Description of 3,180 Courses of Chelation with Dimercaptosuccinic Acid in Children less than or equal to 5 y with Severe Lead Poisoning in Zamfara, Northern Nigeria: A Retrospective Analysis of Programme Data

• Published in: PLoS medicine Vol. 11; no. 10
• Main Authors: Thurtle, Natalie, Greig, Jane, Cooney, Lauren, Amitai, Yona, Ariti, Cono, Brown, Mary Jean, Kosnett, Michael J, Moussally, Krystel, Sani-Gwarzo, Nasir, Akpan, Henry, Shanks, Leslie, Dargan, Paul I
• Format: Journal Article
• Language: English
• Published: 07.10.2014
• ISSN: 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1001739

Jane Greig and colleagues from the medical humanitarian organization Medecins Sans Frontieres describe the use of the oral chelating agent dimercaptosuccinic acid (DMSA) in several thousand young children with severe lead poisoning as a result of an environmental disaster in Zamfara, northern Nigeria. Please see later in the article for the Editors' Summary In 2010, Medecins Sans Frontieres (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 less than or equal to 5 y of age with severe paediatric lead intoxication reported to date to our knowledge. In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children less than or equal to 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 greater than or equal to 45 mu g/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 greater than or equal to 80 mu g/dl and greater than or equal to 120 mu g/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 less than or equal to 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 Lead, a toxic metal that occurs naturally in the earth's crust, is now present throughout the environment because of human activities. For many years, lead was added to paint and gasoline and used in solder for water pipes. In addition, the mining, smelting, and refining of some metallic ores releases lead into the environment. Inhalation of contaminated air, consumption of contaminated food and water, and contact with dust that contains lead raises venous blood lead levels (VBLLs) and causes many health problems, particularly in children. Children who ingest large amounts of lead can develop anemia, muscle weakness, kidney damage, and life-threatening encephalopathy (brain swelling). Although fatal lead poisoning is now rare in resource-rich countries, it nevertheless remains a major global health problem. Over a three-month period in early 2010, for example, about 400 young children died in Zamfara State, Nigeria, from unexplained, intractable fits. By May 2010, it was clear that recently expanded gold mining had caused widespread environmental lead contamination in the region, and an environmental management program was begun to reduce lead levels in the surface soils. In response to the lead poisoning outbreak, the not-for-profit organization Medecins Sans Frontieres (MSF) began a medical management program to reduce VBLLs that included treatment with the oral chelation agent dimercaptosuccinic acid (DMSA). Chelation agents bind metal ions and facilitate their removal from the body, thereby reducing the likelihood of lead moving from the blood to the brain. Lead encephalopathy has been commonly treated by injecting another chelator called CaNa2EDTA, but the discovery of more than 1,000 cases of childhood lead poisoning in rural villages in Nigeria meant that MSF needed a chelation approach that could be applied rapidly in a remote resource-limited setting. Additionally, although CaNa2EDTA has been in common use for severe lead poisoning for longer than DMSA, and is commonly recommended in guidelines, the evidence base does not support one treatment as superior. Here, in a retrospective analysis of MSF program data, the researchers evaluate the changes in VBLLs before and after courses of oral DMSA treatment in children aged five years and below living in Zamfara to gain new insights into this understudied treatment for severe childhood lead poisoning. The researchers measured VBLLs before and after treatment with DMSA in 1,156 children (inpatient and outpatient) with high amounts of lead in their blood who underwent one or more courses of chelation treatment lasting 19 or 28 days by calculating each child's end-course VBLL as a percentage of the child's pre-course VBLL (ECP). Considering all the treatment courses given between June 2010 and June 2011, the mean (average) ECP was 74.5%. That is, on average,...