Chemotherapeutic hope on the horizon for
            <i>Plasmodium vivax</i>
            malaria?

Ridley, Robert G.

doi:10.1073/pnas.232483699

Cited by 23 publications

(17 citation statements)

References 15 publications

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“…Chloroquine-resistant P. vivax is also increasing [2]. P. vivax is relatively little studied compared to the most lethal human malaria, Plasmodium falciparum, primarily because unlike P. falciparum it cannot be cultured in vitro.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Belnoue et al [8] demonstrated protective T cell immunity against P. yoelii liver stages after vaccination with live sporozoites and chloroquine treatment. (2) In both murine (Plasmodium yoelii) and human (P. falciparum) malaria, blood-stage infections suppress T cell responses against liver-stage Ag [8][9][10][11]. Suppression of T cell responses against the liver stages is less likely to occur in P. vivax exposed Fy(-) individuals because they do not develop blood-stage infections.…”

Section: Introductionmentioning

confidence: 99%

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Immune responses toPlasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens

Wang¹,

Arévalo‐Herrera

Gardner³

et al. 2005

Eur. J. Immunol.

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Duffy antigen is the receptor used by Plasmodium vivax to invade erythrocytes. Consequently, individuals lacking Duffy antigen [Fy(-)] do not develop blood-stage infections. We hypothesized that naturally exposed Fy(-) humans may develop immune responses mainly to pre-erythrocytic stages and could be used to study acquired immunity to P. vivax and to identify liver-stage antigens. We report here that antibody and IFN-c responses to known sporozoite antigens were significantly induced by natural exposure in Fy(-) humans, whereas responses to blood-stage antigens were significantly induced in Fy(+) humans. IFN-c responses to sporozoite antigens were lower in Fy(+) than in Fy(-) humans, indicating that in Fy(+) humans blood-stage infections may have suppressed T cell responses to pre-erythrocytic stages. We evaluated the immune responses to 18 novel P. vivax homologs of P. falciparum sporozoite proteins identified from the P. vivax genome sequence. Eight proteins recalled IFN-c responses in P. vivax-exposed but not in unexposed individuals. Of these, 3 antigens elicited IFN-c responses in Fy(-) but not in Fy(+) individuals. These results suggest that differential immune responses observed in naturally exposed Fy(-) and Fy(+) individuals can be exploited to identify P. vivax stage-specific antigens.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune responses toPlasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens

Wang¹,

Arévalo‐Herrera

Gardner³

et al. 2005

Eur. J. Immunol.

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“…Although P. vivax seldom kills, it is nevertheless as prevalent as P. falciparum and carries a morbidity load as large as that of P. falciparum (16,21).…”

mentioning

confidence: 99%

Improved Assessment of Plasmodium vivax Response to Antimalarial Drugs by a Colorimetric Double-Site Plasmodium Lactate Dehydrogenase Antigen Capture Enzyme-Linked Immunosorbent Assay

Druilhe

Brasseur

Blanc

et al. 2007

Antimicrob Agents Chemother

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The occurrence of Plasmodium vivax resistance to chloroquine has been reported in several countries of Asia and South America. However, the resistance of P. vivax is insufficiently documented for three reasons: it has received far less attention than P. falciparum; in vivo investigations are handicapped by the existence of hypnozoites, which make it difficult to distinguish between recrudescences due to drug failure and relapses due to dormant forms in the liver; and in vitro studies are greatly limited by the poor growth of P. vivax. We report on the adaptation to P. vivax of a colorimetric double-site Plasmodium lactate dehydrogenase antigen capture enzyme-linked immunosorbent assay previously developed for P. falciparum. The assay proved remarkably sensitive, as under optimal conditions it could detect P. vivax parasitemia levels as low as 10 ؊8 . The technique, which relies on the detection of protein synthesis by the parasite, yielded steep drug-response curves, leading to the precise determination of the 50% inhibitory concentrations for a high proportion of isolates. Chloroquine-resistant parasites were identified in an area where this phenomenon had been documented by in vivo methods. Thus, the results indicate that the in vitro susceptibility of P. vivax can now be monitored easily and efficiently. The data suggest that the threshold of resistance is similar to that of P. falciparum, i.e., in the range of 100 nM for chloroquine and 15 nM for pyronaridine. However, further studies are required to precisely define the cutoff for resistance and the sensitivity to each drug.The resistance of human malaria parasites to antimalarial compounds has become of considerable concern, particularly in view of the fast speed of emergence of resistant parasites, the fast spread of resistant parasites, and the shortage of novel classes of antimalarial drugs. The vast majority of studies have so far dealt with Plasmodium falciparum, the species responsible for most of the fatalities from malaria.However, over the past decade, several reports have documented the emergence of resistance of P. vivax, at least to chloroquine. Although P. vivax seldom kills, it is nevertheless as prevalent as P. falciparum and carries a morbidity load as large as that of P. falciparum (16,21).The first case of P. vivax resistance to chloroquine was reported from Papua New Guinea in 1989 (22). Further cases were observed as well in Indonesia (1,8,25,26,29,30), Myanmar (15, 17), India (12, 28), the Philippines (2), and Thailand (14), as well as in South America (11,18,23), thereby indicating that it may be a worldwide, yet underestimated, problem.The prevalence of P. vivax resistance is indeed most likely widely underestimated for two reasons: in contrast to P. falciparum, there is no method for the cultivation of P. vivax as effective as that for the cultivation of P. falciparum that can be used for in vitro studies; conversely, under in vivo conditions, the reemergence of parasites following treatment is usually attributed in primary health c...

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“…Malaria causes more than 1 million deaths per year, mainly among children, making it a priority to develop a new safe and effective drug [12]. Still another project aims to develop fixed-dose artemisinin combinations for malaria through collaboration involving TDR, a specialized international organization, i.e.…”

Section: The Potential Of Partnerships In Promotion Of Healthmentioning

confidence: 99%

Improving public health through collaboration in research

Bergquist¹

2004

International Congress Series

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Chemotherapeutic hope on the horizon for Plasmodium vivax malaria?

Cited by 23 publications

References 15 publications

Immune responses toPlasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens

Immune responses toPlasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens

Improved Assessment of Plasmodium vivax Response to Antimalarial Drugs by a Colorimetric Double-Site Plasmodium Lactate Dehydrogenase Antigen Capture Enzyme-Linked Immunosorbent Assay

Improving public health through collaboration in research

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