Tropical Health Matters

Malaria is one of the more than 30 diseases and conditions included in the Elimination Initiative and targeted for elimination in the Region of the Americas by 2030. Colombia provides a useful example of the progress and challenges. Of the over 72,000 reported malaria cases in 2022, About 61% were caused by P. vivax, 38% by P. falciparum, and 1% were mixed. The Ministry of Health explains that unlike other South American countries, the most malaria endemic regions are not in the Amazonian forest but lie in the northwest of the country in the Pacific coastal forests, populated by Afro-Colombian and indigenous communities.

The Ministry also notes that malaria transmission is characterized by the presence of epidemic cycles that occur every 2 to 7 years, related to the occurrence of the Niño-Southern Oscillation phenomenon. Malaria control is particularly challenging in provinces where illegal mining, logging and the growing of illicit crops are conducted. The World Malaria Report of 2023 traced annual malaria trends in Colombia and showed a peak in 2018-19 with a reduction in subsequent years that points toward efforts at elimination

The International Rescue Committee identifies a particular challenge for Colombia. At least 4 million Venezuelans have crossed the border to seek refuge, and that number continues to rise. Venezuela continues to be plagued by malnutrition, lack of medical supplies, high homicide rates and the spread of diseases such as malaria and measles. Since outbreaks of measles, diphtheria and malaria have been reported across Venezuela, it would be surprising that refugees would enter Colombia with malaria infections.

A study of malaria among migrants in a university hospital in Colombia during 2018 found that imported malaria has increased in Colombia since 2015 and has been attributed to migrants coming from Venezuela. To address the challenge, we need to know where are the refugees? Regular migration is usually located in the main cities and in places where tourism or the mining industry are active. Many of the destinations are in areas where malaria is not endemic, onward transmission would be less likely. Unfortunately, the following migration destinations overlap with malaria transmission: Nariño, Antioquia, Cundinamarca, Cauca, and Chocó, such that those migrants can acquire new infections.

The challenge is that as Colombia makes progress toward eliminating malaria, it still must maintain high capacity to tackle imported cases as well as new cases among a particularly vulnerable refugee population.

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 United States has been assisting in the fight against malaria and tropical diseases throughout the tropics. The question now arises is it ready to tackle these diseases on the home front?

In recent months CBS News reported that “Malaria cases in Florida and Texas are first locally acquired infections in U.S. in 20 years,” according to CDC. Local transmission of these 8 cases is the key concern because there are always imported cases from travelers to malaria endemic areas throughout the year. This has led to better planning of mosquito control activities. All of the Florida cases were found in Sarasota County. Although Anopheles mosquitoes still existed in the environment, they had not been infected in recent years.

Likewise Pensacola News Journal noted that, “Rising evidence is pointing to the possibility that leprosy has become endemic in the southeastern U.S. with Florida being named among the top reported states.” The paper explains that these Leprosy cases in central Florida account for nearly 20% of the national total, and that the state is considering instituting contact tracing.

Chagas disease may affect up to 300,000 people from Florida across to California, but an Emerging Pathogens Institute report shared in the Apopka Voice, explained that most cases remain undetected. While Chagas primarily affects people who have immigrated from Latin America, researchers are discovering locally acquired cases because the vector, the kissing bug, has been found in 29 states, and thus local transmission now occurs.

An article in PLoS NTDs explains that Zika, Dengue, and Chikungunya viruses are spread in the southern and Gulf Coast states by members of the Aedes mosquito family, aided by changes in weather and climate patterns. Just as in other countries where NTDs are endemic, the US experience of these diseases also sees that, “poverty equates to substandard housing that exposes residents to insect vectors, a lack of access to sanitation and water, and degraded environments.”

Local, State and National health agencies in the US are starting to awaken to the fact that diseases which we thought were eliminated back in the mid-19^th-century are making a comeback. At a minimum, funding and training are needed to equip our Health Departments with environmentally appropriate vector control measures, appropriate treatment regimens, and disease surveillance tools to tackle the same problems that are threatening the lives of people throughout low- and middle-income countries throughout the world.