Laboratory-Acquired Meningococcal Disease United States, 2000

Transcription

1 FROM THE CENTERS FOR DISEASE CONTROL AND PREVENTION Laboratory-Acquired Meningococcal Disease United States, 2000 MMWR. 2002;51: NEISSERIA MENINGITIDIS IS A LEADING cause of bacterial meningitis and sepsis among older children and young adults in the United States. N. meningitidis usually is transmitted through close contact with aerosols or secretions from the human nasopharynx. Although N. meningitidis is regularly isolated in clinical laboratories, it has infrequently been reported as a cause of laboratory-acquired infection. This report describes two probable cases of fatal laboratory-acquired meningococcal disease and the results of an inquiry to identify previously unreported cases. The findings indicate that N. meningitidis isolates pose a risk for microbiologists and should be handled in a manner that minimizes risk for exposure to aerosols or droplets. Case Reports Case 1. On July 15, 2000, an Alabama microbiologist aged 35 years presented to the emergency department of hospital A with acute onset of generalized malaise, fever, and diffuse myalgias. The patient was given a prescription for oral antibiotics and released. On July 16, the patient returned to hospital A, became tachycardic and hypotensive, and died 3 hours later. Blood cultures were positive for N. meningitidis serogroup C. Three days before the onset of symptoms, the patient had prepared a Gram s stain from the blood culture of a patient who was subsequently shown to have meningococcal disease; the microbiologist also had handled and subcultured agar plates containing cerebrospinal fluid (CSF) cultures of N. meningitidis serogroup C from the same patient. Coworkers reported that in the laboratory, aspiration of materials from blood culture bottles was performed at the open laboratory bench; biosafety cabinets, eye protection, or masks were not used routinely for this procedure. Results of pulsed-field gel electrophoresis (PFGE) and multilocus enzyme electrophoresis (MEE) testing at CDC indicated that the two isolates were indistinguishable. The laboratory at hospital A infrequently processed isolates of N. meningitidis and had not processed another meningococcal isolate during the previous 4 years. Case 2. On December 24, 2000, a Michigan microbiologist aged 52 years had acute onset of sore throat, vomiting, headache, and fever; by December 25, the patient had developed a petechial rash on both legs, which quickly evolved to widespread purpura. The patient presented to the emergency department of hospital B and died later that day of overwhelming sepsis. Blood cultures were positive for N. meningitidis serogroup C. The patient was a microbiologist in the state public health laboratory and had worked on several N. meningitidis serogroup C isolates during the 2 weeks before becoming ill. That laboratory had handled a median of four meningococcal isolates per month (range: 0-11) during the previous 4 years. Co-workers reported that the patient had performed slide agglutination testing and recorded colonial morphology using typical biosafety level 2 (BSL (2) precautions; this did not entail the use of a biosafety cabinet. PFGE was performed at the state public health laboratory and at CDC on all four specimens handled by the microbiologist; results of this testing indicated that the isolates from the patient and from one of the recently handled laboratory samples were indistinguishable. To detect additional cases, on November 11, 2000, a request for information was posted on selected electronic mail discussion groups (i.e., listservs) to members of several infectious disease, microbiology, and infection control professional organizations. A probable case of laboratory-acquired meningococcal disease was defined as confirmed or probable meningococcal disease 1 in a laboratory scientist who had had occupational exposure to a N. meningitidis isolate during the 14 days before onset of illness and who had illness with a serogroup that matched the source isolate. In addition to the two cases described in this report, CDC received an additional 14 reports of probable 1256 JAMA, March 13, 2002 Vol 287, No. 10 (Reprinted) 2002 American Medical Association. All rights reserved.

2 laboratory-acquired meningococcal disease worldwide during the preceding 15 years; six cases occurred in the United States during The source isolates from five of these six U.S. cases were from either blood or CSF; the source of the sixth isolate could not be definitively determined but was most likely CSF or middle ear fluid. Of these 16 previously unreported cases, nine (56%) were caused by N. meningitidis serogroup B, and seven (44%) were caused by serogroup C; eight cases (50%) were fatal (three from serogroup B and five from serogroup C). Case-fatality rates did not differ significantly by serogroups (serogroup C: 71%; serogroup B: 33%; p=0.16). In the 10 cases for which data were available, a median of 4 days (range: 2-10 days) passed between handling the source isolate and symptom onset. Procedures performed on the 16 source isolates included reading plates (50%), making subcultures on agar plates (50%), and performing serogroup identification at the bench (38%). In 15 of the 16 cases, the laboratory reportedly did not perform procedures within a biosafety cabinet. All 16 cases occurred among workers in the micro-biology section of the laboratory; no cases were reported among workers in hematology, chemistry, or pathology. Reported by: J Lofgren, MD, B Whitley, MPH, Alabama Dept of Health. D Johnson, MD, F Downes, DrPH, State Public Health Laboratory; P Somsel, DrPH, B Robinson-Dunn, PhD, J Massey, DrPH, G Stoltman, PhD, MG Stobierski, DVM, S Bidol, MPH, Michigan Dept of Community Health. C Hahn, MD, L Tengelson, DVM, Idaho Dept of Public Health. P Murray, PhD, American Society for Microbiology, Washington, DC. The Infectious Diseases Committee of the American Public Health Laboratories Association, Washington, DC. The College of American Pathologists, Waukegan, Illinois. D Sewell, PhD, National Committee for Clinical Laboratory Standards, Wayne, Pennsylvania. W Schaffner, MD, Vanderbilt Univ School of Medicine, Nashville, Tennessee. D Stephens, Div of Infectious Diseases, Emory Univ School of Medicine, Atlanta, Georgia. M Miller, Div of Healthcare Quality Promotion; J Sejvar, MD, T Popovic, MD, B Perkins, MD, N Rosenstein, MD, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; National Institute for Occupational Safety and Health; Div of Laboratory Systems; Office of Health and Safety, CDC. CDC Editorial Note: Although the risk for disease remains low, 2 laboratoryacquired meningococcal disease represents an occupational hazard to microbiologists. The findings in this report were self-reported and required respondents to have access to electronic media. However, the identification of 14 previously unreported cases and the additional two cases reported to CDC in 2001 suggest that either cases of laboratoryacquired meningococcal disease are underreported or the incidence of laboratory-acquired meningococcal disease has increased. The case-fatality rate of 50% in this report is substantially higher than that observed among communityacquired cases; this might reflect underreporting of mild cases or might be a result of the highly virulent strains and high concentration of organisms encountered in the laboratory setting. Each year in the United States, approximately 3,000 isolates of invasive N. meningitidis are cultured 3 ; on the basis of standard practices used for isolation and identification of N. meningitidis, each of the clinical samples and isolates is handled by an average of three microbiologists during the course of a laboratory investigation, resulting in an estimated 9,000 microbiologists exposed per year. During in the United States, six cases of probable laboratory-acquired meningococcal disease were detected, for an attack rate of 13 per 100,000 population (95% confidence interval [CI] =5-29) at risk per year, compared with approximately 0.2 per 100,000 population among adults aged in the United States (CDC, unpublished data, 2001), the age group of most laboratory scientists. If the three cases from 2000 are excluded from this estimate, the attack rate is seven (95% CI=1-19). N. meningitidis is classified as a biosafety level 2 organism. 4 Guidelines recommend the use of a biosafety cabinet for mechanical manipulations of samples that have a substantial risk for droplet formation or aerosolization such as centrifuging, grinding, and blending procedures. 4,5 Less is known about the risk associated with routine isolate manipulation. The exclusive occurrence of probable laboratory-acquired cases in microbiologists suggests that exposure to isolates of N. meningitidis, and not patient samples, increases the risk for infection. Nearly all the microbiologists in this report were manipulating isolates and performing subplating with an inoculation loop on an open laboratory bench. A recent study indicated that manipulating suspensions of N. meningitidis outside a biosafety cabinet is associated with a high risk for contracting disease. 3 Isolates obtained from a respiratory source are in general less pathogenic and represent a lower risk for microbiologists. Although the exact mechanism of transmission in the laboratory setting is unclear, use of a biosafety cabinet during manipulation of sterile site isolates of N. meningitidis would ensure protection. Alternative methods of protection (e.g., splash guards and masks) from droplets and aerosols require additional assessment. If a biosafety cabinet or other means of protection is unavailable, manipulation of these isolates should be minimized, and workers should consider sending specimens to laboratories possessing this equipment. Education of microbiologists and strict adherence to these safety precautions when manipulating meningococcal isolates should further minimize the risk for infection. To address these safety issues, the governing bodies of organizations responsible for setting policy for laboratory safety will be reassessing current guidelines about the handling of N. meningitidis. Although primary prevention should focus on laboratory safety, laboratory workers also should make informed decisions about vaccination. The quadrivalent meningococcal polysaccharide vaccine, which includes serogroups A, C, Y, and W-135, will decrease but not eliminate the risk for infection. 6 Research and industrial laboratory scientists who are exposed routinely to N. meningitidis in solutions that might be aerosolized also should consider vaccination. 6-8 In addition, vaccination might be used as an adjunctive measure by microbiologists in clinical laboratories American Medical Association. All rights reserved. (Reprinted) JAMA, March 13, 2002 Vol 287, No

3 Laboratory scientists with percutaneous exposure to an invasive N. meningitidis isolate from a sterile site should receive treatment with penicillin; those with known mucosal exposure should receive antimicrobial chemoprophylaxis. 6 (Table 1). Microbiologists who manipulate invasive N. meningitidis isolates in a manner that could induce aerosolization or droplet formation (including plating, subculturing, and serogrouping) on an open bench top and in the absence of effective protection from droplets or aerosols also should consider antimicrobial chemoprophylaxis. CDC has instituted prospective surveillance for laboratory-acquired meningococcal disease. Hospitals, laboratories, and public health departments that are aware of suspected cases should report these cases through their state public health department to CDC, telephone available Barriers to Dietary Control Among Pregnant Women With Phenylketonuria United States, MMWR. 2002;51: tables omitted NEWBORNS IN THE UNITED STATES ARE screened for phenylketonuria (PKU), a metabolic disorder that when left untreated is characterized by elevated blood phenylalanine (phe) levels and severe mental retardation (MR). An estimated 3,000-4,000 U.S.-born women of reproductive age with PKU have not gotten severe MR because as newborns their diets were severely restricted in the intake of protein-containing foods and were supplemented with medical foods (e.g., amino acid-modified formula and modified low-protein foods). 1-4 When women with PKU do not adhere to their diet before and during pregnancy, infants born to them have a 93% risk for MR and a 72% risk for microcephaly. 5-6 These risks result from the toxic effects of high maternal blood phe levels during pregnancy, not because the infant has PKU. 5-6 The restricted diet, which should be maintained for life, often is discontinued during adolescence This report describes the pregnancies of three women with PKU and underscores the importance of overcoming the barriers to maintaining the recommended dietary control of blood phe levels before and during pregnancy. For maternal PKU-associated MR to be prevented, studies are needed to determine effective approaches to overcoming barriers to dietary control. During the fall of 2000, CDC conducted an interview-based study of women with PKU who were aged 18 years and pregnant during (index pregnancy), regardless of dietary management or pregnancy outcome. Women were recruited from three metabolic clinics that provided services funded by state and private sources and were interviewed using a structured questionnaire that was completed in person or by telephone. Medical records were requested to document timing of diet initiation, control of blood phe levels (defined as 2-6 mg/dl), and pregnancy outcome. The study protocol was approved by CDC s Institutional Review Board, and informed consent was obtained from each respondent. A total of 30 women met the interview criteria; two could not be contacted. Of the 28 remaining women, 24 were interviewed (17 in person and seven by telephone). The median age was 28 years (range: years); 75% were married, 96% were white, and 50% had a high school education or less. A total of 51 pregnancies had occurred among 24 women. Among the 24 index pregnancies, 18 (75%) resulted in live-born infants; 11 (46%) pregnancies were intended. The use of formula-based medical foods before conception was reported more often among the 11 women who were trying to conceive than among those who were not (risk ratio=3.5; 95% confidence interval= ). Use of modified, low-protein medical foods to diversify the diet was reported only among women trying to conceive. No difference was reported in avoiding high-protein foods between women who were and who were not trying to conceive. One woman remained on the restricted diet throughout adulthood; 23 women had been off the diet for 6-24 years (average: 16 years). At the time of the interview, 17 (71%) women were not using medical foods (65% because of the unpleasant taste). A total of 22 women had resumed the diet before or during their index pregnancy, eight (33%) women had contacted the metabolic clinic before conception, and 11 (46%) had contacted the metabolic clinic after conception but by week 10 of gestation. Of the 22 medical records available, 12 (55%) records indicated controlled blood phe levels before 10 weeks of gestation. All of the women expressed confidence in their metabolic clinic staff s knowledge of a phe-restricted diet and maternal PKU; eight (33%) perceived that their obstetricians were knowledgeable about maternal PKU. Approximately equal numbers of women used public assistance and private insurance to cover the costs associated with clinic visits. Costs of medical foods were more often covered by public assistance than by private insurance. Among the 13 women who used public assistance, nine (69%) reported that proof of pregnancy was required to receive services. When the data were stratified by state of residence, women in state C had the lowest rate of live births resulting from their pregnancies, lowest use of formula before pregnancy, fewest women achieving metabolic control before 10 weeks gestation, and longest commutes to a metabolic clinic. These differences were not significant by Fisher exact test JAMA, March 13, 2002 Vol 287, No. 10 (Reprinted) 2002 American Medical Association. All rights reserved.

4 Case Reports Case 1. A woman aged 21 years discontinued formula use in early adolescence and lost contact with the metabolic clinic. Although she was aware of the need to follow the diet during pregnancy, she did not seek care when she became pregnant. PKU was listed in her prenatal medical records; however, her obstetrician did not refer her to a metabolic clinic or a maternal-fetal specialist and did not recommend dietary intervention or regular monitoring of her phe levels. Her pregnancy resulted in an infant with microcephaly and developmental delay. Case 2. A woman aged 21 years discontinued formula use in early adulthood because of limited financial resources. She reported willingness to adhere to the diet during pregnancy, but lack of transportation, financial constraints, and inability to take time off from work prohibited her from accessing care at the nearest metabolic clinic, which was 3 hours away. She met with local health department staff several months into the pregnancy to acquire formula. PKU was included in her prenatal medical records, and she was referred to a maternal-fetal specialist; however, her blood phe levels were not monitored, and she was not referred to a metabolic clinic. Her pregnancy resulted in an infant with microcephaly. Case 3. A woman aged 27 years remained on the PKU diet throughout adulthood, planned her pregnancy, and had her blood phe levels in control before conception. Her private insurance covered part of her diet-related medical treatment costs. She estimated that out-of-pocket expenses for the portion of the metabolic clinic visits not paid by insurance were $2,300 during her pregnancy. Her insurer denied coverage for formula, lowprotein foods, and blood tests to examine her full amino acid profile. The metabolic clinic provided the formula without reimbursement from the insurance company. Her pregnancy resulted in a healthy infant. Reported by: PM Fernhoff, MD, R Singh, PhD, Div of Medical Genetics, Dept of Pediatrics, Emory Univ School of Medicine, Atlanta, Georgia. S Waisbren, PhD, F Rohr, MS, Children s Hospital, Boston, Massachusetts. DM Frazier, PhD, Div of Genetics and Metabolism, Univ of North Carolina, Chapel Hill. SA Rasmussen, MD, AA Kenneson, PhD, MA Honein, PhD, National Center on Birth Defects and Developmental Disabilities; ML Gwinn, MD, Office of Genetics and Disease Prevention, National Center for Environmental Health; and AS Brown, PhD, JM Morris, PhD, P MacDonald, PhD, EIS officers, CDC. CDC Editorial Note: This report highlights some barriers that prevent metabolic control of blood phe levels before pregnancy among women with PKU. Two thirds of the women in this study had not followed the diet before becoming pregnant. This demonstrates limited adherence to prepregnancy medical recommendations among these women. Women also reported limited confidence in obstetricians knowledge of maternal PKU management and inconsistencies between medical recommendations and health insurance coverage. Following the lifelong diet also was complicated by the unpleasant taste of medical foods. The findings in this report are subject to at least three limitations. First, the sample size was small and consisted mostly of women who received dietary management from metabolic clinics during pregnancy. These women might have had access to more resources or been more willing to adhere to medical recommendations than women who had not received such care. Second, at the time of the interviews, most of the women were not following their diets; persons with PKU who are not on the diet might have difficulties with concentration and memory that could compromise the accuracy of their responses. Third, the three clinics participating in this study do not represent all U.S. metabolic clinics. To improve pregnancy outcomes for women with PKU, health-care providers should be trained to advise women to plan their pregnancies, return to diet, and stay on the diet for life. Additional evaluation is needed to ascertain the knowledge needed by obstetricians to guide women with PKU; third-party payers could identify disparities in financial assistance available to pregnant women with PKU and determine the most cost-effective approaches. Additional examination of these barriers would allow public health programs to establish effective methods to reduce obstacles and improve pregnancy outcomes for women with PKU. 1. American College of Obstetrics and Gynecology Committee on Genetics Opinion. Maternal phenylketonuria. Int J Gynaecol Obstet 2001;72: Luder AS, Greene CL. Maternal phenylketonuria and hyperphenylalaninemia: implications for medical practice in the United States. Am J Obstet Gynecol 1989;161: MacCready RA. Admissions of phenylketonuric patients to residential institutions before and after screening programs of the newborn infant. J Pediatr 1974; 85: Koch R, Levy HL, Matalon R, Rouse B, Hanley W, Azen C. The North American collaborative study of maternal phenylketonuria. Am J Dis Child 1993;147: Lenke RR, Levy HL. Maternal phenylketonuria and hyperphenylalaninemia: an international survey of the outcome of untreated and treated pregnancies. N Engl J Med 1980;303: Platt LD, Koch R, Hanley WB, et al. The international study of pregnancy outcome in women with maternal phenylketonuria: report of a 12-year study. Am J Obstet Gynecol 2000;182: National Institutes of Health. Phenylketonuria: screening and management. National Institutes of Health consensus statement online Bethesda, Maryland: National Institutes of Health. October 16-18, 2000; vol. 17, no. 3:1-28. Available at odp.od.nih.gov/consensus/cons/113/113_statement.htm. Accessed July Schuett VE, Gurda RF, Brown ES. Diet discontinuation policies and practices of PKU clinics in the United States. Am J Public Health 1980;70: Waisbren SE, Schnell RR, Levy HL. Diet termination in children with phenylketonuria: a review of psychological assessments used to determine outcome. J Inherit Metab Dis 1980;3: Kirkman HN, Frazier DM. Maternal PKU: thirteen years after epidemiological projections. Inter Peds 1996;11: Lyme Disease United States, 2000 MMWR. 2002;50:29-31 March 13 LYME DISEASE (LD) IS CAUSED BY THE tickborne spirochete Borrelia burgdorferi sensu lato and is the most common vectorborne disease in the United States. CDC initiated LD surveillance in 1982, and the Council of State and Territorial Epidemiologists designated it a nationally notifiable disease in This report summarizes the 17,730 cases of LD reported to CDC 2002 American Medical Association. All rights reserved. (Reprinted) JAMA, March 13, 2002 Vol 287, No

5 during 2000, which indicates that more LD cases were reported in 2000 than in any previous reporting year and that the reported incidence of LD is greatest in the northeastern, mid-atlantic, and north-central regions of the United States. LD can be prevented by reducing tick populations, avoiding tickinfested habitats, using repellents, promptly removing attached ticks, and vaccination. For surveillance purposes, LD is defined as the presence of a physiciandiagnosed erythema migrans (EM) rash 5 cm in diameter or at least one manifestation of musculoskeletal, neurologic, or cardiovascular disease with laboratory confirmation of B. burgdorferi infection. 1 Incidence was calculated using 2000 population data from the U.S. Census Bureau. During 2000, a total of 17,730 LD cases (incidence * : 6.3 cases) were reported from 44 states and the District of Columbia, an 8% increase over 1999 (16,273 cases) and a 5% increase over 1998 (16,801 cases). As in previous years, most cases were reported from the northeastern, mid-atlantic, and north-central regions. State incidence was higher than the national incidence in Connecticut (110.8), Rhode Island (64.4), New Jersey (29.2), New York (22.8), Delaware (21.3), Pennsylvania (19.1), Massachusetts (18.2), Maryland (13.0), Wisconsin (11.8), Minnesota (9.5), New Hampshire (6.8), and Vermont (6.6); these 12 states accounted for 16,877 (95%) of nationally reported cases. During , 24 states and the District of Columbia reported increases in the number of cases, 19 reported decreases, and seven reported no change. In 2000, no cases were reported in six states (Colorado, Georgia, Hawaii, Montana, New Mexico, and South Dakota). Based on data for 17,570 (99%) LD cases, 723 (23%) of 3,143 U.S. counties reported at least one case; approximately 90% of the cases were reported from 124 counties. Reported incidence was 100 cases in 24 counties in Connecticut, Maryland, Massachusetts, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin; the highest incidence (943) was reported in Columbia County, New York. Among 17,551 LD patients with age reported, distribution was bimodal and the median age was 39 years (range: 1-98 years). The highest reported incidence occurred among children aged 5-9 years (9.3) and adults aged years (8.2). Among 17,663 patients with sex reported, 9,472 (53.6%) were males, who had a higher incidence compared with females in all age groups. Among 12,977 (73.2%) patients with month of illness onset reported, 7,427 (57.2%) occurred during June (27.3%) and July (29.9%); 5.8% occurred during January, February, and December Reported by: State and District of Columbia health depts. S Marshall, MPH, E Hayes, MD, D Dennis, MD, Div of Vector-borne Infectious Diseases, National Center for Infectious Diseases, CDC. CDC Editorial Note: During , the reported incidence of LD nearly doubled. Most cases continued to occur in northeastern, mid- Atlantic, and north-central states, 2,3 and the largest proportion of cases continued to be reported among persons aged 5-9 years and years, possibly as a result of greater exposure than other groups to infected ticks, less frequent use of personal protective measures, differential use of health-care services, and/or reporting bias. The large number of reported LD cases during June and July reflects the seasonal peak of host-seeking activities of infective nymphal-stage vector ticks during May and June in areas where LD is endemic. 4 The findings in this report are subject to at least three limitations. First, because LD is reported through passive surveillance, LD is underreported, and the distribution and demographics of reported cases could be biased. Second, LD is underreported in areas where disease is endemic and might be overreported in areas where disease is nonendemic. Third, not all LD patients present with typical manifestations; other conditions might be confused with LD and laboratory testing might be inaccurate. LD can be prevented by reducing tick populations, avoiding tick-infested areas, using repellents, promptly removing attached ticks, and vaccination. Booster doses may be required, but the optimal schedule for this has not been determined. A vaccine was licensed in 1998 that is 76% effective in preventing LD among recipients of 3 doses. 5 New strategies for reducing tick vectors of LD include applying acaricides to the principal animal hosts of Ixodes scapularis ticks (i.e., a device for killing ticks on white-tailed deer and a bait box for killing ticks on rodents) ( 6, CDC, unpublished data, 2001). In 2001, community-based LD prevention projects were initiated in Connecticut, Massachusetts, New Jersey, and New York. Through the application of integrated prevention strategies in communitybased programs, CDC and state health departments hope to achieve the 2010 national health objective of reducing the incidence of LD to 9.7 in states where LD is endemic (objective 14-8). 1. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(No. RR-10): Orloski KA, Hayes EB, Campbell GL, Dennis DT. Surveillance for Lyme disease United States. In: CDC surveillance summaries (April 28, 2000). MMWR 2000; 49(No. SS-3): CDC. Lyme disease United States, MMWR 2001;50(No. RR-10): Dennis DT. Epidemiology, ecology, and prevention of Lyme disease. In: Rahn DW, Evans J, eds. Lyme Disease. Philadelphia, Pennsylvania: American College of Physicians, 1998: CDC. Recommendations for the use of Lyme disease vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48(No. RR-7): Pound JM, Miller JA, George JE, Lemeilleur CA. The 4-poster passive topical treatment device to apply acaricide for controlling ticks (Acari: Ixodidae) feeding on white-tailed deer. J Med Entomol 2000;37: *Per 100,000 population JAMA, March 13, 2002 Vol 287, No. 10 (Reprinted) 2002 American Medical Association. All rights reserved.