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ABSTRACT There have been several sustained-release materials containing anti-tuberculosis drug to enhance concentration in foci of spinal tuberculosis but what map by which composite drug delivery system is released is not known. Isoniazid (INH) lactic-co-glycolic acid (PLGA) and INH hydroxyapatite (HA) microspheres were prepared, respectively. The rabbits were modeled by tuberculosis strains and sustained-release microspheres were incubated in the foci. INH concentrations in the HA group were higher than those of INH and PLGA groups at L3, L4, and L5 vertebra 2 days after the drugs were embedded ( p < 0.05). INH concentrations in the HA group were higher than those of INH and PLGA groups in L3 vertebra 4 days after the drugs were embedded ( p < 0.05). INH concentrations in the PLGA group were higher than those of INH and HA groups in L5 vertebra; INH concentrations of the HA group were higher than those of INH and PLGA groups in L4 vertebra 6 days after the drugs were embedded ( p < 0.05). These microspheres can enhance INH concentration in the foci. Furthermore, HA microspheres elicit osteogenic effects. HA is better than PLGA in terms of infiltration, but PLGA is better than HA in terms of distribution. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:200-208, 2017. [ABSTRACT FROM AUTHOR]

Animal tuberculosis ( TB) control is globally important for public health, economics and conservation. Wildlife species are often part of the M ycobacterium tuberculosis complex ( MTC) maintenance community, complicating TB control attempts., We describe the current knowledge on global TB distribution and the significance of wildlife hosts; identify insufficiently known aspects of host pathology, ecology and epidemiology; present selected time series in wildlife TB; and summarize ongoing research on TB control, providing additional insight on vaccination., Six specific research needs are identified and discussed, namely: 1) complete the world map of wildlife MTC reservoirs and describe the structure of each local MTC host community; 2) identify the origin and behaviour of generalized diseased individuals within populations, and study the role of factors such as co-infections, re-infections and individual condition on TB pathogenesis; 3) quantify indirect MTC transmission within and between species; 4) define and harmonize wildlife disease monitoring protocols, and apply them in a way that allows proper population and prevalence trend comparisons in both space and time; 5) carry out controlled and replicated wildlife TB control experiments using single intervention tools; 6) analyse cost-efficiency and consider knowledge transfer aspects in promising intervention strategies., We believe that addressing these six points would push ahead our capacities for TB control. A remaining question is whether or not interventions on wildlife TB are at all justified. The answer depends on the local circumstances of each TB hotspot, and is likely to evolve during our collective progress towards TB control in livestock and in wildlife. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) has evolved within the human immune system as both host and reservoir. The study of genes required for its growth and persistence in vivo thus offers linked insights into its pathogenicity and host immunity. Studies of Mtb mutants have implicated metabolic adaptation (consisting of carbon, nitrogen, vitamin, and cofactor metabolism), intrabacterial pH homeostasis, and defense against reactive oxygen and reactive nitrogen species, as key determinants of its pathogenicity. However, the mechanisms of host immunity are complex and often combinatorial. Growing evidence has thus begun to reveal that the determinants of Mtb's pathogenicity may serve a broader and more complex array of functions than the isolated experimental settings in which they were initially found. Here, we review select examples, which exemplify this complexity, highlighting the distinct phases of Mtb's life cycle and the diverse microenvironments encountered therein. [ABSTRACT FROM AUTHOR]

Non-human primates, primarily macaques, have been used to study tuberculosis for decades. However, in the last 15 years, this model has been refined substantially to allow careful investigations of the immune response and host-pathogen interactions in Mycobacterium tuberculosis infection. Low-dose challenge with fully virulent strains in cynomolgus macaques result in the full clinical spectrum seen in humans, including latent and active infection. Reagents from humans are usually cross-reactive with macaques, further facilitating the use of this model system to study tuberculosis. Finally, macaques develop the spectrum of granuloma types seen in humans, providing a unique opportunity to investigate bacterial and host factors at the local (lung and lymph node) level. Here, we review the past decade of immunology and pathology studies in macaque models of tuberculosis. [ABSTRACT FROM AUTHOR]

Despite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis ( TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co-infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here, we discuss recent progress in so-called 'host-directed therapeutics' ( HDTs), focusing on two general mechanistic strategies: (i) HDTs that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDTs that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDTs hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic-resistant strains, and may have activity against non-replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDTs to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDTs as effective adjunctive treatment options for TB. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) has been evolving with its human host for over 50 000 years and is an exquisite manipulator of the human immune response. It induces both a strong inflammatory and a strong acquired immune response, and Mtb then actively regulates these responses to create an infectious lesion in the lung while maintaining a relatively ambulatory host. The CD4+ T cell plays a critical yet contradictory role in this process by both controlling disseminated disease while promoting the development of the lesion in the lung that mediates transmission. In light of this manipulative relationship between Mtb and the human immune response, it is not surprising that our ability to vaccinate against tuberculosis ( TB) has not been totally successful. To overcome the current impasse in vaccine development, we need to define the phenotype of CD4+ T cells that mediate protection and to determine those bacterial and host factors that regulate the effective function of these cells. In this review, we describe the initiation and expression of T cells during TB as well as the fulminant inflammatory response that can compromise T-cell function and survival. [ABSTRACT FROM AUTHOR]

The expression of ten tuberculosis candidate genes in lung and lymph nodes of cynomologus macaques vaccinated and experimentally infected with Mycobacterium tuberculosis (Mtb) was quantified. The expression of TNFα, IL10, IL1β, TLR4, IL17, IL6, IL12, and iNOS in the lungs of vaccinated animals was higher than that of non-vaccinated animals. [ABSTRACT FROM AUTHOR]

Summary Relevance and accuracy of experimental mouse models of tuberculosis (TB) are the subject of constant debate. This article briefly reviews genetic aspects of this problem and provides a few examples of mycobacterial diseases with similar or identical genetic control in mice and humans. The two species display more similarities than differences regarding both genetics of susceptibility/severity of mycobacterial diseases and the networks of protective and pathological immune reactions. In the opinion of the author, refined mouse models of mycobacterial diseases are extremely useful for modelling the corresponding human conditions, if genetic diversity is taken into account. [ABSTRACT FROM AUTHOR]

The problems of tuberculosis (TB) and its drug resistances are very severe in China. New therapeutic agents or regimens to treat multi-drug-resistant tuberculosis (MDR-TB) are urgently needed. We studied the effects of Ag85A DNA vaccine alone or in combination with rifampin (RFP) or pyrazinamide (PZA) for the treatment of MDR-TB in mice. Ag85A DNA vaccine significantly increased the production of IFN-γ, but lowered the production of IL-4. Seventy female BALB/c mice infected with Mycobacterium tuberculosis clinical isolate HB361, which was resistant to RFP and isoniazid but sensitive to PZA, were treated with plasmid pVAX1, RFP, PZA, M. vaccae vaccine, Ag85A DNA, Ag85A DNA combined with RFP or PZA, respectively. Ag85A DNA vaccine alone or in combination with RFP or PZA reduced the pulmonary and splenic bacterial loads by 1.03-1.38 logs, respectively. Ag85A DNA combined with conventional chemotherapy for the treatment of MDR-TB might result in cure of MDR-TB in developing countries. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the professional rates in tuberculosis (TB) testing in veterinary medicine.

The article announces the invitation of the Department for Environment, Food and Rural Affairs (Defra) to people to give their opinions on strengthening cattle bovine tuberculuosis (TB) controls in Great Britain. According to Defra, TB pre-movement testing exemption for movements within Sole Occupancy Authorities (SOAs) in annual TB testing areas in England should be abolished.