Tuberculosis disease and infection among household contacts of bacteriologically confirmed and non-confirmed tuberculosis patients.

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.

OBJECTIF: Comparer la prévalence de l'infection et de la maladie tuberculeuses chez les contacts familiaux des patients atteints de tuberculose confirmée bactériologiquement et les contacts de maladies non bactériologiquement confirmées dans l'ouest du Kenya. MÉTHODES: Nous avons recruté des patients indice nouvellement diagnostiqués et leurs contacts familiaux de mars 2014 à juin 2016. Tous les contacts ont été évalués à l'aide d'un questionnaire sur les symptômes, le test cutané à la tuberculine (TCT) et le test VIH. Une évaluation clinique et des tests d'expectoration ont été effectués pour les personnes présentant des symptômes, un résultat positif au TCT ou une infection par le VIH. RÉSULTATS: Nous avons recruté 1.155 contacts de 330 patients index avec une tuberculose confirmée bactériologiquement et 192 contacts de 55 patients indice avec une tuberculose non confirmée bactériologiquement. 3,5% des contacts des patients atteints de tuberculose confirmée bactériologiquement ont été diagnostiqués avec la tuberculose, alors qu'aucun contact des patients indice avec une tuberculose non bactériologiquement confirmée ne l'a été. Parmi les personnes diagnostiquées avec une tuberculose, 58,5% ont signalé des symptômes, 34,1% n'ont signalé aucun symptôme mais avaient des résultats positifs au TCT, et 7,3% n'avaient ni symptômes ni TCT positifs mais étaient VIH positifs. Parmi 872 contacts avec un résultat TCT, 50,9% des contacts des patients indice avec une tuberculose confirmée bactériologiquement et 41,0% des contacts des patients indice avec une tuberculose non bactériologiquement confirmée avaient un résultat positif (rapport de prévalence = 1,16, intervalle de confiance à 95%: 0,92-1,48 ). CONCLUSION: Dans un contexte de charge élevée, la maladie tuberculose était plus fréquente chez les contacts des patients atteints de tuberculose confirmée bactériologiquement que chez les contacts des patients atteints de la maladie non bactériologiquement confirmée. Le TCT était réalisable et a aidé à détecter les cas qui auraient été ratés si seuls les contacts symptomatiques avaient été évalués.

Decreased HIV-associated mortality rates during scale-up of antiretroviral therapy, 2011-2016.

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, whereas 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.

High yield of new HIV diagnoses during active case-finding for tuberculosis.

OBJECTIVE: To evaluate the utility of a broad and nonspecific 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 for 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 3818 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% confidence interval (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 in health facilities = 2.58, 95% CI 1.65-4.05; adjusted prevalence ratio 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. Use of integrated tuberculosis and HIV screening could help close the detection gap for both conditions.

Indirect Effects of 10-Valent Pneumococcal Conjugate Vaccine Against Adult Pneumococcal Pneumonia in Rural Western Kenya.

BACKGROUND: Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high human immunodeficiency virus (HIV) burden are limited. We examined adult pneumococcal pneumonia incidence before and after PCV introduction in Kenya in 2011. METHODS: From 1 January 2008 to 31 December 2016, we conducted surveillance for acute respiratory infection (ARI) among ~12 000 adults (≥18 years) in western Kenya, where HIV prevalence is ~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. 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 incidences 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 a baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI]: 1.0-1.3). In each post-PCV year (2012-2016), the incidence was significantly lower than baseline; with incidence rate ratios (IRRs) 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) adults. CONCLUSIONS: Adult pneumococcal pneumonia declined in western Kenya following PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas.

Assessing the impact of antiretroviral therapy on tuberculosis notification rates among people with HIV: a descriptive analysis of 23 countries in sub-Saharan Africa, 2010-2015.

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.

HIV incidence in western Kenya during scale-up of antiretroviral therapy and voluntary medical male circumcision: a population-based cohort analysis.

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.

Reduction of HIV-associated excess mortality by antiretroviral treatment among tuberculosis patients in Kenya.

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.

Drivers of Tuberculosis Transmission.

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 γ-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.

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children.

BACKGROUND: A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia. METHODS: This was a nationwide, multi-cluster survey in children aged 6-11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods. RESULTS: TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8-10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47-7.37] and the ARTI was 0.75% [95%CI 0.60-0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence. CONCLUSIONS: This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools.

Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands.

The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.

Biomarkers Can Identify Pulmonary Tuberculosis in HIV-infected Drug Users Months Prior to Clinical Diagnosis.

BACKGROUND: Current diagnostic tests cannot identify which infected individuals are at risk for progression to tuberculosis (TB). Our aim was to identify biomarkers which can predict the development of TB prior to clinical diagnosis. METHOD: In a retrospective case-control study, RNA of 14 HIV-infected drug users obtained before TB diagnosis (cases) and of 15 who did not develop TB (controls) was analyzed for the expression of 141 genes by dcRT-MLPA followed by Lasso regression analysis. FINDINGS: A combined analysis of IL13 and AIRE had the highest discriminatory power to identify cases up to 8 months prior to clinical diagnosis. Cases expressing IL13 had a gene expression pattern strongly enriched for type I IFN related signaling genes, suggesting that these genes represent processes that contribute to TB pathogenesis. INTERPRETATION: We here demonstrated that biomarkers, such as IL13-AIRE, can identify individuals that progress to TB within a high risk population, months prior to clinical diagnosis.

Prospective evaluation of a complex public health intervention: lessons from an initial and follow-up cross-sectional survey of the tuberculosis strain typing service in England.

BACKGROUND: The national tuberculosis strain typing service (TB-STS) was introduced in England in 2010. The TB-STS involves MIRU-VNTR typing of isolates from all TB patients for the prospective identification, reporting and investigation of TB strain typing clusters. As part of a mixed-method evaluation, we report on a repeated cross-sectional survey to illustrate the challenges surrounding the evaluation of a complex national public health intervention. METHODS: An online initial and follow-up questionnaire survey assessed the knowledge, attitudes and practices of public health staff, physicians and nurses working in TB control in November 2010 and March 2012. It included questions on the implementation, experience and uptake of the TB-STS. Participants that responded to both surveys were included in the analysis. RESULTS: 248 participants responded to the initial survey and 137 of these responded to the follow-up survey (56% retention). Knowledge: A significant increase in knowledge was observed, including a rise in the proportion of respondents who had received training (28.6% to 67.9%, p = 0.003), and the self-rated knowledge of how to use strain typing had improved ('no knowledge' decreased from 43.2% to 27.4%). Attitudes: The majority of respondents found strain typing useful; the proportion that reported strain typing to be useful was similar across the two surveys (95.7% to 94.7%, p = 0.67). Practices: There were significant increases between the initial and follow-up surveys in the number of respondents who reported using strain typing (57.0% to 80.5%, p < 0.001) and the proportion of time health protection staff spent on investigating TB (2.74% to 7.08%, p = 0.04). CONCLUSIONS: Evaluation of a complex public health intervention is challenging. In this example, the immediate national roll-out of the TB-STS meant that a controlled survey design was not possible. This study informs the future development of the TB-STS by identifying the need for training to reach wider professional groups, and argues for its continuation based on service users' perception that it is useful. By highlighting the importance of a well-defined sampling frame, collecting baseline information, and including all stakeholders, it provides lessons for the implementation of similar services in other countries and future evaluations of public health interventions.

Risk of tuberculosis after recent exposure. A 10-year follow-up study of contacts in Amsterdam.

RATIONALE: The lifetime risk of tuberculosis (TB) for infected contacts is often mentioned to be 5-10%, but these estimates are based on studies conducted decades ago, and thus may not reflect current epidemiologic conditions. OBJECTIVES: To estimate the risk of TB among contacts with evidence of infection and to compare this with estimates often stated in the literature. METHODS: A retrospective cohort study was performed using records on contacts of pulmonary TB patients at the Public Health Service Amsterdam, 2002-2011. The Public Health Service Amsterdam TB electronic registration system identified TB cases during follow-up until October 2012; these were defined as coprevalent if diagnosed less than or equal to 180 days and incident if diagnosed greater than 180 days after TB diagnosis of index patient. Cumulative TB risk was estimated with Kaplan-Meier curves. MEASUREMENTS AND MAIN RESULTS: Of 9,332 contacts of pulmonary TB patients, 4,774 were screened for latent TB infection (LTBI) of whom 739 (16%) had evidence of infection. Among these the 5-year Kaplan-Meier TB cumulative risk was 9.5% (95% confidence interval, 7.5-11.9). This varied by age: 33.3% of 36 contacts aged less than 5 years, 19.1% of 84 contacts aged 5-14 years, and 6.7% of 619 contacts aged greater than or equal to 15 years (log rank, P < 0.001). Of 739 contacts with evidence of infection, 57 had coprevalent TB and 14 developed incident TB. Of patients without coprevalent TB but with LTBI diagnosis, 45% received preventive therapy. Five-year risk of incident TB was 2.4% (95% confidence interval, 1.2-4.7) among contacts with LTBI who did not start preventive therapy. CONCLUSIONS: Five-year risk of TB among contacts with evidence of infection was higher compared with older estimates, and differed considerably by age. Incidence of TB among contacts with LTBI was low, suggesting limited impact may be expected of expanding preventive therapy.

Yield of tuberculosis contact investigations in Amsterdam: opportunities for improvement.

We aimed to determine the coverage and yield of tuberculosis contact investigation, and compliance with guidelines, and to identify opportunities for improvement. Data were extracted from records on contacts of pulmonary tuberculosis patients at the Public Health Service (Amsterdam, the Netherlands) from 2008 to 2011. Additional data were obtained from the national tuberculosis register. Among 3743 contacts of 235 pulmonary tuberculosis index patients, 2337 (62%) were screened for latent tuberculosis infection (LTBI). Those less likely to be screened for LTBI included contacts of sputum smear-negative index patients (adjusted odds ratio (aOR) 0.6, 95% CI 0.4-0.9) and bacille Calmette Guérin (BCG)-vaccinated contacts (aOR 0.06, 95% CI 0.04-0.09). Among BCG-vaccinated contacts, the proportion screened increased from 9% in 2008 to 43% in 2011 (p-value for trend <0.001). LTBI diagnosis among contacts screened was associated with non-Dutch nationality (aOR 2.8, 95% CI 1.9-4.1) and being a close contact (aOR 4.0, 95% CI 1.9-8.3). Of the 254 contacts with LTBI diagnosis, 142 (56%) started preventive treatment. Starting treatment was associated with Dutch nationality (aOR 2.6, 95% CI 1.2-5.4) and being a close contact (aOR 10.5, 95% CI 1.5-70.7). Treatment completion was achieved by 129 (91%) of the 142 contacts who started treatment. Two areas for improvement were identified: further expanding LTBI screening, particularly among BCG-vaccinated contacts and contacts of sputum smear-negative index patients, and expanding preventive treatment among contacts with LTBI.

A novel approach - the propensity to propagate (PTP) method for controlling for host factors in studying the transmission of Mycobacterium tuberculosis.

RATIONALE: Understanding the genetic variations among Mycobacterium tuberculosis (MTB) strains with differential ability to transmit would be a major step forward in preventing transmission. OBJECTIVES: To describe a method to extend conventional proxy measures of transmissibility by adjusting for patient-related factors, thus strengthening the causal association found with bacterial factors. METHODS: Clinical, demographic and molecular fingerprinting data were obtained during routine surveillance of verified MTB cases reported in the Netherlands between 1993 and 2011, and the phylogenetic lineages of the isolates were inferred. Odds ratios for host risk factors for clustering were used to obtain a measure of each patient's and cluster's propensity to propagate (CPP). Mean and median cluster sizes across different categories of CPP were compared amongst four different phylogenetic lineages. RESULTS: Both mean and median cluster size grew with increasing CPP category. On average, CPP values from Euro-American lineage strains were higher than Beijing and EAI strains. There were no significant differences between the mean and median cluster sizes among the four phylogenetic lineages within each CPP category. CONCLUSIONS: Our finding that the distribution of CPP scores was unequal across four different phylogenetic lineages supports the notion that host-related factors should be controlled for to attain comparability in measuring the different phylogenetic lineages' ability to propagate. Although Euro-American strains were more likely to be in clusters in an unadjusted analysis, no significant differences among the four lineages persisted after we controlled for host factors.

Tuberculosis in healthcare workers and infection control measures at primary healthcare facilities in South Africa.

BACKGROUND: Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers. METHODS: One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained. RESULTS: The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08). CONCLUSION: The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.