scholarly journals Resolving the cause of recurrent Plasmodium vivax malaria probabilistically

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aimee R. Taylor ◽  
James A. Watson ◽  
Cindy S. Chu ◽  
Kanokpich Puaprasert ◽  
Jureeporn Duanguppama ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Blood Stage ◽  
High Dose ◽  
Time To Event ◽  
Liver Stage ◽  
Plasmodium Vivax Malaria ◽  
Blood Stage Infection ◽  
Stage Infection

AbstractRelapses arising from dormant liver-stage Plasmodium vivax parasites (hypnozoites) are a major cause of vivax malaria. However, in endemic areas, a recurrent blood-stage infection following treatment can be hypnozoite-derived (relapse), a blood-stage treatment failure (recrudescence), or a newly acquired infection (reinfection). Each of these requires a different prevention strategy, but it was not previously possible to distinguish between them reliably. We show that individual vivax malaria recurrences can be characterised probabilistically by combined modelling of time-to-event and genetic data within a framework incorporating identity-by-descent. Analysis of pooled patient data on 1441 recurrent P. vivax infections in 1299 patients on the Thailand–Myanmar border observed over 1000 patient follow-up years shows that, without primaquine radical curative treatment, 3 in 4 patients relapse. In contrast, after supervised high-dose primaquine only 1 in 40 relapse. In this region of frequent relapsing P. vivax, failure rates after supervised high-dose primaquine are significantly lower (∼3%) than estimated previously.

scholarly journals A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

iScience ◽  
2020 ◽  
Vol 23 (8) ◽  
pp. 101381
Author(s):  
Carola Schäfer ◽  
Wanlapa Roobsoong ◽  
Niwat Kangwanrangsan ◽  
Martino Bardelli ◽  
Thomas A. Rawlinson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Plasmodium Vivax ◽  
Blood Stage ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Liver Stage ◽  
Blood Stage Infection ◽  
Stage Transition ◽  
Stage Infection

Plasmodium vivax Latent Liver Stage Infection and Relapse: Biological Insights and New Experimental Tools

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Carola Schäfer ◽  
Gigliola Zanghi ◽  
Ashley M. Vaughan ◽  
Stefan H.I. Kappe
Keyword(s):  
Plasmodium Vivax ◽  
Blood Stage ◽  
Annual Review ◽  
Publication Date ◽  
Liver Stage ◽  
Human Malaria Parasite ◽  
Treatment And Prevention ◽  
Parasite Stage ◽  
Blood Stage Infection ◽  
Stage Infection

Plasmodium vivax is the most widespread human malaria parasite, in part because it can form latent liver stages known as hypnozoites after transmission by female anopheline mosquitoes to human hosts. These persistent stages can activate weeks, months, or even years after the primary clinical infection; replicate; and initiate relapses of blood stage infection, which causes disease and recurring transmission. Eliminating hypnozoites is a substantial obstacle for malaria treatment and eradication since the hypnozoite reservoir is undetectable and unaffected by most antimalarial drugs. Importantly, in some parts of the globe where P. vivax malaria is endemic, as many as 90% of P. vivax blood stage infections are thought to be relapses rather than primary infections, rendering the hypnozoite a major driver of P. vivax epidemiology. Here, we review the biology of the hypnozoite and recent discoveries concerning this enigmatic parasite stage. We discuss treatment and prevention challenges, novel animal models to study hypnozoites and relapse, and hypotheses related to hypnozoite formation and activation. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

2003 ◽  
Vol 197 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Carlos Ocaña-Morgner ◽  
Maria M. Mota ◽  
Ana Rodriguez
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Blood Stage ◽  
Liver Stage ◽  
Cell Responses ◽  
Blood Stage Infection ◽  
Stage Infection

Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease.

scholarly journals High-dose Primaquine Regimens against Relapse of Plasmodium vivax Malaria

2008 ◽  
Vol 78 (5) ◽  
pp. 736-740 ◽  
Author(s):  
Srivicha Krudsood ◽  
Nantaporn Phophak ◽  
Gary M. Brittenham ◽  
Sornchai Looareesuwan ◽  
Noppadon Tangpukdee ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
High Dose ◽  
Plasmodium Vivax Malaria

Blood Stage Antimalarial Efficacy of Primaquine in Plasmodium vivax Malaria

1994 ◽  
Vol 169 (4) ◽  
pp. 932-935 ◽  
Author(s):  
S. Pukrittayakamee ◽  
S. Vanijanonta ◽  
A. Chantra ◽  
R. Clemens ◽  
N. J. White
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Blood Stage ◽  
Plasmodium Vivax Malaria

scholarly journals Phenotypic profiling of CD8+ T cells during Plasmodium vivax blood-stage infection

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Natália Satchiko Hojo-Souza ◽  
Dhelio Batista Pereira ◽  
Lívia Silva Araújo Passos ◽  
Pedro Henrique Gazzinelli-Guimarães ◽  
Mariana Santos Cardoso ◽  
...  
Keyword(s):  
T Cells ◽  
Plasmodium Vivax ◽  
Cd8 T Cells ◽  
Blood Stage ◽  
Blood Stage Infection ◽  
Stage Infection

scholarly journals Artemisinin or chloroquine for blood stage Plasmodium vivax malaria in Vietnam*

2002 ◽  
Vol 7 (10) ◽  
pp. 858-864 ◽  
Author(s):  
Giao T. Phan ◽  
Peter J. de Vries ◽  
Binh Q. Tran ◽  
Hung Q. Le ◽  
Nam V. Nguyen ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Blood Stage ◽  
Plasmodium Vivax Malaria

Case report: recurrence of Plasmodium vivax malaria due to defective cytochrome P450 2D6 function in Pos Lenjang, Pahang, Malaysia

2020 ◽  
Vol 114 (9) ◽  
pp. 700-703
Author(s):  
Noor Hafizan Mat Salleh ◽  
Mohd Faizal Abdul Rahman ◽  
Samsiah Samsusah ◽  
Jeremy Ryan De Silva ◽  
David Chun-Ern Ng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cytochrome P450 ◽  
Case Report ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Microsatellite Analysis ◽  
Cytochrome P450 2D6 ◽  
Liver Stage ◽  
Plasmodium Vivax Malaria ◽  
P450 2D6

Abstract Five children in Pos Lenjang, Pahang, Malaysia were PCR-positive for vivax malaria and were admitted to the hospital from 5 to 26 July 2019. One of the patients experienced three episodes of recurrence of vivax malaria. Microsatellite analysis showed that reinfection is unlikely. Drug resistance analysis indicated that Riamet (artemether–lumefantrine) is effective. Cytochrome P450 2D6 (CYP2D6) testing showed that this patient has defective CYP2D6 function. Primaquine failure to clear the Plasmodium vivax hypnozoites may be the cause of recurring infections in this patient. This report highlights the need for the development of liver-stage curative antimalarials that do not require metabolism by the CYP2D6 enzyme.

scholarly journals Plasmodium vivax Relapse Rates Following Plasmodium falciparum Malaria Reflect Previous Transmission Intensity

2019 ◽  
Vol 220 (1) ◽  
pp. 100-104 ◽  
Author(s):  
Elizabeth A Ashley ◽  
Aung Pyae Phyo ◽  
Verena I Carrara ◽  
Kyaw Myo Tun ◽  
Francois Nosten ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Falciparum Malaria ◽  
Vivax Malaria ◽  
Substantial Reduction ◽  
Plasmodium Falciparum Malaria ◽  
Transmission Intensity ◽  
Fold Reduction ◽  
Plasmodium Vivax Malaria

Abstract From 2003 through 2009, 687 of 2885 patients (23.8%) treated for Plasmodium falciparum malaria in clinical studies in Myanmar or on the Thailand-Myanmar border had recurrent Plasmodium vivax malaria within 63 days, compared with 18 of 429 patients (4.2%) from 2010 onward (risk ratio [RR], 0.176; 95% confidence interval, .112–.278; P < .0001). Corresponding data from 42 days of follow-up revealed that 820 of 3883 patients (21.1%) had recurrent P. vivax malaria before 2010, compared with 22 of 886 (2.5%) from 2010 onward (RR, 0.117; 95% CI, .077–.177; P < .0001). This 6-fold reduction suggests a recent decline in P. vivax transmission intensity and, thus, a substantial reduction in the proportion of individuals harboring hypnozoites.

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