title: Doing no harm? Adverse events in a nation-wide cohort of patients with multidrug-resistant tuberculosis in Nigeria.
abstract: BACKGROUND
  Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria.
  
  
  METHODS
  This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed.
  
  
  RESULTS
  Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28-42] and median weight was 51 kg (IQR: 45-59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1-2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs.
  
  
  CONCLUSIONS
  Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated.
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Yohanna Kamabi
authors.initials: YK
authors.lastname: Avong
authors.affiliation: Médecins Sans Frontières, Operational Research Unit, Luxembourg City, Luxembourg.
authors.forename: Petros
authors.initials: P
authors.lastname: Isaakidis
authors.affiliation: Centre for International Health, University of Bergen, Bergen, Norway.
authors.forename: Sven Gudmund
authors.initials: SG
authors.lastname: Hinderaker
authors.affiliation: Médecins Sans Frontières, Operational Research Unit, Luxembourg City, Luxembourg.
authors.forename: Rafael
authors.initials: R
authors.lastname: Van den Bergh
authors.affiliation: Médecins Sans Frontières, Operational Research Unit, Luxembourg City, Luxembourg.
authors.forename: Engy
authors.initials: E
authors.lastname: Ali
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Bolajoko Oladunni
authors.initials: BO
authors.lastname: Obembe
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Ernest
authors.initials: E
authors.lastname: Ekong
authors.affiliation: Institute of Human Virology, Abuja, Nigeria; University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Clement
authors.initials: C
authors.lastname: Adebamowo
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Nicaise
authors.initials: N
authors.lastname: Ndembi
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: James
authors.initials: J
authors.lastname: Okuma
authors.affiliation: National Agency for Food and Drug Administration Control, Abuja, Nigeria.
authors.forename: Adeline
authors.initials: A
authors.lastname: Osakwe
authors.affiliation: Zankli Medical Centre, Abuja, Nigeria; Liverpool School of Tropical Medicines, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Olanrewaju
authors.initials: O
authors.lastname: Oladimeji
authors.affiliation: National Tuberculosis and Leprosy Control Program, Abuja, Nigeria.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Akang
authors.affiliation: National Tuberculosis and Leprosy Control Program, Abuja, Nigeria.
authors.forename: Joshua Olusegun
authors.initials: JO
authors.lastname: Obasanya
authors.affiliation: Damien Foundation Belgium, Nigeria Project, Ibadan, Nigeria.
authors.forename: Osman
authors.initials: O
authors.lastname: Eltayeb
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Aderonke Vivian
authors.initials: AV
authors.lastname: Agbaje
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Alash'le
authors.initials: A
authors.lastname: Abimiku
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Charles Olalekan
authors.initials: CO
authors.lastname: Mensah
authors.affiliation: Institute of Human Virology, Abuja, Nigeria.
authors.forename: Patrick Sunday
authors.initials: PS
authors.lastname: Dakum
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009549:Nigeria / Q000453:epidemiology; D060735:Pharmacovigilance; D012189:Retrospective Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology*