MALARIA Disease , parasites of MALARIA , life cycle and treatment of MALARIA and Beneficial effects of MALARIA.

 Malaria

One of the most prevalent infectious diseases and a major public health issue is malaria. A protozoan parasite of the species Plasmodium, sometimes known as malaria parasites, is what causes the illness.

The word "malaria" comes from the Medieval Italian phrase "mala aria," which means "foul air." The disease was once known as "marsh fever" because of its connection to marshes.

History

The first time malarial parasites were discovered inside the red blood cells of malaria patients was in 1880 by Charles Louis Alphonse Laveran, a French army physician working at the military hospital in Algeria. He received the 1907 Nobel Prize for Physiology or Medicine for these findings and others. Ettore Marchiafava and Angelo Celli, two Italian biologists, gave the protozoan the name Plasmodium.

A year later, Carlos Finlay, a Cuban physician who was treating yellow fever patients in Havana, made the first mention of mosquitoes spreading disease to people. However, it was Sir Ronald Ross, who was based in India, who in 1898 established conclusively that mosquitoes transmit malaria to birds. From the salivary glands of mosquitoes that had consumed diseased birds, he was able to isolate malarial parasites. Ross won the 1902 Nobel Prize in Medicine for this study. A medical panel led by Walter Reed in 1900 agreed with the conclusions of Finlay and Ross.

Malaria Parasites

Plasmodium parasites are protozoan parasites that cause malaria (Phylum Apicomplexa). P. falciparum, P. malariae, P. ovale, and P. vivax are the parasites that cause malaria in humans; the last one is the most prevalent and is thought to be the cause of roughly 80% of cases. P. falciparum, however, is the most lethal one, causing 15% of infections but 90% of fatalities. Rodents, primates, chimps, birds, reptiles, and reptiles are all infected by parasitic Plasmodium species. Several simian species of malaria, including P. knowlesi, P. inui, P. cynomolgi, P. simiovale, P. brazilianum, P. schwetzi, and P. simium, have been linked to human illnesses.

Life Cycle

Anopheles genus female mosquitoes are the prime (definitive) hosts and vectors of the parasite. When a mosquito consumes blood from an infected person, it contracts the disease. After being consumed, the gametocytes of the parasite separate into male or female gametes that mate to generate zygotes in the mosquito's gut. The zygote, also known as an ookinete, breaks through the stomach wall and develops into an oocyst outside the stomach wall.

Inside the oocyst, the diploid zygote divides through several fissions after undergoing reduction division to form haploid sporozoites. Sporozoites are released when the oocyst bursts and travel through the mosquito's body to the salivary glands, where they are prepared to infect a new human host when the insect bites a healthy man. Anterior station transfer is another name for this kind of transmission. Male mosquitoes do not spread the disease since only female mosquitoes feed on blood.

Exoerythrocytic (hepatic) and erythrocytic phases are how human malaria develops. Sporozoites in the saliva of an infected mosquito that has pierced a person's skin to feed on blood enter the bloodstream and move to the liver. They infect hepatocytes after 30 minutes of being given to the human host, reproducing asexually to generate schizont for a period of 6 to 15 days.

Once inside the liver, they release a large number of secondary metacryptozoites and cryptozoites, which break out and infect red blood cells, starting the erythrocytic stage of the life cycle. By encasing themselves in the host liver cell's cell membrane, the parasites can leave the liver unnoticed. The parasites continue to grow inside red blood cells, generating schizont that explode to release roughly two hundred merozoites that invade brand-new red blood cells. Such cycles continue to happen every 48 hours, resulting in fever and chills at the time when merozoites are released from RBCs.

Some P. vivax and P. ovale sporozoites create hypnozoites instead of exoerythrocytic merozoites right away, which can last anywhere between six months and three years. They go into hibernation, then wake up and start making merozoites. In these two types of malaria, hypnozoites are to blame for late relapses and lengthy incubation periods.

Because it spends the majority of its life hidden from immune surveillance within the liver and blood cells, the parasite is defended against attack by the body's immune system. However, the spleen kills contaminated blood cells that are still in circulation. In order to prevent this, P. falciparum secretes adhesive proteins on the surface of infected blood cells. These proteins cause the blood cells to adhere to the walls of smaller blood vessels, blocking the parasite's passage through the spleen and general circulation.

The primary cause of the hemorrhagic problems linked to falciparum malaria is the stickiness of RBCs. Masses of these diseased red blood cells can adhere and clog the smallest branches of the circulatory system. In cerebral malaria, sequestered red blood cells have the potential to cross the blood-brain barrier, which could result in coma.

Despite being exposed to the immune system, the red blood cell surface adhesive proteins (also known as PfEMP1, or Plasmodium falciparum erythrocyte membrane protein 1) are not effective immunological targets due to their enormous variety. These proteins come in at least 60 different varieties inside a single parasite and maybe an infinite variety across all parasite populations. Additionally, the parasite alternates between a wide variety of PfEMP1 surface proteins to avoid detection by the pursuing immune system.

Treatment

The quinine-containing cinchona tree bark was the first successful therapy for malaria. This tree primarily grows in Peru on the foothills of the Andes.

• Treatment with Chloroquine

Day 1

4 tablets (600 mg base), or a starting dose of 10 mg/kg.

5 mg/kg or 2 tablets (300 mg base) given 6–8 hours later.

Day 2

5 mg/kg or 2 tablets (300 mg base).

Day 3

5 mg/kg or two tablets (300 mg base)

coming 14 days

Tablets of primaquine, two (each tablet contains 7.5 mg base daily with food).

The majority of medications used to treat malaria are effective against blood-stage parasites and include the following:

Chloroquine

Combination of sulfadoxine and pyrimethamine

Mefloquine

Atovaquone and proguanil together

Quinine

Doxycycline

Alternatives to artemisinin

Primaquine also works to kill the hypnozoites, a parasite that lies dormant in the liver and prevents relapses. Pregnant ladies and those who are G6PD weak shouldn't take primaquine (glucose-6-phosphate dehydrogenase).

Mefloquine is a blood schizonticide and an antimalarial drug. It works well against all types of malaria (P. falciparum, P. vivax, P. malariae and P. ovale). Its precise mode of action is unknown. Mefloquine works against Plasmodium species in their erythrocytic stages. Exoerythrocytic (hepatic) stages of the parasite and mature gametocytes are immune to the drug's effects. Mefloquine works well against malaria parasites that are resistant to proguanil, pyrimethamine, and combinations of pyrimethamine and sulphonamide, as well as chloroquine and other 4-aminoquinoline derivatives.

For three days straight, take four tablets a day of Malarone (Atovaquone 250 mg plus Proguanil 100 mg). Though it is very new and seems to be quite effective, this combination therapy is also very pricey.

Chinese people have been using the leaves of the sweet wormwood plant, Artemisia annua, to treat malaria for more than 1,500 years. Artemisinin, the drug's anti-malarial component, wasn't discovered and extracted until the late 1960s. According to recommendations made by the World Health Organization in 2001, artemisinin is now regarded as the preferred medication for treating straightforward falciparum malaria.

Beneficial Effects Of Malaria

• Sickle-cell Disease

Occurrence of malaria. The blood condition sickle-cell disease is the one where the impact of the malaria parasite on the human genome is well understood. A mutation in the HBB gene, which codes for the beta globin portion of hemoglobin, causes sickle-cell disease. At amino acid position six of the beta globin protein, the normal allele codes for glutamate, while the sickle-cell allele codes for valine. As a result of this transition from a hydrophilic to a hydrophobic amino acid, hemoglobin molecules are more likely to link together and polymerize, causing red blood cells to take on the appearance of a sickle. Such malformed blood cells are quickly removed for destruction and recycling, primarily in the spleen.

The malaria parasite inhabits red blood cells during the merozoite stage of its life cycle, and its metabolism alters the internal chemistry of the red blood cell. If a red blood cell includes a combination of sickle and regular haemoglobin, it is likely to become malformed and be destroyed before the daughter parasites appear. Infected cells typically survive until the parasite reproduces. Therefore, those who are heterozygous for the mutant allele, often known as the sickle-cell trait, may have a very low level of anaemia that is typically inconsequential, but they also have a very low risk of developing a severe case of malaria. This is an illustration of heterozygote advantage in action.

In traditional communities, people who are homozygous for the gene have full-blown sickle-cell disease and rarely live through puberty. However, the prevalence of sickle-cell genes is only about 10% in areas where malaria is endemic. The fact that sickle-type haemoglobin has four distinct haplotypes shows that this mutation has independently appeared at least four times in malaria-endemic locations, further illustrating its evolutionary benefit in such affected areas. There are further HBB gene variants that result in haemoglobin molecules with similar malaria infection resistance. Haemoglobin types HbE and HbC, which are prevalent in Southeast Asia and Western Africa, respectively, are produced by these mutations.

Thalassemia

The mutations producing thalassemias, a group of blood illnesses, have also been linked to malaria in the human genome. According to research conducted in Papua New Guinea and Sardinia, the prevalence of?-thalassaemias in a population is correlated with the disease's endemicity. According to a study conducted on more than 500 kids in Liberia, people with?-thalassaemia had a 50% lower likelihood of contracting clinical malaria. In the?+ variant of?-thalassemia, similar investigations have discovered connections between gene frequency and malaria endemicity. These genes have likely also undergone selection during the course of human evolution due to the malaria epidemic.

Duffy Antigens

The Duffy antigens are chemokine receptors that are expressed on red blood cells and other bodily cells. Fy genes encode the expression of Duffy antigens on blood cells (Fya, Fyb, Fyc etc.). The Duffy antigen is used by Plasmodium vivax malaria to penetrate blood cells. However, due to the absence of Fy genes (Fy-/Fy-), it is conceivable for red blood cells to express no Duffy antigen. Complete resistance to P. vivax infection is conferred by this genotype. Although the genotype is extremely uncommon in people from Europe, Asia, and America, it is practically universal in West and Central African native groups. This is believed to be a result of populations in Africa having recently had significant levels of exposure to P. vivax.

G6PD

An enzyme called glucose-6-phosphate dehydrogenase (G6PD) generally shields red blood cells from the effects of oxidative stress. However, this enzyme is genetically more resistant to severe malaria, increasing protection.

HLA and INTERLEUKIN-4

There is a modest risk of developing severe malaria and HLA-B53. T-Cells are shown liver stage and sporozoite antigens by this MHC class I molecule. T cells that have been activated release interleukin-4, which encourages the growth and differentiation of B cells that make antibodies. The IL4-524T allele has been linked to higher levels of antibodies against malaria antigens, according to research on Burkinabe Fulani people, raising the idea that this may contribute to greater resistance to malaria. 

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