INTRODUCTION:

Malaria is the most important parasite of humans, affecting more than 2 billion people and causing hundreds of millions of clinical cases of malaria every year. Five species of the malaria parasite cause disease in humans, namely, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi. Of these species, P. falciparum causes the most severe disease and is the leading cause of death in children under the age of 5 years in Africa.

The discovery in the 1940s that the synthetic drug chloroquine (CQ) could effectively treat individuals safely and cheaply helped spur malaria eradication efforts in the 1950s. However, the emergence of CQ resistance diminished its therapeutic efficacy and doomed initial efforts to eradicate the disease.¹

What is Malaria?

Plasmodium, which causes malaria, is a mosquito-borne disease that is spread through the bite of an infected female anophele's mosquito. The word "malaria" is an Italian word that means "poor air." The disease malaria is well-known among humans. The Plasmodium parasite is spread from person to person by female anophele's mosquitoes. Two hosts: mosquito (sexual) and human other organisms (asexual). The symptoms include chills, fever, sweat, exhaustion, splenomegaly and anemia. Malaria is both an acute and chronic condition. Humans and other animals can contract the infectious disease malaria, which is spread by mosquitoes. Frequent signs of malaria include fever, exhaustion, nausea, and headaches.²If the individual does. not continue to be exposed to malaria, this partial over the course of months to years. Plasmodium group single-celled microbes are the primary cause of malaria. It only spreads by mosquito bites from infected Anopheles species.^3,4

Types of Malaria:

There are five types of Malaria:

· Plasmodium falciparum (P. faliparum) The most serious form of the disease.

It is most common in Africa, especially sub-Saharan Africa. Current data indicates that cases are now being reported in areas of the world where this type was thought to have been eradicated.

· Plasmodium vivax (P. vivax) Milder form of the disease, generally not fatal.

However, infected animal still need treatment because their untreated progress can also cause a host of health problems. This type has the widest geographic distribution globally. About 60% of infections in India are due to P. vivax. This parasite has a liver stage and can remain in the body for years without causing sickness. If the patient is not treated, the liver stage may re-activate and cause relapses malaria attacks after months, or even years without symptoms.

· Plasmodium malariae (P. malariae) - Milder form of the disease, generally not fatal. However, the infected animal still needs treatment because no treatment can also lead to a host of health problems. This type of parasite has been known to stay in the blood of some people for several decades.

· Plasmodium ovale (P. ovale) milder form of the disease, generally not fatal However, the infected human still needs to be treated because it may progress and cause a host of health problems. This parasite has a liver stage and can remain in the body for years without causing sickness. If the patient is not treated, the liver stage may re-activate and cause relapses malaria attacks after months, or even years without symptoms.

· Plasmodium knowlesi (P. knowlesi) causes malaria in macaques but can also infect humans.⁵

Etiology:

Malaria is caused by the bite of an infected female Anopheles mosquito that introduces the sporozoites of the following:

It can also be caused by blood transfusion in rare cases.

· Plasmodium falciparum

· Plasmodium vivax

· Plasmodium malariae

· Plasmodium ovale⁶

Pathogenesis:

When a person is bitten by an infected female Anopheles mosquito, sporozoites of the Plasmodium species, which cause malaria, are released into the bloodstream. In the following 7-10 days, the sporozoites multiply asexually in the liver. 8 No symptoms are present at this time. The parasites, which have changed into merozoites, release from the liver cells in vesicles and go through the digestive tract to the lungs capillaries. The merozoites are finally released from the vesicles and enter the bloodstream. The erythrocytes they penetrate, where they grow. More erythrocytes are invaded by the parasites when the cells burst. The onset of clinical symptoms, such as fever, coincides with the rupture of infected. erythrocytes and the subsequent release of parasite and erythrocyte debris, such as malarial pigment (hemozoin) and glycophosphatidylinositol, the purported "malaria toxin, as well as the malarial pigment (hemozoin),^7,8 In some infected blood cells, the merozoites develop into sexual forms (gametocytes), which circulate in the bloodstream and are swallowed during mosquito bites, as opposed to reproducing asexually. In the mosquito, the ingested gametocytes mature into adult sex cells (gametes), which then transform into ookinetes, which actively borrow through the mosquito's midgut wall to create oocysts, during which hundreds of active sporozoites develop. The oocyst. eventually bursts, releasing sporozoites that visit the salivary glands of the mosquito. The cycle of human infection begins again when the mosquito bites another person.⁹

First, parasitized red blood cells (PRBCs) adhere to receptors expressed by brain microvascular endothelial cells, such as intercellular adhesion molecule 1 (ICAM1), through surface expression of Plasmodium falciparum erythrocyte membrane protein 1 (EMP1). When merozoites are released from PRBCs-4 hours later, parasite glycosylphosphatidylinositol (GPI), which is either released into the blood or present in parasite membranes, functions as a pathogen-associated molecular pattern and toxin, thereby inducing an inflammatory response A local acute-phase response then occurs, which involves activation of the endothelium and local production of cytokines and chemokines and this results in upregulation of expression of cell- adhesion molecules by endothelial cells Within the next 24hours, this cycle is perpetuated and exacerbated, owing to increasing parasite numbers and further binding of PRBCs to endothelial cells that have upregulated expression of cell- adhesion molecules. GPI can also function as a ligand for CDId-restricted natural killer T (NKT) cells, leading to their activation. Activated NKT cells can regulate the differentiation of CD4 T cells into T helper 1 (T1) or Tg2 cells, depending on which natural-killer-complex loci are expressed, so activation and involvement of CD4 T cells occurs.

In addition, chemokines recruit monocytes and activate neutrophils (although neutrophils are not known to infiltrate brain microvessels in humans or mice with cerebral malaria). Recruited monocytes can then differentiate into macrophages and become arrested in brain microvessels. Macrophages can also be activated by GPI, a process that is amplified by interferon-. Local activated macrophages produce more chemokines, which are released systemically, thereby amplifying infiltration of cells, sequestration of PRBCs and release of microparticles (which are probably of endothelial-cell origin). After several more cycles, T cells and CDS T cells might become involved, releasing more chemokines and cytokines both systemically and locally and possibly inducing perforin-mediated lesions in the endothelium. Together with locally arrested macrophages, platelets are sequestered and participate in altering endothelial-cell functions. More microparticles of platelet, endothelial- cell and monocyte origin are released, which leads to the dissemination of pro- inflammatory and pro-coagulant effects. Finally, damage to the endothelium, with possible perivascular haemorrhage, axonal injury, and neurotransmitter and metabolic changes, can ensue. The overall disease spectrum in humans might depend on whether all of these processes occur or only some of them.¹⁰

Epidemiology:

Susceptible species: About 65 Plasmodium sp. have been isolated from over 1,000 different species of birds. Few of the Plasmodium sp. which has been identified appears to be natural parasites of domestic poultry. A number of other species of Plasmodia that occur primarily in passerine birds can infect or have been experimentally transmitted to the domestic fowl.

Susceptible host:

Plasmodium can be pathogenic to penguins, domestic poultry, ducks, canaries, falcons, and pigeons, but is most commonly carried asymptomatically by passerine birds.

Human, reptiles, and other mammals, and non-human primates.

Susceptible age- The majority of cases (65%) occur in children under 15 years old.

Susceptible sex: Pregnant women are also especially vulnerable: about 125million pregnant women are at risk of infection each year.

Malaria statistics:

· Malaria exists in parts of Africa, Asia, the Middle East, Central/South America, Hispaniola, and Oceania

· 350-500 million people each year are diagnosed with Malaria

· Over 1 million people die from malaria each year

· Most malaria deaths occur in sub-Saharan Africa

· Most people who die of malaria are children

· Malaria was the 4th cause of childhood death in developing countries in 2002

· 10.7% of childhood deaths in developing countries were caused by malaria in 2002.

Mode of Transmission:

Mother to the growing foetus (congenital malaria):

Congenital malaria, also known as transmission of parasites from an infected mother's red blood cells to her child during labour or trans placentally, can cause malaria in the new born. Congenital malaria appears to be uncommonly documented, and it has traditionally been assumed that non immune people experience it more frequently than people in endemic locations. All four of the Plasmodium species that typically infect people have been linked to congenital malaria cases, however the majority of these occur when the mother has P. falciparum or P. vivax malaria^11,12.

Due to P. malaria's extended host persistence, congenital malaria cases may be disproportionately more common in non- endemic regions. During the initial pregnancy, congenital malaria develops more frequently.^13,14

Transfusion Malaria:

The most common way that blood transfusions from infected donors spread malaria is transfusion-transmitted malaria is one of the most prevalent illnesses nowadays and was first described in 1911.^15,16 In nonendemic nations like the United States, the risk of contracting transfusion malaria is quite low (1 case per 4 million), whereas it is substantially greater (>50 cases per million donor units) in endemic nations.¹⁷

Following a malaria infection, a person may continue to be contagious for weeks, months, or even years if only P. malariae is present. As a result, people who carriers should never give blood. Just in the case of transfusions of plasma, plasma components, or derivatives devoid of intact red blood cells, the danger of transmission is incredibly low.¹⁸ Malaria infection is challenging to detect in donated blood samples. assays.^19,20 in cases of infection, particularly in nonimmune patients, the infection can advance quickly into a deadly sickness in addition to the usual symptoms of fever, and headache.^21,22 exoerythrocytic phase.²³

Injury from needles:

Cases of malaria transmission by needle-stick injuries, unintentionally among medical personnel (some even deadly), or because drug addicts share needles have also been documented.²⁴

Transmission of malaria:

Life cycle of the malaria parasite:

The life cycle of the Malaria parasite:

(Plasmodium) is complicated and involves two hosts, -humans and Anopheles mosquitoes. The disease is transmitted to humans when an infected Anopheles mosquito bites a person and injects the malaria para- sites (sporozoites) into the blood.

Sporozoites travel through the bloodstream to the liver, mature, and eventually infect the human red blood cells. While in red blood cells, the parasites again develop until a mosquito takes a blood meal from an infected human and ingests human red blood cells containing the parasites. Then the parasites reach the Anopheles mosquito's stomach and eventually invade the mosquito salivary glands. When an Anopheles mosquito bites a human, these sporozoites complete and repeat the complex Plasmodium life cycle. P. ovale and P. vivax can further complicate the cycle by producing dormant stages (hypnozoites) that may not develop for weeks to years.²⁵

Sign and Symptoms:

The symptoms characteristic of malaria include:

1. Flulike illness with systemic fever

2. Chills, Sweating

3. Muscle aches (Fatigue, Pain)

4. Central headache.

5. Nausea

6. Vomiting

7. Dry Cough

8. Diarrhea

9. Spleen enlargement.²⁵

Diagnosis: Laboratory Tests:

Malaria is typically diagnosed by the microscopic examination of blood using blood films or using antigen-based rapid diagnostic tests (RDT).

The most economic, preferred, and reliable diagnosis of malaria is microscopic examination of blood films because each of the four major parasite species has distinguishing characteristics. Two sorts of blood film are traditionally used. Thin films are similar to usual blood films and allow species identification because the parasite's appearance is best preserved in this preparation. Thick films allow the microscopist to screen a larger volume of blood and are about eleven times more sensitive than the thin film From the thick film, an experienced microscopist can detect parasite levels (or parasitemia) as few as 5 parasites/µL blood. Diagnosis of species can be difficult because the early trophozoites ("ring form") of all four species look identical and it is never possible to diagnose species on the basis of a single ring form, species identification is always based on several trophozoites.

Blood films:

Antigen tests:

Antigen-based rapid diagnostic tests (RDTs) are often more accurate than blood smears at predicting the presence of malaria parasites.

For areas where microscopy is not available, or where laboratory staff are not experienced at malaria diagnosis, there are RDTs that require only a drop of blood. Immunochromatographic tests have been developed, distributed and field tested. These tests use finger-stick of venous blood, the completed test takes a total of 15-20 minutes, and the results are read visually as the presence or absence of colored stripes on the dipstick, so they are suitable for use in the field. One disadvantage is that dipstick tests are qualitative but not quantitative they can determine if parasites are present in the blood, but not how many

Tentative Diagnosis:

Areas that cannot afford laboratory diagnostic tests often use only a history of tentative fever as the indication to treat for malaria. Using Giemsa-stained blood smears from patient, one study showed that when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than using only a history of subjective fevers, a correct diagnosis increased from 2% to 41% of cases, and unnecessary treatment for malaria was significantly decreased.²⁶

Diagnostic Methods:

1. Light Microscopy:

Light microscopy has long been considered the 'gold standard' for malaria diagnosis. When performed under optimal conditions, light microscopy can detect parasitemia as low as 5 parasites/µL or 0.0001% on thick blood smears. Microscopy also allows the identification of the species of malaria and quantification of the density of parasite infection, especially on thin smears. Speciation is important clinically because it guides treatment choice - particularly when P. vivax or P. ovale are identified. These species may have dormant liver hypnozoites that cannot be detected with current diagnostic tools and require eradication with primaquine therapy. Because microscopy can provide a quantitative evaluation of parasitemia, it is the preferred method for monitoring response to treatment in patients with severe malaria. It also permits differentiation between asexual parasite stages, which are clinically significant, and gametocytes, which contribute to ongoing transmission of the parasite but which do not contribute to illness.

2. Immunochromatographic Rapid Diagnostic Tests:

Since the early 1990s, a variety of different rapid diagnostic tests (RDTs) have been produced to detect antigens derived from malaria parasites. These tests utilize a monoclonal antibody to a parasite antigen on an immunochromatographic strip to detect the presence of parasites in peripheral blood. The RDTs are typically manufactured in cassette or dipstick forms that contain a control line and a test line of monoclonal antibody that changes color when antigen is present. The currently available RDTs target P. falciparum histidine-rich protein 2(HRP2), Plasmodium lactate dehydrogenase (pLDH), or aldolase. Some RDTs are species specific (e.g. HRP2-based tests only detect P. falciparum) while others detect antigens that are common to all four species of human malaria. RDTs are not suitable for determining whether a patient has responded appropriately to therapy, as they do not allow for quantification of malaria parasitemia, and HRP2-based RDTs may remain positive for up to 3 weeks after treatment. RDTs may also record false- positive results in the absence of asexual parasitemia when gametocytes are present in the peripheral blood.

3. Polymerase Chain Reaction (PCR):

PCR is increasingly being used as the 'gold standard for malaria diagnosis in research and reference laboratory settings in malaria endemic and non-endemic regions. It is capable of de- tecting parasites below the threshold for microscopic identifica- tion. When performed under optimal conditions, PCR is reportedly capable of detecting a single parasite per mm³ of blood; however, under typical use it may not be substantially more sensitive than expert light microscopy. PCR may be particularly useful in diagnosing malaria in patients who have taken hemoprophylaxis or have very low levels of circulating parasites. PCR can also be used for species identification in cases where parasite morphology on microscopy is difficult to classify, in cases where parasite morphology is distorted because of prior antimalarial exposure or poor preparation and/or storage conditions, or in identifying human cases of what are typically animal forms of malaria.

Human infection with P. knowlesi, a macaque form of malaria, has been well documented in several countries but it is frequently mistaken for P. malariae on microscopy; only through molecular examination using PCR and DNA sequencing was the increasing importance of P. knowlesi as a human pathogen identified. PCR is also used in in vivo efficacy studies of antimalarial drugs to differentiate between recrudescence and reinfection. Because of the significant expense and requirement for specialized laboratory equipment and technical expertise, PCR will likely remain unsuitable for routine diagnostic purposes.

4. Serologic Diagnosis:

Serologic diagnosis with the indirect fluorescent antibody (IFA) test or enzyme- linked immunosorbent assay (ELISA) may be useful in determining prior exposure to malaria parasites. Because of the time required to develop antibodies to malaria parasites and the persistence of these antibodies, neither method of serologic diagnosis is suitable for the routine diagnosis of acute malaria infection. Also, because serologic testing by IFA requires a fluorescence microscope, it is not practical for settings without electricity. In malaria-endemic settings, the detection of antibodies to malaria is of little diagnostic value as the majority of the population will have had significant exposure before their first birthday. Serology is therefore most useful in non-endemic regions when the diagnosis of malaria is in question, in epidemiological investigations of suspected transfusion-induced malaria, or when a patient has been previously treated for suspected malaria without the species being known.²⁷

Challenges in Malaria Diagnosis in Non-Endemic Regions:

Malaria diagnosis in non-endemic regions is challenging for a variety of reasons. First, the majority of patients will be non- immune natives of non-endemic regions and immigrants from endemic regions who were partially immune, but have lost their immunity. Because of their lack of immunity to malaria, these patients can become severely ill with relatively few parasites. Secondly, many of these patients may have taken chemoprophylaxis with an antimalarial agent that can distort parasite morphology and/or further reduce malaria parasite density. And, finally, because relatively few cases of malaria are seen in non-endemic regions, laboratory technicians and physicians may be inexperienced in identifying malaria parasites.

Challenges in Malaria Diagnosis in Endemic Areas:

The biology and epidemiology of malaria in endemic areas create unique diagnostic challenges. Malaria transmission intensity varies widely in malaria endemic areas of the world; transmission intensity affects many aspects of malaria illness that in turn influence how malaria diagnostic tests are applied and interpreted. We focus on the diagnostic challenges in areas of high transmission, but many endemic countries have low, intermediate, or multiple transmission zones that may require a range of approaches for diagnosing malaria.²⁷

Treatment:

Malaria is treated using antimalarial medications, however which ones are utilised depending on the type and severity of the disease²⁸. Although fever-relieving drugs are frequently prescribed, their effects on outcomes are unclear. When used properly, giving free antimalarial drugs to households may lower childhood mortality.

Uncomplicated malaria- Oral drugs can be used to treat malaria that is simple or uncomplicated. Drugs containing artemisinin are efficient and secure for treating simple malaria. Artemisinin- combination treatment (ACT), which combines artemisinin with additional antimalarials, is around 90% successful in treating uncomplicated malaria.²⁹ The most successful treatment for P. falciparum infection is the use of ACT, which lowers resistance to any one medicine component.³⁰ The six-dose artemether-lumefantrine regimen is more effective at treating falciparum malaria than the four-dose artemether-lumefantrine regimen or other regimens that do not include artemisinin derivatives. Another potential combination is piperaquine and dihydroartemisinin.^31,32 Artemisinin-naphthoquine combination therapy emonstrated encouraging outcomes in the treatment of falciparum malaria. Amodiaquine plus sulfadoxine-pyrimethamine may result in fewer treatment failures as compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria. There are insufficient evidence on the use of chlorproguanil- dapsone to treat uncomplicated falciparum malaria.³³ Primaquine, when used in combination with an artemisinin-based therapy, lowers falciparum malaria transmission on days 3-4 and 8 after infection. In terms of preventing treatment failure at day, sulfadoxine-pyrimethamine plus artesunate performs better than sulfadoxine-pyrimethamine with amodiaquine. However, the latter outperforms the former in reducing gametocyte levels in blood at day 7. In order to treat malaria during pregnancy, the WHO recommends quinine plus clindamycin in the first trimester and ACT in the second and third.^34,35

Severe and complicated malaria Infection with P. falciparum is almost always the cause of severe and complex malaria cases. The only disease caused by the other species is often febrile.³⁶ Due to the significant (10% to 50%) mortality rates associated with malaria, severe and complex cases are considered medical emergencies.³⁷ The intravenous administration of antimalarial medications is advised as a treatment for severe malaria. In a different systematic study, quinine and the artemisinin derivatives Arteether and artemether were equally efficacious at treating pediatric cerebral malaria³⁸. For the treatment of severe malaria in both children and adults, parenteral artesunate proved more effective than quinine.³⁹ However, giving rectal artesunate prior to hospital transfer may lower the mortality rate for children with severe malaria. Intrarectal quinine is equally effective intreating uncomplicated and complicated falciparum malaria as intravenous or intramuscular quinine. The most severe neurological symptoms of malaria, known as cerebral malaria, are present in this form of the disease.⁴⁰

Medication of Malaria:

Each antimalarial drug is considered by chemical structure and mechanism of action.

1. Quinine and related agents: Quinine is an alkaloid obtained from cinchona acts as a blood schizonticidal and weak gametocide against Plas-modium vivax and Plasmodium malariae. Quinine is accumulated in the food vacuoles of Plasmodium species, especially Plasmodium falciparum and inhibit the hemozoin biocrystallization, thus facilitating an aggregation of cytotoxic heme. Quinine is very effective and widely used in the treatment of acute cases of severe P. falciparum but it is less effective and more toxic than chloro-quine. Mostly useful in areas where high level of resistance to chloroquine, mefloquine, and sulfa drug combinations with pyrimethamine.

2. Quinine related agents: Quinimax and quinidine are the two most commonly used alkaloids. Quinimax is a combination of four alkaloids (quinine, quinidine, cinchonine and cinchonidine). Due to a synergistic action between the four cinchona derivatives this combination has been shown more effective than quinine. Quinidine is a distereoisomer of quinine with simi-lar anti-malarial properties and recommended only for the treatment of severe cases of malaria. Warburg's Tincture was a febrifuge developed by Dr Carl Warburg in 1834, which included quinine as a key - ingredient. Warburg's Tincture appeared in Martindale: The complete drug reference from 1883 until about 1920. The formula was published in The Lancet 1875.

3. Chloroquine: Chloroquine was least expensive, best tested safest and the most widely used anti-malarial. It was the original prototype from which most methods of treatment are derived. The emergence of drug-resistant parasitic strains is rapidly decreasing its effectiveness. Now Chloroquine is suggested to used in combination. with other antimalarial drugs to extend its effective usage. Popular drugs based on chloroquine phosphate (also called nivaquine) are Chloroquine FNA. Resochin and Dawaquin. Chloroquine is a 4-aminoquinolone compound which is believed to reach high concentrations in the vacuoles of the parasite and raises the internal pH. It controls the conversion of toxic heme to hemozoin by inhibiting the biocrystallization of hemozoin, thus poisoning the parasite through excess levels of toxicity.

4. Amodiaquine: Amodiaquine is a 4-aminoquinolone anti-malarial drug similar in structure and mechanism of action to chloroquine. Amodiaquine has tended to be administered in areas of chloroquine resistance while some patients prefer its tendency to cause less itching than chloroquine. Adverse reactions are generally similar in severity and type to that seen in chloroquine treatment.

Pyrimethamine: Pyrimethamine is used in the treatment of uncomplicated malaria, particularly in cases of chloroquine resistant P. falciparum strains when combined with sulfadoxine. It acts by inhibiting dihydrofolate reductase in the parasite thus preventing the biosynthesis of purines and pyrimidines, thereby halting the processes of DNA replication, cell division and reproduction. It acts primar-ily on the schizonts during the erythrocytic phase, and nowadays is only used in concert with a sulfonamide.

Proguanil: Proguanil (chloroguanide) is a biguanide a synthetic pyrimidine derivative. It has many mechanisms of action but primarily is mediated through conversion to the active metabolite cycloguanil. This inhibits the malarial dihydrofolate reductase enzyme. It has a weak blood schizoticidal activity and is not recommended for therapy acute infection. However it is useful in prophylaxis when combined with atovaquone or chloroquine (in areas where there is no chloroquine resistance). 3 mg/kg is the advised dosage per day, (hence approximate adult dosage is 200 mg).

Sulfonamides: Sulfadoxine and sulfamethoxypyridazine are specific inhibitors of the enzyme dihydropteroate synthetase in the tetrahydrofolate synthesis pathway of malaria parasites. Sulfonamides act on the schizont stages of the erythrocytic cycle. When sulfonamides are co-administration with the antifolate pyrimethamine, most commonly as fixed-dose sulfadoxine-pyrimethamine (Fansidar), produce synergistic effects sufficient to cure sensitive strains of malaria.

Primaquine: Primaquine is a highly active 8-aminoquinolone drug effective against gametocytes but also acts on hypnozoites, blood schizonticytes and the dormant plasmodia in P. vivax and P. ovale. It is the only known drug to cure both relapsing malaria infections and acute cases. The mechanism of action is not fully understood. but it is thought to block oxidative metabolism in Plasmodium. For the prevention of relapse in P. vivax and P. ovale 0.15 mg/kg should be given for 14 days. As a gametocytocidal drug in P. falciparum infections a single dose of 0.75 mg/kg repeated 7 days later is sufficient. This treatment method is only used in conjunction with another effective blood schizonticidal drug.

Artemisinin and derivatives: Artemisinin is a Chinese herb (qinghaosu). Derived from the plant Artemisia annua, used in the treatment of fevers for over 1,000 years," thus predating the use of Quinine in the western world. Artemisinin is a successful therapeutic agent in the treatment of malaria is in 340 AD by Ge Hong in his book Zhou Hou Bei Ji Fang (A Handbook of Prescriptions for Emergencies). The active compound was isolated first in 1971 and named artemisinin which is sesquiterpene lactone with a chemically rare peroxide bridge linkage. It is also only given in combination with other antimalarials. Artemisinin has a very rapid action and the vast majority of acute patients treated show significant improvement within 1-3 days of receiving treatment. Semi-synthetic artemisinin derivatives (e.g. artesunate, arte mether) are easier to use than the parent compound and are converted rapidly once in the body to the active com-pound dihydroartemisinin. ⁴¹

CONCLUSION:

In conclusion, while significant progress has been made in combating malaria through the use of artemisinin-based combination therapies, the emergence of parasite resistance to these drugs, coupled with increasing insecticide resistance in mosquito vectors, poses a major threat to malaria control efforts.

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Received on 18.02.2025 Revised on 11.11.2025

Accepted on 17.04.2026 Published on 10.07.2026

Available online from July 14, 2026

Res.J. Pharmacology and Pharmacodynamics.2026;18(3):238-246.

DOI: 10.52711/2321-5836.2026.00032

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