Although bovine Onchocerca infections suffer the disadvantages
of any work involving cattle, they provide natural host-parasite systems
in which the full life-cycle of the parasite is permitted. As such, they
are an important resource for the EMCF program, since only the chimpanzee
can be used to support experimental infections with O. volvulus.
Moreover, some of the former limitations of investigations into the immune
response in cattle are fast disappearing with the steady increase in the
range of T cell markers and cytokine assays (either by ELISA or by detection
of message with appropriate PCR primers) which are now available for cattle.
These developments are being watched closely in our laboratory because
they greatly increase the quality of data that we can expect to obtain following
vaccination and/or infection of cattle with Onchocerca parasites.
In conjuction with colleagues from Cameroon, the African bovine filarial
species,
O. ochengi, is now being utilized to both study the immune response
of cattle to Onchocerca parasites and to recombinant antigens, and
to evaluate candidate chemotherapeutic agents. In that it is very closely
related to O. volvulus, O. ochengi is potentially one of
the most useful species as a model infection. This species forms intradermal
nodules which permit ready detection and quantification (one female worm/nodule)
of adult infections and, following nodulectomy, detailed qualitative assessment
of the condition of the worms; all of this can be accomplished without killing
the host. Our primary objective is to exploit these aspects of parasite
biology in the creation of a practical model for onchocerciasis.
Funded by the EMCF, we have begun to experimentally transmit O. ochengi
infections outside the enzootic area in Africa and to evaluate immune responses
to the parasite and to
O. volvulus recombinant antigens. Experimental infections have
been established in Liverpool in cattle infected with L3 larvae generated
in British simuliids inoculated with O. ochengi microfilariae (mf)
cryopreserved in Cameroon. These highly controlled infections are permitting
detailed, longitudinal observations of the immune response, and initial
results indicate notable parallels with O. volvulus infection.
In particular, proliferation of post-infection PBMCs to onchocercid antigen
is downregulated coincident with the onset of microfiladermia. Antibody
responses assayed by ELISA have shown a two-step response which may be related
to the larval molts. In collaboration with Dr. Alfons Renz, an experiment
to investigate the protection produced by irradiated L3 larvae is ready
to begin. In a separate study, Dr. Renz, together with Cameroonian collaborators
and Dr. Bill Harnett at Strathclyde University, has also been studying aspects
of the immune response to natural infections with O. ochengi in
African cattle.
In addition to the projects discussed above, a macrofilaricide screening
study, funded by the WHO Macrofil program, is underway in northern Cameroon.
This area, studied for many years by Alfons Renz, has a high prevalence
of O. ochengi. Initial chemotherapy results have shown that O.
ochengi is susceptible to ivermectin in exactly the same manner as
O. volvulus. Adult worms are not killed (even at sustained high
doses), but embryogenesis is completely arrested and an accumulation in
utero of dead mf is evident. Suramin is only partially macrofilaricidal,
although there are effects on embryogenesis. After nodulectomy, most female
worms are motile and biochemically active (based on MTT reduction); however,
degenerative changes are apparent histologically. This rather poor efficacy
was, at first, surprising but it is clear from a recently published study
that suramin is only partially macrofilaricidal against
O. volvulus in man, at least up to one year post-treatment. By
veterinary standards, suramin is a very poor antihelminthic. Currently,
the prophylactic effects of ivermectin are being investigated in naturally
challenged calves and this experiment promises to shed light on a question
which is very difficult to address in human infections.
To aid the long-term monitoring of putative nodules in all these studies,
we are now investigating the use of subcutaneously implanted transponders
to uniquely identify nodules. These transponders, which are manufactured
for the permanent identification of animals, are introduced adjacent to
nodules through a 12g needle, and their unique ten digit number is read
by superficial scanning. We are hopeful that these will greatly aid studies
on the fate of nodules and their retrospective identification after nodulectomy,
even in multiply infected animals. The microchip identified nodule has
arrived!
A. J. Trees -
A. E. Bianco - Liverpool School of Tropical Medicine
A. Renz - Tubingen
Field studies in Cameroon were done in collaboration with the Director,
Dr. V. Tanya, and the staff of the Institut de Recherches Zootechnique,
Wakwa. Their help has been, and continues to be, invaluable.