Great Ape Self-Medication and Human Traditional Medicine- A Bio-Cultural
Approach to Evaluating Herbal Anthelmintics for Humans and Production
Animals in Africa
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Huffman1, M.A., Waller2, P.J, Ohigashi1, H., Yole3, D., Mwenda3, J.,
Nkunya4, M.H.H., Mbago4, F., Elias5 R., Gasquet5 M., Boegh6, H.,
Kalunde7 M.S.,
1 Kyoto University (Japan), 2SWEPAR, National Veterinary Institute
(Sweden), 3Institute of Primate Research (Kenya), 4University of Dar es
Salaam (Tanzania), 5Universite de la Mediterranee Aix-Marseille II
(France), 6Danish Center for Experimental Parasitology (Denmark), 7
Tanzania National Parks (Tanzania)
Parasite resistance to modern anthelmintics is an increasingly serious
problem in human health care and particularly livestock husbandry in
Africa and around the world. The study of host-parasite relationships in
nature can provide alternatives and important insights into dealing with
this problem. Multi-disciplinary investigations of chimpanzee behavioral
strategies in the wild and ethnoveterinary / ethnomedicinal surveys of
traditional African medicine for the control of parasite infection are
being conducted by our multiregional, multidiscplinary research group.
This paper reviews some recent findings and outlines future directions
of our research.
In wild chimpanzees of western Tanzania and Uganda, ingestion of the
medicinal plant Vernonia amygdalina and the non-nutritional use of
bristly leaves from other species has been shown to reduce worm burdens
of Oesophagostomum and Bertiella spp. providing temporary relief from
gastrointestinal upset in this primate species (Huffman et al., 1993;
1996a; Wrangham, 1995). In vitro pharmacological assays demonstrated
antischistosomal and antimalarial activities in some of these plant
species (Ohigashi et al., 1994). For numerous African ethnic groups, a
concoction made from V. amygdalina is prescribed treatment for malarial
fever, schistosomiasis, amoebic dysentery, several other intestinal
parasites and stomach aches. These striking similarities between the use
of this plant species in both chimpanzees and humans suggest strong
bio-cultural patterns in the selection and use of some natural medicines
(Huffman, Koshimizu, Ohigashi, 1996). Cross-comparison of primate and
human medicinal plant use for similar diseases makes use of two highly
selective strategies of parasite control for the identification and
evaluation of promising anthelmintics.
A variety of non-nutritional plant secondary compounds are found in the
primate diet, but little is known about the possible medicinal
consequences of their ingestion. Detailed behavioral, pharmacological
and parasitological investigations are currently underway to elucidate
the full potential of the primate diet for the prevention and control of
illness and in particular parasite infection. The hypothesis currently
being developed from our investigations of self-medication in the great
apes (chimpanzee, bonobo, lowland gorilla, orangutan) is that such
behavior aids in the control of intestinal parasites and provides relief
from gastrointestinal upset (Huffman et al., 1996a).
Parasites are the cause of a variety of diseases that affect the
behavior and reproductive fitness of an individual and make the need to
counteract such pressure of extreme importance to the host. Such
adaptive responses to parasite infection are undoubtedly the products of
a long evolutionary process. The amount of detailed information on
self-medication gathered thus far is greatest for the African great
apes, however, given the obvious adaptive significance that
self-medication implies, it is expected to occur in other non-human
primates and other animal species as well (Huffman, 1997).
It has been convincingly argued that the herbal medicines and modern
pharmaceuticals used by humans today have replaced the non-nutritive
chemicals commonly present in extant primate and early hominid diets.
There is a fine line between what may be ‘medicine’ and what is ‘food’
in primates, making the difference often seem transparent. Much of what
is consumed daily contains an array of secondary compounds. J. Berry
(Division of Biological Sciences, Cornell University) has found up to
30% of the herbaceous diet of mountain gorillas to possess antibacterial
properties. In many traditional human societies as well food and
medicine greatly overlap in the diet. For example, in Japanese the
saying ‘ishoku dougen’ means medicine and food are of the same origin.
N. Etkin (University of Hawaii) found that 30% of the plant species
identified as foods among the Hausa of Nigeria in Western Africa were
also used as medicine. Likewise, 89% of species used to treat symptoms
of malaria were also used in a dietary context (Etkin, 1996; Etkin and
Ross, 1983). From this view point, it is clear that we have much to
gain by taking a closer look at the pharmacological characteristics of
both the proposed self-medicative and daily dietary items and behavior
of animals in the wild.
GREAT APE CHEMICAL ECOLOGY
Chimpanzees, bonobos and lowland gorillas are largely frugivorous but
also consume the leaves, pith, seeds, flowers, bark and sap of many
species. A variety of interesting secondary compounds have been
isolated from some of these plant parts (Koshimizu et al., 1993;
Koshimizu, Ohigashi, Huffman, 1994; Ohigashi et al., 1991). Secondary
compounds as well as inorganic materials are a plant’s defense against
most herbivorous predators. These products are toxic to the consumer or
inhibit consumption by reducing palatability or digestibility, yet a
number of items under this category can be found in the great ape diet.
Many are also recognized ethnomedicinal plants.
Ethnomedicinal uses of secondary compound rich fruits and leaves
The secondary compound rich content of nutritious foods in the diet
eaten under apparently normal situations may play a significant role in
the maintenance of health. A literature search was made for plant foods
reported to be ingested by the Mahale chimpanzees in western Tanzania
using references on African ethnomedicine in order to estimate the
potential contribution to parasite control by medicinal plants included
in the diet.
From the 192 recognized plant food species, 172 were selected for this
analysis on the basis that they are not cultigens and that a positive
scientific identification has been made. While it was common for some
species to have multiple ethnomedicinal uses, 43 (22%) of these 172
species were reported to be used to treat parasitic or gastrointestinal
related illnesses. While not all 43 species may be ingested by
chimpanzees in such a way as to benefit from these potential medicinal
properties, 33% (20/63) of the plant parts ingested from 16 of these
species corresponded to the parts utilized by humans for the treatment
of intestinal parasites and gastrointestinal illness (Huffman et al.,
1998).
Interestingly, for those 16 species there is a significant trend for
them to be ingested more frequently during the rainy season months, as
are the medicinally used species described below which are proposed to
be used solely for the control of nodular worm infections (Huffman et
al., 1996b).
SELF-MEDICATIVE BEHAVIORS OF THE AFRICAN GREAT APES
Among chimpanzees, gorillas and bonobos, two proposed types of
self-medicative behavior, bitter pith chewing and leaf swallowing, have
been documented to date.
The behavioral ecology of bitter pith chewing
Bitter pith chewing aids in the control of intestinal nematode
infection and relief from gastrointestinal upset via pharmacological
action. The hypothesis that bitter pith chewing has medicinal value for
chimpanzees was first proposed from detailed behavioral observations and
later from parasitological and phytochemical analyses of patently ill
chimpanzees ingesting Vernonia amygdalina Del. (Asteraceae) at Mahale by
Huffman and Mohamedi Seifu Kalunde (Huffman and Seifu, 1989).
When ingesting the pith of young shoots of V. amygdalina, Mahale
chimpanzees first remove the outer bark and leaves to chew only on the
exposed inner part, from which they extract the bitter juice. The amount
of pith ingested for a single dose is relatively small, ranging from
portions of 5 to 120 cm in length X 1 cm in diameter. The entire
process, depending on the amount ingested takes anywhere from less that
one to 8 minutes.
Regardless of year-round availability, use by chimpanzees is rare and
highly seasonal. Bitter pith chewing occurs mainly just after the onset
of the rainy season. A three year longitudinal study of the individual
parasite infection levels of Mahale chimpanzees has demonstrated a
significant rainy season increase in the incidence of infections for
individuals infected by Oesophagostomum stephanostomum (nodule worm),
but not for other nematode species. Nodular worm infections were
associated significantly more frequently with bitter pith chewing and
leaf swallowing, than either Strongyloides fullebornii (whip worms) or
Trichuris trichiura (thread worms).
Detailed observations of bitter pith chewers demonstrate ill health
(diarrhea, malaise and nematode infection) at the time of use. In two
closely monitored cases of bitter pith chewing in sick individuals,
recovery was noted within 20-24 hr. In one case the eggs per gram feces
(EPG) level of a nodular worm infection was found to have dropped from a
count of 130 to 15 within 20 hours. No change occurred in this
individual’s concurrent whip worm infection. In most individuals
monitored at the same time, nodular worm EPG levels increased over time
(Huffman and Seifu, 1989; Huffman et al., 1993). The recognized
increases in EPG levels represent the overall trend for increased
reinfection by nodular worms at the beginning of the rainy season. It is
at this time that individuals begin to reduce the number of worms
parasitizing them.
The behavioral ecology of leaf swallowing
Leaf swallowing also aids in the control of nodule worm infections and
is believed to relieve pain caused by tapeworm infection via the
expulsion of these intestinal parasites. Both phytochemical and physical
mechanisms for parasite removal have been proposed.
Leaf swallowing behavior was first recorded for chimpanzees at Gombe
and Mahale. As of January 1, 2000, leaf swallowing behavior involving 34
different plant species has been noted to occur in 9 populations of
chimpanzees, 3 of bonobos and one of eastern lowland gorillas at 13
sites across Africa. The common property linking all of these plants is
their bristly, rough-surfaced leaves (Huffman, 1997). The hairs or
trichomes on the leaf surface vary from long and slender, thorn like,
hooked to sharply spiked.
The distal half of these leaves are selected one at a time, folded by
tongue, lips and palate as they are slowly pulled into the mouth and
then individually swallowed whole. An individual may swallow anywhere
from one to 55 leaves in a single bout, repeatedly over a day. Like
bitter pith chewing, leaf swallowing is an extremely rare behavior.
Although the leaves of all species selected are available year-round,
like bitter pith chewing at Mahale, use is most common after the
beginning of the rainy season.
Behavioral and health profiles collected concurrently with direct
observations of leaf swallowing reveal signs of diarrhea, malaise and
suggestion of abdominal pain. Nematode infection has been demonstrated
in 83% of all leaf swallowing cases observed directly or documented
indirectly from dung containing leaves. The occurrence of adult worms in
the dung is rare (3% 9/254) and has thus far been limited to leaf
swallowing. All such worms recovered have been identified as nodular
worms of the species O. stephanostomum.
A strong relationship is recognized between leaf swallowing and the
expulsion of these nodular worms. The relationship is statistically
highly significant. Leaves are typically swallowed first thing in the
morning on an empty stomach. This is observed to result in at least a
17.4 h reduction in transit time. The leaves have been measured to pass
through the GI tract as quickly as 6 hours. All worms recovered are
alive and motile at the time of inspection eliminating the possibility
of a chemically induced nematocidal property in the leaves. Instead,
the purging of worms largely via the leaves’ physical properties is
hypothesized to be the main mechanism of leaf swallowing (Huffman and
Caton, in press).
Similar reports exist for the expulsion of Ascaris by a leaf swallowing
domestic dog in Tanzania, of tapeworms by brown bears in Alaska and
similarly by snow geese in Canada (Huffman, 1997; Huffman and Caton, in
press).
PHARMACOGNOSY AND ETHNOPHARMACOLOGY OF CHIMPANZEE SELF-MEDICATIVE
BEHAVIORS
Bitter pith chewing
Among numerous African ethnic groups, a concoction made from V.
amygdalina is used to treat malarial fever, schistosomiasis, amoebic
dysentery, several other intestinal parasites and stomachaches. The
noted recovery time of 20-24 hours after bitter-pith chewing in two M
group chimpanzees is comparable to that of local human inhabitants, the
Tongwe, who use cold concoctions of this plant as a treatment for
parasite infection, diarrhea and stomach upset (Huffman et al., 1993).
Some of the other species with bitter piths ingested by chimpanzees
elsewhere have a number of ethnomedicinal and pharmacological properties
worth mentioning. V. colorata and V. amygdalina, very closely related
species, are not distinguished from each other by traditional African
healers with regard to their medicinal properties and folk
classification (Dalziel, 1937). Alkaloids found in the pith, as well as
flower and leaf of V. hochstetteri may possess some sort of biological
activity. P. hirsuta and E. macrocarpa are used in west African
ethnomedicine for the treatment of upset stomachs, colic, as an
antiseptic and analgesic and for venereal disease. Molluscicidal
activity has also been reported for P. hirsuta (Abbiw, 1990; Okunji and
Iwu, 1988).
Phytochemical analysis of V. amygdalina samples collected at Mahale
from plants known to be used by chimpanzees reveal the presence of two
major classes of bioactive compounds. To date, a total of 4 known
sesquiterpene lactones, 7 new stigmastane-type steroid glucosides and 2
freely occurring aglycones of these glucosides have been isolated
(Jisaka et al., 1992 a; 1993).
Supportive of the ethnomedicinal literature, the sesquiterpene
lactones present in V. amygdalina, V. colorata and a number of other
Vernonia spp., are well known for their anthelmintic, antiamoebic,
antitumor, and antibiotic properties (e.g. Burkill, 1985; Dalziel, 1937;
Watt and Breyer-Brandwijk, 1962). From crude methanol extracts of the
leaves, we also found inhibition of tumor promotion and immunosupressive
activities (Jisaka et al., 1992 a, b).
In vitro tests on the antischistosomal activity of the pith's most
abundant steroid glucoside (vernonioside B1) and sesquiterpene lactone
(vernodaline) showed significant inhibition of movement of the adult
parasites and adult females’ egg-laying capacity (Jisaka et al., 1992
b). These findings are consistent with the observed decline in nodular
worm EPG level 20 hours after an adult female chimpanzee at Mahale
ingested V. amygdalina pith (Huffman et al., 1993).
While abundant in the leaves and bark, the highly toxic vernodaline
occurs in only insignificant amounts in the pith. This may explain why
chimpanzees normally avoid ingesting leaves and bark in preference for
the pith, with its greater abundance of steroid glucosides and their
aglycones (Ohigashi et al., 1994).
In vitro tests on the antiparasitic activity of both the sesquiterpene
lactones and the steroid glucosides, using Leishmania infantum,
Entamoeba histolytica, and a K1 multi-drug resistant strain of
Plasmodium falciparum have also been conducted. The sesquiterpene
lactones showed significant plasmodicidal activity although the IC50
values were more than 20 times higher than that of the common commercial
agent, chloroquine diphosphate. The steroid glucosides showed weaker
plasmodicidal activity. However, as in the case described above, the
activity of their aglycones was significantly higher in both
plasmodicidal and amoebicidal testing. In particular, a significant
increase in the plasmodicidal activity of vernoniol A4 was noted
(Ohigashi et al., 1994).
Leaf swallowing
Behavioral, parasitological and physiological observations pertaining
to leaf swallowing have been integrated to elucidate the mechanism
likely responsible for the expulsion and control of nodule worm
infections by the ape host. Physical irritation produced by bristly
leaves swallowed on an empty stomach, were associated with an increase
in motility and secretion resulting in diarrhea which rapidly moved the
swallowed leaves through the GI tract in about 6 hours, or about 17
hours faster than normal. In the proximal hindgut, the site of L3
(third stage larvae) cyst formation and adult worm attachment, motility,
secretion and the scouring effect of rough leaves is proposed to be
greatly enhanced by haustral contractions and peristalsis-
antiparistaltis. Frequently, at the peak of reinfection, a proportion
of non-encysted L3 (stage of parasite that is ingested by the host
leading to infection) is predictably vulnerable to this. These factors
are proposed to result in the disruption of the life cycle of
Oesophagostomum spp. Repeated flushing during peak periods of
reinfection is believed responsible for the observed long-run reduction
of worm burdens at certain times of the year (Huffman et al., 1997). In
this light, leaf-swallowing can be viewed as a deliberate adaptive
behavioral strategy with physiological consequences for the host. The
expulsion of worms based on the activation of basic physiological
responses in the host is a novel hitherto undescribed form of parasite
control (Huffman and Caton, in press).
NEW STRATEGIES FOR THE TREATMENT OF PARASITE DISEASE AND ANTHELMINTIC
RESISTANCE?
Some nodular worm species are a significant pathogen in domestic
livestock, non-human primate and occasionally human hosts. Symptoms of
moderate to heavy infections of O. stephanostomum, O. bifurcum and O.
aculeatum reportedly range from weight loss, enteritis, diarrhea, anemia
and lethargy to anorexia and intense pain simulating appendicitis.
Pathology includes hemorrhagic cysts containing larvae, septicimia
resultant from bacterial invasion of lesions in the colon, blockage of
the colon due to gross thickening of the wall, epigastric or
periumbilical masses clearly visible from the outside. Gross lesions in
submucosal or suberserosal nodules (5 - 20 mm diameter) are associated
with the larvae. These cysts or nodules contain caseous, necrotic
centers in a fibrous capsule. Histology includes intense inflamatory
cell reaction accompanied by high levels of neutrophils and eosinophils
associated with the nodules (above reviewed from Polderman and Blotkamp,
1995). Control of such infections by the host is of obvious adaptive
significance.
Anthelmintic resistance is a serious problem for livestock management
and resistance to drugs used in treating life threatening diseases such
as schistosomiasis and malaria in humans is a global problem urgently in
need of solutions (Geerts and Dorny, 1995; Jackson, 1993). The
widespread geographical occurrence and broad taxonomical representation
of great ape species exhibiting leaf swallowing and bitter pith chewing
behaviors suggests that these self-medicative behaviors represent a
stable biological strategy for parasite control. Can the study of
self-medication in the great apes and other animals offer new ways of
countering chemoresistance?
According to S. Geerts and colleagues factors selecting for
anthelmintic resistance are mass treatment, frequent use of the same
class of drugs over long periods of time and under dosing (Geerts and
Dorny, 1995). Theoretically therefor the converse approach may help
stem anthelmintic resistance. Indeed, it has been recommended that:
I. minimizing treatments,
II. rotating or combining different chemotherapies, and
III. proper dosage
be practiced to stem or control anthelmintic resistance in livestock and
human treatment programs (Geerts, Coles and Gryseels, 1997; Kremsner et
al., 1997). The observations of chimpanzee self-medication support these
recommendations and suggest that further detailed behavioral and
chemo-ecological studies of great ape behavior may provide significant
insight into more natural systems of parasite control which inhibit the
development of parasite chemoresistance and effectively maintain the
health of animals under human care.
A number of ethnomedicinally recognized plants used for the treatment
of intestinal parasite infections and related illness were found in the
diet of great apes (Huffman et al., 1998). A preliminary look at both
the real and potential pharmacological activity of plants used and the
ways they are ingested suggests that the Mahale chimpanzees’
self-medicative and dietary behavior mirrors recommendations I and II
above. The ‘control of nematode infection hypothesis’ predicts that
since nodular worm infections are typically self-limiting, the total
infection may be controllable if a chimpanzee responds to these symptoms
during the most likely period of reinfection. At Mahale, the peak period
of reinfection by the nodular worm O. stephanostomum was largely limited
in time to the one or two months after the onset of the rainy season.
The occurrence of bitter pith chewing and leaf swallowing at Mahale
peaks during these first few months of the rainy season and supports the
principle of minimizing treatment to periods of peak infection. That is,
chimpanzees are likely responding only to the discomfort of higher level
infections, thus maintaining them as best as possible at manageable
sub-clinical levels most of the year.
Bitter pith chewing and leaf swallowing compliment each other in
proposed function but appear to differ greatly in their mode of action.
As noted above, the pith of V. amygdalina contains constituents from at
least two distinct classes of bioactive compounds, the sesquiterpene
lactones and the steriod glucosides. Both bitter pith chewing and leaf
swallowing are sometimes displayed by the same individual on the same
day. With the apparent bimodal action of these two different behaviors
together they may act more effectively towards the control of nodular
worm infections. This trend parallels the principle of combining
treatments and employing complex chemotherapy. As this study suggests,
this may be even further enhanced by the contribution of a secondary
compound rich diet.
FUTURE DIRECTIONS AND GOALS
As the forgoing discussions have suggested, the study of the
pharmacognosy of great ape diet, self-medicative behaviors and their
corrrelations with documented ethnomedicinal practices promise to
provide important leads to future sources of natural medicine for the
treatment of parasitosis. In addition to this, a closer look into the
manner in which great apes use these natural products or combine them
with antiparasitic behavior may provide novel insights into viable
strategies for suppressing or slowing down the rate of acquisition of
chemoresistance by these parasites.
The next step is to conduct in vivo tests to determine direct
anthelmintic efficacy in a wide range of parasites, using a number of
different host species. Preliminary studies using the pig as a model
for monogastric animals (including man) have been conducted on
preparations of V. amygdalina at the Center for Experimental
Parasitology, Denmark. Preliminary results were inconclusive but future
tests using this and other plant species are in the planning stages.
The freshness of samples, the way they are preserved and transported as
well as the location of collection may have important effects on
material used. These and other factors will be further investigated.
Differences in metabolism, drug pharmacokinetics etc. between
monogastric and ruminant livestock necessitates further screening
activities in the latter class of animals. Protocols for testing
herbal preparations against nematode parasites of ruminants, using sheep
as the model system, are underway in the Department of Parasitology,
National Veterinary Institute, Sweden and the International Livestock
Research Institute, Kenya. We are also currently planning for the
initiation of in vitro / in vivo model testing of plant extract and raw
plant material as foliage on schistosomiasis in baboons and
leishmaniasis in vervet monkeys.at the Institute of Primate Research,
National Museums of Kenya, Karen Nairobi.
Basic broad spectrum biological assays of insecticidal and
plasmodicidal activity of promising plants and the elucidation of their
chemical constitutents are undereway in the Laboratoire de
Pharmacognosie - Homeopathie, Parasitologie Universite de la
Mediterranee (Aix-Marseile II), France and the Department of Chemistry
University of Dar es Salaam, Tanzania. Technical support on parasite
and plant identification is provided by the Departments of Zoology and
Botany-Herbarium at the University of Dar es Salaam, Tanzania.
Collaborative support from interested institutions and individuals in
other areas of Africa are always welcome.
This truly multidisciplinary approach to research, where biological
activity of novel, plant derived compounds is being assessed against a
whole range of parasite species found across a wide range of hosts,
maximises the chance of success. At the same time the research
consortium recognizes the importance of preserving the intellectual
property rights of the regions/countries to any new discoveries derived
from indigenous plant material. A prime objective of this research is
to integrate our results into local health care and livestock management
systems so that locally available plants can be properly used to the
benefit of all.
REFERENCES
Abbiw DK (1990) Useful Plants of Ghana. Kew: Intermediate Technology
Publications and Royal Botanic Gardens.
Burkill HM (1985) The Useful Plants of West Tropical Africa. (2nd ed.),
Vol 1. Kew, Royal Botanical Gardens.
Dalziel JM (1937) The Useful Plants of West Tropical Africa. In J
Hutchinson and JM Dalziel (eds.): Appendix to Flora of West Tropical
Africa. London, Whitefriars Press.
Etkin N.L. 1996. Medicinal cuisines: Diet and ethnopharmacology. Int. J.
Pharmacog. 34(5): 313-326.
Etkin, N.L., Ross, P.J. 1983. Malaria, Medicine, and Meals: Plant use
among the Hausa and its impact on disease. Pages 231-259 in
Romanucci-Ross, L., Moerman, D.E. and Tancredi L.R. eds, The
Anthropology of Medicine: From Culture to Method, New York: Praeger.
Geerts, S. and Dorny, P (1995) Anthelmintic resistance in helminths of
animals and man in the tropics. Bull. Sean. Acad. R. Sci. Otr-Mer
Meded. Zitt. K. Acad. Overzeese Wet. 41: 401-424.
Geerts, S., Coles, G.C., and Gryseels, B. (1997). Anthelmintic
resistance in human helminths: Learning from the problems with worm
control in livestock. Parasitology Today, 13: 149-151.
Huffman MA (1997) Self-medication in primates. Yrbk. Physical Anthro.
40: 171-200.
Huffman MA, and Seifu M (1989) Observations on the illness and
consumption of a possibly medicinal plant Vernonia amygdalina (Del.), by
a wild chimpanzee in the Mahale Mountains National Park, Tanzania.
Primates, 30:51-63.
Huffman MA, Gotoh S, Izutsu D, Koshimizu K, amd Kalunde MS (1993)
Further observations on the use of Vernonia amygdalina by a wild
chimpanzee, its possible effect on parasite load, and its
phytochemistry. African Study Monogr. 14(4): 227-240.
Huffman MA, Page JE, Sukhdeo MVK, Gotoh, S, Kalunde MS, Chandrasiri, T,
Towers GHN (1996a) Leaf-swallowing by chimpanzees: A behavioral
adaptation for the control of strongyle nematode infections. Int. J.
Primatol.. 72(4): 475-503.
Huffman MA, Koshimizu K, and Ohigashi H (1996b) Ethnobotany and
zoopharmacognosy of Vernonia amygdalina, a medicinal plant used by
humans and chimpanzees. In PDS Caligari and DJN Hind (Eds.): Compositae:
Biology & Utilization Vol 2., Kew, The Royal Botanical Gardens, pp.
351-360.
Huffman MA, Gotoh S, Turner LA, Hamai M, and Yoshida K (1997) Seasonal
trends in intestinal nematode infection and medicinal plant use among
chimpanzees in the Mahale Mountains, Tanzania. Primates 38(2): 111-125.
Huffman, M.A., Ohigashi, H., Kawanaka, M., Page, J.E., Kirby, G.C.,
Gasquet, M., Murakami, A. & Koshimizu, K. (1998). African great ape
self-medication: A new paradigm for treating parasite disease with
natural medicines. In: Towards Natural Medicine Research in the 21st
Century, Ebizuka, Y. (ed.), Elsevier Science B.V. Excerpta Medica,
Amsterdam, pp. 113-123.
Huffman MA (1997) Self-medication in primates. Yrbk. Physical Anthro.
40: 171-200.
Huffman and Caton, in press, Self-induced Increase of Gut Motility and
the Control of Parasite Infections in Wild Chimpanzees. Int. J.
Primatol.
Jackson, F (1993) Anthelmintic resistance. The state of play. British
Veterinary Journal 149: 123-138.
Jisaka M, Ohigashi H, Takagaki T, Nozaki H, Tada T, Hirota M, Irie R,
Huffman MA, Nishida T, Kaji M, and Koshimizu K (1992a) Bitter steroid
glucosides, vernoniosides A1, A2, and A3 and related B1 from a possible
medicinal plant Vernonia amygdalina, used by wild chimpanzees.
Tetrahedron, 48:625-632.
Jisaka, M, Kawanaka M, Sugiyama H, Takegawa K, Huffman MA, Ohigashi H,
Koshimizu K (1992b) Antischistosomal activities of sesquiterpene
lactones and steroid glucosides from Vernonia amygdalina, possibly used
by wild chimpanzees against parasite-related diseases. Biosci., Biotech.
and Biochem. 56(5): 845-846.
Jisaka, M., H. Ohigashi, H. Takegawa, M. Hirota, R. Irie, M.A. Huffman,
K. Koshimizu., 1993. Further steroid glucosides from Vernonia
amygdalina, a possible chimpanzee medicinal plant. Phytochemistry
34:409-413.
Koshimizu K, Ohigashi H, Huffman MA, Nisihda T, Takasaki H (1993)
Physiological activities and the active constituents of potentially
medicinal plants used by wild chimpanzees of the Mahale Mountains,
Tanzania. Int. J. Primatol. 14(2): 345-356.
Koshimizu K, Ohigashi H, and Huffman MA (1994) Use of Vernonia
amygdalina: Possible roles of its bitter and related constituents.
Physiology & Behavior. 56(6): 1209-1216.
Kremsner, P.G., Lufty, AJF and Graninger, W. (1997) Combination
chemotherapy for Plasmodium falciparum Malaria. Parasitology Today.
13(5): 167- 168.
Ohigashi, H., Takagaki, T., Koshimizu, K., Watanabe, K., Kaji M.,
Hoshino, J., Nishida, T., Huffman, M.A., Takasaki, H., Jato, J., and
Muanza, D.N. (1991 a). Biological activities of plant extracts from
tropical Africa. Afric. Study Monogr. 12(4):201-210.
Ohigashi H, Huffman MA, Izutsu D, Koshimizu K, Kawanaka M, Sugiyama H,
Kirby GC, Warhurst DC, Allen D, Wright CW, Phillipson JD, Timmon-David
P, Delnas F, Elias R, Balansard G (1994a) Toward the chemical ecology of
medicinal plant-use in chimpanzees: The case of Vernonia amy gdalina
Del.. A plant used by wild chimpanzees possibly for parasite-related
diseases. J. Chem. Ecol. 20: 541-553.
Okunji CO, and Iwu MM (1988) Control of schistomsomiasis using Nigerian
medicinal molluscicides. Int. J. Crude Drug Research 26(4): 246-252.
Polderman AM & Blotkamp J. (1995). Oesophagostomum infections in humans.
Parasitology Today 11(12): 451-456.
Watt, J.M. & Breyer-Brandwinjk, M.G. (1962). The Medicinal and Poisonous
Plants of Southern and East Africa. E. and S. Livingstone Ltd.,
Edinburgh.
Wrangham, R.W. (1995). Relationship of chimpanzee leaf-swallowing to a
tapeworm infection. Am. J. Phys. Primatol. 37: 297-303.
Approach to Evaluating Herbal Anthelmintics for Humans and Production
Animals in Africa
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Huffman1, M.A., Waller2, P.J, Ohigashi1, H., Yole3, D., Mwenda3, J.,
Nkunya4, M.H.H., Mbago4, F., Elias5 R., Gasquet5 M., Boegh6, H.,
Kalunde7 M.S.,
1 Kyoto University (Japan), 2SWEPAR, National Veterinary Institute
(Sweden), 3Institute of Primate Research (Kenya), 4University of Dar es
Salaam (Tanzania), 5Universite de la Mediterranee Aix-Marseille II
(France), 6Danish Center for Experimental Parasitology (Denmark), 7
Tanzania National Parks (Tanzania)
Parasite resistance to modern anthelmintics is an increasingly serious
problem in human health care and particularly livestock husbandry in
Africa and around the world. The study of host-parasite relationships in
nature can provide alternatives and important insights into dealing with
this problem. Multi-disciplinary investigations of chimpanzee behavioral
strategies in the wild and ethnoveterinary / ethnomedicinal surveys of
traditional African medicine for the control of parasite infection are
being conducted by our multiregional, multidiscplinary research group.
This paper reviews some recent findings and outlines future directions
of our research.
In wild chimpanzees of western Tanzania and Uganda, ingestion of the
medicinal plant Vernonia amygdalina and the non-nutritional use of
bristly leaves from other species has been shown to reduce worm burdens
of Oesophagostomum and Bertiella spp. providing temporary relief from
gastrointestinal upset in this primate species (Huffman et al., 1993;
1996a; Wrangham, 1995). In vitro pharmacological assays demonstrated
antischistosomal and antimalarial activities in some of these plant
species (Ohigashi et al., 1994). For numerous African ethnic groups, a
concoction made from V. amygdalina is prescribed treatment for malarial
fever, schistosomiasis, amoebic dysentery, several other intestinal
parasites and stomach aches. These striking similarities between the use
of this plant species in both chimpanzees and humans suggest strong
bio-cultural patterns in the selection and use of some natural medicines
(Huffman, Koshimizu, Ohigashi, 1996). Cross-comparison of primate and
human medicinal plant use for similar diseases makes use of two highly
selective strategies of parasite control for the identification and
evaluation of promising anthelmintics.
A variety of non-nutritional plant secondary compounds are found in the
primate diet, but little is known about the possible medicinal
consequences of their ingestion. Detailed behavioral, pharmacological
and parasitological investigations are currently underway to elucidate
the full potential of the primate diet for the prevention and control of
illness and in particular parasite infection. The hypothesis currently
being developed from our investigations of self-medication in the great
apes (chimpanzee, bonobo, lowland gorilla, orangutan) is that such
behavior aids in the control of intestinal parasites and provides relief
from gastrointestinal upset (Huffman et al., 1996a).
Parasites are the cause of a variety of diseases that affect the
behavior and reproductive fitness of an individual and make the need to
counteract such pressure of extreme importance to the host. Such
adaptive responses to parasite infection are undoubtedly the products of
a long evolutionary process. The amount of detailed information on
self-medication gathered thus far is greatest for the African great
apes, however, given the obvious adaptive significance that
self-medication implies, it is expected to occur in other non-human
primates and other animal species as well (Huffman, 1997).
It has been convincingly argued that the herbal medicines and modern
pharmaceuticals used by humans today have replaced the non-nutritive
chemicals commonly present in extant primate and early hominid diets.
There is a fine line between what may be ‘medicine’ and what is ‘food’
in primates, making the difference often seem transparent. Much of what
is consumed daily contains an array of secondary compounds. J. Berry
(Division of Biological Sciences, Cornell University) has found up to
30% of the herbaceous diet of mountain gorillas to possess antibacterial
properties. In many traditional human societies as well food and
medicine greatly overlap in the diet. For example, in Japanese the
saying ‘ishoku dougen’ means medicine and food are of the same origin.
N. Etkin (University of Hawaii) found that 30% of the plant species
identified as foods among the Hausa of Nigeria in Western Africa were
also used as medicine. Likewise, 89% of species used to treat symptoms
of malaria were also used in a dietary context (Etkin, 1996; Etkin and
Ross, 1983). From this view point, it is clear that we have much to
gain by taking a closer look at the pharmacological characteristics of
both the proposed self-medicative and daily dietary items and behavior
of animals in the wild.
GREAT APE CHEMICAL ECOLOGY
Chimpanzees, bonobos and lowland gorillas are largely frugivorous but
also consume the leaves, pith, seeds, flowers, bark and sap of many
species. A variety of interesting secondary compounds have been
isolated from some of these plant parts (Koshimizu et al., 1993;
Koshimizu, Ohigashi, Huffman, 1994; Ohigashi et al., 1991). Secondary
compounds as well as inorganic materials are a plant’s defense against
most herbivorous predators. These products are toxic to the consumer or
inhibit consumption by reducing palatability or digestibility, yet a
number of items under this category can be found in the great ape diet.
Many are also recognized ethnomedicinal plants.
Ethnomedicinal uses of secondary compound rich fruits and leaves
The secondary compound rich content of nutritious foods in the diet
eaten under apparently normal situations may play a significant role in
the maintenance of health. A literature search was made for plant foods
reported to be ingested by the Mahale chimpanzees in western Tanzania
using references on African ethnomedicine in order to estimate the
potential contribution to parasite control by medicinal plants included
in the diet.
From the 192 recognized plant food species, 172 were selected for this
analysis on the basis that they are not cultigens and that a positive
scientific identification has been made. While it was common for some
species to have multiple ethnomedicinal uses, 43 (22%) of these 172
species were reported to be used to treat parasitic or gastrointestinal
related illnesses. While not all 43 species may be ingested by
chimpanzees in such a way as to benefit from these potential medicinal
properties, 33% (20/63) of the plant parts ingested from 16 of these
species corresponded to the parts utilized by humans for the treatment
of intestinal parasites and gastrointestinal illness (Huffman et al.,
1998).
Interestingly, for those 16 species there is a significant trend for
them to be ingested more frequently during the rainy season months, as
are the medicinally used species described below which are proposed to
be used solely for the control of nodular worm infections (Huffman et
al., 1996b).
SELF-MEDICATIVE BEHAVIORS OF THE AFRICAN GREAT APES
Among chimpanzees, gorillas and bonobos, two proposed types of
self-medicative behavior, bitter pith chewing and leaf swallowing, have
been documented to date.
The behavioral ecology of bitter pith chewing
Bitter pith chewing aids in the control of intestinal nematode
infection and relief from gastrointestinal upset via pharmacological
action. The hypothesis that bitter pith chewing has medicinal value for
chimpanzees was first proposed from detailed behavioral observations and
later from parasitological and phytochemical analyses of patently ill
chimpanzees ingesting Vernonia amygdalina Del. (Asteraceae) at Mahale by
Huffman and Mohamedi Seifu Kalunde (Huffman and Seifu, 1989).
When ingesting the pith of young shoots of V. amygdalina, Mahale
chimpanzees first remove the outer bark and leaves to chew only on the
exposed inner part, from which they extract the bitter juice. The amount
of pith ingested for a single dose is relatively small, ranging from
portions of 5 to 120 cm in length X 1 cm in diameter. The entire
process, depending on the amount ingested takes anywhere from less that
one to 8 minutes.
Regardless of year-round availability, use by chimpanzees is rare and
highly seasonal. Bitter pith chewing occurs mainly just after the onset
of the rainy season. A three year longitudinal study of the individual
parasite infection levels of Mahale chimpanzees has demonstrated a
significant rainy season increase in the incidence of infections for
individuals infected by Oesophagostomum stephanostomum (nodule worm),
but not for other nematode species. Nodular worm infections were
associated significantly more frequently with bitter pith chewing and
leaf swallowing, than either Strongyloides fullebornii (whip worms) or
Trichuris trichiura (thread worms).
Detailed observations of bitter pith chewers demonstrate ill health
(diarrhea, malaise and nematode infection) at the time of use. In two
closely monitored cases of bitter pith chewing in sick individuals,
recovery was noted within 20-24 hr. In one case the eggs per gram feces
(EPG) level of a nodular worm infection was found to have dropped from a
count of 130 to 15 within 20 hours. No change occurred in this
individual’s concurrent whip worm infection. In most individuals
monitored at the same time, nodular worm EPG levels increased over time
(Huffman and Seifu, 1989; Huffman et al., 1993). The recognized
increases in EPG levels represent the overall trend for increased
reinfection by nodular worms at the beginning of the rainy season. It is
at this time that individuals begin to reduce the number of worms
parasitizing them.
The behavioral ecology of leaf swallowing
Leaf swallowing also aids in the control of nodule worm infections and
is believed to relieve pain caused by tapeworm infection via the
expulsion of these intestinal parasites. Both phytochemical and physical
mechanisms for parasite removal have been proposed.
Leaf swallowing behavior was first recorded for chimpanzees at Gombe
and Mahale. As of January 1, 2000, leaf swallowing behavior involving 34
different plant species has been noted to occur in 9 populations of
chimpanzees, 3 of bonobos and one of eastern lowland gorillas at 13
sites across Africa. The common property linking all of these plants is
their bristly, rough-surfaced leaves (Huffman, 1997). The hairs or
trichomes on the leaf surface vary from long and slender, thorn like,
hooked to sharply spiked.
The distal half of these leaves are selected one at a time, folded by
tongue, lips and palate as they are slowly pulled into the mouth and
then individually swallowed whole. An individual may swallow anywhere
from one to 55 leaves in a single bout, repeatedly over a day. Like
bitter pith chewing, leaf swallowing is an extremely rare behavior.
Although the leaves of all species selected are available year-round,
like bitter pith chewing at Mahale, use is most common after the
beginning of the rainy season.
Behavioral and health profiles collected concurrently with direct
observations of leaf swallowing reveal signs of diarrhea, malaise and
suggestion of abdominal pain. Nematode infection has been demonstrated
in 83% of all leaf swallowing cases observed directly or documented
indirectly from dung containing leaves. The occurrence of adult worms in
the dung is rare (3% 9/254) and has thus far been limited to leaf
swallowing. All such worms recovered have been identified as nodular
worms of the species O. stephanostomum.
A strong relationship is recognized between leaf swallowing and the
expulsion of these nodular worms. The relationship is statistically
highly significant. Leaves are typically swallowed first thing in the
morning on an empty stomach. This is observed to result in at least a
17.4 h reduction in transit time. The leaves have been measured to pass
through the GI tract as quickly as 6 hours. All worms recovered are
alive and motile at the time of inspection eliminating the possibility
of a chemically induced nematocidal property in the leaves. Instead,
the purging of worms largely via the leaves’ physical properties is
hypothesized to be the main mechanism of leaf swallowing (Huffman and
Caton, in press).
Similar reports exist for the expulsion of Ascaris by a leaf swallowing
domestic dog in Tanzania, of tapeworms by brown bears in Alaska and
similarly by snow geese in Canada (Huffman, 1997; Huffman and Caton, in
press).
PHARMACOGNOSY AND ETHNOPHARMACOLOGY OF CHIMPANZEE SELF-MEDICATIVE
BEHAVIORS
Bitter pith chewing
Among numerous African ethnic groups, a concoction made from V.
amygdalina is used to treat malarial fever, schistosomiasis, amoebic
dysentery, several other intestinal parasites and stomachaches. The
noted recovery time of 20-24 hours after bitter-pith chewing in two M
group chimpanzees is comparable to that of local human inhabitants, the
Tongwe, who use cold concoctions of this plant as a treatment for
parasite infection, diarrhea and stomach upset (Huffman et al., 1993).
Some of the other species with bitter piths ingested by chimpanzees
elsewhere have a number of ethnomedicinal and pharmacological properties
worth mentioning. V. colorata and V. amygdalina, very closely related
species, are not distinguished from each other by traditional African
healers with regard to their medicinal properties and folk
classification (Dalziel, 1937). Alkaloids found in the pith, as well as
flower and leaf of V. hochstetteri may possess some sort of biological
activity. P. hirsuta and E. macrocarpa are used in west African
ethnomedicine for the treatment of upset stomachs, colic, as an
antiseptic and analgesic and for venereal disease. Molluscicidal
activity has also been reported for P. hirsuta (Abbiw, 1990; Okunji and
Iwu, 1988).
Phytochemical analysis of V. amygdalina samples collected at Mahale
from plants known to be used by chimpanzees reveal the presence of two
major classes of bioactive compounds. To date, a total of 4 known
sesquiterpene lactones, 7 new stigmastane-type steroid glucosides and 2
freely occurring aglycones of these glucosides have been isolated
(Jisaka et al., 1992 a; 1993).
Supportive of the ethnomedicinal literature, the sesquiterpene
lactones present in V. amygdalina, V. colorata and a number of other
Vernonia spp., are well known for their anthelmintic, antiamoebic,
antitumor, and antibiotic properties (e.g. Burkill, 1985; Dalziel, 1937;
Watt and Breyer-Brandwijk, 1962). From crude methanol extracts of the
leaves, we also found inhibition of tumor promotion and immunosupressive
activities (Jisaka et al., 1992 a, b).
In vitro tests on the antischistosomal activity of the pith's most
abundant steroid glucoside (vernonioside B1) and sesquiterpene lactone
(vernodaline) showed significant inhibition of movement of the adult
parasites and adult females’ egg-laying capacity (Jisaka et al., 1992
b). These findings are consistent with the observed decline in nodular
worm EPG level 20 hours after an adult female chimpanzee at Mahale
ingested V. amygdalina pith (Huffman et al., 1993).
While abundant in the leaves and bark, the highly toxic vernodaline
occurs in only insignificant amounts in the pith. This may explain why
chimpanzees normally avoid ingesting leaves and bark in preference for
the pith, with its greater abundance of steroid glucosides and their
aglycones (Ohigashi et al., 1994).
In vitro tests on the antiparasitic activity of both the sesquiterpene
lactones and the steroid glucosides, using Leishmania infantum,
Entamoeba histolytica, and a K1 multi-drug resistant strain of
Plasmodium falciparum have also been conducted. The sesquiterpene
lactones showed significant plasmodicidal activity although the IC50
values were more than 20 times higher than that of the common commercial
agent, chloroquine diphosphate. The steroid glucosides showed weaker
plasmodicidal activity. However, as in the case described above, the
activity of their aglycones was significantly higher in both
plasmodicidal and amoebicidal testing. In particular, a significant
increase in the plasmodicidal activity of vernoniol A4 was noted
(Ohigashi et al., 1994).
Leaf swallowing
Behavioral, parasitological and physiological observations pertaining
to leaf swallowing have been integrated to elucidate the mechanism
likely responsible for the expulsion and control of nodule worm
infections by the ape host. Physical irritation produced by bristly
leaves swallowed on an empty stomach, were associated with an increase
in motility and secretion resulting in diarrhea which rapidly moved the
swallowed leaves through the GI tract in about 6 hours, or about 17
hours faster than normal. In the proximal hindgut, the site of L3
(third stage larvae) cyst formation and adult worm attachment, motility,
secretion and the scouring effect of rough leaves is proposed to be
greatly enhanced by haustral contractions and peristalsis-
antiparistaltis. Frequently, at the peak of reinfection, a proportion
of non-encysted L3 (stage of parasite that is ingested by the host
leading to infection) is predictably vulnerable to this. These factors
are proposed to result in the disruption of the life cycle of
Oesophagostomum spp. Repeated flushing during peak periods of
reinfection is believed responsible for the observed long-run reduction
of worm burdens at certain times of the year (Huffman et al., 1997). In
this light, leaf-swallowing can be viewed as a deliberate adaptive
behavioral strategy with physiological consequences for the host. The
expulsion of worms based on the activation of basic physiological
responses in the host is a novel hitherto undescribed form of parasite
control (Huffman and Caton, in press).
NEW STRATEGIES FOR THE TREATMENT OF PARASITE DISEASE AND ANTHELMINTIC
RESISTANCE?
Some nodular worm species are a significant pathogen in domestic
livestock, non-human primate and occasionally human hosts. Symptoms of
moderate to heavy infections of O. stephanostomum, O. bifurcum and O.
aculeatum reportedly range from weight loss, enteritis, diarrhea, anemia
and lethargy to anorexia and intense pain simulating appendicitis.
Pathology includes hemorrhagic cysts containing larvae, septicimia
resultant from bacterial invasion of lesions in the colon, blockage of
the colon due to gross thickening of the wall, epigastric or
periumbilical masses clearly visible from the outside. Gross lesions in
submucosal or suberserosal nodules (5 - 20 mm diameter) are associated
with the larvae. These cysts or nodules contain caseous, necrotic
centers in a fibrous capsule. Histology includes intense inflamatory
cell reaction accompanied by high levels of neutrophils and eosinophils
associated with the nodules (above reviewed from Polderman and Blotkamp,
1995). Control of such infections by the host is of obvious adaptive
significance.
Anthelmintic resistance is a serious problem for livestock management
and resistance to drugs used in treating life threatening diseases such
as schistosomiasis and malaria in humans is a global problem urgently in
need of solutions (Geerts and Dorny, 1995; Jackson, 1993). The
widespread geographical occurrence and broad taxonomical representation
of great ape species exhibiting leaf swallowing and bitter pith chewing
behaviors suggests that these self-medicative behaviors represent a
stable biological strategy for parasite control. Can the study of
self-medication in the great apes and other animals offer new ways of
countering chemoresistance?
According to S. Geerts and colleagues factors selecting for
anthelmintic resistance are mass treatment, frequent use of the same
class of drugs over long periods of time and under dosing (Geerts and
Dorny, 1995). Theoretically therefor the converse approach may help
stem anthelmintic resistance. Indeed, it has been recommended that:
I. minimizing treatments,
II. rotating or combining different chemotherapies, and
III. proper dosage
be practiced to stem or control anthelmintic resistance in livestock and
human treatment programs (Geerts, Coles and Gryseels, 1997; Kremsner et
al., 1997). The observations of chimpanzee self-medication support these
recommendations and suggest that further detailed behavioral and
chemo-ecological studies of great ape behavior may provide significant
insight into more natural systems of parasite control which inhibit the
development of parasite chemoresistance and effectively maintain the
health of animals under human care.
A number of ethnomedicinally recognized plants used for the treatment
of intestinal parasite infections and related illness were found in the
diet of great apes (Huffman et al., 1998). A preliminary look at both
the real and potential pharmacological activity of plants used and the
ways they are ingested suggests that the Mahale chimpanzees’
self-medicative and dietary behavior mirrors recommendations I and II
above. The ‘control of nematode infection hypothesis’ predicts that
since nodular worm infections are typically self-limiting, the total
infection may be controllable if a chimpanzee responds to these symptoms
during the most likely period of reinfection. At Mahale, the peak period
of reinfection by the nodular worm O. stephanostomum was largely limited
in time to the one or two months after the onset of the rainy season.
The occurrence of bitter pith chewing and leaf swallowing at Mahale
peaks during these first few months of the rainy season and supports the
principle of minimizing treatment to periods of peak infection. That is,
chimpanzees are likely responding only to the discomfort of higher level
infections, thus maintaining them as best as possible at manageable
sub-clinical levels most of the year.
Bitter pith chewing and leaf swallowing compliment each other in
proposed function but appear to differ greatly in their mode of action.
As noted above, the pith of V. amygdalina contains constituents from at
least two distinct classes of bioactive compounds, the sesquiterpene
lactones and the steriod glucosides. Both bitter pith chewing and leaf
swallowing are sometimes displayed by the same individual on the same
day. With the apparent bimodal action of these two different behaviors
together they may act more effectively towards the control of nodular
worm infections. This trend parallels the principle of combining
treatments and employing complex chemotherapy. As this study suggests,
this may be even further enhanced by the contribution of a secondary
compound rich diet.
FUTURE DIRECTIONS AND GOALS
As the forgoing discussions have suggested, the study of the
pharmacognosy of great ape diet, self-medicative behaviors and their
corrrelations with documented ethnomedicinal practices promise to
provide important leads to future sources of natural medicine for the
treatment of parasitosis. In addition to this, a closer look into the
manner in which great apes use these natural products or combine them
with antiparasitic behavior may provide novel insights into viable
strategies for suppressing or slowing down the rate of acquisition of
chemoresistance by these parasites.
The next step is to conduct in vivo tests to determine direct
anthelmintic efficacy in a wide range of parasites, using a number of
different host species. Preliminary studies using the pig as a model
for monogastric animals (including man) have been conducted on
preparations of V. amygdalina at the Center for Experimental
Parasitology, Denmark. Preliminary results were inconclusive but future
tests using this and other plant species are in the planning stages.
The freshness of samples, the way they are preserved and transported as
well as the location of collection may have important effects on
material used. These and other factors will be further investigated.
Differences in metabolism, drug pharmacokinetics etc. between
monogastric and ruminant livestock necessitates further screening
activities in the latter class of animals. Protocols for testing
herbal preparations against nematode parasites of ruminants, using sheep
as the model system, are underway in the Department of Parasitology,
National Veterinary Institute, Sweden and the International Livestock
Research Institute, Kenya. We are also currently planning for the
initiation of in vitro / in vivo model testing of plant extract and raw
plant material as foliage on schistosomiasis in baboons and
leishmaniasis in vervet monkeys.at the Institute of Primate Research,
National Museums of Kenya, Karen Nairobi.
Basic broad spectrum biological assays of insecticidal and
plasmodicidal activity of promising plants and the elucidation of their
chemical constitutents are undereway in the Laboratoire de
Pharmacognosie - Homeopathie, Parasitologie Universite de la
Mediterranee (Aix-Marseile II), France and the Department of Chemistry
University of Dar es Salaam, Tanzania. Technical support on parasite
and plant identification is provided by the Departments of Zoology and
Botany-Herbarium at the University of Dar es Salaam, Tanzania.
Collaborative support from interested institutions and individuals in
other areas of Africa are always welcome.
This truly multidisciplinary approach to research, where biological
activity of novel, plant derived compounds is being assessed against a
whole range of parasite species found across a wide range of hosts,
maximises the chance of success. At the same time the research
consortium recognizes the importance of preserving the intellectual
property rights of the regions/countries to any new discoveries derived
from indigenous plant material. A prime objective of this research is
to integrate our results into local health care and livestock management
systems so that locally available plants can be properly used to the
benefit of all.
REFERENCES
Abbiw DK (1990) Useful Plants of Ghana. Kew: Intermediate Technology
Publications and Royal Botanic Gardens.
Burkill HM (1985) The Useful Plants of West Tropical Africa. (2nd ed.),
Vol 1. Kew, Royal Botanical Gardens.
Dalziel JM (1937) The Useful Plants of West Tropical Africa. In J
Hutchinson and JM Dalziel (eds.): Appendix to Flora of West Tropical
Africa. London, Whitefriars Press.
Etkin N.L. 1996. Medicinal cuisines: Diet and ethnopharmacology. Int. J.
Pharmacog. 34(5): 313-326.
Etkin, N.L., Ross, P.J. 1983. Malaria, Medicine, and Meals: Plant use
among the Hausa and its impact on disease. Pages 231-259 in
Romanucci-Ross, L., Moerman, D.E. and Tancredi L.R. eds, The
Anthropology of Medicine: From Culture to Method, New York: Praeger.
Geerts, S. and Dorny, P (1995) Anthelmintic resistance in helminths of
animals and man in the tropics. Bull. Sean. Acad. R. Sci. Otr-Mer
Meded. Zitt. K. Acad. Overzeese Wet. 41: 401-424.
Geerts, S., Coles, G.C., and Gryseels, B. (1997). Anthelmintic
resistance in human helminths: Learning from the problems with worm
control in livestock. Parasitology Today, 13: 149-151.
Huffman MA (1997) Self-medication in primates. Yrbk. Physical Anthro.
40: 171-200.
Huffman MA, and Seifu M (1989) Observations on the illness and
consumption of a possibly medicinal plant Vernonia amygdalina (Del.), by
a wild chimpanzee in the Mahale Mountains National Park, Tanzania.
Primates, 30:51-63.
Huffman MA, Gotoh S, Izutsu D, Koshimizu K, amd Kalunde MS (1993)
Further observations on the use of Vernonia amygdalina by a wild
chimpanzee, its possible effect on parasite load, and its
phytochemistry. African Study Monogr. 14(4): 227-240.
Huffman MA, Page JE, Sukhdeo MVK, Gotoh, S, Kalunde MS, Chandrasiri, T,
Towers GHN (1996a) Leaf-swallowing by chimpanzees: A behavioral
adaptation for the control of strongyle nematode infections. Int. J.
Primatol.. 72(4): 475-503.
Huffman MA, Koshimizu K, and Ohigashi H (1996b) Ethnobotany and
zoopharmacognosy of Vernonia amygdalina, a medicinal plant used by
humans and chimpanzees. In PDS Caligari and DJN Hind (Eds.): Compositae:
Biology & Utilization Vol 2., Kew, The Royal Botanical Gardens, pp.
351-360.
Huffman MA, Gotoh S, Turner LA, Hamai M, and Yoshida K (1997) Seasonal
trends in intestinal nematode infection and medicinal plant use among
chimpanzees in the Mahale Mountains, Tanzania. Primates 38(2): 111-125.
Huffman, M.A., Ohigashi, H., Kawanaka, M., Page, J.E., Kirby, G.C.,
Gasquet, M., Murakami, A. & Koshimizu, K. (1998). African great ape
self-medication: A new paradigm for treating parasite disease with
natural medicines. In: Towards Natural Medicine Research in the 21st
Century, Ebizuka, Y. (ed.), Elsevier Science B.V. Excerpta Medica,
Amsterdam, pp. 113-123.
Huffman MA (1997) Self-medication in primates. Yrbk. Physical Anthro.
40: 171-200.
Huffman and Caton, in press, Self-induced Increase of Gut Motility and
the Control of Parasite Infections in Wild Chimpanzees. Int. J.
Primatol.
Jackson, F (1993) Anthelmintic resistance. The state of play. British
Veterinary Journal 149: 123-138.
Jisaka M, Ohigashi H, Takagaki T, Nozaki H, Tada T, Hirota M, Irie R,
Huffman MA, Nishida T, Kaji M, and Koshimizu K (1992a) Bitter steroid
glucosides, vernoniosides A1, A2, and A3 and related B1 from a possible
medicinal plant Vernonia amygdalina, used by wild chimpanzees.
Tetrahedron, 48:625-632.
Jisaka, M, Kawanaka M, Sugiyama H, Takegawa K, Huffman MA, Ohigashi H,
Koshimizu K (1992b) Antischistosomal activities of sesquiterpene
lactones and steroid glucosides from Vernonia amygdalina, possibly used
by wild chimpanzees against parasite-related diseases. Biosci., Biotech.
and Biochem. 56(5): 845-846.
Jisaka, M., H. Ohigashi, H. Takegawa, M. Hirota, R. Irie, M.A. Huffman,
K. Koshimizu., 1993. Further steroid glucosides from Vernonia
amygdalina, a possible chimpanzee medicinal plant. Phytochemistry
34:409-413.
Koshimizu K, Ohigashi H, Huffman MA, Nisihda T, Takasaki H (1993)
Physiological activities and the active constituents of potentially
medicinal plants used by wild chimpanzees of the Mahale Mountains,
Tanzania. Int. J. Primatol. 14(2): 345-356.
Koshimizu K, Ohigashi H, and Huffman MA (1994) Use of Vernonia
amygdalina: Possible roles of its bitter and related constituents.
Physiology & Behavior. 56(6): 1209-1216.
Kremsner, P.G., Lufty, AJF and Graninger, W. (1997) Combination
chemotherapy for Plasmodium falciparum Malaria. Parasitology Today.
13(5): 167- 168.
Ohigashi, H., Takagaki, T., Koshimizu, K., Watanabe, K., Kaji M.,
Hoshino, J., Nishida, T., Huffman, M.A., Takasaki, H., Jato, J., and
Muanza, D.N. (1991 a). Biological activities of plant extracts from
tropical Africa. Afric. Study Monogr. 12(4):201-210.
Ohigashi H, Huffman MA, Izutsu D, Koshimizu K, Kawanaka M, Sugiyama H,
Kirby GC, Warhurst DC, Allen D, Wright CW, Phillipson JD, Timmon-David
P, Delnas F, Elias R, Balansard G (1994a) Toward the chemical ecology of
medicinal plant-use in chimpanzees: The case of Vernonia amy gdalina
Del.. A plant used by wild chimpanzees possibly for parasite-related
diseases. J. Chem. Ecol. 20: 541-553.
Okunji CO, and Iwu MM (1988) Control of schistomsomiasis using Nigerian
medicinal molluscicides. Int. J. Crude Drug Research 26(4): 246-252.
Polderman AM & Blotkamp J. (1995). Oesophagostomum infections in humans.
Parasitology Today 11(12): 451-456.
Watt, J.M. & Breyer-Brandwinjk, M.G. (1962). The Medicinal and Poisonous
Plants of Southern and East Africa. E. and S. Livingstone Ltd.,
Edinburgh.
Wrangham, R.W. (1995). Relationship of chimpanzee leaf-swallowing to a
tapeworm infection. Am. J. Phys. Primatol. 37: 297-303.
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