title: Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data.
abstract: BACKGROUND
  In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge.
  
  
  RESULTS
  In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for.
  
  
  CONCLUSIONS
  Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary.
authors.affiliation: Médecins Sans Frontières, Amsterdam, Holland.
authors.forename: Natalie
authors.initials: N
authors.lastname: Thurtle
authors.affiliation: Médecins Sans Frontières, London, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Greig
authors.affiliation: Médecins Sans Frontières, Amsterdam, Holland.
authors.forename: Lauren
authors.initials: L
authors.lastname: Cooney
authors.affiliation: Department of Management, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Yona
authors.initials: Y
authors.lastname: Amitai
authors.affiliation: London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Cono
authors.initials: C
authors.lastname: Ariti
authors.affiliation: Healthy Homes/Lead Poisoning Prevention Program, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Mary Jean
authors.initials: MJ
authors.lastname: Brown
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kosnett
authors.affiliation: Médecins Sans Frontières, Amsterdam, Holland.
authors.forename: Krystel
authors.initials: K
authors.lastname: Moussally
authors.affiliation: Department of Public Health, Federal Ministry of Health, Abuja, Nigeria.
authors.forename: Nasir
authors.initials: N
authors.lastname: Sani-Gwarzo
authors.affiliation: Federal Ministry of Health, Abuja, Nigeria; Federal Ministry of Communication Technology, Abuja, Nigeria.
authors.forename: Henry
authors.initials: H
authors.lastname: Akpan
authors.affiliation: Médecins Sans Frontières, Amsterdam, Holland.
authors.forename: Leslie
authors.initials: L
authors.lastname: Shanks
authors.affiliation: Médecins Sans Frontières, Amsterdam, Holland; Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Paul I
authors.initials: PI
authors.lastname: Dargan
mesh_terms: D000284:Administration, Oral; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007855:Lead Poisoning / Q000097:blood / Q000188:drug therapy*; D008297:Male; D009549:Nigeria; D012189:Retrospective Studies; D004113:Succimer / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D002614:Chelating Agents; D004113:Succimer