Impact of the COVID-19 restrictions on the epidemiology of Cryptosporidium spp. in England and Wales, 2015-2021

Background In England and Wales, cryptosporidiosis cases peak in spring and autumn, usually associated with zoonotic and environmental exposures ( Cryptosporidium parvum , spring/autumn) and with overseas travel and water-based activities ( Cryptosporidium hominis , autumn). Restrictions to control the COVID-19 pandemic prevented social mixing and access to swimming pools and restaurants for many months. Foreign travel from the UK also reduced by 74% in 2020. However, these restrictions potentially increased environmental exposures as people sought alternative countryside activities locally. To inform and strengthen surveillance programmes, we investigated the impact of COVID-19 restrictions on the epidemiology of C. hominis and C. parvum cases. Methods Cryptosporidium -positive stools, with case demographic data, are referred routinely for genotyping to the national Cryptosporidium Reference Unit (CRU). Cases were extracted from the CRU database (01 January 2015 to 31 December 2021). We defined two periods for pre- and post-COVID-19 restrictions implementation corresponding to the first UK-wide lockdown on 23 March 2020: “pre-restrictions” between week 1, 2015 and week 12, 2020, and “post restrictions-implementation” between week 13, 2020 and week 52, 2021. We conducted an interrupted time-series analysis, assessing differences in C. parvum and C. hominis incidence, trends and periodicity between these periods using negative binomial regression with linear-splines and interactions. Results There were 21,304 cases between 01 January 2015 and 31 December 2021 ( C. parvum = 12,246; C. hominis = 9,058). Post restrictions-implementation incidence of C. hominis dropped by 97.5% (95%CI: 95.4%-98.6%; p<0.001). The decreasing incidence-trend observed pre-restrictions (IRR=0.9976; 95%CI: 0.9969-0.9982; p<0.001) was not observed post restrictions-implementation (IRR=1.0081; 95%CI: 0.9978-1.0186; p=0.128) due to lack of cases. No periodicity change was observed post restrictions-implementation. Where recorded, 22% of C. hominis cases had travelled abroad. There was also a strong social gradient, with those who lived in deprived areas experiencing a higher proportion of cases. This gradient did not exist post restrictions-implementation, but the effect was exacerbated for the most deprived: 27.2% of cases from the most deprived decile compared to 12.7% in the pre-restrictions period. For C. parvum , post restrictions-implementation incidence fell by 49.0% (95%CI: 38.4%-58.3%; p<0.001). There was no pre-restrictions incidence-trend (IRR=1.0003; 95%CI: 0.9997-1.0009; p=0.322) but a slight increasing incidence-trend existed post restrictions-implementation (IRR=1.0071; 95%CI: 1.0038-1.0104; p<0.001). A periodicity change was observed for C. parvum post restrictions-implementation, peaking one week earlier in spring and two weeks later in autumn. Where recorded, 8% of C. parvum cases had travelled abroad. The social gradient observed for C. parvum was inverse to that for C. hominis , and was stable pre-restrictions and post restrictions-implementation. Conclusion C. hominis cases were almost entirely arrested post restrictions-implementation, reinforcing that foreign travel is a major driver of seeding infections. Increased hand-hygiene, reduced social mixing, limited access to swimming pools and limited foreign travel affected incidence of most gastrointestinal (GI) pathogens, including Cryptosporidium , in the same period. C. parvum incidence fell sharply but recovered throughout the post restrictions-implementation period, back to pre-restrictions levels by the end of 2021; this is consistent with relaxation of restrictions, reduced compliance and increased countryside use. The effect on our results of changes in health-seeking behaviours, healthcare access and diagnostic laboratory practices post restrictions-implementation is uncertain, but it is likely that access to GPs and specimen referral rate to CRU decreased. Future exceedance reporting for C. hominis should exclude the post restrictions-implementation period but retain it for C. parvum (except the first six weeks post restrictions-implementation where the incidence fell sharply). Advice on infection prevention and control should be improved for people with GI symptoms, including returning travellers, to ensure hand hygiene and appropriate swimming pool avoidance. Data summary Cryptosporidium is a notifiable agent in the UK which diagnostic laboratories must report to local health protection teams. Submission of Cryptosporidium -positive stools to the CRU is voluntary, but allows characterisation of the species. We used these data, where the specimen originated from English and Welsh diagnostic laboratories, to describe the epidemiology of Cryptosporidium spp. between 2015 and 2021. Impact statement Cryptosporidium infections in industrialised countries can cause serious disease and lead to complicated and lasting sequelae, especially in the immunocompromised. Even in the general population, as well as long term gastrointestinal upset, joint pain, headache and eye pain have also been identified more frequently following cryptosporidiosis ([1][1]). There is an established association between cryptosporidiosis and colorectal cancer, although no conclusive evidence regarding causality in either direction ([2][2]–[5][3]). There has never been such a dramatic reduction in international travel in the modern era than during the COVID-19 pandemic, which is a key driver of C. hominis infections. Conversely, pressure on outdoor amenities has rarely been higher, which posed an increase in the likelihood of infection and cross-contamination for C. parvum infections. There have been few time-series analyses of cryptosporidiosis; in order to inform and strengthen surveillance programmes, we aimed to assess if there was a significant change to the epidemiology of C. parvum and C. hominis during the COVID-19 pandemic. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No additional funding was received to undertake this time-series analysis; Cryptosporidium genotyping is part of the core service of the Cryptosporidium Reference Unit and surveillance represents part of the core duties of the Communicable Disease Surveillance Centre. Both teams are part of Public Health Wales Health Protection and Microbiology Division. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical oversight of the project was provided by the Public Health Wales Research and Development Division. As this work was carried out using routinely collected surveillance data, PHW Research and Development Division advised that NHS research ethics approval was not required. Data were held and processed under PHW information governance arrangements, in compliance with the Data Protection Act, Caldicott Principles and PHW guidance on the release of small numbers. No data identifying protected characteristics of an individual were released outside of the project team. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors * AIC : Akaike information criterion C. hominis : Cryptosporidium hominis C. parvum : Cryptosporidium parvum CI : confidence interval GI : gastrointestinal illness IPC : infection prevention and control IRR : incidence rate ratio PCR : polymerase chain reaction CRU : Cryptosporidium Reference Unit MLVA : multi-locus variable number of tandem repeats analysis UK : United Kingdom TSA : time series analysis [1]: #ref-1 [2]: #ref-2 [3]: #ref-5