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Dive into the research topics where Francis Varaine is active.

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Featured researches published by Francis Varaine.


European Respiratory Journal | 2011

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update

Dennis Falzon; Ernesto Jaramillo; H. J. Schünemann; M. Arentz; Melissa Bauer; Jaime Bayona; Léopold Blanc; Jose A. Caminero; Charles L. Daley; C. Duncombe; Christopher Fitzpatrick; Agnes Gebhard; Haileyesus Getahun; M. Henkens; Timothy H. Holtz; J. Keravec; S. Keshavjee; Aamir J. Khan; R. Kulier; Vaira Leimane; Christian Lienhardt; Chunling Lu; A. Mariandyshev; Giovanni Battista Migliori; Fuad Mirzayev; Carole D. Mitnick; Paul Nunn; G. Nwagboniwe; Olivia Oxlade; Domingo Palmero

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.


Nature Genetics | 2015

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage

Matthias Merker; Camille Blin; Stefano Mona; Nicolas Duforet-Frebourg; Sophie Lecher; Eve Willery; Michael G. B. Blum; Sabine Rüsch-Gerdes; Igor Mokrousov; Eman Aleksic; Caroline Allix-Béguec; Annick Antierens; Ewa Augustynowicz-Kopeć; Marie Ballif; Francesca Barletta; Hans P eter Beck; Clifton E. Barry; Maryline Bonnet; Emanuele Borroni; Isolina Campos-Herrero; Daniela M. Cirillo; Helen Cox; Suzanne M. Crowe; Valeriu Crudu; Roland Diel; Francis Drobniewski; Maryse Fauville-Dufaux; Sebastien Gagneux; Solomon Ghebremichael; M. Hanekom

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.


Tropical Medicine & International Health | 2002

Increasing transparency in partnerships for health - introducing the Green Light Committee

Rajesh K. Gupta; J. Peter Cegielski; Marcos A. Espinal; Myriam Henkens; Jim Yong Kim; Catherina S. B. Lambregts-van Weezenbeek; Jong-Wook Lee; Mario Raviglione; Pedro G. Suarez; Francis Varaine

Public–private partnerships have become central to efforts to combat infectious diseases. The characteristics of specific partnerships, their governance structures, and their ability to effectively address the issues for which they are developed are being clarified as experience is gained. In an attempt to promote access to and rational use of second‐line anti‐tuberculosis (TB) drugs for the treatment of multidrug‐resistant TB, a unique partnership known as the Green Light Committee (GLC) was established by the World Health Organization. This partnership relies on five categories of actors to achieve its goal: academic institutions, civil society organizations, bilateral donors, governments of resource‐limited countries, and a specialized United Nations agency. While the for‐profit private sector is involved in terms of supplying concessionally priced drugs it is excluded from decision‐making. The effectiveness of the partnership emerges from its review process, flexibility to modify its modus operandi to overcome obstacles, independence from the commercial sector, and its ability to link access, rational use, technical assistance, and policy development. The GLC mechanism may be useful in the development of other partnerships needed in the rational allocation of resources and tools for combating additional infectious diseases.


Journal of Clinical Microbiology | 2002

Outbreaks of Disease Suspected of Being Due to Human Monkeypox Virus Infection in the Democratic Republic of Congo in 2001

Hermann Meyer; Mathilde Perrichot; Markus Stemmler; Petra Emmerich; Herbert Schmitz; Francis Varaine; Robert Shungu; Florimond Tshioko; Pierre Formenty

ABSTRACT Seven outbreaks of disease characterized by a pustular rash and suspected to have been caused by human monkeypox virus were investigated. The outbreaks occurred between February and August 2001 in the province of Equateur in the Democratic Republic of Congo. The outbreaks involved a total of 31 persons and caused five deaths. Specimens from 14 patients were available and were analyzed by electron microscopy, virus isolation, and PCR assays specific for monkeypox virus and varicella-zoster virus. We provide evidence that two outbreaks were indeed caused by monkeypox virus (16 cases, with four deaths), that in two outbreaks both monkeypox and varicella-zoster virus were involved (seven cases, with one death), and that two outbreaks were cases of chickenpox caused by infection with varicella-zoster virus (six cases, with no deaths). In one outbreak, no evidence for either monkeypox or chickenpox was found (two cases, with no deaths).


AIDS | 2006

Tuberculosis after HAART initiation in HIV-positive patients from five countries with a high tuberculosis burden.

Maryline Bonnet; Loretxu Pinoges; Francis Varaine; Barbara Bo Oberhauser; Daniel Do O'brien; Yared Yk Kebede; Cathy Hewison; Rony Zachariah; Laurent Ferradini

Background:HAART reduces tuberculosis (TB) incidence in people living with HIV/AIDS but those starting HAART may develop active TB or subclinical TB may become apparent in the immune reconstitution inflammatory syndrome. Objective:To measure the incidence rate of notified TB in people receiving HAART in five HIV programmes occurring in low-resource countries with a high TB/HIV burden. Methods:A retrospective review in five Médecins Sans Frontières programmes (Cambodia, Thailand, Kenya, Malawi and Cameroon) allowed incidence rates of notified TB to be calculated based on follow-up time after HAART initiation. Results:Among 3151 patients analysed, 90% had a CD4 cell count of < 200 cells/μl. Median follow-up time ranged from 3.7 months in Thailand or Kenya to 11.1 months in Cambodia. Incidence rates were 7.6, 10.4, 17.6, 14.3 and 4.8/100 person-years for pulmonary TB and 12.7, 4.3, 6.9, 2.1 and 0/100 person-years for extra-pulmonary TB in the programmes in Cambodia, Thailand, Kenya, Malawi and Cameroon, respectively. Overall, 62.3% of pulmonary TB and 54.9% of extra-pulmonary TB were diagnosed within 3 months after HAART initiation. Conclusion:High incidence rates of notified TB under HAART in programmes held in poor-resource countries were observed; these were likely to include both undiagnosed prevalent TB at HAART initiation and subclinical TB developing during the immune reconstitution inflammatory syndrome. This raises operational issues concerning TB diagnosis and treatment of TB/HIV-coinfected patients and prompts for urgent TB and HIV care integration.


PLOS ONE | 2013

Whole Genome Sequencing Reveals Complex Evolution Patterns of Multidrug-Resistant Mycobacterium tuberculosis Beijing Strains in Patients

Matthias Merker; Thomas A. Kohl; Andreas Roetzer; Leona Truebe; Elvira Richter; Sabine Rüsch-Gerdes; Lanfranco Fattorini; Marco R. Oggioni; Helen Cox; Francis Varaine; Stefan Niemann

Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR) variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS) to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and molecular drug resistance tests. Furthermore, high resolution WGS analysis is necessary to accurately detect exogenous re-infection as classical genotyping lacks discriminatory power in high incidence settings.


European Respiratory Journal | 2016

Compassionate use of new drugs in children and adolescents with multidrug-resistant and extensively drug-resistant tuberculosis: early experiences and challenges

Marina Tadolini; Anthony J. Garcia-Prats; Lia D'Ambrosio; Catherine Hewison; Rosella Centis; H. Simon Schaaf; Ben J. Marais; Hannetjie Ferreira; Jose A. Caminero; Sylvie Jonckheere; Animesh Sinha; Krzysztof Herboczek; Zarema Khaidarkhanova; Armen Hayrapetyan; Naira Khachatryan; Ia Urtkmelidze; Carolina Loreti; Susanna Esposito; Alberto Matteelli; Jennifer Furin; Francis Varaine; Giovanni Battista Migliori

The World Health Organization (WHO) estimated that 480 000 new multidrug-resistant (MDR) tuberculosis (TB) cases occurred globally in 2014, with 190 000 deaths. Limited data are available on the burden of MDR-TB in children. A recent systematic review estimated that 32 000 children acquire MDR-TB annually; of these, very few are correctly diagnosed and provided with appropriate treatment [1]. First experience and challenges of compassionate use of new anti-TB drugs to treat MDR- and XDR-TB in children http://ow.ly/SWXF300a0UX


Clinical Infectious Diseases | 2008

Bleach Sedimentation: An Opportunity to Optimize Smear Microscopy for Tuberculosis Diagnosis in Settings of High Prevalence of HIV

Maryline Bonnet; Andrew Ramsay; W. Githui; Laramie Gagnidze; Francis Varaine; Philippe J Guerin

BACKGROUND The purpose of the study was to evaluate the performance and feasibility of tuberculosis diagnosis by sputum microscopy after bleach sedimentation, compared with by conventional direct smear microscopy, in a setting of high prevalence of HIV. METHODS In a community-based study in Kenya (a population in which 50% of individuals with tuberculosis are infected with HIV), individuals with suspected pulmonary tuberculosis submitted 3 sputum specimens during 2 consecutive days, which were examined by blind evaluation. Ziehl-Neelsen-stained smears were made of fresh specimens and of specimens that were processed with 3.5% household bleach followed by overnight sedimentation. Two different cutoffs for acid-fast bacilli (AFB) per 100 high-power fields (HPF) were used to define a positive smear: >10 AFB/100 HPF and 1 AFB/100 HPF. Four smear-positive case definitions, based on 1 or 2 positive smears with the 1 AFB or 10 AFB cutoff, were used. RESULTS Of 1879 specimens from 644 patients, 363 (19.3%) and 460 (24.5%) were positive by bleach sedimentation microscopy, compared with 301 (16.0%) and 374 (19.9%) by direct smear microscopy, with use of the 10 AFB/100 HPF (P < .001) and 1 AFB/100 HPF (P < .001) cutoffs, respectively. Regardless of the case definition used, bleach sedimentation microscopy detected significantly more positive cases than did direct smear microscopy: 26.7% (172 of 644) versus 21.7% (140 of 644), respectively, with the case definition of 1 positive smear and the 1 AFB/100 HPF cutoff (P < .001), and 21.4% (138 of 644) versus 18.6% (120 of 644), respectively, with the case definition of 1 positive smear and the 10 AFB/100 HPF cutoff (P < .001). Inter- and intrareader reproducibility were favorable, with kappa coefficients of 0.83 and 0.91, respectively. Bleach sedimentation was relatively inexpensive and was not time consuming. CONCLUSIONS Bleach sedimentation microscopy is an effective, simple method to improve the yield of smear microscopy in a setting of high prevalence of HIV. Further evaluation of this method, under operational conditions, is urgently needed to determine its potential as a tool for tuberculosis control.


Journal of Clinical Microbiology | 2005

Cetyl-Pyridinium Chloride Is Useful for Isolation of Mycobacterium tuberculosis from Sputa Subjected to Long-Term Storage

Manuela Pardini; Francis Varaine; Elisabetta Iona; Erchanik Arzumanian; Francesco Checchi; Marco R. Oggioni; Graziella Orefici; Lanfranco Fattorini

ABSTRACT Recovery of Mycobacterium tuberculosis from sputa treated with cetyl-pyridinium chloride (CPC) and stored for 20 ± 9 days was significantly higher than that from sputa that were untreated and processed by the N-acetyl-l-cisteine-NaOH method. Addition of CPC is useful for isolation of M. tuberculosis from sputa subjected to long-term storage received from remote areas of the world.


Infection and Drug Resistance | 2015

New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid.

Grania Brigden; Cathy Hewison; Francis Varaine

The current treatment for drug-resistant tuberculosis (TB) is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB). Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis.

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Maryline Bonnet

Institut de recherche pour le développement

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Cathy Hewison

Médecins Sans Frontières

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Maryline Bonnet

Institut de recherche pour le développement

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Andrew Ramsay

Liverpool School of Tropical Medicine

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W. Githui

Kenya Medical Research Institute

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Lanfranco Fattorini

Istituto Superiore di Sanità

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Helena Huerga

Médecins Sans Frontières

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Philipp du Cros

Médecins Sans Frontières

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