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.”

The Demographic and Health Survey Program (DHS) has been a mainstay for tracking malaria indicators in endemic countries over the past three decades. When visiting the website now, one is met with the following message, “Due to the on-going review of US foreign assistance programs, The DHS Program is currently on pause. We are unable to respond to any data or other requests at this time. We ask for your patience.” Surveys completed and published before the end of 2024 are still available to view and download, but work that wan is progress has halted.

The example of Nigeria is instructive. One finds a table on the Nigeria Country page that summarizes 25 national level health and development indicators from 1990 to 2021 using either the DHS or the Malaria Indicator Survey (MIS). A 2024 DHS survey was undertaken and a preliminary report is available, but the final detailed report was not written before the transition in administrations.

The 1990-2021 summary table included one malaria variable, children under five years of age sleeping under an insecticide-treated net the night prior to the study. Out of interest the information is posted in a chart herein. Of note, no bednet data were available for 1990. fortunately the 2024 preliminary MIS includes this.

Of note is the coverage in the context of earlier targets of 80% in 2010 and subsequent efforts to cover all children as time passed. The chart shows a slow start reaching only 29% of children by 2010 and then dropping to 17% in 2013. over the next four surveys, the coverage rate hovered in the mid 40% range topping 50% only once.

The Nigeria  National Malaria Control Program changed its name some time ago to National Malaria Elimination Program in hopes that this new moniker might lead to improved efforts. Unfortunately this was not to be the case. The value of the DHS/MIS was that countries could easily see progress and challenges and plan accordingly.

The Federal Ministry of Health, Nigeria, in collaboration with the National Population Commission (NPC) have been the local implementers of these surveys over the years. In addition to USAID, other partners such as WHO, UNFPA, The Bill & Melinda Gates Foundation, and the Global Fund have provided assistance in conducting the surveys.

Hopefully Nigeria (and other countries) and various partners will continue to see value in obtaining national and sub-national health and development statistics that document progress and help plan the future efforts to rid endemic populations of malaria and other scourges.

Bright C. Orji, Charity I. Anoke, William Robert Brieger presented a poster at ASTMH 2024 in New Orleans that analyzed the ability of national surveys to detect health program outcomes.

Intermittent preventive treatment of malaria in pregnant women (IPTp) promotes health of the mother and unborn child. One noteworthy benefit is reduction of low birth weight (LBW, less than 2.5kg). Large survey data sets aid learning about such benefits on a national scale.

We analyzed data from the 2018 Nigeria Demographic and Health Survey (DHS) to document the impact of IPTp on birth weight. Key variables included IPTp which based on national guidelines is given monthly at antenatal clinics from the 13th week, aiming to provide a minimum of 3 doses. DHS obtained this information from women giving birth in the previous two years.

Birth weight included women giving birth in the previous five years. A quarter had a record of newborn weight reported from a health facility.

Since many did not, women were also asked to estimate the size of the baby at birth: very small, smaller than average, average, larger than average, and very large. We combined the latter three categories into “average or larger”.

Of those giving birth in the past 2 years, 23% took only one dose, 24% took 2 doses, while 17% had 3 or more doses. In the broader sample of those giving birth in the previous 5 years 2.8% estimated that their baby was very small.

Among those women with a record of birth weight, 7% were LBW. Preliminary analysis comparing perceived size and IPTp doses found 3% receiving only one dose thought their baby was “very small” at birth, as did 3% of those taking 2 doses and 4% receiving 3 or more.

Among the subset with a recorded birth weight, 9% who took only one dose of IPTp had LBW baby, as did 7% who received 2 doses, and 6% who got 3 or more doses. It appears possible to compare outcomes (LBW) with interventions (IPTp), but data type and availability may limit conclusions.

Even though a smaller subset of women had access to a recorded birth weight (most women delivered outside a health facility), birth weight appears to provide a better indication of IPTp effectiveness than subjective perceptions of child’s size at birth.

The findings even with limitations show the value of national surveys to justify policies protecting pregnant women from malaria.