Nobel Prize for Discovery of Ivermectin and Artemisinin – What is the Importance of these Drugs in Tropical Medicine?

Kaushik Bharati, PhD

This year’s Nobel Prize in Physiology or Medicine has been awarded to three distinguished scientists for their work on parasitic diseases. One half of the prize was jointly awarded to William C. Campbell and Satoshi ĹŚmura “for their discoveries concerning a novel therapy against infections caused by roundworm parasites”. The other half of the prize was awarded to Youyou Tu “for her discoveries concerning a novel therapy against malaria” (Nobelprize.org). Professors Campbell and ĹŚmura discovered the drug ivermectin, while Professor Tu discovered the Chinese herbal antimalarial drug artemisinin. 

Ivermectin: An Essential Drug for the Treatment of Parasitic Worm Infestations

Ivermectin is a broad-spectrum antiparasitic drug in the avermectin family. It is administered orally or used topically, depending on the condition to be treated. Importantly, it is included in the WHO's List of Essential Medicines.

Ivermectin is a very important drug for the treatment of Onchocerciasis in Africa. This is a parasitic disease caused by the filarial worm Onchocerca volvulus. The worm is transmitted by the blackfly that breeds in rivers, and the disease causes blindness, for which it is commonly known as ‘river blindness’.

Filariasis is also treated with ivermectin. Filariasis in humans is caused by infection with three species of filarial worms, namely, Wuchereria bancrofti, Brugia malayi and Brugia timori. It is spread by Anopheles, Culex, Aedes and Mansonia spp. mosquitoes. Infection with W. bancrofti is also called bancroftian filariasis, while brugian filarisis refers to infection by the other two species. It should be noted that bancroftian filariasis is much more prevalent than brugian filariasis. The major clinical features of lymphatic filariasis are lymphedema, elephantiasis and hydrocele. Ivermectin is a potent killer of microfilariae and is very effective in many parts of Africa, where onchocerciasis and/or loiasis are co-endemic. Ivermectin is not able to kill macrofilariae. Therefore, the drug has to be administered every six months in order to keep the level of microfilariae in the blood as low as possible.

Ivermectin can also be used for other infestations. Cutaneous larva migrans (CLM) (also known by various other names, such as creeping eruption, sandworm, plumber’s itch and duck hunter’s itch) is a cutaneous eruption resulting from exposure of the skin to the infective filariform larvae of non-human hookworm, usually present in racoons. A single oral dose of 12 mg ivermectin gives cure rates of 81-100%. Strongyloidiasis is caused by Strongyloides sterocoralis and ivermectin is the drug of choice for this disease, while for Lagochilascariasis, it is recommended as a second line of therapy. Ivermectin is also effective against Ascaris, hookworm and scabies infestations.

Advantages of Ivermectin:

• It effectively kills microfilariae.
• It reduces the risk of blindness by 50%.
• The production of microfilariae by the adult female worm is inhibited for at least 6 months.
• A single dose every 6-12 months eliminates microfilariae.
• It is safe for mass distribution to entire communities.
• The drug is easily administered by the oral route.

Contraindications of Ivermectin:

• Children < 5 years.
• During pregnancy.
• Nursing mothers.
• Severely ill patients.

Adverse Reactions to Ivermectin: This is by-and-large a safe drug. However, complications can occur in patients with Loa loa infections. Side-effects of the drug include allergic reactions on the skin and systemic symptoms such as fever, headache, edema, body ache etc. Other side-effects include low blood pressure and asthma attacks, but these are relatively rare.

Artemisinin: The Treatment of Choice for Uncomplicated Plasmodium falciparum Malaria

Artemisinin is used in the treatment of malaria. Malaria is the most important parasitic disease of man. Approximately 5% of the world’s population is infected, and it causes over 1 million deaths each year. Malaria is a protozoal disease that is transmitted by female anopheles mosquitoes. There are four species of the protozoan parasite, belonging to the genus Plasmodium that infect humans. However, almost all deaths and severe disease are caused by P. falciparum.

Artemisinin (also known as Qinghaosu) has been used for centuries in traditional Chinese medicine for reducing fever. Artemisinin is chemically a lactone peroxide extracted from the leaves of the shrub Artemisia annua. It has four derivatives: Artemether, Artemotil (formerly known as Arteether), Artesunate and Dihydroartemisinin (DHA). Artemisinin is 5-10 times less active than its derivatives, which are the most rapidly acting of all known antimalarials. The artemisinin derivatives are safe in children and can be administered rectally in young children suffering from severe malaria, who cannot take the drug orally. These drugs are generally not recommended in the first trimester of pregnancy, but can be used in severe malaria during pregnancy at any gestational age as the benefits far outweigh the risks.

Artemisinin Combination Therapy (ACT) is rapidly effective and generally a reliable treatment modality. ACT is now the treatment of choice for uncomplicated P. falciparum malaria in endemic areas. The artemisinin derivatives induce a rapid resolution of fever and illness, and also improve absorption of the combination partner (mefloquine, lumefantrine). ACT administration over a 3-day course, reduces parasites counts to less than hundred million times than when treatment was started! This reflects the superiority of ACT over other treatments.

Conclusion

This year’s Nobel Prize for discoveries in the area of parasitic diseases gives a boost to the fight against Neglected Tropical Diseases (NTDs). It should be noted that NTDs affect the poorest of the poor, who are marginalized, and have “no voice” in society. This year’s Nobel Prize has given that much needed “voice” for NTDs. It strongly sends out the message that there is a need for effective therapies for diseases that affect the poor, who have “no say” in the policy-making process, and who do not have the means to bear the cost of the drugs. This coveted prize will undoubtedly provide the impetus and encourage many more scientists to focus on this much neglected area of bio-medical research.