Background and Objectives. Chronic hepatitis B and C infections are capable of progressing to liver cirrhosis and hepatocellular carcinoma. Globally, it has been estimated that over 2 billion and 170 million people are living with hepatitis B and C infections, respectively. Ghana remains one of the highly endemic countries challenged by the continuous spread of these viral agents in Africa. This study was aimed at determining the seroprevalence and trend of Hepatitis B and C coinfections among blood donors in Saboba District of the Northern Region of Ghana. Methods. A five-year hospital-based retrospective study was carried out among 8605 blood donors comprising 8517 males and 88 females using data on blood donors from Saboba Assemblies of God Hospital located in the Saboba District in the Northern Region of Ghana from 2013 to 2017. Blood bank records on HBV and HCV potential blood donors who visited the hospital to donate blood were retrieved. Donor demographic details, i.e., age and gender, were also recovered. Donors who were registered to the hospital but were not residents of the Northern Region were excluded from the study. Donors with incomplete records were also excluded from the study. The data was managed using Microsoft Excel spreadsheet 2016 and analysed using GraphPad Prism statistical software. Results. The overall prevalence of asymptomatic viral hepatitis B and C infections in the general adult population was 9.59% (95% CI: 9.00-10.20) and 12.71% (95% CI: 12.00-13.40), respectively, with an HBV/HCV coinfection rate of 2.23% (95% CI: 1.90-2.60). The number of donors generally declined with advancement in years from 2038 (23.68%) since 2013 to as low as 1169 (13.59%) in 2016, except for 2017 where a sharp increase of 1926 (22.38%) was observed. The first and second highest proportions of donors fell within the age categories of 20-29 (51.53% (4434)) and 30-39 (32.90% (2831)) respectively. The seroprevalence rate of HBV, HCV, and HBV/HCV coinfection rates were generally higher among the female group than those observed among the male category. The year-to-year variation in HBV, HCV, and HBV/HCV infections was statistically significant. The highest year-to-year HBV seropositivity rate was 11.48% in the year 2013, while that for HCV and HBV/HCV coinfection was 16.24% and 5.85%, respectively, both documented in the year 2014. HBV and HBV/HCV coinfection rates were highest among donors aged <20 years old, while HCV seroprevalence was highest among donors aged 50-59 years old. Significantly higher odds of HBV/HCV coinfection (OR=5.2; 95% CI:3.3-8.1) was observed in the 2014 compared to the year 2013. Donors aged <20years were at higher risks of HBV and HBV/HCV coinfection rates compared to the other age groups. Conclusion. The seroprevalence of HBV and HCV among donors in the Saboba District of the Northern Region of Ghana is endemic. The HBV/HCV coinfection rate also raises serious concern owing to its high prevalence rate among the younger age. Intensive public health education coupled with mobile screening and mass vaccination of seronegative individuals is advised so as to help curb further spread of the infection and in effect help safeguard the health status of potential donors in the district.

Background: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. Methods: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 810 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 3014 of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 mu g of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. Results: 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, >= 97.4% (3+0 schedule) and >= 96.4% (2+1 schedule) of infants had antibody concentrations >= 0.2 mu g/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. Conclusion: Immune responses to the 10 PHiD-CV polysaccharide conjugates-administered vaccines were not altered by addition of dPly and PhtD. (C) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.

Background Using prospective blood donors as a proxy, this study was aimed at estimating the burden and five-year (2012–2016) trend of viral hepatitis (HBV and HCV) infection among asymptomatic adult population in Ho. Materials and Methods A retrospective analysis was done on secondary data extracted from the hospital archives comprising 4,180 prospective blood donors from January 2012 to December 2016. Demographic variables included age and sex, as well as place of residence. Screening results of serum infectious markers (HBV and HCV) were obtained. Results The prevalence of asymptomatic viral hepatitis (HBV and HCV) infection in the general adult population was 6.94% and 1.84%, respectively. Females recorded a higher burden of HBV and HCV (8.3% and 5.0%) compared to their male peers (6.8% and 1.4%). A significant age variation in HBV antigenaemia was seen with HBV seropositivity peaking among the younger population (less than 20 years' group) at 11.24% and troughed among the older population (above 50 years' group) at 0.92%. Conclusion Asymptomatic viral hepatitis among adult population in the Ho Municipality is estimated at the intermediate to high endemicity level. Preventive measures to reduce the burden are urgently needed and should be targeted at the younger generation.

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 in children who slept closest to a case who smoked within the same home compared with a nonsmoking case (OR: 8.0 [95% CI: 2.74-23.29] versus 2.4 [95% CI: 1.17-4.92], P < 0.001). SHS exposure as an effect modifier appears to greatly increase the risk of M. tuberculosis infection in children exposed to PTB cases. Smoking cessation campaigns may be important for reducing transmission of M. tuberculosis to children within households.

BACKGROUND:Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. METHODS:In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8-10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2-3-4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2-4-9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5-9-12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. RESULTS:1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60-67%) and non-10VT (55-61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI -21.5, 19.5) and 2.1% (-20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (-22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. CONCLUSIONS:In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. FUNDING:PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2–4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2–4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

Background: Vitamin D is essential in the host defence against tuberculosis (TB) as an immune modulator. The aim of this study was to determine the level of 25-hydroxyvitamin D (25 (OH) D) from adult TB index cases before and after treatment and their exposed household contacts (HHC) in The Gambia.Methods: Serum from adult index TB cases and their TB-exposed household contacts (HHC) was analysed for 25(OH) D and Vitamin D binding protein (VDBP) concentrations. Tuberculin skin test (TST) status was used as a measure of Mycobacterium tuberculosis (Mtb) infectivity in the HHC. In addition, HHC who later progressed to active TB (incident cases) were assessed alongside non-progressors to determine the influence of 25 (OH) D levels on TB risk.Results: Eighty-three TB cases, 46 TST+ and 52 TST- HHC were analysed. Generally levels of 25(OH) D were considered insufficient in all subjects. However, median levels of 25(OH) D and VDBP were significantly higher in TB cases compared to both TST+ and TST- HHC at recruitment and were significantly reduced after TB therapy (p < 0.0001 for all). In addition, levels of serum 25(OH) D at recruitment were significantly higher in TB progressors compared to non-progressors (median (IQR): 25.0(20.8-29.2) in progressors and 20.3 (16.3-24.6) ng/ml in non-progressors; p = 0.007).Conclusion: In The Gambia, an equatorial country, 25(OH) D levels are higher in serum of TB progressors and those with active disease compared to latently infected and uninfected subjects. These results contrast to findings in non-equatorial countries. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

OBJECTIVE:To establish haematological and biological reference values for Gambian infants.METHODS:Basic haematological and biochemical indices were analysed in blood samples obtained from healthy infants from Sukuta in the Western Division of The Gambia. The 2.5 and the 97.5 centiles for these indices were estimated.RESULTS:Reference ranges for haematological and biochemical indices were determined. Haemoglobin, total white cell count (WBC) and platelet levels decreased with age (P < 0.001), whereas most of the white cell count subsets except monocytes did not vary with age. Potassium and alkaline phosphatase fell significantly with increasing age (P < 0.001; P < 0.001), whereas urea and creatinine rose with increasing age (P = 0.002; P < 0.001, respectively).CONCLUSION:Our set of haematological and biochemical reference values for healthy infants in The Gambia differs from values in other settings, thus underscoring the importance of establishing region-specific paediatric reference ranges to ensure optimal patient management and evaluate the impact of interventions in clinical research.

Background The identification of Mycobacterium-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN–γ release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN–γ may help to define markers of early Mtb infection. Methods We assessed the TST status of Mtb-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST+); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST−). We assessed their short- and long-term immune responses to PPD and ESAT–6/CFP–10 (EC) via IFN–γ ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages. Results After 1 and 6 days stimulation with EC, 12 cytokines (IFN–γ, IL–2, IP–10, TNF–α, IL–13, IL–17, IL–10, GMCSF, MIP–1β, MCP–3, IL–2RA and IL–1A) were not different in TSTC compared to TST+ suggesting that robust adaptive Mtb-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN–γ ELISPOT to EC in combination with TST results revealed that IP–10 and IL–17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection. Conclusion We describe a detailed analysis of Mtb-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for ‘at-risk’ populations beyond TST and IGRA.

We evaluated the candidate tuberculosis vaccine M72/AS01 in Bacille-Calmette-Guerin (BCG)-vaccinated infants after or concomitantly with Expanded-Programme-on-Immunization (EPI) vaccines.Methods: In a Phase-II study in The Gambia (NCT01098474), 2 cohorts of 150 BCG-vaccinated infants each were randomized 1 : 1 : 1. The 'Outside-EPI' cohort received one or two M72/AS01 doses, or meningitis vaccine, 1-2 months after primary EPI vaccination. The 'Within-EPI' cohort received one or two M72/AS01 doses concomitantly with the third or last two doses of their primary EPI-regimen, respectively, or EPI vaccines alone. Safety, M72-specific humoral (ELISA) and cell-mediated (whole-blood ICS) responses, and humoral responses to EPI vaccines were assessed.Results: M72/AS01 was acceptably tolerated with no vaccine-related serious adverse events reported. Seropositivity/seroprotection rates against EPI antigens in the Within-EPI cohort were comparable between groups, irrespective of M72/AS01 co-administration. Up to one year post M72/AS01 vaccination, M72-specific humoral and CD4(+) T-cell responses were higher after 2 doses versus 1 dose in both cohorts (p < 0.0001), and comparable between cohorts after either 1 or 2 doses (p > 0.05).Conclusion: M72/AS01 given to infants after or concomitantly with EPI vaccines had an acceptable safety profile. Our results suggest no interference of immunogenicity profiles occurred following coadministration of M72/AS01 and EPI vaccines. Two M72/AS01 doses elicited higher immune responses than one dose. (C) 2014 The Authors. Published by Elsevier Ltd.

Rationale: Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required.Objectives: To evaluate ESAT-6 and CFP-10 (EC) IFN-gamma ELISPOT as a biomarker for treatment efficacy in LTBI.Methods: This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants.Measurements and Main Results: Participants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT-positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time.Conclusions: In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen specific T-cell responses over time. IFN-gamma ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI.Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).

BACKGROUND:The high positive responses obtained in active TB indicate that IGRAs may be useful in diagnosing active TB. This study aimed at evaluating the usefulness of Quantifer on-TB Gold-in Tube test (QFT-IT) in the diagnosis of active TB among Nigerians.METHODS:This study prospectively enrolled sputum smear positive TB cases and healthy disease free controls. Basic demographic and clinical data were collected using a structured questionnaire. Venous blood was collected into the QTF-IT tubes, incubated for 16-24 hours, serum harvested and stored at -200C till analysed in a batch. Tuberculin skin test (TST) was also done using 5TU and read within 48-72 hours. The performances of QFT-IT and TST among the cases and controls were compared.RESULTS:Sixty one TB cases and 41 controls were enrolled. The mean (SD) age of the TB cases was higher than the controls, 35.14+4.3 yrs v 27.8 + 2.1, p<0.001. Forty three (70.5%), 13 (21.3%) and 5 (8.2%) of the cases had a positive, negative and indeterminate QFT-IT results respectively compared with 14 (34.1%), 25 (61%), and 2 (4.9%) of the controls respectively, p values <0.001, 0.005 and 0.05 respectively. Fifty eight(95%) and 29(70.7%) of the TB cases and controls had a positive TST result respectively while 3 (5%) and 12( 29.3%) of the TB cases and controls had a negative TST result respectively, p values 0.003 each .QFT-IT had a sensitivity of 76% (95% CI 61.8 -85.2%) while the sensitivity of TST was 96.6% (95% CI 88.5 -98.3%), p = 0.07. The specificity of QFT-IT was 63.7% (95% CI 46-76%) and 30% (95% CI 20- 56%) for TST, p =0.001. Positive Likelihood ratio was 1.7 (95% CI 1.06-2.85) for QFT-IT and 1.4 (95%CI 1.06-1.8) for TST, p =0.002. Among the cases, both TST and QFT-IT were positive in 43(70.5%) and both negative in 1 (1.6%), and overall test .agreement was 77.7% (Kappa =0.13; p= 0.07). Female sex and higher total lymphocytes count were significantly associated with a positive QFT results.CONCLUSION:IGRA has a higher specificity and positive likelihood ratio in TB cases. Our findings indicate that QFT-IT may be a good adjunct tool to diagnose TB disease.

INTRODUCTION:Interferon-γ (IFN-γ) is essential for defence against Mycobacterium tuberculosis; however, levels in patients with active tuberculosis (TB) and changes during treatment have not been documented in our tuberculosis patients in Nigeria, hence this study has been carried out.OBJECTIVE:To determine variations, treatment kinetics, and predictive value of IFN-γ levels during treatment of active tuberculosis.DESIGN:Patients with pulmonary tuberculosis were recruited and subsequently followed up for 3 months during treatment with anti-TB. Peripheral blood was collected for IFN-γ assays, C-reactive protein and others followed by a Mantoux test. IFN-γ levels produced by stimulation with TB antigens were determined by ELISA and repeated measurement of IFN-γ were done at 1 and 3 months of anti-TB therapy. Chi Associations and correlations between IFN-γ were determined. Regression analysis was done to determine association between serial IFN-γ and treatment outcome.RESULTS:We recruited 47 patients with active tuberculosis with a mean age of 34.8 ± 3.6 years and M:F ratio of 1.12:1. Six (11%) were HIV positive. The mean level of IFN-γ induced by TB antigens was 629 ± 114.1 pg/ml, higher for HIV-negative PTB patients compared with HIV-positive PTB patients, 609.78 ± 723.9 pg/ml and 87.88 ± 130.0 pg/ml, respectively, P-value = 0.000. The mean level of IFN-γ induced by TB antigen increased significantly from 629 ± 114.1 pg/ml to 1023.46 + 222.8 pg/ml, P-value = 0.03 and reduced to 272.3 ± 87.7 pg/ml by the third month on anti-TB drugs, P-value = 0.001. Negative correlation was observed between the mean of baseline and chest X-ray involvement, P = 0.03. There was no significant correlation between sputum smear grade with baseline and follow-up IFN-γ levels. Three-month IFN-γ level among cured patients were higher than those with treatment failure, regression analysis showed that it does not predict outcome.CONCLUSION:IFN-γ may be useful in early detection and monitoring response; however, large scale studies are needed.

In West Africa, Mycobacterium tuberculosis strains co-circulate with M. africanum, and both pathogens cause pulmonary tuberculosis in humans. Given recent findings that M. tuberculosis T-cell epitopes are hyperconserved, we hypothesized that more immunogenic strains have increased capacity to spread within the human host population. We investigated the relationship between the composition of the mycobacterial population in The Gambia, as measured by spoligotype analysis, and the immunogenicity of these strains as measured by purified protein derivative–induced interferon-γ release in ELISPOT assays of peripheral blood mononuclear cells. We found a positive correlation between strains with superior spreading capacity and their relative immunogenicity. Although our observation is true for M. tuberculosis and M. africanum strains, the association was especially pronounced in 1 M. africanum sublineage, characterized by spoligotype shared international type 181, which is responsible for 20% of all tuberculosis cases in the region and therefore poses a major public health threat in The Gambia.

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 between IGRAs was 85.4% with relatively poor concordance (κ=0.25 [0.14-0.36, p=0.01]). In M. africanum compared to M. Tuberculosis cases, there was a trend towards lower sensitivity; lower median spots with T-SPOT and IFN-γ concentrations with QFT-GIT but these did not reach statistical significance. Conclusion: IGRAs are significantly more sensitive than TST for the diagnosis of TB disease in The Gambia as a proxy for LTBI. The utility of the sensitivity gained by combining IGRA and TST for LTBI if any is unclear. The impact of infecting Mycobacteria strain on IGRA test characteristics requires further investigation

Plasma samples before and one week after vaccination were analysed using a Bio-Rad 17-plex kit according to the manufacturer's instructions.50 μl of bead suspension was added to each well and washed twice.50 μl of samples and standards were added and the plate incubated for 1 hour at 300 rpm.The plate was washed 3 times then 25 μl of detection antibody added and the plate incubated for 30 min.After washing, 50 μl of 1X Streptavidin-PE (Phycoerythrin) was added to each well and incubated for 10 min.The plate was again washed and resuspended in 125 μl of assay buffer for reading using Bio-plex manager software (version 4.0) and a low photomultiplier tube setting.

This study aimed to evaluate the durability of the immunogenicity of MVA85A beyond infancy. Participants in an immunogenicity study of MVA85A administered at age of 4 months had additional evaluation 14 months after initial vaccination for IFN-γ ELISPOT responses to Ag85A peptide and ESAT6/CFP-10 and tuberculin skin test (TST). 112 children participated in this study. The anthropometry, biochemical and haematological safety profile were similar between the MVA85A recipients and controls. MVA85A recipients still had significantly higher immune responses to Ag85A compared to the controls. The majority of these children had negative responses to the TST as well as the ESAT6/CFP-10 antigens. In summary, MVA85A-vaccinated children had a persistently higher Ag85A immune response 14 months following vaccination than controls. All the children had negligible evidence of latent infection with M. tuberculosis (Mtb), suggesting that deploying a prophylactic vaccine against Mtb infection at this age could still be effective in this setting.

Coadministration with standard vaccines may reduce immunogenicity of tuberculosis vaccine.

BACKGROUND:We compared the performance of tuberculin skin test (TST), Quantiferon-TB Gold in-tube (QFT-GIT), and T-SPOT.TB in diagnosing latent tuberculosis (LTBI) among childhood TB contacts in a TB endemic setting with high BCG coverage. We evaluated the performance of interferon gamma release assays (IGRAs) and TST when combined in an algorithm. METHODS:Childhood contacts of newly diagnosed TB patients were tested with TST, QFT-GIT, and T-SPOT. The level of exposure in contacts was categorized according to whether they slept in the same room, same house, or a different house as the index case. For the evaluation of combined test performance, prior estimates for prevalence of latent TB were used in Bayesian models that assumed conditional dependence between tests. RESULTS:A total of 285 children were recruited. Overall, 26.5%, 33.0%, and 33.5% were positive for TST, T-SPOT, or QFT-GIT, respectively. All 3 tests responded to the gradient of sleeping proximity to the index case. Neither TST nor IGRA results were confounded by BCG vaccination. There was moderate agreement (kappa = 0.40-0.68) between all 3 tests. Combination of either IGRA with TST increased sensitivity (by 9.3%-9.6%) especially in contacts in the highest exposure category but was associated with loss of specificity (9.9%-11.3%). CONCLUSION:IGRAs and TST are similar in their diagnostic performance for LTBI. An approximate 10% sensitivity benefit for using the TST and an IGRA in combination is associated with a slightly greater specificity loss. Testing strategies combining an IGRA and TST with an "or" statement may be useful only in situations where there is a high pretest probability of latent infection.