scholarly journals Plasmodium knowlesi – Clinical Isolate Genome Sequencing to Inform Translational Same-Species Model System for Severe Malaria

2021 ◽  
Vol 11 ◽  
Author(s):  
Damilola R. Oresegun ◽  
Cyrus Daneshvar ◽  
Janet Cox-Singh
Keyword(s):  
Severe Malaria ◽  
Plasmodium Knowlesi ◽  
Sequence Data ◽  
Severe Disease ◽  
Model System ◽  
Clinical Samples ◽  
Laboratory Model ◽  
High Morbidity ◽  
Parasite Diversity ◽  
Sub Saharan

Malaria is responsible for unacceptably high morbidity and mortality, especially in Sub-Saharan African Nations. Malaria is caused by member species’ of the genus Plasmodium and despite concerted and at times valiant efforts, the underlying pathophysiological processes leading to severe disease are poorly understood. Here we describe zoonotic malaria caused by Plasmodium knowlesi and the utility of this parasite as a model system for severe malaria. We present a method to generate long-read third-generation Plasmodium genome sequence data from archived clinical samples using the MinION platform. The method and technology are accessible, affordable and data is generated in real-time. We propose that by widely adopting this methodology important information on clinically relevant parasite diversity, including multiple gene family members, from geographically distinct study sites will emerge. Our goal, over time, is to exploit the duality of P. knowlesi as a well-used laboratory model and human pathogen to develop a representative translational model system for severe malaria that is informed by clinically relevant parasite diversity.

scholarly journals Getting close to nature – Plasmodium knowlesi reference genome sequences from contemporary clinical isolates

2021 ◽  
Author(s):  
Damilola R Oresegun ◽  
Peter Thorpe ◽  
Ernest Diez Benavente ◽  
Susana Campino ◽  
Muh Fauzi ◽  
...  
Keyword(s):  
Plasmodium Knowlesi ◽  
Sequence Data ◽  
Family Members ◽  
Gene Families ◽  
Core Gene ◽  
Clinical Isolates ◽  
Clinical Samples ◽  
Cell Agglutination ◽  
Sequencing Platform ◽  
Kir Genes

Plasmodium knowlesi, a malaria parasite of old-world macaque monkeys, is used extensively to model Plasmodium biology. Recently P. knowlesi was found in the human population of Southeast Asia, particularly Malaysia. P. knowlesi causes un-complicated to severe and fatal malaria in the human host with features in common with the more prevalent and virulent malaria caused by Plasmodium falciparum. As such P. knowlesi presents a unique opportunity to inform an experimental model for malaria with clinical data from same-species human infections. Experimental lines of P. knowlesi represent well characterised genetically static parasites and to maximise their utility as a backdrop for understanding malaria pathophysiology, genetically diverse contemporary clinical isolates, essentially wild-type, require comparable characterization. The Oxford Nanopore PCR-free long-read sequencing platform was used to sequence P. knowlesi parasites from archived clinical samples. The sequencing platform and assembly pipeline was designed to facilitate capturing data on important multiple gene families, including the P. knowlesi schizont-infected cell agglutination (SICA) var genes and the Knowlesi-Interspersed Repeats (KIR) genes. The SICAvar and KIR gene families code for antigenically variant proteins that have been difficult to resolve and characterise. Analyses presented here suggest that the family members have arisen through a process of gene duplication, selection pressure and variation. Highly evolving genes tend to be located proximal to genetic elements that drive change rather than regions that support core gene conservation. For example, the virulence-associated P. falciparum erythrocyte membrane protein (PfEMP1) gene family members are restricted to relatively unstable sub-telomeric regions. In contrast the SICAvar nd KIR genes are located throughout the genome but as the study presented here shows, they occupy otherwise gene-sparse chromosomal locations. The novel methods presented here offer the malaria research community new tools to generate comprehensive genome sequence data from small clinical samples and renewed insight into these complex real-world parasites.

Maternal infection in pregnancy

2020 ◽  
pp. 2671-2677
Author(s):  
Rosie Burton
Keyword(s):  
Hiv Infection ◽  
Maternal Mortality ◽  
Pregnant Women ◽  
Severe Malaria ◽  
Perinatal Death ◽  
Severe Disease ◽  
Neonatal Morbidity ◽  
Reproductive Age ◽  
Sub Saharan ◽  
In Pregnancy

This chapter will consider infection with human immunodeficiency virus (HIV), tuberculosis, and malaria in pregnancy. The global roll-out of antiretroviral therapy has significantly improved survival for people living with HIV and reduced mother-to-child transmission, but HIV infection remains a leading cause of maternal mortality, infant death, and early childhood death. Most women with HIV infection are in sub-Saharan Africa, where the highest prevalence is among young women of reproductive age. Meanwhile, tuberculosis is a major cause of maternal mortality. Active tuberculosis also adversely affects pregnancy outcomes, with an increased risk of preterm delivery, growth restriction, and perinatal death. Malaria is a major cause of maternal and neonatal morbidity and mortality. Pregnant women are more susceptible to malaria, have more severe disease, and may deteriorate rapidly. In severe malaria, mortality is 15–20% in non-pregnant women, compared to 50% in pregnancy. Primigravidae are at highest risk of severe malaria and death.

scholarly journals Microbial metagenomic approach uncovers the first rabbit haemorrhagic disease virus genome in Sub-Saharan Africa

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anise N. Happi ◽  
Olusola A. Ogunsanya ◽  
Judith U. Oguzie ◽  
Paul E. Oluniyi ◽  
Alhaji S. Olono ◽  
...  
Keyword(s):  
Virus Genome ◽  
Sub Saharan Africa ◽  
High Morbidity ◽  
Vp60 Gene ◽  
Band Size ◽  
Rabbit Haemorrhagic Disease ◽  
Sub Saharan ◽  
Domestic Rabbits ◽  
Haemorrhagic Disease ◽  
Pcr Targeting

AbstractRabbit Haemorrhagic Disease (RHD) causes high morbidity and mortality in rabbits and hares. Here, we report the first genomic characterization of lagovirus GI.2 virus in domestic rabbits from sub-Saharan Africa. We used an unbiased microbial metagenomic Next Generation Sequencing (mNGS) approach to diagnose the pathogen causing the suspected outbreak of RHD in Ibadan, Nigeria. The liver, spleen, and lung samples of five rabbits from an outbreak in 2 farms were analyzed. The mNGS revealed one full and two partial RHDV2 genomes on both farms. Phylogenetic analysis showed close clustering with RHDV2 lineages from Europe (98.6% similarity with RHDV2 in the Netherlands, and 99.1 to 100% identity with RHDV2 in Germany), suggesting potential importation. Subsequently, all the samples were confirmed by RHDV virus-specific RT-PCR targeting the VP60 gene with the expected band size of 398 bp for the five rabbits sampled. Our findings highlight the need for increased genomic surveillance of RHDV2 to track its origin, understand its diversity and to inform public health policy in Nigeria, and Sub-Saharan Africa.

Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies

2009 ◽  
Vol 101 (02) ◽  
pp. 233-238 ◽  
Author(s):  
Sara Gastoldi ◽  
Erica Daina ◽  
Daniela Belotti ◽  
Enrico Pogliani ◽  
Paolo Perseghin ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Therapeutic Option ◽  
Severe Disease ◽  
Renal Involvement ◽  
First Episode ◽  
High Morbidity ◽  
Sustained Remission ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Haemolytic Anemia

SummaryThrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.

scholarly journals Identification of a Third Human Polyomavirus

2007 ◽  
Vol 81 (8) ◽  
pp. 4130-4136 ◽  
Author(s):  
Tobias Allander ◽  
Kalle Andreasson ◽  
Shawon Gupta ◽  
Annelie Bjerkner ◽  
Gordana Bogdanovic ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Large Scale ◽  
Severe Disease ◽  
Amino Acid Identity ◽  
Human Polyomavirus ◽  
Clinical Samples ◽  
Human Pathogens ◽  
Human Respiratory Tract ◽  
Ki Polyomavirus ◽  
Virus Screening

ABSTRACT We have previously reported on a system for large-scale molecular virus screening of clinical samples. As part of an effort to systematically search for unrecognized human pathogens, the technology was applied for virus screening of human respiratory tract samples. This resulted in the identification of a previously unknown polyomavirus provisionally named KI polyomavirus. The virus is phylogenetically related to other primate polyomaviruses in the early region of the genome but has very little homology (<30% amino acid identity) to known polyomaviruses in the late region. The virus was found by PCR in 6 (1%) of 637 nasopharyngeal aspirates and in 1 (0.5%) of 192 fecal samples but was not detected in sets of urine and blood samples. Since polyomaviruses have oncogenic potential and may produce severe disease in immunosuppressed individuals, continued searching for the virus in different medical contexts is important. This finding further illustrates how unbiased screening of respiratory tract samples can be used for the discovery of diverse virus types.

scholarly journals High Frequency of Multidrug-resistant (Mdr) Klebsiella Pneumoniae Harboring Several β-lactamase and Integron Genes Collected From Several Hospitals in the North of Iran

2021 ◽  
Author(s):  
Mojgan Farhadi ◽  
Mohammad Ahanjan ◽  
Hamid Reza Goli ◽  
Mohammad Reza Haghshenas ◽  
Mehrdad Gholami
Keyword(s):  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Antimicrobial Susceptibility ◽  
Hospitalized Patients ◽  
Clinical Samples ◽  
High Morbidity ◽  
Drug Resistant ◽  
The North ◽  
Agar Diffusion Test ◽  
North Of Iran

Abstract Background: Klebsiella pneumoniae is one of the leading causes of hospital outbreaks worldwide. Also, antibiotic-resistant K. pneumoniae is progressively being involved in invasive infections with high morbidity and mortality. The aim of the current study was to determine antimicrobial susceptibility patterns and the incidences of resistance genes (integron types and β-lactamase-encoded genes) among clinical isolates of K. pneumoniae. Methods: In this cross-sectional study, a total of 100 clinical samples were obtained from hospitalized patients in three teaching hospitals in the north of Iran, from November 2018 and October 2019. Antimicrobial susceptibility testing was performed using disk agar diffusion test in line with CLSI recommendation. For colistin, minimum inhibitory concentration (MIC) was determined using broth microdilution. Based on antibiogram, multi-drug resistant (MDR) and extensive-drug resistant (XDR) strains were detected. Finally, integron types and β-lactamase resistance genes were identified using polymerase chain reaction technique.Results. The most and least clinical samples were related to the urine and bronchoalveolar lavage, respectively. Based on the antibiogram results, amikacin and gentamicin exhibited good activity against K. pneumoniae strains in vitro. High resistance rate (93%) to ampicillin/sulbactam also predict the limited efficacy of this antibiotic. Among all the 100 isolates, the frequency of MDR and XDR strains were 58% and 13%, respectively, while no pan-drug resistant (PDR) isolates were found. The prevalence of blaSHV, blaTEM, blaCTX-M-15, blaKPC, blaOXA-48, blaNDM β-lactamase genes were 91.4%, 82.7%, 79.3%, 29.3%, 36.2% and 6.9%, respectively, however 58% of the isolates were carrying intI gene. Class II and III integrons were not detected in any isolates. Conclusion: The MDR K. pneumoniae is becoming a serious problem in hospitals, with many strains developing resistance to most available antimicrobials. Our results indicate co-presence of a series of β-lactamase and integron types on the MDR strains recovered from hospitalized patients. The increasing rate of these isolates emphasizes the importance of choosing an appropriate antimicrobial regimen based on antibiotic susceptibility pattern.

scholarly journals Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Phelim Bradley ◽  
N. Claire Gordon ◽  
Timothy M. Walker ◽  
Laura Dunn ◽  
Simon Heys ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mycobacterium Tuberculosis ◽  
Sequence Data ◽  
Error Rates ◽  
Graph Representation ◽  
Clinical Samples ◽  
Resistant Bacteria ◽  
Independent Validation ◽  
Validation Set ◽  
Sensitivity Specificity

Abstract The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package (‘Mykrobe predictor’) that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes.

A testudinid herpesvirus 1 (TeHV1)-associated disease outbreak in a group of Horsfield’s tortoises (Testudo horsfieldii)

2021 ◽  
Vol 49 (06) ◽  
pp. 462-467
Author(s):  
Lisa Schüler ◽  
Pierre Picquet ◽  
Christoph Leineweber ◽  
Janosch Dietz ◽  
Elisabeth Müller ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Histological Examination ◽  
Inclusion Bodies ◽  
Severe Disease ◽  
Disease Outbreak ◽  
High Morbidity ◽  
Intranuclear Inclusion ◽  
Upper Respiratory ◽  
Herpesvirus 1 ◽  
Mycoplasma Spp

AbstractIn spring 2020, a severe disease outbreak with high morbidity and mortality was observed in a collection of 15 Horsfield’s tortoises (Testudo horsfieldii). Affected tortoises showed upper respiratory- and gastrointestinal tract signs, including rhinitis and stomatitis. Testudinid herpesvirus 1 (TeHV1) and Mycoplasma spp. were detected by PCR in oral swabs of affected animals. Histological examination of one deceased animal showed intranuclear inclusion bodies typical for herpesvirus infections in liver, spleen and oesophagus. The virus was likely introduced into the collection 2 years earlier by a clinically healthy Horsfield’s tortoise that was tested positive for TeHV1 by PCR.

scholarly journals Complete Genome Sequences of Dengue Virus Type 2 Strains from Kilifi, Kenya

2019 ◽  
Vol 8 (4) ◽  
Author(s):  
Everlyn Kamau ◽  
Charles N. Agoti ◽  
Joyce M. Ngoi ◽  
Zaydah R. de Laurent ◽  
John Gitonga ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Complete Genome ◽  
Sequence Data ◽  
Dengue Infection ◽  
Clinical Samples ◽  
Genome Sequences ◽  
Coastal Kenya ◽  
Dengue Virus Type 2

Dengue infection remains poorly characterized in Africa and little is known regarding its associated viral genetic diversity. Here, we report dengue virus type 2 (DENV-2) sequence data from 10 clinical samples, including 5 complete genome sequences of the cosmopolitan genotype, obtained from febrile adults seeking outpatient care in coastal Kenya.

scholarly journals Distinct Lineages of Feline Parvovirus Associated with Epizootic Outbreaks in Australia, New Zealand and the United Arab Emirates

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1155 ◽  
Author(s):  
Kate Van Brussel ◽  
Maura Carrai ◽  
Carrie Lin ◽  
Mark Kelman ◽  
Laura Setyo ◽  
...  
Keyword(s):  
New Zealand ◽  
United Arab Emirates ◽  
Sequence Data ◽  
Common Factor ◽  
Unknown Origin ◽  
Primary Vaccination ◽  
Vaccine Virus ◽  
Clinical Samples ◽  
Eastern Australia ◽  
Feline Parvovirus

Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events.

Sign in / Sign up

Export Citation Format

Share Document