Bibliography of Journal

Kata Pengantar

Dalam upaya peningkatan pendayagunaan ilmu pengetahuan danteknologi di bidang kesehatan serta membantu para pemakai jasainformasi dalam penelusuran kembali informasi yang diinginkan, BadanPenelitian dan Pengembangan Kesehatan sebagai National Focal Point dariJaringan Layanan Perpustakaan, Literatur dan Informasi Kesehatan atauHELLIS (Health Literature and Information System) menerbitkan Bibliography of Journaldengan topik Tuberculosis. Bibliography of Journal dengan topik Tuberculosis, datainformasinya ini mengambil bersumber dari E-Jurnal berlanggananPerpustakaan Badan Litbang Kesehatan yaitu : Cengage-Gale, Science AAAS danBetham Direct tahun 2014.

Bibliography of Journal merupakan alat bantu penelusuran (Literatursekunder) yang diterbitkan 1 (satu) tahun sekali. Kami informasikanjuga bahwa Bibliography of journal pertama terbit tahun 2012-2013 denganmemiliki topik Malaria dan Nutrition. Bagi para pembaca yang inginmendapatkan informasi yang lebih detail mengenai Bibliography of journaldapat merujuk ke alamat website yang dicantumkan dalam referensi topikjurnal ada didalamnya.

Besar harapan kami , agar pada masa yang akan datang bentukterbitan Bibliography of Journal akan terus disempurnakan.Dan, cangkupantema yang ada bisa diperluas guna mempermudah pemanfaatannya bagisetiap pemakai jasa Perpustakaan Badan Litbang Kesehatan dan JaringanLayanan Perpustakaan, Literatur dan Informasi Kesehatan. Karena itu,kami mengharapkan saran dan kritik pembaca atau pengguna agarmenunjang perbaikan terbitan Bibliography of Journal yang akan datang.

Jakarta, Agustus 2014

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Sekretaris Badan Penelitian dan Pengembangan Kesehatan

Ria Sukarno, SKM, MCN NIP 195711281980122001

DAFTAR ISI

Kata Pengantar ….……..………………………………………………………………………….................................... 1Daftar isi............ ………………………………………………………………………………....................................... 2-3

1. ADENOSINE DEAMINASE ..……………………............………………………......................................... 42. ANTIBIOTICS, ANTI TUBERCULAR ...…………………………………………………………………………………... 53. ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE ..……..……………………………………………………......... 64. BREAST …...................................……………………………………………………………………..................… 75. BRONCHOALVEOLAR LAVAGE ….............................……………………………………………………………. 86. COHORT STUDIES ……...........…………………………………..................……………………………………...… 97. COMMUNITY HEALTH WORKERS ….................................…………………………………………………… 108. CYTOKINES …........................................…………………………………………………………………….......... 11

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9. DOSR PROTEIN, MYCOBACTERIUM TUBERCULOSIS ……..................................................…... 1210. DRUG RESISTANCE ……….................................................................................………………….. 13-1411. EPIDEMIOLOGIC STUDIES ….....................................……………………………………………….........… 1512. EPIDEMIOLOGICAL MONITORING …………………………....................……………………………………... 1613. ETHAMBUTOL …...............................................................................………………………………… 1714. FIBROBLAST ………………………………………………………………………………………………………….....……. 1815. GENOME ….......................................................………………………………………………………........... 19-2016. GENOTYPING TECHNIQUES …………………………………………………………………………………………...... 2117. HEALTHCARE DISPARITIES ……………………………………………………………………..........................… 2218. HEALTH PROMOTION ………………………………………………………………………................................. 2319. HEALTH SERVICES …………………………………………………………………………………………………........... 2420. HIV …..........................................…………………………………………………………………….................. 25-2621. HOSPITALS, PEDIATRIC ………..……………………………………………………………………………………….... 2722. HOUSEHOLDS ……………………………………………………………………………………………………………....... 2823. ISONIAZID …………………………………………………………………………………………………………………....... 2924. KNOWLEDGE ………………………………………………………….....…………………………………………………… 30-3125. LENGTH OF STAY ………………………………………………………………………………………………………..…… 3226. LIVER ………………………………………………………………………………………………………………………......... 3327. MEDICINE, TRADITIONAL ………………………………………………………………………..………………………. 3428. MOBILE APPLICATIONS …………………………………………………………………………………………………... 3529. MONOCYTES ………………………………………........……………………………………..…………………….........

3630. MUNICIPAL HOSPITALS …………………………………………………………………………………………………... 3731. MYCOBACTERIUM AVIUM …………………………………………...…………………………………………………. 3832. MYCOBACTERIUM TUBERCULOSIS ………………………………………………...………………………………..

39-40

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33. NECROSIS ………………………………………………………..................………………………………………………. 4134. OUTCOMES ASSESSMENT ……………………………………………………………………………………………..... 42-4335. PEPTIDE FRAGMENTS …………………………………….....…………......................……………………........ 4436. PEPTIDOGLYCAN ………………………………………………………………………………………………….............

4537. POLYPROTEINS ….............……………………………………………………………………………..................... 4638. QUALITATIVE RESEARCH ………....................………………………………………………………………........ 4739. RISK ………………………………………………………………………………………………………...............……...... 4840. SKIN TEST ………………...............…………………………………………………………………........……............ 49-5041. THERAPEUTIC …………………………………………………………………………………………………………..........

5142. TOMOGRAPHY……………………................………………………………………………………….…................ 5243. TRANSMISSION ……………………................……………………………………………………..……................ 5344. TRENDS ................……………………………………………………..….....................................…............ 5445. TUBERCULOSIS, BOVINE ................………………………..….....................................…....... 5546. TUBERCULOSIS, PLEURAL ................................................................................................... 5647. TUBERCULOSIS, PULMONARY ............................................................................................. 5748. VACCINATION ..................................................................................................................... 58INDEX PENGARANG…………………………………………………………………………………………………………………. 59-65

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1. ADENOSINE DEAMINASE

QV 136

5

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) fortuberculous pericarditis compared to adenosine deaminase andunstimulated interferon-γ in a high burden setting: a prospectivestudy/ Shaheen Pandie…[et al.].—South Africa : Bio MeD Central,2014. 10 hlm.

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculouspericarditis compared to adenosine deaminase and unstimulated interferon-γ in ahigh burden setting: a prospective study

Shaheen Pandie, Jonathan G Peter, Zita S Kerbelker, Richard Meldau, Grant Theron, Ureshnie Govender, Mpiko Ntsekhe, Keertan Dheda and Bongani M Mayosi

ABSTRACT

Tuberculous pericarditis (TBP) is associated with high morbidityand mortality, and is an important treatable cause of heartfailure in developing countries. Tuberculous aetiology ofpericarditis is difficult to diagnose promptly. The utility ofthe new quantitative PCR test (Xpert MTB/RIF) for the diagnosisof TBP is unknown. This study sought to evaluate the diagnosticaccuracy of the Xpert MTB/RIF test compared to pericardialadenosine deaminase (ADA) and unstimulated interferon-gamma(uIFNγ) in suspected TBP.

From October 2009 through September 2012, 151 consecutivepatients with suspected TBP were enrolled at a single centre inCape Town, South Africa. Mycobacterium tuberculosis cultureand/or pericardial histology served as the reference standard fordefinite TBP. Receiver-operating-characteristic curve analysiswas used for selection of ADA and uIFNγ cut-points.

Of the participants, 49% (74/151) were classified as definiteTBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. Atotal of 105 (74%) participants were human immunodeficiency virus(HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity(95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100%

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(85.6% to 100%), respectively. Concentration of pericardial fluidby centrifugation and using standard sample processing did notimprove Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and anegative likelihood ratio of 0.05 (0.02 to 0.10). However, thespecificity and positive likelihood ratio of uIFNγ was higherthan ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at anestimated background prevalence of TB of 30%. The sensitivity andnegative predictive value of both uIFNγ and ADA were higher thanXpert-MT/RIF (P < 0.001).Conclusions: uIFNγ offers superior accuracy for the diagnosis ofmicrobiologically confirmed TBP compared to the ADA assay and theXpert MTB/RIF test.

Keywords: Tuberculous pericarditis, Adenosine deaminase,Interferon γ, Xpert MTB/RIF test, Diagnosis

BMC Medicine 2014, 12:101http://www.biomedcentral.com/1741-7015/12/101

2. ANTIBIOTICS, ANTI TUBERCULAR

QV 268

MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis/ Jean-Pierre Flandrois…[et al.].—France : BMC Bioinformatics, 2014. 9hlm.

MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis

Jean-Pierre Flandrois, Gérard Lina and Oana Dumitrescu

ABSTRACT

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http://www.biomedcentral.com/1741-7015/12/101

Tuberculosis is an infectious bacterial disease caused byMycobacterium tuberculosis. It remains a major health threat,killing over one million people every year worldwide. An earlyantibiotic therapy is the basis of the treatment, and theemergence and spread of multidrug and extensively drug-resistantmutant strains raise significant challenges. As these bacteriagrow very slowly, drug resistance mutations are currentlydetected using molecular biology techniques. Resistance mutationsare identified by sequencing the resistance-linked genes followedby a comparison with the literature data. The only onlinedatabase is the TB Drug Resistance Mutation database (TBDReaMdatabase); however, it requires mutation detection before use,and its interrogation is complex due to its loose syntax andgrammar.

The MUBII-TB-DB database is a simple, highly structured text-based database that contains a set of Mycobacteriumtuberculosismutations (DNA and proteins) occurring at sevenloci:rpoB,pncA,katG;mabA(fabG1)-inhA, gyrA,gyrB, andrrs.Resistance mutation data were extracted after the systematicreview of MEDLINE referenced publications before March 2013.MUBII analyzes the query sequence obtained by PCR-sequencingusing two parallel strategies: i) a BLAST search against a set ofpreviously reconstructed mutated sequences and ii) the alignmentof the query sequences (DNA and its protein translation) with thewild-type sequences. The post-treatment includes the extractionof the aligned sequences together with their descriptors(position and nature of mutations). The whole procedure isperformed using the internet. The results are graphs (alignments)and text (description of the mutation, therapeutic significance).The system is quick and easy to use, even for technicians withoutbioinformatics training.

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MUBII-TB-DB is a structured database of the mutations occurringat seven loci of major therapeutic value in tuberculosismanagement. Moreover, the system provides interpretation of themutations in biological and therapeutic terms and can evolve bythe addition of newly described mutations. Its goal is to provideeasy and comprehensive access through a client–server model overthe Web to an up-to-date database of mutations that lead to theresistance of M. tuberculosis to antibiotics.

Keywords:Tuberculosis, Antibiotics, Mutation database, Sequence database, Web

BMC Bioinformatics 2014, 15:107http://www.biomedcentral.com/1471-2105/15/107

3. ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE

QV 268.5

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa / Aida Asmelash…[et al.].—Botswana : BMC Infectious Diseases, 2014. 7hlm.

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa

Aida Asmelash, Yu Zheng, Kara Wools Kaloustian, Douglas Shaffer, Fred Sawe, Anthony Ogwu,Robert Salata, Judith Currier, Michael D Hughes and Shahin Lockman

ABSTRACT

A subset of HIV-1 infected patients starting highly activeantiretroviral treatment (HAART) experience suboptimal CD4response (SCR) despite virologic suppression. We studied the rateof and risk factors for SCR among women starting HAART in the

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ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL wererandomized to start HAART with Tenofovir/Emtricitabine pluseither Nevirapine or Lopinavir/Ritonavir.

This analysis includes the 625 women who remained on-studythrough 48 weeks without experiencing protocol-defined virologicfailure. We defined SCR as < 100 CD4 cells/μL increase frombaseline and absolute CD4 cell count < 350 cells/μL, both at 48weeks after HAART initiation.

The baseline characteristics for the 625 women prior to HAARTinitiation were: median age 33 years, screening CD4 count 134cells/μL, and HIV-1 RNA 5.1 log10 copies/mL; 184 (29%) were WHOStage 3 or 4. Seventy one (11%) of these 625 women experiencedSCR. Baseline factors independently associated with increasedodds of SCR included older age, lower HIV-1 RNA, positiveHepatitis B surface antigen, and site location. At 96 weeks, only6% of the SCR group had CD4 ≥ 350 cells/μL compared with 67% inthe non SCR group.

After starting HAART, 11% of women with virologic suppressionthrough 48 weeks experienced SCR. These patients were also lesslikely to achieve CD4 ≥ 350 cells/μL by 96 weeks. The underlyingcauses and long term clinical implications of SCR deserve furtherinvestigation.

Keywords: HIV, Antiretroviral therapy, HAART, Immune response, CD4

BMC Infectious Diseases 2014, 14:331http://www.biomedcentral.com/1471-2334/14/331

4. BREAST

WP 815

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Breast tuberculosis in Northeast Iran: review of 22 cases/ Behnaz Khodabakhshi, Fatemeh Mehravar.—Iran : BMC Women's Health,2014. 4hlm.

Breast tuberculosis in Northeast Iran: review of 22 cases

Behnaz Khodabakhshi and Fatemeh Mehravar

ABSTRACT

Breast tuberculosis (breast TB) is an extremely rare disease, socase reviews are also rare.

This study is a retrospective review of patients with breast TBwho were treated between 2002 and 2012 at the Health Center ofGorgan City.

All 22 patients were females, their mean age was 32.4 years, andall were new cases. Patients presented with swelling of thebreast (22%), lump (55%) and excretion from the involved breast(27%), and breast pain (55%). The highest rate of breast TBoccurred in 2011 (27%). All patients received the DOTS regimenfor a mean duration of 7.3 ± 0.7 months; in addition, segmentalresection was performed on 11 patients (50%).

The findings confirmed that breast TB in Iran should beconsidered as a differential diagnosis of breast masses. Allpatients in our study received the daily and ‘Directly ObservedTreatment Short-course’ (DOTS) regimens. Anti-tubercular therapyfor six months with or without minimal surgical interventioncurrently is the main treatment.

Keywords: Breast tuberculosis, Mammary tuberculosis, Tuberculosistreatment, IRAN

BMC Women's Health 2014, 14:72http://www.biomedcentral.com/1472-6874/14/72

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5. BRONCHOALVEOLAR LAVAGE

WF 600

Elevated CXCL-8 expression in bronchoalveolar lavage correlates with disease severity in patients with acute respiratory distress syndrome resultingfrom tuberculosis/ Seyed Mohamad Reza Hashemian…[et al.].—Iran : Journal of Inflammation, 2014. 9 hlm.

Elevated CXCL-8 expression in bronchoalveolar lavage correlates with disease severity in patients with acute respiratory distress syndrome resultingfrom tuberculosis

Seyed Mohamad Reza Hashemian, Esmaeil Mortaz, Payam Tabarsi, Hamidreza Jamaati, Zohreh Maghsoomi,Adnan Khosravi, Johan Garssen, Mohamad Reza Masjedi, Ali Akbar Velayati, Gert Folkerts,Peter J Barnes and Ian M Adcock

ABSTRACT

Tuberculosis (TB) is a rare but known cause of acute respiratorydistress syndrome (ARDS). The role of inflammatory cytokines inthe progression of ARDS in TB patients is unknown.Objectives: In this study we investigated the possible linkbetween the levels of inflammatory cytokines in bronchoalveolarlavage (BAL) in patients with TB or ARDS alone or in patientswith TB-induced ARDS (ARDS + TB).

90 patients were studied: 30 with TB alone, 30 with ARDS alone and 30 with ARDS + TB. BAL was collected by fiberoptic bronchoscopy and the concentrations of interleukin(IL)-6, CXCL8, TNF-α and IL-1β and the amounts of total protein were measured byELISA and bicinchoninic acid assay (BCA) methods respectively. The correlation between disease severity measured by Murray

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scores, SOFA and APACHE II analysis and BAL mediators and cells was also determined.

CXCL8 levels in BAL were significantly higher in the ARDS + TBgroup compared to TB and ARDS alone groups. Disease severity inthe ARDS + TB group as determined by Murray score correlated withBAL CXCL8 and neutrophils but not with IL-6, IL-1β and TNF-αconcentrations. In addition, CXCL8 levels and neutrophils wereincreased in non-miliary TB versus miliary TB. This difference inCXCL8 was lost in the presence of ARDS.

BAL CXCL8 levels were significantly higher in patients with ARDSinduced by TB and could suggest an important role of CXCL8 in thepathogenesis of this form of ARDS. This further suggests thatCXCL8 inhibitors or blockers may be useful to control the onsetand/or development of these combined diseases

Keywords: ARDS, TB, CXCL8 and neutrophils

Journal of Inflammation 2014, 11:21http://www.journal-inflammation.com/content/11/1/21

6. COHORT STUDIES

WA 950

Neighborhood socioeconomic position and tuberculosis transmission: a retrospective cohort study/ Eyal Oren.--United States of America : BMC Infectious Diseases, 2014. 11 hlm.

Neighborhood socioeconomic position and tuberculosis transmission: a retrospective cohort study

Eyal Oren, Masahiro Narita, Charles Nolan and Jonathan Mayer

ABSTRACT

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http://www.journal-inflammation.com/content/11/1/21

Current understanding of tuberculosis (TB) genotype clustering inthe US is based on individual risk factors. This study sought to identify whether area-based socioeconomic status (SES) was associated with genotypic clustering among culture-confirmed TB cases.

A retrospective cohort analysis was performed on data collected on persons with incident TB in King County, Washington, 2004–2008. Multilevel models were used to identify the relationship between area-level SES at the block group level and clustering utilizing a socioeconomic position index (SEP).

Of 519 patients with a known genotyping result and block group, 212 (41%) of isolates clustered genotypically.Analyses suggested an association between lower area-based SES and increased recent TB transmission, particularly among US-born populations. Models in which community characteristics were measured at the block group level demonstrated that lower area-based SEP was positivelyassociated with genotypic clustering after controlling for individual covariates. However, the trend in higher clustering odds with lower SEP index quartile diminished when additional block-group covariates.

Stress the need for TB control interventions that take area-basedmeasures into account, with particular focus on poor neighborhoods. Interventions based on area-based characteristics,such as improving case finding strategies, utilizing location-based screening and addressing social inequalities, could reduce recent rates of transmission.

Keywords:Tuberculosis, Genotyping, Socioeconomic status, Infectious disease transmission, Multilevel, Molecular epidemiology


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7. COMMUNITY HEALTH WORKERS

W 21.5

The provision of TB and HIV/AIDS treatment support by lay health workers in South Africa: a time-and-motion study/ Willem AOdendaal, Simon Lewin.—South Africa : Human Resources for Health,2014. 7 hlm.

The provision of TB and HIV/AIDS treatment support by lay health workers in South Africa: a time-and-motion study

Willem A Odendaal and Simon Lewin

ABSTRACT

Lay or community health workers (LHWs) are an important humanresource in primary health care,and contribute to improvingaccess to care. However, optimal use of LHWs within the healthsystem is often hampered by a poor understanding of how thiscadre organizes its work. This study aimed to better understandhow LHWs organize and structure their time in providing treatmentand adherence support to people on TB treatment and/orantiretroviral therapy (ART) in South Africa.

Fourteen LHWs participated across three low-income peri-urbancommunities in Cape Town. Each LHW was observed by a researcherfor one day, and data collected on each activity and the timespent on it. Data were summarized in the following categories:travel to the patient’s home, waiting time and patient contacttime.

Ninety-seven attempted visits to patients were observed, andpatients were located in 69 of these. On average, LHWs conductedsix visits per day, each lasting an average of nine minutes.Forty-six percent of the observed time was spent with patients,with the balance spent on ‘non-contact’ activities, including

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walking to and waiting for patients. The average walking timebetween patients was 8 minutes (range: 3 to 15 minutes).Activities during visits comprised medical care (that is ensuringthat medication was being taken correctly and that patients werenot experiencing side-effects) and social support. Other tasksincluded conducting home assessments to determine risks totreatment adherence, and tracing patients who had defaulted fromtreatment.

Because of their tasks and working environment, LHWs providingsupport to people on TB treatment and ART in South Africa spend asubstantial proportion of their time on ‘non-contact’ activities.Programme managers need to take this into account when developingjob descriptions and determining patient case-loads for thiscadre. More research is also needed to explore whether thesefindings apply to other tasks and settings. Strategies should beexplored to mitigate the challenges that LHWs experience inlocating and supporting patients, including the use of newtechnologies, such as mobile phones.

Keywords: Antiretroviral therapy, Community health workers, HIV/AIDS, Lay health workers, Low-income, Primary health care, TB, Time-and-motion study, Treatment support

Human Resources for Health 2014, 12:18http://www.human-resources-health.com/content/12/1/18

8. CYTOKINES

QW 568

The changes and its significance of Th17 and treg cells and related cytokines in patients with tuberculosis pleurisy/ Guo-qiang Wang…[et al.].—Republic of China : Journal Allergy, Asthma & Clinical Immunology, 2014. 6 hlm.

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http://www.human-resources-health.com/content/12/1/18

The changes and its significance of Th17 and treg cells and related cytokines in patients with tuberculosis pleurisy

Guo-qiang Wang, Cai-ling Yang, Dong-fang Yue, Li-hong Pei Hua Zhong and Ju-xia Niu

ABSTRACT

Tuberculous pleurisy is a kind of tuberculosis, it is well knownthat Th1 lymphocytes play a key rolein the treatment oftuberculosis infection. However, latest studies show that Th17lymphocyte may also play an important role tuberculosisinfection. There is close relationship between Treg and Thl7cells, and changes in the number or the function of the two kindsof cells may lead to diseases. The current researches on Thl7 andTregcells maily focus on autoimmune diseases, however, reportsabout their role in tuberculosis are limited. In this study, weinvestigate the function of th17 and Treg cells and the abovecytokines in the pathogenesis of tuberculosis pleurisy; bydetermining the expression of Th17 and Treg cells in peripheralCD4 T cells and the related cytokines in patients withtuberculous compared with healthy people.

Th17 cells in patients were higher than that in the Healthycontrol group, expression of Treg cells in patients were lowerthan that in the healthy group; IL-17, IL-23 levels in peripheralblood and hydrothorax from thepatients were higher than that inthe healthy group; IL-17, IL-23 and IL-6 levels in hydrothoraxwere higher thanthat in peripheral blood. There was no differencein IL-6 level in peripheral blood between the patients andhealthy control; TGF-βlevel in peripheral blood from the healthygroup was higher than that in peripheral blood andhydrothoraxfrom the patients. And there were no differences in TGF-βlevelbetween peripheral blood andhydrothorax. Th17 cells werenegatively correlated with Treg cells ,but were positivecorrelation with IL-17, IL-23,IL-6 levels in peripheral blood;TGF- βlevel was positive correlation with Treg cells in theperipheral blood, but no correlation with Th17 cells.

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Th17 and Treg cells may be involved in the immune pathologicalmechanism of tuberculous pleurisy and changes of relatedcytokines may be involved in the differentiation of Th17 and Tregcells and inflammatory response. Thus, Th17 and Treg cells andrelated cytokines may be important immunopathogenesis fortuberculous pleurisy.

Keyword:Th17 cell, Treg cell, Tuberculous pleurisy, Flow cytometry, Cytokine

Journal Allergy, Asthma & Clinical Immunology 10/28/2014http://www.aacijournal.com/content/10/1/28

9. DOSR PROTEIN, MYCOBACTERIUM TUBERCULOSIS

QW 125.5.M9

DevR (DosR) mimetic peptides impair transcriptional regulation and survival of Mycobacterium tuberculosis under hypoxia by inhibiting the autokinase activity of DevS sensor kinase/ Kohinoor Kaur…[et al.].—India : BMC Microbiology, 2014. 9hlm.

DevR (DosR) mimetic peptides impair transcriptional regulation and survival of Mycobacterium tuberculosis under hypoxia by inhibiting the autokinase activity of DevS sensor kinase

Kohinoor Kaur, Neetu Kumra Taneja, Sakshi Dhingra and Jaya S Tyagi

ABSTRACT

Two-component systems have emerged as compelling targets forantibacterial drug design for a number of reasons including thedistinct histidine phosphorylation property of their constituent

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http://www.aacijournal.com/content/10/1/28

sensor kinases. The DevR-DevS/DosT two component system ofMycobacterium tuberculosis (M. tb) is essential for survivalunder hypoxia, a stress associated with dormancy development invivo. In the present study a combinatorial peptide phage displaylibrary was screened for DevS histidine kinase interactingpeptides with the aim of isolating inhibitors of DevR-DevSsignaling.

DevS binding peptides were identified from a phage displaylibrary after three rounds of panning using DevS as bait. Thepeptides showed sequence similarity with conserved residues inthe N-terminal domain of DevR and suggested that they mayrepresent interacting surfaces between DevS and DevR. Two DevRmimetic peptides were found to specifically inhibit DevR-dependent transcriptional activity and restrict the hypoxicsurvival of M. tb. The mechanism of peptide action is majorlyattributed to an inhibition of DevS autokinase activity.

These findings demonstrate that DevR mimetic peptides impede DevSactivation and that intercepting DevS activation at an early stepin the signaling cascade impairs M. tb survival in a hypoxiapersistence model.

Keywords: Phage display, DevRS peptides, Inhibition of autokinase, Hypoxia

BMC Microbiology 2014, 14:195http://www.biomedcentral.com/1471-2180/14/195

10. DRUG RESISTANCE

QW 45

Sequence analysis for detection of drug resistance in Mycobacterium tuberculosis complex isolates from the Central Region of Cameroon/ Emmanuel Mouafo Tekwu…[et al.].—Germany : BMC Microbiology, 2014. 10 hlm.

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Sequence analysis for detection of drug resistance in Mycobacterium tuberculosis complex isolates from the Central Region of Cameroon

Emmanuel Mouafo Tekwu, Larissa Kamgue Sidze, Jean-Paul Assam Assam, Jean-Claude Tedom,Serges Tchatchouang, Gaëlle Guiewi Makafe, Anne-Laure Tchokote Wetewale,Christopher Kuaban,Sara Eyangoh, Francine Ntoumi Véronique N Penlap Beng and Matthias Frank

ABSTRACT

The potential of genetic testing to rapidly diagnose drugresistance has lead to the development of new diagnostic assays.However, prior to implementation in a given setting, theassociation of specific mutations with specific drug resistancephenotypes should be evaluated. The purpose of this study was toevaluate molecular markers in predicting drug resistance in theCentral Region of Cameroon.

From April 2010 and March 2011, 725 smear positive pulmonarytuberculosis patients were enrolled and all positive cultureswere tested for drug susceptibility. A total of 63 drug resistantand 100 drug sensitive Mycobacterium tuberculosis complexclinical isolates were screened for genetic mutations in katG,inhA, ahpC, rpoB, rpsL, rrs, gidB and embCAB loci using DNAsequencing. Of the 44 isoniazid resistant (INHR) isolates (24high level,1 μg/ml and 20 low level, 0.2 μg/ml), 73% (32/44) carried thekatG315 and/or the −15 inhA promoter mutations. Of the 24 highlevel INHR, 17 (70.8%) harbored katG315 mutation, 1 a pointmutation (−15C→T) in the inhA promoter and 6 were (25.0%) wildtypes. Thus, for INHR high level detection, katG315 mutation hada specificity and a sensitivity of 100% and 70.8% respectively.Of the 20 low level INHR, 10 (50.0%) had a −15C→T mutation in theinhA promoter region, and 1 (2.2%) a −32G→A mutation in the ahpCpromoter region. All of the 7 rifampicin resistant (RIFR)isolates carried mutations in the rpoB gene (at codons Ser531Leu

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(71.4%), His526Asp (14.3%), and Asp516Val (14.3%)). Of the 27streptomycin resistant (SMR) isolates, 7 carried mutations at therpsL and the gidB genes. 1 of the 2 ethambutol resistant (EMBR)isolates displayed a mutation in embB gene.

This study provided the first molecular investigation assessingthe correlation of phenotypic to genotypic characteristics on MTBisolates from the Central Region of Cameroon using DNAsequencing. Mutations on rpoB, katG315 and −15 point mutations ininhA promoter loci could be used as markers for RIF and INH -resistance detection respectively.

Keywords: Phenotype, Mutation, Drug resistance, Mycobacterium tuberculosis, Cameroon


DRUG RESISTANCE

QW 45

Treatment outcomes from community-based drug resistant tuberculosis treatment programs:a systematic review and meta-analysis/ Pamela Weiss…[et al.].—Canada : BMC Infectious Diseases, 2014. 9 hlm.

Treatment outcomes from community-based drug resistant tuberculosis treatment programs:a systematic review and meta-analysis

Pamela Weiss, Wenjia Chen, Victoria J Cook and James C Johnston

ABSTRACT

There is increasing evidence that community-based treatment ofdrug resistant tuberculosis (DRTB) is a feasible and cost-effective alternative to centralized, hospital-based care.

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Although several large programs have reported favourable outcomesfrom community-based treatment, to date there has been nosystematic assessment of community-based DRTB treatment programoutcomes. The objective of this study was to synthesize availableevidence on treatment outcomes from community based multi-drugresistant (MDRTB) and extensively drugresistant tuberculosis (XDRTB) treatment programs.

We performed a systematic review and meta-analysis of thepublished literature to examine treatment outcomes fromcommunity-based MDRTB and XDRTB treatment programs. Studiesreporting outcomes from programs using community-based treatmentstrategies and reporting outcomes consistent with WHO guidelineswere included for analysis. Treatment outcomes, includingtreatment success, default, failure, and death were pooled foranalysis. Meta-regression was performed to examine forassociations between treatment outcomesand program or patient factors.Overall 10 studies reporting outcomes on 1288 DRTB patients wereincluded for analysis. Of this population, 65% [95% CI 59-71%] ofpatients had a successful outcome, 15% [95% CI 12-19%] defaulted,13% [95% CI 9-18%] died, and 6% [95% CI 3-11%] failed treatmentfor a total of 35% [95% CI 29-41%] with unsuccessful treatmentoutcome. Meta-regression failed to identify any factorsassociated with treatment success, including studyyear, age of participants, HIV prevalence, XDRTB prevalence,treatment regimen, directly observed therapy (DOT) location orDOT provider.

Outcomes of community-based MDRTB and XDRTB treatment outcomesappear similar to overall treatment outcomes published in threesystematic reviews on MDRTB therapy. Work is needed to delineateprogram characteristics associated with improved treatmentoutcomes.

Keywords: Tuberculosis, Multidrug-resistant, Treatment, Communitybased

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11. EPIDEMIOLOGIC STUDIES

WA 950

The epidemiology of childhood tuberculosis in the Netherlands: still room for prevention/ Connie GM Erkens…[et al.].—Netherlands : BMC Infectious Diseases, 2014. 9 hlm.

The epidemiology of childhood tuberculosis in the Netherlands: still room for prevention

Connie GM Erkens, Gerard de Vries, Sytze T Keizer, Erika Slump and Susan van den Hof

ABSTRACT

The occurrence of tuberculosis (TB) among children has long beenneglected as a public health concern. However, any child with TBis a sentinel event indicating recent transmission. Vaccination,early case finding and treatment of those latently infected withTB can prevent cases, severe morbidity and unnecessary death.

The objective of the study was to describe the occurrence of TBevents among children in the Netherlands which may be avoidedthrough preventive measures. For this purpose we performed atrend analysis of routine Dutch TB and LTBI (surveillance data in1993–2012 and a descriptive analysis of children with TB and withLTBI diagnosed in 2005–2012).

Overall childhood TB incidence has declined over the last twodecades from 3.6 in 1993 to 1.9 per 100,000 children in 2012. Thedecline was stronger among Dutch-born children compared toforeign-born children. In 2005–2012 64% of childhood TB caseswere detected through active case finding. Foreign-born children

23


with TB were less likely to be detected through active casefinding, when not detected through post-entry TB screening.Childhood TB diagnosis was culture confirmed in 68% of passivelydetected cases and 12% of actively detected cases.Of 1,049children with LTBI started on preventive treatment in 2005–2012,90% completed treatment. In 37% of all childhood TB cases therewas at least one ‘missed opportunity’ for prevention. Thirty ninepercent of child TB patients eligible for BCG were notvaccinated.

Children with TB in the Netherlands are generally detected at anearly stage and treatment completion rates are high. However,more TB cases among children can be prevented through enhancingTB case finding and screening and preventive treatment of latentTB infection among migrant children, and improving the coverageof BCG vaccination among eligible risk groups.

Keywords: Tuberculosis, Latent tuberculosis infection, Children, Preventive therapy, Contact investigation, Prevention


12. EPIDEMIOLOGICAL MONITORING

WA 110

Clinical and epidemiological characteristics of individualsresistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda/ Ningning Ma…[et al.].—Uganda : BMC Infectious Diseases, 2014. 10 hlm.

Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

24


Ningning Ma, Sarah Zalwango, LaShaunda L Malone, Mary Nsereko, Eddie M Wampande, Bonnie A Thiel,Brenda Okware, Robert P Igo Jr.,Moses L Joloba, Ezekiel Mupere,Harriet Mayanja-Kizza,W Henry Boom, Catherine M Stein,for the Tuberculosis Research Unit (TBRU)

ABSTRACT

Despite sustained exposure to a person with pulmonarytuberculosis (TB), some M. Tuberculosis (Mtb) exposed individualsmaintain a negative tuberculin skin test (TST). Our objective wasto characterize these persistently negative TST (PTST-)individuals and compare them to TST converters (TSTC) andindividuals who are TST positive at study enrollment.

During a TB household contact study in Kampala, Uganda, PTST-,TSTC, and TST + individuals were identified. PTST- individualsmaintained a negative TST over a 2 year observation perioddespite prolonged exposure to an infectious tuberculosis (TB)case. Epidemiological and clinical characteristics were compared,a risk score developed by another group to capture risk for Mtbinfection was computed, and an ordinal regression was performed.When analyzed independently, epidemiological risk factorsincreased in prevalence from PTST- to TSTC to TST+. An ordinalregression model suggested age (p < 0.01), number of windows (p <0.01) and people (p = 0.07) in the home, and sleeping in the sameroom (p < 0.01) were associated with PTST- and TSTC. As thesefactors do not exist in isolation, we examined a risk score,which reflects an accumulation of risk factors. This compoundexposure score did not differ significantly between PTST-, TSTC,and TST+, except for the 5–15 age group (p = 0.009).

Though many individual factors differed across all three groups,an exposure risk score reflecting a collection of risk factorsdid not differ for PTST-, TSTC and TST + young children andadults. This is the first study to rigorously characterize theepidemiologic risk profile of individuals with persistentlynegative TSTs despite close exposure to a person with TB.

25

Additional studies are needed to characterize possibleepidemiologic and host factors associated with this phenotype.

Keywords: Transmission risk factors, Latent Mtb infection,Exposure, Household characteristics, PPD test


13. ETHAMBUTOL

QV 268

Evaluation of a microcolony growth monitoring method for therapid determination of ethambutol resistance in Mycobacterium tuberculosis/ Alice L den Hertog…[et al.].—Netherlands : BMC Infectious Diseases, 2014. 9 hlm.

Evaluation of a microcolony growth monitoring method for the rapid determination of ethambutol resistance in Mycobacterium tuberculosis

Alice L den Hertog, Sandra Menting, Ernst T Smienk, Jim Werngren,Sven Hoffner and Richard M Anthony

ABSTRACT

Due to the increasing prevalence of Mycobacterium tuberculosisstrains resistant to one or more antibiotics, there is a need fornew quantitative culture methods both for drug susceptibilitytesting and for validation of mutations putatively associatedwith drug resistance. We previously developed a (myco) bacterialculture method, in which multiple growing microcolonies aremonitored individually. Transfer of the growing microcolonies toselective medium allows the effect on the growth rate of eachindividual colony to be determined. As entire growing coloniesare exposed to antibiotics rather than re-subbed, a second lagphase is

26


avoided and results are obtained more rapidly. Here weinvestigate the performance of the microcolony method todifferentiate between ethambutol (EMB) resistant, intermediateand susceptible strains.

One week old microcolonies from a reference panel of four strainswith known EMB susceptibility were transferred to differentconcentrations of EMB. Growth rates during the 1st 2 days ofexposure were used to set up classification criteria to test andclassify a blinded panel of 20 tuberculosis strains withdifferent susceptibilities.

For 18 strains (90%) reference culture results corresponded toour classifications based on data collected within 9 days ofinoculation. A single strain was classified as Intermediateinstead of Susceptible, and 1 strain could not be classified dueto a contamination.Conclusions: Using a microcolony growth monitoring method we wereable to classify, within 9 days after inoculation, a panel ofstrains as EMB susceptible, intermediate or resistant with 90%correlation to the reference methods.

Keywords: Ethambutol, Drug susceptibility testing, Mycobacteriumtuberculosis, Culture


14. FIBROBLAST

QU 107

Expression of fibroblast specific protein-1 in pleural tuberculosis and its clinical biological significance/ Zhong-min Sun…[et al.].—Republic of China : World Journal of Surgical Oncology, 2014. 4 hlm.

27


Expression of fibroblast specific protein-1 in pleural tuberculosis and its clinical biological significance

Zhong-min Sun, Fei-yan Li, Lei Wang, Hong-yan Wang, Yuan Deng andYan Yao

ABSTRACT

Fibroblast specific protein-1 (S100A4) is related with manyfibrotic diseases, but its role in the pathogenesis of pleuralfibrosis has not been fully elucidated. Then we aim toinvestigate the expression and effect of fibroblast specificprotein-1 (S100A4) in pleural tuberculosis and, subsequently,pleural fibrosis.

The expression of S100A4 in pleura was examined in 30 patientswith pleural tuberculosis and 5 control (disease-free) patientsby immunohistochemistry using the streptavidin-peroxidase (S-P)conjugated method.The expression of S100A4 in pleura was mainly distributed in thenucleus and cytoplasm of fibroblasts and vascular endothelialcells, and the positive rate was 90.0% (27 out of 30 patientswith pleural tuberculosis). There were no expressions of S100A4in the control group. In the pleura of all 30 patients withpleural tuberculosis, S100A4 had a higher expression in the two-to eight-week duration of the disease.

S100A4 plays an important role in the phenotypic transformationof pleural mesothelial cells and the development of pleuralfibrosis.

Keywords: Pleural tuberculosis, Fibroblast specific protein-1, Pleural mesothelial cells, Pleural fibrosis

World Journal of Surgical Oncology 2014, 12:151http://www.wjso.com/content/12/1/151

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http://www.wjso.com/content/12/1/151

15. GENOME

QU 470

Genome analysis reveals three genomospecies in Mycobacteriumabscessus/ Mohamed Sassi, Michel Drancourt.—France : BMC Genomics, 2014. 10 hlm.

16.Genome analysis reveals three genomospecies in Mycobacterium abscessus

Mohamed Sassi and Michel Drancourt

ABSTRACT

Mycobacterium abscessuscomplex, the third most frequentmycobacterial complex responsible forcommunity- and health care-associated infections in developed countries, comprises ofM.abscessussubsp.abscessus and M. abscessus subsp.bolletiireviouslyreferred as Mycobacterium bolletiiand Mycobacterium massiliense.The diversity of this group of opportunistic pathogens is poorlydescribed.

In-depth analysis of 14 published M. abscessuscomplex genomesfound a pan-genome of 6,153 proteins and core-genome of 3,947(64.1%) proteins, indicating a non-conservative genome. Analysingthe average percentage of amino-acid sequence identity (from94.19% to 98.58%) discriminates three main clusters C1, C2 andC3: C1 comprises strains belonging to M. abscessus, C2 comprisesstrains belonging to M. massilienseand C3 comprises strainsbelongingtoM. bolletii; and two sub-clusters in clusters C2 and C3. Thephylogenomic network confirms these three clusters. The genomelength (from 4.8 to 5.51-Mb) varies from 5.07-Mb in C1, 4.89-Mbin C2A, 5.01-Mb in C2B and 5.28-Mb in C3. The mean number ofprophage regions (from 0 to 7) is 2 in C1; 1.33 in C2A; 3.5 inC2B and five in C3. A total of 36 genes are uniquely present inC1, 15 in C2 and 15 in C3. These genes could be used for thedetection and identification of organisms in each cluster.

29

Further, the mean number of host-interaction factors (includingPE, PPE, LpqH, MCE, Yrbe and type VII secretion system ESX3 andESX4) varies from 70 in cluster C1, 80 in cluster C2A, 74 incluster C2B and 93 in clusters C3A and C3B. No significantdifferences in antibiotic resistance genes were observed betweenclusters, in contrast to previously reported in-vitro patterns ofdrug resistance. They encode both penicillin-binding proteinstargeted byβ-lactam antibiotics and an Ambler class Aβ-lactamasefor which inhibitors exist.

Our comparative analysis indicates that M. abscessuscomplexcomprises three genomospecies,corresponding to M. abscessus, M.bolletii,andM. massiliense. The genomics data here reportedindicate differences in virulence of medical interest; andsuggest targets for the refined detection and identification ofM. abscessus.

Keywords:Mycobacterium abscessus, Mycobacterium bolletii,Mycobacterium massiliense, Araucaria, Mycobacteriophage,Prophage

BMC Genomics 2014, 15:359http://www.biomedcentral.com/1471-2164/15/359

GENOME

QU 470

Genome-wide Mycobacterium tuberculosis variation (GMTV) database: a new tool for integrating sequence variations and epidemiology/ Ekaterina N Chernyaeva…[et al.].—Russia :BMC Genomics, 2014. 8 hlm.

Genome-wide Mycobacterium tuberculosis variation (GMTV) database: a new tool for integrating sequence variations and epidemiology

Ekaterina N Chernyaeva, Marina V Shulgina, Mikhail S Rotkevich,Pavel V Dobrynin, Serguei A Simonov, Egor A Shitikov, Dmitry SIschenko, Irina Y Karpova, Elena S Kostryukova, Elena N Ilina,

30


Vadim M Govorun,Vyacheslav Y Zhuravlev, Olga A Manicheva, Peter KYablonsky, Yulia D Isaeva, Elena Y Nosova,Igor V Mokrousov, AnnaA Vyazovaya, Olga V Narvskaya, Alla L Lapidus and Stephen JO’Brien

ABSTRACT

Tuberculosis (TB) poses a worldwide threat due to advancingmultidrug-resistant strains and deadly co-infections with Humanimmunodeficiency virus. Today large amounts of Mycobacteriumtuberculosis whole genome sequencing data are being assessedbroadly and yet there exists no comprehensive online resourcethatconnects M. tuberculosis genome variants with geographicorigin, with drug resistance or with clinical outcome.

Here we describe a broadly inclusive unifying Genome-wideMycobacterium tuberculosis Variation (GMTV) database,(http://mtb.dobzhanskycenter.org) that catalogues genomevariations of M. tuberculosisstrains collected across Russia.GMTV contains a broad spectrum of data derived from differentsources and related to M. tuberculosis molecular biology,epidemiology, TB clinical outcome, year and place of isolation,drug resistance profiles and displays the variants across thegenome using a dedicated genome browser. GMTV database, whichincludes 1084 genomes and over 69,000 SNP or Indel variants, canbe queried about M. tuberculosisgenomevariation and putativeassociations with drug resistance, geographical origin, andclinical stages and outcomes.

Implementation of GMTV tracks the pattern of changes of M.tuberculosisstrains in different geographical areas, facilitatesdisease gene discoveries associated with drug resistance ordifferent clinical sequelae, and automates comparative genomicanalyses among M. tuberculosisstrains.

Keywords:Mycobacterium tuberculosis, Genome variations, Mutation,Genetic diversity, Whole genome sequencing,Database Background

31


16. GENOTYPING TECHNIQUES

QW 125.5.M9

Optimizing multiplex SNP-based data analysis for genotyping of Mycobacterium tuberculosis isolates/ Sarah Sengstake…[et al.].—Netherlands : BMC Genomics, 2014. 11 hlm.

Optimizing multiplex SNP-based data analysis for genotyping of Mycobacterium tuberculosis isolates

Sarah Sengstake, Nino Bablishvili, Anja Schuitema, Nino Bzekalava, Edgar Abadia, Jessica de Beer,Nona Tadumadze, Maka Akhalaia, Kiki Tuin, Nestani Tukvadze, Rusudan Aspindzelashvili, Elizabeta Bachiyska,Stefan Panaiotov, Christophe Sola, Dick van Soolingen, Paul Klatser, Richard Anthony and Indra Bergval

ABSTRACT

Multiplex ligation-dependent probe amplification (MLPA) is apowerful tool to identify genomic polymorphisms. We havepreviously developed a single nucleotide polymorphism (SNP) andlarge sequence polymorphisms (LSP)-based MLPA assay using a readout on a liquid bead array to screen for 47 genetic markers inThe Mycobacterium tuberculosisgenome. In our assay we obtaininformation regarding the Mycobacteriumtuberculosis lineage and drug resistance simultaneously.Previously we called the presence or absence of a genotypicmarker based on a threshold signal level. Here we present a moreelaborate data analysis method to standardize and streamline theinterpretation of data generated by MLPA. The new data analysismethod also identifies intermediate signals in addition toclassification of signals as positive and negative. Intermediatecalls can

32


be informative with respect to identifying the simultaneouspresence of sensitive and resistant alleles or infection withmultiple differentMycobacterium tuberculosisstrains.

To validate our analysis method 100 DNA isolates of Mycobacteriumtuberculosisextracted from cultured patient material collected atthe National TB Reference Laboratory of the National Center forTuberculosis and Lung Diseases in Tbilisi, Republic of Georgiawere tested by MLPA. The data generated were interpreted blindlyand thencompared to results obtained by reference methods. MLPA profilescontaining intermediate calls are flagged for expert reviewwhereas the majority of profiles, not containing intermediatecalls, were called automatically. No intermediate signals wereidentified in 74/100 isolates and in the remaining 26 isolates atleast one genetic marker produced an intermediate signal.

Based on excellent agreement with the reference methods weconclude that the new data analysis method performed well. Thestreamlined data processing and standardized data interpretationallows the comparison of theMycobacterium tuberculosis MLPAresults between different experiments. All together this willfacilitate the implementation of the MLPA assay in differentsettings.

Keywords:Mycobacterium tuberculosis, MLPA, Data analysis, SNP typing, MAGPIX, Drug resistance, MTBC lineage,Republic of Georgia


17. HEALTHCARE DISPARITIES

W 76

33


Gender and regional disparities of tuberculosis in Hunan, China/ Mengshi Chen…[et al.].—Republic of China : International Journal for Equity in Health, 2014. 6 hlm.

Gender and regional disparities of tuberculosis in Hunan, China

Mengshi Chen, Abuaku Benjamin Kwaku, Youfang Chen, Xin Huang, Hongzhuan Tan and Shi Wu Wen

ABSTRACT

Major efforts have been made to improve the health care system inHunan province, China. The aims of this study were to assesswhether and to what extent these efforts have impacted on genderand regional disparities of Tuberculosis (TB) incidence in recentyears, especially for less developed areas.

We obtained data from the 2005–2009 China Information System forDisease Control and Prevention (CISDCP)to conduct this study inHunan province. Counties within the province were divided intofour regions according to quartiles based on the 2007 per capitaGDP. Index of Disparity (ID) and Relative Index of Inequality(RII) were used to measure the disparities of TB incidence inrelation to gender and region. Bootstrap technique was used toincrease the precision.

The average annual incidence of TB was 111.75 per 100,000 inmales and 43.44 per 100000 in females in Hunan. The genderdisparity was stable, with ID from 42.34 in 2005 to 43.92 in2009. For regional disparity, ID, RII (mean) and RII (ratio)decreased significantly from 2005 to 2009 in males (P < 0.05) butremained stable among the female population.

As interventions such as introduction of the New RuralCooperative Scheme put in place to reduce health disparities inChina, regional disparity in relation to incidence of TBdecreased significantly, but the gender disparity remains in theHunan province.

34

Keywords: Health Disparity, TB, Gender, Region

International Journal for Equity in Health 2014, 13:32http://www.equityhealthj.com/content/13/1/32

18. HEALTH PROMOTION

WA 590

Framework of behavioral indicators for outcome evaluation of TB health promotion: a Delphi study of TB suspects and Tb patients/ Ying Li…[et al.].—Republic of China : BMC Infectious Diseases, 2014. 14 hlm.

Framework of behavioral indicators for outcome evaluation of TB health promotion: a Delphi study of TB suspects and Tb patients

Ying Li, John Ehiri, Daiyu Hu, Yanqi Zhang, Qingya Wang, Shun Zhang and Jia Cao

ABSTRACT

Health promotion for prevention and control of Tuberculosis (TB)is implemented worldwide because of its importance, but fewreports have evaluated its impact on behavior due to a lack ofstandard outcome indicators. The objective of this study was toestablish a framework of behavioral indicators for outcomeevaluation of TB health promotion among TB suspects and patients.

A two-round modified Delphi method involving sixteen TB controlexperts was used to establish a framework of behavioralindicators for outcome evaluation of TB health promotion targetedat TB suspects and patients.

Sixteen of seventeen invited experts in TB control (authorityscore of 0.91 on a 1.0 scale) participated in round 1 survey. Allsixteen experts also participated in a second round survey. After

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http://www.equityhealthj.com/content/13/1/32

two rounds of surveys and several iterations among the experts,there was consensus on a framework of indicators for measuringoutcomes of TB health promotionfor TB suspects and patients. For TB suspects, the expertsreached consensus on 2 domains (“Healthcare seeking behavior”and“Transmission prevention”), 3 subdomains (“Seeking care afteronset of TB symptoms”, “Pathways of seekingcare”and“Interpersonal contact etiquette”), and 8 indicators(including among others, “Length of patient delay”). For TBpatients, consensus was reached on 3 domains (“Adherence totreatment”, “Healthy lifestyle”and “Transmission prevention”), 8subdomains (including among others, “Adherence to theirmedication”), and 14indicators (including “Percentage of patients who adhered totheir medication”). Operational definitions and data sources wereprovided for each indicator.

The findings of this study provide the basis for debate amonginternational experts on a framework for achieving globalconsensus on outcome indicators for TB health promotioninterventions targeted at TB patients and suspects. Suchconsensus will help to increase effectiveness of TB healthpromotion, while ensuring international comparability of outcomedata.

Keywords:Health promotion, Outcome evaluation, TB suspect, TB patient, Indicator


19. HEALTH SERVICES

WA 330

Health-service performance of TB treatment for indigenous and non-indigenous populations in Brazil: a cross-sectional

36


study/ Everton Ferreira Lemos…[et al.].—Brazil : BMC Health Services Research, 2014. 9 hlm.

Health-service performance of TB treatment for indigenous and non-indigenous populations in Brazil: a cross-sectional study

Everton Ferreira Lemos, Aline Mara da Silva Alves, Giovana de Castro Oliveira, Marcella Paranhos Rodrigues,Natália Daiane Garoni Martins and Julio Croda

ABSTRACT

Health-service evaluation studies are fundamental for proposinginterventions and ensuring improvements in healthcare quality.The present study assesses the performance of health services forindigenous and non-indigenous populations with regard totuberculosis (TB) control.

Interviews with TB patients who underwent treatment between 2009and 2011 were conducted using The Primary Care AssessmentTooladapted for TB care in Brazil.

Primary healthcare (PHC) was the first treatment for mostpatients at symptom onset, and the diagnoses were typicallyperformed by specialized services. Many patients experienceddelayed TB diagnoses that required more than three medicalappointments (51% and 47% for indigenous and non-indigenouspopulations, respectively). Indigenous people received socialsupport, such as basic-needs grocery packages (2.19 ± 1.63 vs.1.13 ± 0.49 for non-indigenous people, p < 0.01) and home visitsfrom health professionals, with an emphasis on the performance ofdirectly observed treatment strategies (DOT; 4.57 ± 0.89 vs. 1.68± 1.04 for non-indigenous people, p < 0.01).

Regardless of the differences between indigenous and non-indigenous populations, the timeneeded to receive a TB diagnosiswas unsatisfactory for both groups. Furthermore, DOT must beperformed with better coverage among non-indigenous patients.

37

Keywords:Tuberculosis, Indigenous, Prevention, Control, HealthservicesBMC Health Services Research 2014, 14:237http://www.biomedcentral.com/1472-6963/14/237

20. HIV

QW 168.5.H6

The impact of HAART initiation timing on HIV-TB co-infectedpatients, a retrospective cohort study/ Chin-Hui Yang…[et al.].—Taiwan : BMC Infectious Diseases, 2014. 10 hlm.

The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study

Chin-Hui Yang, Kuan-Jung Chen, Jih-Jin Tsai, Yu-Hui Lin, Shu-Hsing Cheng, Kwei-Feng Wang and Hung-Yi Chiou

ABSTRACT

Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan.

A population-based retrospective cohort study was conductedthrough linking the HIV and TB registries of Taiwan Centers forDisease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immunereconstitution inflammatory syndrome (IRIS), was collectedthrough medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Coxproportional hazard model was used to explore the probability ofdeath and IRIS after TB diagnosis by adjusting for confounding

38


factors and factors of interest. The probability of survival andTB IRIS were calculated by the Kaplan-Meier method and comparedbetween different HAART initiation timing groups by the log-ranktest.

There were 229 HIV-TB co-infected patients included for analysisand 60 cases (26.2%) died within one year.Besides decreasing ageand increasing CD4 lymphocyte count, having started HAART duringTB treatment was significantly associated with better survival(adjusted Hazard Ratio was 0.11, 95% CI 0.06–0.21). As to thetiming of HAART initiation, there was only non-significantbenefit on survival among cases initiating HAART within 15 days,at 16–30 days and at 31–60 days of TB treatment than initiatingafter 60 days. Cases with HAART initiated after 30 days had lowerrisk in developing IRIS than cases with HAART initiated earlier.Cases with IRIS had significantly higher rate ofrehospitalization (49% vs. 4%, p < 0.001) and prolongedhospitalization (28 days vs. 18.5 days, p < 0.01).

The present study found that starting HAART during TB treatmentis associated with better one-year survival, although earlierinitiation within 60 days of TB treatment did not showstatistical differences in survival than later initiation.Initiation of HAART within 30 days appeared to increase the riskof IRIS. Deferring HAART to 31–60 days of TB treatment might beoptimal after considering the risks and benefits.

Keywords:Tuberculosis, HIV, Mortality, HAART


HIV

QW 168.5.H6

39


Factors associated with tuberculosis by HIV status in the Brazilian national surveillance system: a cross sectional study/ Thiago Nascimento do Prado…[et al.].—Brazil : BMC Infectious Diseases, 2014. 8 hlm.

Factors associated with tuberculosis by HIV status in the Brazilian national surveillance system: a cross sectional study

Thiago Nascimento do Prado, Angélica Espinosa Miranda, Fernanda Mattos de Souza,Elias dos Santos Dias, Lorena Kellen Fernandes Sousa, Denise Arakaki-Sanchez, Mauro N Sanchez,Jonathan E Golub and Ethel Leonor Maciel

ABSTRACT

Over the last decade tuberculosis (TB) incidence and mortality inBrazil have been steadily declining. However, this downward trendhas not been observed among HIV-infected patients. We describethe epidemiological and clinical profile of TB patients by HIVstatus using the Brazilian National Surveillance System.

All TB diagnoses with HIV status information between January 1,2007 and December 31, 2011 were categorized as either HIV or non-HIV at time of TB diagnosis. Co-infected patients (TB-HIV) werecompared to TB patients with no HIV-infection using ahierarchical logistic regression model using Stata 13.0.

The prevalence of TB-HIV co-infection was 19% among adults ≥ 15years of age. We analyzed data from 243,676 individuals, of whom46,466 were TB-HIV and 197,210 were only TB cases. The followingfactors increased risk of co-infection: male sex (OR: 1.06, 95%CI 1.03-1.10), 20 to 39 years of age (OR = 4.82, 95% CI 4.34-5.36), black (OR = 1.08,95% CI 1.04-1.13), 4–7 years of education(OR = 1.13, 95% CI 1.19-1.28), diagnosed following default (OR =2.65, 95% CI1.13-6.25), presenting with pulmonary and extra-pulmonary forms of TB simultaneously (OR = 2.80, 95% CI 1.56-5.02), presenting with histopathologic examination suggestive ofTB (OR = 2.15, 95% CI 1.13-4.07). Co-infected patients were less

40

likely to live in rural areas (OR = 0.45, 95% CI 0.42-0.48), havediabetes (OR = 0.45, 95% CI 0.40-0.50) andbe smear positive (OR = 0.55, 95% CI 0.32-0.95), and co-infectedpatients had higher risk of default (OR = 2.96, 95% CI 2.36-3.71)and death from TB (OR = 5.16, 95% CI 43.04-5.77).The prevalence of co-infection with HIV among TB patients is 19%in Brazil. By identifying predictors of co-infection targetedinterventions can be developed to prevent both TB and HIV, and todiagnose each disease earlier and ultimately decrease poortreatment outcomes and death.

Keywords: Tuberculosis, HIV, Coinfection, Logistic regression


21. HOSPITALS, PEDIATRIC

WS 27-28 Pulmonary Tuberculous: Symptoms, diagnosis and treatment. 19-year experience in a third level pediatric hospital/ Napoleón González Saldaña…[et al.].—Mexico : BMC Infectious Diseases, 2014. 7 hlm.

Pulmonary Tuberculous: Symptoms, diagnosis and treatment. 19-year experience in a third level pediatric hospital

Napoleón González Saldaña, Mercedes Macías Parra, Marte HernándezPorras, Pedro Gutiérrez Castrellón,Valeria Gómez Toscano and HugoJuárez Olguin

ABSTRACT

Pulmonary tuberculosis (PTB) is an infectious disease thatinvolves the lungs and can be lethal in many cases. Tuberculosis(TB) in children represents 5 to 20% of the total TB cases.However, there are few updated information on pediatric TB,

41


reason why the objective of the present study is to know the realsituation of PTB in the population of children in terms of itsdiagnosis and treatment in a third level pediatric hospital.

A retrospective study based on a revision of clinical files ofpatients less than 18 years old diagnosed with PTB from January1994 to January 2013 at Instituto Nacional de Pediatria, MexicoCity was carried out. A probable diagnosis was based on 3 or moreof the following: two or more weeks of cough, fever, tuberculinpurified protein derivative (PPD) +, previous TB exposure,suggestive chest X-ray, and favorable response to treatment.Definitive diagnosis was based on positive acid-fast bacilli(AFB) or culture.

In the 19-year period of revision, 87 children were diagnosedwith PTB; 57 (65.5%) had bacteriologic confirmation with ZNstaining or culture positive (in fact, 22 were ZN and culturepositive), and 30 (34.5%) had a probable diagnosis; 14(16.1%)were diagnosed with concomitant disease, while 69/81 wereimmunized. Median evolution time was 21 days (5–150). Fever wasfound in 94.3%, cough in 77%, and weight loss in 55.2%. Historyof contact with TB was established in 41.9%. Chest X-ray showedconsolidation in 48.3% and mediastinal lymph node in 47.1%. PPDwas positive in 59.2%, while positive AFB was found in 51.7%cases. Culture was positive in 24/79 patients (30.4%), PCR in20/27 (74.1%). 39 (44.8%) patients were treated with rifampin,isoniazid, and pyrazinamide while 6 (6.9%) received the formerdrugs plus streptomycin and 42 (48.3%) the former plusethambutol. There were three deaths.

PTB in pediatric population represents a diagnostic challenge forthe fact that clinical manifestations are unspecific and thediagnosis is not confirmed in all cases; that is why clinicalsuspicion, X-ray findings and PPD are indispensable for opportunestart of treatment.

Keywords: Tuberculosis, Pulmonary tuberculosis, Tuberculosis in children

42


22. HOUSEHOLDS

WA 288

Decreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township/ Keren Middelkoop…[et al.].—South Africa :BMC Infectious Diseases, 2014. 7 hlm.

Decreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township

Keren Middelkoop, Linda-Gail Bekker, Carl Morrow, Namee Lee and Robin Wood

ABSTRACT

Tuberculosis (TB) transmission rates are exceptionally high inendemic TB settings. Adolescence represents a period ofincreasing TB infection and disease but little is known as towhere adolescents acquire TB infection. We explored therelationship between residential exposure to adult TB cases andinfection in children and adolescents in a South Africancommunity with high burdens of TB and HIV.

TB infection data were obtained from community, school-basedtuberculin skin test (TST) surveys performed in 2006, 2007 and2009. A subset of 2007 participants received a repeat TST in2009, among which incident TB infections were identified. Usingresidential address, all adult TB cases notified by the communityclinic between 1996 and 2009 were cross-referenced with childhoodand adolescent TST results. Demographic and clinic data includingHIV status were abstracted for TB cases. Multivariate logisticregression models examined the association of adult TB exposure

43


with childhood and adolescent prevalent and incident TBinfection.

Of 1,100 children and adolescents included in the prevalent TBinfection analysis, 480 (44%) were TST positive and 651 (59%)were exposed to an adult TB case on their residential plot.Prevalent TB infection in children aged 5–9 and 10–14 years waspositively associated with residential exposure to an adult TBcase (odds ratio [OR]:2.0; 95% confidence interval [CI]: 1.1-3.6and OR:1.5; 95% CI: 1.0-2.3 respectively), but no association wasfound in adolescents≥15 years (OR:1.4; 95% CI: 0.9-2.0). HIV status of adult TB caseswas not associated with TB infection (p= 0.62). Of 67 previouslyTST negative children, 16 (24%) converted to a positive TST in2009. These incident infections were not associated withresidential exposure to an adult TB case (OR: 1.9; 95% CI: 0.5-7.3).

TB infection among young children was strongly associated withresidential exposure to an adult TB case,but prevalent andincident TB infection in adolescents was not associated withresidential exposure. The HIV-status of adult TB cases was not arisk factor for transmission. The high rates of TB infection anddisease among adolescents underscore the importance ofidentifying where infection occurs in this age group.

Keywords:Tuberculosis, Infection, Transmission, Adolescents


23. ISONIAZID

QV 268

Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic

44


Reviews/ Lisa V Adams…[et al.].—United States of America : BMCInfectious Diseases, 2014. 10 hlm.

Interventions to improve delivery of isoniazid preventive therapy: an overview of systematicReviews

Lisa V Adams, Elizabeth A Talbot, Karen Odato, Heather Blunt andKaren R Steingart

ABSTRACT

Uptake of isoniazid preventive therapy (IPT) to preventtuberculosis has been poor, particularly in the highest riskpopulations. Interventions to improve IPT delivery could promoteimplementation. The large number of existing systematic reviewson treatment adherence has made drawing conclusions a challenge.To provide decision makers with the evidence they need, weperformed an overview of systematic reviews to compare differentorganizational interventions to improve IPT delivery as measuredby treatment completion among those at highest risk for thedevelopment of TB disease, namely child contacts or HIV-infectedindividuals.

We searched the Cochrane Database of Systematic Reviews, theDatabase of Abstracts of Reviews of Effects (DARE), and MEDLINEup to August 15, 2012. Two authors used a standardized dataextraction form and the AMSTAR instrument to independently assesseach review.Six reviews met inclusion criteria. Interventions includedchanges in the setting/site of IPT delivery, use of qualitymonitoring mechanisms (e.g., directly observed therapy), IPTdelivery integration into other healthcare services, and use oflay health workers. Most reviews reported a combination ofoutcomes related to IPT adherence and treatment completion ratebut without a baseline or comparison rate. Generally, we foundlimited evidence to demonstrate that the studied interventionsimproved treatment completion.

45

While most of the interventions were not shown to improve IPTcompletion, integration of tuberculosis and HIV services yieldedhigh treatment completion rates in some settings. The lack ofdata from high burden TB settings limits applicability. Furtherresearch to assess different IPT delivery interventions,including those that address barriers to care in at-riskpopulations, is urgently needed to identify the most effectivepractices for IPT delivery and TB control in high TB burdensettings.

Keywords: Tuberculosis, HIV, Adherence, Latent tuberculosisinfection


24. KNOWLEDGE

W 26.55.A7

Tuberculosis patients’ knowledge and beliefs about tuberculosis: a mixed methods study from the Pacific Island nation of Vanuatu/ Kerri A Viney…[et al.].—Australia : BMC PublicHealth, 2014. 12 hlm.

Tuberculosis patients’ knowledge and beliefs about tuberculosis: a mixed methodsstudy from the Pacific Island nation of Vanuatu

Kerri A Viney, Penelope Johnson, Markleen Tagaro, Saen Fanai, Nguyen N Linh, Paul Kelly,David Harley and Adrian Sleigh

ABSTRACT

The setting for this study was the Pacific island nation ofVanuatu, an archipelago of 82 islands, located in the South

46


Pacific Ocean. Our objective was to assess the knowledge,attitudes and practices of tuberculosis (TB) patients towards TB.

This was a descriptive study using qualitative and quantitativemethods. Quantitative analysis was based on the responsesprovided to closed questions, and we present frequencies todescribe the TB patients’ knowledge, attitudes and practicerelating to TB. Qualitative analysis was based on open questionspermitting fuller explanations. We used thematic analysis anddeveloped a posteriori inductive categories to draw conclusions.

Thirty five TB patients were interviewed; 22 (63%) were male.They attributed TB to cigarettes, kava, alcohol, contaminatedfood, sharing eating utensils and “kastom” (the local term forthe traditional way of life, but also for sorcery). Most (94%)did not attribute TB to a bacterial cause. However, almost all TBpatients (89%) thought that TB was best treated at a hospitalwith antibiotics. Three quarters (74%) experienced stigma aftertheir TB diagnosis.Seeking health care from a traditional healerwas common; 54% of TB patients stated that they would firstconsult a traditional healer for any illness. When seeking adiagnosis for signs and symptoms of TB, 34% first consulted atraditional healer. Patients cited cost, distance and beliefsabout TB causation as reasons for first consulting a traditionalhealer or going to the hospital. Of the TB patients who consulteda traditional healer first, there was an average of two weeksdelay before they consulted the health service. In some cases,however, the delay was up to six years.

The majority of the TB patients interviewed did not attribute TBto a bacterial cause. Consulting a traditional healer for healthcare, including while seeking a diagnosis for TB symptoms, wascommon and may have delayed diagnosis. People require betterinformation about TB to correct commonly held misperceptionsabout the disease. Traditional healers could also be engaged withthe national TB programme, in order to refer people with signsand symptoms of TB to the nearest health service.

47

Keywords: Tuberculosis, Vanuatu, Health-seeking, Diagnosis,Mixed-methods

BMC Public Health 2014, 14:467http://www.biomedcentral.com/1471-2458/14/467

25. LENGTH OF STAY

WX 158

Longer hospital stay is associated with higher rates of tuberculosis-related morbidity and mortality within 12 months after discharge in a referral hospital in Sub-Saharan Africa/ Nicola M Zetola…[et al.].—Botswana : BMC Infectious Diseases, 2014. 11 hlm.

Longer hospital stay is associated with higher rates of tuberculosis-related morbidity and mortality within 12 months after discharge in a referral hospital in Sub-Saharan Africa

Nicola M Zetola, Nenad Macesic, Chawangwa Modongo, Sanghuk Shin, Ronald Ncube and Ronald G Collman

ABSTRACT

Nosocomial transmission of pulmonary tuberculosis (PTB) is aproblem in resource-limited settings. However, the degree of TBexposure and the intermediate- and long-term morbidity andmortality of hospital-associated TB is unclear. In this study wedetermined: 1) the nature, patterns and intensity of TB exposureoccurring in the context of current TB cohorting practices inmedical centre with a high prevalence of TB and HIV; 2) the one-year TB incidence after discharge; and 3) one-year TB-relatedmortality after hospital discharge.

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Factors leading to nosocomial TB exposure were collected dailyover a 3-month period. Patients were followed for 1-year afterdischarge. TB incidence and mortality were calculated andlogistic regression was used to determine the factors associatedwith TB incidence and mortality during follow up.

1,094 patients were admitted to the medical wards between May 01and July 31, 2010. HIV was confirmed in 690/1,094 (63.1%) ofthem. A total of 215/1,094 (19.7%) patients were diagnosed withPTB and 178/1,094 (16.3%) patients died during the course oftheir hospitalization; 12/178 (6.7%) patients died from TB-related complications. Eventually, 916(83.7%) patients were discharged and followed for one year afterit. Of these, 51 (5.6%) were diagnosed with PTB during the yearof follow up (annual TB rate of 3,712 cases per 100,000 personper year). Overall, 57/916 (6.2%) patients died during the followup period, of whom 26/57 (45.6%) died from confirmed TB. One-yearTB incidence rate and TB-associated mortality were associatedwith the number of days that the patient remained hospitalized,the numberof days spent in the cohorting bay (regardless of whether thepatient was eventually diagnosed with TB or not), and the numberand proximity to TB index cases. There was no difference in theperformance of each of these 3 measurements of nosocomial TBexposure for the prediction of one-year TB incidence.

Substantial TB exposure, particularly among HIV-infectedpatients, occurs in nosocomial settings despite implementation ofcohorting measures. Nosocomial TB exposure is strongly associatedwith one-year TB incidence and TB-related mortality. Furtherstudies are needed to identify strategies to reduce such exposureamong susceptible patients.

Keywords: Tuberculosis, Transmission, Nosocomial, Infectioncontrol, HIV, Morbidity, Mortality


49


26. LIVER

WI 702

The risk factors for tuberculosis in liver or kidney transplant recipients/ Jia Liu…[et al.].—Republic of China : BMC Infectious Diseases, 2014. 6 hlm.

The risk factors for tuberculosis in liver or kidney transplant recipients

Jia Liu, Jin Yan, Qiquan Wan, Qifa Ye and Yisheng Huang

ABSTRACT

Liver or kidney transplant recipients are at a higher risk ofdeveloping tuberculosis (TB) than general population. We aimed toclarify the incidence density of and risk factors for TB in liveror kidney transplant recipients in the present study.

All patients with TB following liver or kidney transplantationwere investigated retrospectively at the Third Xiangya Hospital,Central South University, Changsha, China. The incidence densityof TB was calculated. We performed a nested case–control study(1:1) to investigate by univariate and multivariate logisticregression analysis the potential risk factors for TB.

From January 2000 to August 2013, 1748 kidney and 166 livertransplant recipients were performed at a university teachinghospital. Among the 1914 recipients, 45 cases (2.4%) of TB werereported. The incidence density was 506 cases per 105 patient-years in kidney or liver transplant recipients, which was 7 timeshigher than in the general Chinese population (around 70 casesper 105 person-years). The median time to develop TB was 20.0months (interquartile ratio: 5.0-70.0). The receipt of a graftfrom a cadaveric donor (odds ratio [OR] = 3.7; 95%

50

confidence interval [CI] = 1.4-10.0; P = 0.010) and thepreoperative evidence of latent TB (OR = 6.8; 95% CI = 2.0-22.7;P = 0.002) were identified as two risk factors for developing TBin liver or kidney transplant recipients.

The incidence density of TB among liver or kidney transplantrecipients was much higher than in the general Chinesepopulation. Recipients receiving a graft from a cadaveric donorand the preoperative evidence of latent TB were two major riskfactors for developing TB in liver or kidney transplantrecipients

Keywords: Tuberculosis, Infection, Transplantation, Risk factor


27. MEDICINE, TRADITIONAL

WB 55

Traditional healers and the potential for collaboration with the national tuberculosis programme in Vanuatu: results froma mixed methods study/ Kerri Viney…[et al.].—Australia : BMC Public Health, 2014. 9 hlm.

Traditional healers and the potential for collaboration with the national tuberculosis programme in Vanuatu: results from a mixed methods study

Kerri Viney, Penelope Johnson, Markleen Tagaro, Saen Fanai, Nguyen N Linh, Paul Kelly, David Harley and Adrian Sleigh

This study was conducted in the Pacific island nation of Vanuatu.Our objective was to assess knowledge, attitudes and practice oftraditional healers who treat lung diseases and tuberculosis(TB), including their willingness to collaborate with thenational TB programme.

51


This was a descriptive study using both qualitative andquantitative methods. Quantitative analysis was based on theresponses provided to closed-ended questions, and we useddescriptive analysis (frequencies) to describe the knowledge,attitudes and practice of the traditional healers towards TB.Qualitative analysis was based on open-ended questions permittingfuller explanations. We used thematic analysis and developed aposterioriinductive categories to draw original and unbiased conclusions.

Nineteen traditional healers were interviewed; 18 were male.Fifteen of the healers reported treating short wind (a local termto describe lung, chest or breathing illnesses) which theyattributed to food, alcohol, smoking or pollution from contactwith menstrual blood, and a range of other physical and spiritualcauses. Ten said that they would treat TB with leaf medicine.Four traditional healers said that they would not treat TB.Twelve of the healers had referred someone to a hospital for astrong wet-cough and just over half of the healers (9) reported aprevious collaboration with the Government health care system.Eighteen of the traditional healers would be willing tocollaborate with the national TB programme, with or withoutcompensation.

Traditional healers in Vanuatu treat lung diseases including TB.Many have previously collaborated with the Government fundedhealth care system, and almost all of them indicated awillingness to collaborate with the national TB programme. Theengagement of traditional healers in TB management should beconsidered, using an evidence based and culturally sensitiveapproach.

Keywords: Tuberculosis, Pacific, Traditional healers, Health care


52


28. MOBILE APPLICATIONS

Q 350-390

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0/ Alex M Clark, Alex M Clark, Sean Ekins.—United States of America : Journal of Cheminformatics, 2014. 17 hlm.

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0

Alex M Clark, Malabika Sarker and Sean Ekins

ABSTRACT

We recently developed a freely available mobile app (TB Mobile)for both iOS and Android platforms that displays Mycobacteriumtuberculosis (Mtb) active molecule structures and their targetswith links to associated data. The app was developed to maketarget information available to as large an audience as possible.We now report a major update of the iOS version of the app. Thisincludes enhancements that use an implementation of ECFP_6fingerprints that we have made open source. Using thesefingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape.Proposed compounds can also be compared to existing target data,using a näive Bayesian scoring system to rank probable targets.We have curated an additional 60 new compounds and their targetsfor Mtb and added these to theoriginal set of 745 compounds. We have also curated 20 furthercompounds (many without targets in TB Mobile) to evaluate thisversion of the app with 805 compounds and associated targets.

TB Mobile can now manage a small collection of compounds that canbe imported from external sources, or exported by various means

53

such as email or app-to-app inter-process communication. Thismeans that TB Mobile can be used as a node within a growingecosystem of mobile apps for cheminformatics. It can also clustercompounds and use internal algorithms to help identify potentialtargets based on molecular similarity. TB Mobile represents avaluable dataset, data-visualization aid and target predictiontool.

Keywords: Mobile app, Mycobacterium tuberculosis, TB mobile,Tuberculosis, Target prediction

Journal of Cheminformatics 2014, 6:38http://www.jcheminf.com/content/6/1/3829. MONOCYTES

WH 200

The association between the ratio of monocytes: lymphocytesat age 3 months and risk of tuberculosis (TB) in the first two years of life/ Vivek Naranbhai…[et al.].—South Africa : BMC Medicine, 2014. 6 hlm.

The association between the ratio of monocytes: lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life

Vivek Naranbhai, Soyeon Kim, Helen Fletcher, Mark F Cotton, Avy Violari, Charles Mitchell,Sharon Nachman, George McSherry, Helen McShane, Adrian VS Hill, Shabir A Madhi

ABSTRACT

Recent transcriptomic studies revived a hypothesis suggested byhistorical studies in rabbits that the ratio of peripheral bloodmonocytes to lymphocytes (ML) is associated with risk oftuberculosis (TB) disease. Recent data confirmed the hypothesisin cattle and in adults infected with HIV.

54

http://www.jcheminf.com/content/6/1/38

We tested this hypothesis in 1,336 infants (540 HIV-infected, 796HIV-exposed, uninfected (HEU)) prospectively followed in arandomized controlled trial of isoniazid prophylaxis in SouthernAfrica, the IMPAACT P1041 study. We modeled the relationshipbetween ML ratio at enrollment (91 to 120 days after birth) andTB disease or death in HIV-infected children and latentMycobacterium tuberculosis (MTB) infection, TB disease or deathin HEU children within 96 weeks (with 12 week window) ofrandomization. Infants were followed-up prospectively androutinely assessed for MTB exposure and outcomes. Coxproportional hazards models allowing for non-linear associationswere used; in all cases linear models were the most parsimonious.

Increasing ML ratio at baseline was significantly associated withTB disease/death within two years (adjusted hazard ratio (HR)1.17 per unit increase in ML ratio; 95% confidence interval (CI)1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocytecounts alone were associated with TB disease. The association wasnot statistically dissimilar between HIV infected and HEUchildren. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It wasstrongest when restricted to probable and definiteTB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore,per 0.1 unit increase in the ML ratio at three to four months ofage, the hazard of probable or definite TB disease before twoyears was increased by roughly 4%(95% CI 1.7% to 6.6%).

Elevated ML ratio at three- to four-months old is associated withincreased hazards of TB disease before two years among childrenin Southern Africa. While significant, the modest effect sizesuggests that the ML ratio plays a modest role in predicting TBdisease-free survival; its utility may, therefore, be limited tocombination with existing tools to stratify TB risk, or to informunderlying pathophysiologic determinants of TB disease.

Keywords: Tuberculosis, HIV, combination antiretroviraltherapy,monocytes,lymphocytes

55

BMC Medicine 2014, 12:120http://www.biomedcentral.com/1741-7015/12/120

30. MUNICIPAL HOSPITALS

WX 162-162.5

Collaboration between municipal and specialist public healthcare in tuberculosis screening in Norway/ Ingunn Harstad, Anne H Henriksen, Eli Sagvik.—Norwegia : BMC Health Services Research, 2014. 7 hlm.

Collaboration between municipal and specialist public health care in tuberculosis screening in Norway

Ingunn Harstad, Anne H Henriksen and Eli Sagvik

ABSTRACT

About 90% of new tuberculosis (TB) cases in Norway appear amongimmigrants from high incidence countries. There is a compulsorygovernmental tuberculosis screening programme for immigrants;immigrants with positive screening results are to be referredfrom municipal health care to the specialist health care forfollow-up. Recent studies of the screening programme have showninadequate follow-up. One of the main problems has been thatpatients referred for follow-up have not attended theirappointment at the specialist health care.TB screening in themunicipality of Trondheim is done by two different teams: theRefugee Healthcare Centre (RHC) screens refugees and theVaccination and Infection Control Office (VICO) screens all theother groups. Patients with positive findings on screening arereferred to the hospital’s Pulmonary Out-patient Department(POPD). The municipal and referral level public health care

56


initiated a project aiming to improve follow-up through closercollaboration.

An intervention group and a pre-intervention control group wereestablished for each screening group.During meetings betweenstaff from the municipality and the POPD, inadequacies in thescreening process were identified, and changes in procedures forsummoning patients, and time and place for tests wereimplemented.For both the intervention group and the controlgroup, time from referral until consultation at the POPD andnumber of patients that attended their first appointment wereregistered and compared.

In the VICO group, 97/134 (72%) of the controls and 109/123 (89%)of the intervention group attended their first appointment at thePOPD after 30 weeks (median) and 10 weeks, respectively. In theRHC group 28/46 (61%) of the controls and 55/59 (93%) in theintervention group attended their first appointment after 15 and8 weeks (median) respectively.

Increased collaboration between the municipal and specialisthealth care can improve the follow-up of positive TB screeningresults.

Keywords:Tuberculosis,Screening,Asylumseekers,Refugees,Contacttracing,Collaboration

BMC Health Services Research 2014, 14:238http://www.biomedcentral.com/1472-6963/14/238

31. MYCOBACTERIUM AVIUM

WC 302

Disruption of Mycobacterium avium subsp.paratuberculosis-specific genes impairsin vivo fitness/ Joyce Wang…[et al.].—Canada : BMC Genomics, 2014. 10 hlm.

57


Disruption of Mycobacterium avium subsp.paratuberculosis-specific genes impairsin vivo fitness

Joyce Wang, Justin R Pritchard, Louis Kreitmann, Alexandre Montpetit and Marcel A Behr

ABSTRACT

Mycobacterium aviumsubsp.paratuberculosis(MAP) is an obligateintracellular pathogen that infects many ruminant species. Theacquisition of foreign genes via horizontal gene transfer hasbeen postulated to contribute to its pathogenesis, as thesegenetic elements are absent from its putative ancestor,M.aviumsubsp. hominissuis(MAH), an environmental organism withlesser pathogenicity. In this study, high-throughput sequencingofMAP transposon libraries were analyzed to qualitatively andquantitatively determine the contribution of individual genes tobacterial survival during infection.

Out of 52384 TA dinucleotides present in the MAP K-10 genome,12607 had a MycoMarT7 transposon in the input pool, interrupting2443 of the 4350 genes in the MAP genome (56%). Of 96 genessituated in MAP-specific genomic islands, 82 were disrupted inthe input pool, indicating that MAP-specific genomic regions aredispensable forin vitro growth (odds ratio = 0.21). Following 5independentin vivo infections with this pool of mutants, thecorrelation between output pools was high for 4 of 5 (R = 0.49 to0.61) enabling us to define genes whose disruption reproduciblyreduced bacterial fitnessin vivo. At three different thresholdsfor reduced fitness in vivo, MAP-specific genes were over-represented in the list of predicted essential genes. We alsoidentified additional genes that were severely depleted afterinfection, and several of them have orthologues that areessential genes in M. tuberculosis.

This work indicates that the genetic elements required for theinvivo survival of MAP represent a combination of conserved

58

mycobacterial virulence genes and MAP-specific genes acquired viahorizontal gene transfer. In addition, thein vitro andin vivoessential genes identified in this study may be furthercharacterized to offer a better understanding of MAPpathogenesis, and potentially contribute to the discovery ofnovel therapeutic and vaccine targets.

Keywords:Mycobacterium avium, M. aviumsubsp.paratuberculosis, Transposon insertion sequencing, Horizontal gene transfer, Mycobacterial pathogenesis


32. MYCOBACTERIUM TUBERCULOSIS

QW 125.5.M9

Evaluation of the anti-mycobacterium tuberculosis activity andin vivo acute toxicity of Annona sylvatic/ Rafaele CP Araujo…[et al.].—Brazil : BMC Complementary and Alternative Medicine, 2014. 10 hlm.

Evaluation of the anti-mycobacterium tuberculosis activity andin vivo acute toxicity of Annona sylvaticRafaele CP Araujo, Francisco AR Neves, Anelise SN Formagio, Candida AL Kassuya, Maria EA Stefanello,Vanessa V Souza, FernandoR Pavan and Julio Croda

ABSTRACT

The recent emergence of extensively multidrug-resistantMycobacterium tuberculosisstrains has furthercomplicated the control of tuberculosis. There is an urgent needfor the development of new molecular candidates antituberculardrugs. Medicinal plants have been an excellent source of leadsfor the development of drugs. The aim of this study was to

59


evaluate thein vitro activity of 28 alcoholic extracts andessential oils of native and exotic Brazilian plantsagainstMycobacterium tuberculosisand to further study theseextracts through chemical fractionation, the isolation of theirconstituents, and an evaluation of the in vivo acute toxicity ofthe active extracts. To the best of our knowledge this is thefirst chemical characterization, antituberculosis activity andacute toxicity evaluation of Annona sylvatica.

The anti-mycobacterial activity of these extracts and theirconstituent compounds was evaluated using the resazurin reductionmicrotiter assay (REMA). To investigate the acute toxicity ofthese extracts in vivo, female Swiss mice were treated with theextracts at doses of 500, 1000 and 2000 mg · kg−1 of body weight.The extracts were characterized by LC-MS, and the constituentswere isolated and identified by chromatographic analysis ofspectroscopic data.

Of the 28 extracts, the methanol extract obtained from the leavesofAnnona sylvatica showed anti-mycobacterial activity with anminimal inhibitory concentration (MIC) of 184.33μg/mL, and theethyl acetate fraction (EAF) resulting from liquid-liquidpartitioning of the A. sylvaticaextract showed an MIC of115.2μg/mL. The characterization of this extract by LC-MSidentified flavonoids and acetogenins as its main constituents.The phytochemical study of theA. sylvaticaEAF resulted in theisolation of quercetin, luteolin, and almunequin.

Among the compounds isolated from the EAF, luteolin andalmunequin were the most promising, with MICs of 236.8μg/mL(827.28μM) and 209.9μg/mL (328.48μM), respectively. The acuteadministration of the EAF fraction in doses of 500, 1000, and2000 mg · kg−1 of body weight did not cause signs of toxicity inthe treated animals.

60

Keywords:Mycobacterium tuberculosis, Annona sylvatica, Resazurin reduction toxicity, Luteolin, Almunequin

BMC Complementary and Alternative Medicine 2014, 14:209http://www.biomedcentral.com/1472-6882/14/209

MYCOBACTERIUM TUBERCULOSIS

QW 125.5.M9

Acid suppressive agents and risk of Mycobacterium Tuberculosis: case–control study/ Wen-Hung Hsu…[et al.].—Taiwan :BMC Gastroenterology, 2014. 7 hlm.

Acid suppressive agents and risk of Mycobacterium Tuberculosis: case–control study

Wen-Hung Hsu, Chao-Hung Kuo, Sophie SW Wang, Chien-Yu Lu, Chung-Jung Liu, Seng-Kee Chuah,Fu-Chen Kuo, Yen-Hsu Chen, Yaw-Bin Huang, Ming-Feng Hou, Deng-Chyang Wu and Huang-Ming Hu

ABSTRACT

The acid-suppressive agents have been linked with an increasedrisk of infectious disease. The relationship between these drugsandMycobacterium Tuberculosis(TB) was not been reported.

We conducted a case–control study using data from National HealthInsurance research database of Taiwan.From 1996 till 2008, and6541 cases were defined as TB infection/activation (ICD-9 codingplus prescription two of four first-line anti-TB regimen for atleast one month). Control subjects who were matched to the TBcases by age and sex were selected with 10:1 ratio. Medicalrecords including acid-suppressive agent prescription andcomorbidity, and socioeconomic status were analyzed.

TB infection/activation was more frequent to comorbidity withchronic diseases, alcohol abuse,

61


malignancy, immune deficient/suppression status and acid-relateddisease (peptic ulcer, reflux esophagitis).Among the TB cases,there was higher exposure record to acid-suppressive agentswithin 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90(1.68-2.14) for proton pump inhibitor (PPI) and histamine 2receptorantagonist (H2RA) respectively). After adjustingconfounding factors, PPIs prescription 3 months before TB indexdate had an association of TB infection/activation (adjusted OR1.63(1.61-1.63)). Similar result was found in H2RA user (adjustedOR 1.51(1.50-1.52)). The association of acid-suppressive agentsin TB infection/activation was fade gradually when the drugprescription period extended.

Recent prescription of acid-suppressive agent seems to associatethe TB infection/activation. In the society where TB wasprevalent, evaluation of pulmonary TB before prescription of PPIor H2RA is warranted.

Keyword:Proton pump inhibitor, Histamine2-receptor antagonist,Mycobacterium Tuberculosis, National health insurance database, Taiwan

BMC Gastroenterology 2014, 14:91http://www.biomedcentral.com/1471-230X/14/91

33. NECROSIS

QZ 180

Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages/ Patricia A Assis…[et al.].—Brazil : BMC Microbiology, 2014, 10 hlm.

Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages

62

http://www.biomedcentral.com/1471-230X/14/91

Patricia A Assis, Milena S Espíndola, Francisco WG Paula-Silva, Wendy M Rios,Priscilla AT Pereira, Sylvia C Leão,Célio L Silva and Lúcia H Faccioli

ABSTRACT

Phospholipases C (PLCs) are virulence factors found in severalbacteria. In Mycobacterium tuberculosis (Mtb) they exhibitcytotoxic effects on macrophages, but the mechanisms involved inPLC-induced cell death are not fully understood. It has beenreported that induction of cell necrosis by virulent Mtb iscoordinated by subversion of PGE2, an essential factor in cellmembrane protection.

Using two Mtb clinical isolates carrying genetic variations inPLC genes, we show that the isolate 97-1505, which bears plcA andplcB genes, is more resistant to alveolar macrophage microbicidalactivity than the isolate 97-1200, which has all PLC genesdeleted. The isolate 97-1505 also induced higher rates ofalveolar macrophage necrosis, and likewise inhibited COX-2expression and PGE2 production. To address the direct effect ofmycobacterial PLC on cell necrosis and PGE2 inhibition, bothisolates were treated with PLC inhibitors prior to macrophageinfection. Interestingly, inhibition of PLCs affected the abilityof the isolate 97-1505 to induce necrosis, leading to cell deathrates similar to those induced by the isolate 97-1200. Finally,PGE2 production by Mtb 97-1505-infected macrophages was restoredto levels similar to those produced by 97-1200-infected cells.

Mycobacterium tuberculosis bearing PLCs genes induces alveolarmacrophage necrosis, which is associated to subversion of PGE2production.

Keywords: Mycobacterium, Lipid mediator, Phospholipase C, Cell death, Macrophage necrosis, Prostaglandins


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34. OUTCOMES ASSESSMENT

W 84.4

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012/ Hongjo Choi…[et al.].—Republic of Korea : BMC Infectious Diseases, 2014. 12 hlm.

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012

Hongjo Choi, Myungsun Lee, Ray Y Chen, Youngran Kim, Soyoung Yoon,Joon SungJoh,Seung Kyu Park,Lori E Dodd, Jongseok Lee, Taeksun Song, Ying Cai, Lisa C Goldfeder, Laura E Via,Matthew W Carroll,Clifton E Barry and Sang-Nae Cho

ABSTRACT

Tuberculosis remains an important health concern in manycountries. The aim of this study was to identify predictors ofunfavorable outcomes at the end of treatment (EOT) and at the endof study (EOS; 40 months after EOT) in South Korea.

New or previously treated tuberculosis patients were recruitedinto a prospective observational cohort study at two hospitals inSouth Korea. To identify predictors of unfavorable outcomes atEOT and EOS, logistic regression analysis was performed.

The proportion of multidrug-resistant tuberculosis (MDR-TB) was8.2% in new cases and 57.9% in previously treated cases. Of newcases, 68.6% were cured, as were 40.7% of previously treatedcases. At EOT, diabetes, ≥3 previous TB episodes, ≥1 significantregimen change, and MDR-TB were significantly associated withtreatment failure or death. At EOS, age ≥35, body-mass index

64

(BMI) <18.5, diabetes, and MDR-TB were significantly associatedwith treatment failure, death, or relapse. Among cases that werecured at EOT, age ≥50 and a BMI <18.5 were associated withsubsequent death or relapse during follow-up to EOS. Treatmentinterruption was associated with service sector employees orlaborers, bilateral lesions on chest X-ray, and previoustreatment failure or treatment interruption history.

Risk factors for poor treatment outcomes at EOT and EOS includeboth patient factors (diabetes status, age, BMI) and diseasefactors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetesmellitus and MDR-TB were risk factors for poor treatment outcomesand relapse. Measures to help ensure that the first tuberculosistreatment episode is also the last one may improve treatmentoutcomes. Trial registration: ClinicalTrials.gov ID: NCT00341601registered on June 19, 2006

Keywords: Multidrug-resistant tuberculosis, Tuberculosis,Diabetes, Unfavorable outcome, Long-term follow up,South Korea


OUTCOMES ASSESSMENT

W 84.4

Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang,Malaysia/ Muhammad Atif…[et al.].—Pakistan : BMC Infectious Diseases, 2014. 8 hlm.

Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang,Malaysia

Muhammad Atif, Syed Azhar Syed Sulaiman, Asrul Akmal Shafie, Irfhan Ali,Muhammad Asif and Zaheer-Ud-Din Babar

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ABSTRACT

According to the World Health Organization’s recent report, inMalaysia, tuberculosis (TB) treatment success rate for new smearpositive pulmonary tuberculosis (PTB) patients is still below theglobal success target of 85%. In this study, we evaluated TBtreatment outcome among new smear positive PTB patients, andidentified the predictors of unsuccessful treatment outcome andlonger duration of treatment (i.e., > 6 months).

The population in this study consisted of all new smear positivePTB patients who were diagnosed at the chest clinic of PenangGeneral Hospital between March 2010 and February 2011. During thestudy period, a standardized data collection form was used toobtain socio-demographic, clinical and treatment related data ofthe patients from their medical charts and TB notification forms(Tuberculosis Information System; TBIS). These data sources werereviewed at the time of the diagnosis of the patients and then atthe subsequent follow-up visits until their final treatmentoutcomes were available. The treatment outcomes of the patientswere reported in line with six outcome categories recommended byWorld Health Organization. Multiple logistic regression analysiswas used to find the independent risk factors for unsuccessfultreatment outcome and longer treatment duration. Data wereanalyzed using the PASW (Predictive Analysis SoftWare, version19.0. Armonk, NY: IBM Corp).

Among the 336 PTB patients (236 male and 100 female) notifiedduring the study period, the treatment success rate was 67.26% (n= 226). Out of 110 patients in unsuccessful outcome category, 30defaulted from the treatment, 59 died and 21 were transferred toother health care facilities. The mean duration of TB treatmentwas 8.19 (SD 1.65) months. In multiple logistic regressionanalysis, risk factors for unsuccessful treatment outcome wereforeign nationality, male gender and being illiterate. Similarly,risk factors for mortality due to TB includedhigh-grade sputumand presence of lung cavities at the start of treatment, being

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alcoholic and elderly. Likewise, concurrent diabetes, presence oflung cavities at the start of the treatment and being a smokerwere the significant predictors of longer treatment duration.

Our findings indicated that the treatment success rate among thenew smear positive PTB patients was less than the success targetset by World Health Organization. The proportion of patients inthe successful outcome category may be increased by closelymonitoring the treatment progress of the patients withaforementioned high risk characteristics. Similarly, moreaggressive follow-up of the treatment defaulters and transferredout patients could also improve the TB treatment success rate.

Keywords: Smear positive , Treatment outcomes, outcome,Tuberculosis treatment duration,


35. PEPTIDE FRAGMENTS

WK 185

A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response/ Sachin Kumar Samuchiwal…[et al.].—India : BMC Infectious Diseases, 2014. 11 hlm.

A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response

Sachin Kumar Samuchiwal, Sultan Tousif, Dhiraj Kumar Singh, Arun Kumar,Anamika Ghosh, Kuhulika Bhalla,Prem Prakash, Sushil Kumar, Maitree Bhattacharyya, Prashini Moodley, Gobardhan Das and Anand Ranganathan

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ABSTRACT

Tuberculosis (TB) is one of the most prevalent infectiousdiseases affecting millions worldwide. The currently availableanti-TB drugs and vaccines have proved insufficient to containthis scourge, necessitating an urgent need for identification ofnovel drug targets and therapeutic strategies. The disruption ofcrucial protein-protein interactions, especially those that areresponsible for virulence in Mycobacterium tuberculosis – forexample the ESAT-6:CFP10 complex – are a worthy pursuit in this direction.

We therefore sought to improvise a method to attenuate M.tuberculosis while retaining the latter’s antigenic properties.We screened peptide libraries for potent ESAT-6 binders capableof dissociating CFP10 from ESAT-6. We assessed the disruption bya peptide named HCL2, of the ESAT-6:CFP10 complex and studied itseffects on mycobacterialsurvival and virulence.

We found that HCL2, derived from the human cytochrome c oxidasesubunit 3 (COX3) protein, disrupts ESAT-6: CFP10 complex, bindsESAT-6 potently, disintegrates bacterial cell wall and inhibitsextracellular as well as intracellular mycobacterial growth. Inaddition, an HCL2 expressing M. tuberculosis strain induces bothTh1 and Th17 host protective responses.

Disruption of ESAT-6:CFP10 association could, therefore, be analternate method for attenuating M. tuberculosis, and a possibleroute towards future vaccine generation.

Keywords: Tuberculosis, Human COX3, ESAT-6, CFP10, Protein-protein interactions, Th1, Th17


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36. PEPTIDOGLYCAN

QU 136

Mycobacterium tuberculosis Rv1096 protein: gene cloning,protein expression, and peptidoglycan deacetylase activity/Shufeng Yang…[et al.].—Republic of China : BMC Microbiology,2014. 9 hlm.

Mycobacterium tuberculosis Rv1096 protein: gene cloning, protein expression, andpeptidoglycan deacetylase activity

Shufeng Yang, Fei Zhang, Jian Kang, Wenli Zhang, Guoying Deng Yi Xin and Yufang Ma

ABSTRACT

Many bacteria modulate and evade the immune defenses of theirhosts through peptidoglycan (PG) deacetylation. The PGdeacetylases from Streptococcus pneumonia, Listeria monocytogenesand Lactococcus lactis have been characterized. However, thusfar, the PG deacetylase of Mycobacterium tuberculosis has notbeen identified.

In this study, we cloned the Rv1096 gene from the M. tuberculosisH37Rv strain and expressed Rv1096 protein in both Escherichiacoli and M. smegmatis. The results showed that the purifiedRv1096 protein possessed metallo-dependent PG deacetylaseactivity, which increased in the presence of Co2+. The kineticparameters of the PG deacetylase towards M. smegmatis PG as asubstrate were as follows: Km, 0.910 ± 0.007 mM; Vmax, 0.514 ±0.038 μMmin−1; and Kcat = 0.099 ± 0.007 (S−1). Additionally, theviability of M. smegmatis in the presence of over-expressedRv1096 protein was 109-fold higher than that of wild-type M.smegmatis after lysozyme treatment. Additionally, lightmicroscopy and scanning electron microscopy showed that in thepresence of over-expressed Rv1096 protein, M. smegmatis kept its

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regular shape, with an undamaged cell wall and smooth surface.These results indicate thatRv1096 caused deacetylation of cell wall PG, leading to lysozymeresistance in M. smegmatis.

We have determined that M. tuberculosis Rv1096 is a PGdeacetylase. The PG deacetylase activity of Rv1096 contributed tolysozyme resistance in M. smegmatis. Our findings suggest thatdeacetylation of cell wall PG may be involved in evasion of hostimmune defenses by M. tuberculosis.

Keywords: Mycobacterium tuberculosis, Cell wall, Rv1096,Peptidoglycan deacetylase, Lysozyme


37. POLYPROTEINS

WH 400 IgG, IgM and IgA antibodies against the novel polyprotein in active tuberculosis/ Xiaoyan Feng…[et al.].—Republic of China : BMC Infectious Diseases, 2014. 9 hlm.

42)IgG, IgM and IgA antibodies against the novel polyprotein in active tuberculosis

Xiaoyan Feng, Xiqin Yang, Bingshui Xiu, Shuang Qie, Zhenhua Dai, Kun Chen, Ping Zhao, Li Zhang,Russell A Nicholson, Guohua Wang, Xiaoguo Song and Heqiu Zhang

ABSTRACT

Background: The present study was aimed to evaluate whether IgG,IgM and IgA antibodies levels detected against a novelMycobacterium tuberculosis polyprotein 38 F-64 F (with 38 F beingthe abbreviation for 38kD-ESAT6-CFP10 and 64 F for Mtb8.4-MPT64-

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TB16.3-Mtb8) are suitable for diagnosing active tuberculosis, andfor monitoring the efficacy of chemotherapy on TB patients.Methods: In this study, a total of 371 active TB patients withouttreatment were selected and categorized into S+/C+ group (n =143), S-/C+ group (n = 106) or S-/C- group (n = 122). A series ofserum samples were collected from 82 active TB patients who hadundergone anti-TB chemotherapy for 0–6 months at one monthinterval. Humoral responses (IgG, IgM and IgA) were determinedfor the novel Mycobacterium tuberculosis polyprotein usingindirectELISA methods in all of serum samples.Results: For S+/C+, S-/C+ and S-/C- active tuberculosis patientsbefore anti-TB chemotherapy, the sensitivities of tests based onIgG were 65.7%, 46.2% and 52.5% respectively; the sensitivitiesbased on IgM were 21.7%, 24.5% and 18.9%; and the sensitivitiesbased on IgA were 25.2%, 17.9% and 23.8%. By combination of threeisotypes, for all active tuberculosis patients, the testsensitivity increased to 70.4% with the specificity being 91.5%.After anti-TB chemotherapy, there were no significant differencesbetween groups with different courses of anti-TB chemotherapy.Conclusions: The novel Mycobacterium tuberculosis polyprotein 38F-64 F represents potential antigen suitable for measuring IgG,IgM and IgA antibodies. However, the serodiagnostic test based onthe 38 F-64 F polyprotein appears unsuitable for monitoring theefficacy of chemotherapy.

Keyword: Tuberculosis, Serodiagnosis, Polyprotein


38. QUALITATIVE RESEARCH

W 20.5 Assessing the impact of multidrug-resistant tuberculosis in children: an exploratory qualitative study/ Caroline Franck…[et al.].—English United Kingdom : BMC Infectious Diseases, 2014. 10 hlm.

71


Assessing the impact of multidrug-resistant tuberculosis in children: an exploratory qualitative study

Caroline Franck, James A Seddon, Anneke C Hesseling, H Simon Schaaf, Donald Skinner and Lucy Reynolds

ABSTRACT

While the prevalence of multidrug-resistant (MDR) tuberculosis (TB) is high among children in the Western Cape of South Africa, the psychosocial implications of treatment for children with MDR-TB remain poorly understood. We sought to explore how MDR-TB and its treatment impact children on an individual, familial, and social level.

Semi-structured interviews were conducted with 20 children and caregivers purposively sampled from a prospective clinical cohortof children. The sample was stratified by age at the start of treatment (children >10 years, and 5-10 years). Caregiver proxy interviews were conducted with younger children, supplemented with child interviews; older children were interviewed directly, supplemented with caregiver proxy interviews. Data were analysed usinggrounded theory.

Findings revealed pill volume and adverse effects produced significant physical, psychological and academic disturbances in children. Adverse effects related to the medication were important obstacles to treatment adherence. While there appear tobe no long-lasting effects in younger children, a few older children showed evidence of persisting internalised stigma. Caregivers suffered important treatment-related financial and psychological costs. Community support, notably through the continued involvement of children in strong social networks, promoted resilience among children and their families.We found that the current treatment regimen for childhood MDR-TB has significant psychological, academic, and financial impacts on

72

children and their families. There is a need for psychosocial support of children and caregivers to mitigate the negative effects of community stigma, and to manage the stressors associated with chronic illness.

Keywords: South Africa, Childhood MDR-TB, Psychosocial impact, Qualitative research


39. RISK

WA 900

Smear positive pulmonary tuberculosis and its risk factors among tuberculosis suspect in South East Ethiopia; a hospital based cross sectional study/ Begna Tulu…[et al.].—Ethiopia : BMC Research Notes, 2014. 6 hlm.

Smear positive pulmonary tuberculosis and its risk factors among tuberculosis suspect in South East Ethiopia; a hospital based cross sectional study

Begna Tulu, Nagasa Dida, Yibeltal Kassa and Biruhalem Taye

ABSTRACT

Tuberculosis remains a deadly infectious disease, affectingmillions of people worldwide. Ethiopia ranks seventh among thetwenty two high tuberculosis burden countries. The aim of thisstudy was to determine the prevalence of smear positive pulmonarytuberculosis and its associated risk factors in Goba and Robehospitals of Bale zone.

A cross-sectional study was conducted on tuberculosis suspectedpatients from February-May 2012. Sputum samples were examined foracid fast bacilli using Ziehl-Neelsen staining and interview was

73


conducted for each patient. Descriptive statistics, binarylogistic and multivariable logistic regression analyses wereemployed to identify factors associated with pulmonarytuberculosis infection.

The prevalence of smear positive tuberculosis was 9.2%. Age >36(AOR = 3.54, 95% CI = 1. 3–9.82), marital status (AOR = 8.40, 95%CI = 3.02-23.20), family size (AOR = 4. 10, 95% CI = 1.60-10.80),contact with active tuberculosis patient (AOR = 5. 90; 95% CI =2. 30–15.30), smoking cigarette regularly (AOR = 3. 90; 95% CI =1.20–12.40), and human immunodeficiency virus sero-status (AOR =11. 70; 95% CI = 4. 30–31.70) were significantly associated withsmear positive pulmonary tuberculosis.

The prevalence of smear positive pulmonary tuberculosis was highin the study area. Age, marital status, family size, history ofcontact with active tuberculosis patient, smoking cigarettes, andHIV sero-status were among the risk factors significantlyassociated with acquiring tuberculosis. Hence, strict pulmonarytuberculosis screening of HIV patients and intensification ofhealth education to avoid risk factors identified arerecommended.

Keywords: Smear positive PTB, Prevalence, Risk factors

BMC Research Notes 2014, 7:285http://www.biomedcentral.com/1756-0500/7/285

40. SKIN TEST

QY 260

Agreement between QuantiFERON®-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts/ Lilly M Verhagen…[et al.].—Venezuela : BMC Infectious Diseases, 2014. 13 hlm.

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Agreement between QuantiFERON®-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts

Lilly M Verhagen, Mailis Maes, Julian A Villalba, Adriana d’Alessandro, Lazaro Perez Rodriguez,Mercedes F España, Peter WM Hermans and Jacobus H de Waard

ABSTRACT

Interferon-gamma release assays have emerged as a more specificalternative to the tuberculin skin test (TST) for detection oftuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people.We determined the prevalence ofMycobacterium tuberculosis infection by TST and QuantiFERON®-TBGold In-Tube (QFT-GIT) and assessed agreement between the twotest methods and factors associated with positivity in eithertest in Warao Amerindian children in Venezuela. Furthermore,progression to active TB disease was evaluated for up to 12months.

163 HIV-negative childhood household contacts under 16 years ofage were enrolled for TST, QFT-GIT and chest X-ray (CXR). Follow-up was performed at six and 12 months. Factors associated withTST and QFT-GIT positivity were studied using generalizedestimation equations logistic regression models.

At baseline, the proportion of TST positive children was similarto the proportion of children with a positive QFT-GIT (47% vs.42%, p = 0.12). Overall concordance between QFT-GIT and TST wassubstantial (kappa 0.76, 95% CI 0.46-1.06). Previous BCGvaccination was not associated with significantly increasedpositivity in either test (OR 0.68,95% CI 0.32-1.5 for TST and OR0.51, 95% CI 0.14-1.9 for QFT-GIT). Eleven children werediagnosed with active TB at baseline. QFT-GIT had a highersensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95%CI 24-83%) while specificities were similar (respectively 58% and

75

55%). Five initially asymptomatic childhood contacts progressedto active TB disease during follow-up.

Replacement of TST by the QFT-GIT for detection of M.tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantialconcordance and TST positivity was not affected by previous BCGvaccination. The QFT-GIT had a higher sensitivity than the TSTfor the detection of TB disease. However, the value of the QFT-GIT as an adjunct in diagnosing TB disease is limited by a highvariability in QFT-GIT results over time.

Keywords: Tuberculosis, Indigenous children, Diagnostics, Child tuberculosis contacts


SKIN TEST

QY 260

Post-exposure rate of tuberculosis infection among health care workers measured with tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital/ Alba Muzzi…[et al.].—Italy : BMC Infectious Diseases, 2014. 7 hlm.

Post-exposure rate of tuberculosis infection among health care workers measuredwith tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital

Alba Muzzi, Elena Seminari, Tiziana Feletti, Luigia Scudeller, Piero Marone, Carmine Tinelli, Lorenzo Minoli, Carlo Marena, Patrizia Mangiarotti and Maurizio Strosselli

ABSTRACT

76


This study assesses the risk of LTBI at our Hospital among HCWswho have been exposed to TB patients with a delayed diagnosis andrespiratory protection measures were not implemented.

All HCWs exposed to a patient with cultural confirmed pulmonaryTB and respiratory protection measures were not implemented wereincluded. Data on TST results performed in the past (defined asT0) were recorded. TST was performed twice: first, immediatelyafter exposure to an index patient (T1) and three months later(T2). The period of time between T0 and T1 was used to calculatehe annual rate of tuberculosis infection (ARTI), while le periodof time between T1 and T2 was used to calculate the post exposureannual rate of tuberculosis infection (PEARTI).Fourteen index patients were admitted; sputum smear was positivein 7 (58.3%), 4 (28.6%) were non-Italian born patients. 388 HCWswere exposed to index patients, a median of 27 (12-39) HCW pereach index patient. One hundred eighty (46.4%) HCWs received BCGin the past. One hundred twenty two HCWs (31%) were TST positiveat a previous routine screening and not evaluated in this subset.Among the remaining 255 HCWs with negative TST test in the past,TST at T1 was positive in 11 (4.3%). ARTI was 1.6 (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, thatwere TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100PY. At univariate analysis, older age was associated with postexposure latent tuberculosis infection (HR 1.12; 95% CI 1.03-1.22, p=0.01).

PEARTI was considerably higher among HCWs exposed to indexpatients than ARTI. These data underscore the overwhelmingimportance of performing a rapid diagnosis, as well asimplementing adequate respiratory protection measures when TB issuspected.

Keywords: Tuberculosis, Occupational TB, Infection control


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41. THERAPEUTIC

WT 166

Intuitive weights of harm for therapeutic decision making insmear-negative pulmonary Tuberculosis: an interview study of physicians in India, Pakistan and Bangladesh/ Chandrashekhar T Sreeramareddy…[et al.].—Malaysia : BMC Medical Informatics and Decision Making, 2014. 9 hlm.

Intuitive weights of harm for therapeutic decision making in smear-negative pulmonary Tuberculosis: an interview study of physicians in India, Pakistan and Bangladesh

Chandrashekhar T Sreeramareddy, Mahbubur Rahman, HN Harsha Kumar,Mohsin Shah,Ahmed Manadir Hossain, Md Abu Sayem, Juan M Moreira and Jef Van den Ende

ABSTRACT

To estimate the amount of regret and weights of harm by omissionand commission during therapeutic decisions for smear-negativepulmonary Tuberculosis.

An interviewer-administered survey was done among youngphysicians in India, Pakistan and Bangladesh with a previouslyused questionnaire. The physicians were asked to estimateprobabilities of morbidity and mortality related with disease andtreatment and intuitive weights of omission and commission fortreatment of suspected pulmonary Tuberculosis. A comparison withweights based on literature data was made.

A total of 242 physicians completed the interview. Their mean agewas 28 years, 158 (65.3%) were males. Median probability (%) ofmortality and morbidity of disease was estimated at 65% (interquartile range [IQR] 50-75) and 20% (IQR 8-30) respectively.Median probability of morbidity and mortality in case of

78

occurrence of side effects was 15% (IQR 10-30) and 8% (IQR 5-20)respectively. Probability of absolute treatment mortality was0.7% which was nearly eight times higher than 0.09% reported inthe literature data. The omission vs. commission harm ratiosbased on intuitive weights, weights calculated with literaturedata, weights calculated with intuitive estimates of determinantsadjusted without and with regret were 3.0 (1.4-5.0), 16 (11-26),33 (11-98) and 48 (11-132) respectively. Thresholds based on pureregret and hybrid model (clinicians’ intuitive estimates andregret) were 25 (16.7-41.7), and 2(0.75-7.5) respectively bututility-based thresholds for clinicians’ estimates and literaturedata were 2.9 (1-8.3) and 5.9 (3.7-7.7) respectively.

Intuitive weight of harm related to false-negatives was estimatedhigher than that to false-positives. The mortality related totreatment was eightfold overestimated. Adjusting expected utilitythresholds for subjective regret had little effect.

Keywords: Tuberculosis, Treatment morbidity and mortality,Medical decision making, South Asia

BMC Medical Informatics and Decision Making 2014, 14:67http://www.biomedcentral.com/1472-6947/14/67

42. TOMOGRAPHY

WG 141.5.T6

Comparative chest computed tomography findings of non-tuberculous mycobacterial lung diseases and pulmonary tuberculosis in patients with acid fast bacilli smear-positive sputum/ Mei-Kang Yuan…[et al.].—Taiwan : BMC Pulmonary Medicine, 2014. 6 hlm.

Comparative chest computed tomography findings of non-tuberculous mycobacterial lung diseases and pulmonary tuberculosis in patients with acid fastbacilli smear-positive sputum

79


Mei-Kang Yuan, Cheng-Yu Chang, Ping-Huang Tsai, Yuan-Ming Lee, Jen-Wu Huang and Shih-Chieh Chang

ABSTRACT

Early diagnosis and treatment of nontuberculous mycobacteriallung diseases (NTM-LD) and pulmonary tuberculosis (PTB) areimportant clinical issues. The present study aimed to compare andidentify the chest CT characteristics that help to distinguishNTM lung disease from PTB in patients with acid-fast bacilli(AFB) smear-positive sputum.

From January 2009 to April 2012, we received 467 AFB smear-positive sputum specimens. A total of 95 CT scans obtained fromthe 159 patients were analyzed, 75 scans were from patients withPTB and 20 scans from NTM-LD. The typical chest CT findings ofmycobacterial diseases were analyzed.In patients with PTB, the prevalence of pleural effusion (38.7%vs. 15.0%; P =0.047), nodules < 10 mm in size (76.0% vs. 25.0%; P< 0.001), tree-in-bud pattern (81.3% vs. 55.0%; P =0.021), andcavities (31.1% vs. 5.0%; P =0.018) were significantly higherthan patients with NTM. Of the 20 patients with NTM lungdiseases, bronchiectasis and cystic changes weresignificantlyhigher than patients with PTB (20.0% vs. 4.0%; P = 0.034). Inmultivariate analysis, CT scan findings of nodules wasindependently associated with patients with diagnoses of PTB(odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02-0.30).Presence of bronchiectasis and cystic changes in CT scans wasstrongly associated with patients with NTM-LD (OR, 33.04; 95% CI,3.01-362.55).

The CT distinction between NTM-LD and PTB may help radiologistsand physicians to know the most likely diagnoses in AFB-smearpositive patients and avoid unnecessary adverse effects and therelated costs of anti-TB drugs in endemic areas.

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Keywords: Nontuberculous mycobacterial lung disease, Pulmonary tuberculosis, Acid-fast bacilli smear, Bronchiectasis and cystic changes

BMC Pulmonary Medicine 2014, 14:65http://www.biomedcentral.com/1471-2466/14/65

43. TRANSMISSION

WC 503.3

Interpreting measures of tuberculosis transmission: a case study on the Portuguese population/ Joao Sollari Lopes…[et al.].—Portugal : BMC Infectious Diseases, 2014. 9 hlm.

Interpreting measures of tuberculosis transmission: a case study on the Portuguese population

Joao Sollari Lopes, Paula Rodrigues, Suani TR Pinho, Roberto FS Andrade, Raquel Duarte and M Gabriela M Gomes

ABSTRACT

Tuberculosis remains a high burden for Human society despiteconsiderable investments in its control. Unique features in thehistory of infection and transmission dynamics of tuberculosispose serious limitations on the direct interpretation ofsurveillance data and call for models that incorporate latentprocesses and simulate specific interventions.

A transmission model was adjusted to the dataset of activetuberculosis cases reported in Portugal between 2002 and 2009. Weestimated key transmission parameters from the data (i.e. time todiagnosis, treatment length, default proportion, proportion ofpulmonary TB cases). Using the adjusted model to the Portuguesecase, we estimated the total burden of tuberculosis in Portugal.We further performed sensitivity analysis to heterogeneities insusceptibility to infection and exposure intensity.

81


We calculated a mean time to diagnose of 2.81 months andtreatment length of 8.80 months in Portugal.The proportiondefaulting treatment was calculated as 0.04 and the proportion ofpulmonary cases as 0.75. Using these values, we estimated a TBburden of 1.6 million infected persons, corresponding to morethan 15% of the Portuguese population. We further described thesensitivity of these estimates to heterogeneity.

We showed that the model reproduces well the observed dynamics ofthe Portuguese data, thus demonstrating its adequacy for devisingcontrol strategies for TB and predicting the effects ofinterventions.

Keywords: Heterogeneity, Sojourn times, Transmission dynamics, Tuberculosis epidemiology


44. TRENDS

WB 293

Trends in TB case notification over fifteen years: the casenotification of 25 Districts of Arsi Zone of Oromia Regional State, Central Ethiopia/ Shallo Daba Hamusse, Meaza Demissie, Bernt Lindtjørn.—Ethiopia : BMC Public Health, 2014. 10 hlm

Trends in TB case notification over fifteen years: the case notification of 25 Districts of Arsi Zone of Oromia Regional State, Central Ethiopia

Shallo Daba Hamusse, Meaza Demissie and Bernt Lindtjørn

ABSTRACT

82


The aims of tuberculosis (TB) control programme are to detect TB cases and treat them to disrupt transmission, decrease mortality and avert the emergence of drug resistance. In 1992, DOTS strategy was started in Arsi zone and since 1997 it has been fully implemented. However, its impact has not been assessed. Theaim of this study was, to analyze the trends in TB case notification and make a comparison among the 25 districts of the zone.

A total of 41,965 TB patients registered for treatment in the study area between 1997 and 2011 were included in the study. Dataon demographic characteristics, treatment unit, year of treatmentand disease category were collected for each patient from the TB Unit Registers.

The trends in all forms of TB and smear positive pulmonary TB (PTB+) case notification increased from 14.3 to 150 per 100,000 population, with an increment of 90.4% in fifteen years. Similarly, PTB+ case notification increased from 6.9 to 63 per 100,000 population, an increment of 89% in fifteen years. The fifteen-year average TB case notification of all forms varied from 60.2 to 636 (95% CI: 97 to 127, P<0.001) and PTB+ from 10.9 to 163 per100,000 population (95% CI: 39 to 71, p<0.001) in the 25 districts of the zone. Rural residence (AOR, 0.23; 95% CI: 0.21 to 0.26) and districts with population ratio to DOTS sites of more than 25,000 population (AOR, 0.40; 95% CI: 0.35 to 0.46) were associated with low TB case notification. TB case notifications were significantly more common among 15-24 years ofage (AOR, 1.19; 95% CI:1.03 to 1.38), PTB- (AOR, 1.46; 95% CI: 1.33 to 64) and EPTB (AOR, 1.49; 95% CI; 1.33 to 1.60) TB cases.

The introduction and expansion of DOTS in Arsi zone has improved the overall TB case notification. However, there is inequality inTB case notification across 25 districts of the zone. Further research is, recommended on the prevalence, incidence of TB and TB treatment outcome to see the differences in TB distribution

83

and performance of DOTS in treatment outcomes among the districts.

Keywords: TB, Trends, Case notification, Arsizone, Ethiopia


45. TUBERCULOSIS, BOVINE

SF 967.T8

Evaluation of ethanol vortex ELISA for detection of bovine tuberculosis in cattle and deer/ Ashutosh Wadhwa…[et al.].—UnitedStates of America : BMC Veterinary Research, 2014. 6 hlm.

Evaluation of ethanol vortex ELISA for detection of bovine tuberculosis in cattle and deer

Ashutosh Wadhwa, Rachel E Johonson, Keiko Eda, W Ray Waters, Mitchell V Palmer, John P Bannantine and Shigetoshi Eda

ABSTRACT

BThe use of serological assays for diagnosis of bovinetuberculosis (TB) has been intensively studied and use ofspecific antigens have aided in improving the diagnostic accuracyof the assays. In the present study, we report an in-house enzymelinked immunosorbent assay (ELISA), developed by using ethanolextract of Mycobacterium bovis (M. bovis). The assay, named(ethanol vortex ELISA [EVELISA]), was evaluated for detection ofanti- M. bovis antibodies in the sera of cattle and white-taileddeer.

By using the EVELISA, we tested sera obtained from two species ofanimals; cattle (n = 62 [uninfected, n = 40; naturally infected,n = 22]) and white-tailed deer (n = 41 [uninfected, n = 25;

84


naturally infected, n = 7; experimentally infected, n = 9]). Todetect species specific molecules, components in the ethanolextract were analyzed by thin layer chromatography and westernblotting.

Among the tested animals, 77.2% of infected cattle and 87.5% ofinfected deer tested positive for anti- M. bovis antibody. Therewere only minor false positive reactions (7.5% in cattle and 0%in deer) in uninfected animals. M. bovis -specific lipids andprotein (MPB83) in the ethanol extract were detected by thinlayer chromatography and western blotting, respectively.

The results warrant further evaluation and validation of EVELISAfor bovine TB diagnosis of traditional and alternative livestockas well as for free-ranging animal species.

Keywords: Bovine tuberculosis, Cattle, White-tailed deer, ELISA, Mycobacterium bovis, EVELISA

BMC Veterinary Research 2014, 10:147http://www.biomedcentral.com/1746-6148/10/147

46. TUBERCULOSIS, PLEURAL

WF 390

Comparison of same day diagnostic tools including Gene Xpertand unstimulated IFN-γ for the evaluation of pleural tuberculosis: a prospective cohort study/ Richard Meldau…[et al.].—South Africa : BMC Pulmonary Medicine, 2014. 10 hlm.

Comparison of same day diagnostic tools including Gene Xpert and unstimulated IFN-γ for the evaluation of pleural tuberculosis: a prospective cohort study

Richard Meldau, Jonny Peter, Grant Theron, Greg Calligaro, Brian Allwood, Greg Symons, Hoosain Khalfel,Gina Ntombenhle, Ureshnie Govender, Anke Binder, Richard van Zyl-Smit and Keertan Dheda

85


ABSTRACT

The accuracy of currently available same-day diagnostic tools (smear microscopy and conventional nucleic acid amplification tests) for pleural tuberculosis (TB) is sub-optimal. Newer technologies may offer improved detection.

Smear-microscopy, adenosine deaminase (ADA), interferon gamma (IFN-γ), and Xpert MTB/RIF [using an unprocessed (1 ml) and centrifuged (~20 ml) sample] test accuracy was evaluated in pleural fluid from 103 consecutive patients with suspected pleural TB. Culture for M.tuberculosis and/or histopathology (pleural biopsy) served as the reference standard. Patients were followed prospectively to determine their diagnostic categorisation.

Of 93 evaluable participants, 40 had definite-TB (reference positive), 5 probable-TB (not definite but treated for TB) and 48non-TB (culture and histology negative, and not treated for TB). Xpert MTB/RIF sensitivity and specificity (95% CI) was 22.5% (12.4 - 37.6) and 98% (89.2 - 99.7), respectively, and centrifugation did not improve sensitivity (23.7%). The Xpert MTB/RIF internal positive control showed no evidence of inhibition. Biomarker specific sensitivity, specificity, PPV, andNPVs were: ADA (48.85 IU/L; rule-in cut-point) 55.3% (39.8 - 69.9), 95.2% (83.9 - 98.7), 91.4 (73.4 - 95.4), 69.7% (56.7 - 80.1); ADA (30 IU/L; clinically used cut-point) 79% (63.7 - 89), 92.7% (80.6 - 97.5), 91.0 (73.4 - 95.4), 82.7% (69.3 - 90.1); andIFN-γ (107.7 pg/ml; rule-in cut-point) 92.5% (80.2 - 97.5), 95.9%(86.1 - 98.9), 94.9% (83.2 - 98.6), 93.9% (83.5 - 97.9), respectively (IFN-γ sensitivity and NPV better than Xpert [p < 0.05] and rule-in ADA [p < 0.05]).

The usefulness of Xpert MTB/RIF to diagnose pleural TB is limitedby its poor sensitivity. IFN-γ is an excellent rule-in test and, compared to ADA, has significantly better sensitivity and rule-out value in a TB-endemic setting.

86

Keywords: Tuberculosis, Diagnosis, Xpert MTB/RIF, Interferon gamma, Adenosine deaminase, Pleural fluid

BMC Pulmonary Medicine 2014, 14:58http://www.biomedcentral.com/1471-2466/14/58

47. TUBERCULOSIS, PULMONARY

WF 300-360

Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputumsmear positive in pulmonary tuberculosis/ Maria Luiza de Souza-Galvão…[et al.].—Spain : BMC Infectious Diseases, 2014. 9 hlm.

Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputum smear positive in pulmonary tuberculosis

Maria Luiza de Souza-Galvão, Irene Latorre, Neus Altet-Gómez, María Ángeles Jiménez-Fuentes,Celia Milà, Jordi Solsona, Maria Asunción Seminario, Adela Cantos, Juan Ruiz-Manzano and José Domínguez

ABSTRACT

The aim of the study was to assess the correlation between thetuberculin skin test (TST) andin vitro interferon-gamma releasedassays (IGRAs) with risk factors for the spread of infection insmear positive pulmonary tuberculosis (TB) contacts.

We recruited prospective contacts with smear positive pulmonaryTB cases. We looked at human immunodeficiency virus (HIV)infection and other conditions of immunosuppression, presence ofBCG vaccination and the degree of exposure to the index case.Patients underwent the TST, chest radiography, sputum analysiswhen necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB).

87


Presence of cough, diagnostic delay (days between first symptomsand TB diagnostic), contact conditions: room size (square meters)and index of overcrowding (square meters per person) wereinvestigated in the index case.

156 contacts (119 adults, 37 children) of 66 TB patients wereenrolled, 2.4 (1-14) contacts per TB case. The positivity of theTST did not correlate with the risk factors studied: presence ofcough (p = 0.929); delayed diagnosis(p=0.244); room size(p=0.462); overcrowding (p= 0.800). Both QFN-G-IT and T-SPOT.TB,showed significant association with cough (p=0.001, and p= 0.007)and room size (p=0.020, and p= 0.023), respectively.

Both IGRA associated better than TST with certain host-relatedrisk factors involved in the transmission of disease, such as thepresence of cough.

Keywords:Tuberculosis infection, Tuberculin skin test, Interferongamma release assays, IGRA, Overcrowding, Diagnostic delay, Cough


48. VACCINATION

SF 757.2

Inflammatory and myeloid-associated gene expression before and one day after infantvaccination with MVA85A correlates with induction of a T cell response/ Magali Matsumiya…[et al.].—English United Kingdom : BMCInfectious Diseases, 2014. 14 hlm.

Inflammatory and myeloid-associated gene expression before and one day after infantvaccination with MVA85A correlates with induction of a T cell response

88


Magali Matsumiya, Stephanie A Harris, Iman Satti, Lisa Stockdale,Rachel Tanner,Matthew K O’Shea,Michelle Tameris, Hassan Mahomed, Mark Hatherill, Thomas J Scriba, Willem A Hanekom, Helen McShane and Helen A Fletcher

ABSTRACT

Tuberculosis (TB) remains a global health problem, withvaccination likely to be a necessary part of a successful controlstrategy. Results of the first Phase 2b efficacy trial of acandidate vaccine, MVA85A, evaluated in BCG-vaccinated infantswere published last year. Although no improvement in efficacyabove BCG alone was seen, cryopreserved samples from this trialprovide an opportunity to study the immune response tovaccination in this population.We investigated blood samples taken before vaccination (baseline)and one and 28 days post-vaccination with MVA85A or placebo(Candin). The IFN-γ ELISpot assay was performed at baseline andon day 28 to quantify the adaptive response to Ag85A peptides.Gene expression analysis was performed at all three timepoints toidentify early gene signatures predictive of the magnitude of thesubsequent adaptive T cell response using the significanceanalysis of microarrays (SAM) statistical package and gene setenrichment analysis.

One day post-MVA85A, there is an induction of inflammatorypathways compared to placebo samples. Modules associated withmyeloid cells and inflammation pre- and one day post-MVA85Acorrelate with a higher IFN-γ ELISpot response post-vaccination.By contrast, previous work done in UK adults shows earlyinflammation in this population is not associated with a strong Tcell response but that induction of regulatory pathways inverselycorrelates with the magnitude of the T cell response. This may beindicative of important mechanistic differences in how T cellresponses develop in these two populations following vaccinationwith MVA85A.

89

The results suggest the capacity of MVA85A to induce a stronginnate response is key to the initiation of an adaptive immuneresponse in South African infants but induction of regulatorypathways may be more important in UK adults. Understandingdifferences in immune response to vaccination between populationsis likely to be an important aspect of developing successfulvaccines and vaccination strategies.

Keywords: Tuberculosis, Vaccine, Innate immunity,Transcriptomics, MVA85A


INDEX PENGARANG

AAbuaku Benjamin Kwaku 22

Adela Cantos 56Adnan Khosravi 8Adrian Sleigh 30,33

90


Adrian VS Hill 35Adriana d’Alessandro 48Ahmed Manadir Hossain 50Aida Asmelash 6Alba Muzzi 49Alice L den Hertog 17Aline Mara da Silva 24Ali Akbar Velayati 8Alla L Lapidus 20Alex M Clark 34Alexandre Montpetit 37Anand Ranganathan 43Anneke C Hesseling 46Angélica Espinosa Miranda 26Anamika Ghosh 43Anelise SN Formagio 38Anja Schuitema 21Anke Binder 55Anna A Vyazovaya 20

Anne H Henriksen 36Anne-Laure Tchokote W 13Anthony Ogwu 6Arun Kumar 43Ashutosh Wadhwa 54Asrul Akmal Shafie 42Avy Violari 35

BBehnaz Khodabakhshi 7Begna Tulu 47Bernt Lindtjørn 53Bingshui Xiu 45Biruhalem Taye 47

Bongani M Mayosi 5 Bonnie A Thiel 16Brenda Okware 16

91

Brian Allwood 55

CCai-ling Yang 11Candida AL Kassuya 38Carmine Tinelli 49Caroline Franck 46Catherine M Stein 16Carl Morrow 28Carlo Marena 49Célio L Silva 40Celia Milà 56Chandrashekhar T S 50Charles Mitchell 35Charles Nolan 9Chao-Hung Kuo 39Chawangwa Modongo 31Cheng-Yu Chang 51Chien-Yu Lu 39Chin-Hui Yang 25

Chung-Jung Liu 39Christopher Kuaban 13Christophe Sola 21Clifton E Barry 41Connie GM Erkens 15

DDaiyu Hu 23David Harley 30,33Denise Arakaki-Sanchez 26Deng-Chyang Wu 39Dick van Soolingen 21Dhiraj Kumar Singh 43Dmitry S Ischenko 20Donald Skinner 46Dong-fang Yue 11Douglas Shaffer 6

EEddie M Wampande 16Edgar Abadia 21

92

Egor A Shitikov 20Ekaterina N Chernyaeva 20Elena N Ilina 20Elena Seminari 49Elena S Kostryukova 20Elena Y Nosova 20Eli Sagvik 36Elias dos Santos Dias 26Elizabeta Bachiyska 21Elizabeth A Talbot 29Emmanuel Mouafo Tekwu 13Erika Slump 15Ernst T Smienk 17Esmaeil Mortaz 8Ethel Leonor Maciel 26Everton Ferreira Lemos 24Eyal Oren 9Ezekiel Mupere 16

F

Fatemeh Mehravar 7Fei-yan Li 18Fei Zhang 44Fernanda Mattos de Souza 26Fernando R Pavan 39Francine Ntoumi Véronique 13Francisco AR Neves 38Francisco WG Paula-Silva 40Fred Sawe 6Fu-Chen Kuo 39

GGaëlle Guiewi Makafe 13George McSherry 35Gert Folkerts 8Gerard de Vries 15Gérard Lina 5Gina Ntombenhle 55Giovana de Castro 24Gobardhan Das 43

93

Grant Theron 4,55Greg Calligaro 55Greg Symons 55Guo-qiang Wang 11Guohua Wang 45Guoying Deng Yi Xin 44HHamidreza Jamaati 8Harriet Mayanja-Kizza 16Hassan Mahomed 57Heather Blunt 29Helen Fletcher 35,57Helen McShane 35,57Heqiu Zhang 45H Simon Schaaf 46HN Harsha Kumar 50Hong-yan Wang 18Hongzhuan Tan 22Hongjo Choi 41Hoosain Khalfel 55

Huang-Ming Hu 39Hugo Juárez Olguin 27Hung-Yi Chiou 25

IIan M Adcock 8Irfhan Ali 42Igor V Mokrousov 20Iman Satti 57Indra Bergval 21Ingunn Harstad 36Irene Latorre 56Irina Y Karpova 20

JJacobus H de Waard 49Jaya S Tyagi 12James A Seddon 46James C Johnston 14Jen-Wu Huang 51Jean-Claude Tedom 13

94

Jean-Paul Assam Assam 13Jean-Pierre Flandrois 5Jef Van den Ende 50Jessica de Beer 21Jia Cao 23Jia Liu 32 Jian Kang 44Jih-Jin Tsai 25Jin Yan 32Jim Werngren 17Joao Sollari Lopes 52, John Ehiri 23John P Bannantine 54Johan Garssen 8Jonathan G Peter 4Jonathan E Golub 26Jonathan Mayer 9Jongseok Lee 41Jonny Peter 55

Joon SungJoh 41Jordi Solsona 56José Domínguez 56Joyce Wang 37Juan M Moreira 50Juan Ruiz-Manzano 56Judith Currier 6Julian A Villalba 48Julio Croda 24,38Justin R Pritchard 37Ju-xia Niu 11

KKara Wools Kaloustian 6Karen Odato 29Karen R Steingart 29Keertan Dheda 4,55Keiko Eda 54Keren Middelkoop 28Kerri A Viney 30,33

95

Kiki Tuin 21Kohinoor Kaur 12Kuan-Jung Chen 25Kuhulika Bhalla 43Kun Chen 45Kwei-Feng Wang 25

LLarissa Kamgue Sidze 13LaShaunda L 16Lazaro Perez Rodriguez 48Laura E Via 41Lei Wang 18Lilly M Verhagen 48Linda-Gail Bekker 28Lisa C Goldfeder 41Lisa Stockdale 57Lisa V Adams 29Li-hong Pei Hua Zhong 11Li Zhang 45

Lorena Kellen Fernandes S 26Lorenzo Minoli 49Lori E Dodd 41Louis Kreitmann 37Lúcia H Faccioli 40Lucy Reynolds 46Luigia Scudeller 49

MMagali Matsumiya 57Mahbubur Rahman 50Mailis Maes 48Maitree Bhattacharyya 43Maka Akhalaia 21Malabika Sarker 34Marcella Paranhos Rodrigues 24Marcel A Behr 37María Ángeles Jiménez-F 56Maria Asunción Seminario 56Maria EA Stefanello 38

96

Maria Luiza de Souza 56Marina V Shulgina 20Mark F Cotton 35Mark Hatherill 57Markleen Tagaro 30,33Marte Hernández Porras 27Mary Nsereko 16Masahiro Narita 9Matthew K O’Shea 57Matthew W Carroll 41Matthias Frank 13Mauro N Sanchez 26Maurizio Strosselli 49Md Abu Sayem 50Meaza Demissie 53Mei-Kang Yuan 51Mengshi Chen 22Mercedes F España 48Mercedes Macías Parra 27

M Gabriela M Gomes 52Michael D Hughes 6Michelle Tameris 57Michel Drancourt 19Mikhail S Rotkevich 20Milena S Espíndola 40Mitchell V Palmer 54Ming-Feng Hou 39Muhammad Asif 42Muhammad Atif 42Mohamad Reza Masjedi 8Mohamed Sassi 19Mohsin Shah 50Moses L Joloba 16Mpiko Ntsekhe 4Myungsun Lee 41

NNagasa Dida 47Napoleón González Saldaña 27

97

Natália Daiane Garoni 24Namee Lee 28Neetu Kumra Taneja 12Nenad Macesic 31Nestani Tukvadze 21Neus Altet-Gómez 56Nguyen N Linh 30,33Nicola M Zetola 31Ningning Ma 16Nino Bablishvili 21Nino Bzekalava 21Nona Tadumadze 21

OOana Dumitrescu 5Olga A Manicheva 20Olga V Narvskaya 20

PPamela Weiss 14Patricia A Assis 40

Patrizia Mangiarotti 49Paul Kelly 30,33 Paul Klatser 21Paula Rodrigues 52Pavel V Dobrynin 20Payam Tabarsi 8Pedro Gutiérrez Castrellón 27Penelope Johnson 30,33Peter J Barnes 8Peter K Yablonsky 20Peter WM Hermans 48Ping-Huang Tsai 51Ping Zhao 45Piero Marone 49Prashini Moodley 43Prem Prakash 43Priscilla AT Pereira 40

QQingya Wang 23

98

Qifa Ye 32Qiquan Wan 32

RRafaele CP Araujo 38Rachel E Johonson 54Rachel Tanner 57Raquel Duarte 52Ray Y Chen 41Richard Meldau 4,55Richard Anthony 21Richard M Anthony 17Richard van Zyl-Smit 55Robert P Igo Jr 16Robert Salata 6Roberto FS Andrade 52Robin Wood 28Ronald G Collman 31Ronald Ncube 31Rusudan Aspindzelashvili 21

Russell A Nicholson 45

SSachin Kumar Samuchiwal 43Saen Fanai 30,33Sakshi Dhingra 12Sandra Menting 17Sanghuk Shin 31Sang-Nae Cho 41Sara Eyangoh 13Sarah Sengstake 21Sarah Zalwango 16Sean Ekins 34Seng-Kee Chuah 39Serges Tchatchouang 13Serguei A Simonov 20Seung Kyu Park 41Seyed Mohamad Reza Hashemian 8Shabir A Madhi 35

99

Shaheen Pandie 4Shahin Lockman 6Shallo Daba Hamusse 53Sharon Nachman 35Shi Wu Wen 22Shigetoshi Eda 54Shih-Chieh Chang 51Shu-Hsing Cheng 25Shufeng Yang 44Shun Zhang 23Shuang Qie 45Simon Lewin 10Stefan Panaiotov 21Stephanie A Harris 57Stephen J O’Brien 20Suani TR Pinho 52Sushil Kumar 43Sophie SW Wang 39Soyeon Kim 35

Soyoung Yoon 41Susan van den Hof 15Sultan Tousif 43Sven Hoffner 17Syed Azhar Syed Sulaiman 42Sylvia C Leão 40Sytze T Keizer 15

TTaeksun Song 41Thomas J Scriba 57Tiziana Feletti 49Thiago Nascimento do Prado

26

UUreshnie Govender 4,55

VVadim M Govorun 20Valeria Gómez Toscano 27Vanessa V Souza 38Victoria J Cook

14100

Vivek Naranbhai 35Vyacheslav Y Zhuravlev 20

WW Henry Boom 16W Ray Waters 54Wen-Hung Hsu 39Wenli Zhang 44Wendy M Rios 40Wenjia Chen 14Willem A Hanekom 57Willem A Odendaal

10

XXiaoguo Song 45Xiaoyan Feng 45Xiqin Yang 45Xin Huang 22

YYan Yao 18Yanqi Zhang 23

Yaw-Bin Huang 39Yen-Hsu Chen 39Yibeltal Kassa 47Ying Cai 41Ying Li 23Yisheng Huang 32Youfang Chen 22Youngran Kim 41Yufang Ma 44Yu-Hui Lin 25Yu Zheng 6Yuan Deng 18Yuan-Ming Lee 51Yulia D Isaeva 20

ZZaheer-Ud-Din Babar 42Zhenhua Dai 45

101

Zita S Kerbelker4

Zhong-min Sun 18Zohreh Maghsoomi 8

102

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