scholarly journals Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans

mBio ◽  
2021 ◽  
Author(s):  
Anastasia K. Pickford ◽  
Lucas Michel-Todó ◽  
Florian Dupuy ◽  
Alfredo Mayor ◽  
Pedro L. Alonso ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Functional Properties ◽  
Human Blood ◽  
Clinical Symptoms ◽  
Expression Patterns ◽  
Malaria Parasites ◽  
Adaptive Process ◽  
Variant Genes

The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites.

scholarly journals Expression patterns of Plasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans

2021 ◽  
Author(s):  
Anastasia K. Pickford ◽  
Lucas Michel-Todó ◽  
Florian Dupuy ◽  
Alfredo Mayor ◽  
Pedro L. Alonso ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Human Blood ◽  
Clinical Symptoms ◽  
Expression Patterns ◽  
Specific Gene ◽  
Parasite Line ◽  
Natural Conditions ◽  
Epigenetic Patterns ◽  
Variant Genes

AbstractClonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum parasites to the fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail only for a few specific gene families. Here we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in non-immune human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occur in CVGs. Specifically, we observed a major increase in the transcript levels of most members of the pfmc-2tm and gbp families and of specific genes of other families, in addition to previously reported changes in var and clag3 genes expression. Large transcriptional differences correlate with changes in the distribution of heterochromatin, confirming their epigenetic nature. The analysis of parasites collected at different time points along the infection indicates that when parasites pass through transmission stages, the epigenetic memory at CVG loci is lost, resulting in a reset of their expression state and reestablishment of new epigenetic patterns.ImportanceThe ability of malaria parasites to adapt to changes in the human blood environment, where they produce long term infection associated with clinical symptoms, is fundamental for their survival. Clonally variant genes, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in antigenic and functional alterations that enable immune evasion and provide phenotypic plasticity. However, the way these genes are expressed under the natural conditions of the human circulation or how their expression is affected by passage through transmission stages is not well understood. Here we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro cultured parasites and also distinctive alterations between different families of clonally variant genes. We also show that epigenetic patterns are erased and reestablished during transmission stages.

scholarly journals 10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity

2021 ◽  
Vol 6 ◽  
pp. 79
Author(s):  
John W.G. Addy ◽  
Yaw Bediako ◽  
Francis M. Ndungu ◽  
John Joseph Valetta ◽  
Adam J. Reid ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Symptoms ◽  
Clinical Malaria ◽  
Multiple Infections ◽  
Acquired Immunity ◽  
Large Variability ◽  
Antibody Titres ◽  
Using Data ◽  
Malaria Episodes

Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

scholarly journals 10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity

2021 ◽  
Vol 6 ◽  
pp. 79
Author(s):  
John W.G. Addy ◽  
Yaw Bediako ◽  
Francis M. Ndungu ◽  
John Joseph Valetta ◽  
Adam J. Reid ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Symptoms ◽  
Clinical Malaria ◽  
Multiple Infections ◽  
Acquired Immunity ◽  
Large Variability ◽  
Antibody Titres ◽  
Using Data ◽  
Malaria Episodes

Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

scholarly journals Endoscopically controlled surgery with open hemilaminectomy for the treatment of intradural extramedullary tumors: an operative technique and short-term outcomes of 20 consecutive cases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaorong Yan ◽  
Huiqing Wang ◽  
Cai Li ◽  
Yuanxiang Lin ◽  
Lin Lin ◽  
...  
Keyword(s):  
Surgical Technique ◽  
Spinal Deformity ◽  
Tumor Recurrence ◽  
Clinical Symptoms ◽  
Short Term ◽  
Before And After ◽  
Intradural Extramedullary ◽  
Controlled Surgery

Abstract Background To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique. Methods In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis. Results All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity. Conclusion The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

scholarly journals Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yifat Ofir-Birin ◽  
Hila Ben Ami Pilo ◽  
Abel Cruz Camacho ◽  
Ariel Rudik ◽  
Anna Rivkin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Cerebral Malaria ◽  
Survival Strategy ◽  
Parasitic Disease ◽  
Malaria Parasites ◽  
Sensing System ◽  
Rich Domain ◽  
Cargo Delivery ◽  
Low Levels

AbstractPathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf ‘decision-sensing-system’ controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3’UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

scholarly journals COVID-19 in an Asymptomatic Renal Transplant Recipient Employed in the Health Care Setting: A Case Report

2021 ◽  
Author(s):  
Harsha Adnani ◽  
Akshay Khatri ◽  
Nirav Agrawal ◽  
Ernesto Molmenti ◽  
Madhu Bhaskaran
Keyword(s):  
Health Care ◽  
Renal Transplant ◽  
Transplant Recipient ◽  
Renal Transplant Recipient ◽  
Clinical Symptoms ◽  
Severe Disease ◽  
Care Facility ◽  
Health Care Facility ◽  
Asymptomatic Patients

AbstractDuring the ongoing pandemic, there have been varying presentations of coronavirus disease 2019 (COVID-19) infection, with the concern that patients who are immunosuppressed (due to underlying medical conditions and/or therapies) are at higher risk of severe disease. We report the case of an elderly renal transplant recipient working in a long-term health care facility who was being monitored by weekly surveillance testing and tested positive for COVID-19 by polymerase chain reaction (PCR) testing, despite having no clinical symptoms. He recovered with supportive care, despite being on multiple long-term immunosuppressant drugs and having multiple comorbidities. Additionally, it was found that he did not mount an antibody response, when he tested negative by serologic testing. Through this case, we wish to highlight the unique clinical scenario of asymptomatic patients who may have an underwhelming immune response to COVID-19, but may nevertheless be an important source of dissemination. We further discuss the probable mechanism of such asymptomatic presentations in immunosuppressed patients, while reinforcing the importance of self-isolation of COVID-19 patients (particularly in asymptomatic health care workers).

scholarly journals Confounding influences of malnutrition and Plasmodium falciparum and Schistosoma haematobium infections on haematological parameters in school children in Muyuka, Cameroon

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Irene Ule Ngole Sumbele ◽  
Ofon Vitalis Otia ◽  
Lorraine Francis ◽  
Orelien Sylvain Mtopi Bopda ◽  
Calvin Bisong Ebai ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Blood Cell ◽  
Cell Count ◽  
Schistosoma Haematobium ◽  
Haemoglobin Concentration ◽  
Haematological Parameters ◽  
Blood Cell Count ◽  
Malaria Parasites ◽  
Mean Cell Volume ◽  
Distribution Width

Abstract Background School-aged children (SAC) are a high-risk demographic group for infectious diseases and malnutrition. The objective of this study was to assess the burden and the effect of Plasmodium falciparum and Schistosoma haematobium infections on the haematological indices in SAC and the confounding influence of malnutrition on the outcomes. Methods This cross-sectional study was conducted in SAC 4–14 years old living in Ikata, Bafia and Mile 14-Likoko in Muyuka, Cameroon. Anthropometric measures of malnutrition were obtained and blood samples collected were used for detection of malaria parasites by Giemsa-stained blood films using light microscopy and complete blood count analysis using an automated haematology analyser. Urine samples collected were used to detect micro haematuria with the aid of reagent strips and the eggs of S. haematobium by urine filtration technique. Multiple linear regression model was used to examine influence of independent variables on haematological parameters. Results Out of the 606 SAC examined, the prevalence of single infections with Plasmodium or S. haematobium and co-infection with both parasites was 16.2, 16.3 and 8.3%, respectively. Overall, malaria parasite (MP), urogenital schistosomiasis, malnutrition, anaemia, haematuria, microcytosis and thrombocytopenia was prevalent in 24.4, 24.6, 25.9, 74.4, 12.2, 45.4 and 11.1% of SAC, respectively. A significant linear decline (P = 0.023) in prevalence of P. falciparum infection with the severity of stunting was observed. Factors that significantly influenced haematological parameters included haemoglobin: age, stunting and MP; haematocrit: age and MP; white blood cell count: age; red blood cell count; age and MP; lymphocyte counts: stunting; mean cell volume: age; mean cell haemoglobin: age and stunting; mean cell haemoglobin concentration: sex, stunting and red cell distribution width-coefficient of variation: sex, age and stunting. Conclusions Malnutrition, Plasmodium and S. haematobium infections are common while anaemia is a severe public health problem in Muyuka, Cameroon. The interaction between haematological parameters with malaria parasites as well as linear growth index was negative and other interactions indicate systemic inflammation. While findings provide contextual intervention targets to ensure the judicious use of the limited resources, there is need for regular monitoring and proper treatment to improve the health of the underserved population.

scholarly journals Clinical characteristics and outcomes of COVID-19 long-term nucleic acid positive patients

2021 ◽  
pp. 1-10
Author(s):  
Xuan Zhu ◽  
Xinxin Zhu ◽  
Min Wang ◽  
Fang Yang ◽  
Zhibing Sun ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Control Group ◽  
Viral Shedding ◽  
Imaging Characteristics ◽  
And Gender ◽  
Acid Test ◽  
Pulmonary Ct

OBJECTIVE: This study aimed to investigate the clinical characteristics and outcomes of coronavirus disease-19 (COVID-19) long-term nucleic acid positive patients (hereinafter referred to as CLTAPs). METHODS: Patients were recruited from the Xiaogan Central Hospital between 16 January 2020 and 28 March 2020. Among the 562 cases of patients with laboratory-identified COVID-19 infection by real-time polymerase chain reaction (qtPCR), 19 cases of COVID-19 patients with more than 41 days from the first to the last time of nucleic acid test were selected as the study group, and 76 cases of age- and gender-matched COVID-19 patients were selected as the control group (hereinafter referred to as C-CLTAPs). Demographic characteristics, clinical symptoms, laboratory examination and computed tomography (CT) imaging characteristics were retrospectively analyzed. RESULTS: On admission, among the 562 cases of patients with COVID-19, there were 398 cases of ordinary COVID-19 patients, 99 cases of severe COVID-19 patients and 99 cases of critical COVID-19 patients. CLTAPs had milder clinical symptoms and longer viral shedding time in comparison to C-CLTAPs. Compared to C-CLTAPs, CLTAPs had a lower infection index at admission. CLTAPs used less oxygen therapy and a higher proportion of hydroxychloroquine treatment in comparison to C-CLTAPs. In comparison to C-CLTAPs, CLTAPs showed slower pulmonary CT progression and faster pulmonary CT absorption. CONCLUSION: In this study, out of the 562 cases, we found 19 CLTAPs. The clinical differences between CLTAPs and C-CLTAPs were compared and analyzed. We hope that these finding can provide a theoretical basis for the treatment of CLTAPs.

scholarly journals Molecular characterization of Polychromophilus parasites of Scotophilus kuhlii bats in Thailand

Parasitology ◽  
2020 ◽  
pp. 1-5
Author(s):  
Chatree Chumnandee ◽  
Nawarat Pha-obnga ◽  
Oskar Werb ◽  
Kai Matuschewski ◽  
Juliane Schaer
Keyword(s):  
Blood Cells ◽  
Clinical Symptoms ◽  
Temperate Climate ◽  
Diverse Group ◽  
Malaria Parasites ◽  
Climate Zones ◽  
Haemosporidian Parasites ◽  
South And Southeast Asia ◽  
Molecular Investigation

Abstract Parasites of the haemosporidian genus Polychromophilus have exclusively been described in bats. These parasites belong to the diverse group of malaria parasites, and Polychromophilus presents the only haemosporidian taxon that infects mammalian hosts in tropical as well as in temperate climate zones. This study provides the first information of Polychromophilus parasites in the lesser Asiatic yellow bat (Scotophilus kuhlii) in Thailand, a common vespertilionid bat species distributed in South and Southeast Asia. The gametocyte blood stages of the parasites could not be assigned to a described morphospecies and molecular analysis revealed that these parasites might represent a distinct Polychromophilus species. In contrast to Plasmodium species, Polychromophilus parasites do not multiply in red blood cells and, thus, do not cause the clinical symptoms of malaria. Parasitological and molecular investigation of haemosporidian parasites of wildlife, such as the neglected genus Polychromophilus, will contribute to a better understanding of the evolution of malaria parasites.

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