identify individual genes influencing tuberculosis susceptibility. Methods:AffectedsiblingpairanalysisinSouthAfricanandMalawian populations. Independent case-control
Graham S. Cooke; Sarah J. Campbell; Steve Bennett; Christian Lienhardt; Keith P. W. J. McAdam; Oumou Sow; Per Gustafson; Frank Mwangulu; Paul van Helden; Paul Fine; Eileen G. Hoal; Adrian V. S. Hill
We report an unusual case of miliary tuberculosis in a 77-year-old Filipino man with hypertension, diabetes mellitus, nephrolithiasis status-post left nephrectomy, presenting with 1 month of fever, generalised weakness and weight loss. Laboratory data were significant for anaemia, hypercalcaemia and acute kidney injury. Chest radiograph showed ground glass opacities and interstitial infiltrates. Extensive workup was performed to evaluate fever and hypercalcaemia. Malignancy, hormonal and septic workup were all unremarkable. Tuberculin skin test was negative. Sputum, pleural fluid, bronchoalveolar lavage and cerebrospinal fluid were acid-fast bacilli (AFB) smear negative. Remarkably, urine AFB smear was positive. Caseating granulomas were seen on transbronchial biopsy. Antituberculosis therapy was initiated which lead to defervescence and initial clinical improvement. However, hospital course became complicated by small bowel obstruction and respiratory failure. He subsequently developed pulseless electrical activity and expired. An autopsy confirmed the presence of tuberculosis in multiple organs including his remaining kidney. PMID:24569260
So, Edison; Bolger, Dennis Thomas
Tuberculosis is itself a major Public health problem in Nepal and the emergence HIV further complicated the issue. A cross-sectional analytical study was conducted between January 2004 and August 2005, with a general objective to determine the Tuberculosis co-infection status in HIV/AIDS cases of Nepal. Altogether 100 HIV infected persons visiting different Voluntary counseling and testing centers (VCT) and HIV/AIDS care centers located in Kathmandu valley were enrolled in the study. Investigation of tuberculosis was done by standard method prescribed by WHO using sputum specimen. Among 100 HIV infected cases, 66 (66.0%) were males and 34 (34.0%) were females. Majority of the HIV cases were in the age group 21-30 (60.0%) followed by 31-40 (31.0%). Tuberculosis was detected in 23 cases with highest prevalence in the age group 21-30 years (65.2%). No significant relationship could be established between gender and TB (c2 = 0.83, p > 0.01).Significant relationship was established between smoking/alcoholic habit and the subsequent development of tuberculosis (c2 = 7.24, p < 0.05 for smoking habit; c2 = 4.39, p < 0.05 for alcoholic habit at 1 degree of freedom). Among 22 culture positive isolates the predominant was Mycobacterium avium complex (40.9%) followed by M. tuberculosis (27.3%), M. kansasii (18.2%), M. fortuitum (9.1%) and M. chelonae (4.5%). Among the 23 cases of tuberculosis, 22 cases were diagnosed by cultural technique of which 4 cases were smear positive while the remaining one case was diagnosed by direct microscopy although it was culture negative. Smear negative Tuberculosis is found to be alarmingly higher in HIV positive individuals of productive age group. The disease significantly higher in smokers and alcoholics. PMID:18828430
Dhungana, G P; Ghimire, P; Sharma, S; Rijal, B P
Objectives People living with HIV/AIDS (PLWHA) who develop tuberculosis disease are at greater mortality-risk. This study aimed to assess tuberculosis disease incidence among all PLWHA in Israel and identify populations at high-risk for developing tuberculosis. Design and Methods Retrospective cohort-study based on the National HIV and Tuberculosis Registries, which were cross-matched and followed for the last 28-years. PLWHA who developed tuberculosis were compared to those who did not by the Cox-proportional analysis to generate hazard-ratios, and survival-analysis was performed by Log-Rank test. Results Of all the 6579 PLWHA reported between 1983 and 2010, corresponding to 55737 person-years, 384 (5.8%) developed tuberculosis. Of those, 14 were Israeli-born and 370 were non-Israeli born. The overall tuberculosis incidence-density was 6.9 cases/1000 person-years (95% CI 1.8–12.0). The cumulative tuberculosis-incidence among PLWHA in 2010 was 586 times higher than in HIV-negative individuals (3400 and 5.8 cases per 100000 population, respectively). Higher hazard-ratios to developing tuberculosis were found in migrant citizens PLWHA who were males, non-Israeli born, those who were diagnosed with HIV/AIDS after 1997, those who originated in high-tuberculosis prevalence country and those who acquired HIV by heterosexual or drug-injection transmission. PLWHA who developed tuberculosis had higher odds of dying than other PLWHA (36.5% and 16.6%, respectively, p<0.001, odds ratio?=?2.8, 95% confidence-interval 2.3–3.6). In survival-analysis, time to develop tuberculosis was shorter among males than females, in PLWHA who were reported with HIV after 1997, in heterosexual who originated in high-tuberculosis countries, followed by injecting drug-users, heterosexual from low-tuberculosis burden countries and men who have sex with men. Conclusion Tuberculosis-incidence is higher among non-Israeli born PLWHA, with decreasing trends from 1991. Despite the moderate TB-rate disease among PLWHA, it remains an important cause for severe morbidity and mortality. Tuberculosis in PLWHA reflects mainly the tuberculosis-burden in the originating country and possibly also the mode of HIV-transmission.
Mor, Zohar; Lidji, Moshe; Cedar, Noa; Grotto, Itamar; Chemtob, Daniel
Tuberculosis of the breast is an uncommon disease even in countries where the incidence of pulmonary and extrapulmonary tuberculosis is high. Clinical presentation is usually of a solitary, ill-defined, unilateral hard lump situated in the upper outer quadrant of the breast. This disease can present a diagnostic problem on radiological and microbiological investigations, and thus a high index of suspicion is needed. Incorporating a highly sensitive technique like polymerase chain reaction (PCR) may be helpful in establishing the usefulness of such technology and can aid in conforming the diagnosis early. The disease is curable with antitubercular drugs, and surgery is rarely required
Female genital tuberculosis (TB) remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome (AIDS). Genital TB is commonly asymptomatic, and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools, such as computerized tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpingography is still the standard screening test for evaluation of tubal infertility and a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and "leopard skin tube". Part II describes adverse effects of tuberculosis on structure of endometrium and radiological specific findings such as "dwarfed" uterus with lymphatic intravasation and occluded tubes, "T-shaped" tuberculosis uterus, "pseudounicornuate" uterus and "Collar-stud abscess", which have not been encountered in the majority of non-tuberculosis cases.
Ahmadi, Firoozeh; Zafarani, Fatemeh; Shahrzad, Gholam
Female genital tuberculosis (TB) remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome (AIDS). Genital TB is commonly asymptomatic, and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools, such as computerized tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpingography is still the standard screening test for evaluation of tubal infertility and a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and "leopard skin tube". Part II describes adverse effects of tuberculosis on structure of endometrium and radiological specific findings such as "dwarfed" uterus with lymphatic intravasation and occluded tubes, "T-shaped" tuberculosis uterus, "pseudounicornuate" uterus and "Collar-stud abscess", which have not been encountered in the majority of non-tuberculosis cases. PMID:24520493
Ahmadi, Firoozeh; Zafarani, Fatemeh; Shahrzad, Gholam
Background: Genital tuberculosis is a chorionic disease and mostly occurs by haematogenous spread from extra genital source like lungs, peritoneum, lymph nodes and bones. Transmission through a sexual intercourse is also possible. Since the majority of patients are in reproductive ages, involvement of fallopian tubes and endometrium cause infertility in patients. Cases: Reviewing 4 cases of female genital tuberculosis, which referred to an infertility treatment center with various symptoms, we encountered various appearances on hysterosalpingography (HSG). Conclusion: The genitourinary tract is the most common site of extra pulmonary TB. The primary focus of genital tuberculosis is fallopian tubes, which are almost always affected bilaterally but not symmetrically. Because of common involvement of fallopian tubes and endometrial cavity, disease causes infertility. Diagnosis is not easy because genital tuberculosis has a wide range of clinical and radiological manifestations with slow growing symptoms. Detailed hysterosalpingography finding may be helpful in better diagnosis of the disease. This case series aims to depict the various hystrosalpingographic appearances and pathology produced by tuberculosis and related literatures are reviewed in order to establish a better diagnostic evaluation of genital tuberculosis. PMID:24639787
Afzali, Nargess; Ahmadi, Firoozeh; Akhbari, Farnaz
Background: Genital tuberculosis is a chorionic disease and mostly occurs by haematogenous spread from extra genital source like lungs, peritoneum, lymph nodes and bones. Transmission through a sexual intercourse is also possible. Since the majority of patients are in reproductive ages, involvement of fallopian tubes and endometrium cause infertility in patients. Cases: Reviewing 4 cases of female genital tuberculosis, which referred to an infertility treatment center with various symptoms, we encountered various appearances on hysterosalpingography (HSG). Conclusion: The genitourinary tract is the most common site of extra pulmonary TB. The primary focus of genital tuberculosis is fallopian tubes, which are almost always affected bilaterally but not symmetrically. Because of common involvement of fallopian tubes and endometrial cavity, disease causes infertility. Diagnosis is not easy because genital tuberculosis has a wide range of clinical and radiological manifestations with slow growing symptoms. Detailed hysterosalpingography finding may be helpful in better diagnosis of the disease. This case series aims to depict the various hystrosalpingographic appearances and pathology produced by tuberculosis and related literatures are reviewed in order to establish a better diagnostic evaluation of genital tuberculosis.
Afzali, Nargess; Ahmadi, Firoozeh; Akhbari, Farnaz
Credit PSR. View looking north northeast (12°) across surface remains of North Base swimming pool. The southeast edge of the pool appearing in the foreground may seem to be a sidewalk to the casual observer; the wavy inside edge of this walk matches the pool side visible in historic construction photos (See HAER photo CA-170-Q-2). The telephone pole in the midground of the view is inside the pool proper. Building 4312 (Liquid Oxygen Repair Facility) appears in left background, Building 4456 (Fire House No. 4) in middle background, and Building 4444 (Communications Building) in right background - Edwards Air Force Base, North Base, Swimming Pool, Second Street, Boron, Kern County, CA
Background While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital. Methods A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression. Result A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31–40 years. Previous history of tuberculosis (OR?=?4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR?=?6.67 95% CI 2.78-16.90), history of underlying diseases (OR?=?2.79 95% CI 1.15-6.78) and income (OR?=?12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary tuberculosis infection. Conclusion The prevalence of smear positive extra pulmonary tuberculosis infection in Gondar is high. Screening of lymph node and other body fluid specimens for extra pulmonary tuberculosis could help for treatment, control and prevention of the disease.
NASA's Chandra X-ray Observatory has found a cosmic "ghost" lurking around a distant supermassive black hole. This is the first detection of such a high-energy apparition, and scientists think it is evidence of a huge eruption produced by the black hole. This discovery presents astronomers with a valuable opportunity to observe phenomena that occurred when the Universe was very young. The X-ray ghost, so-called because a diffuse X-ray source has remained after other radiation from the outburst has died away, is in the Chandra Deep Field-North, one of the deepest X-ray images ever taken. The source, a.k.a. HDF 130, is over 10 billion light years away and existed at a time 3 billion years after the Big Bang, when galaxies and black holes were forming at a high rate. "We'd seen this fuzzy object a few years ago, but didn't realize until now that we were seeing a ghost", said Andy Fabian of the Cambridge University in the United Kingdom. "It's not out there to haunt us, rather it's telling us something - in this case what was happening in this galaxy billions of year ago." Fabian and colleagues think the X-ray glow from HDF 130 is evidence for a powerful outburst from its central black hole in the form of jets of energetic particles traveling at almost the speed of light. When the eruption was ongoing, it produced prodigious amounts of radio and X-radiation, but after several million years, the radio signal faded from view as the electrons radiated away their energy. HDF 130 Chandra X-ray Image of HDF 130 However, less energetic electrons can still produce X-rays by interacting with the pervasive sea of photons remaining from the Big Bang - the cosmic background radiation. Collisions between these electrons and the background photons can impart enough energy to the photons to boost them into the X-ray energy band. This process produces an extended X-ray source that lasts for another 30 million years or so. "This ghost tells us about the black hole's eruption long after it has died," said co-author Scott Chapman, also of Cambridge University. "This means we don't have to catch the black holes in the act to witness the big impact they have." This is the first X-ray ghost ever seen after the demise of radio-bright jets. Astronomers have observed extensive X-ray emission with a similar origin, but only from galaxies with radio emission on large scales, signifying continued eruptions. In HDF 130, only a point source is detected in radio images, coinciding with the massive elliptical galaxy seen in its optical image. This radio source indicates the presence of a growing supermassive black hole. People Who Read This Also Read... Milky Way's Super-efficient Particle Accelerators Caught in The Act NASA Joins "Around the World in 80 Telescopes" Celebrate the International Year of Astronomy Galaxies Coming of Age in Cosmic Blobs "This result hints that the X-ray sky should be littered with such ghosts," said co-author Caitlin Casey, also of Cambridge, "especially if black hole eruptions are as common as we think they are in the early Universe." The power contained in the black hole eruption was likely to be considerable, equivalent to about a billion supernovas. The energy is dumped into the surroundings and transports and heats the gas. "Even after the ghost disappears, most of the energy from the black hole's eruption remains", said Fabian. "Because they're so powerful, these eruptions can have profound effects lasting for billions of years." The details of Chandra's data of HDF 130 helped secure its true nature. For example, in X-rays, HDF 130 has a cigar-like shape that extends for some 2.2 million light years. The linear shape of the X-ray source is consistent with the shape of radio jets and not with that of a galaxy cluster, which is expected to be circular. The energy distribution of the X-rays is also consistent with the interpretation of an X-ray ghost. NASA's Marshall Space Flight Center in Huntsville, Ala., manages the Chandr
1. VIEW OF CRUSHING PLANT (FEATURE 19). THE REMAINS OF THE FINE ORE MILL (FEATURE 20) ARE IN THE BACKGROUND ON LEFT. CONCRETE RESERVOIR (FEATURE 22) IS SHOWN AT THE RIGHT EDGE OF PHOTOGRAPH FACING SOUTHWEST. - Copper Canyon Camp of the International Smelting & Refining Company, Crushing Plant, Copper Canyon, Battle Mountain, Lander County, NV
To address the training needs of health care providers about tuberculosis, the American Thoracic Society and the Division of Tuberculosis Control, Centers for Disease Control launched the National Tuberculosis Training Initiative (NTTI). Input from 22 nat...
... Prevention Division of Tuberculosis Elimination Mycobacterium bovis (Bovine Tuberculosis) in Humans What is Mycobacterium bovis? In the United States, the majority of tuberculosis (TB) cases in people are caused by Mycobacterium ...
Background Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. Early diagnosis of MDR-TB patients is essential for minimizing the risk of Mycobacterium tuberculosis (MTB) transmission. The conventional drug susceptibility testing (DST) methods for detection of drug-resistant M.tuberculosis are laborious and cannot provide the rapid detection for clinical practice. Methods The aim of this study was to develop a pyrosequencing approach for the simultaneous detection of resistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) in M. tuberculosis clinical isolates and sputum samples from re-treatment pulmonary tuberculosis (PTB) patients. We identified the optimum conditions for detection mutation of rpoB, katG, rpsl, embB, gyrA and rrs gene by pyrosequencing. Then this approach was applied to detect 205 clinical isolates and 24 sputum samples of M. tuberculosis from re-treatment PTB patients. Results The mutations of rpoB and gyrA gene were detected by pyrosequencig with the SQA mode, and the mutations of katG, rpsl, embB, gyrA and rrs gene were detected by pyrosequencing with SNP mode. Compared with the Bactec MGIT 960 mycobacterial detection system, the accuracy of pyrosequencing for the detection of RIF, INH, EMB, SM, AMK and OFL resistance in clinical isolates was 95.0%, 79.2%, 70.3%, 84.5%, 96.5% and 91.1%, respectively. In sputum samples the accuracy was 83.3%, 83.3%, 60.9%, 83.3%, 87.5% and 91.7%, respectively. Conclusions The newly established pyrosequencing assay is a rapid and high-throughput method for the detection of resistance to RIF, INH, SM, EMB, OFL and AMK in M.tuberculosis. Pyrosequencing can be used as a practical molecular diagnostic tool for screening and predicting the resistance of re-treatment pulmonary tuberculosis patients.
Background Purified protein derivative (PPD) has been used for more than half a century as an antigen for the diagnosis of tuberculosis infection based on delayed type hypersensitivity. Although designated as “purified,” in reality, the composition of PPD is highly complex and remains ill-defined. In this report, high resolution mass spectrometry was applied to understand the complexity of its constituent components. A comparative proteomic analysis of various PPD preparations and their functional characterization is likely to help in short-listing the relevant antigens required to prepare a less complex and more potent reagent for diagnostic purposes. Results Proteomic analysis of Connaught Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M. tuberculosis, was carried out in this study. PPD-CT68 is the protein component of a commercially available tuberculin preparation, Tubersol, which is used for tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass spectrometer, we identified 265 different proteins. The identified proteins were compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from previous mass spectrometry-based studies. In all, 142 proteins were found to be shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M. tuberculosis–derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37 proteins were found to be shared with M. avium PPD and 80 were shared with M. bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung infecting bacteria revealed a number of similar proteins (206 bacterial proteins shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved in causing cross-reactivity. The data have been deposited to the ProteomeXchange with identifier PXD000377. Conclusions Proteomic and bioinformatics analysis of different PPD preparations revealed commonly and differentially represented proteins. This information could help in delineating the relevant antigens represented in various PPDs, which could further lead to development of a lesser complex and better defined skin test antigen with a higher specificity and sensitivity.
When archaeological sites are associated with human remains, it is relevant to be able to date those valuable remains for different reasons. The main one is that it avoids the stratigraphical problems which can be due to intrusive burials in the sequence. The other reason consists in the fact that human bones may be encountered out of established stratigraphical context.
Y. Yokoyama; C. Falguères
An effective new vaccine for the control of tuberculosis is badly needed. While current research attempts to improve vaccination are concentrating on new prophylactic or immunotherapeutic vaccines, virtually no emphasis has been placed on boosting individuals already inoculated with Mycobacterium bovis BCG. It is shown here that mice vaccinated with BCG gradually lose their capacity to resist an aerosol challenge
JASON V. BROOKS; ANTHONY A. FRANK; MARC A. KEEN; JOHN T. BELLISLE; IAN M. ORME
Background Tuberculosis remains a major world-wide health threat which demands the discovery and characterisation of new drug targets in order to develop future antimycobacterials. The regeneration of methionine consumed during polyamine biosynthesis is an important pathway present in many microorganisms. The final step of this pathway, the conversion of ketomethiobutyrate to methionine, can be performed by aspartate, tyrosine, or branched-chain amino acid aminotransferases depending on the particular species examined. Results The gene encoding for branched-chain amino acid aminotransferase in Mycobacterium tuberculosis H37Rv has been cloned, expressed, and characterised. The enzyme was found to be a member of the aminotransferase IIIa subfamily, and closely related to the corresponding aminotransferase in Bacillus subtilis, but not to that found in B. anthracis or B. cereus. The amino donor preference for the formation of methionine from ketomethiobutyrate was for isoleucine, leucine, valine, glutamate, and phenylalanine. The enzyme catalysed branched-chain amino acid and ketomethiobutyrate transamination with a Km of 1.77 – 7.44 mM and a Vmax of 2.17 – 5.70 ?mol/min/mg protein, and transamination of ketoglutarate with a Km of 5.79 – 6.95 mM and a Vmax of 11.82 – 14.35 ?mol/min/mg protein. Aminooxy compounds were examined as potential enzyme inhibitors, with O-benzylhydroxylamine, O-t-butylhydroxylamine, carboxymethoxylamine, and O-allylhydroxylamine yielding mixed-type inhibition with Ki values of 8.20 – 21.61 ?M. These same compounds were examined as antimycobacterial agents against M. tuberculosis and a lower biohazard M. marinum model system, and were found to completely prevent cell growth. O-Allylhydroxylamine was the most effective growth inhibitor with an MIC of 78 ?M against M. marinum and one of 156 ?M against M. tuberculosis. Conclusion Methionine formation from ketomethiobutyrate is catalysed by a branched-chain amino acid aminotransferase in M. tuberculosis. This enzyme can be inhibited by selected aminooxy compounds, which also have effectiveness in preventing cell growth in culture. These compounds represent a starting point for the synthesis of branched-chain aminotransferase inhibitors with higher activity and lower toxicity.
Venos, Erik S; Knodel, Marvin H; Radford, Cynthia L; Berger, Bradley J
Background Travelers to countries with high tuberculosis incidence can acquire infection during travel. We sought to compare four screening interventions for travelers from low-incidence countries, who visit countries with varying tuberculosis incidence. Methods Decision analysis model: We considered hypothetical cohorts of 1,000 travelers, 21 years old, visiting Mexico, the Dominican Republic, or Haiti for three months. Travelers departed from and returned to the United States or Canada; they were born in the United States, Canada, or the destination countries. The time horizon was 20 years, with 3% annual discounting of future costs and outcomes. The analysis was conducted from the health care system perspective. Screening involved tuberculin skin testing (post-travel in three strategies, with baseline pre-travel tests in two), or chest radiography post-travel (one strategy). Returning travelers with tuberculin conversion (one strategy) or other evidence of latent tuberculosis (three strategies) were offered treatment. The main outcome was cost (in 2005 US dollars) per tuberculosis case prevented. Results For all travelers, a single post-trip tuberculin test was most cost-effective. The associated cost estimate per case prevented ranged from $21,406 for Haitian-born travelers to Haiti, to $161,196 for US-born travelers to Mexico. In all sensitivity analyses, the single post-trip tuberculin test remained most cost-effective. For US-born travelers to Haiti, this strategy was associated with cost savings for trips over 22 months. Screening was more cost-effective with increasing trip duration and infection risk, and less so with poorer treatment adherence. Conclusion A single post-trip tuberculin skin test was the most cost-effective strategy considered, for travelers from the United States or Canada. The analysis did not evaluate the use of interferon-gamma release assays, which would be most relevant for travelers who received BCG vaccination after infancy, as in many European countries. Screening decisions should reflect duration of travel, tuberculosis incidence, and commitment to treat latent infection.
Tan, Michael; Menzies, Dick; Schwartzman, Kevin
Background Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis. It remains a major health threat, killing over one million people every year worldwide. An early antibiotic therapy is the basis of the treatment, and the emergence and spread of multidrug and extensively drug-resistant mutant strains raise significant challenges. As these bacteria grow very slowly, drug resistance mutations are currently detected using molecular biology techniques. Resistance mutations are identified by sequencing the resistance-linked genes followed by a comparison with the literature data. The only online database is the TB Drug Resistance Mutation database (TBDReaM database); however, it requires mutation detection before use, and its interrogation is complex due to its loose syntax and grammar. Description The MUBII-TB-DB database is a simple, highly structured text-based database that contains a set of Mycobacterium tuberculosis mutations (DNA and proteins) occurring at seven loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs. Resistance mutation data were extracted after the systematic review of MEDLINE referenced publications before March 2013. MUBII analyzes the query sequence obtained by PCR-sequencing using two parallel strategies: i) a BLAST search against a set of previously reconstructed mutated sequences and ii) the alignment of the query sequences (DNA and its protein translation) with the wild-type sequences. The post-treatment includes the extraction of the aligned sequences together with their descriptors (position and nature of mutations). The whole procedure is performed using the internet. The results are graphs (alignments) and text (description of the mutation, therapeutic significance). The system is quick and easy to use, even for technicians without bioinformatics training. Conclusion MUBII-TB-DB is a structured database of the mutations occurring at seven loci of major therapeutic value in tuberculosis management. Moreover, the system provides interpretation of the mutations in biological and therapeutic terms and can evolve by the addition of newly described mutations. Its goal is to provide easy and comprehensive access through a client–server model over the Web to an up-to-date database of mutations that lead to the resistance of M. tuberculosis to antibiotics.
For 20 years, bovine tuberculosis (BTB) has been spreading in Great Britain (England, Wales and Scotland) and is now endemic in the southwest and parts of central England and in southwest Wales, and occurs sporadically elsewhere. Although its transmission pathways remain poorly understood, the disease's distribution was previously modelled statistically by using environmental variables and measures of their seasonality. Movements
M. Gilbert; A. Mitchell; D. Bourn; J. Mawdsley; R. Clifton-Hadley; W. Wint
We describe an unusual case of multidrug-resistant miliary tuberculosis diagnosed 9 months after the commencement of infliximab treatment for psoriasis despite negative pretreatment tuberculosis screening, including chest X-ray and interferon-gamma release assay. After 4 months' treatment with amikacin, ethambutol, pyrazinamide and moxifloxacin, infliximab was restarted with concomitant anti-TB medications. No recurrence of tuberculosis has been detected 12 months after recommencing infliximab. PMID:23713793
Gin, Alexander; Dolianitis, Con
Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain. These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues; rising and disturbing rates of multidrug- and extensively drug-resistant TB; the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co-epidemic. Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first- and second-line TB drugs. Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient age. This article reviews the challenges faced by those trying to develop these novel regimens and the key agents currently in clinical testing for TB; the latter are organized for discussion into three categories: (i) novel drugs (TMC207, SQ109, sudoterb [LL3858]); (ii) present first-line TB drugs being re-evaluated to optimize their efficacy (rifampicin, rifapentine); and (iii) currently licensed drugs for other indications and 'next-generation' compounds of the same chemical class being repurposed for TB (gatifloxacin and moxifloxacin; linezolid, PNU100480 and AZD5847; metronidazole, OPC-67683 and PA-824). PMID:21080738
Ginsberg, Ann M
Tuberculosis remains a major infectious disease in Taiwan. Here we present the draft genome sequence of the Mycobacterium tuberculosis C2 strain, belonging to the Latin American–Mediterranean lineage. The draft genome sequence comprises 4,453,307 bp with a G+C content of 65.6%, revealing 4,390 coding genes and 45 tRNA genes.
Liao, Yu-Chieh; Chen, Yih-Yuan; Lin, Hsin-Hung; Chang, Jia-Ru; Su, Ih-Jen; Huang, Tsi-Shu
Objective: The prevalence of pulmonary tuberculosis remains high in several areas of the world, and pneumonectomy is often necessary to treat the disease. We retrospectively analyzed the morbidities, mortalities, and long-term outcomes after pneumonectomy for the treatment of active tuberculosis or its sequelae. Materials and methods: Between 1981 and 2001, 94 patients underwent either pneumonectomy or pleuropneumonectomy for the treatment
Young Tae Kim; Hong Kwan Kim; Sook-Whan Sung; Joo Hyun Kim
Psoriasis is a chronic, relapsing and remitting inflammatory skin and joint disease that has a prevalence of 2-3% in the world's population, whereas of 1–2% in Europe. The traditional concept of psoriasis as the “healthy people's” disease has been recently revised because of ever-increasing reports of associations with various pathological conditions (hypertension, Crohn's disease, type II diabetes mellitus, obesity, dyslipidemia, metabolic syndrome, infectious conditions). Particularly, advances in psoriasis therapies have introduced biologic agents. All the tumor necrosis factor-alpha inhibitors are associated with an increased risk of developing active disease in patients with latent tuberculosis infection, because of TNF-? key role against Mycobacterium tuberculosis. For this reason, exclusion of active tuberculosis and treatment of latent tuberculosis infection are clinical imperatives prior to starting this therapy. Moreover active surveillance for a history of untreated or partially treated tuberculosis or latent form has already been shown to be effective in reducing the number of incident tuberculosis cases.
Balato, Nicola; Di Costanzo, Luisa; Ayala, Fabio; Balato, Anna; Sanduzzi, Alessandro; Bocchino, Marialuisa
Background: A new rapid Immunochromatographic test (ICT) kit (SDBioline TB Ag MPT64RAPID(®)) developed by Standard Diagnostics, South Korea was evaluated for rapid differentiation of M. tuberculosis from non tuberculous mycobacteria (NTM). It detects MPT 64 antigen in M. tuberculosis isolates using mouse monoclonal MPT 64 antibody. The kit was assessed for routine identification of the Acid Fast Bacilli(AFB) isolated in our laboratory. Materials and Methods: Two hundred eight culture isolates of Mycobacteria were tested using ICT test kit for detection of MPT 64 antigen from liquid and solid culture. H37Rv strain was employed as the positive reference control. Any negative result was referred for confirmation by Gen Probe Accu Probe assay for MTB Complex (Gen-Probe, San Diego, Calif.). Speciation of NTM was performed using genotypic Mycobacterium CM assay (Hain's life sciences, Germany). Results: Of the 208 culture positive isolates tested, 182 (87.5%) were found positive for Mycobacterium tuberculosis Complex and remaining 26 (12.5%) were considered as NTM. These results were further confirmed by Gen Probe Accu probe assay that served as the reference method for detection of MTBC. H37Rv reference strain was taken as a control for ICT test and molecular tests. The reference strain showed the presence of MPT64 antigen band in the ICT test. Similar bands were formed in all MTBC (182) isolates tested, proving 100 per cent sensitivity and no bands were detected in 48 (100%) NTM isolates tested, proving 100 per cent specificity of the ICT kit. Conclusion: Tuberculosis is a global pandemic. Rapid identification of Mycobacteria as MTB complex or non-tuberculous Mycobacteria from culture is important for treatment of infected cases and drug susceptibility testing of the culture isolate. MPT 64 TB antgen detection using SD Bioline Immunochromatographic test is a simple and cost effective method for differentiation of Mycobacterial cultures as MTB complex from non- tuberculous Mycobacteria. PMID:24959442
Shenoy, Vishnu Prasad; Mukhopadhyay, Chiranjay
Background: A new rapid Immunochromatographic test (ICT) kit (SDBioline TB Ag MPT64RAPID®) developed by Standard Diagnostics, South Korea was evaluated for rapid differentiation of M. tuberculosis from non tuberculous mycobacteria (NTM). It detects MPT 64 antigen in M. tuberculosis isolates using mouse monoclonal MPT 64 antibody. The kit was assessed for routine identification of the Acid Fast Bacilli(AFB) isolated in our laboratory. Materials and Methods: Two hundred eight culture isolates of Mycobacteria were tested using ICT test kit for detection of MPT 64 antigen from liquid and solid culture. H37Rv strain was employed as the positive reference control. Any negative result was referred for confirmation by Gen Probe Accu Probe assay for MTB Complex (Gen-Probe, San Diego, Calif.). Speciation of NTM was performed using genotypic Mycobacterium CM assay (Hain’s life sciences, Germany). Results: Of the 208 culture positive isolates tested, 182 (87.5%) were found positive for Mycobacterium tuberculosis Complex and remaining 26 (12.5%) were considered as NTM. These results were further confirmed by Gen Probe Accu probe assay that served as the reference method for detection of MTBC. H37Rv reference strain was taken as a control for ICT test and molecular tests. The reference strain showed the presence of MPT64 antigen band in the ICT test. Similar bands were formed in all MTBC (182) isolates tested, proving 100 per cent sensitivity and no bands were detected in 48 (100%) NTM isolates tested, proving 100 per cent specificity of the ICT kit. Conclusion: Tuberculosis is a global pandemic. Rapid identification of Mycobacteria as MTB complex or non-tuberculous Mycobacteria from culture is important for treatment of infected cases and drug susceptibility testing of the culture isolate. MPT 64 TB antgen detection using SD Bioline Immunochromatographic test is a simple and cost effective method for differentiation of Mycobacterial cultures as MTB complex from non- tuberculous Mycobacteria.
The association between tuberculosis and underlying risk factors was evaluated in Texas patients hospitalized in the 15 counties along the Mexico border within the remaining non-border counties. A case control analysis of the hospital discharge dataset from the Texas Health Care Information Council was performed for the years 1999–2001. A discharge diagnosis of tuberculosis identified cases (N = 4,915). Deep venous thrombosis, pulmonary embolism, and acute appendicitis conditions identified controls (N = 70,808). Risk factors associated with tuberculosis were identified by logistic regression. Diabetes patients were almost twice as likely to have tuberculosis after adjusting by sex, age, and race/ethnicity. The association was strong for the population in the Texas border region, where there are higher incidence rates of tuberculosis (odds ratio [OR]adj = 1.82; 95% CI = 1.57–2.12) compared with non-border counties (ORadj = 1.51; 95% CI = 1.36–1.67).
PEREZ, ADRIANA; BROWN, H. SHELTON; RESTREPO, BLANCA I.
BACKGROUND: There is paucity of data on seasonal variation in pulmonary tuberculosis (TB) in developing countries contrary to recognized seasonality in the TB notification in western societies. This study examined the seasonal pattern in TB diagnosis among migrant workers from developing countries entering Kuwait. METHODS: Monthly aggregates of TB diagnosis results for consecutive migrants tested between January I, 1997 and
Saeed Akhtar; Hameed GHH Mohammad
Parotid gland involvement is extremely rare, even in countries in which tuberculosis is endemic. Clinically, it usually presents as a slow-growing mass indistinguishable from a malignancy. On imaging too, tuberculosis of the parotid may mimic neoplasm. The diagnosis of parotid tuberculosis needs a high degree of clinical suspicion. This paper highlights the clinical presentation, imaging findings, and importance of FNAC in diagnosis of this rare entity.
Gupta, Vivek; Patankar, Kiran; Shinde, Archana; Bhosale, Charu; Tamhane, Ajitey
Recent reports suggest an increased incidence of abdominal tuberculosis in the United States, particularly in high-risk groups.\\u000a The aim of this study was to review the spectrum of abdominal tuberculosis and its surgical management at a tertiary referral\\u000a center in the United States. The medical records of patients treated for abdominal tuberculosis at our institution between\\u000a January 1992 and June
Imran Hassan; Emmanouil S. Brilakis; Rodney L. Thompson; Florencia G. Que
Background The statistics of disease clustering is one of the most important tools for epidemiologists to detect and monitor public health disease patterns. Nowadays, tuberculosis (TB) – an infectious disease caused by the Mycobacterium tuberculosis – presents different (development in populations and antibiotics resistance) patterns and specialists are very concerned with it and its association to several other diseases and factors. Each year, tuberculosis kills about three million people in the world. In particular, it is responsible for the death of more than one-third of HIV-infected people, who prove particularly susceptible due to a decline in their immune defences. The purpose of this study is to determine if there are spatiotemporal tuberculosis incidence clusters in continental Portugal. The presented case study is based on the notification of new tuberculosis cases (disease incidence), between 2000 and 2004. In methodological terms, the spatial scan statistic, used to identify spatiotemporal clusters, was improved by including two new approaches: definition of window sizes in the cluster scanning processes considering empirical mean spatial semivariograms and an independent and posterior validation of identified clusters (based on geostatistical simulations). Results Continental Portugal is organized in 18 districts with 278 sub-districts. For this case study, the number of new notified cases of TB, per sub-district and per year (2000–2004) was available. TB incidence presents clear spatial patterns: a semivariogram consistent with 40% of nugget effect and 60% of spatial contribution, following an exponential model with a range of 143 kilometres. Temporal semivariograms were not conclusive, as only 5 years of data were available. The spatial and temporal persistence of clusters were analyzed considering different models. Significant high incidence rate space-time clusters were identified in three areas of Portugal (between 2000 and 2004) and a purely temporal cluster was identified covering the whole country, during 2002. Conclusion In terms of spatiotemporal clustering of tuberculosis disease, the proposed methodology allowed the identification of critical spatiotemporal areas. In Portugal there were 3 critical districts (Porto, Setúbal and Lisbon) with high rates of notified incidences between 2000 and 2004. In methodological terms, semivariogram parameters were successfully applied to define spatiotemporal scan window sizes and shapes (ellipsoidal cylinders), showing very good results and performances in the case study. After defining the clusters, these were authenticated through a validation method, based on geostatistical simulations.
A conceptual framework to study the epidemiologic basis of tuberculosis control is provided. The basic model to discuss the epidemiology of tuberculosis is based on a classification of tuberculosis based on its pathogenesis with exposure, latent infection, tuberculosis, and death from tuberculosis, showing the conditional probabilities leading from one to the next step in the chain of events. Historical data are utilized to demonstrate how the dynamics of tuberculosis over multiple decades have contributed to shape the present. It is shown that the key concept to understand the dynamics is related to current and past incidence and prevalence of latent infection with M. tuberculosis. The dynamics of the epidemic are shaped both by the behaviour of the causative organism of tuberculosis as well as the population structure and changes that take place in parallel in which M. tuberculosis thrives. Both the present and the future shape of the epidemic, as well as the principles applied to its control lie very much in the past of a society. While new risk factors such as HIV or diabetes have been or are emerging more strongly, it is noted that the majority of all new cases emerging cannot be pinned to one or the other such factor. It is the historical experience of a population that offers the most valuable key to understanding the present and the future. PMID:24640341
Rieder, Hans L
Latent tuberculosis infection is a key stage in the natural history of tuberculosis, and provides an important period where strategies to prevent the development of disease may be implemented. The treatment of latent tuberculosis infection is well described in many national guidelines. In this review, we attempt to help pneumonologists to implement these guidelines accurately and appropriately, prescribing preventive treatment when the benefit-risk ratio is optimal, providing treatment most safely, performing therapeutic education and incorporating preventive treatment into the full array of measures against tuberculosis. PMID:22542415
Renal involvement in tuberculosis occurs due to lympho-hematogenous dissemi-nation. However, glomerular involvement is an uncommon event. Crescentic nephritis compli-cating tuberculosis is a therapeutic dilemma and weighs the risk of worsening the infection after immunosuppressive therapy. We present here a case of miliary tuberculosis with immune com-plex crescentic nephritis with advanced renal injury requiring renal replacement therapy. A diagnosis of miliary tuberculosis was made on the basis of positive sputum AFB, lymph node biopsy showing caseating granulomas and urinary polymerase chain reaction being positive for mycobacterial antigens. The patient recovered renal function with anti-tuberculous therapy with-out requiring immunosuppressive therapy. PMID:24969205
Waikhom, Rajesh; Sarkar, Dipankar; Bennikal, Mahesh; Pandey, Rajendra
Background Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. Methods We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. Results During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73–1.14, P?=?0.4299). Conclusions Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.
Wu, Chueh-Hung; Chen, Li-Sheng; Yen, Ming-Fang; Chiu, Yueh-Hsia; Fann, Ching-Yuan; Chen, Hsiu-Hsi; Pan, Shin-Liang
BACKGROUND: Tuberculosis (TB) in migrants is an ongoing challenge in several low TB incidence countries since a large proportion of TB in these countries occurs in migrants from high incidence countries. To meet these challenges, several countries utilize TB screening programs. The programs attempt to identify and treat those with active and\\/or infectious stages of the disease. In addition, screening
Gonzalo G Alvarez; Brian Gushulak; Khaled Abu Rumman; Ekkehardt Altpeter; Daniel Chemtob; Paul Douglas; Connie Erkens; Peter Helbling; Ingrid Hamilton; Jane Jones; Alberto Matteelli; Marie-Claire Paty; Drew L Posey; Daniel Sagebiel; Erika Slump; Anders Tegnell; Elena Rodríguez Valín; Brita Askeland Winje; Edward Ellis
Being an obligate aerobe, Mycobacterium tuberculosis faces a number of energetic challenges when it encounters hypoxia and environmental stress during intracellular infection. Consequently, it has evolved innovative strategies to cope with these unfavorable conditions. Here, we report a novel flavohemoglobin (MtbFHb) from M. tuberculosis that exhibits unique features within its heme and reductase domains distinct from conventional FHbs, including the absence of the characteristic hydrogen bonding interactions within the proximal heme pocket and mutations in the FAD and NADH binding regions of the reductase domain. In contrast to conventional FHbs, it has a hexacoordinate low-spin heme with a proximal histidine ligand lacking imidazolate character and a distal heme pocket with a relatively low electrostatic potential. Additionally, MtbFHb carries a new FAD binding site in its reductase domain similar to that of d-lactate dehydrogenase (d-LDH). When overexpressed in Escherichia coli or Mycobacterium smegmatis, MtbFHb remained associated with the cell membrane and exhibited d-lactate:phenazine methosulfate reductase activity and oxidized d-lactate into pyruvate by converting the heme iron from Fe3+ to Fe2+ in a FAD-dependent manner, indicating electron transfer from d-lactate to the heme via FAD cofactor. Under oxidative stress, MtbFHb-expressing cells exhibited growth advantage with reduced levels of lipid peroxidation. Given the fact that d-lactate is a byproduct of lipid peroxidation and that M. tuberculosis lacks the gene encoding d-LDH, we propose that the novel d-lactate metabolizing activity of MtbFHb uniquely equips M. tuberculosis to balance the stress level by protecting the cell membrane from oxidative damage via cycling between the Fe3+/Fe2+ redox states.
Gupta, Sanjay; Pawaria, Sudesh; Lu, Changyuan; Hade, Mangesh Dattu; Singh, Chaahat; Yeh, Syun-Ru; Dikshit, Kanak L.
Being an obligate aerobe, Mycobacterium tuberculosis faces a number of energetic challenges when it encounters hypoxia and environmental stress during intracellular infection. Consequently, it has evolved innovative strategies to cope with these unfavorable conditions. Here, we report a novel flavohemoglobin (MtbFHb) from M. tuberculosis that exhibits unique features within its heme and reductase domains distinct from conventional FHbs, including the absence of the characteristic hydrogen bonding interactions within the proximal heme pocket and mutations in the FAD and NADH binding regions of the reductase domain. In contrast to conventional FHbs, it has a hexacoordinate low-spin heme with a proximal histidine ligand lacking imidazolate character and a distal heme pocket with a relatively low electrostatic potential. Additionally, MtbFHb carries a new FAD binding site in its reductase domain similar to that of D-lactate dehydrogenase (D-LDH). When overexpressed in Escherichia coli or Mycobacterium smegmatis, MtbFHb remained associated with the cell membrane and exhibited D-lactate:phenazine methosulfate reductase activity and oxidized D-lactate into pyruvate by converting the heme iron from Fe(3+) to Fe(2+) in a FAD-dependent manner, indicating electron transfer from D-lactate to the heme via FAD cofactor. Under oxidative stress, MtbFHb-expressing cells exhibited growth advantage with reduced levels of lipid peroxidation. Given the fact that D-lactate is a byproduct of lipid peroxidation and that M. tuberculosis lacks the gene encoding D-LDH, we propose that the novel D-lactate metabolizing activity of MtbFHb uniquely equips M. tuberculosis to balance the stress level by protecting the cell membrane from oxidative damage via cycling between the Fe(3+)/Fe(2+) redox states. PMID:22437825
Gupta, Sanjay; Pawaria, Sudesh; Lu, Changyuan; Hade, Mangesh Dattu; Singh, Chaahat; Yeh, Syun-Ru; Dikshit, Kanak L
BACKGROUND: Tuberculosis is a major cause of morbidity and mortality globally. Recent scholarly attention to public health ethics provides an opportunity to analyze several ethical issues raised by the global tuberculosis pandemic. DISCUSSION: Recently articulated frameworks for public health ethics emphasize the importance of effectiveness in the justification of public health action. This paper critically reviews the relationship between these
Geetika Verma; Ross EG Upshur; Elizabeth Rea; Solomon R Benatar
Background: Nutritional support is often recommended as part of the treatment of tuberculosis, but it has never been properly tested. Objective: We assessed the effects of early nutritional intervention on lean mass and physical function in patients with tuberculosis and wasting. Design: Patients who started antituberculous therapy within the previous 2 wk were randomly assigned to receive standard nutri- tional
Nicholas I Paton; Yueh-Khim Chua; Arul Earnest; Cynthia BE Chee
Background Timely tuberculosis treatment initiation and compliance are the two key factors for a successful tuberculosis control program. However, studies to understand patents’ perspective on tuberculosis treatment initiation and compliance have been limited in Ethiopia. The aim of this study is to attempt to do that in rural Ethiopia. Methods This qualitative, phenomenological study conducted 26 in-depth interviews with tuberculosis patients. A thematic content analysis of the interviews was performed using the Open Code software version 3.1. Results We found that lack of geographic access to health facilities, financial burdens, use of traditional healing systems and delay in diagnosis by health care providers were the main reasons for not initiating tuberculosis treatment timely. Lack of geographic access to health facilities, financial burdens, quality of health services provided and social support were also identified as the main reasons for failing to fully comply with tuberculosis treatments. Conclusions This study highlighted complexities surrounding tuberculosis control efforts in Dabat District. Challenges of geographic access to health care facilities and financial burdens were factors that most influenced timely tuberculosis treatment initiation and compliance. Decentralization of tuberculosis diagnosis and treatment services to peripheral health facilities, including health posts is of vital importance to make progress toward achieving tuberculosis control targets in Ethiopia.
Background The coexistence of breast cancer and tuberculosis is very rare. This can create a dilemma in the diagnosis and treatment as there are no pathognomonic symptoms or signs to distinguish both diseases. Case presentation A female patient was seen in the breast clinic for a right breast lump. Clinical examination and investigation confirmed cancer and tuberculosis of the right breast. She underwent right mastectomy and axillary clearance and received chemo and radiotherapy. Unfortunately, she died of wide spread metastases. Conclusion The simultaneous occurrence of these two major illnesses in the breast can lead to many problems regarding diagnosis and treatment. Though rare, surgeons, pathologists and radiologists should be aware of such condition.
Alzaraa, Ahmed; Dalal, Neha
Background Knowledge about symptoms and transmission of tuberculosis determines health seeking behavior and helps in prevention of tuberculosis transmission in the community. Such data is useful for policy makers to formulate information, education and communication strategies for tuberculosis control. Methods A secondary data analysis of India demographic and health survey, 2005/6 was carried out. Questions about self-reported tuberculosis, transmission and curability of tuberculosis were analysed. Correct knowledge (without misconceptions) about tuberculosis transmission was used as a dependant variable and the explanatory variables tested were: demographic data, education, wealth quintiles, frequency of exposure to media and the curability of tuberculosis. Determinants of correct knowledge without misconceptions were tested by univariate and multivariate analyses using national weighting factor to adjust for complex sampling design. Results A total of 109,070 households (response rate of 93.5%) and 198,718 participants (response rate of 91.6%) completed the survey. The samples of men and women interviewed were 74,360 and 124,358 respectively. Prevalence rate of self-reported tuberculosis was 445 per 100,000 usual household residents and 4.60 per 1,000 participants. The number of respondents who had “heard of an illness called tuberculosis” was 177,423 (89.3%). Of these 47,487 (26.8%) participants did not know and 55.5% knew about the correct mode of tuberculosis transmission i.e. “Through the air when coughing or sneezing”. The common misconceptions about transmission were “Through food” (32.4%), “Sharing utensils” (18.2%), and “Touching a person with tuberculosis” (12.3%). Only 52,617 (29.7%) participants had correct knowledge without misconceptions. Being male (aOR 1.17, 95% CIs 1.14, 1.21), being a Hindu (aOR 1.20, 95% CIs 1.14, 1.26) or Muslim (aOR 1.26, 95% CIs 1.18, 1.34), listening to radio (aOR 1.08, 95% CIs 1.04, 1.13) and “Tuberculosis can be cured” (aOR 1.47, 95% CIs 1.41, 1.53) were associated with correct knowledge without misconceptions. Conclusions Knowledge about tuberculosis transmission is very poor and misconceptions still exist. Among the traditional mass media, the frequency of listening to radio was associated with correct knowledge about tuberculosis transmission. Strategies to deliver information, education and communication campaigns could be improved.
Background.?Patients with multidrug-resistant (MDR) tuberculosis may have phenotypic heterogeneity in results of drug-susceptibility tests (DSTs). However, the impact of this on clinical outcomes among patients treated for MDR tuberculosis is unknown. Methods.?Phenotypic DST heterogeneity was defined as presence of at least 1 Mycobacterium tuberculosis isolate susceptible to rifampicin and isoniazid recovered <3 months after MDR tuberculosis treatment initiation from a patient with previous documented tuberculosis due to M. tuberculosis resistant to at least rifampicin and isoniazid. The primary outcome was defined as good (ie, cure or treatment completion) or poor (ie, treatment failure, treatment default, or death). A secondary outcome was time to culture conversion. Cox proportional hazard models were used to determine the association between phenotypic DST heterogeneity and outcomes. Results.?Phenotypic DST heterogeneity was identified in 33 of 475 patients (7%) with MDR tuberculosis. Poor outcome occurred in 126 patients (28%). Overall, patients with MDR tuberculosis who had phenotypic DST heterogeneity were at greater risk of poor outcome than those with MDR tuberculosis but no phenotypic DST heterogeneity (adjusted hazard ratio [aHR], 2.1; 95% confidence interval [CI], 1.2-3.6). Among HIV-infected patients with MDR tuberculosis, the adjusted hazard for a poor outcome for those with phenotypic DST heterogeneity was 2.4 (95% CI, 1.3-4.2) times that for those without phenotypic DST heterogeneity, whereas among HIV-negative patients with MDR tuberculosis, the adjusted hazard for those with phenotypic DST heterogeneity was 1.5 (95% CI, .5-4.3) times that for those without phenotypic DST heterogeneity. HIV-infected patients with MDR tuberculosis with phenotypic DST heterogeneity also had a longer time to culture conversion than with HIV-infected patients with MDR tuberculosis without phenotypic DST heterogeneity (aHR, 2.9; 95% CI, 1.4-6.0). Conclusions.?Phenotypic DST heterogeneity among persons with HIV infection who are being treated for MDR tuberculosis is associated with poor outcomes and longer times to culture conversion. PMID:24443546
Zetola, Nicola M; Modongo, Chawangwa; Moonan, Patrick K; Ncube, Ronald; Matlhagela, Keikantse; Sepako, Enoch; Collman, Ronald G; Bisson, Gregory P
Background The increase in urban migrants is one of major challenges for tuberculosis control in China. The different characteristics of tuberculosis cases between urban migrants and local residents in China have not been investigated before. Methodology/Principal Findings We performed a retrospective study of all pulmonary tuberculosis patients reported in Songjiang district, Shanghai, to determine the demographic, clinical and microbiological characteristics of tuberculosis cases between urban migrants and local residents. We calculated the odds ratios (OR) and performed multivariate logistic regression to identify the characteristics that were independently associated with tuberculosis among urban migrants. A total of 1,348 pulmonary tuberculosis cases were reported during 2006–2008, among whom 440 (32.6%) were local residents and 908 (67.4%) were urban migrants. Urban migrant (38.9/100,000 population) had higher tuberculosis rates than local residents (27.8/100,000 population), and the rates among persons younger than age 35 years were 3 times higher among urban migrants than among local residents. Younger age (adjusted OR per additional year at risk?=?0.92, 95% CI: 0.91–0.94, p<0.001), poor treatment outcome (adjusted OR?=?4.12, 95% CI: 2.65–5.72, p<0.001), and lower frequency of any comorbidity at diagnosis (adjusted OR?=?0.20, 95% CI: 0.13–0.26, p?=?0.013) were significantly associated with tuberculosis patients among urban migrants. There were poor treatment outcomes among urban migrants, mainly from transfers to another jurisdiction (19.3% of all tuberculosis patients among urban migrants). Conclusions/Significance A considerable proportion of tuberculosis cases in Songjiang district, China, during 2006–2008 occurred among urban migrants. Our findings highlight the need to develop and implement specific tuberculosis control strategies for urban migrants, such as more exhaustive case finding, improved case management and follow-up, and use of directly observed therapy (DOT).
Shen, Xin; Xia, Zhen; Li, Xiangqun; Wu, Jie; Wang, Lili; Li, Jing; Jiang, Yuan; Guo, Juntao; Chen, Jing; Hong, Jianjun; Yuan, Zheng'an; Pan, Qichao; DeRiemer, Kathryn; Sun, Guomei; Gao, Qian; Mei, Jian
Background Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). The annotation of functional genome and signaling network in M. tuberculosis are still not systematic. Essential gene modules are a collection of functionally related essential genes in the same signaling or metabolic pathway. The determination of essential genes and essential gene modules at genomic level may be important for better understanding of the physiology and pathology of M. tuberculosis, and also helpful for the development of drugs against this pathogen. The establishment of genomic operon database (DOOR) and the annotation of gene pathways have felicitated the genomic analysis of the essential gene modules of M. tuberculosis. Method Bibliometric approach has been used to perform a High-throughput screen for essential genes of M. tuberculosis strain H37Rv. Ant colony algorithm were used to identify the essential genes in other M. tuberculosis reference strains. Essential gene modules were analyzed by operon database DOOR. The pathways of essential genes were assessed by Biocarta, KEGG, NCI-PID, HumanCyc and Reactome. The function prediction of essential genes was analyzed by Pfam. Results A total approximately 700 essential genes were identified in M. tuberculosis genome. 40% of operons are consisted of two or more essential genes. The essential genes were distributed in 92 pathways in M. tuberculosis. In function prediction, 61.79% of essential genes were categorized into virulence, intermediary metabolism/respiration,cell wall related and lipid metabolism, which are fundamental functions that exist in most bacteria species. Conclusion We have identified the essential genes of M. tuberculosis using bibliometric approach at genomic level. The essential gene modules were further identified and analyzed.
Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers. PMID:24766367
Hanrahan, Colleen F; Shah, Maunank
In 2012, tuberculosis (TB) remains a global health threat and is exacerbated both by the emergence of drug resistant Mycobacterium tuberculosis strains and its synergy with HIV infection. The waning effectiveness of current treatment regimens necessitates the development of new or repurposed anti-TB therapeutics for improved combination therapies against the disease. Exploiting atomic resolution structural information of proteins in complex with their substrates and/or inhibitors can facilitate structure-based rational drug design. Since our last review in 2009, there has been a wealth of new M. tuberculosis protein structural information. Once again, we have compiled the most promising structures with regards to potential anti-TB drug development and present them in this updated review.
Chim, Nicholas; Owens, Cedric P.; Contreras, Heidi; Goulding, Celia W.
The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human isolates. The latter also likely derived from a human pathogenic lineage, supporting the hypothesis of an original human host. Using Bayesian statistics and experimental data on the variability of the mycobacterial markers in infected patients, we estimated the age of the MTBC at 40,000 years, coinciding with the expansion of “modern” human populations out of Africa. Furthermore, coalescence analysis revealed a strong and recent demographic expansion in almost all M. tuberculosis lineages, which coincides with the human population explosion over the last two centuries. These findings thus unveil the dynamic dimension of the association between human host and pathogen populations.
Wirth, Thierry; Hildebrand, Falk; Allix-Beguec, Caroline; Wolbeling, Florian; Kubica, Tanja; Kremer, Kristin; van Soolingen, Dick; Rusch-Gerdes, Sabine; Locht, Camille; Brisse, Sylvain; Meyer, Axel
Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination. PMID:22608339
Raviglione, Mario; Marais, Ben; Floyd, Katherine; Lönnroth, Knut; Getahun, Haileyesus; Migliori, Giovanni B; Harries, Anthony D; Nunn, Paul; Lienhardt, Christian; Graham, Steve; Chakaya, Jeremiah; Weyer, Karin; Cole, Stewart; Kaufmann, Stefan H E; Zumla, Alimuddin
OBJECTIVES: This research studied the relative contribution of diabetes mellitus to the increased prevalence of tuberculosis in Hispanics. METHODS: A case-control study was conducted involving all 5290 discharges from civilian hospitals in California during 1991 who had a diagnosis of tuberculosis, and 37,366 control subjects who had a primary discharge diagnosis of deep venous thrombosis, pulmonary embolism, or acute appendicitis. Risk of tuberculosis was estimated as the odds ratio (OR) across race/ethnicity, with adjustment for other factors. RESULTS: Diabetes mellitus was found to be an independent risk factor for tuberculosis. The association of diabetes and tuberculosis was higher among Hispanics (adjusted OR [ORadj] = 2.95: 95% confidence interval [CI] = 2.61, 3.33) than among non-Hispanic Whites (ORadj = 1.31: 95% CI = 1.19. 1.45): among non-Hispanic Blacks, diabetes was not found to be associated with tuberculosis (ORadj = 0.93: 95% CI = 0.78, 1.09). Among Hispanics aged 25 to 54, the estimated risk of tuberculosis attributable to diabetes (25.2%) was equivalent to that attributable to HIV infection (25.5%). CONCLUSIONS: Diabetes mellitus remains a significant risk factor for tuberculosis in the United States. The association is especially notable in middle-aged Hispanics.
Pablos-Mendez, A; Blustein, J; Knirsch, C A
Background Control of the global Tuberculosis (TB) burden is hindered by the lack of a simple and effective diagnostic test that can be utilized in resource-limited settings. Methods We evaluated the performance of Truenat MTB™, a chip-based nucleic acid amplification test in the detection of Mycobacterium tuberculosis (MTB) in clinical sputum specimens from 226 patients with suspected pulmonary tuberculosis (TB). The test involved sputum processing using Trueprep-MAG™ (nanoparticle-based protocol run on a battery-operated device) and real-time PCR performed on the Truelab Uno™ analyzer (handheld, battery-operated thermal cycler). Specimens were also examined for presence of MTB using smear microscopy, liquid culture and an in-house nested PCR protocol. Results were assessed in comparison to a composite reference standard (CRS) consisting of smear and culture results, clinical treatment and follow-up, and radiology findings. Results Based on the CRS, 191 patients had “Clinical-TB” (Definite and Probable-TB). Of which 154 patients are already on treatment, and 37 were treatment naïve cases. Remaining 35 were confirmed “Non-TB” cases which are treatment naïve cases. The Truenat MTB test was found to have sensitivity and specificity of 91.1% (CI: 86.1–94.7) and 100% (CI: 90.0–100) respectively, in comparison to 90.58% (CI: 85.5–94.3) and 91.43% (CI: 76.9–98.2) respectively for the in-house nested PCR protocol. Conclusion This preliminary study shows that the Truenat MTB test allows detection of TB in approximately one hour and can be utilized in near-care settings to provide quick and accurate diagnosis.
Nikam, Chaitali; Jagannath, Manjula; Narayanan, Manoj Mulakkapurath; Ramanabhiraman, Vinaya; Kazi, Mubin; Shetty, Anjali; Rodrigues, Camilla
Background: 'RETREATMENT' for Tuberculosis (TB) has long been a neglected area in global TB control. While other components of the Stop TB Strategy have garnered appropriate focus and, increasingly, sufficient resources, issues related to the TB of patients previously treated for tuberculosis remain under examined and under-resourced. Methods: A longitudinal study was designed and the patients registered under Revised National Tuberculosis Control Programme (RNTCP) category II from June 2010 to December 2011.Out of total 607 patients registered during this period under category II of RNTCP in Chandigarh (India), 545 consented to participate in the study. These were followed up to September 2012 till the completion of treatment. Statistical Analysis: The analysis was done by using SPPS-18 statistical software package. Chi- square test was used for testing association of different characteristics. Results: Four Hundred Thirty (78.9%) of the patients had pulmonary TB and 115(21.1%) of the patients had extra pulmonary TB. In the study cohort of category II patients 264(48.4%) were relapse patients,167(30.6%) belonged to others category, 75(13.8%) were on treatment after default, 39(7.2%) were failure cases. The mean age of patients was 35.92 ± 15.42 (p = 0.928). Maximum patients belonged to age group of 25-34 years (25.3%). Seventy Three (13.4%) were Illiterate. In treatment after default group only 65.3% patients were cured. Maximum deaths 8% were seen in treatment after default group of patients. The overall default in the study was 5.9%. Conclusion: The findings of this study suggest that it is essential to monitor re-treatment patients with same vigour to reduce default and improve their treatment outcome. PMID:24701481
Sarpal, Sandeep Singh; Goel, Naveen Krishan; Kumar, Dinesh; Janmeja, A K
Background: ‘RETREATMENT’ for Tuberculosis (TB) has long been a neglected area in global TB control. While other components of the Stop TB Strategy have garnered appropriate focus and, increasingly, sufficient resources, issues related to the TB of patients previously treated for tuberculosis remain under examined and under-resourced. Methods: A longitudinal study was designed and the patients registered under Revised National Tuberculosis Control Programme (RNTCP) category II from June 2010 to December 2011.Out of total 607 patients registered during this period under category II of RNTCP in Chandigarh (India), 545 consented to participate in the study. These were followed up to September 2012 till the completion of treatment. Statistical Analysis: The analysis was done by using SPPS-18 statistical software package. Chi- square test was used for testing association of different characteristics. Results: Four Hundred Thirty (78.9%) of the patients had pulmonary TB and 115(21.1%) of the patients had extra pulmonary TB. In the study cohort of category II patients 264(48.4%) were relapse patients,167(30.6%) belonged to others category, 75(13.8%) were on treatment after default, 39(7.2%) were failure cases. The mean age of patients was 35.92 ± 15.42 (p = 0.928). Maximum patients belonged to age group of 25-34 years (25.3%). Seventy Three (13.4%) were Illiterate. In treatment after default group only 65.3% patients were cured. Maximum deaths 8% were seen in treatment after default group of patients. The overall default in the study was 5.9%. Conclusion: The findings of this study suggest that it is essential to monitor re-treatment patients with same vigour to reduce default and improve their treatment outcome.
Sarpal, Sandeep Singh; Goel, Naveen Krishan; Kumar, Dinesh; Janmeja, A.K.
SUMMARY BACKGROUND Antiretroviral therapy (ART) significantly reduces tuberculosis (TB) incidence among persons with human immunodeficiency virus (HIV), but the safety and effectiveness of concomitant treatment for both diseases remain unclear. OBJECTIVE To evaluate the impact of ART and anti-tuberculosis treatment on survival and risk of adverse events (AE) among co-infected individuals. METHODS In a retrospective cohort study, clinical data were collected from 618 TB-HIV patients treated with rifampin, isoniazid and pyrazinamide ± ethambutol between 1 January 1995 and 31 December 2003. Patients were categorized into two groups: highly active ART (HAART) or no ART. Different HAART regimens were evaluated. Bivariate analysis, multivariate logistic regression and survival analysis using Cox proportional hazards regression were used. RESULTS One-year mortality was lower for patients receiving HAART (adjusted hazard ratio [aHR] 0.17, 95%CI 0.09–0.31) compared to no ART. HAART increased the risk of AE (aHR 2.08, 95%CI 1.29–3.36). The odds of AE when receiving a ritonavir + saquinavir HAART regimen was eight-fold higher compared to no ART (OR 8.31, 95%CI 3.04–22.69), while efavirenz-based HAART was not associated with a significantly increased risk of AE (OR 1.42, 95%CI 0.76–2.65). CONCLUSION HIV patients with TB have significantly better survival if they receive HAART during anti-tuberculosis treatment. Efavirenz-based HAART is associated with fewer AEs than protease inhibitor-based HAART.
dos Santos, A. P. G.; Pacheco, A. G.; Staviack, A.; Golub, J. E.; Chaisson, R. E.; Rolla, V. C.; Kritski, A. L.; Passos, S. R. L.; de Queiroz Mello, F. C.
Although drug resistance in tuberculosis is by no means a new problem, multiple drug resistance is a cause of increasing concern. This study investigated first-line drug resistance in Mycobacterium tuberculosis strains isolated in a hospital environment and strains submitted as the Reference Center from 2000 to 2010. A total of 650 cultures were tested against first-line using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 142 strains, (21.85%). A total of 2% were multiresistant (MDR). Of the strains resistant to first-line drugs, the greatest resistance was found to isoniazid (7.38 %) followed by rifampin and streptomycin (3.85%), pyracinamide (2%), and ethambutol 1.23%. Only one strain was resistant to four drugs. Values. In view of the resistance observed, careful surveillance of drug resistance is recommended. PMID:24399346
Gutiérrez-Aroca, Juan Bautista; Ruiz, Pilar; Casal, Manuel
A 37-year-old male healthcare worker presented to the medical assessment unit complaining of a 3-month history of lethargy, weight loss, night sweats and intermittent abdominal discomfort. On examination there was some dullness to percussion at the right lung base and decreased breath sounds. He had mild generalised tenderness in his abdomen. Blood tests were normal. Chest x-ray and CT of the thorax showed small bilateral pleural effusions with no other abnormality. CT of the abdomen and pelvis however, showed ascites with extensive thickening of the peritoneum and marked induration of the mesentery and omentum. Mantoux test was positive. Laparoscopy was undertaken to outrule intra-abdominal malignancy and confirmed the diagnosis of tuberculosis. Peritoneal wall biopsies were taken from which Mycobacterium was isolated confirming peritoneal tuberculosis. He was started on rifampicin, isoniazid, pyrazinamide and ethambutol and completed a 6-month course without further complications. PMID:23784766
Clancy, C; Bokhari, Y; Neary, P M; Joyce, M
Tuberculosis of the spine is one of the most common spine pathology in India. Over last 4 decades a lot has changed in the diagnosis, medical treatment and surgical procedures to treat this disorder. Further developments in diagnosis using molecular genetic techniques, more effective antibiotics and more aggressive surgical protocols have become essential with emergence of multidrug resistant TB. Surgical procedures such as single stage anterior and posterior stabilization, extrapleral dorsal spine anterior stabilization and endoscopic thoracoscopic surgeries have reduced the mortality and morbidity of the surgical procedures. is rapidly progressing. It is a challenge to treat MDR-TB Spine with late onset paraplegia and progressive deformity. Physicians must treat tuberculosis of spine on the basis of Culture and sensitivity.
Agrawal, Vinod; Patgaonkar, P. R.; Nagariya, S. P.
Tuberculous infection of the oral tissues is a rare finding. An interesting case of primary tuberculosis of mouth is described, presenting as persistent discharge of pus from the lower wisdom tooth region. Incisional biopsy revealed features of an infected dentigerous cyst while histopathological examination of the excised lesion showed keratinizing cyst with secondary infection. Non-healing of the bony defect prompted curettage of the area and the submitted sample microscopically showed granuloma with characteristic Langhans' giant cells, raising the suspicion of underlying systemic tuberculosis. The importance to the dental surgeon in the recognition, especially by use of pathological examination, is emphasized and also the value of diagnosis for the patients and the community. PMID:23540089
Sharma, Preeti; Saxena, Susmita; Aggarwal, Pooja; Reddy, Vandana
The syndemic of human immunodeficiency virus (HIV)/tuberculosis (TB) co-infection has grown as a result of the considerable sociogeographic overlaps between the two epidemics. The situation is particularly worrisome in countries with high or intermediate TB burden against the background of a variable HIV epidemic state. Early diagnosis of TB disease in an HIV-infected person is paramount but suffers from lack of sensitive and specific diagnostic tools. Enhanced symptom screening is currently advocated, and the wide application of affordable molecular diagnostics is urgently needed. Treatment of TB/HIV co-infection involves the concurrent use of standard antiretrovirals and antimycobacterials during which harmful drug interaction may occur. The pharmacokinetic interaction between rifamycin and antiretrovirals is a case in point, requiring dosage adjustment and preferential use of rifabutin, if available. Early initiation of antiretroviral therapy is indicated, preferably at 2 weeks after starting TB treatment for patients with a CD4 of <50 cells/?L. Development of TB-immune reconstitution inflammatory syndrome (TB-IRIS) is however more frequent with early antiretroviral therapy. The diagnosis of TB-IRIS is another clinical challenge, and cautious use of corticosteroids is suggested to improve clinical outcome. As a preventive measure against active TB disease, the screening for latent TB infection should be widely practiced, followed by at least 6-9 months of isoniazid treatment. To date tuberculin skin test remains the only diagnostic tool in high TB burden countries. The role of alternative tests, for example, interferon-? release assay, would need to be better defined for clinical application. PMID:23682586
Lee, Shui Shan; Meintjes, Graeme; Kamarulzaman, Adeeba; Leung, Chi Chiu
Thirty-fourth monthly installment of our "What A Year!" website project, introducing life science breakthroughs to middle and high school students and their teachers. About 2 billion people are walking around infected by tuberculosis. But they don't it, because they don't have any symptoms of this terrible disease. The trick with TB is to catch it early and prevent ever-widening circles of infection.
. During the period 1990–1994 a total of 578 operations were performed in 502 patients with various forms of tuberculosis.\\u000a Most of the patients (68%) were men aged 20 to 50 years (70%). Sputum cultures were positive in 55% of the patients. More\\u000a than half of all patients were chronic smokers, and about 10% were alcoholics or drug addicts. There
Mikhail I. Perelman; Victor P. Strelzov
\\u000a Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates,\\u000a Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor\\u000a to come into existence
Marina Gheorghiu; Micheline Lagranderie; Anne-Marie Balazuc
...2012-04-01 false Mycobacterium tuberculosis immunofluorescent reagents... § 866.3370 Mycobacterium tuberculosis immunofluorescent reagents...Identification. Mycobacterium tuberculosis immunofluorescent...
...2011-04-01 false Mycobacterium tuberculosis immunofluorescent reagents... § 866.3370 Mycobacterium tuberculosis immunofluorescent reagents...Identification. Mycobacterium tuberculosis immunofluorescent...
Background The melanocortin-3-receptor (MC3R) is a member of the G-protein coupled receptor family that mediate cellular response through the cyclic adenosine monophosphate signalling pathway. In the promoter region of MC3R the polymorphism rs6127698 has previously been shown to be strongly associated with tuberculosis susceptibility. It is predicted to generate an alternative transcription factor binding site. Findings We investigated the functional impact of rs6127698 by luciferase assay to assess if this polymorphism is capable of altering protein expression. Our results did not show any significant protein expression changes when comparing the two alleles of rs6127698. Conclusions Our experiments demonstrate that the rs6127698 polymorphism does not influence protein translation. A functional role of the predicted alternative transcription factor binding site could therefore not be confirmed. These results suggest rs6127698 has no direct role in tuberculosis susceptibility. The possibility remains that this polymorphism is linked to an adjacent functional genetic variant, acting as a surrogate marker for disease risk.
Background QuantiFERON®-TB Gold in-Tube (QFT) assay is a recently developed test to assess latent tuberculosis infection in contagious tuberculosis (TB) contact subjects. To assess the QFT assay in recently exposed contacts of active tuberculosis patients in a French area with low TB incidence but high Bacille Calmette-Guerin coverage, and evaluate progression rates to TB disease. Methodology/Principal Findings Between January 2007 and December 2009, 687 contacts of culture-confirmed tuberculosis cases underwent the QFT assay, with tuberculin skin test (TST) in 473, and a 34 months mean follow-up. Of 687 contacts, 148 were QFT positive, while 526 were negative and 13 indeterminate. QFT was positive in 35% of individuals with TST ?10 mm, 47.5% with TST ?15 mm or phlyctenular, but in 21% of cases in which two-step TST (M0 and M3) remained negative. Conversely, QFT was negative in 69% of cases with two-step TST showing conversion from negative to positive. All indeterminate QFT were associated with TST induration <10 mm in diameter. For 29 QFT-positive subjects, no chemoprophylaxis was given due to medical contraindications. Of the remaining 119 QFT-positive contacts, 97accepted chemoprophylaxis (81.5%), and 79 (81.4%) completed the treatment. Two contacts progressed to TB disease: one subject was QFT positive and had declined chemoprophylaxis, while the other one was QFT negative. QFT positive predictive value for progression to TB was 1.96% (1/51) with a 99.8% (525/526) negative predictive value. Conclusions/Significance Our results confirm the safety of the QFT-based strategy for assessing the TB chemoprophylaxis indication, as only one contact developed TB disease out of 526 QFT-negative subjects.
Bergot, Emmanuel; Haustraete, Eglantine; Magnier, Romain; Salaun, Marie-Anne; Zalcman, Gerard
Background: Tuberculosis (TB) is still a major worldwide concern. There is no pathognomonic clinical feature or imaging findings for definite diagnosis of extra pulmonary TB. Therefore, TB involvement of Gastrointestinal or Genitourinary tract can be easily confused with peritoneal carcinomatosis and advanced ovarian carcinoma. Our aim is to emphasize the importance of considering the disease based upon the epidemiologic clues of the patients, while interpreting the positive results for a suspicious ovarian malignancy. Cases: This paper illustrates 8 cases of ovarian or peritoneal tuberculosis, whose initial diagnoses were malignant processes of the GU tract. Conclusion: Tuberculosis (TB) should be always being considered in the differential diagnosis of advanced ovarian cancer, especially in the regions that are endemic for the disease.
Hasanzadeh, Malihe; Naderi, Hamid Reza; Hoshyar, Azamossadat Hoseine; Shabane, Shima; Shahidsales, Soodabeh
This report presents and interprets groundwater background data collected from the unconfined aquifer beneath the Hanford Site, a U.S. Department of Energy complex located near Richland, Washington. Characterization of background composition is an importa...
Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…
Hwang, Shu-Ling; Bedford, Olwen
Since 1980, the U.S. Environmental Protection Agency (EPA) has conducted extensive research to assess the performance of hazardous waste thermal destruction processes. Some members of the scientific and the environmental action community remain concerned about the long-term safet...
This study, conducted at the University of Tennessee's Anthropological Research Facility (ARF), lists and ranks the primary chemical constituents which define the odor of decomposition of human remains as detected at the soil surface of shallow burial sites. Triple sorbent traps were used to collect air samples in the field and revealed eight major classes of chemicals which now contain 478 specific volatile compounds associated with burial decomposition. Samples were analyzed using gas chromatography-mass spectrometry (GC-MS) and were collected below and above the body, and at the soil surface of 1.5-3.5 ft. (0.46-1.07 m) deep burial sites of four individuals over a 4-year time span. New data were incorporated into the previously established Decompositional Odor Analysis (DOA) Database providing identification, chemical trends, and semi-quantitation of chemicals for evaluation. This research identifies the 'odor signatures' unique to the decomposition of buried human remains with projected ramifications on human remains detection canine training procedures and in the development of field portable analytical instruments which can be used to locate human remains in shallow burial sites.
Vass, Arpad Alexander [ORNL; Smith, Rob R [ORNL; Thompson, Cyril V [ORNL; Burnett, Michael N [ORNL; Dulgerian, Nishan [ORNL; Eckenrode, Brian A [ORNL
The concept of the mean remaining life function is extended to the multivariate case. Some general characterization properties of multivariate mean remaning life functions (mmrl) are studied, it is shown that they determine the joint pdf uniquely. Inter alia a basic convergence result is proved for a sequence of mmrl functions. The multivariate loss of memory property of a pdf
Barry C. Arnold; Hassan Zahedi
Although the overall prevalence of tuberculosis has decreased in the United States, with the increasing prevalence of tuberculosis globally, higher rates of tuberculosis in some states and localities have been reported, with some component probably related to immigrant populations. We report a case of primary pulmonary tuberculosis in a malnourished adolescent.
Zawaideh, Mazen; Chao, Cherng; Poole, Patricia; Naheedy, John
There were several outbreaks of pulmonary tuberculosis among employees and customers of public saunas in Shijuku, a large office, shopping and amusement quarter in Tokyo. Twenty four patients with pulmonary tuberculosis were found between March 1994 and November 1996. Restriction fragment length polymorphism analysis of DNA derived from Mycobacterium tuberculosis isolated from eighteen patients with positive cultures was used to analyze the transmission route. The DNA probe was derived from the insertion sequence IS6110. There were 14 different DNA patterns of the M. tuberculosis isolated from 18 patients. Of 14 patterns, three patterns were shared by 2 patients, patients and 3 patients, respectively. The remaining 11 patterns were observed in 11 patients, thus one pattern for each patient. These data suggest that the infection of M. tuberculosis resulted from different origins. The saunas in amusement areas like Shinjuku have been used as hotels. Many customers from different places are using the saunas for overnight stay, and in particular homeless people have been using the saunas as their "home". The sauna can be a place where groups of people with high risk for tuberculosis congregate and the potential for an outbreak of tuberculosis can occur. PMID:9436385
Nakanishi, Y; Oyama, Y; Takahashi, M; Mori, T
Background: Big cities were particularly affected by tuberculosis in the 1990s. Methods: We studied 141 cases of extrapulmonary tuberculosis in patients not infected by HIV in the northeastern suburbs of Paris. Results: A total of 84 men and 57 women were included in the study. Their average age at diagnosis was 42.2 years. Some 73.6% of the patients were foreign-born. A total of 182 sites were identified in 141 patients. There was an association with pulmonary tuberculosis in 38 cases. The sites were: lymph node (48.9%), pleural (25.5%), skeletal (22.7%), genitourinary (5.7%), and meninges (5%). Unfavorable social conditions were frequently observed. The average duration of treatment was 10 months. Twenty-four adverse drug effects were noted. Sixty-eight strains of Mycobacterium tuberculosis were isolated. Five cases of primary resistance to at least one antituberculous drug and only one case of multidrug resistance were observed. Some 95.7% of the 93 patients who were not lost to follow up were cured. Conclusion: Independently of HIV infection, extrapulmonary tuberculosis is still present, particularly in the suburbs of big cities, where social conditions are poor. The significant number of patients lost to follow-up demands that measures be adapted for the therapeutic management of these patients. PMID:10854820
Fain; Lortholary; Lascaux; Amoura; Babinet; Beaudreuil; Boudon; Cruaud; Desrues; Djouab; Glowinski; Lhote; Kettaneh; Malbec; Mathieu; Taleb; Guillevin; Thomas
Background Mycobacterium tuberculosis infection is an ongoing public health problem in Taiwan. The National Tuberculosis Registry Campaign, a case management system, was implemented in 1997. This study examined this monitoring system to identify and characterize delayed treatment of TB patients. Methods Records of all tuberculosis cases treated in Taiwan from 2002 through 2005 were obtained from the National Tuberculosis Registry Campaign. Initiation of treatment more than 7 days after diagnosis was considered a long treatment delay. Results The study included 31,937 patients. The mean day of delayed treatment was 3.6 days. Most patients were treated immediately after diagnosis. The relationship between number of TB patients and days of delayed treatment after diagnosis exhibited a Power-law distribution. The long tail of the power-law distribution indicated that an extreme number occur cannot be neglected. Tuberculosis patients treated after an unusually long delay require close observation and follow up. Conclusion This study found that TB control is generally acceptabl in Taiwan; however, delayed treatment increases the risk of transmission. Improving the protocol for managing confirmed TB cases can minimize disease transmission.
Chern, Jimmy PS; Chen, Duan-Rung; Wen, Tzai-Hung
Background: Pulmonary tuberculosis is still the most common form of tuberculosis in HIV infected patients having different presentations according to the degree of immunosuppression. This study appraised the impact of HIV infection on clinical, laboratory and radiological presentations of tuberculosis. Methods: The clinical, laboratory and radiological presentations of pulmonary TB in 56 HIV-infected patients were compared with 56 individually sex and age matched HIV-seronegative ones, admitted to Imam Hospital in Tehran (1999–2006) using paired t-test in a case control study. Results: All cases and the controls were male. Fever was found in 83.9% of the HIV positive patients compared to 80% of the HIV negative ones. Cough was the most common clinical finding in the HIV negative group (89.3% vs. 82.1% in HIV positive group). Among radiological features, cavitary lesions, upper lobe and bilateral pulmonary involvement were observed significantly less often in the HIV-infected group. On the contrary, lymphadenopathy was just present in the HIV positive group in this series of patients (12%) and primary pattern tuberculosis was more common, as well (71% vs. 39%, P= 0.02). The Tuberculin test was reactive in 29% of the HIV/TB patients. Conclusion: The coexistence of both infections alters the picture of tuberculosis in many aspects and should be taken into account when considering a diagnosis of HIV infection and its potential for TB co-infection, and vice-versa.
Hadadi, A; Tajik, P; Rasoolinejad, M; Davoudi, S; Mohraz, M
Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed. PMID:22325421
Payen, M C; De Wit, S; Martin, C; Sergysels, R; Muylle, I; Van Laethem, Y; Clumeck, N
Female genital tuberculosis is an uncommon type of tuberculosis that can lead to infertility. The present review describes the disease, reports available epidemiological data, and focuses on examinations and procedures necessary for the early diagnosis and the management of this curable disease. PMID:21438789
Neonakis, Ioannis K; Spandidos, Demetrios A; Petinaki, Efthimia
Thrombocytopenia associated with Mycobacterium tuberculosis infection de veloped concurrently in a mother and son. Antiplatelet antibodies were dem onstrated in the serum of both patients. It is suggested that this and possibly other hematologic complications associated with tuberculosis are immune me diated.
Stephen S. Jurak; Richard Aster; Hadi Sawaf
Mycobacterium tuberculosis is a successful pathogen responsible for the vast majority of deadly tuberculosis cases in humans. It rests in a dormant form in contaminated people who constitute the reservoir with airborne interhuman transmission during pulmonary tuberculosis. M. tuberculosis is therefore regarded majoritary as a human pathogen. Here, we review the evidence for anthroponotic M. tuberculosis infection in non-human primates, other mammals and psittacines. Some infected animals may be sources for zoonotic tuberculosis caused by M. tuberculosis, with wild life trade and zoos being amplifying factors. Moreover, living animals and cadavers can scatter M. tuberculosis in the environment where it could survive for extended periods of time in soil where amoebae could play a role. Although marginal in the epidemiology of human tuberculosis, these data indicate that M. tuberculosis is not uniquely adapted to humans. PMID:24119770
Ghodbane, Ramzi; Drancourt, Michel
Background Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. Methods In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status - new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). Results Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. Conclusions We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem.
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world’s population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. Because of the global health problems of TB, the development of potent new anti-TB drugs without cross-resistance with known antimycobacterial agents is urgently needed. In this study, we have
Fan Chen; Jing Zhou; Fengling Luo; Al-Bayati Mohammed; Xiao-Lian. Zhang
Rationale:MultipleinfectionswithdifferentstrainsofMycobacterium tuberculosis may occur in settings where the infection pressure is high. The relevance of mixed infections for the patient, clinician, and control program remains unclear. Objectives: This study aimed to describe reinfection and mixed infection as underlying mecha- nisms of changing drug-susceptibility patterns in serial sputum cul- tures. Methods: Serial M. tuberculosis sputum cultures from patients diagnosed with multi-drug-resistant
Annelies van Rie; Thomas C. Victor; Madalene Richardson; Gian D. van der Spuy; Emma J. Murray; Nico C. Gey van Pittius; Paul D. van Helden; Robin M. Warren
This illustration of the Comet-Shoemaker/Levy collision shows the first piece of the remains of the comet crashing into Jupiter. This event occurred in 1994 after tidal forces from Jupiter caused the comet to break up into 21 separate pieces. Although on a very different scale, the physical mechanism for the breakup of Shoemaker/Levy also caused the tidal disruption of the star in RX J1242-11. (Illustration: SEDS/D. Seal (edited by CXC/M. Weiss)
Drug-resistant tuberculosis is a globally emerging problem with a rising incidence. According to the WHO in 2008, 17% of strains of Mycobacterium tuberculosis, in untreated cases were resistant to at least one drug and 3.6% were resistant to rifampicin and isoniazid, which is called multidrug-resistant tuberculosis. The problem is greater in patients previously treated and in some countries, where rates of multidrug resistance reach 60%. Approximately 5% of multidrug-resistant tuberculosis patients are also resistant to any fluoroquinolone and at least one injectable drug, being called extensively drug-resistant tuberculosis. The treatment of these forms of tuberculosis requires the use of second-line drugs, which causes higher cost, higher toxicity and a longer duration of treatment. There is a need for new compounds with efficacy and safety profiles better than those currently used to treat these forms of tuberculosis. In the last decade different drugs have being reassessed and appeared, which are at different stages of development. PMID:23540388
Ramírez Lapausa, Marta; Pascual Pareja, José Francisco; Noguerado Asensio, Arturo
ABSTRACT Triosephosphate isomerase (TPI) catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). This reaction is required for glycolysis and gluconeogenesis, and tpi has been predicted to be essential for growth of Mycobacterium tuberculosis. However, when studying a conditionally regulated tpi knockdown mutant, we noticed that depletion of TPI reduced growth of M. tuberculosis in media containing a single carbon source but not in media that contained both a glycolytic and a gluconeogenic carbon source. We used such two-carbon-source media to isolate a tpi deletion (?tpi) mutant. The ?tpi mutant did not survive with single carbon substrates but grew like wild-type (WT) M. tuberculosis in the presence of both a glycolytic and a gluconeogenic carbon source. (13)C metabolite tracing revealed the accumulation of TPI substrates in ?tpi and the absence of alternative triosephosphate isomerases and metabolic bypass reactions, which confirmed the requirement of TPI for glycolysis and gluconeogenesis in M. tuberculosis. The ?tpi strain was furthermore severely attenuated in the mouse model of tuberculosis, suggesting that M. tuberculosis cannot simultaneously access sufficient quantities of glycolytic and gluconeogenic carbon substrates to establish infection in mice. IMPORTANCE The importance of central carbon metabolism for the pathogenesis of M. tuberculosis has recently been recognized, but the consequences of depleting specific metabolic enzymes remain to be identified for many enzymes. We investigated triosephosphate isomerase (TPI) because it is central to both glycolysis and gluconeogenesis and had been predicted to be essential for growth of M. tuberculosis. This work identified metabolic conditions that make TPI dispensable for M. tuberculosis growth in culture and proved that M. tuberculosis relies on a single TPI enzyme and has no metabolic bypass for the TPI-dependent interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in glycolysis and gluconeogenesis. Finally, we demonstrate that TPI is essential for growth of the pathogen in mouse lungs. PMID:24757211
Trujillo, Carolina; Blumenthal, Antje; Marrero, Joeli; Rhee, Kyu Y; Schnappinger, Dirk; Ehrt, Sabine
Many developed countries are faced with the problem of reorganizing their tuberculosis-control programme to bring it into line with modern conditions. The study reported was undertaken to provide guidelines for this reorganization. It was begun in the district of Kolín, Czechoslovakia, with a population of some 100 000, in 1961 and is still in progress. The paper covers the first 4 years of the study. In 1961 a thorough check-up was made on all persons registered as having active or inactive tuberculosis, or fibrotic lung lesions. In 1961 and 1963 a mass X-ray and tuberculin-testing campaign, with 95% coverage, was carried out for all persons over 14 years of age. All persons with active tuberculosis received adequate treatment. Persons registered as having tuberculosis or suspected tuberculosis were subjected to regular photofluorographic and bacteriological investigations. Newborn infants were given BCG vaccination, and persons aged 14 years and 19 years with negative tuberculin reactions were vaccinated. The prevalence of bacillary tuberculosis fell from 150 cases in 1960 to 91 in 1964, mainly owing to a decrease in the number of chronic cases. The incidence of bacillary tuberculosis detectable by direct smear microscopy, however, remained at about 25 cases throughout the period 1961-64. The risk of developing tuberculosis was found to be highest in persons with fibrotic lung lesions or inactive tuberculosis, and in men above 45 years of age and women above 65 with previously normal photofluorograms. It is concluded from the study that in developed countries priority should be given to adequate treatment of all persons with active tuberculosis, and to early diagnosis in persons consulting physicians and in the high-risk population groups.
Styblo, K.; Dankova, D.; Drapela, J.; Galliova, J.; Jezek, Z.; Krivanek, J.; Kubik, A.; Langerova, M.; Radkovsky, J.
Reported Tuberculosis in the United States, 2009 presents summary data for tuberculosis (TB) cases verified and counted in 2009. Reports of verified cases of tuberculosis (RVCT) are submitted to the Division of Tuberculosis Elimination (DTBE), Centers for...
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most devastating human diseases, and is responsible for ~ 2 million deaths worldwide each year. The nutritional requirements for the growth of mycobacteria have been extensively studied since the discovery of M. tuberculosis, but the essential nutrients for M. tuberculosis inside the human host and the identity of the corresponding transporters remain unknown. The UgpABCE transporter of M. tuberculosis is one of five putative permeases for carbohydrate uptake, and is genetically predicted to be an sn-glycerol 3-phosphate importer. We have determined the 1.5-Å crystal structure of M. tuberculosis UgpB, which has been reported to be a promising vaccine candidate against TB. M. tuberculosis UgpB showed no detectable binding activity for sn-glycerol 3-phosphate by isothermal titration calorimetry, but instead showed a preference for glycerophosphocholine (GPC). M. tuberculosis UgpB largely resembles its Escherichia coli homolog, but with the critical Trp169 in the substrate-binding site of E. coli UgpB replaced by Leu205. Mutation of Leu205 abolishes GPC binding, suggesting that Leu205 is a determinant of GPC binding. The work reported here not only contributes to our understanding of the carbon and phosphate sources utilized by M. tuberculosis inside the human host, but will also promote improvements in TB chemotherapy. Database: Structural data are available in the Protein Data Bank database under the accession number PDB 4MFI. PMID:24299297
Jiang, Dunquan; Zhang, Qingqing; Zheng, Qianqian; Zhou, Hao; Jin, Jin; Zhou, Weihong; Bartlam, Mark; Rao, Zihe
Introduction: Tuberculosis remains a formidable threat to global public health. Multidrug-resistant tuberculosis presents increasing burden on the control strategy. D-Cycloserine (DCS) is an effective second-line drug against Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis. Though less potent than isoniazid (INH) and streptomycin, DCS is crucial for antibiotic-resistant tuberculosis. One advantage of DCS is that less drug-resistant M. tuberculosis is reported in comparison with first-line antituberculosis drugs such as INH and rifampin. Areas covered: In this review, we summarise our current knowledge of DCS, and review the drug target and low-level resistance of DCS in M. tuberculosis. We summarise the metabolism of D-alanine (D-Ala) and peptidoglycan biosynthesis in bacteria. We first compared the amino acid similarity of Mycobacterium alanine racemase and D-Ala:D-alanine ligase and quite unexpectedly found that the two enzymes are highly conserved among Mycobacterium. Expert opinion: We summarise the drug targets of DCS and possible mechanisms underlying its low-level resistance for the first time. One significant finding is that ubiquinone and menaquinone metabolism-related genes are novel genes underlying DCS resistance in Escherichia coli and with homologues in M. tuberculosis. Further understanding of DCS targets and basis for its low-level resistance might inspire us to improve the use of DCS or find better drug targets. PMID:24773568
Hong, Weiling; Chen, Lifang; Xie, Jianping
Bacillus Calmette–Guérin (BCG), the only approved tuberculosis vaccine, provides only limited protection. Previously, we generated a recombinant derivative (BCG ?ureC::hly), which secretes the pore-forming toxin listeriolysin O (LLO) of Listeria monocytogenes. This vaccine shows superior protection against tuberculosis in preclinical models and is safe in humans. Here we describe two new vaccine strains which express human interleukin-7 (hIL)-7 or hIL-18 in the genetic background of BCG ?ureC::hly to modulate specific T cell immunity. Both strains exhibited an uncompromised in vitro growth pattern, while inducing a proinflammatory cytokine profile in human dendritic cells (DCs). Human DCs harbouring either strain efficiently promoted secretion of IL-2 by autologous T cells in a coculture system, suggesting superior immunogenicity. BALB/c mice vaccinated with BCG ?ureC::hly, BCG ?ureC::hly_hIL7 or BCG ?ureC::hly_hIL18 developed a more robust Th1 response than after vaccination with parental BCG. Both strains provided significantly better protection than BCG in a murine Mycobacterium tuberculosis challenge model but efficacy remained comparable to that afforded by BCG ?ureC::hly. We conclude that expression of hIL-7 or hIL-18 enhanced specific T cell responses but failed to improve protection over BCG ?ureC::hly in mice.
Rao, Martin; Vogelzang, Alexis; Kaiser, Peggy; Schuerer, Stefanie; Kaufmann, Stefan H. E.; Gengenbacher, Martin
BACKGROUND: Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients. METHODS: A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care
Chandrashekhar T Sreeramareddy; Kishore V Panduru; Sharat C Verma; Hari S Joshi; Michael N Bates
Background Enzyme-linked-immunospot (ELISpot) is an increasingly widely-used interferon-gamma release assay (IGRA) for diagnosing tuberculosis infection but it is unknown whether positive results are prognostic of active tuberculosis. Objective To determine the prognostic value of this T-cell-based interferon-gamma biomarker. Design Longitudinal cohort study of child tuberculosis contacts recruited from October 2002 to April 2004. Setting Community-based contact investigations in Turkey. Patients 908 children and adolescents with recent household tuberculosis exposure. Intervention ELISpot, incorporating Early Secretory Antigenic Target-6 and Culture Filtrate Protein-10, and tuberculin skin test (TST) were performed at baseline. Measurements Incidence rates of progression to active tuberculosis for contacts with positive TST and ELISpot results and relative incidence rates comparing test-positive and test-negative contacts. Results 688 (76%) contacts received isoniazid preventive therapy in accordance with local guidelines. Fifteen contacts developed active tuberculosis over 1201 person-years follow-up. Of 381 ELISpot-positive contacts, 11 developed active tuberculosis over 536 person-years follow-up (incidence rate 21 per 1000 person-years [95% CI 10.2, 36.7]) and of 550 TST-positive contacts, 12 developed active tuberculosis over 722 person-years of follow-up (17 per 1000 person-years [95% CI 8.6, 29.0]). Limitations Only 3 of the 15 incident cases were culture-confirmed. Conclusion Although tuberculosis contacts with positive ELISpot results have a similar incidence rate of tuberculosis compared to contacts with positive TST results, ELISpot testing could allow more focussed targeting of preventive therapy to fewer contacts.
Bakir, Mustafa; Millington, Kerry A; Soysal, Ahmet; Deeks, Jonathan J; Efee, Serpil; Aslan, Yasemin; Dosanjh, Davinder P S; Lalvani, Ajit
BACKGROUND—The ligase chain reaction Mycobacterium tuberculosis assay uses ligase chain reaction technology to detect tuberculous DNA sequences in clinical specimens. A study was undertaken to determine its sensitivity and specificity as a primary screening tool for the detection of culture positive tuberculosis.?METHODS—The study was conducted on 2420 clinical specimens (sputum, bronchoalveolar lavage fluid, pleural fluid, urine) submitted for primary screening for Mycobacterium tuberculosis to a regional medical microbiology laboratory. Specimens were tested in parallel with smear, ligase chain reaction, and culture.?RESULTS—Thirty nine patients had specimens testing positive by the ligase chain reaction assay. Thirty two patients had newly diagnosed tuberculosis, one had a tuberculosis relapse, three had tuberculosis (on antituberculous therapy when tested), and three had healed tuberculosis. In the newly diagnosed group specimens were smear positive in 21 cases (66%), ligase chain reaction positive in 30 cases (94%), and culture positive in 32 cases (100%). Using a positive culture to diagnose active tuberculosis, the ligase chain reaction assay had a sensitivity of 93.9%, a specificity of 99.8%, a positive predictive value of 83.8%, and a negative predictive value of 99.9%.?CONCLUSIONS—This study is the largest clinical trial to date to report the efficacy of the ligase chain reaction as a primary screening tool to detect Mycobacterium tuberculosis infection. The authors conclude that ligase chain reaction is a useful primary screening test for tuberculosis, offering speed and discrimination in the early stages of diagnosis and complementing traditional smear and culture techniques.??
O'Connor, T; Sheehan, S; Cryan, B; Brennan, N; Bredin, C
Background There is a paucity of published data on the pattern of pulmonary tuberculosis among migrant workers entering Middle Eastern countries particularly Kuwait. The objectives of this study were to use routine health surveillance data i) to estimate the prevalence of pulmonary tuberculosis among migrant workers at entry in Kuwait and ii) to determine the occurrence of any time trends in the proportions of pulmonary tuberculosis positive workers over the study period. Methods The monthly aggregates of daily number of migrants tested and the number of pulmonary tuberculosis cases detected during routine health examinations of migrant workers from tuberculosis high-prevalence countries were used to generate the monthly series of proportions (per 100,000) of pulmonary tuberculosis cases over 120 months between January 1, 1997 and December 31, 2006 and analysed using time series methods. Results The overall prevalence (per 100,000) of documented pulmonary tuberculosis cases among screened migrants was 198 (4608/2328582). Year-specific prevalence (per 100,000) of tuberculosis cases consistently declined from 456 (95% CI: 424 – 490) in 1997 to 124 (95% CI: 110 – 140) in 2002 before showing a steady increase up to 183 (95% CI: 169–197) in 2006. The second-order polynomial regression model revealed significant (P < 0.001) initial decline, followed by a significant (P < 0.001) increasing trend thereafter in monthly proportions of tuberculosis cases among migrant workers. Conclusion The proportions of documented tuberculosis cases among migrant workers showed a significant nonlinear pattern, with an initial decline followed by a significant increasing trend towards the end of the study period. These findings underscore the need to maintain the current policy of migrants' screening for tuberculosis at entry. The public health authorities in Kuwait and perhaps other countries in the region may consider complementing the current screening protocol with interferon-? assays to detect migrants with latent Mycobacterium tuberculosis infection. An appropriate curative or preventive chemotherapy of detected tuberculosis cases may help in further minimizing the risk of local transmission of M. tuberculosis, while contributing in global efforts to control this public health menace.
Akhtar, Saeed; Mohammad, Hameed GHH
Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers. PMID:23531388
Lawn, Stephen D; Mwaba, Peter; Bates, Matthew; Piatek, Amy; Alexander, Heather; Marais, Ben J; Cuevas, Luis E; McHugh, Timothy D; Zijenah, Lynn; Kapata, Nathan; Abubakar, Ibrahim; McNerney, Ruth; Hoelscher, Michael; Memish, Ziad A; Migliori, Giovanni Battista; Kim, Peter; Maeurer, Markus; Schito, Marco; Zumla, Alimuddin
SUMMARY Mycobacterium tuberculosis parasitizes host macrophages and subverts host innate and adaptive immunity. A number of cytokines elicited by the tubercle bacilli have been recognized as mediators of mycobacterial clearance or pathology in tuberculosis. Surprisingly, interleukin-1? (IL-1?), a major pro-inflammatory cytokine activated by processing upon assembly of a specialized protein complex termed the inflammasome, has not been implicated in host-pathogen interactions in tuberculosis. Here, we show that M. tuberculosis prevents inflammasome activation and IL-1? processing, and that a functional M. tuberculosis zmp1 gene is required for this process. Infection of macrophages with the zmp1 null M. tuberculosis triggered activation of caspase-1/IL-1? inflammasome, resulting in increased secretion of IL-1?, enhanced mycobacterial phagosome maturation into phagolysosomes, improved mycobacterial clearance by macrophages, and lower bacterial burden in the lungs of aerosol-infected mice. Thus, we uncovered the previously masked role for IL-1? in control of M. tuberculosis, and the existence of a mycobacterial system that prevents IL-1?/inflammasome activation.
Master, Sharon S.; Davis, Alexander. S.; Rampini, Silvana K.; Keller, Christine; Ehlers, Stefan; Springer, Burkhardt; Sander, Peter; Deretic, Vojo
A resurgence of tuberculosis has occurred in recent years in the United States and abroad. Deteriorating public health services, increasing numbers of immigrants from countries of endemicity, and coinfection with the human immunodeficiency virus (HIV) have contributed to the rise in the number of cases diagnosed in the United States. Outbreaks of resistant tuberculosis, which responds poorly to therapy, have occurred in hospitals and other settings, affecting patients and health care workers. This review covers the pathogenesis, epidemiology, clinical presentation, laboratory diagnosis, and treatment of Mycobacterium tuberculosis infection and disease. In addition, public health and hospital infection control strategies are detailed. Newer approaches to epidemiologic investigation, including use of restriction fragment length polymorphism analysis, are discussed. Detailed consideration of the interaction between HIV infection and tuberculosis is given. We also review the latest techniques in laboratory evaluation, including the radiometric culture system, DNA probes, and PCR. Current recommendations for therapy of tuberculosis, including multidrug-resistant tuberculosis, are given. Finally, the special problem of prophylaxis of persons exposed to multidrug-resistant tuberculosis is considered.
Sepkowitz, K A; Raffalli, J; Riley, L; Kiehn, T E; Armstrong, D
Examination was undertaken of skeletonized remains contained within 2 rubber boots dredged by a fishing boat from a depth of 145 m, approximately 185 km off the southern Australian coast in the Great Australian Bight. The boots had been manufactured in Australia in July 1993 and were of a type commonly used by local fishermen. Examination of the lower legs and feet revealed well-preserved bones with arthritic changes in keeping with an older male. DNA analyses using reference samples taken from relatives of fishermen who had disappeared in the area resulted in the identification of the victim as a 52-year-old prawn fisherman who had been swept off a boat over a decade earlier. DNA stability had been maintained by the low light, cold temperatures, and alkaline pH of the ocean floor. Integration of pathologic, anthropologic, and biologic analyses with police investigations enabled a positive identification to be made despite the unusual nature of the location of the remains and the time lapse since the disappearance of the victim. PMID:19749621
Byard, Roger W; Both, Katrin; Simpson, Ellie
Millions to billions of DNA sequences can now be generated from ancient skeletal remains thanks to the massive throughput of next-generation sequencing platforms. Except in cases of exceptional endogenous DNA preservation, most of the sequences isolated from fossil material do not originate from the specimen of interest, but instead reflect environmental organisms that colonized the specimen after death. Here, we characterize the microbial diversity recovered from seven c. 200- to 13 000-year-old horse bones collected from northern Siberia. We use a robust, taxonomy-based assignment approach to identify the microorganisms present in ancient DNA extracts and quantify their relative abundance. Our results suggest that molecular preservation niches exist within ancient samples that can potentially be used to characterize the environments from which the remains are recovered. In addition, microbial community profiling of the seven specimens revealed site-specific environmental signatures. These microbial communities appear to comprise mainly organisms that colonized the fossils recently. Our approach significantly extends the amount of useful data that can be recovered from ancient specimens using a shotgun sequencing approach. In future, it may be possible to correlate, for example, the accumulation of postmortem DNA damage with the presence and/or abundance of particular microbes. PMID:24612293
Der Sarkissian, C; Ermini, L; Jónsson, H; Alekseev, A N; Crubezy, E; Shapiro, B; Orlando, L
Background.?Only a minority of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis. Genetic epidemiological evidence suggests that pulmonary tuberculosis has a strong human genetic component. Previous genetic findings in Mendelian predisposition to more severe mycobacterial infections, including by M. tuberculosis, underlined the importance of the interleukin 12 (IL-12)/interferon ? (IFN-?) circuit in antimycobacterial immunity. Methods.?We conducted an association study in Morocco between pulmonary tuberculosis and a panel of single-nucleotide polymorphisms (SNPs) covering 14 core IL-12/IFN-? circuit genes. The analyses were performed in a discovery family-based sample followed by replication in a case-control population. Results.?Out of 228 SNPs tested in the family-based sample, 6 STAT4 SNPs were associated with pulmonary tuberculosis (P = .0013–.01). We replicated the same direction of association for 1 cluster of 3 SNPs encompassing the promoter region of STAT4. In the combined sample, the association was stronger among younger subjects (pulmonary tuberculosis onset <25 years) with an odds ratio of developing pulmonary tuberculosis at rs897200 for GG vs AG/AA subjects of 1.47 (1.06–2.04). Previous functional experiments showed that the G allele of rs897200 was associated with lower STAT4 expression. Conclusions.?Our present findings in a Moroccan population support an association of pulmonary tuberculosis with STAT4 promoter-region polymorphisms that may impact STAT4 expression.
Sabri, Ayoub; Grant, Audrey V.; Cosker, Kristel; El Azbaoui, Safa; Abid, Ahmed; Abderrahmani Rhorfi, Ismail; Souhi, Hicham; Janah, Hicham; Alaoui-Tahiri, Kebir; Gharbaoui, Yasser; Benkirane, Majid; Orlova, Marianna; Boland, Anne; Deswarte, Caroline; Migaud, Melanie; Bustamante, Jacinta; Schurr, Erwin; Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent; Abel, Laurent; El Baghdadi, Jamila
BACKGROUND: The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV\\/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis
Observation and statistics are offered on treatment of tuberculosis in sanatoria during the lifespan of those institutions with special reference to one where the first author's medical life was mainly spent as patient, physician, surgeon and superintendent. Despite the rapid decrease in morbidity and mortality of tuberculosis, the change in direction, and the change in treatment programs, vigilance is still required. It is only because of the commitment of those involved over the many years in the treatment of tuberculosis that we are now at this enviable position. Imagesp-ap56-a
Paine, A. L.; Hershfield, Earl S.
The Tuberculosis educational game and related reading, are based on the 1905 Nobel Prize in Physiology or Medicine, which was awarded for investigations and discoveries concerning the disease tuberculosis, "TB". In this game you will try to repeat Robert Koch's remarkable successes. Carry out your own experiments using Koch's methods and discover the bacteria causing tuberculosis. Rather than scoring points and doing things quickly, this game rewards figuring out what to do in the correct order to allow you to move on and reach the end!
This paper reports on drilling activity which remains high off Northern Europe, drawing in newly built rigs and units from other parts of the world. Midway through the region's peak summer drilling season there were 138 rigs available in northern Europe - eight more than at the same time last year. Of these, 13 were idle (seven semis, five jack ups, and a drillship). Ninety-four of the rigs were drilling, six more than last year. The rest were being used as accommodation or production units or were undergoing conversion or maintenance. Britain continues to dominate the drilling activity. Sixty of the 94 drilling units were in U.K. waters, five more than in summer 1990. Norway accounted for 15 active rigs, compared with 11 at the same time last year.
The safety assessment and licensing of liquid-metal fast breeder reactors (LMFBRs) requires an analysis on the capability of the reactor primary system to sustain the consequences of a hypothetical core-disruptive accident (HCDA). Although computational methods and computer programs developed for HCDA analyses can predict reasonably well the response of the primary containment system, and follow up the phenomena of HCDA from the start of excursion to the time of dynamic equilibrium in the system, there remain areas in the HCDA analysis that merit further analytical and experimental studies. These are the analysis of fluid impact on reactor cover, three-dimensional analysis, the treatment of the perforated plates, material properties under high strain rates and under high temperatures, the treatment of multifield flows, and the treatment of prestressed concrete reactor vessels. The purpose of this paper is to discuss the structural mechanics of HCDA analysis in these areas where improvements are needed.
This publication, Reported Tuberculosis in the United States, 2005, presents summary data for TB cases reported to DTBE, verified, and counted in 2005. It is similar to previous publications and contains six major sections. The first section presents tren...
Background Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004–2006). It identified 129 patterns: 105 (n?=?568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1– ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2– modern/TbD1?/PGG1 group (Beijing, CAS), group 3– evolutionary recent/TbD1?/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n?=?5, CAS n?=?1), and 3 strains (BOV_1 n?=?2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n?=?114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the “evolutionary recent” TbD1?/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco.
Lahlou, Ouafae; Millet, Julie; Chaoui, Imane; Sabouni, Radia; Filali-Maltouf, Abdelkarim; Akrim, Mohammed; El Mzibri, Mohammed; Rastogi, Nalin; El Aouad, Rajae
Background Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis. Methods The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli. Results Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak  intraabdominal abscess ) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months). Conclusion Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.
Saluja, Sundeep S; Ray, Sukanta; Pal, Sujoy; Kukeraja, Manu; Srivastava, Deep N; Sahni, Peush; Chattopadhyay, Tushar K
BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment. METHODS We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival. RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 per 100 person-years in the rifampin–isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance. CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid.
Martinson, Neil A.; Barnes, Grace L.; Moulton, Lawrence H.; Msandiwa, Reginah; Hausler, Harry; Ram, Malathi; McIntyre, James A.; Gray, Glenda E.; Chaisson, Richard E.
MTB ranks as the first worldwide pathogen latently infecting one third of the population and the second leading cause of death from a single infectious agent, after the human immunodeficiency virus (HIV). The development of vigorous and apparently appropriate immune response upon infection with M. tuberculosis in humans and experimental animals conflict with failure to eradicate the pathogen itself and with its ability to undergo clinical latency from which it may exit. From a clinical standpoint, our views on MTB infection may take advantage from updating the overall perspective, that has quite changed over the last decade, following remarkable advances in our understanding of the manipulation of the immune system by M. tuberculosis and of the role of innate components of the immune response, including macrophages, neutrophils, dendritic cells and NK cells in the initial spread of MTB and its exit from latency. Scope of this review is to highlight the major mechanisms of MTB escape from immune control and to provide a supplementary translational perspective for the interpretation of innate immune mechanisms with particular impact on clinical aspects.
Bozzano, Federica; Marras, Francesco; De Maria, Andrea
The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults. PMID:24564419
Piccini, Paola; Chiappini, Elena; Tortoli, Enrico; de Martino, Maurizio; Galli, Luisa
The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults.
Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is the severest form of Mycobacterium tuberculosis (M.Tb) infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF). At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional “gold standard” based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional “gold standard”, the various molecular-based methods including nucleic acid amplification (NAA) assay technique, particularly polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented.
Takahashi, Teruyuki; Tamura, Masato; Takasu, Toshiaki
Tuberculosis remains the biggest infectious threat to humanity with one-third of the population infected and 1.4 million deaths and 8.7 million new cases annually. Current tuberculosis therapy is lengthy and consists of multiple antimicrobials, which causes poor compliance and high treatment dropout, resulting in the development of drug-resistant variants of tuberculosis. Therefore, alternate methods to treat tuberculosis are urgently needed. Mycobacterium tuberculosis evades host immune responses by inducing T helper (Th)2 and regulatory T (Treg) cell responses, which diminish protective Th1 responses. Here, we show that animals (Stat-6?/?CD4-TGF?RIIDN mice) that are unable to generate both Th2 cells and Tregs are highly resistant to M. tuberculosis infection. Furthermore, simultaneous inhibition of these two subsets of Th cells by therapeutic compounds dramatically reduced bacterial burden in different organs. This treatment was associated with the generation of protective Th1 immune responses. As these therapeutic agents are not directed to the harbored organisms, they should avoid the risk of promoting the development of drug-resistant M. tuberculosis variants.
Bhattacharya, Debapriya; Dwivedi, Ved Prakash; Maiga, Mamoudou; Maiga, Mariama; Van Kaer, Luc; Bishai, William R.; Das, Gobardhan
Tuberculosis remains the world's leading cause of death due to a single infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10 million new cases per year. The infection initiates in the lungs and can then spread rapidly to other tissues. The availability of the entire M. tuberculosis genome sequence and advances in gene disruption technologies have led to the identification of several mycobacterial determinants involved in virulence. However, no virulence factor specifically involved in the extrapulmonary dissemination of M. tuberculosis has been identified to date. Here we show that the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette-Guérin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA) markedly affects mycobacterial interactions with epithelial cells, but not with macrophage-like cells. When nasally administered to mice, the mutant strains were severely impaired in spleen colonization, but not in lung colonization. Coating wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination after intranasal infection. These results provide evidence that adhesins such as HBHA are required for extrapulmonary dissemination, and that interactions with non-phagocytic cells have an important role in the pathogenesis of tuberculosis. They also suggest that antibody responses to HBHA may add to immune protection against tuberculosis. PMID:11449276
Pethe, K; Alonso, S; Biet, F; Delogu, G; Brennan, M J; Locht, C; Menozzi, F D
Background Macrophage cell death following infection with Mycobacterium tuberculosis plays a central role in tuberculosis disease pathogenesis. Certain attenuated strains induce extrinsic apoptosis of infected macrophages but virulent strains of M. tuberculosis suppress this host response. We previously reported that virulent M. tuberculosis induces cell death when bacillary load exceeds ?20 per macrophage but the precise nature of this demise has not been defined. Methodology/Principal Findings We analyzed the characteristics of cell death in primary murine macrophages challenged with virulent or attenuated M. tuberculosis complex strains. We report that high intracellular bacillary burden causes rapid and primarily necrotic death via lysosomal permeabilization, releasing hydrolases that promote Bax/Bak-independent mitochondrial damage and necrosis. Cell death was independent of cathepsins B or L and notable for ultrastructural evidence of damage to lipid bilayers throughout host cells with depletion of several host phospholipid species. These events require viable bacteria that can respond to intracellular cues via the PhoPR sensor kinase system but are independent of the ESX1 system. Conclusions/Significance Cell death caused by virulent M. tuberculosis is distinct from classical apoptosis, pyroptosis or pyronecrosis. Mycobacterial genes essential for cytotoxicity are regulated by the PhoPR two-component system. This atypical death mode provides a mechanism for viable bacilli to exit host macrophages for spreading infection and the eventual transition to extracellular persistence that characterizes advanced pulmonary tuberculosis.
Lee, Jinhee; Repasy, Teresa; Papavinasasundaram, Kadamba; Sassetti, Christopher; Kornfeld, Hardy
Background: worldwide, the frequency of tuberculosis among older people almost triples that observed among young adults. Objective: to describe clinical and epidemiological consequences of pulmonary tuberculosis among older people. Methods: we screened persons with a cough lasting more than 2 weeks in Southern Mexico from March 1995 to February 2007. We collected clinical and mycobacteriological information (isolation, identification, drug-susceptibility testing and IS6110-based genotyping and spoligotyping) from individuals with bacteriologically confirmed pulmonary tuberculosis. Patients were treated in accordance with official norms and followed to ascertain treatment outcomes, retreatment, and vital status. Results: eight hundred ninety-three tuberculosis patients were older than 15 years of age; of these, 147 (16.5%) were 65 years of age or older. Individuals ?65 years had significantly higher rates of recently transmitted and reactivated tuberculosis. Older age was associated with treatment failure (OR = 5.37; 95% CI: 1.06–27.23; P = 0.042), and death due to tuberculosis (HR = 3.52; 95% CI: 1.78–6.96; P < 0.001) adjusting for sociodemographic and clinical variables. Conclusions: community-dwelling older individuals participate in chains of transmission indicating that tuberculosis is not solely due to the reactivation of latent disease. Untimely and difficult diagnosis and a higher risk of poor outcomes even after treatment completion emphasise the need for specific strategies for this vulnerable group.
Cruz-Hervert, Luis Pablo; Garcia-Garcia, Lourdes; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Cano-Arellano, Bulmaro; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Baez-Saldana, Renata; Tellez-Vazquez, Norma; Nava-Mercado, Ariadna; Juarez-Sandino, Luis; Delgado-Sanchez, Guadalupe; Fuentes-Leyra, Cesar Alejandro; Montero-Campos, Rogelio; Martinez-Gamboa, Rosa Areli; Small, Peter M.; Sifuentes-Osornio, Jose; Ponce-de-Leon, Alfredo
The purpose of the International Standards for Tuberculosis Care (ISTC) is to describe a widely accepted level of care that all practitioners, public and private, should seek to achieve in managing patients who have, or are suspected of having, tuberculos...
The authors describe a case of tuberculosis after kidney transplantation. They discuss diagnostic and therapeutical problems arising from the specific course of this disease which appears in patients with chronic renal insufficiency treated with immunosuppressives after kidney transplantation. PMID:2790890
Nouza, M; Jirka, J; Reneltová, I; Chadimová, M; Dráb, K; Krofta, K
Tubercle bacilli are spread by the blood stream to the kidney in miliary fashion from the primary pulmonary lesion. Activation, followed by arrest, may delay development of the disease in the kidney for many years or “healing” may occur. Renal ulcerative lesions are the most frequent source of infection of other genitourinary organs. In pyelograms there is no particular characteristic of lesions of tuberculosis. Cellular elements in the urine of a patient with tuberculosis of other organs should lead to urine culture and guinea pig inoculation for mycobacterium tuberculosis. Treatment with streptomycin, isonicotinic acid and/or para-aminosalicylic acid should be started as soon as genitourinary tuberculosis is proved. Patients with advanced lesions usually receive great benefit from these medications; even though organisms may not be eliminated they are definitely diminished in activity. Excision of diseased organs or tissue may be necessary in a few cases.
Malcolm, Donald C.
Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5% and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB. There is also a high TB incidence during the first few months of ART (much of which is prevalent disease missed by baseline screening) and long-term rates remain several-fold higher than background. We identify three groups of patients entering ART programmes for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-tuberculosis treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay. Second, patients with a diagnosis of active TB need optimised case management, which includes early initiation of ART (with timing now defined by randomised controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of co-morbidity. Third, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require optimised immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multi-drug resistant TB (MDR-TB). Finally, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated health care delivery for TB, HIV and other co-morbidities.
Lawn, Stephen D.; Harries, Anthony D.; Meintjes, Graeme; Getahun, Haileyesus; Havlir, Diane V.; Wood, Robin
Background Proteins that are involved in regulation of cell division and cell cycle progression remain undefined in Mycobacterium tuberculosis. In addition, there is a growing appreciation that regulation of cell replication at the point of division is important in establishing a non-replicating persistent state. Accordingly, the objective of this study was to use a systematic approach consisting of consensus-modeling bioinformatics, ultrastructural analysis, and transcriptional mapping to identify septum regulatory proteins that participate in adaptive metabolic responses in M. tuberculosis. Results Septum site determining protein (Ssd), encoded by rv3660c was discovered to be an ortholog of septum site regulating proteins in actinobacteria by bioinformatics analysis. Increased expression of ssd in M. smegmatis and M. tuberculosis inhibited septum formation resulting in elongated cells devoid of septa. Transcriptional mapping in M. tuberculosis showed that increased ssd expression elicited a unique response including the dormancy regulon and alternative sigma factors that are thought to play a role in adaptive metabolism. Disruption of rv3660c by transposon insertion negated the unique transcriptional response and led to a reduced bacterial length. Conclusions This study establishes the first connection between a septum regulatory protein and induction of alternative metabolism consisting of alternative sigma factors and the dormancy regulon that is associated with establishing a non-replicating persistent intracellular lifestyle. The identification of a regulatory component involved in cell cycle regulation linked to the dormancy response, whether directly or indirectly, provides a foundation for additional studies and furthers our understanding of the complex mechanisms involved in establishing a non-replicating state and resumption of growth.
Background Free tuberculosis control fail to protect patients from substantial medical and non-medical expenditure, thus a greater degree of disaggregation of patient cost is needed to fully capture their context and inform policymaking. Methods A retrospective cross-sectional study was conducted on a convenience sample of six health districts of Southern Benin. From August 2008 to February 2009, we recruited all smear-positive pulmonary tuberculosis patients treated under the national strategy in the selected districts. Direct out-of-pocket costs associated with tuberculosis, time delays, and care-seeking pattern were collected from symptom onset to end of treatment. Results Population description and outcome data were reported for 245 patients of whom 153 completed their care pathway. For them, the median overall direct cost was USD 183 per patient. Payments to traditional healers, self-medication drugs, travel, and food expenditures contributed largely to this cost burden. Patient, provider, and treatment delays were also reported. Pre-diagnosis and intensive treatment stages were the most critical stages, with median expenditure of USD 43 per patient and accounting for 38% and 29% of the overall direct cost, respectively. However, financial barriers differed depending on whether the patient lived in urban or rural areas. Conclusions This study delivers new evidence about bottlenecks encountered during the TB care pathway. Financial barriers to accessing the free-of-charge tuberculosis control strategy in Benin remain substantial for low-income households. Irregular time delays and hidden costs, often generated by multiple visits to various care providers, impair appropriate patient pathways. Particular attention should be paid to pre-diagnosis and intensive treatment. Cost assessment and combined targeted interventions embodied by a patient-centered approach on the specific critical stages would likely deliver better program outcomes.
Laokri, Samia; Amoussouhui, Arnaud; Ouendo, Edgard M.; Hounnankan, Athanase Cossi; Anagonou, Severin; Gninafon, Martin; Kassa, Ferdinand; Tawo, Leon; Dujardin, Bruno
Background Relapse of tuberculosis (TB) may develop as the result of reactivation of the endogenous primary infection, or as a result of a exogenous reinfection. This survey evaluated the rate of reactivation versus recent transmission among Iranian and Afghan relapse cases. Methods The sputum specimens were digested, examined microscopically for acid-fast bacilli, and inoculated into Löwenstein-Jensen slants by standard procedures. Thereafter, the susceptibility and identification tests were performed on culture positive specimens. Subsequently, the strains that were identified as Mycobacterium tuberculosis (258 isolates) were subjected to IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping. Additional patient's information was collected for further epidemiological analysis. Patients whose isolates had identical genotyping patterns were considered a cluster with recent transmission episode. Results Out of 258 available isolates, 72(28%) had multi-drug resistant (MDR-TB) in ratio and 42 (16.2%) had other resistant. Notably, 38 of MDR-TB cases (52%) were isolated from Afghan patients. By IS6110-RFLP typing method, 65 patients (25%) were clustered in 29 clusters. In cluster cases, the intra-community transmissions between Iranian and Afghan patients were 41%. All MDR-TB patients in clusters had either Haarlem I or Beijing characteristic. The risk factors like sex, family history, close contact, living condition, PPD test result and site of TB infection were not associated with clustering. Although, the MDR-TB strains were more frequent in non-cluster cases (31%) than cluster one(18%) (P < 0.05). Majority of M. tuberculosis strains isolated from non-cluster cases were belong to EAI3 (51; 30%) and CASI(32;18.6%) superfamilies. Conclusion During the studied period, reactivation of a previous infection remain the more probable cause of recurrence. Although, the evidence of intra- community transmission between Iranian and Afghan TB cases, highlighted the impact of afghan immigrants in national tuberculosis control program (NTP) of Iran.
Parissa-Farnia; Masjedi, Mohammad Reza; Varahram, Mohammad; Mirsaeidi, Mehdi; Ahmadi, Mojtaba; Khazampour, Mehdi; Tabarsi, Payam; Baghei, Parvaneh; Marjane, Mojtaba; Bahadori, Muslam; Zarifi, Abolhasan Zia; Velayati, Ali Akbar
Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between myco- bacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human
ROBERT S. WALLIS; SHRIPAD PATIL; SEON-HEE CHEON; KAY EDMONDS; MANIJEH PHILLIPS; MARK D. PERKINS; MOSES JOLOBA; ALICE NAMALE; JOHN L. JOHNSON; LUCILEIA TEIXEIRA; REYNALDO DIETZE; SALMAN SIDDIQI; ROY D. MUGERWA; KATHLEEN EISENACH
We are reporting a case of thyroid gland tuberculosis presenting as a painless hard nodular swelling of the thyroid with concomitant pulmonarytuberculosis in a 53-year-old adult diabetic male. Fine needle aspiration cytology showed epitheloid cell granuloma without any acid fast bacillus. He made an uneventful recovery with anti tuberculous drugs. Though rare, tuberculosis should be considered as a differential diagnosis of nodular or diffuse enlargement of thyroid gland. PMID:23236703
Das, S K; Bairagya, T D; Bhattacharya, S; Barman, D C
Genital tuberculosis is a bacterial infection still frequent in less developed countries where lots of cases are not diagnosed nor treated. In this work we describe a rare case of primary endometrial tuberculosis in a woman of 50 years old. The diagnosis was confirmed by an ultrasonography of the pelvis and an endometrial biopsy followed by a histological examination. The patient after the diagnosis was put under antiturbecular treatment for six months with complete healing. PMID:21793289
Iovenitti, P; Ruggeri, G; Tatangelo, R; Palermo, P; Carta, G
Tuberculosis remains a leading cause of morbidity and mortality worldwide. In 2011, there were 8.7 million new cases and 1.4 million deaths from the disease, with >95% of these deaths taking place in low- and middle-income countries . Contact tracing prevents the spread of tuberculosis by identifying and screening a case's contacts and referring symptomatic individuals to health care providers. Traditionally, contact tracing has been conducted with paper forms, which can lead to considerable inefficiencies in data collection, storage, and retrieval. These inefficiencies are problematic as tuberculosis can continue to spread if disruption of disease transmission is delayed. Mobile health approaches to tuberculosis contact tracing remain largely unaddressed and limited to management and monitoring of multidrug-resistant tuberculosis .To address these limitations, a mobile health application that digitizes and automates contact tracing was developed. This poster presents work currently underway to evaluate this new approach in Botswana, which has the tenth highest incidence rate of tuberculosis in the world . Operational considerations for implementing a mobile health approach to contact tracing in resource-limited settings are also presented. PMID:23920962
Ha, Yoonhee P; Littman-Quinn, Ryan; Antwi, Cynthia; Seropola, Gorewang; Green, Rebecca S; Tesfalul, Martha A; Ho-Foster, Ari; Luberti, Anthony A; Holmes, John H; Steenhoff, Andrew P; Kovarik, Carrie L
Background Transmission of tuberculosis (TB) in prisons has been reported worldwide to be much higher than that reported for the corresponding general population. Methods and Findings A systematic review has been performed to assess the risk of incident latent tuberculosis infection (LTBI) and TB disease in prisons, as compared to the incidence in the corresponding local general population, and to estimate the fraction of TB in the general population attributable (PAF%) to transmission within prisons. Primary peer-reviewed studies have been searched to assess the incidence of LTBI and/or TB within prisons published until June 2010; both inmates and prison staff were considered. Studies, which were independently screened by two reviewers, were eligible for inclusion if they reported the incidence of LTBI and TB disease in prisons. Available data were collected from 23 studies out of 582 potentially relevant unique citations. Five studies from the US and one from Brazil were available to assess the incidence of LTBI in prisons, while 19 studies were available to assess the incidence of TB. The median estimated annual incidence rate ratio (IRR) for LTBI and TB were 26.4 (interquartile range [IQR]: 13.0–61.8) and 23.0 (IQR: 11.7–36.1), respectively. The median estimated fraction (PAF%) of tuberculosis in the general population attributable to the exposure in prisons for TB was 8.5% (IQR: 1.9%–17.9%) and 6.3% (IQR: 2.7%–17.2%) in high- and middle/low-income countries, respectively. Conclusions The very high IRR and the substantial population attributable fraction show that much better TB control in prisons could potentially protect prisoners and staff from within-prison spread of TB and would significantly reduce the national burden of TB. Future studies should measure the impact of the conditions in prisons on TB transmission and assess the population attributable risk of prison-to-community spread. Please see later in the article for the Editors' Summary
Baussano, Iacopo; Williams, Brian G.; Nunn, Paul; Beggiato, Marta; Fedeli, Ugo; Scano, Fabio
Summary Whereas intracellular carbon metabolism has emerged as an attractive drug target, the carbon sources of intracellularly replicating pathogens, such as the tuberculosis bacillus Mycobacterium tuberculosis, which causes long-term infections in one-third of the world’s population, remain mostly unknown. We used a systems-based approach—13C-flux spectral analysis (FSA) complemented with manual analysis—to measure the metabolic interaction between M. tuberculosis and its macrophage host cell. 13C-FSA analysis of experimental data showed that M. tuberculosis obtains a mixture of amino acids, C1 and C2 substrates from its host cell. We experimentally confirmed that the C1 substrate was derived from CO2. 13C labeling experiments performed on a phosphoenolpyruvate carboxykinase mutant revealed that intracellular M. tuberculosis has access to glycolytic C3 substrates. These findings provide constraints for developing novel chemotherapeutics.
Beste, Dany J.V.; Noh, Katharina; Niedenfuhr, Sebastian; Mendum, Tom A.; Hawkins, Nathaniel D.; Ward, Jane L.; Beale, Michael H.; Wiechert, Wolfgang; McFadden, Johnjoe
Background We present a novel conformal Bayesian network (CBN) to classify strains of Mycobacterium tuberculosis Complex (MTBC) into six major genetic lineages based on two high-throuput biomarkers: mycobacterial interspersed repetitive units (MIRU) and spacer oligonucleotide typing (spoligotyping). MTBC is the causative agent of tuberculosis (TB), which remains one of the leading causes of disease and morbidity world-wide. DNA fingerprinting methods such as MIRU and spoligotyping are key components in the control and tracking of modern TB. Results CBN is designed to exploit background knowledge about MTBC biomarkers. It can be trained on large historical TB databases of various subsets of MTBC biomarkers. During TB control efforts not all biomarkers may be available. So, CBN is designed to predict the major lineage of isolates genotyped by any combination of the PCR-based typing methods: spoligotyping and MIRU typing. CBN achieves high accuracy on three large MTBC collections consisting of over 34,737 isolates genotyped by different combinations of spoligotypes, 12 loci of MIRU, and 24 loci of MIRU. CBN captures distinct MIRU and spoligotype signatures associated with each lineage, explaining its excellent performance. Visualization of MIRU and spoligotype signatures yields insight into both how the model works and the genetic diversity of MTBC. Conclusions CBN conforms to the available PCR-based biological markers and achieves high performance in identifying major lineages of MTBC. The method can be readily extended as new biomarkers are introduced for TB tracking and control. An online tool (http://www.cs.rpi.edu/~bennek/tbinsight/tblineage) makes the CBN model available for TB control and research efforts.
We investigated the spatial distribution, and social and economic correlates, of tuberculosis in Brazil between 2002 and 2009 using municipality-level age/sex-standardized tuberculosis notification data. Rates were very strongly spatially autocorrelated, being notably high in urban areas on the eastern seaboard and in the west of the country. Non-spatial ecological regression analyses found higher rates associated with urbanicity, population density, poor economic conditions, household crowding, non-white population and worse health and healthcare indicators. These associations remained in spatial conditional autoregressive models, although the effect of poverty appeared partially confounded by urbanicity, race and spatial autocorrelation, and partially mediated by household crowding. Our analysis highlights both the multiple relationships between socioeconomic factors and tuberculosis in Brazil, and the importance of accounting for spatial factors in analysing socioeconomic determinants of tuberculosis. PMID:24269879
Harling, Guy; Castro, Marcia C
A 71-year-old man operated for a sigmoid tumour remained in the surveillance after adjuvant chemotherapy. After 3 years, a left axillary lymph node was visible on CT scan. The biopsy revealed a necrotising and abscessed granulomatous lymphadenitis, suggestive of cat scratch disease. The patient confirmed having been scratched by a cat and the serology for Bartonella henselae was IgM+/IgG-. Direct and culture examinations for tuberculosis were negative. The patient was treated for cat scratch disease. One year later, the CT scan showed increased left axillary lymph nodes and a left pleural effusion. Direct and cultural examinations to exclude tuberculosis were again negative. Interferon-? release assay testing for tuberculosis was undetermined and then positive. Lymph node and pleural tuberculosis were diagnosed and treated with a good radiological response. This article has provides evidence of the importance of continued search for the right diagnosis and that two diagnoses can happen in the same patient. PMID:24334464
Matias, M; Marques, T; Ferreira, M A; Ribeiro, L
Tuberculosis remains the leading cause of death worldwide from a single infectious organism. Approximately 32% of the world's population is infected and an estimated two million people die annually from this treatable disease. Over the past 50 years, with medical treatment and standard public health practices, tuberculosis diminished in developed countries and resulted in a loss of interest and funding for research in improving diagnostic and treatment options. In developing countries, efforts including BCG vaccination have failed to control tuberculosis and the disease continues to spread as the world becomes more globalized. At the same time, multidrug resistant tuberculosis has emerged, challenging even the most advance treatment centers. Better diagnostic techniques, control measures and treatment options are desperately needed but advances require worldwide commitment to battle this age-old disease. PMID:15482144
Smith, Kim Connelly; Armitige, Lisa; Wanger, Audrey
Background Tuberculosis (TB) infections caused by multidrug-resistant Mycobacterium tuberculosis (MDR MTB) remain a significant public health concern worldwide. Georgia has a high prevalence of MDR MTB. The genetic mechanisms underlying the emergence of MDR MTB strains in this region are poorly understood and need to be determined for developing better strategies for TB control. This study investigated the frequency of major drug resistance mutations across rpoB, katG and inhA loci of Georgian MDR MTB strains and explored differences between new and previously treated patients. A total of 634 MTB strains were examined for which an MDR phenotype had been previously determined by the proportions method. The GenoType®MTBDRplus system was applied to screen the strains for the presence of rpoB (S531L, H526D, H526Y, and D516V), katG (S315T) and inhA promoter region (C15T and T8C) mutations. The target loci were amplified by PCR and then hybridized with the respective site-specific and wild type (control) probes. Results Out of the 634 isolates tested considered by phenotypic testing to be resistant to RIF and INH, this resistance was confirmed by the GenoType®MTBDRplus assay in 575 (90.7%) isolates. RIF resistance was seen in 589 (92.9%) and INH resistance was seen in 584 (92.1%); 67.2% and 84.3% of MDR strains harbored respectively rpoB S531L and katG S315T mutations (generally known as having low or no fitness cost in MTB). The inhA C15T mutation was detected in 22.6% of the strains, whereas rpoB H526D, rpoB H526Y, rpoB D516V and inhA T8C were revealed at a markedly lower frequency (?5.2%). The specific mutations responsible for the RIF resistance of 110 isolates (17.4%) could not be detected as no corresponding mutant probe was indicated in the assay. There was no specific association of the presence of mutations with the gender/age groups. All types of prevailing mutations had higher levels in new cases. A great majority of the Georgian MDR MTB strains have a strong preference for the drug resistance mutations carrying no or low fitness cost. Thus, it can be suggested that MDR MTB strains with such mutations will continue to arise in Georgia at a high frequency even in the absence of antibiotic pressure.
Shubladze, N.; Tadumadze, N.; Bablishvili, N.
According to a growing consensus among biomedical researchers, community engagement can improve the ethics and outcomes of clinical trials. Although successful efforts to develop community engagement practices in HIV/AIDS research have been reported, little attention has been given to engagement with the community in tuberculosis research. This article aims to draw attention to some existing community engagement initiatives in tuberculosis research and to resources that might help tuberculosis researchers to establish and implement community engagement programmes for their trials. One of these resources-the good participatory practice guidelines for tuberculosis drug trials-offers a conceptual framework and practical guidance for community engagement in tuberculosis research. To build momentum and to improve community engagement, lessons need to be shared, and formal assessment strategies for community engagement initiatives need to be developed. To build successfully on the promising activities described in this personal view, research funders and sponsors should show leadership in allocation of resources for the implementation and assessment of community engagement programmes in tuberculosis trials. PMID:23531390
Boulanger, Renaud F; Seidel, Stephanie; Lessem, Erica; Pyne-Mercier, Lee; Williams, Sharon D; Mingote, Laia Ruiz; Scott, Cherise; Chou, Alicia Y; Lavery, James V
The different concepts treating of "residual curarization" were presented according to two directions: the analysis of their contents--epidemiologic, clinical, instrumental--and the description of the pharyngeal striated muscles functions in these contexts. It appears that certain, too marked, "residual curarization" levels remain a well-evidenced factor increasing some morbidities in numerous clinical situations. All the methods of instrumental monitoring of the level of curarization--mecanography, electromyography, accelerometry--appeared useful to document the levels of "residual curarization" before patient's extubation or awakening. Today, for our speciality, it became particularly clear that: neither the selected muscle-- adductor pollicis--, neither the test currently privileged--train-of-four 2Hz--, nor the thresholds currently selected--0.90 or 1.00--did not constitute the unavoidable proof of a "residual curarization" complete absence. For the healthy volunteer receiving a curare, a train of four of the adductor pollicis greater than 0.90 can exist in presence of spirometric alterations evidencing the lack of adequate pharyngeal dilatation. In daily routine, the pharyngeal control is already disturbed by numerous molecules including: benzodiazepines, halogenated vapours, propofol, i.e. even under non-hypnotic concentrations. Faced to such evidences, our medical speciality will, undoubtedly, have to acquire new knowledge to develop muscle relaxant management control processes eliminating the surmorbidities related to "residual curarization". These tests must be validated also to exclude morbidity-prone dysfunctions of the pharyngeal striated muscles. Considering this new paradigm would be a major safety evolution for our speciality. PMID:19854607
d'Hollander, A-A; Bourgain, J-L
Background Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect. Methods We assessed the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), with fully integrated sample processing in 1730 patients with suspected drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients in Peru, Azerbaijan, South Africa, and India provided three sputum specimens each. Two specimens were processed with N-acetyl-l-cysteine and sodium hydroxide before microscopy, solid and liquid culture, and the MTB/RIF test, and one specimen was used for direct testing with microscopy and the MTB/RIF test. Results Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124 of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of 609 patients without tuberculosis (99.2%). Among patients with smear-negative, culture-positive tuberculosis, the addition of a second MTB/RIF test increased sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing resolved all but two cases in favor of the MTB/RIF assay. Conclusions The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time. (Funded by the Foundation for Innovative New Diagnostics.)
Boehme, Catharina C.; Nabeta, Pamela; Hillemann, Doris; Nicol, Mark P.; Shenai, Shubhada; Krapp, Fiorella; Allen, Jenny; Tahirli, Rasim; Blakemore, Robert; Rustomjee, Roxana; Milovic, Ana; Jones, Martin; O'Brien, Sean M.; Persing, David H.; Ruesch-Gerdes, Sabine; Gotuzzo, Eduardo; Rodrigues, Camilla; Alland, David; Perkins, Mark D.
Tuberculosis (TB) has become a curable disease thanks to the discovery of antibiotics. However, it has remained one of the most difficult infections to treat. Most current TB regimens consist of six to nine months of daily doses of four drugs that are highly toxic to patients. The purpose of these lengthy treatments is to completely eradicate Mycobacterium tuberculosis, notorious for its ability to resist most antibacterial agents, thereby preventing the formation of drug resistant mutants. On the contrary, the prolonged therapies have led to poor patient adherence. This, together with a severe limit of drug choices, has resulted in the emergence of strains that are increasingly resistant to the few available antibiotics. Here we review our current understanding of molecular mechanisms underlying the profound drug resistance of M. tuberculosis. This knowledge is essential for the development of more effective antibiotics that not only are potent against drug resistant M. tuberculosis strains but also help shorten the current treatment courses required for drug susceptible TB.
Smith, Tasha; Wolff, Kerstin A.; Nguyen, Liem
ABSTRACT Genetic engineering has contributed greatly to our understanding of Mycobacterium tuberculosis biology and has facilitated antimycobacterial and vaccine development. However, methods to generate M. tuberculosis deletion mutants remain labor-intensive and relatively inefficient. Here, methods are described that significantly enhance the efficiency (greater than 100-fold) of recovering deletion mutants by the expression of mycobacteriophage recombineering functions during the course of infection with specialized transducing phages delivering allelic exchange substrates. This system has been successfully applied to the CDC1551 strain of M. tuberculosis, as well as to a ?recD mutant generated in the CDC1551 parental strain. The latter studies were undertaken as there were precedents in both the Escherichia coli literature and mycobacterial literature for enhancement of homologous recombination in strains lacking RecD. In combination, these measures yielded a dramatic increase in the recovery of deletion mutants and are expected to facilitate construction of a comprehensive library of mutants with every nonessential gene of M. tuberculosis deleted. The findings also open up the potential for sophisticated genetic screens, such as synthetic lethal analyses, which have so far not been feasible for the slow-growing mycobacteria.
Tufariello, JoAnn M.; Malek, Adel A.; Vilcheze, Catherine; Cole, Laura E.; Ratner, Hannah K.; Gonzalez, Pablo A.; Jain, Paras; Hatfull, Graham F.; Larsen, Michelle H.
Mycobacterium bovis infection in wild animals attracted little attention in Canada until the disease was almost eliminated from domestic livestock. Tuberculosis was endemic in plains bison and occurred in elk, moose, and mule deer in Buffalo National Park (BNP), Alberta during the 1920s and 1930s. Bison were moved from BNP to Wood Buffalo National Park (WBNP), where tuberculosis became, and remains, endemic in bison, posing a risk to efforts to restore bison in northern Canada. Tuberculosis was found in a white-tailed deer in Ontario in 1959, and in an infected elk near Riding Mountain National Park (RMNP), Manitoba in 1992. Intense surveillance has resulted in detection of 40 elk, 8 white-tailed deer, and 7 cattle herds infected between 1997 and 2008 in the RMNP area. The strains of M. bovis in the RMNP area are different from strains tested from cattle and bison elsewhere in Canada. Management of tuberculosis in cattle and wild animals is challenging because of uncertainty about the ecology of the disease in various species, difficulty in obtaining samples and population data from wildlife, lack of validated tests, overlapping jurisdictions and authority, and conflicting values and opinions among stakeholders.
Isoxyl (ISO), a thiourea derivative that was successfully used for the clinical treatment of tuberculosis during the 1960s, is an inhibitor of the synthesis of oleic and mycolic acids in Mycobacterium tuberculosis. Its effect on oleic acid synthesis has been shown to be attributable to its inhibitory activity on the stearoyl-coenzyme A desaturase DesA3, but its enzymatic target(s) in the mycolic acid pathway remains to be identified. With the goal of elucidating the mode of action of ISO, we have isolated a number of spontaneous ISO-resistant mutants of M. tuberculosis and undertaken their genotypic characterization. We report here the characterization of a subset of these strains carrying mutations in the monooxygenase gene ethA. Through complementation studies, we demonstrate for the first time that the EthA-mediated oxidation of ISO is absolutely required for this prodrug to inhibit its lethal enzymatic target(s) in M. tuberculosis. An analysis of the metabolites resulting from the in vitro transformation of ISO by purified EthA revealed the occurrence of a formimidamide allowing the formulation of an activation pathway in which the oxidation of ISO catalyzed by EthA is followed by chemical transformations involving extrusion or elimination and, finally, hydrolysis.
Kordulakova, Jana; Janin, Yves L.; Liav, Avraham; Barilone, Nathalie; Dos Vultos, Tiago; Rauzier, Jean; Brennan, Patrick J.; Gicquel, Brigitte; Jackson, Mary
The authors deal with the problem of tuberculosis in patients after transplantation of the kidney. They give an account of eight cases of the disease in 647 patients where during the last 22 years transplantations where performed in the Institute for Clinical and Experimental Medicine. The lungs were affected in six patients, incl. three with miliary dissemination affecting also other organs incl. the graft. In one instance the patient's own kidney was affected and once the talar joint. The authors emphasize this atypical course of the disease and the necessity to search for BK in patients where the febrile condition does not recede after corresponding antibiotic treatment. In case of early antituberculotic treatment the prognosis is on the whole favourable. PMID:2790881
Nouza, M; Jirka, J; Dráb, K; Krofta, K
Most high-income countries implement tuberculosis (TB) infection control programs to reduce the risk for nosocomial transmission. However, such control programs are not routinely implemented in India, the country that accounts for the largest number of TB cases in the world. Despite the high prevalence of TB in India and the expected high probability of nosocomial transmission, little is known about nosocomial and occupational TB there. The few available studies suggest that nosocomial TB may be a problem. We review the available data on this topic, describe factors that may facilitate nosocomial transmission in Indian healthcare settings, and consider the feasibility and applicability of various recommended infection control interventions in these settings. Finally, we outline the critical information needed to effectively address the problem of nosocomial transmission of TB in India. PMID:17073077
Pai, Madhukar; Kalantri, Shriprakash; Aggarwal, Ashutosh Nath; Menzies, Dick; Blumberg, Henry M
A 26-year-old man (human immunodeficiency virus-positive and not taking highly active antiretroviral treatment [HAART]) presented to the emergency room with 2 months of malaise, 20 kg weight loss, high spiking fevers, generalized lymph nodes, night sweats, dry cough, and chest pain when swallowing. On physical examination, he had multiple cervical lymphadenopathies. Suspecting a systemic opportunistic infection, a contrasted chest computed tomography (CT) was done, showing an esophageal to mediastinum fistulae. Two days after admission, a fluoroscopic contrasted endoscopy was done that showed two esophageal fistulae from scrofula to esophagus and then, to mediastinum. A bronchoalveolar lavage and a cervical lymphadenopathy biopsy were done, both showing multiple acid-fast bacillae, where cultures grew Mycobacterium tuberculosis. PMID:23740190
Cataño, Juan; Cardeño, John
BACKGROUND: The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by
Rocio Lopez-Alvarez; Claudia Badillo-Lopez; Jorge F Cerna-Cortes; Ivan Castillo-Ramirez; Sandra Rivera-Gutierrez; Addy C Helguera-Repetto; Diana Aguilar; Rogelio Hernandez-Pando; Sofia Samper; Jorge A Gonzalez-y-Merchand
BACKGROUND: Mycobacterium tuberculosis DNA topoisomerase I is an attractive target for discovery of novel TB drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product. It shares a common transesterification domain with other type IA DNA topoisomerases. There is, however, no homology between the C-terminal DNA binding domains of Escherichia coli and M. tuberculosis DNA topoisomerase I proteins.
Thirunavukkarasu Annamalai; Neil Dani; Bokun Cheng; Yuk-Ching Tse-Dinh
Background Tuberculosis of the breast is an uncommon disease with non-specific clinical, radiological and histological findings. Misdiagnosis is common as biopsy specimens are pauci-bacillary and investigations such as microscopy and culture are frequently negative. Case presentation We report a case of a breast abscess in a 34-year old Bangladeshi woman attributed to tuberculosis infection. Equivocal histology, negative Ziehl-Neelsen stain and culture for acid-fast bacilli resulted in the abscess initially being diagnosed as granulomatous mastitis and treated accordingly. However failure to respond to therapy raised suspicion of culture negative breast tuberculosis. Treatment with standard antituberculosis drugs was associated with complete resolution of the breast abscess. Conclusion This case highlights the difficulty in differentiating culture negative tuberculosis from granulomatous mastitis and the importance of a high index of clinical suspicion.
Sriram, KB; Moffatt, D; Stapledon, R
Reports of verified cases of tuberculosis (RVCT) are submitted to the Division of Tuberculosis Elimination (DTBE), Centers for Disease Control and Prevention (CDC), by 60 reporting areas (the 50 states, the District of Columbia, New York City, Puerto Rico...
Reports of verified cases of tuberculosis (RVCT) are submitted to the Division of Tuberculosis Elimination (DTBE), Centers for Disease Control and Prevention (CDC), by 60 reporting areas (the 50 states, the District of Columbia, New York City, Puerto Rico...
Tuberculosis is an infectious disease that causes inflammation, the formation of tubercules and other growths within tissue, ... death. These chest x-rays show advanced pulmonary tuberculosis. There are multiple light areas (opacities) of varying ...
Background Two types of lechwe antelopes exclusively exist in their natural ecosystems in Zambia; the Black lechwe (Kobus leche smithemani) and the Kafue lechwe (Kobus leche kafuensis). Despite inhabiting similar ecosystems, tuberculosis has been reported in Kafue lechwe without its documentation in Black lechwe antelopes. However, the past few decades have seen a drastic decline in both lechwe populations. Whereas studies have postulated that infectious diseases such as tuberculosis are having a negative impact on the Kafue lechwe population, no information is available on Black lechwe antelopes. Thus this study was conducted to investigate tuberculosis in Black lechwe antelopes of the Bangweulu swamps in comparison with the Kafue lechwe antelopes of Lochinvar. Findings A total of 44 lechwe antelopes (Black (n = 30): Kafue (n = 14) were sampled from Bangweulu and Lochinvar respectively. A positive case was defined with findings of gross lesions with Ziehl Nielsen and culture confirmation. Out of the 14 animals examined in Lochinvar, 21.4% [95% CI: 15.4, 44.4%] had necropsy lesions consistent with tuberculosis. The corresponding samples from 30 Black lechwe of Bangweulu yielded negative results on all the three tests. Conclusions Current findings from this study intimate the possible absence of tuberculosis in Black lechwe antelopes whilst confirming the presence of tuberculosis in Kafue lechwe of the Kafue basin. The absence of tuberculosis in the Black lechwe suggests that the observed population decline may not be caused by tuberculosis. However, without detailed molecular epidemiological studies it is not possible to determine the association of M. bovis infection in sympatric animal populations. The possible role of transmission of tuberculosis between wildlife and cattle is discussed herein. Findings
BACKGROUND—The guidelines on chemotherapy and management of tuberculosis in the United Kingdom have been reviewed and updated.?METHODS—A subcommittee was appointed by the Joint Tuberculosis Committee (JTC) of the British Thoracic Society to revise the guidelines published in 1990 by the JTC. In preparing the revised guidelines the authors took account of new published evidence and graded the strength of evidence for their recommendations. The guidelines have been approved by the JTC and the Standards of Care Committee of the British Thoracic Society.?RECOMMENDATIONS—(1) Patients with tuberculosis should be notified. (2) In view of the rising incidence of drug resistance, bacteriological confirmation and drug susceptibility testing should be sought whenever possible. (3) A six month short course regimen, with four drugs in the initial phase, should be used for all forms of tuberculosis, except meningitis, in both adults and children. (4) The fourth drug (ethambutol) in the initial phase can be omitted in certain circumstances. (5) Treatment of all patients should be supervised by physicians with full training in the management of tuberculosis and with direct working access to tuberculosis nurse specialists or health visitors. (6) Advice is given on (a) management in special situations and patient groups, (b) drug interactions, and special precautions and pretreatment screening, (c) chemoprophylaxis for different groups, and (d) the management of single and multiple drug resistance. (7) Advice is given on follow up after treatment and the organisational framework for tuberculosis services. (8) The role of directly observed therapy is discussed. (9) The management of multidrug resistant tuberculosis is explained in outline: such patients should be managed by physicians with special experience and in close liaison with the Mycobacterium Reference Units, and in hospitals with appropriate isolation facilities. (10) Infection control and segregation for such patients and for patients with dual infection with human immunodeficiency virus (HIV) and tuberculosis are covered in an appendix.??
Background Tuberculosis (TB) is still a big threat to human health, especially in children. However, an isolation of Mycobacterium tuberculosis culture from pediatric cases remains a challenge. In order to provide some scientific basis for children TB control, we investigated the genotyping and drug resistance characteristics of M. tuberculosis isolates from pediatric cases in China. Methodology/Principal Findings In this study, a total of 440 strains including 90 from children (<15 years), 159 from adolescents (15–18 years) and 191 from adults (>18 years) isolated in 25 provinces across China were subjected to spoligotyping and drug susceptibility testing. As a result, Beijing family strains were shown to remain predominant in China (85.6%, 81.1% and 75.4% in three above groups, respectively), especially among new children cases (91.0% vs. 69.6% in previously treated cases, P?=?0.03). The prevalence of the Beijing genotype isolates was higher in northern and central China in the total collection (85.1% in northern and 83.9% in central vs. 61.6% in southern China, P<0.001) and a similar trend was seen in all three age groups (P?=?0.708, <0.001 and 0.025, respectively). In adolescents, the frequencies of isoniazid (INH)-resistant and ethambutol (EMB)-resistant isolates were significantly higher among Beijing strains compared to non-Beijing genotype strains (P?=?0.028 for INH and P?=?0.027 for EMB). Furthermore, strong association was observed between resistance to rifampicine (RIF), streptomycin (STR) and multidrug resistance (MDR) among Beijing compared to non-Beijing strains in previously treated cases of children (P?=?0.01, 0.01 and 0.025, respectively). Conclusion/Significance Beijing family was more prevalent in northern and central China compared to southern China and these strains were predominant in all age groups. The genetic diversity of M. tuberculosis isolates from children was similar to that found in adolescents and adults. Beijing genotype was associated with RIF, STR and MDR resistance in previously treated children.
Zhao, Xiuqin; Dong, Fang; Dong, Haiyan; Huang, Hairong; Tian, Jianling; Li, Qinjing; Lian, Lulu; Yin, Qingqin; Song, Wenqi; Wan, Kanglin; Shen, A-dong
Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions.
Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya
Background. It is highly cost effective to detect a seasonal trend in tuberculosis in order to optimize disease control and intervention. Although seasonal variation of tuberculosis has been reported from different parts of the world, no definite and consistent pattern has been observed. Therefore, the study was designed to find the seasonal variation of tuberculosis in Delhi, India. Methods. Retrospective record based study was undertaken in a Directly Observed Treatment Short course (DOTS) centre located in the south district of Delhi. Six-year data from January 2007 to December 2012 was analyzed. Expert modeler of SPSS ver. 21 software was used to fit the best suitable model for the time series data. Results. Autocorrelation function (ACF) and partial autocorrelation function (PACF) at lag 12 show significant peak suggesting seasonal component of the TB series. Seasonal adjusted factor (SAF) showed peak seasonal variation from March to May. Univariate model by expert modeler in the SPSS showed that Winter's multiplicative model could best predict the time series data with 69.8% variability. The forecast shows declining trend with seasonality. Conclusion. A seasonal pattern and declining trend with variable amplitudes of fluctuation were observed in the incidence of tuberculosis. PMID:24778871
Kumar, Varun; Singh, Abhay; Adhikary, Mrinmoy; Daral, Shailaja; Khokhar, Anita; Singh, Saudan
BACKGROUND—Although some studies have reported the presence of Mycobacterium tuberculosis (MTb) DNA in tissues affected by sarcoidosis, the data are conflicting. The aim of this study was to collect prospectively tissue from patients with sarcoidosis in whom tuberculosis had been excluded, and to use polymerase chain reaction (PCR) to search for DNA sequences specific for MTb.?METHODS—Fresh tissue samples (node or lung biopsy) taken from 23 patients with newly diagnosed sarcoidosis, 10 with other respiratory disease, and four patients with culture positive tuberculosis were analysed using PCR to amplify a 123 bp fragment of IS6110, the insertion element present in MTb, and nested PCR to further amplify an 85 bp sequence within the 123 bp product. DNA was also extracted from formalin fixed tissue from eight additional patients with sarcoidosis.?RESULTS—MTb DNA was not detected in any of the tissue samples from patients with sarcoidosis or other respiratory disease but was found in all four patients with tuberculosis.?CONCLUSIONS—This study has shown the absence of MTb DNA in lymph node and lung biopsy samples from patients with sarcoidosis. MTb is therefore unlikely to be a factor in the pathogenesis of this disease.??
Wilsher, M; Menzies, R; Croxson, M
Background: Predicting the incidence of tuberculosis (TB) plays an important role in planning health control strategies for the future, developing intervention programs and allocating resources. Objectives: The present longitudinal study estimated the incidence of tuberculosis in 2014 using Box-Jenkins methods. Materials and Methods: Monthly data of tuberculosis cases recorded in the surveillance system of Iran tuberculosis control program from 2005 till 2011 was used. Data was reviewed regarding normality, variance equality and stationary conditions. The parameters p, d and q and P, D and Q were determined, and different models were examined. Based on the lowest levels of AIC and BIC, the most suitable model was selected among the models whose overall adequacy was confirmed. Results: During 84 months, 63568 TB patients were recorded. The average was 756.8 (SD = 11.9) TB cases a month. SARIMA (0,1,1)(0,1,1)12 with the lowest level of AIC (12.78) was selected as the most adequate model for prediction. It was predicted that the total nationwide TB cases for 2014 will be about 16.75 per 100,000 people. Conclusions: Regarding the cyclic pattern of TB recorded cases, Box-Jenkins and SARIMA models are suitable for predicting its prevalence in future. Moreover, prediction results show an increasing trend of TB cases in Iran.
Moosazadeh, Mahmood; Nasehi, Mahshid; Bahrampour, Abbas; Khanjani, Narges; Sharafi, Saeed; Ahmadi, Shanaz
Background Currently available tools cannot be used to distinguish between sub-species of the M. tuberculosis complex causing latent tuberculosis (TB) infection. M. africanum causes up to half of TB in West- Africa and its relatively lower progression to disease suggests the presence of a large reservoir of latent infection relative to M. tuberculosis. Methods We assessed the immunogenicity of the TbD1 region, present in M. africanum and absent from "modern" M. tuberculosis, in an ELISPOT assay using cells from confirmed M. africanum or M. tuberculosis infected TB patients without HIV infection in the Gambia. Results Antigens from the TbD1 region induced IFN? responses in only 35% patients and did not discriminate between patients infected with M. africanum vs. M. tuberculosis, while PPD induced universally high responses. Conclusions Further studies will need to assess other antigens unique to M. africanum that may induce discriminatory immune responses.
Background Despite major public health initiatives and the existence of efficacious treatment regimes, tuberculosis (TB) remains a threat, particularly in resource-limited settings. A significant part of the problem is the difficulty of rapidly identifying infected individuals, and as a result, there has been renewed interest in developing better diagnostics for infection or disease caused by Mycobacterium tuberculosis. Many of the existing tools, however, have limitations such as poor sensitivity or specificity, or the need for well-equipped laboratories to function effectively. Serodiagnostic approaches in particular have long drawn attention, due to their potential utility in large field studies, particularly in resource-poor settings. Unfortunately none of the serodiagnostic approaches have so far proven useful under field conditions. Results We screened a large panel of antigens with serodiagnostic potential by ELISA and selected a subpanel that was strongly and broadly recognised by TB patients, but not by controls. These antigens were then formulated into a simple immuno-chromatographic lateral flow assay format, suitable for field use, and tested against panels of plasma and blood samples from individuals with different clinical status (confirmed TB patients, household contacts, and apparently healthy community controls), recruited from Ethiopia (a highly TB-endemic country) and Turkey (a TB meso-endemic country). While specificity was good (97-100% in non TB-endemic controls), the sensitivity was not as high as expected (46-54% in pulmonary TB, 25-29% in extra-pulmonary TB). Conclusions Though below the level of sensitivity the consortium had set for commercial development, the assay specifically identified M. tuberculosis-infected individuals, and provides a valuable proof of concept.
Tuberculosis globally results in almost 2 million human deaths annually, with 1 in 4 deaths from tuberculosis being human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related. Primarily a pathogen of the respiratory system, aerobic Mycobacterium tuberculosis complex (MTBC) infects the lungs via the inhalation of infected aerosol droplets generated by people with pulmonary disease through coughing. This review focuses on M. tuberculosis transmission, epidemiology, detection methods and technologies.
Talip, Balkis A.; Sleator, Roy D.; Lowery, Colm J.; Dooley, James S.G.; Snelling, William J.
Pathognomonic metacarpal undermining is a skeletal pathology that has been associated with Mycobacterium tuberculosis in bovids. Postcranial artiodactyl, perissodactyl, and carnivore skeletons were examined in major university and museum collections of North America and Europe for evidence of this and other pathology potentially attributable to tuberculosis. Among nonproboscidean mammals from pre-Holocene North America, bone lesions indicative of tuberculosis were restricted
Bruce M. Rothschild; Larry D. Martin
...2010-01-01 2010-01-01 false Tuberculosis. 311.2 Section 311.2 Animals...ADULTERATED CARCASSES AND PARTS Â§ 311.2 Tuberculosis. The following principles shall...the difference in the pathogenesis of tuberculosis in swine, cattle, sheep,...
...2009-01-01 2009-01-01 false Tuberculosis. 311.2 Section 311.2 Animals...ADULTERATED CARCASSES AND PARTS Â§ 311.2 Tuberculosis. The following principles shall...the difference in the pathogenesis of tuberculosis in swine, cattle, sheep,...
...2013-07-01 2013-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection Â§ 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...
Conclusions.\\\\p=m-\\\\Theminimum percentage of cases due to primary tuberculosis in the homeless was estimated to be 53%, compared with the traditional estimate of 10% in the general population. The results suggest that primary tuberculosis caused the majority of tuberculosis cases in this population of the urban homeless in central Los Angeles. (JAMA. 1996;275:305-307)
Peter F. Barnes; Hiyam El-Hajj; Susan Preston-Martin; M. Donald Cave; Brenda E. Jones; Michiko Otaya; Janice Pogoda; Kathleen D. Eisenach
...2012-01-01 2012-01-01 false Tuberculosis. 311.2 Section 311.2 Animals...ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The following principles shall...the difference in the pathogenesis of tuberculosis in swine, cattle, sheep,...
...2012-07-01 2012-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...
...2011-07-01 2011-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...
...2010-07-01 2010-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...
...2011-01-01 2011-01-01 false Tuberculosis. 311.2 Section 311.2 Animals...ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The following principles shall...the difference in the pathogenesis of tuberculosis in swine, cattle, sheep,...
Background Tuberculosis rates in the world remain high, especially in low- and middle-income countries. International tuberculosis (TB) policy generally recommends the use of directly observed therapy (DOT) to ensure treatment adherence. Objective This article examines a change in TB treatment support that occurred in 2005 in South Africa, from DOT to the enhanced TB adherence programme (ETA). Design Seven key individuals representing academics, policy makers and service providers involved in the development of the ETA programme or knowledgeable about the issue were purposively sampled and interviewed, and participant observation was conducted at ETA programme steering group meetings. Qualitative content analysis was used to analyse the data, drawing on the Kingdon model of agenda setting. This model suggests that three independent streams – problem, policy and politics – come together at a certain point, often facilitated by policy entrepreneurs, to provide an opportunity for an issue to enter the policy agenda. Results The results suggest the empowerment-oriented programme emerged through the presence of policy entrepreneurs with access to resources. Policy entrepreneurs were influenced by a number of simultaneously occurring challenges including problems within the existing programme; a perceived mismatch between patient needs and the existing TB treatment model; and the TB-HIV co-epidemic. Policy entrepreneurs saw the ART approach as a possible solution to these challenges. Conclusions The Kingdon model contributed to describing the process of policy change. Research evidence seemed to influence this change diffusely, through the interaction of policy entrepreneurs and academics.
Atkins, Salla; Lewin, Simon; Ringsberg, Karin C.; Thorson, Anna
This book provides an introduction to the physics, astrophysics and cosmology of the cosmic microwave background radiation. Adopting the Standard Big Bang model of the universe, the authors cover topics including the origin of the background, intrinsic fluctuations, and the universe and background radiation after recombination. Finally they present measurement of the radiation and its anisotropies, along with a review
Marc Lachièze-Rey; Edgard Gunzig
The major objectives of tuberculosis (TB) control are to reduce morbidity and mortality via an early and appropriate treatment of the disease, to prevent carriers of the Mycobacterium tuberculosis bacillus from transmitting it to others, and to prevent latent tuberculosis infection (LTB) sufferers from progressing to the disease. To achieve these objectives, it is imperative to start an appropriate, effective antituberculosis treatment as early as possible, as well as identify contacts of the infected TB patient and others at risk of LTB progressing to TB, in order to establish an appropriate treatment for them. Here we review the bases for treating TB and LTB infections, including those produced by strains resistant to anti-TB drugs. PMID:21420566
Pérez-Camacho, Inés; Rivero-Juárez, Antonio; Kindelán, José María; Rivero, Antonio