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        <title>Frontiers in Malaria | Pathogenesis section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/malaria/sections/pathogenesis</link>
        <description>RSS Feed for Pathogenesis section in the Frontiers in Malaria journal | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-04-05T02:40:21.146+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2026.1751312</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2026.1751312</link>
        <title><![CDATA[Non-linear effects of parasite density on symptom burden and hematologic indices in pediatric Plasmodium falciparum malaria]]></title>
        <pubdate>2026-03-31T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Olugbenga Ayodeji Mokuolu</author><author>Mohammed Baba Abdulkadir</author><author>George Oche Ambrose</author><author>Joseph Oladele Ole</author><author>Toluwani Mokuolu</author><author>Lukman Lawal</author><author>Adegboyega Joshua Agboola</author><author>Kafayat Oluwafunke Suleiman</author><author>Selimat Ibrahim</author><author>Samuel Whyte Jegede</author><author>Alexander Idu Entonu</author><author>Abdur-Rasheed Opeyemi Makinde</author><author>Okikiola Sobuur Fagbolade</author><author>Aroniyo Opeyemi Omolehin</author><author>Fuhad Damilola Azeez</author><author>Daniel Oluwagbenga Abegunde</author><author>Rahmatullah Ahuoiza Ogirima</author><author>Kolawole Temidayo Ajayi</author><author>Oluwaseun Oluwafemi Ayorinde</author><author>Akinmeji Kateanah Ibukun</author>
        <description><![CDATA[BackgroundThe clinical and hematologic manifestations of pediatric Plasmodium falciparum malaria vary across transmission settings, and the extent to which parasite density predicts symptom burden and routine laboratory abnormalities at first presentation remains uncertain. This study aimed to characterize the non-linear associations between parasite density, clinical symptom burden, and hematologic indices among children with acute P. falciparum malaria using spline-based regression models.MethodsWe conducted a cross-sectional analysis of 357 Nigerian children aged 6 months to 10 years with microscopy-confirmed malaria at enrollment prior to treatment initiation. Twenty-one symptoms were recorded with graded severity, and parasite density was log-transformed for analysis. Non-linear associations were modeled using natural cubic splines within generalized regression frameworks, adjusting for axillary temperature and smear density unit where appropriate. Hemoglobin, platelet, and white blood cell counts were examined using spline-based linear models.ResultsHeadache and vomiting were the most frequently reported symptoms, and most presentations were clinically mild. Parasite density demonstrated a non-linear positive association with overall symptom burden. Higher parasite densities were associated with greater symptom severity and an upward trend in total symptom count, with an increased likelihood of severe symptoms observed in the upper density range. No significant association was identified between parasite density and anemia severity or severe hematologic events. In contrast, thrombocytopenia showed a strong density-dependent association and moderate discriminatory performance. Hemoglobin and white blood cell counts demonstrated weak and non-significant relationships with parasite density.ConclusionsAt initial presentation, parasite density is non-linearly associated with increased clinical symptom burden, while thrombocytopenia emerges as a sensitive hematologic correlate of contemporary parasitemia. Hemoglobin and white blood cell counts appear to be poor real-time proxies of parasite load. Integrating structured symptom grading with platelet counts may enhance early triage and risk stratification in resource-limited endemic settings.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2025.1687355</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2025.1687355</link>
        <title><![CDATA[Prevalence and Plasmodium species distribution of asymptomatic malaria parasitemia among blood donors at the Lilongwe blood transfusion center]]></title>
        <pubdate>2025-11-27T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Collins Bowa</author><author>Ndagha Kalonga</author><author>Benjamin Mbonshi</author><author>Lungowe Sitali</author><author>Joseph Simwela</author><author>Evarister Kudowa</author><author>Amazing-Grace Tepeka</author>
        <description><![CDATA[BackgroundBlood transfusions are vital for treating anemia, yet in malaria-endemic regions such as Malawi, the risk of infection transmission remains significant. Owing to constrained resources and infrastructure, many blood centers have inadequate capacity for malaria detection, leading to the absence of routine screening protocols. This study aimed to explore the prevalence of asymptomatic malaria parasitemia, identify Plasmodium species, and investigate associated factors among blood donors at the Lilongwe Centre of the Malawi Blood Transfusion Service (MBTS).MethodsThis study employed a cross-sectional research design conducted at the Lilongwe Branch of the Malawi Blood Transfusion Service, a pivotal center for blood collection and distribution in Malawi’s central region. The research focused on a population of voluntary asymptomatic blood donors who presented themselves at designated donation centers. The prevalence of asymptomatic malaria parasitemia was determined using two methods: Plasmodium falciparum histidine-rich protein 2 (PfHRP2) rapid diagnostic tests (RDTs) for detecting Plasmodium falciparum parasites and microscopic analysis for confirmation and identification of other Plasmodium species, along with density quantification. Identification of factors associated with malaria transmission among blood donors was done using structured questionnaire. The study was conducted over a two-week period at the MBTS, with data analysis performed using R version 4.3.1, with statistical significance set at p-value < 0.05.ResultsThe study identified an overall malaria prevalence of 13.5% (51/377) among the participants, with 13.4% (9/67) of females and 13.5% (42/310) of males testing positive. Of the positive cases, 85.4% (41/48) were due to Plasmodium falciparum, 8.3% (4/48) were mixed infections of Plasmodium falciparum and Plasmodium malariae, and 6.3% (3/48) were solely Plasmodium malariae. Significant demographic factors influencing species distribution included age, occupation and residence. Other significant factors were blood group, repellent use, and travel history. A multivariate logistic regression model was used, but no significant associations were identified at the 0.05 significance level.ConclusionThe detection of a substantial burden of asymptomatic malaria parasitemia among blood donors highlights a potential risk for transfusion-transmitted malaria in Malawi. This finding underscores the urgent need to strengthen malaria screening protocols and diagnostic capacity within blood transfusion services.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2025.1725748</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2025.1725748</link>
        <title><![CDATA[Editorial: Women in malaria research]]></title>
        <pubdate>2025-11-03T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Alena Pance</author><author>Elena Gómez-Díaz</author><author>Sarah Reece</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2025.1553466</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2025.1553466</link>
        <title><![CDATA[Specificity and kinetics of human candidate cerebral malaria biomarkers in mice]]></title>
        <pubdate>2025-09-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Cláudia Gomes</author><author>Lizeth Chicas</author><author>Kelly A. Crotty</author><author>Isaac Salzano</author><author>Davidi Tawfiles</author><author>Ana Rodriguez</author>
        <description><![CDATA[Cerebral malaria (CM) is a complication of infection with Plasmodium falciparum that can lead to cognitive sequelae and death. The diagnosis of CM is based on clinical criteria, which leads to frequent misdiagnosis as it is confused with other infections that induce coma in children. There is currently no possibility of early diagnosis of this complication, since CM is only identified after the presentation of neurological signs, which greatly decreases treatment success and also precludes the analysis of patient’s early samples for the identification of predictive/prognostic biomarkers. Here we have used the mouse model for CM (infection with Plasmodium berghei-ANKA) and compared it to a non-CM model (infection with P. berghei-NK65) to evaluate the early kinetics and specificity of two candidate biomarkers that are elevated in the plasma of patients with CM: Angiopoietin-2 and Angiopoietin-like 4. The mouse experimental CM (ECM) model allows for the study of the biomarker’s kinetics throughout infection, starting before neurological signs are evident, and for their specificity for ECM as compared to the non-cerebral model. Our results indicate that, similar to findings in P. falciparum malaria patients, Angiopoietin-2 and Angiopoietin-like-4 are significantly elevated in plasma during P. berghei infection in mice. In mice infected with P. berghei-NK65 there was a direct correlation with the levels of parasitemia, suggesting that this may be contributing to the increased levels of both candidate biomarkers during infection, however this was not observed in P. berghei-ANKA infected mice. In these mice, a high proportion developed ECM and showed elevated levels of Angiopoietin-like 4, which were not observed in mice with non-cerebral infections. Angiopoietin-like 4 levels were directly correlated with severity of ECM. This observation is similar to previous findings in human malaria patients and provide basis for the use of mice as a model to investigate early kinetics and specificity of potential biomarkers for human severe and cerebral malaria.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2025.1620450</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2025.1620450</link>
        <title><![CDATA[Molecular polymorphism of Plasmodium vivax Duffy binding protein domain II from Nicaragua, and global diversity patterns]]></title>
        <pubdate>2025-09-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>René Ortega-Monroy</author><author>Hugo A. Tomasini-Ovilla</author><author>Frida Santillan-Valenzuela</author><author>Alberto Montoya</author><author>Lilia Gonzalez-Ceron</author>
        <description><![CDATA[BackgroundPlasmodium vivax Duffy binding protein domain II (PvBDPII) is a promising vaccine candidate due to its crucial role in reticulocyte invasion. However, polymorphism is a concern as it may confer evasion of blocking antibodies. In this study, nucleotide and protein polymorphism were analyzed in parasites collected during a decline in malaria cases in Nicaragua.MethodsGenomic DNA was extracted from P. vivax blood samples obtained from symptomatic patients in Nicaragua during 2012–2013. The PvdbpII gene was amplified and sequenced, and genetic structure, genealogical relationships, and amino acid polymorphism were analyzed. For comparison and to elucidate global variation of this gene, homologous sequences from other geographical regions were included.ResultsSixty-three consensus sequences from Nicaragua were obtained, revealing 12 non-synonymous mutations and 6 haplotypes (Hd=0.704). Nucleotide diversity was lower (π=0.0044) than in other endemic regions. The Z test of selection (dN/dS) was positive (3.17; p < 0.001), similar to parasite populations worldwide (Latin America, Middle East, Asia, Southeast Asia, Africa, Papua New Guinea). Network analysis revealed that Nicaraguan pvdbpII haplotypes differed by 3–12 mutational steps. High-frequency haplotypes from six other Latin American countries were shared, showing signs of diversification and limited population structure. Five Nicaraguan haplotypes corresponded to the 10 most frequent globally. Haplotypes defined solely by amino acid changes at positions 417, 437, and 503 were of the Sal-I type (NWI), NWK, and KRK. These, along with KRI, were shared across most regions at varying frequencies. Based on these variations, two main divergent groups were identified.ConclusionsThe low diversity observed in pvdbpII suggests a population contraction aligning with the decline of malaria cases in Nicaragua during the sampling period. The PvDBPII haplotypes found may represent those best adapted in Nicaragua and in other endemic regions globally, encompassing both Sal-I-related and divergent types. It would be beneficial to assess the ability of the most frequent and persistent haplotypes to elicit phenotype-transcending immunity, which is critical for the development of a multicomponent vaccine and for monitoring its effectiveness.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2024.1511568</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2024.1511568</link>
        <title><![CDATA[Burden and clinical characteristics of recurrent Plasmodium vivax infections, and impact of primaquine for radical cure: a systematic scoping review in India]]></title>
        <pubdate>2024-12-12T00:00:00Z</pubdate>
        <category>Systematic Review</category>
        <author>Loick Pradel Kojom Foko</author><author>Vineeta Singh</author>
        <description><![CDATA[BackgroundIndia accounts for the bulk of Plasmodium vivax burden in South East Asia. Primaquine (PQ) is the only currently available drug for treating relapses in P. vivax malaria. MethodsHere, we provide an overview of the epidemiology and clinical characteristics of P. vivax recurrent infections in India and discuss current knowledge gaps and priority research areas for further investigations, with emphasis on relapses and their radical cure with PQ. Results and discussionA total of 27 studies involving ~27,000 P. vivax infected patients were finally included. Recurrent infections with P. vivax malaria are common, especially in young males. The burden of P. vivax relapse greatly varies across Indian regions, with a proportion range of 1.47 to 6% based on the included studies which all used low (very low) PQ dose. There is a need for more empirical data on the effectiveness and safety of weekly administration of PQ at 0.75 mg/Kg for eight weeks in G6PD–deficiency patients in India, especially in children. Further research priorities should also be focused on the epidemiology of confounding factor, such as CQ-resistance, mixed infections, or Pv genetic diversity are needed. The clinical impact of P. vivax relapses (e.g., severe malaria, mortality) is also of valuable interest in upcoming studies. More studies addressing the above-mentioned missing links should be implemented to inform malariologists, clinicians, populations, and policy makers on real situation of P. vivax relapses and the clinical impact of PQ in India. All taken together, these would have important implications for P. vivax malaria control and elimination in endemic areas.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2024.1484359</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2024.1484359</link>
        <title><![CDATA[Proteomic profile of plasma-derived extracellular vesicles from Colombian pregnant women with Plasmodium-soil transmitted helminths coinfection]]></title>
        <pubdate>2024-11-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jahnnyer A. Martínez-Moreno</author><author>Alberto Ayllon-Hermida</author><author>Berta Barnadas-Carceller</author><author>Carmen Fernández-Becerra</author><author>Hernando A. del Portillo</author><author>Jaime Carmona-Fonseca</author><author>Eliana M. Arango-Flórez</author>
        <description><![CDATA[IntroductionExtracellular vesicles (EVs) are lipid bilayer membrane-enclosed nanoparticles, secreted by all cell types. Information regarding EVs and their molecular cargo in gestational parasitic infections, particularly those caused by Plasmodium and soil-transmitted helminths (STH), remains largely unexplored. This study aimed to perform isolation and molecular characterization of plasma-derived EVs from Colombian pregnant women and compare quantity, size, concentration and protein cargo of those EVs according to the infectious status, to investigate if parasite-derived proteins could be detected as biological cargo of circulating EVs of pregnant women infected with Plasmodium, STH and co-infections.Materials and methodsA descriptive study with 5 groups was performed: 1) Pregnant women with Plasmodium infection (n=10). 2) Pregnant women with STH infection (n=14). 3) Pregnant women with coinfection Plasmodium and STH (n=14). 4) Pregnant women without infection with Plasmodium nor STH (n=10). 5) Non-pregnant women without infection with Plasmodium nor STH (n=6). Plasma-derived EVs were isolated by size exclusion chromatography (SEC) and fractions containing EVs identified by a bead-based flow cytometric assay for CD9; the size and concentration of EVs were quantified by nanoparticle tracking analysis, and proteins associated with EVs were identified by liquid chromatography-mass spectrometry in a pool of samples per study group.ResultsThere were no statistical differences in expression of the CD9 EVs marker among study groups. The size range of EVs was more variable in the three infected groups (100-700 nm) compared to the size range of the uninfected groups (50-300 nm). A total of 823 quantifiable proteins with measurable abundance values were identified within the five study groups. Of the total quantifiable proteins, 758 were identified as human, six proteins pertained to P. vivax, fifteen to Trichiuris trichiura, and one to hookworms. Data are available via ProteomeXchange with identifier PXD051270.DiscussionThis is the first study that identifies proteins from Plasmodium and STH in EVs isolated from pregnant women. The identification of such proteins from neglected tropical parasites accounting for a major burden of disease worldwide, open the possibilities of studying their physiological role during infections as well as exploring them for antigen discovery, vaccine development and biomarker discovery.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2024.1365770</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2024.1365770</link>
        <title><![CDATA[Red blood cell dynamics during malaria infection challenge the assumptions of mathematical models of infection dynamics]]></title>
        <pubdate>2024-08-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Madeline A. E. Peters</author><author>Aaron A. King</author><author>Nina Wale</author>
        <description><![CDATA[For decades, mathematical models have been used to understand the course and outcome of malaria infections (i.e., infection dynamics) and the evolutionary dynamics of the parasites that cause them. The extent to which this conclusion holds will in part depend on model assumptions about the host-mediated processes that regulate RBC availability, i.e., removal (clearance) of uninfected RBCs and supply of RBCs. Diverse mathematical functions have been used to describe host-mediated RBC supply and clearance in rodent malaria infections; however, the extent to which these functions adequately capture the dynamics of these processes has not been quantitatively interrogated, as in vivo data on these processes has been lacking. Here, we use a unique dataset, comprising time-series measurements of erythrocyte (i.e., mature RBC) and reticulocyte (i.e., newly supplied RBC) densities during Plasmodium chabaudi malaria infection, and a quantitative data-transformation scheme to elucidate whether RBC dynamics conform to common model assumptions. We found that RBC supply and clearance dynamics are not well described by mathematical functions commonly used to model these processes. Indeed, our results suggest said dynamics are not well described by a single-valued function at all. Furthermore, the temporal dynamics of both processes vary with parasite growth rate in a manner again not captured by existing models. Together, these finding suggest that new model formulations are required if we are to explain and ultimately predict the within-host population dynamics and evolution of malaria parasites.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2024.1386266</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2024.1386266</link>
        <title><![CDATA[How to quantify developmental synchrony in malaria parasites]]></title>
        <pubdate>2024-05-15T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Megan A. Greischar</author><author>Nicholas J. Savill</author><author>Sarah E. Reece</author><author>Nicole Mideo</author>
        <description><![CDATA[Malaria infections represent an iconic example of developmental synchrony, where periodic fevers can result when the population of parasites develops synchronously within host red blood cells. The level of synchrony appears to vary across individual hosts and across parasite species and strains, variation that—once quantified—can illuminate the ecological and evolutionary drivers of synchrony. Yet current approaches for quantifying synchrony in parasites are either biased by population dynamics or unsuitable when population growth rates vary through time, features ubiquitous to parasite populations in vitro and in vivo. Here we develop an approach to estimate synchrony that accounts for population dynamics, including changing population growth rates, and validate it with simulated time series data encompassing a range of synchrony levels in two different host-parasite systems: malaria infections of mice and human malaria parasites in vitro. This new method accurately quantifies developmental synchrony from per capita growth rates using obtainable abundance data even with realistic sampling noise, without the need to sort parasites into developmental stages. Our approach enables variability in developmental schedules to be disentangled from even extreme variation in population dynamics, providing a comparative metric of developmental synchrony.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2024.1362644</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2024.1362644</link>
        <title><![CDATA[Optical tweezers to measure the elasticity of red blood cells: a tool to study the erythrocyte response to antimalarials]]></title>
        <pubdate>2024-03-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Doriana Dorta</author><author>Patrick Padmore</author><author>Ricardo Correa</author><author>Laura Pineda</author><author>Carmenza Spadafora</author><author>Erick Sarmiento-Gómez</author><author>Lorena M. Coronado</author>
        <description><![CDATA[The Plasmodium falciparum parasite infected more than 240 million people and killed around 600,000 patients last year alone. A key aspect of the pathophysiology of P. falciparum is the increased rigidity and adhesiveness of the membrane of infected red blood cells (iRBC). Optical tweezers (OT) have been proposed as a tool to evaluate and screen potential drugs because they can provide valuable information to determine a drug’s mechanism of action. The OT experimental design of this study was used to compare the plasma membrane stiffness of uninfected RBCs (uRBCs) and iRBCs, showing that the iRBCs were four times more rigid. The increased rigidity was more evident in those RBCs infected by the P. falciparum schizont stage. We also characterized the membrane deformability of iRBCs in vitro under the active concentration of common antimalarials on drug-resistant and non-drug-resistant P. falciparum strains. In addition, we also determined that the increased membrane rigidity of uRBCs during P. falciparum infection, known as the bystander effect, is partially reversed by antimalarial drugs. These findings suggest that single-cell mechanical measurements have potential uses in personalized medicine by characterizing the response to malaria treatment.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2024.1241933</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2024.1241933</link>
        <title><![CDATA[Meeting the challenges and strategies regarding malaria elimination: qualitative evaluation of perceptions from a local population in Colombia]]></title>
        <pubdate>2024-03-18T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Angélica Knudson Ospina</author><author>Elkin Leonardo Simanca Castro</author><author>Yenny Marcela Barreto-Zorza</author><author>Olga Lucía Ospina Rodríguez</author><author>María Alejandra Parada Aguilar</author><author>Daniel Perilla Roa</author><author>Yoseth Ariza-Araújo</author><author>Carlos Felipe Castillo</author><author>Luz Adriana Olaya Másmela</author><author>Giovanni Apráez Ippolito</author><author>Anderson Hair Piamba Dorado</author><author>Ricardo Sánchez Pedraza</author><author>Vladimir Corredor Espinel</author>
        <description><![CDATA[“One Health” and “Social Determinants of Health” approaches are crucial for implementation of sustainable strategies for the control and elimination of infectious diseases such as malaria. These approaches highlight the importance of the social component in the design of elimination strategies, as well as the communities’ involvement in the implementation of these measures at local levels. Qualitative analysis approaches for malaria research can be useful for assessing population acceptance of intervention measures and for addressing negative perceptions that can threaten the success of control goals by undermining the community’s trust in interventions. In this paper, we explore some observations and interpretations from the qualitative content analysis of two open-ended questions about malaria, from a survey conducted between September and November 2016 in Guapi, a high risk transmission area in the Colombian Pacific Region. Using the spatial transmission unit concept for the analysis of the conditions and factors involved in malaria transmission under the “One Health” and “Social Determinants of Health” approaches, we reveal that responders’ perceptions reflects both the need and requirement for continuous assistance to solve local problems and also a comprehensive problem-solving effort by the government that includes basic sanitation. From the analyses, we present a graphic model that illustrates how to address the problem of malaria control and elimination from the perspectives of the community’s perceptions in Guapi, highlighting the need for joint efforts of community, academy, and government to achieve the goal of controlling and eliminating malaria in the region.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fmala.2023.1161750</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fmala.2023.1161750</link>
        <title><![CDATA[Heme promotes sexual conversion of Plasmodium falciparum in human erythrocytes]]></title>
        <pubdate>2023-06-26T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Bethany Flage</author><author>Matthew R. Dent</author><author>Jesús Tejero</author><author>Linda Eva Amoah</author><author>Solomon Fiifi Ofori-Acquah</author>
        <description><![CDATA[Between 2018 and 2020, the global population experienced a 55% increase in deaths attributed to the most prominent malaria-causing pathogen, Plasmodium falciparum. Transmission of P. falciparum from a human host to the mosquito vector is completely reliant on the formation of sexual stage gametocytes, which arise from asexually replicating parasites during the intraerythrocytic stage of infection. Defining specific factors that promote the formation of transmissible sexual stages from the disease-causing asexual stages is important for developing new malaria control methods. Malaria infection rates are known to be affected by genetic variation of the hemoglobin (Hb) protein, and epidemiological studies have shown that Hb variants may positively influence the production of sexual stage parasites. However, the mechanisms involved are poorly defined. Here, we show P. falciparum sexual conversion rates (SCR) are significantly higher in erythrocytes expressing Hb S compared to those that express Hb A. We then found parasitic enzyme-mediated digestion of Hb S to occur more rapidly than Hb A, suggesting an increased release of heme groups carried by each Hb subunit. Upon manipulating both intracellular and extracellular heme concentrations, we found significant increases in SCR, ultimately indicating heme acts as an inducer of sexual conversion (SC). As levels of both intracellular and extracellular heme are increased in individuals with Hb variants, we propose heme to be a contributing factor for increased sexual stage conversion observed in these populations. These findings support further investigation into how heme concentrations may be directly manipulated to prevent commitment to sexual-stage formation and ultimately disease transmission.]]></description>
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