Recurrent tuberculosis in the Netherlands - a 24-year follow-up study, 1993 to 2016.

BackgroundNot all treated tuberculosis (TB) patients achieve long-term recovery and reactivation rates reflect effectiveness of TB treatment.AimWe aimed to estimate rates and risk factors of TB reactivation and reinfection in patients treated in the Netherlands, after completed or interrupted treatment.MethodsRetrospective cohort study of TB patients with available DNA fingerprint data, registered in the Netherlands Tuberculosis register (NTR) between 1993 and 2016. Reactivation was defined as an identical, and reinfection as a non-identical Mycobacterium tuberculosis strain in sequential episodes.ResultsReactivation rate was 55/100,000 person-years (py) for patients who completed, and 318/100,000 py for patients who interrupted treatment. The risk of reactivation was highest in the first 5 years after treatment in both groups. The incidence rate of reactivation was 228/100,000 py in the first 2 years and 57/100,000 py 2-5 years after completed treatment. The overall rate of reinfection was 16/100,000 py. Among those who completed treatment, patients with male sex, mono or poly rifampicin-resistant TB and a previous TB episode had significantly higher risk of reactivation. Extrapulmonary TB was associated with a lower risk. Among patients who interrupted treatment, directly observed treatment (DOT) and being an undocumented migrant or people experiencing homelessness were associated with a higher risk of reactivation.ConclusionsBoth patients who completed or interrupted TB treatment should be considered as risk groups for reactivation for at least 2-5 years after treatment. They patients should be monitored and guidelines should be in place to enhance early detection of recurrent TB.

Characteristics of peer play in children with visual impairments.

BACKGROUND: Although many studies report children with vision impairments (VIs) experience play difficulties compared to sighted peers, large variation is present within the population of children with VIs. AIMS: The present study investigated peer play variation in 70 elementary school-aged children with VIs (M age = 8;11 years, SD = 2.25) and associations with specific child characteristics in sub-groups of participants. Also, it was examined how play materials with supportive auditory cues affected social play in children with varying cooperative play skills. METHODS AND PROCEDURES: Play behavior was coded while participants used play materials with and without auditory cues and parents filled in questionnaires about child characteristics. Data were analyzed using binomial logistic regression analyses. OUTCOMES AND RESULTS: Although the profoundness of the VI was not associated to cooperative or symbolic play, age, language ability and gender did predict the demonstration of these play behaviors. Furthermore, auditory cues were particularly facilitative of social play in children with VIs with low cooperative play capabilities. CONCLUSIONS AND IMPLICATIONS: In sum, this emphasizes that child characteristics other than the VI can play a significant role during peer play and interaction, and that individual variation should be considered when providing peer play support.

Progress towards lymphatic filariasis elimination in Ghana from 2000-2016: Analysis of microfilaria prevalence data from 430 communities.

BACKGROUND: Ghana started its national programme to eliminate lymphatic filariasis (LF) in 2000, with mass drug administration (MDA) with ivermectin and albendazole as main strategy. We review the progress towards elimination that was made by 2016 for all endemic districts of Ghana and analyze microfilaria (mf) prevalence from sentinel and spot-check sites in endemic districts. METHODS: We reviewed district level data on the history of MDA and outcomes of transmission assessment surveys (TAS). We further collated and analyzed mf prevalence data from sentinel and spot-check sites. RESULTS: MDA was initiated in 2001-2006 in all 98 endemic districts; by the end of 2016, 81 had stopped MDA after passing TAS and after an average of 11 rounds of treatment (range 8-14 rounds). The median reported coverage for the communities was 77-80%. Mf prevalence survey data were available for 430 communities from 78/98 endemic districts. Baseline mf prevalence data were available for 53 communities, with an average mf prevalence of 8.7% (0-45.7%). Repeated measurements were available for 78 communities, showing a steep decrease in mean mf prevalence in the first few years of MDA, followed by a gradual further decline. In the 2013 and 2014 surveys, 7 and 10 communities respectively were identified with mf prevalence still above 1% (maximum 5.6%). Fifteen of the communities above threshold are all within districts where MDA was still ongoing by 2016. CONCLUSIONS: The MDA programme of the Ghana Health Services has reduced mf prevalence in sentinel sites below the 1% threshold in 81/98 endemic districts in Ghana, yet 15 communities within 13 districts (MDA ongoing by 2016) had higher prevalence than this threshold during the surveys in 2013 and 2014. These districts may need to intensify interventions to achieve the WHO 2020 target.

The Incidence of Non-Tuberculous Mycobacteria in Infants in Kenya.

There is inadequate understanding of the epidemiology of Non-Tuberculous Mycobacteria (NTM) among infants in high tuberculosis burden countries. The objective of this study was to document the incidence and diversity of NTM disease or colonisation in sputum specimens from infants with presumptive TB, the risk factors, and clinical characteristics, in a high TB and HIV burden setting in Western Kenya. A cohort of 2900 newborns was followed for 1-2 years to assess TB incidence. TB investigations included collection of induced sputa and gastric aspirates for culture and speciation by HAIN®, Tuberculin Skin Testing (TST), HIV testing, and chest radiography. The American Thoracic Society Criteria (ATS) were applied to identify NTM disease. Among 927 (32% of 2900) with presumptive TB, 742 (80%) were investigated. NTM were isolated from 19/742 (2.6%) infants. M. fortuitum was most frequently speciated (32%). Total person-time was 3330 years. NTM incidence was 5.7/1,000 person-years, 95% CI (3.5, 8.7). Infants diagnosed with TB were more likely to have NTM isolation (odds ratio 11.5; 95% CI 3.25, 41.0). None of the infants with NTM isolated met the criteria for NTM disease. The incidence of NTM isolation was comparable to similar studies in Africa. NTM isolation did not meet ATS criteria for disease and could represent colonisation. TB disease appears to be structural lung disease predisposing to NTM colonisation.

The use of augmented toys to facilitate play in school-aged children with visual impairments.

BACKGROUND: Children with visual impairments (VIs) face challenges in social play activities, which limits their opportunities to practice social skills. AIMS: We investigated whether augmented toys were effective to facilitate play in 52 children with VIs who attended special schools for students with visual impairments and blindness. METHODS AND PROCEDURES: 52 children with VIs (mean age: 9.22 years, SD = 2.07) played three times with both an augmented and a non-augmented toy. A Playmobil® knight's castle was augmented with Radio Frequency Identification (RFID) technology, such that each play figure produced audio feedback during play. The RFID-technology could be activated and deactivated. Social and cognitive aspects of play were coded from video and data were analyzed using multilevel logistics. OUTCOMES AND RESULTS: Children showed less disengagement and more parallel play, but less cooperative play when they used the augmented versus the non-augmented castle. This pattern persisted after repeated play sessions with both toys. CONCLUSIONS: The addition of sounds to physical toys increased shared attention between children with VIs during the exploration of play materials, yet it interfered with social interaction during peer play.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control.

Background: Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods: We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results: Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions: Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Predictors of post neonatal mortality in Western Kenya: a cohort study.

INTRODUCTION: to determine the predictors of mortality in infants in Siaya, western Kenya, ahead of novel tuberculosis (TB) vaccine trials in the same population. METHODS: in a study to determine tuberculosis incidence, 2900 infants aged 0-45 days, weighing ≥ 1700g were enrolled. Four monthly follow up visits were conducted for at least 12 months. HIV testing was done at six weeks of age. Free ancillary care was provided. Deaths were reported by parents, study staff and community workers. Cox proportional Hazard analysis was used to identify risk factors. The period of analysis commenced at six weeks old and was censored at 12 months of age. RESULTS: included in the analysis were 2528 infants with 2020 person years of follow up (pyo). There were 117 deaths (4.6 %). The post-neonatal mortality rate was 58 (95% CI: 48, 69) per 1000 pyo. In multivariate analysis, health facility births were protective against mortality (Hazard Ratio (HR) 0.54; 95% CI: 0.34, 0.84) and infant HIV infection at baseline was associated with increased mortality (HR 10.3; 95% CI: 6.40, 16.7). HIV uninfected infants born to HIV infected mothers had increased hazards of mortality (HR 1.73; 95% CI: 1.03, 2.90). Gender, weight at six weeks, maternal education and occupation were not significant predictors of mortality. CONCLUSION: infant mortality was high and was associated with being born outside a health facility, maternal HIV infection and HIV infection of the infant. Measures to decrease mother to child transmission and other HIV control measures need to be strengthened further to see incremental reductions in infant mortality.

Risk factors associated with loss to follow-up from tuberculosis treatment in Tajikistan: a case-control study.

BACKGROUND: There are very few studies on reasons for loss to follow-up from TB treatment in Central Asia. This study assessed risk factors for LTFU and compared their occurrence with successfully treated (ST) patients in Tajikistan. METHODS: This study took place in all TB facilities in the 19 districts with at least 5 TB patients registered as loss to follow-up (LTFU) from treatment. With a matched case control design we included all LTFU patients registered in the selected districts in 2011 and 2012 as cases, with ST patients from the same districts being controls. Data were copied from patient records and registers. Conditional logistic regressions were run to analyse associations between collected variables and LTFU as dependent variable. RESULTS: Three hundred cases were compared to 592 controls. Half of the cases had migrated or moved. In multivariate analysis, risk factors associated with increased LTFU were migration to another country (OR 10.6, 95% CI 6.12-18.4), moving within country (OR 11.0, 95% CI 3.50-34.9), having side effects of treatment (OR 3.67, 95% CI 1.68-8.00) and being previously treated for TB (OR 2.03, 95% CI 1.05-3.93). Medical staff also mentioned patient refusal, stigma and family problems as risk factors. CONCLUSIONS: LTFU of TB patients in Tajikistan is largely a result of migration, and to a lesser extent associated with side-effects and previous treatment. There is a need to strengthen referral between health facilities within Tajikistan and with neighbouring countries and support patients with side effects and/or previous TB to prevent loss to follow-up from treatment.

Feasibility of district wide screening of health care workers for tuberculosis in Zambia.

BACKGROUND: Many health care workers (HCWs) are at increased risk for tuberculosis (TB). The World Health Organization (WHO) recommends screening HCWs for TB in high burden settings but this is often not implemented in countries with a high TB incidence. We assessed the feasibility of TB screening among HCWs, including participation rate and yield, as part of a project introducing facility specific TB interventions. METHODS: This study had a cross-sectional design. HCWs (including paid staff and community volunteers) from 13 clinics and two hospitals in the Ndola district of Zambia participated. HCWs were screened by a designated person in their own facility. The agreed screening algorithm for HCWs included annual symptom screening, with sputum smear, culture (or Xpert) and chest x-ray offered to HCWs with at least one TB symptom, i.e. those with presumptive TB. RESULTS: A total of 1011 out of 1619 (62%) staff and 71 out of 138 (51%) community volunteers were screened within one year, total 1082/1757 (62%). Five percent (52/1082) of those screened were presumptive TB patients. Seventy-three percent (38/52) of presumptive TB patients received all diagnostic tests according to the agreed algorithm. Eighteen out of 1757 staff and volunteers combined were diagnosed with TB within a calendar year, showing a notified TB incidence of 1%. At least five of them were diagnosed during the screening appointment (0.5% of those screened). One of the 18 HCWs died of TB. Seventy-six percent (822/1082) of screened HCWs indicated that they already knew their HIV status. Screening was considered feasible if confidentiality can be guaranteed although challenges such as the time required for screening and sample transport were reported. CONCLUSIONS: It is feasible to conduct and implement screening programs for TB among HCWs in hospitals and clinics, and the notified incidence and yield is high. Advocacy is needed to educate managers and HCWs on the importance of screening and the implementation of locally relevant screening algorithms. It is essential to ensure access to TB infection control, diagnostics, treatment and confidential registration for HCW.

Infection control and tuberculosis among health care workers in Viet Nam, 2009-2013: a cross-sectional survey.

BACKGROUND: Data on tuberculosis (TB) among health care workers (HCW) and TB infection control (TBIC) indicators are rarely available at national level. We assessed multi-year trends in notification data of TB among HCW and explored possible associations with TBIC indicators. METHODS: Notified TB incidence among HCW and 3 other TBIC indicators were collected annually from all 64 provincial and 3 national TB facilities in Vietnam. Time trends in TB notification between 2009 and 2013 were assessed using linear regression analysis. Multivariate regression models were applied to assess associations between the facility-specific 5-year notification rate and TBIC indicators. RESULTS: Forty-seven (70 %) of 67 facilities contributed data annually over five years; 15 reported at least one HCW with TB in 2009 compared to six in 2013. The TB notification rate dropped from 593 to 197 per 100,000 HCW (ptrend = 0.02). Among 104 TB cases reported, 30 were employed at TB wards, 24 at other clinical wards, ten in the microbiology laboratory, six at the MDR-TB ward, and 34 in other positions. The proportion of facilities with a TBIC plan and focal person remained relatively stable between 70 % and 84 %. The proportion of facilities providing personal protective equipment (PPE) to their staff increased over time. Facilities with a TBIC focal person were 7.6 times more likely to report any TB cases than facilities without a focal person. CONCLUSIONS: The TB notification rates among HCW seemed to decrease over time. Availability of PPE increased over the same period. Appointing a TBIC focal person was associated with reporting of TB cases among HCW. It remains unclear whether TBIC measures helped in reduction of the TB notification rates in HCW.

The incidence of tuberculosis among hiv-positive individuals with high CD4 counts: implications for policy.

BACKGROUND: Intensified case finding (ICF) and earlier antiretroviral therapy (ART) initiation are strategies to reduce burden of HIV-associated tuberculosis (TB). We describe incidence of and associated factors for TB among HIV-positive individuals with CD4 counts > 350 cells/µl in South Africa. METHODS: Prospective cohort study of individuals recruited for a TB vaccine trial. Eligible individuals without prevalent TB were followed up at 6 and 12 months after enrolment. Cox proportional hazards regression was used to determine factors associated with risk of incident TB. RESULTS: Six hundred thirty-four individuals were included in the analysis [80.9 % female, 57.9 % on ART, median CD4 count 562 cells/µl (IQR 466-694 cells/µl)]. TB incidence was 2.7 per 100 person-years (pyrs) (95 % CI 1.6-4.4 per 100 pyrs) and did not differ significantly between those on ART and those not on ART [HR 0.65 (95 % CI 0.24-1.81)]. Low body mass index (BMI <18.5 kg/m(2)) was associated with incident TB [HR 3.87 (95 % CI 1.09-13.73)]. Half of the cases occurred in the first 6 months of follow up and may have been prevalent or incubating cases at enrolment. CONCLUSIONS: TB incidence was high and associated with low BMI. Intensified case finding for TB should be strengthened for all HIV positive individuals regardless of their CD4 count or ART status.

A blood RNA signature for tuberculosis disease risk: a prospective cohort study.

BACKGROUND: Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. METHODS: In this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease. FINDINGS: Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2-68·9) and a specificity of 80·6% (79·2-82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6-64·3) and a specificity of 82·8% (76·7-86) in the 12 months preceding tuberculosis. INTERPRETATION: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. FUNDING: Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.

Prevalence and risk factors of latent Tuberculosis among adolescents in rural Eastern Uganda.

BACKGROUND: Latent Tuberculosis treatment is a key tuberculosis control intervention. Adolescents are a high risk group that is not routinely treated in low income countries. Knowledge of latent Tuberculosis (TB) burden among adolescents may influence policy. OBJECTIVES: We determined the prevalence and risk factors of latent TB infection among adolescents in rural Uganda. METHODS: We analyzed baseline data from a study that assessed the prevalence and incidence of Tuberculosis disease among adolescents. We extracted socio-demographics, medical assessment information, and tuberculin skin test results and estimated prevalence ratios (PR) of latent TB infection risk factors by binomial regression. RESULTS: The prevalence of latent TB was 16.1%, 95% CI (15.1 - 17.2). Significant risk factors were: a BCG scar, APR 1.29 (95% CI 1.12 - 1.48); male gender, APR 1.37 (95% CI 1.21 - 1.56); age 17 -18 years, APR 1.46 (95% CI 1.24 - 1.71) and 15-16 years, APR 1.25 (95% CI 1.07 - 1.46) compared to 12-14 years; being out of school, APR 1.31 (95% CI 1.05 - 1.62); and a known history of household TB contact in last 2 years, APR 1.91 (95% CI 1.55 - 2.35). CONCLUSION: Targeted routine latent TB treatment among adolescents out of school may be crucial for TB disease control in low income countries.

Two year mortality and associated factors in a cohort of children from rural Uganda.

BACKGROUND: As part of site development for clinical trials in novel TB vaccines, a cohort of infants was enrolled in eastern Uganda to estimate the incidence of tuberculosis. The study introduced several mortality reduction strategies, and evaluated the mortality among study participants at two years. The specific of objective of this sub-study was to estimate 2 year mortality and associated factors in this community-based cohort. METHODS: A community based cohort of 2500 infants was enrolled from birth up to 8 weeks of age and followed for 1-2 years. During follow up, several mortality reduction activities were implemented to enhance cohort survival and retention. The verbal autopsy process was used to assign causes of death. RESULTS: A total of 152 children died over a median follow up period of 2.0 years. The overall crude mortality rate was 60.8/1000 or 32.9/1000 person years with 40 deaths per 1000 for children who died in their first year of life. Anaemia, malaria, diarrhoeal diseases and pneumonia were the top causes of death. There was no death directly attributed to tuberculosis. Significant factors associated with mortality were young age of a mother and child's birth place not being a health facility. CONCLUSION: The overall two year mortality in the study cohort was unacceptably high and tuberculosis disease was not identified as a cause of death. Interventions to reduce mortality of children enrolled in the cohort study did not have a significant impact. Clinical trials involving infants and young children in this setting will have to strengthen local maternal and child health services to reduce infant and child mortality.

The tuberculin skin test in school going adolescents in South India: associations of socio-demographic and clinical characteristics with TST positivity and non-response.

BACKGROUND: India has generally used 1 TU purified protein derivative (PPD) as opposed to 2 TU PPD globally, limiting comparisons. It is important to assess latent TB infection in adolescents given that they may be a target group for new post-exposure TB vaccines. The aim of this study is to describe the pattern and associations of tuberculin skin test (TST) responses (0.1 ml 2 TU) in adolescents in South India. METHODS: 6643 school-going adolescents (11 to <18 years) underwent TST. Trained tuberculin reader made the reading visit between 48 and 96 hours after the skin test RESULTS: Of 6608 available TST results, 9% had 0 mm, and 12% ≥10 mm responses. The proportion of TST positive (≥10 mm) was higher among older children, boys, those with a history of TB contact and reported BCG immunization Those with no TST response (0 mm) included younger participants (<14 years), those whose mothers were illiterate and those with a recent history of weight loss. Those of a higher socio-economic status (houses with brick walls, LPG gas as cooking fuel) and those with a visible BCG scar were less likely to be non-responders. CONCLUSION: Proportion of non-responders was lower than elsewhere in the world. Proportion of TST positivity was higher in those already exposed to TB and in children who had been BCG immunized, with a zero response more likely in younger adolescents and those with recent weight loss.

Implementation of tuberculosis infection control in health facilities in Mukono and Wakiso districts, Uganda.

BACKGROUND: Tuberculosis infection control (TBIC) is rarely implemented in the health facilities in resource limited settings. Understanding the reasons for low level of implementation is critical. The study aim was to assess TBIC practices and barriers to implementation in two districts in Uganda. METHODS: We conducted a cross-sectional study in 51 health facilities in districts of Mukono and Wakiso. The study included: a facility survey, observations of practices and eight focus group discussions with health workers. RESULTS: Quantitative: Only 16 facilities (31%) had a TBIC plan. Five facilities (10%) were screening patients for cough. Two facilities (4%) reported providing masks to patients with cough. Ventilation in the waiting areas was inadequate for TBIC in 43% (22/51) of the facilities. No facility possessed N95 particulate respirators. Qualitative: Barriers that hamper implementation of TBIC elicited included: under-staffing, lack of space for patient separation, lack of funds to purchase masks, and health workers not appreciating the importance of TBIC. CONCLUSION: TBIC measures were not implemented in health facilities in the two Ugandan districts where the survey was done. Health system factors like lack of staff, space and funds are barriers to implement TBIC. Effective implementation of TBIC measures occurs when the fundamental health system building blocks--governance and stewardship, financing, infrastructure, procurement and supply chain management are in place and functioning appropriately.

Burden of tuberculosis disease among adolescents in a rural cohort in Eastern Uganda.

BACKGROUND: The world health organization (WHO) declared tuberculosis (TB) a global emergency, mainly affecting people in sub-Saharan Africa. However there is little data about the burden of TB among adolescents. We estimated the prevalence and incidence of TB and assessed factors associated with TB among adolescents aged 12-18 years in a rural population in Uganda in order to prepare the site for phase III clinical trials with novel TB vaccines among adolescents. METHODS: In a prospective cohort study, we recruited 5000 adolescents and followed them actively, every 6 months, for 1-2 years. Participants suspected of having TB were those who had any of; TB signs and symptoms, history of TB contact or a positive tuberculin skin test (TST) of ≥10 mm. Laboratory investigations included sputum smear microscopy and culture. RESULTS: Of the 5000 participants, eight culture confirmed cases of TB were found at baseline: a prevalence of 160/100,000 (95% confidence interval (CI), 69-315). There were 13 incident TB cases detected in an average of 1.1 person years: an incidence of 235/100,000 person years (95% CI, 125-402). None of the confirmed TB cases were HIV infected. Predictors for prevalent TB disease were: a history of TB contact and a cough ≥ 2 weeks at baseline and being out of school, while the only predictor for incident TB was a positive TST during follow-up. CONCLUSION: The TB incidence among adolescents in this rural part of Uganda seemed too low for a phase III TB vaccine trial. However, the study site demonstrated capability to handle a large number of participants with minimal loss to follow-up and its suitability for future clinical trials. Improved contact tracing in TB program activities is likely to increase TB case detection among adolescents. Future studies should explore possible pockets of higher TB incidence in urban areas and among out of school youth.

Screening for TB in high school adolescents in a high burden setting in South Africa.

Screening for tuberculosis (TB) disease is important for TB control and TB vaccine efficacy trials but this has not been evaluated in adolescents. We conducted a study to determine the prevalence of active TB and performance of specific screening tests for TB in adolescents in a high burden setting. Adolescents aged 12-18 years were recruited from high schools in a rural town in South Africa. Participants were screened for active TB using symptoms, household TB contact, positive interferon gamma release assay (IGRA) and positive tuberculin skin test (TST). Of 6363 adolescents recruited, 21 were newly diagnosed with TB of whom 19 were culture positive. After exclusions, the derived prevalence of smear positive TB was 16/5682 = 3/1000 (95% confidence interval (CI) 1-4/1000). The sensitivity of TST and IGRA for active TB were 85% (95% CI 62-100%) and 94% (95% CI 79-100%) respectively. None of the methods alone or in combination had positive predictive values greater than 2%. The screening tools evaluated in this study may not be practical for routine use owing to low positive predictive values but may be useful in TB vaccine clinical trials.