A  CAJM  article on clinical testing and treatment   for bilharziasis.The studies of the effects of treatment on individual patients suffering from bilharziasis has been a feature of the work of this Laboratory for some years (Blair et al. 1969b). From this work has emerged some interesting information on the disappearance and re-appearance of eggs and miracidia when treatment has failed. The earlier work was based on specimens of urine and stool passed by the patients from Monday to Friday only

Blair, D.M.

Warburton, B.

Weber, M.G.

Central African Journal of Medicine

English

IDS OpenDocs

The Central African Journal of Medicine
Editor-.
M ICHAEL GELFAND, C.B.E., M.D., F.R.C.P.
Assistant Editor-. 
JOSEPH RITCHKEN, M.D.
Volume Nineteen 
JANUARY - DECEMBER 
1973
I
Sa lisb u r y
ciPceM fSZ
R h od esia
A Long-term Study of a Case of 
Schistosoma Mansoni Subjected 
to Repeated Courses of 
Treatment
BY
BRIDGET W ARBURTON,
M. G. WEBER
AND
D. M. BLAIR
Blair Research Laboratory, Salisbury, Rhodesia. 
I n tro d u c tio n .
The studies of the effects of treatment on in­
dividual patients suffering from bilharziasis has 
been a feature of the work of this Laboratory 
for some years. (Blair et al. 1969b). From this 
work has emerged some interesting information 
on the disappearance and re-appearance of eggs 
and miracidia when treatment has failed. The 
earlier work was based on specimens of urine 
and stool passed by the patients from Monday 
to Friday only.
The subject, Lovemore Manyoso, came to 
hand in March, 1971. He was an African male 
aged about 18 years and weighing 53 kg. The 
specimens of urine were collected and prepared 
as described in Blair et al. (1969b), and the 
stools as described in Blair et al. (1969a).
Miracidia hatching examinations were carried 
out at 1000, 1200 and 1500 hours, using the 
techniques described by Weber (1973).
M e t h o d .
Stool and urine specimens were obtained from 
this patient for a few days prior to the first 
treatment to be sure he understood how to pass 
his mid-day terminal urine and take a sample 
of stool. No attempt was made to show him 
what part of the stool should be taken for ex­
amination, especially as at this stage his stool 
was not formed.
Specimens taken by the patient on Saturday, 
Sunday and Monday were processed on M on­
day. Miracidial hatching examinations were 
carried out at 1000, 1200 and' 1500 hours, which 
meant that each tube was examined at least 
eight times —  twice the day of processing the 
stool, and three times on each of the following 
two days. When the week-end broke the routine, 
one examination was done on Saturday morn­
ing and carried on three times on Monday.
T h e  T r ial .
It was established that the patient had a 
double schistosome infection; S. haematobium 
in the urine and S. mansoni in the stool. The 
urinary infection was very light, showing only 
10 to 20 eggs in a mid-day terminal urine 
sample. Miracidia were freely hatched. This 
infection disappeared completely after the first 
course of treatment.
In the case of his stool infection, the egg 
counts on the samples of early morning stool 
ranged from 260 to 430 S. mansoni eggs, and 
miracidia were seen at each examination of the 
specimens over a three-day period, ranging 
from +  to 4 +  , the latter being the second 
highest categorv in estimation of miracidia 
seen.
The grading of active miracidia seen cannot 
be done with accuracy for such fast-moving 
larval forms, but does give a reliable index of 
the numbers present when estimated by experi­
enced observers.
■ .Physically the patient was a stockily-built 
youth and had no other signs or symptoms ex­
cept that the liver was easily palpable under 
the right costal margin, and was tender in this 
area on deep palpation.
T r e a t m e n t .
The following attempts at therapy were 
made: —
1. On 27th March, 1971, with the patient’s 
weight at 53 kg he was given an intramus­
cular injection of 160 mg hycanthon (Etre- 
nol Winthrop), a dose of 3,0 mg/kg. The 
egg counts in urine and stool on the day of 
treatment were 10 and 4309 respectively,
v and miracidia hatched in each case in the 
stool up to a 4 +  rating. He showed no 
toxic or any other side-effects to treat-, 
ment.
2. From 17th to 22nd May, 1917, he was 
given niridazole (Ambilhar. CIBA), 750 
mg each morning and 1 000 mg in the 
evening for six days. As his weight was 
now 54 kg this represents a daily dose of 
32,4 mg/kg. He carried on his work as 
a gardener without interruption, but ad­
mitted he had slight nausea on the after­
noon of the third day of treatment.
3. On 17 th August, 1971, he began a second 
course of niridazole. His weight was now 
55 kg and he was given 750 mg morning 
and evening for six days; 27,3 mg/kg. 
One hour after the first dose of niridazole 
was taken he was given an intravenous
■ injection of 65 mg sodium antimony tar­
trate (S.A.T.) This was given in the hope
49
MULTIPLE TREATMENTS
that the antimony might free the hold 
of schistosome worms in the smaller tri­
butaries of the portal vein and allow 
themselves to be swept up to the liver 
where they might be subjected to higher 
concentrations of niridazole. The only 
side-effect experienced was some joint 
pain, including pain in the temporo-man- 
dibular joints, a site where pain had been 
reported previously after niridazole 
therapy. Prior to this treatment the liver 
was easily palpable below the costal mar­
gin and there was slight tenderness on 
palpation in the mid-line.
4. On 26th October, 1971, his weight was 
56 kg and he was given 180 mg of hycan- 
thone intramuscularly; 3,2 mg/kg. An 
hour later he was given 100 mg S.A.T. 
intravenously with the same objective 
as described above.
5. On 4th April, 1972, his weight had fallen 
to 54,5 kg, his liver was easily palpable 
and slightly tender in the mid-line. He 
was given an intramuscular injection of 
hycanthone; total dose 170 mg; i.e., 3,1 
mg/kg.
F o l l o w -U p A n a l y s is .
Table I summarises the egg counts and 
hatching estimations before and after each 
treatment.
It will be seen that hatching miracidia gen­
erally continued to be observed after micro­
scopic evidence of eggs had disappeared, and
that miracidia re-appeared generally before the 
presence of eggs was detectable on microscopic 
examination.
From March, 1971, to May, 1972, a morning 
stool sample was taken by the patient on 398 
days, and the following is the summary of the 
findings. They were:
231 days on which eggs were seen and mira­
cidia hatched;
9 days on which eggs were seen, but no mira­
cidia were hatched;
105 days on which no eggs were seen, but 
miracidia were hatched; and
55 days when there were no eggs seen and no 
miracidia were hatched.
Despite five separate treatments during this 
period the patient continued to pass eggs 
or miracidia were hatched on all the days 
observed except for 55 days; this is rather 
surprising.
The results demonstrate very well the value 
of miracidia hatching as a sensitive and reliable 
method of diagnosis in S. mansoni bilharziasis, 
especially in the follow-up programme after 
treatment when eggs are sparse in the stool 
specimen. Over this period, relying only on 
microscopic examination for eggs, evidence 
would have been found on 240 days while by 
miracidial hatching alone this would have been 
seen on 335 days. Using only microscopic 
methods of examination, only 70 per cent, of 
the days when evidence of stool infection existed 
would be detected, while using miracidial 
hatching, 97 per cent, would be detected.
Table I.
D a ily  S. m a n s o n i E ggs and  M iracidial H a tc h in g  in  R elatio n  to  R epeated
T r e a t m e n t .
No. and 
date of 
treatment Drug Used Pre-treatment
No. of days to 
disappearance of
No. of days of 
absence of
No. of days from end 
of treatments to 
return to steady 
, output of eggs and 
miracidia
Eggs Hatch Eggs Hatch Eggs Hatch
D 17-3-71 Hycanthone 430 4 + 16 21 14 9 44
2 ' 17-5-71
to
23-5-71
Niridazole 130 3 + 21 21 5 5 49
3 17-8-71
to
23-8-71
Niridazole 
+  S.A.T.
301 + 5 11 10 3 17
4 26-11-71 Hycanthone 
+  S.A.T.
90 3 + 8 18 24 3 63
5 4-4-72 Hycanthone 60 + 17 17 15 15 59
50
MULTIPLE TREATMENTS
S. mansoni egg output:
Prior to treatment, the patient’s weekly egg 
count was established to be over 2 000 per week. 
The three re-treatments, given in May, August 
and October, 1971, were given as soon as it 
was obvious from the egg count levels and the 
miracidial hatching that the previous treatment 
had not destroyed all S. mansoni worms. After 
the fourth treatment given on 26th October, 
1971, had also failed to achieve this objective, 
it was decided to continue the daily follow-up 
examinations for a longer period in order to 
see whether there was any trend in the daily 
egg production and miracidia hatching.
When only a small number of eggs were to 
be counted in the week’s specimens, and mira­
cidial hatching was scanty, it is probably better 
to study the result of summing the eggs counted 
in the seven daily specimens examined in a week. 
Miracidial output intensity and duration was 
assessed by summing for one week’s samples the 
number of times the samples were examined 
over a three-day period, generally eight times 
for each. The procedure is best illustrated by 
an example of miracidial hatching. On a speci­
men. of 7th July, 1972, the first day at 12 noon 
and 1500 hours, and on the second and third 
dav at 1 000, 1200 and 1500 hours, the mira­
cidia hatch ratings were + ,  2 +  , + ,  +  , +  , 2 
—, + ,  — ; a total of eight in eight examinations. 
The summing of the miracidial hatchings for 
this week was, in fact, 48 in 56 observations. 
From the week commencing 7 th May, 1971, no 
eggs were seen for three weeks, 10 in the fourth 
week, and the miracidia hatch was very scanty 
and were seen in only 6/59, 3/56, 15/57 and 
15/58. For the week commencing 5th Decem­
ber, 1971, eggs seen totalled 70, and miracidia 
seen on 13 occasions in 57 observations. Four 
weeks later, the week commencing 2nd January, 
1972, egg output was 150 and miracidia seen 
43/58. A  further five weeks later, during the 
week beginning 6th February, egg output was 
630 and miracidia 47/58. Thereafter the weekly 
egg output ranged from 300 to 500 and on a 
number of occasions each week 2 +  miracidia 
hatchings - were recorded. The situation was 
that after over a year’s observation and four 
treatments with schistosomacidal drugs, the egg 
output was reduced to about 10 per cent, of the 
pre-treatment level, but there was no doubt 
about the viability of the surviving worms and 
their eggs. The fifth course of treatment was 
given on 4th April, 1972.
Twelve weeks later, the week beginning 2nd 
July, 1972, 110 eggs and miracidia seen on 
48/56 observations and 2 +  hatches were regis­
tered on three occasions. The weekly egg output 
was now down to about five per cent, of the
pre-treatment level, but there was still no doubt 
of the viability of the infection. It was decided 
at this stage to desist from any further attempts 
to treat him with hycanthone and niridazole.
D is c u s s io n .
The conditions of Lovemore Manyoso’s en- 
such that re-infection during this time can be 
ruled out. Nevertheless he, in company with 
vironment during the course of this study were 
his cousins, the Mavida brothers, whose 
accounts appear in earlier papers of this supple­
ment (Blair & Weber, 1973) and in the previous 
issues of this Journal, show the same pattern of 
marked reduction in S.mansoni egg output and 
imracidia output after their first course of treat­
ment, but a continuance of evidence of infection 
at a lower level. The persisting infection showed 
a disappointing response to repeated treatment.
The disappearance of eggs and miracadia 
after treatment, the freedom from eggs and 
miracidia, and the eventual return of eggs and 
miracidia, show the value of miracidial hatching 
as a means of observing infections after treat­
ment. There appears to be no significant diff­
erence in the disappearance, absence and re­
appearance of eggs and miracidia after each 
treatment, except in the case of the second 
niridazole treatment on 17th August, 1971. In 
this treatment, although eggs and miracidia 
disappeared from the daily stool specimens soon 
after the end of treatment, the days from the 
end of treatment to a return of steady output of 
eggs and miracidia was only 17 days, which is 
less than one-third of the time taken to get back 
to this level after the other four treatments. 
Neither drug —  three treatments of hycanthone 
and two with niridazole —  caused any incon­
venience to the patient, or any real toxic side- 
effects. Field trials in Rhodesia have shown that 
either drug will “ cure” about 75 per cent, of 
patients and the other 25 per cent, will show 
“ improvement” with great reduction in the 
number of eggs passed, and improvements in 
their health and physical condition. Further 
and repeated treatment with one or other of 
the two drugs mentioned produces very little 
reduction in egg output: Improved and more 
sensitive methods of the diagnosis of S. mansoni 
bilharziasis show that many patients whose 
follow-up examinations include routine and 
proper miracidia hatching, will be found not to 
be cured; many of these patients would have 
been assessed as “ cured”  if the examination 
consisted of only a single microscopic examina­
tion of stool, perhaps only on a simple direct 
smear.
The fate of the 25 per cent, of S. mansoni 
patients who are not cured by a single course
51
MULTIPLE TREATMENTS
of treatment with one of the modern agents 
has been a matter of great interest and concern 
over the past four years. The disappointing 
results of repeated treatments has raised a num­
ber of controversial points as to what action, if 
any, should be taken.
There is no doubt that one treatment will 
“ cure” or “ improve” the great majority of 
patients. Re-treatment of those who are not 
“ cured” shows disappointing results, and up to 
10 courses of treatment have been given with­
out eliminating all stool egg production.
1. Are some strains of S. mansoni resistant to
the newer drugs?
It is interesting to note that three young Afri­
cans suffering from S. mansoni infections, who 
come from the same locality, were not cured 
easily. O n . the other hand, similar poor results 
on repeated treatment have been observed and 
reported from other areas in Rhodesia uncon­
nected with the Zambesi Valley area. Failure 
to cure has not been an exclusive feature of 
young patients, but is also seen quite frequently 
in adults —  even older adults. At one stage it 
was thought that the livers of younger patients 
are less damaged than those of their elders, and 
so metabolise the drugs speedily before they 
could exercise their full effect on the worms.
2. Where in the portal system do the modern
drugs act on the worms?
In the days up to and immediately after 
World War II when antimonials reigned 
supreme in the treatment of bilharziasis, much 
attention was directed to the study of the “ liver 
shift”  of worms, which was said to occur when 
antimony was administered. Cautions were 
stated that any schedule of treatment which 
caused a massive shift of worms to the liver 
could be dangerous causing severe and even 
fatal liver damage. The suggestion was that the 
worms had to be encouraged to shift from their 
egg-laying sites to the liver to be subjected to 
the lethal effects of anitomy. With the newer 
drugs, niridazole and hycanthone, one hears 
fewer comments on the danger of “ liver shift” 
of worms and damage to the liver. Do these 
drugs circulate from the liver to the arteries 
serving the organs where worms are sited and 
causing them to be swept up to the liver where 
the drug would eventually destroy the worms? 
Perhaps the modern drugs are much less effec­
tive than antimony in releasing the hold of the 
worms in the mucosa of bowel, although they 
seem, from experience of cure, to be so effective 
in destroying S. haematobium worms This 
might explain why S. mansoni worms 
remaining in their egg-laying sites cease egg 
production after treatment, only to start again
when the drug is no longer present. Perhaps 
further treatment of the same nature has just 
as little effect on the lives of the worms as the 
first treatment.
3. Should one be satisfied with “ cure”  of say, 
75 per cent, of patients and reduction of 
worm load in the remainder after a single 
course of treatment?
From the public health viewpoint such a 
result is of great value in the reduction of in­
fection of surface waterbodies. The younger age 
groups of the population show the highest preva­
lence of bilharziasis; they generally have greater 
individual worm burdens; their habits and 
actions often result in fouling of surface water- 
bodies and so a big reduction in the output of 
hatchable eggs is bound to reduce the infection 
potential of the water environment. The im­
provement in general health, weight gain, im­
provement in skin tone and conditions, and in 
mental and physical achievement, is difficult to 
measure, but undoubtedly occurs, although so 
far few studies have produced valid scientific 
evidence to this effect.
The presence of a few residual worms in the 
bowel wall laying a small number of eggs may 
actually be an advantage to the host. If only 
minimal damage is done at the egg-laying sites, 
this may help the host to maintain and develop 
a resistance to future challenge infections.
Su m m a r y .
A patient with an S. mansoni infection was 
treated and re-treated on a total of five occa­
sions with hycanthone or niridazole over a 
period of 15 months, and still continues to-pass 
hatchable S. mansoni eggs in the stool at a level 
of about five percent, of that existing prior to 
treatment. Certain suggestions and thoughts are 
put forward concerning re-treatment and how 
far this should go.
A c k n o w l e d g m e n t s .
We are grateful to Sterling Winthrop for 
supplies of Etrenol for this case; to Dr. V . de V. 
Clarke, Director of the Blair Research Labora­
tory; and Dr. M. H. Webster, O.B.E., Secretary 
for Health, Rhodesia, for permission to submit 
the paper for publication; and, of course, a 
special tribute to the co-operation we received 
from our patient.
R e f e r e n c e s .
B lair , D. M., W e b e r , M. C. & V. de V. C lar ke
(1969a) Cent. Afr. J. Med IS, Supp. No. 10, 2.
_______________ (1969b) ibid. 15, Supp. No. 10, 11.
B lair , D. M. & W eber , M. C. (1973) ibid. 19, Supp.
No. 9. 39.
W eber , M. C. (1973) ibid Cent. Afr. J. Med. 19,
Supp. No. 9. 11.
52
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A Long-Term Study Of A Case Of Schistosoma Mansoni Subjected To Repeated Courses Of Treatment

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A Long-Term Study Of A Case Of Schistosoma Mansoni Subjected To Repeated Courses Of Treatment

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