On 22 June 1996, a press release from the Minister of Health of Haiti warned the public of a high number of cases detected during the past months of renal insufficiency in children. The statement went on to say that, with the cooperation of the United States Centers for Disease Control (CDC), the PAHO/WHO Country Office and the Caribbean Epidemiology Center, the cause of the outbreak was identified to be a toxic substance in two specific brands of acetaminophen (paracetamol) syrups. The Minister announced that such products would be withdrawn from pharmacy shelves by the police and warned the population against their use.
Subsequent investigation of the incident revealed that the first case occurred in November 1995. At the time of the press release, 67 cases had been identified, and 24 children had died. Kidney specimens examined in the USA showed extensive acute tubular necrosis, most likely due to a toxin. Analysis at the CDC of the medications revealed the presence of diethylene glycol. Patient bottles of Afebril and Valodon tested positive, as well as bottles for distribution and samples retained at the local factory. The identification was made by mass spectra and nuclear magnetic resonance. Once again, as in previous poisonings in the USA, Nigeria, Bangladesh and Argentina, diethylene glycol was the culprit. This chemical is a known renal and hepatotoxin and leads to acute renal failure.
Within days following the public announcement, a United States Food and Drug Administration inspector arrived in Haiti to assist in tracing the supply and distribution of the contaminated medications that were produced by the local laboratory (Pharval). His inspection revealed that there were "essentially no quality control measures in effect". A Pharval internal examination revealed contaminated glycerin raw material. Interpol was contacted for information on CTC, the supplier of the suspected shipment. Most worrisome was the finding that some barrels of glycerin from the suspected shipment were sent to other pharmacies in Haiti, where they may have been used to prepare a variety of liquid medications. On 16 July, the government shut down Pharval and prohibited the sale of all locally-made syrup medications. The suspected solvent was imported from Germany and, according to an anonymous source cited in an Associated Press article, was made in China and resold through a trader to the German company. Other sources indicated that the barrels of glycerin produced in China had been shipped to the Netherlands for a German company, sold to a Dutch company and sold again to another German company without ever having left the Netherlands, from where it was shipped to Haiti via Puerto Rico. Authorities from the USA, Germany and the Netherlands are conducting investigations to confirm the source and channels of distribution.
A WHO Alert dated 28 June was distributed worldwide based on a 25 June press release from PAHO which stated that of 68 reported cases at that date, at least 30 had died. PAHO's last press release on 3 July stated that 89 cases had been reported and at least 49 children had died. Ten children were flown to US hospitals. The number of dead children, all under 5 years, increased to 61 by 9 July, though no new confirmed cases were reported after June.
The CDC published an excellent summary of the intoxication in its Morbidity and Mortality Weekly Report of 2 August 1996. The final death toll was 77 children. On 22 August, WHO issued a second Alert on this subject that emphasized the need to be aware of possible contamination of glycerin and other raw materials with diethylene glycol. The US FDA and the Canadian Health Protection Branch, with the coordination and support of the PAHO/WHO Country Office are assisting the Haitian authorities to put in place measures aimed at implementing good manufacturing practices and quality control procedures.
This incident clearly highlights the importance for pharmaceutical manufacturers to know their sources of supply of raw materials as well as to verify the quality of the purchased materials and that of the finished products.
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