Timing of therapy for latent tuberculosis infection among immigrants presenting to a U.S. public health clinic: a retrospective study

<p>Abstract</p> <p>Background</p> <p>In the U.S. more than half of incident tuberculosis (TB) cases occur in immigrants. Current guidelines recommend screening and treatment for latent TB infection (LTBI) within 5 years of arrival to the U.S. This study evaluates the timing of LTBI therapy among immigrants presenting for care to a public health TB clinic.</p> <p>Methods</p> <p>Retrospective chart review of patients prescribed LTBI treatment based on medical records from Prince Georges County Health Department.</p> <p>Results</p> <p>1882 immigrants received LTBI therapy at Prince Georges County Health Department between 1999 and 2004. 417 of these patients were diagnosed with LTBI through contact investigations and were excluded from the analysis. Among the remaining 1465 individuals, median time from arrival to the U.S. until initiation of LTBI therapy was 5 months (range 0–42.4 years). 16% of all immigrants initiated therapy more than 5 years after arrival to the U.S. A logistic regression model using risks identified on univariate analysis revealed that referral for therapy by non-immigration proceedings was the strongest predictor of initiation of therapy more than 5 years after arrival to the U.S. Other factors associated with > 5 year U.S. residence prior to initiation of LTBI therapy included female gender (adjusted odds ratio (AOR) 1.8, 95% CI 1.2–2.6), age ≥ 35 (AOR = 4.1, 95% 2.5–6.6), and originating from Latin American and the Caribbean (AOR = 1.9, 95% CI 1.3–3.0).</p> <p>Conclusion</p> <p>Foreign-born individuals who are not referred for LTBI therapy through immigration proceedings are less likely to receive LTBI therapy within 5 years of arrival to the U.S. These data highlight the need to explore other mechanisms for timely LTBI screening beyond services provided by immigration.</p

Mechanisms of pulmonary fibrosis: role of activated myofibroblasts and NADPH oxidase

A common feature of pathological fibrosis involving the lung and other organs is the persistent activation of myofibroblasts in injured tissues. Recent evidence supports the role of a member of the NADPH oxidase (NOX) gene family, NOX4, in myofibroblast differentiation, matrix synthesis and contractility. Additionally, NOX4 may contribute directly or indirectly to alveolar epithelial cell death, while myofibroblasts themselves acquire an apoptosis-resistant phenotype. Thus, NOX4 may be responsible for the cardinal features of progressive fibrosis - myofibroblast activation and epithelial cell dysrepair. Therapeutic targeting of NOX4 is likely to be effective in progressive cases of fibrosis involving multiple organs

Skin-Test Screening and Tuberculosis Transmission among the Homeless1

We describe the implementation of a mandatory tuberculosis (TB) screening program that uses symptom screening and tuberculin skin testing in homeless shelters. We used the results of DNA fingerprinting of Mycobacterium tuberculosis isolates to evaluate the effect of the program on TB incidence and transmission. After the program was implemented, the proportion of cases among homeless persons detected by screening activities increased, and the estimated TB incidence decreased from 510 to 121 cases per 100,000 population per year. Recent transmission, defined by DNA fingerprinting analysis as clustered patterns occurring within 2 years, decreased from 49% to 14% (p=0.03). Our results suggest that the shelter-based screening program decreased the incidence of TB by decreasing its transmission among the homeless

Universal Genotyping in Tuberculosis Control Program, New York City, 2001–2003

Real-time universal genotyping decreased unnecessary treatment

The draft genome of the parasitic nematode Trichinella spiralis

Genome evolution studies for the phylum Nematoda have been limited by focusing on comparisons involving Caenorhabditis elegans. We report a draft genome sequence of Trichinella spiralis, a food-borne zoonotic parasite, which is the most common cause of human trichinellosis. This parasitic nematode is an extant member of a clade that diverged early in the evolution of the phylum, enabling identification of archetypical genes and molecular signatures exclusive to nematodes. We sequenced the 64-Mb nuclear genome,which is estimated to contain 15,808 protein-coding genes,at ~35-fold coverage using whole-genome shotgun and hierarchal map–assisted sequencing. Comparative genome analyses support intrachromosomal rearrangements across the phylum, disproportionate numbers of protein family deaths over births in parasitic compared to a non-parasitic nematode and a preponderance of gene-loss and -gain events in nematodes relative to Drosophila melanogaster. This genome sequence and the identified pan-phylum characteristics will contribute to genome evolution studies of Nematoda as well as strategies to combat global parasites of humans, food animals and crops

Treatment outcomes of adult patients with recurrent tuberculosis in relation to HIV status in Zimbabwe: a retrospective record review

<p>Abstract</p> <p>Background</p> <p>Zimbabwe is a Southern African country with a high HIV-TB burden and is ranked 19^thamong the 22 Tuberculosis high burden countries worldwide. Recurrent TB is an important problem for TB control, yet there is limited information about treatment outcomes in relation to HIV status. This study was therefore conducted in Chitungwiza, a high density dormitory town outside the capital city, to determine in adults registered with recurrent TB how treatment outcomes were affected by type of recurrence and HIV status.</p> <p>Methods</p> <p>Data were abstracted from the Chitungwiza district TB register for all 225 adult TB patients who had previously been on anti-TB treatment and who were registered as recurrent TB from January to December 2009. The Chi-square and Fischer's exact tests were used to establish associations between categorical variables. Multivariate relative risks for associations between the various TB treatment outcomes and HIV status, type of recurrent TB, sex and age were calculated using Poisson regression with robust error variance.</p> <p>Results</p> <p>Of 225 registered TB patients with recurrent TB, 159 (71%) were HIV tested, 135 (85%) were HIV-positive and 20 (15%) were known to be on antiretroviral treatment (ART). More females were HIV-tested (75/90, 83%) compared with males (84/135, 62%). There were 103 (46%) with relapse TB, 32 (14%) with treatment after default, and 90 (40%) with "retreatment other" TB. There was one failure patient. HIV-testing and HIV-positivity were similar between patients with different types of TB. Overall, treatment success was 73% with transfer-outs at 14% being the most common adverse outcome. TB treatment outcomes did not differ by HIV status. However those with relapse TB had better treatment success compared to "retreatment other" TB patients, (adjusted RR 0.81; 95% CI 0.68 - 0.97, <it>p </it>= 0.02).</p> <p>Conclusions</p> <p>No differences in treatment outcomes by HIV status were established in patients with recurrent TB. Important lessons from this study include increasing HIV testing uptake, a better understanding of what constitutes "retreatment other" TB, improved follow-up of true outcomes in patients who transfer-out and better recording practices related to HIV care and treatment especially for ART.</p

Transmission dynamics of pulmonary tuberculosis between autochthonous and immigrant sub-populations

<p>Abstract</p> <p>Background</p> <p>The overall incidence of tuberculosis (TB) in Western Europe has been declining since the 19^thCentury. However, immigrant sub-groups from high-prevalence countries are slowing down this trend. The aim of this study was to describe how immigration influences TB transmission in Germany. For that we prospectively investigated the dynamics of TB transmission between TB high-prevalence immigrant and TB low-prevalence local populations with molecular epidemiological methods and conventional contact investigations. Besides, we assessed transmission in relation to social mixing using an innovative tool that measures the integration of immigrants into the local social environment.</p> <p>Methods</p> <p>A prospective study of confirmed culture positive cases of pulmonary TB and their contacts was carried out in a German federal state from 2003 to 2005. Data for the study included: 1) case data routinely collected by the local public health staff and transmitted to the state health office and the national surveillance centre, 2) a study questionnaire designed to capture social interactions of relevance for TB transmission and 3) molecular genotyping data (IS<it>6110 </it>DNA fingerprint and spoligotyping). The proportion of German cases caused by foreign-born cases, and vice versa, was estimated and an integration index was computed using a selected set of questions from the study questionnaire.</p> <p>Results</p> <p>A total of 749 cases of culture-positive pulmonary tuberculosis voluntarily enrolled in the study, representing 57.8% of all registered cases diagnosed over the study period. Data that included study questionnaire and DNA fingerprinting were available for 41% (n = 308) of the study participants. Forty-seven clusters, defined as a least two cases infected by the same TB strains, were identified by molecular methods and included 132 (17%) of the study participants. Epidemiological links were identified for 28% of the clusters by conventional epidemiological data. In mixed clusters, defined as clusters including German and foreign-born individuals, the probability of cases to be caused by foreign-born cases was estimated at 18.3%. We observed a trend to mixed clusters with increasing time spent by immigrants in the host country. This group also presented comparatively higher integration indexes than immigrants in immigrant-only clusters.</p> <p>Conclusion</p> <p>Our results confirm the findings of other studies that there is no significant TB transmission from TB high-prevalence immigrant to TB low-prevalence autochthonous population. This may be explained by the good performance of tuberculosis screening programmes for certain groups arriving in Germany from high- prevalence countries, by a low degree of mixing of immigrants with the local population or by a combination of both.</p

Effective and specific in planta RNAi in cyst nematodes: expression interference of four parasitism genes reduces parasitic success

Cyst nematodes are highly evolved sedentary plant endoparasites that use parasitism proteins injected through the stylet into host tissues to successfully parasitize plants. These secretory proteins likely are essential for parasitism as they are involved in a variety of parasitic events leading to the establishment of specialized feeding cells required by the nematode to obtain nourishment. With the advent of RNA interference (RNAi) technology and the demonstration of host-induced gene silencing in parasites, a new strategy to control pests and pathogens has become available, particularly in root-knot nematodes. Plant host-induced silencing of cyst nematode genes so far has had only limited success but similarly should disrupt the parasitic cycle and render the host plant resistant. Additional in planta RNAi data for cyst nematodes are being provided by targeting four parasitism genes through host-induced RNAi gene silencing in transgenic Arabidopsis thaliana, which is a host for the sugar beet cyst nematode Heterodera schachtii. Here it is reported that mRNA abundances of targeted nematode genes were specifically reduced in nematodes feeding on plants expressing corresponding RNAi constructs. Furthermore, this host-induced RNAi of all four nematode parasitism genes led to a reduction in the number of mature nematode females. Although no complete resistance was observed, the reduction of developing females ranged from 23% to 64% in different RNAi lines. These observations demonstrate the relevance of the targeted parasitism genes during the nematode life cycle and, potentially more importantly, suggest that a viable level of resistance in crop plants may be accomplished in the future using this technology against cyst nematodes