A drug that both cures malaria and prevents the transmission of the deadly disease may be one step closer, research suggests.
Scientists found inhibiting the protein PfCLK3 blocks several stages that are critical to the complex life cycle of the parasite behind the killer illness.
Tests showed it prevented the parasite inside mice from developing into the ‘mature phase’ that infects humans through mosquitoes.
One expert called the study by researchers at the University of Glasgow ‘exciting’.
But they added multiple approaches are needed to combat treatment resistance, with ‘no one drug being able to eradicate malaria’.
Scientists may be one step closer to developing an anti-malarial drug that both cures the infection and prevents its transmission via mosquitoes, research suggests (stock)
Earlier this week, the World Health Organization (WHO) warned malaria will not be wiped out in the near future with ‘the tools we have today’.
More than 200million cases occur every year worldwide, causing around 500,000 deaths, the researchers wrote in the journal Science.
Attempts to control outbreaks have been hindered by the parasites’ slowly growing resistance to drugs.
There is, therefore, an ‘urgent need for novel strategies to cure malaria while also preventing transmission’.
To edge closer to this, the researchers screened more than 24,000 compounds that are thought to be involved in a malaria parasite’s development.
They focused on Plasmodium falciparum, which is the most common species worldwide and the most likely to be fatal.
PfCLK3 was identified as having a ‘central role’ in regulating the parasite’s gene expression.
To put this to the test, mice were infected with Plasmodium falciparum. The researchers then blocked PfCLK3 within the parasites in the rodents.
This suppressed the activity of more than 400 genes that are ‘essential’ to the pathogen’s survival.
In turn, this prevented the pathogen from multiplying in the animals’ red blood cells. Eventually, these cells burst, which causes a sufferer to experience the tell-tale malaria fever.
Blocking PfCLK3 also prevented other forms of the parasite from circulating in the mice’s blood.
WHAT IS MALARIA?
Malaria is a life-threatening tropical disease spread by mosquitoes.
It is one of the world’s biggest killers, claiming the life of a child every two minutes, according to the World Health Organization (WHO).
Most of these deaths occur in Africa, where 250,000 youngsters die from the disease every year.
Malaria is caused by a parasite called Plasmodium, of which five cause malaria.
The Plasmodium parasite is mainly spread by female Anopheles mosquitoes.
When an infected mosquito bites a person, the parasite enters their bloodstream.
- Feeling hot and shivery
- Muscle pain
These usually appear between a week and 18 days of infection, but can taken up to a year or occasionally even more.
People should seek medical attention immediately if they develop symptoms during or after visiting a malaria-affected area.
Malaria is found in more than 100 countries, including:
- Large areas of Africa and Asia
- Central and South America
- Haiti and the Dominican Republic
- Parts of the Middle East
- Some Pacific Islands
A blood test confirms a diagnosis.
In very rare cases, malaria can be spread via blood transfusions.
For the most part, malaria can be avoided by using insect repellent, wearing clothes that cover your limbs and using an insecticide-treated mosquito net.
Malaria prevention tablets are also often recommended.
Treatment, which involves anti-malaria medication, usually leads to a full recovery if done early enough.
Untreated, the infection can result in severe anaemia. This occurs when the parasites enter red blood cells, which then rupture and reduce the number of the cells overall.
And cerebral malaria can occur when the small blood vessels in the brain become blocked, leading to seizures, brain damage and even coma.
Source: NHS Choices
When a mosquito bites an infected human, it ingests these parasites. These then make their way to the insect’s salivary glands, enabling it to infect others.
Overall, inhibiting PfCLK3 ‘was highly effective at clearing rodent malaria parasites from infected mice’.
The approach also led to ‘anti-parasite activity’ against the malaria species Plasmodium berghei, which infects certain rodents, and knowlesi, which largely affects macaque monkeys.
This suggests blocking PfCLK3 could work across ‘multiple malaria species’.
However, the researchers note the same approach may not be effective in humans.
Dr Jake Baum, professor of cell biology and infectious diseases at Imperial College London, said: ‘We stand at a key cross-roads in malaria control and eradication.
‘There is rising drug resistance in south east Asia and we have stalled in our efforts to reduce malaria incidence globally.
‘As such, there is an urgent need, just like with antibiotic resistance, to find new drugs with new modes of action.
‘This is where the current study fits in, looking at an exciting class of drugs that indeed works in a new way.’
He added: ‘So far, in this paper, the authors show the drug has robust activity, targeting the malaria parasite at several stages in its lifecycle.
‘It is still very early in development and there’s a long way to go before these drugs would even be put into testing in humans, but we need a full pipeline for the long road if we are to achieve global eradication.’
Professor Baum added, however, ‘no one drug will eradicate malaria’. He said: ‘We need not just a replacement but a pipeline of replacements.
‘It’ll always be a revolving door – new drugs in, old ones out as nature always finds a way to evolve resistance. We should be clear, no drug alone will eradicate malaria.’
Michael Chew, infection and immunobiology portfolio manager at the Wellcome Trust, added: ‘This study has identified a compound that disrupts a specific target on multiple species of the malaria parasite, at each stage of the life cycle.
‘This effectively kills it before it can cause disease or be transmitted to others via mosquito bites.
‘It needs to now be developed further and be tested in clinical trials. If successful this could lead to urgently needed new drugs to tackle malaria, which affects around 200 million people each year.’
The WHO warned earlier this week it is not yet possible to put a date on when malaria may be eradicated.
Dr Pedro Alonso, the body’s global malaria director, said: ‘With the tools we have today, it is most unlikely eradication could be achieved.
Between 2000 and 2015, an ongoing drive to eliminate the disease saw worldwide malaria deaths drop from 864,000 to 429,000 per year.
‘The world is at a crossroads. Historical progress that has been achieved over the last decade is clearly slowing down,’ Dr Alonso said.
A WHO report predicts even given its ‘most optimistic scenarios and projections… we will still have 11million cases in Africa in 2050.’