Cross-sectional household transmission study of Cryptosporidium shows that C. hominis infections are a key risk factor for spread.

BACKGROUND: Infection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. The incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project aimed to explore potential transmission in the home and attempt to identify asymptomatic infections, which might play a role in transmission. Risk factors and characteristics associated with spread of infection in the home were described including any differences between Cryptosporidium species. METHODS: The study identified cryptosporidiosis cases from North West England and Wales over a year and invited them and their household to take part. Each household was sent a study pack containing study information and a questionnaire, and stool sample kits to provide samples from consenting household members. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, were characterised using molecular methods to help describe any patterns of transmission. Characteristics of households with and without additional cases were described, and compared using odds ratios (OR) and a multivariable logistic regression identified independent risk factors for household transmission. Data collection ran for one year, beginning in September 2018 with an initial pilot phase. RESULTS: We enrolled 128 index cases and their households. Additional illness occurred in over a quarter of homes, each reporting an average of two additional cases. The majority of these were undiagnosed and unreported to surveillance. This burden was even greater in households where the index case was infected with C. hominis versus C. parvum, or the index case was under five years old, with mums and siblings most at risk of secondary infection. Only having an index case of C. hominis was independently associated with transmission in the multivariable model (OR 4.46; p = 0.01). CONCLUSIONS: Cryptosporidium was a considerable burden in the home. At-risk homes were those where the index was less than five years old and/or infected with C. hominis. Of particular risk were female caregivers and siblings. Hygiene advice should be specifically directed here. This work provides evidence for humans as sources of C. hominis infection and that person-person is a key pathway. We recommend that all stools submitted for the investigation of gastrointestinal pathogens are tested for Cryptosporidium to better capture cases, inclusion of speciation data in routine surveillance, and the consideration of specific clinical advice on prevention for high-risk homes.

Cross-sectional investigation of household transmission of Cryptosporidium in England and Wales: the epiCrypt study protocol.

INTRODUCTION: Infection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. Risk factors are often estimated from outbreak investigations, and in the UK include ingestion of contaminated water and food, farm/animal contact and person-to-person spread in institutions. However, reported outbreaks only represent about 10% of cases and the transmission routes for sporadic disease may not be the same. Contact with other people has been highlighted as a factor in the transmission of Cryptosporidium, but the incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project will estimate the amount of secondary spread that occurs in the home and potentially identify asymptomatic infections which might have a role in transmission. Risk factors and characteristics associated with secondary spread will be described including any differences in transmission between Cryptosporidium species. METHODS AND ANALYSIS: The study will prospectively identify cryptosporidiosis cases from North West England and Wales over 1 year and invite them and their household to take part. Each household will complete a questionnaire and each household member will be asked to provide a stool sample. Clinical, demographic and home variables will be described, and further analyses undertaken to investigate associations with secondary spread in the home. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, will be characterised using molecular methods to describe patterns of transmission. Data collection is expected to take 1 year, beginning in September 2018. ETHICS AND DISSEMINATION: The study has been approved by the North West-Liverpool East NHS Research Ethics Committee (Reference: 18/NW/0300) and the Confidentiality and Advisory Group (Reference 18/CAG/0084). Outputs will include scientific conferences and peer-reviewed publications. In addition, a short, lay report of findings will be produced for participants, who can opt to receive this when they take part. TRIAL REGISTRATION NUMBER: CPMS ID: 39458.

Exposures associated with infection with Cryptosporidium in industrialised countries: a systematic review protocol.

BACKGROUND: Cryptosporidium is a protozoan parasite of humans and other animals worldwide and is one of the greatest contributors to human diarrhoeal illness. Transmission can occur indirectly via contaminated food or water, or directly via contact with animals or other infected people. Risk exposures are often identified from outbreak investigations, but a subset of cases remains unexplained, and sources for sporadic disease and pathways to infection are still unclear. Given the few systematic syntheses of reported evidence in industrialised populations, the aim of this review is to consolidate the literature to describe exposures associated with human cryptosporidiosis in industrialised countries, specifically including the UK, and describe any differences between outbreak-associated and sporadic disease. METHODS/DESIGN: Where relevant, methods will follow the recommendations made in the Cochrane Handbook for Systematic Reviews of Interventions. Three steps will be used to identify the literature including electronic database searching using PubMed, Scopus, Embase and Web of Science; reference list trawling; and an exploration of the grey literature. Screening of results will be undertaken by two reviewers using pre-defined criteria. Studies conducted in industrialised countries and reporting on human subjects will be included. All observational studies will be included where they report exposures and relevant quantitative results. Data will be extracted using a standardised form. Study quality will be assessed using the ROBINS-I tool. Data will be summarised presenting the papers' main findings including population under study, outcomes, and exposures, and whether these were considered outbreak or sporadic cases. A narrative summary will also be included. Where populations are appropriate, available data will be pooled in a meta-analysis combining the significant exposures across studies. DISCUSSION: This review aims to consolidate the evidence for transmission routes and exposures for Cryptosporidium in industrialised countries, with particular reference to how these may apply to the UK. In addition, the review will seek to describe differences between outbreak and sporadic cases. This will help to identify those most vulnerable, highlighting pathways where interventions and public health response may be appropriate. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42017056589 .

An Outbreak of Cryptosporidium parvum across England & Scotland Associated with Consumption of Fresh Pre-Cut Salad Leaves, May 2012.

BACKGROUND: We report a widespread foodborne outbreak of Cryptosporidium parvum in England and Scotland in May 2012. Cases were more common in female adults, and had no history of foreign travel. Over 300 excess cases were identified during the period of the outbreak. Speciation and microbiological typing revealed the outbreak strain to be C. parvum gp60 subtype IIaA15G2R1. METHODS: Hypothesis generation questionnaires were administered and an unmatched case control study was undertaken to test the hypotheses raised. Cases and controls were interviewed by telephone. Controls were selected using sequential digit dialling. Information was gathered on demographics, foods consumed and retailers where foods were purchased. RESULTS: Seventy-four laboratory confirmed cases and 74 controls were included in analyses. Infection was found to be strongly associated with the consumption of pre-cut mixed salad leaves sold by a single retailer. This is the largest documented outbreak of cryptosporidiosis attributed to a food vehicle.

Evaluation of the national Notifiable Diseases Surveillance System for dengue fever in Taiwan, 2010-2012.

BACKGROUND: In Taiwan, around 1,500 cases of dengue fever are reported annually and incidence has been increasing over time. A national web-based Notifiable Diseases Surveillance System (NDSS) has been in operation since 1997 to monitor incidence and trends and support case and outbreak management. We present the findings of an evaluation of the NDSS to ascertain the extent to which dengue fever surveillance objectives are being achieved. METHODOLOGY: We extracted the NDSS data on all laboratory-confirmed dengue fever cases reported during 1 January 2010 to 31 December 2012 to assess and describe key system attributes based on the Centers for Disease Control and Prevention surveillance evaluation guidelines. The system's structure and processes were delineated and operational staff interviewed using a semi-structured questionnaire. Crude and age-adjusted incidence rates were calculated and key demographic variables were summarised to describe reporting activity. Data completeness and validity were described across several variables. PRINCIPAL FINDINGS: Of 5,072 laboratory-confirmed dengue fever cases reported during 2010-2012, 4,740 (93%) were reported during July to December. The system was judged to be simple due to its minimal reporting steps. Data collected on key variables were correctly formatted and usable in > 90% of cases, demonstrating good data completeness and validity. The information collected was considered relevant by users with high acceptability. Adherence to guidelines for 24-hour reporting was 99%. Of 720 cases (14%) recorded as travel-related, 111 (15%) had an onset >14 days after return, highlighting the potential for misclassification. Information on hospitalization was missing for 22% of cases. The calculated PVP was 43%. CONCLUSIONS/SIGNIFICANCE: The NDSS for dengue fever surveillance is a robust, well maintained and acceptable system that supports the collection of complete and valid data needed to achieve the surveillance objectives. The simplicity of the system engenders compliance leading to timely and accurate reporting. Completeness of hospitalization information could be further improved to allow assessment of severity of illness. To minimize misclassification, an algorithm to accurately classify travel cases should be established.

Control selection methods in recent case-control studies conducted as part of infectious disease outbreaks.

Successful investigation of national outbreaks of communicable disease relies on rapid identification of the source. Case-control methodologies are commonly used to achieve this. We assessed control selection methods used in recently published case-control studies for methodological and resource issues to determine if a standard approach could be identified. Neighbourhood controls were the most frequently used method in 53 studies of a range of different sizes, infections and settings. The most commonly used method of data collection was face to face interview. Control selection issues were identified in four areas: method of identification of controls, appropriateness of controls, ease of recruitment of controls, and resource requirements. Potential biases arising from the method of control selection were identified in half of the studies assessed. There is a need to develop new ways of selecting controls in a rapid, random and representative manner to improve the accuracy and timeliness of epidemiological investigations and maximise the effectiveness of public health interventions. Innovative methods such as prior recruitment of controls could improve timeliness and representativeness of control selection.