The World Health Organisation’s (WHO) recent decision to endorse a vaccine for malaria, clinically known as the RTS,S vaccine and colloquially called Mosquirix, was a massive milestone in the campaign to eradicate the disease. Malaria has plagued mankind for tens of thousands of years and the pesky mosquito, which serves as the host or vector for the disease, has killed more human beings than any other creature in existence, facilitating 400,000 deaths annually.
Early evidence of malaria exists dating back to 2700 BC with the disease said to have contributed to the decline of the Roman Empire, the weakening of indigenous populations during the colonisation of the Americas, huge losses for British forces during the Revolutionary War, and the death of thousands of American forces in the Indo-Pacific during World War Two. Recognising the deadly toll of malaria, most Western countries successfully eliminated the disease by the 1950s. This was largely done through supply-side interventions that reduced the prevalence of mosquitos in those regions.
However, malaria still devastates large parts of Africa and Asia, with Sub-Saharan countries in particular, accounting for the vast majority of cases and deaths. Mosquirix could provide those regions with a potential, albeit limited, lifeline though challenges prevail in terms of administration, production, and complimentary antimalarial interventions.
Why is Malaria more prevalent in some regions over others?
Dr Prakash Srinivasan, an Assistant Professor at Johns Hopkins School of Public Health and expert on malaria vaccines, tells indianexpress.com that “Western states, with developed economies, have been able to eradicate malaria carrying mosquitos due to improved sanitation and other control measures like insecticides and drugs.” However, just because malaria isn’t currently prevalent in those regions, doesn’t mean that the situation will remain that way. Many strains of malaria have developed immunity to insecticides and, according to Srinivasan, “with global climate change, countries are getting warmer, and it is possible that malaria can re-emerge without proper control measures.”
Unlike in Europe and North America, countries in Asia and Africa have a long way to go before eradicating malaria. According to Srinivasan, there are a number of reasons why malaria has not been eradicated in Africa and Asia, ranging from logistical challenges to the evolution of the disease and socio-economic factors that hinder intervention.
For now, however, the problem is primarily centred around Africa, which accounts for 94 per cent of global malaria cases. This is partially because mosquitos thrive in tropical climates, where the heat and humidity increase the lifespan of the mosquito which gives the disease time to metastasise.
Malaria is primarily transmitted by Anopheles mosquitoes, which develop faster in the temperate waters found in the tropics. Given that the disease likely originated in Africa, Srinivasan also claims that mosquitos evolved in tandem with humans and thus are more resilient in those regions. Srinivas says humans have actually developed a greater resistance to the diseases in Africa. “African adults are probably bitten by several malaria-carrying mosquitos over the course of their lifespan,” he explains. “Most of them develop some sort of antibodies that protect them which is why children under the age of five, who don’t have those antibodies, are particularly vulnerable.”
Countries in Africa also have lower standards of living and poor sanitation conditions. This prevents them from implementing control measures like the use of mosquito nets, pesticides, and rapid treatment. Once the symptoms of malaria appear, it can take under 24 hours for the disease to kill its host and without access to healthcare, people in poor countries are particularly vulnerable. Lack of proper sanitation measures also mean that those countries have inadequate water management techniques, which in turn, provides breeding grounds for the mosquitos.
According to Srinivasan, because malaria is seen as a “tropical disease,” there is little impetus for industries and the governments of developed economies to research a vaccine. “Unlike Covid,” he says, “the malaria vaccine has been in trials for over 25 years.”
However, in terms of net investment, relatively little has been spent on eradication because it poses less of a risk to developed economies. Countries that have achieved at least three consecutive years of zero indigenous cases are declared malaria-free by the WHO. Thus far, only 11 countries have reached that benchmark. However, globally, the elimination net is widening. In 2019, 27 countries reported fewer than 100 indigenous cases of malaria compared to six countries in 2000.
Mosquirix
“The World Health Organization’s recommendation of RTS,S/AS01 for use as a complementary malaria prevention tool is a historic milestone in vaccine development, scientific innovation for malaria and long-term public-private partnerships,” says a representative of the Bill and Melinda Gates Foundation.
However, Srinivasan was quick to clarify that while the WHO has endorsed the vaccine, it has not yet approved it. Produced currently by GlaxoSmithKline, Mosquirix is still a long way away from being found at doctors’ offices or in pharmacies. “What the WHO has done is give a strong recommendation for its wide-spread use,” says Srinivasan, adding that the final approval will still come from regulatory agencies of respective countries.
Although researchers knew that the vaccine was effective in clinical trials for many years, questions remained surrounding its suitability in real world settings. However, since 2019, Mosquirix, has been administered to approximately one million people in Malawi, Kenya, and Ghana, three countries with high rates of malaria. The efficacy of the vaccine in those settings ranges around 30 per cent which is modest compared to vaccines designed to prevent diseases such as polio and Covid, but nonetheless significant.
When asked why this was such a seminal moment given the context of the Covid vaccine being developed so quickly and efficiently, Srinivasan explains: “First, because parasites are far more complex pathogens, malaria in particular codes for around 5000 proteins in its genome so the challenge is what do you target. For Covid in comparison there are only a handful of proteins and only one major protein on the surface. Also, the parasites have multiple forms. There are forms that are found in the red blood cells which cause the disease but there are also forms that are found in the saliva, found during the reproductive phase and so on.”
He explains that the RTS,S vaccine targets the stage of the parasite called sporozoites that are transmitted by the mosquitos. “It does so by generating antibodies to sufficient levels to prevent the sporozoite from entering the liver, the phase known as the silent phase because it doesn’t cause any clinical symptoms. Once it exits the liver, it enters the red-blood cells, causing the disease.”
The complexity of the disease makes Mosquirix ground-breaking. However, combined with the high mortality rate of malaria, the results are even more impressive.
“We should be aiming higher than 30 per cent,” states Srinivasan, but the context is relevant given that there are over 400,000 deaths annually from malaria. Even though the 30 per cent won’t translate directly into a 30 per cent reduction of deaths, it will still save tens of thousands of lives per year according to WHO estimates.
Additionally, according to Srinivasan, “getting the seal of approval goes a long way in allaying fears, especially because the current data which the WHO used as the basis of its recommendation was based on real-life evaluation of this vaccine under real-life conditions. This means that the tests were not administered in doctors’ offices but rather in conditions under which the vaccine would regularly be given, like with measles or polio.”
This in turn demonstrated that wide-spread availability could be accepted by the local populations and that bodes well for the vaccine because it shows that people understand its importance.
Challenges
Distribution will remain complicated however and given that the vaccine requires four doses spread across one year, making sure that people complete the dose will be a challenge. Additionally, there are questions over how the vaccine will be manufactured and according to Srinivasan, “licensing of this technology will be crucial, alongside distribution.”
Moreover, prevention is still more effective than treatment. Srinivasan and other experts argue that Mosquirix alone will have a limited impact unless paired with other anti-malarial strategies. Drugs and vaccines become less effective the more they are used as they give malaria parasites more opportunities to develop resistance.
Since 2000, most progress in malaria control has resulted from expanded access to vector control interventions, particularly, sleeping inside an insecticide-treated net (ITN). ITNs can reduce contact between people and mosquitos and since 2019, an estimated 46 per cent of all people at risk of malaria in Africa were protected by an ITN, compared to 2 per cent in 2000. However, ITN coverage has been limited since 2016.
According to the representative from the Gates Foundation, “while the addition of RTS,S gives countries with high malaria burden another option to consider, accelerating progress against and saving more lives now from malaria requires significantly scaling up a range of current and cost-effective tools, including improved long-lasting insecticide nets (LLINs), seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy and infancy (IPTp and IPTi).”
Another prevention tactic is the use of indoor residual spraying (IRS), which involves spraying the inside of housing structures with an insecticide, typically once or twice annually. Globally, IRS protection declined from 5 per cent in 2010 to 2 per cent in 2019, in part, because the disease was generating resistance to the insecticides. According to the WHO’s latest World Malaria Report, 73 countries reported mosquito resistance to at least one of the four commonly used insecticides in the period between 2019-2019. In 28 countries, mosquito resistance was reported to all the main insecticide classes.
Additionally, according to the report, “gaps in access to life-saving tools are undermining global efforts to curb the disease, and the COVID-19 pandemic is expected to set back the fight even further.”
Funding for malaria eradication has also decreased over the years and in 2019, total funding reached $ 3 billion against a target of $ 5.6 billion. Calling it a plateau in progress, the report states that, “in 2019, the global tally of malaria cases was 229 million, an annual estimate that has remained virtually unchanged over the last 4 years.” Progress has slowed in recent years and gaps in funding threaten to roll-back gains made since 2000, a timeframe in which malaria deaths reduced by 44 per cent.
Disruptions in the supply of anti-malarial treatment in Sub-Saharan Africa caused by Covid, could similarly have devastating effects. For example, the report finds that a “10 per cent disruption in access to effective antimalarial treatment in sub-Saharan Africa could lead to 19,000 additional deaths in the region. Disruptions of 25 per cent and 50 per cent in the region could result in an additional 46 000 and 100 000 deaths, respectively.” According to WHO global projections, the 2020 target for reductions in malaria case incidence will be missed by 37 per cent and the mortality reduction target will be missed by 22 per cent.
The Mosquirix vaccine will undoubtedly catalyse the campaign to eradicate malaria, especially amongst vulnerable populations living in Africa. However, in order for it to succeed, three main criteria must be met. First, the vaccine must be licensed to production centres across the globe, similar to how Covishield is produced by the Serum Institute of India, using a formula developed by AstraZeneca. Second, there must be parallel efforts to ramp up measures and healthcare infrastructure that will prioritise prevention and rapid treatment. Lastly, the vaccine should not deter future funding for malaria research and the global community must avoid becoming complacent in the face of this recent progress.
According to the representative from the Gates Foundation, “achieving malaria eradication will require more than the tools we have today. The first-ever malaria vaccine brings us a major step forward in our goal of developing a highly effective, all ages elimination vaccine. Additional investment in transformative tools is critical to saving millions more lives, reducing the burden on health systems and ending the disease for good.”
Written by Mira Patel
Source: Indian Express, 13/10/21
