SETTING: Siaya County, with the highest tuberculosis notification rates in Kenya. OBJECTIVE: To determine the incidence of active tuberculosis and one year cohort retention in 12-18 year old adolescents, in preparation for Phase III tuberculosis vaccine trials. METHODS: Adolescents were enrolled and followed up for 1-2 years to determine tuberculosis incidence. Adolescents with a positive tuberculin skin test (TST), history of cohabitation with a tuberculosis case, or at least one tuberculosis symptom received clinical and sputum examination and a chest radiograph. Definite tuberculosis cases were bacteriologically confirmed and clinical cases diagnosed by a clinician based on a suggestive chest radiograph and having clinical symptoms. Risk factors were explored using Poisson regression. RESULTS: Among 4934 adolescents without tuberculosis at baseline, 26 tuberculosis cases were identified during follow up with a corresponding incidence density of 4.4 (95% CI, 3.0-6.4) events per 1000 person years of observation, 12 definite tuberculosis cases; incidence density of 2.0 (95% CI, 0.9-3.1). Having previous tuberculosis (RR= 12.5, CI 1.8, 100) and presence of TST conversion (RR=3.4, CI 1.5, 7.7) were significantly associated with higher risk of tuberculosis. Overall (4086/4925) 83.0% of adolescents were retained in the study after 1 year of follow up. Being female, older, out of school and being orphaned were significant risk factors for loss to follow up. CONCLUSION: The tuberculosis incidence in adolescents will help inform future tuberculosis vaccine trial sample size calculations for this setting. The predictive factors for tuberculosis and retention can be further explored in future trials.

OBJECTIVE: The aim was to determine the prevalence of tuberculosis in adolescents in Western Kenya. METHODS: We conducted a cohort study of 5004 adolescents aged 12-18 years. Adolescents were screened for prevalent tuberculosis using clinical criteria, history of TB contact, and a mantoux test. TB suspects were investigated through 2 sputum examinations (microscopy and liquid culture), and chest radiography. RESULTS: Out of 5004 adolescents enrolled, 1960 (39.2%) were identified as a TB suspect including 1544 with a positive mantoux (prevalence 1544/4808 32.1%), 515 having symptoms suggestive of TB (10.3%) and 144 (2.9%) with household TB contact. Sixteen culture-confirmed (definite) and 18 probable pulmonary TB (PTB) cases were identified reflecting a prevalence estimate of 3.2/1,000 (definite) and 6.8/1,000 all PTB respectively. Only one smear-positive case was detected. The case notification rate among 12-18 year old adolescents for all TB was 101/100,000 yielding a patient diagnostic rate of 0.13 (95% CI 0.03,3.7) cases detected per person-year for all TB. CONCLUSION: The prevalence of PTB among adolescents is high with the majority of cases not detected routinely. Innovative active case finding including wider use of Xpert MTB/RIF is needed, to detect smear-negative TB among adolescents.

BACKGROUND: The findings of a prevalence survey conducted in western Kenya, in a population with 14.9% HIV prevalence suggested inadequate case finding. We found a high burden of infectious and largely undiagnosed pulmonary tuberculosis (PTB), that a quarter of the prevalent cases had not yet sought care, and a low case detection rate. OBJECTIVE AND METHODS: We aimed to identify factors associated with inadequate case finding among adults with PTB in this population by comparing characteristics of 194 PTB patients diagnosed in a health facility after self-report, i.e., through passive case detection, with 88 patients identified through active case detection during the prevalence survey. We examined associations between method of case detection and patient characteristics, including HIV-status, socio-demographic variables and disease severity in univariable and multivariable logistic regression analyses. FINDINGS: HIV-infection was associated with faster passive case detection in univariable analysis (crude OR 3.5, 95% confidence interval (CI) 2.0-5.9), but in multivariable logistic regression this was largely explained by the presence of cough, illness and clinically diagnosed smear-negative TB (adjusted OR (aOR) HIV 1.8, 95% CI 0.85-3.7). Among the HIV-uninfected passive case detection was less successful in older patients aOR 0.76, 95%CI 0.60-0.97 per 10 years increase), and women (aOR 0.27, 95%CI 0.10-0.73). Reported current or past alcohol use reduced passive case detection in both groups (0.42, 95% CI 0.23-0.79). Among smear-positive patients median durations of cough were 4.0 and 6.9 months in HIV-infected and uninfected patients, respectively. CONCLUSION: HIV-uninfected patients with infectious TB who were older, female, relatively less ill, or had a cough of a shorter duration were less likely found through passive case detection. In addition to intensified case finding in HIV-infected persons, increasing the suspicion of TB among HIV-uninfected women and the elderly are needed to improve TB case detection in Kenya.

OBJECTIVES: To evaluate excess mortality and risk factors for death during anti-tuberculosis treatment in Western Kenya. METHODS: We abstracted surveillance data and compared mortality rates during anti-tuberculosis treatment with all-cause mortality from a health and demographic surveillance population to obtain standardised mortality ratios (SMRs). Risk factors for excess mortality were obtained using a relative survival model, and for death during treatment using a proportional hazards regression model. RESULTS: The crude mortality rate during anti-tuberculosis treatment was 18.0 (95%CI 16.8-19.2) per 100 person-years. The age and sex SMR was 8.8 (95%CI 8.2-9.4). Excess mortality was greater in human immunodeficiency virus (HIV) positive TB patients (excess hazard ratio [eHR] 2.1, 95%CI 1.5-3.1), and lower in patients who were female or started treatment in a later year. Mortality was high in patients with unknown HIV status (HR 2.9, 95%CI 2.2-3.8) or, if HIV-positive, not on antiretroviral treatment (ART; HR 3.3, 95%CI 2.5-4.5) or not known to be on ART (HR 2.8, 95%CI 2.1-3.7). The attributable fraction of incomplete uptake of HIV testing and ART on mortality was 31% (95%CI 15-45) compared to HIV-positive patients on ART. CONCLUSION: Increasing the uptake of HIV testing and ART would further reduce mortality during anti-tuberculosis treatment by an estimated 31%.

BACKGROUND: We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding. METHODS: All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture. RESULTS: Presence of any abnormality on CXR had 94% (95%CI 88-98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68-77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for 'any TB symptom' which had 90% (95%CI 84-95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30-34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97-100) sensitivity. Specificity was 65% (95%CI 61-68). Sequential application of first a symptom screen for 'any symptom', followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%. CONCLUSION: CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.

RATIONALE: Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high HIV-prevalence. OBJECTIVE: To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB), the fraction attributable to HIV, and evaluate case detection. METHODS: Residents ≥15 years old, from 40 randomly sampled clusters, provided two sputum samples for microscopy; those with chest radiograph abnormalities or symptoms suggestive of PTB provided one additional sputum for culture. MEASUREMENTS: PTB was defined by a culture positive for M.tuberculosis or 2 positive smears. Persons with PTB were offered HIV-testing, and interviewed on care seeking behavior. We estimated the population attributable fraction of HIV on prevalent and notified PTB, the patient diagnostic rate (PDR), and case detection rate (CDR), using provincial TB notification data. MAIN RESULTS: Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1000 (95% CI 4.6-7.4) for all PTB and 2.5/1000 (1.6-3.4) for smear-positive PTB. Of 101 prevalent TB cases tested, 52 (51%) were HIV-infected, and 58 (64%) of 91 cases who were not on treatment and were interviewed had not sought care. Forty-eight percent of prevalent and 65% of notified PTB cases were attributable to HIV. For smear-positive and smear-negative PTB combined, the PDR was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for HIV-uninfected, corresponding to CDRs of 56% and 65%, respectively. CONCLUSIONS: Undiagnosed PTB is common in this community. TB case finding needs improvement, through intensified case finding, rigorous HIV-testing, and improved diagnosis of smear-negative TB.