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Background: Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. Methods: In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). Findings: After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 3

BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 2

Background Tens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood. Methods In this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protoco

© FEMS 2019. Serological assays can be used to investigate the population burden of infection and potentially sequelae from Chlamydia. We investigated the PGP3 ELISA as a sero-epidemiological tool for infection or sub-fertility in Australian and Samoan women. The PGP3 ELISA absorbance levels were compared between groups of women with infertility, fertile, and current chlamydial infections. In the Australian groups, women with chlamydial tubal factor infertility had significantly higher absorbance levels in the PGP3 ELISA compared to fertile women (P < 0.0001), but not when compared to women with current chlamydial infection (P = 0.44). In the Samoan study, where the prevalence of chlamydial infections is much higher there were significant differences in the PGP3 ELISA absorbance levels between chlamydial sub-fertile women and fertile women (P = 0.003). There was no difference between chlamydial sub-fertile women and women with a current infection (P = 0.829). The results support that the PGP3 assay is effective for sero-epidemiological analysis of burden of infection, but not for evaluation of chlamydial pathological sequelae such as infertility.

© FEMS 2019. Serological assays can be used to investigate the population burden of infection and potentially sequelae from Chlamydia. We investigated the PGP3 ELISA as a sero-epidemiological tool for infection or sub-fertility in Australian and Samoan women. The PGP3 ELISA absorbance levels were compared between groups of women with infertility, fertile, and current chlamydial infections. In the Australian groups, women with chlamydial tubal factor infertility had significantly higher absorbance levels in the PGP3 ELISA compared to fertile women (P < 0.0001), but not when compared to women with current chlamydial infection (P = 0.44). In the Samoan study, where the prevalence of chlamydial infections is much higher there were significant differences in the PGP3 ELISA absorbance levels between chlamydial sub-fertile women and fertile women (P = 0.003). There was no difference between chlamydial sub-fertile women and women with a current infection (P = 0.829). The results support that the PGP3 assay is effective for sero-epidemiological analysis of burden of infection, but not for evaluation of chlamydial pathological sequelae such as infertility.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence. METHODS: We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2-59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia. FINDINGS: We investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2-11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7-36) in 2014-15. In the

SETTING: Greater Banjul and Upper River Regions, The Gambia. OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

© 2016 Menon et al. Background: In our recent village-based cross-sectional study, the prevalence of nucleic acid amplification technique (NAAT) diagnosed Chlamydia trachomatis (CT) in sexually active Samoan women was very high (36%), and test positivity was associated with sub-fertility. We conducted a serological and epidemiological analysis in these participants to identify if serological data can provide further insight into the potential contribution of CT to sub-fertility in this population. Methods: Serological prediction of CT associated sub-fertility was conducted using a series of commercial tests. The correlation between fertility or sub-fertility, behavioral factors, and serologically predicted CT associated sub-fertility was determined. Results: A positive antibody reaction against the Chlamydia Major Outer Membrane Protein (MOMP) was significantly associated with sub-fertility, with 50% of infertile women being positive. Serum IgG and IgA antibodies against MOMP correlated with current infection measured by urine NAAT, suggesting longer term infections are common in this population. Chlamydia pneumoniae antibodies were frequently detected in this population (84%), and unexpectedly, were significantly associated with sub-fertility. Conclusions: The high prevalence of chlamydial infection and of positive chlamydial sub-fertility results suggests that CT is an important and frequent contributory factor to sub-fertility in this population.

© 2016 Menon et al. Background: In our recent village-based cross-sectional study, the prevalence of nucleic acid amplification technique (NAAT) diagnosed Chlamydia trachomatis (CT) in sexually active Samoan women was very high (36%), and test positivity was associated with sub-fertility. We conducted a serological and epidemiological analysis in these participants to identify if serological data can provide further insight into the potential contribution of CT to sub-fertility in this population. Methods: Serological prediction of CT associated sub-fertility was conducted using a series of commercial tests. The correlation between fertility or sub-fertility, behavioral factors, and serologically predicted CT associated sub-fertility was determined. Results: A positive antibody reaction against the Chlamydia Major Outer Membrane Protein (MOMP) was significantly associated with sub-fertility, with 50% of infertile women being positive. Serum IgG and IgA antibodies against MOMP correlated with current infection measured by urine NAAT, suggesting longer term infections are common in this population. Chlamydia pneumoniae antibodies were frequently detected in this population (84%), and unexpectedly, were significantly associated with sub-fertility. Conclusions: The high prevalence of chlamydial infection and of positive chlamydial sub-fertility results suggests that CT is an important and frequent contributory factor to sub-fertility in this population.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae.

Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers. These barriers are largely resolvable, and proposed solutions such as the adoption of symptom-based screening and shorter drug regimens are discussed. Integrated multicomponent and site-specific solutions need to be developed and evaluated within a public health framework to overcome the policy-practice gap and provide functional PT programmes for children in endemic settings.

Philip Campbell Hill and colleagues propose using a health needs assessment framework, research tools, and a strategy for clinical evaluation to help better manage child contacts of adult TB cases.

Background: Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings: We first examined M. tuberculosis-specific IFN-c and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-c responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04). Conclusions/Significance: H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and

Background: Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings: We first examined M. tuberculosis-specific IFN-c and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-c responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04). Conclusions/Significance: H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and

BACKGROUND: Studies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results. METHODS AND FINDINGS: After initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370-830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression. CONCLUSIONS: The incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just

BACKGROUND: Very little longitudinal information is available regarding the performance of T cell-based tests for Mycobacterium tuberculosis infection. To address this deficiency, we conducted a longitudinal assessment of the enzyme-linked immunosorbent spot test (ELISPOT) test in comparison to the standard tuberculin skin test (TST). METHODS AND FINDINGS: In tuberculosis (TB) contacts we repeated ELISPOT tests 3 mo (n = 341) and 18 mo (n = 210) after recruitment and TSTs at 18 mo (n = 130). We evaluated factors for association with conversion and reversion and investigated suspected cases of TB. Of 207 ELISPOT-negative contacts, 51 (24.6%) had 3-mo ELISPOT conversion, which was associated with a positive recruitment TST (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.0-5.0, p = 0.048) and negatively associated with bacillus Calmette-Guérin (BCG) vaccination (OR 0.5, 95% CI 0.2-1.0, p = 0.06). Of 134 contacts, 54 (40.2%) underwent 3-mo ELISPOT reversion, which was less likely in those with a positive recruitment TST (OR 0.3, 95% CI 0.1-0.8, p = 0.014). Between 3 and 18 mo, 35/132 (26.5%) contacts underwent ELISPOT conversion and 28/78 (35.9%) underwent ELISPOT reversion. Of the 210 contacts with complete results, 73 (34.8%) were ELISPOT negative at all three time points; 36 (17.1%) were positive at all three time points. Between recruitment and 18 mo, 20 (27%) contacts had ELISPOT conversion; 37 (50%) had TST conversion, which was associated with a positive recruitment ELISPOT (OR 7.2, 95% CI 1.4-37.1, p = 0.019); 18 (32.7%) underwent ELISPOT reversion; and five (8.9%) underwent TST reversion. Results in 13 contacts diagnosed as having TB were mixed, but suggested higher TST sensitivity. CONCLUSIONS: Both ELISPOT conversion and reversion occur after M. tuberculosis exposure. Rapid ELISPOT reversion may reflect M. tuberculosis clearance or transition into dormancy and may contribute to the relatively low reported ELISPOT conversion rate. Therefore, a negative EL

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 non-tuberculous 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.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 x 105 cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. CONCLUSION: Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted.