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2. Does BCG vaccination protect against infection with M. tuberculosis?

Author

Pelzer, P. T., Smit, Y., Tiemersma, E. W., Huong, N. T., Nhung, N. V., Cobelens, F., Global Health, Graduate School, AII - Infectious diseases, APH - Methodology, APH - Global Health, and APH - Quality of Care

Subjects
Pulmonary and Respiratory Medicine, Infectious Diseases, tuberculosis, tuberculin skin test, BCG, vaccine efficacy, infection
Abstract

BACKGROUND: Protection against infection by the bacille Calmette-Guérin vaccine against Mycobacterium tuberculosis remains a subject of controversy. We investigated the association between BCG vaccination at birth and infection by M. tuberculosis.MATERIAL and METHODS: This was a secondary analysis of data from tuberculin skin test (TST) surveys in Vietnamese schoolchildren between 1988 and 2001. We investigated whether a BCG scar was associated with a lower prevalence of TST positivity, adjusting for BCG-induced variation by varying cut-off values for a positive TST.RESULTS: We found a positive association between BCG scar and TST positivity. The strength of the association decreased with increasing TST cut-off values; however, it never inverted significantly, irrespective of geographic region and survey year.CONCLUSION: In Vietnam, BCG vaccination was not associated with reduced M. tuberculosis infection prevalence as measured using TST. This in contrary to a similar study conducted in Tanzania. These contradictory findings may be explained by geographical differences and the relatively high prevalence in Vietnam of the M. tuberculosis Beijing genotype, which is reported to be capable of circumventing BCG-induced immunity.

Published
2022
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3. Country differences and determinants of yield in programmatic migrant TB screening in four European countries

Author

Menezes, D., primary, Zenner, D., additional, Aldridge, R., additional, Anderson, S. R., additional, de Vries, G., additional, Erkens, C., additional, Marchese, V., additional, Matteeli, A., additional, Muzyamba, M., additional, Nederby-Öhd, J., additional, van Rest, J., additional, Spruijt, I., additional, Were, J., additional, Lönnroth, K., additional, Abubakar, I., additional, and Cobelens, F., additional

Published
2022
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4. Drivers determining active TB screening yield in different European screening programmes: a comparative analysis.

Author

Zenner, D, primary, Brals, D, additional, Erkens, C, additional, Matteeli, A, additional, Nederby Öhd, J, additional, Menezes, D, additional, De Vries, G, additional, Muzyamba, M, additional, Van Rest, J, additional, Marchese, V, additional, Aldridge, R, additional, Spruijt, I, additional, Were, J, additional, Anderson, S, additional, Lönnroth, K, additional, Abubakar, I, additional, and Cobelens, F, additional

Published
2022
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6. Baseline assessment of pharmacovigilance activities in four sub-Saharan African countries: a perspective on tuberculosis.

Author

Tiemersma, EW, Ali, I, Alemu, A, Avong, YK, Duga, A, Elagbaje, C, Isah, A, Kay, A, Mmbaga, BT, Mmari, E, Mwamwitwa, K, Nhlabatsi, S, Sintayehu, K, Arefayne, A, Teferi, M, Cobelens, F, Härmark, L, Tiemersma, EW, Ali, I, Alemu, A, Avong, YK, Duga, A, Elagbaje, C, Isah, A, Kay, A, Mmbaga, BT, Mmari, E, Mwamwitwa, K, Nhlabatsi, S, Sintayehu, K, Arefayne, A, Teferi, M, Cobelens, F, and Härmark, L

Abstract

BACKGROUND: New medicines have become available for the treatment of drug-resistant tuberculosis (DR-TB) and are introduced in sub-Saharan Africa (SSA) by the national TB programs (NTPs) through special access schemes. Pharmacovigilance is typically the task of national medicines regulatory agencies (NMRAs), but the active drug safety monitoring and management (aDSM) recommended for the new TB medicines and regimens was introduced through the NTPs. We assessed the strengths and challenges of pharmacovigilance systems in Eswatini, Ethiopia, Nigeria and Tanzania, focusing on their capacity to monitor safety of medicines registered and not registered by the NMRAs for the treatment of DR-TB. METHODS: Assessment visits were conducted to all four countries by a multidisciplinary team. We used a pharmacovigilance indicator tool derived from existing tools, interviewed key stakeholders, and visited health facilities where DR-TB patients were treated with new medicines. Assessment results were verified with the local NMRAs and NTPs. RESULTS: Most countries have enabling laws, regulations and guidelines for the conduct of pharmacovigilance by the NMRAs. The relative success of NTP-NMRA collaboration is much influenced by interpersonal relationships between staff. Division of roles and responsibilities is not always clear and leads to duplication and unfulfilled tasks (e.g. causality assessment). The introduction of aDSM has increased awareness among DR-TB healthcare providers. CONCLUSION: aDSM has created awareness about the importance of pharmacovigilance among NTPs. In the future, a push for conducting pharmacovigilance through public health programs seems useful, but this needs to coincide with increased collaboration with between public health programs and NMRAs with clear formulation of roles and responsibilities.

Published
2021

7. Monocyte-to-lymphocyte ratio as a predictor of TB among people living with HIV

Author

Gatechompol, S., Sophonphan, J., Kerr, S.J., Ubolyam, S., Avihingsanon, A., van Leth, F., Cobelens, F., Gatechompol, S., Sophonphan, J., Kerr, S.J., Ubolyam, S., Avihingsanon, A., van Leth, F., and Cobelens, F.

Abstract

B A C K G R O U N D: Diagnostic tools to identify incipient or subclinical TB stages will be helpful for preventive intervention. A simple biomarker to predict TB may be the monocytes to lymphocytes ratio (ML ratio) in peripheral blood. M E T H O D S: We assessed the relationship between multiple time-updated ML ratio measurements and incidence of TB in people living with HIV (PLWH) after antiretroviral therapy (ART) was initiated. The ML ratio was updated at least every 6 months. TB incidence with corresponding 95% confidence intervals stratified according to time-updated ML ratio was calculated using ML ratio in quartiles. R E S U L T S: A total of 1305 PLWH were included in the analyses: 46 had incident TB and 1259 remained TB-free. The TB incidence rate was 10.3 (95% CI 7.1–14.9) cases/1000 patient-years (PYR) among participants with ML ratio ≥0.25 compared with 1.1/1000 PYR (95% CI 0.4–2.9) among those with ML ratio,0.15. At cut-point 0.23, the ML ratio provided a diagnostic area under the receiver operating characteristics curve (AROC) of 0.849 (95% CI 0.784–0.914) and a sensitivity of 85% and specificity of 71%. C O N C L U S I O N: Increased ML ratio was predictive of incident TB among PLWH on or after ART. The ML ratio can be a simple tool to stratify the risk of TB in PLWH.

Published
2021
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11. The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: a cluster randomised trial

Author

Von Seidlein, L, Peto, TJ, Landier, J, Nguyen, T-N, Tripura, R, Phommasone, K, Pongvongsa, T, Lwin, KM, Keereecharoen, L, Kajeechiwa, L, Thwin, MM, Parker, DM, Wiladphaingern, J, Nosten, S, Proux, S, Corbel, V, Tuong-Vy, N, Phuc-Nhi, TL, Son, DH, Huong-Thu, PN, Tuyen, NTK, Tien, NT, Dong, LT, Hue, DV, Quang, HH, Nguon, C, Davoeung, C, Rekol, H, Adhikari, B, Henriques, G, Phongmany, P, Suangkanarat, P, Jeeyapant, A, Vihokhern, B, Van Der Pluijm, RW, Lubell, Y, White, LJ, Aguas, R, Promnarate, C, Sirithiranont, P, Malleret, B, Rénia, L, Onsjö, C, Chan, XH, Chalk, J, Miotto, O, Patumrat, K, Chotivanich, K, Hanboonkunupakarn, B, Jittmala, P, Kaehler, N, Cheah, PY, Pell, C, Dhorda, M, Imwong, M, Snounou, G, Mukaka, M, Peerawaranun, P, Lee, SJ, Simpson, JA, Pukrittayakamee, S, Singhasivanon, P, Grobusch, MP, Cobelens, F, Smithuis, F, Newton, PN, Thwaites, GE, Day, NPJ, Mayxay, M, Hien, TT, Nosten, FH, Dondorp, AM, White, NJ, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Department of Infectious Diseases [Amsterdam, Netherlands] (Academic Medical Center), University of Amsterdam [Amsterdam] (UvA)-Center for Tropical and Travel Medicine [Amsterdam, Netherlands], Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], Savannakhet Provincial Health Department [Lao People’s Democratic Republic], Savannakhet Province [Lao People’s Democratic Republic], Department of Clinical Tropical Medicine [Bangkok, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok], Department of Population Health and Disease Prevention [Irvine, CA, USA], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institute of Malariology, Parasitology, and Entomology [Ho Chi Minh City, Vietnam] (IMPE), Center for Malariology, Parasitology and Entomology [Ninh Thuan Province, Vietnam] (CMPE), Institute of Malariology, Parasitology, and Entomology [Quy Nhon, Vietnam] (IMPE), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Provincial Health Department [Battambang, Cambodia] (PHD), Department of Pathogen Molecular Biology [London, UK], London School of Hygiene and Tropical Medicine (LSHTM), WWARN Asia Regional Centre [Bangkok, Thailand], Department of Microbiology & Immunology [Singapore] (Yong Loo Lin School of Medicine), National University of Singapore (NUS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Department of Oncology, Clinical and Experimental Medicine, Faculty of Health Sciences [Linköping University ], Linköping University (LIU), Wellcome Trust Sanger Institute [Hinxton, UK], Department of Molecular Tropical Medicine and Genetics [Bangkok, Thailand] (Faculty of Tropical Medicine), Department of Tropical Hygiene [Bangkok, Thailand] (Faculty of Tropical Medicine), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Epidemiology and Biostatistics [Victoria, Australia], University of Melbourne-Melbourne School of Population and Global Health [Victoria, Australia], Royal Society of Thailand [Bangkok, Thailand], Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Institute of Research and Education Development [Vientiane, Lao People’s Democratic Republic], University of Health Sciences [Vientiane, Laos] (UHS), NJW is the recipient of the Wellcome Trust Award Number: 101148/Z/13/Z. AMD is the recipient of the Bill and Melinda Gates Foundation Award Number: OPP1081420. JAS is the recipient of the National Health and Medical Research Council Award Number: 1104975., Dupuis, Christine, Mahidol Oxford Tropical Medicine Research Unit, University of Oxford [Oxford]-Mahidol University [Bangkok], University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust, Shoklo Malaria Research Unit [Mae Sot, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok]-Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Wellcome Trust, Laboratoire de Lutte contre les Insectes Nuisibles, National Institute of Malariology, Parasitology and Entomology, National Center for Parasitology, Entomology, and Malaria Control, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Faculty of Tropical Medicine [Bangkok, Thailand], University of Oxford [Oxford], Faculty of Tropical Medicine, University of Oxford-Mahidol University [Bangkok], National Institute of Malariology, Parasitology and Entomology [Hanoi] (NIMPE), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], University of Oxford [Oxford]-University of Oxford [Oxford], University of California [Irvine] (UCI), University of California-University of California, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, APH - Global Health, APH - Methodology, Global Health, Infectious diseases, APH - Health Behaviors & Chronic Diseases, and APH - Quality of Care

Subjects
Male, Plasmodium, Myanmar, Medical and Health Sciences, Geographical Locations, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Cluster Analysis, Malaria, Falciparum, Child, Asia, Southeastern, ComputingMilieux_MISCELLANEOUS, Cross-Over Studies, Pharmaceutics, Drugs, Drug Resistance, Multiple, Vietnam, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Mass Drug Administration, Female, Cambodia, Research Article, Adult, Drug Administration, Asia, Adolescent, Elimination, Plasmodium falciparum, Microbiology, Antimalarials, Young Adult, Drug Therapy, Microbial Control, General & Internal Medicine, Parasite Groups, parasitic diseases, Parasitic Diseases, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Disease Eradication, Pharmacology, Biology and Life Sciences, Tropical Diseases, Malaria, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, People and Places, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antimicrobial Resistance, Apicomplexa
Abstract

Background The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People’s Democratic Republic, where artemisinin resistance is prevalent. Methods and findings After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention. Conclusions Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination. Trial registration ClinicalTrials.gov NCT01872702, In a cluster-randomized trial, Lorenz von Seidlin & colleagues investigate whether mass drug administration can accelerate malaria elimination in the Greater Mekong Subregion., Author summary Why was this study done? The emergence and spread of multidrug resistance in the Greater Mekong Subregion (GMS) threaten regional and global malaria control. Mass drug administrations (MDAs) are controversial but could be useful in the control and elimination of malaria. We wanted to know whether well-resourced MDAs can accelerate malaria elimination in the GMS. What did the researchers do and find? We randomised 16 villages (clusters) to receive MDAs with antimalarial drugs (dihydroartemisinin-piperaquine [DP] plus low-dose primaquine) either in year 1 or year 2 of the study. The entire village population (except pregnant women and children under the age of 6 months) was invited to take 3 consecutive daily doses of antimalarial drugs 3 times at monthly intervals. Everyone was followed up for 1 year; all malaria cases were recorded, and quarterly malaria surveys were conducted using highly sensitive high-volume PCR detection. Most (87%) of the villagers completed at least 1 round of the antimalarial drugs, which were well tolerated. The intervention had a substantial impact on the prevalence of P. falciparum infections by month 3 after the start of the MDAs. Over the subsequent 9 months, P. falciparum infections returned but stayed below baseline levels. What do these findings mean? MDAs might be a useful tool to accelerate falciparum malaria elimination in low-endemicity settings. The effectiveness of MDAs depends on continued support for village health workers, adequate drug efficacy, high levels of community participation, and carefully planned roll out to minimise the risk of malaria reintroduction.

Published
2019
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12. Active contact tracing beyond the household in multidrug resistant tuberculosis in Vietnam: a cohort study

Author

Hoang, T, Nguyen, V, Dinh, N, Thwaites, G, Nguyen, T, Van Doorn, H, Cobelens, F, Wertheim, H, Global Health, AII - Infectious diseases, APH - Global Health, APH - Methodology, and APH - Quality of Care

Subjects
Adult, Aged, 80 and over, Male, Adolescent, lcsh:Public aspects of medicine, Infant, Newborn, Infant, lcsh:RA1-1270, Middle Aged, Cohort Studies, Young Adult, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Contact tracing, Vietnam, Child, Preschool, Tuberculosis, Multidrug-Resistant, Humans, Female, Child, Multi drug resistance tuberculosis, Research Article, Aged
Abstract

Background Currently in Vietnam contact tracing for multidrug-resistant tuberculosis (MDR-TB) entails passive case finding among symptomatic household contacts who present themselves for diagnosis. Close contacts of MDR-TB cases are therefore not identified adequately. We assessed the added value of active contact tracing within and beyond households using social network questionnaires to identify close contacts of MDR-TB patients in Vietnam. Methods We conducted a cohort study using social network questionnaires in which contacts were identified by MDR-TB patients, including contacts from ‘high risk’ places like work. Contacts of MDR-TB patients were followed up and screened over a period of at least 6 months. This included two active screenings and any unscheduled passive screening of self-referred contacts during the study period. Results Four hundred seventeen contacts of 99 index cases were recruited, 325 (77.9%) and 160/417 (38.4%) contacts participated in the first and second screenings, respectively. The first screening detected one TB case but the bacteria were not MDR. From passive screening, a household contact was diagnosed with TB meningitis but not through our active approach. Social network analysis showed that only 1/17 (5.9%) high-risk places agreed to cooperate and were included in the screening, and no MDR-TB cases were detected. There were two pairs of index cases (identified separately) who were found to be contacts of each other and who had been diagnosed before the study started. Conclusions No new MDR-TB cases were detected using social network analysis of nearly 100 MDR-TB index cases, likely due to a relatively short follow up time, and loss to follow up (lack of cooperation from contacts or high risk places and lack of available resources in the National Tuberculosis Control Programme). Electronic supplementary material The online version of this article (10.1186/s12889-019-6573-z) contains supplementary material, which is available to authorized users.

Published
2019

15. Active contact tracing beyond the household in multidrug resistant tuberculosis in Vietnam: a cohort study

Author

Hoang, T.T., Nguyen, V.N., Dinh, N.S., Thwaites, G., Nguyen, Tat T., Doorn, H.R. van, Cobelens, F., Wertheim, H.F.L., Hoang, T.T., Nguyen, V.N., Dinh, N.S., Thwaites, G., Nguyen, Tat T., Doorn, H.R. van, Cobelens, F., and Wertheim, H.F.L.

Abstract

Contains fulltext : 202911.pdf (publisher's version ) (Open Access), BACKGROUND: Currently in Vietnam contact tracing for multidrug-resistant tuberculosis (MDR-TB) entails passive case finding among symptomatic household contacts who present themselves for diagnosis. Close contacts of MDR-TB cases are therefore not identified adequately. We assessed the added value of active contact tracing within and beyond households using social network questionnaires to identify close contacts of MDR-TB patients in Vietnam. METHODS: We conducted a cohort study using social network questionnaires in which contacts were identified by MDR-TB patients, including contacts from 'high risk' places like work. Contacts of MDR-TB patients were followed up and screened over a period of at least 6 months. This included two active screenings and any unscheduled passive screening of self-referred contacts during the study period. RESULTS: Four hundred seventeen contacts of 99 index cases were recruited, 325 (77.9%) and 160/417 (38.4%) contacts participated in the first and second screenings, respectively. The first screening detected one TB case but the bacteria were not MDR. From passive screening, a household contact was diagnosed with TB meningitis but not through our active approach. Social network analysis showed that only 1/17 (5.9%) high-risk places agreed to cooperate and were included in the screening, and no MDR-TB cases were detected. There were two pairs of index cases (identified separately) who were found to be contacts of each other and who had been diagnosed before the study started. CONCLUSIONS: No new MDR-TB cases were detected using social network analysis of nearly 100 MDR-TB index cases, likely due to a relatively short follow up time, and loss to follow up (lack of cooperation from contacts or high risk places and lack of available resources in the National Tuberculosis Control Programme).

Published
2019

16. Where is the 'global' in the European Union's Health Research and Innovation Agenda?

Author

Berner-Rodoreda, A, Rehfuess, EA, Klipstein-Grobusch, K, Cobelens, F, Raviglione, M, Flahaut, A, Casamitjana, N, Fröschl, G, Skordis-Worral, J, Abubakar, I, Ashrafian, H, Agardh, A, Visser, L, Schultsz, C, Plasència, A, Jahn, A, Norton, R, Van Leeuwen, R, Hagander, L, Bärnighausen, T, Berner-Rodoreda, A, Rehfuess, EA, Klipstein-Grobusch, K, Cobelens, F, Raviglione, M, Flahaut, A, Casamitjana, N, Fröschl, G, Skordis-Worral, J, Abubakar, I, Ashrafian, H, Agardh, A, Visser, L, Schultsz, C, Plasència, A, Jahn, A, Norton, R, Van Leeuwen, R, Hagander, L, and Bärnighausen, T

Abstract

Global Health has not featured as prominently in the European Union (EU) research agenda in recent years as it did in the first decade of the new millennium, and participation of low-income and middle-income countries (LMICs) in EU health research has declined substantially. The Horizon Europe Research and Innovation Framework adopted by the European Parliament in April 2019 for the period 2021-2027 will serve as an important funding instrument for health research, yet the proposed health research budget to be finalised towards the end of 2019 was reduced from 10% in the current framework, Horizon 2020, to 8% in Horizon Europe. Our analysis takes the evolvement of Horizon Europe from the initial framework of June 2018 to the framework agreed on in April 2019 into account. It shows that despite some improvements in terms of Global Health and reference to the Sustainable Development Goals, European industrial competitiveness continues to play a paramount role, with Global Health research needs and relevant health research for LMICs being only partially addressed. We argue that the globally interconnected nature of health and the transdisciplinary nature of health research need to be fully taken into account and acted on in the new European Research and Innovation Framework. A facilitated global research collaboration through Horizon Europe could ensure that Global Health innovations and solutions benefit all parts of the world including EU countries.

Published
2019

17. The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial

Author

Beeson, JG, von Seidlein, L, Peto, TJ, Landier, J, Thuy-Nhien, N, Tripura, R, Phommasone, K, Pongvongsa, T, Lwin, KM, Keereecharoen, L, Kajeechiwa, L, Thwin, MM, Parker, DM, Wiladphaingern, J, Nosten, S, Proux, S, Corbel, V, Nguyen, T-V, Truong, LP-N, Do, HS, Pham, NH-T, Nguyen, TKT, Nguyen, TT, Le, TD, Dao, VH, Huynh, HQ, Nguon, C, Davoeung, C, Rekol, H, Adhikari, B, Henriques, G, Phongmany, P, Suangkanarat, P, Jeeyapant, A, Vihokhern, B, van der Pluijm, RW, Lubell, Y, White, LJ, Aguas, R, Promnarate, C, Sirithiranont, P, Malleret, B, Renia, L, Onsjo, C, Chan, XH, Chalk, J, Miotto, O, Patumrat, K, Chotivanich, K, Hanboonkunupakarn, B, Jittmala, P, Kaehler, N, Cheah, PY, Pell, C, Dhorda, M, Imwong, M, Snounou, G, Mukaka, M, Peerawaranun, P, Lee, SJ, Simpson, JA, Pukrittayakamee, S, Singhasivanon, P, Grobusch, MP, Cobelens, F, Smithuis, F, Newton, PN, Thwaites, GE, Day, NPJ, Mayxay, M, Tran, TH, Nosten, FH, Dondorp, AM, White, NJ, Beeson, JG, von Seidlein, L, Peto, TJ, Landier, J, Thuy-Nhien, N, Tripura, R, Phommasone, K, Pongvongsa, T, Lwin, KM, Keereecharoen, L, Kajeechiwa, L, Thwin, MM, Parker, DM, Wiladphaingern, J, Nosten, S, Proux, S, Corbel, V, Nguyen, T-V, Truong, LP-N, Do, HS, Pham, NH-T, Nguyen, TKT, Nguyen, TT, Le, TD, Dao, VH, Huynh, HQ, Nguon, C, Davoeung, C, Rekol, H, Adhikari, B, Henriques, G, Phongmany, P, Suangkanarat, P, Jeeyapant, A, Vihokhern, B, van der Pluijm, RW, Lubell, Y, White, LJ, Aguas, R, Promnarate, C, Sirithiranont, P, Malleret, B, Renia, L, Onsjo, C, Chan, XH, Chalk, J, Miotto, O, Patumrat, K, Chotivanich, K, Hanboonkunupakarn, B, Jittmala, P, Kaehler, N, Cheah, PY, Pell, C, Dhorda, M, Imwong, M, Snounou, G, Mukaka, M, Peerawaranun, P, Lee, SJ, Simpson, JA, Pukrittayakamee, S, Singhasivanon, P, Grobusch, MP, Cobelens, F, Smithuis, F, Newton, PN, Thwaites, GE, Day, NPJ, Mayxay, M, Tran, TH, Nosten, FH, Dondorp, AM, and White, NJ

Abstract

BACKGROUND: The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent. METHODS AND FINDINGS: After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, th

Published
2019

18. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement

Author

Domínguez J, Boettger E C, Cirillo D, Cobelens F, Eisenach K D, Gagneux S, Hillemann D, Horsburgh R, Molina-Moya B, Niemann S, Tortoli E, Whitelaw A, and Lange C

Abstract

The emergence of drug resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture based methods have been regarded as the gold standard for drug susceptibility testing (DST) molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG inhA rpoB embB rrs rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients pending the results of in vitro DST. However false positive and false negative results in detecting resistance associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

Published
2016
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23. Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

Author

Bastos, Mayara L., Hussain, Hamidah, Weyer, Karin, Garcia-Garcia, Lourdes, Leimane, Vaira, Leung, Chi Chiu, Narita, Masahiro, Penã, Jose M., Ponce-de-Leon, Alfredo, Seung, Kwonjune J., Shean, Karen, Sifuentes-Osornio, José, Van der Walt, Martie, Van der Werf, Tjip S., Yew, Wing Wai, Menzies, Dick, Ahuja, S., Ashkin, D., Avendaño, M., Banerjee, R., Bauer, M., Becerra, M., Benedetti, A., Burgos, M., Centis, R., Chan, E.D., Chiang, C.Y., Cobelens, F., Cox, H., D'Ambrosio, L., de Lange, W.C.M., DeRiemer, K., Enarson, D., Falzon, D., Flanagan, K., Flood, J., Gandhi, N., Garcia-Garcia, L., Granich, R.M., Hollm-Delgado, M.G., Holtz, T.H., Hopewell, P., Iseman, M., Jarlsberg, L.G., Keshavjee, S., Kim, H.R., Koh, W.J., Lancaster, J., Lange, C., Leimane, V., Leung, C.C., Li, J., Menzies, D., Migliori, G.B., Mitnick, C.M., Narita, M., Nathanson, E., Odendaal, R., O'Riordan, P., Pai, M., Palmero, D., Park, S.K., Pasvol, G., Pena, J., Pérez-Guzmán, C., Ponce-de-Leon, A., Quelapio, M.I.D., Quy, H.T., Riekstina, V., Robert, J., Royce, S., Salim, M., Schaaf, H.S., Seung, K.J., Shah, L., Shean, K., Shim, T.S., Shin, S.S., Shiraishi, Y., Sifuentes-Osornio, J., Sotgiu, G., Strand, M.J., Sung, S.W., Tabarsi, P., Tupasi, T.E., Vargas, M.H., van Altena, R., van der Walt, M., van der Werf, T.S., Viiklepp, P., Westenhouse, J., Yew, W.W., and Yim, J.J.

Abstract

The clinical validity of drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line antituberculosis drugs is uncertain. In an individual patient data meta-analysis of 8955 patients with confirmed multidrug-resistant tuberculosis, DST results for these drugs were associated with treatment outcomes

Published
2017

25. Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs

Author

Bastos, Mayara L., Hussain, Hamidah, Weyer, Karin, Garcia-Garcia, Lourdes, Leimane, Vaira, Leung, Chi Chiu, Narita, Masahiro, Penã, Jose M., Ponce-de-Leon, Alfredo, Seung, Kwonjune J., Shean, Karen, Sifuentes-Osornio, José, Van der Walt, Martie, Van der Werf, Tjip S., Yew, Wing Wai, Menzies, Dick, Ahuja, S., Ashkin, D., Avendaño, M., Banerjee, R., Bauer, M., Becerra, M., Benedetti, A., Burgos, M., Centis, R., Chan, E.D., Chiang, C.Y., Cobelens, F., Cox, H., D'Ambrosio, L., de Lange, W.C.M., DeRiemer, K., Enarson, D., Falzon, D., Flanagan, K., Flood, J., Gandhi, N., Garcia-Garcia, L., Granich, R.M., Hollm-Delgado, M.G., Holtz, T.H., Hopewell, P., Iseman, M., Jarlsberg, L.G., Keshavjee, S., Kim, H.R., Koh, W.J., Lancaster, J., Lange, C., Leimane, V., Leung, C.C., Li, J., Menzies, D., Migliori, G.B., Mitnick, C.M., Narita, M., Nathanson, E., Odendaal, R., O'Riordan, P., Pai, M., Palmero, D., Park, S.K., Pasvol, G., Pena, J., Pérez-Guzmán, C., Ponce-de-Leon, A., Quelapio, M.I.D., Quy, H.T., Riekstina, V., Robert, J., Royce, S., Salim, M., Schaaf, H.S., Seung, K.J., Shah, L., Shean, K., Shim, T.S., Shin, S.S., Shiraishi, Y., Sifuentes-Osornio, J., Sotgiu, G., Strand, M.J., Sung, S.W., Tabarsi, P., Tupasi, T.E., Vargas, M.H., van Altena, R., van der Walt, M., van der Werf, T.S., Viiklepp, P., Westenhouse, J., Yew, W.W., Yim, J.J., and Microbes in Health and Disease (MHD)

Subjects
Microbiology (medical), Drug, Adult, Male, medicine.medical_specialty, Tuberculosis, media_common.quotation_subject, Extensively Drug-Resistant Tuberculosis, PULMONARY TUBERCULOSIS, CITY, CALIFORNIA, Antitubercular Agents, drug susceptibility test, Microbial Sensitivity Tests, treatment outcomes, Pharmacology, THERAPY, Young Adult, Pharmacotherapy, Risk Factors, Internal medicine, Tuberculosis, Multidrug-Resistant, medicine, Odds Ratio, STANDARDIZED REGIMENS, MANAGEMENT, PROGRAM, Humans, COHORT, Articles and Commentaries, Ethambutol, media_common, business.industry, multidrug resistant, Extensively drug-resistant tuberculosis, Odds ratio, Pyrazinamide, Middle Aged, medicine.disease, Multiple drug resistance, meta-analysis, Infectious Diseases, Treatment Outcome, tuberculosis, Female, business, FOLLOW-UP, medicine.drug
Abstract

Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.

Published
2014

26. Abstracts of the Eighth EDCTP Forum, 6-9 November 2016.

Author

Makanga, M, Beattie, P, Breugelmans, G, Nyirenda, T, Bockarie, M, Tanner, M, Volmink, J, Hankins, C, Walzl, G, Chegou, N, Malherbe, S, Hatherill, M, Scriba, TJ, Zak, DE, Barry, CE, Kaufmann, SHE, Noor, A, Strub-Wourgaft, N, Phillips, P, Munguambe, K, Ravinetto, R, Tinto, H, Diro, E, Mahendrahata, Y, Okebe, J, Rijal, S, Garcia, C, Sundar, S, Ndayisaba, G, Sopheak, T, Ngoduc, T, Van Loen, H, Jacobs, J, D'Alessandro, U, Boelaert, M, Buvé, A, Kamalo, P, Manda-Taylor, L, Rennie, S, Mokgatla, B, Bahati, Ijsselmuiden, C, Afolabi, M, Mcgrath, N, Kampmann, B, Imoukhuede, E, Alexander, N, Larson, H, Chandramohan, D, Bojang, K, Kasaro, MP, Muluka, B, Kaunda, K, Morse, J, Westfall, A, Kapata, N, Kruuner, A, Henostroza, G, Reid, S, Alabi, A, Foguim, F, Sankarganesh, J, Bruske, E, Mfoumbi, A, Mevyann, C, Adegnika, A, Lell, B, Kranzer, K, Kremsner, P, Grobusch, M, Sabiiti, W, Ntinginya, N, Kuchaka, D, Azam, K, Kampira, E, Mtafya, B, Bowness, R, Bhatt, N, Davies, G, Kibiki, G, Gillespie, S, Lejon, V, Ilboudo, H, Mumba, D, Camara, M, Kaba, D, Lumbala, C, Fèvre, E, Jamonneau, V, Bucheton, B, Büscher, P, Chisenga, C, Sinkala, E, Chilengi, R, Chitundu, H, Zyambo, Z, Wandeler, G, Vinikoor, M, Emilie, D, Camara, O, Mathurin, K, Guiguigbaza-Kossigan, D, Philippe, B, Regassa, F, Hassane, S, Bienvenu, SM, Fabrice, C, Ouédraogo, E, Kouakou, L, Owusu, M, Mensah, E, Enimil, A, Mutocheluh, M, Ndongo, FA, Tejiokem, MC, Texier, G, Penda, C, Ndiang, S, Ndongo, J-A, Guemkam, G, Sofeu, CL, Afumbom, K, Faye, A, Msellati, P, Warszawski, J, Vos, A, Devillé, W, Barth, R, Klipstein-Grobusch, K, Tempelman, H, Venter, F, Coutinho, R, Grobbee, D, Ssemwanga, D, Lyagoba, F, Magambo, B, Kapaata, A, Kirangwa, J, Nannyonjo, M, Nassolo, F, Nsubuga, R, Yebra, G, Brown, A, Kaleebu, P, Nylén, H, Habtewold, A, Makonnen, E, Yimer, G, Burhenne, J, Diczfalusy, U, Aklillu, E, Steele, D, Walker, R, Simuyandi, M, Beres, L, Bosomprah, S, Ansumana, R, Taitt, C, Lamin, JM, Jacobsen, KH, Mulvaney, SP, Leski, T, Bangura, U, Stenger, D, De Vries, S, Zinsou, FJ, Honkpehedji, J, Dejon, JC, Loembe, MM, Bache, B, Pakker, N, Van Leeuwen, R, Hounkpatin, AB, Yazdanbakhsh, M, Bethony, J, Hotez, P, Diemert, D, Bache, BE, Fernandes, JF, Obiang, RM, Kabwende, AL, Grobusch, MP, Krishna, S, Kremsner, PG, Todagbe, AS, Nambozi, M, Kabuya, J-B, Hachizovu, S, Mwakazanga, D, Kasongo, W, Buyze, J, Mulenga, M, Geertruyden, J-P, Gitaka, J, Chan, C, Kongere, J, Kagaya, W, Kaneko, A, Kabore, N, Barry, N, Kabre, Z, Werme, K, Fofana, A, Compaore, D, Nikiema, F, Some, F, Djimde, A, Zongo, I, Ouedraogo, B, Kone, A, Sagara, I, Björkman, A, Gil, JP, Nchinda, G, Bopda, A, Nji, N, Ambada, G, Ngu, L, Tchadji, J, Sake, C, Magagoum, S, Njambe, GD, Lisom, A, Park, CG, Tait, D, Sibusiso, H, Manda, O, Croucher, K, Van Der Westhuizen, A, Mshanga, I, Levin, J, Nanvubya, A, Kibengo, F, Jaoko, W, Pala, P, Perreau, M, Namuniina, A, Kitandwe, P, Tapia, G, Serwanga, J, Yates, N, Fast, P, Mayer, B, Montefiori, D, Tomaras, G, Robb, M, Lee, C, Wagner, R, Sanders, E, Kilembe, W, Kiwanuka, N, Gilmour, J, Kuipers, H, Vooij, D, Chinyenze, K, Priddy, F, Ding, S, Hanke, T, Pantaleo, G, Ngasala, B, Jovel, I, Malmberg, M, Mmbando, B, Premji, Z, Mårtensson, A, Mwaiswelo, R, Agbor, L, Apinjoh, T, Mwanza, S, Chileshe, J, Joshi, S, Malunga, P, Manyando, C, Laufer, M, Dara, A, Niangaly, A, Sinha, I, Brodin, D, Fofana, B, Dama, S, Dembele, D, Sidibe, B, Diallo, N, Thera, M, Wright, K, Gil, J, Doumbo, O, Baraka, V, Nabasumba, C, Francis, F, Lutumba, P, Mavoko, H, Alifrangis, M, Van Geertruyden, J-P, Sissoko, S, Sangaré, C, Toure, S, Sanogo, K, Diakite, H, Doumbia, D, Haidara, K, Julé, A, Ashurst, H, Merson, L, Olliaro, P, Marsh, V, Lang, T, Guérin, P, Awuondo, K, Njenga, D, Nyakarungu, E, Titus, P, Sutamihardja, A, Lowe, B, Ogutu, B, Billingsley, P, Soulama, I, Kaboré, M, Coulibaly, A, Ouattara, M, Sanon, S, Diarra, A, Bougouma, E, Ouedraogo, A, Sombie, B, Kargougou, D, Ouattara, D, Issa, N, Tiono, A, Sirima, S, Chaponda, M, Dabira, E, Dao, F, Dara, N, Coulibaly, M, Tolo, A, Maiga, H, Ouologuem, N, Niangaly, H, Botchway, F, Wilson, N, Dickinson-Copeland, CM, Adjei, AA, Wilson, M, Stiles, JK, Hamid, MA, Awad-Elgeid, M, Nasr, A, Netongo, P, Kamdem, S, Velavan, T, Lasry, E, Diarra, M, Bamadio, A, Traore, A, Coumare, S, Soma, B, Dicko, Y, Sangare, B, Tembely, A, Traore, D, Haidara, A, Dicko, A, Diawara, E, Beavogui, A, Camara, D, Sylla, M, Yattara, M, Sow, A, Camara, GC, Diallo, S, Mombo-Ngoma, G, Remppis, J, Sievers, M, Manego, RZ, Endamne, L, Hutchinson, D, Held, J, Supan, C, Salazar, CLO, Bonkian, LN, Nahum, A, Sié, A, Abdulla, S, Cantalloube, C, Djeriou, E, Bouyou-Akotet, M, Mordmüller, B, Siribie, M, Sirima, SB, Ouattara, SM, Coulibaly, S, Kabore, JM, Amidou, D, Tekete, M, Traore, O, Haefeli, W, Borrmann, S, Kaboré, N, Kabré, Z, Nikèma, F, Compaoré, D, Somé, F, Djimdé, A, Ouédraogo, J, Chalwe, V, Miller, J, Diakité, H, Greco, B, Spangenberg, T, Kourany-Lefoll, E, Oeuvray, C, Mulry, J, Tyagarajan, K, Magsaam, B, Barnes, K, Hodel, EM, Humphreys, G, Pace, C, Banda, CG, Denti, P, Allen, E, Lalloo, D, Mwapasa, V, Terlouw, A, Mwesigwa, J, Achan, J, Jawara, M, Ditanna, G, Worwui, A, Affara, M, Koukouikila-Koussounda, F, Kombo, M, Vouvoungui, C, Ntoumi, F, Etoka-Beka, MK, Deibert, J, Poulain, P, Kobawila, S, Gueye, NG, Seda, B, Kwambai, T, Jangu, P, Samuels, A, Kuile, FT, Kariuki, S, Barry, A, Bousema, T, Okech, B, Egwang, T, Corran, P, Riley, E, Ezennia, I, Ekwunife, O, Muleba, M, Stevenson, J, Mbata, K, Coetzee, M, Norris, D, Moneke-Anyanwoke, N, Momodou, J, Clarke, E, Scott, S, Tijani, A, Djimde, M, Vaillant, M, Samouda, H, Mensah, V, Roetynck, S, Kanteh, E, Bowyer, G, Ndaw, A, Oko, F, Bliss, C, Jagne, YJ, Cortese, R, Nicosia, A, Roberts, R, D'Alessio, F, Leroy, O, Faye, B, Cisse, B, Gerry, S, Viebig, N, Lawrie, A, Ewer, K, Hill, A, Nebie, I, Tiono, AB, Sanou, G, Konate, AT, Yaro, BJ, Sodiomon, S, Honkpehedji, Y, Agobe, JCD, Zinsou, F, Mengue, J, Richie, T, Hoffman, S, Nouatin, O, Ngoa, UA, Edoa, JR, Homoet, A, Engelhon, JE, Massinga-Louembe, M, Esen, M, Theisen, M, Sim, KL, Luty, AJ, Moutairou, K, Dinko, B, King, E, Targett, G, Sutherland, C, Likhovole, C, Ouma, C, Vulule, J, Musau, S, Khayumbi, J, Okumu, A, Murithi, W, Otu, J, Gehre, F, Zingue, D, Kudzawu, S, Forson, A, Mane, M, Rabna, P, Diarra, B, Kayede, S, Adebiyi, E, Kehinde, A, Onyejepu, N, Onubogu, C, Idigbe, E, Ba, A, Diallo, A, Mboup, S, Disse, K, Kadanga, G, Dagnra, Y, Baldeh, I, Corrah, T, De Jong, B, Antonio, M, Musanabaganwa, C, Musabyimana, JP, Karita, E, Diop, B, Nambajimana, A, Dushimiyimana, V, Karame, P, Russell, J, Ndoli, J, Hategekimana, T, Sendegeya, A, Condo, J, Binagwaho, A, Okonko, I, Okerentugba, P, Opaleye, O, Awujo, E, Frank-Peterside, N, Moyo, S, Kotokwe, K, Mohammed, T, Boleo, C, Mupfumi, L, Chishala, S, Gaseitsiwe, S, Tsalaile, L, Bussmann, H, Makhema, J, Baum, M, Marlink, R, Engelbretch, S, Essex, M, Novitsky, V, Saka, E, Kalipalire, Z, Bhairavabhotla, R, Midiani, D, Sherman, J, Mgode, G, Cox, C, Bwana, D, 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Andriamihaja, R, Rasamoelina, T, Cornet, M, De Dieu Randria, MJ, Benet, T, Vanhems, P, Andrianarivelo, MR, Chirwa, U, Michelo, C, Hamoonga, R, Wandiga, S, Oduor, P, Agaya, J, Sharma, A, Cavanaugh, S, Cain, K, Mukisa, J, Mupere, E, Worodria, W, Ngom, JT, Koro, F, Godwe, C, Adande, C, Ateugieu, R, Onana, T, Ngono, A, Kamdem, Y, Ngo-Niobe, S, Etoa, F-X, Kanengoni, M, Ruzario, S, Ndebele, P, Shana, M, Tarumbiswa, F, Musesengwa, R, Gutsire, R, Fisher, K, Thyagarajan, B, Akanbi, O, Binuyo, M, Ssengooba, W, Respeito, D, Mambuque, E, Blanco, S, Mandomando, I, Cobelens, F, Garcia-Basteiro, A, Tamene, A, Topp, S, Mwamba, C, Padian, N, Sikazwe, I, Geng, E, Holmes, C, Sikombe, K, Hantuba, Czaicki, N, Simbeza, S, Somwe, P, Umulisa, M, Ilo, J, Kestelyn, E, Uwineza, M, Agaba, S, Delvaux, T, Wijgert, J, Gethi, D, Odeny, L, Tamandjou, C, Kaindjee-Tjituka, F, Brandt, L, Cotton, M, Nel, E, Preiser, W, Andersson, M, Adepoju, A, Magana, M, Etsetowaghan, A, Chilikwazi, M, Sutcliffe, C, Thuma, P, Sinywimaanzi, K, Matakala, H, Munachoonga, P, Moss, W, Masenza, IS, Geisenberger, O, Agrea, P, Rwegoshora, F, Mahiga, H, Olomi, W, Kroidl, A, Kayode, G, Amoakoh-Coleman, M, Ansah, E, Uthman, O, Fokam, J, Santoro, M-M, Musolo, C, Chimbiri, I, Chikwenga, G, Deula, R, Massari, R, Lungu, A, Perno, C-F, Ndzengue, G, Loveline, N, Lissom, A, Flaurent, T, Sosso, S, Essomba, C, Kpeli, G, Otchere, I, Lamelas, A, Buultjens, A, Bulach, D, Baines, S, Seemann, T, Giulieri, S, Nakobu, Z, Aboagye, S, Owusu-Mireku, E, Danso, E, Hauser, J, Hinic, V, Pluschke, G, Stinear, T, Yeboah-Manu, D, Elshayeb, A, Siddig, ME, Ahmed, AA, Hussien, AE, Kabwe, M, Tembo, J, Chilukutu, L, Chilufya, M, Ngulube, F, Lukwesa, C, Enne, V, Wexner, H, Mwananyanda, L, Hamer, D, Sinyangwe, S, Ahmed, Y, Klein, N, Maeurer, M, Zumla, A, Bates, M, Beyala, L, Etienne, G, Anthony, N, Benjamin, A, Ateudjieu, J, Chibwe, B, Ojok, D, Tarr, CA, Perez, GM, Omeonga, S, Kibungu, F, Meyer, A, Lansana, P, Mayor, A, Onyango, P, Van Loggerenberg, F, Furtado, T, Boggs, L, Segrt, A, Dochez, C, Burnett, R, Mphahlele, MJ, Miiro, G, Mbidde, E, Peshu, N, Kivaya, E, Ngowi, B, Kavishe, R, Maowia, M, Sandstrom, E, Ayuo, E, Mmbaga, B, Leisegang, C, Thorpe, M, Batchilly, E, N'Guessan, J-P, Kanteh, D, Søfteland, S, Sebitloane, M, Vwalika, B, Taylor, M, Galappaththi-Arachchige, H, Holmen, S, Gundersen, SG, Ndhlovu, P, Kjetland, EF, Kombe, F, Toohey, J, Pienaar, E, Kredo, T, Cham, PM, Abubakar, I, Dondeh, BL, Vischer, N, Pfeiffer, C, Burri, C, Musukwa, K, Zürcher, S, Mwandu, T, Bauer, S, Adriko, M, Mwaura, P, Omolloh, K, Jones, C, Malecela, M, Hamidu, BA, Jenner, TE, Asiedu, LJ, Osei-Atweneboana, M, Afeke, I, Addo, P, Newman, M, Durnez, L, Eddyani, M, Ammisah, N, Abas, M, Quartey, M, Ablordey, A, Akinwale, O, Adeneye, A, Ezeugwu, S, Olukosi, Y, Adewale, B, Sulyman, M, Mafe, M, Okwuzu, J, Gyang, P, Nwafor, T, Henry, U, Musa, B, Ujah, I, Agobé, JCD, Grau-Pujol, B, Sacoor, C, Nhabomba, A, Casellas, A, Quintó, L, Subirà, C, Giné, R, Valentín, A, Muñoz, J, Nikiema, M, Ky-Ba, A, Comapore, KAM, Sangare, L, Oluremi, A, Michel, M, Camara, Y, Sanneh, B, Cuamba, I, Gutiérrez, J, Lázaro, C, Mejia, R, Adedeji, A, Folorunsho, S, Demehin, P, Akinsanya, B, Cowley, G, Da Silva, ET, Nabicassa, M, De Barros, PDP, Blif, MM, Bailey, R, Last, A, Mahendradhata, Y, Gotuzzo, E, De Nys, K, Casteels, M, Nona, SK, Lumeka, K, Todagbe, A, Djima, MM, Ukpong, M, Sagay, A, Khamofu, H, Torpey, K, Afiadigwe, E, Anenih, J, Ezechi, O, Nweneka, C, Idoko, J, Muhumuza, S, Katahoire, A, Nuwaha, F, Olsen, A, Okeyo, S, Omollo, R, Kimutai, R, Ochieng, M, Egondi, T, Moonga, C, Chileshe, C, Magwende, G, Anumudu, C, Onile, O, Oladele, V, Adebayo, A, Awobode, H, Oyeyemi, O, Odaibo, A, Kabuye, E, Lutalo, T, Njua-Yafi, C, Nkuo-Akenji, T, Anchang-Kimbi, J, Mugri, R, Chi, H, Tata, R, Njumkeng, C, Dodoo, D, Achidi, E, Fernandes, J, Bache, EB, Matakala, K, Searle, K, Greenman, M, and Rainwater-Lovett, K

Published
2017

27. Role of pyrazinamide in the emergence of extensively drug-resistant tuberculosis: a multi-strain mathematical model

Author

Fofana, MO, Shrestha, S, Knight, GM, Cohen, T, White, RG, Cobelens, F, and Dowdy, DW

Abstract

Several infectious diseases of global importance-e.g., HIV infection and tuberculosis (TB)-require prolonged treatment with combination antimicrobial regimens typically involving high-potency core agents coupled with additional companion drugs that protect against the de novo emergence of mutations conferring resistance to the core agents. Often, the most effective (or least toxic) companion agents are reused in sequential (first-line, second-line, etc.) regimens. We used a multistrain model of Mycobacterium tuberculosis transmission in Southeast Asia to investigate how this practice might facilitate the emergence of extensive drug resistance, i.e., resistance to multiple core agents. We calibrated this model to regional TB and drug resistance data using an approximate Bayesian computational approach. We report the proportion of data-consistent simulations in which the prevalence of pre-extensively drug-resistant (pre-XDR) TB-defined as resistance to both first-line and second-line core agents (rifampin and fluoroquinolones)-exceeds predefined acceptability thresholds (1 to 2 cases per 100,000 population by 2035). The use of pyrazinamide (the most effective companion agent) in both first-line and second-line regimens increased the proportion of simulations in which the prevalence exceeded the pre-XDR acceptability threshold by 7-fold compared to a scenario in which patients with pyrazinamide-resistant TB received an alternative drug. Model parameters related to the emergence and transmission of pyrazinamide-resistant TB and resistance amplification were among those that were the most strongly correlated with the projected pre-XDR prevalence, indicating that pyrazinamide resistance acquired during first-line treatment subsequently promotes amplification to pre-XDR TB under pyrazinamide-containing second-line treatment. These findings suggest that the appropriate use of companion drugs may be critical to preventing the emergence of strains resistant to multiple core agents.

Published
2016

29. Cost-effectiveness of the Xpert® MTB/RIF assay for tuberculosis diagnosis in Brazil

Author

Pinto, M., Steffen, R. E., Cobelens, F., van den Hof, S., Entringer, A., Trajman, A., Global Health, and Infectious diseases

Abstract

The Xpert® MTB/RIF assay is being implemented as a substitute for sputum smear microscopy (SSM) in many low and high tuberculosis (TB) burden countries, including Brazil, a country with low multidrug resistance and moderate human immunodeficiency virus co-infection rates. Brazilian National TB Programme (NTP). We estimated the incremental cost-effectiveness ratio (ICER) of Xpert as a substitute for two SSM tests in the diagnosis of drug-susceptible TB. The costs for confirming each additional case and for avoiding treatment due to false-positive empirical diagnoses were estimated. The ICER was US$943 for each additional TB diagnosis and US$356 for each additional TB diagnosis with bacteriological confirmation, assuming 80% specificity of clinical diagnosis using both strategies. For every 100 000 patients with suspected TB, the NTP would spend an additional US$1.2 million per year to confirm 3344 more TB patients. The model was highly sensitive to specificity of clinical diagnosis after a negative test. Although the NTP has no threshold for cost-effectiveness, our model can provide support for decision makers in Brazil and other countries with a low prevalence of drug resistance among TB patients. Financial benefit can potentially be expected if physicians rely more on a negative Xpert result and empirical treatment is reduced

Published
2016

30. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement

Author

Domínguez, J, Boettger, E C, Cirillo, D, Cobelens, F, Eisenach, K D, Gagneux, S, Hillemann, D, Horsburgh, R, Molina-Moya, B, Niemann, S, Tortoli, E, Whitelaw, A, Lange, C, University of Zurich, and Domínguez, J

Subjects
10179 Institute of Medical Microbiology, 2740 Pulmonary and Respiratory Medicine, 570 Life sciences, biology, 610 Medicine & health, 2725 Infectious Diseases
Published
2016
Full Text
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32. Tuberculosis drug resistance in Southern Mozambique: results of a population-level survey in the district of Manhiça

Author

Valencia, S., primary, Respeito, D., additional, Blanco, S., additional, Ribeiro, R. M., additional, López-Varela, E., additional, Sequera, V. G., additional, Saavedra, B., additional, Mambuque, E., additional, Morillo, M. Gómez, additional, Bulo, H., additional, Cobelens, F., additional, Macete, E., additional, Alonso, P. L., additional, Caminero, J. A., additional, and García-Basteiro, A. L., additional

Published
2017
Full Text
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33. Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis

Author

Gomez, G. B., primary, Dowdy, D. W., additional, Bastos, M. L., additional, Zwerling, A., additional, Sweeney, S., additional, Foster, N., additional, Trajman, A., additional, Islam, M. A., additional, Kapiga, S., additional, Sinanovic, E., additional, Knight, G. M., additional, White, R. G., additional, Wells, W. A., additional, Cobelens, F. G., additional, and Vassall, A., additional

Published
2016
Full Text
View/download PDF

35. Challenges in detection and treatment of multidrug resistant tuberculosis patients in Vietnam.

Author

Hoang, T.T., Nguyen, N.V., Dinh, S.N., Nguyen, H.B., Cobelens, F., Thwaites, G., Nguyen, H.T., Nguyen, A.T., Wright, P., Wertheim, H.F.L., Hoang, T.T., Nguyen, N.V., Dinh, S.N., Nguyen, H.B., Cobelens, F., Thwaites, G., Nguyen, H.T., Nguyen, A.T., Wright, P., and Wertheim, H.F.L.

Abstract

Contains fulltext : 154743.pdf (publisher's version ) (Open Access)

Published
2015

36. Making innovations accessible to the poor through implementation research

Author

Squire, Bertie, Ramsay, Andrew, van den Hof, S., Millington, Kerry, Langley, Ivor, Bello, G., Kritski, A., Detjen, A., Thomson, Rachael, Cobelens, F, and Mann, Gillian

Subjects
wa_30, wa_395, wf_200
Abstract

Within countries, poorer populations have greater health needs, and less access to good medical care than better off populations. This is particularly true for tuberculosis (TB), the archetypal disease of poverty. Similarly, innovations tend to become available to better off populations well before they become available to those who need them the most. In a new era of innovations for TB diagnosis and treatment, it is increasingly important not only to be sure that these innovations can work in terms of accuracy and efficacy, but also that they will work, especially for the poor. We argue that after an innovation, or a group of innovations has been endorsed based on demonstrated accuracy and/or efficacy, introduction into routine practice should proceed through implementation by research. Cluster-randomised, pragmatic trials are suited to this approach, and permit the prospective collection of evidence needed for full impact assessment according to a previously published framework. The novel approach of linking transmission modelling with operational modelling provides a methodology for expanding and enhancing the range of evidence, and can be used alongside evidence from pragmatic implementation trials. This evidence from routine practice should then be used to ensure that innovations in TB control are used for positive action for all, and particularly the poor

Published
2011

37. Household expenditure and tuberculosis prevalence in VietNam: prediction by a set of household indicators

Author

Hoa, N. B., Tiemersma, E. W., Sy, D. N., Nhung, N. V., Gebhard, A., Borgdorff, M. W., Cobelens, F. G. J., Amsterdam institute for Infection and Immunity, Global Health, Amsterdam Public Health, Epidemiology and Data Science, and Infectious diseases

Abstract

To study the association between TB and household expenditure in a nationwide TB prevalence survey in Viet Nam using nine household characteristics. To assess the prevalence of TB in Viet Nam, a nationwide stratified cluster sample survey was conducted from 2006 to 2007. Nine household characteristics used in the second Viet Nam Living Standards Survey (VLSS) were scored per household. In the VLSS dataset, we regressed these nine characteristics against household expenditure per capita, and used the coefficients to predict household expenditure level (in quintiles) in our survey and assess its relation with TB prevalence. The prevalence of bacteriologically confirmed TB was 307 per 100 000 population in persons aged ≥15 years (95%CI 249-366). After adjustment for confounders, prevalence was found to be associated with household expenditure level: the rate was 2.5 times higher for those in the lowest household expenditure quintile (95%CI 1.6-3.9) than those in the highest quintile. With a set of nine household characteristics, we were able to predict household expenditure level fairly accurately. There was a significant association between TB prevalence rates and estimated household expenditure level, showing that TB is related to poverty in Viet Nam

Published
2011

39. National anti-tuberculosis drug resistance study in Tanzania

Author

Chonde, T. M., Basra, D., Mfinanga, S. G. M., Range, N., Lwilla, F., Shirima, R. P., Deun, A., Zignol, M., Cobelens, F. G., Egwaga, S. M., Frank van Leth, Global Health, and Infectious diseases

Subjects
Bacterial diseases, Africa, East, Mycobacterium tuberculosis, Surveys, Multidrug resistance, Assessment, National, Tanzania, Clusters, Drug resistance, Retreatment, Prevalence, Tuberculosis, Relapses
Abstract

OBJECTIVE: To assess the prevalence of anti-tuberculosis drug resistance in a national representative sample of tuberculosis (TB) patients in Tanzania according to recommended methodology. DESIGN: Cluster survey, with 40 clusters sampled proportional to size, of notified TB patients from all diagnostic centres in the country. RESULTS: The survey enrolled 1019 new and 148 re-treatment patients. The adjusted prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line drugs in new patients was 8.3%, while the prevalence of multidrug-resistant TB (MDR-TB) was 1.1%. In retreatment patients, the crude prevalence for any resistance and for MDR-TB was respectively 20.6% and 3.9%. The prevalence of drug resistance did not differ in relapse patients compared to failure patients. These estimates are among the lowest in those African countries with an estimated level of drug resistance in the last 5 years. CONCLUSION: The low levels of drug resistance in Tanzania are likely due to a well performing TB control programme and the absence of noticeable involvement of the private sector in TB treatment

Published
2010

40. Liquid culture for Mycobacterium tuberculosis: proceed, but with caution

Author

Richard Anthony, Cobelens, F. G. J., Gebhard, A., Klatser, P. R., Lumb, R., Rüsch-Gerdes, S., Soolingen, D., KIT: Biomedical Research, Global Health, and Infectious diseases

Abstract

Attempts to improve the diagnosis of tuberculosis (TB) in high-burden countries has resulted in significant funding and initiatives to change the method of diagnosis of TB from light microscopy supplemented with X-ray to a sophisticated diagnostic algorithm based on the latest technological innovations. Such activities are overdue and should be welcomed, but the lack of skills and support available to interpret and use the results represents a danger. The introduction of new diagnostic methods, particularly liquid culture, should be carefully structured according to the local situation, failing which frustration and the disruption of previously underdeveloped but adequately functioning laboratories may result

Published
2009

41. Tuberculosis prevalence surveys: rationale and cost

Author

Philippe Glaziou, Mj, Werf, Onozaki I, Dye C, Mw, Borgdorff, Cy, Chiang, Cobelens F, Da, Enarson, Pg, Gopi, Th, Holtz, Sj, Kim, van Leth F, Wj, Lew, Lonnroth K, van Maaren P, Pr, Narayanan, and Williams B

Subjects
Adult, Adolescent, Cost of Illness, Population Surveillance, Prevalence, Humans, Mass Screening, Guidelines as Topic, Middle Aged, Health Surveys, Tuberculosis, Pulmonary, Aged
Abstract

This article is the first of the educational series 'Assessing tuberculosis (TB) prevalence through population-based surveys'. The series will give overall guidance in conducting cross-sectional surveys of pulmonary TB (PTB) disease. TB prevalence surveys are most valuable in areas where notification data obtained through routine surveillance are of unproven accuracy or incomplete, and in areas with an estimated prevalence of bacteriologically confirmed TB of more than 100 per 100,000 population. To embark on a TB prevalence survey requires commitment from the national TB programme, compliance in the study population, plus availability of trained staff and financial resources. The primary objective of TB prevalence surveys is to determine the prevalence of PTB in the general population agedor=15 years. Limitations of TB prevalence surveys are their inability to assess regional or geographic differences in prevalence of TB, estimate the burden of childhood TB or estimate the prevalence of extra-pulmonary TB. The cost of a prevalence survey is typically US$ 4-15 per person surveyed, and up to US$ 25 per person with radiographic screening. A survey of 50,000 people, of limited precision, would typically cost US$ 200,000-1,250,000.

Published
2008

42. Tuberculosis prevalence surveys: rationale and cost

Author

Glaziou, P., van der Werf, M. J., Onozaki, I., Dye, C., Borgdorff, M. W., Chiang, C.-Y., Cobelens, F., Enarson, D. A., Gopi, P. G., Holtz, T. H., Kim, S. J., van Leth, F., Lew, W.-J., Lonnroth, K., van Maaren, P., Narayanan, P. R., Williams, B., Amsterdam Public Health, Epidemiology and Data Science, Infectious diseases, and Global Health

Abstract

This article is the first of the educational series 'Assessing tuberculosis (TB) prevalence through population-based surveys'. The series will give overall guidance in conducting cross-sectional surveys of pulmonary TB (PTB) disease. TB prevalence surveys are most valuable in areas where notification data obtained through routine surveillance are of unproven accuracy or incomplete, and in areas with an estimated prevalence of bacteriologically confirmed TB of more than 100 per 100,000 population. To embark on a TB prevalence survey requires commitment from the national TB programme, compliance in the study population, plus availability of trained staff and financial resources. The primary objective of TB prevalence surveys is to determine the prevalence of PTB in the general population aged >or=15 years. Limitations of TB prevalence surveys are their inability to assess regional or geographic differences in prevalence of TB, estimate the burden of childhood TB or estimate the prevalence of extra-pulmonary TB. The cost of a prevalence survey is typically US$ 4-15 per person surveyed, and up to US$ 25 per person with radiographic screening. A survey of 50,000 people, of limited precision, would typically cost US$ 200,000-1,250,000

Published
2008

43. Hiv-testbeleid bij tuberculosepatiënten in Nederland

Author

Haar, C. H., Cobelens, F. G. J., Kalisvaart, N. A., van der Have, J. J., van Deutekom, H., Global Health, and Infectious diseases

Subjects
virus diseases
Abstract

OBJECTIVE: To compare the proportion of tuberculosis patients tested for HIV infection, before and after introduction of highly active antiretroviral therapy (HAART) in the Netherlands, and to analyse predictive factors for performing an HTV-test in this population. DESIGN: Retrospective. METHOD: Whether patients had been tested for HIV, was investigated in random samples consisting of 200 patients, who were registered in the Netherlands Tuberculosis Register (NTR) in the years 1995 and 2001 respectively. RESULTS: The number of patients tested for HIV was 29 out of 84 (16%) in 1995, and 39 out of 190 (21%) in 2001 (not significant). HIV-tests had been carried out most frequently among homeless patients (71%), drug addicts (56%) and alcohol-abusing patients (60%). Significant predictive factors for HIV testing were place of residence (city), localisation of disease (pulmonary tuberculosis in combination with extrapulmonary tuberculosis) and place of origin (sub-Saharan Africa). CONCLUSION: Despite introduction of HAART during this period, in the Netherlands the proportion of tuberculosis patients tested for HIV did not significantly increase between 1995 and 2001. HIV testing was mainly limited to tuberculosis patients from risk groups

Published
2007

49. Combined species identification, genotyping, and drug resistance detection of Mycobacterium tuberculosis cultures by MLPA on a bead-based array

Author

Bergval, I., Sengstake, S., Brankova, N., Levterova, V., Abadia, E., Tadumaze, N., Bablishvili, N., Akhalaia, M., Tuin, K., Schuitema, A., Panaiotov, S., Bachiyska, E., Kantardjiev, T., Zwaan, R. de, Schurch, A., Soolingen, D. van, Hoog, A. van 't, Cobelens, F., Aspindzelashvili, R., Sola, C., Klatser, P., Anthony, R., Bergval, I., Sengstake, S., Brankova, N., Levterova, V., Abadia, E., Tadumaze, N., Bablishvili, N., Akhalaia, M., Tuin, K., Schuitema, A., Panaiotov, S., Bachiyska, E., Kantardjiev, T., Zwaan, R. de, Schurch, A., Soolingen, D. van, Hoog, A. van 't, Cobelens, F., Aspindzelashvili, R., Sola, C., Klatser, P., and Anthony, R.

Abstract

Contains fulltext : 124255.pdf (publisher's version ) (Open Access), The population structure of Mycobacterium tuberculosis is typically clonal therefore genotypic lineages can be unequivocally identified by characteristic markers such as mutations or genomic deletions. In addition, drug resistance is mainly mediated by mutations. These issues make multiplexed detection of selected mutations potentially a very powerful tool to characterise Mycobacterium tuberculosis. We used Multiplex Ligation-dependent Probe Amplification (MLPA) to screen for dispersed mutations, which can be successfully applied to Mycobacterium tuberculosis as was previously shown. Here we selected 47 discriminative and informative markers and designed MLPA probes accordingly to allow analysis with a liquid bead array and robust reader (Luminex MAGPIX technology). To validate the bead-based MLPA, we screened a panel of 88 selected strains, previously characterised by other methods with the developed multiplex assay using automated positive and negative calling. In total 3059 characteristics were screened and 3034 (99.2%) were consistent with previous molecular characterizations, of which 2056 (67.2%) were directly supported by other molecular methods, and 978 (32.0%) were consistent with but not directly supported by previous molecular characterizations. Results directly conflicting or inconsistent with previous methods, were obtained for 25 (0.8%) of the characteristics tested. Here we report the validation of the bead-based MLPA and demonstrate its potential to simultaneously identify a range of drug resistance markers, discriminate the species within the Mycobacterium tuberculosis complex, determine the genetic lineage and detect and identify the clinically most relevant non-tuberculous mycobacterial species. The detection of multiple genetic markers in clinically derived Mycobacterium tuberculosis strains with a multiplex assay could reduce the number of TB-dedicated screening methods needed for full characterization. Additionally, as a proportion of the marke

Published
2012

50. Tropische ziekten en importaandoeningen bij 1763 patiënten op de polikliniek voor Tropische Ziekten van het Academisch Medisch Centrum, Amsterdam (1996-1997)

Author

Wetsteyn, J. C., Driessen, S. O., de Vries, P. J., Cobelens, F. G., Kager, P. A., and Other departments

Abstract

OBJECTIVE: To describe an analysis of the patients seen at the Outpatient Department (OPD) for Tropical Diseases in the Academic Medical Centre, Amsterdam, during 1996 and 1997. DESIGN: Descriptive cross-sectional study. METHOD: From our database of OPD-patients the following data were analysed: age, country of birth, travel destination and most frequent complaints at presentation. These were further analysed in relation to travel destination, diagnosis and need of admission. RESULTS: In 1996 and 1997 1763 patients visited the OPD. Abdominal complaints, fever, general malaise and skin diseases were the main problems. Abdominal complaints were more often acquired in Asia, fever in sub-Saharan Africa and skin problems in South America. General malaise was not related to a specific travel destination. Abdominal complaints, fever and general malaise were more often caused by parasites, and skin problems by bacteria. Plasmodia were the most frequently encountered microbial cause. Malaria was found in 1 out of every 3 Dutch, and 9 out of every 10 Ghanaian patients with fever from Africa. CONCLUSION: The analysis of the database yielded useful information regarding patients with import diseases in the Netherlands and with respect to travellers to tropical areas

Published
2000

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