Thesis (MSc)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: Children in socioeconomically disadvantaged communities in the Western Cape and elsewhere in South
Africa are frequently infected by Trichuris trichiura. Although albendazole and mebendazole are listed
as essential drugs for treatment of humans, it is well known that trichuriasis is relatively refractory to
anthelmintic treatment. There are some reports that mebendazole is more effective against Trichuris and
it is available as generics that are relatively cheap. On the other hand, albendazole is better for
hookworm and may have some effect against Giardia duodenalis, which is common in the same
communities. Moreover, albendazole is used in a deworming programme in KwaZulu-Natal, at a dose
o f400 mg stat, given once or twice a year depending on the health region in that province.
In terms of diagnosis, infection by intestinal helminthiasis can be determined and monitored by simple,
non-invasive, sustainable and cost effective methods. The epidemiological significance of high
prevalence extends far beyond the worms per se because they are an index of environmental conditions
that pose a risk of several other diseases. These include infection by organisms that can cause epidemics
of enteric disease. These facts pertain within a deteriorating milieu in terms of human ecology, because
the informal sector of the population is burgeoning under dynamic forces that include urbanisation,
migration, poverty and disease.
The study reported in this thesis had three main objectives within the context and concepts of the
realities described in the previous two paragraphs. The first was to review and consider all information
on trichuriasis that could be detected in the literature, and to relate the result to South African needs.
The second was to test efficacy of albendazole against trichuriasis in children from a community where
it is the predominant worm infection, by means of a well designed and controlled study. Finally, it was necessary to consider other results associated with treatment. These included possible drug resistance
and effects on growth, eosinophilia, iron status and toxicity.
The literature survey established that South Africa lags behind many other developing countries in
defining and addressing the problem of helminthiasis as a whole. The conventional epidemiology of
trichuriasis as described in the literature is based mainly on studies in the West Indies. Surveys
completed recently in the Western Cape Province of South Africa confirm some of the epidemiological
concepts, with two notable exceptions. First, the age-related prevalence peaked in children who were
14 years old in a suburb of Cape Town. This is older that in West Indian children. The second
difference is probably more important and was detected in children at schools serving the informal sector
o f Khayelitsha. This is densely populated and the sanitation is often not effective and is sometimes
totally lacking. The distribution of egg counts in 316 Khayelitsha children was not overdispersed to low
counts, which is perceived as invariably the situation in the West Indies. In the Khayelitsha survey,
approximately 25% of children had more than 10 000 eggs per g of faeces.
The randomised controlled treatment trial tested a series of four albendazole treatments, at doses of400,
800 and 1200 mg (given as 400 mg/day), repeated at intervals of approximately four months in matched
groups of children. Results indicate that mass deworming programmes in South Africa should not use
albendazole at a dose o f400 mg stat for control of infection by Trichuris trichiura. The package insert
of the product tested (Zentel®, SmithKline Beecham) recommends that "in heavy mixed infestation
involving Trichuris, a single daily dose may be inadequate and the dose may be given for three
consecutive days". This statement is not accurate because even when infection by Trichuris was not
intense, as defined internationally in terms of egg counts per g of faeces, and it was the only helminth
present, the cure rate achieved by repeated doses of 400 mg of albendazole was not satisfactory.
Moreover, 48% (15/31) of treated children remained continuously infected, although egg counts were clearly reduced. This result demonstrates that continuous use of a dose of 400 mg which is the
maximum stat dose permitted in South Africa, is likely to facilitate development of true genetic
resistance to albendazole by T. trichiura. Doses of 800 and 1200 mg were more efficacious and
continuous infection reduced to 21% (9/43) and 2.5% (1/39), respectively. A dose of 800 mg for
routine use in mass deworming programmes, as 400 mg/day, can be recommended on the basis of
sufficiently efficacious treatment, simplification of compliance, and reduction of cost. The frequency
of treatment within such programmes should probably be three times per year when prevalence of severe
infection exceeds 10% ("severe infection" is defined internationally as an egg count of more that 10 000
per g of faeces). When severe infection is less frequent, treatment could be less often, but more
definitive research of this aspect is necessary under local conditions. There was some evidence that
incidence increased seasonally during summer and autumn in the community concerned.
A range of other results was recorded. The possibility of genetic resistance to albendazole by Trichuris
trichiura was not excluded. There was significant reduction of eosinophiha during treatment with
albendazole. This may have immunological implications for incidence, prevention and progression of
other diseases. Treatment appeared to be beneficial in terms of growth and iron status, but there was
not sufficient statistical power to confirm this. No evidence of toxicity at the highest dose (1200 mg
given as 400 mg/day for three days) was detected. / AFRIKAANSE OPSOMMING: Kinders in sosio-ekonomiese agterblewe gemeenskappe in die Wes-Kaap en ook elders in Suid-Afrika
toon gereelde infeksies met Trichuris trichiura. Albendazool en mebendazool word gelys as
noodsaaklike medikasie vir menslike behandeling, maar dit is wel bekend dat Trichuris relatief moeilik
is omte behandel. Daar word gerapporteer dat mebendazool meer effektief is teen Trichuris en maklik
beskikbaar is as goedkoper generiese medikasie. Albendazool, aan die ander kant, is effektief teen
haakwurm en kan ook ‘n effek het teen Giardia duodenalis, wat voorkom in dieselfde gemeenskappe.
‘n Dosis van 400 mg albendazool, een of twee keer per jaar, word huidelik gebruik in ‘n
onwurmingsprogram in KwaZulu-Natal. Die frekwensie van behandeling word bepaal deur die
gesondheids streek binne die provinsie.
In terme van diagnose, kan infeksie deur intestinale helminte bepaal en gemonitor word deur eenvoudige,
nie-invallende, koste effektiewe maniere. Die epidemiologiese betekenis van ‘n hoe voorkoms strek
verder as net die wurms omdat hulle ‘n indeks is van omgewings besoedeling wat kan dui op die risiko
van verskeie ander siektes. Dit sluit in infeksies deur organismes wat epidemies van enteriese siektes
veroorsaak. Hierdie feite pas binne die agteruitgang in terme van menslike ekologie, want die informele
sektor van die bevolking is onder dinamiese druk wat verstedeliking, migrasie armoede en siektes insluit.
Die studie, waarvan verslag gegee word in hierdie tesis, het drie vemame objektiewe binne die konteks
en konsepte van die realiteite soos beskryf in die vorige twee paragrawe. Die eerste objektief was om
alle informasie aangaande trichuriase in die literatuur in oorsig te neem en dit in verband te bring met
Suid-Afrikaanse behoeftes. Die tweede was om die werksaamheid van albendazool teen trichuriase te
toets in kinders van ‘n gemeenskap waar wurm infeksies oorheers, deur middel van ‘n goed beplande
en gekontroleerde studie. Laastens was dit nodig om ander resultate, geassosieer met behandeling, in ag te neem. Dit sluit in moontlike weerstand teen die medikasie en die effek op groei, ysterstatus en
toksisiteit.
Die literatuur oorsig toon dat Suid-Afrika ‘n agterstand het met baie ander ontwikkelende lande om die
omslag van die probleem van helminte te bepaal en ook om dit aan te pak. Die konvensionele
epidemiologie van trichuriase, soos beskryf in die literatuur, is gegrond op studies in die Wes-Indies.
Opnames wat onlangs in die Wes-Kaap gedoen is, bevestig sekere epidemiologiese konsepte met twee
vemame uitsonderings. Die eerste is die ouderdoms verwante voorkoms wat ‘n hoogtepunt bereik in
14 jarige kinders in ‘n voorstad van Kaapstad. Dit is ouer as in die Wes-Indiese kinders. Die tweede
verskil is miskien meer belangrik en was vasgestel in skool kinders in ‘n informele sektor van
Khayelitsha. Dit is ‘n dig bewoonde area met oneffektiewe of ‘n totale gebrek aan sanitasie. Die
verspreiding van eier tellings in 316 Khayelitsha kinders was nie oor-versprei tot lae tellings nie, wat
andersins die geval in die Wes-Indies was. In die Khayelitsha studie het ongeveer 25% van kinders meer
as 10 000 epg stoelgang.
Die gekontrolleerde ewekansigheidstoets soos bespreek in hierdie tesis het ‘n reeks van vier albendazool
behandelings, by dosisse van 400, 800 en 1200 mg (gegee as 400 mg/dag), herhaal by pouses van
ongeveer vier maande in gelyke groepe van kinders, ge-evalueer. Die resultate toon dat massa
ontwurmings programme in Suid-Afrika nie die 400 mg dosis vir kontrole van Trichuris trichiura moet
gebruik nie. Die pakkie insetsel van die produk wat getoets was (Zentel®, SmithKline Beecham) dui
aan dat in swaar gemengde infeksies waar Trichuris betrokke is, ‘n enkele dosis onvoldoende is en dat
die dosis vir drie agtereenvolgende dae gegee mag word. Hierdie stelling is onakkuraat want al is die
infeksie deur Trichuris nie swaar nie, soos intemasionaal gedefinieer in terme van eier telling per gram
stoelgang, en al is dit die enigste intestinale wurm teenwoordig, is die genesingsyfer wat behaal is met
herhaalde dossise van 400 mg albendazool nie bevredigend nie. Inteendeel, 48% (15/31) van behandelde kinders was aanhoudend besmet, al was eier tellings duidelik verminder.
Hierdie resultaat wys dat herhaaldelike gebruik van ‘n 400 mg dosis, wat die maksimim dosis toelaatbaar
in Suid-Afrika is, genetiese weerstand van albendazool deur Trichuris trichiura kan fasiliteer. Die 800
mg en 1200 mg dosis was meer doeltreffend en het herhaalde infeksie verminder tot 21 % (9/43) en 2.5%
(1/39) onderskeidelik. Die 800 mg dosis as 400 mg/dag word aanbeveel vir roetine gebruik in massa
ontwurmings programme. Dit is meer doeltreffend, behandeling word vereenvoudig en koste word
verminder. Die frekwensie van behandeling binne sulke programme moet waarskynlik drie keer per jaar
wees wanneer die prevalensie van swaar infeksies meer as 10% is (“swaar infeksie” word intemasionaal
gedefinieer, wanneer eier tellings meer as 10 000 eiers per g stoelgang is). As swaar infeksies minder
voorkom, kan behandeling minder gereeld wees, maar meer bepaalde navorsing onder plaaslike kondisies
is nodig. Daar is sekere bewysse dat insidensie seisoenaal verminder, tydens somer en herfs, in hierdie
gemeenskap.
‘n Reeks van ander resultate was ook aangeteken. Die moontlikheid van genetiese weerstand van
Trichuris trichiura teen albendazool word nie uitgesluit nie. Daar was ‘n aanmerklike vermindering van
eosinophillia tydens behandeling met albendazool. Dit mag immunologiese implikasies vir insidensie,
voorkoming en voortgang van ander siektes voorspel. Dit blyk of behandeling groei en yster status
bevoordeel het, maar daar was nie genoegsame statistiese mag om dit te bevestig nie. Geen bewys van
vergiftiging by die hoogste dosis (1200 mg gegee as 400 mg/dag vir drie dae) is waargeneem nie.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/52041 |
| Date | 12 1900 |
| Creators | Arendse, Vera Jane |
| Contributors | Fincham, J. (John), Joubert, J. (Johan), Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
| Format | 139 p. : ill. |
| Rights | Stellenbosch University |
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