Treatment of Human Parasitosis in Traditional Chinese Medicine

274 Pages·2014·1.61 MB·English

by  Heinz Mehlhorn (auth.)

Parasitology Research Monographs 6
Heinz Mehlhorn
Zhongdao Wu
Bin Ye Editors
Treatment of
Human Parasitosis
in Traditional
Chinese Medicine
6 TraditionalChineseMedicinesAgainstMalaria 77
estimated that traditional plants are used as a first-line treatment for malaria by
25%ofpeopleinmalaria-endemiccountries(andupto75%insomeareas),and
over 1,277 plant species from 60 families are used in this way (Willcox and
Bodeker 2004); therefore, traditional medicine was suggested as complementary
oralternativesolutioninmalariacontrolprograms(Grazetal.2011).Asignificant
development was the setting up in 1999 of Research Initiative on Traditional
Antimalarial Methods (RITAM) by Dr. G. Bodeker of the Global Initiative for
Traditional System of Health (GIFTS of Health). RITAM is an international
network of researchers and others interested in the use and evaluation of local
herbalmedicinesusedforthepreventionand/ortreatmentofmalariaandalsolocal
methodsofvectorcontrol(http://giftsofhealth.org/ritam/).
Although many natural plants have a great potential efficacy for malaria treat-
ment, their effects are usually unstable duetothe diverse preparation approaches.
Greateffortshavebeenmadetoextracttheactiveconstituentsfromtheantimalarial
plants,whichcouldleadtotheproductionofnewerdrugs.
There are two major classes of natural products, alkaloids and nonalkaloids,
which exhibit antimalarial activity. Over 100 alkaloids from higher plants have
been reportedtoexhibithighactivityagainstmalariaparasites,andsomeofthese
weremorepotentthanchloroquine.Accordingtothestructure,antimalarialalkaloids
could be grouped into bisbenzylisoquinoline, naphthoquinones, indoloquinoline,
furoquinoline, tetrahydroquinoline, indole alkaloids, benzofenantridine alkaloids,
and acridone alkaloids (Oliveira et al. 2009). Nonalkaloidal natural products with
antimalarial activity belong to the classes of terpenes, limonoids, flavonoids,
chromones, xanthones, and anthraquinones (Batista et al. 2009). Alternatively, the
antimalarial natural products could be divided into another two groups: one is the
highly active compound, but with complex structure, so that no possibility of
practicalsynthesiscanbeforeseen,andanotheroneiswithmoderatetolowactivity
butrelativesimplestructures,andtheirsynthesisand/oroftheiranalogouscouldbe
undertaken. Plant species producing compounds of the first group are potential
candidates for the development of phytomedicines, whereas the second group
wouldrepresenttemplatestosyntheticdrugs.
However,theantiplasmodialactivityofmostnaturalproductsfrommanyplant
species onlyhavebeenevaluatedinvitroassay,fewofthemhave beenevaluated
in vivo for their antimalarial activity and cytotoxicity (Batista et al. 2009; Bero
et al. 2009; Oliveira et al. 2009), and fewer was moved to clinical research. In
addition, many of antiplasmodial natural products were in low concentrations in
plant species and usually as part of complex mixtures making their isolation and
purificationhighlyexpensive.Thishampersthedevelopmentofphytomedicines,as
theactivecompoundsshouldbeusedaschemical–biologicalmarkerstoguarantee
theproductquality.
Furthermore, the antimalarial activity of most natural products was evaluated
againstthebloodstage,theireffectsonbothliverandmosquitostagesandmosquito
shouldbestressedinthefuture,whichcouldnotonlypreventtheonsetandrelapse
ofmalariabutalsoblockthemalariatransmission.
78 W.Xu
References
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Chapter 7
Liver Diseases (Abscesses, Tissue Cysts
and Tumours) Caused by Parasites
AchimHarderandHeinzMehlhorn
Abstract Avarietyofparasites—protozoans,cestodes,trematodes,nematodesor
pentastomida—reside in the human liver or invade this organ and are responsible
for inflammation resulting in hepatitis. Among the protozoans Entamoeba
histolytica is of high importance. In the cyst fluid of the liver abscess, not only
purulent components are visible but also some amoeba so-called magna forms.
Among cestodes Echinococcus granulosus and E. multilocularis preferentially
resideintheliverleadingtooftenlargecysts.Those ofE.multilocularisgrowby
propagation of tiny omnipotent cells similar to typical cancer cells. Within the
trematodes Schistosoma spp., Clonorchis sinensis, Opisthorchis viverrini and the
juvenilestagesofFasciolahepaticahavetobeconsidered,sincetheymayinitiate
truelivercarcinoma.Amongthelargegroupofhumannematodes,onlyCapillaria
hepatica, migrating nematode larvae (such as larva 2) and the adults of Ascaris
lumbricoides,larvaeofStrongyloidesstercoralis,hookworms,Toxocaracanisand
microfilariae of different filariae play a role in inducing liver inflammation, but
neverleadtocysts,abscessesorevencarcinomas.
Keywords Liverdiseases(cid:129)Hepatitis(cid:129)Abscesses(cid:129)Tissuecysts(cid:129)Tumour(cid:129)Cancer(cid:129)
Entamoeba histolytica (cid:129) Amoebom (cid:129) Echinococcosis (cid:129) Echinococcus species (cid:129)
Trematodes (cid:129) Schistosoma species (cid:129) Opisthorchis species (cid:129) Clonorchis sinensis (cid:129)
Fasciolahepatica(cid:129)Bilharziosis(cid:129)Schistosomiasis(cid:129)Capillariahepatica
A.Harder
InstituteforBiology,Heinrich-Heine-University,40225Du¨sseldorf,Germany
H.Mehlhorn(*)
DepartmentofParasitology,Heinrich-Heine-University,40225Du¨sseldorf,Germany
e-mail:[email protected]
H.Mehlhornetal.(eds.),TreatmentofHumanParasitosisinTraditional 79
ChineseMedicine,ParasitologyResearchMonographs6,
DOI10.1007/978-3-642-39824-7_7,©Springer-VerlagBerlinHeidelberg2014
80 A.HarderandH.Mehlhorn
7.1 Abscesses Caused by Protozoa
7.1.1 Entamoebiasis: Entamoeba histolytica
Taxonomy
Subregnum Protozoa
Phylum Amoebozoa
Class Lobosea
Order Amoebida
Family Entamoebidae
ThelifecycleofEntamoebahistolyticacomprisestwomorphologicallydistinct
developmentalstages:thevegetativestages(minutaandmagnaforms),alsoknown
astrophozoites,andthecyststage(Figs.7.1,7.2and7.3)(Mehlhorn2008;Tannich
andBurchard2010;WHO1997).
Trophozoites are uninucleate cells with a diameter of 20–40 μm containing a
typical nucleus (spherical and central karyosome); they show pronounced gliding
movements by formation of a single apical pseudopodium; cysts are spherical,
quadrinucleate and have diameters from 10 to 20 μm. Entamoeba histolytica is
usually transmitted by the faecal–oral route by ingestion of infectious cysts
(contaminated food), but transmission through relevant homosexual practices is
also possible. Multiplication of Entamoeba histolytica takes place only in the
intestine. After ingestion of the typically quadrinucleate cysts, which unlike the
trophozoites can remain infectious outside the body for months and are not
destroyedbytheacidcontentsofthestomach,theuninucleatetrophozoitescapable
of multiplication develop in the small intestine. In the lower colon renewed
encystmentwithtwosubsequentnucleardivisionstakesplace.Aninfectedperson
can pass up to 500 million cysts per day along with the faeces. The incubation
period of amoebiasis is very variable. The time between infection and the occur-
renceofclinicalsymptomscanvarybetweenafewdaysandweeks.Therearealso
cases, where no symptoms occur. The average incubation period for an amoebic
liverabscessisupto5months.
NaturalinfectionswithEntamoebahistolyticaarelimitedtomanandafewOld
World monkey species. People in tropical and subtropical countries in whom
Entamoeba histolytica is endemic are usually associated with low socioeconomic
status and poor hygienic conditions; travellers to such countries and male
homosexuals are endangered. Worldwide half a billion of people are infected
with E. histolytica, ten millions of these suffer from invasive amoebiasis and
about100,000peoplearehitbycomplications,especiallyfromliverabscesses.
The prevalence of Entamoeba histolytica depends primarily on the number of
cyst passers and the local hygienic conditions. Under the hygienic conditions,
which are standard in Western Europe, the infection usually does not or poorly
spread.
7 LiverDiseases(Abscesses,TissueCystsandTumours)CausedbyParasites 81
Fig.7.1 Lightmicrograph
(LM)ofaminutaformof
Entamoebahistolytica
Fig.7.2 Lightmicrograph
ofamagnaformof
Entamoebahistolytica
Fig.7.3 LMofacystof
Entamoebahistolytica
(N¼nucleus,W¼wall)
82 A.HarderandH.Mehlhorn
ThepathogenicityofEntamoebahistolyticaisbasedprimarilyontheabilityto
destroy host tissue and cells. Surface receptors, cysteine proteinases and pore-
formingpeptides,calledamoebopores, oftheamoebaeplayadecisiveroleinthis
process. The virulence of individual amoeba isolates can vary depending on the
levelofexpressionofthesemolecules,whichhowever,areessentialtopenetratethe
intestinalwallandthusbecomeamagnaform.Antigenvariabilityhasnotyetbeen
shownforEntamoebahistolytica.
7.1.1.1 IntestinalEntamoebiasis
Intestinal amoebiasis is linked with enteritis or colitis of varying severity. Typi-
cally, there areulcerative mucosal lesions with diarrhoealstoolscontaining blood
andmucus(Fig.7.4).
7.1.1.2 ExtraintestinalEntamoebiasis
Magna forms of the amoebae can spread to other organs by haematogenous
dissemination and lead to abscess formation. In more than 90 % of these cases,
thereareextraintestinalmanifestationsintheliver(Fig.7.5).Inrarecases,therecan
becomplicationssuchasperitonitisafterperforationofanamoebicliverabscessor
migration from the liver into the lung or pericardium. Infections with Entamoeba
histolytica regularly induce a specific B- and T-cell response. Even in the case of
asymptomaticintestinalinfections,serumantibodiestoEntamoebahistolyticacan
bedetectedinmorethan80%ofcases.
7.1.1.3 DifferentialDiagnosisandDiagnosis
Inthecaseofenteritisorcolitis,otherintestinalinfectiouspathogensshouldalways
beruledout.Inthecaseofmarkedmucosallesions,anulcerativecolitisshouldbe
considered. An amoebic liver abscess should be differentiated from a bacterial
abscess.Furtherdifferentialdiagnosesareechinococcosisoranecrotictumour.
Thediagnosticworkupofinvasiveamoebiasisdependsonthesiteofmanifesta-
tion of the illness. (a) In the case of intestinal amoebiasis, rectoscopic or
colonoscopic detection of appropriate mucosal lesions and direct detection of the
pathogenaretheprimarymeasures.Thelatterisperformedbyexaminationofthe
stools (Figs. 7.1, 7.2 and 7.3) or by histological detection of amoebae in biopsy
material.(b) Inextraintestinal amoebiasis,imagingprocedures such asultrasound
andcomputedtomographyareusedtodetectappropriateorganmanifestationsand
structuraldefects.Atthesametime,serologicaldetectionofspecificantibodiesto
Entamoebahistolyticaisanimportant,oftenpivotaldiagnostictool.
7 LiverDiseases(Abscesses,TissueCystsandTumours)CausedbyParasites 83
Fig.7.4 Slimy,bloody
diarrhoea(dysenteriae)as
resultofaninfectionwith
Entamoebahistolytica
Fig.7.5 Macrophotoofa
liverwithabscessesdueto
E.histolytica
For differentiation from other apathogenic intestinal amoebae (e.g. Entamoeba
dispar),particularlyinthecaseofasymptomaticinfections,Entamoebahistolytica
shouldalsobecharacterisedimmunologicallyorgenetically.
Immunological characterisation using monoclonal antibodies to specific
epitopes of Entamoeba histolytica is also available as well as the genetic
characterisationonthebasisofspecificDNAsequences,e.g.withintherRNAgene.
ThegenomeofEntamoebahistolyticaiscurrentlybeingsequenced.Itprobably
comprises20megabases,whicharedistributedover14chromosomes.
7.1.1.4 Treatment
Infections with Entamoeba histolytica must always be treated (Chac´ın-Bonilla
2012).AsymptomaticintestinalEntamoebahistolyticainfectionsshouldbetreated
with diloxanide furoate or paromomycin for 10 days. All Entamoeba histolytica
infectionswithintestinalorextraintestinalclinicalmanifestationsshouldbetreated
firstwithmetronidazole(30mg/kgbodyweight/daydividedintothreedailydoses
for10days)tokillamoebae,whichhavealreadypenetratedthetissues,followedby
treatment with diloxanide furoate or paromomycin to eliminate the remaining
84 A.HarderandH.Mehlhorn
intraluminal forms. Drug resistance to metronidazole has been suspected in indi-
vidualcasesbuthasnotyetbeenscientificallyconfirmed.
7.2 Hepatitis Caused by Cestodes
7.2.1 Hydatidosis, Echinococcosis, Echinococciasis:
Echinococcus granulosus
Taxonomy
Subregnum Animalia
Phylum Platyhelminthes
Class Cestoda
Order Cyclophyllidea
Family Taeniidae
7.2.1.1 LifeCycleandTransmission
The 2–5-mm-long adult tapeworm with its 2–5-mm-long strobila lives in the
intestine of the dog and some other carnivores, is provided with 37–42-μm-long
large and29–34-μm-long smallhooksatthe rostellum, 3–4(–6)proglottidsanda
uterus with lobed lateral sacculations (Figs. 7.6 and 7.7). The cystic larva
(metacestode) takes the form of a fluid-filled, generally unilocular cyst (hydatid)
thatgrowsbyexpansion(Figs.7.8,7.9and7.10),itmaycontaindaughtercystsin
itsinteriorandinextremecasesitattainsadiameterofupto30cm.Protoscolices
(Fig.7.10)budfrombloodcapsulesoftheinnergerminallayerandmaybreakfree.
In the fluid, these together with calcareous corpuscles form what is known as
hydatidsand(Mehlhorn2008;Kernetal.2000a,b;WHO1996,1997).
Transmissiontohumans(andotherintermediatehosts)takesplacebymeansof
oral ingestion of the eggs of E. granulosus originating from the faeces of dogs or
otherdefinitivehosts(foxesandcats).
TheadultformsofE.granulosusparasitisingtheintestineofthedefinitivehost
contain 500–1,000 taeniid eggs (32–39 (cid:2) 24–26 μm) in their gravid proglottids
(Fig. 7.11). After the terminal proglottids with eggs are excreted with the faeces,
they are orally ingested by an intermediate host. Here occurs hatching in the
intestinaltractofthelarva(oncosphere)presentintheeggmembrane,penetration
of the wall of the intestine. Oncospheres spread via the bloodstream to the liver,
wherethemajoritysettle.Otheroncospheresaretransportedfurthertothelungsand
continue to develop there. Approximately 10–20 % passes through the lung and
thentravelviathesystemiccirculationtoawiderangeoforgans.Theoncosphere
developsintoavesicularstructurethatgrowsbymeansofexpansiontoformacyst
7 LiverDiseases(Abscesses,TissueCystsandTumours)CausedbyParasites 85
Fig.7.6 Lightmicrograph
ofanadultEchinococcus
granulosusworm
Fig.7.7 Scanningelectron
micrographofadultsof
Echinococcusgranulosus
andE.multilocularis(right)
worms