Malaria is a life-threatening blood disease caused by parasites transmitted to humans through the bite of the Anopheles mosquito. Once an infected mosquito bites a human and transmits the parasites, those parasites multiply in the host's liver before infecting and destroying red blood cells.
The disease can be controlled and treated if diagnosed early on. Unfortunately, this is not possible in some areas of the world lacking in medical facilities, where malaria outbreaks can occur.
Researchers are working hard on improving the prevention of malarial infection, early diagnosis and treatment, with just one malaria vaccine close to being licensed so far.
You will also see introductions at the end of some sections to any recent developments that have been covered by MNT's news stories. Also look out for links to information about related conditions.
Fast facts on malaria
Here are some key points on malaria. More detail and supporting information is in the main article.
Malaria was first identified in 1880 as a disease caused by parasitic infection1
The name of the disease comes from the Italian word mal'aria, meaning "bad air"
Malaria is transmitted to humans through bites by infected mosquitoes
The most common time for these mosquitoes to be active is between dusk and dawn
Worldwide, there were an estimated 198 million cases of malaria in 2013 and 584,000 deaths
Malaria occurs mostly in poor, tropical and subtropical areas of the world
Malaria was eliminated from the US in the early 1950s, but the mosquitos that carry and transmit the malaria parasite still remain, creating a constant risk of reintroduction
Reported malaria cases in the US reached a 40-year high of 1,925 in 2011
A malaria vaccine for humans is close to being approved for use in Europe
An estimated 3.4 billion people in 106 countries and territories are at risk of malaria - nearly half of the world's population10
Annual funding for malaria control in 2013 was three times the amount spent in 2005, yet it represented only 53% of global funding needs2
Malaria incidence rates are estimated to have fallen by 30% globally between 2000 and 2013 while estimated mortality rates fell by 47%
The World Health Organization (WHO) has set out to reduce all malaria cases and deaths by 90% by 2030.3
What is malaria?
Derived from the Italian word for "bad air," it was originally thought swamp fumes in Rome were the cause of malaria, as outbreaks were a regular occurrence there.4
If left untreated, malaria can be fatal due to the fast reproduction of the parasite within a host's bloodstream.
There are more than 100 types of Plasmodium parasites,5 which can infect a variety of species. Scientists have identified five types that specifically infect humans,6 they are:
P. falciparum - located worldwide in tropical and suburban areas, but predominately in Africa. An estimated 1 million people are killed by this strain every year. The strain can multiply rapidly and can adhere to blood vessel walls in the brain, causing rapid onset of severe malaria including cerebral malaria.
P. vivax - located in Latin America, Africa, and Asia, it is arguably the most widespread due to the high population of Asia. This strain has a dormant liver stage that can activate and invade the blood after months or years, causing many patients to relapse.
P. ovale - located mainly in West Africa, it is biologically and morphologically very similar to P. vivax. However, unlike P. vivax, this strain can affect individuals who are negative with the Duffy blood group, which is the case for many residents of sub-Saharan Africa. This explains the greater prevalence of P. ovale (rather than P. vivax) in most of Africa.
P. malariae - located worldwide and the only human malaria parasite to have a three-day cycle. If left untreated, P. malariae can cause a long-lasting, chronic infection that can last a lifetime and which may cause the nephrotic syndrome.
P. knowlesi - located in Southeast Asia and associated with macaques (a type of monkey). This strain has a 24 hour cycle and can, therefore, multiply rapidly once a patient is infected, causing an uncomplicated case to become serious very quickly. Fatal cases of infection with this strain have been reported.
Causes of malaria
Malaria is caused by the bites from the female Anopheles mosquito, which then infects the body with the parasite Plasmodium. This is the only mosquito that can cause malaria.
The successful development of the parasite within the mosquito depends on several factors, the most important being humidity and ambient temperatures.
When an infected mosquito bites a human host, the parasite enters the bloodstream and lays dormant within the liver. For the next 5-16 days, the host will show no symptoms but the malaria parasite will begin multiplying asexually.7
The new malaria parasites are then released back into the bloodstream when they infect red blood cells and again begin to multiply. Some malaria parasites, however, remain in the liver and are not released until later, resulting in recurrence.
An unaffected mosquito becomes infected once it feeds on an infected individual, thus beginning the cycle again.
The video below from the Howard Hughes Medical Institute visualizes how a single bite from an infected mosquito can quickly turn into the life-threatening disease.
Symptoms of malaria
According to the Centers for Disease Control and Prevention (CDC), malaria symptoms can be classified in two categories: uncomplicated and severe malaria.
Uncomplicated malaria is diagnosed when symptoms are present, but there are no clinical or laboratory signs to indicate a severe infection or the dysfunction of vital organs. Individuals suffering from this form, can eventually develop severe malaria if the disease is left untreated, or if they have poor or no immunity to the disease.
Symptoms of uncomplicated malaria typically last 6-10 hours and occur in cycles that occur every second day, although some strains of the parasite can cause a longer cycle or mixed symptoms. Symptoms are often flu-like and may be undiagnosed or misdiagnosed in areas where malaria is less common. In areas where malaria is common, many patients recognize the symptoms as malaria and treat themselves without proper medical care.
Uncomplicated malaria typically has the following progression of symptoms through cold, hot and sweating stages:
Sensation of cold, shivering
Fever, headaches, and vomiting (seizures sometimes occur in young children)
Sweats followed by a return to normal temperature, with tiredness.
Severe malaria is defined by clinical or laboratory evidence of vital organ dysfunction. This form has the capacity to be fatal if left untreated. As a general overview, symptoms of severe malaria include:
Fever and chills
Prostration (adopting a prone or prayer position)
Deep breathing and respiratory distress
Abnormal bleeding and signs of anemia
Clinical jaundice and evidence of vital organ dysfunction.
On the next page, we will look at the tests, diagnosis and treatments for malaria.
Tests and diagnosis of malaria
Early diagnosis of malaria is critical for a patient's recovery. Any individual showing signs of malaria should be tested immediately. The WHO strongly advise parasitological confirmation by microscopy or a rapid diagnostic test (RDT).8
The choice of testing method is, of course, dependent on the medical facilities available. RDT has become popular worldwide due to its capacity to provide a quick diagnosis.
RDTs are increasingly used as health care professionals seek to not only improve testing methodologies, but also to ensure that the opportunity for testing reaches a wider audience. The number of RDTs distributed by national malaria control programs around the world has increased substantially. In 2005, less than 200,000 RDTs were provided, in 2012 this number had risen to 108 million.9
The signs and symptoms of the disease are non-specific. However, malaria is clinically suspected on the basis of fever, or a history of fever. Unfortunately, there is no combination of symptoms that can reliably distinguish the disease from other causes, hence the importance of a parasitological test.
In some malaria-endemic areas, such as sub-Saharan Africa, the disease is so intense that a large proportion of the local population can develop a mild immunity to the disease. As a result, some people can still carry the parasites in their bloodstream, but do not fall ill.
Treatments for malaria
If left untreated, malaria can be fatal. The aim of treatment is to eliminate the Plasmodium parasite from the patient's bloodstream. Even those who are asymptomatic may be treated for infection so as to reduce the risk of disease transmission in the general populace.
Anti-malaria drugs are more accessible than ever before, but further challenges lie ahead until the disease is eradicated.
Artemisinin-based combination therapy (ACT) is recommended by the WHO to treat uncomplicated malaria. Artemisinin is derived from the plant Artemisia annua, better known as sweet wormwood, and is known for its ability to reduce quickly the number of Plasmodium parasites in the bloodstream.
ACT is artemisinin combined with a partner drug. The role of artemisinin is to reduce the number of parasites within the first three days while the partner drugs eliminate the rest.
Expanding the access to ACTs has been integral to the global fight against the disease. In 2013, 392 million ACT treatment courses were obtained by endemic countries, a substantial rise from 11 million in 2005.
However, there is growing concern about the increase of cases of malaria resistant to the effects of ACTs. As of February 2015, artemisinin resistance has been confirmed in five countries: Cambodia, Laos, Myanmar, Thailand and Vietnam. For these cases, individuals were still successfully treated, but the ACT must contain an effective partner drug.
The WHO has warned that as no alternatives to artemisinin are likely to become available for several years, and because ACTs are the main treatment for P. falciparum malaria, it is of paramount importance that steps be taken to prevent the spread of ACT-resistant strains. National malaria control programs are now being asked to regularly monitor the efficacy of antimalarial medicines in use to ensure that treatments remain efficacious.
Research is ongoing to develop safe and effective vaccines for malaria, with one vaccine close to being licensed for use in Europe.
The development of an effective malaria vaccine poses major challenges as a comprehensive vaccine would need to be effective against a number of strains of malaria parasites. As such, the majority of vaccines in development are focused on the most serious and deadly parasite, Plasmodium falciparum. The development of a vaccine against P. vivax is complicated by the associated relapses and hypnozoite stages of infection with this parasite.
The malaria vaccine that may soon be approved for use in humans is called RTS,S/AS01 and was developed through a partnership between GlaxoSmithKline Biologicals (GSK) and the PATH Malaria Vaccine Initiative (MVI), with support from the Bill & Melinda Gates Foundation.
This vaccine has completed Phase III testing and, in 2015, the European Medicines Agency (EMA) issued "a European scientific opinion" that indicated that they had assessed the vaccine as favourable in terms of its risk/benefit from a regulatory perspective. Although the vaccine is not licensed or approved for use in Europe, this statement may help regulatory authorities in Africa reach a decision on licensure.11
This vaccine is effective against P. falciparum only; it affords no protection against P. vivax malaria.
The malaria vaccine has been tested for efficacy in 5-17 month old children and 6-12 week old infants. Researchers found that the vaccine was 39% effective in the older children who received four doses on a 0, 1, 2, 20 month schedule. The vaccine was 31.5% effective against severe malaria in these 5-17 month old children, but no protection was conferred against severe malaria if children did not receive the fourth dose.
In the younger infants (6-12 weeks), the vaccine was 27% effective when the first three doses were given at 6, 10 and 14 weeks of age, and a fourth dose 18 months later. The vaccine was 18% effective in the children who did not receive the fourth dose. The vaccine was not seen to be effective against severe malaria in this age group, however.
Testing revealed some unexplained phenomenon in those children receiving the vaccine, including an increase in febrile seizures, meningitis and cerebral malaria. It is not yet known if these issues are related to the vaccine itself or are due to some other cause.
Approval of RTS,S/AS01 in Europe represents the first approval of a vaccine for a disease caused by parasites; all other vaccines are for use against diseases caused by either viruses or bacteria