A research paper on the effectiveness of a new  technological method  to ascertain HIV antigens in the blood of Zimbabwean patients in the  early 1990's.Over a three-year period, 646 sera from 630 patients with signs and symptoms compatible with neurocysticercosis were investigated for antibodies to cysticcrcal antigens using an ELISA test. Overall, 12 pc specimens were positive. The sensitivity of the ELISA, when compared with a limited number of computerised tomography investigations, was over 70 pc. False negative serology was associated with HIV infection in some patients. The positive predictive value was 87 pc and the negative predictive value was 85 pc when patients with active infection, potentially amenable to chemotherapy, were considered. The specificity, determined from serological tests of patients with a variety of trematode, cestode and other infections, was over 90 pc. Three of 11 patients with intestinal taeniasis, and each of two patients with hydatid disease were seropositive.
The results suggest the value of ELIS A serology as a more cost-effective diagnostic method for all patients with suspected cysticercosis

Gwanzura, L.

Houston, S.

Mason, P.

Central African Journal of Medicine

English

IDS OpenDocs

The
Central African 
Journal 
of
Medicine
Supplementary Issue to 1992 Volume 38,
1991 University of Zimbabwe Annual Research Day
Vol.3S,N o. 4, April, 1992
Neurocysticercosis: 
experience with diagnosis 
by ELISA serology and 
computerised tomography 
in Zimbabwe
P MASON*, S HOUSTON**, L GWANZURA* 
SUMMARY
Over a three-year period, 646 sera from 630 patients 
w ith signs and sym ptom s com patib le  with 
neurocysticercosis were investigated for antibodies 
to cysticcrcal antigens using an ELISA test. Overall, 
12 pc specimens were positive. The sensitivity of the 
ELISA, when compared with a limited number of 
computerised tomography investigations, was over 
70 pc. False negative serology was associated with 
HIV infection in some patients.
The positive predictive value was 87 pc and the 
negative predictive value was 85 pc when patients 
with active infection, potentially amenable to 
chemotherapy, were considered. The specificity, 
determined from serological tests of patients with a 
variety of trematode, cestode and other infections, 
was over 90 pc. Three of 11 patients with intestinal 
taeniasis, and each of two patients with hydatid 
disease were seropositive.
The results suggest the value of ELIS A serology as 
a more cost-effective diagnostic method for all 
patients with suspected cysticercosis.
D epartm ents o f M edical M icrobiology* and C lin ical 
Pharmacology* *
University of Zimbabwe Medical School 
Harare, Zimbabwe
**Current address: Division o f Infectious Diseases, 2E4.11 
W. C. Mackenzie Centre 
University o f Alberta 
Edmonton
Alberta T6G 2B7, Canada 
Correspondence to 
P R Mason
Department o f Medical Microbiology 
University o f Zimbabwe Medical School 
PO Box A 178 
Avondale
Harare, Zimbabwe
149
INTRODUCTION
Ncurocysticercosis (NCC) is the most important 
parasitic disease of the central nervous system 
worldwide and is a significant public health problem 
in many developing countries. '"  It has been reported 
in up to 3,6 pc of autopsies in Mexico City and was 
found to account for about 10 pc of neurology 
admissions there. In a study of mine workers with 
newly diagnosed epilepsy in South Africa, computed 
tomography (CT) showed 37 pc to have calcified or 
inactive lesions and 14 pc to have viable cysts.4 NCC 
was considered to be the cause in 30 pc of patients 
presenting with “ idiopathic epilepsy” in Natal.5 In 
Zimbabwe, calcified cyslicerci are not uncommon 
incidental findings on chest or limb X-rays and NCC 
is an occasional diagnosis at surgery for intracranial 
or spinal lesions. A study in Bulawayo found calcified 
cyslicerci in 11 pc of patients presenting with seizures 
in whom thigh X-rays were taken.6
The early diagnosis of NCC has become important 
because of the success of chemotherapy, using 
albendazole or praziquantel, for treatment of patients 
with viable cysticerci. Clinical diagnosis is highly 
unreliable and X-ray examinations will reveal only 
calcified cysts which are not amenable to treatment. 
While CT is widely regarded as the best method for 
detecting cysticerci, it is unlikely to be widely 
available in developing countries because of its cost.
There is thus a need for an inexpensive and reliable 
diagnostic test suitable for use in developing 
coun tries. R ecent atten tion  has focused on 
immunological diagnosis ' and in Zimbabwe an 
ELISA test was developed for detecting scrum 
antibodies to antigens extracted from the fluid of live 
cysticerci.11 Limited experience demonstrated a 
good correlation between positive serology and 
active cysticercosis, though responses in patients 
with inactive, calcified lesions were more variable.11 
We here report on our experience with diagnosing 
NCC over a three-year period during which the 
ELISA test was made available as a routine clinical 
service, and in which funds were available for a 
limited number of CT scans.
CENTRAL AFRICAN
JOURNAL OF MEDICINE
Vol. 38, No. 4, April, 1992
MATERIALS AND METHODS
Patients: Patients were recruited from several 
sources. Staff at the two Harare teaching hospitals 
were encouraged to send clotted blood specimens 
from all in- or out-patients presenting with seizures, 
suspected mass lesions or other neurological 
syndromes compatible with NCC. We attempted to 
contact all patients with positive serology to obtain a 
CT scan. In addition, a number of patients who had 
NCC diagnosed on CT scan in the course of their 
clinical investigation or as part of a study on 
in trac ran ia l m ass lesions and H IV -rcla lcd  
neurological disorders, were included in this study, 
and clotted blood was obtained from them. Blood and 
CT scans were also requested from a few patients in 
whom a diagnosis of cysticercosis was made by 
biopsy.
In order to obtain information on NCC in other 
groups of patients, we reviewed 68 CT scans from 
patients with a history of acute stroke, and we 
obtained clotted blood from patients with a variety of 
ccstode, trematode and other infectious diseases 
common in Zimbabwe, as well as from 61 patients 
enrolled in a community study of seizure treatment. 
CT Scans: The CT scans were performed in most 
cases both with and without contrast enhancement 
and the scans were interpreted by a neurologist 
experienced in both CT and NCC. Examples of the 
scans obtained and their interpretation arc shown in 
Figures I—III.
ELISA serology: Sera were separated from the
clotted blood specimens and were stored frozen at
-°C before testing. The NCC ELISA was carried out
using a method modified from that described 
1 1
previously. Briefly, micro-titre ELISA plates were 
coated overnight at4°C with antigen (prepared from 
fluid expressed from live cysticerci and stored at 
-70°C) containing 10 jig protein in 100 pi carbonate 
buffer (pH 9). After washing three times with 
phosphate buffered saline containing 0,05 pc Tween 
20 (PBST, pH 7,3), 50 pi scrum (diluted 1/200 in 
PBST) was added to duplicate wells and incubated 
for 45 minutes at 37°C. Appropriate positive and 
negative sera were included with each run. After 
w ashing  as above , 50pl peroxidase-labelled 
anti-human IgG (Cooper Biomedical, USA, diluted 
1/3000 with PBST) was added to the wells and plates
150
CENTRAL AFRICAN
JOURNAL OF MEDICINE
VoL 38, No. 4, April, 1992
Figure 1: CT scan showing "owl eye" lesions typical Figure II: Multiple large parenchymal cysticerci with 
o f cysticercosis midline shift
Figure III: Multiple calcified cysticerci were reincubatcd at 37°C for 45 minutes. After w ash ing  ag a in , 50 pi su b s tra te  (0 ,04 pc 
orthophenylcne diamine in 0,2M acetate buffer, pH 
5,5, with 0,6 pi20-Vol hydrogen peroxide to each ml 
of substate added immediately before use) was added 
to each well. Colour development was allowed to 
continue for 10 minutes at room temperature before 
being stopped by the addition o f 50 p.1 4N 
hydrochloric acid. Optical densities were read 
immediately on a Titertek Multiskan ELIS A reader at 
492nm. The delta OD was calculated as the difference 
between the mean of duplicate antigen positive wells 
and the mean of the duplicate antigen negative wells 
for the same serum, as described previously.11
A delta OD>0,3 was considered positive, and <0,2 
was considered negative. Sera giving intermediate 
values were retested, and if the same result was 
obtained, they were regarded as positive but 
suggestive of old, inactive cysticercosis.
Statistics: Sensitivity was determined as the 
percen tage sera from CT or biopsy proven 
cysticercosis patients giving a positive NCC ELISA.
151
CENTRAL AFRICAN
JOURNAL OF MEDICINE
V d .3 8 .N o . 4, April. 1992
The positive predictive value was determined as the 
percentage of all patients with apositiveNCC ELISA 
whose CT or biopsy confirmed active cysticercosis.
The negative predictive value was determined as the 
percentage of all patients with an NCC ELISA of 0.2 
whose CT scan showed no evidence of active 
cysticercosis. While it would have been preferable to 
perform CT scans on all patients in this study, in order 
to determine specificity, this was not possible 
because of costs. Specificity was therefore calculated 
from patients with infections other than cysticercosis 
giving a negative NCC ELISA.
RESULTS
Over the three-year period that this study was 
continued, serological tests were carried out on 646 
specimens from 630 patients with neurological signs ct? 
or symptoms compatible with NCC. Overall, 80 (20 
pc) specimens from 67 (11 pc) patients were positive - a . 
(Figure IV). The prevalence was higher in men °  
(66/377, 18 pc) than in women (10/149,7 pc) where <J 
the sex was recorded on the request form. Among 332 
patients for whom the age was given, less than 10 pc 
of those under 20 years were seropositive, compared 
with 11 pc aged 20-29,22 pc aged 30-39,23 pc aged 
40-49 and 27 pc aged 50 years or more.
Forty-eight sera were obtained from 42 patients 
with CT or biopsy evidence of active NCC, and of 
these 40 had a delta OD >0,2 and 34 had a delta OD 
>0,3, giving sensitivities of 83 pc and 71 pc at these 
two levels. False negative serology was associated 
with HIV infection in three patients, but could not be 
accounted for in the others. Of 22 specimens from 20 
patients with CT or X-ray evidence of calcified cysts 
only, 12 (55 pc) had a delta<0,2, four (18 pc) had a 
delta OD >0,3 and six (27 pc) had intermediate 
values. Negative serology (delta OD <0,2) was found 
in 35/38 (92 pc) specimens from CT negative 
patients, while two gave intermediate values, and one 
was seropositive (delta OD >0,3). The positive 
predictive value was thus 75 pc (40/53) at a delta OD 
level o f  >0,2 and 87 pc (34/39) at >0,3 and the 
negative predictive value was 65 pc (35/55) of 
patients with no evidence of infection at all, and 85 
pc (47/55) of patients with no evidence of active 
infection.
N one o f 25 p a tien ts  w ith  in te s tin a l 
hymenolepiasis, 30 patients with schistosomiasis, 30
Figure IV: ELISA serology fo r  cysticercosis. Delta 
OD valuesfor patients with active neurocysticercosis, 
patients with calcified cysts only and patients with 
negative computerised tomography scan
ONLY
patients with leprosy, 21 patients with acute malaria, 
30 patients with positive syphilis serology and 30 
patients with pyrexia of unknown origin were NCC 
ELISA positive. Three of 11 (27 pc) patients with 
intestinal taeniasis, and each of two patients with 
biopsy prove hydatid disease were seropositive.
Of the 61 patients from the community epilepsy 
treatment study, two (3 pc) had positive serology. One 
had died of undetermined causes before he could be 
traced, and the other had calcified lesions on CT. Six 
(9 pc) of the 68 CT scans from the stroke study 
showed calcifications compatible with inactive 
cysticercosis, but none had active cysticerci.
152
CENTRAL AFRICAN
JOURNAL OF MEDICINE
Vol. 38, No. 4, April, 1992
DISCUSSION
In this study we obtained evidence of active NCC in 
11 pc of patients attending a neurology clinic, and in 
3 pc of outpatients enrolled in a community study of 
seizure treatment. The frequency and seriousness of 
NCC and the availability of effective chcmolheraphy 
militate in favour of an active approach to diagnosis 
using a more effective technique than CT scanning. 
Our experience suggests that all patients presenting 
with unexplained seizures or other neurologic 
syndromes compatible with NCC should be tested for 
anti-cysticcrcal antibodies. Because of the high 
positive predictive value of the test in our setting, 
patients with positive serology, particularly those 
giving a delta OD >0,3 should be considered for 
chem otherapy  w ith o u t fu rth e r d iag n o stic  
investigations.
For patients with an intermediate result (delta OD 
0,2-0,3) it would be advisable to obtain CT or other 
evidence of active infection before commencing 
treatment. False positive serology appeared to be 
limited largely to patients with intestinal tacniasis or 
with hydatid disease. The former may be at risk of 
developing or transmitting NCC and would be treated 
effectively, if excessively, by the therapy for NCC. 
Human hydatid disease occurs so rarely in Zimbabwe 
as to be a rare source of diagnostic confusion. We 
have found no evidence of false positivity due to 
common parasitic or other infections.
False negative results were occasionally recorded 
in patients with viable CNS cysticcrci, and while 
some of these patients were known to be HI V positive 
and therefore possibly immunocompromised, this 
was not the case in all. Failure to detect many cases 
of infection with inactive, non-viable cysticerp is of 
limited concern since these lesions do not benefit 
from chemotherapy.
Many studies have documented improvement or 
resolution of NCC lesions following treatment with 
praziquantel or albendazole.12' 14 There is clear 
consensus that brain parenchymal cysts, particularly 
those that are large and lacking in inflammatory 
response, benefit from treatment, but a number of 
issues remain controversial. A reaction ranging from 
headache to seizures and obtundation may sometimes 
follow soon after commencing anthelminthic
therapy, presumably related to the release of antigens 
from dying parasites.
Some authorities recommend the administration of 
glucocorticosteroids prophylactically while others 
suggest they should be used only when severe 
reactions occur.15, 16 In children, NCC is often 
characterised by multiple inflammatory lesions 
which resolve without specific anthelminthic 
therapy, and the role of such therapy is thus not 
clear.17 The efficacy of anthelminthic therapy 
appears to be low in basal meningitis or subarachnoid 
cysts, negligible in intraventricular or intraocular 
cysts,19' 20 unestablished in spinal cysts and, of 
course, absent in calcified cysts.
There is good evidence that albendazole is at least 
as effective as praziquantel for chemotherapy of 
NCC, and although the optimal dose has not yet been 
established, the cost of treatment is likely to be 
considerably lower. Because of the possibility of 
reactions, treatment should be commenced in 
hospital. Every effort should be made to obtain CT 
scan or neurosurgical opinion for patients with 
findings of raised intracranial pressure, and 
ventricular shunting is advised before anticysticercal 
treatment in patients with hydrocephalus.
In summary, NCC is a common cause of 
neurological disease in Zimbabwe, and serological 
diagnosis appears to be a useful and practical 
approach to diagnosis, with the ELISA test showing 
high specificity and sensitivity. Further studies are 
needed to determine the efficacy of a diagnostic 
strategy based on serology rather than CT, and to 
establish whether serology can be used to follow up 
patients and confirm cure.
ACKNOWLEDGEMENTS
This study was funded by the University of 
Zimbabwe Research Board. The CT Centre in Harare 
performed scans at a greatly reduced charge in order 
to enable this study to be completed, and we are 
grateful for their assistance. Dr C. Thornton reviewed 
the CT scans, Dr J. Matenga made available the CT 
scans from the stroke study, and Dr C. Nhachi made 
available the sera from the community seizure 
treatment study. Prof L. Levy and Mr S. Makarawo 
are thanked for their support in referring a large 
number of patients to this study.
153
CENTRAL AFRICAN
JOURNAL OF MEDICINE
Vol. 38, No. 4, April, 1992
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Neurocysticercosis: experience with diagnosis by ELISA serology and computerised tomography in Zimbabwe

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Neurocysticercosis: experience with diagnosis by ELISA serology and computerised tomography in Zimbabwe

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