HIV positive patient with GBS-like syndrome

Introduction. Guillain–Barré Syndrome (GBS) is an acute demyelinating polyneuropathy which can occur post-infection. Criteria of diagnosis of GBS include areflexia with progressive bilateral weakness in arms and legs. GBS can lead to severe respiratory and cardiac complications. The fatality rate can be up to 5 % in patients, depending on the severity of the symptoms. HIV can cause a range of neurological disorders including, on rare occasions, GBS. GBS can occur at any stage of HIV infection, highlighting the complexity of diagnosis of GBS within HIV patients. Case presentation. A 57 year old female with lumbar back pain radiating to the legs, poor mobility and tiredness, with reports of a viral-like illness four days previously, was initially diagnosed with a lower respiratory tract infection and discharged. Seventeen days later the patient was readmitted to hospital with progressive lower and upper limb weakness, areflexia and sensory loss. She was diagnosed with GBS and was unexpectedly discovered to be HIV-positive. HIV avidity was low indicating a recently acquired HIV infection. The patient was treated with intravenous immunoglobulin for five days for the GBS and commenced antriretrovirals for HIV. The patient was discharge from hospital 53 days after admission with walking aids and regular physiotherapy follow-up. Conclusion. This case highlighted the need for all clinicians to be aware that patients with symptoms of GBS, regardless of clinical history should be offered an HIV test. GBS can be the first sign a patient is HIV-positive

Tracking TCRß sequence clonotype expansions during antiviral therapy using high-throughput sequencing of the hypervariable region

To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of >35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences

Efficacy and safety of COVID-19 vaccines in older people

Declaration of Conflicts of Interest R.L.S. is a principal investigator in the Novavax COVID-19 vaccine trial. C.S. is a sub-investigator in the Novavax COVID-19 vaccine trial. E.C.T. has no conflicts of interest to declare. Views expressed are the authors’ own.Peer reviewedPostprin

Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers

Objectives Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool. Methods Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays. Results In total, 11/40 patients were diagnosed with a viral infection. Standard of care diagnostics revealed 5 viral infections using plasma samples; dengue virus 1 (n = 2), hepatitis E (n = 1), Ebola virus (n = 1) and hepatitis A (n = 1), all of which were detected by MNGS. Three additional patients with Chikungunya virus (n = 2) and mumps virus were diagnosed by MNGS only. Respiratory infections detected by nasal/throat swabs only were not detected by MNGS of plasma. One patient had infection with malaria and mumps virus during the same admission. Conclusions MNGS analysis of plasma samples improves the sensitivity of diagnosis of viral infections and has potential as an all-in-one diagnostic test. It can be used to identify infections that have not been considered by the treating physician, co-infections and new or emerging pathogens. Summary Next generation sequencing (NGS) has potential as an all-in-one diagnostic test. In this study we used NGS to diagnose returning travellers with acute febrile illness in the UK, highlighting cases where the diagnosis was missed using standard methods

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

COVID-19: the new immune challenge

Do you want to know more about Coronavirus infection? What has actually happened and why now? How big is the virus? How does it harm people? Where did the virus come from, and how did it spread to humans? Or maybe you want to know how your body defends itself from the virus. Well, you can find the answers to all these questions in this short article. We hope you will enjoy reading

GLUE: a flexible software system for virus sequence data

Background: Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics and outbreaks. To facilitate interpretation, such data must be organised and processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is a data-centric bioinformatics environment for building such resources. The GLUE core data schema organises sequence data along evolutionary lines, capturing not only nucleotide data but associated items such as alignments, genotype definitions, genome annotations and motifs. Its flexible design emphasises applicability to different viruses and to diverse needs within research, clinical or public health contexts. Results: HCV-GLUE is a case study GLUE resource for hepatitis C virus (HCV). It includes an interactive public web application providing sequence analysis in the form of a maximum-likelihood-based genotyping method, antiviral resistance detection and graphical sequence visualisation. HCV sequence data from GenBank is categorised and stored in a large-scale sequence alignment which is accessible via web-based queries. Whereas this web resource provides a range of basic functionality, the underlying GLUE project can also be downloaded and extended by bioinformaticians addressing more advanced questions. Conclusion: GLUE can be used to rapidly develop virus sequence data resources with public health, research and clinical applications. This streamlined approach, with its focus on reuse, will help realise the full value of virus sequence data

Hepatitis C and the absence of genomic data in low-income countries: a barrier on the road to elimination?

Following the development of highly effective direct acting antiviral (DAA) compounds for the treatment of the hepatitis C virus (HCV), WHO has set out plans for disease eradication by 2030. Many barriers must be surmounted before this can be achieved, including buy-in from governments and policy makers, reduced drug costs, and improved infrastructure for the pathway from diagnosis to treatment. A comprehensive set of guidelines was produced by WHO in 2014, updated in 2016, and they are due to be revised later this year

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

An update on the mosquito species composition and diversity in western and North Western Uganda

Although the west and north western parts of Uganda are historically known homes to a number of mosquito species and arboviruses associated with morbidity and mortality, early studies were highly focal and limited to specific collection methods. We aimed to update mosquito species composition in areas where a febrile illness study had shown evidence of arboviruses circulating. Adult mosquito sampling was done outside and inside houses using light traps baited with solid carbon dioxide and pyrethrum spray respectively. All collected mosquitoes were identified using appropriate morphological identification keys. A total of 22,455 mosquitoes from 89 species, 22 sub species and 11 genera were collected from Arua and Kasese districts. Overall abundance was found to be higher in Kasese (n=13446, 59.9%) than Arua district (n = 9009, 40.1%), though no significant differences were observed across villages in Arua and Kasese districts (Kruskal Wallis, X2 = 2, df = 3, p>0.05). Collection numbers were highest for genus Coquillettidia (n = 7942, 35.4%), followed by Culex (n = 7642, 34.03%), Mansonia (n = 3414, 15.2%), Anopheles (n = 1970, 8.8%) and Aedes (n = 1349, 6.01%). Other species were across 6 genera Eretmopodites (n = 59, 0.26%), Uranoteania (n = 36, 0.16%), Lutzia (n = 26, 0.12%), Mimomyia (n = 13, 0.06%), Aediomyia (n = 3, 0.01%) and Toxorhynchites (n = 1, 0.004%) appeared low in both districts. Species richness was comparatively higher in Kasese than Arua district, however across villages, it was evenly distributed with no significant differences observed, and species diversity was significantly higher in Arua than Kasese (Mann Whitney U test, p<0.05). A number of species identified here have been implied in arbovirus transmission. Moreover, we show the first description of Culex (Culex) litwakae Harbach mosquito in Uganda, a species previously described in the coastal regions of Kenya. The existence of a mosquito species previously not documented in Uganda suggests a likelihood of many invasive species whose potential to transmit viruses to humans and animals remains largely unknown