Core Skills — 11 August 2024 at 2:40 pm

Clinical Update: Malaria Prevention and Vaccination 2024

Dr Tom Everett and Dr Constance Osborne

Public Health England (PHE) have published updated guidance on malaria prevention for travellers from the UK. You can read the full guidance via this link.

Here are some take home messages:

A  Avoidance of travel to malarious areas if the person is at high risk of severe or fatal malaria. For example pregnant women, children, the elderly, people without a spleen and those with complex comorbidities or immunosuppression.

B  Bite prevention. Reducing the number of bites you receive reduces your chance of developing Malaria.

  • Full-length, loose-fitting clothing and socks.
  • Particular caution at dusk and dawn.
  • Screening of doors and windows.
  • 50% DEET (N,N-Diethyl-meta-toluamide) based insect repellent is first line on exposed areas of skin. This should be applied after sunscreen. Alternatives to DEET are available including Icaridin and IR3535.
  • Bed nets. The World Health Organisation (WHO) have made strong recommendation that pyrethroid-only long-lasting insecticidal nets (LLINs) should be deployed for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission. Pyrethroid-chlorfenapyr insecticide treated nets (ITNs) should be deployed instead of pyrethroid-only LLINs for prevention of malaria in adults and children in areas with pyrethroid resistance.
  • Indoor residual spraying (IRS). The WHO also makes recommendation for IRS where certain listed requirements are met, including that people mainly sleep indoors at night.
  • If electricity is available, an electric pyrethroid vapouriser or coils can be used.

C Chemoprophylaxis should be prescribed based on an individual risk assessment. Consider the need for standby emergency medication if a person will be in a remote area. This is not a replacement for chemoprophylaxis, it is an adjunct.

D Diagnose promptly and treat without delay. The WHO Global Malaria Programme will be the focus for malaria control and elimination. The key message is Test, Track and Trace.

Vaccination

Despite research since the 1960s, the international community has struggled to produce a malaria vaccine. This was partly due to the complexity of the life cycle of Plasmodium and its high mutation rate, but more importantly the long-standing lack of urgency and funding behind malaria research in general. In 2015 the final results from breakthrough Phase III trials were published in the Lancet; they showed that children from 5 to 17 months old who received three doses of the RTS,S/AS01 (RTS,S) vaccine plus a booster, would have a 29% reduced risk of severe malaria.

In 2019, the WHO introduced a pilot implementation of malaria RTS,S vaccine in Malawi, Ghana and Kenya. Four years on, over 6 million doses of vaccine have been administered through the Malaria Vaccine Implementation Programme (MVIP), coordinated by WHO and funded by Gavi, the Vaccine Alliance, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and Unitaid.

Demand is very high for the first malaria vaccine, RTS,S, recommended by WHO for the prevention of Plasmodium falciparum malaria in children living in regions with moderate to high malaria transmission. It is the first licensed vaccine against human parasitic disease. Also known as Mosquirix, the vaccine is given to children aged 6 weeks to 17 months to protect against malaria caused by Plasmodium falciparum.

It consists of two parts. The first is a recombinant protein which is normally secreted by the Plasmodium parasite during its sporozoite phase; this is the phase in which the parasite enters the human body from the mosquito. This protein is combined with the surface antigen of the hepatitis B virus (HBsAg) to form a soluble, virus-like particle. The second part of the vaccine is an adjuvant chemical which helps to boost the immune response.

Impact and evidence supporting RTS,S malaria vaccine

  • Pilot introductions resulted in a 13% drop in mortality among children age-eligible for vaccination and substantial reduction in severe malaria.
  • Estimated 1 life saved for every 200 children vaccinated.
  • Phase 3 trial (2009-2014) of vaccine showed malaria cases dropped by over half in the first year after vaccination and a 40% reduction in malaria episodes over 4 years of follow up.
  • Phase 3 trial (2017-2020) of vaccine provided just prior to peak malaria season in areas with highly seasonal malaria found vaccine efficacy similar to efficacy of Seasonal Malaria Chemoprevention (SMC), shown to prevent around 75% of malaria cases.
  • Safety demonstrated after nearly 4 million vaccine doses given to more than 1.2 million children

The RTS,S vaccine is prequalified by WHO. Gavi is investing an initial nearly $USD 160 million for broader vaccine roll-out in endemic countries (2022-2025). Click this link to explore the Framework by which vaccine doses are being allocated.

Further Vaccination

In July 2022, Gavi, the Vaccine Alliance, opened a funding window to support Gavi-eligible countries in rolling out this vaccine and other malaria vaccines as they become available. Since then, over 28 countries expressed interest. Fourteen applications, submitted to Gavi by countries in the first two application opportunities, were recommended for approval by Gavi’s Independent Review Committee (IRC) following the standard Gavi processes. The available vaccine supply for the period 2023-2025 is currently limited to 18 million doses.

WHO has added the R21/Matrix-M malaria vaccine to its list of prequalified vaccines, recommending it’s use in October 2023. This prequalification allows vaccine procurement by UNICEF and funding support for deployment by Gavi, the Vaccine Alliance. This second malaria vaccine is approved by WHO for widespread use for the prevention of malaria in children following the advice of the WHO Strategic Advisory Group of Experts (SAGE) on Immunization and the Malaria Policy Advisory Group. It has been shown to have high efficacy when given before the high transmission season and in an age-based schedule. This new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Further reporting on safety and efficacy of the vaccine in a phase 3 trial enrolled over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites.

WHO currently recommends the programmatic use of malaria vaccines for the prevention of P. falciparum malaria in children living in malaria endemic areas, prioritizing areas of moderate and high transmission. This now applies to both RTS,S/AS01 and R21/Matrix-M vaccines.

There has not yet been a trial that directly compares the RTS,S and R21 vaccinations, yet both have demonstrated good efficacy and will tackle the fact that demand outweighs supply for these life-saving vaccines. Both vaccines are shown to be safe and effective in clinical trials, for preventing malaria in children. When implemented broadly, along with other recommended malaria control interventions, they are expected to have a high public health impact.

Climate

Each year, WHO’s World malaria report provides a comprehensive and up-to-date assessment of trends in malaria control and elimination across the globe. This year’s report includes, for the first time, a dedicated chapter focused on the intersection between climate change and malaria. Malaria places a particularly high burden on children in the African Region, where nearly half a million children die from the disease each year. Globally, in 2022, there were an estimated 249 million malaria cases and 608 000 malaria deaths across 85 countries.

Climate variability, such as changes in temperature and rainfall, can impact the behaviour and survival of the malaria-carrying Anopheles mosquito. Extreme weather events such as heatwaves and flooding may lead to increases in the transmission and burden of the disease.

A changing climate has indirect effects on malaria, too. As an example, population displacement may lead to more malaria as people without immunity migrate to endemic areas. Climate variability has also led to malnutrition in many places, a risk factor for severe malaria among young children and pregnant women.

WHO World malaria report conclusions

Last year, 49 million children were reached with seasonal malaria chemoprevention in 17 African countries, up from just 170,000 in 2012. Additionally, a new generation of dual-ingredient insecticide-treated bed nets, recommended earlier this year by WHO, has been shown to have greater impact against pyrethroid-resistant mosquitoes compared to standard pyrethroid-only nets.

Meanwhile, the goal of malaria elimination has been achieved in a widening circle of countries. This year alone, three more countries were certified by WHO as malaria-free: Azerbaijan, Belize, and Tajikistan. Several others are on track to eliminate the disease in the coming year.

These and other advances are a testament to both national commitment and global resolve to control and eliminate the disease. However, amid extreme weather events, scarce resources and a growing number of biological threats, there is still a long way to go to achieve our vision of a world free from malaria.

A substantial pivot with much greater resourcing, data-driven strategies and new tools is needed to rebuild momentum in the fight against malaria. With the added threat of climate change, sustainable and resilient malaria responses are needed now more than ever.

References