Density-Dependent Blood Stage Plasmodium falciparum Suppresses Malaria Super-Infection in a Malaria Holoendemic Population

Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W.; Moormann, Ann M.; Davenport, Miles P.

doi:10.4269/ajtmh.13-0049

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…This cohort has been described in detail in several publications [6][7][8][9]. Immediately after collection of blood samples, all participants were given a 6-dose regimen of artemether-lumefantrine to clear blood-stage infection without foreknowledge of whether the individual's blood smear was P. falciparum positive or negative.…”

Section: Study Participants and Designmentioning

confidence: 99%

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Dent¹,

Nakajima²,

Liang³

et al. 2015

J Infect Dis.

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Background. Immunoglobulin G antibodies (Abs) to Plasmodium falciparum antigens have been associated with naturally acquired immunity to symptomatic malaria.Methods. We probed protein microarrays covering 824 unique P. falciparum protein features with plasma from residents of a community in Kenya monitored for 12 weeks for (re)infection and symptomatic malaria after administration of antimalarial drugs. P. falciparum proteins recognized by Abs from 88 children (aged 1-14 years) and 86 adults (aged ≥18 years), measured at the beginning of the observation period, were ranked by Ab signal intensity.Results. Abs from immune adults reacted with a total 163 of 824 P. falciparum proteins. Children gradually acquired Abs to the full repertoire of antigens recognized by adults. Abs to some antigens showed high seroconversion rates, reaching maximal levels early in childhood, whereas others did not reach adult levels until adolescence. No correlation between Ab signal intensity and time to (re)infection was observed. In contrast, Ab levels to 106 antigens were significantly higher in children who were protected from symptomatic malaria compared with those who were not. Abs to antigens predictive of protection included P. falciparum erythrocyte membrane protein 1, merozoite surface protein (MSP) 10, MSP2, liver-stage antigen 3, PF70, MSP7, and Plasmodium helical interspersed subtelomeric domain protein.Conclusions. Protein microarrays may be useful in the search for malaria antigens associated with protective immunity.

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Section: Study Participants and Designmentioning

confidence: 99%

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Dent¹,

Nakajima²,

Liang³

et al. 2015

J Infect Dis.

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“…The model assumes that for a given EIR, infective bites arrive randomly with exponentially distributed waiting times (13,34,35). Each bite infection then has a probability of reaching the blood stage, which is determined by the baseline probability of success (R b ) and the level of induced resistance at a given time [R(t)].…”

Section: ) (E) Parasite Liver Loads In Reinfected Ifnar1mentioning

confidence: 99%

“…To take these dynamics into consideration, we developed a stochastic model of malaria infection that takes into account more-complex factors such as multiple consecutive bites and gradual acquisition and loss of immunity. Our model is based on four assumptions: (i) infective bites arrive randomly at a given biting rate (13,34,35); (ii) only a proportion of bites result in infection (e.g., in a number of cases, mosquito injection of sporozoites is unsuccessful or sporozoites remain in the skin); (iii) a successful liver-stage infection (i.e., an infection that progresses to the blood stage) induces strong host resistance and thus inhibits the establishment of a subsequent liver-stage infection; and (iv) a liver-stage infection that is blocked by innate immunity and does not progress to a blood-stage infection nonetheless induces a small amount of resistance to subsequent infections.…”

Section: Induction Of Type I Ifn and Ifn-␥ By A First P Berghei Livementioning

confidence: 99%

“…These studies have revealed that host resistance to blood-stage infection is complex and mediated by both the innate immune system, which limits the initial growth of all blood-stage parasites, irrespective of Plasmodium species or strain, and adaptive immunity, which is genotype specific (reviewed in references 9, 10, and 11). In addition, recent studies have suggested that high levels of blood-stage parasitemia protect the host from secondary or superinfection, by inhibiting liver-stage reinfection (12,13). In mice, this increased resistance seems to be mediated by the iron-regulatory hormone hepcidin, which impairs parasite growth by restricting iron availability in the liver (12).…”

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confidence: 99%

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Innate Immunity Induced by Plasmodium Liver Infection Inhibits Malaria Reinfections

et al. 2015

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bFollowing transmission through a mosquito bite to the mammalian host, Plasmodium parasites first invade and replicate inside hepatocytes before infecting erythrocytes and causing malaria. The mechanisms limiting Plasmodium reinfections in humans living in regions of malaria endemicity have mainly been explored by studying the resistance induced by the blood stage of infection. However, epidemiologic studies have suggested that in high-transmission areas, preerythrocytic stages also activate host resistance to reinfection. This, along with the recent discovery that liver infections trigger a specific and effective type I interferon (IFN) response, prompted us to hypothesize that this pre-erythrocyte-stage-induced resistance is linked to liver innate immunity. Here, we combined experimental approaches and mathematical modeling to recapitulate field studies and understand the molecular basis behind such resistance. We present a newly established mouse reinfection model and demonstrate that rodent malaria liver-stage infection inhibits reinfection. This protection relies on the activation of innate immunity and involves the type I IFN response and the antimicrobial cytokine gamma IFN (IFN-␥). Importantly, mathematical simulations indicate that the predictions based on our experimental murine reinfection model fit available epidemiological data. Overall, our study revealed that liver-stage-induced innate immunity may contribute to the preerythrocytic resistance observed in humans in regions of malaria hyperendemicity. Malaria accounts for over half a million deaths per year and is thus the most prevalent parasitic human disease worldwide (1). The disease is caused by an intracellular protozoan parasite of the genus Plasmodium that infects multiple hosts, such as Anopheles mosquitoes and humans and other mammalians (2). Infection begins with a bite of a female mosquito that injects a few Plasmodium sporozoites, which represent the mosquito-transmitted parasite form, into the skin of the mammalian host. After migrating through skin cells (3), sporozoites enter the bloodstream and are then rapidly and specifically retained in the liver sinusoids. Sporozoites then cross the sinusoidal barrier (4) and traverse several liver cells until individual parasites invade a final hepatocyte with the formation of a parasitophorous vacuole (5). Inside this vacuolar niche, sporozoites asymptomatically develop and replicate into thousands of erythrocyte-infective parasites, termed merozoites (6). Finally, merozoites are released into the bloodstream and rapidly infect erythrocytes, initiating the blood stage and the clinical phase of infection (7).Malaria reinfections are common, especially in regions of high malaria transmission. Plasmodium parasites present an extraordinarily high rate of polymorphism; consequently, the host can be reinfected by different parasites that repeatedly escape the immune response (8). Therefore, efficient immunity to reinfection in one individual is obtained only after many years of facing recurrent infe...

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“…The relative importance of co-inoculation versus superinfection is setting dependent and not yet fully understood. Previous studies found that parasite density in blood-stage can limit subsequent development of new sporozoites supporting the parasite population of first-inoculated genotype [47,48]. Hence, superinfection may be limited.…”

Section: Methodsmentioning

confidence: 98%

Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax

Ayala

Villela

2020

PLoS Comput Biol

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The spread of drug resistance of Plasmodium falciparum and Plasmodium vivax parasites is a challenge towards malaria elimination. P. falciparum has shown an early and severe drug resistance in comparison to P. vivax in various countries. In fact, P. vivax differs in its life cycle and treatment in various factors: development and duration of sexual parasite forms differ, symptoms severity are unequal, relapses present only in P. vivax cases and the Artemisinin-based combination therapy (ACT) is only mandatory in P. falciparum cases. We compared the spread of drug resistance for both species through two compartmental models using ordinary differential equations. The model structure describes how sensitive and resistant parasite strains infect a human population treated with antimalarials. We found that an early transmission,i.e., before treatment and low effectiveness of drug coverage, supports the prevalence of sensitive parasites delaying the emergence of resistant P. vivax. These results imply that earlier attention of both symptomatic cases and reservoirs of P. vivax are essential in controlling transmission but also accelerate the spread of drug resistance.

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Density-Dependent Blood Stage Plasmodium falciparum Suppresses Malaria Super-Infection in a Malaria Holoendemic Population

Cited by 6 publications

References 19 publications

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Innate Immunity Induced by Plasmodium Liver Infection Inhibits Malaria Reinfections

Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax

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