title: Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings.
abstract: The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.
authors.affiliation: School of Medicine, University of St Andrews, St Andrews, UK.
authors.forename: W
authors.initials: W
authors.lastname: Sabiiti
authors.affiliation: Mbeya Medical Research Centre, National Institute of Medical Research, Mbeya, Tanzania.
authors.forename: B
authors.initials: B
authors.lastname: Mtafya
authors.affiliation: Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
authors.forename: D
authors.initials: D
authors.lastname: Kuchaka
authors.affiliation: Instituto Nacional de Saude, Ministerio da Saude, Maputo, Mozambique.
authors.forename: K
authors.initials: K
authors.lastname: Azam
authors.affiliation: Instituto Nacional de Saude, Ministerio da Saude, Maputo, Mozambique.
authors.forename: S
authors.initials: S
authors.lastname: Viegas
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: A
authors.initials: A
authors.lastname: Mdolo
authors.affiliation: School of Medicine, University of St Andrews, St Andrews, UK.
authors.forename: E C W
authors.initials: EC
authors.lastname: Farmer
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: M
authors.initials: M
authors.lastname: Khonga
authors.affiliation: Centre for Clinical Microbiology, University College London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Evangelopoulos
authors.affiliation: Centre for Clinical Microbiology, University College London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Honeyborne
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; German Center for Infection Research, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rachow
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; German Center for Infection Research, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Heinrich
authors.affiliation: Mbeya Medical Research Centre, National Institute of Medical Research, Mbeya, Tanzania.
authors.forename: N E
authors.initials: NE
authors.lastname: Ntinginya
authors.affiliation: Instituto Nacional de Saude, Ministerio da Saude, Maputo, Mozambique.
authors.forename: N
authors.initials: N
authors.lastname: Bhatt
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi; Institutes of Global Health & Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Davies
authors.affiliation: Instituto Nacional de Saude, Ministerio da Saude, Maputo, Mozambique.
authors.forename: I V
authors.initials: IV
authors.lastname: Jani
authors.affiliation: Centre for Clinical Microbiology, University College London, London, UK.
authors.forename: T D
authors.initials: TD
authors.lastname: McHugh
authors.affiliation: Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
authors.forename: G
authors.initials: G
authors.lastname: Kibiki
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; German Center for Infection Research, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: School of Medicine, University of St Andrews, St Andrews, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Gillespie
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D003955:Diagnostic Tests, Routine / Q000592:standards*; D016903:Drug Monitoring / Q000592:standards*; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000592:standards*; D011237:Predictive Value of Tests; D015397:Program Evaluation; D011933:Reagent Kits, Diagnostic / Q000592:standards*; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission
chemical_list: D000995:Antitubercular Agents; D011933:Reagent Kits, Diagnostic