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NEWS: WHO recommends groundbreaking malaria vaccine for children at risk

October 6, 2021 - 17:55 -- Malaria World

Historic RTS,S/AS01 recommendation can reinvigorate the fight against malaria

6 October 2021 News release Geneva

The World Health Organization (WHO) is recommending widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children in sub-Saharan Africa and in other regions with moderate to high P. falciparum malaria transmission. The recommendation is based on results from an ongoing pilot programme in Ghana, Kenya and Malawi that has reached more than 800 000 children since 2019.

“This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Using this vaccine on top of existing  tools to prevent malaria could save tens of thousands of young lives each year.”

Malaria remains a primary cause of childhood illness and death in sub-Saharan Africa. More than 260 000 African children under the age of five die from malaria annually.

In recent years, WHO and its partners have been reporting a stagnation in progress against the deadly disease.

"For centuries, malaria has stalked sub-Saharan Africa, causing immense personal suffering,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “We have long hoped for an effective malaria vaccine and now for the first time ever, we have such a vaccine recommended for widespread use. Today’s recommendation offers a glimmer of hope for the continent which shoulders the heaviest burden of the disease and we expect many more African children to be protected from malaria and grow into healthy adults.”

WHO recommendation for the RTS,S malaria vaccine

Based on the advice of two WHO global advisory bodies, one for immunization and the other for malaria, the Organization recommends that:

WHO recommends that in the context of comprehensive malaria control the RTS,S/AS01 malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO.  RTS,S/AS01 malaria vaccine should be provided in a schedule of 4 doses in children from 5 months of age for the reduction of malaria disease and burden.

Summary of key findings of the malaria vaccine pilots

Key findings of the pilots informed the recommendation based on data and insights generated from two years of vaccination in child health clinics in the three pilot countries, implemented under the leadership of the Ministries of Health of Ghana, Kenya and Malawi. Findings include:

  • Feasible to deliver: Vaccine introduction is feasible, improves health and saves lives, with good and equitable coverage of RTS,S seen through routine immunization systems. This occurred even in the context of the COVID-19 pandemic.
  • Reaching the unreached: RTS,S increases equity in access to malaria prevention.
    • Data from the pilot programme showed that more than two-thirds of children in the 3 countries who are not sleeping under a bednet are benefitting from the RTS,S vaccine.
    • Layering the tools results in over 90% of children benefitting from at least one preventive intervention (insecticide treated bednets or the malaria vaccine).
  • Strong safety profile: To date, more than 2.3 million doses of the vaccine have been administered in 3 African countries – the vaccine has a favorable safety profile.
  • No negative impact on uptake of bednets, other childhood vaccinations, or health seeking behavior for febrile illness. In areas where the vaccine has been introduced, there has been no decrease in the use of insecticide-treated nets, uptake of other childhood vaccinations or health seeking behavior for febrile illness.
  • High impact in real-life childhood vaccination settings: Significant reduction (30%) in deadly severe malaria, even when introduced in areas where insecticide-treated nets are widely used and there is good access to diagnosis and treatment.
  • Highly cost-effective: Modelling estimates that the vaccine is cost effective in areas of moderate to high malaria transmission.

Next steps for the WHO-recommended malaria vaccine will include funding decisions from the global health community for broader rollout, and country decision-making on whether to adopt the vaccine as part of national malaria control strategies.

Financial support

Financing for the pilot programme has been mobilized through an unprecedented collaboration among three key global health funding bodies: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Note to editors:

  • The malaria vaccine, RTS,S, acts against P. falciparum, the most deadly malaria parasite globally, and the most prevalent in Africa.
  • The Malaria Vaccine Implementation Programme is generating evidence and experience on the feasibility, impact and safety of the RTS,S malaria vaccine in real-life, routine settings in selected areas of Ghana, Kenya and Malawi.
  • Pilot malaria vaccine introductions are led by the Ministries of Health of Ghana, Kenya and Malawi.
  • The pilot programme will continue in the 3 pilot countries to understand the added value of the 4th vaccine dose, and to measure longer-term impact on child deaths.
  • The Malaria Vaccine Implementation Programme is coordinated by WHO and supported by in-country and international partners, including PATH, UNICEF and GSK, which is donating up to 10 million doses of the vaccine for the pilot.
  • The RTS,S malaria vaccine is the result of 30 years of research and development by GSK and through a partnership with PATH, with support from a network of African research centres.
  • The Bill & Melinda Gates Foundation provided catalytic funding for late-stage development of RTS,S between 2001 and 2015.

WHO recommends groundbreaking malaria vaccine for children at risk

Comments

Submitted by Pierre Lutgen on

The deafening media noise and tam-tam made by WHO-GSK-Gates on a new malaria vaccine for African children is alarming. It is claimed that it has a preventive efficacy of 35%, which in fact is similar to results of previous trials as documented in the film Malaria Business by Bernard Crutzen in 2016. 35% efficacy of a vaccine on Africans living in malaria endemic countries is almost meaningless. Natural immunity gained after multiple infections is probably much higher.

Peer reviewed papers even find that the efficacy vanishes with time and ultimately increases the number of infected children. The scientific literature also describes severe  side effects.                             

Clinical trials run by Africans in several countries have shown that the prophylactic activity of Artemisia afra infusions is extraordinary. In schools and communities where children drink several cups of Artemisia infusions per week malaria completely disappeared. More important, the infusion not only acts on sporozoites and merozoites but also on gametocytes, which are radically eliminated. Without transmission eradication becomes possible.

More research work should be devoted on the prophylactic effect of herbal medicine. Some recent papers indicate that the lysine content of the Artemisia plant might play a key role.

    Meireles P, Brás D, Fontinha D, Chora ÂF, Serre K, Mendes AM, Prudêncio M. Elimination of Hepatic Rodent Plasmodium Parasites by Amino Acid Supplementation. iScience. 2020 Nov 6;23(12):101781. doi: 10.1016/j.isci.2020.101781.

    Lutgen P. Prophylaxis of malaria by Artemisia infusions: The key role of lysine. Pharm Pharmacol Int J. 2021;9(5):210‒211. DOI: 10.15406/ppij.2021.09.00346

And as doctor Jerôme Munyangi stated last week : « L’histoire de la médecine africaine sera écrite par les Africains »

Submitted by Pierre Lutgen on

It is established by now that chloroquine may have contributed to the persistence of malaria in many countries. This drug is still of large use in tropical countries where ACT antimalaria drugs are too expensive. A 5-fold increase in gametocytogenesis in Plasmodium falciparum has been documented. And this renders malaria eradication by other means illusory.

           Buckling A, Read AF. Chloroquine increases Plasmodium falciparum gametocytogenesis in vitro. Parasitology, 1999, 118, 339-46

The situation also appears to be disastrous for mefloquine monotherapy. Patients treated with mefloquine had a high risk for mosquito infectivity and transmissibility. A disaster is pending for Africa. Lariam is now forbidden in several European countries and remaining stocks are sold in Africa.

         Akintunde Sowunmi, Oluchi O Nkogho , Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children. Malar J. 2009; 8: 297.

The situation is as dramatic for the RTS,S vaccine which protects only against sporozoites but does not induce clinical immunity against blood-stage parasites. The vaccine showed evidence of 35,9% efficacy in the first year after vaccination, but efficacy fell to 2.5% in the fourth year. The cohort with a high exposure index even showed a negative efficacy during the fifth year(i.e. a higher infection rate).

        A Olutu, G Fegan, P Bejon. Seven-year efficacy of RTS, S/AS01 malaria vaccine amoung young African children. NEJM, 2016, 374, 2519-2529

Naturally acquired or vaccine injected antibodies do not confer sterile immunity and the mechanisms of action are still unclear. Most studies have focused on the inhibitory effect of antibodies, but a recent paper from Uganda reviews both the beneficial as well as the potentially harmful roles of naturally acquired antibodies, as well as autoantibodies formed in malaria

        Tijani, M.K.; Lugaajju, A.; Persson, K.E.M. Naturally Acquired Antibodies against Plasmodium falciparum: Friend or Foe? Pathogens 2021, 10, 832. https://doi.org/10.3390/pathogens10070832

Another recent study discovered blocking antibodies. They are not inhibitory but interfere with inhibitory antibody activity by competing for binding to the merozoite surface. This suggests an immune evasion mechanism to avoid the action of protective antibodies. The importance of inhibitory antibodies for the clinical outcome of infection and the development of vaccines will need to be analyzed in a larger longitudinal study.   

     Roseangela I. Nwuba, Olugbemiro Sodeinde, Chiaka I. Anumudu, Yusuf O. Omosun, Alexander B. Odaibo, Anthony A. Holder. The Human Immune Response to Plasmodium falciparum Includes Both Antibodies That Inhibit Merozoite Surface Protein 1 Secondary Processing and Blocking Antibodies . ASM Journals.  Infection and Immunity.  2020 Vol. 70, No. 9 DOI: https://doi.org/10.1128/IAI.70.9.5328-5331.2002

These inhibitory antibodies had also been found in malaria-exposed Kenyan children and adults. The findings of that study suggest that variation in invasion phenotype might have evolved as a mechanism that facilitates immune evasion by Plasmodium falciparum

      Persson KE, McCallum FJ, Reiling L, Lister NA, Stubbs J, Cowman AF, Marsh K, Beeson JG. Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies. J Clin Invest. 2008 Jan;118(1):342-51. doi: 10.1172/JCI32138.

The invasion of red blood cells (RBC) by merozoites is a target for vaccine development. Although anti-merozoite antibodies can block invasion in vitro, there is no efficacy in vivo. A study found that a monoclonal antibody directed against the merozoite and human polyclonal IgG from merozoite vaccine recipients enhanced RBC invasion. These results demonstrate, contrary to current views, that complement activation in conjunction with antibodies can paradoxically aid parasites invade RBCs and should be considered in future design and testing of merozoite vaccines.

        Biryukov S, Angov E, Landmesser ME, Spring MD, Ockenhouse CF, Stoute JA. Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites. EBioMedicine. 2016 Jul;9:207-216. doi: 10.1016/j.ebiom.2016.05.015. Epub 2016 May 14. PMID: 27333049; PMCID: PMC4972486.

If antibodies introduced by a vaccine can enhance the growth of parasites, this is an efficient way for parasites to avoid getting cleared by the human immune system.