Malaria (Plasmodium): A-Level Biology Revision Notes microbiologystudy

Malaria is an infectious disease that is caused by one of five species of protozoa Plasmodium. Plasmodium is an unicellular obligate parasite that infects the red blood cells, liver and brain. Among 150 species of Plasmodium, only five can affect human and they are:

• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium ovale
• Plasmodium malariae
• Plasmodium knowlesi

Among these species of this parasite, Plasmodium falciparum is the deadliest species which dominates the African continent whereas Plasmodium vivax is the most prevalent in other tropical and subtropical countries and is the main cause of relapse of malaria. Overall, the other three species are less prevalent world-wide. The dominantly widespread effect of this parasite is due to its transmission through the vector Mosquito.

Transmission of Malaria

Malaria does not directly transmit from an infected person to a healthy person, but there are various indirect routes that can help spread the disease. These are briefly discussed below:

1. Vector

The malarial parasite mostly transmits through a mosquito vector, specifically the infected female Anopheles mosquito. Thus, malaria is classified as a vector-borne disease. Infected female Anopheles mosquitoes transmit the infective-stage parasites to a healthy person during blood feeding, where the exchange of mosquito saliva occurs before blood can be sucked.

2. Blood Transfusion and contaminated needles

Sometimes malaria also gets transmitted when the blood of infected individuals comes in contact with the blood/bloodstream of healthy individuals. This usually happens during blood transfusion and/or during the sharing of needles. Nowadays, blood transfusion is usually preceded by numerous blood screening tests, which greatly eliminate the risks of such transmission. However, the spread of parasites from individuals who share or reuse the contaminated needles, especially drug users, are still prevalent.

3. Mother to fetus

A pregnant woman who has malaria is capable of transmitting the parasite to her fetus through the placental route. However, in such cases the infection of the placenta itself is much more probable than the fetus getting infected. An infected placenta will prevent oxygen and nutrients from being passed to the baby, leading to severe outcomes such as miscarriage.

The life cycle of Plasmodium is that of a cyclic nature that alternates between the female Anopheles mosquito and humans.

1. Human (Gametocyte and Merozoite life cycle)

The parasite initially proliferates in the liver cells and then the red blood cells of humans. Within the red blood cells, Plasmodium develops into schizonts, which rupture the RBC to invade other neighboring RBCs. The schizonts then develop into merozoites. This stage of the Plasmodium life cycle is responsible for causing symptoms of malaria.

Some parasites differentiate to form sexual erythrocytes which are known as gametocytes. Eventually, the gametocyte forms of the parasite are ingested by the female Anopheles mosquito vector during blood meals, which signals the start of the second life cycle.

2. Mosquito (Sporozoite life cycle)

The gametocytes mate in the gut of the mosquito and begin a new cycle of proliferation. After about 2 weeks, a form of the parasite known as sporozoites travel to the salivary glands of the mosquito. When the female mosquito begins a blood meal on a healthy human, a certain amount of mosquito saliva is transferred into the blood to act as an anticoagulant. This causes the transfer of the Plasmodium sporozoite into the human bloodstream. The sporozoite then migrates to the liver through the bloodstream, beginning the human life cycle anew. Note: When female anopheles mosquitoes bite humans, they seek for proteins present in the blood which are needed for the development of their eggs. Thus, only female mosquitoes are responsible for mosquito bites and thus play a role in the transmission of malaria.

Clinical Features of Malaria

Incubation period

The incubation period in humans after getting bitten by an infected mosquito is usually 10-18 days long, with 2 weeks on average. 

Symptoms of Malaria

The primary symptoms of malaria include, but are not limited to:

• Fatigue
• Unconsciousness
• Convulsions and muscle spasms
• Breathing complications
• Dark or bloody urine
• Jaundice, usually characterized by yellowing eyes or skin
• Abnormal bleeding

In some cases, Malarial symptoms may be mild for people,especially those who have already been infected by the parasite beforehand. 

Complications

For some specific population groups, the onset of malaria can be especially fatal. These include infants, children under 5 years of age, pregnant women, travelers and HIV/AIDS patients. When left undiagnosed, these cases can quickly turn fatal.

Diagnosis of Malaria

Malaria is one of the deadliest diseases and requires a thorough and immediate response. Usually diagnostic methods involve identification of the parasite itself or the products produced. Although it seems simple, the efficiency of diagnosis depends and can be influenced by various factors such as the five different species, drug resistance, stage of life cycle etc. 

Clinical Diagnosis of Malaria

It is the least expensive and widely practiced method where malaria is endemic. It is based on examining the signs and symptoms of the patient. Sometimes there may be non-specific clinical signs that lead to over treatment of malaria or not treating malaria at all. Although this method does not accurately diagnose, it is usually paired with laboratory findings to further improve the accuracy. 

Laboratory Diagnosis of Malaria

1. Microscopic diagnosis

Both thick and thin stained blood smear is studied under a microscope. Thick blood smear is studied for screening of presence of malarial parasites whereas thin blood smear helps to confirm the malarial species. Usually giemsa stain is used to visualize the parasite.

2. QBC technique

This involves the extraction of parasitic DNA and then staining using fluorescent dyes for example acridine orange. After the observation under the fluorescent microscope, parasitic nuclei are bright green in color and cytoplasms seem yellow-orange in color. Although this method is simple and more reliable, it is costly for installation and does not inform us about the number and species of parasites.

3. Rapid diagnostic tests

When microscopes are not available, RDTs are necessary for urgent diagnosis of malaria. RDTs are based on the detection of malarial antigen where the blood flows over a membrane containing specific anti malaria antibodies. Various companies have produced RDTs specific for particular species.

4. Serological tests

Immunofluorescence antibody testing is one of the serological tests for malaria where it uses the concept of detection of antibodies against asexual blood stage malaria parasites. It is very time consuming and specific in nature.

Treatment of Malaria

Due to its status as a serious infection, the treatment of malaria is very extensive and relies on a couple of different factors other than available medication. Some common factors that must be considered before administering treatment are:

• The type of malarial parasite
• The weight, age and BMI of the patient
• Underlying health issues (e.g. diabetes) and/or any conditions (e.g. pregnancy)

The most widely used medicines for malaria are:

1. Artemisinin-based combination therapy (for P. falciparum infections): Combination therapy refers to the use of multiple therapeutics for a single infection/condition. 
2. Chloroquine (for P. vivax infections)
3. Primaquine (for P. vivax and P. ovale infections)

Note: Due to the widespread use of these pills, a phenomenon known as Antimalarial Drug Resistance is becoming more and more prevalent. This simply means that the pathogenic organism has slowly developed resistance against the treatment that is being used. In Africa, resistance against Artemisinin has been rampant in the Mekong subregion, whereas Chloroquine is nowadays only prescribed if the parasite is sensitive to it, as most strains have developed resistance to it as well. 

Prevention of Malaria

The prevention of malaria is a multi-step process that usually begins at the individual and household level, and progresses up to the government and medical facility provider level.

At the individual level, the most effective prevention method is vector control. Like most vector-borne diseases, malaria can be very effectively controlled by managing and eliminating mosquito populations in prone areas. This can be done by:

• Using mosquito nets and repellents
• Using window screens and coils
• Wearing protective clothing
• Filling potholes and other surfaces where water may deposit during mosquito breeding season
• Personal and community hygiene

Apart from these, there are several other methods through which malaria can be prevented. They are briefly discussed below:

Chemoprophylactic drugs

For most travelers, a chemoprophylaxis for malaria is advised 2-3 weeks before the travel begins. For this, a medical provider will determine the appropriate drug to be used based on the destination. This method not only prevents individual malaria infection, but also helps to break the transmission cycle in the community. 

Preventive Chemotherapy

This method is usually performed in regions where the population is most susceptible to malaria infections. This involves providing a full course of antimalarial treatments to the population during the time of the greatest risk, regardless of the infection status of each individual. This is most common in schools in the African continent, where children are mass-treated during peak malaria season.

Malaria Vaccine

In October of 2021, WHO recommended the use of the RTS,S/AS01 malaria vaccine in children living in the most at-risk areas of Africa for malaria prevention. This vaccine has shown moderate to high efficacy against P. falciparum infections, and reduced the number of severe malaria and fatal malaria in young children. Similarly, a novel vaccine R21/Matrix-M has been recommended since October of 2023.

Questions on Malaria

References

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