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Measles: Lessons from an outbreak
Measles: Lessons from an outbreak Inge Gurevich, RN, MA Ricardo A. Barzarga, MD Burke A. Cunha, MD Mineola and Stony Brook, New York
Background: Measles outbreaks continue to be a problem for infection control in
hospitals-patients, personnel, and employee health service. Guidelines for measles outbreaks are not clear for medical personnel in the hospital. Methods: Outbreak investigation in a university-affiliated teaching hospital. Results: Four primary cases resulted in 607 staff exposures and two secondary cases. Forty-seven medical personnel were furloughed and 88 were vaccinated for measles. Minimal serologic criteria for immunity were found to be inadequate in the outbreak setting. Conclusions: We found that serologic guidelines for assessing immunity to measles are inadequate. During the outbreak, we arbitrarily doubled the acceptable enzyme-linked immunosorbent assay titers that we would consider protective, >_2, to decrease the possibility of further secondary cases. Employees with enzyme-linked immunosorbent assay measles titers less than 2 and without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination would confer in persons with low antibody titer. (AJIC AM J INFECTCONTROL1992;20:319-25)
Measles is highly contagious. R e c e n t o u t b r e a k s also d e m o n s t r a t e t h a t it c a n be a serious disease, w i t h the m o s t serious m a n i f e s t a t i o n s in adults a n d infants. B e c a u s e i n f e c t e d health c a r e w o r k ers p o s e a p o t e n t i a l risk to susceptible p a t i e n t s a n d o t h e r s u s c e p t i b l e h e a l t h c a r e w o r k e r s , outb r e a k i n v e s t i g a t i o n a n d c o n t r o l in h e a l t h c a r e institutions is t i m e - c o n s u m i n g , disruptive, a n d expensive. In April a n d July 1990, after several m e a s l e s o u t b r e a k s i n N e w York State, the N e w York State H e a l t h D e p a r t m e n t a n d the A m e r i c a n H o s p i t a l Association r e c o m m e n d e d t h a t hospitals follow revised guidelines f r o m the I m m u n i z a t i o n Advisory C o m m i t t e e of the U n i t e d States Public H e a l t h S e r v i c e ) These r e c o m m e n d a t i o n s state that hospitals s h o u l d r e q u i r e e v i d e n c e of m e a s l e s i m m u nity for n e w staff m e m b e r s w h o will h a v e d i r e c t c o n t a c t w i t h patients. The N e w York State D e p a r t m e n t of H e a l t h r e c o m m e n d e d that hospitals m a k e m e a s l e s v a c c i n e available to all susceptible hospiFrom the Infectious Disease Division, Winthrop-University Hospital. Mineola, and the State University of New York School of Medicine, Stony Brook, New York. Reprint requests: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501.
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tal e m p l o y e e s , volunteers, a n d p h y s i c i a n s b o r n after 1956 w h o do n o t h a v e a h i s t o r y of physiciand o c u m e n t e d measles, do n o t h a v e serologic evid e n c e of measles, o r h a v e not r e c e i v e d two doses of live m e a s l e s v a c c i n e a f t e r t h e i r first birthday. B e f o r e w e w e r e able to c o m p l y with t h e s e r e c o m m e n d a t i o n s , w e h a d o u r first case of nosoc o m i a l m e a s l e s in a h o u s e p h y s i c i a n on the infectious disease service w h o w a s exposed to a p a t i e n t w i t h m e a s l e s in the e m e r g e n c y departm e n t . H e h a d r e c e i v e d o n e d o s e of killed-virus v a c c i n e in t h e past; b e c a u s e his m e a s l e s e n z y m e linked i m m u n 0 s o r b e n t assay (ELISA) titer was 2.32 he w a s c o n s i d e r e d i m m u n e . Guidelines in the l i t e r a t u r e a n d texts w e r e n o n e x i s t e n t or u n helpful for assessing i m m u n i t y u n d e r o u t b r e a k conditions. DESCRIPTION OF OUTBREAK W i n t h r o p - U n i v e r s i t y I~/ospital is a 550-bed a c u t e c a r e ' c o m m u n i t y t e a c h i n g hospital with 3000 e m p l o y e e s a n d a n active e m e r g e n c y d e p a r t m e n t t h a t s e r v e s a b o u t 36,000 patients/year. The e m e r g e n c y d e p a r t m e n t was u n d e r g o i n g extensive renovations in the s u m m e r of 1990; this r e q u i r e d r e l o c a t i o n of isolation r o o m s a n d it was d u r i n g this d i s l o c a t i o n t h a t the first e x p o s u r e s o c c u r r e d . F r o m July_ 18 to August 28, 1990, t h e r e w e r e 319
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four more cases of measles in our hospital. These cases required contact investigations of more than 800 employees and patients and resulted in 607 actual exposures and a n u m b e r of staff furloughs. Some of these investigations, exposures, and furloughs could have been avoided had w e followed a more expeditious testing and vaccination schedule before the outbreak occurred. Exposure was defined as having been in the same r o o m with the patient, or within two adjoining rooms (same airspace) of patients not in negative-pressure isolation rooms. Other "air space" definitions are given for each case. Case 1
A 39-year-old white w o m a n who is an emergency department nurse at another institution was seen in our emergency department on July 6, 1990, for high fever and productive cough 2 days in duration. The patient stated that 2 weeks earlier she had had flulike symptoms for 3 days, which had resolved. Five days before admission (July I, 1990), she had a temperature of 102 ° F and a productive cough. She was seen by her attending physician and an antibiotic was prescribed, On her admission to our emergency department, the patient's temperature was 104 ° F and she had bilateral conjunctivitis. H e r face was erythematous b u t no rash was noted. The patient's white blood cell count was 3800 cells/mm 3, with 80% polymorphonuclear leukocytes. A chest x - r a y film showed questionable right lower lung infiltrate, and doxycycline was started for possible Legionella pneumonia. Both Legionella and measles fiters were obtained and the patient was admitted for observation and placed in respiratory isolation. Because a rash did not develop, isolation was discontinued after 24, hours. On the fifth hospital day, July 10, 1990, the patient had a maculopapular rash on her trunk that progressively involved her extremities. A clinical diagnosis of measles was made. The patient was placed in respiratory isolation again. H e r clinical condition slowly improved as the rash faded. H e r measles IgM titer was greater than 80. A titer of at least 20 by immunofluorescent antibody method is considered to indicate immunity. When the patient first came to the emergency department, she was placed in a nonisolation private r o o m because the designated isolation r o o m was occupied. Unfortunately, her room was not u n d e r negative or even equal air pressure. The air from this r o o m was recirculated throughout
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the emergency department. Although the patient was placed in respiratory isolation}signs were not posted and several staff m e m b e r s entered the r o o m without masking. These staff m e m b e r s were considered to be direct exposures, as were any patients in adjoining rooms for 2 hours or more. These patients w e r e considered to have shared her air space. One day after transfer from the emergency department to her hospital room, the patient's isolation was discontinued because she did not have a rash and her attending physician did not believe that she had measles. On day 5, however, a rash typical of measles broke out and the patient was placed in isolation once again. Because of the atypical development of her disease, she exposed two populations within the hospital to measles while not in isolation. Case 2
This patient was a 28-year-old house physician w h o was seen in the employee health clinic for fever and generalized maculopapular rash on July 19, 1990. He reported generalized body aches, frontal headache, a temperature of 102 ° F, a dry cough, and blurred vision. The patient denied having measles b u t had a history of chickenpox. Measles was diagnosed and the patient was discharged. Routine contact investigation revealed that he had been involved with patient 1 in the emergency department. On June 30, 1990, his p r e e m p l o y m e n t measles ELISA titer was 2.32; although he was considered to have direct exposure to patient I in the emergency department, he had not b e e n furloughed because he was considered " i m m u n e " by the titer criterion (Fig. I). He also reported a previous vaccination with killedvirus vaccine. B e c a u s e he was not feeling well before the development of the rash, he had limited his activities in the hospital to attendinglectures without seeing patients. He still exposed 77 employees. Measles titers were obtained from those contacts for w h o m measles titers were not on record and w h o did not have a history of measles. Case 3
A 65-year-old m a n was admitted to the hospital for a work-up of a right cerebral mass. The patient had been well until 2 weeks earlier, at which time he had gradual onset of left-handed weakness and clumsiness. Magnetic resonance imaging showed a right posterior parietal mass. The patient was scheduled for diagnostic and therapeutic craniotomy.
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I CASE3
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8/12 August 1990
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8/19
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l = Primary Cases = Secondary Cases Fig. 1. Primary and secondary measles cases during the 1990 outbreak.
Two days before operation he was started on a regimen of dexamethasone (Decadron), 4 mg intravenously every 6 hours. On the eleventh hospital day the patient u n d e r w e n t craniotomy with excision of the mass. The postoperative course of the patient was uneventful and he was started on a regimen of phenytoin (Dilantin). Also on the eleventh hospital day, on the recommendation of the oncologist, radiation therapy at 200 rads/day was started. During his eleventh day of radiation therapy (22 days after admission), the ,patient started to b e c o m e lethargic. He became progressively somnolent. On the 20th day of radiation therapy (July 18, 1990), d a y 31 of hospitalization, coryza, a temperature of 101 ° F, and a m a c u l o p a p u l a r rash on the face and chest developed. The diagnosis of rash as a side effect of phenytoin was made. The patient's fever worsened over the next few days, reaching 102.8 ° F. Two days later the rash b e c a m e morbilliform on the patient's chest, back, abdomen, and u p p e r extremities. When purulent conjunctivitis and dry cough developed, a diagnosis of measles was made and the patient was placed in respiratory isolation. On examination the patient was an acutely i11, well-developed man. He h a d erythema of the face with bilateral purulent conjunctivitis. The skin of the patient showed morbilliform rash on the chest, back, abdomen, u p p e r arms, and both lower extremities. At that time the hematocrit was 37%, the white cell count was 5900 cells/mm 3 (82% neutrophils, 10% lymphocytes, a n d 7% monocytes) and his measles ELISA IgM antibody titer was 4.38. The patient was unable to recall a measles disease or vaccination history. Because of the delay in recognizing the rash in this 65-year-old
m a n as being a s y m p t o m measles, extensive contact investigation was needed. Measles titers were obtained for 183 health care personnel w h o were in that patient care area during the time the patient was not in isolation. Also included were his r o o m m a t e and the patients in the two flanking rooms, all of w h o m shared at least part of the air space of his original r o o m because the air was not vented to the outside but was partially recirculated. Case 4
This patient was a 23-year-old white w o m a n w h o w a s seen in t h e emergency department on July 26, 1990, for fever, generalized rash, u p p e r respiratory tract infection symptoms of mild cough and nasal congestion, frontal headache, and back and joint pain. On examination, the patient was a young white w o m a n , acutely ill with a temperature of 102 ° F and a maculopapular rash on the face, neck, chest, trunk, and extremities. She was not placed in respiratory isolation until Koplick spots were noted. A diagnosis of rubeola was made and the patient was immediately discharged to h e r home. The patient was a nurse in our institution with no k n o w n exposure to anyone with measles and she had been on vacation. Because of her placem e n t in a nonisolation r o o m in the emergency department, she exposed 44 hospital employees w h o shared air space with her for an extended period. Case 5
A 34-year-old white w o m a n came into the emergency department on August 12, 1990, be-
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cause of epigastric discomfort, fever, and extreme fatigue of 3 days' duration. The patient was well until 2 days before consultation, w h e n she had bitemporal headaches. She also had fever as great as 103 ° F associated with shaking chills. She went to the emergency d e p a r t m e n t on her second day of illness, was deemed to have a viral syndrome, and was discharged h o m e with follow-up by her private medical doctor. The patient w e n t to her private medical doctor's office because of abdominal discomfort and vomiting. Because she felt extremely w e a k and the fever continued, she was sent back to the emergency department the next day, August 14, 1990, for an abdominal sonogram. The patient remained in the emergency department overnight. She was then noted to have a m a c u l o p a p u l a r rash on the face and later had a dry c o u g h and eye irritation. She was seen by the infectious disease service on the next day, August 15, and the diagnosis of measles was made. Examination of the patient revealed an alert, oriented young w o m a n with a temperature of 100.8 ° F. She h a d maculopapular lesions on her face, chest, back, and extremities and bilateral conjunctivitis. Other results of the physical examination were unremarkable. Laboratory findings revealed a white blood cell count of 3900 cells/mm 3 (76% polymorphonuclear leukocytes, !2% lymphocytes, 7% monocytes, and 2% atypical lymphocytes). Hematocrit was 4 2 % . H e r IgG measles titer was 1.6 and her IgM titer was greater than 1.8. Because of the delayed diagnosis at this patient's readmission and the fact that she had visited the e m e r g e n c y department 2 days before onset of the rash, at which time she was retrospectively considered to be infectious (see the Discussion section), she exposed 243 employees w h o had shared her air space during her prolonged stays. Case 6
A female nurse was seen in the infectious disease clinic on August 28, 1990, with a selfdiagnosis of measles. This was confirmed by the Infectious Disease physicians. This patient was a nurse in our e m e r g e n c y department who had been in the emergency department 13 days earlier. She had been furloughed because of the exposure to patient 5 and a negative measles titer. She could not be reached before August 20, day 5 of her furlough, and was then recalled for vaccination. She had p r o d r o m a l manifestations of measles 2 days after her vaccination (August 22). At her
diagnosis she was isolated, w h i c h d i d not result in any further exposures. C o n t a c t i n v e s t i g a t i o n s a n d titers
Altogether 607 employees and several patients were exposed to five of the six patients with measles and two secondary infections occurred (cases 2 a n d 6; Table 1). The second patient was hospitalized for approximately 1 month before he showed the signs and symptoms of measles and was therefore considered to have a nosocomial case. He had, however, not been exposed to any of o u r k n o w n cases and was presumably infected by a visitor. If measles ELISA titers were not available from exposed employees from previous testing, they were obtained on all those exposed. According to the ELISA method (Whittaker Measlestat; Whittaker Bioproducts, Walkersville, Md.), those with titers of _< 1 are considered nonimmune, those with titers 1 to 2.5 are considered low positive, those with titers 2.5 to 4.3 are considered intermediate, and those >4.3 are considered immune. However, we decided to vaccinate and/or furlough anyone without a reliable history of measles or with an ELISA titer < 2. Eighty-eight employees were vaccinated in the immediate period b e t w e e n July 25 and August 20. Forty-seven employees w h o had contact with a case and w e r e not i m m u n e were furloughed. DISCUSSION
Before 1988, serologic titers for rubella were obtained on all hospital employees, as m a n d a t e d by the Department of Health. Varicella titers w e r e also d r a w n because of continuous extensive exposures of o u r people to chicken pox, both in house and in the community. Keeping a record of susceptibility or immunity avoided extensive casedriven testing at times of exposure. Beginning in 1988, outbreaks of measles occurred in surrounding communities and in several states in the country, and we began routine testing for rubeola of n e w employees and those who were seen for their annual physicals. Our experience wit h varicelia immunity demonstrated that a history of varicella zoster did not necessarily correspond with the titers we obtained, but we relied on IgG titers _> 1 by ELISA as indicating immunity w h e n testing for measles. After the Health Department letter was received, a review of Employee Health Service records showed that about 155 of our regular employees either did not have protective titers (ELISA titer < 1 was considered to indicate susceptibility) or
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Table 1. Measles outbreak: Epidemiologic and vaccination summary of exposed staff
Case 1 2 3 4 5 6 - TOTAL
Date of exposure
Number of staff exposed
Number vaccinated
Number furloughed
Number secondary cases
< 1 (no.)
1-2 (no.)
> 2 (no.)
7/6 7/19 7/20 7/26 8/12 8/22
60 77 183 44 243 0 607
0 9 28 7 44 0 88
1 11 22 9 4 0 47
1 0 0 0 1 0 2
NA 4 7 2 27 0 40
NA 12 34 7 46 0 99
NA 61 142 35 170 0 408
did not yet have titers on record. A letter was sent to all these employees and their department heads to r e c o m m e n d that the employees contact their own physicians to obtain measles vaccination. Only seven employees responded to the letter. An accelerated testing of employees with u n k n o w n titers was begun so that we could evaluate h o w many doses of measles vaccine we would need and h o w best to undertake a vaccination program. Then case 1 occurred, with its extensive exposures, and the hospital decided to begin a vaccination p r o g r a m as soon as possible (Table 1). We intended to administer measles-mumps-rubella vaccine as r e c o m m e n d e d by the Immunization Practices Advisory Committee and the Health Department. Female employees of childbearing age were tested for p r e g n a n c y and vaccinated the following d a y if t h e test result was negative. They were informed to avoid becoming pregnant for 3 months and their consent slips included that information. Some of our employees were asked at the time of testing or vaccination if they had had measles in the past. R e c o r d s that were available show that of 36 employees questioned, seven were unsure or did not know, 20 had not had measles to the best of their knowledge, and only nine had had the disease. Of the nine people who had had measles or previous vaccine, all had ELISA titers of between 1 and 2. B e c a u s e of the large n u m b e r of contacts investigated, tested and vaccinated in the short period of time, the records are not clear about the correlation of titers with history in those who were unsure or believed that they had not had the disease. It is our policy to furlough any susceptible employee w h o had contact with a patient or was in the vicinity of a patient with measles if isolation in a pressure-negative or pressure-equal r o o m was not in effect. Patients 1 and 4 exposed a large n u m b e r of employees because they were not placed in the designated emergency department
ELISA measles titers
isolation r o o m but were kept in a private r o o m with an air system that recirculates its air throughout the d e p a r t m e n t (Table 1). Intensive in-service training has improved r o o m assignments for patients with suspected airborne infections. Personnel connected with case 1 also mistakenly believed that placing a m a s k on the patient, rather than on personnel in contact with t h e patient, prevents shedding of pathogens into the environm e n t and t h u s protects the staff. That this is not true has been documented. 2 It m a y be protective for e x t r e m e l y short periods and is better than nothing at all w h e n a patient is being transported, but isolation for airborne pathogens requires wearing of m a s k s by personnel susceptible to the disease, not by the patient. 3 The resident (case 2) w a s not furloughed after exposure to case 1 because his ELISA titer of 2.32 taken June 30, 1990, suggested immunity. His IgM titer taken 3 days after his diagnosis was < 1.20, and IgG titer was 3.97. Two w e e k s later, his IgM titer was 7.69 and the IgG was _>80. Thus this resident's serologic response to measles was confirmed. We believe that the originaI IgG ELISA titer of 2.32 was caused b y a killed measles vaccination he had received that was not protective. 4 We therefore instituted the following policies. Employees with a history of clinical measles o r two documented live measles vaccinations are considered i m m u n e without further titer testing. Those born before 1957 require vaccination ff their measles ELISA titers are ___1. All others without a history of measles or an ELISA titer of _<2.49 should be vaccinated. The cost to the hospital of the furloughs alone from the six cases described here resulted in 329 lost work days and costs of about $48,000. Vaccination of all exposed susceptible employees was in effect by the time patient 5 was admitted to the emergency department. Those vaccinated
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within 72 h o u r s were allowed to continue to work. The nurse (case 6) could not be reached until day 5 after exposure, when she was vaccinated and remained on furlough. Not surprisingly, she subsequently had symptoms and measles was diagnosed days later, 9 days after her exposure. Emergency departments should determine the airflow in their rooms used for isolation of patients with airborne infections, and only rooms with negative pressure and non recirculating air m a y be used for these patients. It appears that patient 6 became infected by sharing the emergency department air space for a prolonged period. The extreme infectivity of measles is well recognized and isolation precautions such as ours and are n o w required by the N e w York State Department of Health. s It is critically important that all potential measles cases be placed in airborne isolation until evaluation by an experienced clinician. We therefore r e c o m m e n d that all hospitals require p r o o f of immunity to measles along with rubella immunity before or for continuing employment. 5 Alternatively, hospitals should obtain measles histories and vaccination titers on current employees. During outbreaks, a level above the m i n i m u m accepted value for "protective" immunity, such as _2.5, should be established for furloughs. All exposed employees, regardless of history, titer, or vaccination status, should be instructed to report immediately any clinical signs and symptoms that m a y indicate the development of measles and to stay home for 48 hours after noting such signs to ensure that they do not have measles. Anyone exposed to a measles case who is susceptible should be vaccinated within 72 hours or be furloughed. This is also a recommendation from the N e w York State Department of Health. s Nonspecific p r o d r o m a l signs and symptoms, including malaise, fever, cough, eye discomfort, or conjunctivitis should be evaluated by an clinician experienced with measles. The m a i n difficulties in assessing and containing our measles outbreak were the lack of guidelines for assessing measles immunity and the lack of vaccination guidelines in our employee population. The existing literature was not helpful in the outbreak setting for determining protective antibody levels and assessing the quality of immunity conferred by natural measles infections.6-s We therefore considered any employee with a definite history of naturally acquired measles to be imm u n e with any positive titer or even a negative
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titer. The quality of natural immunity resulting from a natural measles infection appears to be superior to that achieved after vaccination. Our experience confirmed this; no one in this category developed clinical measles after exposure. Previously, we found serologic guidelines to assess immunity in chickenpox inadequate. We thought that a similar situation would be the case with "protective" ELISA measles titers. 9"11 We therefore arbitrarily doubled the acceptable ELISA titers that we would consider protective to _>2.5. We reasoned that by using more stringent guidelines we w o u l d decrease the possibility of further secondary cases because suggested "protective" ELISA levels of 1 m a y not be fully protective. Employees with ELISA measles titers of < 2 without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination confers in persons with low titer. N o n i m m u n e pregnant employees were administered i m m u n e s e r u m globulin during the outbreak and vaccinated after the delivery because the use of live vaccines is contraindicated during pregnancy. H a d we had the guidelines that we developed as this outbreak progressed, we could have brought the outbreak under control in a more efficient manner. We hope that our experience will be of value to others having to control measles outbreaks in institutions. We acknowledge the cooperation of Joan Richardson, RN, Barbara Gianelli, RN, and Judith Armstrong, RN, of Employee Health Service, Linda Jensen, MT, Department of Pathology, and Stephanie Overton, Infection Control Practitioner, in the preparation of data in this article.
References
1. ACIP. Measles prevention: recommendations of the Immunization Practices Committee. MMWR 1989;38 (13). 2. NoffsingerMA, Halpern AA.The ORmask; what protection does it afford? Infect Surg 1990;9:17-20. 3. Garner JS, Simmons BP. Isolation precautions in hospitals. Infect Control 1983;4:245-349. 4. Nkowane BM. Bart SW, Orenstein WA, Baltier H. Measles outbreak in a vaccinated school population: epidemiology, chains of transmission, and the role of vaccine failure. Am J Public Health 1987;77:434-8. 5. New York State Department of Health Immunization Program. Measles outbreak control strategy. Albany: NYSDOH, August, 1990. 6. Crawford GE, Gremillion DH. Epidemic measles and rubella in air force recruits: impact of immunization. J Infect Dis 1981;144:403-10.
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7. Preblud SR, Gross F, Halsey NA, Hinman AR, Herrmann KL, Koplan JP. Assessment of susceptibilityto measles and rubella. JAMA 1982;247:1134-7. 8. Chen RT, Markowitz LE, Albrecht P, et al. Measles antibody: reevaluation of protective titers. J Infect Dis 1990;162:1036-42. 9. Gurevich I, Jensen L, Kalter R, Cunha BA. Chickenpox in
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apparently immune hospital workers. Infect Control Hosp Epidemiol 1990;11:510-1. 10. Centers for Disease Control. Measles outbreakWashington, 1989: failure of delayed postexposure prophylaxis with vaccine. MMWR 1990;39:617-9, 11. Biberi-Moreanu SM. Measles vaccination. Arch Roum Pathol Exp Microbiol 1982;41:347-55.
Practice Forum articles should address infection prevention and control practices and related applications of epidemiology. Items should be limited to two to five typed double-spaced pages. Please send items to the Editor, Mary Castle White, RN, MPH, PhD, 155 Marston Ave., San Francisco, CA 94112.
Background: Measles outbreaks continue to be a problem for infection control in
hospitals-patients, personnel, and employee health service. Guidelines for measles outbreaks are not clear for medical personnel in the hospital. Methods: Outbreak investigation in a university-affiliated teaching hospital. Results: Four primary cases resulted in 607 staff exposures and two secondary cases. Forty-seven medical personnel were furloughed and 88 were vaccinated for measles. Minimal serologic criteria for immunity were found to be inadequate in the outbreak setting. Conclusions: We found that serologic guidelines for assessing immunity to measles are inadequate. During the outbreak, we arbitrarily doubled the acceptable enzyme-linked immunosorbent assay titers that we would consider protective, >_2, to decrease the possibility of further secondary cases. Employees with enzyme-linked immunosorbent assay measles titers less than 2 and without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination would confer in persons with low antibody titer. (AJIC AM J INFECTCONTROL1992;20:319-25)
Measles is highly contagious. R e c e n t o u t b r e a k s also d e m o n s t r a t e t h a t it c a n be a serious disease, w i t h the m o s t serious m a n i f e s t a t i o n s in adults a n d infants. B e c a u s e i n f e c t e d health c a r e w o r k ers p o s e a p o t e n t i a l risk to susceptible p a t i e n t s a n d o t h e r s u s c e p t i b l e h e a l t h c a r e w o r k e r s , outb r e a k i n v e s t i g a t i o n a n d c o n t r o l in h e a l t h c a r e institutions is t i m e - c o n s u m i n g , disruptive, a n d expensive. In April a n d July 1990, after several m e a s l e s o u t b r e a k s i n N e w York State, the N e w York State H e a l t h D e p a r t m e n t a n d the A m e r i c a n H o s p i t a l Association r e c o m m e n d e d t h a t hospitals follow revised guidelines f r o m the I m m u n i z a t i o n Advisory C o m m i t t e e of the U n i t e d States Public H e a l t h S e r v i c e ) These r e c o m m e n d a t i o n s state that hospitals s h o u l d r e q u i r e e v i d e n c e of m e a s l e s i m m u nity for n e w staff m e m b e r s w h o will h a v e d i r e c t c o n t a c t w i t h patients. The N e w York State D e p a r t m e n t of H e a l t h r e c o m m e n d e d that hospitals m a k e m e a s l e s v a c c i n e available to all susceptible hospiFrom the Infectious Disease Division, Winthrop-University Hospital. Mineola, and the State University of New York School of Medicine, Stony Brook, New York. Reprint requests: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501.
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tal e m p l o y e e s , volunteers, a n d p h y s i c i a n s b o r n after 1956 w h o do n o t h a v e a h i s t o r y of physiciand o c u m e n t e d measles, do n o t h a v e serologic evid e n c e of measles, o r h a v e not r e c e i v e d two doses of live m e a s l e s v a c c i n e a f t e r t h e i r first birthday. B e f o r e w e w e r e able to c o m p l y with t h e s e r e c o m m e n d a t i o n s , w e h a d o u r first case of nosoc o m i a l m e a s l e s in a h o u s e p h y s i c i a n on the infectious disease service w h o w a s exposed to a p a t i e n t w i t h m e a s l e s in the e m e r g e n c y departm e n t . H e h a d r e c e i v e d o n e d o s e of killed-virus v a c c i n e in t h e past; b e c a u s e his m e a s l e s e n z y m e linked i m m u n 0 s o r b e n t assay (ELISA) titer was 2.32 he w a s c o n s i d e r e d i m m u n e . Guidelines in the l i t e r a t u r e a n d texts w e r e n o n e x i s t e n t or u n helpful for assessing i m m u n i t y u n d e r o u t b r e a k conditions. DESCRIPTION OF OUTBREAK W i n t h r o p - U n i v e r s i t y I~/ospital is a 550-bed a c u t e c a r e ' c o m m u n i t y t e a c h i n g hospital with 3000 e m p l o y e e s a n d a n active e m e r g e n c y d e p a r t m e n t t h a t s e r v e s a b o u t 36,000 patients/year. The e m e r g e n c y d e p a r t m e n t was u n d e r g o i n g extensive renovations in the s u m m e r of 1990; this r e q u i r e d r e l o c a t i o n of isolation r o o m s a n d it was d u r i n g this d i s l o c a t i o n t h a t the first e x p o s u r e s o c c u r r e d . F r o m July_ 18 to August 28, 1990, t h e r e w e r e 319
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four more cases of measles in our hospital. These cases required contact investigations of more than 800 employees and patients and resulted in 607 actual exposures and a n u m b e r of staff furloughs. Some of these investigations, exposures, and furloughs could have been avoided had w e followed a more expeditious testing and vaccination schedule before the outbreak occurred. Exposure was defined as having been in the same r o o m with the patient, or within two adjoining rooms (same airspace) of patients not in negative-pressure isolation rooms. Other "air space" definitions are given for each case. Case 1
A 39-year-old white w o m a n who is an emergency department nurse at another institution was seen in our emergency department on July 6, 1990, for high fever and productive cough 2 days in duration. The patient stated that 2 weeks earlier she had had flulike symptoms for 3 days, which had resolved. Five days before admission (July I, 1990), she had a temperature of 102 ° F and a productive cough. She was seen by her attending physician and an antibiotic was prescribed, On her admission to our emergency department, the patient's temperature was 104 ° F and she had bilateral conjunctivitis. H e r face was erythematous b u t no rash was noted. The patient's white blood cell count was 3800 cells/mm 3, with 80% polymorphonuclear leukocytes. A chest x - r a y film showed questionable right lower lung infiltrate, and doxycycline was started for possible Legionella pneumonia. Both Legionella and measles fiters were obtained and the patient was admitted for observation and placed in respiratory isolation. Because a rash did not develop, isolation was discontinued after 24, hours. On the fifth hospital day, July 10, 1990, the patient had a maculopapular rash on her trunk that progressively involved her extremities. A clinical diagnosis of measles was made. The patient was placed in respiratory isolation again. H e r clinical condition slowly improved as the rash faded. H e r measles IgM titer was greater than 80. A titer of at least 20 by immunofluorescent antibody method is considered to indicate immunity. When the patient first came to the emergency department, she was placed in a nonisolation private r o o m because the designated isolation r o o m was occupied. Unfortunately, her room was not u n d e r negative or even equal air pressure. The air from this r o o m was recirculated throughout
December 1992
the emergency department. Although the patient was placed in respiratory isolation}signs were not posted and several staff m e m b e r s entered the r o o m without masking. These staff m e m b e r s were considered to be direct exposures, as were any patients in adjoining rooms for 2 hours or more. These patients w e r e considered to have shared her air space. One day after transfer from the emergency department to her hospital room, the patient's isolation was discontinued because she did not have a rash and her attending physician did not believe that she had measles. On day 5, however, a rash typical of measles broke out and the patient was placed in isolation once again. Because of the atypical development of her disease, she exposed two populations within the hospital to measles while not in isolation. Case 2
This patient was a 28-year-old house physician w h o was seen in the employee health clinic for fever and generalized maculopapular rash on July 19, 1990. He reported generalized body aches, frontal headache, a temperature of 102 ° F, a dry cough, and blurred vision. The patient denied having measles b u t had a history of chickenpox. Measles was diagnosed and the patient was discharged. Routine contact investigation revealed that he had been involved with patient 1 in the emergency department. On June 30, 1990, his p r e e m p l o y m e n t measles ELISA titer was 2.32; although he was considered to have direct exposure to patient I in the emergency department, he had not b e e n furloughed because he was considered " i m m u n e " by the titer criterion (Fig. I). He also reported a previous vaccination with killedvirus vaccine. B e c a u s e he was not feeling well before the development of the rash, he had limited his activities in the hospital to attendinglectures without seeing patients. He still exposed 77 employees. Measles titers were obtained from those contacts for w h o m measles titers were not on record and w h o did not have a history of measles. Case 3
A 65-year-old m a n was admitted to the hospital for a work-up of a right cerebral mass. The patient had been well until 2 weeks earlier, at which time he had gradual onset of left-handed weakness and clumsiness. Magnetic resonance imaging showed a right posterior parietal mass. The patient was scheduled for diagnostic and therapeutic craniotomy.
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I CASE3
> ~ J
C~EI
I,
! 7/8
7/I
i
!
7/15 July 1990
CASE4 !
7/22
C~E5 I
I
7/29
8/5
!
8/12 August 1990
I
8/19
I
8/26
I
LEGEND:
l
l = Primary Cases = Secondary Cases Fig. 1. Primary and secondary measles cases during the 1990 outbreak.
Two days before operation he was started on a regimen of dexamethasone (Decadron), 4 mg intravenously every 6 hours. On the eleventh hospital day the patient u n d e r w e n t craniotomy with excision of the mass. The postoperative course of the patient was uneventful and he was started on a regimen of phenytoin (Dilantin). Also on the eleventh hospital day, on the recommendation of the oncologist, radiation therapy at 200 rads/day was started. During his eleventh day of radiation therapy (22 days after admission), the ,patient started to b e c o m e lethargic. He became progressively somnolent. On the 20th day of radiation therapy (July 18, 1990), d a y 31 of hospitalization, coryza, a temperature of 101 ° F, and a m a c u l o p a p u l a r rash on the face and chest developed. The diagnosis of rash as a side effect of phenytoin was made. The patient's fever worsened over the next few days, reaching 102.8 ° F. Two days later the rash b e c a m e morbilliform on the patient's chest, back, abdomen, and u p p e r extremities. When purulent conjunctivitis and dry cough developed, a diagnosis of measles was made and the patient was placed in respiratory isolation. On examination the patient was an acutely i11, well-developed man. He h a d erythema of the face with bilateral purulent conjunctivitis. The skin of the patient showed morbilliform rash on the chest, back, abdomen, u p p e r arms, and both lower extremities. At that time the hematocrit was 37%, the white cell count was 5900 cells/mm 3 (82% neutrophils, 10% lymphocytes, a n d 7% monocytes) and his measles ELISA IgM antibody titer was 4.38. The patient was unable to recall a measles disease or vaccination history. Because of the delay in recognizing the rash in this 65-year-old
m a n as being a s y m p t o m measles, extensive contact investigation was needed. Measles titers were obtained for 183 health care personnel w h o were in that patient care area during the time the patient was not in isolation. Also included were his r o o m m a t e and the patients in the two flanking rooms, all of w h o m shared at least part of the air space of his original r o o m because the air was not vented to the outside but was partially recirculated. Case 4
This patient was a 23-year-old white w o m a n w h o w a s seen in t h e emergency department on July 26, 1990, for fever, generalized rash, u p p e r respiratory tract infection symptoms of mild cough and nasal congestion, frontal headache, and back and joint pain. On examination, the patient was a young white w o m a n , acutely ill with a temperature of 102 ° F and a maculopapular rash on the face, neck, chest, trunk, and extremities. She was not placed in respiratory isolation until Koplick spots were noted. A diagnosis of rubeola was made and the patient was immediately discharged to h e r home. The patient was a nurse in our institution with no k n o w n exposure to anyone with measles and she had been on vacation. Because of her placem e n t in a nonisolation r o o m in the emergency department, she exposed 44 hospital employees w h o shared air space with her for an extended period. Case 5
A 34-year-old white w o m a n came into the emergency department on August 12, 1990, be-
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cause of epigastric discomfort, fever, and extreme fatigue of 3 days' duration. The patient was well until 2 days before consultation, w h e n she had bitemporal headaches. She also had fever as great as 103 ° F associated with shaking chills. She went to the emergency d e p a r t m e n t on her second day of illness, was deemed to have a viral syndrome, and was discharged h o m e with follow-up by her private medical doctor. The patient w e n t to her private medical doctor's office because of abdominal discomfort and vomiting. Because she felt extremely w e a k and the fever continued, she was sent back to the emergency department the next day, August 14, 1990, for an abdominal sonogram. The patient remained in the emergency department overnight. She was then noted to have a m a c u l o p a p u l a r rash on the face and later had a dry c o u g h and eye irritation. She was seen by the infectious disease service on the next day, August 15, and the diagnosis of measles was made. Examination of the patient revealed an alert, oriented young w o m a n with a temperature of 100.8 ° F. She h a d maculopapular lesions on her face, chest, back, and extremities and bilateral conjunctivitis. Other results of the physical examination were unremarkable. Laboratory findings revealed a white blood cell count of 3900 cells/mm 3 (76% polymorphonuclear leukocytes, !2% lymphocytes, 7% monocytes, and 2% atypical lymphocytes). Hematocrit was 4 2 % . H e r IgG measles titer was 1.6 and her IgM titer was greater than 1.8. Because of the delayed diagnosis at this patient's readmission and the fact that she had visited the e m e r g e n c y department 2 days before onset of the rash, at which time she was retrospectively considered to be infectious (see the Discussion section), she exposed 243 employees w h o had shared her air space during her prolonged stays. Case 6
A female nurse was seen in the infectious disease clinic on August 28, 1990, with a selfdiagnosis of measles. This was confirmed by the Infectious Disease physicians. This patient was a nurse in our e m e r g e n c y department who had been in the emergency department 13 days earlier. She had been furloughed because of the exposure to patient 5 and a negative measles titer. She could not be reached before August 20, day 5 of her furlough, and was then recalled for vaccination. She had p r o d r o m a l manifestations of measles 2 days after her vaccination (August 22). At her
diagnosis she was isolated, w h i c h d i d not result in any further exposures. C o n t a c t i n v e s t i g a t i o n s a n d titers
Altogether 607 employees and several patients were exposed to five of the six patients with measles and two secondary infections occurred (cases 2 a n d 6; Table 1). The second patient was hospitalized for approximately 1 month before he showed the signs and symptoms of measles and was therefore considered to have a nosocomial case. He had, however, not been exposed to any of o u r k n o w n cases and was presumably infected by a visitor. If measles ELISA titers were not available from exposed employees from previous testing, they were obtained on all those exposed. According to the ELISA method (Whittaker Measlestat; Whittaker Bioproducts, Walkersville, Md.), those with titers of _< 1 are considered nonimmune, those with titers 1 to 2.5 are considered low positive, those with titers 2.5 to 4.3 are considered intermediate, and those >4.3 are considered immune. However, we decided to vaccinate and/or furlough anyone without a reliable history of measles or with an ELISA titer < 2. Eighty-eight employees were vaccinated in the immediate period b e t w e e n July 25 and August 20. Forty-seven employees w h o had contact with a case and w e r e not i m m u n e were furloughed. DISCUSSION
Before 1988, serologic titers for rubella were obtained on all hospital employees, as m a n d a t e d by the Department of Health. Varicella titers w e r e also d r a w n because of continuous extensive exposures of o u r people to chicken pox, both in house and in the community. Keeping a record of susceptibility or immunity avoided extensive casedriven testing at times of exposure. Beginning in 1988, outbreaks of measles occurred in surrounding communities and in several states in the country, and we began routine testing for rubeola of n e w employees and those who were seen for their annual physicals. Our experience wit h varicelia immunity demonstrated that a history of varicella zoster did not necessarily correspond with the titers we obtained, but we relied on IgG titers _> 1 by ELISA as indicating immunity w h e n testing for measles. After the Health Department letter was received, a review of Employee Health Service records showed that about 155 of our regular employees either did not have protective titers (ELISA titer < 1 was considered to indicate susceptibility) or
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Table 1. Measles outbreak: Epidemiologic and vaccination summary of exposed staff
Case 1 2 3 4 5 6 - TOTAL
Date of exposure
Number of staff exposed
Number vaccinated
Number furloughed
Number secondary cases
< 1 (no.)
1-2 (no.)
> 2 (no.)
7/6 7/19 7/20 7/26 8/12 8/22
60 77 183 44 243 0 607
0 9 28 7 44 0 88
1 11 22 9 4 0 47
1 0 0 0 1 0 2
NA 4 7 2 27 0 40
NA 12 34 7 46 0 99
NA 61 142 35 170 0 408
did not yet have titers on record. A letter was sent to all these employees and their department heads to r e c o m m e n d that the employees contact their own physicians to obtain measles vaccination. Only seven employees responded to the letter. An accelerated testing of employees with u n k n o w n titers was begun so that we could evaluate h o w many doses of measles vaccine we would need and h o w best to undertake a vaccination program. Then case 1 occurred, with its extensive exposures, and the hospital decided to begin a vaccination p r o g r a m as soon as possible (Table 1). We intended to administer measles-mumps-rubella vaccine as r e c o m m e n d e d by the Immunization Practices Advisory Committee and the Health Department. Female employees of childbearing age were tested for p r e g n a n c y and vaccinated the following d a y if t h e test result was negative. They were informed to avoid becoming pregnant for 3 months and their consent slips included that information. Some of our employees were asked at the time of testing or vaccination if they had had measles in the past. R e c o r d s that were available show that of 36 employees questioned, seven were unsure or did not know, 20 had not had measles to the best of their knowledge, and only nine had had the disease. Of the nine people who had had measles or previous vaccine, all had ELISA titers of between 1 and 2. B e c a u s e of the large n u m b e r of contacts investigated, tested and vaccinated in the short period of time, the records are not clear about the correlation of titers with history in those who were unsure or believed that they had not had the disease. It is our policy to furlough any susceptible employee w h o had contact with a patient or was in the vicinity of a patient with measles if isolation in a pressure-negative or pressure-equal r o o m was not in effect. Patients 1 and 4 exposed a large n u m b e r of employees because they were not placed in the designated emergency department
ELISA measles titers
isolation r o o m but were kept in a private r o o m with an air system that recirculates its air throughout the d e p a r t m e n t (Table 1). Intensive in-service training has improved r o o m assignments for patients with suspected airborne infections. Personnel connected with case 1 also mistakenly believed that placing a m a s k on the patient, rather than on personnel in contact with t h e patient, prevents shedding of pathogens into the environm e n t and t h u s protects the staff. That this is not true has been documented. 2 It m a y be protective for e x t r e m e l y short periods and is better than nothing at all w h e n a patient is being transported, but isolation for airborne pathogens requires wearing of m a s k s by personnel susceptible to the disease, not by the patient. 3 The resident (case 2) w a s not furloughed after exposure to case 1 because his ELISA titer of 2.32 taken June 30, 1990, suggested immunity. His IgM titer taken 3 days after his diagnosis was < 1.20, and IgG titer was 3.97. Two w e e k s later, his IgM titer was 7.69 and the IgG was _>80. Thus this resident's serologic response to measles was confirmed. We believe that the originaI IgG ELISA titer of 2.32 was caused b y a killed measles vaccination he had received that was not protective. 4 We therefore instituted the following policies. Employees with a history of clinical measles o r two documented live measles vaccinations are considered i m m u n e without further titer testing. Those born before 1957 require vaccination ff their measles ELISA titers are ___1. All others without a history of measles or an ELISA titer of _<2.49 should be vaccinated. The cost to the hospital of the furloughs alone from the six cases described here resulted in 329 lost work days and costs of about $48,000. Vaccination of all exposed susceptible employees was in effect by the time patient 5 was admitted to the emergency department. Those vaccinated
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within 72 h o u r s were allowed to continue to work. The nurse (case 6) could not be reached until day 5 after exposure, when she was vaccinated and remained on furlough. Not surprisingly, she subsequently had symptoms and measles was diagnosed days later, 9 days after her exposure. Emergency departments should determine the airflow in their rooms used for isolation of patients with airborne infections, and only rooms with negative pressure and non recirculating air m a y be used for these patients. It appears that patient 6 became infected by sharing the emergency department air space for a prolonged period. The extreme infectivity of measles is well recognized and isolation precautions such as ours and are n o w required by the N e w York State Department of Health. s It is critically important that all potential measles cases be placed in airborne isolation until evaluation by an experienced clinician. We therefore r e c o m m e n d that all hospitals require p r o o f of immunity to measles along with rubella immunity before or for continuing employment. 5 Alternatively, hospitals should obtain measles histories and vaccination titers on current employees. During outbreaks, a level above the m i n i m u m accepted value for "protective" immunity, such as _2.5, should be established for furloughs. All exposed employees, regardless of history, titer, or vaccination status, should be instructed to report immediately any clinical signs and symptoms that m a y indicate the development of measles and to stay home for 48 hours after noting such signs to ensure that they do not have measles. Anyone exposed to a measles case who is susceptible should be vaccinated within 72 hours or be furloughed. This is also a recommendation from the N e w York State Department of Health. s Nonspecific p r o d r o m a l signs and symptoms, including malaise, fever, cough, eye discomfort, or conjunctivitis should be evaluated by an clinician experienced with measles. The m a i n difficulties in assessing and containing our measles outbreak were the lack of guidelines for assessing measles immunity and the lack of vaccination guidelines in our employee population. The existing literature was not helpful in the outbreak setting for determining protective antibody levels and assessing the quality of immunity conferred by natural measles infections.6-s We therefore considered any employee with a definite history of naturally acquired measles to be imm u n e with any positive titer or even a negative
December 1992
titer. The quality of natural immunity resulting from a natural measles infection appears to be superior to that achieved after vaccination. Our experience confirmed this; no one in this category developed clinical measles after exposure. Previously, we found serologic guidelines to assess immunity in chickenpox inadequate. We thought that a similar situation would be the case with "protective" ELISA measles titers. 9"11 We therefore arbitrarily doubled the acceptable ELISA titers that we would consider protective to _>2.5. We reasoned that by using more stringent guidelines we w o u l d decrease the possibility of further secondary cases because suggested "protective" ELISA levels of 1 m a y not be fully protective. Employees with ELISA measles titers of < 2 without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination confers in persons with low titer. N o n i m m u n e pregnant employees were administered i m m u n e s e r u m globulin during the outbreak and vaccinated after the delivery because the use of live vaccines is contraindicated during pregnancy. H a d we had the guidelines that we developed as this outbreak progressed, we could have brought the outbreak under control in a more efficient manner. We hope that our experience will be of value to others having to control measles outbreaks in institutions. We acknowledge the cooperation of Joan Richardson, RN, Barbara Gianelli, RN, and Judith Armstrong, RN, of Employee Health Service, Linda Jensen, MT, Department of Pathology, and Stephanie Overton, Infection Control Practitioner, in the preparation of data in this article.
References
1. ACIP. Measles prevention: recommendations of the Immunization Practices Committee. MMWR 1989;38 (13). 2. NoffsingerMA, Halpern AA.The ORmask; what protection does it afford? Infect Surg 1990;9:17-20. 3. Garner JS, Simmons BP. Isolation precautions in hospitals. Infect Control 1983;4:245-349. 4. Nkowane BM. Bart SW, Orenstein WA, Baltier H. Measles outbreak in a vaccinated school population: epidemiology, chains of transmission, and the role of vaccine failure. Am J Public Health 1987;77:434-8. 5. New York State Department of Health Immunization Program. Measles outbreak control strategy. Albany: NYSDOH, August, 1990. 6. Crawford GE, Gremillion DH. Epidemic measles and rubella in air force recruits: impact of immunization. J Infect Dis 1981;144:403-10.
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7. Preblud SR, Gross F, Halsey NA, Hinman AR, Herrmann KL, Koplan JP. Assessment of susceptibilityto measles and rubella. JAMA 1982;247:1134-7. 8. Chen RT, Markowitz LE, Albrecht P, et al. Measles antibody: reevaluation of protective titers. J Infect Dis 1990;162:1036-42. 9. Gurevich I, Jensen L, Kalter R, Cunha BA. Chickenpox in
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apparently immune hospital workers. Infect Control Hosp Epidemiol 1990;11:510-1. 10. Centers for Disease Control. Measles outbreakWashington, 1989: failure of delayed postexposure prophylaxis with vaccine. MMWR 1990;39:617-9, 11. Biberi-Moreanu SM. Measles vaccination. Arch Roum Pathol Exp Microbiol 1982;41:347-55.
Practice Forum articles should address infection prevention and control practices and related applications of epidemiology. Items should be limited to two to five typed double-spaced pages. Please send items to the Editor, Mary Castle White, RN, MPH, PhD, 155 Marston Ave., San Francisco, CA 94112.