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They’re hermaphrodites, not more than 25 millimetres long. They’re flat.
They wiggle. They live for years in the livers, lungs or even brains of
at least 40 million people in the world. Some of them produce a deadly form
of liver cancer that kills thousands of people every year. And they cost
the world billions of dollars a year. No, you are not likely to know what
they are because, as one expert puts it, we’re talking about ‘one of humanity’s
most widespread but hidden scourges’.

The expert is Ken Mott and he’s talking about infections caused by a
group of parasitic flatworms, called trematodes or flukes. They spend part
of their lives in freshwater fish and shellfish or attached to certain edible
plants. People who eat trematode-carrying foods uncooked, or unwashed in
the case of plants, are almost certain to become infected. Now, for the
first time, a report on flukes being prepared by the WHO puts the spotlight
on this scourge in an attempt to alert health authorities to their importance.

Lack of awareness about such infections is due, says Mott, to the daunting
biological complexity of flukes, the difficulty of detecting them and the
huge effort required to eradicate them. Another reason, according to the
WHO’s food safety chief, Fritz Kaferstein, is that because they affect mainly
developing countries ‘they’ve been cut off from the main interests of the
Western world’. In some places, such as the former Soviet Union, their presence
– in nearly half the territory of Russia – was until recently a state secret.

‘We’ve just swept the subject under the carpet and forgotten about it,’
says Mott, who is head of the WHO’s unit for the control of schistosomiasis
and other diseases caused by worms. ‘We’re in some kind of an ostrich-like
vicious circle. We don’t know about these flukes, so we don’t look for them.
We don’t look for them, so we don’t see them.’ Such an attitude, he warns,
is reckless: ‘These flukes are serious menaces to public health and are
growing in importance.’

Indeed, as the report estimates, at least 40 million people are infected
by food-borne flukes. Of these, 21 million people carry flukes of the Paragonimus
species which can cause lung and brain diseases . A further 17 million people
are infected with the Clonorchis and Opisthorchis flukes, which cause various
liver diseases. All three flukes enter the body as larvae carried in freshwater
fish and shellfish. The fourth fluke that causes damage is Fasciola. Although
it prefers animals, the WHO estimates that about 2 million people have become
infected with this fluke after eating contaminated watercress and other
aquatic plants. Most do not have significant symptoms, but the fluke sometimes
produces an unpleasant liver disease.

Host of hosts

The risk of infection is highest in developing countries with poor sanitation,
where human and animal faeces carrying eggs from a fluke can contaminate
water. The eggs hatch in the water. The tiny larvae find a suitable snail
in which they begin maturing, and then leave the snail for their second
intermediate host – the fish, shellfish or plant. When a human (or animal)
eats the intermediate host, he or she becomes the fluke’s definitive host,
and the cycle starts another turn. But people living in the ‘sanitised’
developed world face a potential risk with the escalation of international
trade in foodstuffs from parts of Asia, Africa and Latin America where
the flukes are prevalent.

John Race is chairman of the Fish and Fishery Products Committee of
the Codex Alimentarius Commission (CAC), the body that sets international
food safety standards. For him, the problem ‘is that we’ve all been unaware
of these infections. We’ve just not taken them into account from a food
safety standpoint.’ Indeed, nowhere among the 27 volumes of food standards,
guidelines and principles established by the CAC since it was set up in
1962 is there any mention of the flukes. Nor do the CAC’s 12 international
codes of practice for fish and shellfish contain any reference to them.

Even the WHO is blushing. ‘We’re all ashamed,’ Kaferstein admits with
disarming frankness. ‘The WHO believes illness from contaminated food to
be perhaps the most common health problem in the world today, but it’s been
quite unaware of the importance of these food-borne trematodes.’ He holds
up a copy of the WHO’s Ten Golden Rules for preparing food and points to
one that says heating food up to 70 degree C will kill any pathogens in
it: ‘That’s 10 degrees below what I now suspect is really needed to kill
these flukes.’ The WHO’s 1994 edition of International Travel and Health
doesn’t even mention them in its table of ‘agents of important food-borne
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Mott and Kaferstein have decided it is time to pull the world’s head
out of the sand and assess the danger from fluke infections. Last October,
with the help of Chinese worm expert Yu Sen-Hai, they brought together 20
experts in Manila, capital of the Philippines. A wide range of disciplines
was represented – parasitic diseases, cancer, lung diseases, food safety,
international fish trade, agriculture, animal husbandry. The meeting’s conclusions
form the basis of the report Control of Food-borne Trematode Infections
to be published this autumn.

The Manila gathering, Mott says, produced ‘surprises galore for just
about everybody present, including the experts’. The first surprise to emerge
is that, at an ‘extremely conservative’ estimate, there are 750 million
people living under the threat of infection in the 56 countries where the
worms are abundant. And the number of people infected is almost certainly
considerably higher than 40 million.

Soviet secrets

The second surprise came when a group of scientists from Moscow’s Martsinovsky
Institute of Medical Parasitology and Tropical Medicine revealed data, kept
secret under the former Soviet regime, showing that the Opisthorchis fluke
is highly prevalent in nearly 46 per cent of Russian territory. The WHO
has now estimated that about 1.2 million of the 240 million people that
live in these regions are infected. And in western Siberia, between 80 000
and 96 000 new cases of Opisthorchis infection (opisthorchiasis) occur every
year among the 12 million inhabitants. In parts of this 500 000 square
kilometre area, everyone – men, women and children – is infected.

Another severely affected part of the world is northeastern Thailand,
where a quarter of the general population and half of the workforce carry
the Opisthorchis fluke. In some districts, more than 90 per cent of the
inhabitants are infected. A likely culprit is koi pla, or chopped raw carp,
which is an extremely popular dish during the rainy season. Carp is a favourite
host of Opisthorchis. To complete the picture, northeastern Thailand has
the highest incidence in the world of a lethal form of liver cancer, cholangiocarcinoma.
The cancer is found in 85 males and 37 females per 100 000 of the population,
compared with 0.5 and 2 respectively elsewhere. The reason for the especially
high incidence in males is not known.

Flukey cancer

This suggests a causal relationship between fluke infection and cholangiocarcinoma
– not altogether surprising given that the fluke lives in the liver, notably
in the bile ducts where the cancer arises. Indeed, a study in Thailand by
Maxwell Parkin of the International Agency for Research on Cancer in Lyons,
France, showed that a person carrying the Opisthorchis fluke is five times
more likely to develop cholangiocarcinoma than an uninfected person. Parkin
and his colleagues suggest that the worm could set off the cancer-forming
process by releasing substances, such as nitrosamines, that damage cellular
DNA.

The Manila meeting, Mott says, ‘certainly added to my sense of frustration’
that so many millions of people suffer from diseases that are curable in
a day or two with the drug praziquantel. Even more frustrating is the fact
that, because of a lack of awareness about fluke infections, millions of
dollars a year are being wasted by treating the wrong disease. For example,
the Paragonimus fluke can cause paragonimiasis, a lung disease that produces
the cough and bloody sputum typical of tuberculosis. This has resulted in
countless patients receiving months, even years, of needless treatment for
TB, if the experience of health services in Ecuador and India are anything
to go by.

Ronald Guderian, of the Vozandes Hospital in Quito, Ecuador’s capital,
says that of the patients being treated for TB in one clinic, 13 per cent
turned out to be infected not with TB but with paragonimiasis. Paragonimus
infects almost half of Ecuador’s rural population and a fifth of the country’s
total population of 10 million. And in Manipur state in northeastern India,
health officials, on learning of the existence of paragonimiasis in 1982,
conducted a survey among patients who had been receiving treatment for TB
for at least a year. They found 60 per cent of them to be suffering from
paragonimiasis.

TB requires at least six months’ treat-ment with several drugs at a
total cost of between $13 and $50. By contrast, a single dose of the drug
praziquantel can wipe out paragonimiasis in 100 per cent of cases at a cost
of less than $1 – at least until the next infection.

No way to treat a fluke

Unfortunately, praziquantel is not effective against fascioliasis –
the liver disease caused by the Fasciola flukes – and there is no satisfactory
treatment available, at least for humans. But Mott reports that triclabendazole,
a new drug reserved for veterinary use until now, is ‘performing extremely
well’ in clinical trials being run by the WHO and the Swiss manufacturer,
Ciba-Geigy, in Iran, Bolivia, Chile, Cuba and Ecuador. Mott is optimistic
that triclabendazole will be ready for registration for human use ‘within
a year or two’.

As for the chances of a vaccine against the flukes, these are dim indeed.
There is no evidence that the antibodies the flukes provoke in infected
people protect against further infection, although they are convenient
markers of past or current infection. Researchers have, it is true, identified
an enzyme of the glutathione-S-transferase group in Fasciola hepatica,
the most extensively studied Fasciola species. The enzyme gives a degree
of protection against infection when injected into large ruminants. But
just how it works, and whether it will work in humans, is not yet known.

Availability of drugs or vaccines, though, is not the main problem.
‘It’s lack of awareness that’s keeping these worms in business,’ says Mott.
As an example, he refers to the World Bank’s annual World Development Report;
last year its theme was health and the disease burden in developing countries,
‘and it didn’t mention these trematodes once’, he says.

Henri Belvege, head of the unit responsible for health inspection of
fish at the European Commission in Brussels, says: ‘We have no instructions
about trematode infections, we don’t have any epidemiological information
about them and our food inspectors don’t look for them.’ But he is convinced
that the amount of freshwater fish imported unfrozen into Europe must be
extremely small and so ‘can’t be much of a problem’.

Although France holds the European record for human cases of fascioliasis
– at least 250 known cases a year – a health ministry spokeswoman in Paris
says: ‘We have no data about the national prevalence of this disease, but
it’s not a notifiable condition and is certainly not a public health problem.’

Even in the developing countries where the flukes are most prevalent,
most people don’t know they exist. ‘That’s the problem,’ Mott explains.
‘They’re part of the everyday life of people who are caught in a vicious
cycle of poverty, overpopulation and disease and who often take all three
for granted.’

Another reason these infections have been able to hide from the public
view is the difficulty of detecting them. People in the early, acute stages
can show several combinations of symptoms, none specific to food-borne trematodes.
Physicians mistake them for other conditions, such as viral hepatitis or
the roundworm infections toxocariasis and toxoplasmosis, not to mention
TB, epilepsy and meningitis in the case of Paragonimus.

Microscopic evidence of trematode eggs in the faeces is the standard
diagnostic method, but it requires an ability to recognise fluke eggs under
the microscope – rarely part of medical training. Ultrasound can reveal
the worms in the liver and blood tests can discover antibodies against them.
But these procedures are usually only resorted to in developed countries
for a patient with persistent, otherwise unaccountable, liverish symptoms
who is known to have eaten unwashed watercress or to have visited a part
of the world where the worms are endemic.

Mott believes that the complicated life cycles of the flukes, which
are not readily encapsulated in simple public health messages, are partly
responsible for the universal ignorance about them. The malaria parasite
with only two hosts – its mosquito carrier and its human or animal host
– is complicated enough to defeat all but the most massive attempts at eradication.
But the flukes have three hosts. To further complicate the picture, there
are more than 100 species of snails that can play nursemaid to the larvae
of the four most common species of trematodes, and at least 150 species
of freshwater fish, some 60 species of shellfish and about 20 species of
plants (including dandelion, water chestnut, water hyacinth and duckweed
as well as watercress) to act as the second host. The number of mammalian
species, including humans, that obligingly keep the worms’ life cycle turning
by excreting their eggs into rivers and ponds would have a job fitting
in Noah’s Ark.

Attempts at prevention come slap up against human habits – some nice,
such as eating raw fish delicacies, some not so nice, such as defecating
into ponds and rivers – that perpetuate the cycle of infection. In some
parts of the world, people even use raw fish or crab as traditional medicines.
‘You just can’t make people abandon lifestyles overnight that they’ve been
used to for generations,’ says Mott.

But prevention is possible. Take Japan, a country of raw fish eaters
if ever there was one. At one time, Clonorchis and Paragonimus infections
‘posed a national problem’, says Tokyo parasitologist Moriyasu Tsuji. But
through special laws enacted since the 1930s, the Japanese have gradually
brought the problem under control.

Health inspectors conduct nationwide microscopy examination of faeces,
mainly in children, every five years and give drugs to those infected. Heavy
fines are meted out to people found defecating in places that could contaminate
ponds and rivers. The government has paid cities, towns and villages to
improve their sanitary services, particularly faecal disposal. Primary schoolchildren
receive regular instruction about food sources of infection and the life
cycles of the trematodes. As a result, national stool surveys conducted
two years ago among more than 1 million people showed none to be infected
with either Clonorchis or Paragonimus.

In the introduction to its report, the WHO warns health authorities
in developing countries that ‘if proper precautions are not taken . . .
dramatic spread (of fishborne trematode infections) can be foreseen’. The
first step, the report advises, is for officials concerned with public health,
agriculture, fisheries, aquaculture, the food industry, food safety and
education, to join forces in planning preventive strategies.

In the short term, the WHO report should spotlight the glaring deficiencies
of legislation, codes and recommendations concerning the international fish
trade and the industrial processing of fish. Race says the Fish and Fishery
Products Committee of CAC will discuss the issue at its meeting in Bergen,
Norway, in May and set in motion the process of change, but ‘it will be
several years before recommendations are actually incor-porated (into its
food codes)’. An urgent priority, he says, is ‘to conduct research to find
out exactly what the risk of infection with these flukes is for people in
developed countries eating imported raw fish that may not have been shipped
in conditions guaranteed to kill the flukes’.

Kaferstein believes that at present such a risk is minimal or nonexistent
because freshwater fish is invariably transported frozen from countries
such as China and Thailand where the flukes are prevalent. Food frozen for
at least five days ‘should, as far as we know from our meagre data, be safe
to eat’, he says. He is, however, ‘extremely worried’ about the growing
trade in freshwater fish.

‘We are likely,’ says Kaferstein, ‘to witness a tremendous upsurge in
the movement of freshwater fish throughout the world, with Asian producers
seeking lucrative markets in the developed world.’ His worry is that some
producers, wishing to gain a competitive edge in an explosive market, may
start shipping unfrozen fish by air. ‘That could raise the risk of infection
in developed countries.’ There is little risk, though, that the flukes introduced
into temperate climes by such practices would ‘take root’ and start spreading.
The other hosts in their transmission cycle – the snails and freshwater
fish or crustaceans – are present only in existing endemic areas.

Lurking hazards for tourists

International travel could raise the incidence of infection in developed
countries, according to the Manila report. Tourism is growing almost exponentially,
with the number of tourists to east Asia and the Pacific – where flukes
are only one of many lurking health hazards – likely to jump from 58 million
in 1992 to 101 million by 2000.

Migrants and displaced persons also face an increased risk, the Manila
report notes. In 1992, more than a million of the world’s 18 million refugees
were in Southeast Asia and the Western Pacific. In some refugee camps, notably
in Cambodia and Laos, the incidence of Opisthorchis infection is reported
to be 20 per cent. Other studies have found that between 10 and 20 per cent
of immigrants arriving in France and the US from Southeast Asia are infected
with either Opisthorchis or Clonorchis.

There is clear evidence, too, that ethnic communities originally from
areas where the flukes are endemic continue to expose themselves to infection
by eating imported raw fish or shellfish. The people at greatest risk of
infection are those living close enough to Asian ‘fluke territory’ to import
unfrozen fish – Hong Kong, Macao, Singapore and Malaysia, for example, where
levels of Opisthorchis and Clonorchis infection (and the incidence of cholangiocarcinoma)
are relatively high. But if, as Kaferstein fears, trade with China opens
up to the world, enterprising fish producers may start putting their wares
on long-distance flights – to the delight (and danger?) of the 13 million
or so ethnic Chinese now living in the US.

For Mott and Kaferstein, the Manila meeting may be the first step in
deflating the worldwide threat of these flukes. ‘For the first time,’ says
Mott, ‘all the different sectors – health, food safety, veterinary medicine,
trade – are going to work together to bring these worms out of the cold
and to map the risks they pose. Knowing about the menace is the first step.
Pitting that knowledge against these infections comes next.

John Maurice is a freelance medical writer based in France.

* * *

Flukes galore

Of the many flukes that exist in nature, four types cause most damage:

The various Paragonimus species (21 million people infected), are prevalent
in most of Asia, especially China, but also in Africa and parts of Latin
America.

The different Opisthorchis and Clonorchis species (10.3 and 7 million
people infected, respectively), are abundant in Asia and Eastern Europe.

The two main Fasciola species, F. hepatica and F. gigantica (2 million
people infected), are the most widespread liver flukes in the world, infecting
more than 300 million cattle and 250 million sheep worldwide.

Paragonimus waits for its human victims in freshwater crabs, crayfish
and other shellfish, but once in the body it attacks the lungs, causing
TB-like symptoms – bouts of coughing with production of blood-tinged sputum.
This fluke can also invade the brain, and cause epileptic seizures, convulsions,
paralysis and mental retardation.

People become infected with Opisthorchis and Clonorchis by eating freshwater
fish, especially of the carp family, which carry fluke larvae. Abdominal
pain and discomfort mark the early stages, becoming more frequent and longer-lasting
as the infection progresses, culminating in lassitude, loss of taste and
appetite, diarrhoea and malnutrition.

With repeated infection over many years, up to 20 per cent of patients
develop gallstones or a life-threatening form of jaundice. About 7 per cent
suffer severe inflammation of the pancreas. A few patients die from septic
shock. In highly endemic areas, such as parts of northeastern Thailand,
where more than 90 per cent of the population carries Opisthorchis, about
10 per cent of those infected develop cholangiocarcinoma, a rapidly fatal
cancer of the liver’s bile ducts.

The Fasciola flukes infect people who eat watercress and other aquatic
plants that play host to the worms’ larvae. They cause a liver disease (fascioliasis)
involving chronic inflammation of the bile ducts (cholangitis) that may
be complicated by internal bleeding. Mild cases are marked by fever, sweating,
abdominal pain, dizziness and a cough; severe cases by anaemia and malnutrition.
Some cases – just how many is not known – are fatal.

If you think about it, though, it’s surprising that these flukes, which
can live for up to 40 years in a person’s body, churning out between one
and two thousand eggs a day, have never been declared public menaces.