CIRAD-EMVT, Montpellier, France
For a cattle owner in Africa, there has been apparently no change in the CBPP situation for many decades. The same vaccines have been used for 40 years, antibiotics are still used in the field. The improvement that was observed after the JP15 vaccination campaigns, associating rinderpest with CBPP vaccination is now gone. As a consequence, CBPP is again a top priority now. However, there are many indications that the situation may change rapidly as research has started to produce some results and more is to come in the near future.
The past decade has seen a number of technological improvements in diagnostic procedures. The direct detection and identification of the causative agent is now obtained by various specific PCR techniques. Furthermore, groups of Mycoplasma mycoides subspecies mycoised small colony biotype (Mmm SC) strains correlated with geographic origins can now be characterized thanks to Southern Blotting and Multilocus sequence typing. Finally, the T1 vaccine strains can be identified by a specific PCR. Serology techniques have also evolved recently with the development of specific competition assays or ELISA. More is to come in the different steps that can play a role when studying a disease and trying to improve CBPP control. Schematically, four of these steps can be defined: the pathogen itself, the interaction of the pathogen with the host, the transmission of the disease within a herd and, finally, the transmission of the disease on a wider scale.
Dramatic technological improvements have allowed the sequencing of bacterial genomes including those of mycoplasmas that are among the smallest of "free living organisms". The genome sequence of strain PG1 has been obtained by a Swedish team. Unfortunately it has not been put in the public domain, although this project had been started more than 6 years ago. In any case, other strains will be sequenced in the near future, as what is really needed is the sequence of a pathogenic strain. Technological advances are now allowing the study of the transcription of genes or even the totality of the proteins that are synthesized. These tools will allow the comparison of strains of high and low virulence and enable the identification of virulence factors. In addition, novel plasmid constructions allow the transformation of mycoplasmas and the inactivation of some specific genes. This should allow an experimental proof of the involvement of specific genes in virulence mechanisms.
The host pathogen interactions
Unlike other bacteria, Mmm SC is devoid of established virulence factors such as toxins for example. The most likely explanation for its virulence is to be found in the interaction between this bacteria and the host immune response. Lesions are the result of an exacerbated local inflammatory response and death occurs when animals are unable to regulate this response rapidly enough. New tools such as microarray analysis will now allow a very fine and comprehensive study of the kinetics of the immune response in infected animals. This will allow us to understand which mycoplasmal antigens are responsible for this response and which bovine cells are the key effectors of this response. This will help us to design vaccines that are devoid of residual virulence. In parallel, the identification of the type of immune response that leads to protection and not to sensitisation will allow the identification of protective antigens and delivery systems.
The transmission of CBPP in the field
One of the main limitations for CBPP studies is the absence of a laboratory animal model. Accordingly, all experimental trials have to be done in cattle. The situation is even complicated by the fact that there is a very pronounced variation of individual susceptibilities. This is the reason why experimental trials have to include large groups of animals or they are to be duplicated many times before statistically significant results can be obtained. This is the reason why some key parameters for the study of CBPP epidemiology are still uncharacterised. One example is the infectivity of CBPP chronic carriers although this type of cattle may play a very important role in the persistence of the disease or in reintroduction to disease-free zones. Mathematical models may play a very important role. Firstly, they may allow an identification of the key parameters that may influence the long-term persistence of the disease. This, in turn, will pinpoint the biological assays that will have to be performed in order to determine the value of these parameters. Secondly, they may be used to simulate the effect of various combinations of control measures. This should help in defining the most cost-effective strategies.
Whatever new tools are developed in the near future, it should be recognized that the success of CBPP control would depend mainly on the commitment of the various stakeholders in the field. Designing new tools, such as more potent vaccines, should diminish the cost of CBPP control and therefore, make more realistic, the eradication of this disease. This is not a mere dream. CBPP transmission is quite simple compared to other diseases, there is no reservoir in wildlife, transmission is direct and mycoplasmas are rapidly inactivated outside their host. These are very favourable conditions for control.