Foreword

Autor: 

The Editors indicate in the title of the book, that creative tuberculosis (TB) vaccine research is in the realm of science as well as art. This aspect is further emphasized by attaching one artwork to each of the chapters. My perception of this approach is, that the art images perhaps reflect the challenges felt by the scientists when endeavouring to invent and develop effective means for alleviating the suffering which TB still imposes on mankind. Reference to art may also imply, that researchers need to complement rational scientific design and interpretation with some degree of intuitive guesswork. Moreover, the inspiration for the presented art images might reflect the human impact of this devastating disease on the mainly socio-economically underprivileged individuals and populations of the world. Integrating art to a book, appears to be uniquely original for a monograph of any scientific discipline. Hence, the Editors deserve to be praised not only for adopting this format, but also for attracting artists who felt inspired by the associations with TB and for suitably matching their images with the respective scientific chapters.

Despite extensive research efforts and major advances, current knowledge of the fundamental mechanisms of host resistance against TB retains a number of gaps and paradoxes. In such circumstances, the procedures currently used for controlling the disease are still failing to reduce its enormous impact on global health. Hence, it is pertinent to quote Maurice Lefford, who wrote in 1974, that ‘much as one might wish otherwise, the drop in the prevalence in TB is not attributable to the undoubted scientific contributions (pasteurization of milk, immunization, chemotherapy), but was a consequence of improved socio-economic conditions’. The continued validity of this statement is apparent from the striking disparity in TB prevalence between countries and also between communities within the same country, with disparate levels of marginalization and poverty. Taking this into account, the research strategies aimed at TB control need to take into consideration their scope for implementation to populations living in poor socio-economic conditions. One may quote as a striking example of this problem the case of chemotherapy of TB, which is extremely successful under controlled trial conditions, but suffering from poor compliance—due to the need for protracted (at least six months) treatment—in poor countries with the highest disease incidence. The complexity of the socio-economic, geographical, and environmental aspects are being discussed in this book by Graham AW Rook (Chapter 28), pointing out how environmental mycobacteria cause resistance to TB and may wipe off any additional protection following vaccination. He also elaborates how elevated levels of Th 2 cytokines (mainly IL-4 and TGF-β), due to helminthic infections and a high bacterial infection load in overcrowded accommodation, may affect resistance to natural infection and perhaps also to vaccination. Hence, he poses the question whether ‘we might need to consider different types of vaccine for different populations and environments’.

Vaccination against infectious diseases has been credited with the highest merits for achieving their global elimination in an efficient and cost-effective manner. Therefore, vaccine development has attracted a predominant share of current funding for TB research from both governmental and charitable sources. While the emphasis is on moving novel TB vaccines and regimens (e.g. prime-boost) to the stage of evaluation in human trials, our understanding of the immunobiology of TB retained a number of unresolved paradoxes. These can be listed as follows: a) It is generally assumed that protection against TB is mediated by IFNγ, produced predominantly by Th1 lymphocytes; however, patients with active TB have abundant IFNγ production and recombinant IFNγ has not been therapeutic; b) Natural infection and all vaccine-imparted host resistance drives the dividing tubercle bacilli (MTB) into latency, from which they have the capacity to reactivate at a later stage. In contrast, vaccines which had been successful in eradicating other infectious diseases (e.g. smallpox, polio) impart sterile immunity; c) About 95 per cent of the human population is naturally resistant to reactivated dormant infection and therefore vaccination needs to target the 5 per cent susceptible individuals. However, the stimuli which lead to reactivation in otherwise healthy young individuals (the bulk of adult TB), and the mechanisms of their action, remain virtually unknown.

 
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