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
Type of Spiritual Experience
A description of the experience
PLoS Med. 2014 Oct 7;11(10):e1001739. doi: 10.1371/journal.pmed.1001739. eCollection 2014.
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.
Thurtle N1, Greig J2, Cooney L1, Amitai Y3, Ariti C4, Brown MJ5, Kosnett MJ6, Moussally K1, Sani-Gwarzo N7, Akpan H8, Shanks L1, Dargan PI9.
- 1Médecins Sans Frontières, Amsterdam, Holland.
- 2Médecins Sans Frontières, London, United Kingdom.
- 3Department of Management, Bar Ilan University, Ramat Gan, Israel.
- 4London School of Hygiene & Tropical Medicine, London, United Kingdom.
- 5Healthy Homes/Lead Poisoning Prevention Program, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
- 6Division of Clinical Pharmacology and Toxicology, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado, United States of America.
- 7Department of Public Health, Federal Ministry of Health, Abuja, Nigeria.
- 8Federal Ministry of Health, Abuja, Nigeria; Federal Ministry of Communication Technology, Abuja, Nigeria.
- 9Médecins Sans Frontières, Amsterdam, Holland; Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
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.
METHODS AND FINDINGS:
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.
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.