Therapeutics and Vaccines for Parasitic Infections: A Quick Overview and Rececnt Advances

Key Takeaways

• The WHO estimates that 1.5 billion people, or about 24% of the global population, are infected with soil-transmitted helminths; children are among the groups most affected. Malaria caused an estimated 597,000 deaths in 2023, most of them among children younger than five.

• Vector-borne diseases account for more than 17% of infectious diseases and cause more than 700,000 deaths annually. They include parasitic, bacterial, and viral diseases.

• Treatment options vary by parasite and disease. Some infections require lengthy or repeated treatment, and access to diagnosis and medicines can be limited in high-burden settings. Adverse effects and drug resistance also complicate care, underscoring the need for better prevention and treatment options.

• Two malaria vaccines, RTS,S/AS01 and R21/Matrix-M, are recommended by the WHO for children in malaria-endemic areas. Vaccine development for other parasitic diseases remains challenging because parasites can vary genetically, move through multiple life stages, and evade host immune responses.

• Improved understanding of parasite biology and resistance mechanisms is helping researchers identify potential drug targets and vaccine strategies. RNA platforms, gene editing, and new delivery systems are among the technologies being investigated, though most candidates remain at an early stage.

Parasitic infections are caused by organisms that live on or in a host and obtain nutrients at the host’s expense. Three main groups can cause human disease: protozoa, helminths, and ectoparasites. Protozoa are single-celled organisms; helminths are parasitic worms; and ectoparasites, including ticks, fleas, lice, and mites, live on or burrow into the skin.¹

Protozoa can live in the intestines, blood, or tissues. Intestinal protozoa are commonly transmitted through contaminated food or water or by person-to-person contact via the fecal–oral route. Blood- and tissue-dwelling protozoa are often transmitted by insect vectors, including mosquitoes and sand flies.¹

Helminths include flatworms, thorny-headed worms, and roundworms. Adult worms are generally visible to the naked eye. Many live in the gastrointestinal tract, while some species or life stages can affect the blood, lymphatic system, or subcutaneous tissues.¹

Ectoparasites include ticks, fleas, lice, and mites that attach to or burrow into the skin. Mosquitoes may also be described as ectoparasites because they take blood meals, but they are more often discussed as vectors that transmit other pathogens.1

Parasites can spread from animals to people, through insect vectors, via infected blood, or through contaminated food, water, or soil. Some infections can also spread from person to person.¹

Parasitic diseases with substantial health burdens include malaria; soil-transmitted helminth infections such as ascariasis, hookworm disease, and trichuriasis; schistosomiasis; amebiasis; giardiasis; Chagas disease; leishmaniasis; and toxoplasmosis. The burden varies by disease, region, and population.^2–4

Soil-transmitted helminths infect an estimated 1.5 billion people worldwide, about 24% of the global population, according to the World Health Organization (WHO). Malaria is a major cause of parasitic-disease mortality: WHO estimated 597,000 malaria deaths in 2023, with children younger than five accounting for most deaths. Vector-borne diseases overall cause more than 700,000 deaths annually, but this group includes viral and bacterial diseases as well as parasitic infections.^4–6

The distribution of parasitic diseases is shaped by climate, travel, land use, sanitation, and access to health care. Changes in temperature and rainfall can alter the range or seasonality of some vectors and parasites, while travel can transport infections to new locations. These effects differ across diseases and regions.⁷

Foodborne parasitic infections also occur outside tropical regions. In 2026, the United States experienced an unusually large cyclosporiasis season: the Centers for Disease Control and Prevention (CDC) reported more than 20,000 laboratory-confirmed domestically acquired cases by October. Surveillance data can change as cases are investigated, and underdiagnosis is likely because not everyone who becomes ill seeks care or is tested.⁸

Monitoring parasitic infections is difficult where diagnostic services, trained personnel, and surveillance systems are limited. Complex life cycles and varied routes of transmission can further complicate detection. Timely diagnosis matters for patient care and for recognizing changes in transmission; drug resistance adds another challenge.^7,9,10

Malaria is the leading parasitic vector-borne disease by mortality. Other important vector-borne parasitic diseases include leishmaniasis, Chagas disease, human African trypanosomiasis, lymphatic filariasis, and onchocerciasis. Their burdens are concentrated in tropical and subtropical regions and are shaped by environmental conditions, socioeconomic factors, and access to health services.^4,11

Treatment depends on the parasite species, the site and severity of infection, and the stage of the organism’s life cycle. Some infections require repeated doses or combination therapy, while others can be treated with shorter regimens. The complexity of parasite life cycles is also one obstacle to vaccine development.^12,13

Antiparasitic medicines work through different mechanisms, including disrupting parasite metabolism, cellular structures, or neuromuscular function. The choice of medicine depends on the organism and clinical context. Antiprotozoal drugs include agents such as artemisinin derivatives, metronidazole, tinidazole, chloroquine, atovaquone–proguanil, pentamidine, and pyrimethamine; they are not interchangeable across infections.¹³

Anthelmintic medicines used against parasitic worms include albendazole, praziquantel, diethylcarbamazine, and ivermectin, depending on the infection. Ectoparasite infestations may be treated with medicines such as topical permethrin or ivermectin, as appropriate.¹³

Two malaria vaccines, RTS,S/AS01 and R21/Matrix-M, are recommended by the WHO for children in areas with moderate-to-high malaria transmission. RTS,S targets the Plasmodium falciparum circumsporozoite protein. R21 uses the same antigen with a different adjuvant formulation. The WHO recommends both vaccines; they have not been compared head-to-head.¹⁴

Treatment can become more difficult when diagnosis is delayed, disease is severe, or the parasite occupies tissues that are difficult for a medicine to reach. Regimens also vary by species and life stage. Genetic diversity can limit how broadly a vaccine or drug works, although the degree of species specificity differs by intervention.^12,15

For zoonotic infections, continued exposure to animal or environmental sources can lead to reinfection even after successful treatment. Some parasitic diseases cause substantial chronic morbidity without high mortality, making their full effects on health and well-being difficult to capture with mortality statistics alone.^7,11

In many high-burden settings, limited laboratory capacity and health-care access can delay diagnosis and treatment. Depending on the disease, treatment may involve multiple doses, monitoring, or medicines with significant adverse effects. Resistance has been documented for particular parasites and drugs, but its prevalence and clinical impact vary by organism, geography, and treatment.^9,10,13

Vaccines can prevent infections and may reduce the need for some treatments, but their effect on antiparasitic drug resistance will depend on the disease and vaccine’s uptake and effectiveness. Vaccine development is difficult because parasites can be genetically diverse, express different antigens across life stages, and evade immune responses.^12,16

Antiparasitic drug resistance is an important concern, but the evidence and clinical implications differ across organisms and medicines. Resistance to antimalarial drugs is monitored closely; other examples include reduced susceptibility to anthelmintics in veterinary settings. Broad claims that resistance is rising rapidly across all parasite groups require disease-specific evidence.^9,10,17

Inappropriate use of antiparasitic medicines can contribute to selection pressure. Examples include treatment without diagnostic confirmation when testing is available, unnecessary mass treatment, and underdosing. The risks and appropriate stewardship measures differ between human and veterinary medicine.^9,10

Documented resistance mechanisms in protozoa include changes in drug transport, mutations in drug targets, altered gene expression or copy number, metabolic adaptation, and persistence in less susceptible stages. The mechanisms vary by species and drug.¹⁷

Research into antiparasitic drugs and vaccines is drawing on improved knowledge of parasite metabolism, biology, immune evasion, and resistance. These findings are helping identify candidate targets and strategies, but many remain at the discovery or preclinical stage.^15,17,18

Recent work has identified several potential avenues for intervention. One study reported that ibuprofen can activate gasdermin C and promote a type 2 immune response in the gut; this is an early mechanistic finding, not an antiparasitic treatment recommendation. Another study mapped mitochondrial proteins across protozoan parasites and identified candidates for further target validation.^19,20 Moxidectin, a U.S. Food and Drug Administration (FDA)-approved treatment for onchocerciasis in adults, is also being studied in other filarial infections; those findings should be distinguished from its approved indication.^21–23

Cipargamin (KAE609 or NITD609) is an investigational antimalarial that targets the Plasmodium P-type cation-translocating ATPase PfATP4, disrupting sodium homeostasis in the parasite.²⁴ Novartis is also developing KLU156, a combination of ganaplacide and lumefantrine. In November 2025, Novartis reported that the phase III KALUMA trial met its primary endpoint of noninferiority to artemether–lumefantrine, the standard-of-care comparator. The result does not establish superiority, and KLU156 remains investigational.^25,26

A 2026 study described IID432, a cyanotriazole candidate that inhibited Trypanosoma cruzi topoisomerase II and produced a sterile cure after short-term treatment in a chronic infection model. This is preclinical evidence and does not establish a one-time human treatment.²⁷ Separately, acoziborole is an oral treatment candidate for gambiense human African trypanosomiasis developed by DNDi and Sanofi. In February 2026, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use adopted a positive scientific opinion for use outside the European Union; that opinion is distinct from an EU marketing authorization.²⁸ Acoziborole received registration approval in the Democratic Republic of the Congo in June 2026. Clinical studies reported cure rates of up to 96%, while the single-dose regimen may offer practical advantages over existing multi-day treatment.^28,29

Nanotechnology-based delivery systems are being investigated to improve the solubility, stability, bioavailability, or tissue distribution of antiparasitic agents and vaccines. Approaches include liposomes, solid lipid nanoparticles, nanosuspensions, polymer-based particles, and metal nanoparticles. Most reported applications remain in preclinical research.^18,30

Liposomal amphotericin B is an established formulation used to treat visceral leishmaniasis; WHO guidance recommends liposomal amphotericin B in specific treatment regimens. Other nanoparticle formulations for antimalarial, antitrypanosomal, and anti-Chagas medicines remain under investigation, with evidence ranging from laboratory studies to animal models. Their clinical value will depend on safety, efficacy, manufacturability, and access.³¹

RNA-based approaches are also being explored for parasitic disease. Research includes RNA vaccines and therapeutic candidates, often delivered using lipid nanoparticles. These approaches remain largely preclinical, and efficacy will need to be demonstrated for each parasite and indication.^16,31

New delivery and gene-editing technologies are supporting research into vaccines for parasitic diseases. Approaches under investigation include messenger RNA (mRNA) vaccines, genetically modified live-attenuated parasites, and drug-induced or “chemo-attenuated” vaccine strategies. Each approach has distinct safety, manufacturing, and efficacy questions.^16,31,32

Early parasite-vaccine research included attenuated or inactivated whole organisms. Recombinant subunit vaccines were developed in part to improve control over antigen composition and safety. For these vaccines, antigen selection and adjuvant choice are central design decisions.¹⁶

RTS,S/AS01 and R21/Matrix-M are the two malaria vaccines recommended by WHO. The clinical pipeline remains active, but candidate counts depend on the database, date, and definition of an active program; any numerical snapshot should be tied to a dated source. Vaccine research for leishmaniasis and other parasitic diseases has also produced clinical candidates, though few have advanced far in development.^14,16

Some parasitic pathogens live inside host cells, making cellular immune responses an important research goal. mRNA and genetically modified live-attenuated parasite platforms are being studied for their ability to induce both antibody and T cell responses.¹⁶

mRNA platforms can encode one or more antigens and may be adapted to target antigens expressed at different parasite life stages. Their potential advantages in parasitic disease remain under study; safety and efficacy must be assessed for each candidate and indication.³¹

Researchers are exploring conventional mRNA, circular RNA, and self-amplifying RNA for parasitic-disease vaccines. Candidates have been reported for malaria, leishmaniasis, toxoplasmosis, and other infections, but most remain in early preclinical development.^16,31

Many candidate RNA vaccines use lipid nanoparticles for delivery, while other formulations and delivery vehicles are also being explored. The field is at an early stage, and platform feasibility should not be conflated with demonstrated vaccine efficacy.^16,31

Gene editing, including CRISPR/Cas9, has enabled development of genetically modified live-attenuated parasite candidates. Researchers use targeted genetic changes to reduce parasite virulence while preserving immunogenicity. These candidates require careful evaluation for genetic stability, safety, and manufacturing control; most remain preclinical.¹⁶

Chemo-attenuated strategies aim to use a drug to interrupt parasite development in a way that exposes the immune system to noninfectious parasite material. In a preclinical study, the dual protease inhibitor MK-7602, which targets malaria plasmepsins IX and X, cleared late liver-stage infection in mice and generated defective, noninfectious merozoites associated with protection against later challenge. The reported protection lasted up to two years in mice. Translating this result into a safe and effective human intervention remains an open research question.³²

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2. Kaminsky, Ronald, and Pascal Mäser. “Global Impact of Parasitic Infections and the Importance of Parasite Control.” Frontiers in Parasitology. 4:1546195 (2025).

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8. “Cyclospora Case Data.” Centers for Disease Control and Prevention.Updated 23 Oct. 2026.

9. “Antiparasitic Resistance.” U.S. Food and Drug Administration. Accessed 03 Nov. 2026.

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11. Zhang, M., et al. “Global Epidemiology of Vector-Borne Parasitic Diseases: Burden, Trends, Disparities, and Forecasts (1990–2036).” Pathogens. 14(9):844 (2025).

12. Ro, Christine. “Why It’s So Challenging to Develop Vaccines for Parasitic Diseases.” BBC Future, 4 June 2024.

13. Campbell, Susan, and K. Soman-Faulkner. “Antiparasitic Drugs.” In StatPearls. Updated 29 May 2023.

14. “Malaria Vaccines.” Centers for Disease Control and Prevention. 2 Apr. 2024.

15. White, Susan. “Novel Therapeutic Targets for Treating Parasitic Infections.” African Journal of Parasitology. 11(8) (2023).

16. Teixeira, Santuza Maria Ribeiro, et al. “Next-Generation Vaccines Against Neglected Diseases: New Promises from Genetically Modified Live-Attenuated Parasites and RNA Vaccines.” Microorganisms. 14(5):1112 (2026).

17. Uduwela, Kavithma, and Koshila Ranasinghe. “Molecular Mechanisms Underlying Drug Resistance in Protozoan Parasites: Emerging Mechanisms and Therapeutic Perspectives.” Frontiers in Parasitology. 5:1934996 (2026).

18. Thompson, M. “Parasitic Infection Treatment: Evolving Strategies and Future Directions.” Journal of Parasitic Diseases Diagnosis and Therapy. 10(3):227 (2025).

19. Morreale, Brian G. “New Discovery Improves Treatment Against Parasitic Infections.” Labroots. 24 July 2025.

20. Naddaf, Miryam. “Unprecedented Atlas Explores Mitochondria Across the Tree of Life.” Nature. 19 Oct. 2026.

21. “First New Treatment for River Blindness Approved by U.S. FDA in 20 Years.” World Health Organization. 14 June 2018.

22. “U.S. FDA Expands Indication for Moxidectin to Treat River Blindness in Children as Young as Four.” Medicines Development for Global Health. 20 Feb. 2025.

23. DeSalvio, Serina. “A Faster Route to Eliminating Parasitic Infection Endemic to Africa.” Washington University Medicine. 7 May 2025.

24. Bouwman, SAM, et al. “The Early Preclinical and Clinical Development of Cipargamin (KAE609), a Novel Antimalarial Compound.” Travel Medicine and Infectious Disease. 36:101765 (2020).

25. Kupferschmidt, Kai. “‘A Sigh of Relief’: New Malaria Drug Succeeds in Large Clinical Trial.” Science. 12 Nov. 2025.

26. “Phase III Trial for Next-Generation Malaria Treatment KLU156 Meets Primary Endpoint of Noninferiority to Standard of Care.” Novartis. 12 Nov. 2025.

27. René, Olivier, et al. “Discovery of IID432 for Chagas Disease: A Cyanotriazole Inhibitor of Trypanosoma cruzi Topoisomerase II Achieves Sterile Cure After Short-Term Treatment in a Chronic Infection Model.” Journal of Medicinal Chemistry. 69(2):1135–1153 (2026).

28. “Acoziborole Winthrop: Summary of Positive Opinion.” European Medicines Agency. 24 Feb. 2026.

29. “DRC Approves the Use of Acoziborole, a Breakthrough One-Day Oral Treatment Against Sleeping Sickness.” Drugs for Neglected Diseases initiative. 12 June 2026.

30. Tiwari, R., et al. “Nanotechnology-Based Strategies in Parasitic Disease Management: From Prevention to Diagnosis and Treatment.” ACS Omega. 8(45):42014–42027 (2023).

31. Hasan, Muhammad Waqqas, Jiajia Pan, Ningbo Xia, and Wenjie Chen. “mRNA Based Vaccines and Therapeutics for Parasitic Infections: A Comprehensive Review.” Journal of Nanobiotechnology. 24:23 (2026).

32. Tran, L. “Parasitic Drugs Create an Attenuated Vaccine In Vivo.” The Scientist. 24 Sept. 2026.