Malaria: Symptoms, Causative Agents, and Treatment

Malaria is a very serious disease that has caused death of millions of human lives. The causative organism is a protozoan belonging to the genus Plasmodium. The members of the genus is characterized by having a life-cycle in which alteration of an asexual cycle with a sexual cycle accompanied with an alteration of host occurs. Asexual cycle or Schizogony occurs in the RBC of a vertebrate (like man) and sexual cycle or Sporogony occurs within invertebrate host (like female mosquito).

Distribution

Malarial parasites are found to infect man almost throughout the world, although the tropical area is the endemic home of malarial disease.

The different types of malarial diseases caused by four species of malarial parasites are named differently, mainly on the basis of the period of recurrence of fever and the causative s species of Plasmodium.

Considering the entire world, malaria is one of the most important diseases, which causes a large percentage of death. In addition, millions suffer illness, loss of vigor and often prolonged inefficiency also results from this disease. The agricultural development of certain countries have been greatly retarded due to this disease.

Human Malarial Parasites

It is noteworthy that only four different species of Plasmodium cause malarial fever in man. It may so happen that different species of malaria parasites develop in the same mosquito and such an infected mosquito can transmit the infection to man giving rise to cases of ‘mixed infection’.

The word Malaria (mala=bad and aria=air) literally means bad air-Laverson, 1980.
Four species of Plasmodium are responsible for human infection which are as follows:

  1. Plasmodium vivax
  2. Plasmodium falciparum
  3. Plasmodium malaria and
  4. Plasmodium ovale.
    Although the same mosquito and another such an infected mosquito can also transmit the infections to man giving rise to cases of ‘mixed infection’. However, it should be noted that several other species of Plasmodium cause malarial disease to other animals including many which are domesticated by man. The following table shows types of malaria, causative species, recurrences of fever and death rate.
Malaria TypesCausative OrganismsRecurrence of feverDeath Rate
Benign tertian Malaria or vivaxPlasmodium vivaxEvery 48 hoursLow
Malignant tertian malariaPlasmodium falciparumEvery 36 or 48 hoursVery high
Quartan MalariaPlasmodium malariaeEvery 72 hourLow
Ovale or mild tertian malariaPlasmodium ovaleEvery 48 hoursInsignificant

Life History of Plasmodium vivax

Life history of Plasmodium vivax is completed by two hosts: In this case, mosquito is the definitive host and human body is the intermediate host.

Life Cycle of Plasmodium vivax in Mosquito


A female Anopheles during its blood meal from an infected person, ingests both the sexual and asexual forms of the parasite. But, the mature sexual forms can only thrive in the body of the mosquito, others die off immediately.

The sexual cycle occurs within the body of the mosquito and completes it within a span of about ten days when the infective forms , the sporozoites, are formed. These sporozoites have a special predilection towards the salivary glands of mosquito and they finally reach a maximum concentration in the salivary ducts. At this stage, a single bite of the mosquito is sufficient to cause the infection. As the presence of sporozoites in the salivary glands is a positive proof of the development of the malarial parasite in the species of Anopheles mosquito, it is taken as the criterion for determining the species of Anopheles in the spread of the disease.

Life Cycle of Plasmodium vivax in the Human Body

In the human body, it starts with the inoculation of the sporozoite stage of Plasmodium when an infected female Anopheles mosquito bites a person of normal health to obtain its blood meal. The sporozoites, several thousands in number, reach the cells of the liver.

In Liver, each sporozoite is a minute, slender and spindle-shaped structure. It is 14 µ long and one µ broad. These are motile and capable of performing gliding and vibratory movements. In the liver cells, the sporozoites grow into large bodies or schizonts which divide to form about one thousand smaller bodies, the merozoites or cryptozoites. Thus, they reproduce in the liver cells by an asexual method (Schizogony) to increase their number. The second phage of asexual reproduction occurs when these cryptozoites re-enter the liver cells and the schizogony cycle is repeated. Finally, several thousands of metacrypto-merozoites are produced when they leave the liver cells and come to the blood stream. Now, each such parasite enters erythrocytes (RBC). The time taken since the infection of man by sporozoites till the merozoites enter the blood stream is known as the incubation period. The time is variable in different species of Plasmodium but usually the variation ranges between 8 to 9 days. The merozoites entering the RBC becomes rounded and grows in size.

Life Cycle of Plasmodium vivax in the Red Blood Cells (RBC)

In this case, a vacuole develops in the parasite merozoite which gradually increases in size and pushes the nucleus to one side and thus look ring like structure. This particular form of parasite, now known as trophozoites, is called signet ring. Gradually with the growth, the vacuole disappears and the haemoglobin of the RBC is broken down into its protein component and haematin. The protein portion is used as food by the parasite, while the haematin forms the haemozoin pigment. Trophozoite is the feeding stage of the parasite which soon gets ready to reproduce asexually. Since, this schizogony or asexual reproduction occurs within the erythrocyte, it is known as erythrocytic schizogony. As a result of 20 to 30 divisins, the trophozoite is transformed into numerous erythrocytic merozoites and RBC can no longer hold them. Consequently, the cell membrane of the RBC bursts and the merozoites are liberated with toxic products in the blood plasma. Some of merozoites are destroyed by theleucocytes or WBC while most of them attack fresh and healthy erythrocytes. The cycle is repeated and every time the merozoites and the toxic products liberated in the blood plasma develops clinical symptoms, namely, shivering and rise in temperature. Erythrocytic cycle(also known as the cycle of Golgi) is completed in 48 to 72 hours in different human species of Plasmodium.

Image Showing Life Cycle of Plasmodium Vivax. Image credit: CDC

The duration period between infection and first appearance of the parasite in blood is known as pre-patent period, which may vary between 6 to 15 days according to the species(in Plasmodium vivax, it is about 8 days).

Thus, a good many number of erythrocytes (Red Blood Cells) are attacked and destroyed through the infection of the parasite, while a few of them (merozoites) develop into the sexual forms. These are compact rounded bodies, known as gametocytes or gamonts. The RBC containing this form do not circulate in the blood but remain in the blood vessels of spleen or marrow. Within about 96 hours these become matured and are distributed into small sized male or micro-gametocyte and big sized female or macro-gametocyte. Further development of the gametocytes do not occur in man and if they are not taken up by a female mosquito with its blood meal these are destroyed after s weak. However, in mosquito the RBC are destroyed. With the bite of the mosquito the gametocytes are liberated, when the sexual cycle occurs.

Macro-gametes and micro-gametes unite in the gut of the mosquito and the zygote (2n) passes through different development phases giving rise to the sporozoites (n), the infective forms.

Method of Malarial disease Transmission or Infection of Malaria in The Human Body

Transmission Process

The female Anopheles mosquitoes act as intermediary in the act of transmitting the human infection. While taking its blood meal from an infected person, both sexual and asexual forms are also ingested. In the alimentary canal of the mosquito the sexual forms thrive only whereas all other stages die out. The parasite undergoes sexual cycle in the mosquito leading to various developmental changes seem to have a predilection towards the salivary glands of the mosquito, where from they concentrate in the salivary ducts.

The infection is transmitted by the inoculative method. In the act of biting, the mosquito pierces the skin of man by its proboscis and in course of this act the salivary secretion is injected into the punctured wound. The droplet of secretion carries a alrge number of sporozoites and these are directly introduced into the blood stream. However, a single bite of such a mosquito is capable of infecting a new host.

Transmitting Agents: Infected female Anpheles moswquitoes
Port of entry: Human skin
Infective forms: Sporozoites
Media of transmission: Blood stream
Site of Localization: First in liver cells and subsequently in erythrocytes (RBC)

Symptoms of Malaria

The following symptoms are exhibited during a malarial infection. Mild symptoms appear even during the incubation period, one or two days before the onset of fever. The more evident symptoms are given below:
Intermittent fever: High temperature accompanied with chill and shivering.
Each paroxysm (attack) of fever shows three successive phases:
Cold phase: When the patient feels nausea, suffers from headache and severe chill with tremendous shivering.
Hot phase: When the pulse rates goes up and the temperature rises high.
Sweating phase: When the patient sweats profusely, the fever comes down, temperature gradually becomes normal and the pulse rate also becomes normal.

Besides above symptoms, the following symptoms are also seen:
• General feeling of discomfort
• Diarrhea
• Muscle pain
• Joint pain
• Fatigue
• Nausea and vomiting
• Abdominal pain
• Cough
• Fast breathing
• Fast heart rate

Control of Malaria Disease

For the prevention or control of malaria, various methods are used.
Destruction of vector or Anopheles mosquito is of utmost importance. Obviously, it is the most effective method which can be achieved by using insecticides etc.

Cleaning of swamps to destroy the breeding places of mosquitoes. Further, by burning sulfur, tar-camphor etc. the adult mosquitoes may be destroyed.

Occasional cleaning of sluggish drainage, ditches etc. to speed up the water flow.

Spraying of paraffin oil upon the surface of water when it is not possible to drain swamps nd lakes. The thin film will not allow the larvae to respire air and thus they will be killed. Large areas of water should be treated with Panama larvicide, paris green. In the process, one part of Paris green is mixed with three parts of dust and blown over the surface of water scarcity.
Biological control is effected through cultivating foshes like Gambusia.Minnows, Panchax, etc. which are specially fond of mosquito larvae and pupae. The tadpoles are also used in controlling the mosquito (larvae) population.

Diagnosis

  • For making diagnosis of malaria, physicians should know the recent traveling background and medical history of the patients. In this case, doctor conduct blood tests and physical exam of the patients. The tests include:
  • Scanning malarial parasite in the blood;
  • Analysis of symptoms for identifying the malarial parasite species. In this case, PCR is most useful tool for confirming the types of malarial parasite species.

Prevention of Mosquito bites

Mosquito nets and clothings should be used to keep the insects away from the human body.

Citronella oil (Kerosene oil), anti-mosquito creams (odomos) can be used for application on the exposed parts of the body.

In mosquito infected areas, the rooms should be provided with close-netted windows and doors.

Treatment

There are various drugs are available in the market to treat malaria by killing the parasites. In this case, the length of treatment varies which depends on the following criteria:
• Age of patient;
• Type of malarial parasite;
• Condition of symptoms;
• Pregnancy for female patient;

Medications

The following antimalarial drugs are used to treat the malarial disease:
Chloroquine phosphate: It is an antimalarial drug. It is taken as direction by doctor. In this case, the dosage and length of treatment depend on the medical condition of the patient and its response to treatment. In the case of children, weight is the basic factor to take this medication. You should usually take this drug once a weak. If you travel in the malaria’s area, you should take drug usually 1 to 2 weeks before travelling and you should continue to take it weekly basis while in the area. You should also take drug 4 to 8 weeks after leaving that area.

Primaquine phosphate: Primaquine is a antimalarial drug which is used to treat Plasmodium vivax malaria. You may use it alone or with other drugs. Each tablet contains 26.3 mg of Primaquine phosphate. If you take this , it may cause the following side effects:
• Fever
• Hives
• Weakness
• Dark colored urine may occur
• Skin becomes pale or yellowish
• Swelling
• Confusion
• Nausea
• Dizziness
• Vomiting
• Irregular heartbeats, etc

Other most common antimalarial drugs include:
• Malarone or Atovaquone-proguanil
• Qualaquin or Quinine sulfate with doxycycline

Risk Factors

If you live in or visit the diseased prone areas you may face the greatest risk factor for developing malaria. The risk factors depend on the control of malaria, the rates of seasonal changes of malaria and the preventive measures you take to control or prevent the bites of mosquitoes: The following regions are the highly diseased prone areas:
• Central America;
• Northern South America
• Sub-Saharan Africa
• Pacific Islands
• South and Southeast Asia

In these above areas, the following peoples are very much susceptible to malarial disease:
• Older people;
• Infants and young children;
• Pregnant women;
• Unborn children;
• Visitors coming from areas with no malaria;

Complications

According to WHO (World Health Organization), about 94% of all malaria deaths occur in Africa. Among them, the majority are children under the age of 5. These death occurs by the infection of malarial parasite, Plasmodium species.
These type of malarial deaths are usually related to the following one or more serious complications:

Anemia: In many cases, malaria destroy the RBC causing anemia as a result sufficient oxygen supply does not occur in the body tissues.
Cerebral malaria: If your blood contains malarial parasite which can block the blood vessels to brain causing cerebral malaria. In this case, brain damage may occur causing seizures and coma.
Breathing problems: Malarial parasite may accumulate fluid in the lungs causing breathing problems.
Organ failure: The kidney, liver or the spleen are damaged if you attacked by the malaria. This condition can be life-threatening.
Low blood sugar: In you suffer from sever forms of malaria causing hypoglycemia which can result in coma or death.