CDC January 5, 2001/ Vol. 49 / Nos. 51 & 52 NMW/? MORBIDITY AND MORTALITY WEEKLY REPORT Serious Adverse Events Attributed to Nevirapine Regimens for Postexposure Prophylaxis After HIV Exposures — Worldwide, 1997-2000 In September 2000, two instances of life-threatening hepatotoxicity were reported in health-care workers taking nevirapine (NVP) for postexposure prophylaxis (PEP) after occupational human immunodeficiency virus (HIV) exposure*. In one case, a 43-year old female health-care worker required liver transplantation after developing fulminant hepatitis and end-stage hepatic failure while taking NVP, zidovudine, and lamivudine as PEP following a needlestick injury (7). In the second case, a 38-year-old male physician was hospitalized with life-threatening fulminant hepatitis while taking NVP, zidovudine, and lamivudine as PEP following a mucous membrane exposure. To characterize NVP associated PEP toxicity, CDC and the Food and Drug Administration (FDA) reviewed MedWatch reports of serious adverse events in persons taking NVP for PEP received by FDA (Figure 1). This report summarizes the results of that analysis and indicates that healthy persons taking abbreviated 4-week NVP regimens for PEP are at risk for serious adverse events. Clinicians should use recommended PEP guidelines and dosing instruc tions to reduce the risk for serious adverse events. MedWatch is a voluntary reporting system for adverse events and problems with drugs, medical devices, biologics, and special nutritional products. For this analysis, a serious adverse event was defined as any event that was life-threatening, permanently disabling, required or prolonged hospitalization, required intervention to prevent perma nent impairment or damage, or any other event that required medical attention. Including the two case reports of fulminant hepatitis, FDA received reports of 22 cases of serious adverse events related to NVP taken for PEP from March 1997 through September 2000. These 22 events included hepatotoxicity (12), skin reaction (14), and rhabdomyolysis (one); four cases involved both hepatotoxicity and skin reac tion, and one case involved both rhabdomyolysis and skin reaction. The median age of affected persons was 36.5 years (range: 12-50 years; age was not reported for four cases); 12 were female, and 12 occurred in the United States. Reasons for administra tion of PEP were occupational needlestick or other sharps injury (12), other occupational exposure (four), sexual exposure (three), nonoccupational (pediatric) needlestick injury (one), other nonoccupational exposure (one), and unknown (one). Nine persons took a maximum NVP dose of 200 mg per day, and 12 persons took a maximum dose of 200 mg twice per day (the dose of NVP was not recorded for one *Information included in this report does not represent Food and Drug Administration approval or approved labeling for the particular product or indications in question. U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES 1154 January 5, 2001 Nevirapine Regimens Continued FIGURE 1. Number of cases of serious adverse events associated with nevirapine regimens for human immunodeficiency virus postexposure prophylaxis, by quarter and year — Worldwide, 1997-2000* °T | Number 1998 | 1999 Quarter and Year * n=22 person). Among the 12 persons taking a maximum dose of 200 mg twice daily, six were first given a lead-in dose of 200 mg per day for 3-14 days. Concomitant antiretroviral agents used with NVP for PEP included zidovudine and lamivudine (10); stavudine and lamivudine (three); zidovudine and didanosine (two); stavudine and didanosine (one); stavudine and indinavir (one); didanosine and indinavir (one); stavudine, didanosine, and ritonavir (one); lamivudine, didanosine, and nelfinavir (one); stavudine, lamivudine, nelfinavir, and saquinavir (one); and none (one). Among the 12 persons with hepatotoxic reactions, one developed liver failure (requiring liver transplantation), seven had clinical hepatitis (e.g., jaundice, fever, nausea, vomiting, abdominal pain, and/or hepatomegaly), and four had elevations in serum liver enzymes (i.e., alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) without reports of clinical hepatitis Baseline liver function tests were reported for six patients and were within normal limits. Abnormal liver function tests were reported during PEP for 10 patients; median peak ALT was 215 U/L (range: 182-2790 U/L; normal: 10-34 U/L), median peak AST was 375 U/L (range: 96-2370 U/L; normal: 10-34 U/L), and median peak total bilirubin was 7.5 mg/dL (range: 2.0—33.7 mg/dL; normal: 0.2—-1.0 mg/dL). The median time from initia- tion of NVP use to first abnormal liver function tests was 21 days (range: 13-36 days). In six cases, hepatitis A, B, and C serologies were reported; all were negative. Eleven persons reported symptoms, including fever, malaise, and abdominal pain. The median onset of these symptoms was 14 days after beginning NVP for PEP (range: 3-36 days). The 14 reports of skin rash included one documented and two possible cases of Stevens- Johnson syndrome. The median onset of rash occurred 9 days after beginning PEP (range: 6-36 days). Vol. 49 / Nos. 51 & 52 Nevirapine Regimens Continued Reported by: D Boxwell, Pharm D, Office of Postmarketing Drug Risk Assessment; H Haverkos MD, S Kukich, MD, K Struble, Pharm D, H Jolson, MD, Div of Anti-Viral Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration. Prevention and Evaluation Br, Div of Healthcare Quality Promotion [proposed], National Center for Infectious Diseases, CDC Editorial Note: Severe, life-threatening, and fatal cases of hepatotoxicity and skin reactions have occurred among HIV-infected patients treated with NVP (2,3) and are described in a box warning on the NVP label (Viramune™ [package insert]', Boehringer ingelheim/Roxane Laboratories, Inc., Ridgefield, Connecticut, 1998). This report suggests that persons taking NVP regimens for PEP after HIV exposures also are at risk for serious adverse events. In 1996, the U.S. Public Health Service (PHS) first recommended PEP after certain occupational exposures to HIV (4). These recommendations, updated in 1998 (5), are being revised to include other antiretroviral agents that have been approved by FDA for use in HIV-infected persons. NVP is not recommended for basic or expanded PEP regi mens. However, data on the safe and effective use of single-dose NVP to prevent perina tal HIV transmission (6,7) and a theoretical advantage of more rapid activity (i.e., NVP does not require phosphorylation for activation) have prompted clinicians to include NVP in PEP regimens following HIV exposures. In the HIV PEP registry, which collected data on occupational HIV PEP use from October 1995 through March 1999, six cases of serious adverse events related to PEP were reported among 492 registered participants; a severe skin reaction occurred in one of 11 health-care workers taking a regimen that included NVP (8). Because most occupational HIV exposures do not result in transmission of HIV (9), clinicians considering prescribing PEP for exposed persons must balance the risk for HIV transmission represented by the exposure and the exposure source against the poten tial toxicity of the specific agent(s) used (4). In many circumstances, the risks associated with NVP as part of a PEP regimen outweigh the anticipated benefits. When PEP is pre scribed, the manufacturer's package insert should be consulted for dosing instructions, possible side effects, and potential drug interactions The findings in this report are subject to at least three limitations. First, MedWatch is a voluntary, passive reporting system, and it is unlikely that all serious adverse events in persons taking NVP for PEP have been reported. Second, data about administration of a lead-in dose and results of baseline liver function tests and hepatitis serologies were not included in all reports. In six cases, the initial dose of NVP was 200 mg twice daily without the recommended 2-week dose escalation, which may have increased the likelihood of adverse events (10). Third, available denominator data about the use of NVP for PEP were insufficient to calculate accurate rates of adverse events. The findings in this report do not apply to NVP use in other settings. Single-dose NVP is one of the regimens recommended by PHS for prevention of perinatal HIV transmis sion (7). No serious toxicity has been reported among mother-infant pairs using this regimen. Combination antiretroviral regimens containing NVP may be used in HIV infected persons after weighing the risks and benefits and monitoring adverse reactions. Health-care providers and the public can assist in monitoring the safety of antiretrovirals and other agents by reporting adverse reactions to the FDA MedWatch program: telephone, (800) 332-1088, fax, (800) 332-0178, World-Wide Web, http: www.FDA.gov/medwatch, or mail, MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857. ' Use of trade names and commercial sources is for identification only and does not constitute endorsement by CDC or the U.S. Department of Health and Human Services. 1156 January 5, 2001 Nevirapine Regimens Continued References 1. Johnson S, Baraboutis JG, Sha BE, Proia LA, Kessler HA. Adverse effects associated with use of nevirapine in HIV postexposure for 2 health care workers [Letters]. JAMA 2000;284:2722-3 Cattelan AM, Erne E, Slatino A, et al. Severe hepatic failure related to nevirapine treatment Clin Infect Dis 1999;29:455-6 Sidley P. South Africa to tighten control on drug trials after five deaths. Br Med J 2000;320: 1028 CDC. Update: provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR 1996;45:468-72 CDC. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR 1998:47(no. RR-7) Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomized trial. Lancet 1999;354:795-802 US Public Health Service. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interven tions to reduce perinatal HIV-1 transmission in the United States. Available at http: hivatis.org/guidelines/perinatal/Nov_00/text/index.htm!. Accessed January 2001 Wang SA, Panlilio AL, Doi PA, et al. Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: findings of the HIV Postexposure Prophy laxis Registry. Infect Control Hosp Epidemiol! 2000;21:780-5 Bell DM. Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview. Am J Med 1997;102:9-15 Soriano AP, Jiménez-Nacher |, Rodriguez-Rosado R, Dona MC, Barreiro PM, Gonzalez Lahoz J. Incidence of rash and discontinuation of nevirapine using two different escalat ing initial doses [Letter]. AIDS 1999;13:524 Nosocomial Poisoning Associated With Emergency Department Treatment of Organophosphate Toxicity — Georgia, 2000 Emergency department (ED) staff caring for patients contaminated with toxic chemi- cals are at risk for developing toxicity from secondary contamination. This report describes three cases of occupational illnesses associated with organophosphate toxic- ity caused by exposure to a contaminated patient and underscores the importance of using personal protection equipment (PPE) and establishing and following decontamina tion procedures in EDs and other areas of acute care hospitals. Patient 1 On April 11, a 40-year-old man intentionally ingested approximately 110 g of a veteri nary insecticide concentrate. The insecticide contained 73% naphthalene, xylene, and surfactant, and 11.6% phosmet. On clinical examination at a local hospital ED approxi mately 20 minutes after the ingestion, the patient had profuse oral and bronchial secre tions, vomiting, bronchospasm, and respiratory distress. He was intubated for airway management and ventilation. To control secretions, he received 4 g pralidoxime and 22 mg atropine during the next 24 hours. The patient improved over a 9-day period and was transferred to a psychiatric facility. The patient was brought to the ED by a friend, not by emergency medical services, and the friend developed symptoms that required treatment. ED personnel exposed to Vol. 49 / Nos. 51 & 52 Organophosphate Toxicity Continued the patient had symptoms within an hour of his arrival. The staff noted a chemical odor in the ED and contacted the regional poison center, which recommended decontaminating the patient's skin and placing gastric contents in a sealed container to minimize evapora tion; however, no decontamination was performed. Health-Care Worker 1 A 45-year-old ED nursing assistant providing care to patient 1 developed respiratory distress, profuse secretions, emesis, diaphoresis, and weakness. She had contact with the patient's skin, respiratory secretions, and emesis. She was admitted to the hospital and required intubation for 24 hours to support respiration. After medical management and serial doses of atropine and pralidoxime for 7 days, her respiratory function improved, and she was discharged after 9 days of hospitalization. Health-Care Worker 2 A 32-year-old ED nurse had diaphoresis, confusion, hypersalivation, nausea, and abdominal cramps while caring for patient 1. Although she did not have skin contact with his secretions or emesis, she had shared his breathing space. After treatment with 10 mg of atropine and pralidoxime over the next 12 hours, her symptoms resolved Health-Care Worker 3 A 56-year-old nurse providing care for patient 1 was admitted to the hospital with dyspnea, confusion, and headache. Although she did not have skin contact with secre tions or emesis from patient 1, she had shared his breathing space. She was given 6 mg of atropine without relief of the dyspnea. As a possible result of excessive atropine, she experienced hallucinations. On recommendation of the regional poison center, she received intravenous lorazepam and was observed until the episode resolved. She improved overnight and was discharged. Reported by: RJ Geller, MD, KL Singleton, MD, ML Tarantino, Georgia Poison Center, Atlanta CL Drenzek, DVM, KE Toomey, MD, State Epidemiologist, Georgia Div of Public Heaith. Div of Surveillance, Hazard Evaluations, and Field Studies, National Institute for Occupational Safety and Health; National Pharmaceutical Stockpile Br, Div of Emergency and Environmental Health Svcs; Div of Environmental Hazards and Health Effects; National Center for Environmental Health, CDC. Editorial Note: During the incident in this report, health-care workers were exposed to a patient contaminated with an organophosphate insecticide. These health-care workers were not wearing appropriate respiratory or skin protective equipment while caring for the patient. As a result, three health-care workers developed symptoms consistent with organophosphate intoxication and required treatment. This was the third episode reported during 2000 to the Georgia Poison Center of nosocomial poisoning of ED staff involved in the care of patients who had intentionally ingested a concentrated organophosphate mixed with xylene and other hydrocarbon solvents. Similar incidents have occurred elsewhere (7). During 1987-1998, the National Institute for Occupational Safety and Health identified 46 health-care workers who had acute pesticide-related illness after providing care to a pesticide-contaminated patient (G. Calvert, CDC, personal communication, 2000) The Joint Commission on Accreditation of Healthcare Organizations requires hospi tals to have a plan to manage contaminated patients (2 ); however, these recommenda tions do not include a plan to protect health-care workers caring for contaminated patients. During 1996-1998, surveys of hospitals in Georgia and at level 1 trauma centers nationally indicated that few acute care hospitals had trained staff, equipment, and procedures to safely care for contaminated patients (3-5 ). 1158 January 5, 2001 Organophosphate Toxicity — Continued Depending on the extent of the contamination, health-care workers caring for chemi- cally contaminated patients should use level C protection (i.e., full face mask and powered/nonpowered canister/cartridge filtration respirator) or level B protection (i.e., supplied air respirator or self-contained breathing apparatus) (6). The type of canister/ cartridge should be appropriate to the agent; if the agent cannot be identified, an organic vapor/HEPA filter is recommended (6). To prevent dermal absorption, chemical barrier protection appropriate to the contaminant is needed; latex medical gloves are of little protection against many chemicals. in addition to the need for surface decontamination of patients, body fluids also must be contained to prevent dermal and inhalational expo- sure. To limit distant spread of the contaminant, the EDs ventilation exhaust should be directed away from the hospital’s main ventilation system. EDs may have to care for persons contaminated with chemicals resulting from self- inflicted contamination, industrial incidents, and terrorist events (7). To protect health- care workers caring for these patients, EDs should adhere to existing guidelines (6,8,9 ) and decontamination protocols, train staff in the use of PPE, and maintain adequate quantities of antidotes (170). If sufficient quantities of antidote are not available, the National Pharmaceutical Stockpile at CDC maintains a mechanism to procure and deliver large quantities of pharmaceuticals to state health departments within 12 hours. Coordi- nation among health-care facilities, poison centers, and state and local health depart- ments could provide surveillance of a chemical agent release, facilitate the expeditious procurement of supplies from outside sources, protect health-care workers, and inform the public about contaminants. References 1. Burgess JL. Hospital evacuations due to hazardous materials incidents. Am J Emerg Med 1999; 17:50-2. . Joint Commission on Accreditation of Healthcare Organizations. Accreditation standards for hospitals, 2000. Oakbrook Terrace, !Ilinois: Joint Commission on Accreditation of Healthcare Organizations, 2000; sections EC1.5e, EC1.5i, and EC1.6/. . Sharp TW, Brennan RJ, Keim M, Williams RJ, Eitzen E, Lillibridge S. Medical preparedness for a terrorist incident involving chemical or biological agents during the 1996 Atlanta Olympic games. Ann Emerg Med 1998;32:214-23. . Meehan P, Toomey KE, Drinnon J, Cunningham S, Anderson N, Baker E. Public health response for the 1996 Olympic games. JAMA 1998;279:1469-73. Ghilarducci D, Pirallo R, Hegmann K. Hazardous materials readiness of United States level 1 trauma centers. J Emerg Med 2000;42:683-92. . Macintyre A, Christopher G, Eitzen E, et al. Weapons of mass destruction events with contaminated casualties. JAMA 2000;283:242-9. . Okumura T, Takasu N, Ishimatsu S, et al. Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med 1996;28:129-35. . Burgess JL, Kirk M, Borron SW, Cisek J. Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999;34:205-12. . Pons P, Dart RC. Chemical incidents in the emergency department: if and when. Ann Emerg Med 1999;34:223-5. . Dart RC, Goldfrank LR, Chyka PA, et al. Combined evidence based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States. Ann Emerg Med 2000;36:126-32. Vol. 49 / Nos. 51 & 52 FIGURE I. Selected notifiable disease reports, United States, comparison of provisional 4-week totals ending December 23, 2000, with historical data CASES CURRENT DISEASE DECREASE INCREASE 4 WEEKS HepatitisA 425 Hepatitis B 318 Hepatitis C; Non-A, Non-B Legionellosis Measles, Tota Meningococcal Infections Mumps Pertussis Rubella Ratio (Log Scale)” Beyond Historical Limits Ratio of current 4-week total to mean of 15 4-week totals (from previous, comparable, and subsequent 4-week periods for the past 5 years). The point where the hatched area begins is based on the mean and two standard deviations of these 4-week totals TABLE |. Summary of provisional cases of selected notifiable diseases, United States, cumulative, week ending December 23, 2000 (51st Week) Cum. 2000 Cum. 2000 Psittac yclosporiasis”* Rabies, humar Diphtheria Rocky Mountain spotted fev or (RMSF) Ehrlichiosis ruman granulocyt HGE Rubella, congenital sy human monocytic HME)* otreptococcal disease ve, groupA Encephalitis California serogroup vira Streptococcal toxic-s drome eastern equine* Syphilis ngenital' St. Louis* etanus western equine* Toxic-shock syndrome Hansen disease (leprosy)* Trichinosis Hantavirus pulmonary syndrome”* Tularemia* Hemolytic uremic syndrome, postdiarrheal* Typhoid fever HIV infection, pediatric* Yellow fever Plague No reported cases *Not notifiable in all states Updated weekly from reports to the Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases (NCID) Updated monthly from reports to the Division of HIV/AIDS Prevention Surveillance and Epidemiology, National Center for HIV STD, and TB Prevention (NCHSTP). Last update Novernber 26, 2000 ‘Updated from reports to the Division of STD Prevention, NCHSTP. MMWR January 5, 2001 TABLE Il. Provisional cases of selected notifiable disea ses, United States, weeks ending December 23, 2000, and December 25, 1999 (51st Week) Escherichia coli 0157:H7* CRMNMUNJoa.aNE RHnsinIWe rsnn Tp eEo rDt EiNnSGgT LAAATrNEeDSa 326C11,0,u,05018m94308%3173634 °1 7 AIDS 4C21,u98m949 8 Chiamydi6a32'90C2 1,1,,u,697946230m429 77603775 598009 2CC,2r5u01y100mp260 t osporidiosis 2000 NETSS 3C,1u94900m9329329% 3C2,u023470m300 PHL|US MUIpD.s taAtTeL ANTN.YI C 7,770055 599N PNNa.L JY City 954279992 2,221090135 E.N. CENTRAL 3,442 590 Ohid o 534526 8,976431 Mi! ch 2311,787147 Wis 14,295 MW.iNn.n CENTRAL 7,037331 io?) iowa 4,804 ese Mo 117 N. Dak m® S. Dak = Nebr R Kans S. ATLANTI( Del Md dD. W.S. CENTRAL Ark Okl3 a Tex MOUNTAIN Mont Idaho Wyo Colo N. Mex Ariz Utah Nev PACIFIC 113,080 Wash 12,898 Oreg Calif 5,140 AHlaawsakiai 8922,,478139543 3,122 U U NC*A :.m HCUITNeenBphNr.ad odl.MiltP aa.vt r1tmihe ndey SvouddeatLa inilmataf bmoii ooocaarnanbr .laste eetfh seolr Lrysayc s attnf oI r unobgpfmeedo n arirrtmteeeaaUpp l:too irNrUotitonnsnev a fdeve tScamotty ibihtsleohratnerobe su lm Dge i2hc 6v a,(i uPsbsH2ioLe0otI0dnhS 0 ) ot bfhy e HCINUU.Va N /ttoAir oIanrDcaeShlp o omrPaEtrtleeeidcvs\U t e. rn otnciiaToscoen tsa lTs— el rUU{ See ucproovrmetmiCeul.dlnN .aiMntc.oc1a .et:t UUU hi eao nnCdDso i mvEimSpsyioidsonetnwm eeimUoUoa f l lfoStogTrhy D, S uPorfrvN eeaNvitoelinrlottnaihanoelcn re, n C e(nNMNtEaCeTrrHSi SSafUUUT)no aPr aHnIIVsd,l atnShdTesD ,P ubaiincd Vol. 49 / Nos. 51 & 52 TABLE Ii. (Cont'd) Provisional cases of selected notifiable diseases, United States, weeks ending December 23, 2000, and December 25, 1999 (51st Week) Hepatitis C; Lyme Gonorrhea Non-A, Non-B Legionellosis Listeriosis Disease Cum | Cum Cum Cum Cum. | Cum Cum Cum Cum Reporting Area 2000° 1999 1999 2000 1999 2000 1999 UNITED STATES 329,352 352,669 2,913 931 1,024 653 15,301 NEW ENGLAND 6,166 6,507 16 4,478 9 MID. ATLANTK Upstate N N.Y N.Y. City N.J Pa \. CENTRAL Not notifiable available January 5, 2001 TABLE Il. (Cont’d) Provisional cases of selected notifiable diseases, United States, weeks ending December 23, 2000, and December 25, 1999 (51st Week) Saimonetlosis* Malaria Rabies, Animal NETSS PHUS Cum Cum Cum Cum Cum Cum Reporting Area 1999 2000 1999 1999 2000 1999 UNITED STATES 1,484 5,786 6,476 38,202 30,469 32,354 NEW ENGLAND 813 876 2,202 2,152 2,226 Maine 5 wt 132 176 131 97 N.H 21 47 4 141 141 vt 57 &B 92 119 Mass 272 222 197 189 RA 61 ca) 129 158 Conn 248 512 448 MID. ATLANTIC > iS)n N 282 359 424 Upstate N.Y 910 402 281 NPN..aYJ . City N 3—B 9Si { 414953 884922193 E.N. CENTRAL 5 53 / 416 Ohio 2 5 352 Ind 5 5 571 iW 176 Mich 921 Wis 396 W.N. CENTRAL y 473 Minn . 656 lowa € 25 312 Mo 5 894 N. Dak 2 ¢ 1 5 S. Dak s 105 Nebr 140 Kans 291 S. ATLANTIC 352 Del cS) 6 166 140 Md 26 1 406 1 f 846 768 D.C 1 & 72 U Va Cx 228 839 W.Va d y 112 169 148 N.C d g 1,13 310 1,096 S.C 13 659 540 Ga q 3 1,584 570 Fla 2 636 251 E.S. CENTRAL ] 205 1,668 Ky 3 412 262 Tenn 573 755 Ala 5 599 521 Miss ! , 621 130 W.S. CENTRAL 3,705 4,094 Ark 656 632 La ‘ 721 768 Ykla ‘ 2 } 452 289 Tex . 1.276 2,405 MOUNTAIN 3,010 2,199 Mont é & Idaho c 134 37 Wyo Z 70 51 Colo 16 665 N. Mex ‘ 364 182 Ariz ] 9 ; f 895 134 Utat r 552 470 579 Nev 196 49 PACIFIC 5,504 4,691 4,689 Wash e<) 656 670 837 Oreg 2 4 420 348 467 Calif é 4,044 3,424 3,070 Alaska : ee z3 3 Hawai 1 2 330 226 282 Guam 37 U U PR 5 80 73 0 659 U U VI U U U U J U U U Amer. Samoa U U U U U U U U C.N.M.1 U U U U U U U U N: Not notifiable U: Unavailable No reported cases * Individual cases can be reported through both the National Electronic Telecommunications System for Surveillance (NETSS) and the Public Health Laboratory Information System (PHLIS)