SPOTLIGHT
In this series , we look at blood disorders through a global lens , from international trends in disease treatment to innovative initiatives in developing countries .
Is Gene Editing the Answer to Eradicating Malaria in Africa ?
● In 2018 , there were 228 million cases of malaria worldwide . The overwhelming majority of those cases – more than 90 % – were in sub-Saharan Africa , where the disease is endemic . Nearly half a million of those infected died from the disease . 1
Those numbers are devastating , but that is still far fewer cases and deaths than there were in the early 2000s . “ Beginning around 2010 , there was a concerted effort led by numerous organizations , [ including ] the World Health Organization , to eradicate malaria from endemic countries ,” Stephanie James , PhD , Director of Science at the Foundation of the National Institutes of Health ( FNIH ), told ASH Clinical News .
The approach was multipronged – encouraging the use of bed nets and insecticides to prevent the spread of the mosquito-borne disease and providing access to appropriate antimalarial drugs to treat the illness . Although it was initially successful , progress on the initiative stalled in 2018 . The techniques responsible for the progress of the previous decade no longer have the same impact on the parasites or on the mosquitoes who carry the disease .
Now , researchers are looking at a new technique to eradicate malaria : Engineering mosquitoes with a “ gene drive ” – a gene that when inserted into mosquitoes ( or other organisms ) will be passed on to nearly 100 % of the offspring in the next generation , rather than just half the offspring – that rapidly spreads a mutation that removes the insects ’ ability to spread the malaria-causing parasite . This is still an investigational technique and one that has generated controversy .
“ We have not yet reached the stage where we can release the gene-drive mosquitoes into the population ,” Charles Mbogo , PhD , Founder and President of the Pan African Mosquito Control Association ( PAMCA ), told ASH Clinical News . “ But there are several other approaches , such as the sterile insect technique , that have been used in agriculture for many , many years and worked very well .”
ASH Clinical News spoke with Drs . James and Mbogo , as well as other scientists working in the field of infectious disease and gene editing , about innovative – and controversial – efforts to control this bloodborne parasitic disease .
Old Problems , New Solutions
Controlling malaria today is quite challenging , and many of those challenges are a result of resistance that has evolved to the methods that worked in years past . For example , malaria-transmitting mosquitoes are no longer susceptible to some of the pesticides used to keep them out of homes and beds . The malaria parasites have developed resistance to some of the drugs used to treat patients once they contract the disease . Bed nets were once a highly effective intervention , but now malariatransmitting insects have started biting earlier in the evening before people go to bed , or later in the morning after they have risen .
“ It ’ s widely recognized now that we need new tools for malaria control to overcome these issues ,” said Dr . James , who works on the FNIH ’ s GeneConvene Global Collaborative , a project to determine best practices for using gene editing to improve public health .
In addition to these biologic problems , Dr . Mbogo said , “ our health systems are not strong enough to diagnose malaria .” He explained that some of the cases are occurring in rural areas , where there is no electricity , making examination of blood smears under microscopy virtually impossible . “ Countries are now trying to use rapid diagnostic tests in those areas , but because of the financing – which is another major challenge – some of the countries may not be able to afford [ to test people ] all across the country ,” he said .
Clinicians and researchers in malaria-endemic sub-Saharan Africa are also fighting another disease : sickle cell disease ( SCD ). 2 While the heterozygous trait for sickle cell may confer some protection against severe malaria , when patients with homozygous SCD are infected with malaria , they tend to have poor outcomes . Malaria parasites infect the red blood cells and cause a host of hematologic complications that can be especially detrimental to people living with SCD , including severe anemia and thrombosis . Thrombocytopenia also is a well-documented and frequent complication in malaria – occurring in an estimated 50 to 80 % of patients .
Gene Drive Goals
Rather than focusing on patient-level interventions , investigators are now targeting the source of the infectious parasite – the mosquitoes themselves . “ There is a widespread call for development of innovative new tools ,” said Dr . James . “ We think that genetically modified , and specifically gene drive – modified mosquitoes , have an important role to play there . Because the preventive measures are actually carried by the mosquitoes themselves ,
ASHClinicalNews . org ASH Clinical News
35