Increased case-fatality rate associated with outbreaks of Neisseria meningitidis infection, compared with sporadic meningococcal disease, in the United States, 1994-2002.

BACKGROUND: Outbreaks of meningococcal disease are infrequent but important public health events. We characterize outbreak-associated cases in the United States and compare them with sporadic disease. METHODS: Outbreaks of meningococcal disease that occurred during the period of 1 July 1994 through 30 June 2002 were identified through state health departments, Centers for Disease Control and Prevention records, and a review of newspapers and the medical literature. Cases associated with outbreaks were compared with sporadic cases identified through population-based surveillance. RESULTS: We identified 69 outbreaks of Neisseria meningitidis infection (median, 9.5 outbreaks per year; range, 3-14 outbreaks per year), which involved 229 patients from 30 states. Forty-three (62%) of the outbreaks involved N. meningitidis serogroup C, 17 (25%) involved serogroup B, and 9 (13%) involved serogroup Y. Twenty-five outbreaks (36%) occurred in communities, and 44 (64%) were organization based, including 12 that occurred in colleges and universities, 19 that occurred in primary and secondary schools, and 8 that occurred in nursing homes. Vaccination campaigns (with the A/C/Y/W-135 meningococcal polysaccharide vaccine) were conducted for 31 outbreaks (28 involving serogroup C and 3 involving serogroup Y). After controlling for age, serogroup, and clinical presentation, outbreak-associated cases were associated with a higher case-fatality rate than were sporadic cases (21% vs. 11%; odds ratio, 3.3; 95% confidence interval, 2.0-5.5). CONCLUSIONS: Outbreaks remain an important but infrequent public health issue, representing <2% of all cases of meningococcal disease. However, given the increased case-fatality rate found among outbreak-related cases of N. meningitidis infection, additional investigation of factors that favor the transmission and virulence of outbreak-related strains is warranted.

Assessing the risk of laboratory-acquired meningococcal disease.

Neisseria meningitidis is infrequently reported as a laboratory-acquired infection. Prompted by two cases in the United States in 2000, we assessed this risk among laboratorians. We identified cases of meningococcal disease that were possibly acquired or suspected of being acquired in a laboratory by placing an information request on e-mail discussion groups of infectious disease, microbiology, and infection control professional organizations. A probable case of laboratory-acquired meningococcal disease was defined as illness meeting the case definition for meningococcal disease in a laboratorian who had occupational exposure to an N. meningitidis isolate of the same serogroup within 14 days of illness onset. Sixteen cases of probable laboratory-acquired meningococcal disease occurring worldwide between 1985 and 2001 were identified, including six U.S. cases between 1996 and 2000. Nine cases (56%) were serogroup B; seven (44%) were serogroup C. Eight cases (50%) were fatal. All cases occurred among clinical microbiologists. In 15 cases (94%), isolate manipulation was performed without respiratory protection. We estimated that an average of three microbiologists are exposed to the 3,000 meningococcal isolates seen in U.S. laboratories yearly and calculated an attack rate of 13/100,000 microbiologists between 1996 and 2001, compared to 0.2/100,000 among U.S. adults in general. The rate and case/fatality ratio of meningococcal disease among microbiologists are higher than those in the general U.S. population. Specific risk factors for laboratory-acquired infection are likely associated with exposure to droplets or aerosols containing N. meningitidis. Prevention should focus on the implementation of class II biological safety cabinets or additional respiratory protection during manipulation of suspected meningococcal isolates.

Cost-effectiveness of conjugate meningococcal vaccination strategies in the United States.

CONTEXT: The US Food and Drug Administration approved a meningococcal conjugate A/C/Y/W-135 vaccine (MCV-4) for use in persons aged 11 to 55 years in January, 2005; licensure for use in younger age groups is expected in 2 to 4 years. OBJECTIVE: To evaluate and compare the projected health and economic impact of MCV-4 vaccination of US adolescents, toddlers, and infants. DESIGN: Cost-effectiveness analysis from a societal perspective based on data from Active Bacterial Core Surveillance (ABCs) and other published and unpublished sources. Sensitivity analyses in which key input measures were varied over plausible ranges were performed. SETTING AND PATIENTS: A hypothetical 2003 US population cohort of children 11 years of age and a 2003 US birth cohort. INTERVENTIONS: Hypothetical routine vaccination of adolescents (1 dose at 11 years of age), toddlers (1 dose at 1 year of age), and infants (3 doses at 2, 4, and 6 months of age). Each vaccination scenario was compared with a "no-vaccination" scenario. MAIN OUTCOME MEASURES: Meningococcal cases and deaths prevented, cost per case prevented, cost per life-year saved, and cost per quality-adjusted life-year saved. RESULTS: Routine MCV-4 vaccination of US adolescents (11 years of age) would prevent 270 meningococcal cases and 36 deaths in the vaccinated cohort over 22 years, a decrease of 46% in the expected burden of disease. Before program costs are counted, adolescent vaccination would reduce direct disease costs by $18 million and decrease productivity losses by $50 million. At a cost per vaccination (average public-private price per dose plus administration fees) of $82.50, adolescent vaccination would cost society $633000 per meningococcal case prevented and $121000 per life-year saved. Key variables influencing results were disease incidence, case-fatality ratio, and cost per vaccination. The cost-effectiveness of toddler vaccination is essentially equivalent to adolescent vaccination, whereas infant vaccination would be much less cost-effective. CONCLUSIONS: Routine MCV-4 vaccination of US children would reduce the burden of disease in vaccinated cohorts but at a relatively high net societal cost. The projected cost-effectiveness of adolescent vaccination approaches that of recently adopted childhood vaccines under conditions of above-average meningococcal disease incidence or at a lower cost per vaccination.

An overview of adverse events reported by participants in CDC's anthrax vaccine and antimicrobial availability program.

PURPOSE: The CDC's Anthrax Vaccine and Antibiotic Availability Program was implemented under an Investigational New Drug (IND) application to provide additional post-exposure prophylaxis for individuals potentially exposed to Bacillus anthracis in the fall of 2001. Participants were provided with two options: (1) 40 additional days of antimicrobial prophylaxis (i.e., ciprofloxacin, doxycycline, or amoxicillin); or (2) 40 additional days of antimicrobial prophylaxis plus three doses of anthrax vaccine adsorbed (AVA). METHODS: Participants were monitored for adverse events (AEs). Participants were asked to complete 2-week AE diaries for 6 weeks post-enrollment, and approximately 2 months after enrollment, active surveillance was conducted through telephone interviews with 1113 (64%) participants. RESULTS: A total of 1727 of approximately 10 000 previously prophylaxed persons enrolled to receive 40 additional days of antibiotics. Of these, 199 opted at enrollment to receive three doses of AVA in addition to the additional 40 days of antibiotic. Overall, 28% of participants reported at least one AE on their diaries. Results varied by surveillance mechanism, the diary data indicated differences in the proportion reporting AEs between participants receiving antibiotic only and participants receiving antibiotic and AVA. However, during the active 2-month telephone follow-up, the rates of AEs reported for both the antibiotic only and antibiotic plus AVA treatment regimens were similar. Additionally, ciprofloxacin and doxycycline had similar AE profiles, with only rigors reported significantly more often among ciprofloxacin recipients. CONCLUSIONS: Overall, the rates of AEs experienced by all participants were acceptable given the seriousness of potential B. anthracis exposure.

Neisseria meningitidis serogroup W-135 carriage among US travelers to the 2001 Hajj.

In 2000, a large international outbreak of meningococcal disease caused by Neisseria meningitidis serogroup W-135 was identified among pilgrims returning from the Hajj in Saudi Arabia. To assess ongoing risk, we evaluated N. meningitidis carriage among US travelers to the 2001 Hajj. Of 25 N. meningitidis isolates obtained, 15 (60%) were nongroupable and 8 (32%) were serogroup W-135 when tested by standard slide-agglutination techniques. Two additional nongroupable isolates were characterized as serogroup W-135 when tested by polymerase chain reaction. Nine of 10 serogroup W-135 isolates were indistinguishable from the Hajj-2000 clone. None of the departing, but 9 (1.3%) of the returning, pilgrims carried serogroup W-135 (P=.01); all carriers reported previous vaccination. Carriage of N. meningitidis serogroup W-135 increased significantly in pilgrims returning from the Hajj. Although the risk of disease to pilgrims appears to be low, the risk of spread to others of this pathogenic strain remains a concern.

Responding to detection of aerosolized Bacillus anthracis by autonomous detection systems in the workplace.

Autonomous detection systems (ADSs) are under development to detect agents of biologic and chemical terror in the environment. These systems will eventually be able to detect biologic and chemical hazards reliably and provide approximate real-time alerts that an agent is present. One type of ADS that tests specifically for Bacillus anthracis is being deployed in hundreds of postal distribution centers across the United States. Identification of aerosolized B. anthracis spores in an air sample can facilitate prompt on-site decontamination of workers and subsequent administration of postexposure prophylaxis to prevent inhalational anthrax. Every employer who deploys an ADS should develop detailed plans for responding to a positive signal. Responding to ADS detection of B. anthracis involves coordinating responses with community partners and should include drills and exercises with these partners. This report provides guidelines in the following six areas: 1) response and consequence management planning, including the minimum components of a facility response plan; 2) immediate response and evacuation; 3) decontamination of potentially exposed workers to remove spores from clothing and skin and prevent introduction of B. anthracis into the worker's home and conveyances; 4) laboratory confirmation of an ADS signal; 5) steps for evaluating potentially contaminated environments; and 6) postexposure prophylaxis and follow-up.

SARS surveillance during emergency public health response, United States, March-July 2003.

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.

Use of real-time PCR to resolve slide agglutination discrepancies in serogroup identification of Neisseria meningitidis.

Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in children and young adults in the United States. Rapid and reliable identification of N. meningitidis serogroups is crucial for judicious and expedient response to cases of meningococcal disease, including decisions about vaccination campaigns. From 1997 to 2002, 1,298 N. meningitidis isolates, collected in the United States through the Active Bacterial Core surveillance (ABCs), were tested by slide agglutination serogrouping (SASG) at both the ABCs sites and the Centers for Disease Control and Prevention (CDC). For over 95% of isolates, SASG results were concordant, while discrepant results were reported for 58 isolates. To resolve these discrepancies, we repeated the SASG in a blinded fashion and employed ctrA and six serogroup-specific PCR assays (SGS-PCR) to determine the genetic capsule type. Seventy-eight percent of discrepancies were resolved, since results of the SGS-PCR and SASG blinded study agreed with each other and confirmed the SASG result at either state health laboratories or CDC. This study demonstrated the ability of SGS-PCR to efficiently resolve SASG discrepancies and identified the main cause of the discrepancies as overreporting of these isolates as nongroupable. It also reemphasized the importance of adherence to quality assurance procedures when performing SASG and prompted prospective monitoring for SASG discrepancies involving isolates collected through ABCs in the United States.

Opportunities for control of meningococcal disease in the United States.

The United States currently has relatively low rates of meningococcal disease caused by Neisseria meningitidis. Serogroups Y, C, and B are most common. Although most cases are sporadic, a minority are associated with outbreaks. Pediatric populations have disproportionately higher rates of disease, but nearly two thirds of all cases occur in persons aged 15 years and older. The major challenge to control of domestic meningococcal disease is the absence of a vaccine to prevent sporadic cases spanning many age groups. The quadrivalent A/C/Y/W-135 meningococcal polysaccharide vaccine is licensed in the United States, but because of its limited efficacy in children under two years of age, it is recommended for high-risk groups and outbreak response rather than routine childhood immunization. New conjugate meningococcal vaccines have successfully reduced endemic disease in the United Kingdom, and similar vaccines promise to have a dramatic impact on the burden of meningococcal disease in the United States.

Serious adverse events among participants in the Centers for Disease Control and Prevention's Anthrax Vaccine and Antimicrobial Availability Program for persons at risk for bioterrorism-related inhalational anthrax.

On 20 December 2001, the Centers for Disease Control and Prevention (CDC) initiated the Anthrax Vaccine and Antibiotic Availability Program (hereafter, the "Program") under an investigational new drug application with the US Food and Drug Administration. This Program provided options for additional preventive treatment for persons at risk for inhalation anthrax as a result of recent bioterrorism attacks who had concluded or were concluding a 60-day course of antimicrobial prophylaxis. Participants were offered an additional 40 days of antibiotic therapy (with ciprofloxacin, doxycycline, or amoxicillin) or antibiotic therapy plus 3 doses of anthrax vaccine. By 11 February 2002, a total of 5420 persons had received standardized education about the Program and 1727 persons (32%) had enrolled. Twelve participants have been identified as having serious adverse events (SAEs). One SAE, which occurred in a participant with ciprofloxacin-induced allergic interstitial nephritis, was considered to be probably associated with treatment received in the Program. No SAEs were associated with anthrax vaccine. CDC will continue to monitor Program participants during the next 2 years.

Neonatal meningococcal disease in the United States, 1990 to 1999.

BACKGROUND: Although neonatal bacterial meningitis is common, the rate of invasive meningococcal disease in the United States among children < or =30 days old has not been defined. Most relevant literature consists of case reports or case series, which note high case-fatality ratios but do not describe the overall burden of disease. METHODS: We used active, population-based surveillance data from the Active Bacterial Core Surveillance program to estimate the incidence of neonatal meningococcal disease in the United States from 1990 to 1999. A case of neonatal meningococcal disease was defined as isolation of Neisseria meningitidis from a normally sterile site in a resident of the surveillance area < or =30 days of age. RESULTS: The median annual number of neonates under surveillance was 25 900. Between 1990 and 1999, 22 cases of neonatal meningococcal disease were identified. Three (14%) patients died. The average annual incidence was 9 per 100 000. CONCLUSIONS: The rate of neonatal meningococcal disease in the United States is higher than previous estimates. Meningococcal disease is uncommon in neonates, but its rate is similar to that of meningococcal disease in 6- to 23-month-old children.

Serogroup W-135 meningococcal disease during the Hajj, 2000.

An outbreak of serogroup W-135 meningococcal disease occurred during the 2000 Hajj in Saudi Arabia. Disease was reported worldwide in Hajj pilgrims and their close contacts; however, most cases were identified in Saudi Arabia. Trends in Saudi meningococcal disease were evaluated and the epidemiology of Saudi cases from this outbreak described. Saudi national meningococcal disease incidence data for 1990 to 2000 were reviewed; cases from January 24 to June 5, 2000, were retrospectively reviewed. The 2000 Hajj outbreak consisted of distinct serogroup A and serogroup W-135 outbreaks. Of 253 identified cases in Saudi Arabia, 161 (64%) had serogroup identification; serogroups W-135 and A caused 93 (37%) and 60 (24%) cases with attack rates of 9 and 6 cases per 100,000 population, respectively. The 2000 Hajj outbreak was the first large serogroup W-135 meningococcal disease outbreak identified worldwide. Enhanced surveillance for serogroup W-135, especially in Africa, is essential to control this emerging epidemic disease.

Identification of Haemophilus influenzae serotypes by standard slide agglutination serotyping and PCR-based capsule typing.

To resolve discrepancies in slide agglutination serotyping (SAST) results from state health departments and the Centers for Disease Control and Prevention (CDC), we characterized 141 of 751 invasive Haemophilus influenzae isolates that were identified in the United States from January 1998 to December 1999 through an active, laboratory-based, surveillance program coordinated by the CDC. We found discrepancies between the results of SAST performed at state health departments and those of PCR capsule typing performed at the CDC for 56 (40%) of the isolates characterized: 54 isolates that were identified as a particular serotype by SAST were shown to be unencapsulated by PCR, and two isolates that were reported as serotypes b and f were found to be serotypes f and e, respectively, by PCR. The laboratory error most likely to affect the perceived efficacy of the conjugate H. influenzae type b (Hib) vaccine was the misidentification of isolates as serotype b: of 40 isolates identified as serotype b by SAST, 27 (68%) did not contain the correlating capsule type genes. The frequency of errors fell substantially when standardized reagents and routine quality control of SAST were used during a study involving three laboratories. An overall 94% agreement between SAST and PCR results showed that slide agglutination could be a valid and reliable method for serotyping H. influenzae if the test was performed correctly, in accordance with standardized and recommended procedures. An ongoing prospective analysis of all H. influenzae surveillance isolates associated with invasive disease in children less than 5 years old will provide more accurate national figures for the burden of invasive disease caused by Hib and other H. influenzae serotypes.

First case of bioterrorism-related inhalational anthrax in the United States, Palm Beach County, Florida, 2001.

On October 4, 2001, we confirmed the first bioterrorism-related anthrax case identified in the United States in a resident of Palm Beach County, Florida. Epidemiologic investigation indicated that exposure occurred at the workplace through intentionally contaminated mail. One additional case of inhalational anthrax was identified from the index patient's workplace. Among 1,076 nasal cultures performed to assess exposure, Bacillus anthracis was isolated from a co-worker later confirmed as being infected, as well as from an asymptomatic mail-handler in the same workplace. Environmental cultures for B. anthracis showed contamination at the workplace and six county postal facilities. Environmental and nasal swab cultures were useful epidemiologic tools that helped direct the investigation towards the infection source and transmission vehicle. We identified 1,114 persons at risk and offered antimicrobial prophylaxis.

Vaccines for the prevention of meningococcal disease in children.

Neisseria meningitidis is one of the most feared infections in pediatrics as the result of its rapid progression, high fatality rate, and frequent occurrence of sequelae. The 5 major meningococcal serogroups associated with disease are A, B, C, Y, and W-135. Currently available polysaccharide vaccines are effective in preventing disease caused by serogroups A, C, Y, and W-135 in older children and adults but do not elicit good long-term protection in young children. Vaccines that protect against serogroup B disease are still in development. As with the Haemophilus influenzae type b and pneumococcal polysaccharide vaccines, conjugation of the polysaccharide vaccine to a protein carrier dramatically changes vaccine characteristics, with resulting efficacy in infants. New meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being developed. A serogroup C conjugate vaccine has been introduced successfully into the routine childhood schedule in the United Kingdom. New meningococcal conjugate vaccines are likely to have a dramatic effect on the burden of meningococcal disease within the next decade.

Vaccinating first-year college students living in dormitories for Meningococcal disease: an economic analysis.

BACKGROUND: Surveillance of meningococcal disease among U.S. college students found an elevated rate of this disease among first-year students living in dormitories. OBJECTIVE: This study examines the economics of routinely vaccinating a cohort of 591,587 incoming first-year students who will live in dormitories for > or =1 years. METHODS: A cost-benefit model (societal perspective) was constructed to measure the net present value (NPV) of various vaccination scenarios, as well as the cost/case and cost/death averted. Input values included hospitalization costs from $10,924 to $24,030 per hospitalization; immunization costs (vaccine plus administration costs) from $54 to $88 per vaccine; 30 nonfatal, vaccine-preventable cases over a 4-year period (includes 3 with sequelae); 3 premature deaths; value of human life from $1.2 million to $4.8 million; and long-run sequelae costs from $1298 to $14,600. Sensitivity analyses were also conducted on vaccine efficacy (80% to 90%); discount rate (0% to 5%); and coverage (60% to 100%). RESULTS: The costs of vaccination outweighed the benefits gained with NPVs ranging from -$11 million to -$49 million. The net cost per case averted ranged from $0.6 million to $1.9 million. The net cost per death averted ranged from $7 million to $20 million. The break-even costs of vaccination (when NPV=$0) at 60% coverage ranged from $23 (90% vaccine efficacy) to $5 (80% efficacy). CONCLUSIONS: The model showed that the vaccination program is not cost-saving. Key variables influencing the results were the low number of vaccine-preventable cases and the high cost of vaccination. However, from the perspective of students and parents, the cost of vaccination might be worth the real or perceived benefit of reducing the risk to an individual student of developing meningococcal disease.

Genotype-specific carriage of Neisseria meningitidis in Georgia counties with hyper- and hyposporadic rates of meningococcal disease.

Carriage of Neisseria meningitidis in a Georgia county with hypersporadic incidence of meningococcal disease ("hypersporadic county") and in a county with no cases of meningococcal disease was determined by a cross-sectional pharyngeal culture study of high school students. Among 2730 students from whom culture samples were obtained, meningococcal carriage was 7.7% (140/1818) in the hypersporadic county and 6.1% (56/912) in the comparison county. Carriage rates by serogroup and genetic type (i.e., electrophoretic type [ET]) did not differ significantly between counties, but apartment or mobile home residency was a risk factor for carriage in the hypersporadic county. Although most cases of meningococcal disease in the hypersporadic county were caused by members of the serogroup C ET-37 clonal group, no ET-37 meningococcal isolates were recovered from carriers in this county. However, 38% of all meningococcal isolates recovered from carriers in both counties were members of the serogroup Y ET-508 clonal group, an emerging cause of meningococcal disease in Georgia and throughout the United States during 1996-2001. Shifts in carriage and transmission of meningococcal strains with different pathogenic potential are important determinants of meningococcal disease incidence.

Outbreak of W135 meningococcal disease in 2000: not emergence of a new W135 strain but clonal expansion within the electophoretic type-37 complex.

In 2000, >400 cases of disease caused by Neisseria meningitidis serogroup W135 (MenW135), the largest MenW135 outbreak reported to date, occurred worldwide among Hajj pilgrims and their contacts. To elucidate the origin of the outbreak strains and to investigate their relatedness to major clonal groups, genotypic and phenotypic subtyping was performed on 26 MenW135 outbreak-associated isolates and 50 MenW135 isolates collected worldwide from 1970 through 2000. All outbreak-associated isolates were members of a single clone of the hypervirulent electrophoretic type (ET)-37 complex, designated the "(W)ET-37 clone"; 19 additional MenW135 strains were also members of this clone, and the remaining 31 MenW135 strains were clearly distinct. The 2000 MenW135 outbreak was not caused by emergence of a new MenW135 strain but rather by expansion of the (W)ET-37 clone that has been in circulation at least since 1970; the strains most closely related to those causing the 2000 outbreak have been isolated in Algeria, Mali, and The Gambia in the 1990s.