Tuberculosis Relapse Research Articles

Effect of drug resistance on negative conversion of sputum culture in patients with pulmonary tuberculosis.

Negative conversion of sputum culture is a useful marker for predicting treatment outcome and relapse of pulmonary tuberculosis (TB). The effect of drug resistance on negative conversion of sputum culture with treatment was evaluated in this study. A total of 535 patients with culture-proven pulmonary TB were classified into three groups: drug-susceptible (DS), other drug-resistant (ODR), and multidrug-resistant/extensively drug-resistant (MDR/XDR). Rates of conversion of sputum culture at 4, 8, and 12 weeks were compared. At 4 weeks of treatment, the conversion rate in the DS group (52.7%) was higher than that in the ODR group (30.8%, p=0.003), but was not different compared with the MDR group (45.7%, p=0.427). At 8 weeks, the conversion rate in the DS group (76.3%) was higher than that in the ODR (63.5%, p=0.042) and MDR groups (60.0%, p=0.031). At 12 weeks, the conversion rate in the DS group (85.9%) tended to be higher than that in the MDR group (74.3%, p=0.062), but was not different from that in the ODR group (84.6%, p=0.796). The pattern of resistance to anti-TB drugs affects culture conversion rates in the early phase of treatment and also prolongs the time to culture conversion.

Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment.

Background. Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years.Methods. Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays.Results. At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell-mediated killing. Results were confirmed by real-time quantitative reverse-transcription polymerase chain reaction analysis in a wider patient cohort.Conclusions. These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development.

Immigrants and tuberculosis in Hong Kong

To examine the impact of immigrant populations on the epidemiology of tuberculosis in Hong Kong. Longitudinal cohort study. Hong Kong. Socio-demographic and disease characteristics of all tuberculosis notifications in 2006 were captured from the statutory tuberculosis registry and central tuberculosis reference laboratory. Using 2006 By-census population data, indirect sex- and age-standardised incidence ratios by place of birth were calculated. Treatment outcome at 12 months was ascertained from government tuberculosis programme record forms, and tuberculosis relapse was tracked through the notification registry and death registry up to 30 June 2013. Moderately higher sex- and age-standardised incidence ratios were observed among various immigrant groups: 1.06 (Mainland China), 2.02 (India, Pakistan, Bangladesh), 1.59 (Philippines, Thailand, Indonesia, Nepal), and 3.11 (Vietnam). Recent Mainland migrants had a lower sex- and age-standardised incidence ratio (0.51 vs 1.09) than those who immigrated 7 years ago or earlier. Age younger than 65 years, birth in the Mainland or the above Asian countries, and previous treatment were independently associated with resistance to isoniazid and/or rifampicin. Older age, birth in the above Asian countries, non-permanent residents, previous history of treatment, and resistance to isoniazid and/or rifampicin were independently associated with poor treatment outcome (other than cure/treatment completion) at 1 year. Birth outside Hong Kong was an independent predictor of relapse following successful completion of treatment (adjusted hazard ratio=1.76; 95% confidence interval, 1.07-2.89; P=0.025). Immigrants carry with them a higher tuberculosis incidence and/or drug resistance rate from their place of origin. The higher drug resistance rate, poorer treatment outcome, and excess relapse risk raise concern over secondary transmission of drug-resistant tuberculosis within the local community.

PECULIARITIES OF CHEMIORESISTANT TUBERCULOSIS SPREAD IN TERNOPIL REGION IN RECENT YEARS

<p><em>The article presents the</em><em> results of the study of susceptibility of M. tuberculosis isolated from patients with pulmonary tuberculosis in 2007 to -2013 in the Ternopol region (Ukraine)</em><em> </em><em>The positive tendency of increasing the rate</em><em> of susceptibility of M. tuberculosis anti-TB drugs in 2013 in comparison 2007 in patients with new tuberculosis and other cases of tuberculosis but not recidivation was marked in Ternopil region</em><em>.</em><em></em></p><p><em>I</em><em>n</em><em> patients with new tuberculosis the number of pathogens which were susceptible to anti-TB drugs of the first line I for this period increased on 12,6%, while in patients with re-treatment of pulmonary tuberculosis, except recidivation - increased in 1,7 times, and in patients</em><em> </em><em>with</em><em> </em><em>of</em><em> </em><em>pulmonary</em><em> </em><em>tuberculosis relapses this index fluctuated between </em><em>27,1-47,6</em><em>%. </em></p><p><em>T</em><em>he</em><em> </em><em>relative</em><em> </em><em>amount</em><em> </em><em>of</em><em> </em><em>multiresistant</em><em> </em><em>strains</em><em> </em><em>during</em><em> </em><em>this</em><em> </em><em>period</em><em> </em><em>has deeply increased</em><em>. Thus, </em><em>in</em><em> patients with new pulmonary tuberculosis twofold increase of the rate of multidrug-resistant strains in 2012 compared to 2010-2011 years was revealed. The same trend was observed in patients with tuberculosis recidivation. </em><em></em></p><p><em>The attention was paid to </em><em>the </em><em>priority of the introduction of modern</em><em> express methods of tuberculosis diagnosis and examination of susceptibility of its causative agents to antimycobacterial drugs. It will permit to correct antimycobacterial treatment in time, and reduce the number of relapses and appearance of chronic pulmonary tuberculosis in patients with multiresistant pathogens.</em><em></em></p>

Disseminated Penicillium marneffei mimicking paradoxical response and relapse in a non-HIV patient with pulmonary tuberculosis

Clinical deterioration during the treatment of tuberculosis remains a diagnostic challenge. We describe the case of a 46-year-old man with a history of oral cancer status after a radical operation who had pulmonary tuberculosis with pleura and neck lymph node involvement. The clinical condition improved after antituberculosis therapy. However, the patient suffered from low-grade fever, progressive dyspnea, and cough after 7 weeks of the therapy. The findings of chest plain films were relapse and progression of left lung haziness. The deterioration was caused by disseminated Penicillium marneffei infection. Disseminated P. marneffei in a non-HIV patient with tuberculosis is rarely seen, and the manifestations are similar to a paradoxical response and relapse of pulmonary tuberculosis, thereby making it difficult to establish a diagnosis.

Exogenous reinfection of tuberculosis in a low-burden area.

Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.

Thoracic manifestations of paradoxical immune reconstitution inflammatory syndrome during or after antituberculous therapy in HIV-negative patients.

Immune reconstitution inflammatory syndrome (IRIS) is a consequence of exaggerated and dysregulated host's inflammatory response to invading microorganism, leading to uncontrolled inflammatory reactions. IRIS associated with tuberculosis (TB) is well recognized among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy, but it is less common among HIV-negative patients. IRIS can manifest as a paradoxical worsening or recurring of preexisting tuberculous lesions or development of new lesions despite successful antituberculous treatment. Hence, the condition might be misdiagnosed as superimposed infections, treatment failure, or relapse of TB. This pictorial essay reviewed diagnostic criteria and various thoracic manifestations of the paradoxical form of TB-associated IRIS (TB-IRIS) that might aid in early recognition of this clinical entity among HIV-negative patients. The treatment and outcomes of TB-IRIS were also discussed.

Protein energy malnutrition during vaccination has limited influence on vaccine efficacy but abolishes immunity if administered during Mycobacterium tuberculosis infection.

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse of Mycobacterium tuberculosis, as well as increased pathology, in both Mycobacterium bovis BCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ(+) TNF-α(+) and IFN-γ(+) cells). PEM during M. tuberculosis infection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine against M. tuberculosis infection.

Profil clinique, microbiologique et évolutif des patients en situation d’échecs et de rechutes de tuberculose en Côte d’Ivoire

Multidrug-resistant tuberculosis (MDR-TB) is a major obsession for TB control. The main risk factor for MDR-TB remains a history of TB treatment especially bad conduct. The objective of this study is to describe the profile of patients in situations of failure and relapse of tuberculosis. We performed a retrospective survey of the analysis of records of patients starting TB retreatment for failure or relapse of tuberculosis. We used 193 cases with results of culture-sensitivity. The proportion of failure is 59/193 (30.6 %) and cases of relapse are 134/193 (69.4 %). The proportion of married life is 23.4 % (11/47) in chess against 41.5 % (51/123) in relapse of TB [P=0.021, OR=0.431 (0.201 to 0.927)]. Patients failing therapy have more chest pain [5.8 % (3/52) versus 0 % (0/126) with P=0.024]. The proportion of MDR-TB was 61.4 (38/59) in case of failure against 41 % (55/134) in case of relapse [P=0.002, OR=2.599 (1.378 to 4.902)]. The evolution is the same whatever the indication of reprocessing. The proportion of MDR-TB is very important in case of reprocessing failure and relapse of tuberculosis.

A Rare Case of Flare-Up of PID in Infertility Treatment

Case Presentation. Mrs. X, 35 years old, case of primary infertility, was diagnosed to have genital tuberculosis on the basis of PCR positive and hysterolaparoscopy findings and received category I ATT for 6 months. Following ATT completion, her USG revealed no evidence of tuboovarian mass or hydrosalpinx. Since her tubes were patent, she underwent 3 cycles of ovulation induction and 2 cycles of IUI. The women presented with acute PID, five days after IUI, and was conservatively managed. She again presented 24 days after IUI with persistent low grade fever and abdominal pain. Suspecting relapse of genital tuberculosis, she was started on category II ATT. She had acute episodes of high grade fever with chills 2 weeks after starting ATT and MRI revealed bilateral TO masses suggestive of pyosalpinx. Emergency laparotomy was done, pus was drained, and cyst wall was removed and HPE was suggestive of chronic inflammation with few granulation tissues. ATT was continued for one year and the woman improved. Conclusion. The possibility of flare-up of PID (pelvic inflammatory disease) in treated case of tuberculosis undergoing infertility management should be kept in mind and aggressive management should be done.

Treatment of Drug Susceptible Pulmonary Tuberculosis.

Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs.

NOS2A Gene Polymorphism in Susceptibility to Pulmonary Tuberculosis

Event Abstract Back to Event NOS2A Gene Polymorphism in Susceptibility to Pulmonary Tuberculosis Eloisa Lara Gonzalez1, Fernando A. Hernandez1 and Mercedes T. Fernandez Mestre1* 1 Instituto Venezolano de Investigaciones Cientificas, Centro de Medicina Experimental, Venezuela Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which primarily affects the lungs causing pulmonary tuberculosis. In the World Health Organization (WHO) Global Tuberculosis Report for 2014 there were 9.0 million new TB cases in 2013 and 1.5 million TB deaths (1.1 million among HIV-negative and 0.4 million among HIV-positive) of which 218,875 new cases and relapses occurred in the Americas. In Venezuela, according to the WHO, the incidence of new and relapse TB cases is among 20-49 per 100,000 inhabitants. The first interaction between Mycobacterium tuberculosis and the host occurs in pulmonary alveoli, where bacillus is phagocytosed by dendritic cells and macrophages. Nitric oxide (NO) plays a major role in the host-defense mechanism in response to infections and is implicated in bacteriostatic as well as bactericidal processes. NO is produced by three enzyme nitric oxide synthase (NOS) different: NOS1, NOS2 and NOS3. In the promoter region of the gene NOS2 has been identified polymorphisms that affect the binding of transcription factors affecting the concentrations of NO. Since that genetic polymorphism in the promoter of the NOS2 gene could modulate production of NO we investigated in this study the potential association between the NOS2G-954C polymorphism and the development of tuberculosis. Sixty nine patients with pulmonary TB and 94 apparently healthy individuals who have been exposed to Mycobacterium tuberculosis were genotyped for the NOS2G-954C polymorphism by PCR-RFLP. Our results showed not significant association between -954G/C NOS2A variant and susceptibility to either infection or the development of tuberculosis. Furthermore, we found no correlation between different genotypes -954G/C and the concentration of nitrite in plasma. However, we observed in the group of controls with tuberculin skin test positive (TST+) high concentrations of nitrite. In conclusion, the production of nitric oxide would control the Mycobacterium tuberculosis and the presence of other variants of NOS2A gene could determine its concentrations. Acknowledgements The authors are grateful to the persons that participated in this study. This study was supported by CRP - ICGEB Research Grant- CRP/VEN11-01 References Burgner, D. Rockett, K., Kwiatkowski, D. 1999. Nitric oxide and infectious diseases. Dis Childhood 81: 185-188. Kun, J. F., Mordmϋller, B., Perkins, D. J., May, J., Mercereau-Puijalon, O., Alpers, M., Weinberg, J. B., Kremsner, P. G. 2001. Nitric Oxide Synthase 2Lambaréné (G-954C), Increased Nitric Oxide Production, and Protection against Malaria. J. Infect. Dis. 184: 330-336. World Health Organization. Global Tuberculosis Report. 2014. Disponible en: http://www.who.int/tb/publications/global_report/en/ Yang, CH., Yuk, JM. y Jo, EK. 2009. The Role of Nitric Oxide in Mycobacterial Infections. Immun. Netwk. 9: 46-52. Keywords: Polymorphism, Genetic, Tuberculosis, Pulmonary, Nitric Oxide, Nitric Oxide Synthase, TST Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Immunogenetics Citation: Lara Gonzalez E, Hernandez FA and Fernandez Mestre MT (2015). NOS2A Gene Polymorphism in Susceptibility to Pulmonary Tuberculosis. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00110 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Apr 2015; Published Online: 14 Sep 2015. * Correspondence: Dr. Mercedes T Fernandez Mestre, Instituto Venezolano de Investigaciones Cientificas, Centro de Medicina Experimental, Caracas, Distrito Capital, 21827, Caracas 1020A, Venezuela, mfernandezmestre@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Eloisa Lara Gonzalez Fernando A Hernandez Mercedes T Fernandez Mestre Google Eloisa Lara Gonzalez Fernando A Hernandez Mercedes T Fernandez Mestre Google Scholar Eloisa Lara Gonzalez Fernando A Hernandez Mercedes T Fernandez Mestre PubMed Eloisa Lara Gonzalez Fernando A Hernandez Mercedes T Fernandez Mestre Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms.

Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following "sterilizing" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we measure the single-cell dynamics of Mycobacterium tuberculosis replication and ribosomal activity using quantitative time-lapse microscopy and a reporter of ribosomal RNA gene expression. Single-cell dynamics exhibit heterogeneity under standard growth conditions, which is amplified by stressful conditions such as nutrient limitation, stationary phase, intracellular replication, and growth in mouse lungs. Additionally, the lungs of chronically infected mice harbor a subpopulation of nongrowing but metabolically active bacteria, which are absent in mice lacking interferon-γ, a cytokine essential for antituberculosis immunity. These cryptic bacterial forms are prominent in mice treated with the antituberculosis drug isoniazid, suggesting a role in postchemotherapeutic relapses. Thus, amplification of bacterial phenotypic heterogeneity in response to host immunity and drug pressure may contribute to tuberculosis persistence.

A Study on the Relapse Rate of Tuberculosis and Related Factors in Korea Using Nationwide Tuberculosis Notification Data

ObjectivesFrom the perspective of public health, tuberculosis (TB) remains an important issue that threatens health. Korea is an intermediate burden country with a TB incidence of 97/100,000 individuals. Among many TB control measures, a relapse rate of TB is one indicator that can be used to indirectly assess the level of TB control in countries and in communities. Relapse TB has an approximately 12% yearly incidence in Korea. This study aims to estimate the relapse rate of TB and to investigate the associated factors by using nationwide TB notification data in Korea. MethodsThe nationwide TB notification data in 2005 was used with the exclusion criteria of duplicated reporting, foreign-born patients, outcome–died, and outcome–diagnosis changed. The data were double-checked as to whether they were reported again during 2006–2010 and the estimated relapse rate of TB. Associated factors were analyzed by multivariate logistic regression with the variables of age, sex, registration type, results of sputum smear test, medication, and outcome of treatment. ResultsAmong 45,434 TB patients in 2005, 4,371 patients were again reported as TB patients from 2006 to 2010. Five hundred and sixty-four patients were reported more than twice and the cumulative number of relapses was 5,072 cases. The 5-year relapse rate was estimated as 9.62%. The relapse rate decreased yearly: 4.8% in 2006, 2.4% in 2007, 1.6% in 2008, 1.4% in 2009, and 1.0% in 2010. Age, sex, registration type, tuberculosis type, and medication were independently associated with a relapse of TB. In the multivariate logistic regression analysis, the following factors were related: male sex, 40–49 years old; registration type, relapse, treatment after failure, treatment after default, transfer in, and other, the sputum smear-positive pulmonary TB, and medications (including individuals taking 2–5 drugs). ConclusionThis study has estimated a 5-year relapse rate of TB in Korea that is slightly lower than the rate of relapse TB in the annual reports. This study could be conducted and cross-checked with data from the National Health Insurance in the future.

Smoking adversely affects treatment response, outcome and relapse in tuberculosis.

The impact of smoking on tuberculosis outcome was evaluated in a territory-wide treatment programme. 16,345 consecutive patients undergoing chemotherapy for active tuberculosis in government chest clinics in Hong Kong from 2001 to 2003 were followed up prospectively for 2 years for treatment outcome and subsequently tracked through the territory-wide tuberculosis notification registry for relapse until the end of 2012. Smoking was associated with more extensive lung disease, lung cavitation and positive sputum smear and culture at the baseline. In both current smokers and ex-smokers, sputum smears and cultures were significantly more likely to remain positive after 2 months of treatment. Both categories of smokers were significantly less likely to achieve cure or treatment completion within 2 years. Overall, 16.7% of unsuccessful treatment outcomes were attributable to smoking, with the key contributor being default in current smokers and death in ex-smokers. Among successful treatment completers, there was a clear gradient (hazard ratios of 1.00, 1.33 and 1.63) of relapse risk from never-smokers to ex-smokers and current smokers, with an overall population attributable risk of 19.4% (current smokers: 12.2%; ex-smokers: 7.2%). Smoking adversely affects baseline disease severity, bacteriological response, treatment outcome and relapse in tuberculosis. Smoking cessation likely reduces relapse and secondary transmission.

Increased risk of tuberculosis in patients with type 1 diabetes mellitus: results from a population-based cohort study in Taiwan.

The studies on the risk of tuberculosis (TB) in patients with type 1 diabetes mellitus (T1DM) alone are limited. We examined this relationship using a population-based retrospective cohort study. From claims data of the National Health Insurance system of Taiwan, we identified 5195 patients with T1DM newly diagnosed from 2002 to 2011 and 20,780 randomly selected controls without T1DM, frequency matched by age, sex, and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the risk of TB. The overall incidence of TB was 4.07-fold higher in the T1DM cohort than in the control cohort (1.18 vs 0.29 per 1000 person-years, P < 0.001). Compared with the controls, the Cox model estimated adjusted hazard ratios (HRs) of TB in patients with T1DM were greater in men than in women (4.62 vs 3.59) and in adults than in children (4.06 vs 3.37), but not significant. The adjusted HR was much greater for those with comorbidities than those without comorbidities (14.6 vs 1.62, P < 0.001). Compared with the controls, the patients with T1DM were also more likely to develop TB with multiple emergency room visits (adjusted HR: 116.1, 95% confidence interval [CI] = 43.8–307.4) or hospitalizations (adjusted HR: 86.5, 95% CI = 33.7–222.4). Patients with T1DM are at elevated risks of developing TB with much higher HRs for those with comorbidities, within the first year of diagnosis, and with frequent emergency cares or hospitalizations.

Lymphoma and Tuberculosis

Tuberculosis can often be seen in patients undergoing chemotherapy for lymphoma, especially in endemic countries. As both tuberculosis and lymphoma can lead to hypermetabolic lesions of F-FDG PET/CT, a diagnostic dilemma often ensues. We present the sequential F-FDG PET/CT images of a 22-year-old female patient with Hodgkin lymphoma who developed tuberculosis and later relapse of lymphoma. These images present the temporal evaluation of the dual pathology on F-FDG PET/CT.

Difficulties in controlling HIV and TB infections in multi-experienced patients

The treatment of extra pulmonary tuberculosis in HIV infected patients experienced to antiretroviral therapy raises major issues of adherence, drug interactions, side effects and limited antiretroviral alternatives. This is the case of a 24 year old woman from countryside, most probably infected in 1989. She was diagnosed with HIV infection in 2000 after repeated admissions in hospital for pneumonia. She started ART when diagnosed with a favorable evolution: CD4 cell count increased from 200 to 674 cells/cmm, and HIV RNA levels became undetectable. She turned 18 in 2008 and refused to take her treatment for almost two years. She returned to the hospital in April 2010 with a CD4 cell count of 140 cells/cmm. She started again antiretroviral therapy with ABC+3TC+FPV/r. In April 2013 she is admitted with night sweats, chills and fever. At that time her CD4 cell count was 144 cells/cmm and had 461,000 copies/mL RNA-HIV. Her chest XR showed right pleural effusion, widened mediastinum and the CT revealed infiltrative-like lesion at subcarinal and retrocarinal level. Biopsy was performed and she was diagnosed with ganglionary tuberculosis. She started anti-TB treatment HRZE 7/7 and the ART was changed to ABC+RAL+T20. The anti-TB regimen is changed after three months to rifampicin and isoniazid 7/7 because she accused arthralgias, tingling of the extremities, blurred vision and decreased visual acuity. She was diagnosed with hyperuricemia (pyrazinamide) and optic and peripheral neuritis (ethambutol). New visit at the clinic for fatigability, after 7 months of antiretroviral therapy with ABV+RAL+T20. The CD4 cell count was 9 cells/cmm and RNA-HIV was 61,000 copies/mL. She admits taking 1 cp of Raltegravir BID, but denies any other adherence problem. The resistance test showed evidence of resistance to some NRTIs, to all NNRTIs, to RAL and no resistance to PIs. The tropism test showed that maraviroc can be used. We have excluded relapse of tuberculosis and other diseases associated. The ART was changed again to TDF+DRV/r+MRV and the anti-TB treatment is change to isoniazid and moxifloxacin. Adherence can be an important issue when treating patients for long periods of time. Other important issues are the drug-drug interactions (rifampicin – PIs) and the increased side effects which may lead to loss of good friends (Raltegravir). The poor outcome for this patient may be due to poor HIV and tuberculosis control.

Diabetes and Risk of Tuberculosis Relapse: Nationwide Nested Case-Control Study

The aim of this study was to investigate the association between diabetes mellitus (DM) and tuberculosis (TB) relapse using the nationwide TB registry in Taiwan. We conducted a case-control study nested within a nationwide cohort of all incident cases of pulmonary TB that were notified during 2006–2007 and had completed anti-TB treatment. The relapse of TB was confirmed by bacteriological or pathological findings. For each relapse case, one control was selected from the study cohort matching by time since treatment completion. DM status was ascertained by medical chart review and cross-matching with the National Health Insurance claims database. A total of 305 cases of relapse were identified after a median follow-up of 3 years (relapse rate: 488 per 100,000 person-year; 95% confidence interval (CI): 434–546). Presence of DM during previous anti-TB treatment was 34.0% and 22.7% in cases and controls, respectively. After adjusting for other potential confounders, DM was associated with increased risk of TB relapse (adjusted odds ratio: 1.96, 95% CI: 1.22–3.15). Only one-third of the DM-TB patients in our study received glycaemic monitoring using HbA1c during anti-TB treatment. Presence of DM was independently associated with risk of TB relapse. TB programs should seriously consider rigorous glucose control in DM-TB patients.

The Temporal Dynamics of Relapse and Reinfection Tuberculosis After Successful Treatment: A Retrospective Cohort Study

There is increasing evidence from tuberculosis high-burden settings that exogenous reinfection contributes considerably to recurrent disease. However, large longitudinal studies of endogenous reactivation (relapse) and reinfection tuberculosis are lacking. We hypothesize a relationship between relapse vs reinfection and the time between treatment completion and recurrent disease. Population-based retrospective cohort study on all smear-positive tuberculosis cases successfully treated between 1996 and 2008 in a suburban setting in Cape Town, South Africa. Inverse gaussian distributions were fitted to observed annual rates of relapse and reinfection, distinguished by DNA fingerprinting of Mycobacterium tuberculosis strains recultured from diagnostic samples. Paired DNA fingerprint data were available for 130 (64%) of 203 recurrent smear-positive tuberculosis cases in the 13-year study period. Reinfection accounted for 66 (51%) of 130 recurrent cases overall, 9 (20%) of 44 recurrent cases within the first year, and 57 (66%) of 86 thereafter (P < .001). The relapse rate peaked at 3.93% (95% confidence interval [CI], 2.35%-5.96%) per annum 0.35 (95% CI, .15-.45) years after treatment completion. The reinfection tuberculosis rate peaked at 1.58% (95% CI, .94%-2.46%) per annum 1.20 (95% CI, .55-1.70) years after completion. To our knowledge, this is the first study of sufficient size and duration using DNA fingerprinting to investigate tuberculosis relapse and reinfection over a lengthy period. Relapse occurred early after treatment completion, whereas reinfection dominated after 1 year and accounted for at least half of recurrent disease. This temporal relationship may explain the high variability in reinfection observed across smaller studies. We speculate that follow-up time in antituberculosis drug trials should take reinfection into account.