A CAJM article on "suppressive management" of bilharziasis.The concept of “suppressive management” in the control of bilharziasis has long been an attractive idea. If it were possible to administer a dose of a schistosomicidal drug once a week, particularly to children attending school, a significant reduction in egg output and an improvement in health would make the method worthy of careful consideration in bilharziasis control programmes

Blair, D.M.

Weber, M.G.

Central African Journal of Medicine

English

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The Central African Journal of Medicine
Editor-.
MICHAEL GELFAND, C.B.E., M.D., F.R.C.P.
Assistant Editor-. 
JOSEPH RITCHKEN, M.D.
Volum e Nineteen 
JANUARY - DECEMBER 
1973
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A Study of the Effects of W eekly  
Doses of Niridazole on Schisto­
some Egg Output and M iricidial 
Hatching in  a Patient suffering  
from  Bilharziasis
BY
D. M. BLAIR
AND
M. G. WEBER
Blair Res e ar c h Laboratory , Salisbury, Rhodes ia
I n t r o d u c t io n .
The concept of “suppressive management” in 
the control of bilharziasis has long been an 
attractive idea. If it were possible to administer 
a dose of a schistosomicidal drug once a week, 
particularly to children attending school, a sig­
nificant reduction in egg output and an im­
provement in health would make the method 
worthy of careful consideration in bilharziasis 
control programmes.
Children are undoubtedly the chief source of 
schistosome eggs for infection of waterbodies in 
endemic areas. If this could be substantially 
reduced by the administration of a single dose 
of a non-toxic drug, one day a week throughout 
a school term, the method, if economic, would 
be simple to apply.
Lees (1968) described a trial of a weekly 
dose of 500 mg Lucanthone hydrochloride, the 
tablets being coated with a cellulose acetate, 
Phthalate, at a school on the West Indian Is­
land of St. Lucia. He found the Schistosoma mansoni prevalence to be 80 per cent, in the 
age group 10-14 years. Prior to the commence­
ment of the trial for the 10 weeks of a school 
term the diagnosis was established 'by finding S. mansoni eggs in stools after sedimentation 
and concentration of eggs. The egg output 
level was thereafter established on a single whole 
stool using a filtration ninhydrin staining tech­
nique (Bell, 1963). Sixty infected children were 
chosen for the trial and the effect assessed by 
follow-up stool examinations 4 and 16 weeks 
after the completion of the 10 weeks of “sup­
pressive management”. It was possible to fol­
low-up 49 of the children and it was estimated 
that an 89 per cent, reduction in egg output 
was achieved. The “cure” rate (the number of 
cases not passing any eggs) was, however, only 
36,7 per cent, and all of these were in children 
who were passing less than 10 000 eggs, the 
group with the lightest egg loads and no com­
plaints of side-effects were noted.
i
39
SUPPRESSION USING NIRIDAZOLE
It had been decided to carry out a “suppres­
sive management” trial at a school on the 
Mazoe • Citrus Estate 30 miles from Salisbury, 
and groups of children were given uncoated 
Lucanthone hydrochloride, Niridazole and en­
teric-coated Hycanthone tablets to roughly 
comparable groups of children suffering from 
S. haematobium, S. mansoni and double infec­
tions with these parasites.
It was felt that it would be interesting to 
study, in more detail, in the Laboratory, a 10- 
week “suppressive management” course in a 
single patient. Niridazole was the drug selected.
A well-built young African, Town Mavida, 
aged about 19 years, volunteered for the trial. 
A general physical examination showed no signs 
of disease and his weight on 15th January, 
1969, was 62,7 kg. Examination of urine 
showed him to have a light S. haematobium 
infection — 20 to 40 eggs being counted in 
deposits from mid-day terminal urine specimens. 
From them a good miracidial hatch was ob­
tained. This was a light infection and seemed 
to cause him no inconvenience. He was also 
passing S. mansoni eggs and about 250 eggs 
were present in each sedimented and centri­
fuged stool deposit examined. Profuse mira­
cidial hatching was obtained from the stool 
sediments..
The patient had come to Salisbury early in 
1969, so it was most likely that he had con­
tracted both infections in the same area as his 
elder brother, Foster Mavida (Blair et al. 1969).
O b je c t  o f  t h e  St u d y .
The objective was to study the effect of a 
weekly dose of Niridazole on the egg output 
in urine and stool and the effect on hatchability 
of the eggs and any effect in his weight and 
general health.
M e t h o d .
The subject was given two 500 mg tablets of 
Niridazole (Ambilhar (§) GIB A) at mid-day 
each Wednesday from 15th January to 19th 
March, 1969. Over this period he was weighed 
at the time of dosing and his weight ranged 
from 62,7 to 64,5 kg.
Each morning, Monday to Friday, the subject 
passed a stool at 0800 hours into a plastic con­
tainer 25 x 17 x 8 cm deep. From the specimen 
two samples were taken without selection; each 
was about one gram in weight and was placed 
in screw-topped glass jars each containing 40 
ml of hypertonic saline. One sample was pro­
cessed at once, the other being kept for 24 
hours at room temperature and processed the
following day. The processing followed the 
methods of Blair et al {op. cit.). From each 
stool deposit 0,05 ml was taken and examined 
microscopically and eggs counted, and the 
remainder of the deposit subjected to hatching 
of miracidia in an examination rack (Meeser et al 1948). Each specimen was examined for 
hatched miracidia at 1200 and 1500 hours on 
the day it was examined microscopically, and 
at 1000, 1200 and 1500 hours on the following 
two days. By this means each sample was 
examined at least eight times.
The extent of miracidial hatching was esti­
mated on a rating of 1+ to 5+ ai each obser­
vation time. These observations not only give 
an indication of the amount of miracidia 
hatched at the time of observation, but also by 
persistence of hatching in the second, third and 
occasionally subsequent days of observation give 
some indication of the number of eggs showing 
delayed hatching. It is difficult to decide on the 
best way to reduce the information to figures. 
It is conceded that miracidia hatched and seen 
at one observation may also be seen and again 
counted in the next observation. It is, however, 
highly unlikely that miracidia hatched and 
active on any one day will still be active on the 
next day. It was therefore decided to record 
the maximum hatching rate recorded on each 
of the three days and by adding together the 
totals for each of the three days and the two 
samples of stool of the day, a figure is obtained 
which reflects the extent of miracidial hatching.
During the period of the trial the subject pro­
duced at 1200 hours each day, Monday to 
Friday, a specimen of terminal urine and his 
urine egg output estimated. He had, in fact, 
a light S. haematobium infection, but neverthe­
less during the course of the trial, miracidia 
were observed even on those instances where no 
eggs had been seen in the 0,05 ml of the centri­
fuged deposit which was examined microscopi­
cally. On only one day, 7th February, 1969,. no 
eggs were seen and no miracidia hatched.
R e s u l t s .
The weekly dose of 1 g. of Niridazole repre­
sents only 15,7 mg/kg or 157 mg/kg spread 
over 10 weeks as compared with the standard 
course of treatment used here of 30 mg/kg 
daily for six days — a total of 180 mg/kg, so 
no curative dose a t . this level could really be 
expected. This is especially so as Faigle and 
Keberle (1965) have shown in experimental 
work on animals that it is necessary to main­
tain a concentration of the drug in the blood 
for 100 hours and in order to maintain the blood 
level doses have to be given every 12 hours. 
They show that a single dose of Niridazole 
persists in the blood for only 10 to 15 hours.
40
SUPPRESSION USING NIRIDAZOLE
Table I shows the daily egg output over the 
10 week treatment period and the succeeding 
five weeks. It will be noted that the day with the lowest average egg output was Thursday, 
24 hours after the administration of the drug; 
and the average daily eggs fell from 34 in week 
one to 12 in week five; rose to 75 in week 
seven and then settled back to its previous level 
of about 34. When the 10-week dose period 
was over, the average egg output on Thursdays 
and Fridays was much higher than the other 
three days, and the weekly egg output was 
higher than during the treatment period. It 
would appear that the drug did have an imme­
diate depressant effect on egg output on the day 
following dosing, and did depress the weekly 
average over the first six weeks; thereafter and 
continuing throughout the five-week follow-up 
period, there was, if anything, an increased 
output of S. haematobium eggs with no evi­
dence of any diminution in hatching potential.
The results of the examination of stool speci­
mens is set out in Table II. This shows that in 
the 10-week period of the trial over one-third 
of the total eggs were seen in the Monday 
specimens. In the observations (Blair et al, op. cit.) on the stools of Foster Mavida, the sub­
ject’s brother, a similar increase in eggs on 
Mondays was observed, but not to the extent 
observed in the present series of observations. 
It will be noted that in the stools, egg output 
was at its lowest in weeks two and three, but 
thereafter recovered to the former level; this 
was maintained during the five weeks of obser­
vation after the completion of the trial.
The last column of Table II sets out average 
daily miracidia hatch before the trial, during 
the trial and for five weeks after. The lowest 
average hatch was in the third week, but by the 
eleventh and twelfth week the active hatch was 
back to the level above the first week, but dis­
tinctly lower than the pre-trial hatch figures.
Table I.
M id -D ay  T e r m in a l  U r in e  E gg C o u n t s  D u r in g  10 W e e k s  w h e n  S u b je c t  w a s  
G iv e n  O n e  G ram  N ir id a zo le  a t  1200 H o u r s  e a c h  W e d n e s d a y .
Average
Week Thurs. Fri. Sat. Sun. Mon. Tues. Wednes. Total daily eggs
0 — 30 — — 40 20 20 100 28
1 50 60 __ __ 30 20 10 170 34
2 0 20 --- --- 50 40 40 150 . 30
3 10 0 --- --- 60 20 40 130 26
4 40 0(a) --- --- 30 0 20 90 18
5 0 40 --- --- 0 0 20 60 12
6 . 20 50 --- --- 0 10 0 80 16
7 20 50 --- --- 30 180 80 360 75
8 20 50 --- --- 0 90 10 170 34
- 9 30 40 --- --- ■ 0 30 50 150 30
10 10 60 — — 110 30 10 220 44
Total 
1-10 weeks
200 370 — — 310 420 280 1 580 32
Daily
Average 20 37 --- --- 31 42 28 32 _
- 11 20 '■ 40 __ __ ■ 20 0 60 140 28
12 140 — Easter — 0 20 160 53
13 60 160 --- --- 80 80 100 480 96
14 100 ■ 40 - --- --- 10 0 60 210 42
15 40 110 — — 30 0 60 240 48
Total 360 350 __ __ 140 80 300 1 230 54
11-15 weeks
Daily
Average 72 87 — — 35 16 60 54 —
(a) No miracidia hatched, the only occasion this was observed.
41
SUPPRESSION USING NIRIDAZOLE
Table II.
Stool Egg C o u n t s , S u m  o f  T w o  Sa m p l e s  from  D aily  M orning S tool, O ne 
Processed  a t  O nce , t h e  O t h e r  A fter  24 H o urs S torage, for a 10-W eek  
Period W h e n  O ne Gram  o f  N iridazole w a s  A dministered  each  W ednesday
at 1200 H o u r s .
Week Thurs. Fri. Sat. Sun. Mon. Tues. Wed. Total
Av.
daily
eggs
Average 
miracidia 
hatch 
each day
0 — — 600 600 750 1 950 650 15
1 330 270 530 980 680 2 790 558 11
2 370 210 460 220 380 1 640 328 14
3 150 190 130 150 200 820 164 8
4 390 220 3 240 460 570 4 480 896 13
5 260 310 1 570 540 290 2 970 594 10
6 840 400 2 170 560 640 4610 922 13
7 220 330 1 450 410 480 2 890 578 10
8 370 440 700 720 280 2510 502 10
9 260 300 210 910 650 2 430 486 12
10 940 250 490 680 280 2 530 506 11
Total
weeks
1-10 4 130 2 920 10 950 5 630 4 450 28 080 562
Av. daily
eggs weeks
1-10 413 292 1 104 563 435
Av. mira-
cidia
hatch 10 8 13 12 12
11 540 210 680 470 230 2 230 446 9
12 510 — Easter — 490 640 1 640 547 10
13 580 530 350 290 210 1 960 342 10
14 240 410 710 1 240 540 3 190 638 13
15 340 410 730 1 140 250 2 870 574 11
Total
11-15
weeks 2 260 1 660 2 470 3 630 1 870 11 890 517
Av. daily
eggs 11-
15 weeks 452 415 617 726 374 517
Av. mira-
cidia
hatch 9 9 12 13 10
42
| The hatch figures for the Monday, Tuesday and 
j Wednesday, prior to taking the first dose of 
[ Niridazole, were 18, 16 and 12, respectively, 
f In the ten weeks of the trial period it will be 
seen that average figures for miracidia hatching 
for each day of the week corresponds to the 
average number of .eggs counted on that day. In 
general this agreement is evident also in the five- 
week post-treatment observations.
D is c u s s io n .
The concept of “suppressive management” in 
the control of bilharziasis is an attractive one 
and if by the administration on a weekly basis 
of a schistosomicidal drug, even if only a signi­
ficant reduction in egg load was achieved, the 
method might merit'more widespread use.
Town Mavida was a good deal heavier than 
an average African school child, and so, of 
course, the dose of Ambilhar of 1 gram per 
week resulted in a much lower concentration 
of drug in his case than would be the case when 
treating school children in the same way. How­
ever, despite the lack of any real reduction in S. mansoni output, there seemed to be a signifi­
cant reduction in the miracidia hatching ratio. 
In the case of the subject’s S. haematobium in­
fection, the results were frankly very disappoint­
ing, and, in fact, the drug seems to have stimu­
lated egg output to reach a higher level. Town 
Mavida’s weight remained unaffected by the 
course of treatment, which would seem to in­
dicate that worm destruction was not really 
being achieved.
A c k n o w l e d g m e n t .
We are grateful to Dr. E. Burnett Smith, 
Acting Secretary for Health, Rhodesia, for per­
mission to publish.
R e fe r e n c e s .
Be ll , D. R. (1963) Bull. Wld. Hlth. Org. 29, 525.
Blair , D. M ., W eber , M . C. & C larke  V . de V . 
(1969) Cent. Afr. J. Med.  15, (Suppl. No. 10,
p. 11).
F aigle,  J. W. & K eberle , H. (1965) Acta. Trop. 
Supp. 9, 8.
L e e s , R..E . M . (1968) Trans, roy. Soc .  trop. Med.  
Hyg.  61, 782.
M eese r , C. V ., Ross, W. F. & B lair , D. M . (1948) 
/. trop.  Med.  Hyg.  51, 54.
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A Study Of The Effects Of Weekly Doses Of Niridazole On Schistosome Egg Output And Miricidial Hatching In A Patient Suffering From Bilharziasis

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A Study Of The Effects Of Weekly Doses Of Niridazole On Schistosome Egg Output And Miricidial Hatching In A Patient Suffering From Bilharziasis

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