17th June 2024

Parasitic worm infections

Trematode infections

Trematodes, also known as flatworms or flukes, are parasitic worms that can cause human disease.

Blood flukes – Schistosomiasis

Schistosomiasis is a condition caused by trematodes of the genus Schistosoma. Various species are widely distributed across the tropics. Infection is caused by the larval stage cercariae penetrating the skin in freshwater. This can cause a pruritic rash known as “swimmer’s itch”, though this is less likely to occur with repeated infection. Likewise, the acute inflammatory reaction associated with initial egg production several weeks after larval entry is more likely in immune-naïve patients. Signs and symptoms of this inflammatory reaction, known as Katayama fever, include fever, rash, wheeze, and hepatosplenomegaly. Eosinophilia can be noted on a full blood count. The release of eggs from the body causes the main chronic symptoms. Schistosoma haematobium resides in the pelvic veins and causes urogenital schistosomiasis, with haematuria often being present. Chronic S. haematobium infection can lead to reproductive tract pathology, obstructive uropathy, and squamous cell bladder cancer. Other species of Schistosoma, including Schistosoma mansoni and Schistosoma japonicum, reside in the mesenteric veins. Egg passage through the bowel can cause small amounts of blood loss and anaemia over time. Portal hypertension can result from eggs and associated inflammatory responses within the portal veins. This, in turn, can lead to hepatosplenomegaly and oesophageal varices. Diagnosis may involve microscopic visualisation of eggs in urine or stool, though this can lack sensitivity. Stool and urine PCR can improve sensitivity, and rapid antigen detection point of care tests for urine samples are also available. Serology can be useful for returned travellers but is less useful for patients in endemic areas. Praziquantel is used to treat all species causing schistosomiasis.

Lung Flukes

Ingestion of freshwater crustaceans can lead to infection with the lung fluke genus Paragonimus. Paragonimus westermani is the main species to know about, being largely responsible for paragonimiasis in Asia. The disease is more rarely documented in Central Africa and South America. The immature flukes excyst through the duodenum and reach the lung via the peritoneum. This may cause a pneumothorax. The mature flukes then release eggs in the lung, which are coughed up and either released through the mouth or swallowed and released after passing through the digestive tract. Symptoms include initial abdominal pain followed by fever, wheeze, cough, and haemoptysis. Diagnosis is made either serologically or by identification of eggs in sputum or stool. Treatment is with praziquantel.

Liver Flukes

The main causative fluke for fascioliasis is Fasciola hepatica, which is found on every populated continent. Infection is via ingestion of contaminated freshwater plants. In a similar fashion to Paragonimus, immature Fasciola flukes excyst through the duodenum, though eventually invade the biliary ducts via the peritoneum. Similar symptoms are present during this stage, such as fever and abdominal pain. The infection may then be asymptomatic, aside from occasional pain from intermittent biliary obstruction. Pancreatitis and cholecystitis can also occur. Serology and stool culture can be useful in diagnosis. CT imaging can show hypodense liver lesions. Similarly, ultrasound can highlight hypoechoic liver lesions. Praziquantel – usually a safe bet for trematode treatment – is not effective for fascioliasis; triclabendazole is used instead.

Trematodes of the genus Clonorchis and Opisthorchis cause a similar clinical presentation to fascioliasis. Encysted larvae are introduced through the ingestion of freshwater fish. Infection occurs in Asia only, except in the case of rare international imports. Larvae enter the biliary tract through the ampulla of vater rather than through the peritoneum and inhabit smaller bile ducts than Fasciola. Chronic infection can lead to the development of cholangiocarcinoma. Praziquantel is the treatment of choice.

Nematode infections – Filarial disease

There are several important types of filarial disease. All are caused by nematode worms and are transmitted by diverse insect vectors.

Onchocerciasis

Onchocerca volvulus is the causative nematode in onchocerciasis, or “river blindness”. It is a major cause of preventable blindness across Central Africa. There is also some endemicity across Central and South America. Simulium blackflies allow passage of the larval stage into the subcutaneous tissue, where adult female worms mature over a period of around one year, before producing microfilariae for up to 15 years if left untreated. Dying microfilariae cause the signs and symptoms of onchocerciasis, which include depigmented skin lesions and gradual loss of sight as microfilariae die within various parts of the eye. Diagnosis can be made by microscopy and direct visualisation of microfilariae, with PCR being used on the sample if visualisation is not possible. Microfilariae can also be observed on slit lamp examination of the eye. Diethylcarbamazine (DEC) causes rapid death of microfilariae and can lead to the Mazzotti reaction, a life-threatening immunological reaction characterised by fever, hypotension, urticaria, and lymphadenopathy. This phenomenon can be exploited for diagnostic purposes, using small patches to invoke a localised immune response. Ivermectin is microfilaricidal, however is less likely to cause the Mazzotti reaction as its mechanism of action is slower. Wolbachia is an endosymbiotic bacterium found within all the filarial species we will discuss, except for Loa loa. It is, therefore, a useful target in treating adult worms. Doxycycline causes Wolbachia death and is therefore useful as an agent against adult worms (macrofilaricidal).

Loiasis

Loiasis, caused by Loa loa, is transmitted by the Chrysops fly, which resides in the rainforests of West and Central Africa. As in onchocerciasis, adult female worms develop in the subcutaneous tissue and begin to produce microfilariae after several months. Again, the adult worms may be viable for over a decade. Microfilariae are found in various bodily fluids. As the Chrysops fly is a day biter, evolution has dictated that the microfilariae are most likely to be found in the blood during this time in order to complete the lifecycle. Migration of the adult worm causes most signs and symptoms. It can be visible in the patient’s eye at times, usually causing transient local inflammation without permanent damage to sight. Calabar swellings are skin swellings associated with adult worm migration through the subcutaneous tissue. Diagnosis can be clinical, or microfilariae can be found on blood films taken from the patient during the daytime. DEC kills both adult worms and microfilariae but must be used with caution in areas where onchocerciasis is endemic. Ivermectin treatment prior to DEC administration will reduce the chance of the Mazzotti reaction on patients with both diseases. Unfortunately, treatment with both agents can precipitate encephalopathy due to rapid microfilarial death. If microfilarial load is high in blood samples, then prior treatment with albendazole (which limits the production of viable microfilaria) and concurrent use of steroids may reduce the likelihood of treatment-related encephalopathy. As there is no Wolbachia endosymbiosis, doxycycline is not effective.

Lymphatic filariasis

Lymphatic filariasis, often caused by Wuchereria bancrofti, is prevalent across much of the tropics and subtropics. The infective process is similar to other filarial disease, with mosquitos acting as the vectors. However, the adult worms reside within the lymphatics rather than subcutaneous tissue. Microfilarial death within the pulmonary capillaries may cause a syndrome called tropical pulmonary eosinophilia, characterised by an asthma-like clinical picture, with low-grade fever and eosinophilia. Chest X rays may be normal or demonstrate a reticulonodular or miliary appearance. Chronic lymphatic filariasis is associated with lymphoedema due to lymphatic obstruction, causing disfiguring leg and scrotal swelling. A blood film obtained during the night has the best chance of identifying microfilaria. Ultrasound may show adult worms. Serological tests are also available. Ideally, lymphatic filariasis is treated with DEC. However, this may precipitate the Mazzotti reaction or encephalopathy if there is concurrent infection with Onchocerca volvulus or Loa loa, respectively. Albendazole and ivermectin combination therapy may also be used. Doxycycline can be useful as there is Wolbachia endosymbiosis. Mass drug administration in areas of high helminth endemicity is a viable public health intervention, though the complex overlap of filarial diseases in certain regions and reactions to specific treatments makes this challenging.

Other nematode infections

Strongyloidiasis

Strongyloides stercoralis is a nematode parasite of the small intestine. Although more common in warmer climates, it has a worldwide distribution. Infection is caused by penetration of the larvae through open skin. They then migrate via the bloodstream and lymphatics to the lungs before subsequently being coughed up and swallowed. The mature female produces eggs from the intestine, with the resultant larvae capable of causing autoinfection by penetrating the intestine or perianal skin. The autoinfection stage of strongyloidiasis can cause an itchy, rapidly spreading but transient skin eruption called larva currens. Symptoms can also include cough and abdominal pain, however strongyloidiasis can often be asymptomatic over a period of years. The main worry is the potential for life-threatening strongyloidiasis hyperinfection if a patient becomes immunocompromised. Diagnosis can be made by stool microscopy or serology. Treatment is with standard anti-helminth drugs such as ivermectin or albendazole.

Cystic helminth disease and key differentials

Hydatid disease

Cystic echinococcosis, or hydatid disease, is caused by ingestion of the eggs of Echinococcus granulosus, a cestode (tapeworm). This can lead to cystic disease of a variety of organs, mainly the liver and lungs. Hydatid cysts can be asymptomatic for years and detected on incidental imaging. Right upper quadrant pain may occur due to cyst growth. Rupture of lung cysts may cause pulmonary manifestations such as a pneumothorax. A variety of stages can be observed using different imaging modalities, with a WHO classification system existing for ultrasound diagnosis. The water lily sign is caused by the detachment of the endocyst membrane, which then floats within the cystic fluid. Serology can also be used to help with the diagnosis. Due to the slow growth of cysts caused by E. granulosus, a watchful waiting approach can be taken to see if the cyst growth has ceased. Active treatment strategies may involve chemotherapy with albendazole, with or without more invasive management. PAIR – Puncture, Aspiration, Injection (of a scolicidal agent such as hypertonic saline), Reaspiration – is a radiologically-guided technique that can be used to avoid formal surgery. Surgery can then be reserved for more complicated cases or calcified cysts. Alveolar echinococcosis is a rarer disease caused by E. multilocularis, which involves rapid destruction and invasion of tissue, requiring more complex management.

It is important to be able to differentiate hydatid liver cysts from amoebic liver abscesses caused by the protozoa Entamoeba histolytica. Occurring worldwide, there is a strong association between poor sanitation and hygiene and amoebiasis. Amoebiasis is generally a self-limiting gastrointestinal infection, causing abdominal pain and loose stools with blood or mucus. The most common extra-intestinal manifestation is amoebic liver abscess. Abscesses are usually isolated in nature, though multiple can be present. Right upper quadrant pain and fever are the predominant symptoms. In terms of diagnosis, stool microscopy is not brilliant as it is difficult to differentiate E. histolytica from E. dispar, a non-pathogenic species. Stool antigen tests may be of use. Serology is often preferred, though it can give a false negative in early disease and a false positive if the patient has been previously infected. Amoebic liver cysts are similar in appearance to pyogenic liver cysts on imaging. Medical therapy with metronidazole is usually first line for amoebiasis and amoebic liver cysts. Aspiration and drainage are reserved for special circumstances. These include diagnostic uncertainty, failure of medical therapy, clinical or radiological evidence of impending rupture, and left-sided liver cysts (which may rupture into the pericardium). Fluid obtained from amoebic liver cysts is normally thick and brown, as opposed to the thin, clear fluid found in hydatid cysts.

Neurocysticercosis

Another tapeworm cyst to be aware of is that of Taenia solium. Once again acquired via the faecal-oral route, cysticercosis is a result of larval migration to tissues and organs including muscles and the brain, with the latter termed neurocysticercosis. Consumption of infected meat simply leads to intestinal tapeworm infection. Neurocysticercosis is a leading cause of seizures in the tropics and East Asia. As this is a pig tapeworm, cases are rarer in areas where pigs are not reared for religious reasons. Diagnosis of neurocysticercosis is usually based on imaging and clinical history. Treatment includes anti-epileptics and, if anti-helminth medication is to be used, steroids can prove useful in preventing morbidity and mortality from the ensuing inflammatory response.

References

• WHO Schisotosomiasis factsheet [Internet]. WHO.int [cited April 2022]. Available from: https://www.who.int/news-room/fact-sheets/detail/schistosomiasis
• Squire B, Stothard R. Schistosomiasis. In: Beeching N, Gill G, ed. by. Tropical Medicine Lecture Notes. 7th ed. West Sussex: Wiley Blackwell; 2014. p. 151-162
• Blair D. Paragonomiasis. In: Toledo R, Fried B, ed. by. Digenetic Trematodes. Advances in Experimental Medicine and Biology. Vol 766. New York: Springer; 2014. https://doi.org/10.1007/978-1-4939-0915-5_5
• CDC paragonimiasis factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/parasites/paragonimus/index.html
• CDC fascioliasis factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/parasites/fasciola/index.html
• Dusak A, Onur M, Cicek M et al. Radiological Imaging Features of Fasciola hepatica Infection – A Pictorial Review. J Clin Imaging Sci. 2012;2:2. doi:10.4103/2156-7514.92372
• CDC Clonorchis factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/parasites/clonorchis/index.html
• CDC Opisthorchis factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/parasites/opisthorchis/index.html
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• Mullerpattan J, Udwadia Z, Udwadia F. Tropical pulmonary eosinophilia–a review. Indian J Med Res. 2013;138(3):295-302
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