Toxoplasmosis Outbreak Associated With Toxoplasma gondii-Contaminated Venison-High Attack Rate, Unusual Clinical Presentation, and Atypical Genotype.

BACKGROUND: During 2017, in response to a physician's report, the Wisconsin Department of Health Services, Division of Public Health, began investigating an outbreak of febrile illness among attendees of a retreat where never frozen, intentionally undercooked, locally harvested venison was served. Preliminary testing tentatively identified the illness as toxoplasmosis. METHODS: Confirmatory human serology panels and testing of the venison to confirm and categorize the presence and type of Toxoplasma gondii were completed by French and American national reference laboratories. All 12 retreat attendees were interviewed; medical records were reviewed. RESULTS: All attendees were male; median age was 51 years (range: 22-75). After a median incubation period of 7 days, 9 (82%) of 11 exposed persons experienced illness lasting a median of 12 days. All 9 sought outpatient healthcare for symptoms including fever, chills, sweats, and headache (100%) and ocular disturbances (33%). Testing confirmed the illness as toxoplasmosis and venison as the infection source. Multiple laboratory results were atypical for toxoplasmosis, including transaminitis (86%), lymphocytopenia (88%), thrombocytopenia (38%), and leukopenia (63%). One exposed but asymptomatic person was seronegative; the other had immunity from prior infection. The T. gondii strain was identified as closely related to an atypical genotype (haplogroup 12, polymerase chain reaction restriction fragment length polymorphism genotype 5) common in North American wildlife but with previously uncharacterized human clinical manifestations. CONCLUSIONS: The T. gondii strain contaminating the venison might explain the unusual clinical presentations. In North America, clinicians and venison consumers should be aware of risk for severe or unusual presentations of acute toxoplasmosis after consuming undercooked game meat.

Elevated Blood Lead Levels Associated with Retained Bullet Fragments - United States, 2003-2012.

An estimated 115,000 firearm injuries occur annually in the United States, and approximately 70% are nonfatal (1). Retained bullet fragments (RBFs) are an infrequently reported, but important, cause of lead toxicity; symptoms are often nonspecific and can appear years after suffering a gunshot wound (2,3). Adult blood lead level (BLL) screening is most commonly indicated for monitoring of occupational lead exposure; routine testing of adults with RBFs is infrequent (3). States collaborate with CDC's National Institute for Occupational Safety and Health (NIOSH) to monitor elevated BLLs through the Adult Blood Lead Epidemiology and Surveillance (ABLES) program (4,5). To help assess the public health burden of RBFs, data for persons with BLLs ≥10 µg/dL reported to ABLES during 2003-2012 were analyzed. An RBF-associated case was defined as a BLL ≥10 µg/dL in a person with an RBF. A non-RBF-associated case was defined as a BLL ≥10 µg/dL without an RBF. During 2003-2012, a total of 145,811 persons aged ≥16 years with BLLs ≥10 µg/dL were reported to ABLES in 41 states. Among these, 457 RBF-associated cases were identified with a maximum RBF-associated BLL of 306 µg/dL. RBF-associated cases accounted for 0.3% of all BLLs ≥10 µg/dL and 4.9% of BLLs ≥80 µg/dL. Elevated BLLs associated with RBFs occurred primarily among young adult males in nonoccupational settings. Low levels of suspicion of lead toxicity from RBFs by medical providers might cause a delay in diagnosis (3). Health care providers should inquire about an RBF as the potential cause for lead toxicity in an adult with an elevated BLL whose lead exposure is undetermined.

Syphilis Time to Treatment at Publicly Funded Sexually Transmitted Disease Clinics Versus Non-Sexually Transmitted Disease Clinics--Maricopa and Pima Counties, Arizona, 2009-2012.

Delays in syphilis treatment may contribute to transmission. We evaluated time to treatment for symptomatic patients with syphilis by clinical testing site in 2 Arizona counties. Fewer patients were tested and treated at publicly funded sexually transmitted disease clinics, but received the timeliest treatment; these clinics remain crucial to syphilis disease control.

Association of short-term exposure to ground-level ozone and respiratory outpatient clinic visits in a rural location - Sublette County, Wyoming, 2008-2011.

OBJECTIVE: Short-term exposure to ground-level ozone has been linked to adverse respiratory and other health effects; previous studies typically have focused on summer ground-level ozone in urban areas. During 2008-2011, Sublette County, Wyoming (population: ~10,000 persons), experienced periods of elevated ground-level ozone concentrations during the winter. This study sought to evaluate the association of daily ground-level ozone concentrations and health clinic visits for respiratory disease in this rural county. METHODS: Clinic visits for respiratory disease were ascertained from electronic billing records of the two clinics in Sublette County for January 1, 2008-December 31, 2011. A time-stratified case-crossover design, adjusted for temperature and humidity, was used to investigate associations between ground-level ozone concentrations measured at one station and clinic visits for a respiratory health concern by using an unconstrained distributed lag of 0-3 days and single-day lags of 0 day, 1 day, 2 days, and 3 days. RESULTS: The data set included 12,742 case-days and 43,285 selected control-days. The mean ground-level ozone observed was 47 ± 8 ppb. The unconstrained distributed lag of 0-3 days was consistent with a null association (adjusted odds ratio [aOR]: 1.001; 95% confidence interval [CI]: 0.990-1.012); results for lags 0, 2, and 3 days were consistent with the null. However, the results for lag 1 were indicative of a positive association; for every 10-ppb increase in the 8-h maximum average ground-level ozone, a 3.0% increase in respiratory clinic visits the following day was observed (aOR: 1.031; 95% CI: 0.994-1.069). Season modified the adverse respiratory effects: ground-level ozone was significantly associated with respiratory clinic visits during the winter months. The patterns of results from all sensitivity analyzes were consistent with the a priori model. CONCLUSIONS: The results demonstrate an association of increasing ground-level ozone with an increase in clinic visits for adverse respiratory-related effects in the following day (lag day 1) in Sublette County; the magnitude was strongest during the winter months; this association during the winter months in a rural location warrants further investigation.

Comparison of 3 school-based influenza surveillance indicators: lessons learned from 2009 pandemic influenza A (H1N1)--Denver Metropolitan Region, Colorado.

CONTEXT: Early in the 2009 pandemic influenza A (H1N1) experience, children aged 5 to 17 years were determined to be disproportionately affected compared with recent influenza seasons. OBJECTIVE: To characterize the pandemic among school-aged children, to enable timely influenza outbreak identification, and to determine which school-based influenza surveillance indicator correlated most closely with a laboratory-based standard influenza indicator (standard) and, therefore, might be most useful for future school-based influenza surveillance. DESIGN: : During the 2009-2010 school year, we monitored students using 3 different surveillance indicators: (1) all-cause absenteeism, (2) influenza-like illness (ILI)-related absenteeism, (3) and ILI-related school health office visits. Thresholds were set for each indicator to identify individual school outbreaks. Each surveillance indicator was compared with the standard, confirmed influenza cases among hospitalized patients. SETTING: Tri-County (Denver metropolitan area), Colorado. PARTICIPANTS: Prekindergarten through 12th-grade students in public schools. MAIN OUTCOME MEASURES: Correlation coefficients comparing each influenza surveillance indicator with the standard and graphs comparing weekly rates for each influenza surveillance indicator or weekly outbreak counts with the standard. RESULTS: Correlation between the surveillance indicators and the standard varied greatly. All-cause absenteeism correlated most poorly with the standard (Pearson's r = 0.33) and ILI-related health office visits correlated moderately well (r = 0.63). Influenza-like illness-related absenteeism correlated best (r = 0.92) and could be improved (r = 0.97) by shifting ILI-absenteeism data later by 1 week. Graphs of weekly rates or weekly outbreak counts also illustrated that ILI-related absenteeism correlated best with the standard. CONCLUSIONS: For influenza surveillance among school-aged children, when feasible, we recommend using ILI-related absenteeism, which correlated best and its rate peaked more than 1 week sooner than the standard. The other 2 surveillance indicators might be useful in certain situations, such as when resources are limited.

Assessing rodents as carriers of pathogenic Leptospira species in the U.S. Virgin Islands and their risk to animal and public health.

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

Veterinary public health capacity in the United States: opportunities for improvement.

OBJECTIVES: In 2006, the Association of American Veterinary Medical Colleges reported that the shortage (≥ 1,500) of public health veterinarians is expected to increase tenfold by 2020. In 2008, the Centers for Disease Control and Prevention (CDC) Preventive Medicine Fellows conducted a pilot project among CDC veterinarians to identify national veterinary public health workforce concerns and potential policy strategies. METHODS: Fellows surveyed a convenience sample (19/91) of public health veterinarians at CDC to identify veterinary workforce recruitment and retention problems faced by federal agencies; responses were categorized into themes. A focus group (20/91) of staff veterinarians subsequently prioritized the categorized themes from least to most important. Participants identified activities to address the three recruitment concerns with the highest combined weight. RESULTS: Participants identified the following three highest prioritized problems faced by federal agencies when recruiting veterinarians to public health: (1) lack of awareness of veterinarians' contributions to public health practice, (2) competitive salaries, and (3) employment and training opportunities. Similarly, key concerns identified regarding retention of public health practice veterinarians included: (1) lack of recognition of veterinary qualifications, (2) competitive salaries, and (3) seamless integration of veterinary and human public health. CONCLUSIONS: Findings identified multiple barriers that can affect recruitment and retention of veterinarians engaged in public health practice. Next steps should include replicating project efforts among a national sample of public health veterinarians. A committed and determined long-term effort might be required to sustain initiatives and policy proposals to increase U.S. veterinary public health capacity.

Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019-2020.

Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free.

Mongooses (Urva auropunctata) as reservoir hosts of Leptospira species in the United States Virgin Islands, 2019-2020.

During 2019-2020, the Virgin Islands Department of Health investigated potential animal reservoirs of Leptospira spp., the bacteria that cause leptospirosis. In this cross-sectional study, we investigated Leptospira spp. exposure and carriage in the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus), an invasive animal species. This study was conducted across the three main islands of the U.S. Virgin Islands (USVI), which are St. Croix, St. Thomas, and St. John. We used the microscopic agglutination test (MAT), fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and bacterial culture to evaluate serum and kidney specimens and compared the sensitivity, specificity, positive predictive value, and negative predictive value of these laboratory methods. Mongooses (n = 274) were live-trapped at 31 field sites in ten regions across USVI and humanely euthanized for Leptospira spp. testing. Bacterial isolates were sequenced and evaluated for species and phylogenetic analysis using the ppk gene. Anti-Leptospira spp. antibodies were detected in 34% (87/256) of mongooses. Reactions were observed with the following serogroups: Sejroe, Icterohaemorrhagiae, Pyrogenes, Mini, Cynopteri, Australis, Hebdomadis, Autumnalis, Mankarso, Pomona, and Ballum. Of the kidney specimens examined, 5.8% (16/270) were FAT-positive, 10% (27/274) were culture-positive, and 12.4% (34/274) were positive by rt-PCR. Of the Leptospira spp. isolated from mongooses, 25 were L. borgpetersenii, one was L. interrogans, and one was L. kirschneri. Positive predictive values of FAT and rt-PCR testing for predicting successful isolation of Leptospira by culture were 88% and 65%, respectively. The isolation and identification of Leptospira spp. in mongooses highlights the potential role of mongooses as a wildlife reservoir of leptospirosis; mongooses could be a source of Leptospira spp. infections for other wildlife, domestic animals, and humans.

Risk Factors Associated With Bordetella pertussis Among Infants ≤4 Months of Age in the Pre-Tdap Era: United States, 2002-2005.

BACKGROUND: In the United States, infants have the highest reported pertussis incidence and death rates. Improved understanding of infant risk factors is needed to optimize prevention strategies. METHODS: We prospectively enrolled infants ≤4 months of age with incident-confirmed pertussis from 4 sites during 2002-2005 (preceding pertussis antigen-containing vaccination recommendations for adolescents/adults); each case-patient was age and site matched with 2 control subjects. Caregivers completed structured interviews. Infants and their contacts ≥11 years of age were offered serologic testing for IgG; being seropositive was defined as ≥94 antipertussis toxin IgG enzyme-linked immunosorbent assay units per milliliter. RESULTS: Enrolled subjects (115 case-patients; 230 control subjects) had 4396 contacts during incubation periods; 83 (72%) case-patients had ≥1 contact with prolonged (≥5 days) new cough in primary or secondary households. In multivariable analysis, the odds for pertussis were higher for infants with primary/secondary household contacts who had a prolonged new cough, compared with infants who did not. These contacts included mother [adjusted matched odds ratio (aMOR), 43.8; 95% confidence interval (CI), 6.45-298.0] and ≥1 nonmother contact (aMOR, 20.1; 95% CI, 6.48-62.7). Infants receiving breast milk with 0-1 formula feedings daily had decreased pertussis odds (aMOR, 0.27; 95% CI, 0.08-0.89), compared with those receiving more formula. Of 41 tested case-patients, 37 (90%) were seropositive. CONCLUSIONS: Pertussis in infants was associated with prolonged new cough (≥5 days) in infants' household contacts. Findings suggest that breastfeeding protects against pertussis and warrants recommendation with pertussis prevention strategies, which currently include pertussis vaccination of pregnant mothers and infants' close contacts.

Outbreak of pertussis among healthcare workers in a hospital surgical unit.

BACKGROUND: In September 1999, a pertussis outbreak was detected among surgical staff of a 138-bed community hospital. Patients were exposed to Bordetella pertussis during the 3-month outbreak period. OBJECTIVE: To describe the outbreak among surgical staff, to evaluate implemented control measures, and to determine whether nosocomial transmission occurred. METHODS: Clinical pertussis was defined as acute cough illness with a duration of 14 days or more without another apparent cause; persons with positive culture, PCR, or serologic test results were defined as having laboratory-confirmed pertussis. Surgical healthcare workers (HCWs) were interviewed regarding pertussis symptoms, and specimens were obtained for laboratory analysis. Patients exposed to B. pertussis during an ill staff member's 3-week infectious period were interviewed by phone to determine the extent of nosocomial spread. PARTICIPANTS: A total of 53 HCWs assigned to the surgical unit and 146 exposed patients. HCWs with pertussis were defined as case subjects; HCWs without pertussis were defined as non-case subjects. RESULTS: Twelve (23%) of 53 HCWs had clinical pertussis; 6 cases were laboratory confirmed. The median cough duration in the 12 case subjects was 27 days (range, 20-120 days); 10 (83%) had paroxysms. Eleven (92%) of 12 case subjects and 28 (86%) of 41 non-case subjects received antibiotic treatment or prophylaxis. Seven case subjects (58%) reported they always wore a mask when near patients. Of 146 patients potentially exposed to pertussis from the 12 case subjects, 120 (82%) were interviewed; none reported a pertussis-like illness. CONCLUSIONS: Surgical staff transmitted B. pertussis among themselves; self-reported data suggests that these HCWs did not transmit B. pertussis to their patients, likely because of mask use, cough etiquette, and limited face-to-face contact. Control measures might have helped limit the outbreak once pertussis was recognized.

Alcohol Production, Prevention Strategies, and Inmate Knowledge About the Risk for Botulism From Pruno Consumption in a Correctional Facility--Arizona, 2013.

During July to November 2012, two botulism outbreaks (12 cases total) occurred in one all-male prison; both were associated with illicitly brewed alcohol (pruno) consumption. Inmate surveys were conducted to evaluate and develop prevention and education strategies. Qualitative surveys with open-ended questions were performed among inmates from rooms where outbreaks occurred to learn about pruno consumption. Quantitative surveys assessed knowledge gained after the outbreaks and preferred information sources. For the quantitative surveys, 250 inmates were randomly selected by bed from across the correctional facility and 164 inmates were interviewed. Only 24% of inmates reported any botulism knowledge before the outbreaks and education outreach, whereas 73% reported knowledge after the outbreaks (p < .01). Preferred information sources included handouts/fliers (52%) and the prison television channel (32%).

Infant pertussis: who was the source?

BACKGROUND: In the United States in the 1990s, the incidence of reported pertussis in adults, adolescents and infants increased; infants younger than 1 year of age had the highest reported incidence. METHODS: In 4 states with Enhanced Pertussis Surveillance, we examined the epidemiology of reported pertussis cases to determine the source of pertussis among infants. A source was defined as a person with an acute cough illness who had contact with the case-infant 7-20 days before the infant's onset of cough. RESULTS: The average annual pertussis incidence per 100,000 infants younger than 1 year of age varied by state: 22.9 in Georgia; 42.1 in Illinois; 93.0 in Minnesota; and 35.8 in Massachusetts. Family members of 616 (80%) of 774 reported case-infants were interviewed; a source was identified for 264 (43%) of the 616 case-infants. Among the 264 case-infants, mothers were the source for 84 (32%) and another family member was the source for 113 (43%). Of the 219 source-persons with known age, 38 (17%) were age 0-4 years, 16 (7%) were age 5-9 years, 43 (20%) were age 10-19 years, 45 (21%) were age 20-29 years and 77 (35%) were age > or =30 years. CONCLUSIONS: The variation in reported pertussis incidence in the 4 states might have resulted from differences in awareness of pertussis among health care providers, diagnostic capacity and case classification. Among case-infants with an identifiable source, family members (at any age) were the main source of pertussis. Understanding the source of pertussis transmission to infants may provide new approaches to prevent pertussis in the most vulnerable infants.

Surveillance for transmission and antibiotic adverse events among neonates and adults exposed to a healthcare worker with pertussis.

BACKGROUND: During a hospital obstetric rotation, a medical student demonstrated classic symptoms of pertussis. The diagnosis was confirmed by isolation of Bordetella pertussis. Because this exposure occurred in a high-risk hospital setting, control measures were undertaken to prevent transmission and illness. OBJECTIVES: To identify secondary cases of pertussis, to determine compliance with chemoprophylaxis recommendations, and to monitor for adverse events associated with chemoprophylaxis following a hospital exposure to pertussis. PATIENTS: More than 500 individuals were potentially exposed, including 168 neonates; antimicrobial chemoprophylaxis was administered to 281 individuals. Fifty-eight neonates and 194 adults began azithromycin chemoprophylaxis; 18 neonates and 2 adults began erythromycin chemoprophylaxis. METHODS: Active surveillance was instituted for (1) secondary cases of pertussis among healthcare coworkers, obstetric patients, their neonates, and labor companions and (2) antibiotic compliance and tolerance. RESULTS: No secondary cases of pertussis were confirmed by laboratory tests; however, 26 suspected cases and 5 clinically compatible cases were identified. Antibiotic courses were completed by 95% of the individuals who initiated therapy. Neonates taking azithromycin had statistically significantly less gastrointestinal distress compared with neonates taking erythromycin (12% vs 50%; P = .002); there were no cases of infantile hypertrophic pyloric stenosis. CONCLUSIONS: Although it was not possible to assess the effectiveness of the antibiotic regimens, the lack of laboratory-confirmed secondary cases suggests control measures were successful. Data from the 58 neonates who received azithromycin suggest it may be well tolerated in this age group.

Trends in pertussis among infants in the United States, 1980-1999.

CONTEXT: Reported cases of pertussis among adolescents and adults have increased since the 1980s, despite increasingly high rates of vaccination among infants and children. However, severe pertussis morbidity and mortality occur primarily among infants. OBJECTIVE: To describe the trends and characteristics of reported cases of pertussis among infants younger than 12 months in the United States from 1980 to 1999. DESIGN, SETTING, AND PARTICIPANTS: Cases of pertussis in infants younger than 12 months in the United States reported to the National Notifiable Disease Surveillance System of the Centers for Disease Control and Prevention between 1980 and 1999, and detailed case data from the Supplementary Pertussis Surveillance System. MAIN OUTCOME MEASURES: Incidence and demographic and clinical characteristics of cases. RESULTS: The incidence of reported cases of pertussis among infants increased 49% in the 1990s compared with the incidence in the 1980s (19 798 vs 12 550 cases reported; 51.1 cases vs 34.2 cases per 100 000 infant population, respectively). Increases in the incidence of cases and the number of deaths among infants during the 1990s primarily were among those aged 4 months or younger, contrasting with a stable incidence of cases among infants aged 5 months or older. The proportion of cases confirmed by bacterial culture was higher in the 1990s than in the 1980s (50% and 33%, respectively); the proportion of hospitalized cases was unchanged (67% vs 68%, respectively). Receipt of fewer doses of vaccine was associated with hospitalization, when cases were stratified by age in months. CONCLUSIONS: The incidence of reported cases of pertussis among infants increased in the 1990s compared with the 1980s. The limited age group affected, the increased rate of bacteriologic confirmation, and the unchanged severity of illness suggest that an increase in infant pertussis has occurred apart from any change in reporting. Strategies are needed to prevent the morbidity and mortality from pertussis among infants too young to be fully vaccinated, according to the current recommended schedules of vaccination in the United States.

Healthcare-Associated Pertussis Outbreak in Arizona: Challenges and Economic Impact, 2011.

An outbreak investigation identified 15 pertussis cases among 5 infants and 10 healthcare professionals at 1 hospital's neonatal intensive care unit (NICU). The cost of the outbreak to this hospital was $97 745. Heightened awareness of pertussis in NICUs is key to preventing healthcare-associated spread and minimizing outbreak-control-related costs. Bordetella pertussis is a highly communicable bacterial pathogen that causes a prolonged cough illness and is spread by respiratory droplet transmission. Infants aged ≤6 months are most susceptible to B pertussis infection and pertussis-associated complications, including pneumonia, encephalopathy, and death, and are commonly hospitalized for treatment [ 1]. Despite a universal pertussis vaccination program, 27 550 pertussis cases were reported in the United States during 2010 [ 2]. Pertussis outbreaks in healthcare settings can be challenging and costly to control [3]. On September 13, 2011 and September 15, 2011, 3 pertussis cases, including 2 confirmed by B pertussis isolation, among preterm infants discharged ≤30 days previously from a 71-bed NICU of a general hospital (NICU A) were reported by Hospital B, a large pediatric facility, to Maricopa County Department of Public Health. This report describes the outbreak, examines outbreak-associated costs and risk factors that might have contributed to healthcare-associated transmission, and provides guidance to prevent outbreaks in healthcare settings.

Utility of composite reference standards and latent class analysis in evaluating the clinical accuracy of diagnostic tests for pertussis.

Numerous evaluations of the clinical sensitivity and specificity of PCR and serologic assays for Bordetella pertussis have been hampered by the low sensitivity of culture, the gold standard test, which leads to biased accuracy estimates. The bias can be reduced by using statistical approaches such as the composite reference standard (CRS) (e.g., positive if culture or serology positive; negative otherwise) or latent class analysis (LCA), an internal reference standard based on a statistical model. We illustrated the benefits of the CRS and LCA approaches by reanalyzing data from a 1995 to 1996 study of cough illness among 212 patients. The accuracy of PCR in this study was evaluated using three reference standards: culture, CRS, and LCA. Using specimens obtained 0 to 34 days after cough onset, estimates of the sensitivity of PCR obtained using CRS (47%) and LCA (34%) were lower than the culture-based estimate (62%). The CRS and LCA approaches, which utilized more than one diagnostic marker of pertussis, likely produced more accurate reference standards than culture alone. In general, the CRS approach is simple, with a well-defined disease status. LCA requires statistical modeling but incorporates more indicators of disease than CRS. When three or more indicators of pertussis are available, these approaches should be used in evaluations of pertussis diagnostic tests.

Mixture model analysis for establishing a diagnostic cut-off point for pertussis antibody levels.

Previous studies of pertussis (whooping cough) that have derived diagnostic cut-off points for pertussis antibody levels have assumed a single distribution for antibody levels and have used small sample sizes. In a recent study of 5409 serum samples from the Third National Health and Nutrition Examination Survey (NHANES III), a finite mixture model was developed to examine the distribution of immunoglobulin G (IgG) antibody levels against pertussis toxin (PT), an antigen specific to the Bordetella pertussis bacterium. The mixture model identified three component populations with antibody levels greater than the quantitative assay's lower limit of quantitation (LLQ) and included a point distribution located at or below the LLQ to account for the excess number of antibody values that fell below the LLQ. The mixture model analysis accounted for the NHANES III design. A cut-off point for anti-PT IgG levels was chosen to have a 99 per cent model specificity based on the two overlapping normal distributions assumed for the two component populations with the highest antibody levels. This cut-off point may have a higher diagnostic sensitivity for acute B. pertussis infection than other cut-off points derived by assuming a single distribution for antibody levels.