OBJECTIVE: To compare the prevalence of tuberculosis infection and disease in household contacts of patients with bacteriologically confirmed tuberculosis disease and contacts of non-bacteriologically confirmed disease in western Kenya. METHODS: We enrolled newly diagnosed index patients and their household contacts from March 2014 to June 2016. All contacts were evaluated with a symptom questionnaire, tuberculin skin test (TST), and HIV test. Clinical evaluation and sputum testing were performed for those with symptoms, positive TST result, or HIV infection. RESULTS: We enrolled 1155 contacts of 330 index patients with bacteriologically confirmed tuberculosis and 192 contacts of 55 index patients with non-bacteriologically confirmed tuberculosis. 3.5% of contacts of patients with bacteriologically confirmed tuberculosis were diagnosed with tuberculosis, whereas no contacts of index patients with non-bacteriologically confirmed tuberculosis were. Of those diagnosed with tuberculosis disease, 58.5% reported symptoms, 34.1% reported no symptoms but had positive TST results, and 7.3% had neither symptoms nor positive TST but were HIV-positive. Among 872 contacts with a TST result, 50.9% of contacts of index patients with bacteriologically confirmed tuberculosis and 41.0% of contacts of index patients with non-bacteriologically confirmed tuberculosis had a positive result (prevalence ratio = 1.16, 95% confidence interval 0.92-1.48). CONCLUSION: In a high-burden setting, tuberculosis disease was more prevalent among contacts of patients with bacteriologically confirmed tuberculosis than contacts of patients with non-bacteriologically confirmed disease. TST was feasible to perform and helped to detect cases that would have been missed had only symptomatic contacts been evaluated.

OBJECTIVE: HIV-associated mortality rates in Africa decreased by 10%-20% annually in 2003-2011, after the introduction of antiretroviral therapy (ART). We sought to document HIV-associated mortality rates in the general population in Kenya after 2011 in an era of expanded access to ART. DESIGN: We obtained data on mortality rates and migration from a health and demographic surveillance system (HDSS) in Gem, western Kenya, and data for HDSS residents aged 15-64 years from home-based HIV-counseling and testing (HBCT) rounds in 2011, 2012, 2013, and 2016. METHODS: Mortality trends were determined among a closed cohort of residents who participated in at least the 2011 round of HBCT. RESULTS: Of 32,467 eligible HDSS residents, 22,688 (70%) participated in the 2011 round and comprised the study cohort. All-cause mortality rates declined from 10.0 (95% confidence interval [CI] 8.4-11.7) per 1000 in 2011 to 7.4 (95% CI 5.7-9.0) in 2016, while the mortality rate was stable among HIV-uninfected residents, at 5.7 per 1000 person-years. Among HIV-infected residents, mortality rates declined from 30.5 per 1000 in 2011 to 15.9 per 1000 in 2016 (average decline, 6% per year). The HIV-infected group receiving ART had higher mortality rates than the HIV-uninfected group (adjusted rate ratio (aRR), 2.8; 95% CI 2.2-3.4), as did the HIV-infected group who did not receive ART (aRR, 5.3; 95% CI 4.5-6.2). CONCLUSIONS: Mortality rates among HIV-infected individuals declined substantially during ART expansion between 2011 and 2016, though less than during early ART introduction. Mortality trends among HIV-infected populations are critical to understanding epidemic dynamics.

OBJECTIVE: To evaluate the utility of a broad and non-specific symptom screen for identifying people with undiagnosed HIV infection. DESIGN: Secondary analysis of operational data collected during implementation of a cluster-randomized trial for tuberculosis case detection. METHODS: As part of the trial, adults reporting cough, fever, night sweats, weight loss, or difficulty breathing of any duration in the past month were identified in health facilities and community-based mobile screening units in western Kenya. Adults reporting any symptom were offered HIV testing. We analysed the HIV testing data from this study, using modified Poisson regression to identify predictors of new HIV diagnoses among adults with symptoms and initially unknown HIV status. RESULTS: We identified 3,818 symptomatic adults, referred 1424 (37%) for testing, of whom 1065 (75%) accepted, and 107 (10%) were newly diagnosed with HIV. The prevalence of new HIV diagnoses was 21% (95% CI: 17-25%) among those tested in health facilities and 5% (95% CI 4-7%) among those tested in mobile units. More men were diagnosed with HIV than women despite fewer men being screened. People who reported 4-5 symptoms were over twice as likely to be diagnosed with HIV compared to those reporting 1-3 symptoms (adjusted prevalence ratio [aPR] in health facilities = 2.58, 95% CI, 1.65-4.05; aPR in mobile units = 2.63, 95% CI, 1.37-5.03). CONCLUSION: We observed a high yield of new HIV diagnoses among adults identified by active application of a broad symptom screen. Integrated tuberculosis and HIV screening using could help close the detection gap for both conditions.

OBJECTIVE: To evaluate the utility of a broad and non-specific symptom screen for identifying people with undiagnosed HIV infection. DESIGN: Secondary analysis of operational data collected during implementation of a cluster-randomized trial for tuberculosis case detection. METHODS: As part of the trial, adults reporting cough, fever, night sweats, weight loss, or difficulty breathing of any duration in the past month were identified in health facilities and community-based mobile screening units in western Kenya. Adults reporting any symptom were offered HIV testing. We analysed the HIV testing data from this study, using modified Poisson regression to identify predictors of new HIV diagnoses among adults with symptoms and initially unknown HIV status. RESULTS: We identified 3,818 symptomatic adults, referred 1424 (37%) for testing, of whom 1065 (75%) accepted, and 107 (10%) were newly diagnosed with HIV. The prevalence of new HIV diagnoses was 21% (95% CI: 17-25%) among those tested in health facilities and 5% (95% CI 4-7%) among those tested in mobile units. More men were diagnosed with HIV than women despite fewer men being screened. People who reported 4-5 symptoms were over twice as likely to be diagnosed with HIV compared to those reporting 1-3 symptoms (adjusted prevalence ratio [aPR] in health facilities = 2.58, 95% CI, 1.65-4.05; aPR in mobile units = 2.63, 95% CI, 1.37-5.03). CONCLUSION: We observed a high yield of new HIV diagnoses among adults identified by active application of a broad symptom screen. Integrated tuberculosis and HIV screening using could help close the detection gap for both conditions.

SETTING: Efficient tuberculosis (TB) active case-finding strategies are important in settings with high TB burdens and limited resources, such as those in western Kenya. OBJECTIVE: To guide efforts to optimize screening efficiency, we identified the predictors of TB among people screened in health facilities and communities. DESIGN: During February 2015-June 2016, adults aged >/=15 years reporting any TB symptom were identified in health facilities and community mobile screening units, and evaluated for TB. We assessed the predictors of TB using a modified Poisson regression with generalized estimating equations to account for clustering according to screening site. RESULTS: TB was diagnosed in 484 (20.3%) of 2394 symptomatic adults in health facilities and 39 (3.4%) of 1424 in communities. In health facilities, >10% of symptomatic adults in all demographic groups had TB, and no predictors were associated with a >/=2-fold increased risk. In communities, the independent predictors of TB were male sex (adjusted prevalence ratio [aPR] = 4.26, 95%CI 2.43-7.45), HIV infection (aPR 2.37, 95%CI 1.18-4.77), and household TB contact in the last 2 years (aPR 2.84, 95%CI 1.62-4.96). CONCLUSION: Our findings support the notion of general TB screening in health facilities and evaluation of the adult household contacts of TB patients.

Setting: Although Kenya has a high burden of tuberculosis (TB), only 46% of cases were diagnosed in 2016. Objective: To identify strategies for increasing attendance at community-based mobile screening units. Design: We analysed operational data from a cluster-randomised trial, which included community-based mobile screening implemented during February 2015-April 2016. Community health volunteers (CHVs) recruited individuals with symptoms from the community, who were offered testing for human immunodeficiency virus (HIV) and sputum collection for Xpert((R)) MTB/RIF testing. We compared attendance across different mobile unit sites using Wilcoxon rank-sum test. Results: A total of 1424 adults with symptoms were screened at 25 mobile unit sites. The median total attendance among sites was 54 (range 6-134, interquartile range [IQR] 24-84). The median yields of TB diagnoses and new HIV diagnoses were respectively 2.4% (range 0.0-16.7, IQR 0.0-5.3) and 2.5% (range 0.0-33.3, IQR 1.2-4.2). Attendance at urban sites was variable; attendance at rural sites where CHVs were paid a daily minimum wage was significantly higher than at rural sites where CHVs were paid a nominal monthly stipend (P < 0.001). Conclusion: Mobile units were most effective and efficient when implemented as a single event with community health workers who are paid a daily wage.

BACKGROUND: Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high HIV burden are limited. We examined adult pneumococcal pneumonia incidence before and after 10-valent PCV introduction in Kenya in 2011. METHODS: From 1/1/2008 to 12/31/2016, we conducted surveillance for acute respiratory infection (ARI) among ~12,000 adults (>/=18 years) in western Kenya, where HIV prevalence ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature >/=38.0 C or oxygen saturation <90%) presenting to a clinic underwent blood culture and pneumococcal urine antigen testing (UAT). We calculated ARI incidence and adjusted for healthcare seeking using data from household visits. The proportion of ARI cases with pneumococcus detected among those with complete testing (blood culture and UAT) was multiplied by adjusted ARI incidence to estimate pneumococcal pneumonia incidence. RESULTS: Pre-PCV (2008-2010), crude and adjusted ARI incidence were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI] 1.0-1.3). In each post-PCV year (2012-2016), pneumococcal pneumonia incidence was significantly lower than baseline; with incidence rate ratios (IRR) of 0.53 (95%CI 0.31-0.61) in 2012 and 0.13 (95%CI 0.09-0.17) in 2016. Similar declines were observed in HIV-infected (IRR 0.13, 95%CI 0.08-0.22), and HIV-uninfected (IRR 0.10, 95%CI 0.05-0.20). CONCLUSIONS: Adult pneumococcal pneumonia declined in western Kenya following 10-valent PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas.

BACKGROUND: HIV is a major driver of the tuberculosis epidemic in sub-Saharan Africa. The population-level impact of antiretroviral therapy (ART) scale-up on tuberculosis rates in this region has not been well studied. We conducted a descriptive analysis to examine evidence of population-level effect of ART on tuberculosis by comparing trends in estimated tuberculosis notification rates, by HIV status, for countries in sub-Saharan Africa. METHODS: We estimated annual tuberculosis notification rates, stratified by HIV status during 2010-2015 using data from WHO, the Joint United Nations Programme on HIV/AIDS, and the United Nations Population Division. Countries were included in this analysis if they had >/=4 years of HIV prevalence estimates and >/= 75% of tuberculosis patients with known HIV status. We compared tuberculosis notification rates among people living with HIV (PLHIV) and people without HIV via Wilcoxon rank sum test. RESULTS: Among 23 included countries, the median annual average change in tuberculosis notification rates among PLHIV during 2010-2015 was -5.7% (IQR -6.9 to -1.7%), compared to a median change of -2.3% (IQR -4.2 to -0.1%) among people without HIV (p-value = 0.0099). Among 11 countries with higher ART coverage, the median annual average change in TB notification rates among PLHIV was -6.8% (IQR -7.6 to -5.7%) compared to a median change of -2.1% (IQR -6.0 to 0.7%) for PLHIV in 12 countries with lower ART coverage (p = 0.0106). CONCLUSION: Tuberculosis notification rates declined more among PLHIV than people without HIV, and have declined more in countries with higher ART coverage. These results are consistent with a population-level effect of ART on decreasing TB incidence among PLHIV. To further reduce TB incidence among PLHIV, additional scale-up of ART as well as greater use of isoniazid preventive therapy and active case-finding will be necessary.

BACKGROUND: Tuberculosis (TB) case finding is an important component of TB control because it can reduce transmission of Mycobacterium tuberculosis (MTB) through prompt detection and treatment of infectious patients. METHODS: Using population-based infectious disease surveillance (PBIDS) platforms with links to health facilities in Kenya we implemented intensified TB case finding in the community and at the health facilities, as an adjunct to routine passive case finding conducted by the national TB program. From 2011 to 2014, PBIDS participants >/=15 years were screened either at home or health facilities for possible TB symptoms which included cough, fever, night sweats or weight loss in the preceding 2 weeks. At home, participants with possible TB symptoms had expectorated sputum collected. At the clinic, HIV-infected participants with possible TB symptoms were invited to produce sputum. Those without HIV but with symptoms lasting 7 days including the visit day had chest radiographs performed, and had sputum collected if the radiographs were abnormal. Sputum samples were tested for the presence of MTB using the Xpert MTB/RIF assay. TB detection rates were calculated per 100,000 persons screened. RESULTS: Of 11,191 participants aged >/=15 years screened at home at both sites, 2695 (23.9%) reported possible TB symptoms, of whom 2258 (83.8%) produced sputum specimens. MTB was detected in 32 (1.4%) of the specimens resulting in a detection rate of 286/100,000 persons screened. At the health facilities, a total of 11,762 person were screened, 7500 (63.8%) had possible TB symptoms of whom 1282 (17.1%) produced sputum samples. MTB was detected in 69 (5.4%) of the samples, resulting in an overall detection rate of 587/100,000 persons screened. The TB detection rate was higher in persons with HIV compared to those without at both home (HIV-infected - 769/100,000, HIV-uninfected 141/100,000, rate ratio (RR) - 5.45, 95% CI 3.25-22.37), and health facilities (HIV-infected 3399/100,000, HIV-uninfected 294/100,000, RR 11.56, 95% CI 6.18-18.44). CONCLUSION: Facility-based intensified TB case finding detected more TB cases per the number of specimens tested and the number of persons screened, including those with HIV, than home-based TB screening and should be further evaluated to determine its potential programmatic impact.

BACKGROUND: In Kenya, coverage of antiretroviral therapy (ART) among people with HIV infection has increased from 7% in 2006, to 57% in 2016; and, in western Kenya, coverage of voluntary medical male circumcision (VMMC) increased from 45% in 2008, to 72% in 2014. We investigated trends in HIV prevalence and incidence in a high burden area in western Kenya in 2011-16. METHODS: In 2011, 2012, and 2016, population-based surveys were done via a health and demographic surveillance system and home-based counselling and testing in Gem, Siaya County, Kenya, including 28 688, 17 021, and 16 772 individuals aged 15-64 years. Data on demographic variables, self-reported HIV status, and risk factors were collected. Rapid HIV testing was offered to survey participants. Participants were tracked between surveys by use of health and demographic surveillance system identification numbers. HIV prevalence was calculated as a proportion, and HIV incidence was expressed as number of new infections per 1000 person-years of follow-up. FINDINGS: HIV prevalence was stable in participants aged 15-64 years: 15% (4300/28 532) in 2011, 12% (2051/16 875) in 2012, and 15% (2312/15 626) in 2016. Crude prevalences in participants aged 15-34 years were 11% (1893/17 197) in 2011, 10% (1015/10 118) in 2012, and 9% (848/9125) in 2016; adjusted for age and sex these prevalences were 11%, 9%, and 8%. 12 606 (41%) of the 30 520 non-HIV-infected individuals enrolled were seen again in at least one more survey round, and were included in the analysis of HIV incidence. HIV incidence was 11.1 (95% CI 9.1-13.1) per 1000 person-years from 2011 to 2012, and 5.7 (4.6-6.9) per 1000 person-years from 2012 to 2016. INTERPRETATION: With increasing coverage of ART and VMMC, HIV incidence declined substantially in Siaya County between 2011 and 2016. VMMC, but not ART, was suggested to have a direct protective effect, presumably because ART tended to be given to individuals with advanced HIV infection. HIV incidence is still high and not close to the elimination target of one per 1000 person-years. The effect of further scale-up of ART and VMMC needs to be monitored. FUNDING: Data were collected under Cooperative Agreements with the US Centers for Disease Control and Prevention, with funding from the President's Emergency Fund for AIDS Relief.

BACKGROUND: Mortality from TB continues to be a global public health challenge. TB ranks alongside Human Immunodeficiency Virus (HIV) as the leading infectious causes of death globally. HIV is a major driver of TB related morbidity and mortality while TB is the leading cause of mortality among people living with HIV/AIDS. We sought to determine excess mortality associated with HIV and the effect of antiretroviral therapy on reducing mortality among tuberculosis patients in Kenya. METHODS: We conducted a retrospective analysis of Kenya national tuberculosis program data of patients enrolled from 2013 through 2014. We used direct standardization to obtain standardized mortality ratios for tuberculosis patients compared with the general population. We calculated the population attributable fraction of tuberculosis deaths due to HIV based on the standardized mortality ratio for deaths among TB patients with HIV compared to TB patients without HIV. We used Cox proportional hazards regression for assessing risk factors for mortality. RESULTS: Of 162,014 patients included in the analysis, 6% died. Mortality was 10.6 (95% CI: 10.4-10.8) times higher among TB patients than the general population; 42% of deaths were attributable to HIV infection. Patients with HIV who were not receiving ART had an over four-fold risk of death compared to patients without HIV (aHR = 4.2, 95% CI 3.9-4.6). In contrast, patients with HIV who were receiving ART had only 2.6 times the risk of death (aHR = 2.6, 95% CI 2.5-2.7). CONCLUSION: HIV was a significant contributor to TB-associated deaths in Kenya. Mortality among HIV-infected individuals was higher among those not on ART than those on ART. Early initiation of ART among HIV infected people (a "test and treat" approach) should further reduce TB-associated deaths.

Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon gamma-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed.

THE PROVISION of antiretroviral therapy (ART) has | changed the face of the human immunodeficiency | (HIV) epidemic. In high HIV burden settings it has | improved survival and contributed to declining HIV | incidence.1,2 Declining HIV incidence has been followed by declining tuberculosis (TB) incidence in some | high TB-HIV burden countries, presumably through | declining HIV prevalence among young adults, and | through a declining prevalence of advanced immunodeficiency attributable to ART.3–6 While the incidence | of TB among HIV-infected individuals on ART | remains higher than among HIV-negative individuals, | including from an increased risk of recurrent TB, it is | much lower than among HIV-infected individuals not | on ART.7–9 Survival of TB patients with advanced HIV | co-infection is improved with early start of ART.10 | Thus, ART has also had major benefits for TB | treatment and control. | There are two potential areas of concern from the | increased use of ART that need further clarification to | better predict the full impact of ART on TB epidemiology. One is the lifetime risk of TB, the other is the | infectiousness of HIV-infected TB patients on ART. | ART reduces the risk per year among HIV-infected | individuals of developing TB,11 but at the same time it | increases their life expectancy.1 As a result, the impact | of ART on the lifetime risk of developing TB is | unclear.12 While postponing the development of TB is | likely to represent a net benefit not only for the | individual concerned, but also for the general population, further information on the lifetime risk of TB | would be helpful to determine the net direct benefit of | ART on TB incidence. Obviously, as ART is expected | to reduce HIV transmission and thus HIV incidence, | this by itself is expected to reduce TB incidence.

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.

There is limited published information on mortality rates after successful completion of tuberculosis treatment. While tuberculosis treatment outcomes are routinely recorded, monitoring patients after completion of treatment is not recommended in WHO guidelines, except for one year post-treatment monitoring of drug-resistant TB patients to identify recurrent TB (1,2). | In this issue Shuldiner et al. assessed post-treatment mortality through linkage of the national TB registry and civil registry in a cohort of 3250 successfully treated Israeli TB patients who had started treatment in the period 2000–2010 (3). These successfully treated patients had a 3.7 (95% CI 3.4–4.1) times higher risk of death than the general Israeli population. The standardized mortality ratio was highest in the age group 25–44 years and somewhat higher among men (4.2) than women (3.2). | Shuldiner et al. suggest that increased mortality after successful tuberculosis treatment may be due to pulmonary impairment caused by tuberculosis and/or to shared risk factors, such as smoking, for tuberculosis and conditions such as lung cancer. Tuberculosis is more likely to occur in patients with underlying conditions such as cancer and diabetes, in patients with specific risk factors such as smoking and HIV infection, as well as in those with more general socio-economic determinants, owing to living and working conditions with a higher risk of exposure to Mycobacterium tuberculosis and less access to high-quality health care (4), all of which are also independently associated with increased mortality rates. Thus, it is possible that the increased mortality rates post-tuberculosis treatment would reflect the risks associated with these other risk factors and underlying conditions rather than lung damage after tuberculosis.

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.

Tuberculosis control is extremely challenging in settings with a high prevalence of human immunodeficiency virus (HIV) infection. It was recognized years ago that the World Health Organization (WHO) directly observed therapy short-course (DOTS) strategy in isolation was insufficient to control tuberculosis in such settings [1]. Since then, various additional interventions have been considered, including the scale up of antiretroviral therapy (ART) [2, 3], enhanced tuberculosis case finding and household interventions [4], and isoniazid preventive therapy [5]. While the uptake of preventive therapy is challenging [6], the effectiveness of mass preventive therapy was disappointing [7], and the effectiveness of intensified case finding remains unproven [4, 8, 9], the scale up of ART appears promising [3, 10], particularly since the latest expansion of the WHO eligibility criteria for ART [11]. The long-term effect of ART on tuberculosis incidence may be less favorable, as the increasing life expectancy of HIV-infected individuals may increase their cumulative tuberculosis risk [12].

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.

We conducted a case-control study to investigate risk factors for multidrug-resistant tuberculosis (MDR TB) in the People's Republic of China. Genotyping analysis was used to estimate the percentage of cases from recent transmission among 100 MDR TB case-patients hospitalized during April 2007-July 2009. Molecular subtyping of isolates showed that 41% of MDR TB strains clustered. Beijing genotype was found in 94% of the MDR TB isolates and 79% of the pan-susceptible isolates. In multivariate analysis, MDR TB was independently associated with Beijing genotype, retreatment for TB, symptoms lasting >3 months before first evaluation at the hospital, lack of health insurance, and being a farmer (vs. being a student). MDR TB was associated with Beijing genotype and lower socioeconomic status. A large percentage of MDR TB cases seemed to result from recent transmission. Early detection, effective treatment, and infection control measures for MDR TB are needed to reduce transmission.

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.