Malaria fight: Scientists shift focus to vaccine, GMO mosquitoes

As Uganda joins the world today to commemorate World Malaria Day, government scientists have said they are looking at the use of vaccines, mass treatment and also investigating the possibility of using genetically modified mosquitoes to eliminate the disease. 

Malaria, according to statistics from the World Health Organisation (WHO) and the government, still kills around 10,000 Ugandans annually and causes an estimated economic loss of Shs2.4 trillion. This signals limited effectiveness of the country’s malaria response strategies. 

Prof Pontiano Kaleebu, the director of the Uganda Virus Research Institute (UVRI), said their scientists are conducting studies to find effective ways to address the malaria burden. “We have a very strong entomology department that looks at vectors (mosquitoes) that transmit malaria. We are planning studies to do genetic modification of some of these vectors so that they don’t transmit,” he told this publication on April 23.

Prof Kaleebu said this work is being done in collaboration with the international research consortium Target Malaria, and a United Kingdom-based biotech company Oxitec. He said they are seeing increasing cases of resistance of mosquitoes to insecticides. 

The management of Target Malaria explained to this publication that they aim to “develop modified mosquitoes that carry a genetic trait that will result in the reduction of malaria mosquito populations and that could complement existing methods of malaria control.”

The research collaboration also said they are investigating two different ways of reducing mosquito reproduction. “First, we are investigating ways of making the mosquito population consist predominantly of males. As the population becomes increasingly male, the lack of females would cause the number of Anopheles mosquitoes to decline. Second, we are also investigating ways of making female mosquitoes unable to reproduce,” Target Malaria said.

“If most female mosquitoes cannot reproduce, then this will cause the numbers of Anopheles mosquitoes to decline. As part of this stepwise approach, the team in Uganda has been studying local wild-type mosquitoes and is preparing for work on genetically modified mosquitoes in containment, if regulatory approval is received,” the consortium added.

However, the plan to develop genetically modified mosquitoes (GMM) has attracted mixed reactions in Uganda and other parts of the world. Environmentalists in Uganda told this reporter earlier that developing GMM should be discouraged because it could affect the ecosystem.

“In science, we talk about the precautionary principle. If you don’t know much about something, you shouldn’t tamper with it. The concern is that we don’t know how these modified genes will react in the organisms that feed on mosquitoes,” Dr Edward Nector Mwavu, an ecologist at Makerere University College of Agriculture and Environment Sciences, said. 

Prof Kaleebu said apart from GMM, they are also doing research on the resistance of malaria parasites to common drugs. “We are beginning to do, see resistance to some of the drugs, Artemether-based drugs. The study is being done in eastern and northern Uganda where there’s a lot of malaria,” he said.

Dr Jimmy Opigo, the manager of the Malaria Control Programme at the Health ministry, said the country is struggling to attain the targets for reducing malaria because of emerging issues with the parasites and mosquitoes. He said a lot is being done to address these. 

“We are looking at what is happening to the parasite, how it is becoming resistant to the medicine and causing more severe disease. We are looking at mosquitoes; they have changed resting and biting behaviours,” he said.

He continued: “Traditionally they (mosquitoes) bite from 10pm to 5am, but now they start early before you enter into the mosquito net and they bite up to 8am. So you can sleep in the mosquito net and they still catch you.”

“Studies have shown that if they see the home is protected, they follow the children to school. We also now have more mosquitoes that are biting outside and yet our focus has been on preventing indoor bites. Also, we are looking at the introduction of a malaria vaccine,” he added.   

Dr Michael Baganizi, the head of immunisation programme at the Health ministry, said they intend to start vaccinating children against malaria late this year.

“Uganda has planned to begin (malaria vaccinations) in October. It is four doses at six, seven, eight and 18 months,” he said. 

Dr Catherine Maiteki, the deputy manager for the Malaria Control Programme of the Ministry also said last year their request for RTS,S malaria vaccines has been approved by GAVI ahead of the planned rollout. She said a total of one million doses of RTS,S will be funded by GAVI for the country’s first round of malaria vaccination.

“The [malaria] vaccine is safe and effective in preventing severe disease. The vaccine will be given to children below five years,” Dr Maiteki said.

Dr Opigo said that to eliminate malaria: “We want to combine malaria vaccine, mosquito control and use of medicines for prevention. If you clear malaria parasites out of people, there will be nothing for mosquitoes to pick from one person to another.” 

More deaths than Covid
According to information from the WHO, 10,000 malaria deaths occur in Uganda every year. This is about three times higher than the 3632 Covid-19 deaths which have been reported in the country (for four years) since the pandemic began in 2020.  

“Malaria has killed more people than Covid,” Dr Diana Atwine, the permanent secretary of the Health ministry noted, adding: “Malaria continues to be the biggest killer of our people in our country.”

Referring to a new report from the World Health Organisation, which indicates that there are cases of mixed infection with different species of malaria parasites, Dr Atwine said there is a need to change the approach to malaria response. 

“We thought they (those other species of malaria parasites) were of less importance but now there are complications such as black water fever and renal failure in children [with malaria] and we are seeing the possibility of co-infection with other parasites that make malaria more complicated to treat. This causes more death and more morbidity,” she said. 

She continued: “We should not be losing people to malaria when we know exactly how it spreads, how it can be prevented. So we are now wondering what we are not doing right to deal with malaria. We want to see how everyone can be an agent of change in management and prevention of malaria.”

Dr Opigo on his part explained that they are seeing that in “20 percent of people who die, have mixed infections [by different species of malaria parasite].”

“They can first have Plasmodium falciparum (commonest species of malaria parasite) but also they have (other species of malaria parasites) Plasmodium malaria, Plasmodium ovale and Plasmodium Vivax,” Dr Opigo explained.

Dr Opigo said that to reduce malaria deaths, there is a need to improve the quality of treatment and emergency care.

“It is known that when you initiate severe malaria treatment within seven hours, the chance of death is cut by half. We know that if you get simple malaria –headache, fever, vomiting and you start treatment you don’t get a severe form of malaria. That is same-day treatment of malaria and if you have some danger signs your treatment should be handled as an emergency within two to six hours,” Dr Opigo said. 

The information about the high burden of the disease in the country is coming amid threats from development partners that they would reduce their support to Uganda for fighting malaria fight. 

However, Mr Thomas Tayebwa, the Deputy Speaker of Parliament said the Minister of Health, Dr Jane RuthAceng should present a strategy for eradicating malaria to the Parliament.

“In order to achieve our goals for socio-economic transformation, we must eradicate malaria. I am pleased to see that 25 billion has been allocated for test kits in the upcoming Financial Year, but we need to do more as the donors, who have been providing 95 percent of our malaria fighting budget, have informed us in advance of their intention to withdraw their support,” he said.

Loss to economy, families 
Dr Opigo said their figures show that “Government alone spends close to $150 million (Shs572 billion) in treatment of malaria every year. He said this excludes what families spend. 

“We know that to treat simple malaria costs the household about 50,000 shillings and to treat severe malaria where you are hospitalised, costs around 150,000 to 200,000 shillings, that excludes the ones who go on to require dialysis because of kidney injury induced by the infection,” he said. 

However, with resistance of parasites to common drugs, some patients are undergoing treatment twice because of failure of the initial treatment. Treatment cost also varies in the country with patients in urban areas like Kampala spending more, especially to access treatment in private facilities. 

The latest figures from the Health ministry indicate that there were 166,772 confirmed cases of malaria and 24 deaths reported by health facilities in one week stretching from February 26 to March 3 of this year. Not all health facilities are reporting figures to the Ministry. Some people also die at home, private health facilities and clinics and the data may not reach the ministry, according to Dr Opigo. 

The 166,772 cases mean if all were mild malaria infections treated at the lowest cost of around 50,000, the patients could have lost Shs8.3 billion in one week. However, some patients also access free drugs in public facilities. 

Mr Tayebwa has in the past said the country loses Shs2.4 trillion annually due to malaria. The monetary loss is majorly due to treatment costs and work time lost while undergoing treatment and recovering from the illness.

EFFORTS IN DEVELOPING MALARIA VACCINE
1965:  The search for malaria vaccines was started by Dr Ruth Nussenzweig, an Austrian-Brazilian immunologist specialising in the development of malaria vaccines.

1987: The RTS,S vaccine was created in 1987, as a result of a collaboration that began in 1984 between the multinational pharmaceutical company GSK and the America’s Walter Reed Army Institute of Research.

1988: Candidate vaccine (SPf66 candidate), emerged in Colombia and had an acceptable efficacy in humans and animals but it was disappointing when field studies in Africa and Asia demonstrated insufficient efficacy.

1996:  A study among 46 healthy individuals aged 18 to 35 years showed that the malaria vaccine regimens were safe and could produce immune response against malaria.
    
2007:  A study among 894 children aged 5 to 17 months in Kenya and Tanzania showed that the efficacy was 49 percent in stopping malaria disease.

2006-2008: A study among 540 children in Ghana found that three dose schedules produced better immunity than 2 dose schedules.

2009-2011: 8,922 children (age 5-17 months) and 6,537 young infants (age 6-12 weeks) were enrolled in seven African countries for phase 3 clinical trial. The researchers found that efficacy was enhanced by administering a booster dose in both age categories. 

2015: The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) documented that the RTS,S/AS01 vaccine had an acceptable safety profile that was to be continually monitored.

Late 2015: Two main WHO groups, the Strategic Advisory Group of Experts (SAGE) and the Malaria Policy Advisory Group (MPAG), reviewed the findings of the Phase III clinical trial on RTS,S.

2016: Based on the recommendations of both advisory groups, the WHO approved a pilot implementation program on RTS,S vaccine in three moderate and high-transmission African countries using the four-dose protocol.

2019: The pilot vaccination programme commenced in 2019 in Kenya, Ghana and Malawi and about 800,000 young children have so far been vaccinated.

2021: The WHO approved the first malaria vaccine and parasitic vaccine, RTS,S/AS01 (RTS,S, also known as Mosquirix™) for widespread use.
 
2023: WHO announces approval of second malaria vaccine R21/Matrix-M.

2024: Cameroon starts using malaria vaccine in January and Uganda announces that they would start malaria vaccination in October 2024.

Sources: Egyptian Researchers Amal A. El-Moamly And Mohamed A. El-Sweify; and WHO and MOH

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