Background Information
Malaria is a serious infection spread by mosquitos that damages red blood cells and the liver. It is widespread in tropical countries and in poor, low income countries it is a leading cause of death. It is caused by a parasite made up of only one cell called Plasmodium. There are four different types of plasmodium called falciparum, ovale, vivax and malariae. These different types all cause malaria but require different drugs to prevent and/or treat the malaria they cause adding to the complexity of this disease. Plasmodium Falciparum causes the most serious malaria.
Around 200 million people are infected with malaria each year.
Without treatment malaria can be fatal and around half a million people per year die from malaria. (1)
UNICEF has calculated that 67% of these deaths are in children aged five and under. In 2019, there were 229 million malaria cases globally that led to 409,000 deaths. Of these deaths, 274,000 were in children under the age of five. Every single day 750 children aged five and under die from malaria. To put this in even starker terms, every two minutes a child aged under five dies of malaria. (2)
Cause
The malaria parasite is transmitted by the mosquito. The mosquito spreads the parasite by biting an infected person and then biting another person thereby passing the parasite on to them. It cannot pass directly from person to person in the way, for example, the common cold can.
Plasmodium falciparum is the malaria parasite most commonly found in Africa and is the cause of most malaria deaths. Plasmodium vivax is found in Asia and South America. These are the two most common causes of malaria. The other types are rarer and usually found in Africa.
Symptoms
Symptoms usually appear 1 to 3 weeks after being bitten by the mosquito although in some people it can be several months or even a year before they develop symptoms. Hence medical advice should be sort if malaria is suspected even when travel to a high risk area was not recent.
Once symptoms appear they often come in waves of attacks every 3 to 4 days. Symptoms include:
High temperature
Sweating profusely but feeling shivery and cold
Headache
Muscle pains
Vomiting
Diarrhoea
Jaundice (yellowing of the skin caused by red blood cells breaking down)
In severe, life threatening cases symptoms include:
Confusion and delirium
Convulsions (fitting)
Coma
People who progress into coma rarely recover.
Diagnosis
A simple blood test can identify the malaria parasite and which of the four types it is. Sometimes the blood tests can be falsely negative, ie no parasite is seen but the person does have malaria. If a test is negative, but malaria is still suspected, then the blood test should be repeated.
Treatment
There are drugs available to treat malaria but which ones are used depends on the type of malaria parasite identified.
95% of people will recover from malaria if they receive the correct treatment. Recovery can be slow and it is not unusual to suffer relapses for months or sometimes even years from when first diagnosed.
Prevention
Prevention for Travellers
There is no vaccine against malaria for travellers but the drugs used to treat malaria can be taken to try and prevent malaria. They are up to 90% effective when taken correctly. The different malaria parasites have developed resistance to some of the anti-malaria drugs available so the particular drugs given to the traveller will be tailored to the part of the world they are visiting.
It is vital to seek advice for each and every trip to areas at risk of malaria. Never use stockpiled supplies of anti-malarial drugs from previous trips as they may not offer any protection in a different part of the world. Also the guidelines as to which drug should be used in any one country can change from time to time depending on the emergence of resistant strains of the parasite. For example, 20 years ago the same two drugs (proguanil and chloroquine) could be used virtually anywhere in the world but the falciparum form of the parasite is now completely resistant to them. Whilst they can still be used in a few Asian countries they offer no protection in Africa.
The drugs need to be started a few days or weeks before travel depending on the particular drug being used and continued for up to 4 weeks after returning from travel.
For travellers prevention also centres round trying to avoid being bitten by infected mosquitos. Mosquitos usually bite at dusk and during the night. Most seasoned travellers are familiar with the measures they need to take.
These include:
Sleeping under a mosquito net at night
Using insect repellent containing DEET (most mosquito bites happen at dawn and dusk so repellent should always be used at these times but preferably throughout the day as well)
Wear clothes that protect the skin, eg: long trousers and long sleeved shirts not shorts and T-shirts, shoes not sandals. The more skin that is covered the less that is available for the mosquitos to bite.
Prevention for Local Populations/Long Term Visitors
For people who live in areas affected by malaria extra measures should be taken. These include protecting the house with window screens, regular cleaning of water storage containers and removing “man-made” habitats where mosquitos can thrive, eg don’t allow water to gather and stagnate in old containers.
The World Health Organisation recommends the spraying of insecticide indoors and using mosquito nets impregnated with insecticide to try and control the mosquito population in at risk areas.
In certain parts of Africa where the malaria risk is severe pregnant women and infants are given preventive drugs against malaria.
On 6 October 2021 the WHO (World Health Organisation) announced a significant and historical breakthrough in the prevention of malaria – the licencing of a malaria vaccine for use in babies and children in countries where malaria is endemic. (3)
The Malaria Vaccine
Initially called RTS,S and now named Mosquirix, this new vaccine will first be rolled out to children in places with high levels of malaria. It has been trialled for two years in three sub-Saharan African countries - Malawi, Kenya and Ghana – and is the first ever malaria vaccine to be approved. The vaccine is given as four separate doses and 800,000 children in these three countries have received it during the trials.
How Effective Is It?
The vaccine prevents about 30% of severe malaria cases and therefore the ones most likely to lead to death. This level of effectiveness is well below that of other vaccines - the current COVID-19 vaccines are in the region of 90%+ effective and the measles vaccine is 97% effective. (4) (5)
The WHO’s goal is that a vaccine should be 75%+ effective.
A 30% efficacy is certainly modest in comparison to other vaccines but, given the huge number of children that die from malaria, that could still mean the prevention of tens of thousands deaths from malaria in young children every year. One model suggests that the deaths of at least 23,000 children per year will be prevented. (6)
As the WHO director-general Tedros Adhanom Ghebreyesus said at a press briefing: “The RTS,S malaria vaccine — more than 30 years in the making — changes the course of public health history.” (7)
Why did it take 30 years to develop?
Given the speed with which the COVID-19 vaccines were developed, a 30 year process to develop a malaria vaccine is certainly a sharp contrast.
However, there are both scientific and political reasons as to why it took so long.
The malaria parasite is very complex, more complicated than the coronavirus or measles virus for example. There are different types of malaria parasites and a vaccine against one type doesn’t work against the other types. The parasites have some features in common, they all cause malaria, but are also very different in others.
It is a little like saying dogs and cats can both bite you so they must be the same – but they are not. The end result may be the same, a nasty bite, but the two creatures are very different.
For a long time there was little political will amongst western leaders to fund and develop research into a vaccine for a disease their own countries were not affected by. Pharmaceutical companies had little financial incentive to develop a vaccine that would not be needed by, and therefore not purchased by, the rich and affluent nations.
Work on the Mosquirix vaccine began in 1987 and was funded by the Bill & Melinda Gates Foundation in Seattle and the London-based pharmaceutical firm GlaxoSmithKline (GSK).
Development has cost in the region of US$750 million.
GSK has pledged to make 15 million doses available at cost price each year but to reach all the children at risk requires more than 100 million doses per year. (8)
The Future
A vaccine with just 30% efficacy is disappointing in many ways. The WHO’s own benchmark is that a vaccine should be at least 75% effective
However, a vaccine that has been shown to be safe and reduces the number of deaths in children from a disease that is one of the world’s biggest killers, and until now has defied responding to a vaccine, is a significant and historical step.
This vaccine will be the starting point from which other vaccines are developed.
Work is ongoing on other vaccines with one in particular, developed by a group including Oxford University, the Serum Institute of India and the pharmaceutical company Novavax, about to enter its final Phase III trials of testing. This vaccine candidate has shown an efficacy of 75% in its earlier trials. If this is replicated when it is scaled up to Phase III trials another breakthrough in the fight against malaria will have been achieved. (9)
Other possibilities for the future management of malaria include combining a vaccine with the concomitant administration of drugs used to treat malaria to increase the ability of the individual’s immune response to fight infection with the parasite. (10)
Genetic modification of mosquitos to either reduce their numbers or make them less likely to spread malaria are approaches also being worked on. Genetically modified mosquitos would be released into the wild but this approach will need to be proven to be safe before any implementation is carried out. (11)
Summary
The world’s first malaria vaccine was approved by the WHO on 6 October 2021.
The WHO recommends its use in children aged five and under in sub-Saharan Africa, home to the deadliest malaria parasite, Plasmodium falciparum.
The vaccine will NOT be given to adults at this stage.
The vaccine will NOT be given to overseas travellers to countries where malaria is endemic and will not be available as part of any travel vaccination regime.
This first vaccine is only around 30% effective but work is ongoing to develop more effective vaccines. As resistance to front-line malaria drugs becomes an increasing problem production of an effective vaccine is ever more vital.
Although the development of the first ever malaria vaccine is a defining moment in world history, existing malaria control measures - from mosquito nets and the use of DEET sprays at an individual level to mass insecticide programmes at an environmental level - must be continued for the foreseeable future.
(6) Hogan, A. B., Winskill, P. & Ghani, A. C. PLoS Med. 17, e1003377 (2020)
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