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An evaluation of a rapid portable gold-nanotechnology measuring SARS-CoV-2 IgM, IgA and IgG antibody response to spike 1 (S1), spike 2 (S) and nucleocapsid (N) antigens using serum from 74 RNA(+) patients and RNA(+) 47 control patients.
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BackgroundViral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2... more
BackgroundViral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and their impact on diagnostic test performance.ObjectivesTo evaluate the capacity of Abbott molecular, antigen, and serologic assays to detect the SARS-CoV-2 B.1.1.7, B.1.351 and the P.1 variants.Study designVirus variant culture stock dilutions (B.1.1.7, BEI NR-54011; B.1.351, BEI NR-54008 and 54009; P.1, BEI NR-54982) and clinical samples from patients with confirmed B.1.1.7 variant infection were run on the Abbott ID NOW COVID-19, m2000 RealTime SARS-CoV-2, Alinity m SARS-CoV-2, and Alinity m Resp-4-Plex molecular assays; the BinaxNOW COVID-19 Ag Card and Panbio COVID-19 Ag Rapid Test Device; and the ARCHITECT/Alinity i SARS-CoV-2 IgG and AdviseDx IgM assays, Panbio COVID-19 IgG assay, and ARCHITECT/Alinity i AdviseDx SARS-CoV-2 ...
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There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody... more
There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential as diagnostic tools. A highly specific in-house ELISA was developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays – a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs) – on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that perform...
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Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification... more
Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting. Methods This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines. Re...
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ABSTRACTMany healthcare facilities report SARS-CoV-2 outbreaks but transmission analysis is complicated by the high prevalence of infection and limited viral genetic diversity. The contribution of different vectors to nosocomial infection... more
ABSTRACTMany healthcare facilities report SARS-CoV-2 outbreaks but transmission analysis is complicated by the high prevalence of infection and limited viral genetic diversity. The contribution of different vectors to nosocomial infection or the effectiveness of interventions is therefore currently unclear. Detailed epidemiological and viral nanopore sequence data were analysed from 574 consecutive patients with a PCR positive SARS-CoV-2 test between March 13th and March 31st, when the pandemic first impacted on a large, multisite healthcare institution in London. During this time the first major preventative interventions were introduced, including progressive community social distancing (CSD) policies leading to mandatory national lockdown, exclusion of hospital visitors, and introduction of universal surgical facemask-use by healthcare-workers (HCW). Incidence of nosocomial cases, community SARS-CoV-2 cases and infection in a cohort of 228 HCWs followed the same dynamic course, d...
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Objectives: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults and children. Design: Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for... more
Objectives: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults and children. Design: Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. Setting: Early post 'first-wave' SARS-CoV-2 transmission period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. Participants: 110 (72 adults, 38 children, age range 0-83 years, 52.7% female (n=58)). Interventions: Patient serum from vetted referrals tested on CE marked and internally validated lateral flow immunoassay (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 spike proteins, with result and clinical interpretation provided to the direct care team. Main outcome measures: Performance characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit f...
Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how... more
Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up...
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Background: The need for a fast and reliable test for COVID-19 is paramount in managing the current pandemic. A cost effective and efficient diagnostic tool as near to the point of care (PoC) as possible would be a game changer in current... more
Background: The need for a fast and reliable test for COVID-19 is paramount in managing the current pandemic. A cost effective and efficient diagnostic tool as near to the point of care (PoC) as possible would be a game changer in current testing. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 minutes, alongside standard methods in a real-life clinical setting. Methods: This service improvement project piloted a research RT-LAMP method on nasal and pharyngeal swabs on 21 residents in an NHS Category 1 care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We calculated the sensitivity, specificity, positive and negative predictive values of a single RT-LAMP swab compared to RT-PCR, as per STARD guidelines. We also recorded vital signs of patients to correlate clinical and laboratory information. Findings: The novel method accurately detected 8/10 PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a 'gold standard', the sensitivity and specificity of the novel test were 80% and 73% respectively. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 83%. We also observed hypothermia to be a significant early clinical sign in a number of COVID-19 patients in this setting. Interpretation: RT-LAMP testing for SARS-CoV-2 was found to be promising, fast, easy to use and to work equivalently to RT-PCR methods. Definitive studies to evaluate this method in larger cohorts are underway. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the point of care. This method could be deployed in mobile testing units in the community, care homes and hospitals to detect disease early and prevent spread.
Some people who are receiving dialysis treatment have virus infection such as hepatitis B, hepatitis C and/or HIV that is present in their blood. These infections can be transmitted to other patients if blood is contaminated by the blood... more
Some people who are receiving dialysis treatment have virus infection such as hepatitis B, hepatitis C and/or HIV that is present in their blood. These infections can be transmitted to other patients if blood is contaminated by the blood of another with a viral infection. Haemodialysis is performed by passing blood from a patient through a dialysis machine, and multiple patients receive dialysis within a dialysis unit. Therefore, there is a risk that these viruses may be transmitted around the dialysis session. This documents sets out recommendations for minimising this risk. There are sections describing how machines and equipment should be cleaned between patients. There are also recommendations for dialysing patients with hepatitis B away from patients who do not have hepatitis B. Patients should be immunised against hepatitis B, ideally before starting dialysis if this is possible. There are guidelines on how and when to do this, for checking whether immunisation is effective, a...
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A 34-year-old man recently diagnosed with advanced human immunodeficiency virus infection (CD4 cell count of 139 cells/mm3), not yet started on antiretroviral medications, presented to hospital with a ten-day history of left leg weakness... more
A 34-year-old man recently diagnosed with advanced human immunodeficiency virus infection (CD4 cell count of 139 cells/mm3), not yet started on antiretroviral medications, presented to hospital with a ten-day history of left leg weakness and difficulty walking. He described a childhood history of chickenpox with previous shingles over his buttock over three years ago. Examination revealed reduced power in the left hip and knee flexors and absent knee and adductor reflexes. Lumbar punctures were performed and polymerase chain reaction (PCR) detected varicella-zoster virus (VZV) DNA. Concurrent serum samples for VZV PCR were negative. The patient was diagnosed with VZV radiculopathy and treated with high-dose intravenous acyclovir. Within two days, neurological signs improved. Previous case reports define VZV radiculopathy by a temporal and geographical relationship with a zoster rash. Our diagnosis was based on a clinical picture of radiculopathy with virological evidence in CSF and ...
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Therapies that halt progression of chronic hepatitis B virus (HBV) and achieve a cure for chronic hepatitis C virus (HCV) have encouraged development of innovative strategies to diagnose and link patients to care. We describe the... more
Therapies that halt progression of chronic hepatitis B virus (HBV) and achieve a cure for chronic hepatitis C virus (HCV) have encouraged development of innovative strategies to diagnose and link patients to care. We describe the prevalence and risk factors for HBV and HCV infections and use of an opt-out hepatitis testing and integrated linkage to care pathway in a London Emergency Department (ED). ED patients aged ≥16 years having routine blood tests from 15 February-28 March 2016 were tested for hepatitis, unless opted out. Hepatitis B surface antigen (HBsAg) and hepatitis C antibody tests (HCV-Ab, including a confirmatory hepatitis C antigen test (HCV-Ag)) were pre-selected on electronic blood test requests. Linkage to care (attending one clinic appointment) was offered to HBsAg and HCV-Ag patients (new or known-disengaged with care diagnoses). Weighted prevalence estimates and risk factors for seropositivity adjusted by demographics and survey weights were calculated using logi...
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Hepatitis A is a self-limiting infection caused by the hepatitis A virus (HAV), transmitted predominantly by the faecal–oral route including some sexual practices. Outbreaks are commonly reported in the men who have sex with men... more
Hepatitis A is a self-limiting infection caused by the hepatitis A virus (HAV), transmitted predominantly by the faecal–oral route including some sexual practices. Outbreaks are commonly reported in the men who have sex with men (population. Previous exposure is thought to provide life-long immunity against subsequent infections with the development of an HAV IgG response. This paper reports a case of acute Hepatitis A infection, despite evidence of a previously positive Hepatitis A IgG results in an HIV-positive individual.
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Objectives Molecular diagnostic methods on lower respiratory specimens for Pneumocystis pneumonia (PCP) are recommended, but specimens can be difficult to obtain. This study examined the diagnostic utility of PCP PCR (polymerase chain... more
Objectives Molecular diagnostic methods on lower respiratory specimens for Pneumocystis pneumonia (PCP) are recommended, but specimens can be difficult to obtain. This study examined the diagnostic utility of PCP PCR (polymerase chain reaction) on oropharyngeal wash (OPW) and blood vs. sputum (spontaneous and induced) to find faster, simpler and less invasive diagnostic methods. Methods We prospectively recruited consenting adults with symptoms consistent with PCP. Real-time PCR targeted the Pneumocystis mitochondrial large subunit ribosomal RNA gene, using the aforementioned specimens. Clinical data were collected from routine records. Results 45 participants provided 45 sputa, 31 OPW and 41 blood samples. Median age was 39 years and 41 (91%) were male, with median CD4 count 64 cells/µL. Sputum PCR was positive in 27/45 (60%). Comparative sensitivity of OPW was 9/19 (47%, 95% confidence interval [CI] 23, 71) and blood 12/24 (50%, 95% CI 29, 71), both with specificity 100%. Including only samples obtained <=2 days after treatment start, sensitivity of OPW was 80% (8/10, 95% CI 51, 100); blood 57% (8/14, 95% CI 29, 86) and combined tests 88% (14/16, 95% CI 70,100). In 14/16 individuals with PCP and specimens <=2 days after treatment start, diagnosis was possible using non-respiratory samples. Conclusions Despite moderate sensitivity of individual tests, combined PCP PCR on early blood and OPW specimens had high sensitivity and could reduce need for invasive procedures. There were no false-positive results on non-respiratory samples. Sampling and laboratory methods use technology frequently employed in this patient group and so require few additional resources.
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The Enigma® MiniLab™ assay for Influenza A, B and RSV was compared to a centralized laboratory respiratory virus panel. The positive and negative per cent agreement for influenza A, Influenza B and RSV were 79.2% (95% CI 57.8-92.9%),... more
The Enigma® MiniLab™ assay for Influenza A, B and RSV was compared to a centralized laboratory respiratory virus panel. The positive and negative per cent agreement for influenza A, Influenza B and RSV were 79.2% (95% CI 57.8-92.9%), 99.4% (95% CI 98.4-99.9), 100% (95% CI 47.8-100%), 100% (95% CI 99.3-100%), 98.5% (95% CI 94.6-99.8%), 94.5% (95% CI 91.9-96.4%), respectively.
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Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria. In this prospective study, we... more
Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria. In this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death. Patients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean ± SD) was elevated in severe malaria (8.2 mEq/L ± 4.5) and severe sepsis (8.6 mEq/L ± 7.7) compared with uncomplicated malaria (6.0 mEq/L ± 5.1) and encephalopathy (6.6 mEq/L ± 4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6-7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5-7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81). Newly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.
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We describe the performance of bleach-digested Zeihl-Neelsen (ZN) smears in TB suspects with/without HIV. In total, 51 (26%) and 62 (31%) out of the first 198 spot and digested smears were positive. Seven of the 30 HIV-positive patients... more
We describe the performance of bleach-digested Zeihl-Neelsen (ZN) smears in TB suspects with/without HIV. In total, 51 (26%) and 62 (31%) out of the first 198 spot and digested smears were positive. Seven of the 30 HIV-positive patients had TB and their ZN smears were negative, scanty or 1 +. Six of seven digested smears were scanty. Forty-two of 115 HIV-negative patients had TB. Eleven (26%) of their digested smears were negative, 12 (29%) scanty and 19 (45%) positive. Despite the lower bacilli numbers of HIV-positive patients, the technique had sensitivity and specificity similar to that in HIV-negative patients.