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.

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.

Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials.

BACKGROUND: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. METHODS: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive. RESULTS: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3). CONCLUSION: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

Epidemiology of Pediatric Tuberculosis in Kenya and Risk Factors for Mortality during Treatment: A National Retrospective Cohort Study.

OBJECTIVES: To describe the epidemiology of childhood tuberculosis (TB) in Kenya, assess the magnitude of TB/human immunodeficiency virus (HIV) co-infection and identify risk factors for mortality during TB treatment. STUDY DESIGN: We conducted a retrospective analysis of the Kenyan national TB program data for patients enrolled from 2013 through 2015. A total of 23 753 children aged less than 15 years were included in the analysis. Survival analysis was performed with censorship at 9 months and mortality was the main outcome. We used Cox proportional hazards regression for assessing risk factors for mortality. RESULTS: Childhood TB accounted for 9% (n = 24 216) of all patients with TB; 98% of the notified children (n = 23 753) were included in the analysis. TB/HIV co-infection was 28% (n = 6112). Most TB cases (71%; n = 16 969) were detected through self-referral. Treatment was successful in 90% (n = 19 088) and 4% (n = 1058) died. Independent risk factors for mortality included being HIV infected but not on antiretroviral therapy (adjusted hazard ratio [aHR], 4.84; 95% CI, 3.59-6.51), being HIV infected and on antiretroviral therapy (aHR, 3.69; 95% CI, 3.14-4.35), children aged less than 5 years (aHR, 1.25; 95% CI, 1.08-1.44), and being diagnosed with smear negative pulmonary disease (aHR, 1.68; 95% CI, 1.27-2.24). CONCLUSIONS: Most childhood TB cases in Kenya were detected through passive case finding. TB/HIV co-infection is high among children on treatment for TB, and HIV is associated with an increased risk of death. There is a need to intensify active case finding among children. TB prevention interventions among HIV-infected children, early diagnosis of HIV, and early antiretroviral therapy initiation among children on TB treatment should be strengthened.

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.

Tuberculosis case finding using population-based disease surveillance platforms in urban and rural Kenya.

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.

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.

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.

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.

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.

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.

Clustering of tuberculosis cases based on variable-number tandem-repeat typing in relation to the population structure of Mycobacterium tuberculosis in the Netherlands.

The population structure of 3,776 Mycobacterium tuberculosis isolates was determined using variable-number tandem-repeat (VNTR) typing. The degree of clonality was so high that a more relaxed definition of clustering cannot be applied. Among recent immigrants with non-Euro-American isolates, transmission is overestimated if based on identical VNTR patterns.

Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data.

BACKGROUND: Mycobacterium tuberculosis is characterised by limited genomic diversity, which makes the application of whole genome sequencing particularly attractive for clinical and epidemiological investigation. However, in order to confidently infer transmission events, an accurate knowledge of the rate of change in the genome over relevant timescales is required. METHODS: We attempted to estimate a molecular clock by sequencing 199 isolates from epidemiologically linked tuberculosis cases, collected in the Netherlands spanning almost 16 years. RESULTS: Multiple analyses support an average mutation rate of ~0.3 SNPs per genome per year. However, all analyses revealed a very high degree of variation around this mean, making the confirmation of links proposed by epidemiology, and inference of novel links, difficult. Despite this, in some cases, the phylogenetic context of other strains provided evidence supporting the confident exclusion of previously inferred epidemiological links. CONCLUSIONS: This in-depth analysis of the molecular clock revealed that it is slow and variable over short time scales, which limits its usefulness in transmission studies. However, the superior resolution of whole genome sequencing can provide the phylogenetic context to allow the confident exclusion of possible transmission events previously inferred via traditional DNA fingerprinting techniques and epidemiological cluster investigation. Despite the slow generation of variation even at the whole genome level we conclude that the investigation of tuberculosis transmission will benefit greatly from routine whole genome sequencing.

Role of the QuantiFERON(R)-TB Gold In-Tube assay in screening new immigrants for tuberculosis infection.

This study aimed to estimate the risk of progression to active tuberculosis (TB) within 2 yrs after entry in newly arriving immigrants who were screened with the QuantiFERON®-TB Gold In-Tube assay (QFT-GIT; Cellestis, Carnegie, Australia). In a case-base design, we determined the prevalence QFT-GIT-positive subjects among a representative sample of immigrants aged ≥ 18 yrs who arrived between April 2009 and March 2011 (the base cohort). Active TB patients (cases) within 2 yrs post-arrival in 2005, 2006 or 2007 were extracted from the Netherlands Tuberculosis Register. The risk of progression to active TB was estimated using Bayesian analyses to adjust for the sensitivity of QFT-GIT. Among the base cohort, 20% of 1,468 immigrants were QFT-GIT positive. Stratified by TB incidence in the person's country of origin as low (<100 cases per 100,000 population), intermediate (100-199 cases per 100,000) or high (≥ 200 cases per 100,000), the risk of progression to active TB per 100,000 arriving immigrants if QFT-GIT positive (95% credibility interval) was 456 (95% CI 307-589), 590 (397-762) and 386 (259-499), respectively, compared with 18 (0-46), 38 (0-97) and 28 (0-71) if QFT-GIT negative. Screening newly arriving immigrants with QFT-GIT contributes to detecting those at high risk of subsequent TB reactivation within 2 yrs after entry, which offers opportunities for prevention by targeted interventions.

High prevalence of pulmonary tuberculosis and inadequate case finding in rural western Kenya.

RATIONALE: Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV. OBJECTIVES: To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection. METHODS: Residents aged 15 years and older, 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 sample for culture. MEASUREMENTS AND MAIN RESULTS: PTB was defined by a culture positive for Mycobacterium tuberculosis or two 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, and case detection rate using provincial TB notification data. Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1,000 (95% confidence interval, 4.6-7.4) for all PTB and 2.5/1,000 (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 patient diagnostic rate was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for those who were HIV uninfected, corresponding to case detection rates of 56 and 65%, respectively. CONCLUSIONS: Undiagnosed PTB is common in this community. TB case finding needs improvement, for instance through intensified case finding with mobile smear microscopy services, rigorous HIV testing, and improved diagnosis of smear-negative TB.

Missed opportunities in tuberculosis control in The Netherlands due to prioritization of contact investigations.

BACKGROUND: The Dutch contact investigation guidelines stipulate that Public Health Services should examine contacts around all pulmonary tuberculosis (TB) patients to prevent disease and further transmission. Our objective was to assess to what extent these guidelines were applied and whether patient characteristics were associated with having contacts investigated. METHODS: We extracted the records of all reported pulmonary TB patients from the nationwide surveillance register covering 2006-07. Patient characteristics associated with having contacts investigated were assessed by multivariable logistic regression analysis. RESULTS: Out of the 1236 pulmonary TB patients reported, 909 (74%) patients were eligible for analysis, since 133 (11%) patients had incomplete records and 194 (16%) patients were registered by Public Health Services who did not report contact investigation results. For 710 (78%) out of the 909 patients contacts were investigated. Compared with Dutch patients, contacts were significantly less often investigated around immigrant patients (84 vs. 75%, OR: 0.60; 95% CI: 0.40-0.92). Contacts were significantly more often investigated for smear positive patients (OR: 3.52; 95% CI: 2.23-5.55) and culture positive patients (OR: 2.71; 95% CI: 1.76-4.16), compared with smear negative and culture negative patients, respectively. CONCLUSION: Initiating contact investigations appear to be prioritized based on the infectiousness, but also on the ethnicity of pulmonary TB patients. By not investigating the contacts of 25% of the immigrant patients, there is a risk of missing a significant number of infected and diseased contacts, since the incidence in this group is markedly higher than in the Dutch population.

Mycobacterial factors relevant for transmission of tuberculosis.

BACKGROUND: Tuberculosis (TB) transmission is associated with patient-related risk factors. However, DNA fingerprint analysis has provided anecdotal evidence suggesting a role for bacteriological factors. METHODS: To examine the importance of the bacteriological component in TB transmission, we investigated the number of tuberculin skin test-positive (TST induration, ≥ 10 mm) contacts and secondary cases observed in contact investigations around TB cases in relation to the size of the genotype cluster the patient belonged to at the time of diagnosis. We also compared the number of TST-positive contacts and secondary cases of patients with drug-resistant and drug-susceptible TB. RESULTS: Larger clusters were independently associated with an increased number of positive contacts. The mean number of positive contacts ranged from 3.8 for clusters of 2 cases, to 4.7 for clusters of 3-10 cases, to 6.0 for cases in clusters of >10 cases (mean increase in number of positive contacts for every extra case in the cluster, 0.21; 95% confidence interval, 0.09-0.26). The mean number of positive contacts was significantly lower among index cases with isoniazid-monoresistant TB (1.6) than among index cases with pan-susceptible TB (4.6; relative number, 0.45; 95% confidence interval, 0.22-0.92). CONCLUSION: These results suggest that spread of tuberculosis also depends on bacteriological factors.

Inappropriate tuberculosis treatment regimens in Chinese tuberculosis hospitals.

This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to control multidrug-resistant TB in China.

Multidrug-resistant tuberculosis, People's Republic of China, 2007-2009.

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.