Dr Dolly Jackson-Sillah - Academia.edu (original) (raw)

Papers by Dr Dolly Jackson-Sillah

Freshly isolated PBMC from 10 TB patients were cultured in the presence of ESAT-6-CFP10 ... more Freshly isolated PBMC from 10 TB patients were cultured in the presence of ESAT-6-CFP10 or without antigen for 6 days. Harvested cells were then stained for the expression of CD25 and Foxp3 within the CD4− (B & D) and CD4+ (A & C) T cell populations. The figure illustrates the mean proportions (horizontal lines) of CD4+ and CD4− T cells expressing both CD25 and FoxP3 (A & B) or CD25 with high fluorescent intensity (CD25hi) and Foxp3 (C & D) after subtracting the responses obtained in unstimulated cultures. The dots are the individual responses and the error bars represent the standard errors of the mean. The repeated measures one-way ANOVA with Sidak’s multiple comparison tests was used for comparison of longitudinal data with the baseline results in patients. The Mann Whitney p-value was used in the comparison of baseline results from TB patients with healthy donors (**P<0.05 in longitudinal comparison and * P<0.05 in unpaired variables) Abbreviations are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068121#pone-0068121-g001" target="_blank">Figure 1</a>.</p

BMC infectious diseases, Jan 30, 2006

New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced a... more New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (9...

Clinical Infectious Diseases, 2004

Background: Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) ... more Background: Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are Mycobacterium tuberculosis (Mtb)–specific antigens that are secreted by actively metabolising bacteria and contribute to the virulence of the bacteria. Their ability to induce Treg and Th2 responses, particularly during the first two weeks of treatment, has not been comprehensively examined to date. The purpose of this work was to characterise Th1, Th2 and Treg responses to rESAT-6-CFP10 fusion protein in TB patients before and during the intensive phase of treatment and in healthy M.bovis BCG vaccinated donors. Methods: Forty-six newly diagnosed, HIV-negative, smear-positive pulmonary TB patients and 20 healthy donors were recruited in the UK and Ghana. Their peripheral blood mononuclear cells (PBMC) were used in ex vivo ELISPOT and in vitro cultures to identify immunological parameters of interest. Results: The study confirmed that protective immune responses to rESAT-6-CFP10 are i...

and the European Commission. The funders had no role in study design, data collection and analysi... more and the European Commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: RHB has a patent relating to ex vivo ELISPOT

Cytokine response to selected MTB antigens in Granzyme B, IL-17 and sIL-2R-α increased during wee... more Cytokine response to selected MTB antigens in Granzyme B, IL-17 and sIL-2R-α increased during week two, but it was significant for only Rv1733-specific production of Granzyme B (P = 0. 013). The median frequency of antigen specific IFN-γ + CD4 T cells increased at week two; however, Mensah et al. BMC Infectious Diseases 2014, 14:495

Background. Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-... more Background. Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209-336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. Methods and Findings. A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209-336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the-336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2x2 x 2 =7.47, P = 0.0...

© 2006 Hill et al; licensee BioMed Central Ltd. This is an Open Access article distributed under ... more © 2006 Hill et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License

Background. Currently, reliable efficacy markers for assessment of new interventions against tube... more Background. Currently, reliable efficacy markers for assessment of new interventions against tuberculosis (TB) are limited to disease and death. More precise measurement of the human immune response to Mycobacterium tuberculosis infection may be important. A qualitative enzyme-linked immunospot assay (ELISPOT) result for early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) offers improved specificity over the purified protein derivative (PPD) skin test reaction in the detection of M. tuberculosis infection. We evaluated the quantitative ELISPOT and PPD skin test responses to recent M. tuberculosis exposure. Methods. We studied quantitative PPD skin test and PPD ELISPOT results in 1052 healthy household contacts of index patients with cases of sputum smear–positive and culture-positive TB in The Gambia, according to a positive or negative ex vivo interferon g ELISPOT response to M. tuberculosis–specific antigens (ESAT-6/CFP-10). We then studied the qua...

International Journal of TROPICAL DISEASE & Health, 2015

This article cites 14 articles, 8 of which can be accessed free at:

Immuno

Existing tools (including GeneXpert) for diagnosis of multidrug resistant TB (MDR-TB) have limite... more Existing tools (including GeneXpert) for diagnosis of multidrug resistant TB (MDR-TB) have limited utility when sputum samples for microbiological analyses cannot be obtained. There is the need for immunological biomarkers which could serve as putative diagnostic markers of MDR-TB. We measured and compared the serum cytokine levels of inflammatory cytokines (IFN-γ, TNF-α, IL12p70, IL-17A, granzyme B) and anti-inflammatory cytokines (IL-10, IL-6, IL-4) among MDR-TB, drug-susceptible (DS)-TB and healthy controls (no-TB) using the Human Magnetic Luminex Multiplex Immunoassay. Levels of IFN-γ and IL-4 were respectively 1.5 log lower and 1.9 log higher in MDR-TB compared to DS-TB cases. Moreover, IFN-γ, TNF-α, IL-10, IL-6, and IL-4 levels were significantly higher in individuals with MDR-TB and DS-TB cases compared to healthy controls. Pairs of cytokines, IL-4 and IFN-γ (p = 0.019), IL-4 and TNF (p = 0.019), and Granzyme B and TNF-α (p = 0.019), showed significant positive correlation in...

The International Journal of Mycobacteriology

Mycobacterial Diseases, 2016

BMC public health, Jan 19, 2006

The tuberculosis (TB) epidemic in Africa is on the rise, even in low-HIV prevalence settings. Few... more The tuberculosis (TB) epidemic in Africa is on the rise, even in low-HIV prevalence settings. Few studies have attempted to identify possible reasons for this. We aimed to identify risk factors for pulmonary tuberculosis in those attending a general outpatients clinic in The Gambia, a sub-Saharan African country with relatively low HIV prevalence in the community and in TB patients. We conducted a case control study at the Medical Research Council Outpatients' clinic in The Gambia. Pulmonary TB cases were at least 15 years old, controls were age and sex matched clinic attendees. Participants were interviewed using a structured questionnaire. 100 sputum smear positive TB cases and 200 clinic controls were recruited. HIV prevalence was 6.1% in cases and 3.3% in controls. Multivariable assessment of host factors showed that risk of TB was increased among the Jola ethnic group and smokers, and decreased in those in a professional occupation. Assessment of environmental factors showe...

PLoS ONE, 2007

Background. Repeat tuberculin skin tests may be false positive due to boosting of waned immunity ... more Background. Repeat tuberculin skin tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT test could identify tuberculosis (TB) contacts with boosting of immunity to nontuberculous mycobacterial exposure. Methodology/Principal Findings. We conducted tuberculin and ELISPOT tests in 1665 TB contacts: 799 were tuberculin test negative and were offered a repeat test after three months. Those with tuberculin test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72%) contacts had a repeat tuberculin test; 176 (25%) had test conversion, which increased with exposure to a case (p = 0.002), increasing age (p = 0.0006) and BCG scar (p = 0.06). 114 tuberculin test converters had ELISPOT results: 16(14%) were recruitment positive/follow-up positive, 9 (8%) positive/negative, 34 (30%) negative/positive, and 55 (48%) were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin test converters (p = 0.038). Estimates of boosting ranged from 32%-41% of skin test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment. Conclusions/Significance. We estimate that approximately one third of tuberculin skin test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with tuberculin test conversion that would benefit most from prophylactic treatment.

PLoS ONE, 2006

Background. Options for intervention against Mycobacterium tuberculosis infection are limited by ... more Background. Options for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia. Methodology/Principal Findings. Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6-35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p,0.0001). With increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive contacts who were PPD skin test positive increased (p,0.0001), and the proportion of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased (p,0.0001); the converse did not occur. Conclusions/Significance. The PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited.