A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r² = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.     

The efficacy of intranasal interferon alpha-2a in respiratory syncytial virus infection in volunteers

In a double-blind, placebo-controlled study, self-administered intranasal interferon alpha-2a or placebo was given both before and after challenge with respiratory syncytial virus. The incidence of colds and the severity of signs and symptoms were reduced in those receiving interferon alpha-2a as compared with those given placebo. In a further double-blind, placebo-controlled study, self-administered interferon alpha-2a or placebo was given only to those volunteers who developed colds following challenge with respiratory syncytial virus. There was no evidence that interferon alpha-2a reduced the severity of the signs and symptoms or shortened the duration of the illness. The similarity of these results to the effect of interferon alpha-2a in rhinovirus infections in volunteers is discussed.     

Epitope specificities and antibody responses to the EG95 hydatid vaccine

Antibody isotype and epitope specificities were examined in sheep immunized with EG95, a protective recombinant vaccine against hydatid disease. All sheep immunized with EG95 as a fusion protein with glutathione S-transferase (GST) produced prominent IgG antibodies against the EG95 portion of the protein. Linear, antibody-binding epitope specificities of EG95 were mapped using a series of 25 overlapping synthetic peptides. Three immunodominant regions were identified which generated specific IgG₁ and IgG₂ antibodies in the majority of vaccinated sheep. These regions corresponded to the EG95-derived sequences SLKAVNPSDPLVYKRQTAKF, DIETPRAGKKESTVMTSGSA and SALTSAIAGFVFSC. An additional immunogenic region was identified which induced almost exclusively IgG₂ antibody. This epitope was located within the sequence TETPLRKHFNLTPV. The anti-parasitic, protective effects of the EG95 vaccine correlated with the detection of specific antibody to two or more of the four linear immunogenic regions. The identification of these immunogenic peptides of EG95 maybe useful in the development of a synthetic peptide vaccine as a derivative of the EG95 recombinant.     

The identification of higher forefoot temperatures associated with peripheral arterial disease in type 2 diabetes mellitus as detected by thermography

Aims

The purpose of this study was to investigate whether heat emitted from the feet of patients with type 2 diabetes (DM) and peripheral arterial disease (PAD) differed from those with type 2 diabetes without complications (DM).

Protection against hydatid disease induced with the EG95 vaccine is associated with conformational epitopes

This paper describes attempts to map the location of host-protective epitopes of a recombinant vaccine antigen by assessing the ability of truncated regions of the antigen to elicit protective immune responses in sheep. Sheep were immunised with three truncated regions (EG95-1, EG95-2 and EG95-3) of the hydatid vaccine antigen, EG95. These regions overlapped each other and corresponded to amino acids 1-70 (EG95-1), 51-106 (EG95-2) and 89-153 (EG95-3) of the full length recombinant protein. Each region elicited antibody which reacted with the parent antigen, although these reactivities were a small proportion of the level of reactivity generated by immunisation with the full length antigen. Antisera raised against each of the truncated proteins reacted with the native parasite antigen. In vaccination and parasite challenge trials in sheep, none of the truncated regions elicited significant protection against challenge infection or antibody which was lethal to the parasite in vitro. Antibodies from sheep immunised with the combination of all three overlapping truncations elicited a comparatively low but significant level of lysis of the parasite in vitro. These antigens did not inhibit anti-EG95 antibody reactivity with EG95 nor did they inhibit in vitro oncosphere killing induced by anti-EG95 antibodies. These results indicate that the major part of the immune response induced by EG95 vaccination is directed against conformational epitopes and that the host-protective epitope(s) is/are conformational.