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Roland Diel,
Robert Loddenkemper,
Jean-Pierre Zellweger, Giovanni Sotgiu,
Lia D'Ambrosio,
Rosella Centis,
Marieke J van der Werf,
Masoud Dara,
Anne Detjen,
Peter Gondrie,
Lee Reichman,
Francesco Blasi,
Giovanni Battista Migliori
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ABSTRACT: The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization post-2015 Strategy allows new discussions on how to direct TB control. The ERS European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities and advances to improve TB control and eventually progress towards TB elimination.While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilizing the pool of latently infected individuals from which future TB cases would be generated.This manuscript describes the three core components which are necessary to implement the elimination strategy fully: 1) improve diagnosis of latent TB infected individuals; 2) improve regimens to treat latent TB infection; and 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available.
European Respiratory Journal 02/2013; · 5.89 Impact Factor
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ABSTRACT: To the Editor: In their historical overview of global efforts to control tuberculosis, Keshavjee and Farmer (Sept. 6 issue)(1) argue that the prioritization of global health funding based on measurable outcomes and high-return investments contributed to the fragmentation of primary health care. We agree but acknowledge that it can be difficult to strike the right balance between the improved efficiencies provided by vertical programs and comprehensive primary care. Importantly, international funding should not erode local ownership or investment in comprehensive primary care, which serves as the bedrock of a well-functioning health care system. Global implementation of the DOTS (directly observed . . .
New England Journal of Medicine 01/2013; 368(1):88-90. · 53.30 Impact Factor
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The Journal of Infection in Developing Countries 01/2013; 7(3):289-292. · 1.19 Impact Factor
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Saverio De Lorenzo,
Jan Wilem Alffenaar, Giovanni Sotgiu,
Rosella Centis,
Lia D'Ambrosio,
Simon Tiberi,
Mathieu S Bolhuis,
Richard van Altena,
Piero Viggiani,
Andrea Piana,
Antonio Spanevello,
Giovanni Battista Migliori
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ABSTRACT: Clinical experience on meropenem/clavulanate (MC) to treat tuberculosis (TB) is anedoctal (case-reports on 10 patients). Aim of our case-control study was to evaluate the contribution of MC when added to linezolid-containing regimens in terms of efficacy, safety/tolerability in treating multidrug- (MDR-) and extensively drug-resistant (XDR-) TB cases after 3 months of second-line treatment.Cases with MDR/XDR-TB (37) were prescribed MC (daily dose: 3 g) in addition to a linezolid-containing regimen (dosage range: 300-1,200 mg·day(-1)), designed according to international guidelines, which was prescribed to controls (61).The clinical severity of cases was worse than that of controls (drug susceptibility profile; proportion of sputum smear positive and of re-treatment cases). The group of cases yielded a higher proportion of sputum smear converters (28/32, 87.5% VS. 9/16, 56.3%; p-value: 0.02) and culture converters (31/37, 83.8% VS. 15/24, 62.5%; p-value: 0.06). Excluding XDR-TB patients (11/98, 11.2%), cases scored a significantly higher proportion of culture converters than controls (p-value: 0.03).One case had to withdraw MC due to increased transaminase levels.The results of our study provide: 1) preliminary evidence on effectiveness and safety/tolerability of MC; 2) reference to design further trials and 3) guide to clinicians for its rationale use within salvage/compassionate regimens.
European Respiratory Journal 09/2012; · 5.89 Impact Factor
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Giovanni Sotgiu,
Lia D'Ambrosio,
Rosella Centis,
Graham Bothamley,
Daniela M Cirillo,
Saverio De Lorenzo,
Gunar Guenther,
Kai Kliiman,
Ralf Muetterlein,
Victor Spinu,
Miguel Villar,
Jean-Pierre Zellweger,
Andreas Sandgren,
Emma Huitric,
Christoph Lange,
Davide Manissero,
Giovanni Battista Migliori
European Respiratory Journal 08/2012; 40(2):500-3. · 5.89 Impact Factor
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The Lancet 07/2012; 380(9846):955-7. · 38.28 Impact Factor
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ABSTRACT: Regulation of specific immune responses following exposure to M. tuberculosis in humans and the role of regulatory T (Treg) cells in immune control of latent infection with M. tuberculosis are incompletely understood.Latent infection was assayed by an Interferon-γ Release Assay (IGRA) in health care workers regularly exposed to tuberculosis patients and in household TB contacts in Germany. Immunophenotypes of bronchoalveolar lavage mononuclear cells and peripheral blood mononuclear cells (PBMC) were analysed by fluorescence activated cell sorting.All tuberculosis contacts with latent infection (n=15) had increased (p<0.0001) frequencies of CD4+CD25+CD127- Treg cells (median 2.12%, InterQuartile Range -IQR- 1.63-3.01) among bronchoalveolar lavage (BAL) mononuclear cells compared to contacts (n= 25) with negative IGRA results (0.68%, IQR 0.32-0.96) No differences were seen when PBMC immunophenotypes of IGRA positive and negative TB contacts were compared (IGRA+: median 9.6%, IQR 5.9-10.1; IGRA-: median 7.7%, IQR 4.6-11.3; p=0.47). Five of 25 contacts with negative blood IGRA showed a positive IGRA from BAL cells, possibly indicating a limited local immune response.In Germany, latent infection with M. tuberculosis, as defined by a positive M. tuberculosis-specific IGRA response on cells from the peripheral blood, is characterized by an increased frequency of Treg cells in the BAL.
European Respiratory Journal 03/2012; · 5.89 Impact Factor
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ABSTRACT: Tuberculosis (TB) remains a global emergency and continues to kill 1.4 million people every year. The interaction between noncommunicable and infectious diseases like TB has important implications with regard to the attainment of the Millennium Development Goals (MDGs). Smoking, diabetes mellitus, anti-TNFα drugs and other immunosuppressive therapies are well known major risk factors associated with TB. The purpose of this review is to summarize the recent literature on these risk factors and interventions that reduce the risk.
Mathematical models and aggregate data from the field show that smoking, diabetes and anti-TNFα drugs independently increase the risk of developing active TB. There is consensus on the great need for screening for active TB disease in patients with these conditions and targeted preventive interventions through a combined multidisciplinary approach.
Smoking, diabetes mellitus, anti-TNFα drugs and new immunosuppressive treatments represent important common risk factors for TB. A high degree of clinical awareness of the possibility of TB should be considered in patients with these risk factors, and active screening and prevention should be undertaken. Further operational research is needed to optimize screening for latent Mycobacterium tuberculosis infection, instituting preventive intervention measures.
Current opinion in pulmonary medicine 03/2012; 18(3):233-40. · 3.08 Impact Factor
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The Lancet Infectious Diseases 02/2012; 12(6):425-6. · 17.39 Impact Factor
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Petros Isaakidis,
Bhanumati Varghese,
Homa Mansoor,
Helen S Cox,
Joanna Ladomirska,
Peter Saranchuk,
Esdras Da Silva,
Samsuddin Khan,
Roma Paryani,
Zarir Udwadia,
Giovanni Battista Migliori, Giovanni Sotgiu,
Tony Reid
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ABSTRACT: Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.
Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE.
Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5-42) and the median duration of anti-TB treatment was 10 months (range 0.5-30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen.
AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.
PLoS ONE 01/2012; 7(7):e40781. · 4.09 Impact Factor
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2011; 15(9):1137-8. · 2.73 Impact Factor
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The Lancet Infectious Diseases 09/2011; 11(9):660-661. · 17.39 Impact Factor
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American Journal of Respiratory and Critical Care Medicine 07/2011; 184(2):180-5. · 11.08 Impact Factor
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ABSTRACT: Evaluation of different methods for an initial treatment decision in individuals with suspected pulmonary tuberculosis.
Recently, important advances regarding the diagnosis of pulmonary tuberculosis have been introduced, which influence the decision to initiate anti-tuberculosis treatment.
To evaluate the impact of different methods for the presumed diagnosis of tuberculosis, individuals with suspected tuberculosis were prospectively enrolled following a specific algorithm including initial smear microscopy and Mycobacterium tuberculosis-specific nucleic acid amplification (NAAT) from sputum. In cases of negative initial test results, tuberculin skin testing, bronchoscopy with transbronchial biopsies and interferon-γ release assays (IGRAs) in peripheral blood and bronchoalveolar lavage (BAL) fluid were performed.
Amongst 135 individuals with suspected tuberculosis, 42 had tuberculosis, 10 had nontuberculous mycobacteria pulmonary infection/colonization (one had both tuberculosis and nontuberculous mycobacteria pulmonary infection/colonization) and 84 had an alternative final diagnosis. The sensitivity and specificity were 41% and 99% [positive likelihood ratio (LR+) = 40] for sputum microscopy and 31% and 98% (LR+) = 16) for BAL nucleic acid amplification, respectively. In patients with acid-fast bacilli smear-negative tuberculosis (25/42, 59.5%), M. tuberculosis-specific BAL fluid IGRA was 92% sensitive and 87% specific (LR+) = 7) for the diagnosis of tuberculosis.
None of the microbiological or immunological methods that aim to provide a rapid diagnosis of tuberculosis whilst waiting the confirmation of the M. tuberculosis culture results is on its own accurate enough to diagnose or exclude pulmonary tuberculosis. Negative sputum microscopy and M. tuberculosis-specific NAAT results should prompt bronchoscopy including BAL for M. tuberculosis-specific IGRA in individuals with suspected pulmonary tuberculosis.
Journal of Internal Medicine 03/2011; 270(3):254-62. · 5.48 Impact Factor
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ABSTRACT: More than 22,000 people attended the 2010 European Respiratory Society conference. Numerous scientific sessions discussed TB themes (e.g., European and global epidemiology, management of drug-resistant TB, TB in vulnerable populations, and bacteriological and immunological diagnosis). In particular, several authors emphasized the increasing trend of TB in Europe, highlighting the need for public health programs focused on vulnerable populations: frequently, these populations are infected with drug-resistant strains and their clinical and treatment outcomes could be poor, with the consequence of increasing the risk of ongoing mycobacterial transmission. Other interesting reports were focused on IFN-γ release assays, which show a good diagnostic performance in different clinical conditions, even though their role needs to be clarified in well-designed analytic studies.
Expert Review of Respiratory Medicine 02/2011; 5(1):27-31.
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ABSTRACT: Human papillomavirus (HPV) has been associated with several disorders of the genital tract, skin and oropharynx. The aims of our study were to evaluate the prevalence of HPV infection in women between 15 and 54 years of age in North Sardinia, Italy, to identify the prevalence of High Risk - Human papillomaviruses (HR-HPV) genotypes and to establish a correlation between molecular and cytological results.
From 2007 to 2009 we consecutively enrolled women aged 15-54 years admitted to public and private outpatient settings. All the participants filled in a questionnaire about the socio-cultural state, sexual activity and awareness about HPV. 323 cervical specimens were tested for HPV-DNA and HPV genotypes with INNO-LiPA HPV Genotyping CE Amp kit. Samples showing positivity to some HPV genotypes were re-tested using "in house" quantitative Real-Time PCR assays.
Overall HPV-DNA positivity was detected in 35.9% of the women. The prevalence of HR-HPV infection among HPV positive samples was 93.1% with a specific prevalence of HPV 16, 51, 31, 53 and 18 of 54.3%, 37.9%, 10.3%, 6.9% and 5.2%, respectively. Co-infection with any HPV, HR-HPV, LR-HPV and HR/LR-HPV type was 18.3%, 14.9%, 0.9% and 2.5%, respectively; HPV 16/51 co-infection was detected in 64.6% of the HR-HPV co-infection group. The most frequent HPV-genotypes detected were 16 (32.5%) and 51 (22.7%). Among the 57 patients harboring mono-infection the most prevalent HPV genotypes were 16 (38.6%) and 31(10.5%). A multivariate analysis identified a statistical significant association between HPV infection and age and between HPV infection and previous sexual transmitted diseases. A statistically significant association between cytological cervical lesions and generic HPV exposure was identified.
To our knowledge, this is the first survey evaluating the prevalence of HPV infection in Northern Sardinia and drawing attention to the unusual high proportion of genotype HPV 51. Given the recent implementation of a widespread immunization program with vaccines not containing HPV 51, it has been relevant to prove the high prevalence of this HPV genotype from the start of the vaccination campaign, in order to avoid in the future attributing to the vaccination program a possible selection effect (HPV replacement).
BMC Public Health 01/2011; 11:785. · 2.00 Impact Factor
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Petros Isaakidis,
Helen S Cox,
Bhanumati Varghese,
Chiara Montaldo,
Esdras Da Silva,
Homa Mansoor,
Joanna Ladomirska, Giovanni Sotgiu,
Giovanni B Migliori,
Emanuele Pontali,
Peter Saranchuk,
Camilla Rodrigues,
Tony Reid
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ABSTRACT: India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India.
HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment.
Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment.
Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.
PLoS ONE 01/2011; 6(12):e28066. · 4.09 Impact Factor
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Thorax 09/2010; 65(9):842; author reply 842-3. · 6.84 Impact Factor
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ABSTRACT: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are generally thought to have high mortality rates. However, many cases can be treated with the right combination and rational use of available antituberculosis drugs. This Review describes the evidence available for each drug and discusses the basis for recommendations for the treatment of patients with MDR and XDR tuberculosis. The recommended regimen is the combination of at least four drugs to which the Mycobacterium tuberculosis isolate is likely to be susceptible. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Among the first group (the oral first-line drugs) high-dose isoniazid, pyrazinamide, and ethambutol are thought of as an adjunct for the treatment of MDR and XDR tuberculosis. The second group is the fluoroquinolones, of which the first choice is high-dose levofloxacin. The third group are the injectable drugs, which should be used in the following order: capreomycin, kanamycin, then amikacin. The fourth group are called the second-line drugs and should be used in the following order: thioamides, cycloserine, then aminosalicylic acid. The fifth group includes drugs that are not very effective or for which there are sparse clinical data. Drugs in group five should be used in the following order: clofazimine, amoxicillin with clavulanate, linezolid, carbapenems, thioacetazone, then clarithromycin.
The Lancet Infectious Diseases 09/2010; 10(9):621-9. · 17.39 Impact Factor
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The Lancet 05/2010; 375(9728):1760-1. · 38.28 Impact Factor
