The global burden of Plasmodium vivax malaria is obscure and insidious

Battle, Katherine E.; Baird, J. Kevin

doi:10.1371/journal.pmed.1003799

Cited by 63 publications

(50 citation statements)

References 108 publications

(103 reference statements)

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“…The global P . vivax burden is estimated at 14.3 million cases per year [ 3 ]. In the Americas, malaria continues to be a major problem in poorly developed areas and indigenous communities such as part of the Amazon region, Eastern Panama [ 4 , 5 ] and the Darien gap [ 6 ], while it is under control in urban settings [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, there is currently no system of continuous in vitro culture that would accelerate basic research and development of new drugs, vaccines, and diagnostic tests [ 24 , 25 ]. Therefore, the conventional diagnostic tools that have supported the epidemiological and clinical understanding of vivax malaria may not be adequate for studying the complex biology and epidemiology of this parasite in low transmission settings [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Similar conditions are found in endemic remote regions of Panama, where its inhabitants live in low transmission settings mostly associated with Amerindian reservations [ 8 ]. Such settings contain multiple foci or pockets (“Hot Spots”) of transmission, which can present logistical and technical challenges for malaria control programs due to their remoteness and limited sensitivity of available diagnostic tests (i.e., thick blood smears and rapid diagnostic tests (RDTs) [ 3 , 6 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…vivax presents differences in biological features compared to P . falciparum [ 3 ]. For instance, gametocytes of P .…”

Section: Introductionmentioning

confidence: 99%

“…vivax parasites that has only recently been elucidated, fundamentally changes existing paradigms of P . vivax biology, pathogenesis and epidemiology [ 3 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Comparison of PvLAP5 and Pvs25 qRT-PCR assays for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from remote malaria endemic regions of Panama

et al. 2022

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Background As the elimination of malaria in Mesoamerica progresses, detection of Plasmodium vivax using light microscopy (LM) becomes more difficult. Highly sensitive molecular tools have been developed to help determine the hidden reservoir of malaria transmission in low transmission settings. In this study we compare the performance of PvLAP5 and Pvs25 qRT-PCR assays to LM for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from malaria endemic regions of Panama. Methods For this purpose, we collected a total of 83 malaria field samples during 2017-2020 preserved in RNAprotect (RNAp) of which 63 (76%) were confirmed P. vivax by LM and selected for further analysis. Additionally, 16 blood samples from local healthy malaria smear negative volunteers, as well as, from 15 malaria naïve lab-bred Aotus monkeys were used as controls. To optimize the assays, we first determined the minimum blood volume sufficient for detection of PvLAP5 and Pv18SrRNA using P. vivax infected Aotus blood that was preserved in RNAp and kept either at ambient temperature for up to 8 days before freezing or was snap-frozen at -80° Celsius at the time of bleeding. We then compared the mean differences in gametocyte detection rates of both qRT-PCR assays to LM and performed a multivariate correlation analysis of study variables. Finally, we determined the sensitivity (Se) and specificity (Sp) of the assays at detecting gametocytes compared to LM. Results Blood volume optimization indicated that a blood volume of at least 60 μL was sufficient for detection of PvLAP5 and Pv18SrRNA and no significant differences were found between RNA storage conditions. Both PvLAP5 and Pvs25 qRT-PCR assays showed a 37-39% increase in gametocyte detection rate compared to LM respectively. Strong positive correlations were found between gametocytemia and parasitemia and both PvLAP5 and Pvs25 gametocyte markers. However, no significant differences were detected in the Se and Sp of the Pvs25 and PvLAP5 qRT-PCR assays, even though data from control samples suggested Pvs25 to be more abundant than PvLAP5. Conclusions This study shows that the PvLAP5 qRT-PCR assay is as Se and Sp as the gold standard Pvs25 assay and is at least 37% more sensitive than LM at detecting P. vivax gametocytes in field samples preserved in RNAp at ambient temperature from malaria endemic regions of Panama. Author summary Plasmodium vivax is one of the five species of malaria (P. falciparum, P. malariae, P. ovale and P. knowlesi) that are transmitted to man by the bite of female anopheles mosquitoes. It causes ~14.3 million cases mainly in Southeast Asia, India, the Western Pacific and the Americas annually. In the Americas, malaria remains a major problem in underdeveloped areas and indigenous communities in the Amazon region and eastern Panama, where it is endemic and difficult to eliminate. As malaria elimination progresses, detection of P. vivax by light microscopy (LM) becomes more difficult. Therefore, highly sensitive molecular tools have been developed that use genetic markers for the parasite to help determine the hidden reservoir of malaria transmission. This study compares the performance of two molecular assays based on the genetic markers of mature gametocytes PvLAP5 and Pvs25 with LM. The study shows that the PvLAP5 qRT-PCR assay is as sensitive and specific as the gold standard Pvs25 assay and is at least 37% more sensitive than LM at detecting P. vivax gametocytes. These data suggest that the PvLAP5 qRT-PCR assay can be a useful tool to help determine the hidden reservoir of transmission in endemic foci approaching elimination.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…vivax presents differences in biological features compared to P . falciparum [ 3 ]. For instance, gametocytes of P .…”

Section: Introductionmentioning

confidence: 99%

“…vivax parasites that has only recently been elucidated, fundamentally changes existing paradigms of P . vivax biology, pathogenesis and epidemiology [ 3 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparison of PvLAP5 and Pvs25 qRT-PCR assays for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from remote malaria endemic regions of Panama

et al. 2022

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Superinfection and the hypnozoite reservoir for Plasmodium vivax: a general framework

Mehra,

McCaw,

Taylor

2023

J. Math. Biol.

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A characteristic of malaria in all its forms is the potential for superinfection (that is, multiple concurrent blood-stage infections). An additional characteristic of Plasmodium vivax malaria is a reservoir of latent parasites (hypnozoites) within the host liver, which activate to cause (blood-stage) relapses. Here, we present a model of hypnozoite accrual and superinfection for P. vivax. To couple host and vector dynamics for a homogeneously-mixing population, we construct a density-dependent Markov population process with countably many types, for which disease extinction is shown to occur almost surely. We also establish a functional law of large numbers, taking the form of an infinite-dimensional system of ordinary differential equations that can also be recovered by coupling expected host and vector dynamics (i.e. a hybrid approximation) or through a standard compartment modelling approach. Recognising that the subset of these equations that model the infection status of the human hosts has precisely the same form as the Kolmogorov forward equations for a Markovian network of infinite server queues with an inhomogeneous batch arrival process, we use physical insight into the evolution of the latter process to write down a time-dependent multivariate generating function for the solution. We use this characterisation to collapse the infinite-compartment model into a single integrodifferential equation (IDE) governing the intensity of mosquito-to-human transmission. Through a steady state analysis, we recover a threshold phenomenon for this IDE in terms of a parameter $$R_0$$ R 0 expressible in terms of the primitives of the model, with the disease-free equilibrium shown to be uniformly asymptotically stable if $$R_0<1$$ R 0 < 1 and an endemic equilibrium solution emerging if $$R_0>1$$ R 0 > 1 . Our work provides a theoretical basis to explore the epidemiology of P. vivax, and introduces a strategy for constructing tractable population-level models of malarial superinfection that can be generalised to allow for greater biological realism in a number of directions.

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A hybrid transmission model for Plasmodium vivax accounting for superinfection, immunity and the hypnozoite reservoir

Mehra,

Taylor,

McCaw

et al. 2024

J. Math. Biol.

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Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection. Here, we construct a novel model for the transmission of P. vivax that concurrently accounts for the accrual of the hypnozoite reservoir, (blood-stage) superinfection and the acquisition of immunity. We begin by using an infinite-server queueing network model to characterise the within-host dynamics as a function of mosquito-to-human transmission intensity, extending our previous model to capture a discretised immunity level. To model transmission-blocking and antidisease immunity, we allow for geometric decay in the respective probabilities of successful human-to-mosquito transmission and symptomatic blood-stage infection as a function of this immunity level. Under a hybrid approximation—whereby probabilistic within-host distributions are cast as expected population-level proportions—we couple host and vector dynamics to recover a deterministic compartmental model in line with Ross-Macdonald theory. We then perform a steady-state analysis for this compartmental model, informed by the (analytic) distributions derived at the within-host level. To characterise transient dynamics, we derive a reduced system of integrodifferential equations, likewise informed by our within-host queueing network, allowing us to recover population-level distributions for various quantities of epidemiological interest. In capturing the interplay between hypnozoite accrual, superinfection and acquired immunity—and providing, to the best of our knowledge, the most complete population-level distributions for a range of epidemiological values—our model provides insights into important, but poorly understood, epidemiological features of P. vivax.

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The global burden of Plasmodium vivax malaria is obscure and insidious

Abstract: J. Kevin Baird and colleagues, examine and discuss the estimated global burden of vivax malaria and it’s biological, clinical, and public health complexity.

Cited by 63 publications

References 108 publications

Comparison of PvLAP5 and Pvs25 qRT-PCR assays for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from remote malaria endemic regions of Panama

Comparison of PvLAP5 and Pvs25 qRT-PCR assays for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from remote malaria endemic regions of Panama

Superinfection and the hypnozoite reservoir for Plasmodium vivax: a general framework

A hybrid transmission model for Plasmodium vivax accounting for superinfection, immunity and the hypnozoite reservoir

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