Malignant Catarrhal Fever (MCF), an often-lethal infectious disease, presents as a variablecomplex of lesions in susceptible ungulate species. The disease is caused by a -herpesvirusfollowing transmission from an inapparent carrier host. Two major epidemiological formsexist: wildebeest-associated MCF (WA-MCF), in which the virus is transmitted to susceptiblespecies by wildebeest calves less than approximately four months of age, and sheepassociatedMCF (SA-MCF) in which the virus is spread by sheep (primarily adolescents).Due to the lack of an in-vitro propagation system for the causative agent of the more economicallysignificant SA-MCF, and with the expectation that cross-protective immunity maybe provided, vaccine development has focused on the more easily propagated alcelaphineherpesvirus-1 (AlHV-1) that causes WA-MCF. In 2008 a direct viral challenge trial showedthat a novel vaccine, employing an attenuated AlHV-1 (atAlHV-1) `C5000 virus strain, protectedBritish Friesian-Holstein (FH) cattle against an intranasal challenge with virulentAlHV-1 `C5000 virus. For cattle keeping people living near wildebeest calving areas insub-Saharan Africa an effective vaccine would have value as it would release them fromthe costly annual disease avoidance strategy of having to move their herds away from theoncoming wildebeest. On the other hand, an effective vaccine will release herd owners fromthe need to avoid MCF, allowing them to graze their cattle alongside wildebeest on the highlynutritious pastures of the calving areas. As such conservationists have raised concerns thatthe development of a vaccine might lead to detrimental grazing competition.The principle objective of this study was to test the novel vaccine on Tanzanian shorthornzebu cross cattle (SZC).We did this firstly using a natural challenge field trial (Chapter Two)which demonstrated that immunisation with the atAlHV-1 vaccine was well tolerated andinduced an oro-nasopharyngeal AlHV-1-specific and -neutralising antibody response. Thisresulted in an immunity in SZC cattle that was partially protective and reduced naturallytransmitted infection by 56%. We also demonstrated that non-fatal infections occurred witha much higher frequency than previously thought. Because the calculated efficacy of thevaccine was less than that seen in British FH cattle we wanted to determine whether hostfactors, particular to SZC cattle, had impacted the outcomes of the field trial. To do thiswe repeated the 2008 direct viral challenge trial using SZC cattle (Chapter Four). Duringthis trial we also investigated whether the recombinant bacterial flagellin monomer (FliC),when used as an adjuvant, might improve the vaccine’s efficacy. The findings from this trialindicated that direct challenge with pathogenic AlHV-1 is effective at inducing MCF in SZCcattle and that FliC is not an appropriate adjuvant for this vaccine. Furthermore, with less control group cattle dying of MCF than expected we speculate that SZC cattle may have adegree of resistance to MCF that affords them protection from infection and developing fataldisease. In Chapter Three we investigated aspects of the epidemiology of MCF, specificallywhether wildebeest placenta, long implicated by Maasai cattle owners as a source of MCF,might play a role in viral transmission. Additionally, through comparative sequence analysis,at two specific genes (A9.5 and ORF50) of wild-type and atAlHV-1, we investigatedwhether the `C5000 strain, the source of which was taken from Africa more than 40 yearsago, was appropriate for vaccine development. The detection of AlHV-1 virus in approximately50% of placentae indicated that infection can occur in-utero and that this tissue mightplay a role in disease transmission. And, despite describing three new alleles of the A9.5gene (supporting previous evidence that this gene is polymorphic and encodes a secretoryprotein with interleukin-4 as the major homologue), the observation that the most frequentlydetected haplotypes, in both wild-type and attenuated AlHV-1, were identical suggests thatAlHV-1 has a slow molecular clock and that the attenuated strain was appropriate for vaccinedevelopment. In Chapter Five we present the first quantitative assessment of the annual MCFavoidance costs that Maasai pastoralists incur. In particular we estimated that as a result ofMCF avoidance 64% of the total daily milk yield during the MCF season was not availableto be used by the 81% of the family unit remaining at the permanent boma. This representsan upper-bound loss of approximately 8% of a household0s annual income. Despite theseconsiderable losses we concluded that, given an incidence of fatal MCF in cattle living inwildebeest calving areas of 5% to 10%, if herd owners were to stop trying to avoid MCF byallowing their cattle to graze alongside wildebeest, any gains made through increased availabilityof milk, improved body condition and reduced energy demands would be offset byan increase in MCF-incidence. With the development of an effective vaccine, however, thisalternative strategy might become optimal.The overall conclusion we draw therefore is that, despite the substantial costs incurredeach year avoiding MCF, the partial protection afforded by the novel vaccine strategy is notsufficient to warrant a wholesale change in disease avoidance strategy. Nonetheless, even thepartial protection provided by this vaccine could be of value to protect animals that cannotbe moved, for example where some of the herd remain at the boma to provide milk or whereland-use changes make traditional disease avoidance difficult. Furthermore, the vaccine mayoffer a feasible solution to some of the current land-use challenges and conflicts, providinga degree of protection to valuable livestock where avoidance strategies are not possible, butwith less risk of precipitating the potentially damaging environmental consequences, such as overgrazing of highly nutritious seasonal pastures, that might result if herd owners decidethey no longer need to avoid wildebeest.
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The impact and control of malignant catarrhal fever in Tanzania
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