Jayne S. Sutherland

MRC Unit the Gambia

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Simon Donkor

MRC Unit the Gambia

Martin O. C. Ota

MRC Unit the Gambia

Tom H. M. Ottenhoff

Leiden University Medical Center

Olumuyiwa Owolabi

MRC Unit the Gambia

Gerhard Walzl

Stellenbosch University

Beate Kampmann

London School of Hygiene & Tropical Medicine

Stefan H. E. Kaufmann

Max Planck Institute for Infection Biology

Hazel M. Dockrell

London School of Hygiene & Tropical Medicine

Ifedayo Adetifa

Nigeria Centre for Disease Control

Novel N. Chegou

Stellenbosch University

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MRC Unit the Gambia

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University of Cape Town

London School of Hygiene & Tropical Medicine

Universitat de Barcelona

South African Tuberculosis Vaccine Initiative

Başkent University Hospital

Stellenbosch University

Barcelona Institute for Global Health

European Respiratory Society

South African Medical Research Council

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OC 8435 MULTI-BIOMARKER TEST STRIP FOR POINT-OF-CARE SCREENING FOR ACTIVE TUBERCULOSIS: A FIVE-COUNTRY MULTI-CENTRE TEST EVALUATION

BMJ Global Health (2019)

Paul L. A. M. Corstjens Anouk van Hooij Elisa M. Tjon Kon Fat Shannon Herdigein Anna Ritah Namuganga

Background Inexpensive rapid screening tests that can be used at the point-of-care (POC) are vital to combat tuberculosis. Particularly, less invasive non-sputum-based biomarker tests for all TB forms can help controlling transmission. Availability of such tests would significantly accelerate and streamline diagnostic approaches, improve cost-efficiency and decrease unnecessary costly GeneXpert referrals. Methods Multi-biomarker test (MBT) devices measuring levels of selections of up to six serum proteins simultaneously on a single lateral flow (LF) strip were produced. The strip contains individual capture lines for a biomarker selection allowing discrimination of TB-patients from other respiratory diseases (ORD). Only biomarkers successfully evaluated with singleplex strips (single biomarker tests) were applied to the MBT device. Quantitative signals are recorded with a low-cost handheld reader compatible with the applied luminescent up-converting particle (UCP) label. Biomarker selection and algorithms used to distinguish potential-TB and ORD are flexible. Results Results obtained with MBT strips containing multiple test lines correlate well with singleplex LF strips. Using LF tests for 5 selected biomarkers a sensitivity of 94% and specificity of 96% could be achieved with a confirmed South African selection of 20 TB and 31 non-TB samples. Patients were designated TB positive when scoring a value above the cut-off threshold for at least 3 out of 5 biomarkers. Serum samples of potential TB patients collected at five medical research institutes (Ethiopia, Namibia, South Africa, The Gambia, Uganda) were tested locally with MBT strips comprised of CRP, SAA, IP-10, Ferritin, ApoA-I and IL-6 and results analysed to obtain an overall pan-Africa applicable signature. Conclusion Evaluated POC applicable UCP-LF devices detecting serum biomarker signatures can help to distinguish active TB from other respiratory diseases and as such can prioritise highest-risk patients for further care. Ongoing prospective studies evaluate the MBT strip with fingerstick blood and do not require a laboratory or trained phlebotomist anymore.

Point-of-Care Testing

GeneXpert MTB/RIF

Point of care

Fingerstick

Gaza strip

10.1136/bmjgh-2019-edc.14

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Citations (3)

Use of Resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

Research Square (Research Square) (2020)

Welmoed van Loon Marie P. Gomez Dawda Jobe Kees CLMC Franken Tom H. M. Ottenhoff

Abstract Background Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. Methods Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. Results Interferon gamma production was significantly higher in infected (IGRA+, n=45) than in uninfected (IGRA-, n=20) children after stimulation with RpfA, B, C, and D ( P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73%-92% and 77%-72% respectively, which was similar to and better than 65%-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n=28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation ( P = 0.02 and 0.03, respectively). Conclusion RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.

10.21203/rs.3.rs-22482/v2

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The Risk of Retinoblastoma (RB) and Cost of Screening Relatives of Probands

Investigative Ophthalmology & Visual Science (2006)

M. Ashwin Reddy Élise Héon Jayne S. Sutherland Helen S. L. Chan Brenda L. Gallie

Proband

Retinoblastoma

Source

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Use of lateral flow assays to determine IP-10 and CCL4 levels in pleural effusions and whole blood for TB diagnosis

Tuberculosis (2015)

Jayne S. Sutherland Joseph Mendy Awa Gindeh Gerhard Walzl Toyin Togun

Multiplex

10.1016/j.tube.2015.10.011

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Citations (34)

Differences in RT-MLPA gene expression levels in progressors and non-progressors.

Jayne S. Sutherland Philip C. Hill Ifedayo Adetifa Bouke C. de Jong Simon Donkor

10.1371/journal.pone.0025230.t002

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Assessment of Client's Knowledge, Attitude and Health Seeking Behavior Towards Tuberculosis at Serrekunda Health Center and Brikama District Hospital.

Alpha Omar Jallow Abdou K. Sillah Olumuyiwa Owolabi Jayne S. Sutherland Adama Barrow

Center (category theory)

10.21428/3d48c34a.a43d7c52

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OC 8405 IDENTIFICATION OF AN MTB-SPECIFIC SOLUBLE HOST SIGNATURE FOR RISK OF DEVELOPMENT OF ACTIVE TB IN HIV-POSITIVE MTB-EXPOSED CONTACTS

BMJ Global Health (2019)

Joseph Mendy Novel N. Chegou Harriet Mayanja‐Kizza Kim Stanley Bonnie Thiel

Background With 2 billion people infected with Mycobacterium tuberculosis (Mtb) worldwide, identification of those most at-risk of progressing to active disease would provide a targeted, cost-effective approach for preventative therapy strategies. The GC6–74 project recruited Mtb-exposed HIV-positive (HIV+) contacts from 5 African countries with the aim of identifying molecular and protein signatures for identification of ‘at-risk’ subjects by comparing those who progressed to active disease (progressors) to those who remained asymptomatic (controls). Methods For this arm of the project, we analysed longitudinal samples from 12 HIV +progressors and 28 HIV +matched controls from Uganda (Makerere University, MAK) and South Africa (Stellenbosch University, SUN). Diluted whole blood was stimulated for 7 days with 7 Mtb-specific antigens plus controls. Supernatant was collected and a 38-plex multiplex assay performed following identification of confirmed progressors and controls. Results The median time to progression to active disease was 510 days for SUN and 425 days for MAK participants. Baseline CD4 counts were 163 cells/µl for progressors and 154 cells/µl for controls. Baseline responses showed significantly lower IL-4 production in progressors following ESAT-6/CFP-10 (EC) stimulation (p=0.0309) and significantly higher macrophage-derived chemokine (MDC) following both Rv3019 and TB10.4 stimulation. For the time-point closest to progression, IL-10 production following EC stimulation and IFN-γ production following Rv3019 stimulation were significantly higher in progressors than controls (p=0.0024 and p=0.0028 respectively). A combination of 12 analytes following EC and TB10.4 stimulation gave 84.4% and 91.1% correct classification respectively. Conclusion We have defined a soluble signature for detecting likely progression to active TB in HIV +subjects 1 year prior to progression. Following validation in other cohorts, this could be exploited for development of a field-friendly test for targeted interventional therapy.

10.1136/bmjgh-2019-edc.10

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The inclusion of children and adolescents in tuberculosis diagnostic development and evaluation–a consensus statement

The Lancet Infectious Diseases (2024)

Else M. Bijker Lyn Horn Sylvia M. LaCourse Emily MacLean Ben J. Marais

Delphi Method

10.1016/s1473-3099(24)00339-6

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Citations (2)

Alternative explanations for T-cell response to in-situ gene therapy for prostate cancer: In reply to Fugita et al. (Int J Radiat Oncol Biol Phys 2006;65:84–90)

International Journal of Radiation Oncology*Biology*Physics (2006)

Jeremy Millar Jayne S. Sutherland Richard L. Boyd

Hormonal Therapy

10.1016/j.ijrobp.2006.08.033

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C-reactive protein, Neopterin and Beta2 microglobulin levels pre and post TB treatment in The Gambia

BMC Infectious Diseases (2016)

Joseph Mendy Toyin Togun Olumuyiwa Owolabi Simon Donkor Martin O. C. Ota

Tuberculosis is one of the leading causes of morbidity and mortality in developing countries. Analysis of the host immune response may help with generating point-of-care tests for personalised monitoring. Thus, the aim of this study was to assess the relationship between immune activation markers: C-reactive protein (CRP), Beta2 microglobulin (B2M) and Neopterin, disease severity prior to treatment and response to therapy in adult pulmonary TB patients. HIV negative adult pulmonary TB index cases (n = 91) were recruited from the TB clinic at MRC, The Gambia. Plasma samples were collected at enrolment and at 2 and 6 months following TB treatment initiation. An enzyme linked immunosorbent assay (ELISA) was performed for evaluation of CRP, B2M and Neopterin levels and correlated with clinical and microbiological parameters including strain of infection. Disease severity was determined using Chest X-ray (CXR), Body Mass Index (BMI) and sputum smear grade. Plasma levels of all three markers were highly elevated in patients at recruitment and declined significantly during TB therapy. No correlation with disease severity was seen at recruitment. CRP showed the most significant decrease by 2 months of treatment (p < 0.0001) whereas levels of B2M and Neopterin showed little change by 2 months but a significant decrease by 6 months of treatment (p = 0.0002 and p < 0.0001 respectively). At recruitment, B2M levels were significantly higher in subjects infected with Mycobacterium africanum (Maf) compared with those infected with Mycobacterium tuberculosis sensu stricto (Mtb) (p = 0.0075). In addition, while CRP and Neopterin showed a highly significant decline post-treatment regardless of strain (p < 0.0001 for all), B2M showed differential decline depending on strain (p = 0.0153 for Mtb and p = 0.0048 for Maf) and levels were still significantly higher at 6 months in Maf compared to Mtb infected subjects (p = 0.0051). Our findings suggest that activation markers, particularly CRP, may have a role in identifying good response to TB therapy regardless of the strain of infection and could be further developed as point-of-care tests. In addition, B2M levels may allow differentiation between Mtb and Maf-infected subjects.

Neopterin

Beta-2 microglobulin

10.1186/s12879-016-1447-9

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Citations (25)