Tropical Medicine and International Health

volume 8 no 8 pp 728–732 august 2003

Clinical presentation and diagnostic sensitivity of laboratory

tests for Strongyloides stercoralis in travellers compared
with immigrants in a non-endemic country
Sonali Sudarshi1, Richard Stümpfle1, Margaret Armstrong1, Thomas Ellman1, Simon Parton1,
Prabha Krishnan1, Peter L. Chiodini1,2 and Christopher J. M. Whitty1,2

1 The Hospital for Tropical Diseases, London, UK

2 London School of Hygiene and Tropical Medicine, London, UK

Summary objectives To assess whether the clinical and laboratory methods for diagnosing Strongyloides
stercoralis infection in non-endemic countries is different between those who are chronically exposed
and those who travel.
methods Analysis of laboratory and clinical data from 204 patients having S. stercoralis infection at
the Hospital for Tropical Diseases, London.
results Sixty-four travellers and 128 immigrants from endemic countries had laboratory-proven
strongyloides. In those with microscopically proven disease, serology was 73% sensitive in travellers and
98% sensitive in immigrants (P < 0.001). There was no difference in the eosinophil count between the
two groups with 19% having a normal count. Patterns of symptoms varied between the groups, and
around one-third were asymptomatic in both groups. Serology was of limited use in follow-up.
conclusions Eosinophil count and stool microscopy are insufficiently sensitive to be used alone for
screening strongyloides. The sensitivity of serology is good in immigrants with chronic infection, but
lower in travellers.

keywords S. stercoralis, serology, stool microscopy, eosinophil count, sensitivity, travellers, immigrants

strongyloides infection. Immigrants have often been

Introduction
Strongyloides stercoralis is a common parasite in many
populations, and occurs in returned travellers and immi-
grants to Europe and North America (Libman et al. 1993;
Schulte et al. 2002). Unlike other intestinal nematodes,
autoinfection is possible in the human host and clinical
symptoms can occur many decades after infection (Gill &
Bell 1979; Pelletier et al. 1988). If infection occurs when
patients are immunocompromised, treatment is difficult
and S. stercoralis hyperinfection can be life-threatening
(Chiodini et al. 2000; Adedayo et al. 2001). It is therefore
worth detecting and treating the infection, even in those
who are asymptomatic, and especially in those who are to
undergo immunosuppressive treatment.
Diagnosis of S. stercoralis infection is not easy and there
is no agreed ideal screening strategy. A recent study
reviewed the methods available (Siddiqui & Berk 2001).
Stool microscopy, charcoal culture, serology, agar plate
and hairy string test were tried in various combinations
(Sato et al. 1995; Uparanukraw et al. 1999). In non-
endemic countries, there are two groups who present with
chronically exposed to S. stercoralis along with other
helminths (Nutman et al. 1987). Travellers tend to have
shorter exposures, with their first exposure to helminths
only in adulthood. As in other parasitic infections such as
schistosomiasis and malaria, both clinical presentation and
sensitivity of screening tests for helminthic infections are
significantly different between travellers and immigrants
(Draper & Sirr 1980; Whitty et al. 2000) and it may also
be so in S. stercoralis infection (Carvalho et al. 1983;
Atkins et al. 1997). This study was conducted to explore
the screening strategies for travellers and immigrants in an
operational setting in London, UK.
Methods
All cases of proven or suspected S. stercoralis presenting
to the Hospital for Tropical Diseases (HTD) London
between 1991 and 2001 were identified from initial
diagnostic coding supplemented by microscopy and
serology laboratory record books. Data were collected
from laboratory records, prospectively recorded

728 ª 2003 Blackwell Publishing Ltd

Tropical Medicine and International Health
S. Sudarshi et al. Strongyloides stercoralis testing in travellers and immigrants
diagnostic and demographic data and case-note reviews
for symptomatology.
Patients were classified as travellers if they were born and
reside in a non-endemic country and had recently travelled
to endemic countries. They were classified as immigrants if
they were born and brought up in an endemic country but
were residing in a non-endemic country.
A case of strongyloides was defined as someone with
exposure to strongyloides in an endemic country and with
laboratory-proven strongyloides – either microscopical
identification (definite) or positive serology (probable).
Patients with a clinical diagnosis but without laboratory
confirmation (e.g. eosinophilia and typical symptoms, or
larva currens) were recorded for a more limited analysis.
Microscopy of stool was performed on formol-ether
concentration preparation (Allen & Ridley 1970). Stool
culture was based on the filter paper technique (Harada &
Mori 1955), modified with 50% charcoal and 50% stool
(in-house, HTD). A hairy string test was performed in
selected cases. This involves obtaining a duodenal sample
using nylon yarn coiled inside a capsule that the patient
swallows. Serological tests detect the presence of strong-
yloides immunoglobulin G (IgG) antibody by using antigen
prepared from filariform larvae grown on clean culture
(Neva et al. 1981). An enzyme-linked immunosorbent
assay (ELISA) gave an indication of the level of antibody
present with an optical density (OD) measure. A test was
considered positive if the OD exceeded 0.25 units (between
1991 and 2000), modified to 0.3 units in September
2000 after introducing a different batch of antigen.
Eosinophilia was defined as an absolute eosinophil count
of >0.5 · 109/l.
The treatment for all patients diagnosed with strongyl-
oides changed from albendazole 400 mg bd for
3–7 days to ivermectin 200 lg/kg in 1995 following a
systematic literature review (Gann et al. 1994; Dartry et al.
1995). All patients followed up for more than 3 months
were reviewed for possible treatment failure although as
the patient population served by HTD were itinerant, some
patients could not be followed up. Treatment failure was
defined as the presence of larvae by stool microscopy,
culture or string test. OD values of strongyloides ELISA
and absolute eosinophil count at follow-up were compared
with the initial level.
Results
A total of 204 consecutive cases of clinical strongyloides
infection were identified. Of these, 192 patients had
strongyloidiasis confirmed by laboratory tests; 102 patients
had detectable larvae found by formal-ether concentration
microscopy, culture or string test and 90 patients were
ª 2003 Blackwell Publishing Ltd
volume 8 no 8 pp 728–732 august 2003
identified by serology alone (negative stool in 89 patients,
stool not produced in one). Twelve patients were diag-
nosed clinically. Further analysis was restricted to the 192
patients with laboratory-confirmed strongyloides.
There were 60 women and 132 men (age range
13–82 years) with laboratory-confirmed strongyloides. The
median age at presentation was 35 years for men [inter-
quartile range (IQR) 31–51 years] and 34 years for women
(IQR 26–52 years). Of the 192 patients, 64 (33%) were
travellers and 128 (67%) were immigrants from endemic
areas. Exposure to strongyloides occurred in Africa in 48%
(travellers 47%, immigrants 49%); 34% in Asia (travellers
29%, immigrants 37%); 20% in the Caribbean (travellers
8%, immigrants 11%) and 3% in South America. In 5% of
patients, the maximum exposure site was mixed or not
apparent. A total of 140 (73%) of the 192 patients with
proven strongyloides had symptoms on presentation.
Differences in presentation between travellers and immi-
grants are given in Table 1.
The results of laboratory investigations are given in
Table 2 for immigrants and travellers. Of the 102 patients
who had detectable larvae on microscopy, 76 had sero-
logical tests performed, of whom 67 were positive with a
sensitivity of 88% for serology. Of 187 patients tested, 145
(78%) had eosinophilia at presentation. None were on
steroids. Thirty hairy string tests were performed with 16
positive results. String test and charcoal culture were used
to identify those cases who were not identified by any other
method.
Immigrants were significantly more likely to be positive
by serology (sensitivity 98% against larvae positive) than
travellers (sensitivity 73%) in those with microscopically
proven disease. Stratifying by age, symptoms and time
since last exposure of ‡1 year made no difference to this.
The proportion of immigrants with positive serology alone
(54%) was higher than in travellers (33%).
Seventy-one of 102 patients with initial stool positive for
microscopy returned for follow-up; seven of 24 patients
treated with albendazole had positive stool at follow-up
and one of 46 patients treated with ivermectin had a
Table 1 Reported symptoms in patients with Strongyloides
stercoralis
Travellers Immigrants Significance
n ¼ 64 n ¼ 128 2P
Any symptom 49 (78) 91 (71) 0.39
Bowel upset 30 (48) 37 (29) 0.01
All abdominal symptoms* 31 (49) 51 (41) 0.13
Skin symptoms 23 (37) 26 (21) 0.02
* Abdominal pain, diarrhoea, bloating.
Values in parentheses are percentages.
729
Tropical Medicine and International Health
S. Sudarshi et al. Strongyloides stercoralis testing in travellers and immigrants
Test Travellers Immigrants
Detectable larvae* 67% (43/64) 46% (59/128)
Eosinophilia 78% (47/60) 77% (98/127)
Eosinophilia in patients with 88% (36/41) 76% (44/58)
detectable larvae
Serology positive in patients 73% (22/30) 98% (45/46)
with detectable larvae
Serology in all patients 84% (43/51) 99% (114/115)
* Stool microscopy, culture or string test positive.
positive stool (P < 0.001). Two patients with hyperinfec-
tion and non-responsive to albendazole treatment became
stool-negative following ivermectin treatment. One lym-
phoma patient with human T-cell lymphocytotrophic
virus 1 (HTLV1) developed hyperinfection and was cured
of strongyloides with parenteral ivermectin treatment after
failure of oral albendazole and oral ivermectin (Chiodini
et al. 2000).
A total of 102 patients with positive serology were
followed up for a minimum of 3 months (median
6 months). Whilst on average, there was a fall in OD
(median fall 0.12 points) serology in 70 patients remained
positive throughout follow-up. Whereas all patients with
detectable larvae at follow-up had positive serology, in
25% of patients there was no drop in OD, including those
patients followed up to 2 years, with no evidence of
relapse. Serology rose in 18 patients, despite cessation of
symptoms with clearing of larvae from the stool and a drop
in eosinophil count. Sixty-four patients with initial eosi-
nophilia were followed up for more than 3 months. Fifty
patients became negative or had an eosinophil value that
was half the initial. Of the 14 remaining patients, one had
detectable larvae in the stool at follow-up and five patients
were found to have one or more co-existing worm
infections (three schistosomiasis, two filaria and one
hookworm). There were no differences between travellers
and immigrants.
Discussion
Although Strongyloides infection is common, it is poten-
tially serious if left untreated, especially in elderly or
immunocompromised individuals. It is particularly
important to identify and treat patients who have strong-
yloides if they are likely to undergo immunosuppression by
chemotherapy or high-dose steroids, even if they are
asymptomatic (Morgan et al. 1996). Recent fatalities
reported from hyperinfection highlight this as a real risk
(Suvajdzic et al. 1999; Adedayo et al. 2001). Immigrants
from endemic countries are at sufficient risk to warrant
730
volume 8 no 8 pp 728–732 august 2003
Table 2 Laboratory test results in travel-
Significance (2P) lers and immigrants with Strongyloides
stercoralis
0.005
0.85
0.14
0.001
<0.001
screening prior to immunosuppression, as the treatment is
safe and effective (Muennig et al. 1999). The prevalence of
strongyloidiasis amongst asymptomatic immigrants from
endemic areas has been reported to be around 5% (Lerman
et al. 1982), although estimating population prevalence is
not easy in strongyloides infections. Using Bayesian meth-
ods may be more reliable than using either serology or
stool microscopy alone (Joseph et al. 1995). However,
estimating the specificity of the test is not possible in the
absence of a gold standard, although the use of Bayesian
methods may help (Joseph et al. 1995). Positive tests in the
absence of symptoms or other positive tests may indicate
either subclinical or past infection.
The HTD is a tertiary referral centre, and referrals will
tend to be biased in favour of symptomatic individuals.
Despite this, almost one-third of patients were asympto-
matic, including patients with microscopically proven
infection. Immigrants are always said to have a lower
chance of being symptomatic, and the presentation in this
series would be compatible with this, although referral bias
cannot be excluded. There are reasons to think that
screening strategies are likely to have different operational
sensitivities between those who have been chronically
exposed, especially in childhood, and travellers. There are
reports of significant differences in immune response to
infection depending on presumed length of exposure,
including antibody responses, IgE levels and eosinophil
count (Carvalho et al. 1983; Atkins et al. 1997). As most
suggested screening strategies largely depend on serology
and eosinophil count, they have obvious practical impli-
cations (Gill & Bailey 1989). This observational study of
the performance of diagnostic tests in an operational
setting suggests that these theoretical differences may,
indeed, lead to important differences at the level of clinical
diagnosis between travellers and immigrants.
Eosinophil count, which is the simplest screening
method, was only present in 76% of immigrants and a
non-significantly higher percentage of travellers with
microscopically detectable larvae. It is not sufficiently
sensitive to act as a sole initial screening test in either
ª 2003 Blackwell Publishing Ltd
Tropical Medicine and International Health
S. Sudarshi et al. Strongyloides stercoralis testing in travellers and immigrants
group, and sensitivity has been found to be lower in other
series (Lerman et al. 1982; Libman et al. 1993).
Serological testing is widely used to screen asympto-
matic patients likely to undergo immunosuppression. The
central difference this study highlights is that serological
tests showed a significantly lower sensitivity in those
who were infected during brief exposure when travelling
than in immigrants when compared with the gold
standard of microscopically proven disease. The overall
sensitivity of serology in this series (89%) is similar to
published laboratory series (Gam et al. 1987; Genta
1998). As a single screening test for those about to
undergo immunosuppression this difference would, if
replicated, be important. If checked against those with
microscopically proven disease, ELISA was 98% sensitive
in those chronically exposed, but a quarter of those who
acquired the disease in adult life through travel were
missed. Adjusting for age, time since last exposure and
symptoms did not alter the odds ratio, making it unlikely
that these factors explain this difference. Indirect evi-
dence that serology is likely to be more sensitive in those
chronically exposed is derived from the fact that
published sensitivities in Far East prisoners of war are
98.5% compared with around 90% in a series of mixed
(but undifferentiated) populations (Bailey 1989).
It is likely that some asymptomatic individuals who were
detected by serology alone may have been infected in the
past, but not when the screening took place. Strongyloides
serology can cross-react because of infection by other
filarial worms. In clinical situations where improvements in
specificity are essential, it is possible to improve this by pre-
incubation with Oncocerca antigens (Conway et al. 1993;
Lindo et al. 1994). Since ivermectin treatment appears safe
and is well tolerated, in clinical practice balance of risk is
likely to indicate treatment of all with positive serology,
especially those who are likely to undergo immunosup-
pressive treatment.
Whilst median serology OD dropped in those followed
up, it shifted from positive to negative in a minority, and
was actually higher more than 3 months later in 18%. This
was true for both immigrants and travellers. Studies have
suggested that OD values do drop but results are hetero-
geneous (Kobayashi et al. 1994). This limits the usefulness
of serology in following up both immigrants and travellers
for treatment failure. This study suggests that judged
against microscopically proven disease, serology is sensi-
tive as a screening tool in immigrants with chronic
exposure but less effective in those with short adult
exposure – this needs to be replicated in larger studies.
Eosinophil count and stool microscopy are insufficiently
sensitive to be used alone for screening high-risk cases in
either group.
ª 2003 Blackwell Publishing Ltd
volume 8 no 8 pp 728–732 august 2003
References
Adedayo CO, Grell GA & Bellot P (2001) Case study: fatal
strongyloides associated with human T-cell lymphotropic virus
type 1 infection. American Journal of Tropical Medicine and
Hygiene 65, 650–651.
Allen AW & Ridley DS (1970) Further observations on the formal
ether concentration technique for faecal parasites. Journal of
Clinical Pathology 23(6), 545–546
Atkins NS, Lindo JF, Lee MG et al. (1997) Humoral responses in
human strongyloidiasis: correlations with infection chronicity.
Transactions of the Royal Society of Tropical Medicine and
Hygiene 91, 609–613.
Bailey JW (1989) A serological test for the diagnosis of strongy-
loides antibodies in ex Far East prisoners of war. Annals of
Tropical Medicine and Parasitology 83, 241–247.
Carvalho EM, Andrade TM, Andrade JA & Rocha H (1983)
Immunological features in different clinical forms of strongyl-
oidiasis. Transactions of the Royal Society of Tropical Medicine
and Hygiene 77, 346–349.
Chiodini PL, Reid AJC, Wiselka MJ, Firmin R & Foweraker J
(2000) Parenteral ivermectin in Strongyloides hyperinfection.
Lancet 355, 43–44.
Conway DJ, Atkins NS, Lillywhite JE et al. (1993) Immuno-
diagnosis of Strongyloides stercoralis infection: a method for
increasing the specificity of the indirect ELISA. Transactions
of the Royal Society of Tropical Medicine and Hygiene 87,
173–176.
Dartry A, Hilmarsdottir I, Mayorga-Sagastume R et al. (1995)
Treatment of strongyloides infection with ivermectin compared
with albendazole: results of an open study of 60 cases. Trans-
actions of the Royal Society of Tropical Medicine and Hygiene
89, 342.
Draper CC & Sirr SS. (1980) Serological investigation in retro-
spective diagnosis of malaria. British Medical Journal 280,
1575–1576.
Gam AA, Neva FA & Krotoski WA (1987) Comparative sensi-
tivity and specificity of ELISA and IHA for serodiagnosis of
strongyloides with larval antigens. American Journal of Tropical
Medicine and Hygiene 37, 157–161.
Gann PH, Neva FA & Gam AA (1994) A randomised trial of
single- and two-dose ivermectin versus thiabendazole for treat-
ment of strongyloidiasis. Journal of Infectious Diseases 169,
1076–1079.
Genta RM (1998) Predictive value of an enzyme-linked
immunosorbent assay (ELISA) for the serodiagnosis of
strongyloidiasis. American Journal of Clinical Pathology 89,
391–394.
Gill GV & Bailey JW (1989) Eosinophilia as a marker for chronic
strongyloidiasis-use of a serum ELISA test to detect asympto-
matic cases. Annals of Tropical Medicine and Parasitology 83,
249–252.
Gill GV & Bell DR (1979) Strongyloides stercoralis infection in
former Far East prisoners of war. British Medical Journal 2,
572–574.
Harada Y & Mori O (1955) A new method for culturing
hookworm. Yonago Acta Medica 1, 177–179.
731
Tropical Medicine and International Health volume 8 no 8 pp 728–732 august 2003

S. Sudarshi et al. Strongyloides stercoralis testing in travellers and immigrants

Joseph L, Gyorkos TW & Coupal L (1995) Bayesian estimation of
disease prevalence and the parameters of diagnostic tests in the
absence of a gold standard. American Journal of Epidemiology
141, 263–272.
Kobayashi J, Sato Y, Toma H, Takara M & Shiroma Y (1994)
Application of enzyme immunoassay for postchemotherapy
evaluation of human strongyloidiasis. Diagnosis and
Microbiology of Infectious Diseases 18, 19–23.
Lerman D, Barrett-Connor E & Norcross W (1982) Intestinal
parasites in asymptomatic adult Southeast Asian immigrants.
Journal of Family Practitioners 15, 443–446.
Libman MD, MacLean JD & Gyorkos TW (1993) Screening for
schistosomiasis, filariasis and strongyloidiasis among expatriates
returning from the tropics. Clinical Infectious Diseases 17,
353–359.
Lindo JF, Conway DJ, Atkins NS, Bianco AE, Robinson RD &
Bundy DA (1994) Prospective evaluation of enzyme-linked im-
munosorbent assay and immunoblot methods for the diagnosis
of endemic Strongyloides stercoralis infection. American Journal
of Tropical Medicine and Hygiene 51, 175–179.
Morgan JS, Schafffner W & Stone WJ (1996) Opportunistic
strongyloidiasis in renal transplant recipients. Transplantation
42, 518–524.
Muennig P, Pallin D, Sell RL & Chan MS (1999) The cost effec-
tiveness of strategies for the treatment of intestinal parasites in
immigrants. New England Journal of Medicine 340, 773–779.
Neva FA, Gam AA & Burke J (1981) Comparison of larval anti-
gens in an enzyme-linked immunosorbent assay for strongy-
loides in humans. Journal of Infectious Diseases 144, 427–432.
Nutman TB, Otesen EA, Ieng S et al. (1987) Eosinophilia in
Southeast Asian refugees: evaluation at a referral centre. Journal
of Infectious Diseases 155, 309–313.
Pelletier LL Jr, Baker CB, Gam AA, Nutman TB & Neva FA
(1988) Diagnosis and evaluation of treatment of chronic stron-
gyloidiasis in ex-prisoners of war. Journal of Infectious Diseases
157, 573–576.
Sato Y, Kobayashi J & Shiroma Y (1995) Serodiagnosis of
strongyloidiasis. The application and significance. Revista do
Instituto de Medicina Tropical de Sao Paulo 37, 35–41.
Schulte C, Krebs B, Jelinek T, Nothdurft HD, von Sonnenburg F &
Löscher T (2002) Diagnostic significance of blood
eosinophilia in returning travelers. Clinical Infectious
Diseases 34, 407–411.
Siddiqui A & Berk S. (2001) Diagnosis of Strongyloides stercoralis
infection. Clinical Infectious Diseases 33, 1040–1047
Suvajdzic N, Kranjcic-Zec I, Jovanovic V, Popovic D & Colovic M
(1999) Fatal strongyloidiasis following corticosteroid therapy in
a patient with chronic idiopathic thrombocytopenia. Haemato-
logia (Budapest) 29, 323–326.
Uparanukraw P, Phongsri S & Morakote N (1999) Fluctuations
of larval excretion in Strongyloides stercoralis infection.
American Journal of Tropical Medicine and Hygiene 60,
967–973.
Whitty CJM, Mabey D, Armstrong M, Wright SG & Chiodini PL
(2000) Presentation and outcome of 1107 cases of schistoso-
miasis from Africa diagnosed in a non-endemic country.
Transactions of the Royal Society of Tropical Medicine and
Hygiene 94, 531–534.

Authors
Sonali Sudarshi, Richard Stümpfle, Margaret Armstrong, Thomas Ellman, Simon Parton, Prabha Krishnan and Peter L. Chiodini,
The Hospital for Tropical Diseases, Mortimer Market, Capper St., London WC1E 6AU, UK. E-mail: sonali@doctors.org.uk,
rstumpfle@doctors.org.uk, margaret.armstrong@uclh.org, tomellman@aol.com, peter.chiodini@uclh.org
Christopher J. M. Whitty, London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, UK. Fax: +44–2072 99
472, E-mail: christopher.whitty@ishtm.ac.uk (corresponding author).

732 ª 2003 Blackwell Publishing Ltd