Seminar

Human schistosomiasis
Bruno Gryseels, Katja Polman, Jan Clerinx, Luc Kestens

Lancet 2006; 368: 1106–18 Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle
Institute for Tropical Medicine requires contamination of surface water by excreta, specific freshwater snails as intermediate hosts, and human water
Antwerp, Nationalestraat 155 contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum. According to WHO,
B-2000, Antwerp, Belgium
200 million people are infected worldwide, leading to the loss of 1·53 million disability-adjusted life years, although
(Prof B Gryseels MD,
K Polman PhD, J Clerinx MD, these figures need revision. Schistosomiasis is characterised by focal epidemiology and overdispersed population
Prof L Kestens PhD) distribution, with higher infection rates in children than in adults. Complex immune mechanisms lead to the slow
Correspondence to: acquisition of immune resistance, though innate factors also play a part. Acute schistosomiasis, a feverish syndrome,
Prof Bruno Gryseels is mostly seen in travellers after primary infection. Chronic schistosomal disease affects mainly individuals with long-
[email protected]
standing infections in poor rural areas. Immunopathological reactions against schistosome eggs trapped in the
tissues lead to inflammatory and obstructive disease in the urinary system (S haematobium) or intestinal disease,
hepatosplenic inflammation, and liver fibrosis (S mansoni, S japonicum). The diagnostic standard is microscopic
demonstration of eggs in the excreta. Praziquantel is the drug treatment of choice. Vaccines are not yet available.
Great advances have been made in the control of the disease through population-based chemotherapy but these
required political commitment and strong health systems.

Schistosomiasis or bilharzia is a tropical parasitic disease light and chemical stimuli. After penetrating the snail,
caused by blood-dwelling fluke worms of the genus the miracidia multiply asexually into multicellular
Schistosoma. Adult schistosomes are white or greyish sporocysts and later into cercarial larvae with embryonic
worms of 7–20 mm in length with a cylindrical body that suckers and a characteristic bifurcated tail.
features two terminal suckers, a complex tegument, a The cercariae start leaving the snail 4–6 weeks after
blind digestive tract, and reproductive organs. Unlike infection and spin around in the water for up to 72 h
other trematodes, schistosomes have separate sexes. The seeking the skin of a suitable definitive host. Cercarial
male’s body forms a groove or gynaecophoric channel, in shedding is provoked by light and occurs mainly during
which it holds the longer and thinner female (figure 1). daytime. One snail, infected by one miracidium, can
As permanently embraced couples, the schistosomes live shed thousands of cercariae every day for months. On
within the perivesical (Schistosoma haematobium) or finding a host, the cercariae penetrate the skin, migrate
mesenteric (other species) venous plexus. Schistosomes in the blood via the lungs to the liver, and transform into
feed on blood and globulins through anaerobic glycolysis. young worms or schistosomulae. These mature in
The debris is regurgitated in the host’s blood. 4–6 weeks in the portal vein, mate, and migrate to their
The females produce hundreds (African species) to perivesicular or mesenteric destination where the cycle
thousands (oriental species) of eggs per day. Each ovum starts again. The lifespan of an adult schistosome
contains a ciliated miracidium larva, which secretes averages 3–5 years but can be as long as 30 years. The
proteolytic enzymes that help the eggs to migrate into theoretical reproduction potential of one schistosome
the lumen of the bladder (S haematobium) or the intestine pair is up to 600 billion schistosomes.
(other species). The eggs are excreted in the urine or The main schistosomes infecting human beings are:
faeces and can stay viable for up to 7 days. On contact S mansoni, which is transmitted by Biomphalaria snails
with water, the egg releases the miracidium. It searches and causes intestinal and hepatic schistosomiasis in
for the intermediate host, freshwater snails, guided by Africa, the Arabian peninsula, and South America;
S haematobium, transmitted by Bulinus snails and
causing urinary schistosomiasis in Africa and the
Search strategy and selection criteria Arabian peninsula; and S japonicum, transmitted by the
The literature research for this Seminar started from standard works and recent amphibian snail Oncomelania and causing intestinal
reviews.1–10 We also used our own collections and the library holdings of the Antwerp and hepatosplenic schistosomiasis in China, the
Institute of Tropical Medicine, and searched PubMed and MEDLINE over the past 10 years Philippines, and Indonesia (figure 2). S intercalatum
for the main topics of this paper with the key words “schistosomes OR schistosomiasis OR and S mekongi are only of local importance. S japonicum
schistosoma” PLUS “epidemiology”, “transmission”, “pathology”, “morbidity”, is a zoonotic parasite, which infects a wide range of
“mortality”, “immunology”, “vaccine”, “treatment”, “praziquantel”, “diagnosis”, “control”, animals including cattle, dogs, pigs, and rodents.
“disease burden”, and “genital”. We checked relevant references for accuracy and balance, S mansoni is also found in rodents and primates, but
and where necessary searched secondary references until the original data were found. human beings are the main host. A dozen other
Subjects related to molecular biology, basic immunology, and malacology are beyond the schistosome species are animal parasites, some of which
scope of this Seminar; other papers8–10 are excellent starting points for the interested occasionally infect people.
reader. The distribution of the different species depends
mainly on the ecology of the snail hosts. Natural streams,

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ponds, and lakes are typical sources of infection, but over

the past few decades man-made reservoirs and irrigation
systems have contributed to the spread of schistosomiasis.11
The disease is largely a rural problem, but urban foci can
be found in many endemic areas.12
Snail populations, cercarial density, and patterns of
human water contact show strong temporal and spatial
variations, resulting in a focal distribution of the infection
within countries, regions, and villages (figure 3).13
Typically, rates and intensities of infection increase from
an early age to a peak around age 8–15 years and decrease
A
again in adults. Within populations and age-groups,
schistosomes are overdispersed; a small number of
individuals carry most of the parasites.14 These features
have been attributed both to water-contact patterns and to
innate and acquired immunity. Sex-related patterns vary
in relation to behavioural, professional, cultural, and B

religious factors.2

Acute pathology
The percutanous penetration of cercariae can provoke a
temporary urticarial rash that sometimes persists for
days as papulopruriginous lesions, especially after
primary infections such as occur in tourists and
migrants.15 A similar swimmers’ itch is also frequently E
caused by cercariae of animal trematodes in temperate
climate zones.16 Possibly, cercarial dermatitis often goes
unrecognised in endemic areas.17 C
Acute schistosomiasis (Katayama fever) is a systemic
hypersensitivity reaction against the migrating
schistosomulae, occurring a few weeks to months after
a primary infection.15,18–20 The disease starts suddenly D

with fever, fatigue, myalgia, malaise, non-productive

cough, eosinophilia, and patchy infiltrates on chest
radiography. Abdominal symptoms can develop later,
caused by the migration and positioning of the mature
worms. Most patients recover spontaneously after
2–10 weeks, but some develop persistent and more
serious disease with weight loss, dyspnoea, diarrhoea,
diffuse abdominal pain, toxaemia, hepatosplenomegaly
Figure 1: Transmission cycle of Schistosoma mansoni
and widespread rash. A: paired adult worms (sturdy male holding slender female). B: eggs (left to right, S haematobium, S mansoni,
Katayama fever due to S mansoni or S haematobium is S japonicum). C: ciliated miracidium. D: intermediate host snails (left to right, Oncomelania, Biomphalaria, Bulinus).
rarely seen in chronically exposed populations, possibly E: cercariae.
owing to underdiagnosis or in-utero sensitisation.21 It is
common, however, in tourists, travellers, and other floods.24,25 The manifestations can be severe with persistent
people accidentally exposed to transmission.15,22,23 Most fever, organomegaly, and cachexia, which can evolve
cases in western travel clinics are imported from sub- rapidly to hepatosplenic fibrosis and portal hypertension.
Saharan Africa, many in family or group clusters.
Notorious sources of infection are Lake Malawi, Lake Chronic pathology and morbidity
Victoria, and Lake Volta, the Zambesi and Niger deltas, The main lesions in established and chronic infection
and some lake resorts in South Africa. The contacts with are due not to the adult worms but to eggs that are
infected water include bathing and swimming, scuba trapped in the tissues during the perivesical or peri-
diving, water skiing, and rafting.23 intestinal migration or after embolisation in the liver,
Katayama fever due to S japonicum does also occur in spleen, lungs, or cerebrospinal system. The eggs secrete
people living in endemic areas and with a history of proteolytic enzymes that provoke typical eosinophilic
previous infections. In China, rebound epidemics have inflammatory and granulomatous reactions, which are
been reported in endemic communities exposed to progressively replaced by fibrotic deposits (figure 4).26

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S mansoni
S haematobium
S intercalatum
S japonicum
S mekongi
Mixed S hadematobium/S mansoni
Great rivers and lakes

Figure 2: Global distribution of schistosomiasis

Based on updated and corrected data from Doumenge and Mott.1 Main foci: S mansoni—much of sub-Saharan Africa, northeast Brazil, Surinam, Venezuela, the
Caribbean, lower and middle Egypt, the Arabic peninsula; S haematobium—much of sub-Saharan Africa, Nile valley in Egypt and Sudan, the Maghreb, the Arabian
peninsula; S japonicum—along the central lakes and River Yangtze in China; Mindanao, Leyte, and some other islands in the Philippines; and small pockets in
Indonesia; S mekongi–—central Mekong Basin in Laos and Cambodia; S intercalatum—pockets in west and central Africa.

The severity of the symptoms is thus related both to the spontaneously, which suggests that the renal parenchyma
intensity of infection and to individual immune is compressed but not destroyed in most cases.29
responses. Chronic urinary schistosomiasis is epidemiologically
associated with squamous bladder cancer in Egypt and
Urinary schistosomiasis other African foci. Nitrosamines, β-glucuronidase, and
The eggs of S haematobium provoke granulomatous inflammatory gene damage have been put forward as
inflammation, ulceration, and pseudopolyposis of the possible carcinogenic factors.30 However, an equally
vesical and ureteral walls.27 Common early signs include likely explanation is that schistosomiasis lesions
dysuria, pollakisuria, proteinuria, and especially intensify the exposure of the bladder epithelium to
haematuria.28,29 In endemic areas, this sign is the red flag mutagenetic substrates from tobacco or chemicals.31,32 In
of schistosomiasis in children aged 5–10 years, sometimes Egypt, the incidence of bladder cancer has decreased in
confused with menstruation in girls and even a coming of line with schistosomiasis prevalence over the past few
age in boys.5 Typically, blood is first seen in the terminal decades.33,34
urine, but in severe cases the whole urine sample can be Published evidence does not allow deduction of
dark coloured. Bacterial superinfection and bladder stones epidemiologically valid rates of mortality directly due to
can complicate the clinical picture. These early signs urinary schistosomiasis. Autopsy and clinical observations
become less common after adolescence. However, chronic leave no doubt that patients, particularly older people, die
lesions can evolve to fibrosis or calcification of the bladder of schistosomiasis-induced renal damage.35–37 Other
and lower ureters, resulting in hydroureter and clinical and epidemiological surveys have not shown
hydronephrosis. Chronic compression can eventually lead specific mortality, however.29,38–40
to parenchymal damage and kidney failure.
In non-treated populations exposed to S haematobium, Intestinal schistosomiasis
microhaematuria has been found in 41–100% of infected Schistosome eggs migrating through the intestinal wall
children, gross haematuria in between none and 97%, and provoke mucosal granulomatous inflammation,
radiologically visible lesions in the upper urinary tract in pseudopolyposis, microulcerations, and superficial
2–62%.29 Kidney function is surprisingly well preserved bleeding.27,41 Most lesions are situated in the large bowel
in many cases. Most lesions, including hydronephrosis, and rectum. The most common symptoms and signs are
heal well after antischistosomal treatment or even chronic or intermittent abdominal pain and discomfort,

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Village B Village B Village A

100 100

Village A

er
People (%)

Riv
50 50
Eggs per g faeces
1–100
101–350
351–1000
≥1000
0 0
0 5 10 15 20 30 40 50 ≥60 Total 0 5 10 15 20 30 40 50 ≥60 Total
Age (years) Age (years)

Figure 3: Focal distribution and age dependency of schistosome infections

Derived from Gryseels and Nkulikyinka.13 Age-related distribution of infection and of heavy infection with S mansoni in two hamlets of one village, separated by a dirt
road, in the Rusizi Plain, Burundi. In both, rates of infection and of heavy infection rise sharply in young children to a peak in adolescents, decreasing to a plateau in
adults. However, both rates are much higher and rise more strikingly in one hamlet than in the other, reflecting the focal character of transmission patterns.

loss of appetite, and diarrhoea with or without blood.29,42,43 it is less common and intense in adults.43,47 The
These features are difficult to ascribe unequivocally to frequency and intensity are related to faecal egg counts,
schistosomiasis in people with several infections, as is but they are also subject to methodological variations,
common in endemic areas. Population surveys found immunogenetic predisposition, and other confounding
that diarrhoea was reported in 3–55% of infected people factors.50
and bloody diarrhoea in 11–50%, of which 30–60% was Fibrotic or chronic hepatic schistosomiasis develops
attributable to schistosomal infections.29,44,45 The frequency years later in the course of infection, generally in young
of the symptoms is related to intensity of infection. Field and middle-aged adults with long-standing intense
methods and confounding factors vary substantially, infections and, presumably, some form of immunogenetic
however, and the data cannot be easily compared or predisposition.54,55 The disease results from a massive
pooled. deposition of diffuse collagen deposits in the periportal
spaces, leading to pathognomonic periportal or Symmer’s
Hepatic schistosomiasis pipestem fibrosis.41 This fibrosis leads in turn to
Hepatic schistosomiasis can be caused by progressive occlusion of the portal veins, portal
S mansoni, S japonicum, and S mekongi. The pathological hypertension, splenomegaly, collateral venous circulation,
effects of S intercalatum are limited to mild intestinal portocaval shunting, and gastrointestinal varices. The
disease.46 liver is not necessarily enlarged but is generally hard and
The terms hepatic or hepatosplenic schistosomiasis nodular on palpation. Ultrasonography reveals typical
amalgamate early inflammatory and late fibrotic hepatic fibrotic streaks and portal-vein dilatation, which are not
disease, which are actually two distinct syndromes. The reversible in most cases. In contrast to cirrhosis,
distinction is important not only in clinical practice, but hepatocellular function and indices remain largely
also for morbidity control strategies and the interpretation unaffected. In S mansoni infections, the fibrotic process
of immunological mechanisms.47,48 takes 5–15 years, by which time the infection might no
Inflammatory hepatic schistosomiasis is an early longer be present or detectable.41,51,54 In S japonicum, the
reaction to ova trapped in the presinusoidal periportal progression can be more rapid, in some cases with little
spaces of the liver; it is the main cause of schistosomal or no interval between acute and chronic disease.24
hepatomegaly in children and adolescents.47,49,50 Typical Bleeding from gastro-oesophageal varices is the most
features include sharp-edged enlargement of the left serious, commonly fatal, complication of fibrotic
liver lobe and nodular splenomegaly, extending from a hepatic schistosomiasis. In S mansoni infections, it
few centimetres below the costal arch to below the tends to recur and grow more severe over time; in
umbilicus and even into the pelvis.24,51 Clinical and S japonicum, bleeding is sudden and massive in many
epidemiological differentiation from malaria can be cases.24,49 Repeated or occult bleeding can lead to
difficult.52 Ultrasonography can reveal mild forms anaemia, hypoalbuminaemia, cachexia, and growth
of diffuse fibrosis; in many cases, there is no retardation. Ascites can be caused by a combination of
apparent sign of functional disease.53 This type of hypoalbuminia and portal hypertension.
hepatomegaly is found in up to 80% of infected children; Before the advent of modern schistosomicides,

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Schistosome-induced granuloma and fibrosis mortality due to heavy S mansoni infection has been
estimated at 0·05%, with a case-fatality rate for
A B
oesophageal bleeding of 1·1%.58 Clinical studies from
other areas with high infection rates also found
substantial fatality rates among patients with advanced
liver fibrosis.59–61 In most cross-sectional community
surveys, however, life-threatening conditions were not
detected.29,50 For S japonicum, the best available data
show a case-fatality rate of 1·8% among 278 patients
followed up for 12 years in the Philippines.62 High
mortality rates have been reported among patients with
complicated and even acute schistosomiasis in China,
Urinary schistosomiasis but this evidence is not well documented.24
C D E
Ectopic schistosomiasis
Pulmonary schistosomiasis is due to portal-caval
shunting, allowing ova to leak into the perialveolar
capillary beds. The ensuing granulomas can give rise to
bronchial symptoms and later to fibrosis complicated
by pulmonary hypertension and cor pulmonale. The
symptoms can remain occult for many years.49 In
S mansoni infections, portosystemic leaking of immune
complexes to the mesangial areas can lead to
glomerulonephritis.63
Genital schistosomiasis, due to eggs of S haematobium
Intestinal and hepatic schistosomiasis
and S mansoni in the reproductive organs, is quite
common but mostly occult in some endemic areas and a
F G H I regular finding in travellers.64,65 Symptoms in female
patients include hypertrophic and ulcerative lesions of
the vulva, vagina, and cervix, which might facilitate sexual
transmission of infections. Lesions of the ovaries and the
fallopian tubes can lead to infertility. In men, the
epididymis, testicles, spermatic chord, and prostate can
be affected; haemospermia is a common symptom.
Neuroschistosomiasis is caused by inflammation
around ectopic worms or eggs in the cerebral or spinal
venous plexus, which can evolve to irreversible fibrotic
scars if left untreated.66,67 Ectopic S mansoni and
S haematobium infections seem to cause mainly spinal
Figure 4: Schistosomiasis pathology pathology with transverse myelitis, which is also a
A: Acute liver granuloma around S mansoni egg in liver of an experimentally infected mouse containing many cells, potential complication of acute schistosomiasis in
mainly eosinophils and lymphocytes, and some macrophages; large red cells are intact murine hepatocytes.
B: Chronic liver granuloma around the remains of a schistosome egg in a mouse liver, with dominant (blue-
travellers.68 S japonicum is associated with cerebral
coloured) fibrous tissue; courtesy and copyright of Eric Van Marck, University of Antwerp. C: Macrohaematuria due granulomatous lesions, which can lead to epileptic,
to ulceration of the bladder wall in urinary schistosomiasis. D: Ultrasonography of irregular bladder wall and polyp; paralytic, and meningoencephalitic symptoms.24,67
courtesy of Wellcome Trust International Image Collection, copyright C Hatz. E: Intravenous pyelography showing Sporadically, ectopic schistosomiasis lesions are found in
bilateral hydroureter and hydronephrosis. F: Severe bloody diarrhoea due to heavy infection with S mansoni.
G: 6-year-old boy with gross reactive hepatosplenomegaly. H: 19-year-old man with symptoms of chronic fibrotic
the skin, the peritoneum, or other organs.
hepatic schistosomiasis—splenomegaly, external varices, ascites, and growth retardation. I: ultrasonography of
advanced periportal fibrosis and portal venodilatation; courtesy of Wellcome Trust International Image Collection, Indirect pathology and morbidity
copyright R Davidson. As severe disease becomes less common thanks to
modern drugs, subtle or indirect morbidity such as
advanced schistosomal liver fibrosis with oesophageal fatigue and physical or cognitive impairment has received
bleeding was a common clinical syndrome in Egypt, more attention. Such unspecific and multifactorial
Sudan, Brazil, China, and the Philippines but much morbidity is difficult to measure and to dissociate from
less frequent in most of sub-Saharan Africa.5,6,47,50,56 other poverty-related health problems. Older studies
These regional morbidity patterns have been attributed could not convincingly demonstrate these effects, even in
to ethnic and genetic factors.57 heavily infected people.29 Recent studies, however, have
In a heavily infected population in Sudan, the annual found small but significant associations between

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schistosome infection and anaemia, nutritional status, not easily applicable under field conditions.71,76,77 Such
and cognitive and physiological capacities.69 The assays are important, however, for diagnosis in travellers,
underlying mechanisms could range from social migrants, and other occasionally exposed people.15 They
determinants to complex immune interactions.69,70 can also be useful for incidence studies in children and
in low-transmission or post-control settings.78 Most
Diagnosis routine techniques detect IgG, IgM, or IgE against
The microscopic examination of excreta remains the gold soluble worm antigen or crude egg antigen by EIA,
standard for the diagnosis of schistosomiasis.71 The eggs indirect haemagglutination, or immunofluorescence.
are easy to detect and identify by microscopy owing to Seroconversion generally happens within 4–8 weeks of
their size and shape, their typical lateral or terminal infection, but the interval can be as long as 22 weeks.79
spine, and the living miracidium (in fresh samples) with Most assays have positive results for at least 2 years after
mobile cilia and pulsing excretory cells (figure 5). Direct cure and in many cases much longer.80
wet slides are not very sensitive; if no eggs are found, Somatic schistosome antigens, such as circulating
concentration methods should be used but even these anodic antigen and circulating cathodic antigen, can be
can miss light infections.72,73 detected and quantified with labelled monoclonal
Urine should be concentrated by sedimentation, antibodies in serum or urine of infected individuals.81
centrifugation, or filtration, and samples should be taken Antigen detection in serum is not very sensitive in light
around noon or after physical exercise. To obtain a infections and therefore less useful for clinical
quantitative assessment of the intensity of infection, a applications.82 However, as a specific, direct, and stable
fixed amount (generally 10 mL) of urine is forced over a measure of worm burdens, it is a valuable research tool
paper or nitrocellulose filter, which can be examined and for epidemiological and therapeutic studies.83 The less
eggs counted directly under the microscope. Intensity specific urine-based antigen detection assays have
can then be expressed as eggs per 10 mL. potential for the development of field-applicable reagent
For the intestinal schistosomes, eggs must be sought strips.84
in the faeces. Concentration methods, such as Reagent strips for microhaematuria and simple
sedimentation in a glycerine solution or centrifugation questionnaires for red urine are cheap, easy, and effective
in formolised ether are needed for detection of mild and tools for the screening and rapid epidemiological
light infections. In the field, the faecal thick smear or assessment of urinary schistosomiasis.85 Such indirect
Kato-Katz method is commonly used, because it allows diagnostic methods are less satisfactory for intestinal or
quantification of the infections by egg counts, usually hepatic disease.86,87 Biochemical markers of pathology are
expressed as per g faeces.71 Rectal snips are very sensitive, still under investigation.88
even for S haematobium infection.74 In hospital settings, cystoscopy and endoscopy are used
Quantitative egg counts after standardised urine to visualise bladder lesions and oesophageal varices.49,74,89,90
filtration or in calibrated faecal thick smears are especially Laparoscopy and wedge biopsy can reveal the macroscopic
useful for epidemiological surveys and control, since they and histological appearance of granulomatous
correlate well with worm burdens and morbidity.57 inflammation or periportal fibrosis.91,92
Individual egg counts should not be overinterpreted as a Radiography allows visualisation of renal, ureteral,
measure of disease, however, because they vary and bladder pathology.93 In hepatic schistosomiasis,
substantially within and between stool and urine contrast radiography can show portal-vein distension or
samples.75 gastro-oesophageal varices. CT, myelography, and MRI
Antibody-based assays are quite sensitive but cannot can be useful for detailed imaging, especially for neuro-
distinguish history of exposure from active infection; schistosomiasis.66,93,94 Over the past 10 years, portable
they can also cross-react with other helminths and are ultrasonographic equipment has allowed major

S mansoni (lateral spine) S haematobium (terminal spine) S japonicum (small lateral spine)

20 μm 20 μm 20 μm

Figure 5: Schistosome eggs

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advances in the study of schistosomiasis pathology.95,96 symptoms. In oesophageal bleeding, β blockers,

Standard protocols have been developed to classify endoscopic sclerotherapy, splenectomy, or a portocaval
hepatic fibrosis and urinary-tract lesions. Their use shunt might be indicated.4,49 In advanced urinary
requires specific expertise and experience, however, schistosomiasis, damaged and non-functional kidneys
and is subject to much variation within and between might have to be removed.
observers. Corticosteroids and anticonvulsants are needed as
possible adjuvants to praziquantel in neuroschistosomiasis,
Treatment which needs specialised care.67 Praziquantel should be
Early treatments against schistosomiasis had severe and administered with great caution in the case of concurrent
even lethal side-effects that had to be weighed against the neurocysticercosis.104
benefits for the patient.4,5 The 1970s heralded the advent Oxamniquine acts only on S mansoni and is nowadays
of effective, safe, and simple drugs.34 mainly used in Brazil.4,34 It is as effective as praziquantel
Praziquantel, an acylated quinoline-pyrazine that is but can provoke more pronounced side-effects, most
active against all schistosome species, is now the most notably drowsiness, sleep induction, and epileptic
widely used. It is mostly marketed as 600 mg tablets, seizures.
with a recommended standard regimen of 40 mg/kg Artemisinin derivatives are effective against the
bodyweight in a single dose.6 The drug acts within 1 h of immature stages of S japonicum, S mansoni, and possibly
ingestion by paralysing the worms and damaging the S haematobium.105 Their use in cure or prophylaxis for
tegument. Side-effects are mild and include nausea, acute schistosomiasis, possibly in combination with
vomiting, malaise, and abdominal pain. In heavy praziquantel, is being investigated.106 Widespread use in
infections, acute colic with bloody diarrhoea can occur malaria-endemic areas is not recommended, because it
shortly after treatment, probably provoked by massive might promote artemisinin resistance in malaria
worm shifts and antigen release.97 parasites.
Praziquantel has very low toxicity in animals, and no A derivative of myrrh (an oleo-resin extract of
important long-term safety difficulties have been Commiphora molmol; Mirazid; Pharco Pharmaceuticals,
documented in people so far.98 It is judged safe for Alexandria, Egypt) was heralded as a potent new
treatment of young children and pregnant women.99 schistosomicide but appears to be completely ineffective.107
Praziquantel has little or no effect on eggs and immature Schistosomes can become resistant to hycanthone and
worms. Tissue-dwelling eggs can be excreted for several oxamniquine, in animals as well as in the field. Resistance
weeks after treatment, and during the same period to these drugs has never spread beyond local foci,
prepatent or newly acquired infections can become however.108 Under drug pressure, praziquantel-tolerant
productive. The preferred timing of follow-up is therefore schistosome strains can be quite easily selected in
4–6 weeks after treatment.100 After a single dose of animals.109 In the field, very low cure rates have been
40 mg/kg, 70–100% of patients cease to excrete eggs. In observed in northern Senegal, but they could be explained
most of those not cured, egg counts and antigen by very intense transmission, reinfection, maturing
concentrations are reduced by more than 95%.97,101,102 prepatent infections, and possibly the epidemic nature of
Clinical, radiographic, and sonographic studies have the focus.110 In Egypt, tolerant strains have been isolated
shown the regression over weeks to months of intestinal from people who did not respond well to treatment, but
and vesical lesions, reactive hepatomegaly, and even these observations need to be confirmed.111 The
severe lesions of the upper urinary tract or mild liver catastrophic experience in cattle, with widespread
fibrosis.103 This regimen is therefore recommended for resistance to anthelmintics due to systematic mass
most population-based treatment campaigns. In treatment, shows that caution is needed.112
populations with high initial egg counts exposed to rapid
reinfection, cure rates can be much lower. In these cases, Immunology
the dose can be increased to 60 mg/kg, if possible split in There is longstanding epidemiological and clinical
two and taken several hours apart to avoid side-effects. evidence that people living in endemic areas acquire
60 mg/kg or more in split doses is also advisable for some form of immune resistance after years of exposure.113
individual case management or in people who have left In terms of parasite population dynamics, host-related
the endemic area, to ensure complete cure.101 A repeat factors such as innate or acquired immunity are likely to
dose 6–12 weeks later can be useful to cure prepatent have an important role in truncating the enormous
infections, particularly if eosinophilia, high antibody reproduction potential of schistosomes to the endemic
titres, or symptoms persist. equilibrium of one.114 The acquisition of effective
Katayama fever is primarily treated with corticosteroids immunity is difficult to prove, because the decrease in
to suppress the hypersensitivity reaction and with infection rates after adolescence can also be explained by
praziquantel to eliminate the already matured worms.15,18 reduced water contact.
Since immature worms are not susceptible to praziquantel, Immunological advances, new epidemiological
treatment should be repeated 4–6 weeks after the first approaches, and mathematical modelling corroborate

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the existence of acquired immunity, however.9,113,115 after antiretroviral treatment.130 Schistosomiasis treatment
Comparative studies of reinfection after curative can result in lower viral loads and higher CD4-cell
treatment have shown that children are far more counts.131,132 The clinical and epidemiological significance
susceptible than adults and that these differences cannot of all these observations is still unclear.
be explained by differing water-contact patterns.
Observations in people and in animals suggest that Global burden
acquired immunity is mediated by IgE against antigens Schistosomiasis is highly prevalent, but the associated
of larvae and adult worms, which trigger eosinophils to morbidity is low and variable. Thus, its influence on
release cytotoxines targeting schistosomulae.113 The slow public health and the priority of control measures have
development of acquired immunity is thought to be due long been debated. The discussion has been revived in
to blockage of the IgE receptors by excess antischistosome light of the renewed resources for the fight against
IgG4 and possibly other immunoglobulin isotypes in the poverty-related diseases and the Global Burden of Disease
first years of infection. Some researchers suggest a role Study, which attempted to quantify and rank health
of schistosome-specific IgA, such as anti-Sm28GST, in problems according to disability-adjusted life years
mediating protective immunity in people, or of the slow (DALY).133 This index is calculated from disease-specific
release of somatic antigens of dying worms.115,116 The latter prevalence, mortality, and disability weights. The Global
hypothesis has been invoked to explain increased Burden of Disease Study currently attributes a disability
immunity after treatment, but other studies did not weight of 0·06 and an annual mortality of 14 000 deaths
confirm these observations.117,118 per year to schistosomiasis. Based on the generally
In populations with only recent exposure to accepted number of 200 million infected people
transmission, age-related infection patterns are worldwide, the total number of DALY lost to
surprisingly similar to those in long-standing endemic schistosomiasis is estimated at 1·532 million per year, of
conditions. Since slowly acquired immunity cannot be which 77% are in sub-Saharan Africa. Schistosomiasis
invoked in such circumstances, some form of age-related would therefore account for 0·1% of the total world global
innate resistance could also play an important part in the burden of disease and 0·4% of that in sub-Saharan Africa,
epidemiology of schistosomiasis.119–121 which is of the same order as leishmaniasis and
Most schistosomiasis-related pathology is induced by trypanosomiasis. New meta-analyses of existing data
cellular immune responses. The granulomatous reactions have resulted in proposals to increase the schistosomiasis
around the eggs are orchestrated by CD4-positive T cells disability weight by a factor of between three and 30, and
and involve eosinophils, monocytes, and lymphocytes.26 the mortality estimate up to 280 000 deaths annually in
In mice, a predominantly T-helper-1 reaction in the early sub-Saharan Africa alone.69,134
stages of infection shifts to an egg-induced T-helper-2- Both the Global Burden of Disease Study and the
biased profile, and imbalances between these responses revisions are, however, limited by the lack of representative
lead to severe lesions.122 Although these observations data and of clear case definitions. Where they have been
cannot readily be extrapolated, similar mechanisms could adequately measured, true national prevalences are three
be at the basis of fibrotic pathology in human beings.48 to ten times lower than the WHO estimates that
Much effort has been devoted to the development of extrapolated local surveys without accounting for
vaccines against schistosomiasis. Several antigens are geographic heterogeneity.135–140 By contrast, with standard
judged to be potential vaccine candidates and have been survey methods true prevalence can be underestimated by
tested in animals with varying results.123,124 The recombinant 50% or more.72 The proposed revision of the mortality rates
rShGST-28 (Bilhvax; Eurogentec, Herstal, Belgium) has relies on similar overestimates and would add an
already undergone phase I and II clinical trials.116 unexplained 10% to overall mortality in male adults in sub-
Questions remain about the feasibility, applicability, and Saharan Africa.134 The proposed revision of the disability
relevance of schistosomiasis vaccines, however.124,125 weight is based on a thorough meta-analysis of published
The possible interaction between schistosomiasis and morbidity data; however, owing to the differing methods
HIV/AIDS is receiving increasing attention, given the role and confounding factors, these cannot readily be pooled to
of immune responses in both diseases and the geographic extract precise disability weights.68 New, dedicated field
overlap in distribution in Africa.70 Low CD4-positive T-cell studies would be needed to validate the proposed changes.
counts resulting from HIV infection might increase
susceptibility to schistosome infection and influence egg Control
excretion.126 HIV infection would not affect the efficacy of The aims and strategies of schistosomiasis control have
praziquantel, susceptibility to reinfection, the development shifted fundamentally over the past few decades, since
of fibrosis, or the diagnosis and surveillance of the introduction of modern schistosomicides, particularly
schistosomiasis.126–129 Conversely, schistosomiasis does not praziquantel. As for other parasitic diseases, transmission
interfere with HIV screening or viral-load testing and control aiming at the intermediate host has been largely
should not exacerbate the course of HIV infection, but it replaced by morbidity control through population-based
might contribute to immune reconstitution syndromes chemotherapy. This strategy allows quick gains, but

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careful long-term planning is needed to ensure commitment might wane as morbidity decreases. Also
sustainability and progression to the more demanding the liberalisation of health care could be a threat to control
stages of infection and transmission control. programmes for schistosomiasis and other diseases. In
Snail control with molluscicides, toxic chemicals, is China, market reforms might already have led to the re-
expensive and logistically complex. Substantial human emergence of schistosomiasis in some areas.150
and material resources are needed for efficient application, Low-income countries, especially those in sub-
as well as detailed epidemiological and malacological Saharan Africa, have had greater difficulties in
surveillance. Snail populations can be greatly reduced but implementing and sustaining chemotherapy-based
rarely eliminated, so regular and long-term retreatment is control strategies. Early pilot projects in Mali, Congo,
necessary. The toxicity of molluscicides for other aquatic Madagascar, and Malawi showed promising results in
organisms, including fish, gives rise to ecological and the short term but floundered when foreign assistance
economic concerns. Large-scale chemical snail control is ended.6,47,135 Other programmes were built up more
still used in Egypt and China, but owing to the success of gradually, by improving passive or active case finding
population-based chemotherapy, its cost-effectiveness is through regular health-care structures. Although less
increasingly being questioned.141 Snail control can also be spectacularly successful in the short term, they appeared
pursued by physical measures or biological competitors, to be sustainable with limited national resources.151–153
but such methods are not easy to put into practice.142,143 Renewed efforts are now being made to extend
Schistosomiasis can in principle be eliminated by chemotherapy-based control of schistosomiasis to sub-
behavioural changes, sanitation, and safe water supply, Saharan Africa and to integrate these efforts with
as has been shown in Japan.144 Educational programmes systematic anthelmintic treatment in school-aged
can improve knowledge about the disease and health- children.154 The main vehicles are the Schistosomiasis
care seeking, but behaviour can be difficult to change Control Initiative and the Partners for Parasite Control
without other options for water contact.145,146 The provision Consortium, public-private partnerships supported by the
of safe water supplies and latrines is obviously useful, Bill and Melinda Gates foundation, drug-donating
but for the prevention of schistosomiasis, safe contact companies, WHO, and academic institutes. Following a
sites are also needed.147,148 In the case of S japonicum, resolution by the World Health Assembly, they have set a
transmission control necessitates interventions on the joint global target to provide annual preventive treatment
large and diverse animal reservoir.25 to at least 75% of all school-aged children at risk of
On the recommendation of WHO, population-based morbidity from schistosomiasis or soil-transmitted
treatment with praziquantel is now the main component helminths by the year 2010.155 The programme is by now
of most national control programmes.6 The fundamental active in Burkina Faso, Mali, Niger, Tanzania, Uganda,
aim is to reduce morbidity by keeping down intensity of and Zambia. Proposals are being developed for a further
infection. Various strategies can be applied, including integration with drug-delivery programmes for lymphatic
indiscriminate mass treatment, active case finding, and filariasis, onchocerciasis, and nutritional deficiencies in a
treatment of particular risk groups such as school-aged single package and to link these programmes with those
children. 20 years of experience have shown that against AIDS, malaria, and tuberculosis.156,157 Another
population-based treatment is feasible, safe, and integration challenge lies, however, with the health
effective.6,149 In the absence of ecological or behavioural workers in the field, who must cope with a wide variety of
changes, however, it has little durable effect on vertical programmes in their daily routine. For many,
transmission; regular retreatment is therefore needed provision of accessible care for people with symptoms
for an unknown period.6,114 Sustainability is therefore a will be the first step in a strategy of morbidity control.
key requirement for chemotherapy-based control.
Wide-scale chemotherapy has greatly reduced the The way forward
public-health impact of schistosomiasis in middle-income In theory, doctors and other health workers have adequate
countries such as Egypt, China, Brazil, the Philippines, tools at hand for diagnosis and treatment of most overt
Puerto Rico, Tunisia, Morocco, and Saudi Arabia.6 Key cases of schistosomiasis in outpatient or primary care.
factors to success were national commitment and However, detection of light infections and assessment of
investments, in several cases through loans from the their clinical importance remains more difficult.
World Bank, implementation through regular health Resistance to praziquantel should be avoided at all costs,
services, and concurrent socioeconomic development. and new drugs would be welcome. Improved diagnostic
The challenge for these countries is now to move towards agents and therapeutic strategies are therefore main
control and possibly elimination of infection and topics for further applied research on schistosomiasis. A
transmission. The main technical difficulty lies in truly evidence-based consensus should be built on how
identification of remaining cases and pockets through an to assess and use the available data on disease burden
integrated surveillance and response system. The not just at the global level, but also at national and local
progressive elimination of transmission sources requires levels.
intensive intersectoral collaboration, and political Scientists and funding agencies should also pursue

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more vigorously hypothesis-driven research on the 581–90.

biology, epidemiology, and immunology of 14 Gryseels B, De Vlas SJ. Worm burdens in schistosome infections.
Parasitol Today 1996; 12: 115–19.
schistosomiasis. The relation between human beings
15 Bottieau E, Clerinx J, De Vega MR, et al. Imported Katayama fever:
and schistosomes remains one of the most baffling tricks clinical and biological features at presentation and during
of nature; its elucidation could teach us much about both treatment. J Infect 2006; 52: 339–45.
species. 16 Horak P, Kolarova L. Molluscan and vertebrate immune responses
to bird schistosomes. Parasite Immunol 2005; 27: 247–55.
Enormous progress has been made in the control of 17 Appleton CC. Schistosome dermatitis: an unrecognized problem in
schistosomiasis in many countries. Extension of these South Africa? S Afr Med J 1984; 65: 467–69.
successes to countries with fewer resources, in particular 18 Lambertucci JR. Acute schistosomiasis: clinical, diagnostic and
therapeutic features. Rev Inst Med Trop Sao Paulo 1993; 35: 399–404.
sub-Saharan Africa, is imperative, but the lessons of the
19 Rocha MO, Pedroso ER, Lambertucci JR, et al. Gastro-intestinal
past should not be forgotten. The fight against manifestations of the initial phase of schistosomiasis mansoni.
schistosomiasis is not just a matter of distributing drugs; Ann Trop Med Parasitol 1995; 89: 271–78.
establishment of strong health systems that are able to 20 Rocha MO, Rocha RL, Pedroso ER, et al. Pulmonary manifestations
in the initial phase of schistosomiasis mansoni.
take care of patients and to integrate sustainable control Rev Inst Med Trop Sao Paulo 1995; 37: 311–18.
measures is a far greater and more important challenge. 21 King CL, Malhotra I, Mungai P, et al. B cell sensitization to
A definitive solution to the schistosomiasis problem, helminthic infection develops in utero in humans. J Immunol 1998;
160: 3578–84.
finally, can be achieved only by eliminating its main
22 Hatz C. Schistosomiasis: an underestimated problem in
underlying cause—poverty. industrialised countries? J Travel Med 2005; 12: 1–2.
Contributors 23 Jelinek T, Nothdurft HD, Loscher T. Schistosomiasis in travelers
Bruno Gryseels wrote the initial drafts and the final paper. and expatriates. J Travel Med 1996; 3: 160–64.
Katja Polman contributed to the sections on biology and epidemiology, 24 Chen MG. Schistosoma japonicum and S japonicum-like infections:
diagnosis, and treatment and control. Jan Clerinx contributed to the epidemiology, clinical and pathological aspects. In: Jordan P, Webbe
G, Sturrock FS. Human schistosomiasis. Wallingford: CAB
section on pathology. Luc Kestens contributed to the section on
International, 1993: 237–70.
immunology. All authors contributed to overall revisions and final
25 Ross AG, Sleigh AC, Li Y, et al. Schistosomiasis in the People’s
editing.
Republic of China: prospects and challenges for the 21st century.
Conflict of interest Clin Microbiol Rev 2001; 14: 270–95.
We declare that we have no conflict of interest. 26 Cheever AW, Hoffmann KF, Wynn TA. Immunopathology of
schistosomiasis mansoni in mice and men. Immunol Today 2000;
Acknowledgments 21: 465–66.
We dedicate this Seminar to Dr Peter (Pip) Jordan, who died on May 30,
27 Cheever AW, Kamel IA, Elwi AM, Mosimann JE, Danner R,
2006. He was a great schistosomiasis expert, who made fundamental Sippel JE. Schistosoma mansoni and S haematobium infections in
contributions to the successful control of this disease in large parts of Egypt, III: extrahepatic pathology. Am J Trop Med Hyg 1978; 27:
the world. We thank Kristien Wyants for secretarial assistance, 55–75.
Veerle Demedts and Dirk Schoonbaert for bibliographic support, and 28 Chen MG, Mott KE. Progress in assesment of morbidity due to
Jean-Pierre Wenseleers for the graphic work. The work on this seminar Schistosoma haematobium infection: a review of recent literature.
was solely funded by the Institute of Tropical Institute of Antwerp, Trop Dis Bull 1989; 86: R1–36.
which had no economic interest. 29 Gryseels B. The relevance of schistosomiasis for public health.
Trop Med Parasitol 1989; 40: 134–42.
References
1 Doumenge JP, Mott KE. Global distribution of schistosomiasis: 30 IARC Working Group on the evaluation of carcinogenic risks to
CEGET/WHO atlas. World Health Stat Q 1984; 37: 186–99. humans. Schistosomes, liver flukes and Helicobacter pylori. In:
IARC Monographs on the evaluation of carcinogenic risks to
2 Jordan P, Webbe G, Sturrock FS. Human schistosomiasis.
humans, vol 61. Geneva: World Health Organisation, 1994:
Wallingford: CAB International, 1993.
45–119.
3 Brown DS. Freshwater snails of Africa and their medical
31 Bedwani R, Renganathan E, El Kwhsky F, et al. Schistosomiasis and
importance, 2nd edn. London: Taylor and Francis, 1994.
the risk of bladder cancer in Alexandria, Egypt. Br J Cancer 1998; 77:
4 Olds GR, Dasarathy S. Schistosomiasis. Curr Treat Options Infect Dis 1186–89.
2000; 2: 88–99.
32 Cheever AW. Schistosomiasis and neoplasia. J Natl Cancer Inst 1978;
5 Jordan P. From Katayama to the Dakhla Oasis: the beginning of 61: 13–18.
epidemiology and control of bilharzia. Acta Tropica 2000; 77: 9–40.
33 Koraitim MM, Metwalli NE, Atta MA, el Sadr AA. Changing age
6 WHO Expert Committee. Prevention and control of schistosomiasis incidence and pathological types of schistosoma-associated bladder
and soil-transmitted helminthiasis. Technical report series. Geneva: carcinoma. J Urol 1995; 154: 1714–16.
World Health Organisation, 2002.
34 Fenwick A, Savioli L, Engels D, Robert BN, Todd MH. Drugs for the
7 Ross AG, Bartley PB, Sleigh AC, et al. Schistosomiasis. control of parasitic diseases: current status and development in
N Engl J Med 2002; 346: 1212–20. schistosomiasis. Trends Parasitol 2003; 19: 509–15.
8 Brindley PJ. The molecular biology of schistosomes. Trends Parasitol 35 Forsyth DM, Bradley DJ, McMahon J. Death attributed to kidney
2005; 21: 533–36. failure in communities with endemic urinary schistosomiasis.
9 Mountford AP. Immunological aspects of schistosomiasis. Lancet 1970; 2: 472–73.
Parasite Immunol 2005; 27: 243–46. 36 Smith JH, Elwi A, Kamel IA, Von Lichtenberg F. A quantitative post
10 Raghavan N, Knight M. The snail (Biomphalaria glabrata) genome mortem analysis of urinary schistosomiasis in Egypt, II: evolution
project. Trends Parasitol 2006; 22: 148–51. and epidemiology. Am J Trop Med Hyg 1975; 24: 806–22.
11 Oomen JMV, de Wolf J, Jobin WR. Health and irrigation. ILRI 37 Elem B, Vandal MT. Bilharziasis of the urinary tract in Zambia:
publication 45. Wageningen: ILRI, 1990. observation on 100 consecutive cases. Med J Zambia 1981; 15:
12 Mott KE, Desjeux P, Moncayo A, Ranque P, de Raadt P. Parasitic 48–51.
diseases and urban development. Bull World Health Organ 1990; 68: 38 Lehman JS Jr, Farid Z, Bassily S. Mortality in urinary
691–98. schistosomiasis. Lancet 1970; 2: 822–23.
13 Gryseels B, Nkulikyinka L. The distribution of Schistosoma mansoni 39 Fine J. Hydronephrosis in a series of 3,400 post-mortem
in the Rusizi plain (Burundi). Ann Trop Med Parasitol 1988; 82:

www.thelancet.com Vol 368 September 23, 2006 1115

 Seminar

examinations in Zambia, with special reference to Bilharharzia. study the case fatality rate in Schistosoma japonicum infection in
Med J Zambia 1975; 9: 98–101. the Philippines. Southeast Asian J Trop Med Public Health 1986; 17:
40 Bradley AK, Gilles HM. Malumfashi Endemic Diseases Research 67–70.
Project, XXI: pointers to causes of death in the Malumfashi area, 63 Barsoum R, Harrington JT, Mathew CM, et al. The changing face of
northern Nigeria. Ann Trop Med Parasitol 1984; 78: 265–71. schistosomal glomerulopathy. Kidney Int 2004; 66: 2472–84.
41 Cheever AW. A quantitative post-mortem study of Schistosomiasis 64 Feldmeier H, Leutscher P, Poggensee G, Harms G. Male genital
mansoni in man. Am J Trop Med Hyg 1968; 17: 38–64. schistosomiasis and haemospermia. Trop Med Int Health 1999; 4:
42 Chen MG, Mott KE. Progress in assesment of morbidity due to 791–93.
Schistosoma mansoni infection: a review of recent literature. 65 Poggensee G, Feldmeier H. Female genital schistosomiasis: fact
Trop Dis Bull 1988; 85: R1–56. and hypotheses. Acta Trop 2001; 79: 193–210.
43 Chen MG, Mott KE. Progress in assesment of morbidity due to 66 Naus CW, Chipwete J, Visser LG, Zijlstra EE, Van Lieshout L. The
Schistosoma japonicum infection: a review of recent literature. contribution made by schistosoma infection to non-traumatic
Trop Dis Bull 1988; 85: R1–45. disorders of the spinal cord in Malawi. Ann Trop Med Parasitol
44 Guyatt H, Gryseels B, Smith T, Tanner M. Assessing the public 2003; 97: 711–21.
health importance of Schistosoma mansoni in different endemic 67 Ferrari TC. Involvement of central nervous system in the
areas: attributable fraction estimates as an approach. schistosomiasis. Mem Inst Oswaldo Cruz 2004; 99 (suppl 1): 59–62.
Am J Trop Med Hyg 1995; 53: 660–67. 68 Anon. Schistosomiasis in US Peace Corps volunteers-Malawi, 1992.
45 Booth M, Guyatt HL, Li Y, Tanner M. The morbidity attributable to MMWR Morb Mortal Wkly Rep 1993; 42: 565–70.
Schistosoma japonicum infection in 3 villages in Dongting Lake 69 King CH, Dickman K, Tisch DJ Regauging the cost of chronic
region, Hunan province, PR China. Trop Med Int Health 1996; 1: helminthic infection: meta-analysis of disability-related outcomes
646–54. in endemic schistosomiasis. Lancet 2005; 365: 1561–69.
46 Chen MG, Mott KE. Progress in assesment of morbidity due to 70 Secor WE. Immunology of human schistosomiasis: off the beaten
Schistosoma intercalatum infection: a review of recent literature. path. Parasite Immunol 2005; 27: 309–16.
Trop Dis Bull 1989; 86: R1–18. 71 Feldmeier H, Poggensee G. Diagnostic techniques in
47 Gryseels B, Polderman AM. Morbidity, due to schistosomiasis schistosomiasis control: a review. Acta Trop 1993; 52: 205–20.
mansoni, and its control in Subsaharan Africa. Parasitol Today 1991; 72 De Vlas SJ, Gryseels B. Underestimation of Schistosoma mansoni
7: 244–48. prevalences. Parasitol Today 1992; 8: 274–77.
48 Abath FGC, Morais CNL, Montenegro CEL, Wynn TA, 73 Engels D, Nahimana S, Gryseels B. Comparison of the direct faecal
Montenegro SML. Immunopathogenic mechanisms in smear and two thick smear techniques for the diagnosis of intestinal
schistosomiasis: what can be learnt from human studies? parasitic infections. Trans R Soc Trop Med Hyg 1996; 90: 523–25.
Trends Parasitol 2006; 22: 85–91.
74 Feldmeier H. Diagnosis. In: Jordan P, Webbe G, Sturrock FS.
49 Lambertucci R L. Schistosoma mansoni: pathological and clinical Human schistosomiasis. Wallingford: CAB International, 1993:
aspects. In: Jordan P, Webbe G, Sturrock FS. Human 271–303.
schistosomiasis. Wallingford: CAB International, 1993: 195–235.
75 De Vlas SJ, Gryseels B, van Oortmarssen GJ, Polderman AM,
50 Gryseels B. Morbidity due to infection with Schistosoma mansoni: Habbema JD. A model for variations in single and repeated egg
an update. Trop Geogr Med 1992; 44: 189–200. counts in Schistosoma mansoni infections. Parasitology 1992; 104:
51 Gryseels B, Polderman AM. The morbidity of schistosomiasis 451–60.
mansoni in Maniema (Zaire). Trans R Soc Trop Med Hyg 1987; 81: 76 Tsang VC, Wilkins PP. Immunodiagnosis of schistosomiasis.
202–09. Immunol Invest 1997; 26: 175–88.
52 Booth M, Vennervald BJ, Kenty L, et al. Micro-geographical 77 Rabello A. Diagnosing schistosomiasis. Mem Inst Oswaldo Cruz
variation in exposure to Schistosoma mansoni and malaria, and 1997; 92: 669–76.
exacerbation of splenomegaly in Kenyan school-aged children.
78 Noya O, de Noya BA, Losada S, et al. Laboratory diagnosis of
BMC Infect Dis 2004; 4: 13.
schistosomiasis in areas of low transmission: a review of a line of
53 Kardorff R, Stelma FF, Vocke AK, et al. Ultrasonography in a research. Mem Inst Oswaldo Cruz 2002; 97: 167–69.
Senegalese community recently exposed to Schistosoma mansoni
79 Jones ME, Mitchell RG, Leen CL. Long seronegative window in
infection. Am J of Trop Med Hyg 1996; 54: 586–90.
schistosoma infection. Lancet 1992; 340: 1549–50.
54 Homeida M, Ahmed S, Dafalla A, et al. Morbidity associated with
80 Rabello AL, Garcia MM, Pinto da Silva RA, Rocha RS, Katz N.
Schistosoma mansoni infection as determined by ultrasound: a study
Humoral immune responses in patients with acute Schistosoma
in Gezira, Sudan. Am J Trop Med Hyg 1988; 39: 196–201.
mansoni infection who were followed up for two years after
55 Dessein AJ, Hillaire D, Elwali NE, et al. Severe hepatic fibrosis in treatment. Clin Infect Dis 1997; 24: 304–08.
Schistosoma mansoni infection is controlled by a major locus that is
81 Deelder AM, Qian ZL, Kremsner PG, et al. Quantitative
closely linked to the interferon-gamma receptor gene.
diagnosis of schistosoma infections by measurement of
Am J Hum Genet 1999; 65: 709–21.
circulating antigens in serum and urine. Trop Geogr Med 1994;
56 Macdonald G, Farooq M. The public health and economic 46: 233–38.
importance of schistosomiasis. In: Ansari N, ed. Epidemiology and
82 Van Lieshout L, Polderman AM, Visser LG, Verwey JJ, Deelder AM.
control of schistosomiasis (bilharziasis). Basel: Karger, 1973:
Detection of the circulating antigens CAA and CCA in a group of
337–53.
Dutch travellers with acute schistosomiasis. Trop Med Int Health
57 Jordan P, Webbe G. Epidemiology. In: Jordan P, Webbe G, 1997; 2: 551–57.
Sturrock FS. Human schistosomiasis. Wallingford: CAB
83 Polman K. Epidemiological application of circulating antigen
International, 1993: 87–158.
detection in schistosomiasis [PhD dissertation]. Leiden: University
58 Kheir MM, Eltoum IA, Saad AM, Ali MM, Baraka OZ, of Leiden, 2000.
Homeida MM. Mortality due to schistosomiasis mansoni: a field
84 van Dam GJ, Wichers JH, Ferreira TMF, Ghati D, van Amerongen
study in Sudan. Am J Trop Med Hyg 1999; 60: 307–10.
A, Deelder AM. Diagnosis of schistosomiasis by reagent strip test
59 Kloetzel K. Mortality in chronic splenomegaly due to for detection of circulating cathodic antigen. J Clin Microbiol 2004;
schistosomiasis mansoni: follow-up study in a Brazilian population. 42: 5458–61.
Trans R Soc Trop Med Hyg 1967; 61: 803–05.
85 Lengeler C, Utzinger J, Tanner M. Screening for schistosomiasis
60 Ongom VL, Owor R, Grundy R, Bradley DJ. The epidemiology and with questionnaires. Trends Parasitol 2002; 18: 375–77.
consequences of Schistosoma mansoni infection in West Nile,
86 Lengeler C, Utzinger J, Tanner M. Questionnaires for rapid
Uganda, II: hospital investigation of a sample from the Panyagoro
screening of schistosomiasis in sub-Saharan Africa.
community. Trans R Soc Trop Med Hyg 1972; 66: 852–63.
Bull World Health Organ 2002; 80: 235–42.
61 Williams EH, Hayes RJ, Smith PG. Admissions to a rural hospital
87 Tan HZ, Yang MX, Wu ZG, et al. Rapid screening method for
in the West Nile District of Uganda over a 27 year period.
Schistosoma japonicum infection using questionnaires in flood
J Trop Med Hyg 1986; 89: 193–211.
area of the People’s Republic of China. Acta Tropica 2004; 90: 1–9.
62 Blas BL, Cabrera BD, Santos AT Jr, Nosenas JS. An attempt to

1116 www.thelancet.com Vol 368 September 23, 2006

 Seminar

88 Vennervald BJ, Kahama AI, Reimert CM. Assessment of morbidity 113 Butterworth AE. Immunology of schistosomiasis. In: Jordan P,
in Schistosoma haematobium infection: current methods and future Webbe G, Sturrock FS. Human schistosomiasis. Wallingford: CAB
tools. Acta Tropica 2000; 77: 81–89. International, 1993: 331–66.
89 AbdelWahab MF, Esmat G, Farrag A, Elboraey Y, Strickland GT. 114 Gryseels B. Uncertainties in the epidemiology and control of
Ultrasonographic prediction of esophageal varices in schistosomiasis. Am J Trop Med Hyg 1996; 55 (suppl): 103–08.
schistosomiasis mansoni. Am J Gastroenterol 1993; 88: 560–63. 115 Woolhouse ME, Hagan P. Seeking the ghost of worms past.
90 Richter J, Correia Dacal AR, Vergetti Siqueira JG, et al. Nat Med 1999; 5: 1225–27.
Sonographic prediction of variceal bleeding in patients with liver 116 Capron A, Riveau G, Capron M, Trottein F. Schistosomes: the road
fibrosis due to Schistosoma mansoni. Trop Med Int Health 1998; 3: from host-parasite interactions to vaccines in clinical trials.
728–35. Trends Parasitol 2005; 21: 143–49.
91 Homeida M, Abdel-Gadir AF, Cheever AW, et al. Diagnosis of 117 Mutapi F, Hagan P, Woolhouse ME, Mduluza T, Ndhlovu PD.
pathologically confirmed Symmers’ periportal fibrosis by Chemotherapy-induced, age-related changes in antischistosome
ultrasonography: a prospective blinded study. Am J Trop Med Hyg antibody responses. Parasite Immunol 2003; 25: 87–97.
1988; 38: 86–91. 118 van den Biggelaar AH, Borrmann S, Kremsner P, Yazdanbakhsh M.
92 Hayashi S, Ohtake H, Koike M. Laparoscopic diagnosis and clinical Immune responses induced by repeated treatment do not result in
course of chronic schistosomiasis japonica. Acta Trop 2000; 77: protective immunity to Schistosoma haematobium: interleukin (IL)-5
133–40. and IL-10 responses. J Infect Dis 2002; 186: 1474–82.
93 Palmer PES, Reeder CC. International Registry of Tropical Imaging. 119 Gryseels B. Human resistance to schistosoma Infections: age or
Radiology Department, Uniformed Services University USA 2005. experience? Parasitol Today 1994; 10: 380–84.
http://tmcr.usuhs.mil (accessed April 10, 2006). 120 Ouma JH, Fulford AJ, Kariuki HC, et al. The development of
94 Lambertucci JR, Serufo JC, Gerspacher-Lara R, et al. Schistosoma schistosomiasis mansoni in an immunologically naive immigrant
mansoni: assessment of morbidity before and after control. population in Masongaleni, Kenya. Parasitology 1998; 117: 123–32.
Acta Trop 2000; 77: 101–09. 121 Kabatereine NB, Vennervald BJ, Ouma JH, et al. Adult resistance to
95 Hatz CF. The use of ultrasound in schistosomiasis. Adv Parasitol schistosomiasis mansoni: age-dependence of reinfection remains
2001; 48: 225–84. constant in communities with diverse exposure patterns.
96 Richter J, Hatz C, Haussinger D. Ultrasound in tropical and Parasitology 1999; 118: 101–05.
parasitic diseases. Lancet 2003; 362: 900–02. 122 Pearce EJ. Priming of the immune response by schistosome eggs.
97 Stelma FF, Talla I, Sow S, et al. Efficacy and side effects of Parasite Immunol 2005; 27: 265–70.
praziquantel in an epidemic focus of Schistosoma mansoni. 123 Bergquist RN, Colley DG. Schistosomiasis vaccine: research to
Am J Trop Med Hyg 1995; 53: 167–70. development. Parasitol Today 1998; 14: 99–104.
98 Dayan AD. Albendazole, mebendazole and praziquantel: review of 124 Hewitson JP, Hamblin PA, Mountford AP. Immunity induced by
non-clinical toxicity and pharmacokinetics. Acta Trop 2003; 86: 141–59. the radiation-attenuated schistosome vaccine. Parasite Immunol
99 WHO. Report of the WHO informal consultation on the use of 2005; 27: 271–80.
praziquantel during pregnancy/lactation and albendazole/ 125 Gryseels B. Schistosomiasis vaccines: a devils’ advocate view.
mebendazole in children under 24 months (WHO/CDS/CPE/ Parasitol Today 2000; 16: 46–48.
PVC/2002.4). Geneva: World Health Organization, 2002. 126 Karanja DMS, Colley DG, Nahlen BL, Ouma JH, Secor WE. Studies
100 Renganathan E, Cioli D. An international initiative on praziquantel on schistosomiasis in western Kenya, 1: evidence for immune-
use. Parasitol Today 1998; 14: 390–91. facilitated excretion of schistosome eggs from patients with
101 Davis A. Antischistosomal drugs and clinical practice. In: Jordan P, Schistosoma mansoni and human immunodeficiency virus
Webbe G, Sturrock FS. Human schistosomiasis. Wallingford: CAB coinfections. Am J Trop Med Hyg 1997; 56: 515–21.
International, 1993: 367–404. 127 Mwanakasale V, Vounatsou P, Sukwa TY, Ziba M, Ernest A,
102 Utzinger J, N’Goran EK, N’Dri A, Lengeler C, Tanner M. Efficacy of Tanner M. Interactions between Schistosoma haematobium and
praziquantel against Schistosoma mansoni with particular human immunodeficiency virus type 1: the effects of coinfection on
consideration for intensity of infection. Trop Med Int Health 2000; 5: treatment outcomes in rural Zambia. Am J Trop Med Hyg 2003; 69:
771–78. 420–28.
103 Richter J. The impact of chemotherapy on morbidity due to 128 Mwinzi PNM, Karanja DMS, Kareko I, et al. Evaluation of hepatic
schistosomiasis. Acta Trop 2003; 86: 161–83. fibrosis in persons co-infected with Schistosoma mansoni and human
104 Fong GC, Cheung RT. Caution with praziquantel in immunodeficiency virus 1. Am J Trop Med Hyg 2004; 71: 783–86.
neurocysticercosis. Stroke 1997; 28: 1648–49. 129 Kallestrup P, Zinyama R, Gomo E, et al. Schistosomiasis and HIV-1
105 Xiao SH, Tanner M, N’Goran EK, et al. Recent investigations of infection in rural Zimbabwe: implications of coinfection for
artemether, a novel agent for the prevention of schistosomiasis excretion of eggs. J Infect Dis 2005; 191: 1311–20.
japonica, mansoni and haematobia. Acta Trop 2002; 82: 175–81. 130 Fernando R, Miller R. Immune reconstitution eosinophilia due to
106 Utzinger J, Keiser J, Shuhua X, Tanner M, Singer BH. Combination schistosomiasis. Sex Transm Infect 2002; 78: 76.
chemotherapy of schistosomiasis in laboratory studies and clinical 131 Elliott AM, Mawa PA, Joseph S, et al. Associations between
trials. Antimicrob Agents Chemother 2003; 47: 1487–95. helminth infection and CD4+ T cell count, viral load and cytokine
107 Barakat R, ElMorshedy H, Fenwick A. Efficacy of myrrh in the responses in HIV-1-infected Ugandan adults.
treatment of human Schistosomiasis mansoni. Am J Trop Med Hyg Trans R Soc Trop Med Hyg 2003; 97: 103–08.
2005; 73: 365–67. 132 Kallestrup P, Zinyama R, Gomo E, et al. Schistosomiasis and HIV-1
108 Cioli D, Pica-Mattoccia L, Archer S. Drug resistance in Infection in rural Zimbabwe: effect of treatment of schistosomiasis
schistosomes. Parasitol Today 1993; 9: 162–66. on CD4 cell count and plasma HIV-1 RNA load. J Infect Dis 2005;
109 Fallon PG, Doenhoff MJ. Drug-resistant schistosomiasis: resistance 192: 1956–61.
to praziquantel and oxamniquine induced in Schistosoma mansoni 133 Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL. Global
in mice is drug specific. Am J Trop Med Hyg 1994; 51: 83–88. burden of disease and risk factors. New York/Washington: Oxford
110 Gryseels B, Mbaye A, De Vlas SJ, et al. Are poor responses to University Press/The World Bank, 2006.
praziquantel for the treatment of Schistosoma mansoni infections in 134 van der Werf MJ, De Vlas SJ, Brooker S, et al. Quantification of
Senegal due to resistance? An overview of the evidence. clinical morbidity associated with schistosome infection in sub-
Trop Med Int Health 2001; 6: 864–73. Saharan Africa. Acta Trop 2003; 86: 125–39.
111 Botros S, Sayed H, Amer N, El Ghannam M, Bennett JL, Day TA. 135 Chitsulo L, Engels D, Montresor A, Savioli L. The global status of
Current status of sensitivity to praziquantel in a focus of potential schistosomiasis and its control. Acta Trop 2000; 77: 41–51.
drug resistance in Egypt. Int J Parasitol 2005; 35: 787–91. 136 Utroska JA, Chen MG, Dixon H, et al. An estimate of global needs
112 Geerts S, Gryseels B. Drug resistance in human helminths: current for praziquantel within schistosomiasis control programmes
situation and lessons from livestock. Clin Microbiol Rev 2000; 13: (WHO/SCHISTO/89.102). Geneva: World Health Organization,
207–22. 1989.
137 Brooker S, Rowlands M, Haller L, Savioli L, Bundy DA. Towards an

www.thelancet.com Vol 368 September 23, 2006 1117

 Seminar

atlas of human helminth infection in sub-Saharan Africa: the use 148 El Katsha S WS. Gender, behavior, and health; schistosomiasis
of geographical information systems (GIS). Parasitol Today 2000; transmission and control in rural Egypt. Cairo: American University
16: 303–07. in Cairo Press, 2002.
138 Ratard RC, Kouemeni LE, Bessala MM, Ndamkou CN. Estimation 149 Magnussen P. Treatment and re-treatment strategies for
of the number of cases of schistosomiasis in a country: the schistosomiasis control in different epidemiological settings: a
example of Cameroon. Trans R Soc Trop Med Hyg 1992; 86: review of 10 years’ experiences. Acta Trop 2003; 86: 243–54.
274–76. 150 Bian Y, Sun Q, Zhao Z, Blas E. Market reform: a challenge to public
139 Gryseels B. The epidemiology of schistosomiasis in Burundi and health: the case of schistosomiasis control in China.
its consequences for control. Trans R Soc Trop Med Hyg 1991; 85: Int J Health Plann Manag 2004; 19 (suppl 1): S79–94.
626–33. 151 Ali MI, Byskov J, Mokgweetsinyana SS, Sibiya J, Mott KE.
140 Brinkmann UK, Werler C, Traore M, Korte R. The National Integration of control of schistosomiasis due to S. mansoni within
Schistosomiasis Control Programme in Mali, objectives, primary health care in Ngamiland, Botswana. Trop Med Parasitol
organization, results. Trop Med Parasitol 1988; 39: 157–61. 1989; 40: 195–200.
141 Zhang W, Wong CM. Evaluation of the 1992–1999 world bank 152 Jarallah JS, al Shammari SA, Khoja TA, al Sheikh M. Role of
schistosomiasis control project in China. Acta Trop 2003; 85: primary health care in the control of schistosomiasis: the
303–13. experience in Riyadh, Saudi Arabia. Trop Geogr Med 1993; 45:
142 Cowie RH. Can snails ever be effective and safe biocontrol agents? 297–300.
Int J Pest Manag 2001; 47: 23–40. 153 Engels D, Sindayigaya B, Gryseels B. Sustainability of
143 Laamrani H, Boelee E. The role of irrigation design and water schistosomiasis case detection based on primary health care.
management parameters in the ecology of transmission and Trans R Soc Trop Med Hyg 1995; 89: 599.
control of schistosomiasis in central Morocco. Cahiers d’études et de 154 Fenwick A. New initiatives against Africa’s worms.
recherches francophones/Agricultures 2002; 11: 23–29. Trans R Soc Trop Med Hyg 2006; 100: 200–07.
144 Minai M, Hosaka Y, Ohta N. Historical view of schistosomiasis 155 Fifty-fourth World Health Assembly. Resolution WHA54.19.
japonica in Japan: implementation and evaluation of disease- Schistosomiasis and soil-transmitted helminths. Geneva: World
control strategies in Yamanashi Prefecture. Paras Int 2003; 52: Health Organization, 2001.
321–26. 156 Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”:
145 Sow S, De Vlas SJ, Mbaye A, Polman K, Gryseels B. Low awareness how a policy of integrated control for Africa’s neglected tropical
of intestinal schistosomiasis in northern Senegal after 7 years of diseases could benefit the poor. PLoS Med 2005; 2: e336.
health education as part of intense control and research activities. 157 Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich SS,
Trop Med Int Health 2003; 8: 744–49. Sachs JD. Incorporating a rapid-impact package for neglected
146 Engels D, Ndoricimpa J, Gryseels B. Schistosomiasis mansoni in tropical diseases with programs for HIV/AIDS, Tuberculosis, and
Burundi: progress in its control since 1985. Bull World Health Organ Malaria. PLoS Med 2006; 3: e102.
1993; 71: 207–14.
147 Kloetzel K. Some personal views on the control of schistosomiasis
mansoni. Mem Inst Oswaldo Cruz 1992; 87 (suppl 4): 221–26.

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