Promising practices for school-located vaccination clinics--part I: preparation.

A school-located mass vaccination clinic approach can enable rapid vaccination of a large number of students while minimizing disruption of their school activities and potentially reducing missed work hours by parents. During 3 consecutive influenza seasons beginning in 2005, the Knox County Health Department conducted school-located mass vaccination clinics using live attenuated influenza vaccine. Clinics were held each year throughout the county over 4 weeks in more than 100 public and private schools for more than 65, 000 students in Grades K to 12. Overall, the proportion of all students vaccinated at school each year exceeded 40%. Our experience indicated that careful and thorough planning was essential to program success. Critical planning elements included (1) initial planning with extensive lead time to find the proper lead agency and project leader and to develop sound comprehensive vaccine clinic planning; (2) developing partnerships, especially with schools; (3) communicating successfully with parents, children, school administrators and teachers, medical providers, and the community at large; and (4) educating these groups successfully, using good timing, through local media, school events, direct mailings (including parents receiving information and consent packets), and partners. We review here the details of these key planning elements.

Promising practices for school-located vaccination clinics-- part II: clinic operations and program sustainability.

A school-located mass vaccination program can enable rapid vaccination of a large number of students while minimizing disruption of their school activities. During 3 consecutive influenza seasons beginning in 2005, the Knox County Health Department conducted school-located mass vaccination clinics using live attenuated influenza vaccine. Overall, the proportion of elementary schoolchildren vaccinated with live attenuated influenza vaccine exceeded 40% each year. We describe key lessons learned in clinic operations, including obtaining informed consent, defining the organizational structure and roles, preparing the school, staffing, training, supplies, vaccine management, team communication, and data management. We conclude by discussing program costs and sustainability.

Impact of a school-based influenza immunization program on disease burden: comparison of two Tennessee counties.

Outpatient burden of laboratory-confirmed influenza among children in Knox and Davidson Counties was compared in 2006-2007 when only Knox County had a school-based influenza vaccine campaign. Of 1016 eligible children seeking outpatient care, 87% were enrolled and 20% were influenza-positive. Estimated influenza vaccination coverage was similar in Knox and Davidson for preschool-age children (36% versus 33%) but higher in Knox County for school-age children (44% versus 12%). Influenza detection was higher among Knox than Davidson County preschool-age children (18% versus 10%) but similar among school-age children (28% versus 27%). These data are consistent with a direct effect of the campaign in school-age children.

A shot in the rear, not a shot in the dark: application of a mass clinic framework in a public health emergency.

An outbreak of foodborne hepatitis A infection compelled two regional health departments in eastern Tennessee to implement an emergency mass clinic for providing hepatitis immune serum globulin (ISG) to several thousand potentially exposed people. For the mass clinic framework, we utilized the smallpox post-event clinic plans of the Centers for Disease Control and Prevention (CDC), although the plans had only been exercised for smallpox. Following CDC's guidelines for staffing and organizing the mass clinic, we provided 5,038 doses of ISG during a total of 24 hours of clinic operation, using 3,467 person-hours, or 1.45 ISG doses per person-hour-very close to the 1.58 doses per person-hour targeted in CDC's smallpox post-event clinic plans. The mass clinic showed that CDC's smallpox post-event clinic guidelines were feasible, practical, and adaptable to other mass clinic situations.

Finding blunders in thyroid testing: experience in newborns.

We evaluated thyroxin (T4) and thyroid-stimulating hormone (TSH) data along with clinical information from 600,000 newborns. We looked for certain combinations of tests and clinical data that were questionable and possibly mistaken. Our approach suggests that certain combinations of test results, especially the presence of missing results deserved further evaluation for possible blunders. We found that missing tests were frequently the result of oversight. The laboratory used the well-known standard blood-spot-on-filter paper methods for TSH and T4. For quantitation of TSH and T4, we used the time-resolved fluoroimmunoassay available from Perkin Elmer. We found 56 babies with confirmed primary congenital hypothyroidism (PCH) in a total of 600,000 patients. We also found 18 sets of results in the same 600,000 babies that gave inconsistent findings, had missing values, and (or) possible misinterpretations of the clinical and (or) laboratory data. What is an acceptable mistake rate? All mistakes are unacceptable, but there is likely some irreducible mistake rate, and efforts to reduce the mistake or blunder rate still further may not be cost-effective. What can be done is to study the mistake rate per 600,000 babies from year to year; the mistake rate should be decreasing or not changing. This assumes a stable cohort of babies; an assumption that may be acceptable. We applied a form of pattern recognition to identify cases of possible blunders and missing values in either the laboratory or clinical data. What is clear is that we apparently identified some blunders. The 18 mistakes per 600,000 babies may be "very low" and acceptable. We recommend that seeking ever decreasing mistakes is the way to go, and the level of monitoring the data should be very intense given the serious consequences of mis-diagnosed thyroid disorders.

Ultrastructural localization of heavy metals in the extraradical mycelium and spores of the arbuscular mycorrhizal fungus Glomus intraradices.

Arbuscular mycorrhizal fungi, obligate symbionts of most plant species, are able to accumulate heavy metals, thereby, protecting plants from metal toxicity. In this study, the ultrastructural localization of Zn, Cu, and Cd in the extraradical mycelium and spores of the arbuscular mycorrhizal fungus Glomus intraradices grown in monoxenic cultures was investigated. Zinc, Cu, or Cd was applied to the extraradical mycelium to final concentrations of 7.5, 5.0, or 0.45 mmol/L, respectively. Samples were collected at time 0, 8 h, and 7 days after metal application and were prepared for rapid freezing and freeze substitution. Metal content in different subcellular locations (wall, cytoplasm, and vacuoles), both in hyphae and spores, was determined by energy-dispersive X-ray spectroscopy. In all treatments and fungal structures analysed, heavy metals accumulated mainly in the fungal cell wall and in the vacuoles, while minor changes in metal concentrations were detected in the cytoplasm. Incorporation of Zn into the fungus occurred during the first 8 h after metal addition with no subsequent accumulation. On the other hand, Cu steadily accumulated in the spore vacuoles over time, whereas Cd steadily accumulated in the hyphal vacuoles. These results suggest that binding of metals to the cell walls and compartmentalization in vacuoles may be essential mechanisms for metal detoxification.

Mass distribution of free, intranasally administered influenza vaccine in a public school system.

OBJECTIVE: School-based influenza vaccination programs are a potentially important method of protecting the community against influenza. We evaluated the feasibility and success of a large, school-based influenza vaccination campaign. METHODS: On-site administration of intranasally administered, live attenuated influenza vaccine was offered to all students and staff members in a large, metropolitan public school system in October to December 2005. We evaluated vaccine coverage levels, resources expended, and physician and parent attitudes and knowledge. RESULTS: Of 53,420 public school students, 24,198 were vaccinated with live attenuated influenza vaccine. Of 5841 school staff members, 3626 were vaccinated with live attenuated influenza vaccine or inactivated influenza vaccine. The proportions of students vaccinated were 56% among elementary schools, 45% among middle schools, and 30% among high schools. Schools with larger proportions of black or low-income families had lower vaccine coverage levels. The health department and school system expended 6900 person-hours during the campaign, and various health department clinics were closed for a total of 84 half-days. Community physicians were supportive of the campaign and frequently advised participation for eligible patients. Some physicians had misunderstandings about live attenuated influenza vaccine contraindications. Concern about adverse effects, having asthma, negative physician advice, and nonparticipation in any vaccination program were common reasons for students not participating. CONCLUSIONS: This influenza vaccination campaign in a large public school system achieved relatively high vaccine coverage levels but required a substantial resource commitment from the local health department. This evaluation has critical implications for the ongoing debate regarding immunization policies for school-aged children and preparedness plans for pandemic influenza.

Pathophysiology and diagnostic value of urinary trypsin inhibitors.

Inflammation is an important indicator of tissue injury. In the acute form, there is usually accumulation of fluids and plasma components in the affected tissues. Platelet activation and the appearance in blood of abnormally increased numbers of polymorphonucleocytes, lymphocytes, plasma cells and macrophages usually occur. Infectious disorders such as sepsis, meningitis, respiratory infection, urinary tract infection, viral infection, and bacterial infection usually induce an inflammatory response. Chronic inflammation is often associated with diabetes mellitus, acute myocardial infarction, coronary artery disease, kidney diseases, and certain auto-immune disorders, such as rheumatoid arthritis, organ failures and other disorders with an inflammatory component or etiology. The disorder may occur before inflammation is apparent. Markers of inflammation such as C-reactive protein (CRP) and urinary trypsin inhibitors have changed our appraisal of acute events such as myocardial infarction; the infarct may be a response to acute infection and (or) inflammation. We describe here the pathophysiology of an anti-inflammatory agent termed urinary trypsin inhibitor (uTi). It is an important anti-inflammatory substance that is present in urine, blood and all organs. We also describe the anti-inflammatory agent bikunin, a selective inhibitor of serine proteases. The latter are important in modulating inflammatory events and even shutting them down.

Age-dependent cutoff values in screening newborns for hypothyroidism.

OBJECTIVES: We wanted to develop age-related reference (cutoff) values and an algorithm to identify babies at low, moderate, and high risk for hypothyroidism of any cause. We used thyroid-stimulating hormone (TSH) as the primary tool, and thyroxine (T4) as part of a confirmatory test. Our data permitted us to estimate cutoff values for newborns at <24 h, 24 to 47 h, 48 to 71 h, 72 to 95 h, and > or =96 h after birth. METHODS: We used a time-resolved fluoroimmunoassay method for TSH and T4 with the AutoDELPHIA instrument (Perkin-Elmer Life Sciences, Turku, Finland). TESTING ALGORITHM: We developed a conservative algorithm for TSH and T4 testing. In the initial screening, we used a > or =20 microIU/ml cutoff for TSH to identify those babies of any age who required confirmatory testing on a repunched filter paper blood specimen. RESULTS: In 161,244 newborns tested during 2002, we found 8,035 babies with TSH values > or =20 microIU/ml. Graphs of the values for TSH vs. age in hours revealed the possibility of using more than one cutoff value. The general finding was that the cutoff values decreased with increasing age of the newborn. CONCLUSIONS: Based on our findings, we conclude that testing babies who are <24 h old is not recommended and should only be performed if no other specimen is available. A high TSH in babies <24 h old is unreliable for screening newborns for hypothyroidism. We routinely stipulate that the infant be at least 48 h old for TSH and T4 testing. If not, the cutoff value must be set to a higher value to prevent an excessive number of false-positive results; however, this increases the chance of missing a truly hypothyroid baby. We designated newborns as being at "low" (LR), "moderate" (MR), or at "high" risk (HR) for hypothyroidism. The TSH test continues to be a screening test; and follow-up quantitative testing and clinical evaluation are needed for all babies identified as being at MR or HR for hypothyroidism. SETTING: Newborn Screening Laboratory of the Ohio Department of Health, Columbus, Ohio.

Near-patient testing for infection using urinalysis and immuno-chromatography strips.

Urinary tract infections require costly confirmatory tests such as a urine culture to establish the diagnosis. Elimination of the culture step would save resources; diagnosis and treatment could begin in hours rather than days. We tested a new dip-and-read strip that uses immuno-chromatography (IC) to detect infectious agents in urine. We used a goat-derived polyclonal antibody with reactivity to the cell-wall proteins of Escherichia coli (E. coli). Fluorescein linked to the anti-E. coli antibody served to trap the bacteria on a strip coated with an anti-fluorescein mouse antibody. Blue latex particles were linked to anti-E. coli antibodies by standard methods and were used for detection of E. coli. We found that the combination of leukocyte esterase and nitrite dipsticks gave negative predictive values of 93% for culture-negative urines, i.e., there were very few false-negative results. Using the same dipsticks on culture-positive specimens, the positive predictive values were unacceptably low; we obtained too many false-positive values. By contrast, the IC strips gave negative predictive values of 89%. The major advantage of the IC strips is that the positive predictive values were higher, i.e., there were fewer false-positive results. The combined use of both IC strips and urinalysis dipsticks offers the best strategy for diagnosing infection with dipsticks. The IC strip test could reduce the necessity of a urine culture in patients with suspected infections and provide rapid point-of-care testing.

The uristatin dipstick is useful in distinguishing upper respiratory from urinary tract infections.

BACKGROUND: We determined the diagnostic value of the trypsin inhibitor, uristatin, that is commonly found in urine and plasma in patients with infections or inflammations of any kind. METHODS: We collected urine specimens from patients with infections of the urinary or upper respiratory tract and from healthy controls. We also collected blood from patients with a likely upper respiratory tract infection and healthy controls. A bacterial count of >10(5) organisms/ml in urine was considered to represent infection rather than contamination. RESULTS: The uristatin dipstick test in urine showed acceptable negative predictive values (NPV of up to 93%) for patients without infection or inflammation. Here, the dipsticks could eliminate some urine cultures. For those with infection or inflammation, the positive predictive values (PPV) of the dipsticks were lower (up to 57%). Including the leukocyte esterase and nitrite values increased the PPV of the dipsticks for those with disease. CONCLUSIONS: The uristatin strip was more accurate than the leukocyte and nitrite dipsticks for predicting upper respiratory infections (URI) and C-reactive protein for those with infection or inflammation. The uristatin dipstick was able to detect both the bikunin and uristatin inhibitors.

Detection of low-molecular-weight proteins in urine by dipsticks.

BACKGROUND: Testing of urines with dipsticks for proteinuria, glycosuria, etc., is common practice. A deficiency with currently available dipsticks is their lack of chemical sensitivity and underestimation of low-molecular-weight proteins such as light chains. METHODS: We experimented with a number of dyes that gave an easily recognized color change on dipsticks for various low-molecular-weight proteins such as alpha-1-glycoprotein, alpha-1- and beta-2-microglobulin, and kappa and lambda light chains. We were successful in formulating a dye for impregnating dipsticks that gave a color change with low-molecular-weight proteins. RESULTS: Most dipsticks will measure proteins down to about 1 g/l. Our composite of two dyes (described here as the "TPR" dipsticks) gave reproducible results for protein concentrations of >/=300 mg/l, and detected low-molecular proteins. The TPR reagent is resistant to interferences from many compounds; also, the protein results are not altered in a given urine at a pH between 5 and 8. CONCLUSIONS: We have developed a dipstick that detects low-molecular-weight proteins. The dipsticks are easy to use and are suitable for outpatient or point-of-care testing. The precision of the dipsticks is satisfactory and is only marginally lower than quantitative spectrophotometric methods using pyrogallol red (PYR).

Clinical utility of a rapid test for uristatin.

OBJECTIVES: Uristatin is a trypsin inhibitor present in urine that is increased in most patients with bacterial or viral infections and in many with inflammatory disorders. We included the assay of uristatin as part of a screening program carried out by pediatricians on 4207 Japanese schoolchildren to judge the ability of uristatin to identify those with an infection and (or) inflammation of any cause. We used urine dipsticks for the assay of uristatin, creatinine, albumin, blood, leukocyte esterase, and protein. We also performed quantitative assays for uristatin and creatinine. Another aim was to estimate the reference range for uristatin in schoolchildren, ages 5 to 14 yr. METHODS: We prepared dipstick pads that were impregnated with a chromogenic substrate for trypsin and measured the uristatin-caused inhibition of trypsin in urine. We measured creatinine so that the ratio of uristatin to creatinine could be calculated to correct for urine concentration. RESULTS: We obtained quantitative uristatin and creatinine results for 4207 children. Of these, 177 had an abnormal urine dipstick for albumin or blood or protein or leukocyte esterase or a combination of these. We used data from 3622 children to establish the reference range for the uristatin dipsticks. The 3622 were diagnosed by their pediatricians as free from an infection or inflammation of any cause and with normal urine dipstick tests. We recommend an upper reference limit for uristatin by dipstick of < or = 7.5 mg uristatin/g creatinine. The leftover 408 children ( [4207-3622-177] = 408) fell into two groups: 205 with diagnoses of no infection, possible infection, or possible inflammatory disorders. The remaining 203 children were renal disease follow-up cases. The diagnoses were based on a physical examination, microscopic urinalysis plus urine dipstick tests for albumin, blood, creatinine, protein, leukocyte esterase and a complete blood count. In the 205 children, 46 had an abnormal uristatin dipstick test, 39 had an abnormal uristatin by immunoassay, 41 had an abnormal erythrocyte sedimentation rate (ESR), 27 had an abnormal serum C-reactive protein (CRP), and one had an abnormal urine microscopic exam. For the first 938 children in the study, the agreement was 93% of negative dipstick uristatin results and immunoassays. The agreement of positive uristatin dipsticks with immunoassays was 85%. We assumed that the immunoassay results were correct. In the evaluation of 189 children with fever, 62 also had an abnormal uristatin by dipstick. DISCUSSION: A rapid dipstick test for uristatin read on a reflectance photometer gave values that compared well with a quantitative immunoassay method. The uristatin test is sensitive but not specific for any cause of infection or inflammation. Uristatin is easy to determine and appears to be a better indicator than fever, ESR, or CRP for the diagnosis of an infection or inflammation.