Paragonimiasis

Synonyms include: Oriental lung fluke, Endemic/Parasitic/Manson haemoptysis, Lung Distoma, Pulmonary distomiasis or distomatosis.

The infesting organism is of the phylum Platyhelminthes (flatworms), class Trematodea (flukes), sub class Digenea. There are 10 species of the Paragonimus genus that cause human Paragonimiasis but only 8 are significant. The most common cause is the Oriental lung fluke, Paragonimus westermani.

• Paragonimus westermani is prevalent in the Far East, being endemic in Japan, Taiwan, central China, Philippines, and Korea, and found in Malaysia, Indonesia, Thailand, and India, amongst other countries.
• Other species cause infections in Asia and the Pacific, Africa, Canada, Central and South America.
• Prevalence of infection in endemic areas can vary as from about 1 in 1,000 to 1 in 4.
• Prevalence is higher in females. It rises in childhood to reach a peak in late adolescence and then falls to about 25% of that level by the 6th decade.

• Like Fascioliasis, the intermediate host is a snail. Eggs mature in 2-3 weeks into miracidia which penetrate the snail host. 2-3 months later free-swimming cercariae are released.
• Then it develops through a second intermediate host, crayfish or crabs, which are penetrated by the cercariae, or infected by eating the snails.
• Encysted metacercariae within the crabs or crayfish are consumed by carnivores: dog, cat, wildcat, tiger, leopard, panther, wolf, fox, mink, otter, mongoose, rat, pig, monkeys, and other mammals, including man.
• The metacercariae are released from the cysts in the small intestine, pass through and migrate to the pleural cavity, appearing there after about 14 days.
• After another 2 weeks, young worms enter the lung, maturing over several weeks in parasitic cysts.
• Large quantities of eggs are released into bronchial secretions and an individual may cough up or pass up to 13,000 a day.
• Adult worms usually die within 6 years, but can live for 20 years in humans.

Raw or poorly cooked crustaceans are popular in some societies:

• "Drunken crab" in China is strips of raw crab meat soaked in rice wine
• Raw crab or crayfish in alcohol is a favourite in the Philippines and other countries. The wine kills the crabs but the metacercariae survive for several hours
• "Gye muchim" in Korea is seasoned raw crab
• Sushi crab, "ama ebi" (raw prawn), and "odori - dancing prawns" are popular in Japan

Spitting has long been a habit in many Asian countries, and one which may slowly change with the introduction of fines and "beatings" in the light of SARS and fears of avian influenza.

Acute phase

• Light infection produces no symptoms. About 20% of those who are infected are asymptomatic.
• During the acute phase of invasion and migration of immature flukes, there may be abdominal pain, diarrhoea, and urticaria.
• This may be followed by fever, cough, dyspnoea, chest pain, malaise, and sweats.
• The acute phase lasts several weeks.

Chronic phase

• Predominantly symptoms of a chronic bronchitis or bronchiectasis.
• Dry cough followed by production of tenacious and rusty or golden sputum.¹
• Pulmonary symptoms begin about 6 months after infection and resemble tuberculosis.
• Common symptoms include vague chest discomfort, dyspnoea on exertion, or wheezing.
• Life-threatening haemoptysis may sometimes occur.
• Extra-pulmonary paragonimiasis can occur when wandering parasites or eggs lodge in other organs:
  • Liver
  • Spleen
  • Kidney
  • Brain
  • Intestinal wall
  • Peritoneum
  • Mesenteric lymph nodes
  • Muscle
  • Testis/ovary
  • Subcutaneous tissues
  • Spinal cord

Cerebral paragonimiasis affects less than 1% of patients but is more common in children. Early symptoms resemble meningoencephalitis and may persist a month or two. Chronic phase symptoms include headache, vomiting, or weakness, and resembles cystercercosis, with epilepsy being a frequent manifestation.

Eggs and worms may also cause cysts, abscesses, or granulomas. Cysts may occur in the intestinal wall, liver, spleen, abdominal wall, peritoneal cavity, or mesenteric lymph nodes. Symptoms may include bloody diarrhoea or abdominal pain. Rarely localisation in the skin and subcutaneous tissues produces abscesses

Signs

• Physical findings in pulmonary paragonimiasis tend to be few.
• Clubbing of the fingers sometimes occurs.
• Pneumonia or pleural effusion may produce signs.
• Cerebral paragonimiasis can cause facial palsy, hemiplegia, and paraplegia.
• Ocular disease can impair visual acuity because of optic atrophy, papilloedema, and hemianopia.
• Spinal involvement may produce monoplegia, paraplegia, paraesthesia, or sensory loss.
• Abdominal involvement may cause a palpable mass.
• Haematuria may accompany renal involvement and eggs are sometimes detected in the urine.
• Subcutaneous paragonimiasis can present with migratory swelling or subcutaneous nodules containing immature flukes. These firm, mobile, and tender subcutaneous nodules are often found in the lower abdominal and inguinal region.
• Scrotal paragonimiasis may resemble epididymitis or an obstructed hernia.

• Amoebiasis
• Ancylostoma (hookworm)
• Cystercercosis (tapeworm)
• Causes of bronchiectasis, pneumonia and abscesses
• Meningitis
• Tuberculosis
• Whipworm

Pulmonary paragonimiasis may readily be mistaken for tuberculosis and in those who have been in an endemic area, it should be considered if there is not a firm diagnosis of tuberculosis and there is failure to respond to anti-tuberculous treatment.

Egg detection and antibody tests are standard, the latter being preferred due to low rates of egg detection.

Egg detection

• Sputum, faeces,² pleural fluid, CSF, or pus are examined for worms or eggs.
• Worms or eggs may be found in biopsies from lung, brain, subcutaneous or abdominal nodules or cysts. The specific species can be identified from adult or immature flukes found in surgical specimens but rarely from the sputum.
• Egg detection rates are around 25 to 35% for a single sputum specimen but may reach 50% with multiple examinations. As many as 7 samples have been recommended.
• Stool examination is best for diagnosis in children as they tend to swallow sputum.

Blood tests

• The complement fixation test is sensitive and can be used after therapy because antibody levels fall 6 to 12 months after effective treatment.
• ELISA has 92% sensitivity and is specific but antibody levels may take up to 2 years to return to normal after successful treatment. Low-level positive results may occur with other trematode infections.
• An immunoblot test is 96% sensitive and 99% specific but it cannot differentiate between active and past infection.

Imaging

• CXR is abnormal in 80 to 90% of patients. These may include ring shadows, fibrosis, nodules or linear infiltrates with calcified foci, loculated pleural effusions, and pleural thickening.
• CT or MRI of the head may show cerebral calcification, cystic lesions, or hydrocephalus.³

Other tests

• Intradermal skin testing is very sensitive but results may stay positive for 20 years after cure.
• Skin testing is a useful epidemiological tool.
• Lumbar puncture: Infected CSF is bloody or turbid, containing numerous eosinophils.
• Pleural aspiration: Infected pleural fluid usually is serosanguineous and with over 1000 red cells, eosinophilia⁴ and a low glucose level.
• Lung biopsy specimens usually reveal adult worms or eggs.

Non-drug

Intensive care may be required for convulsions or coma.

Drugs

• Praziquantel is better tolerated than bithionel. It can be used in pregnancy but must not be used to treat ocular disease as this can result in permanent damage to the eyes.
• Triclabendazole has long been use for veterinary purposes but it may well be very effective and well tolerated in humans.⁵
• In cerebral disease, seizures and coma can follow an inflammatory reaction that accompanies worm death. Steroids may reduce this reaction.
• Adverse effects of the drug include abdominal pain, diarrhoea, malaise, dizziness, and headache and less often fever, nausea, rash, and pruritus.
• Epilepsy may need management.

Surgical

• Extra-pulmonary lesions should be excised.
• A shunt may be needed if there is hydrocephalus.

• Untreated heavy infection can cause interstitial pneumonia, bronchitis, and bronchiectasis.
• Later complications can include bronchopneumonia, lung abscess, pleural effusion, or empyema.
• Cerebral complications include seizures and coma.

• The acute phase of infection can be fatal. For survivors, recovery takes 1 to 2 months but symptoms may recur intermittently over several years.
• Untreated cerebral paragonimiasis has a mortality rate of 5%.
• Symptoms resolve rapidly and eggs disappear from the sputum in a few weeks following treatment. A good cure can be obtained in 90 to 100% of patients.
• Untreated pulmonary disease may be self-limited, with lesions resolving in 5 to 10 years in light infections.
• Abnormalities on CXR may take several months to resolve, depending on the duration of the disease.
• Cerebral infections may produce long-term epilepsy.

• In endemic areas, shellfish must be well cooked (heating in water to 55ºC for 5 minutes will kill the metacercariae).
• Freezing at -20ºC for 7 days, or at -35ºC for 15 hours kills parasites in fish/seafood intended for raw consumption - ensuring that the restaurant obtains food from suppliers following such codes of practice will allow one to enjoy such raw foods.
• Social/legal measures to abolish spitting
• As with other parasitic diseases molluscicides may be used

• Most of the discoveries regarding the important human disease flukes were made in the period 1874 to 1918, by zoologists studying animal diseases.
• Like Gnathostoma, Paragonimus was first identified in Bengal tigers in a European zoo.
• Paragonimus westermani is actually named in 1877 by Kerbert (Director of the Netherlands Royal Zoological Society), after the keeper of the Amsterdam zoo.
• Sidney Ringer (the British physiologist of "Ringer's solution" and "Ringer's lactate" fame), was the first to identify the parasite in a human lung in 1879 at post-mortem.
• The Scot, Sir Patrick Manson, who was one of the founders of the London School of Tropical Medicine, and is regarded as the founder of that discipline, described the aetiology of paragonimiasis in 1880 in his study into benign haemoptysis in China, naming it Distoma ringeri in Ringer's honour, the name being later changed to Paragonimus ringeri. Manson is also best remembered for being the first to show that mosquitoes can be host to a developing parasite (Filaria bancrofti), that is the cause of human disease (Filariasis), and was author to the mosquito malaria hypothesis.
• In 1889 Rudolf Leukart (zoologist and founding father of the science of parasitology) demonstrated that the fluke Paragonimus westermani, found in the tiger by Kerbert in 1877, was identical to that responsible for endemic haemoptysis in Formosa and Japan.
• It was left to a host of Japanese workers to describe the whole life cycle in the snail Semisulcospira from 1916 to 1922.