Michele C. Hlavsa

Human Tuberculosis due to Mycobacterium bovis in the United States, 1995-2005

BACKGROUND Understanding the epidemiology of human Mycobacterium bovis tuberculosis (TB) in the United States is imperative; this disease can be foodborne or airborne, and current US control strategies are focused on TB due to Mycobacterium tuberculosis and airborne transmission. The National TB Genotyping Services work has allowed systematic identification of M. tuberculosis-complex isolates and enabled the first US-wide study of M. bovis TB. METHODS Results of spacer oligonucleotide and mycobacterial interspersed repetitive units typing were linked to corresponding national surveillance data for TB cases reported for the period 2004-2005 and select cases for the period 1995-2003. We also used National TB Genotyping Service data to evaluate the traditional antituberculous drug resistance-based case definition of M. bovis TB. RESULTS Isolates from 165 (1.4%) of 11,860 linked cases were identified as M. bovis. Patients who were not born in the United States, Hispanic patients, patients <15 years of age, patients reported to be HIV infected, and patients with extrapulmonary disease each had increased adjusted odds of having M. bovis versus M. tuberculosis TB. Most US-born, Hispanic patients with TB due to M. bovis (29 [90.6%] of 32) had extrapulmonary disease, and their overall median age was 9.5 years. The National TB Genotyping Services data indicated that the pyrazinamide-based case definitions sensitivity was 82.5% (95% confidence interval; 75.3%-87.9%) and that data identified 14 errors in pyrazinamide-susceptibility testing or reporting. CONCLUSIONS The prevalence of extrapulmonary disease in the young, US-born Hispanic population suggests recent transmission of M. bovis, possibly related to foodborne exposure. Because of its significantly different epidemiologic profile, compared with that of M. tuberculosis TB, we recommend routine surveillance of M. bovis TB. Routine surveillance and an improved understanding of M. bovis TB transmission dynamics would help direct the development of additional control measures.

Cryptosporidiosis Associated with Ozonated Apple Cider

We linked an outbreak of cryptosporidiosis to ozonated apple cider by using molecular and epidemiologic methods. Because ozonation was insufficient in preventing this outbreak, its use in rendering apple cider safe for drinking is questioned.

Multilocus Sequence Typing of an Emerging Cryptosporidium hominis Subtype in the United States

ABSTRACT The United States has experienced a substantial increase in the reported incidence of cryptosporidiosis since 2005. Accompanying this is the emergence of a new subtype of Cryptosporidium hominis based on variation at the 60-kDa glycoprotein (gp60) locus, IaA28R4, which has become a frequently identified subtype in both sporadic and outbreak-related cases. In this study, using multilocus sequence typing (MLST) at eight genetic loci, we characterized 62 specimens of IaA28R4 and 33 specimens of three other gp60 subtypes of C. hominis from four U.S. states with increased cryptosporidiosis incidences during the summer of 2008. Extensive genetic heterogeneity was seen within the gp60 subtype IaA28R4, but specimens from Ohio and southwestern states formed two distinct subpopulations, suggesting that there were at least two origins of IaA28R4 within the United States. Discordance in typing results was observed between gp60 and other genetic markers, especially DZ-HRGP, and this discordance was largely the result of genetic recombination within the gp60 subtype IaA28R4. The results of population genetic analyses supported the presence of two subpopulations of IaA28R4 and the occurrence of genetic recombination within this gp60 subtype. Thus, the IaA28R4 subtype at gp60 is likely a fitness marker for C. hominis, and genetic recombination is potentially a driving force in the emergence of the virulent IaA28R4 subtype in the United States. A rapid evolution of IaA28R4 was indicated by the observation of multiple MLST subtypes of IaA28R4 within two large outbreaks that lasted for extended periods and involved multiple swimming pools.

Subtype Analysis of Cryptosporidium Specimens from Sporadic Cases in Colorado, Idaho, New Mexico, and Iowa in 2007: Widespread Occurrence of One Cryptosporidium hominis Subtype and Case History of an Infection with the Cryptosporidium Horse Genotype

ABSTRACT Subtyping was conducted in late 2007 on 57 Cryptosporidium specimens from sporadic cases in Colorado, Idaho, New Mexico, and Iowa. One previously rare Cryptosporidium hominis subtype was indentified in 40 cases (70%) from all four states, and the Cryptosporidium horse genotype was identified in a pet shop employee with severe clinical symptoms.

Multiple risk factors associated with a large statewide increase in cryptosporidiosis

Cryptosporidium species have emerged as a major cause of outbreaks of diarrhoea and have been associated with consumption of contaminated recreational and drinking water and food as well as contact with infected attendees of child-care programmes. In August 2007, the Colorado Department of Public Health and Environment detected an increase in cryptosporidiosis cases over baseline values. We conducted a case-control study to assess risk factors for infection and collected stool specimens from ill persons for microscopy and molecular analysis. Laboratory-confirmed cases (n=47) were more likely to have swallowed untreated water from a lake, river, or stream [adjusted matched odds ratio (aOR) 8.0, 95% confidence interval (CI) 1.3-48.1], have had exposure to recreational water (aOR 4.6, 95% CI 1.4-14.6), or have had contact with a child in a child-care programme or in diapers (aOR 3.8, 95% CI 1.5-9.6). Although exposure to recreational water is commonly implicated in summertime cryptosporidiosis outbreaks, this study demonstrates that investigations of increased incidence of cases in summer should also examine other potential risk factors. This study emphasizes the need for public health education efforts that address the multiple transmission routes for Cryptosporidium and appropriate prevention measures to avoid future transmission.

Giardiasis outbreaks in the United States, 1971-2011.

Giardia intestinalis is the leading parasitic aetiology of human enteric infections in the United States, with an estimated 1·2 million cases occurring annually. To better understand transmission, we analysed data on all giardiasis outbreaks reported to the Centers for Disease Control and Prevention for 1971-2011. The 242 outbreaks, affecting ~41 000 persons, resulted from waterborne (74·8%), foodborne (15·7%), person-to-person (2·5%), and animal contact (1·2%) transmission. Most (74·6%) waterborne outbreaks were associated with drinking water, followed by recreational water (18·2%). Problems with water treatment, untreated groundwater, and distribution systems were identified most often during drinking water-associated outbreak investigations; problems with water treatment declined after the 1980s. Most recreational water-associated outbreaks were linked to treated swimming venues, with pools and wading pools implicated most often. Produce was implicated most often in foodborne outbreaks. Additionally, foods were most commonly prepared in a restaurant and contaminated by a food handler. Lessons learned from examining patterns in outbreaks over time can help prevent future disease. Groundwater and distribution system vulnerabilities, inadequate pool disinfection, fruit and vegetable contamination, and poor food handler hygiene are promising targets for giardiasis prevention measures.

Effect of Cyanuric Acid on the Inactivation of Cryptosporidium parvum under Hyperchlorination Conditions

Cyanuric acid (CYA) is a chlorine stabilizer used in swimming pools to limit UV degradation of chlorine, thus reducing chlorine use and cost. However, CYA has been shown to decrease the efficacy of chlorine disinfection. In the event of a diarrheal incident, CDC recommends implementing 3-log10 inactivation conditions for Cryptosporidium (CT value = 15 300 mg·min/L) to remediate pools. Currently, CYAs impact on Cryptosporidium inactivation is not fully determined. We investigated the impact of multiple concentrations of CYA on C. parvum inactivation (at 20 and 40 mg/L free chlorine; average pH 7.6; 25 °C). At 20 mg/L free chlorine, average estimated 3-log10 CT values were 17 800 and 31 500 mg·min/L with 8 and 16 mg/L CYA, respectively, and the average estimated 1-log10 CT value was 76 500 mg·min/L with 48 mg/L CYA. At 40 mg/L free chlorine, 3-log10 CT values were lower than those at 20 mg/L, but still higher than those of free chlorine-only controls. In the presence of ∼100 mg/L CYA, average 0.8- and 1.4-log10 reductions were achieved by 72 h at 20 and 40 mg/L free chlorine, respectively. This study demonstrates CYA significantly delays chlorine inactivation of Cryptosporidium oocysts, emphasizing the need for additional pool remediation options following fecal incidents.

Swimming in the USA: beachgoer characteristics and health outcomes at US marine and freshwater beaches.

Swimming in lakes and oceans is popular, but little is known about the demographic characteristics, behaviors, and health risks of beachgoers on a national level. Data from a prospective cohort study of beachgoers at multiple marine and freshwater beaches in the USA were used to describe beachgoer characteristics and health outcomes for swimmers and non-swimmers. This analysis included 54,250 participants. Most (73.2%) entered the water; of those, 65.1% put their head under water, 41.3% got water in their mouth and 18.5% swallowed water. Overall, 16.3% of beachgoers reported any new health problem. Among swimmers, 6.6% reported gastrointestinal (GI) illness compared with 5.5% of non-swimmers (unadjusted χ² p < 0.001); 6.0% of swimmers and 4.9% of non-swimmers reported respiratory illness (p < 0.001); 1.8% of swimmers and 1.0% of non-swimmers reported ear problems (p < 0.001); and 3.9% of swimmers and 2.4% of non-swimmers experienced a rash (p < 0.001). Overall, swimmers reported a higher unadjusted incidence of GI illness and earaches than non-swimmers. Current surveillance systems might not detect individual cases and outbreaks of illness associated with swimming in natural water. Better knowledge of beachgoer characteristics, activities, and health risks associated with swimming in natural water can improve disease surveillance and prioritize limited resources.

Antimicrobial and Analgesic Prescribing Patterns for Acute Otitis Externa, 2004-2010

Objective Acute otitis externa (AOE) is a common but preventable ear condition. Clinical guidelines issued in 2006 recommended topical treatments for uncomplicated AOE, but systemic antimicrobials appear to be commonly prescribed. The objective of this analysis was to describe pre- and postguideline prescribing patterns by clinician specialty and antimicrobial type and assess trends over time. Study Design Retrospective longitudinal analysis of a large insurance database. Setting Outpatient departments in the United States. Methods Initial outpatient visits in 2004 to 2010 for AOE (excluding visits with complicating conditions) were extracted from an insurance database. Prescription drug claims were linked and categorized by clinician specialty and antimicrobial type. Results The analysis included 907,261 initial outpatient visits. Use of systemic antimicrobials declined by 4.9% (95% confidence interval [CI], 4.1%, 5.7%) from 36.5% of initial visits in 2004 to 32.1% in 2010. Use of systemic antimicrobials varied by specialty. Systemic antimicrobials were prescribed in 47.1% of 2010 emergency department (ED) visits (−6.9% from 2004, 95% CI −12.3, −1.5), 25.9% of otolaryngologist visits (−1.6%, 95% CI −5.6, 2.4), and 20.4% of pediatrician visits (−6.6%, 95% CI −8.8, −4.4). Penicillins were prescribed most frequently (42.3% of systemic prescriptions in 2010), followed by cephalosporins (19.8%), erythromycin/macrolides (17.4%), and quinolones (11.1%). Opioids were prescribed in 26.4% of ED visits and 9% of outpatient visits. Conclusions Use of systemic antimicrobials declined over time, but one-third of 2010 visits resulted in systemic antimicrobials, despite exclusion of visits with complicating factors. Use of systemic antimicrobials varied by specialty. Further educational efforts and outreach to other specialties might be warranted.

Evolving epidemiology of reported cryptosporidiosis cases in the United States, 1995-2012.

Cryptosporidium is the leading aetiology of waterborne disease outbreaks in the United States. This report briefly describes the temporal and geographical distribution of US cryptosporidiosis cases and presents analyses of cryptosporidiosis case data reported in the United States for 1995-2012. The Cochran-Armitage test was used to assess changes in the proportions of cases by case status (confirmed vs. non-confirmed), sex, race, and ethnicity over the study period. Negative binomial regression models were used to estimate rate ratios (RR) and 95% confidence intervals (CI) for comparing rates across three time periods (1995-2004, 2005-2008, 2009-2012). The proportion of confirmed cases significantly decreased (P < 0·0001), and a crossover from male to female predominance in case-patients occurred (P < 0·0001). Overall, compared to 1995-2004, rates were higher in 2005-2008 (RR 2·92, 95% CI 2·08-4·09) and 2009-2012 (RR 2·66, 95% CI 1·90-3·73). However, rate changes from 2005-2008 to 2009-2012 varied by age group (P interaction < 0·0001): 0-14 years (RR 0·55, 95% CI 0·42-0·71), 15-44 years (RR 0·99, 95% CI 0·82-1·19), 45-64 years (RR 1·47, 95% CI 1·21-1·79) and ⩾65 years (RR 2·18, 95% CI 1·46-3·25). The evolving epidemiology of cryptosporidiosis necessitates further identification of risk factors in population subgroups. Adding systematic molecular typing of Cryptosporidium specimens to US national cryptosporidiosis surveillance would help further identify risk factors and markedly expand understanding of cryptosporidiosis epidemiology in the United States.