Introduction

This article aims to provide a useful summary of the common antiparasitic drugs that are prescribed as the primary treatment for trichinosis. This article will discuss the effectiveness, dosage regimes, and mechanism of action of these antiparasitic drugs. Additionally, the article will provide insight into other treatment options and possible emerging future therapies. 

Understanding trichinosis

Trichinosis, also referred to as trichinellosis, is a food-borne parasitic disease caused by a roundworm infection. These roundworms often infect animals, including domestic pigs, wild boars, bears, and walruses, rather than humans. However, people can be infected with trichinosis through the consumption of the immature form of the roundworm, known as ‘larvae’ in raw or undercooked food, primarily pork.¹ Following ingestion, the roundworm larvae develop into adult worms in the small intestine. These adult worms reproduce, and the subsequent larvae can travel in the bloodstream to other sites in the body, where the larvae then burrow into muscle tissue.²

The severity of infection is dependent on the number of larvae ingested in contaminated food. In mild infections, when only a small number of larvae are ingested, there could be no signs or symptoms.³ In more severe infections, following ingestion of a larger number of larvae, initial symptoms can include: tiredness (fatigue), diarrhoea, stomach pain, nausea and vomiting.¹ Later in the infection, larvae in muscle tissue can result in symptoms such as fever, aching joints, headaches, swelling of eyelids, muscle pains, and itchy skin.¹

Most mild cases will resolve without the need for treatment, and mild infections are often misdiagnosed as other conditions, such as influenza.²  Cases following ingestion of larger numbers of larvae result in more severe and apparent symptoms; therefore, treatment will be required. In these cases, health professionals will typically prescribe anti-inflammatory drugs to manage inflammation alongside antiparasitic drugs used as first-line treatment to manage a trichinosis infection.² Antiparasitic drugs work best when administered early because they kill both adult worms before they lay eggs and early larvae prior to embedding in muscle.² 

Overview of antiparasitic drugs in treating trichinosis

The antiparasitic drugs used to treat trichinosis are sometimes referred to as ‘antihelminthic’ or ‘anthelmintic’ drugs because they target ‘helminths’, another term for parasitic worms. The antihelminthic drugs used to treat trichinosis target worms in the small intestine and have a therapeutic effect against early migrating larvae in muscles. However, these drugs often lack efficacy against larvae encapsulated in muscle as cysts; therefore, early treatment (before cyst development) is desirable.² If treatment does commence late after infection, once cysts have become established in muscle tissue, treatment may not successfully eliminate the infection and associated symptoms.¹⁰ For severe infections, hospitalisation is compulsory and will include treatment regimes with antiparasitic drugs, pain killers, steroids, and treatment for fluid and electrolyte deficits. For milder, benign or asymptomatic infections, treatment is with antihelminthic drugs and possible use of nonsteroidal anti-inflammatory drugs to manage inflammation.⁵

Common antiparasitic drugs used for trichinosis

Antiparasitic drugs used to treat trichinosis are often derivatives of the compound ‘benzimidazole’, including albendazole, fenbendazole, and mebendazole.² The method of action of benzimidazole derivatives is to block the function of parasite microtubules. Microtubules are important for many cell functions, including motility (movement), cell division, and transport in the cell. These antiparasitic drugs prevent the absorption of glucose (sugar) by the parasite; the following lack of glucose leads to energy depletion, resulting in parasite immobilisation and eventual death.^4,8

Albendazole

Albendazole, often sold as ‘Albenza’, was first highlighted to be an effective drug for treating trichinosis in 1978, when treatment with the drug successfully reduced the number of muscle larvae by 67%.⁹ The recommended dose of albendazole is 800mg (15 mg/kg of body weight) daily for 8–15 days. This regimen is suitable for use in adults and children, although evidence suggests albendazole should not be used in children under 2 or during pregnancy.¹⁰ One problem is that albendazole is poorly absorbed through the intestinal tract. To combat this and increase the availability of the drug in the intestine to improve therapeutic efficiency, trials have looked at co-administering albendazole and the drug methimazole to increase drug solubility.⁴ Overall, albendazole at a dose of 800mg daily for 8-15 days alongside methimazole, to increase drug absorption, is an effective treatment for trichinosis.⁴ An advantage of using albendazole over mebendazole is that most patients do not require further monitoring, is not always the case with Mebendazole alone.⁵

Mebendazole

Mebendazole, often sold under the name ‘Emverm’ or ‘Vermox’, is used as an antihelminthic drug. The dosage of mebendazole to treat trichinosis is set at either 5 mg/kg daily for 10–15 days or 200–400 mg 3 times a day for 3 days, followed by 400–500 mg 3 times a day for a further 10 days.⁴ This treatment regimen is suitable for adults and children; however, evidence suggests that mebendazole should not be used in children under 2 or during pregnancy.⁵ Mebendazole was more efficient at killing muscle larvae than albendazole in mice; however, in humans, the effect of mebendazole is limited to killing newborn larvae in lymph nodes and blood vessels, and is ineffective at killing encapsulating larvae in muscle cells.^4,7

Pyrantel

Pyrantel or Combantrin is administered at a dose of 10-20 mg/kg for 2-3 days. Pyrantel is advantageous because it can be used in pregnant women and children; however, it is only effective at targeting adult worms in the gut. Therefore, treatment must commence early following infection to be effective.⁵ 

Steroids (used for symptom management)

While not antiparasitic drugs, steroids could be prescribed in severe cases of trichinosis in combination with antihelminthic drugs to manage inflammation. Steroids that could be prescribed include glucocorticosteroids, such as prednisolone, which is administered at a dose of 30 to 60 mg/day for 10-15 days.⁵

Effectiveness of antiparasitic drugs

Effectiveness depends on the time of administration 

While antiparasitic drugs are effective at killing the parasitic worms responsible for trichinosis in the gut and can successfully target early, mitigating larval stages, many of these drugs are unable to effectively target larvae embedded in muscle tissue. Hence, many antiparasitic treatments are only effective when administered at early stages of the infection; therefore, drug effectiveness is strongly dependent on the time that therapy is administered. If treatment occurs later, there is a higher chance that larvae are present in muscle cells as cysts, which can survive for years despite treatment.⁵ Furthermore, when treatment is prescribed at later stages of the infection, prolonged or repeated courses of treatment could be required.¹⁰

Problem of drug resistance

Concerningly, there have been reports of emerging resistance to albendazole and mebendazole, with treatment failure reported for some parasitic infections such as hookworm infections. Large-scale use and failure to alternate treatment with other drug classes have led to a rise in resistant parasite populations, which can survive treatment with previously effective drugs.⁴ 

Emerging future treatments

The resistance in some parasitic worms has generated a growing interest in developing new antihelminthic drugs. A promising drug candidate is from the plant genus, particularly the species A. vulgaris’, this plant is effective at treating some parasitic infections and has shown promise as an alternative drug for trichinellosis.⁶

Side effects and considerations

The recommended anti-parasitic drugs for treating trichinosis, albendazole and mebendazole, are both considered relatively safe. However, there are some possible side effects to be aware of, including bone marrow suppression.¹⁰ Therefore, it is important that patients taking longer courses of treatment undergo monitoring using blood tests to detect any adverse effects. Neither albendazole nor mebendazole is suitable for use during pregnancy or in children under 2 years old. A single oral dose of albendazole can be used for lactating individuals, while mebendazole is suitable for use in lactating individuals.¹⁰ 

Common side effects of albendazole include headaches and elevated liver enzymes, and a small percentage of patients experience an allergic reaction.⁸ Rare, serious side effects can include anaemia and leukopenia (a reduction in white blood cells). Individuals with pre-existing liver damage are at greater risk of developing these conditions following albendazole use.⁸ Monitoring for longer treatment plans includes liver function tests and complete blood counts. Common side effects of mebendazole include stomach pain, bloating, and diarrhoea, while rarer, serious side effects include liver problems or allergic reactions.¹¹ Parasite death following treatment can result in inflammatory symptoms that could be managed with steroids.⁸ 

Summary 

The main, first-line treatments prescribed for trichinosis are the antihelminthic drugs albendazole and mebendazole. The benzimidazole-derived drugs act to kill roundworm parasites by blocking the function of the parasite microtubules, which are essential for parasite survival. Additionally, they prevent glucose use by the parasite, which leads to parasite death. Antiparasitic drugs are very effective at targeting adult worms in the small intestine and migrating larvae. However, these drugs lack efficacy in targeting larvae embedded in tissue as cysts. Therefore, treatment of trichinosis must occur quickly following infection to minimise the risk of lasting complications. If treatment commences after cysts are established, treatment with antiparasitic drugs may not be able to fully eliminate the infection and subsequent symptoms. Growing resistance to current antihelminthic drugs in some parasite populations has led to growing interest in developing new treatments, and A.vulgaris could be a promising candidate.