Epidemiological Notes and Reports Pentachlorophenol Poisoning in Newborn Infants -- St. Louis, Missouri, April-August 1967
Reprinted below is the text and editorial note of a report published in the October 7, 1967, MMWR. A contemporary Editorial Note follows.
From April to August 1967, nine cases of a clinically distinct illness characterized by fever and profuse sweating occurred in a small nursery for newborns in St. Louis, Missouri. Two of the cases were fatal. Early in the course of the outbreak the disease was felt to be an intoxication, but the nature of the poison and the mode of exposure of the patients remained obscure. Only after the ninth case developed was it discovered that an antimildew agent, containing a high concentration of sodium pentachlorophenate (the sodium salt of pentachlorophenol), was being used in the hospital laundry. All of the clinical, epidemiological, and biochemical evidence indicated that this outbreak resulted from pentachlorophenol poisoning. The only identified mode of exposure was skin absorption of sodium pentachlorophenate residues on diapers and other fabrics, resulting from the misuse of the antimildew agent in the final laundry rinse.
The outstanding clinical feature of the illness was extreme diaphoresis. Attendants consistently noticed that the infants' clothing and brows were drenched with sweat. Nevertheless, the neonates nursed avidly. As the disease progressed, fever rose as high as 103 F, respiratory rates increased, and breathing became labored, though auscultation of the lungs was normal and cyanosis was absent. Other common findings included tachycardia, hepatomegaly, and irritability followed by lethargy. Anorexia, vomiting, and diarrhea were notably absent. Stiffness of the neck, muscular fasciculations, and convulsions were not observed. Skin rashes or evidences of inflammation or irritation of the skin were not seen.
Laboratory tests frequently showed a progressive metabolic acidosis, proteinuria, a rising blood urea nitrogen, and "pneumonia" or "bronchiolitis" on X-ray. Bacterial and viral cultures of blood, cerebrospinal fluid, nose, throat and stool revealed no pathogens. Autopsy findings of the two fatal cases showed fatty metamorphosis of the liver in both cases and fatty vacuolar changes in the renal tubules of one case.
All except one of the seriously ill infants, a fatal case, were transferred to other hospitals for treatment. After the first fatal case occurred, the attending physicians suspected a toxic cause and therefore promptly performed exchange transfusions on each of the seriously ill infants who were subsequently transferred for medical care. This treatment yielded dramatic results. Within minutes to hours, the infants became more responsive and had less respiratory distress. Fever and sweating disappeared, as did metabolic acidosis. Renal function returned to normal during the next few days. Except for the two fatal cases, recovery was apparently complete.
The first four cases developed between April 17 and 19 among a group of 25 infants who were in the nursery during this interval. The first infant to become ill died. The institution was closed on April 24 and thoroughly cleaned and disinfected before re-opening on May 3. A second cluster of four cases occurred between May 10 and 15. One of these also was fatal. The average age of these eight cases, at onset of illness, was 8.9 days. Several additional suspect cases with fever and sweating were detected among 13 infants who had been discharged from the hospital in apparent health between April 17 and May 15.
From the time of the first recognition of the outbreak, an intensive and persistent search was made for toxic substances in the environment of the infants. A solid-stick evaporating deodorizer had been used without change in practice for 4 years. A commercial exterminator had sprayed regularly with a carbamate insecticide monthly for 2 years within the hospital, but never in the nursery. The management of drugs and the preparation of babies' formulas revealed no deviations that were likely to permit the introduction of a toxic substance to this many babies.
For the preceding 10 months, a commercially available disinfectant containing a mixture of synthetic phenolic derivatives had been repeatedly applied to surfaces that came in contact with infants' skin.
One-dimensional thin-layer chromatography of serum specimens obtained from the first eight cases was performed. These tests revealed the presence of a phenolic substance in all test specimens, which was similar to a phenolic ingredient of the disinfectant. This substance was thought to be the toxic chemical causing the disease.
The nursery was closed and recleaned. Use of the suspect disinfectant was abandoned, and all equipment that had been treated with it was discarded or rendered free of phenolic residues by extensive cleaning with alcohol. New linens and diapers were purchased and the nursery reopened July 11.
On August 29, an 8-day-old infant had the acute onset of an illness identical to the previous eight infants. The infant received an exchange transfusion and promptly recovered. A follow-up survey of infants discharged from the hospital in July and August revealed six additional infants who had the characteristic excessive sweating in a milder form of the same syndrome.
The formerly suspect disinfectant was no longer in use. Reinvestigation of laundry procedures disclosed a previously overlooked source of phenols. An antimildew agent, containing 22.9 percent sodium pentachlorophenate and 4.0 percent trichlorocarbanilide, was being used in the terminal rinse of all nursery linens and diapers, despite a warning on the label that the compound "must not be used" in laundering diapers.
This product had been in use in the laundry since March 1966. The recommended quantity was one ounce of powder per laundering cycle, but it was ascertained that the laundry was actually using 3 to 4 ounces.
Thin-layer chromatography of the serum and urine of the new case revealed an abnormal substance with characteristics that were identical to those detected in the previous infants' sera. Further studies in two different laboratories with improved methods of analysis have shown that the chemical in the urine and serum of the new case was pentachlorophenol, and was clearly not one of the phenolic ingredients in the previously suspected disinfectant. Additionally, pentachlorophenol was identified in freshly laundered diapers obtained from the nursery. The quantity of pentachloro-phenol varied from 1.5 to 5.7 mg. per diaper. Pentachlorophenol, when fed to rats, was found to be highly toxic and was isolated from urine of surviving rats in concentrations comparable to that found in the sick child. Unfortunately, no samples from the earlier cases remained for these more sophisticated analyses.
Actions have been instituted to prevent further illnesses that might be caused by the misuse of this product, or two other sodium pentachlorophenate-containing products that are recommended for similar purposes. The manufacturer has been directed to trace all sales and shipments of these products during the past 18 months, and to remove such products from all hospitals and any establishment that is involved in general laundry work. The company has voluntarily ceased sale of these three products. (Reported by J. Earl Smith, M.D., Health Commissioner, Division of Health, Department of Health and Hospitals, City of St. Louis, Missouri; L.E. Loveless, Ph.D., Chemist, Clinical Laboratories, St. Louis, Missouri; E. A. Belden, M.D., Consultant, Communicable Disease Control, Local Health Services Section, Division of Health, Missouri Department of Public Health and Welfare; the Epidemiology and Pesticides Programs of the National Communicable Disease Center, Atlanta, Georgia; the Toxicology Section, Occupational Health Program, National Center for Urban and Industrial Health, Cincinnati, Ohio; and a team of EIS Officers.)
Editorial Note: The clinical, laboratory, epidemiological, and pathological findings, as well as the prompt response to exchange transfusion, all indicate a toxic, rather than an infectious, cause of this outbreak. The fever, sweating, and acidosis are consistent with intoxication with certain phenolic derivatives, which are known to increase the metabolic rate (1). The symptoms described here are remarkably similar to industrial accidental poisonings resulting from overexposure to pentachlorophenol or its sodium salts (2,3). The exact manner in which the infants became poisoned cannot be established, but the most reasonable explanation is absorption through the intact skin as a result of repeated contact with diapers, blankets, and linens containing small, but readily absorbable, quantities of sodium pentachlorophenate. The antimildew agent, which is labelled not for use in laundering diapers or hospital linens, nevertheless, was in use in this hospital. Pediatricians, hospital administrators, housekeepers, and local health authorities should check commercial diaper services and hospital laundries to ensure that this product is not in use. References:
Editorial Note -- 1996: This report, one of the first well-documented accounts of an investigation of a noninfectious disease problem to be published in MMWR after responsibility for the publication had been transferred to CDC, illustrates one of the most difficult challenges facing environmental epidemiologists -- exposure assessment. Even in acute situations such as that described in this report, the search for a toxic agent and the route of exposure is difficult and time consuming. In investigations of chronic and many environmentally related illnesses, exposures that may have occurred over an extended period may be particularly difficult to characterize accurately; the paucity of accurate exposure data has been termed the "Achilles heel" of environmental epidemiology (1).
As illustrated by this investigation in St. Louis in 1967, the use of innovative laboratory methodologies has been critical to improving the accuracy of exposure assessments. For example, during this investigation, epidemiologists initially relied on the laboratory techniques of thin-layer chromotographic analysis of patient specimens to identify a phenol as the probable etiologic agent; more advanced laboratory methods were used to confirm the causative role of this agent and to further focus the investigation. Since 1967, the close collaboration between epidemiologists and laboratory scientists during environmental investigations has continued to strengthen, and the development of biomarkers of exposure, disease, and susceptibility has been critical in assisting public health scientists in exposure assessment (2). Environmental epidemiologists in state and federal health agencies are addressing the difficulties of accurately classifying exposure in other innovative ways. For example, computer mapping techniques, such as Geographic Information Systems, have enabled investigators to more accurately use environmental sampling data to represent individual exposure. Finally, although the investigation in St. Louis was highly focused, the approach to this outbreak underscored the public health benefits of basic "shoe leather epidemiology" for solving problems regardless of their etiology.
Editorial Note by: Health Studies Branch, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC.
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