Outbreak of Acute Renal Failure in Panama in 2006: A Case-Control study/Flambee D'insuffisance Renale Aigue Au Panama En 2006: Etude Cas-temoin/Brote De Insuficiencia Renal Aguda En Panama En 2006: Estudio De Casos Y Controles

Introduction Diethylene glycol (DEG) is a colourless and odourless liquid and a human toxicant. It is commonly used in industry and can be found in commercial products such as resins, antifreeze, inks and glues. In addition, DEG has also been found as a contaminant of raw materials used in the production of pharmaceuticals. (1) As a result, nine known poisoning epidemics associated with DEG-contaminated medications have occurred, worldwide. (2-10) The first and largest outbreak, which resulted in 105 deaths, occurred in the United States of America (USA) in 1937 and led to the passing of the 1938 Federal Food, Drug and Cosmetic Act requiring proof of safety before drugs were introduced into the marketplace. (1) Since that time, there have been no DEG mass poisonings in the USA but many have occurred in the developing world. Most recently, paediatric medicinal syrups contaminated with DEG have led to the deaths of 33 of 36 children known to be affected in India in 1998 (10) and of 85 of 109 children known to be affected in Haiti in 1995-1996. (9) In both outbreaks, patients had unexplained acute renal failure, a characteristic of moderate-to-severe DEG poisoning. (11) In September 2006, a Panamanian physician reported an unusual number of patients with unexplained acute renal failure frequently accompanied by severe neurological dysfunction. Patients typically presented with abdominal symptoms, such as nausea, vomiting, epigastric discomfort and diarrhoea, followed several days later by oliguria or anuria, anorexia and fatigue. Many patients exhibited a spectrum of neurological effects, including cranial nerve palsies, acute flaccid extremity weakness and encephalopathy. All of the affected received health care through the Caja del Seguro Social (CSS) system. Despite dialysis, 12 out of 21 (57%) patients died. When the Ministry of Health of Panama requested assistance from the Centers for Disease Control and Prevention (CDC) in the USA in early October 2006, it remained unclear whether the agent responsible for the outbreak was infectious or toxicological. Three leading hypotheses emerged. First, an infectious etiology was suspected but subsequently ruled out because there had been no known person-to-person transmission and because various bacterial cultures and viral tests for infectious causes of acute flaccid paralysis, such as enteroviruses, arboviruses, herpes viruses and Carnpylobacter jejuni, were negative. Second, an antihypertensive medication was suspected. Approximately 2 months before the outbreak, the CSS hospital system added lisinopril to its formulary as a first-line treatment for hypertension. Astute clinicians recognized that many of the affected patients were taking angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, which resulted in a concern that the formulary change was related to the outbreak. Finally, when two affected patients presented to a specific CSS hospital with bottles of a Panamanian-produced prescription liquid cough syrup, possible contamination of this medication was suspected. Although features of the clinical presentation were consistent with DEC toxicity, the etiology was not confirmed and the source remained unknown. In October 2006, a case-control investigation was conducted to confirm the etiology and to identify the source of the outbreak. Methods Case and control patient selection Case patients were those admitted to a specific CSS hospital (Hospital A) on or after 15 August 2006 with acute renal failure of unknown etiology characterized by oliguria or anuria and a serum creatinine level [greater than or equal to] 2 mg/dl or with an acute worsening of pre-existing chronic renal failure. Control patients were those admitted to Hospital A for any cause other than renal failure. For every case patient we attempted to enrol five matched hospitalized patients as controls. Controls were randomly selected from a daily hospital census and individually matched to cases on the basis of sex, age ([+ or -] 5 years) and date of hospital admission, which had to be no more than 2 days before the admission date of the matched case patient or any time thereafter. …