Simon Donkor - Academia.edu (original) (raw)

Papers by Simon Donkor

The FASEB Journal, 2014

Iron biomarker patterns identify tuberculosis (TB) risk, but evidence of the evolution of iron bi... more Iron biomarker patterns identify tuberculosis (TB) risk, but evidence of the evolution of iron biomarkers from treatment initiation to disease resolution is limited. Plasma/serum ferritin, hepcidin...

Background: IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent Mycobacte... more Background: IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Their performance may depend on assay format and may vary across populations and settings. We compared the diagnostic performance of an in-house T -cell and commercial whole blood-based IGRAs for the diagnosis of LTBI and TB disease in The Gambia. Methods: Newly diagnosed sputum smear positive cases and their household contacts were recruited. Cases and contacts were bled for IGRA and contacts had a Mantoux skin test. We assessed agreement and discordance between the tests and categorized a contact's level of M. tuberculosis exposure according to where s/he slept relative to a case: the same room, same house or a different house. We assessed the relationship between exposure and test results by multiple logistic regression. Results: In 80 newly diagnosed TB cases, the sensitivity of ELISPOT was 78.7% and for QFT-GIT was 64.0% (p = 0.047). Of 194 ho...

Background While T cell responses to Mycobacterium tuberculosis (Mtb) have been extensively studi... more Background While T cell responses to Mycobacterium tuberculosis (Mtb) have been extensively studied, the role of B-cells and antibodies are less well characterised. The aim of this study was to assess levels of Mtb-specific IgG + plasmablasts across the Mtb infection spectrum. Methods Patients with active TB were analysed at baseline and 6 months of therapy (n = 20).Their exposed household contacts (HHC) included individuals with latent TB infection (LTBI; n = 20); evident at baseline; individuals with a negative Tuberculin Skin Test (TST) at baseline who became; positive at 6 months (converters; n = 11) and those who remained negative (non-converters; n = 10). An e x-vivo B-cell ELISPOT was performed to analyse plasmablast responses. Results Frequencies of ESAT-6/CFP-10 (EC)- but not Whole Cell Lysate (WCL)-specific plasmablasts were significantly higher in patients with active TB pre-treatment compared to post-treatment (p = 0.002) and compared to HHC with LTBI (p < 0.0001). Co...

Background: Interferon gamma release assays (IGRAs) perform differently in high TB incidence comp... more Background: Interferon gamma release assays (IGRAs) perform differently in high TB incidence compared to low TB incidence countries. As part of an evaluation of widely available commercial IGRAs for latent TB infection, we assessed the sensitivities of two IGRAs for culture positive TB and the impact of the Mycobacterium tuberculosis strain isolated. Methods: The sensitivities of T-SPOT.TB and Quantiferon-Gold in-tube (QFT-GIT) assay were compared in sputum culture positive cases of TB. The results were stratified according to whether the infecting strain was Mycobacterium tuberculosis or M. africanum. Factors associated with discordance and concordance were examined Results: In 99 TB cases studied, both IGRAs had high sensitivities, 89.7% and 90.1% for TSPOT and QFT-GIT respectively and these were not significantly different (p=0.91). When each was combined with TST, there were gains in sensitivity (96.3% and 100% respectively for TST combined with QFT-GIT and T-SPOT. The agreement...

Clinical Infectious Diseases

Background Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung r... more Background Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. Methods Fresh blood from 42 adult, human immunodeficiency virus (HIV)–negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. Results Total neutrophils decreased by post-treatment compar...

International Journal of Infectious Diseases

The Journal of Infectious Diseases

In Indonesia, BCG protection against M. tuberculosis infection decreased with increasing exposure... more In Indonesia, BCG protection against M. tuberculosis infection decreased with increasing exposure to the pathogen. We aimed to validate these findings in Africa. Poisson regression was used to estimate BCG protection, stratified by exposure using an exposure score, against ELISPOT conversion at 3 months in 220 Gambian case contacts. While the interaction between BCG and exposure was not significant (p=0.13), BCG protection was strongest in the lowest exposure tertile (RR, 0.35 [95% CI,0.15-0.82]; P=0.02), and the RRs for the middle and highest tertile were 0.50 (0.30-0.83; P=0.008) and 0.71 (0.45-1.13; P=0.1) respectively. These results are consistent with those from Indonesia.

BackgroundDespite recent advances in diagnosis and treatment, tuberculosis (TB) remains a major i... more BackgroundDespite recent advances in diagnosis and treatment, tuberculosis (TB) remains a major infectious disease killer in resource-poor settings. Strategies to prevent Mycobacterium tuberculosis (Mtb) infection are urgently required. By characterising natural protective immunity to Mtb infection we aimed to identify correlates of protection to guide vaccine development and other immune based therapies.MethodsTwo groups of Mtb-exposed contacts of TB patients were recruited in The Gambia and assessed for Mtb infection status using either tuberculin skin test (TST) reactivity at baseline and 3 months or QuantiFERON (QFT) reactivity at baseline and 6 months. For both groups, converters were defined as having a negative test at baseline and a positive one at follow-up, while those with a negative test at both time-points were defined as non-converters (Mtb resisters). Participants were analysed using RNA-sequencing and plasma Mtb proteome IgA and IgG arrays.ResultsSeveral genes were f...

BMJ Global Health

BackgroundMethods which use Mycobacterium tuberculosis (Mtb)-specific antigens to measure IFN-γ r... more BackgroundMethods which use Mycobacterium tuberculosis (Mtb)-specific antigens to measure IFN-γ responses (IFN-γ release assays (IGRA)) have been useful in detecting Mtb infection in exposed individuals. We assessed infections in TB cases and their exposed household contacts (HHC) using an in-house optimised IGRA, the QuantiFERON-TB Gold in Tube (QFT-GIT) and QFT-Plus (QFT+).MethodsFor the in-house IGRA, we analysed 266 active TB patients and 759 HHC (256 tuberculin skin test-positive and 503 test-negative, TST+ and TST- respectively) at baseline and 6 months. In a separate study we assessed QFT-GIT and QFT-plus responses using samples from 72 TB cases and 69 HHC at baseline. QFT-GIT has 3 Mtb-specific antigens: ESAT6, CFP10 and TB7.7 while QFT-plus has long and short peptides of ESAT-6 and CFP-10, designed to induce CD4+ and CD8+T cell responses respectively.ResultsIFN-γ responses were lowest in TST- compared to both TST+ and TB patients at baseline (p<0.0001 for both), with 32%...

Journal of global health, 2018

The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed th... more The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient. This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each a...

American journal of respiratory and critical care medicine, Jan 6, 2018

Contacts of tuberculosis (TB) patients constitute an important target population for preventative... more Contacts of tuberculosis (TB) patients constitute an important target population for preventative measures as they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. We investigated biosignatures with predictive ability for incident tuberculosis. In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, polymerase chain reaction (PCR) and the Pair Ratio algorithm in a training/test set approach. Overall, 79 progressors, who developed tuberculosis between 3 and 24 months following exposure, and 328 matched non-progressors, who remained healthy during 24 months of follow-up, were investigated. A four-transcript signature (RISK4), derived from samples in a South African and Gambian training set, predicted progression up to two years before onset of disease in blinded test set samples from South Africa, The Gambia and Ethiopia with little popul...

The American journal of tropical medicine and hygiene, Jan 12, 2017

Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk f... more Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case. Contacts were tested with an enzyme-linked immunospot interferon gamma release assay. In multivariate regression models, M. tuberculosis infection was associated with increasing exposure to a case (odds ratios [OR]: 3.9, 95% confidence interval [CI]: 2.11-71.4, P < 0.001]) and with male gender (OR: 1.5 [95% CI: 1.12-2.11], P = 0.008). Tobacco use caused a 3-fold increase in the odds of M. tuberculosis infection ...

Journal of Infection, 2016

Bulletin of the World Health Organization, 2016

PLoS neglected tropical diseases, May 1, 2016

Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberc... more Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and...

BMC infectious diseases, Jan 8, 2016

Tuberculosis is one of the leading causes of morbidity and mortality in developing countries. Ana... more 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 mark...