Parasite Biomass Research Articles

Neutrophil activation, acute lung injury and disease severity in Plasmodium knowlesi malaria.

The risk of severe malaria from the zoonotic parasite Plasmodium knowlesi approximates that from P. falciparum. In severe falciparum malaria, neutrophil activation contributes to inflammatory pathogenesis, including acute lung injury. The role of neutrophil activation in the pathogenesis of severe knowlesi malaria has not been examined. We evaluated 213 patients with P. knowlesi mono-infection (138 non-severe, 75 severe) and 49 Plasmodium-negative controls from Malaysia. Markers of neutrophil activation (soluble neutrophil elastase [NE], citrullinated histone [CitH3] and circulating neutrophil extracellular traps [NETs]) were quantified in peripheral blood by microscopy and immunoassays. Findings were correlated with malaria severity, ALI clinical criteria, biomarkers of parasite biomass, haemolysis, and endothelial activation. Neutrophil activation increased with disease severity, with median levels higher in severe than non-severe malaria and controls for NE (380[IQR:210-930]ng/mL, 236[139-448]ng/mL, 218[134-307]ng/mL, respectively) and CitH3 (8.72[IQR:3.0-23.1]ng/mL, 4.29[1.46-9.49]ng/mL, 1.53[0.6-2.59]ng/mL, respectively)[all p<0.01]. NETs were higher in severe malaria compared to controls (126/μL[IQR:49-323] vs 51[20-75]/μL, p<0.001). In non-severe malaria, neutrophil activation fell significantly upon discharge from hospital (p<0.03). In severe disease, NETs, NE, and CitH3 were correlated with parasitaemia, cell-free haemoglobin and angiopoietin-2 (all Pearson's r>0.24, p<0.05). Plasma NE and angiopoietin-2 were higher in knowlesi patients with ALI than those without (p<0.008); neutrophilia was associated with an increased risk of ALI (aOR 3.27, p<0.01). In conclusion, neutrophil activation is increased in ALI and in proportion to disease severity in knowlesi malaria, is associated with endothelial activation, and may contribute to disease pathogenesis. Trials of adjunctive therapies to regulate neutrophil activation are warranted in severe knowlesi malaria.

Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections.

Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by Plasmodium vivax. Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the P. vivax spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into P. falciparum 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named P. vivax Spleen-Dependent Protein 1 (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from P. vivax-infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in P. vivax, a major challenge for malaria elimination.

Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections

Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated key biological parameters characterising in vivo PvLDH dynamics based on longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans, with the estimates informed by the ex vivo data as prior knowledge in a Bayesian hierarchical framework. We found that the in vivo accumulation rate of intraerythrocytic PvLDH peaks at 10–20 h post-invasion (late ring stage) with a median estimate of intraerythrocytic PvLDH mass at the end of the life cycle to be 9.4 × 10−3ng. We also found that the median estimate of in vivo PvLDH half-life was approximately 21.9 h. Our findings provide a foundation with which to advance our quantitative understanding of P. vivax biology and will facilitate the improvement of PvLDH-based diagnostic tools.

Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.

Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of immunoglobulin G against several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific immunoglobulin G in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs.

Essential plant nutrients impair post‐germination development of Striga in sorghum

Societal Impact StatementInfestation by the parasitic weed Striga is a major cause of cereal crop production losses on smallholder farms in Africa. Essential plant nutrients play an important indirect role in parasite seed germination, the first prerequisite for successful parasitism. Here, we demonstrate that increasing the nutrient availability for the host plant can also impede Striga development beyond its germination, independent of the resistance levels of the sorghum host. This insight provides additional support for crop protection recommendations to Striga‐affected farmers. Growing a resistant crop variety combined with adequate levels of fertilisers should be the backbone of defence against this parasitic weed.Summary Striga hermonthica is a widespread parasitic weed in sub‐Saharan Africa and an important biotic constraint to sorghum production. Resistant varieties and fertilisers are crucial components of integrated Striga management. N and P fertilisers reduce the production of host‐plant strigolactones, known as Striga germination stimulants, and thereby reduce infection. Whether essential plant nutrients affect the parasite–host interaction beyond Striga germination is unknown. We conducted mini‐rhizotron assays to investigate the effects of macronutrient and micronutrient availability on post‐germination Striga development. Four sorghum genotypes (Framida, IS10978, N13, IS9830) covering the complete array of known mechanisms of post‐attachment resistance were compared with susceptible genotype Ochuti. Plants were infected with pre‐germinated Striga seeds and subjected to four nutrient treatment levels: (1) 25% of the optimal concentration of Long Ashton solution for cereals; (2) 25% macronutrient and optimal micronutrient concentration; (3) optimal macronutrient and 25% micronutrient concentration; and (4) optimal macronutrient and micronutrient concentrations. Compared with the 25% base nutrient level, treatments supplemented with macronutrients reduced the number of viable vascular connections established by pre‐germinated Striga seedlings as well as the total parasite biomass on the sorghum root system. Macronutrient treatment effects were observed across sorghum genotypes, independent of the presence and type of post‐attachment resistance, but appeared to specifically improve mechanical resistance, hypersensitive and incompatibility responses before Striga reaches the host‐root xylem. This study demonstrates, for the first time, that nutrient availability drives Striga parasitism beyond the germination stages. Increased availability of nutrients, in particular macronutrients, enhances host‐plant resistance in post‐attachment stages, reinforcing the importance of current fertiliser recommendations.

Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria.

Enhanced therapeutic efficacy achieved in treating Plasmodium vivax malaria with an 8-aminoquinoline (8-AQ) drug such as primaquine (PQ) together with a partner drug such as chloroquine (CQ) is usually explained as CQ inhibiting asexual parasites in the bloodstream and PQ acting against liver stages. However, PQ's contribution, if any, to inactivating non-circulating, extra-hepatic asexual forms, which make up the bulk of the parasite biomass in chronic P. vivax infections, remains unclear. In this opinion article, I suggest that, considering its newly described mode of action, PQ might be doing something of which we are currently unaware.

Pathogenesis of Cerebral Malaria: New Trends and Insights for Developing Adjunctive Therapies.

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, variations in brain swelling with regard to the age of patients, parasite biomass, and parasite-typing, the essential pathogenetic mechanisms underlying clinical CM have remained elusive. However, a recent series of studies based on molecular, immunologic, and advanced neuroradiologic and machine-learning approaches have unraveled new trends and insights to better understand and focus on the key determinants of CM in humans. This could possibly be the beginning of the design of new and effective adjunctive therapies that may not be common or applicable to the entire malarious world, but that could, rather, be specific to the variations in the determinants of CM.

Prediction of improved antimalarial chemotherapy of artesunate-mefloquine in combination with mefloquine sensitive and resistant Plasmodium falciparum malaria.

Declining in susceptibility of Plasmodium falciparum to mefloquine is reported in South-East Asia. A revisiting on mefloquine pharmacokinetics-pharmacodynamics (PK/PD) could assist in finding new appropriate dosage regimens in combination with artesunate as a three-day course treatment. This study aimed to investigate promising alternative artesunate-mefloquine combination regimens that are effective for the treatment of patients with mefloquine-sensitive and resistant P. falciparum malaria. Data collected during 2008-2009 from 124 patients with uncomplicated P. falciparum malaria were included in the analysis, 90 and 34 patients with sensitive and recrudescence response, respectively. All patients were treated with a three-day combination of artesunate-mefloquine. Population PK-PD models were developed. The developed models were validated with clinically observed data. Simulations of clinical efficacy of alternative mefloquine regimens were performed based on mefloquine sensitivity, patients' adherence and parasite biomass. The developed PK/PD models well described with clinically observed data. For mefloquine-resistant P. falciparum, a three-day standard regimen of artesunate-mefloquine is suitable (>50% efficacy) only when the level of parasite sensitivity was < 1.5-fold of the cut-off level (IC50 < 36 nM). For mefloquine-sensitive parasite with IC50 < 23.19 nM (0.96-fold), all regimens provided satisfactory efficacy. In the isolates with IC50 of 24 nM, regimen-I is recommended. Curative treatment criteria for mefloquine and artesunate were C336h (>408 ng.mL-1) or Cmax/IC50 (>130.1 g.m/M), and Cmax/IC50 (>381.2 g.m/M), respectively. Clinical use of a three-day standard artesunate-mefloquine is suitable only when the IC50 of P. falciparum isolates is lower than 36 nM. Otherwise, other ACT regimens should be replaced. For mefloquine-sensitive parasite, a dose reduction is recommended with the IC50 is lower than 23.19 nM.

Performance of a parasitic plant and its effects on hosts depends on the interactions between parasite seed family and host species.

Root hemiparasitic plants act as keystone species influencing plant community composition through their differential suppression of host species. Their own performance also strongly depends on interactions with host species. However, little is known about the roles of parasite genetic variation vs. plasticity in these interactions. We grew plants from eight maternal families of the root hemiparasite Rhinanthus alectorolophus with six potential host species (two grasses, two legumes and two forbs) and without a host and measured fitness-related and morphological traits of the parasite, host biomass and overall productivity. Parasite biomass and other traits showed strong plastic variation in response to different host species, but were also affected by parasite maternal family. Parasite seed families responded differently to the hosts, indicating genetic variation that could serve as the basis for adaptation to different host plants. However, there were no negative correlations in the performance of families across different hosts, indicating that R. alectorolophus has plastic generalist genotypes and is not constrained in its use of different host species by trade-offs in performance. Parasite effects on host biomass (which may indicate virulence) and total productivity (host + parasite biomass) depended on the specific combination of parasite family and host species. Mean biomass of hosts with a parasite family and mean biomass of that family tended to be negatively correlated, suggesting selection for maximum resource extraction from the hosts. Specialization of generalist root hemiparasites may be restricted by a lack of trade-offs in performance across hosts, together with strong spatial and temporal variation in host species availability. The genetic variation in the effects on different hosts highlights the importance of genetic diversity of hemiparasites for their effects on plant community structure and productivity and for the success of using them to restore grassland diversity.

Monocyte epigenetics and innate immunity to malaria: yet another level of complexity?

Children under the age of 5 years living in areas of moderate to high malaria transmission are highly susceptible to clinical malaria with fever that prompts treatment of blood stage infection with anti-malarial drugs. In contrast, older school age children frequently experience subclinical malaria, i.e. chronic Plasmodium falciparum parasitemia without fever or other clinical symptoms. The role of innate immune cells in regulating inflammation at a level that is sufficient to control the parasite biomass, while at the same time maintaining a disease-tolerant clinical phenotype, i.e., subclinical malaria, is not well understood. Recent studies suggest that host epigenetic mechanisms underlie the innate immune homeostasis associated with subclinical malaria. This Current Opinion article presents evidence supporting the notion that modifications of the host monocyte/macrophage epigenome regulate innate immune functions pertinent to subclinical malaria.

A systematic review and meta-analysis on sub-microscopic Plasmodium infections in India: Different perspectives and global challenges

The long-term maintenance of parasite biomass below the detection threshold of microscopy may stymie malaria elimination. Variation in microscopists’ competencies to detect and correctly identify parasite species reflect in microscopy sensitivity, resulting in incorrect species-specific burden. The study estimated Plasmodium SMI pooled burden from published reports using a random effect model & identifies their hotspots in India. The study applied a prediction model for the first time on Indian data, emphasizing the importance of such models that can predict PCR-prevalence from slide- prevalence. A total of 17,449 samples from 39 districts were examined for Plasmodium by microscopy and PCR. The overall heterogeneity in clinic-based and community-based studies was 91% and 96%, respectively, with the pooled prevalence of 3.63%. The SMI prevalence in individual studies ranged from 38.4% to 0.4%. Sensitivity of microscopy for mono- P. vivax (91%) was found to be better than mono- P. falciparum (82 %). But surprisingly, it was much lower for mixed PfPv (45%). Primary regional data in the form of SMIs hot spots should be generated from countries on the verge of malaria elimination, and genetic monitoring should be integrated into national programs, particularly in key areas for successful malaria elimination. Not applicable.

The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria.

Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 (PfHRP2) have diagnostic and prognostic value in severe malaria. We investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of PfHRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma PfHRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4.

An artificial host system enables the obligate parasite Cuscuta campestris to grow and reproduce in vitro.

Cuscuta campestris is an obligate parasitic plant that requires a host to complete its life cycle. Parasite-host connections occur via a haustorium, a unique organ that acts as a bridge for the uptake of water, nutrients, and macromolecules. Research on Cuscuta is often complicated by host influences, but comparable systems for growing the parasite in the absence of a host do not exist. We developed an axenic method to grow C. campestris on an artificial host system (AHS). We evaluated the effects of nutrients and phytohormones on parasite haustoria development and growth. Haustorium morphology and gene expression were also characterized. The AHS consists of an inert, fibrous stick that mimics a host stem, wicking water and nutrients to the parasite. It enables C. campestris to exhibit a parasitic habit and develop through all stages of its life cycle, including production of new shoots and viable seeds. The phytohormones 1-naphthaleneacetic acid and 6-benzylaminopurine affect haustoria morphology and increase parasite fresh weight and biomass. Unigene expression in AHS haustoria reflects processes similar to those in haustoria on living host plants. The AHS is a methodological improvement for studying Cuscuta biology by avoiding specific host effects on the parasite and giving researchers full control of the parasite environment.

Cestode parasites are depleted in 15N relative to their fish hosts in northern Alberta, Canada

The use of stable isotopes to study trophic interactions and food webs has become a common practice in ecology. Until recently, parasites were largely omitted from these analyses despite their known contribution to ecosystem complexity and function. Long-standing assumptions about the enrichment of δ15N in consumers relative to their resources occasionally placed parasites in trophic positions above their hosts. However, recent literature has shown that unlike consumers to prey, parasites do not reliably exhibit enrichment in δ15N. This is particularly true of helminth endoparasites in the class cestoda, which tend to be depleted in δ15N. We developed empirical estimates of nitrogen and carbon stable isotope ratios from a cestode parasite (Ligula intestinalis) across four fish hosts from two lakes in northern Alberta, Canada. We found that L. intestinalis were depleted in δ15N relative to their hosts across all host fish species, with mean nitrogen discrimination factors (Δ15N) ranging from −1.92 ± 0.24‰ to −2.91 ± 1.17‰. In contrast, δ 13C values did not differ significantly in any direction between hosts and their parasites. Mean carbon discrimination factors (Δ13C) ranged from −0.66 ± 2.69‰ to 0.04 ± 1.53‰. We also tested for relationships between proportional parasite biomass and discrimination factor (Δ15N & Δ13C), and found high variability in strength and direction of these correlations across species. The direction and magnitude of nitrogen discrimination we found for L. intestinalis is similar to that of previous cestode stable isotope studies and may indicate consistency across the class cestoda. However, class cestoda is incredibly diverse and relatively few studies have examined host-parasite discrimination factors within the clade. We encourage additional research into host-parasite discrimination factors for the class cestoda, and across all parasite taxa. This could facilitate the inclusion of these widespread interactions into food web studies, thus improving our knowledge of trophic structure and dynamics.

Host Energetics Explain Variation in Parasite Productivity across Hosts and Ecosystems.

AbstractParasites are thought to play a role in ecosystem energetics, in part because some ecosystems harbor a substantial amount of parasite biomass. Nevertheless, the extent to which parasite biomass accurately reflects the flow of energy from hosts to parasites-and the linkages between their energetics-remains unclear. Here, we estimate parasite community energetics at the host and ecosystem level and test predictions for parasite energetics using the metabolic theory of ecology. Across 27 host species, parasite community abundance declines with average individual parasite energy use Rp as and increases with host metabolic rate Rh as , which is inconsistent with metabolic theory. We next test whether the fraction of host energy that is allocated to parasitism is invariant across hosts. Our empirical analysis demonstrates that 85% of the variation in parasite community energy use can be explained by differences in host metabolic rate. However, parasite community energy use increases allometrically with host metabolic rate Rh as , suggesting that the fraction of host energy used by parasites declines with host metabolic rate. At the ecosystem level, we show that the energy flowing through parasite communities scales allometrically with the total rate of energy use by their fish hosts across three ecosystems. Importantly, directly examining energy flux revealed variation in parasite energy use among ecosystems that was not apparent when examining differences in biomass. Taken together, these results establish strong empirical links between host and parasite energetics, but our findings often did not align with predictions based on metabolic theory.

Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients.

Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study, we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses, and ex vivo assays. Patterns of clinical features, parasite burden, and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation, and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients' signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia, and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, particularly in the haematopoietic niche of bone marrow and spleen.

Determinants of brain swelling in pediatric and adult cerebral malaria.

Cerebral malaria (CM) affects children and adults, but brain swelling is more severe in children. To investigate features associated with brain swelling in malaria, we performed blood profiling and brain MRI in a cohort of pediatric and adult patients with CM in Rourkela, India, and compared them with an African pediatric CM cohort in Malawi. We determined that higher plasma Plasmodium falciparum histidine rich protein 2 (PfHRP2) levels and elevated var transcripts that encode for binding to endothelial protein C receptor (EPCR) were linked to CM at both sites. Machine learning models trained on the African pediatric cohort could classify brain swelling in Indian children CM cases but had weaker performance for adult classification, due to overall lower parasite var transcript levels in this age group and more severe thrombocytopenia in Rourkela adults. Subgrouping of patients with CM revealed higher parasite biomass linked to severe thrombocytopenia and higher Group A–EPCR var transcripts in mild thrombocytopenia. Overall, these findings provide evidence that higher parasite biomass and a subset of Group A–EPCR binding variants are common features in children and adult CM cases, despite age differences in brain swelling.

Simultaneous genotyping of snails and infecting trematode parasites using high-throughput amplicon sequencing.

Several methodological issues currently hamper the study of entire trematode communities within populations of their intermediate snail hosts. Here we develop a new workflow using high-throughput amplicon sequencing to simultaneously genotype snail hosts and their infecting trematode parasites. We designed primers to amplify four snail and five trematode markers in a single multiplex PCR. While also applicable to other genera, we focused on medically and economically important snail genera within the superorder Hygrophila and targeted a broad taxonomic range of parasites within the class Trematoda. We tested the workflow using 417 Biomphalaria glabrata specimens experimentally infected with Schistosoma rodhaini, two strains of Schistosoma mansoni and combinations thereof. We evaluated the reliability of infection diagnostics, the robustness of the workflow, its specificity related to host and parasite identification, and the sensitivity to detect co-infections, immature infections and changes of parasite biomass during the infection process. Finally, we investigated its applicability in wild-caught snails of other genera naturally infected with a diverse range of trematodes. After stringent quality control the workflow allows the identification of snails to species level, and of trematodes to taxonomic levels ranging from family to strain. It is sensitive to detect immature infections and changes in parasite biomass described in previous experimental studies. Co-infections were successfully identified, opening the possibility to examine parasite-parasite interactions such as interspecific competition. Together, these results demonstrate that our workflow provides a powerful tool to analyse the processes shaping trematode communities within natural snail populations.

Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria

AbstractPlasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P falciparum between children with SCA (homozygous sickle cell disease/hemoglobin SS [HbSS]) and normal hemoglobin genotype/hemoglobin AA (HbAA) are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n = 208) or HbSS (n = 22) who presented with severe anemia and P falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion. No child had known SCA at enrollment. Children with HbSS did not differ from children with HbAA in peripheral parasite density, but had significantly lower sequestered parasite biomass. Children with HbSS had greater leukocytosis but significantly lower concentrations of several plasma inflammatory cytokines, including tumor necrosis factor α (TNF-α). In contrast, children with HbSS had threefold greater concentrations of angiopoietin-2 (Angpt-2), a marker of endothelial dysregulation associated with mortality in severe malaria. Lower TNF-α concentrations were associated with increased risk of postdischarge mortality or readmission, whereas higher Angpt-2 concentrations were associated with increased risk of recurrent clinical malaria. Children with SCA have decreased parasite sequestration and inflammation but increased endothelial dysregulation during severe anemia with P falciparum parasitemia, which may ameliorate acute infectious complications but predispose to harmful long-term sequelae.

Does phosphorus influence performance of a native hemiparasite and its impact on a native legume?

Phosphorus (P) is an essential plant nutrient and can become limiting in terrestrial ecosystems where parasitic plant:host associations occur. Yet little is known on how P availability influences parasite performance and its impact on hosts. We investigated the performance of the Australian native stem hemiparasite Cassytha pubescens and its impact on the native leguminous shrub Acacia paradoxa in high or low P conditions in a glasshouse experiment. Infected plants had significantly lower total, shoot, root and nodule biomass and shoot:root ratio than uninfected plants, regardless of P supply. The significant negative effect of infection on arbuscular mycorrhizal colonisation of host roots was more severe in the high P treatment. Infection significantly decreased predawn quantum yield of A. paradoxa in low P but not high P conditions. This finding may be due to the parasite-induced significant enrichment of aluminium in host foliage in low P but not high P treatments. A. paradoxa had significantly lower foliar phosphorus concentration [P] and nitrogen concentration in low P than high P conditions. Parasite biomass and photosynthetic performance were unaffected by P, whereas C. pubescens had significantly lower stem [P] in the low P than high P treatment. Parasite carbon isotope composition was significantly higher than that of the host, especially in low P conditions. Our results show that: (a) native parasite growth and its negative impact on growth of this native shrub was unaffected by P supply and (b) soil P conditions may have no influence on stem hemiparasite:host associations in nature.