Tropical Health Matters

Professor Jane Carlton, PhD, Director of Johns Hopkins Malaria Research Institute was introduced by Dean Ellen MacKenzie to give a Dean’s Lecture entitled “Malaria: History, current status, and the promise of ‘omics and AI.”

Prof. Carlton first gave an overview of JHMRI, which was founded in 2001. She stepped into director role in 2023. She started with the encouraging premise that AI and ‘omics can supercharge our research and pointed out the power of comparative genomics on understanding parasites and disease. Her goal is to translate discovery into real world impact through collaborations.

The talk started with a brief malaria history. Malaria was described as an ancient disease and remains one of top infectious diseases worldwide. There were 2.63 million cases and more than half a million deaths in 83 endemic countries in 2023. Today 44 countries are malaria-free.

Up until now, Prof. Carlton noted, the malaria map has been shrinking. There was a precipitous decline in malaria in India from 23 million cases to 2 million. The disease is a true humanitarian issue with a large impact on people living in resource-limited settings where housing is basic and offers no protection from mosquitoes.

The JHMRI is supported by Bloomberg philanthropies, and from that base faculty research examines, among others, better methods for controlling mosquitoes (see slide), new diagnostic tests and therapeutics, and the next generation of vaccines. Key assets to support research include mosquito insectaries and a malaria parasite core. The insectaries produce 60,000 mosquitoes per week, and with these it is possible to complete the life cycle in the laboratory.

Continuing education is another important function of JHMRI which has three conferences per year including the upcoming World Malaria Day 2025 symposium. One can also learn from the Malaria Minute podcast. The upcoming “Vector Encounter” provides sharing and learning for researchers.

JHMRI studies malaria at field sites in Africa and Asia where country collaborators are partners. Emphasis is on local capacity building in countries like Zambia, Ethiopia, Kenya, and Uganda. Researchers and the national malaria control programs in these countries work hand-in-hand.

JHMRI is involved in developing the next generation of vaccines. One approach if a human monoclonal antibody that prevents malaria infections. Another develops a vaccine that transcends’ malaria parasite strains with structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies. A third example asks “How many parasites does it take to cause malaria?” and assesses infection likelihood through mosquito parasite burden.

To understand the theme of her talk, Prof. Carlton reviewed the promise of ‘omics and AI in the context of her work at a center of excellence in India. Pioneering work using Malaria camps in hard-to-reach villages in Odisha, India. The main activities mobilized villagers to gather for mass screening, treatment, education, and intensified vector control. From there, Indoor Residual Spraying was planned and insecticide treated bednets were distributed. Other maternal and child health activities were incorporated. After three rounds/visits in the remote villages a great drop of malaria cases was seen. WHO lauded the camps.

In addition to lessons about the importance of surveillance, mixed strategies, and community mobilization for controlling malaria, the team learned about the growing challenge of reduced effectiveness of Rapid Diagnostic Tests. The problem arose because tests were dependent on a protein that was no longer being expressed due to Pfhrp2 gene deletions, leading to false negative test results. The team was encouraged to identify more proteins to find a more stable and central one to use in testing. Through machine learning, this work is ongoing but promising.

While we are on the verge of several research and programmatic breakthroughs, Prof. Carlton reminded the audience that we are in calamitous times. She recalled that the United States has been the top donor government to malaria efforts through Presidents Malaria Initiative and Global Fund to Fight AIDS, Tuberculosis, and Malaria. PMI was founded in 2005, and has contributed to a decline in malaria death rates of close to 50%.

With suspension of funding, an estimated increase of 12.5-17.9 million malaria cases and 71,000-166,000 malaria deaths are expected this year. Already there are serious impacts on the supply chain for major malaria commodities as estimated by the Roll Back Malaria Partnership as seen on their RBM dashboard and supply chain gap estimates where six endemic countries have less than a 3-month supply of RDTs and eleven have less than a 6-month supply.

Prof Carlton ended by saying, “I think the hope is in science, right? The hope is in research. There are definitely new initiatives, new tools which are coming to the forefront, some of which I mentioned, and several of which we’re developing here at the malaria Research Institute. I do know the World Health Organization has got together with other countries to provide additional funding and support for those countries who have lost support through PMI.”

In the lead up to World Malaria Day 2025, the Johns Hopkins Malaria Research Institute held an Expert Briefing for the Media to discuss  the Global State of Malaria: New Research, Evolving Risks, and Silver Linings. The session was moderated by Ellen Wilson.

The two experts included Jane M. Carlton, PhD, director of the Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health and a Bloomberg Distinguished Professor in the Department of Molecular Microbiology and Immunology at the School and George Dimopoulos, PhD, MBA, also a professor in the Department of Molecular Microbiology and Immunology.

The speakers discussed and responded to questions regarding the current state of malaria, the need for global commitment to malaria prevention, control, and research, advancing diagnostics and therapeutics, current mosquito vector control methods and their limitations, and the need for an integrated approach to malaria control. As an overview, attendees were told that malaria is a mosquito-borne disease that in 2023 took nearly 600,000 lives in 83 countries, the majority being children under age 5 years in the WHO African Region.  In the U.S., the risk of contracting malaria remains low; however, continued vigilance is needed to prevent increases in both domestic cases from foreign travel and as occurred in 2023 for the first time in 20 years, locally transmitted cases.

Jane Carlton expressed concern that malaria cases had increased from 2022 to 2023, but was hopeful because of innovations such as vaccines, and genetically modified mosquitoes. One could also draw hope from efforts to establish local manufacturing capabilities in endemic countries, including partnerships for African vaccine development and production. And in fact, she noted, in 2022, “one company in Kenya became the first African-based manufacturer to receive WHO pre-qualification for a malaria drug. There is a second Nigerian manufacturer that is making progress.” There are several research organizations and universities in African countries that are working towards new drug and intervention development. Studies are ongoing perhaps to use some local plants as anti-larval treatments.

Prof. Carlton explained that the burden of malaria in India has reduced dramatically. “There’s been about a 70% reduction in cases from just over 6 million in 2017 to 2 million in 2023,” although two million cases is still quite a large number.

Prof. Carlton was also asked about the effect climate change on malaria transmission and the potentially expanding the geographic range of malaria. How are researchers adapting? She observed that, “Yes, that’s a very interesting question. In fact, it goes against intuition in a way but increasing the temperature doesn’t always increase the number of malaria cases. The malaria parasite and the mosquito that carries operate within quite a tight temperature range.

In reality, it can get too hot, but as some areas get wetter and formerly cool areas become warmer due to climate change, malaria transmission can move to new locations. “So, there is an increasing shift and an increasing understanding that surveillance of this particular issue is important,” especially needing to monitor climate contexts. For example, scientists have looking at the invasive Anopheles stephensi, which is severely disrupting activities of National Malaria control programs.

There’s been an analysis from the Oxford Malaria Atlas Project, or MAP, and they have projected that with a freeze for one year of PMI activities, this would result in up to 18 million additional malaria cases and up to 107,000 additional malaria deaths. This represents an increase in morbidity of 13%. This would occur in PMI’s focus geographies across 27 African countries. This analysis doesn’t account for the additional impact of PMI supported diagnostics.

Prof. Carlton observed that “globally, total investments in malaria control reached an estimated $4 billion in 2023, but this already fell short of the $8 billion funding target” of the World Health Organization Roll Back Malaria Partnership.

George Dimopoulos stressed e importance of community engagement in vector control activities. He explained that malaria is one of the diseases of poverty where the poor are disproportionately at risk and impacted. He then responded to a question about gene-drive technology based on the

CRISPR-Cas9 system that can spread mosquito genes in natural populations. “This has advanced very significantly in mosquitoes over the past roughly 10 years.”

Prof. Dimopoulos explained that gene-drive “can also work in all malaria vector species. In this way it becomes a malaria control strategy that could work in all malaria endemic areas.” Prof. Dimopoulos’ team has also done research on the effects of sugars and micro-organisms on the mosquito gut and malaria transmission. “We have shown through our research that the health of the mosquito gut depends on a protein quality control system. With appropriate control interventions, “The mosquitoes become very sick and a large proportion of them will actually die.”

In conclusion, the “Silver Linings” mentioned in the session’s title include advances in both parasite and vector control. Deployment of two malaria vaccines offers one ray of hope. New vector control technologies such as gene-drive, offer another. The speakers encouraged people to attend the upcoming JHU-MRI Malaria Day conference to learn more.

The RBM Partnership to End Malaria has developed a communication kit to help plan for the upcoming World Malaria Day on April 25th. Below are some of the highlights and links they have shared.
To mark World Malaria Day 2025,  the RBM Partnership to End Malaria in collaboration with World Health Organization (WHO) have developed a Messaging Framework and Social Media Toolkit to support partners and individuals in raising awareness and advocating for a malaria-free world.

Objectives for this year include…

• Re-energize efforts at all levels, from global policy to community action, to accelerate progress towards malaria elimination
• Advocate for increased investment in malaria control and elimination programs, including through stepped-up domestic financing and successful replenishments for the Global Fund and Gavi in 2025.
• Promote innovative strategies and approaches to tackle evolving challenges in malaria
• Prioritize country ownership, actively engage communities, and implement data-driven strategies

The emphasis is on three pillars. First in REINVEST, which recognized that “Malaria control and elimination programs don’t just save lives – they’re also a smart economic investment for malaria-endemic countries and their international partners.”

The second pillar calls on us to REIMAGINE. We must Accelerate innovation by investing in the research and development of new and more effective antimalarial drugs, diagnostics, insecticides, vaccines and vector control methods” and turning that research into action.

The third pillar is a call to REIGNITE based on “a renewed sense of urgency and commitment is needed to accelerate the fight against malaria.” This is called the “Big Push against malaria (and) is a multistakeholder effort to drive progress.”

Follow the links to learn more and plan action.

World Malaria Day 2023 is focusing on three key themes, Investment, Innovation, and Implementation, the 3 I’s. The recently approved malaria vaccines and those still under development embody these themes fully.  They all represent decades of investment in innovation, research, and now implementation.

After extensive several decades of clinical research and three years of field implementation in Ghana, Malawi, and Kenya by the World Health Organization and National Malaria and Immunization Programs, the RTS,S/AS01 malaria vaccine is being rolled out with assistance of GAVI, the Global Vaccine Alliance. During the malaria vaccine implementation program (MVIP) and also based on GAVI’s philosophy for vaccine programs generally, a key strategy was to provide RTS,S as routine immunization services alongside other essential services including a comprehensive package of malaria control and elimination interventions. RTS,S is not only being made available to the three MVIP countries, but as supplies come on board, other falciparum malaria endemic countries have started to apply for supplies and funding through GAVI.

It was well known from the beginning that although RTS,s might be first out the gate, other vaccines would be following closely on its heels. The benefits as well as the efficacy limitations of RTS,S were well known.  Therefore, talk was common for new products being available by 2026. Now in 2023, countries have started to move ahead on another vaccine candidate.

BBC reported that “Ghana is the first country to approve a(nother) new malaria vaccine that has been described as a ‘world-changer’ by the scientists who developed it.” R21 appears to be more effective than its predecessor, so Ghana’s drug regulators moved ahead quickly using final trial data on the vaccine’s safety and effectiveness, which is not even public, to approve it. Interestingly, this move is in parallel to the World Health Organization’s consideration of approving the vaccine.  Shortly thereafter, Nigerian medicine regulators also approved R21. Reuters noted that these “approvals are unusual as they have come before the publication of final-stage trial data for the vaccine.” The actual roll out will ultimately depend on official publication of the safety data and sourcing of funds.

As mentioned above, these malaria vaccines represented considerable investment of time and resources, embody the kind of innovation that is needed to tackle malaria as drug and insecticide resistance threaten progress toward elimination, and require detailed planning right down to the grassroots levels to ensure that a malaria vaccine delivery is part of a comprehensive package of malaria and child health services.

We need to return to the theme of investment. While international organizations, universities, ministries of health, and of course pharmaceutical companies have been investing in developing a safe, effective, and feasible product, these innovative products will not save lives until funds are invested for both purchase and service delivery are guaranteed. GAVI and Partners have put together over $200 million in support for RTS,S implementation for three years. The first window was open in September 2022 for the initial three MVIP countries, and a second window for others, depending on available supplies was open in December 2022.

Investment FOR implementation is a challenging subject because GAVI and collaborating agencies are not a bottomless well of money. What level of national investment by a country to protect its own children is feasible? Is there the national political will to contribute and invest in children in endemic countries, and not continue depending heavily on donors?

Malaria vaccines are a perfect example of what the 3 I’s can achieve. But beyond celebrating this addition to the malaria elimination toolkit, will we also be celebrating commitments by endemic countries of local funds to make zero malaria a reality?

In 2001 the first Africa Malaria Day (AMD) was observed. The opportunity to mark progress and exhort increased efforts for the continent continued through 2007. Then in 2008, the concept of World Malaria Day (WMD) took over, though it could not be denied that the bulk of malaria morbidity, mortality and intervention still was focused on African countries. Other countries have made progress such as the recent certification of malaria elimination in Argentina and El Salvador, but twenty years after the first AMD/WMD, Africa is still leading the way for creative, sustained intervention against the disease, despite threats to resources from economic downturns and new pandemic diseases.

Below we go straight to Africa to share activities and observances of WMD 2021 from Jhpiego’s African Malaria Technical Officers. After reading through, please watch “Jhpiego Leaves No One Behind | World Malaria Day, 2021″ on YouTube.

“Saramed” from Guinea reports that Guinea, like other countries in the world, celebrates World Malaria Day under the theme: ” Zero Malaria, Draw a Line on Malaria “. We are currently conducting the following activities:

• Lectures and debates on malaria in medical faculties and health schools;
• Animation of debate programs on malaria in public and private radios and televisions of the country,
• Advocacy and sensitization of religious and other influential people
• Carrying out a package of activities (administration of IPT to pregnant women who have missed their ANC appointment, community distribution of LLINs, screening and treatment of confirmed cases, awareness raising on malaria) in high incidence localities.

These activities is in line with the WHO approach of “high burden, high impact”.

Noella Umulisa reports that the WMD celebration took place in Eastern Province, in Bugesera district in the Mareba sector. Due to COVID-19 pandemic ,only 100 persons were invited to the event.This year’s the national theme is “Zero Malaria starts with me”.

Key activities during the event included …

• Visit of breeding sites under sentinel surveillance
• Visit of indoor residual spraying (IRS) sites
• Launching of the Awareness of the population using drones on the ongoing IRS campaign in this time of COVID-19
• Song by CHWs
• Certificate to Integrated Vector Management (IVM) Training of Trainers who will train others up to village level
• Speech of the Director General ,the guest of honor.

From Burkina Faso, Yousseff Sawadogo and Moumouni Bonkoungou shared photos of the celebration that featured a giant Insecticide-Treated  Net, a speech by the US Ambassador, a malaria song composed by a nurse, an official speech by the President of the National Assembly, and national recognition given to one of the current Jhpiego staff members, Thiery Ouedraogo, who at one time also served as director of the national malaria control program. He was decorated by the country’s authorities as a knight of the order of merit.

Bright Orgi from Jhpiego’s TiPToP malaria in pregnancy project in Nigeria ?? shared photos from a series of compound meetings in the community to mark WMD 2021. The meetings focused on malaria prevention and treatment. Provided opportunities to rural communities to ask questions on malaria issues. Here we can see that observance of WMD must be taken to the people who actually suffer from malaria and need to be actively involved in its solution. Deo Cibinda from the Democratic Republic of the Congo share photos of a national celebration, seen to the left.

Finally, As Kristen Vibbert noted, “These are such amazing World Malaria Day stories. I’m so heartened to see all of these great country efforts to remind everyone of how the fight against malaria must continue despite the Covid-19 pandemic.”  Charles Wanga tweeted, “We know how to defeat #malaria. But that’s not enough. We must do more to save pregnant women and children from the deadly scourge. This #WorldMalariaDay and everyday, because@Jhpiego leaves no one behind in our fight to #EndMalaria for good in Africa, and everywhere”