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.”

Jhpiego was founded in 1973 to provide technical assistance to countries where the risk of maternal mortality and morbidity was quite high.  While focusing on local capacity building from the start, Jhpiego’s model for technical assistance has evolved.  Burkina Faso first benefitted in 1983 by having health staff attend intensive training at Johns Hopkins Hospital.  Subsequently Jhpiego’s work moved to the field, and some of the early trainees became staff on the ground.

Jhpiego established an office in Ouagadougou in 1996, and one of the earliest projects focused on malaria in pregnancy as part of USAID’s flagship program “Maternal and Neonatal Health” (MNH).  It was during that time that Jhpiego collaborated with partners like CDC to do some of the early testing of the intermittent preventive treatment of malaria in pregnancy (IPTp) in West Africa.  The results of this life-saving intervention were published in the American Journal of Tropical Medicine and Hygiene.

Jhpiego continued to provide technical assistance on malaria in pregnancy interventions and capacity building to the Ministry of Health (MOH) in Burkina Faso through the MNH project and into its successor, USAID’s ACCESS project. Jhpiego worked with partners to update malaria guidelines, training materials, supervisory tools and job aids during this period.

In 2009 USAID presented the Maternal and Child Health Integrated Project (MCHIP) with the opportunity to carry out an integrated package of malaria care and prevention strengthening with the MOH and particularly the National Malaria Control Program (NMCP). Over a period of three years Jhpiego, the lead organization in MCHIP, working with together with partners from the NMCP and MOH, was able to accomplish among others the following:

• Updating Malaria policy and guidelines
• Updating Malaria supervisory tools and training of supervisors
• Updating In-service training materials on malaria and training of health facility staff
• Developing a Strategic communications plan and strategy for malaria
• Forming of curriculum update committee on malaria at national training schools for primary health staff
• Training of US Peace Corps Volunteers to support malaria activities in their communities
• Building the capacity and organizational strengthening for the NMCP itself
• Conducting a situation analysis of rapid diagnostic test acceptance and use
• Undertaking a health systems analysis of the strengths and bottlenecks of malaria program implementation in Burkina Faso

Last week, the Burkina Faso office of Jhpiego hosted the organization’s African Malaria Technical Update Workshop with staff from 15 countries participating. Today Jhpiego is taking its 40^th Anniversary celebrations to Ouagadougou.  Jhpiego will express appreciation to local partners in the fight against malaria and threats to maternal and child health.

Jhpiego has been committed on the ground in Burkina Faso to building national capacity for controlling malaria specifically for over 15 years. The recent award by USAID of its bilateral program “Improving Malaria Care” to Jhpiego last October cements Jhpiego’s commitment to the country and to reducing malaria for another five years.

Presented at Jhpiego’s Mini-University, 24 June 2013 in Baltimore by Bill Brieger, Rachel Waxman, Elaine Roman and Ousmane Badolo

Between October 2009 and March 2013, with support from the USAID Malaria Program, the Maternal and Child Health Integrated Program (MCHIP), led by Jhpiego  has worked in close collaboration with the National Malaria Control Program (NMCP) and the Family Health Directorate (MCH) to accelerate malaria prevention and control in Burkina Faso with a focus on nationwide scale up.

Scale up is defined as program coverage nationwide.  During the project years, Jhpiego provided technical and programmatic support to address comprehensive malaria prevention and control with a focus on diagnostics, treatment, and malaria in pregnancy (MIP) in Burkina Faso.  This resulted in: 2,648 health facility providers trained using the integrated malaria training package; these providers in turn, oriented 4,867 of their colleagues.

Other key components of technical support included strengthening- a) supportive supervision; b) pre-service education; c) human capacity (team building); and d) communications and behavior change guidance at national level as well as targeting communication messages to both health facility providers and clients.  Training is US Peace Corps Volunteers helped reinforce that this guidance reached front line health facilities and volunteer community health agents.

Some of the lessons learned in going to scale are balancing reaching providers en mass with quality support; ensuring a link between revised policies and guidelines and both pre-service education and in-service training; and recognizing the need for national level leadership and capacity to ensure effective implementation.

As countries accelerate and scale up their malaria programs, the lessons learned from Burkina Faso a systematic development of an integrated package of malaria policies and guidelines are important to consider moving forward.

Scientific American is known for making the latest scientific advances – from dark matter to disease management – accessible to a wide audience.  An article in the November 2010 issue on malaria vaccine progress is generally a good example. The following passage though, may simplify the history of eradication a bit too much.

In the 1960s an enormous campaign wiped out the disease in many parts of the world and drove down its number in others. But that success ultimately bred its own end. As malaria became perceived as less of a threat, global health agencies became complacent; their chief tool, DDT, was found to be toxic to birds, and they largely abandoned their efforts. Malaria numbers roared back more fiercely than before.

Two specific issues from the foregoing do not paint the full picture. First, bird deaths did not stop malaria eradication, though the toxicity issue is true in its own context. The real end of DDT was bred by mosquitoes developing resistance to the pesticide, which was discerned even before the campaign reached its height. The Lancet in reviewing Randal Packard’s book, The Making of a Tropical Disease, a Short History of Malaria, explained that …

It (the eradication campaign)was far too monodimensional, relied too much on DDT spraying, and neglected the palpable problem that the delivery infrastructure was not in place in too many parts of the malarious world. The emergence of widespread mosquito resistance to DDT, and parasite resistance to the cheap mainstay of therapy, chloroquine, compounded the difficulties.

Secondly, at least for colleagues in the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), malaria research overall did not halt. Surely the funding levels were not as high as we see today, but persistent research provided us with new tools including insecticide treated bednets, artemisinin-based combination therapy, and nearly a dozen insecticides for indoor residual spraying, for which we are thankful.

True, these additional tools do not confer permanent immunity as a vaccine eventually should, but their implementation has driven down the number of malaria deaths in many countries, and when a vaccine comes along to strengthen the toolkit, we will be farther down the long road to elimination. The malaria lifecycle is complex, and health systems designed to deliver malaria interventions is equally complex (and challenging), which means we cannot  and should not expect a magic bullet in the near future.

As Randal Packard pointed out a key lesson from the first eradication campaign needs repetition, lest we again blame it all on the birds. Aside from developing insecticide resistance, there was clear indication that the health systems in the most highly endemic areas were not able to maintain continuous IRS application.

Health systems are stronger today, due in part to recognition by partners (international and internal) that malaria cannot be controlled, much less eliminated, without health system strengthening. It is these same health systems that will also be required to deliver the new malaria vaccines, so they better be strengthened before vaccines are rolled out.

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Another short note of concern about the Scientific American article – in a box entitled “Plan B: Vaccine Alternatives” we are correctly shown that the effort to eliminate malaria has other tools that must be sustained. Unfortunately the text refers to malaria as a ‘virus’, though elsewhere in the article the stress on ‘parasite’ prevails.

If you want to walk fast, walk alone
If you want to walk far, walk together  (Maasai Proverb)

Walking together in partnership was the theme of the launching, held last night, of Kenya’s second national malaria strategy covering the years 2009-2017.  Officials from the Ministry of Public Health and Sanitation acknowledged throughout the ceremony the value of  partnership with the donor, research and civil society communities.

The document had been one year in the making and is accompanied by the Kenya Malaria Monitoring and Evaluation Plan for the same years. Dr Elizabeth Juma, who heads the Division of Malarial Control explained that the two documents are based on an extensive Malaria Program Performance Review, so that it is not a theoretical exercise.

In his keynote address Dr. James Gesami, the Assistant Minister for Public Health and Sanitation, reported that Kenya has made substantial progress in reducing child mortality and hospital admissions for malaria by to date distributing 90 million nets, prescribing 41 million doses of ACTs and protecting 8 million people in targeted areas with IRS.

A new feature of the strategic plan is to make future targeting of these interventions more epidemiologically appropriate based on a new map of malaria prevalence across the country. Dr Gesami said we have fallen short in the past of adequate documentation. Therefore, M&E is intended an a strong companion to the Strategy so that intervention can be monitored and impact measured.

Partnership at all levels was seen as the way to achieve the goals of the new strategy – involvement is needed of the public health sector, the private health sector, civil society, research institutions, donors, the communities and other public and private sector agencies such as agriculture and education. An example of the latter is the malaria free schools initiative enshrined in the Strategy. In short, “Malaria control is not the preserve of the Health Ministries, but is the responsibility of all of us.”

Speakers acknowledged that there are areas where past performance could be better, such as providing Intermittent Preventive Treatment to pregnant woman. There was hope though that the Strategy will guarantee a uniformity of purpose among all partners to achieve targets and result in a malaria free Kenya by 2017.