Artesunate suppositories

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Artesunate suppositories are used for the treatment of malaria. Artesunate is an antimalarial water-soluble derivative of dihydroartemisinin. Artemisinins are sesquiterpene lactones isolated from Artemisia annua , a Chinese traditional medicine. These suppositories are given rectally due to the risk of death from severe malaria, as described below.

The risk of death from severe malaria is largely dependent on the time lag between the onset of symptoms and treatment. Rapid access and administration of effective treatment is therefore essential. For many patients, readily available oral drugs cannot be taken because of their symptoms (e.g., vomiting, convulsions, coma), and hospitals providing alternative, non-oral treatment are often inaccessible. The drug artesunate, given in rectal suppository form, provides a potential solution to this problem: it can be made available in remote areas and thus can be given at the onset of symptoms.

Artesunate is one of a number of artemisinin derivatives discovered and developed by Chinese scientists and registered in China since the 1980s. Since the 1990s, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) have supported studies to assess the properties of the drug. There were already indications that artesunate, given rectally, was effective in severe malaria. Significant work with artemisinin suppositories in severe malaria was conducted in Viet Nam in the early 1990s, [1] [2] [3] and clinical trials of rectal artesunate followed by mefloquine treatment in moderately severe malaria were conducted in the mid-1990s in Thailand. [4] [5]

A major placebo-controlled clinical trial published in 2009 found that "if patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate rectal suppository at the time of referral substantially reduces the risk of death or permanent disability." [6]

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Malaria Mosquito-borne infectious disease

Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.

A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different orifice: Rectal suppositories into the rectum, vaginal suppositories into the vagina, and urethral suppositories into the urethra of a male.

<i>Artemisia annua</i> species of plant

Artemisia annua, also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood, is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North America.

Artemisinin chemical compound

Artemisinin and its semisynthetic derivatives are a group of drugs used against malaria due to Plasmodium falciparum. It was discovered in 1972 by Tu Youyou, who was co-recipient of the 2015 Nobel Prize in Medicine for her discovery. Treatments containing an artemisinin derivative are now standard treatment worldwide for P. falciparum malaria. Artemisinin is isolated from the plant Artemisia annua, sweet wormwood, a herb employed in Chinese traditional medicine. A precursor compound can be produced using a genetically-engineered yeast, which is much more efficient than using the plant.

Hymenolepiasis is infestation by one of two species of tapeworm: Hymenolepis nana or H. diminuta. Alternative names are dwarf tapeworm infection and rat tapeworm infection. The disease is a type of helminthiasis which is classified as a neglected tropical disease.

Hookworm infection Human disease caused by infection by intestinal parasites of the roundworm group

Hookworm infection is an infection by a type of intestinal parasite known as a hookworm. Initially, itching and a rash may occur at the site of infection. Those only affected by a few worms may show no symptoms. Those infected by many worms may experience abdominal pain, diarrhea, weight loss, and tiredness. The mental and physical development of children may be affected. Anemia may result.

Artemether chemical compound

Artemether is a medication used for the treatment of malaria. The injectable form is specifically used for severe malaria rather than quinine. In adults, it may not be as effective as artesunate. It is given by injection in a muscle. It is also available by mouth in combination with lumefantrine, known as artemether/lumefantrine.

Artesunate chemical compound

Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, by mouth, and by rectum.

Artemether/lumefantrine, sold under the trade name Coartem among others, is a combination of the two medications artemether and lumefantrine. It is used to treat malaria caused by Plasmodium falciparum that is not treatable with chloroquine. It is not typically used to prevent malaria. It is taken by mouth.

Dihydroartemisinin chemical compound

Dihydroartemisinin is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs. It is sold commercially in combination with piperaquine and has been shown to be equivalent to artemether/lumefantrine.

Artelinic acid chemical compound

Artelinic acid is an experimental drug that is being investigated as a treatment for malaria. It is a semi-synthetic derivative of the natural compound artemisinin. Artelinic acid has a lower rate of neurotoxicity than the related artemisinin derivatives arteether and artemether, but is three times more toxic than artesunate. At present, artelinic acid seems unlikely to enter routine clinical use, because it offers no clear benefits over the artemesinins already available. Artelinic acid has not yet been evaluated for use in humans.

History of malaria

The history of malaria stretches from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent, except Antarctica. Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the Plasmodium parasites which cause it, research attention has focused on their biology, as well as that of the mosquitoes which transmit the parasites.

Mass drug administration administration of a medication to at-risk individuals in a population without individual diagnosis.

The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration (MDA).

Intermittent preventive therapy or intermittent preventive treatment (IPT) is a public health intervention aimed at treating and preventing malaria episodes in infants (IPTi), children (IPTc), schoolchildren (IPTsc) and pregnant women (IPTp). The intervention builds on two tested malaria control strategies to clear existing parasites and to prevent new infections (prophylaxis).

Pyronaridine chemical compound

Pyronaridine is an antimalarial drug. It was first made in 1970 and has been in clinical use in China since the 1980s.

Piperaquine chemical compound

Piperaquine is an antiparasitic drug used in combination with dihydroartemisinin to treat malaria. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurually similar antimalarial drug chloroquine. Due to widespread parasite resistance to piperaquine, the drug fell out of use as a monotherapy, and is instead used as a partner drug for artemisinin combination therapy. Piperaquine kills parasites by disrupting the detoxification of host heme.

Project 523 is a code name for a 1967 secret military project of the People's Republic of China to find antimalarial medications. Named after the date the project launched, 23 May, it addressed an important threat in the Vietnam War: malaria, which claimed more lives than the battles themselves did. At the behest of Ho Chi Minh, Prime Minister of North Vietnam, Zhou Enlai, the Premier of the People's Republic of China, convinced Mao Zedong, Chairman of the Communist Party of China, to start the mass project "to keep [the] allies' troops combat-ready", as the meeting minutes put it. More than 500 Chinese scientists were recruited. The project was divided into three streams. The one for investigating traditional Chinese medicine discovered and led to the development of a class of new antimalarial drugs called artemisinins. Launched during and lasting throughout the Cultural Revolution, Project 523 was officially terminated in 1981.

Ospemifene chemical compound

Ospemifene is an oral medication indicated for the treatment of dyspareunia – pain during sexual intercourse – encountered by some women, more often in those who are post-menopausal. Ospemifene is a selective estrogen receptor modulator (SERM) acting similarly to an estrogen on the vaginal epithelium, building vaginal wall thickness which in turn reduces the pain associated with dyspareunia. Dyspareunia is most commonly caused by "vulvar and vaginal atrophy."

Liu Xu was a Chinese pharmaceutical chemist known for the discovery of artesunate, a novel antimalarial drug. The discovery of artesunate solves the problem that artemisinin is nearly insoluble in water. Artesunate can be given by intravenous injection, intramuscular injection, by mouth, and by rectum.

References

  1. Hien et al., Trans R Soc Trop Med Hyg, 1992, 86: 582-583
  2. Vinh et al., Trans R Soc Trop Med Hyg, 1997, 91: 465-457
  3. Ashton et al., Clin Pharmacol Ther, 1998, 63 (4): 482-493
  4. Looareesuwan et al., Ann Trop Med Parasitol, 1995, 89 (5): 469-475
  5. Looareesuwan, Am J Trop Med Hyg, 1997, 57(3): 348-353
  6. Gomes et al., Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet, 2009; 373(9663):557-66