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 World Health Organization has prepared an important document entitled “Health is the Argument for Climate Action: COP29Health is the Argument for Climate Action: COP29 Special Report on Climate Change and Health”. Malaria and other vector borne diseases are highlighted.

The report addresses diseases carried by mosquitoes by stating that, “Climate change increases the transmission of deadly infectious diseases such as dengue, malaria, West Nile virus” and others which are temperature and rainfall dependent. In particular, malaria transmission is intricately connected with temperature and rainfall patterns, and extreme weather events have been shown to cause rapid spikes in cases.”

Climate change not only effects environmentsClimate change not only effects environments where these diseases thrive, but impacts the livelihoods of populations, reducing their ability to pay for prevention and treatment. Migration and displacement also may result increasing vulnerability to disease.

Two of the report’s recommendations have special bearing on malaria. One is the need to “develop and implement innovative financing mechanisms, such as a global health insurance scheme for climate-vulnerable nations” and communities. A second is the importance of “Strengthen(ing) health surveillance systems, particularly in low-income countries, to better track and respond to climate-related health impacts.”

Recognizing the climate dependence of malaria will be a crucial step in eliminating the disease.

As President Jimmy Carter nears his 100th birthday, his opponent of nearly four decades, guinea worm disease, is nearing its end. By emphasizing the importance of data and surveillance, the Carter Center has found no reported cases in the first three months of 2024, and only 14 cases in 2023.

The effort to eliminate the disease has been approaching zero annual cases for a decade, but the remote settings where the worm is found coupled with civil strife have made this water borne pathogen a challenging opponent. The remaining cases have been confined to Sahelian countries where clean water is always in short supply and is more serious now with climate change. To add to the challenges, domestic dogs that share seasonal ponds with their humans have also become a reservoir of guinea worm in places like Chad.

The coming months will provide crucial evidence on elimination progress in these countries where the advent of the rainy season when small ponds begin to fill and the small crustaceans that serve as vector or intermediate for the worm larvae emerge. This is a time in which people who might have swallowed the infected crustaceans from local ponds last year may experience the emergence of a subcutaneous worm that may have been growing for the past year. Hopefully 2024 and President Carter’s 100th year will mark the end of guinea worm either with no new dates, or if a few do emerge, they are quickly identified and contained so the affected person does not enter a water source with an open ulcer.

Lack of safe and clean water remains a serious problem throughout the region and always poses a threat for the reintroduction of guinea worm in the 200 countries that have already certified elimination. Progress for human development demands that we continue the fight for safe and reliable water even after there is no more guinea worm.

The 2024 World Malaria Day Theme of “Gender, Health Equity, and Human Rights” cannot be divorced from the inequities of climate change wherein the countries that contribute the least to the problem suffer the most, including the deleterious effects of changing malaria geographics. The current severe drought in Zambia, Zimbabwe, and Malawi is a case in point.

As a recent headline in VOA news states, “UN officials in Zambia to assess worst drought in 20 years.” The government has declared a drought officially where it “has affected a total of 8 provinces across the country with highest impacts in Southern, Central, Eastern, North-western, Western, and Lusaka Provinces.”

Drought should not be confused with a “normal” dry season. What we are seeing in Southern Africa now is an extended dry period in what should have been the rainy season. A study in Mali suggests that adult malaria-carrying mosquitoes “have endured the dry season by aestivating—the hot-weather equivalent of hibernating.” Unfortunately, an extended dry period of a drought may be more difficult to endure for the adults, but possibly the eggs are more resistant. Additional studies paint a more complicated picture.

Weather cycles intensify with climate change. El Niño, which can lead to droughts also produces warming in higher elevations so there tends to be an increase in malaria transmission in areas in the highlands.

Research in Zambia published just two years ago reported increasing trends of malaria in areas covering over 47% of all health facilities, while a declining trend was seen in areas covering 27% of health facilities. The decreasing trend was noticeable in the south, where malaria risk is lowest, and current drought conditions higher. The authors stress the need for continued geographic surveillance and implementation of control strategies geared to the conditions in each area.

A systematic review of the effects of climate change identified “vector borne disease (including malaria, dengue and West Nile Virus)” as a major concern as well as “nutrition-related effects (including general malnutrition and mortality, micronutrient malnutrition, and anti-nutrient consumption),” which compromises the ability of children to fight disease. The review found different impacts of drought ranging from increase mortality a year after a drought, to the disappearance of some vector species. The lesson is that each country needs to monitor their situation carefully. For Zambia, UNICEF reports that, “significant number are children, at risk of food insecurity, acute malnutrition, and disease.”

Research on drought effects on malaria arose from a study that examined the effects of drought on malaria infection (genetic) complexity and transmission in lizards (Plasmodium mexicanum and Sceloporus occidentalis). The authors noted that, “relationship between rainfall and parasite prevalence is somewhat more ambiguous.” Thus, the authors recommended that more information is needed about human malaria parasites and drought since “drought may cause shifts in human disease outcomes independent of any changes to prevalence.”

The United Nations challenges us by observing that, “Due to the complex relationship between malaria and climate change, gaps in knowledge still exist in the mechanisms of the linkage.” Changes in temperature, rainfall, and humidity need to be monitored for effects on vectors, parasites, and human movement. The current situation requires a more nuanced and complex approach to interventions if malaria elimination can be achieved while also preventing gender discrimination, promoting health equity and preserving human rights.

Almost 40 years ago efforts got underway to eradicate another human infectious disease from the face of the earth. Smallpox eradication. Defined as the total elimination of the disease from every country, had been successful, facilitated by the basic technology of an effective vaccine. There were difficult times with the organization and management aspects of smallpox eradication, but the organizers of the campaign were able and willing to adapt their strategies as they learned more about the epidemiological, social, and cultural aspects of the disease.

Praise has been given to guinea worm efforts because of the start contrast between 3.5 million cases in the mid-1980s to only 13 so far verified in 2024. Interestingly, progress has been inching, as one author put it, toward zero for at least 10 years, long after the earlier target date of 1995. Clearly a disease that was theoretically “simple” to eliminate through the provision of clear, safe water supplies, was not so simple after all.

Despite his recent health and family challenges President Jimmy Carter has never waivered from his support to eradicate guinea worm as reported by CNN.  The Carter Center’s 2023 report showed a remarkable reduction in Guinea worm cases, bringing the ancient parasitic disease closer to being eradicated.  Alix Boisson-Walsh provides details in a Lancet Infectious article entitled “Diseases Guinea worm disease inched closer to eradication in 2023.”  The Carter Center shared these highlights for 2023:

• Eradication of Guinea worm disease remains in sight with only 13 provisional human cases reported worldwide in 2023.
• The Carter Center announced Thursday. The number matches the lowest annual total of human cases ever reported, following 13 cases in 2022 and 15 in 2021.
• When The Carter Center assumed leadership of the global Guinea Worm Eradication Program in 1986, an estimated 3.5 million human cases occurred annually in 21 countries in Africa and Asia.

• The grisly parasitic disease has been reduced by 99.99% since eradication efforts began and is poised to become the second human disease and the first parasitic disease eradicated in history.
• Reports of animal infections slightly increased due to expanded surveillance in Angola and Cameroon.

• All figures for humans and animals are provisional until officially confirmed, typically in March. Guinea worm is poised to become the second human disease in history to be eradicated, following smallpox, as well as the first parasitic disease and the first without a medicine or vaccine. Community-based and innovative behavioral change and local mobilization are the key drivers of success.

Building on seven World Health Assembly resolutions and hosted by The Carter Center, Reaching the Last Mile, the UAE, and the WHO, representatives of impacted countries (Angola, Chad, Ethiopia, Mali, South Sudan, Sudan, Democratic Republic of the Congo, and Cameroon) and organizations renewed their commitment to eradicating the debilitating disease by 2030 by signing the Abu Dhabi Declaration on the Eradication of Guinea Worm Disease, in 2022 and pledged to commit resources, energy, and policy initiatives to eradicate Guinea worm disease.

Four decades of disease eradication work may seem like a long time, but like smallpox, guinea worm has been around for millennia. CDC notes that, “In 1959, the World Health Organization (WHO) started a plan to rid the world of smallpox,” and “the 33^rd World Health Assembly declared the world free of this disease on May 8, 1980.”

Malaria eradication efforts started, stalled and resumed beginning with the National Malaria Eradication Program in the USA on July 1, 1947. Subsequently, “the World Health Organization (WHO) submitted at the World Health Assembly in 1955 an ambitious proposal for the eradication of malaria worldwide.” We are still aiming for 2030 and beyond to rid the world of malaria country-by-country.

In 1998 Walter R. Dowdle outlined three indicators that were considered to be of primary importance in eradicating a disease. These included “an effective intervention is available to interrupt transmission of the agent, practical diagnostic tools with sufficient sensitivity and specificity are available to detect levels of infection that can lead to transmission, and humans are essential for the life-cycle of the agent, which has no other vertebrate reservoir and does not amplify in the environment.” In 2000, Aylward and colleagues also posed three criteria including “(1) biological and technical feasibility, (2) costs and benefits, and (3) societal and political considerations.”  Andrews and Langmuir post the awkward reality that “If … the decline in new cases is halted by circumstances which slow it down to a fluctuating equilibrium at some point approaching but not quite reaching zero, the disease may be declared administratively to be under control, though it is certainly not eliminated.”

The persistence of low-level human transmission of guinea worm may appear encouraging when compared to he initial estimate of 3.5 million infections, but we hope that the political and social commitment will persist so that the dwindling cases will eventually reach zero. Additional effort is needed now that one of Dowdle’s criteria has been breached, another vertebrate reservoir (domestic dogs, cats and others who share unsafe water sources with humans). The costs and benefits can be questioned as eradication is drawn out over time. Guinea worm has always epitomized the concept of NTDs wherein not just the disease but the people who suffer from it are neglected. Eradication will only come when that neglect stops.

The concept and goal of eliminating a disease appears simple on the surface, but complications ensue when the words “as a public health problem” are added.  We know that the distinction exists between eradication and elimination with the former being globally and the latter being nationally or regionally. The sum total action of eliminating a disease from all endemic countries therefore results in total global eradication.

The challenge comes when we try to qualify the concept of elimination. The US CDC defined elimination of disease as, “Reduction to zero of the incidence of a specified disease in a defined geographical area as a result of deliberate efforts; continued intervention measures are required.” Thus, there is no more transmission.  Following from this eradication is defined as, “Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts; intervention measures are no longer needed.” Penn Medicine summarized this as, “Elimination means stopping the transmission of a disease in a specific geographic area or country, but not worldwide. Elimination is a crucial step in the path toward eradication, requiring constant monitoring and interventions to keep serious diseases at bay.”

The foregoing definitions seem straightforward, but what does elimination as a public health problem or a disease of public health concern mean? The World Health Organization recently “congratulate(d) Benin and Mali for eliminating trachoma as a public health problem. Concerning another neglected tropical disease (NTD), lymphatic filariasis (LF), global control programs are aiming “to reduce the prevalence of infection below target thresholds and to alleviate the suffering of people affected by lymphoedema and hydrocele.” Wiegand and colleagues in The Lancet Global Health note that, “For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ?50 Schistosoma haematobium eggs per 10 mL of urine or ?400 Schistosoma mansoni eggs per g of stool).” They take issue with the fact that such definitions mean that morbidity still exists, though at very levels, so elimination of transmission has not really occurred for any of these NTDs.

Because the social, environmental, and behavioral conditions that favor transmission may still exists, one cannot guarantee that incidence such diseases may not increase again. All three diseases, LF, Schistosomiasis, and Trachoma have been tackled primarily through preventive chemotherapy, is simply put, using mass drug administration (MDA) over a period of years until active surveillance determines that “infection (is) below target thresholds.” Trachoma does have its SAFE strategy which includes water, sanitation and hygiene interventions, but drugs can reduce the disease without long term achievements in such activities have become sustainable.

Prada et al. in the Journal of Infectious Diseases warn that there can be resurgence of a disease that was documented to be eliminated as a public health problem. They explain that the transmission assessment survey held after several MDA rounds for LF may not be enough to guarantee that low levels of transmission and eventual elimination are achieved. They conclude that, “The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (<5 years), it can still occur outside of the currently recommended post-intervention surveillance period of 4–6 years,” and recommend monitoring beyond this period.

Toor and co-researchers suggest for NTD programs that, “as case numbers drop and elimination comes into prospect, transmission reduction through other interventions, such as vector control and sanitation, becomes crucial in reducing the probability and speed of resurgence, particularly when MDA or screening programs are halted. Surveillance activities for detecting elimination and resurgence become increasingly important to ensure that successes are maintained.”

Ultimately, unless the context of NTD transmission is addressed, elimination will be an elusive goal. Therefore, as WHO advocated on the recent World NTD Day, “Everybody, including leaders and communities, to confront the inequalities that drive NTDs and to make bold, sustainable investments to free the world’s most vulnerable communities affected by NTDs from a vicious cycle of disease and poverty.”

A May 28^th press release from the World Health Organization states that, “Togo eliminates trachoma as a public health problem.” The article explains that …

“Validation of trachoma elimination as a public health problem in Togo was based on evidence. Several population-based trachoma surveys were conducted starting from 2006 to 2017. The 2017 survey using WHO recommended methodology found that the prevalence of key indicators was below the WHO trachoma elimination threshold. There was also evidence that Togo’s health system is able to identify and treat new cases of late complications of trachoma.”

This raises the question, is Trachoma gone from Togo or does trachoma continue to exist at some low level whereby, as WHO notes, Togo has joined, “12 other countries that have been validated by WHO for having eliminated trachoma as a public health problem.”

This description of disease elimination contrasts sharply with the global concerns when “health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was detected in a young child in the capital Lilongwe. This is the first case of wild poliovirus in Africa in more than five years.” Wild polio virus had been declared eliminated in Africa, and just one case in one country grabs international attention.

Would one case of trachoma tomorrow receive the same concern in Togo? Apparently not according to the WHO definition, “Elimination of trachoma as a public health problem is defined as: (i) a prevalence of trachomatous trichiasis (TT) “unknown to the health system” of < 1 case per 1000 total population; and (ii) a prevalence of trachomatous inflammation-follicular (TF) in children aged 1–9 years of < 5%, in each formerly endemic district.”

So, while no cases of smallpox, guinea worm or polio would be tolerated after elimination has been declared, parents of a child who develops trachoma in Togo tomorrow would be told that your child’s case is only 1 in a 1000 and not of concern to public health. The caveat is though that “the health system (must be) able to identify and manage incident TT cases.” Presumably, if such management capacity does not exist, the disease in question could spread and elimination would be eliminated.

Another Neglected Tropical Disease, Lymphatic Filariasis, faces the same challenge in terms of elimination status. WHO explained in its guidance that, “In 1997, the 50th World Health Assembly resolved to eliminate LF as a public-health problem (resolution WHA50.29). In response, WHO proposed a comprehensive strategy for achieving the elimination goal that included interrupting transmission in endemic communities and implementing interventions to prevent and manage LF-associated disabilities The LF guidance stresses “Effective monitoring, epidemiological assessment and evaluation are necessary to achieve the aim of interrupting LF transmission,” or in a word Surveillance. There is clear concern for “absence of transmission” and worries about “recrudescence.”

While polio has a vaccine and guinea worm relies on providing safe community water, LF and Trachoma elimination depends on mass drug administration (MDA) at planned intervals until such time as transmission is reduced. All require a strong health system to implement, but the challenges of maintaining MDAs until such time as elimination has been validated is somewhat more challenging. In this context the communication is extremely important. Just because WHO validates the elimination of a disease as a public health problem, does not give policy makers license to ignore that disease. Advocacy is continually needed such that even after apparent elimination, neglected diseases will not be forgotten and health systems themselves not neglected.

In the past week, news has featured challenges to malaria elimination around the globe. Starting in Papua New Guinea which accounted for accounted for 86% of all cases in the Western Pacific Region in 2020. While there are 39% fewer cases in the region since 2000, there was an increase of 300,000 cases between 2019 and 2020. It is mainly in the six countries of the Greater Mekong subregion where progress has been steady.

Moving east to the Brazilian Amazon, one finds wildcat gold mining operations are not only destroying Native American ecosystems but are carving huge holes in the earth which are perfect breeding conditions for mosquitoes. This means that malaria cases among the Yanomami indigenous people living in the Brazilian Amazon have increased by more than 12 times since 2014.

Also within South America, one finds that although Paraguay was certified by the World Health Organization (WHO) as free of local transmission of malaria in 2018, experts are warning that travelers entering the country from areas with malaria transmission could easily reintroduce the disease. Hence vigilance is urged.

Crossing next to sub-Saharan Africa, one reads of studies showing an increasing link between malaria and agriculture across the region. As population expands in the region, more food, water and agricultural commodities are required. Irrigation and deforestation to clear land for agriculture increase the risk of childhood malaria in sub-Saharan Africa. The experts recommend that African ministries of agriculture, health, and environment need to collaborate on safer development policies and practices, not only to curb malaria, but the devastating effects of climate change.

Finally continuing back to Asia, one finds what might be termed an epidemiological conflict between Nepal, which is nearing malaria elimination for 2025, and its southern neighbor India, which is a source of imported malaria. Although the number of indigenous cases is nearing zero, health authorities fear that imported cases of of malaria from India are so high that local transmission could be reignited.

Malaria is clearly a global health problem. Collaboration and coordination across continents is needed to eliminate the scourge.

A just-published article by Andrea Chaves and colleagues entitled, “Presence and potential distribution of malaria-infected New World primates of Costa Rica”, Specifically their results state that, “PCR analysis for the Plasmodium presence was conducted in 384 samples of four primates …

• Howler monkey [n?=?130]
• White-face monkey [n?=?132]
• Squirrel monkey [n?=?50]
• red spider monkey [n?=?72]),

… from across Costa Rica. Three Plasmodium species were detected in all primate species (P. falciparum, P. malariae/P. brasilianum, and P. vivax). Overall, the infection prevalence was 8.9%, but each Plasmodium species ranged 2.1–3.4%. The niche model approach showed that the Pacific and the Atlantic coastal regions of Costa Rica presented suitable climatic conditions for parasite infections. However, the central pacific coast has a more trustable prediction for malaria in primates.”

Last year, Tobias Mourier et al. reported another human/non-human primate connection in Brazil. According to them, “Analysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.

The connection between human and primate malaria also flows toward humans as traditional human plasmodium infections decrease in prevalence in Malaysia. Lai are co-researchers explain that, “The incidence of zoonotic malaria Plasmodium knowlesi infection is increasing and now has been the major cause of malaria in Malaysia.”

In fact, the 2021 World Malaria Report noted that, “Malaysia had no cases of human malaria for 3 consecutive years, but in 2020 reported 2607 cases of P. knowlesi, a zoonotic malaria.” The report does not specify efforts to handle this issue.

These studies raise a continuing question about the feasibility of eliminating malaria in countries when those plasmodium species that infect humans also infect other primates and vice versa. As we have noted before, monkeys do not use bednets. As long as primate Plasmodium reservoirs exist, our ability to eliminate the disease will remain elusive.