DOCSLIB.ORG

Management of Patients with Multidrug-Resistant Tuberculosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Management of Patients with Multidrug-Resistant Tuberculosis INT J TUBERC LUNG DIS 23(6):645–662 STATE OF THE ART Q 2019 The Union http://dx.doi.org/10.5588/ijtld.18.0622 STATE OF THE ART SERIES MDR-TB Series editors: C Horsburgh, Christoph Lange and Carole Mitnick NUMBER 4 IN THE SERIES Management of patients with multidrug-resistant tuberculosis C. Lange, R. E. Aarnoutse, J. W. C. Alffenaar, G. Bothamley, F. Brinkmann, J. Costa, D. Chesov, R. van Crevel, M. Dedicoat, J. Dominguez, R. Duarte, H. P. Grobbel, G. Gunther,¨ L. Guglielmetti, J. Heyckendorf, A. W. Kay, O. Kirakosyan, O. Kirk, R. A. Koczulla, G. G. Kudriashov, L. Kuksa, F. van Leth, C. Magis-Escurra, A. M. Mandalakas, B. Molina-Moya, C. A. Peloquin, M. Reimann, R. Rumetshofer, H. S. Schaaf, T. Schon, ¨ S. Tiberi, J. Valda, P. K. Yablonskii, K. Dheda Please see Supplementary Data for details of all author affiliations. SUMMARY The emergence of multidrug-resistant tuberculosis availability of novel drugs such as bedaquiline allow us to (MDR-TB; defined as resistance to at least rifampicin design potent and well-tolerated personalised MDR-TB and isoniazid) represents a growing threat to public treatment regimens based solely on oral drugs. In this health and economic growth. Never before in the history article, we present management guidance to optimise the of mankind have more patients been affected by MDR- diagnosis, algorithm-based treatment, drug dosing and TB than is the case today. The World Health Organiza- therapeutic drug monitoring, and the management of tion reports that MDR-TB outcomes are poor despite adverse events and comorbidities, associated with MDR- staggeringly high management costs. Moreover, treat- TB. We also discuss the role of surgery, physiotherapy, ment is prolonged, adverse events are common, and the rehabilitation, palliative care and smoking cessation in majority of affected patients do not receive adequate patients with MDR-TB. We hope that incorporating treatment. As MDR-TB strains are often resistant to one these recommendations into patient care will be helpful in or more second-line anti-TB drugs, in-depth genotypic optimising treatment outcomes, and lead to more MDR- and phenotypic drug susceptibility testing is needed to TB patients achieving a relapse-free cure. construct personalised treatment regimens to improve KEY WORDS: MDR-TB; RESIST-TB; TBNET; TB; treatment outcomes. For the first time in decades, the XDR-TB; personalised treatment TUBERCULOSIS (TB) IS an airborne infectious tuberculosis has complicated TB control and subvert- disease caused by Mycobacterium tuberculosis. The ed the goals of the WHO’s End TB Strategy (95% World Health Organization (WHO) estimates that reduction in deaths due to TB and a 90% reduction in approximately 10.0 million people developed TB, TB incidence rate by the year 2035 compared to and 1.6 million people died from the disease in 2017.1 2015).2 According to WHO TB reports, the number TB is the leading cause of death attributed to a single of patients with a confirmed diagnosis of multidrug- micro-organism worldwide. resistant TB (MDR-TB; defined as resistance of M. The emergence of drug-resistant strains of M. tuberculosis to at least rifampicin [RMP] and isoniazid [INH]) has increased in the past years from ~84 000 in 2012 to ~153 000 in 2017.1 This Previous articles in the series Editorial: Horsburgh C. The MDR-TB development is only partly explained by better epidemic—a status report. Int J Tuberc Lung Dis 2019; 23: 121. Articles: No 1: Cox V, Cox H, Pai M, Stillo J, Citro B, Brigden G. Health care gaps in diagnostic capacities. The estimated total burden of the global burden of drug-resistant tuberculosis. Int J Tuberc Lung Dis patients with MDR-TB is much higher and has 2019; 23: 125–135. No 2: Nathavitharana R R, Lederer P, Tierney D B, Nardell E. Treatment as prevention and other interventions to reduce increased from 450 000 in 2012 to 458 000 in transmission of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2017.1 Extensively drug-resistant TB (XDR-TB), 2019; 23: 396–404. No 3: E. A. Kendall, S. Sahu, M. Pai, et al. What will it really take to eliminate drug-resistant tuberculosis? Int J Tuberc Lung defined as MDR-TB plus resistance to a fluoroquin- Dis 2019; 23: 535–546. olone (FQ) and at least one second-line injectable Correspondence to: Christoph Lange, Clinical Infectious Diseases, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany. e-mail: [email protected] Article submitted 9 September 2018. Final version accepted 2 January 2019. 646 The International Journal of Tuberculosis and Lung Disease agent (amikacin [AMK], capreomycin [CPM] or drugs. To date, gDST is not a fully adequate substitute kanamycin [KM]), was identified in patients from for pDST. For pDST, critical (media-specific) concen- 127 countries in 2017.1 trations (Lowenstein-Jensen,¨ Middlebrook 7H10 or The highest estimated prevalence of MDR-TB is in BACTEC MGITe960e [BD, Sparks, MD, USA]) are India and China. However, the largest number of used to separate susceptible from resistant isolates. patients who have been diagnosed with MDR-TB live One of the limitations of critical concentrations is in the European Region of the WHO. In Belarus, that they treat a continuous variable as though it were Kazakhstan, Kyrgyzstan, the Republic of Moldova, binary. Critical concentrations for anti-TB drugs were the Russian Federation and Ukraine, more than 25% recently revised for second-line drugs, including of all new patients who have not received treatment bedaquiline (BDQ) and delamanid (DLM).19 These for TB in the past, have MDR-TB.1 Less than one phenotypic methods rely on growth of mycobacterial third of notified TB patients worldwide are evaluated culture in the presence of a single drug concentration. with drug susceptibility testing (DST) for RMP; only Although this is not yet a WHO-endorsed method, half of patients with RMP resistance or MDR-TB the minimal inhibitory concentrations (MICs) for 12 undergo DST for FQs and second-line injectable first- and second-line drugs can be determined with drugs.1 Only 20% of MDR-TB cases have access to the Sensititre MycoTB microdilution assay (MY- adequate treatment.3,4 It is predicted that the number COTB; Trek Diagnostic Systems, Cleveland, OH, of patients with MDR-TB and XDR-TB in high- USA).38 burden countries will continue to rise in the coming The Xpertw MTB/RIF assay (Cepheid, Sunnyvale, decades.5 CA, USA) is a frontline gDST, aimed to diagnose TB Treatment for MDR-TB is challenging for patients, and detect RMP resistance.39 Xpertw MTB/RIF Ultra relatives, healthcare providers and health systems.6 (Cepheid) was recently shown to have higher The level of drug resistance of the causative strain of sensitivity but slightly lower specificity than Xpert M. tuberculosis can be highly variable.7 Depending in diagnosing TB, while the performance of the two on the DST results, current WHO treatment recom- tests in detecting RMP resistance was similar (sensi- mendations range from 9 to 20 months of daily tivity 98%).40 combination antibiotic treatment.8 The treatment is DNA sequencing and line-probe assays (LPAs) characterised by a high frequency of adverse drug represent other gDST techniques and are widely used events, often leading to changes in the regimen.9 Due for the detection of resistance to the key drugs—RMP, to high costs, some of the second-line drugs are not INH, the FQs, and second-line injectable drugs. LPAs available in countries where they are needed most.10 for first-line drugs (GenoTypew MTBDRplusV2 Despite all of our efforts, according to the latest [Hain Lifesciences, Nehren, Germany]; Nipro WHO report, only 55% of patients with MDR-TB NTMþMDRTB [Nipro, Osaka, Japan] and AID TB and 34% of patients with XDR-TB achieve a Resistance [Aid Diagnostika, Straberg, Germany) and successful treatment outcome.1 Treatment outcomes second-line drugs (GenoTypew MTBDRsl V2.0 in MDR-TB and XDR-TB are highly dependent upon [Nehren] and AID TB Resistance) have been endorsed available resources. It was recently shown that by the WHO for the detection of drug resistance.14 relapse-free cure-rates in patients with M/XDR-TB The most promising gDST technology is next- can be similar to patients with drug-susceptible TB generation whole-genome sequencing (WGS), which (DS-TB) when sufficient resources are provided,11 allows the simultaneous detection of known resis- and treatment can be personalised.12 tance mutations to all drugs. Emerging reports The aim of the present article is to update previous indicate that WGS can be routinely performed in TBNET (Tuberculosis Network European Trials) early positive MGIT (Mycobacteria Growth Indica- recommendations on the optimal management of tor Tube) culture and potentially directly from patients with M/XDR-TB.6 selected clinical samples,32,41 predicting drug resis- tance in high agreement with pDST. Some of the more common genomic mutations can be associated with MYCOBACTERIUM TUBERCULOSIS DRUG particular MIC ranges.42,43 SUSCEPTIBILITY TESTING Xpert and LPAs together currently target the most The two main methods to identify the best choice of frequently detected and established drug resistance drugs for individualised treatment are phenotypic mutations (Table 1). Treatment regimens that can be DST (pDST; i.e., detecting the growth of an isolate in designed using results obtained with each molecular media containing a specific drug) and genotypic DST test vary greatly.43 Regimens that are designed using (gDST; i.e., detecting established resistance muta- LPAs and/or Xpert
Load more

Recommended publications
  • Bacille Calmette–Guérin Vaccination: the Current Situation in Europe
    EDITORIAL BCG VACCINATION POLICY IN EUROPE | Bacille Calmette–Gue´rin vaccination: the current situation in Europe Masoud Dara1,5, Colleen D. Acosta1,5, Valiantsin Rusovich2, Jean Pierre Zellweger3, Rosella Centis4 and Giovanni Battista Migliori4 on behalf of the WHO EURO Childhood Task Force members6 Affiliations: 1World Health Organization Regional Office for Europe, Copenhagen, Denmark. 2World Health Organization Country Office, Minsk, Belarus. 3Swiss Lung Association, Vaud section (LPVD), Lausanne, Switzerland. 4World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy. 5These authors contributed equally. 6For a list of the WHO EURO Childhood Task Force members and their affiliations, please see the acknowledgements section. Correspondence: G.B. Migliori, World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Via Roncaccio 16, 21049, Tradate, Italy. E-mail: [email protected] @ERSpublications A WHO EURO Task Force provides the latest evidence and a coherent policy to use BCG vaccination in Europe http://ow.ly/pusIU Tuberculosis is a major public health priority. This is not only because of its daunting morbidity and mortality rates, both globally and in Europe (summarised in figs 1 and 2)[1, 3–5], but also because of the natural history of the disease. Active (contagious) tuberculosis disease occurs after a period of latency (or subclinical infection), and different risk factors [6–13], in combination with latent infection, introduce challenges to prevention, diagnosis and treatment of the disease. Vaccination against tuberculosis, if effective, would be therefore critical to control and elimination strategies [14–16].
    [Show full text]
  • Companion Handbook to the WHO Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis ISBN 978 92 4 154880 9
    Companion handbookCompanion tofor the the WHO programmatic guidelines management of drug-resistant tuberculosis Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis ISBN 978 92 4 154880 9 Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis This book is a companion handbook to existing WHO policy guidance on the management of multidrug-resistant tuberculosis, including the WHO guidelines for the programmatic management of drug-resistant tuberculosis, WHO interim policy guidance on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis, and the WHO interim policy guidance on the use of delamanid in the treatment of multidrug-resistant tuberculosis which were developed in compliance with the process for evidence gathering, assessment and formulation of recommendations, as outlined in the WHO Handbook for Guideline Development (version March 2010; available at http://apps.who.int/iris/ bitstream/10665/75146/1/9789241548441_eng.pdf ). WHO Library Cataloguing-in-Publication Data Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. 1.Antitubercular agents – administration and dosage. 2.Tuberculosis, Multidrug-Resistant – drug therapy. 3.Treatment outcome. 4.Guideline. I.World Health Organization. ISBN 978 92 4 154880 9 (NLM classification: WF 360) © World Health Organization 2014 All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.
    [Show full text]
  • Evans Sagwa Aukje K
    Optimizing the Safety of Multidrug-resistant Tuberculosis Therapy in Namibia Evans L. Sagwa Sagwa, EL Optimizing the Safety of Multidrug-resistant Tuberculosis Therapy in Namibia Thesis Utrecht University -with ref.- with summary in Dutch Copyright © 2017 EL Sagwa. All rights reserved. The research presented in this PhD thesis was conducted under the umbrella of the Utrecht World Health Organization (WHO) Collaborating Centre for Pharmaceutical Policy and Regulation, which is based at the Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht Uni- versity, The Netherlands. The Collaborating Centre aims to develop new methods for independent pharmaceutical policy research, evidence-based policy analysis and conceptual innovation in the area of policy making and evaluation in general. ISBN: 978-94-92683-40-3 Layout and printed by: Optima Grafische Communicatie, Rotterdam, the Netherlands Optimizing the Safety of Multidrug-resistant Tuberculosis Therapy in Namibia Verbeteren van de veiligheid van de behandeling van multiresistente tuberculose in Namibië (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op donderdag 24 augustus 2017 des middags te 12.45 uur door Evans Luvaha Sagwa geboren op 17 november 1972 te Kakamega, Kenia Promotor: Prof.dr. H.G.M. Leufkens Copromotor: Dr. A.K. Mantel-Teeuwisse A Quote by Donna Flagg: When the Cure Is Worse Than the Disease “Not only are the folks popping these pills not happy, but they now suffer from new problems that are caused by the drugs themselves”.
    [Show full text]
  • *TREATMENT of Lepro.SY with DIASONE-A PRELIMINARY REPORT
    SUNGEI BULOH LEPER HOSPITAL 17 lepers. They certainly threatened to do so with a regularity that never became monotonous. Indeed I canot recall a week during which they did not threaten to bomb-out or machine gun the whole settlement, The reason why the Japanese confined them­ selves to threats is simply told. The leper settlement contained patients from all over .the Federated Malay States. Under the British regime these various states paid so much per head per day for their lepers maintained at Sungei Buloh. This payment was continued under th.e occupation for the Japanese, terrified of infectious disease, would rather levy money than risk the return of lepers to their various districts. Except for a token payment for the maintenance ot Sungei Buloh this money was retained by the local Japanese Governor for his own use. It will be realised that if he retained one shilling per head per day (which is about correct) for a thousand patients, he was making' a profit of fifteen hundred pounds per month. And so the lepers were spared-they were profitable. When the end came the hospital wards were empty, for no-one was left able to care for the sick. Like wraiths over the untended paths, the patients came out of their houses with un­ certain eyes and waivering gait, to welcome their liberators. *TREATMENT OF LEPRo.SY WITH DIASONE-A PRELIMINARY REPORT By G. H. FAGET, M.D. and R. C. POGGE, M.D., Carville, La. Recently a number of new derivatives of diamino diphenyl sulfone have been tried in the chemotherapy.
    [Show full text]
  • International Standards for Tuberculosis Care (ISTC)
    INTERNATIONAL STANDARDS FOR Tuberculosis Care DIAGNOSIS TREATMENT PUBLIC HEALTH 3RD EDITION, 2014 Developed by TB CARE I with funding by the United States Agency for International Development (USAID) TB CARE I Organizations Disclaimer: The Global Health Bureau, Office of Health, Infectious Disease and Nutrition (HIDN), US Agency for International Development, financially supports this publication through TB CARE I under the terms of Agreement No. AID-OAA-A-10-00020. This publication is made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of TB CARE I and do not necessarily reflect the views of USAID or the United States Government. Suggested citation: TB CARE I. International Standards for Tuberculosis Care, Edition 3. TB CARE I, The Hague, 2014. Contact information: Philip C. Hopewell, MD Curry International Tuberculosis Center University of California, San Francisco San Francisco General Hospital San Francisco, CA 94110, USA Email: [email protected] Available at the following web sites: http://www.tbcare1.org/publications http://www.istcweb.org http://www.currytbcenter.ucsf.edu/international http://www.who.int/tb/publications To access a mobile version of ISTC, go to www.walimu.org/istc INTERNATIONAL STANDARDS FOR Tuberculosis Care DIAGNOSIS TREATMENT PUBLIC HEALTH 3RD EDITION, 2014 Table of Contents Acknowledgments . 1 List of Abbreviations . 2 Preface . 4 Summary . 8 Introduction . 14 Standards for Diagnosis
    [Show full text]
  • The Antidepressant Sertraline Provides a Novel Host Directed Therapy Module For
    bioRxiv preprint doi: https://doi.org/10.1101/2020.05.26.115808; this version posted November 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 The antidepressant sertraline provides a novel host directed therapy module for 2 augmenting TB therapy 3 Deepthi Shankaran1,2, Anjali Singh1,2, Stanzin Dawa1,2, Prabhakar A1,2, Sheetal Gandotra1,2, Vivek 4 Rao1,2* 5 1-CSIR- Institute of genomics and Integrative Biology, Mathura Road, New Delhi-110025 6 India. 7 2- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India 8 *Corresponding author: Tel: +91 11 29879229, E-mail: [email protected] 9 Key words: Mycobacterium tuberculosis/ host directed therapy/ antidepressant/ sertraline 10 Running Title: Sertraline augments antimycobacterial therapy 11 12 ABSTRACT: 13 A prolonged therapy, primarily responsible for development of drug resistance by Mycobacterium 14 tuberculosis (Mtb), obligates any new TB regimen to not only reduce treatment duration but also 15 escape pathogen resistance mechanisms. With the aim of harnessing the host response in 16 providing support to existing regimens, we used sertraline (SRT) to stunt the pro-pathogenic type 17 I IFN response of macrophages to infection. While SRT alone could only arrest bacterial growth, 18 it effectively escalated the bactericidal activities of Isoniazid (H) and Rifampicin (R) in 19 macrophages. This strengthening of antibiotic potencies by SRT was more evident in conditions 20 of ineffective control by these frontline TB drug, against tolerant strains or dormant Mtb. SRT, 21 could significantly combine with standard TB drugs to enhance early pathogen clearance from 22 tissues of mice infected with either drug sensitive/ tolerant strains of Mtb.
    [Show full text]
  • Protocol for the Treatment of Tuberculosis (TB)
    Protocol QH-HSDPTL-040-3:2013 Effective Date: 01 July 2013 Review Date: 01 July 2016 Supersedes: New Protocol Health Service Directive – Tuberculosis Management Protocol for the Treatment of Tuberculosis 1. Purpose This protocol describes the mandatory steps to be taken in the treatment of tuberculosis (TB) cases in Queensland. The goal of clinical management of a TB case is to interrupt TB transmission, prevent acquisition of drug resistance, and cure the patient. 2. Scope This Protocol applies to all Hospital and Health Service (HHS) employees and organisations and individuals acting as an agent HHS’s (including Visiting Medical Officers and other partners, contractors, consultants and volunteers). 3. Process for the Diagnosis and Treatment of Tuberculosis 3.1 Case Management Model of Care • Each metropolitan or regional Tuberculosis Control Unit (TBCU) is to manage each TB case diagnosed within their jurisdiction under a case management team model • The TBCU case management team is responsible for the overall management of the patient which involves the TBCU checking that treatment regimens are correct and that appropriate follow up has been performed, and that all essential data has been provided by the treating team • The medical officer of the relevant TBCU is responsible for review of TB treatment regimens, in collaboration with the treating doctor, to ensure therapy adheres to best practice principles provided case has been notified to the TBCU. 3.1.1 Case Management Team • The case management team is comprised of the treating
    [Show full text]
  • Drug-Resistant Tuberculosis 2020: Where We Stand
    applied sciences Review Drug-Resistant Tuberculosis 2020: Where We Stand Angelo Iacobino , Lanfranco Fattorini * and Federico Giannoni Istituto Superiore di Sanità, Department of Infectious Diseases, Via Regina Elena 299, 00161 Rome, Italy; [email protected] (A.I.); [email protected] (F.G.) * Correspondence: [email protected] Received: 3 March 2020; Accepted: 15 March 2020; Published: 22 March 2020 Featured Application: This comprehensive overview of drug-resistant tuberculosis will be useful for researchers to expand their knowledge beyond mechanisms other than chromosomal mutations, and for the development of novel drugs/drug combinations, hoping to shorten the therapy of the disease. Abstract: The control of tuberculosis (TB) is hampered by the emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, defined as resistant to at least isoniazid and rifampin, the two bactericidal drugs essential for the treatment of the disease. Due to the worldwide estimate of almost half a million incident cases of MDR/rifampin-resistant TB, it is important to continuously update the knowledge on the mechanisms involved in the development of this phenomenon. Clinical, biological and microbiological reasons account for the generation of resistance, including: (i) nonadherence of patients to their therapy, and/or errors of physicians in therapy management, (ii) complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, resulting in resistance development,
    [Show full text]
  • End TB Strategy
    THE END TB STRATEGY G lobal strategy and targets for tuberculosis prevention, care and control after 2015a [A67/11 – 14 March 2014] THE END TB STRATEGY Global strategy and targets for tuberculosis prevention, care and control after 2015a [A67/11 – 14 March 2014] WHO’s declaration of tuberculosis as a global In May 2012, Member States at the Sixty- public health emergency in 1993 ended a fifth World Health Assembly requested the period of prolonged global neglect. Together, DirectorGeneral to submit a comprehensive the subsequent launch of the directly observed review of the global tuberculosis situation treatment, short course (DOTS) strategy; to date, and to present new multisectoral inclusion of tuberculosis-related indicators strategic approaches and new international in the Millennium Development Goals; targets for the post-2015 period to the Sixty- development and implementation of the seventh World Health Assembly in May 2014, Stop TB Strategy that underpins the Global through the Executive Board.b The work to Plan to Stop TB 2006–2015; and adoption of prepare this has involved a wide range of resolution WHA62.15 on the prevention and partners providing substantive input into the control of multidrug-resistant tuberculosis and development of the new strategy, including extensively drug-resistant tuberculosis by the high-level representatives of Member States, Sixty-second World Health Assembly have all national tuberculosis programmes, technical helped to accelerate the global expansion of and scientific institutions, financial partners tuberculosis care and control. and development agencies, civil society, nongovernmental organizations, and the private sector. b See document WHA65/2012/REC/3, summary record of the a See resolution WHA67.1.
    [Show full text]
  • Diagnosis and Epidemiology of Zoonotic Nontuberculous Mycobacteria Among Dromedary Camels and Household Members in Samburu County, Kenya
    DIAGNOSIS AND EPIDEMIOLOGY OF ZOONOTIC NONTUBERCULOUS MYCOBACTERIA AMONG DROMEDARY CAMELS AND HOUSEHOLD MEMBERS IN SAMBURU COUNTY, KENYA LUCAS LUVAI AZAALE ASAAVA (M. Sc.) I84/29435/2014 A THESIS SUBMITTED IN FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF DOCTOR OF PHILOSOPHY (IMMUNOLOGY) IN THE SCHOOL OF PURE AND APPLIED SCIENCES OF KENYATTA UNIVERSITY SEPTEMBER, 2020 ii DECLARATION iii DEDICATION To my parents, family, relatives, and friends. iv ACKNOWLEDGEMENTS I sincerely acknowledge the mentorship, guidance and support from my supervisors Professor Michael M. Gicheru, Kenyatta University and, Dr. Willie A. Githui, Head, Tuberculosis Research laboratory, CRDR, KEMRI. My gratitude goes to the both of them for their guidance in shaping this study through their technical input from conception, fieldwork, laboratory analysis and preparation of this thesis. I wish to thank Kenyatta University for the tutorial fellowship and am greatly indebted to NACOSTI and NRF for the PhD research grant received without which this study would not have been possible. Special thanks to Dr. Willie Githui for accepting to host me at the TB Research Laboratory, CRDR, KEMRI and for material support without which this study would have been impossible. My sincere gratitude goes to Ernest Juma and Ruth Moraa, for guiding me through TB laboratory diagnostic techniques. Special thanks to Kenneth Waititu and Rose Kahurai of Institute of Primate Research- National Museums of Kenya, pathology laboratory for guiding me through histopathology. Special thanks to my field assistants Benedict Lesimir, Adan Halakhe, Leon Lesikoyo as well as the Samburu County veterinary team who were very resourceful. Special thanks to Moses Mwangi and Edwin Mwangi for guiding me through study design, data management and statistical analysis of my data.
    [Show full text]
  • Complete Thesis
    University of Groningen Improving treatment outcomes of tuberculosis Pradipta, Ivan DOI: 10.33612/diss.113506043 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2020 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Pradipta, I. (2020). Improving treatment outcomes of tuberculosis: towards an antimicrobial stewardship program. University of Groningen. https://doi.org/10.33612/diss.113506043 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page
    [Show full text]
  • Multidrug Therapy Against Leprosy
    Multidrug therapy against leprosy Development and implementation over the past 25 years World Health Organization Geneva 2004 WHO Library Cataloguing-in-Publication Data Multidrug therapy against leprosy : development and implementation over the past 25 years / [editor]: H. Sansarricq. 1.Leprosy - drug therapy 2.Leprostatic agents - therapeutic use 3.Drug therapy, Combination 4.Health plan implementation - trends 5.Program development 6.World Health Organization I.Sansarricq, Hubert. ISBN 92 4 159176 5 (NLM classification: WC 335) WHO/CDS/CPE/CEE/2004.46 © World Health Organization 2004 All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. The named authors alone are responsible for the views expressed in this publication. Printed by the WHO Document Production Services, Geneva, Switzerland Contents ________________________________________________ Acknowledgements ……………………………………………………………….
    [Show full text]