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urred after direct exposure to a health-care worker CW) with pertussis. This report describes the outbreak estigation and highlights the importance of following ommendations to administer tetanus toxoid, reduced ➡htheria toxoid, and acellular pertussis (Tdap) vaccine HCWs to prevent transmission of pertussis to patients. mmediately after identification of the six infants with tussis at children's hospital A, hospital staff members ewed newborn nursery charts at general hospital A. One f member (HCW A) was identified as having directly ed for all six infants during their stay in the newborn sery. Review of work logs for all shifts identified four litional hospital workers who had been present while six infants were in the newborn nursery.
rom early to mid-June until July 17, while working in newborn nursery at general hospital A, HCW A had ibited symptoms of pertussis, including cough, ttussive emesis, and dyspnea. Her spouse reportedly had ilar symptoms after he returned from a trip to Califor2-3 weeks before HCW A began exhibiting her symp15. HCW A, aged 24 years, had been fully vaccinated pertussis during early childhood. HCW A and a nurscoworker with cough symptoms were tested for pertusby PCR; only HCW A tested positive. On July 17, HCW vas furloughed from general hospital A for 5 days and ted with erythromycin. Her husband also was prescribed thromycin.
fter obtaining Institutional Review Board approval from institutions involved, staff members at children's hosil A reviewed the charts and laboratory records of all .ents aged <4 months who had received a diagnosis of tussis during June-August 2004. During that period, additional cases of pertussis were reported to the county Ith department from facilities other than children's 'pital A. A case of pertussis was defined in accordance 1 the Council of State and Territorial Epidemiologists TE) case definition for pertussis, with one variation. CSTE case definition for pertussis is a cough illness ing at least 2 weeks with one of the following sympis and no other apparent cause (as reported by a health fessional): paroxysms of coughing, inspiratory “whoop," posttussive vomiting. Confirmatory criteria consist of er isolation of B. pertussis from a clinical specimen or tive PCR assay for B. pertussis. For this investigation, definition was modified to include infants with cough ess of any duration so that the definition might cover s in newborns in the first 2 weeks of life. PCR amplifion and detection of a 114 nucleotide segment of the
B. pertussis IS481 sequence (1) was conducted using nucleic acid extracted from nasopharyngeal swabs.
The review of laboratory records and charts at children's hospital A revealed that 29 infants aged <4 months met the case definition for pertussis during June-August. Of these 29 infants, 11 (including the six previously known patients) had been born at general hospital A and directly exposed to HCW A in the newborn nursery. All 11 had been treated at children's hospital A with erythromycin and recovered; none developed hypertrophic pyloric stenosis, which has been reported as a complication of treatment of infants with erythromycin (2). Five of the infants required admission to the pediatric intensive-care unit (PICU), and four were treated in the general pediatric medical unit; one infant was treated in the emergency department, and one was treated as an outpatient (Table). Median age of the 11 infants born at general hospital A was 31 days at the time of pertussis diagnosis, compared with a median age of 61 days for the other 18 infants with diagnosed pertussis, who were born at 12 other general hospitals during June-August. On July 21, 2004, the county health department directed general hospital A to contact the families of all infants who had been in its newborn nursery during May 31-July 17 so that the infants could be screened for respiratory symptoms and administered antibiotics as needed. Families of 158 infants who had been in the newborn nursery during May 31-July 17 were contacted, and a total of 110 infants returned to general hospital A. Eighteen of the 110 had cough but were PCR negative; they received erythromycin prophylaxis. Two infants had cough and also were PCR positive; they were treated for pertussis, and one was admitted to children's hospital A. In addition, three family members reported cough or runny nose but were PCR negative; they were treated with erythromycin.
During the period that HCW A exhibited symptoms, she directly cared for 113 infants, 11 of whom subsequently had a diagnosis of pertussis, resulting in an attack rate of 9.7%. One other possible case was identified in a sibling aged 3 years. Interviews with families when they brought their infants back to general hospital A for screening, revealed no other exposures to pertussis. No secondary cases of pertussis among HCWs at either general hospital A or children's hospital A were discovered. After HCW A was furloughed and treated, no new cases of pertussis were identified during September-October 2004 in infants born at general hospital A.
Reported by: JL Hood, MPH, DK Murphey, MD, JJ Dunn, PhD, children's hospital A, Texas.
TABLE. Characteristics of 11 infants who received diagnoses of pertussis after being under the direct care of the same health-car worker - Texas, 2004
Editorial Note: Pertussis is a highly contagious, vaccinepreventable illness caused by Bordetella pertussis infection. Complications of pertussis (e.g., seizures, pneumonia, encephalopathy, and cardiovascular compromise) can occur, especially in infants aged <1 year. Deaths from pertussis occur most frequently among infants; the case-fatality rate is 1.8% for newborns and infants aged <2 months (3). From 1980-1989 to 1990-1999, the number of infant deaths from pertussis increased from 61 (1.67 deaths per million) to 93 (2.40 deaths per million) (4). Newborns most commonly acquire pertussis from adults with undiagnosed disease (5). Reports on outbreaks of pertussis in health-care facilities and neonatal nurseries have been published previously (6,7).
In 2004, the reported incidence of pertussis in the United States nearly tripled compared with 2001, and the number of reported cases exceeded any year since 1959 (8). This increase might have resulted, in part, from increased use of more sensitive PCR testing (8). CDC recommendations call for culture confirmation of infection in one or more cases in an outbreak. However, in the outbreak described in this report, no culture confirmation was performed. The medical staff at children's hospital A requested PCR testing, as did the local health department. Current molecular detection methods for detection of B. pertussis have high sensitivity compared with culture, but occasionally can be prone to false positives, depending on the target sequences, interpretation of results, and subjects tested (9). In a recent report describing outbreaks of respiratory illness mistakenly attributed to pertussis, PCR was used inappropriately as a mass screening tool on a large number
of persons who did not meet the CSTE case definition fr pertussis (9). For the infants described in this report, a high index of suspicion for pertussis was based on clinical symp toms, and PCR testing was used to confirm diagnoses of pertussis. HCW A also met the CTSE case definition fc: pertussis.
In 2005, Tdap vaccine was licensed by the Food and Drug Administration for use in adolescents and adults. I December 2006, the Advisory Committee on Immuniza tion Practices (ACIP) recommended use of Tdap vaccine for HCWs with direct patient contact and for adults whi have or might have close contact with infants aged <l months (3). This recommendation was based on the doc mented risk for transmission of pertussis in health-car facilities. Despite the costs involved for health-care facili ties, one study suggests the return on investment from va cinating HCWs with Tdap vaccine is twice the cost of th vaccine (10).
Widespread implementation of Tdap vaccination of ad lescents and adults as recommended by ACIP can redu the risk for pertussis in the community and the incide of pertussis transmission in health-care facilities. This o break also highlights the importance of rapid recogniti of pertussis transmission in health-care settings and rap response from hospital and public health practitioners identify the source and prevent more extensive spread disease, particularly among vulnerable newborns an infants.
The findings in this report are based, in part, on observations h made by S Roderick.
-Kösters K, Riffelmann M, Wirsing von König CH. Evaluation of a real-time PCR assay for detection of Bordetella pertussis and B. parapertussis in clinical samples. J Med Microbiol 2001;50:436-40. CDC. Hypertrophic pyloric stenosis in infants following pertussis prophylaxis with erythromycin-Knoxville, Tennessee, 1999. MMWR r. 1999;48:1117-20.
CDC. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: Recommendations of the Advisory Committee on Immuniza-- tion Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee *(HICPAC), for use of Tdap among health-care personnel. MMWR 2006;55(No. RR-17).
· Vitek CR, Pascual FB, Baughman AL, Murphy TV. Increase in deaths from pertussis among young infants in the United States in the 1990s. Pediatr Infect Dis J 2003;22:628–34.
Bamberger E, Starets-Haham O, Greenberg D, et al. Adult pertussis is hazardous for the newborn. Infect Control Hosp Epidemiol _2006;27:623-5.
Bryant KA, Humbaugh K, Brothers K, et al. Measures to control an outbreak of pertussis in a neonatal intermediate care nursery after exposure to a healthcare worker. Infect Control Hosp Epidemiol 2006;27:541–5.
CDC. Outbreaks of pertussis associated with hospitals—Kentucky, Pennsylvania, and Oregon, 2003. MMWR 2005;54:67-71.
CDC. Summary of notifiable diseases, United States, 2004. MMWR 2006;53(53).
CDC. Outbreaks of respiratory illness mistakenly attributed to pertussis-New Hampshire, Massachusetts, and Tennessee, 2004-2006. MMWR 2007;56:837-42.
Calugar A, Ortega-Sanchez I, Tiwari T, Oakes L, Jahre J, Murphy TV. Nosocomial pertussis: costs of an outbreak and benefits of vaccinating health care workers. Clin Infect Dis 2006;42:981–8.
Public Health Consequences of a False-Positive Laboratory Test Result for Brucella Florida, Georgia, and Michigan, 2005
Human brucellosis, a nationally notifiable disease, is common in the United States. Most human cases have urred in returned travelers or immigrants from regions ere brucellosis is endemic, or were acquired domestiy from eating illegally imported, unpasteurized fresh* eses (1,2). In January 2005, a woman aged 35 years > lived in Nassau County, Florida, received a diagnosis rucellosis, based on results of a Brucella immunoglobuM (IgM) enzyme immunoassay (EIA) performed in a amercial laboratory using analyte specific reagents Rs); this diagnosis prompted an investigation of dairy ducts in two other states. Subsequent confirmatory
sh cheeses, such as cottage cheese and Neufchâtel, also are referred to as soft or ipened cheeses. They are made by curdling milk and draining the whey, with e additional processing, and spoil more quickly than processed hard cheeses.
antibody testing by Brucella microagglutination test (BMAT) performed at CDC on the patient's serum was negative. The case did not meet the CDC/Council of State and Territorial Epidemiologists' (CSTE) definition for a probable or confirmed brucellosis case (3) (Box), and the initial EIA result was determined to be a false positive. This report summarizes the case history, laboratory findings, and public health investigations. CDC recommends that Brucella serology testing only be performed using tests cleared or approved by the Food and Drug Administration (FDA) or validated under the Clinical Laboratory Improvement Amendments (CLIA) and shown to reliably detect the presence of Brucella infection. Results from these tests should be considered supportive evidence for recent infection only and interpreted in the context of a clinically compatible illness and exposure history. EIA is not considered a confirmatory Brucella antibody test; positive screening test results should be confirmed by Brucella-specific agglutination (i.e., BMAT or standard tube agglutination test) methods.
On February 1, 2005, the Nassau County Health Department received a report, based on a positive Brucella antibody test result, of a possible case of brucellosis in a
BOX. CDC/Council of State and Territorial Epidemiologists case definition for human brucellosis for public health surveillance
An illness characterized by acute or insidious onset of fever, night sweats, undue fatigue, anorexia, weight loss, headache, and arthralgia.
Laboratory criteria for diagnosis
• Isolation of Brucella spp. from a clinical specimen, or • Fourfold or greater rise in Brucella agglutination titer between acute- and convalescent-phase serum specimens obtained ≥2 weeks apart and studied at the same laboratory, or
•Demonstration by immunofluorescence of Brucella spp. in a clinical specimen. Case classification
Probable: clinically compatible case that is epidemiologically linked to a confirmed case or that has supportive serology (i.e., Brucella agglutination titer ≥160 in one or more serum specimens obtained after onset of symptoms).
Confirmed: a clinically compatible illness that is laboratory confirmed.
SOURCE: CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(No. RR-10):8–9.
female resident aged 35 years. The woman reported having intermittent fever, chills, sweats, body aches, weakness, headaches, and malaise since October 13, 2004. She was examined first at a local emergency department in November 2004, diagnosed with acute bronchitis, and discharged without a prescription for antimicrobials. She subsequently was examined by an infectious disease specialist on January 3, 2005, at which time brucellosis was considered based on continued nonspecific symptoms, polyarthritis, and an atypical lymphocytosis seen on a peripheral blood smear. Blood was obtained for culture and Brucella antibody testing on January 3 and January 24. Blood cultures were negative after 10 days. The EIA results from a commercial laboratory were interpreted as positive IgM and negative IgG, consistent with early brucellosis. On the basis of these results, on February 1 the patient was prescribed a twice daily, 6-week course of antimicrobial therapy of doxycycline (100 mg) and rifampin (300 mg). She stopped taking both antimicrobials after a short period because of side effects. After confirmatory testing by BMAT of the January 24 serum sample, performed February 14 at CDC, was negative, no further treatment for brucellosis was recommended. No other infectious etiologies were identified as a cause of the patient's symptoms, and she was lost to follow
After the February 1 report, but before receiving the negative BMAT results, Nassau County and Florida epidemiologists began an investigation to identify possible exposures to Brucella species. The patient reported no recent contact with animals or animal fluids. She had eaten goat cheese from several sources while traveling in Michigan during May-July 2004 and while staying at a Georgia youth hostel in July 2004, 3-5 months before her illness onset. No unpasteurized dairy products were discovered at the identified sources that supplied locations where the woman ate. At the youth hostel, all dairy products used for cooking were pasteurized and purchased from local markets; however, guests often contributed food they had brought with them, and exact origins of shared foods were difficult to determine.
Reported by: A Pragle, MS, C Blackmore, DVM, Florida Dept of Health. TA Clark, MD, Div of Bacterial Diseases, National Center for Immunization and Respiratory Diseases; MD Ari, PhD, PP Wilkins, PhD, Div of Foodborne, Bacterial, and Mycotic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; D Gross, DVM, PhD, EJ Stern, MD, EIS officers, CDC.
Editorial Note: Brucellosis is a classic bacterial zoonosis. Common Brucella species that are pathogenic in humans and their usual animal reservoirs include B. melitensis in
sheep and goats, B. abortus in cattle, and B. suis in swir B. melitensis, considered the most pathogenic species humans, has not been reported in animals in the Unit States since 1999. Symptoms of human brucellosis va and include periodic or undulant fever, muscle aches, bad pain, and fatigue. Diagnosis can be difficult because br.cellosis has a prolonged and variable incubation period days to 5 months), often presents as a nonspecific febrile syndrome, and occurs in acute, chronic, and asymptomatic forms.
Definitive diagnosis of brucellosis requires isolation and identification of the Brucella species. More commonly, cases are diagnosed serologically by detection of agglutinating antibodies. The reference method is the standard tube agglutination test (SAT), of which BMAT is a modified format (4). Brucella-specific agglutination tests involve direct agglutination of bacterial antigens by specific antibodies. Agglutination tests detect antibodies of IgM, IgG. and IgA classes. IgM antibodies are predominant in acute infection but decline within weeks, whereas relapses are accompanied by transient elevations of IgG and IgA antibodies but not IgM (5).
Evidence of Brucella antibody by nonagglutination-based tests does not meet the current CDC/CSTE case definition for brucellosis (Box). In the context of a clinically compatible illness, brucellosis is confirmed by a fourfold or greater rise in Brucella agglutination titer between acute- and convalescent-phase serum specimens obtained at least C weeks apart, isolation of Brucellae in culture, or demonstra tion of organism presence by specific immunohistochem cal staining (3). A clinically compatible case that is epidemiologically linked to a confirmed case or that has supportive serology (i.e., Brucella agglutination titer of ≥16 in one or more serum specimens obtained after onset of symptoms) is considered a probable case.
The Brucella EIA reagents used in this investigation were obtained from Panbio, Inc. (Columbia, Maryland); the are sold as ASRs in the United States but elsewhere as com plete test kits. ASRs are used as active components of assays developed by individual clinical laboratories (6 Laboratories that use ASRs are responsible for evaluating and validating their assay and for establishing and main taining assay interpretation and performance criteria including sensitivity and specificity (6). Specificity of the Panbio IgM and IgG EIA, based on a study in a brucellos's endemic area, was reported as 100% (7); IgM detection sensitivities using different EIA formats has been reported as 67%-100%, with limited specificity data (8). Such tests might have different performance characteristics when used
areas with low disease prevalence, such as the United tes. The CDC laboratory has observed that specimens t were positive using EIA tests from commercial laboraies often were negative when tested by BMAT. Results EIA tests must be confirmed by a reference method such BMAT, which is quantitative and provides evidence of ng antibody titers when paired sera are tested. Cross-reactions and false-positive test results can occur Brucella antibody tests. The primary immunodeterminant 1 virulence factor for Brucella species is the cell wall sure lipopolysaccharide, which is antigenically similar to lipopolysaccharide of other gram-negative rods. Falseitive Brucella antibody test results can be caused by crossctivity of antibodies to Escherichia coli O157, Francisella trensis, Moraxella phenylpyruvica, Yersinia enterocolitica, 1 certain Salmonella species (9). Most cross-reacting ibodies are IgM (10), making interpretation of any IgM y difficult because of false positivity. Therefore, results ained using EIA should be confirmed by a reference thod.
This investigation highlights the need to confirm screenserologic test results by using established reference testmethods and to identify the presence of known risk cors before committing a patient to prolonged antimibial therapy for brucellosis or initiating public health estigations. Testing of persons with compatible signs and ptoms for brucellosis should be supported by a thor;h history that reveals likely exposure through travel to area where brucellosis is endemic, consumption of an ›asteurized dairy product, hunting potentially infected dlife species, or laboratory exposure. Testing of persons the absence of a suggestive exposure increases the likelid of false-positive results and lowers the overall positive dictive value of the assay used. Rapid Brucella antibody ys can be useful as screening tools when results are rpreted in the context of performance characteristics of particular test; however, CDC recommends that all itive results obtained by rapid serologic assays be conned with Brucella-specific agglutination testing. For stions about risk factors or to request confirmatory testfor brucellosis in patients with strong evidence of expoe, health-care providers should contact their local or state lth department.
he findings in this report are based, in part, on contributions by eib, Nassau County Health Dept; K Ward, Florida Dept of Health; L Brumble, MD, Mayo Clinic, Jacksonville, Florida.
1. Chomel BB, DeBess EE, Mangiamele DM, et al. Changing trends in the epidemiology of human brucellosis in California from 1973 to 1992: a shift toward foodborne transmission. J Infect Dis 1994;170:1216-23.
2. Thapar MK, Young EJ. Urban outbreak of goat cheese brucellosis. Pediatr Infect Dis 1986;40:677-82.
3. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(No. RR-10):8-9.
4. Brown SL, Klein GC, McKinney FT, Jones WL. Safranin O-stained antigen microagglutination test for detection of Brucella antibodies. J Clin Microbiol 1981;13:398-400.
5. Reddin JL, Anderson RK, Jenness R, Spink WW. Significance of 7S and macroglobulin Brucella agglutinins in human brucellosis. N Engl J Med 1965;272:1263-8.
6. Food and Drug Administration. Guidance for industry and FDA staff. Commercially distributed analyte specific reagents (ASRS): frequently asked questions. Rockville, MD: US Department of Health and Human Services; 2007. Available at http://www.fda.gov/cdrh/oivd/ guidance/1590.pdf.
7. Araj G, Kattar M, Fattouh L, Bajakian KO, Kobeissi SA. Evaluation of the PANBIO Brucella immunoglobulin G (IgG) and IgM enzymelinked immunosorbent assays for diagnosis of human brucellosis. Clin Diag Lab Immun 2005;12:1334–5.
8. Memish ZA, Almuneef M, Mah MW, Qassem LA, Osoba AO. Comparison of Brucella standard agglutination test with the ELISA IgG and IgM in patients with Brucella bacteremia. Diag Microbiol Infect Dis 2002;44:129-32.
9. Corbel MJ. Brucellosis: an overview. Emerg Infect Dis 1997;3: 213-21.
10. Corbel MJ. Recent advances in the study of Brucella antigens and their serological cross-reactions. Vet Bull 1985;55:927–42.
National Cancer Survivors Day was June 1. Throughout the month of June, CDC is focusing attention on the needs of cancer survivors. Currently, approximately 11 million persons in the United States are living with a previously diagnosed cancer, a threefold increase from the estimated 3 million persons who were living with cancer in 1971 (1,2).
Today, approximately 65% of persons diagnosed with cancer are expected to live at least 5 years after diagnosis (2), but disparities in health care can affect survival. Lowincome persons who have inadequate or no health insurance coverage are more likely to be diagnosed with cancer at later stages, when the potential for survival is reduced (3). The National Action Plan for Cancer Survivorship (4), developed by CDC, the Lance Armstrong Foundation, and multiple partners, identified public health needs of cancer survivors and proposed strategies to meet those needs. Additional information, including descriptions of CDC's cancer survivorship research initiatives and partnerships and