The impact and control of malignant catarrhal fever in Tanzania

Lankester, Felix John (2016) The impact and control of malignant catarrhal fever in Tanzania. PhD thesis, University of Glasgow.

Abstract

Malignant Catarrhal Fever (MCF), an often-lethal infectious disease, presents as a variable
complex of lesions in susceptible ungulate species. The disease is caused by a
-herpesvirus
following transmission from an inapparent carrier host. Two major epidemiological forms
exist: wildebeest-associated MCF (WA-MCF), in which the virus is transmitted to susceptible
species by wildebeest calves less than approximately four months of age, and sheepassociated
MCF (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 economically
significant SA-MCF, and with the expectation that cross-protective immunity may
be provided, vaccine development has focused on the more easily propagated alcelaphine
herpesvirus-1 (AlHV-1) that causes WA-MCF. In 2008 a direct viral challenge trial showed
that a novel vaccine, employing an attenuated AlHV-1 (atAlHV-1) `C5000 virus strain, protected
British Friesian-Holstein (FH) cattle against an intranasal challenge with virulent
AlHV-1 `C5000 virus. For cattle keeping people living near wildebeest calving areas in
sub-Saharan Africa an effective vaccine would have value as it would release them from
the costly annual disease avoidance strategy of having to move their herds away from the
oncoming wildebeest. On the other hand, an effective vaccine will release herd owners from
the need to avoid MCF, allowing them to graze their cattle alongside wildebeest on the highly
nutritious pastures of the calving areas. As such conservationists have raised concerns that
the development of a vaccine might lead to detrimental grazing competition.
The principle objective of this study was to test the novel vaccine on Tanzanian shorthorn
zebu 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 and
induced an oro-nasopharyngeal AlHV-1-specific and -neutralising antibody response. This
resulted in an immunity in SZC cattle that was partially protective and reduced naturally
transmitted infection by 56%. We also demonstrated that non-fatal infections occurred with
a much higher frequency than previously thought. Because the calculated efficacy of the
vaccine was less than that seen in British FH cattle we wanted to determine whether host
factors, particular to SZC cattle, had impacted the outcomes of the field trial. To do this
we repeated the 2008 direct viral challenge trial using SZC cattle (Chapter Four). During
this 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 trial
indicated that direct challenge with pathogenic AlHV-1 is effective at inducing MCF in SZC
cattle 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 a
degree of resistance to MCF that affords them protection from infection and developing fatal
disease. In Chapter Three we investigated aspects of the epidemiology of MCF, specifically
whether 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 investigated
whether the `C5000 strain, the source of which was taken from Africa more than 40 years
ago, was appropriate for vaccine development. The detection of AlHV-1 virus in approximately
50% of placentae indicated that infection can occur in-utero and that this tissue might
play a role in disease transmission. And, despite describing three new alleles of the A9.5
gene (supporting previous evidence that this gene is polymorphic and encodes a secretory
protein with interleukin-4 as the major homologue), the observation that the most frequently
detected haplotypes, in both wild-type and attenuated AlHV-1, were identical suggests that
AlHV-1 has a slow molecular clock and that the attenuated strain was appropriate for vaccine
development. In Chapter Five we present the first quantitative assessment of the annual MCF
avoidance costs that Maasai pastoralists incur. In particular we estimated that as a result of
MCF avoidance 64% of the total daily milk yield during the MCF season was not available
to be used by the 81% of the family unit remaining at the permanent boma. This represents
an upper-bound loss of approximately 8% of a household0s annual income. Despite these
considerable losses we concluded that, given an incidence of fatal MCF in cattle living in
wildebeest calving areas of 5% to 10%, if herd owners were to stop trying to avoid MCF by
allowing their cattle to graze alongside wildebeest, any gains made through increased availability
of milk, improved body condition and reduced energy demands would be offset by
an increase in MCF-incidence. With the development of an effective vaccine, however, this
alternative strategy might become optimal.
The overall conclusion we draw therefore is that, despite the substantial costs incurred
each year avoiding MCF, the partial protection afforded by the novel vaccine strategy is not
sufficient to warrant a wholesale change in disease avoidance strategy. Nonetheless, even the
partial protection provided by this vaccine could be of value to protect animals that cannot
be moved, for example where some of the herd remain at the boma to provide milk or where
land-use changes make traditional disease avoidance difficult. Furthermore, the vaccine may
offer a feasible solution to some of the current land-use challenges and conflicts, providing
a degree of protection to valuable livestock where avoidance strategies are not possible, but
with less risk of precipitating the potentially damaging environmental consequences, such as overgrazing of highly nutritious seasonal pastures, that might result if herd owners decide
they no longer need to avoid wildebeest.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: malignant catarrhal fever, alcelaphine herpesvirus 1, herpresvirus, wildebeest, vaccine field trial, vaccine efficacy, Tanzania, economic impact assessment, hedonic price function analysis, bacterial flagellin, flic, Emulsigen, adjuvant, pastoralist, Maasai, milk, shorthorn zebu cross cattle, livestock, placenta.
• Subjects: H Social Sciences > H Social Sciences (General); H Social Sciences > HB Economic Theory; H Social Sciences > HQ The family. Marriage. Woman; R Medicine > R Medicine (General); S Agriculture > S Agriculture (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
• Supervisor's Name: CLeaveland, Prof. Sarah and Russell, Dr. George
• Date of Award: 2016
• Depositing User: Dr. Felix Lankester
• Unique ID: glathesis:2016-7769
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 15 Nov 2016 16:41
• Last Modified: 15 Dec 2016 10:04
• URI: https://theses.gla.ac.uk/id/eprint/7769

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