Pediatrics: November 2008 Archives

If history has taught us anything,* it's that rogue companies will substitute the renal toxin diethylene glycol (DEG) for the more-expensive glycerin in their products—regardless of the known, lethal consequences.

The latest incident involves a Nigerian drug manufacturer, which sold a DEG-contaminated teething formula ("My Pikin") that killed 25 infants and led to the hospitalization of 10 others, according to Reuters. Reports of possible contamination began 1 week ago, and the government has since shut down the responsible company, Barewa Pharmaceuticals, in Lagos.

A list of previous discoveries of DEG in consumer goods:

• Last year, Chinese-made toothpaste was found to be contaminated with low levels of DEG. The tubes, some of which were marketed for pediatric use, were found throughout Latin America, Canada, and the United States. Most of the contaminated toothpaste in the United States was imported through Long Beach, CA. Approximately 78,000 tubes were sold and distributed by at least one importer between December 2005 and May 2007 to prisons, luxury hotels, hospitals, and discount stores. In March of this year, a Los Angeles city attorney filed criminal charges against executives from 2 LA-based importers of the tainted toothpaste. However, it is believed that the low concentration of DEG in the toothpaste, which is unlikely to be consumed in significant quantities, did not result in reportable adverse events.
• In 2006, more than 100 Panamanians died after consuming cough syrup made with contaminated Chinese glycerin. The NYT traced 46 barrels of imported glycerin stock, labeled as 99.5% pure but containing ~24% DEG, from a Panamanian port to Spain to the Taxing Glycerine Factory in the Yangtze Delta.
• In 1998, 36 Indian children developed acute renal failure after consuming a DEG-tainted cough syrup (17.5%), which was produced by a company in Gurgaon; 33 of the children died.
• Between the fall of 1995 and July 1996, 109 children in Haiti experienced acute renal failure after consuming a locally made acetaminophen syrup that was tainted with DEG (14.4%); 91 children died.
• Beginning in 1990 and for several years thereafter, unexplained renal failure was identified in several hundred Bengalese children; 70% died in hospital. Renal failure was believed to be due to the ingestion of paracetamol elixir that was contaminated with DEG.
• In 1990, 47 children died in Nigeria (again) after ingesting paracetamol syrup that was contaminated with DEG.
• In 1986, 14 hospital inpatients died in India after being given glycerol that was contaminated with DEG (18.5%).
• In 1937, more than 100 US citizens—many children—died after consuming Elixir Sulfanilamide, a raspberry-flavored antibiotic syrup manufactured by the S. E. Massengill Pharmaceutical Company of Bristol, TN. The difficult-to-dissolve antibiotic was mixed with DEG by the company's head chemist, Harold Cole Watkins, who reportedly tested the elixir only for its appearance and palatability. The catastrophic event led to the passage of the 1938 Federal Food, Drug, and Cosmetic Act.

While frequently, but mistakenly, described as a component of engine coolants, DEG is chemically related to a common antifreeze ingredient, ethylene glycol. DEG is a cheap substitute for glycerin in the manufacture of consumer products.

HT: Pharmalot

* Other than, "you can kill anybody," according to Michael Corleone in The Godfather: Part II.

Picture of bottle of DEG-tainted Elixir Sulfanilamide from the FDA.

This fall, outbreaks of the vaccine-preventable illness whooping cough (pertussis) have hit counties in Illinois, Iowa, Missouri, Minnesota, Ohio, Nebraska, and South Dakota. The latest outbreak is in Evanston, IL, just north of Chicago, where 5 cases have been confirmed and 2 are suspected, all in children younger than 12 years of age who attend different schools. In Winnebago County, IL, 38 cases of pertussis have been reported since July 1. The county reported 8 cases last year. (11/14/08 addendum: In another northern IL county, McHenry, 4 cases of pertussis during the last month were just reported.)

Since September 1, 43 cases of pertussis have been reported in Springfield, OH. The ages of those affected range from 2 months to 74 years; however, most cases have occurred in children aged 7-10 years. In 2007, 4 cases of whooping cough were documented in Clark County, OH, and 7 occurred in 2006. A report earlier this month indicates that 631 cases of pertussis have occurred in the state this year, as of November 8.

A total of 27 pertussis cases, mostly in children, were reported in 8 counties throughout South Dakota during the last month. In Nebraska, 125 cases of the disease have been confirmed so far this year, with 48 recent cases in the area of Omaha and 5 in distant Lincoln County. In 2007, 70 cases of pertussis were reported in the entire state. More than a dozen people have been diagnosed in Clarke County, IA, with pertussis, and an unspecified number of cases of whooping cough have occurred this fall in west-central Minnesota.

Outside of the Midwest, recent pertussis outbreaks have been reported in North Carolina, Arkansas, Tennessee, Kentucky, New York, and Texas. High schoolers and adults have been affected, as well as children and infants. Older individuals typically have milder disease, but they serve as a vehicle for transmission of the infectious agent to the less protected (see news video here). Those most susceptible to pertussis complications are children younger than 12 months of age and those who are incompletely immunized. According to the CDC, the incidence of pertussis has increased steadily in the United States since the 1980s.

Pertussis is highly contagious, and human-to-human transmission occurs by means of respiratory droplets. The CDC indicates that the average incubation period of the bacterium is 7-10 days, but may be longer. For 1-2 weeks, nonspecific upper respiratory symptoms are typical (excepting some infants), followed by development of the characteristic, paroxysmal whooping cough, which can persist for 2-6 weeks. Vomiting and syncope may accompany the powerful cough, particularly in children. Common complications of the cough include pneumothorax, epistaxis, subconjunctival hemorrhage, subdural hematoma, hernia, rectal prolapse, urinary incontinence, and rib fracture. Antibiotic treatment (eg, erythromycin) of pertussis primarily mitigates spread of the disease. Convalescence, with a nonparoxysmal cough, may take another 2-6 weeks or longer. Affected individuals are susceptible to superimposed viral or other bacterial respiratory infections.

Immunity against the causative agent, the bacterium Bordetella pertussis, is obtained through vaccination; although protection is not absolute.* The DTaP vaccine is administered at 2, 4, 6, and 15-18 months of age and at 4-6 years of age. The Tdap vaccine is recommended at 11 or 12 years of age and in place of at least one 10-year tetanus booster between the ages of 19 and 64 years. A study published in this month's Pediatrics indicates that giving the first DTaP vaccine dose at 6 weeks, instead of 2 months, would prevent approximately 1200 cases of the disease, nearly 900 related hospitalizations, and 7 deaths.

DTaP = diphtheria, tetanus, acellular pertussis; Tdap = tetanus, reduced dose of diphtheria, reduced dose of acellular pertussis.

* According to a CDC report from 2005, pertussis vaccine effectiveness is 84% with 1 or 2 doses, 96% with 3 doses, and 98% with 4 or more doses. Vaccine effectiveness may be enhanced in persons who receive more than 1 type of vaccine (ie, DTP for doses 1-3 and DTaP for dose 4).

Picture of boy diagnosed with pertussis, aka whooping cough, from the CDC.

Addendum: A comparison of monthly data for reported pertussis cases in 2006 and the Google Trends feature for the same year (search terms, "pertussis" and "whooping cough") suggests that the Google feature works better for tracking influenza.