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.

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

Outbreak of Fatal Childhood Lead Poisoning Related to Artisanal Gold Mining in Northwestern Nigeria, 2010.

Background: In May 2010, a team of national and international organizations was assembled to investigate children's deaths due to lead poisoning in villages in northwestern Nigeria. Objectives: To determine the cause of the childhood lead poisoning outbreak, investigate risk factors for child mortality, and identify children aged <5 years in need of emergency chelation therapy for lead poisoning. Methods: We administered a cross-sectional, door-to-door questionnaire in two affected villages, collected blood from children aged 2-59 months, and soil samples from family compounds. Descriptive and bivariate analyses were performed with survey, blood-lead, and environmental data. Multivariate logistic regression techniques were used to determine risk factors for childhood mortality. Results: We surveyed 119 family compounds. One hundred eighteen of 463 (25%) children aged <5 years had died in the last year. We tested 59% (204/345) of children, aged <5 years, and all were lead poisoned (≥10 µg/dL); 97% (198/204) of children had blood-lead levels ≥45 µg/dL, the threshold for initiating chelation therapy. Gold ore was processed inside two-thirds of the family compounds surveyed. In multivariate modeling significant risk factors for death in the previous year from suspected lead poisoning included: the child's age, the mother performing ore-processing activities, community well as primary water source, and the soil-lead concentration in the compound. Conclusion: The high levels of environmental contamination, percentage of children aged <5 years with elevated blood-lead levels (97%, >45 µg/dL), and incidence of convulsions among children prior to death (82%) suggest that most of the recent childhood deaths in the two surveyed villages were caused by acute lead poisoning from gold ore-processing activities. Control measures included environmental remediation, chelation therapy, public health education, and control of mining activities

Association of blood lead level with neurological features in 972 children affected by an acute severe lead poisoning outbreak in Zamfara State, northern Nigeria.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. METHODS AND FINDINGS: We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 µg/dL) to 22.95, 95%CI 10.54-49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years, both vs 3-5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. INTERPRETATION: Increasing VBLL (from ≥80 µg/dL) and age 1-<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols

Flow chart for the engagement of imams in the poliomyelitis eradication initiative.

<p>A flow chart illustrating the different groups that facilitated the recruitment of the Jumu'a (Friday) and regular prayer imams into the PEI. Double-direction arrows indicate collaboration or consultation, while single-direction arrows denote selection or application.</p

Prevalence and Risk Factors of Elevated Blood Lead in Children in Gold Ore Processing Communities, Zamfara, Nigeria, 2012

Background. In March 2010, Medecins Sans Frontieres/Doctors Without Borders detected an outbreak of acute lead poisoning in Zamfara State, northwestern Nigeria, linked to low-technology gold ore processing. The outbreak killed more than 400 children ≤5 years of age in the first half of 2010 and has left more than 2,000 children with permanent disabilities. Objectives. The aims of this study were to estimate the statewide prevalence of children ≤5 years old with elevated blood lead levels (BLLs) in gold ore processing and non-ore-processing communities, and to identify factors associated with elevated blood lead levels in children. Methods. A representative, population-based study of ore processing and non-ore-processing villages was conducted throughout Zamfara in 2012. Blood samples from children, outdoor soil samples, indoor dust samples, and survey data on ore processing activities and other lead sources were collected from 383 children ≤5 years old in 383 family compounds across 56 villages. Results. 17.2% of compounds reported that at least one member had processed ore in the preceding 12 months (95% confidence intervals (CI): 9.7, 24.7). The prevalence of BLLs ≥10 μg/dL in children ≤5 years old was 38.2% (95% CI: 26.5, 51.4) in compounds with members who processed ore and 22.3% (95% CI: 17.8, 27.7) in compounds where no one processed ore. Ore processing activities were associated with higher lead concentrations in soil, dust, and blood samples. Other factors associated with elevated BLL were a child's age and sex, breastfeeding, drinking water from a piped tap, and exposure to eye cosmetics. Conclusions. Childhood lead poisoning is widespread in Zamfara State in both ore processing and non-ore-processing settings, although it is more prevalent in ore processing areas. Although most children's BLLs were below the recommended level for chelation therapy, environmental remediation and use of safer ore processing practices are needed to prevent further exposures. Patient consent. Obtained Ethics approval. The study protocol was approved by the US Centers for Disease Control Institutional Review Board-A and the National Health Research Ethics Committee of Nigeria. Competing Interests. The authors declare no competing financial interests

Poliomyelitis-prevalent states of northern Nigeria.

<p>A line map of Nigeria showing the states (gold) where incident poliomyelitis cases were detected.</p

Pattern of occurrence of cases of wild poliovirus and circulating vaccine-derived poliovirus in Nigeria from 2009 to 2013.

<p>This figure summarizes the number of incident (A) WPV and (B) cVDPV cases in Nigeria during the period from 2009 to 2013. The color scheme represents the increasing intensity of incidence from white (zero) to light yellow, to gold, to orange, to red, and to dark red.</p

Prevalence and Determinants of Childhood Lead Poisoning in Zamfara State, Nigeria

Background. Lead poisoning is a great public health concern in the Nigerian state of Zamfara due to widespread gold ore mining by artisan miners using rudimentary and unsafe processing techniques. Children aged ≤6 years are especially vulnerable to lead poisoning, which accounts for 0.6% of the global burden of disease. We undertook this study to find out the prevalence and determinants of childhood lead poisoning in Kawaye, a village located in Zamfara’s Anka local government area (LGA). Methods. We conducted a cross-sectional study in April 2013. Using simple random sampling technique, 307 eligible children aged ≤6 years were recruited. Data were collected using interviewer-administered semi-structured questionnaires. Blood specimens were collected via venous draw for blood lead level (BLL) assessment and soil at individual households was tested for presence of lead contamination using a portable X-ray fluorescence spectrometer. Statistical tests of Chi-square and multivariable logistic regression analyses were performed to evaluate factors potentially associated with elevated childhood BLL (≥5 μg/dL). Results. A total of 307 children ≤6 years old were sampled, with males constituting 51% of the total (171). Mean age of children = 38.5 months ± 18.5 SD. Parents/guardians of the studied children were predominantly farmers (37%) and miners (15%), with 53.7% having some informal education while 4.2% had no education. Processing of ore within the living compound was reported by 4% of the miners; 7.5% returned home wearing working clothes; 7.2% brought tools home. Thirty percent of parents/guardians were living below the poverty line. The prevalence of lead poisoning (BLL ≥5 μg/dL) among the children studied was 92.5%, with 34 children (11.1%) having BLL ≥45 μg/dL. Fourteen percent of the households had soil lead levels >400 mg/kg. Being age 24–35 months, having childhood anemia, using kohl eye cosmetic and the combination of father’s/guardian’s low level of education and low socioeconomic status were found to be significant risk factors associated with childhood lead poisoning in the regression analyses. Conclusions. The prevalence of childhood lead poisoning was high in Kawaye, which may be attributable to widespread unsafe mining and ore processing activities in the community. We recommended beginning treatment in all cases where severe lead poisoning was identified, and that further targeted interventions should be designed to address the identified risk factors in order to control and prevent further lead poisoning in the village and the state at large. Competing Interests. The authors declare no competing financial interests

Mixed model of ECP using nested random effects for a 19-d (7 d TDS + 12 d BD) DMSA chelation course (<i>n = </i>2,285 in unadjusted analysis; <i>n = </i>2,262 in adjusted analysis limited to patients with data on all covariates).

<p>A positive value of ECP indicates an increase in VBLL; a negative value of ECP indicates a decrease in VBLL. DOT by clinic staff; non-DOT doses administered by caretaker.</p><p>*Total patients in unadjusted analyses<i> = </i>2,285. Final model (<i>n = </i>2,262) excludes those with missing data (1%).</p>†<p>Adjusted for all other variables shown in the table.</p>‡<p>An end-course VBLL was accepted if up to 2 d before and up to 10 d after last dose of DMSA.</p><p>Mixed model of ECP using nested random effects for a 19-d (7 d TDS + 12 d BD) DMSA chelation course (<i>n = </i>2,285 in unadjusted analysis; <i>n = </i>2,262 in adjusted analysis limited to patients with data on all covariates).</p

Histogram of latest VBLL during the entire study period as a percentage of pre-chelation VBLL per child.

<p>As the role of repeated courses on combined overall change cannot be extracted, change includes effect of all courses (e.g., 5-d and CaNa₂EDTA courses). This does not represent the end of treatment in most cases, but rather an interim measure at the end of the study period.</p