John P. Middaugh

Confirmed Previous Infection With Chlamydia pneumoniae (TWAR) and Its Presence in Early Coronary Atherosclerosis

BACKGROUND Chlamydia pneumoniae has been identified in coronary atheroma, but concomitant serum antibody titers have been inconsistently positive and unavailable before the detection of early or advanced atherosclerotic lesions. METHODS AND RESULTS This retrospective investigation was performed on premortem serum specimens and autopsy tissue from 60 indigenous Alaska Natives at low risk for coronary heart disease, selected by the potential availability of their stored specimens. Serum specimens were drawn a mean of 8.8 years (range, 0.7 to 26.2 years) before death, which occurred at a mean age of 34.1 years (range, 15 to 57 years), primarily from noncardiovascular causes (97%). Coronary artery tissues were independently examined histologically and, for C pneumoniae organism and DNA, by immunocytochemistry (ICC) and polymerase chain reaction (PCR) with species-specific monoclonal antibody and primers. Microimmunofluorescence detected species-specific IgG, IgA, and IgM antibody in stored serum. C pneumoniae, frequently within macrophage foam cells, was identified in coronary fibrolipid atheroma (raised lesions, Stary types II through V) in 15 subjects (25%) and early flat lesions in 7 (11%) either by PCR (14, 23%) or ICC (20, 33%). The OR for C pneumoniae in raised atheroma after a level of IgG antibody > or =1:256 >8 years earlier was 6.1 (95% CI, 1.1 to 36.6) and for all coronary tissues after adjustment for multiple potential confounding variables, including tobacco exposure, was 9.4 (95% CI, 2.6 to 33.8). CONCLUSIONS Serological evidence for C pneumoniae infection frequently precedes both the earliest and more advanced lesions of coronary atherosclerosis that harbor this intracellular pathogen, suggesting a chronic infection and developmental role in coronary heart disease.

Acute Fluoride Poisoning from a Public Water System

BACKGROUND Acute fluoride poisoning produces a clinical syndrome characterized by nausea, vomiting, diarrhea, abdominal pain, and paresthesias. In May 1992, excess fluoride in one of two public water systems serving a village in Alaska caused an outbreak of acute fluoride poisoning. METHODS We surveyed residents, measured their urinary fluoride concentrations, and analyzed their serum-chemistry profiles. A case of fluoride poisoning was defined as an illness consisting of nausea, vomiting, diarrhea, abdominal pain, or numbness or tingling of the face or extremities that began between May 21 and 23. RESULTS Among 47 residents studied who drank water obtained on May 21, 22, or 23 from the implicated well, 43 (91 percent) had an illness that met the case definition, as compared with only 6 of 21 residents (29 percent) who drank water obtained from the implicated well at other times and 2 of 94 residents (2 percent) served by the other water system. We estimated that 296 people were poisoned; 1 person died. Four to five days after the outbreak, 10 of the 25 case patients who were tested, but none of the 15 control subjects, had elevated urinary fluoride concentrations. The case patients had elevated serum fluoride concentrations and other abnormalities consistent with fluoride poisoning, such as elevated serum lactate dehydrogenase and aspartate aminotransferase concentrations. The fluoride concentration of a water sample from the implicated well was 150 mg per liter, and that of a sample from the other system was 1.1 mg per liter. Failure to monitor and respond appropriately to elevated fluoride concentrations, an unreliable control system, and a mechanism that allowed fluoride concentrate to enter the well led to this outbreak. CONCLUSIONS Inspection of public water systems and monitoring of fluoride concentrations are needed to prevent outbreaks of fluoride poisoning.

Methyl Tertiary Butyl Ether in Human Blood after Exposure to Oxygenated Fuel in Fairbanks, Alaska

Residents of Fairbanks, Alaska reported health complaints when 15%, by volume, methyl tertiary butyl ether (MTBE) was added to gasoline during an oxygenated fuel program. We conducted an exposure survey to investigate the effect of the program on human exposure to MTBE. We studied 18 workers in December 1992 during the program and 28 workers in February 1993 after the program was suspended. All workers were heavily exposed to motor vehicle exhaust or gasoline fumes. In December, the median post-shift blood concentration of MTBE in the workers was 1.8 micrograms/l (range, 0.2-37.0 micrograms/l), and in February the median post-shift blood concentration of MTBE in the 28 workers was 0.24 micrograms/l (range, 0.05-1.44 micrograms/l; p = .0001). Blood MTBE levels were measurably higher during the oxygenated fuel program in Fairbanks than after the program was suspended.

Fetal alcohol syndrome in Alaska, 1977 through 1992: an administrative prevalence derived from multiple data sources.

OBJECTIVES The prevalence and characteristics of fetal alcohol syndrome cases and the usefulness of various data sources in surveillance were examined in Alaska to guide prevention and future surveillance efforts. METHODS Sixteen data sources in Alaska were used to identify children with fetal alcohol syndrome. Medical charts were reviewed to verify cases, and records were reviewed to provide descriptive data. RESULTS Fetal alcohol syndrome rates varied markedly by birth year and race, with the highest prevalence (4.1 per 1000 live births) found among Alaska Natives born between 1985 and 1988. Screening and referral programs to diagnostic clinics identified 70% of all recorded cases. The intervention program for children 0 to 3 years of age detected 29% of age-appropriate cases, and Medicaid data identified 11% of all cases; birth certificates detected only 9% of the age-appropriate cases. CONCLUSIONS Our findings indicate a high prevalence of fetal alcohol syndrome in Alaska and illustrate that reliance on any one data source would lead to underestimates of the extent of fetal alcohol syndrome in a population.

Human Biomonitoring to Optimize Fish Consumption Advice: Reducing Uncertainty When Evaluating Benefits and Risks

National fish consumption advisories that are based solely on assessment of risk of exposure to contaminants without consideration of consumption benefits result in overly restrictive advice that discourages eating fish even in areas where such advice is unwarranted. In fact, generic fish advisories may have adverse public health consequences because of decreased fish consumption and substitution of foods that are less healthy. Public health is on the threshold of a new era for determining actual exposures to environmental contaminants, owing to technological advances in analytical chemistry. It is now possible to target fish consumption advice to specific at-risk populations by evaluating individual contaminant exposures and health risk factors. Because of the current epidemic of nutritionally linked disease, such as obesity, diabetes, and cardiovascular disease, general recommendations for limiting fish consumption are ill conceived and potentially dangerous.

Apolipoprotein E and atherosclerosis in Alaska Natives

Arterial, liver, and serum specimens were collected from 130 Alaska Natives who underwent forensic necropsy (mean age, 36.9 years; age range, 9-85 years; 38 females and 92 males). Based upon the observed frequencies of the six common apo E genotypes, the estimates of the relative frequencies of the corresponding alleles in the population are 0.020 +/- 0.009 for E2, 0.787 +/- 0.026 for E3 and 0.193 +/- 0.025 for E4. Analysis showed significant differences, by apo E genotype, in the extent of total surface lesion involvement in both the right and left coronary arteries. In all but the abdominal aorta, the pattern of lesion involvement by genotype is consistent with a decrease in lesions for genotypes with the E2 allele and an increase in lesions for the genotypes with the E4 allele, relative to the E3 homozygotes. After adjustment for low + very low density lipoprotein cholesterol (LDL + VLDL-C), the differences fell below statistically significant levels. Analysis by genotype of total serum cholesterol, high density lipoprotein cholesterol (HDL-C) and LDL + VLDL-C showed no statistically significant differences in analyte levels among genotypes. However, evidence is seen of a pattern in which total cholesterol and VLDL + LDL-C is less in genotypes with the E2 allele and greater in those with the E4 allele. We conclude that there does appear to be an effect by apo E genotype upon extent of atherosclerosis in the coronary arteries of Alaska Natives and this effect is likely due to the previously reported effect of apo E polymorphisms on serum cholesterol, particularly LDL + VLDL-C.

Persistence of Botulinum Toxin in Patients’ Serum: Alaska, 1959–2007

Persistence of circulating toxin in patients with foodborne botulism is not well characterized. Recommendations for administration of botulinum antitoxin are ambiguous for patients with late-presenting disease, such as a Florida woman with toxin-positive serum 12 days after toxin ingestion. We reviewed Alaska records of foodborne outbreaks of botulism that occurred during 1959-2007 to examine the period after ingestion during which toxin was detected. Of 64 cases with toxin-positive serum, toxin was detected up to 11 days after ingestion. The findings from Alaska and Florida support administration of antitoxin up to 12 days after toxin ingestion but do not indicate when circulating toxin should no longer be present.

Endemic Foodborne Botulism among Alaska Native Persons—Alaska, 1947–2007

BACKGROUND Foodborne botulism resulting from consumption of uncooked aquatic game foods has been an endemic hazard among Alaska Native populations for centuries. Our review was conducted to help target botulism prevention and response activities. METHODS Records of Alaska botulism investigations for the period 1947-2007 were reviewed. We used the Centers for Disease Control and Prevention case definitions for foodborne botulism and linear regression to evaluate incidence trends and χ(2) or Fishers Exact tests to evaluate categorical data. RESULTS A total of 317 patients (61% of whom were female) and 159 outbreaks were reported. Overall mean annual incidence was 6.9 cases per 100,000 Alaska Native persons; mean incidence was lower in 2000 (5.7 cases per 100,000 Alaska Native persons) than in any period since 1965-1969 (0.8 cases per 100,000 Alaska Native persons). Age-specific incidence was highest (26.6 cases per 100,000 Alaska Native persons) among persons aged ≥60 years. The overall case-fatality rate was 8.2%, and the case-fatality rate was ≤4.0% since 1980. Misdiagnosis was associated with a higher case-fatality rate and delayed antitoxin administration. CONCLUSIONS Foodborne botulism remains a public health problem in Alaska. Incidence might be decreasing, but it remains >800 times the overall US rate (0.0068 cases per 100,000 persons). Prevention messages should highlight the additional risk to female individuals and older persons. Early diagnosis is critical for timely access to antitoxin and supportive care.

Incremental effectiveness of 2 doses of measles-containing vaccine compared with 1 dose among high school students during an outbreak

A measles outbreak occurred among a highly vaccinated population in Alaska during 1998, providing an opportunity to determine the incremental efficacy of >or=2 doses of measles-containing vaccine (MCV) compared with 1 dose. Of 33 confirmed case patients identified, 31 had been vaccinated with 1 dose of MCV, 1 had received 2 doses, and vaccination status was unknown in 1 case. Seventy percent of cases were school-associated; 58% of cases occurred in 2 high schools. Of 3679 students attending the 2 schools, 50.4% and 45.5% had received >or=2 doses of MCV before measles introduction at the schools. The relative risk of developing measles among persons vaccinated with >or=2 doses of MCV compared with 1 dose was 0.06 (95% confidence interval, 0.01-0.44; P<.001), yielding an estimated incremental vaccine efficacy of 94.1% (95% confidence interval, 55.9%-99.2%; P<.001). Rapid implementation of a mandatory second-dose MCV requirement probably limited the extent of this outbreak.

Association of regulatory issues with an echovirus 18 meningitis outbreak at a children's summer camp in Alaska.

We document an echovirus 18 meningitis outbreak occurring at a remote overnight childrens camp in Alaska. The outbreak involved 26% of 113 camp residents, was associated with building overcrowding and occurred in a camp with a contaminated drinking water source. Lack of specific childrens camp regulations and failure to implement and enforce existing regulations may have contributed to the outbreak.