Fatalities Associated with Ingestion of Diethylene
Glycol-Contaminated Glycerin Used to Manufacture Acetaminophen
Syrup -- Haiti, November 1995-June 1996
From November 1995 through June 1996, acute anuric renal
failure was diagnosed in 86 children (aged 3 months-13 years) in
Haiti; most (85%) children were aged less than or equal to 5 years.
On June 14, 1996, a joint investigation was initiated by the
Ministry of Health of Haiti, the University General Hospital in
Port-au-Prince, the Pan American Health Organization/World Health
Organization, the Caribbean Epidemiology Center, and CDC. This
report summarizes the preliminary findings of this ongoing
investigation, which indicate that this outbreak was associated
with diethylene glycol (DEG)-contaminated glycerin used to
manufacture acetaminophen syrup.
Most cases were characterized by a nonspecific febrile
prodromal illness followed within 2 weeks by anuric renal failure,
pancreatitis, hepatitis, and neurologic dysfunction progressing to
coma. Ten children were transferred to medical centers in the
United States for intensive care and dialysis; nine are still
living. Of the 76 children who remained in Haiti, only one is known
to have survived. Histopathology of kidney tissue from four
patients indicated acute tubular necrosis with regeneration
consistent with a toxic exposure.
The investigation indicated that at least 79% of patients had
consumed one of two locally manufactured acetaminophen syrup
preparations ("Afebril" and "Valodon"), which were subsequently
found to contain DEG. On June 22, the Ministry of Health of Haiti
issued an alert to parents not to administer these products and
prohibited their sale. The manufacturing company announced a recall
of these and other syrup products it produces. Following the recall
and an ongoing public information campaign, the number of new cases
declined sharply; the last reported case-patient was admitted to a
hospital on June 29. The traceback investigation, which is being
conducted in collaboration with the U.S. Food and Drug
Administration (FDA), indicates that glycerin used in the
formulation of these syrups was contaminated with DEG. The
contaminated glycerin was imported to Haiti from another country.
Reported by: R Malebranche, MD, Minister of Health, C Hecdivert,
Ministry of Health; A Lassegue, MD, S St. Victor, MD, R Derosena,
MD, K Denerville, MD, CH St. Amand, MD, D Severe, MD, E Compas, MD,
P Cleophat, MD, JH Buteau, MD, D Fabien, MD, J Colimon, MD, RI
Verdier, MD, Univ General Hospital, Port-au-Prince; M Cayemitte,
MD, MF Placide, MD, Child Health Institute of Haiti. J Hospedales,
MD, M Lewis, PhD, Caribbean Epidemiology Center; M-A Diouf, MD, S
Garcia, MD, Pan American Health Organization/World Health
Organization, Haiti. R Parekh, MD, T Bunchman, MD, Univ of
Michigan, Ann Arbor. L Racusen, MD, Johns Hopkins Univ, Baltimore.
Food and Drug Administration. Health Studies Br, Div of
Environmental Hazards and Health Effects, National Center for
Environmental Health; Childhood and Respiratory Diseases Br, Div of
Bacterial and Mycotic Diseases, National Center for Infectious
Diseases, CDC.
Editorial Note
Editorial Note: DEG, a known nephrotoxin and hepatotoxin, is used
in industrial solvents and antifreeze. The mechanism of toxicity is
unknown but probably is different from oxalate toxicity associated
with ethylene glycol poisoning. Management of patients with DEG
toxicity relies on early diagnosis with supportive and symptomatic
care for multi-organ failure. Although data on outcome are limited,
survival with resolution of signs and symptoms has been reported
(1).
The outbreak in Haiti is the fourth large outbreak associated
with pharmaceutical products contaminated with DEG. Previous
outbreaks (in the United States, Nigeria, and Bangladesh) resulted
from ingestion of DEG-contaminated sulfanilamide or acetaminophen
syrups (1-3). In two of the outbreaks, propylene glycol was the
contaminated raw material, and in a third, DEG was used as a
diluent. A cluster of 14 deaths occurred in India among patients in
one hospital who ingested DEG-contaminated glycerin used for
control of intracranial pressure (4).
Glycerin is used as a sweetener in formulations of many
pharmaceutical syrups ingested orally. Complexities in the
distribution of glycerin and other pharmaceutical raw materials
that may involve many handlers (importers and exporters) underscore
the need for manufacturers to adequately identify raw materials and
end products. However, infrared spectroscopy tests required by the
United States Pharmocopoeia (USP) would not have detected this
DEG-contaminated glycerin syrup. A gas chromatography method
capable of separating and detecting glycerin, ethylene glycol, and
DEG can be used to determine that glycerin is free of these
contaminants. The outbreak in Haiti emphasizes the need for
pharmaceutical producers worldwide to be aware of possible
contamination of glycerin and other raw materials with DEG and to
use appropriate quality-control measures to identify and prevent
potential contamination.
References
Hanif M, Mobarak MR, Ronan A, Rahman D, Donovan JJ, Bennish ML.
Fatal renal failure caused by diethylene glycol in paracetamol
elixir: the Bangladesh epidemic. Br Med J 1995;311:88-91.
Okuonghae HO, Ighogboja IS, Lawson JO, Nwana EJ. Diethylene
glycol poisoning in Nigerian children. Ann Trop Paediatr
1992;12:235-8.
Geiling EMK, Cannon PR. Pathologic effects of elixir of
sulfanilamide (diethylene glycol) poisoning. A clinical and
experimental correlation: final report. JAMA 1938;111:919-26.
Pandya SK. An unmitigated tragedy. Br Med J 1988;297:117-9.
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