depar depar depar depar department of health and human ser tment of health and human ser tment of health and human ser tment of health and human ser tment of health and human services vices vices vices vices# Nonfatal Motor-Vehicle Animal Crash-Related Injuries -United States, 2001-2002
In 2000, an estimated 6.1 million light-vehicle (e.g., passenger cars, sport utility vehicles, vans, and pickup trucks) crashes on U.S. roadways were reported to police (1). Of these reported crashes, 247,000 (4.0%) involved incidents in which the motor vehicle (MV) directly hit an animal on the roadway (1). Each year, an estimated 200 human deaths result from crashes involving animals (i.e., deaths from a direct MV animal collision or from a crash in which a driver tried to avoid an animal and ran off the roadway) (2). To characterize nonfatal injuries from these incidents, CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP). This report summarizes the results of that analysis, which indicated that, during 2001-2002, an estimated 26,647 MV occupants per year were involved in crashes from encounters with animals (predominantly deer) in a roadway and treated for nonfatal injuries in U.S. hospital emergency departments (EDs). Cost-effective measures targeting both drivers (e.g., speed reduction and early warnings) and animals (e.g., fencing and underpasses) are needed to reduce injuries associated with MV collisions involving animals.
NEISS-AIP is operated by the Consumer Product Safety Commission and collects data about initial visits for all types and causes of injuries treated in U.S. EDs (3). NEISS-AIP data are drawn from a nationally representative subsample of 66 of 100 NEISS-AIP hospitals selected as a stratified probability sample of hospitals in the United States and its territories with a minimum of six beds and a 24-hour ED. NEISS-AIP provides data on approximately 500,000 injuryand consumer product-related ED cases each year. Data for each case include a comment variable that contains additional information about the circumstances of the injury.
Each case was assigned a sample weight on the basis of the inverse probability of selection; these weights were summed to provide national estimates of MV animal crash-related injuries. Confidence intervals (CIs) were calculated by using a direct variance estimation procedure that accounted for the sample weights and complex sample design. Rates were calculated by using 2001 and 2002 U.S. Census bridged-race population estimates from the National Center for Health Statistics (4).
Data used in this study were obtained from medical records of 676 ED patients treated for nonfatal injuries incurred while driving or riding in a light vehicle and encountering an animal in the roadway. This report focuses on the majority of these patients, who encountered larger animals (e.g., deer, moose, elk, bear, horses, or cattle) entering the roadway. Smaller animals (e.g., dogs, cats, squirrels, raccoons, and possums) were included only in the overall national estimate. No information was obtained on type of vehicle. MV animal crashes were defined as those involving direct collision with an animal on a roadway or those occurring on or off the roadway as a result of trying to avoid hitting the animal. These cases were identified by using a brief narrative captured in the NEISS-AIP database that described the circumstances of the injury incident. An additional 79 patients injured as motorcyclists involved in MV-animal crashes were excluded from this study. During 2001During -2002, an estimated 26,647 (9.3 per 100,000 population; 95% CI = 6.7-11.9) persons were treated annually in U.S. EDs for MV animal crash-related injuries, of which 22,498 (84.8%) were MV occupants in crashes involving larger animals (Table 1). The highest MV large animal crashrelated injury rate (21.1 per 100,000 population) occurred among persons aged 15-24 years (Table 1). The age distribution of those injured in MV large animal crashes was different from those injured during all other types of MV trafficrelated crashes (p<0.03); most of this difference was attributed to an overrepresentation of persons aged 15-24 years (p<0.0001) and an underrepresentation of children aged 0-14 years (p<0.0001) (Figure). Among injured persons aged 15-24 years, 48.9% were driving the vehicle. The MV large animal crash-related injury rate was similar for males and females (Table 1). Approximately 6% of those treated in U.S. EDs required hospitalization for their injuries.
MV large animal crash-related injuries were mostly strains/ sprains (36.5%) and contusions/abrasions (33.9%) and involved the head/face (28.1%), neck (22.7%), and upper trunk (15.3%) (Table 2). The majority (94.5%) of the neck injuries were strains and sprains, and 62.5% of head/face injuries were contusions, abrasions, or lacerations. Persons injured during MV large animal crashes were treated more often during October and November than other months. Deer were the most common large animals involved in these incidents (86.9%). Approximately half (54.4%) of these crashes involved a direct collision with the animal, and the remainder (44.8%) resulted from the driver trying to avoid hitting the animal. Of those incidents in which the animal was avoided, the crash most commonly involved an MV leaving the roadway (29.0%); an MV hitting a tree, pole, or guardrail (21.4%); or an MV rollover (17.3%) (Table 2). Editorial Note: Nationally, nonfatal MV animal crashrelated injuries account for <1.0% of approximately three million MV occupants treated in U.S. EDs annually (5). Direct MV animal crashes represent nearly 4.0% of an estimated 6.1 million light-vehicle crashes reported to police in the United States (1). However, in rural areas with large deer populations, MV animal crashes and associated occupant deaths and injuries, wildlife loss, and property damage are important concerns. For instance, in Wisconsin, MV deer crashes accounted for nearly 16% of all statewide police-reported MV crashes in 2002 (6).
National estimates reported from this study are consistent with state MV animal crash data reported to police. In this study, the majority of MV occupant injuries resulted from encounters between the MV and deer; however, 12% of those injured resulted from MV crashes involving large domesticated animals (e.g., horses and cattle). MV occupant injuries can occur because of a direct MV collision with the large animal or from swerving or maneuvering to avoid a collision with the animal. In this study, 63.8% of younger drivers swerved to avoid the animal, resulting in an MV crash and subsequent injury. Similar to other MV occupant injuries from crashes that occur on U.S. highways, a majority of the injuries were neck sprains/strains, and contusions/abrasions to the head and face. One fourth of MV animal crash-related injuries were treated in October and November at the height of the fall deer hunting, mating, and migration season (7). MV animal crashes are more likely to occur in the early morning hours and especially at dusk, when deer are actively moving about and likely to cross the road in rural areas (6)(7)(8).  The findings of this report are subject to at least three limitations. First, although the risk for MV animal crash-related injury can vary among states and local areas, NEISS-AIP is designed to provide only national estimates and does not provide regional, state, or local estimates or estimates by urban and rural categories. Second, because of the small number of cases reported, this study excluded motorcyclists, who are known to be at higher risk for injury in crashes (6). Finally, NEISS-AIP only provides data on injured persons treated in hospital EDs.
Prevention efforts have focused on warning signs to alert drivers to animal crossings, speed restrictions, roadway fencing and underpasses/overpasses aimed at directing animals toward safe passage, roadside clearing, roadside mirrors and reflectors (i.e., to deflect headlight beams toward the sides of the road to alert deer), and reduction of deer populations through recreational hunting (7,9). Evaluation studies have been conducted to assess the cost and effectiveness of these methods, but the results are inconsistent (10). Interventions with some supportive evidence (e.g., fences combined with underpasses or overpasses) also are among the most expensive to build and maintain.
Primary prevention of MV animal crashes can be accomplished by keeping large animals, especially deer, from entering the roadway or by providing drivers with more time to react to a potentially dangerous situation. The same behaviors that are recommended to help prevent crashes in general are relevant for MV animal crashes. Driving within speed limits, staying alert and reducing distracted and drowsy driving, and eliminating alcohol-impaired driving will give drivers, particularly teenagers and younger adults, more time to react and avoid collisions. Prevention of injury if a crash occurs can be accomplished by the universal use of proper restraints, including safety belts, child safety seats, and booster seats.

# Transmission of Hepatitis B Virus in Correctional Facilities -Georgia, January 1999-June 2002
Incarcerated persons have a disproportionate burden of infectious diseases (1), including hepatitis B virus (HBV) infection. Among U.S. adult prison inmates, the overall prevalence of current or previous HBV infection ranges from 13% to 47%. The prevalence of chronic HBV infection among inmates is approximately 1.0%-3.7%, two to six times the prevalence among adults in the general U.S. population (1). Incarcerated persons can acquire HBV infection in the community or in correctional settings (1). This report summarizes the results of 1) an analysis of hepatitis B cases among Georgia inmates reported to the Georgia Department of Human Resources, Division of Public Health (DPH) during January 1999-June 2002, including a retrospective investigation of cases reported during January 2001-June 2002; and 2) a prevalence survey conducted in prison intake centers during February-March 2003. These efforts identified cases of acute hepatitis B in multiple Georgia prisons and documented evidence of ongoing transmission of HBV in the state correctional system. The findings underscore the need for hepatitis B vaccination programs in correctional facilities.
The Georgia correctional system houses approximately 45,000 inmates in 68 correctional facilities; approximately 16,000 new inmates are admitted each year and processed through one of five intake centers. The correctional system does not routinely screen inmates for HBV infection, and diagnostic testing is left to the judgment of individual physicians. In August 2000, in response to two hepatitis B Online know what matters. e asy.
MMWR Online makes it possible for you to access vital public health reports and news as soon as CDC publishes them. Get the information you want, when you need it, from a trusted source.
Visit cdc.gov/mmwr and stay current on important public health topics -the easy way.
-utbreaks at one Georgia correctional facility (2,3), DPH began to monitor reports of acute hepatitis B cases among inmates at all Georgia correctional facilities, as determined by the inmates' addresses on laboratory reports.
A case of acute HBV infection was defined as a positive serologic test for IgM antibodies to hepatitis B core antigen (IgM anti-HBc) on at least one occasion and at least one additional supporting finding (e.g., compatible symptoms, liver enzyme elevation, or another positive hepatitis B serologic test), received by DPH during January 1999-June 2002. Cases reported during January 2001-June 2002 were confirmed by retrospective review of the inmate's medical and laboratory records. The date of diagnosis of acute HBV infection was defined as the date that alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels were elevated at least two times greater than the upper limit of normal in conjunction with a positive test for IgM anti-HBc. When ALT or AST levels were not available, the date of the blood draw with a positive IgM anti-HBc result was used as the approximate date of diagnosis.
Incarceration histories of inmates with acute HBV infections reported during January 2001-June 2002 were reviewed to identify inmate locations and number of transfers between correctional facilities before illness onset. Persons with asymp-tomatic and symptomatic cases were considered to have been infected while incarcerated if they were in prison or jail during the 12 months or 6 months, respectively, before illness onset.
A prevalence survey to assess the HBV infection status of prisoners on entry was conducted at three Georgia prison intake centers for males and one intake center for females during February-March 2003. Consenting inmates underwent HBV serologic testing; all inmates at intake when the survey was conducted were offered hepatitis B vaccine.
During January 1999-June 2002, a total of 92 cases of acute HBV infection were identified, of which 57 (62%) were reported during January 2001-June 2002 and included in the retrospective investigation (Figure). Among the 57 inmates with HBV infection, the median age was 34 years (range: 18-59 years); 52 (91%) were male, and 35 (61%) were non-Hispanic blacks. Ten (18%) had symptoms that included jaundice, abdominal pain, fever, and vomiting. Seven (12%) subsequently were determined to have chronic infections. The chronic infection status of four inmates was not assessed.
Among the 57 inmates included in the retrospective investigation, the most frequently reported reason for HBV testing was the presence of symptoms or elevated liver enzymes (21 cases ). Other reasons included reported characteristics and behaviors that might be associated with HBV transmission (e.g., tattoos or unprotected sex contacts) (14 ), serologic testing performed as part of initial medical evaluation (13 ), and being positive for human immunodeficiency virus (five ). Prison staff reported counseling and providing medical follow-up for 52 (91%) of the 57 inmates.
The 57 cases were reported from 27 prisons and four probation detention centers in Georgia, with a mean of 1.8 cases per facility and a range of one to three cases for the 30 facilities that were not involved in the previously recognized outbreaks (2,3). The 57 inmates had been incarcerated for a median of 2.2 years (range: 0-23.7 years) before illness onset and had been transferred 1.4 times on average (median: one time; range: one to seven times) during the 12 months before diagnosis. The majority of HBV infections (41 ) were acquired in prison. Of the remaining 16 cases, 13 (81%) occurred in persons who had been in prison or jail for 1-6 months before receiving a diagnosis. The remaining three (19%) inmates were asymptomatic and had been in prison or jail for 10-11 months before receiving a diagnosis.
As of August 2002, the seven inmates who had chronic infections had been transferred among prison facilities 13 times during the cumulative 89 months of incarceration that followed their diagnosis, resulting in a mean of 1.8 transfers per person-year of incarceration (median: two transfers; range: zero to five transfers). Three inmates with chronic infection were released from prison.
Of 546 inmates surveyed at intake during February-March 2003, a total of 489 (90%) consented to serologic testing, and 428 (78%) consented to hepatitis B vaccination. Of the 489 inmates tested, three (0.6%) had acute HBV infections, four (0.8%) had chronic infections, 64 (13%) had evidence of resolved infections, and 374 (76%) were susceptible to HBV infection. Two of three inmates with acute infection had spent 5.5-11.0 months in jail before intake. Editorial Note: HBV is a bloodborne pathogen, transmitted by percutaneous or permucosal exposure to infectious blood or body fluids. The prevalence of chronic infection is higher among prison inmates (1.0%-3.7%) than among the general U.S. population (0.5%) (1), reflecting an overrepresentation of persons entering prison who are at high risk for HBV infection (e.g., injection-drug users and those with reported histories of multiple sex partners). The prevalence of chronic infection among the intake population in this report (0.8%) suggests that high-risk behaviors practiced within the community before incarceration might not account entirely for the burden of HBV infection in correctional facilities. Although studies are limited, transmission of HBV infection within correctional settings has been documented, with incidence ranging from 0.8% to 3.8% per year (2,(4)(5)(6).
The retrospective investigation described in this report identified an increase in HBV infections in Georgia correctional facilities, beginning in January 2001. This increase likely was related to multiple factors, including enhanced surveillance and increased diagnostic testing by correctional medical staff. Changes in diagnostic practices might have occurred because of increased awareness of hepatitis B among medical staff after outbreaks at a Georgia correctional facility in June 2000 and again in June 2001. Nonetheless, the number of reported cases probably underestimates the extent of HBV transmission in the correctional system because the majority of persons with acute HBV infection are asymptomatic and investigations of single cases are not conducted routinely. In the first previous outbreak, one symptomatic patient reported to DPH was associated with a cluster of 11 acute cases, and four chronic HBV infections were identified (2).
The majority of inmates with identified acute HBV infections were housed in multiple Georgia correctional facilities and were infected during their incarceration, suggesting widespread ongoing transmission in multiple facilities. Inmates infected with HBV were transferred frequently among facilities. Thus, potential sources of HBV transmission were distributed throughout the prison system.
In the Georgia correctional system, approximately one third of inmates are released each year (7). Inmates who become chronically infected and subsequently are released represent potential sources of infection for others in the community. In addition, susceptible inmates who are released continue to be at increased risk for HBV infection (1). The majority of inmates in the intake survey were susceptible to HBV infection and consented to vaccination, suggesting that vaccination efforts in correctional facilities might effectively capture susceptible, high-risk populations.
Although data are lacking regarding the overall burden of HBV infection in correctional systems, the ongoing transmission demonstrated in Georgia prisons might be occurring in other states, where similar conditions are likely to exist. All inmates who receive a medical evaluation should be vaccinated to prevent HBV infection (1). However, the majority of state correctional systems in the United States, including the Georgia system, do not have hepatitis B vaccination programs (1). Implementation of such programs in correctional settings nationwide could result in a considerable reduction in the hepatitis B-associated disease burden, not only by eliminating transmission among the incarcerated population, but also by reducing transmission in the community (8).

# Hepatitis B Vaccination of Inmates in Correctional Facilities -Texas, 2000-2002
In December 2002, approximately 2.2 million persons were incarcerated in the United States (1); an estimated 8 million were released to the community that year (2). In 2001, approximately 22,000 acute hepatitis B cases and 78,000 new hepatitis B virus (HBV) infections occurred in the United States (3); an estimated 29% of these cases were in persons who had been incarcerated previously (4). The majority of HBV infections among incarcerated persons are acquired in the community; however, infection also is transmitted within correctional settings (2). Hepatitis B vaccination of incarcerated persons is recommended to prevent transmission in correctional facilities and in previously incarcerated persons on their return to the community (2). In May 2000, the Texas Department of Criminal Justice (TDCJ), which oversees custody of state jail and prison inmates, implemented a hepatitis B vaccination program. To determine hepatitis B vaccination rates of inmates during 2000-2002, TDCJ reviewed charts of inmates released during a 3-day period for documentation of vaccination. This report summarizes the results of that study, which indicated that rates of vaccine acceptance and vaccine series completion among inmates were high. Establishing hepatitis B vaccination programs in prisons and jails can prevent a substantial proportion of HBV infections among adults in the outside community.
During 2000-2002, TDCJ housed approximately 151,000 inmates in 105 adult facilities, including prisons (median sentence of inmates: 9 years; range: 2-99 years) and jails (median sentence of inmates: 1.3 years; range: 3 months-2 years). Approximately 40,000 new offenders enter these facilities annually, and an estimated 1% of inmates are transferred between facilities daily (5,6). In 1999, state funds were appropriated for hepatitis B vaccination of all inmates in jails and prisons.
Before implementation of the vaccination program, a costeffectiveness model was developed that estimated the cost effectiveness of prevaccination testing for immunity to HBV infection among inmates. Stored serum specimens from 889 inmates incarcerated during 1998-1999 were tested for antibodies to hepatitis B core antigen (anti-HBc); HBV prevalence was 18%. The model estimated that at a threshold prevalence of 25%, the cost of a program with prevaccination testing was equivalent to that of vaccination without testing; at lower prevalence, prevaccination testing would not be cost effective (Figure). On the basis of these findings, all of the estimated 40,000 entering inmates were offered vaccine without prevaccination testing.
Entering inmates were offered the first hepatitis B vaccine dose at the time of admission. Persons who were already incarcerated were offered the first dose at the time of their annual health evaluation, which occurred on their anniversary month of incarceration. After vaccination of incarcerated persons, only newly admitted inmates were offered vaccine.
Vaccine was administered on a 0-, 2-, and 4-month schedule. An electronic pharmacy auto-renewal system was used to send second and third vaccine doses to the appropriate facility for each inmate. Health-care workers also recorded vaccine dose administration in each inmate's medical record, enabling inmates to complete the vaccination series despite frequent transfers within the system.
In February 2002, TDCJ evaluated vaccine acceptance and series completion rates. Charts of 232 prison inmates and 211 jail inmates released during a 3-day period were audited for receipt of hepatitis B vaccine; 426 (96%) inmates with no record of previous vaccination or HBV infection were considered to be eligible for vaccination. Lack of documentation of a vaccination encounter was interpreted as a failure to offer vaccine, and only a signed informed refusal form was counted as a vaccination refusal.
Hepatitis B vaccine was offered to 319 (75%) of 426 inmates. Prison inmates were more likely to be offered vaccine (185/220 ) than jail inmates (134/206 ) (p<0.001), which might be related to higher inmate turnover and lack of staff contact time in jails (Table ). However, acceptance of the first vaccine dose was higher among jail inmates (114/134 ) than among prison inmates (134/185 ) (p = 0.005).
Among 125 prison and 99 jail inmates who began vaccination and were incarcerated for >4 months, the 3-dose completion rate was 96% and 54%, respectively. In December 2002, the hepatitis B vaccination program was suspended because of a lack of funds. Editorial Note: Evaluation of the TDCJ hepatitis B vaccination program demonstrated that high vaccine coverage could be achieved for inmates in a state correctional system. Incarceration provides an opportunity to vaccinate persons at high risk typically not served by prevention services in the public or private sectors, and vaccination of incarcerated populations is cost effective (7).
The findings in this report illustrate the need to tailor a program to a particular facility. Completion of the vaccine series is a more feasible goal for long-term facilities; shortterm facilities should initiate the vaccine series, supply an immunization record and, where feasible, provide information at discharge about facilities offering the remaining vaccine doses. Vaccination also can be completed if the person returns to a correctional institution.
Prevaccination testing to detect existing immunity can eliminate the cost of revaccinating persons who were vaccinated previously or infected. TDCJ's decision not to perform prevaccination testing was based on a model that included the costs of testing and vaccination and the series completion rate. The model assumed that all inmates who received the first vaccine dose would return for subsequent doses; if attrition caused by release was included in the model, prevaccination testing would only be cost effective if the prevalence of immunity was higher. Changes in prevalence of immunity to HBV infection or costs (e.g., vaccine, labor, and testing) also would change the cost effectiveness of prevaccination testing. In particular, immunity to HBV infection in young adults is changing rapidly within most communities because of an increase in vaccinated adolescents. If adequate immunization records are not available for inmates, periodic monitoring of the prevalence of immunity to HBV infection using a serologic marker to detect both infection (i.e., anti-HBc) and immunization (i.e., antibodies to hepatitis B surface antigen) will help corrections officials determine when prevaccination testing might reduce costs (2).  The findings in this report are subject to at least two limitations. First, inmates with shorter sentences are more likely to be discharged and might be overrepresented by the sampling. Because inmates with short sentences might not have been incarcerated long enough to complete the vaccination series, more inmates might have completed the vaccination series than this study demonstrated. Second, lack of long-term follow-up precludes evaluation of the eventual series completion by jail inmates, who might have accessed additional doses outside the correctional system or during subsequent incarcerations.

# FIGURE. Cost effectiveness of prevaccination testing for immunity to hepatitis B virus (HBV) infection among jail and prison inmates -Texas
Hepatitis B vaccination of inmates in state correctional facilities is feasible if resources are available to purchase and administer vaccine. In 2000, a survey of state correctional facility medical directors indicated that the majority of prison systems would vaccinate inmates if resources were available (8). Although hepatitis B vaccination of inmates has been recommended since the vaccine first became available in 1982 ( 9), only five states (Hawaii, Michigan, New Mexico, Vermont, and Wisconsin) vaccinate inmates routinely (D. Burnett, M.D., Wisconsin Department of Corrections and F. Pullara, M.D., New Mexico Department of Corrections, personal communications, 2004) (8). Collaborations between public health and corrections authorities at the state and local level are essential to overcome barriers to vaccination program implementation.

# Tuberculosis Associated with Blocking Agents Against Tumor Necrosis Factor-Alpha -California, 2002-2003
The Food and Drug Administration (FDA) has determined that tuberculosis (TB) disease is a potential adverse reaction from treatment with the tumor necrosis factor-alpha (TNF-) antagonists infliximab (Remicade  ), etanercept (Enbrel  ), and adalimumab (Humira  )*; the three products are labeled accordingly (1,2). These products work by blocking TNF-, an inflammatory cytokine, and are approved for treating rheumatoid arthritis and other selected autoimmune diseases. TNF- is associated with the immunology and pathophysiology of certain infectious diseases, notably TB; blocking TNF- can allow TB disease to emerge from latent Mycobacterium tuberculosis infection. In 2002, a California county health department reported three cases of TB disease occurring in association with infliximab therapy. This report summarizes those cases and nine subsequently reported cases and provides interim recommendations for TB prevention and management in recipients of these blocking agents. Healthcare providers should take steps to prevent TB in immunocompromised patients and remain vigilant for TB as a cause of unexplained febrile illness.

# Case Reports
Case 1. In January 2002, a U.S.-born man aged 55 years with rheumatoid arthritis had pulmonary TB disease diagnosed 17 months after starting infliximab therapy. In 1995, he had a positive tuberculin skin test (TST) and reportedly took isoniazid for 12 months; however, his adherence to therapy was questionable. During September 2000-January 2002, he received 13 infusions of infliximab, and his arthritic symptoms decreased. However, in January he had fever and weight loss. Four weeks later, a supraclavicular lymph node became enlarged, and a chest radiograph revealed a rightupper-lobe lung cavity with a nodular infiltrate. M. tuberculosis was isolated from sputum and lymph node specimens, and his condition improved with anti-TB medications. In July 2002, he again lost weight. He had smoked cigarettes for many years and was found to have lung cancer; he died in November 2002.
Case 2. A woman aged 64 years with rheumatoid arthritis had pulmonary and pericardial TB disease diagnosed in June 2002. She had begun infliximab therapy in September 2001 and received 7 doses before onset of fever and weight loss in April 2002. Her chest radiograph revealed a large pericardial effusion and a right-upper-lobe lung infiltrate. M. tuberculosis resistant to isoniazid, rifampin, pyrazinamide, and ethambutol was isolated from sputum and pericardial fluid. The patient was born in the Philippines, where TB often is drug resistant (3). In 1999, she was exposed to a person with drugsusceptible TB in the United States and subsequently had two TSTs with negative results in 2000; however, she was taking prednisone for her arthritis at the time of the TSTs. After 12 months of therapy with second-line anti-TB medications, her medical condition has improved. Case 3. A U.S.-born woman aged 54 years was exposed to contagious TB in 1996; she had a positive TST result during the contact investigation but was not treated for latent TB infection (LTBI). The patient has Crohn's disease and received infliximab in February 2001 and June 2002. Two weeks after her second infusion, but 16 months after her first infusion, she sought care for cough, fever, and abdominal pain. Her chest radiograph revealed upper-lobe lung nodules with a pleural effusion, and sputum specimens yielded M. tuberculosis. She started standard, four-drug anti-TB therapy but experienced gastrointestinal intolerance. Isoniazid was discontinued, and she was free of TB disease after treatment with rifampin, pyrazinamide, and ethambutol.

# Additional Reports
In 2003, the state of California Department of Health Services asked local jurisdictions to report TB cases associated with TNF- antagonists since January 2002. As of September 2003, nine additional reports had been received, for a Eleven of the patients had at least one risk factor for LTBI (e.g., born in countries where TB is prevalent or contact with a person with TB disease). Eight were taking other immunosuppressive therapies at the time of their TB diagnoses. Three patients underwent a medical history for TB risk factors before beginning therapy with a TNF- antagonist. In addition to the patient in case 1, a second patient died (from cardiomyopathy) while being treated for TB disease.
Editorial Note: As of January 2004, FDA's adverse-event reporting system had received several hundred reports, mostly from outside the United States, of TB disease in patients who received TNF- antagonists. Manufacturers of these products are required to report known cases, but reporting is voluntary for others. The majority of the cases probably represent progression of LTBI to TB disease, although the contribution of newly acquired M. tuberculosis infection to the total number of reports is unknown (1). Reports have included atypical presentations, extrapulmonary and disseminated disease, and deaths (1,4,5).
In California, after the initial three reports, nine additional cases of TB disease were reported during January 2002-August 2003 in patients taking TNF- antagonists. Although reporting of TB cases is mandatory in California, reporting the association with TNF- antagonists was voluntary, and an underestimate might have resulted.
Eight of the 12 patients in California were born in countries where TB is prevalent. In certain instances, physicians had not screened for risk factors for M. tuberculosis infection or tested their patients for infection before beginning therapy with TNF- antagonists. In other instances, testing was performed, but LTBI was not diagnosed, possibly because of cutaneous anergy. Many patients who receive TNF- antagonists already are receiving other immunosuppressive therapies, and certain conditions such as rheumatoid arthritis also can decrease sensitivity to tuberculin; therefore, TST results at the time of initiating TNF- antagonist therapy might be falsely negative. Some experts advocate treating for presumed LTBI when a candidate for TNF- antagonists has risk factors for M. tuberculosis infection but a negative TST result (4,5).
TNF-, an inflammatory cytokine expressed by activated macrophages, T-cells, and other immune cells, plays a crucial role in the host response against M. tuberculosis and other intracellular pathogens. Infliximab and adalimumab are monoclonal antibodies; etanercept is a dimeric soluble form of the TNF- receptor. All three products are approved for the treatment of patients with rheumatoid arthritis. Infliximab also is approved for Crohn's disease, and etanercept is approved for specific other arthritides and for psoriasis. Use of these agents has been associated with other life-threatening infectious diseases besides TB, including candidiasis, histoplasmosis, aspergillosis, and listeriosis (1). TNF- antagonists often are used in conjunction with other immunosuppressive therapies, particularly glucocorticoids and methotrexate. Whether the increased rates of TB or other infectious diseases are caused by interactions among these therapies is unknown.
Diagnosing LTBI in candidates for TNF- antagonist therapy is challenging (Box). For patients who undergo treatment for LTBI, the optimal time for starting TNF- antagonist therapy is undetermined. Some experts advocate postponing therapy until LTBI treatment is complete. However, this delay might be impractical (4,6). The risk for TB relapse in patients previously cured of TB disease and subsequently treated with TNF- antagonists is unknown.

# BOX. Recommendations for screening, diagnosis, and treatment of latent TB infection (LTBI) and tuberculosis (TB)
in patients administered or scheduled to receive tumor necrosis factor-alpha (TNF-    ) antagonists   If active TB disease develops during TNF- antagonist therapy, the TNF- antagonist should be discontinued, at least until the anti-TB regimen has been started and the patient's condition has improved. The optimal time for resuming TNF- antagonist therapy is undetermined. Outcomes with other immunosuppressive agents during the treatment of TB disease have been variable. Use of glucocorticosteroids during the treatment of TB disease is considered safe (7), and studies of TB disease in organ transplant recipients suggest that survival is not decreased by the use of cyclosporine or azathioprine (8). Etanercept, administered in a phase-1 clinical trial along with a standard initial anti-TB regimen, did not delay the resolution of TB disease markers in a group of patients coinfected with human immunodeficiency virus in comparison with historical controls; adverse effects were not detected (9). However, use of anti-T-cell agents in transplant recipients with TB disease is associated with increased mortality; whether this increased mortality is because of the suppression of immune response or the dysfunction of the transplanted organ is unclear (8).
7 0 Illinois 0 1 1 2 0 Iowa 1 2 0 3 1 Michigan 1 0 0 1 0 Missouri 1 0 0 1 0 Nebraska 0 1 0 1 0 Nevada 2 0 0 2 0 New Mexico 1 4 0 5 0 New York 2 1 0 3 0 North Dakota 0 1 0 1 0 Ohio 1 0 0 1 1 Pennsylvania 1 0 0 1 0 South Dakota 1 8 0 9 0 Texas 2 1 0 3 1 Wyoming 0 1 0 1 0
Practitioners who prescribe TNF- antagonists should educate their patients about the symptoms of TB disease, with added emphasis on extrapulmonary symptoms, which can include fever, malaise, or development of a mass. A patient with symptoms should undergo diagnostic testing for TB. In addition to following local reporting requirements, healthcare providers should report TB cases associated with TNF- antagonists to FDA's Medwatch system (available at http:// www.fda.gov/medwatch).
Ongoing clinical trials are using both approved and experimental TNF- antagonists in the treatment of additional conditions (4). Novel therapies that inhibit other related inflammatory cytokines are under development. As the use of these blocking agents expands, associated cases of TB might increase. Vigilance for TB in association with these agents is critical to early recognition and successful treatment.

# West Nile Virus Activity -United
States, July 28-August 3, 2004 and Nevada) and in two wild hatchling birds from Ohio. Three seropositive sentinel horses were reported from Puerto Rico. A total of 1,486 WNV-positive mosquito pools have been reported from 24 states (Arizona, Arkansas, California, Colorado, Connecticut, Georgia, Illinois, Indiana, Kansas, Louisiana, Michigan, Mississippi, Missouri, Nebraska, Nevada, New Jersey, New Mexico, Ohio, Pennsylvania, South Dakota, Tennessee, Texas, Utah, and Virginia).
Additional information about national WNV activity is available from CDC at / westnile/index.htm and at .

# Notice to Readers

# Final 2003 Reports of Notifiable Diseases
The    -
- - - - Idaho - - - - - - W y o . - - - - - 2 Colo. N N - - - 621 N . M e x . - - - - 1 4 A r i z . - - - - 5 7 Utah - - - - - - N e v . - 1 - - - 2 PACIFIC - - - - - 2 Wash. - - - - - - Oreg. - - - - - - Calif. - - - - - 2 Alaska - - - - - - H a w a i i - - - - - - Guam - - - - - - P . R . - - - - - - V . I . - - - - - - Amer. Samoa - - - - - - C.N.

# MMWR 697
- No measles cases were reported for the current 4-week period yielding a ratio for week 30 of zero (0).  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.