++
Hundreds of millions of people, particularly those who live in
rural areas or deprived urban settings in the developing world,
are at risk of acquiring foodborne trematodiasis and schistosomiasis.1-3
++
Foodborne trematodiasis include clonorchiasis, paragonimiasis,
fascioliasis, and opisthorchiasis. These and schistosomiasis all
belong to the subclass of Digenea, class of Trematoda, phylum of Platyhelminthes.
The taxonomy of Platyhelminthes is shown in eFigure 335.1. Digeneans,
also known as flatworms, are characterized by dorsoventral flattening,
presence of an oral sucker and often a ventral sucker, and lack of
a circulatory system.4Figure
335-1 shows, by means of scanning electron microscopy, the
head portion of an adult Clonorchis sinensis (a
liver fluke), clearly depicting some of the typical features of
the Digeneans.
++
++
++
The endemic regions of the world, global burden and at risk populations
for infection with clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis,
paragonimiasis, and schistosomiasis are summarized in Table
335-1.3,5-10
++
++
The major species from the subclass Digenea parasitizing humans include
the blood flukes
(5 species of Schistosoma), liver flukes (C
sinensis, Fasciola gigantica, F
hepatica, Opisthorchis felineus, and O
viverrini), lung flukes (Paragonimus spp),
and intestinal flukes (eg, Fasciolopsis buski).
++
Schistosomiasis exhibits the largest geographic distribution;
the disease is endemic in over 70 countries and territories of the world
with an estimated 779 million people at risk and 207 million infections
(eFig. 335.2).3 The
global burden due to schistosomiasis might be as high as 4.5 million
disability-adjusted life years (DALYs). The DALY is a metric used
to express the number of healthy life years lost due to a disease
or injury, taking into account both premature death and living with
disabilities. DALYs are extremely difficult to calculate for helminthic
diseases and other chronic conditions. Schistosoma haematobium and S
mansoni are responsible for the majority of the disease
burden, morbidity and mortality from schistosomiasis, with disease
being concentrated in sub-Saharan Africa.3,11
++
++
An estimated 750 million people are at risk of foodborne trematodiasis
with over 40 million infections. Southeast Asia and the Western Pacific
are the regions most impacted by foodborne trematodiasis.2,12 Estimates
for at-risk populations for clonorchiasis, paragonimiasis, fascioliasis,
and opisthorchiasis are 601 million, 293 million, 91 million, and
greater than 60 million, respectively.
++
The patterns of age distribution of infections are not uniform,
but in general the highest rates of infection with Schistosoma species, Fasciola species,
and F buski is found among school-age children
and young adults.9 On the other hand, in the case
of clonorchiasis and opisthorchiasis, the prevalence of infection
increases with age, and hence adults are more affected than their younger
counterparts.8
++
Profound demographic, ecologic, and socioeconomic transformations
have altered the epidemiology of schistosomiasis and foodborne trematodiasis.
The development and management of water resources (ie, irrigation
schemes and large dams) has resulted in outbreaks of schitosomiasis,
or intensified disease transmission. Indeed, living in close proximity
to such water resources is a key risk factor for acquiring the disease.3 Similarly,
socio-economic changes including the expansion of aquaculture for
production of freshwater fish and shrimp, inadequate sanitation,
domestic migration, and wider distribution networks of food without
proper inspections are some of the key features explaining an increase
in foodborne trematodiasis.6
++
The expansion of schistosomiasis and foodborne trematodiasis
into previously nonendemic areas may also be partly explained by
global warming and human modification of the landscape.9,13 In
the case of foodborne trematodiasis, increases in international travel
and growing consumption of imported aquatic foods may also play
a role. On the other hand, socioeconomic development and implementation
of morbidity control programs dramatically lowered the burden due
to schistosomiasis and foodborne trematodiasis in some regions.3,6
++
eFigure 335.3 shows the life cycle
of the digeneans, distinguishing between schistosomes and foodborne trematodes.
A characteristic feature is the alternation of asexual and sexual
reproductive phases.4 Parasite eggs are excreted
from humans (or a range of domestic animals that can also act as
definitive hosts in the sputum (Paragonimus spp),
feces (C sinensis, Fasciola spp, Opisthorchis spp, Paragonimus spp, S
mansoni, S japonicum, S intercalatum, and S
mekongi), or urine (S haematobium). Once
eggs have reached a freshwater body, they develop and release a
tiny larva, the so-called miracidium, which seeks a specific snail
species (usually small aquatic snails), the first intermediate host.
Within the snail, larval development and asexual multiplication
takes place and cercariae are released from snails.
++
++
Schistosoma cercariae infect humans subcutaneously
when they come into contact with infested freshwater during recreational
(eg, playing in stagnant freshwater ponds) and occupational activities
(eg, irrigated rice farming). The tailless cercariae are transported
through blood or lymphatics to the right side of the heart and lungs.
The adult worms do not multiply inside the human body, but mate
and the female lays eggs about 4 to 6 weeks following cercarial
penetration. This phase of infection can be associated with Katayama
fever (see below) which is believed to result from immune
complex formation with high antigenic stimulation due to the worm
or egg antigens. The female adult worm continues to live for up
to 8 years and lays eggs throughout her life span. The chronic sequelae
of Schistosomiasis are due to immunologic reactions to the eggs trapped
in tissues that lead to a granulomatous reaction.
++
In the case of lung, liver, and intestinal flukes, the cercariae
encyst in the flesh of the second intermediate hosts—fish
(eg, C sinensis, Opisthorchis spp)
or shellfish (eg, Paragonimus spp)—or
encyst on aquatic plants (eg, Fasciola spp, F
buski). Humans become infected when eating raw or undercooked
aquatic products harboring metacercariae.12 Upon
ingestion, the acid environment of the stomach begins the process
of excystment, and in the duodenum the worm burrows through the
intestinal lining into the peritoneal cavity where it traverses
to the lung, or through the liver to the bile ducts, where the mature
worm resides and excretes eggs. The C sinensis, Fasciola spp and Opisthorchis spp
reside in the bile ducts of the liver and eggs are excreted in stool. F
buski resides in the duodenum. Paragonimus reside
in the lungs and eggs are excreted in the sputum, or swallowed and
excreted in stool.
+++
Clinical Manifestations
++
Schistosomiasis denotes a complex of acute, or chronic infections
with varying clinical manifestations at different stages. The clinical
manifestations depend on the species of parasite, intensity of worm
burden, and immunity of the person to the parasite. Cercarial skin
penetration can result in local and temporary irritation and trigger
a dermal rush, manifesting within hours and persisting for a couple
of days as maculopapular lesions.
++
Katayama syndrome is a systemic hypersensitivity
reaction that results from high quantities of antigens being released
by migrating schistosomula, adult worms, or eggs, coupled with significant
levels of circulating IgG. It may occur 2 to 12 weeks after a primary
infection or a heavy reinfection. It occurs more frequently with S
japonicum infections than the other schistosome species.
Typically, the onset of Katayama syndrome is sudden, but symptoms
are non-specific, including fever, headache, general malaise, and
tiredness. Eosinophilia is usually present. Involvement of the lung
can manifest with a dry cough, and can be seen radiologically as
a patchy infiltrate.
++
Following infection, chronic symptoms evolve slowly, being due
to inflammatory reactions to the eggs that are deposited in various
organs. Symptoms vary depending upon the organism. The adult worms
do not cause an immune reaction and are generally not the cause
of symptoms. S haematobium infection causes granulomatous
inflammation of the bladder wall, often causing ulceration resulting in both
microscopic and macroscopic hematuria. Infection can cause substantial
scarring, with ureteral obstruction. The damaged mucosal epithelium
can undergo malignant changes, with squamous cell carcinomas. Fibrosis
and bladder calcification are characteristic of late-stage infections
and can eventually lead to parenchymal damage and kidney failure.11
++
S japonicum and S mansoni,
infection is characterized by egg deposition in the intestine, particularly
in the rectum and distal bowel. The mucosa may ulcerate. Typical
symptoms include abdominal pain and (bloody) diarrhea.15 Eggs
often embolize through the portal vein to the liver where they cause
a granulomatous hepatitis and marked fibrosis. Typically, portal
hypertension develops. The liver disease may progress to cirrhosis
and liver failure.11
+++
Foodborne Trematodiasis
++
Infections with foodborne trematodes have a wide array of clinical
signs and symptoms that are often non-specific. While light infections
are in general asymptomatic, large parasite loads, prolonged durations
of infection, hypersensitivity, or concomitant parasitic infections
can cause considerable morbidity, and the diseases can even be fatal.
++
With regard to liver fluke infections, high fever, hepatitis-like
symptoms and eosinophilia have been described for symptomatic O
felineus infections.8 Symptomatic cases
of clonorchiasis, fascioliasis, and infections with O viverrini are
characterized by abdominal pain, flatulence, dyspepsia, anorexia,
weakness, lassitude, weight loss, fever, rash, swollen abdomen,
or enlargement of the liver. Jaundice, pruritus, and biliary colic
are frequent complications of severe infections with Fasciola species.9 Ascending
cholangitis, obstructive jaundice, and cholangiocarcinoma (bile
duct cancer) are the most serious complication of clonorchiasis
and opisthorchiasis.8,16
++
Clinical features due to an infection with the intestinal fluke F
buski include abdominal pain, fever, nausea, diarrhea,
constipation, eosinophilia, headache, dizziness, and malnutrition.
Heavy infections are associated with generalized toxic and allergic
symptoms such as edema of the face, abdominal wall, and lower extremities.9
++
Clinical symptoms of lung fluke infection include cough, fever,
bloody sputum, loss of appetite, chest pain, and headache in the
early stage of infection. Once the infection has been established,
cough and bloody sputum are common.10 Extrapulmonary
paragonimiasis is caused by migrating worms into ectopic locations,
for example the skin, liver, eye, abdominal organs, or the brain.
Cerebral paragonimiasis is particularly severe and can cause a variety
of neurologic complications (headache, convulsions, paralysis, or
behavioral changes).10
++
The pathologic changes of foodborne trematode infections are
confined to the target organs of the adult flukes. The intestinal
fluke F buski causes extensive duodenal and intestinal
erosions, ulceration, hemorrhage, abscesses, and catarrhal inflammation.9 Pleural
and pulmonary manifestations of paragonimiasis include multifocal
pleural hemorrhage, eosinophilic pleuritis, pleural effusion, pneumothorax,
thickened pleura, peribronchiolar infiltration of lymphocytes and
plasma cells, hyperplasia of bronchioles and peribronchiolar glands,
and chronic active eosinophilic granulomatous pneumonia.10 In
case of liver fluke infections, the bile duct, liver, and gallbladder are
affected. In C sinensis and O viverrini infections,
the biliary epithelium becomes edematous, often accompanied by periductal
infiltrates of mononuclear cells. Metaplasia of the biliary cells
into mucin-producing cells can lead to persistent and high mucus
content of the bile. Desquamation of the biliary epithelium, epithelial
hyperplasia, bile duct hyperplasia, and periductal fibrosis have
been described in chronic infections.8 Finally,
in the parynchymal phase of fascioliasis, mechanical destruction
of the liver tissues, chronic ulceration, desquamation, and hemorrhage
are caused by the migrating flukes. The mechanical liver damage
is accompanied by a cellular inflammatory reaction by the host.
Furthermore, factors produced or induced by the fluke as proteases
might contribute to liver damage.
++
A number of different diagnostic approaches, referred to as direct
parasitologic techniques (detection of parasite eggs in biological
samples), indirect immunologic tests, molecular diagnosis, or noninvasive
diagnostic techniques, are available for the diagnosis of schistosome,
intestinal, liver, and lung fluke infections.
++
The most widely used technique in epidemiologic surveys for diagnosis
of S mansoni and S japonicum is
the Kato-Katz technique, that is, microscopic examination, usually of
approximately 42 mg of stool, prepared as a thick smear on a microscope
slide. This technique is quantitative and allows infection intensity
to be expressed as the number of schistosome eggs per gram of stool.18 Additionally,
direct fecal smears (only a very small amount of stool is examined),
sedimentation of fresh stool samples, or an ether-concentration
method applied on preserved stool samples are used for subsequent
examination under a microscope.18 A wide array
of immunologic tests have been developed and widely used in China
for large-scale population screening of S japonicum.19 For S
haematobium, filtration of 10 mL of urine, preferably collected
between 10 am and 2 pm (coinciding
with maximal egg excretion rates) and subsequent microscopic examination
is the most widely used method in epidemiologic surveys. This method
is quantitative and infection intensity is expressed as the number
of S haematobium eggs per 10 mL of urine. Reagent strip
testing for detection of blood (microhematuria) and protein in urine
(proteinuria) is also widely used and allows semiquantitative appraisal
of infection intensity.18 A convenient method for
appraisal of pathology due to schistosomiasis is ultrasonography
for examination of the liver and bladder. It is mainly applied in
hospital settings, but progress made with portable devices now allows
using ultrasound in epidemiologic surveys.20
+++
Foodborne Trematodiasis
++
Quantitative microscopic coprologic analyses (and sputum in the case
of Paragonimus spp) are the most widely employed
techniques for diagnosis of an infection with foodborne trematodes.
Simple direct smears, simple sedimentation techniques, Kato-Katz
thick smears, Stoll’s dilution egg count technique, or
the formalin-ether concentration technique are used.8,12 However,
multiple stool examinations are warranted to improve upon the diagnostic
sensitivity. Serologic tests, mostly based on the detection of circulating
antibodies, have been developed for the diagnosis of liver and lung fluke
infections and have the advantage that they can be applied during
all stages of the disease. Immunodiagnostic tests include intradermal
tests, an indirect hemagglutination assay, an indirect fluorescent antibody test,
and an indirect ELISA.8,10 Significant progress
has been made in recent years regarding molecular methods, most
notably the use of polymerase chain reaction–based (PCR-based)
methods for the diagnosis of O viverrini, C
sinensis, Paragonimus species, and F
hepatica infections.8,10 Finally, noninvasive
techniques to reveal pathologic alterations include radiology, ultrasound,
computed tomography, or magnetic resonance imaging.
++
There are two drugs currently recommended for the treatment of schistosomiasis
and foodborne trematodiasis; namely praziquantel and triclabendazole
(see Chapter 323 and Table
323-1).21-24
++
Praziquantel is the drug of choice for schistosomiasis, clonorchiasis,
opisthorchiasis, paragonimiasis, and intestinal fluke infections
in adults and children older than 2 years (in the case of schistosomiasis)
and 4 years (in the case of foodborne trematodiasis).2,22 Triclabendazole
is used against fascioliasis in patients aged 6 years and above.24
++
A third drug, bithionol, is still often used for fascioliasis
and paragonimiasis if triclabendazole is not available, praziquantel
failed to cure the infection, or patients displayed previous idiosyncratic
or allergic reactions and praziquantel should not be given. Bithionol
has been used in children below the age of 5 years.2 For
schistosomiasis, oxamniquine has been widely and effectively used
against S mansoni, particularly in Brazil.5 Metrifonate
shows activity against S haematobium and has been
widely used in the 1960s and 1970s, but due to economic, operational,
and therapeutic reasons (eg, multiple doses are necessary to achieve
good clinical outcomes), it has been suggested that schistosomiasis
chemotherapy can do without this drug.5
++
Preventive chemotherapy (eg, regular administration of praziquantel
to at-risk populations without prior diagnosis) is increasingly
promoted by WHO and other international organizations to limit the
morbidity of schistosomiasis and food-borne trematodiasis.1,12,21 However,
this strategy alone falls short of addressing the root behavioral
and environmental causes of foodborne trematodiasis, schistosomiasis,
and other often neglected tropical diseases. Sound information,
education, and communication strategies to change human water contact
behavior (in the case of schistosomiasis), to properly cook fish
and other aquatic products, and to boil water (in the case of foodborne
trematodiasis), as well as food safety measures and improved sanitary conditions,
are key factors to achieve long-lasting effects on the control or
even local elimination of foodborne trematodiasis and schistosomiasis.22,25 Linking
preventive chemotherapy with health education and improved sanitary
conditions, as well as collaboration with different sectors (eg,
educational sectors or the food industry), will be required to ensure
long-term parasite control and in turn boost social and economic
development in areas where schistosomiasis and foodborne trematodiasis
are still rampant.