# Malaria

| Malaria |
| --- |
| *Classification and external resources* |
| Malaria is transmitted by the bite of an infected mosquito |
| ICD-10 | B50.-B54. |
| ICD-9 | 084 |
| OMIM | 248310 |
| DiseasesDB | 7728 |
| MedlinePlus | 000621 |
| eMedicine | med/1385 emerg/305 ped/1357 |
| MeSH | *C03.752.250.552* |

**Malaria** is an infectious disease caused by a parasite, known as plasmodium. It is one of the most common diseases in the world. Every year it infects hundreds of millions of people and kills hundreds of thousands..

Malaria is produced by four species of the protozoan parasite **Plasmodium**, which is endemic in many tropical countries. It is spread by the bite of an infected mosquito. When the parasite enters a person's blood, it causes an infection that can be deadly.

## Epidemiology

Malaria cases declined until the mid-1970s. In the 1950s there were 75 million cases of malaria; in the 1960s, there were only 0.1 million. However, it staged a comeback in the mid-1970s, causing 6.47 million cases in 1976. This increase resulted from several factors - for example, many mosquitoes became resistant to commonly used insecticides.

According to 2011 estimates from the World Health Organization, between 149 million and 274 million people get malaria each year. Of these, around 655,000 people die from the disease. This averages out to one malaria death every minute.

Today, around 90% of people who get malaria live in Africa. However, malaria is endemic and sub-endemic to many parts of the world. For example, 80% of the Indian population lives in malaria risk areas. However, in India, the National Malaria Eradication Programme (NMEP), started in 1958, achieved near complete disappearance of the disease in 1960s (from 75 million cases in 1950s to 0.1 million cases in 1960s).

## Biology

The parasite that causes malaria is a protozoan called *Plasmodium.* Protozoa are organisms with only one cell, but they are not bacteria. Bacteria are smaller and simpler than protozoans.

People usually get malaria from the *Anopheles* or *Culex* mosquitoes Archived 2019-02-28 at the Wayback Machine: they are the vectors of the disease. The *Plasmodium* lives in the mosquito's special saliva. When any mosquito bites a person, it injects an anticoagulant into the person to prevent their blood from clotting. If the mosquito has *Plasmodium* in its saliva, it transmits the parasite to the human along with the anticoagulant.

Female mosquitoes consume blood as a source of protein for their eggs. However, male mosquitoes live on the nectar of flowers. Because of this, only female mosquitoes transmit malaria.

Malaria usually results from mosquito bites. However, there are other methods of transmission. A fetus can get malaria from its mother. (This is called vertical transmission or maternal-fetal transmission.) People can also get malaria from a blood transfusion. In addition, a person can get malaria if they use a needle that someone with the disease used before them.

## Malaria parasite life cycle

**Malaria life cycle** In humans, after being bitten by an infected mosquito the malaria parasites first infects the liver. At this stage there are no symptoms.

The red blood cells are infected next, at this stage symptoms of malaria appear.

When an uninfected mosquito bites an infected human they become infected and continue the cycle.**Malaria infected red blood cell**Colorized electron micrograph of red blood cell infected with malaria parasites (blue).

The small bumps on the infected cell show how the parasite remodels its host cell. Uninfected cells (red) have smoother surfaces. Credit: NIAID/RML
There are several species (kinds) of *Plasmodium* that cause malaria in humans:

* *Plasmodium falciparum* causes the most severe disease and kills the most people
* *Plasmodium malariae,* *Plasmodium ovale,* and *Plasmodium vivax* cause milder disease
* *Plasmodium knowesli* usually affects non-human primates

*P. vivax* and *P. falciparum* cause most malaria cases in humans.

When *Plasmodium* enters the blood, it is in the form of sporozoites. The sporozoites travel to the liver, where they make more sporozoites. Then they change into a different form of *Plasmodium* called merozoites. The merozoites enter the red blood cells, then multiply.

The merozoites break out of the red blood cells again and again. When they do this, the person gets very sick, and shows symptoms of malaria. This happens every few days, and is called a paroxysm.

*P. vivax* and *P. ovale* can survive in the liver for a long time. A person can look well, but still have the *Plasmodium* in their liver. This is called a *dormant phase*. Weeks or months later, the *Plasmodium* can travel from the liver to the blood, and the person will get sick again.

*P. falciparum* is the most dangerous type of malaria. It multiplies more quickly in the blood, so because there are more merezoites, it makes people sicker. Also, with *falciparum* malaria, the red blood cells are sticky and block blood vessels. When a blood vessel is blocked, it cannot bring blood and oxygen to that part of the body. This can hurt that part of the body and cause organ damage.

## Who is affected by malaria

**Malaria western hemisphereMalaria eastern hemisphere**
Children and pregnant woman are worst affected by malaria. When they get malaria, they often get sicker than other people.

40% of people live in a place where there is malaria. These areas are:

* Africa
* Asia (mostly in India, the Middle East, and Southeast Asia)
* Central and South America
* Hispaniola
* Eastern Europe
* South Pacific (the part of the Pacific Ocean south of the equator)

Every year, 300 to 700 million people get malaria. It kills 1 million to 2 million people every year. Most of the people who die from malaria are children. Even if children do not die, many have brain damage.

Many of these deaths might be stopped with medicine or mosquito control. But many of the places malaria may be found are in poor countries. These countries do not have enough money to stop the mosquitoes, or to give people medicine. Money, however, is not the only problem. A country must have an organised medical system to provide services. Many countries in central Africa have been disrupted by warfare and conflict between groups, and general unrest. Also, easy solutions to kill the parasites do not exist as they did 50 years ago. This is because the insects are resistant to many insecticides, and the *Plasmodium* parasite is highly resistant to quinine and most other common drugs. This is a normal evolutionary process: the chemicals weed out the non-resistant organisms, and the offspring of the few resistant organisms multiply.

## Signs and symptoms of malaria

**Jaundice**. Malaria can cause *jaundice*, which causes the skin and the white areas of the eyes (*sclerae*) to turn orange-yellow.
This is caused by *hyperbilirubinemia* - too much bilirubin in the blood. Bilirubin is a pigment which results when the body breaks down old red blood cells.
Symptoms are changes in someone's body that are signs for a disease. Most people who get malaria get symptoms 10–30 days after they get infected (the *Plasmodium* gets in their blood.) But some people can get symptoms after only a week, and some may be infected with malaria and not have symptoms for a year.

The most common symptom of malaria is fever, when the body temperature is high. The fever from malaria usually comes very suddenly. The people who have malaria often feel like they had influenza.

Symptoms of malaria are:

* Arthralgia (pain in joints)
* Headache (pain in head)
* Feeling very tired or sleepy
* Cough
* Chills (feeling very cold)
* Delirium (when people are very confused because of a disease. They may look drunk. They may not be able to talk.)
* Coma (when people are not conscious. They look like they are asleep, but they cannot be woken.)

Signs of malaria:

* Anemia (low red blood cell levels in the blood)
* Diarrhea
* Jaundice (yellow skin and eyes)
* Sweating
* Vomiting
* Fast heart rate
* Low blood pressure
* Enlarged organs. When something becomes enlarged or BIGGER than normal the word often ends in -megaly.
	+ Hepatomegaly -enlarged liver, splenomegaly - enlarged spleen, or both hepatosplenomegaly. When these organs become enlarged it may cause pain in the right upper quadrant of the abdomen.

## Complications from malaria

Complications are problems that happen because of a disease.

Pregnant women and young children have more complications. People who get malaria for the first time have more complications. *Falciparum* malaria has the most complications.

| Complications of malaria |
| --- |
|
Complications of malaria are:
* Cerebral malaria (brain malaria)
	+ To have cerebral malaria, the following must be present:
		- *P. falciparum* in the blood.
		- Coma, many seizures, or long delirium
		- If no treatment is given, death often occurs.
		- Even if treatment is given, 15%-20% of people with it die.
* Seizures (if *only* one seizure happens it is not cerebral malaria)
* Damage to the brain
* Blackwater fever
	+ Many red blood cells break open and the hemoglobin in the cells gets into the blood.
	+ This hemoglobin is put in the urine and makes it look very dark.
	+ Without the right care this can make the kidneys stop working.
* Pulmonary oedema
	+ This is fluid in the lungs that makes it hard to breathe.
	+ Pregnant women get this much more.
	+ 80% of people who get this complication die.
* Very low blood sugar
	+ Children and pregnant women get this more.
	+ This can cause people to look like they are drunk or to be in a coma.
* Hemolysis
	+ This means breakdown of red blood cells.
	+ It can cause blackwater fever, jaundice, and symptoms of anemia.
* Coagulopathy (not being able to stop bleeding)
 |

## Diagnosis

**Malaria Rapid Diagnostic Test (RDT)** being used in Kenya. RDT takes abou 20 minutes to produce a malaria diagnosis. It is useful in areas where laboratory testing is not available, it is not however foolproof.

**Malaria microscopy**|  |  |  |
|  |
| A technician looks for the malaria parasite in blood films (blood smears).
 | Microscopic view of malaria parasites in a blood smear. Arrows point to infected red blood cells. |

### Clinical diagnosis

A clinical diagnosis is based on the signs and symptoms of a disease, it is a diagnosis made without medical testing. In the case of malaria one of the main symptoms which may lead to a clinical diagnosis of malaria is a fever.

Any clinical diagnosis of malaria should be confirmed by a trained professional based upon laboratory results as soon as it is possible.

### Malaria rapid diagnostic test

A Malaria rapid diagnostic test is a blood test which can confirm a diagnosis of malaria in about twenty minutes. RDTs are not foolproof and have a number of drawbacks, and as such a negative rapid diagnostic test should not be accepted at face-value and follow-up with malaria microscopy is necessary.

### Malaria microscopy

To see if patients have malaria, doctors may do a blood test. This test is called a *Giemsa blood smear*. Blood is put on a slide which is a thin piece of glass. The *Giemsa* stain is put on the slide. This stain helps doctors see the malaria. Then they look at the slide under a microscope. The *Plasmodium* is seen in the red blood cells.

## Consequences

Malaria is one of the leading causes of the ruin of families and entire lives around the world. Malaria does not only affect children, who are its primary victims, but also claims the lives of many parents. The death of a parent deeply weakens the family, leading to loss of income, children dropping out of school, long-term poverty, and many other much more serious consequences. Thus, this disease causes not only human suffering but also large-scale social disruption.

## Treatment

**Drug resistant malaria**Malaria evolves resistance to anti-malarial drugs.
The map shows areas in SE Asia where the drug *Mefloquine* no longer works
People with different kinds of malaria need different medicines. The medicine that works for one kind of malaria may not for another kind. So it is very important to know which species of *Plasmodium* the person has.

If the species is not known, the person should be given medicine and care like they have *falciparum* malaria – the worst kind.

It is also important to know *where* the person got malaria. *Plasmodium* in some places is resistant to some medicines. So the medicines to treat malaria in Africa are different from the medicines to treat malaria from South America.

### Treatment of malaria other than *falciparum*

Everywhere except New Guinea, the treatment is the same. In New Guinea most *P. vivax* is resistant to *chloroquine*. It can be treated with quinine, but this medicine can make people sick. Everywhere else, non-*falciparum* malaria is treated with chloroquine.

Chloroquine kills the *Plasmodium* in the blood. But the *Plasmodium* in the liver is not killed by chloroquine. *P. vivax* and *P. ovale* both stay in the liver a *long* time. This is the *dormant phase*. Another medicine must be given with chloroquine for *P. vivax* and *P. ovale*. This is to kill the *Plasmodium* in the liver. The medicine used to kill malaria in the liver is *primaquine*. In southeast Asia, some *P. vivax* is resistant to primaquine. Most other places, *primaquine* works very well.

Some people get very sick from *primaquine*. So people have to be tested to see if they have G6PD-deficiency before they take *primaquine*.

### Treatment of *falciparum* malaria

Falciparum is the worst kind of malaria. People with *falciparum* malaria should be treated in a hospital if they are:

* Very sick
* Children
* Pregnant
* Sick with malaria for the first time
* Not able to take medicines by mouth

Even people who are treated with medicines at home should stay with the doctor for 8 hours. This is to make sure they do not get sicker. It also makes sure they can take the medicines by mouth. Malaria does not start to become a life-threatening disease until it has been a couple of weeks after the bite without being treated.

*Falciparum* malaria also has more resistance to medicines. This makes it much harder to treat. *Falciparum* malaria is always treated with two or more medicines. Doctors choose the medicines by where in the world the person got malaria. Different places have *P. falciparum* that is resistant to different medicines.

The most important resistance is chloroquine-resistance. In some places in the world, *P. falciparum* is killed by chloroquine. In some places it is chloroquine-resistant. This means chloroquine does not kill it. In these places quinine can be used. Quinine is taken by mouth.

## How to prevent malaria

Sleeping under insecticide-treated bed nets (ITNs) helps reduce the risk of getting malaria.
Only pyrethroid insecticides are approved for use on ITNs. These are man-made pesticides similar to the natural pesticide pyrethrum, made by chrysanthemum flowers
There are three ways to prevent malaria:

* Control mosquitoes
* Keep mosquitoes from biting
* Take medicine to keep from getting sick after a bite, especially in those parts of the world where people get malaria.

### Control mosquitoes

Clearing drainage ditches in Kenya
**Anopheles larvae** The anopheles mosquito lays eggs in stagnant water
*Vector control* is one way to stop malaria. Vector means an organism that carries an infectious disease to another organism. For malaria, the vector is the *Anopheles* mosquito.

The most used method of vector control is pesticides. These are chemicals that kill the mosquito. The first pesticide used for vector control was DDT. DDT worked very well for vector control. It killed mosquitoes. It did not make people very sick at the time it was used. It did not cost very much money. Other chemicals for vector control had not been invented yet.

In many places mosquitoes became resistant to DDT. This meant that DDT did not work anymore in these areas. Scientists worried that DDT was making people and animals sick. It killed a lot of wildlife too. DDT also stays in the environment for a long time. For these reasons, people mostly use other chemicals for vector control. *Organophosphate* or *carbonate* pesticides are used, like *malathion* or *bendiocarb*.

Vector control is not the only way to stop malaria. And DDT is not the only chemical that can be used for vector control. The best way to stop malaria is to use a combination of methods. In some places, DDT may be a useful part of a program to stop malaria. This is why DDT is still allowed to be used for controlling malaria.

### Keeping mosquitoes from biting

The mosquito that carries malaria comes more at dawn (when the sun comes up) and dusk (when the sun goes down.) Be most careful at these times. Wear long trousers and shirts with long sleeves. Wear mosquito repellent (this is a chemical that mosquitoes do not like, so they do not bite.) Mosquitoes will bite through thin cloth. So repellent should be used on skin *and clothes*.

Pesticides can be used in rooms to kill mosquitoes. When sleeping outside, people use a mosquito net. This is made from cloth that air can go through but keeps mosquitoes out. It is put over a bed where people sleep to keep mosquitoes out. Sometimes people also use it when they are not sleeping. It is best to use mosquito nets that have been treated with Permethrin, which repels and kills mosquitoes.

### Taking medicine to not get sick

People can take medicine when they are in a place where there is malaria. This reduces the chances that they contract malaria. This is called *prophylaxis*.

Some people take prophylactic medicines for years. Many people in areas where there is malaria do not have the money to buy this medicine.

People who live where there is no malaria usually have *not* had malaria. The first case malaria is usually much worse. So people from places where there is no malaria may take prophylactic medicines when they go to places where there is malaria. The kind of prophylactic medicines people take depends on where they are. This is because not all medicines work on the malaria in every place.

To make them work best, prophylactic medicines have to be taken the right way. The medicine should start *before* going to an area with malaria. Most medicines should be taken for 4 weeks after coming home. One medicine (Malarone) only needs to be used for *one* week after coming home.

## Resistance to malaria

There are some children in Tanzania who are naturally immune to malaria. Researchers are using this to develop a new vaccine. U.S. researchers have found the children produce an antibody which attacks the malaria-causing parasite. Injecting a form of this antibody into mice protected the animals from the disease. The researchers plan to do tests on primates, including humans.

## History

World War Two era poster.
It was Britain's Sir Ronald Ross, working in the Presidency General Hospital in the Kolkata, who finally proved in 1898 that malaria is transmitted by *anopheles* mosquitoes. He did this by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. For this work, Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius. The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900. Its recommendations were used during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.

The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine. This tree grows on the slopes of the Andes, mainly in Peru. The indigenous peoples of Peru made a tincture of cinchona to control malaria. The Jesuits noted the efficacy of the practice and introduced the treatment to Europe during the 1640s, where it was rapidly accepted. It was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by French chemists.

In the early 20th century, before antibiotics became available, Julius Wagner-Jauregg discovered that patients with syphilis could be treated by intentionally infecting them with malaria. The resulting fever would kill the syphilis spirochaetes, and quinine could be administered to control the malaria. Although some patients died from malaria, this was preferable to the almost-certain death from syphilis.

In the twentieth century between 2% and 5% of all deaths were from malaria. Malaria was the largest hazard encountered by U.S. troops in the South Pacific during World War II, where about 500,000 men were infected. Sixty thousand American soldiers died of malaria during the North African and South Pacific campaigns.

## Related pages

* *Plasmodium*
* Antibiotic resistance

## Other websites

* malarial drugs side effect Archived 2020-06-22 at the Wayback Machine
* Video: Life Cycle of Malaria Parasite in the Mosquito
* WHO malaria information Archived 2006-01-06 at the Wayback Machine
* US Centers for Disease Control: Malaria
* Medline Plus about malaria