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.

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.

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.

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.

PMID:

25291378