Thus, the global burden of this species is certainly underestimated. In fact, during chronic infections, numerous epidemiological field studies support that >90% of infections are sub-microscopic and asymptomatic ( Angrisano and Robinson, 2022). However, in low-endemic countries that have been targeting vivax malaria for elimination, an increasing number of asymptomatic infections capable of transmitting to mosquitoes are being reported ( Cheng et al., 2015). vivax can be achieved with the present control tools available. This panorama would indicate that elimination of P. vivax, its burden has dramatically decreased from 11.9-22 million cases in 2013 to 7 million clinical cases in 2020 ( WHO, 2020). Human malaria is a disease caused by five species of plasmodia of which Plasmodium falciparum and Plasmodium vivax represent the vast majority of burden whereas Plasmodium ovale, Plasmodium malaria and the recent zoonosis caused by Plasmodium knowlesi in South East Asia, are likely to contribute to less than 5% of such burden ( Battle et al., 2019). vivax cryptic niches, which perpetuate transmission and burden. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. Recent advances in the development of humanized mouse models and organs-on-a-chip models, offer novel technological frontiers to study human diseases, vaccine validation and drug discovery. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. However, recent evidence indicates that niches outside the liver, in particular in the spleen and the bone marrow, can represent a major source of cryptic chronic erythrocytic infections. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. Plasmodium vivax is the most widely distributed human malaria parasite representing 36.3% of disease burden in the South-East Asia region and the most predominant species in the region of the Americas.
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