Modeling Relapsing Malaria: Emerging Technologies to Study Parasite-Host Interactions in the Liver

Wel, Annemarie Voorberg-van der; Kocken, Clemens H. M.; Zeeman, Anne‐Marie

doi:10.3389/fcimb.2020.606033

Cited by 15 publications

(14 citation statements)

References 109 publications

(146 reference statements)

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“…However, the precise molecular mechanisms that define persisters are not well understood. Persister forms are not limited to bacteria, and have been identified in eukaryotic protozoan parasites such as Plasmodium vivax (hypnozoites) 18 , and Toxoplasma gondii (bradyzoites) 19 , and they have been indicated to have a key role in disease persistence. Recently it has become apparent that persister forms also occur in trypanosomatids.…”

Section: Improved Understanding Of Parasite Biologymentioning

confidence: 99%

Anti-trypanosomatid drug discovery: progress and challenges

et al. 2022

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Leishmaniasis (visceral and cutaneous), Chagas disease and human African trypanosomiasis cause substantial death and morbidity, particularly in low- and middle-income countries. Although the situation has improved for human African trypanosomiasis, there remains an urgent need for new medicines to treat leishmaniasis and Chagas disease; the clinical development pipeline is particularly sparse for Chagas disease. In this Review, we describe recent advances in our understanding of the biology of the causative pathogens, particularly from the drug discovery perspective, and we explore the progress that has been made in the development of new drug candidates and the identification of promising molecular targets. We also explore the challenges in developing new clinical candidates and discuss potential solutions to overcome such hurdles.

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Section: Improved Understanding Of Parasite Biologymentioning

confidence: 99%

Anti-trypanosomatid drug discovery: progress and challenges

et al. 2022

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“…So far, most of the key experimental insights on malaria research was provided either by in vivo rodent models or by the in vitro 2D monoculture ( Voorberg-van der Wel et al., 2020a ). Interestingly, most of these studies use hepatoma-derived cell line model systems such as HepG2, Huh7 and HC-04 ( Hollingdale et al., 1985 ; Kaushansky et al., 2015 ; Ribeiro et al., 2016 ; Tweedell et al., 2019 ).…”

Section: Organs-on-a-chipmentioning

confidence: 99%

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

Aparici-Herraiz

Caires

Castillo-Fernandez

et al. 2022

Front. Cell. Infect. Microbiol.

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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. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. 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. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. 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. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. 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. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. vivax cryptic niches, which perpetuate transmission and burden.

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“…For someone who has actually recovered from malaria, a state of reactivation can occur in malaria due to P. ovale and P. vivax. Reactivation occured due to remaining hypnozoites the liver and manifest with reappearance of: high fever, anemia, hepato-splenomegaly and malnutrition [23,24]. The chronic malaria is usually caused by P. Malariae, which is the most frequently related in glomerulonephritis et causa malaria [25], but the species P. vivax, notwithstanding being appraised as a "benign" organism, causing in insignificant mortality percentages, to some extent has also been involved in severe condition [21].…”

Section: Malaria Pathogenesismentioning

confidence: 99%

Complications of Kidney in Severe Malaria

Siagian

2022

AJRID

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Malaria is an infectious protozoan parasitic disease transmitted by Anopheles spp mosquito. As a disease entity, malaria is still a major global health problem due to its morbidity and mortality that endangered millions of individuals inhabitants in tropical region. Kidney derangement is moderately frequent in severe malaria caused by the species P. falciparum and also P. malariae, but seldom this condition has also been reported in malaria due to P. vivax. Severe or complicated malaria can occur due to delay or failure of treatment. Making correct and early diagnosis is a prerequisite for successful treatment. Actually, a series of events that begins with the entry of blood protozoa into the host which then causes hemodynamic disturbances and loss of normal capillary capacity. Hemodynamic dysfunction, immune response and with addition from the consequences of severe malaria complications in other organs (e.g., liver) leading to worsening of kidney function in severe malaria. This paper cover the recent findings of kidney involvement in severe malaria and other important facts related to this issue.

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Modeling Relapsing Malaria: Emerging Technologies to Study Parasite-Host Interactions in the Liver

Cited by 15 publications

References 109 publications

Anti-trypanosomatid drug discovery: progress and challenges

Anti-trypanosomatid drug discovery: progress and challenges

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

Complications of Kidney in Severe Malaria

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