A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments

Abstract

Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches.

Transmission Modelling for Human Non-Zoonotic Schistosomiasis Incorporating Vaccination: Guiding Decision- and Policymaking

“…The latter impairs susceptibility to predominantly viral pathogens [55], and fertility, e.g., ectopic pregnancy and miscarriage, in addition to progression to malignancies, e.g., squamous cell carcinomas and sandy patches [44,[56][57][58][59]. Notably, ectopic excess egg retention or erroneous worm migration in the central nervous system induces cognitive and physical impairments [60] that are seen in endemic settings [9,48,61].…”

“…Only a few candidates, though not on the market yet, advanced to clinical phases, i.e., Sm14 or S. mansoni fatty acid-binding protein (FABP) in ongoing phase II [2,8,[167][168][169], Sm-TSP-2/Sm-TSP-2Al ® or S. mansoni tetraspanin in phase I [170][171][172][173][174], Smp80/SchistoShield ® or S. mansoni large-subunit calpain in ongoing phase I [52,[175][176][177], and Sh28GST/Bilhvax ® or S. haematobium glutathione S-transferase in phase III [60,[178][179][180][181][182]. The latter was discontinued, lacking efficacy [165].…”

Mechanisms of Arachidonic Acid In Vitro Schistosomicidal Potential

“…Schistosomiasis is still prevalent in 78 developing countries in the tropics and subtropics, with the vast majority of infections caused by Schistosoma mansoni and Schistosoma hematobium. Despite extensive and intensive efforts by the World Health Organization (WHO), an estimated 280,000 deaths are recorded annually, and 800 million people in rural communities, primarily children, are still at risk of the infection. , Increased access to safe water, improved sanitation, health education, efforts to control the intermediate snail hosts with molluscicides, and widespread, mass preventive chemotherapy programs led in 2020 to only 1/78 and in 2023 to 10/78 countries reporting the absence of human infections . Thus, WHO setting 2030 as the goal for transmission interruption in endemic countries does not seem realistic. − …”

“…However, preventive mass drug administration programs rely on the distribution of a single dose to school children and adults at risk. Indeed, each year, millions of school-aged African children receive PZQ at a standard single dose of 40 mg/kg of body weight. − On the one hand, total cure of infection is rarely achieved, as “preventive” only implies the commendable goal of reducing morbidity and mortality . On the other hand, infection-free individuals are subjected to treatment, while the term “preventive” in this case is misleading and may promote complacency in hygiene restrictions.…”

Editorial: Host immune response and regulation to parasitic infections: therapeutic approaches and defence strategies

“…To date, however, licensed vaccines that protect against parasitic diseases are not commercially available, except for malaria. Although drug resistance in most parasites and the absence of vaccines seem to be extremely dangerous in terms of the threat to human life, advancements in immunological research and tools continue to improve our knowledge regarding drug and vaccine development ( 1 , 2 ). This understanding is significant for clinical applications and has facilitated the discovery of novel drugs, vaccines, diagnostics, and treatments to manage a wide array of parasitic diseases such as malaria, schistosomiasis, filariasis, leishmaniasis, and trypanosomiasis.…”