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Biomedical subjects

K L MacDonald

Publications and source records attributed to K L MacDonald.

At least 19 recordsLinked to original sources

Primary respiratory syncytial virus infection: pathology, immune response, and evaluation of vaccine challenge strains in a new mouse model.

Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract illness in young children. Vaccine development has been hampered by the experience of the formalin-inactivated vaccine tested in the 1960's. Currently, several vaccine candidates are under development and immune response to these candidate vaccines must be evaluated closely. We introduce a novel low-dose murine model of RSV infection and a new pathologic scoring system for the resultant pulmonary disease. We have also developed new sensitive methods for measuring cytokine expression. We then used this new model to test vaccine challenge strains of RSV in order to determine their pathogenicity.

Animals↗

The Campylobacter fetus S layer is not essential for initial interaction with HEp-2 cells.

In vitro adherence assays were used to determine whether the S layer mediated interactions between Campylobacter fetus subsp. venerealis strains and HEp-2 cells. At multiplicity of infection ratios ranging from 0.1:1 through 100:1, quantitation of bacterial adherence by light microscopy revealed that S layer deficient isogenic C. fetus 809K and C. fetus 810K were not less efficient in their attachment to HEp-2 cells; either S layer deficient C. fetus strains interacted with HEp-2 cells in greater numbers than the corresponding wild-type parent strains 809 and 810 or there was no significant difference in adherence levels between wild-type and mutant strains. Adherence of C. fetus strains to HEp-2 cells increased most during the first 2 h of a 22-h incubation period with only a slight increase in C. fetus cell numbers occurring subsequent to 2 h. At each assay point throughout this 22-h time period, equivalent numbers of wild-type and S layer deficient C. fetus strains were observed associated with HEp-2 cells. Prior to 2 h, adherence levels of all C. fetus strains exceeded those of Escherichia coli AB264 and Salmonella typhimurium SL1344. And, unlike S. typhimurium, C. fetus did not undergo significant replication following initial adherence to HEp-2 cells. Campylobacter fetus did not adhere to HEp-2 cells in a localized or aggregative pattern but were randomly distributed over individual HEp-2 cells and at no time during the assay with C. fetus were changes in HEp-2 cell morphology apparent. These data suggest that the S layer is not essential for mediating initial interactions between C. fetus and HEp-2 cells.

Bacterial Adhesion↗

Surveillance for Escherichia coli O157:H7 infections in Minnesota by molecular subtyping.

BACKGROUND: Escherichia coli O157:H7 is a leading cause of diarrhea and the hemolytic-uremic syndrome. Current public health surveillance for E. coli O157:H7 requires considerable resources; traditional methods lack the sensitivity and specificity to detect outbreaks effectively. METHODS: During 1994 and 1995, the Minnesota Department of Health requested that all clinical isolates of E. coli O157:H7 be submitted to our laboratory. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE), and patients were interviewed about potential sources of infection. RESULTS: In 1994 and 1995, 344 cases of E. coli O157:H7 infection were reported to the Minnesota Department of Health; 317 (92 percent) were subtyped by PFGE, and 143 distinct PFGE patterns were identified. Ten outbreaks of E. coli O157:H7 were identified; these accounted for 56 (18 percent) of the 317 subtyped cases. Four outbreaks were detected solely as a result of subtype-specific surveillance. In 11 two-week periods, the number of reported cases of E. coli O157:H7 doubled from the previous two weeks. In eight of these instances, the patterns identified were dissimilar and there were no outbreaks. Two of the remaining three increases resulted from multiple simultaneous outbreaks. CONCLUSIONS: Subtype-specific surveillance for E. coli O157:H7 can identify outbreaks that are not detected by traditional methods and can ascertain whether sudden increases in reported cases are due to sporadic isolated cases or to one or more outbreaks.

Adolescent↗

An outbreak of invasive group A streptococcal disease associated with high carriage rates of the invasive clone among school-aged children.

OBJECTIVES: To determine if a common strain of group A streptococcus was responsible for an outbreak of invasive streptococcal disease in southeastern Minnesota and to determine whether this strain was prevalent among residents of this area during the outbreak who either had streptococcal pharyngitis or were asymptomatic streptococcal carriers. DESIGN: Pharyngeal culture survey and case-contact evaluation. SETTING: Three adjacent counties in southeastern Minnesota defined as the outbreak area. Outbreak period, January 1 through March 31, 1995. PATIENTS: Seven patients with invasive streptococcal infection, 1249 patients (adults and children) with sore throat who resided in the outbreak area, children from an elementary school located in 1 community where the majority of invasive cases occurred, and 896 students from 3 schools located in Minnesota counties outside the outbreak area. MEASUREMENTS: Pulsed-field gel electrophoresis (DNA fingerprinting) of group A streptococcal isolates obtained from patients with invasive disease, throat swabs of patients with sore throat, and throat swabs of asymptomatic school-aged children. RESULTS: All patients with outbreak-associated invasive disease had group A streptococcal isolates that were indistinguishable by pulsed-field gel electrophoresis. Additional testing showed that these isolates carried significant virulence factors including pyrogenic exotoxin A and streptococcal superantigen. Five of these 7 patients with invasive disease had underlying medical conditions; 4 developed toxic shock syndrome and died (case fatality, 57%). The outbreak-associated group A streptococcal clone was found in 69 (26.5%) of the 260 patients with sore throat from whom group A streptococcus was isolated. The frequency of the outbreak clone among pharyngeal carriers from the 3 schools outside the outbreak area was significantly less (range, 0%-10%) than in children from the school in the outbreak area (78%; relative risk, 29; 95% confidence interval, 11.1-78.1; P<.001). Four of the 7 patients with outbreak-associated disease had contact with children who attended the school in the outbreak area. CONCLUSIONS: A single clone of group A streptococcus was responsible for 7 cases of invasive streptococcal disease during an outbreak in Minnesota and for a significant number of pharyngitis cases that also occurred during the outbreak. Invasive disease occurred most frequently in persons with underlying medical conditions. This outbreak was also associated with increased carriage rates of the invasive streptococcal clone among community school-aged children. Cases of invasive group A streptococcal infection may therefore reflect the tip of the iceberg with regard to the burden of colonization of a specific invasive streptococcal clone in a community.

Adult↗

A population-based study of sexually transmitted disease incidence and risk factors in human immunodeficiency virus-infected people.

BACKGROUND AND OBJECTIVES: The Minnesota Department of Health conducts active surveillance for cases of human immunodeficiency virus (HIV) infection and passive surveillance for gonorrhea, Chlamydia trachomatis infection, and syphilis. The authors linked two computerized surveillance databases to assess gonorrhea incidence and risk factors for sexually transmitted disease (STD) acquisition among people with known HIV infection. STUDY DESIGN: People diagnosed with adolescent/adult HIV infection before 1993 and still alive as of December 31, 1994 were compared to people diagnosed with gonorrhea, chlamydial infection, or primary/secondary syphilis in 1993 or 1994. Records were matched on name, date of birth, and gender. The incidence of reported gonorrhea was calculated and risk factors for STD acquisition were examined. RESULTS: Thirty (1.3%) of 2,315 HIV-infected people were diagnosed with one or more STDs after HIV diagnosis (median interval: 3 years). There were 31 episodes of gonorrhea, seven episodes of chlamydial infection, and one episode of secondary syphilis. The gonorrhea incidence among HIV-infected people was high compared to the general population in Minnesota, even after stratifying by gender, age, and county of residence. STD acquisition was independently associated with female gender (odds ratio [OR] = 3.8; 95% confidence interval [CI] = 1.7, 8.3) and residence in Hennepin County (OR = 2.9; 95% CI = 1.2, 7.1), the most populous county in Minnesota. CONCLUSIONS: Linkage of STD and HIV surveillance data is useful as a sentinel for high-risk sexual behavior among HIV-infected people, and it can help identify individuals who require additional interventions to prevent HIV transmission. State and local health departments should consider linking these data sources to assess trends and allocate resources.

Adolescent↗

A national outbreak of Salmonella enteritidis infections from ice cream. The Investigation Team.

BACKGROUND: In September 1994, the Minnesota Department of Health detected an increase in the number of reports of Salmonella enteritidis infections. After a case-control study implicated a nationally distributed brand of ice cream (Schwan's) in the outbreak, the product was recalled and further epidemiologic and microbiologic investigations were conducted. METHODS: We defined an outbreak-associated case of S. enteritidis infection as one in which S. enteritidis was cultured from a person who became ill in September or October 1994. We established national surveillance and surveyed customers of the implicated manufacturer. The steps involved in the manufacture of ice cream associated with cases of S. enteritidis infection were compared with those of products not known to be associated with infection matched for the date of manufacture. Cultures for bacteria were obtained from ice cream samples, the ice cream plant, and tanker trailers that had transported the ice cream base (premix) to the plant. RESULTS: We estimate that S. enteritidis gastroenteritis developed in 224,000 persons in the United States after they ate Schwan's ice cream. The attack rate for consumers was 6.6 percent. Ice cream associated with infection contained a higher percentage of premix that had been transported by tanker that had carried nonpasteurized eggs immediately before (P = 0.02). S. enteritidis was isolated from 8 of 226 ice cream products (3 percent), but not from environmental samples obtained from the ice cream plant (n = 157) or tanker trailers (n = 204). CONCLUSIONS: This nationwide outbreak of salmonellosis was most likely the result of contamination of pasteurized ice cream premix during transport in tanker trailers that had previously carried nonpasteurized liquid eggs containing S. enteritidis. To prevent further outbreaks, food products not destined for repasteurization should be transported in dedicated containers.

Adolescent↗

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome.

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group. PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti. RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar. CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Adolescent↗

Screening for tuberculosis infection among secondary school students in Minneapolis-St. Paul: policy implications.

Three students in the St. Paul Public Schools were diagnosed with active tuberculosis (TB) in late 1991 and early 1992. To define the prevalence of TB infection in St. Paul and Minneapolis, we conducted school-based screening projects in the St. Paul and Minneapolis public schools during 1992 and 1993. In St. Paul, 7,596 (74.8%) students in grades six through 12 received Mantoux tests; 268 (3.5%) were reactive. Infection rates varied significantly by country of birth, with students born outside the United States more likely to be Mantoux reactors than U.S.-born students (RR = 20.2; 95% CI = 14.9-27.3; p < 0.001). In Minneapolis, 752 (47.2%) eighth-grade students received Mantoux tests; 23 (3.1%) were reactive. As in St. Paul, infection rates varied by country of birth; students born outside the United States were more likely to have reactive Mantoux tests than students born in this country (RR = 13.2; 95% CI = 5.6-31.4; p < 0.001). We conclude that routine TB screening of school students is not warranted in Minnesota, although school-based screening targeted at the highest risk students, particularly those born outside the United States, may be a beneficial prevention strategy.

Adolescent↗

An outbreak of measles at an international sporting event with airborne transmission in a domed stadium.

An outbreak of measles occurred in conjunction with the International Special Olympics Games in the Minneapolis-St. Paul metropolitan area during July 1991. Sixteen outbreak-associated cases of measles were reported among US residents from seven states, with 9 additional cases resulting from subsequent transmission. The primary case was a track and field athlete from Argentina. Transmission occurred in three settings: the opening ceremonies in a domed stadium, track and field events, and first aid stations. Eight secondary cases had their only potential exposure at the opening ceremonies; 2 of these cases were unrelated spectators sitting in the same section of the upper deck > 30.5 m above the athlete's entrance. These findings demonstrate that the risk of indigenous measles transmission associated with international events in the United States must be considered, even in areas without recent measles activity. Moreover, the dynamic airborne transmission of measles illustrates the potential for transmission in the absence of a recognized exposure.

Adolescent↗

Evaluation of clinical and laboratory aspects of antibody tests for detection of hepatitis C virus infection in blood donors and recipients from a low-risk population.

BACKGROUND: When the first-generation enzyme immunoassay (EIA) for detection of antibody to hepatitis C virus (anti-HCV) was approved in May 1990, blood banking agencies recommended testing of all components in inventory. In many cases, one or more components from these units had already been transfused. STUDY DESIGN AND METHODS: Donors that reacted in first-generation EIAs and recipients of their components were identified, and anti-HCV test methods (including first-generation EIA, second-generation EIA, and recombinant immunoblot assay [RIBA]) were evaluated. RESULTS: Of 66 donors identified as anti-HCV-positive by first-generation EIA, 17 were positive in second-generation EIA. Of these 17, 9 reacted in RIBA; 6 of these showed evidence of HCV infection in polymerase chain reaction (4) and/or probable transmission of HCV to a transfusion recipient (3). Of the 48 specimens that were positive in first-generation EIA and negative in second-generation EIA, only 1 was positive in RIBA; serum was not available for polymerase chain reaction testing, and there were no living transfusion recipients in whom to assess evidence of transmission of HCV. CONCLUSION: This study documents the low predictive value of EIAs for anti-HCV in a low-prevalence blood donor population and emphasizes the need for additional testing to confirm the specificity of samples that react in the screening tests.

Adolescent↗

Physician attitudes and practices regarding universal infant vaccination against hepatitis B infection in Minnesota: implications for public health policy.

Physician attitudes and practices regarding universal infant vaccination against hepatitis B virus infection in Minnesota were assessed approximately 1 year after publication of the Immunization Practices Advisory Committee recommendations. Four-hundred eighteen Minnesota family physicians and pediatricians were sent self-administered questionnaires, with follow-up by telephone. Among physicians who provide care to infants, 67 (29%) of 234 family physicians and 29 (50%) of 58 pediatricians routinely offered hepatitis B vaccine to all infants (overall 33%) (P = 0.002). The recommendations of the Immunization Practices Advisory Committee, the American Academy of Pediatrics and the American Academy of Family Physicians had the greatest positive influence on physicians' opinions regarding routine hepatitis B vaccination. The factors with the greatest negative influence on their opinions were the low prevalence of hepatitis B virus infection in Minnesota and the addition of three injections to the current childhood immunization schedule. Universal infant hepatitis B vaccination remains controversial among Minnesota family physicians and pediatricians. We believe, given the variability in hepatitis B virus incidence and prevalence in the United States and the relatively low risk of most infants, that a single national policy based solely on universal infant immunization may be difficult to implement.

Adult↗