Vaccination of domestic animals against tuberculosis: Review of progress and contributions to the field of the TBSTEP project

Tuberculosis either caused by Mycobacterium bovis or M. caprae is a significant burden to agricultural industries worldwide. Vaccination of domestic ruminant species such as cattle and goats constitutes a potential tool to support disease control. This review will discuss recent progress made to develop tuberculosis vaccines against domestic ruminants as well as approaches to differentiate vaccinated and infected animals (DIVA) and biomarker discovery studies

Scheme of a granuloma surrounded by satellite granulomas (SatG).

<p>Example of TB small lesion in lung consisting of a central granuloma (C) surrounded by 8 smaller SatG (S₁₋₈) characterized by variably sized clusters of inflammatory cells contiguous to the central granuloma, sometimes with presence of MNGC and central necrosis (e.g. S₅). The number of SatG, upon histopathological assessment of small granulomas, was used as a parameter to evaluate the tendency of lesions to disseminate.</p

Viruses used in the standardisation of Margarita strain real-time TaqMan assay.

Viruses used in the standardisation of Margarita strain real-time TaqMan assay.</p

Antigen specific IFN-γ responses after vaccination and <i>M</i>. <i>caprae</i> challenge.

The graphic shows the levels of IFN-γ measured by ELISA. Results are expressed as ΔOD450mn ± 95% CI. (A) Response against Bovine tuberculin (PPD-B). (B) Response against EC antigen cocktail (ESAT-6 / CFP-10). Groups: Control (n = 8), BCG (n = 8), HIMB (n = 7).</p

Evolution of recent and old lesions.

<p>The results show the median of the values represented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010030#pone-0010030-t002" target="_blank">Table 2</a>. The gray bar shows the INH treatment period and vaccine inoculation is represented by the black arrows. CT  =  control group; INH  =  chemotherapy with isoniazid; VAC  =  group treated with vaccine therapy.</p

Evolution of the area of granulomas according to their evolutive phase.

<p>Individual data are presented in relation to the evolutive state of the lesion (<b>A</b>) or its encapsulation status (<b>B</b>). Mean and quartiles are presented in each case. Inter-group differences were determined by Dunn's One Anova on ranks test and are marked with * if statistically significant (p<0.05).</p

Evaluation of the cellular immune response by ELISPOT assay.

<p>Evaluation of ESAT-6, Ag85B, 16 kDa and PPD-specific IFN-γ production after stimulation of PBMCs, as determined by ELISPOT assay. Means and SEM are drawn in black and connected by dotted lines. The black boxes show the period of INH treatment and the black arrows the time of therapeutic vaccination.</p

Verbal intelligence and sleep disorders in children with ADHD

In the present study, WISC-III Verbal IQ and sleep disorders in children with Attention Deficit Hyperactivity Disorder (ADHD) and controls who were matched for age and sex were assessed. 18 children with ADHD, 14 boys and 4 girls, and 18 controls, 14 boys and 4 girls, participated, Polysomnographs were performed for all ADHD children during their night sleep. The Greek version of WISC-III was used to evaluate Verbal IQ. Analysis of the polysomnographs showed that the quality of night sleep of the children with ADHD was very poor, including apneas, low desaturation rates, and awakenings in combination with limb activity and snoring. This agreed with their low Verbal IQ, which was up to 20 points lower than the controls' Verbal IQ. Sleep disorders in ADHD children could contribute to lower Verbal IQ

Microscopic evolution of recent lesions, showing the relationship between the granulomas and the intralobular septa.

<p><b>A–D</b>: Phase I lesions; <b>E</b> and <b>F</b>: Phase II lesions. Images <b>A</b> and <b>B</b> show the initial evolution phase where the granuloma touches an intralobular septa but there is still no fibroblast proliferation. This can be seen in images <b>C</b> and <b>D</b>, where the septa increase in thickness and start to surround the granuloma, as shown by the white dotted lines. Images <b>E</b> and <b>F</b> show how the granuloma is finally surrounded by a thick collagenic mantle. Pictures <b>A</b>, <b>C</b> and <b>D</b> were stained with haematoxylin and eosin (H&E), while <b>B</b>, <b>D</b> and <b>F</b> were stained with Masson's trichromic. The original magnification of the large images is ×40 whereas all insets, except <b>F</b> (x100), are magnified ×400. The green arrows show the septa and the dotted white lines the trajectory of the capsule.</p

Characteristics of the evolution Phase of the lesions.

*<p>Phase I lesions are subdivided in <b>a</b> or <b>b</b> regarding its contact with interlobular septae (in the <b>b</b> case).</p>**<p>N.E. means “not evaluable”.</p