Julia W. Gargano

Surveillance for waterborne-disease outbreaks associated with recreational water: United States, 2001-2002

Provision of safe water in the United States is vital to protecting public health (1). Public health agencies in the U.S. states and territories* report information on waterborne disease outbreaks to CDC through the National Outbreak Reporting System (NORS) (https://www.cdc.gov/healthywater/surveillance/index.html). During 2013-2014, 42 drinking water-associated† outbreaks were reported, accounting for at least 1,006 cases of illness, 124 hospitalizations, and 13 deaths. Legionella was associated with 57% of these outbreaks and all of the deaths. Sixty-nine percent of the reported illnesses occurred in four outbreaks in which the etiology was determined to be either a chemical or toxin or the parasite Cryptosporidium. Drinking water contamination events can cause disruptions in water service, large impacts on public health, and persistent community concern about drinking water quality. Effective water treatment and regulations can protect public drinking water supplies in the United States, and rapid detection, identification of the cause, and response to illness reports can reduce the transmission of infectious pathogens and harmful chemicals and toxins.

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

Objective The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. Materials and Methods Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin–stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. Results Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). Conclusions Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

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.

HPV Genotypes in High Grade Cervical Lesions and Invasive Cervical Carcinoma as Detected by Two Commercial DNA Assays, North Carolina, 2001-2006

Background HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens. Methods Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays. Findings LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions. Conclusions We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction.

Age-Group Differences in Human Papillomavirus Types and Cofactors for Cervical Intraepithelial Neoplasia 3 among Women Referred to Colposcopy

Background: Recommendations for high-risk human papillomavirus (HR-HPV) testing as an adjunct to cytology for cervical cancer screening differ by age group, because HR-HPV tests lack adequate specificity in women aged <30. Here, we assess age-group differences in HPV types and other risk factors for cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) versus CIN0–2 in women from four colposcopy clinics. Methods: Women ages 18 to 69 (n = 1,658) were enrolled and completed structured interviews to elicit data on behavioral risk factors prior to their examinations. HPV genotyping was done on exfoliated cervical cell samples. We estimated relative risks (RR) for HPV types and cofactors for CIN3+, overall and stratified by age group. Results: After 2 years of follow-up, we identified 178 CIN3+, 1,305 CIN0–2, and 175 indeterminate outcomes. Nonvaccine HR-HPV types were only associated with CIN3+ among women ≥30 (RR = 2.3, 95% CI: 1.5–3.4; <30: RR = 0.9). Among all HR-HPV–positive women, adjusting for age, significant cofactors for CIN3+ included current smoking (RR = 1.5), former smoking (RR = 1.8), regular Pap screening (RR = 0.7), current regular condom use (RR = 0.5), and parity ≥5 (RR = 1.6, Ptrend for increasing parity = 0.07). However, the parity association differed by age group (≥30: RR = 1.8, Ptrend = 0.008; <30: RR = 0.9; Ptrend =.55). Conclusion: Subgroup variation by age in the risk of CIN3+ points to the importance of the timing of exposures in relation to CIN3+ detection. Impact: Future screening strategies need to consider natural history and secular trends in cofactor prevalence in the pursuit of appropriately sensitive and specific screening tools applied to appropriate age groups. Cancer Epidemiol Biomarkers Prev; 21(1); 111–21. ©2011 AACR.

Giardiasis and Subsequent Irritable Bowel Syndrome: A Longitudinal Cohort Study Using Health Insurance Data

Background Giardia intestinalis is the most commonly reported human intestinal parasite in the United States. Increased incidence of chronic gastrointestinal complaints has been reported after some giardiasis outbreaks. We examined the relationship between giardiasis diagnosis and irritable bowel syndrome (IBS) diagnosis. Methods We used the 2006-2010 MarketScan commercial insurance database. Persons with at least 1 giardiasis diagnosis were individually matched on age group, sex, and enrollment length in months to 5 persons without a giardiasis diagnosis. Persons diagnosed with IBS before the date of study entry were excluded. We calculated crude incidence rates (IRs) and developed Cox proportional hazards models. Results The matched cohort included 3935 persons with giardiasis and 19663 persons without giardiasis. One-year incidence of IBS was higher in persons with giardiasis (IR = 37.7/1000 person-years vs 4.4/1000 person-years). The unadjusted hazard ratio was 4.8 (95% confidence interval [CI] = 3.6-6.4), attenuated slightly to 3.9 (95% CI = 2.9-5.4) after adjusting for anxiety, depression, and healthcare utilization. Conclusions In a large insurance database, individuals diagnosed with giardiasis were more likely to have a subsequent IBS diagnosis, despite accounting for confounders. Future research on risk factors for IBS among giardiasis patients and the pathophysiology of postinfectious IBS is needed.

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.

Association between Giardia and arthritis or joint pain in a large health insurance cohort: could it be reactive arthritis?

This study aimed to assess the association between giardiasis and subsequent development of arthritis or joint pain using a retrospective cohort of individuals from a large administrative claims database in the United States. Using 2006-2010 data from MarketScan Commercial Claims and Encounters, we conducted a retrospective cohort study in people with an ICD-9-CM code for giardiasis (n = 3301) and persons without giardiasis (n = 14 612) individually matched on age, sex, and enrolment length. We used conditional logistic regression to model the association between giardiasis and arthritis or joint pain documented in the 6 months following initial giardiasis diagnosis or index date for matched controls. After adjusting for healthcare utilization rate, giardiasis was associated with a 51% increase in claims for arthritis or joint pain (odds ratio 1·51, 95% confidence interval 1·26-1·80). In age- and sex-stratified adjusted analyses, the association remained significant across all subgroups (age 0-19 years, age 20-64 years, males, and females). Findings from this study lend epidemiological support for the association between giardiasis and subsequent development of arthritis. Reactive arthritis might occur more frequently than has been reported in the literature. Further research is necessary to determine the mechanisms by which giardiasis could lead to arthritis.

Giardiasis Diagnosis and Treatment Practices Among Commercially Insured Persons in the United States

Background Giardiasis, the most common enteric parasitic infection in the United States, causes an estimated 1.2 million episodes of illness annually. Published clinical recommendations include readily available Giardia-specific diagnostic testing and antiparasitic drugs. We investigated sequences of giardiasis diagnostic and treatment events using MarketScan, a large health insurance claims database. Methods We created a longitudinal cohort of 2995 persons diagnosed with giardiasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 007.1) from 2006 to 2010, and analyzed claims occurring 90 days before to 90 days after initial diagnosis. We evaluated differences in number and sequence of visits, diagnostic tests, and prescriptions by age group (children 1-17 years, adults 18-64 years) using χ2 tests and data visualization software. Results Among 2995 patients (212433 claims), 18% had a Giardia-specific test followed by or concurrent with an effective antiparasitic drug, without ineffective antibiotics. Almost two-thirds of patients had an antiparasitic and 27% had an antibiotic during the study window. Compared with children, adults more often had ≥3 visits before diagnosis (19% vs 15%; P = .02). Adults were also less likely to have a Giardia-specific diagnostic test (48% vs 58%; P < .001) and more likely to have an antibiotic prescription (28% vs 25%; P = .04). When Giardia-specific tests and antiparasitic and antibiotic prescriptions were examined, pediatric clinical event sequences most frequently began with a Giardia-specific test, whereas adult sequences most frequently began with an antiparasitic prescription. Conclusions Giardiasis care infrequently follows all aspects of clinical recommendations. Multiple differences between pediatric and adult care, despite age-agnostic recommendations, suggest opportunities for provider education or tailored guidance.

Giardiasis in the United States – an epidemiologic and geospatial analysis of county-level drinking water and sanitation data, 1993–2010

Giardiasis is the most commonly reported intestinal parasitic infection in the United States. Outbreak investigations have implicated poorly maintained private wells, and hypothesized a role for wastewater systems in giardiasis transmission. Surveillance data consistently show geographic variability in reported giardiasis incidence. We explored county-level associations between giardiasis cases, household water and sanitation (1990 census), and US Census division. Using 368,847 reported giardiasis cases (1993-2010), we mapped county-level giardiasis incidence rates, private well reliance, and septic system reliance, and assessed spatiotemporal clustering of giardiasis. We used negative binomial regression to evaluate county-level associations between giardiasis rates, region, and well and septic reliance, adjusted for demographics. Adjusted giardiasis incidence rate ratios (aIRRs) were highest (aIRR 1.3; 95% confidence interval 1.2-1.5) in counties with higher private well reliance. There was no significant association between giardiasis and septic system reliance in adjusted models. Consistent with visual geographic distributions, the aIRR of giardiasis was highest in New England (aIRR 3.3; 95% CI 2.9-3.9; reference West South Central region). Our results suggest that, in the USA, private wells are relevant to giardiasis transmission; giardiasis risk factors might vary regionally; and up-to-date, location-specific national data on water sources and sanitation methods are needed.