In line with previous studies [13,14,15,16], our data showed that an acute episode of cryptosporidiosis is associated with long-term sequelae. Indeed, 4 months after diagnosis of cryptosporidiosis, several gastrointestinal and non-gastrointestinal symptoms were still occurring at a higher frequency as compared to the period before the onset of acute illness and to the general population (controls). The odds of having non-gastrointestinal symptoms as sequelae were generally higher than those having gastrointestinal symptoms. Yet, when symptom occurrence among cases after illness was compared to the population controls, it appeared that gastrointestinal sequelae were those occurring significantly more often, and that sequelae like joint pain (which occurred significantly more often among cases after illness as compared to before illness) occurred after illness at a rate that was not significantly different from that observed in the general population. At the analysis of the two species separately, results agree with the overall analysis to a major extent, although it is generally more difficult to draw conclusions due to the low numbers of cases. However, the comparison among cases (C. hominis vs. C. parvum) clearly showed that there are no significant differences of one Cryptosporidium species causing significantly more gastrointestinal (and the other one more non-gastrointestinal) sequelae, as originally hypothesised. Indeed, one of the studies describing sequelae following cryptosporidiosis  found that recurrent gastrointestinal symptoms occurred regardless of species, but not the non-gastrointestinal ones (e.g. joint pain, eye pain, headache, dizziness and fatigue). These symptoms were common in cases with C. hominis infection, but not in those infected with C. parvum. The other study found no difference in frequency of persisting symptoms between patients infected with C. parvum or C. homini . In this regard, our results show a more homogeneous picture with no clear separation of symptoms between the two species. The other two studies investigating sequelae reported information only on either C. hominis  or C. parvum , but not the two together, and both gastrointestinal and non-gastrointestinal symptoms were found to be associated with infection.
The age and gender distribution of the cases was in line with the one expected, as generally younger and middle-aged groups are most affected by Cryptosporidium infection. The explanation for the 26–50-year-old age group being particularly affected by diseases like cryptosporidiosis is that this age group often contains parents and child-carers, which are predominantly females, which are thus more likely to be exposed to Cryptosporidium from the children themselves . In our study, cryptosporidiosis in older age groups was also prevalent, as reported before .
The frequency of some symptoms during and after the illness shows the natural course of the disease, e.g. loss of appetite and vomiting were very likely to occur during the acute phase of the illness, but much less so afterwards. The same is true for non-gastrointestinal symptoms like joint pain, eye pain and headache which were very prevalent during the infection as a direct consequence of the acute infection itself, for example as a consequence of fever and malaise. However, the number of people still experiencing symptoms of, e.g. diarrhoea, fatigue, dizziness and weight loss in the follow-up is striking. The finding that some symptoms occurred more frequently among cases even before illness as compared to what is observed in the population controls might be a sign that people acquiring cryptosporidiosis may be a particular group of the population with a generally increased susceptibility to (gastrointestinal) illness per se (e.g. people with underlying chronic conditions), which may also entail an increased likelihood of being diagnosed with cryptosporidiosis due to enhanced medical scrutiny for these patients, as shown for other pathogens [24, 25]. Indeed, high proportions of cases reporting a given symptom after illness had also reported the same symptom before illness (i.e. dizziness 36%, headache 45%, fatigue 54%, weight loss 28%, diarrhoea 50%, loss of appetite 42%, abdominal pain 53%, joint pain 42%, eye pain 32%, vomiting 19%). Results may have also been influenced by substantial recall bias, regarding the symptoms for the period before infection and symptoms occurring after the acute phase were over. Moreover, cases are probably more self-aware due to the initial infection and therefore more prone to remember symptoms after diagnosis. Although there is complete control of between-person confounders, another key limitation of this study design is in the control of within-person confounding, which is still possible for multiple, correlated transient factors that change over time within a subject, such as symptoms related to another acquired illness or injury. Moreover, selection bias may have been introduced by cases being particularly motivated to participate in the follow-up study because of the presence of sequelae. Finally, because the follow-up questionnaire did not emphasise the “chronicity” of sequelae, it was not possible to assess whether symptoms occurred once or several times over the 4-month period after illness.
In conclusion, this study adds to the growing body of evidence for the presence of sequelae following cryptosporidiosis, so far represented by four published studies. While some studies have observed species-specific effects on sequelae, we did not see a clear differentiation between sequelae and the infecting Cryptosporidium species. However, subtype information was not available, and there are studies indicating that some subtypes within the same genotype can manifest in different ways and might be more virulent than others , which could be interesting to address in future investigations. Although our results do not change the general advice for patient care, awareness of medical personnel should be raised that non-gastrointestinal symptoms can be the consequence of enteric infection. As there is no treatment for cryptosporidiosis, the focus should be on preventive measures.