REVIEW

Human cryptosporidiosis in Europe

S. M. Cacciò1 and R. M. Chalmers2

1) European Union Reference Laboratory for Parasites, Istituto Superiore di Sanità, Rome, Italy and 2) Cryptosporidium Reference Unit, Public Health Wales,
Singleton Hospital, Swansea, UK

Abstract

Cryptosporidium has emerged as a significant cause of diarrhoeal disease worldwide, with severe health consequences for very young,
malnourished children living in endemic areas and for individuals with highly impaired T-cell functions. In Europe, as elsewhere, the
burden of disease has been difficult to measure as a result of the lack of appropriate, standardized surveillance and monitoring systems.
The recent occurrence of large water- and foodborne outbreaks in several EU countries, as well as the results of many surveys of human
and animal cryptosporidiosis, indicate that this parasite is widespread. Specific subtypes of the zoonotic Cryptosporidium parvum and the
anthroponotic C. hominis are responsible for the majority of human cases in Europe. No treatment is currently available to clear the
infection, but recent progress in genetic engineering of the parasite, coupled with advances in genomics, have opened important avenues
for future research. Here we explore the possible reasons for underascertainment of cryptosporidiosis and the importance of accurate
diagnosis in clinical management, the epidemiology of human cryptosporidiosis and key messages from recent outbreaks to highlight
important interventions and emerging public health issues.
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Keywords: Cryptosporidiosis, epidemiology, food, outbreaks, water

Article published online: 10 May 2016

can cause persistent symptoms in immunocompetent subjects

Corresponding author: S. M. Cacciò, European Union Reference
Laboratory for Parasites, Istituto Superiore di Sanità, Viale Regina
Elena, 299, 00161 Rome, Italy
E-mail: simone.caccio@iss.it
Introduction
The protozoan parasite Cryptosporidium (Phylum Apicomplexa)
is a well-established cause of sporadic gastroenteritis, as well as
outbreaks characterized by watery diarrhoea, abdominal pain,
nausea, vomiting and low-grade fever. The parasite has a global
distribution, and a number of species are recognized as human
pathogens, although most cases are due to Cryptosporidium
hominis and C. parvum [1]. For the profoundly immunocompro-
mised, such as very young infants, people who are severely
malnourished or people who have a coexisting health problem
(e.g. untreated HIV infection) which leads to T-cell immunode-
ficiency, symptoms can be severe, prolonged and even life-
threatening [2]. Furthermore, infection with Cryptosporidium
that extend beyond the acute illness, as shown by case–control
studies in the United Kingdom [3] and Sweden [4]. Some of these
symptoms may be indicative of postinfectious irritable bowel
syndrome. Two studies have reported that experimental
C. parvum infection of rats triggered long-term pathologic
changes in the lining of the small intestine very similar to those
found in human patients with irritable bowel syndrome [5,6].
Reactive arthropathy has also been reported after cryptospo-
ridiosis [7,8], and in one study in the United Kingdom it was more
likely to be reported as due to C. hominis than C. parvum [3].
Nevertheless, Cryptosporidium is underdiagnosed and under-
reported in most countries, despite being one of the commu-
nicable diseases for which surveillance is mandatory in the
European Union (EU) and European Economic Area (EEA)
countries. This is due to several factors, including healthcare-
seeking behaviour by patients, access to relevant services, poor
awareness in the primary care setting of its role as a cause of
gastrointestinal symptoms leading to a low request rate for
specific testing, variable provision of diagnostic tests and
reporting practices and the lack of harmonized, EU-wide,

Clin Microbiol Infect 2016; 22: 471–480

© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved
http://dx.doi.org/10.1016/j.cmi.2016.04.021
472 Clinical Microbiology and Infection, Volume 22 Number 6, June 2016 CMI

surveillance or monitoring programs (Fig. 1). Individual EU and
EEA countries upload data from their own surveillance systems
to the European Surveillance System (TESSy) for publication in
the annual epidemiologic report for food- and waterborne dis-
eases and zoonoses published by the European Centre for Dis-
ease Control (ECDC). The most recently published 2014 report,
which contains data for 2012 [9], showed that only 19 of 27 EU
countries reported cryptosporidiosis case, whereas cryptospo-
ridiosis is not subjected to official notification in Denmark,
France, Greece, Italy, the Netherlands and Portugal, and Belgium
and Spain do not have a system that covers the whole population
[9]. Five countries reported zero cases, two reported just one
case, and only seven reported 50 or more cases [9].
Diagnosis and Clinical Management
Although cryptosporidiosis is unpleasant and debilitating, and
lasts longer (more than 10 days) than episodes of
gastroenteritis caused by many viruses and bacteria (several
days), in immunocompetent people, it is self-limiting. Accurate
diagnosis is helpful for clinicians, patients and their carers so
that they understand that symptoms of cryptosporidiosis may
persist for a prolonged period and may relapse and remit during
this time [3]. The high numbers of infective oocysts shed in
faeces and the low infectious dose mean that Cryptosporidium is
highly infectious, requiring specific measures for the prevention
of person-to-person spread. For example, UK guidance [10]
states that cases should not attend day care centres, food
handlers and carers of highly susceptible patients should be
excluded from work until 48 hours after diarrhoea has stopped,
and patients should avoid using swimming pools for 2 weeks
after the first normal stool because shedding of oocysts can
continue after cessation of diarrhoea. Secondary transmission is
worthy of further investigation, and influencing factors such as
age, comorbidity and infectivity potential of specific subtypes
need to be considered. Personal hygiene is regarded as a key
intervention [11].

Reported Cryptosporidium cases and estimation

of ascertainment parameters and multipliers in
the EU countries [13]

Germany The England

Netherlands
Factors influencing ascertainment parameters for Cryptosporidium, with examples
Mean annual
reported
1084 314 4128
cases in
(1.29) (1.93) (8.25)
Cases 2001-2005
reported (rate)a

Diagnosis
reported to • SensiƟvity of laboratory methods, 0.99 1.00 0.69
surveillance assumed to be 50% for microscopy [13]

Stool analysed for

• NaƟonal guidance on tesƟng 0.18 0.11 1.00
Cryptosporidium Median
• SelecƟon criteria for tesƟng probability of
parameter
• Cost to paƟent occurring
Case submits a stool 0.19
• Cost to GP 0.34 0.10
sample
• Ease of submission

• symptom severity,
0.34 0.08 0.16
duraƟon
Case visits a GP • opƟons for self-
management 35 000 54 178 62 698
Estimated
• age and sex . cost (43) (330) (130)
median
annual
All symptomaƟc cases of gastroenteriƟs Crypto cases
(at least three loose stools, or any 109 000 651 201 385 961
(rate)a
vomiƟng, in 24 h; excluding diagnosed (130) (4000) (770)
Multiplierb
100 2100 93
non-infecƟous causes)

a rate per 100 000 populaƟon

b the mulƟplier converts each reported case to the esƟmated number of symptomaƟc cases in the populaƟon.

FIG. 1. Surveillance pyramid illustrates where and how underdiagnosis and underreporting of Cryptosporidium in community diarrhoea cases affects
reported data from European Union member states. Reported data underestimate true incidence, which vary by country [12]. Multipliers vary by
country, but this is due in part to uncertainties in parameters used to reconstruct surveillance pyramid. Factors that contribute most to underreporting
and underdiagnosis of Cryptosporidium are differences in healthcare use and laboratory practice.
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 471–480
CMI Cacciò and Chalmers Human cryptosporidiosis in Europe 473

Genuine differences in the occurrence of cryptosporidiosis

may be reflected in case rates but health systems, diagnostic
practice and reporting varies within and between countries,
influencing surveillance data, and direct comparisons between
countries may be misleading [12] as illustrated in Fig. 1; it is
therefore important to understand where the variations lie.
The ECDC’s 2014 annual epidemiologic report [9] considered
that a lack of laboratory diagnosis was an important element of
underreporting cryptosporidiosis cases, which adversely in-
fluences the detection of outbreaks and provision of advice for
prevention of spread. It is important to recognize that Crypto-
sporidium oocysts are too small to be detected reliably during

FIG. 2. Graphic representation of main elements involved in epidemiology of Cryptosporidium hominis (left) and Cryptosporidium parvum (right) in Europe.
examination of faecal samples for ova, cysts and parasites.
Specific tests are available, including acid-fast or fluorescent
stains to stain faecal smears, enzyme immunoassays, immuno-
chromatographic lateral flow assays and molecular methods
[13]. However, not all laboratories test for Cryptosporidium in
the diagnosis of diarrhoea, and many will only test certain pa-
tient groups (e.g. young children, HIV patients and travellers
returning from endemic countries) or if specifically asked to do
so [14]. Diagnostic methods have their limitations. Firstly, they
may not be sufficiently sensitive for diagnosing and monitoring
the most vulnerable patients who may require treatment,
especially methods based on tinctorial stains or rapid lateral
flow immunochromatographic assays [13]. Secondly, they do
not distinguish between species. Only molecular tests identify
species and genotypes, and are undertaken in some specialist
and reference laboratories [13]. In addition to increased labo-
ratory testing, speciation and subtyping of Cryptosporidium iso-
lates were considered important for improved understanding of
the epidemiology of cryptosporidiosis in the EU/EEA [9].

Epidemiology of Cryptosporidiosis

The epidemiology of human cryptosporidiosis is complex,

involving direct (person-to-person and animal-to-person) and
indirect (through water, food and fomites contaminated with
infectious oocysts) transmission routes (Fig. 2). Drinking un-
treated water, consuming water during recreational water ac-
tivities, toileting young children or changing diapers, touching
another person with diarrhoea and engaging in contact with
farm animals increase the risk of becoming infected with Cryp-
tosporidium spp. [1,15]. The main risk factors for C. hominis are
linked to contact with young children, people with diarrhoea or
contamination of water by human waste or wastewater.
Although C. parvum can also be spread between people, the
main risk factors are linked to contact with farm animals,
especially young stock (e.g. at petting farms), or consumption of
water or food contaminated by their faeces. Several recent
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 471–480
474 Clinical Microbiology and Infection, Volume 22 Number 6, June 2016 CMI

reviews provide more information on the epidemiology of
cryptosporidiosis [1,15]. The ECDC’s annual epidemiologic
reports contain yearly trends, age and gender distributions, and
seasonality for reporting EU and EEA countries [9].
Worldwide, cryptosporidiosis is mostly a paediatric infec-
tion, and this is true for Europe as well. The highest prevalence
among children under 5 years likely reflects increased exposure
to the parasite as a result of poorer hygiene as well as a lack of,
or only partial, immunity. However, it is important to note that
infected children are likely to transmit the parasite to their
parents. Indeed, a second, smaller, peak in prevalence is
observed among adults aged 30 to 40 years old, especially
women, and C. hominis is the predominant species involved
[16]. As with young children, the elderly may be more sus-
ceptible to infection and vulnerable to its consequences (e.g.
prolonged diarrhoea can upset electrolyte balance) [17].
Data from the ECDC, and especially the United Kingdom,
indicate that cryptosporidiosis exhibits a strong seasonality in
Europe, with low endemic levels followed by pronounced
seasonal increases, particularly during late spring and late
summer–early autumn. In the United Kingdom, springtime
cases are more often due to C. parvum and are likely the result
of an increased exposure to oocysts shed by young animals, as
this coincides with the calving and lambing seasons [18]. In
recent years, the spring peak has decreased in the United
Kingdom. This was initially explained by the control measures
for an outbreak of foot-and-mouth disease in 2001, involving
reduction in the number of young farm animals and restrictions
of the movement of both farm animals and people in the
countryside. However, the sustained reduction in the spring
peak was later found to be largely due to improved drinking
water supplies [19]. On the other hand, the late summer–early
autumn peak is mainly due to C. hominis and has not reduced in
recent years; it is likely linked to increased travel and exposure
to recreational water at this time of year [16].
Further discrimination of isolates is needed to improve our
understanding of the epidemiology and transmission of Crypto-
sporidium. A literature survey showed that the results of gen-
otyping by sequencing the highly polymorphic gp60 gene of 928
C. parvum and 1043 C. hominis isolates from humans in Europe
has been published (Table 1) [15]. Variability in the sequence of
this marker has been useful for inferring transmission routes; in
addition, different C. hominis and C. parvum gp60 subtypes have
been linked to variable clinical outcomes, producing different
spectra in children [27] and in HIV-positive adults [28].
Notably, a single gp60 allelic family largely predominates
among C. parvum isolates (family IIa, 84.8%) and another among
C. hominis isolates (family Ib, 90.8%). Exceptions include patients
with gastrointestinal disorders, where a greater variety of
C. hominis gp60 families have been reported, and Sweden where
the C. parvum and C. hominis appear to be more diverse than in
other countries studied so far in Europe (Table 1). Further
genetic variability exists even within allelic families, allowing the
identification of gp60 subtypes, for which a specific

TABLE 1. Distribution of Cryptosporidium parvum and Cryptosporidium hominis gp60 families in humans in Europe

C. parvum cases subtyped C. hominis subtyped

EU country Patient group N IIa IIb IIc IId IIe other N Ia Ib Id Ie If Ig Reference

Belgium Sporadic cases 6 4 0 1 1 0 0 13 0 13 0 0 0 0 [15]

France Waterborne outbreak 1 1 0 0 0 0 0 22 0 21 1 0 0 0 [15]
Ireland Sporadic cases 79 78 0 0 1 0 0 25 0 25 0 0 0 0 [15]
Ireland Sporadic cases 170 170 0 0 0 0 0 Not investigated [15]
Italy Unspecified patients None identified 5 0 5 0 0 0 0 [15]
Italy AIDS patients 8 4 0 4 0 0 0 1 1 0 0 0 0 0 [15]
Netherlands Sporadic cases 13 9 0 1 3 0 0 64 0 63 1 0 0 0 [15]
Northern Ireland Waterborne outbreak, sporadic cases 52 52 0 0 0 0 0 68 1 67 0 0 0 0 [15]
Portugal Unspecified 4 1 0 3 0 0 0 3 2 0 0 0 1 0 [15]
Portugal HIV-positive adults 25 9 1 7 8 0 0 15 1 10 1 2 1 0 [15]
Romania Children 4 0 0 4 0 0 Not investigated [20]
Slovak Republic Family members Not investigated 1 0 1 0 0 0 0 [15]
Slovenia Children and adults 31 29 0 1 0 0 1 2 1 1 0 0 0 0 [15]
Slovenia Patients with gastrointestinal disorders 21 21 0 0 0 0 0 71 0 53 12 0 1 5 [15]
Slovenia Unspecified 3 3 0 0 0 0 0 None identified [15]
Spain Children with gastrointestinal disorders 3 3 0 0 0 0 0 41 6 35 0 0 0 0 [21]
Spain Patients with gastrointestinal disorders 164 146 0 0 3 0 IIn (14) 318 3 289 23 3 0 0 [22]
Spain Sporadic cases 7 6 0 0 1 0 0 60 0 54 1 1 2 0 [23]
Spain Patients with gastrointestinal disorders 12 7 0 1 4 0 0 89 0 85 0 4 0 0 [24]
Sweden 2 foodborne outbreaks 27 4 0 0 23 0 0 2 0 1 1 0 0 0 [15]
Sweden Sporadic cases 107 69 0 11 24 1 IIo (2) 63 5 44 10 1 3 0 [15]
Switzerland HIV positive 2 1 0 0 1 0 0 3 0 2 1 0 0 0 [15]
UK Sporadic and outbreaks 87 82 0 1 1 0 IIg (3) 65 16 46 2 1 0 0 [25,26]
UK Unspecified None identified 3 0 3 0 0 0 0 [15]
UK Sporadic cases 69 56 0 1 9 0 3 Not investigated [15]
UK Outbreak cases 22 22 0 0 0 0 0 [15]
UK Patients from farms 11 11 0 0 0 0 0 Not investigated [15]
UK Sporadic cases Not investigated 101 5 93 0 0 1 2 [15]

Updated from reference [15].

© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 471–480
CMI
nomenclature has been proposed [29]. Direct zoonotic trans-
mission of C. parvum is well documented in Europe, and several
IIa subtypes—including IIaA15G2R1, which is particularly
prevalent in young cattle; IIaA19G1R1, which has caused out-
breaks where lambs were present [11,30]; and IIaA20G2R1
[31]—have been implicated in both sporadic cases and out-
breaks involving animals (Table 2). Notably, subtypes belonging
to allelic family IId also cause human cryptosporidiosis (Tables 1
and 2). This family is also often responsible for infection of
lambs but has been reported in cattle in Sweden.
In contrast, the C. hominis subtype IbA10G2 largely pre-
dominates in sporadic and outbreak cases in Europe (Fig. 2,
Tables 1 and 2). This subtype is highly prevalent worldwide and
has caused outbreaks in Australia and the United States, and
thus it may be endowed with a particular virulence or a higher
transmissibility compared to other subtypes [44].
While gp60 is certainly a useful epidemiologic marker, the
discrimination among parasite isolates is increased by the use of
a multilocus subtyping scheme, particularly when highly poly-
morphic markers (mini- and microsatellites) are included [45].
However, there is still no standardized multilocus subtyping
scheme for Cryptosporidium. The establishment of such a
scheme would be valuable for both interlaboratory surveillance
and outbreak investigations.
Outbreaks of Cryptosporidiosis in Europe
The identification of outbreaks of cryptosporidiosis is reliant on
accurate diagnosis and surveillance, which was established
formally in some countries much earlier than in others. For
example, in England and Wales, surveillance for Cryptosporidium
cases began in 1983 and for outbreaks of infectious intestinal
disease in 1992 [46]. Over the last decade, outbreaks of
cryptosporidiosis have been detected in many EU countries
associated with drinking and recreational waters (mainly
swimming pools), food consumption, animal contact, outdoor
activities and person-to-person spread in the home and in in-
stitutions [47–49]. However, Cryptosporidium is often consid-
ered and tested only after bacterial and viral causes of
symptoms have been excluded [35]. Here we have used data
from selected, recent outbreaks to highlight some emerging
aspects of cryptosporidiosis (Table 2).
Firstly, waterborne outbreaks of cryptosporidiosis can be
very large, and this has allowed analytical epidemiologic studies
to investigate the long-term health sequelae, which are prob-
ably underestimated. In 2010–2011, Sweden registered the two
largest outbreaks ever reported in Europe, together affecting an
estimated 47 000 persons [39,40]. Both outbreaks were caused
by C. hominis gp60 subtype IbA10G2. High consumption of tap
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 471–480
Cacciò and Chalmers Human cryptosporidiosis in Europe 475
water or living in a specific water supply region were identified
as the most important risk factors for having cryptosporidiosis,
and the high attack rate (28–45%) confirmed the high infectivity
of this C. hominis subtype and the susceptibility of the local
population to infection and disease. An important follow-up
study revealed the extent of postinfection health conse-
quences 2.5 to 8.5 months after the outbreak in Östersund, and
2.5 to 11.5 months after the outbreak in Skellefteå [39].
Outbreak cases were more likely to occur in patients reporting
diarrhoea, watery diarrhoea, abdominal pain, joint pain, fatigue
and nausea compared to nonoutbreak cases, and indicate a
significant burden of illness even after outbreaks are over. Some
differences were observed between the two sites: cases in
Östersund also reported weight loss, loss of appetite, stiff joints
and headache and generally stronger measures of association
than in Skellefteå, which the authors speculatively attributed to
the possibly greater contamination of the water supply leading
to more frequent and severe infections and sequelae in
Östersund [39].
Secondly, outbreaks have been also caused by Cryptospo-
ridium species that were not considered previously to be
important human pathogens. Cryptosporidium cuniculus, a para-
site of rabbits, caused a waterborne outbreak in North-
amptonshire, UK, involving 23 laboratory-confirmed cases and
an estimated 422 cases of cryptosporidiosis above baseline [42].
Investigation of this outbreak revealed an unusual distribution
of cases in terms of age (lack of cases in children under 5) and
sex (girls and women were overrepresented); interestingly, a
similar age distribution was found during subsequent investi-
gation of sporadic cases attributed to C. cuniculus [50], sug-
gesting that exposure and risk factors are parasite-specific.
Another species, C. meleagridis, was confirmed in one case
during an outbreak involving three farm workers at an organic
farm in Sweden [38]. This species infects many host classes
including birds, mostly farmed poultry, and has a clear zoonotic
potential, but it has not been regarded thus far as an important
human pathogen in Europe [4].
Thirdly, adverse climatic events, including heavy rainfall and
river flooding, are globally on the rise and can cause epidemics
of gastroenteritis. For example, an outbreak in August 2013 in
the city of Halle, Germany [33], began 6 weeks after the river
Saale overflowed the floodplain and parts of the city centre.
The outbreak was caused by C. hominis, subtype IbA9G2, sug-
gesting that human waste was the source of water contamina-
tion. Analysis of environmental samples showed high levels of
oocysts (up to 592 oocysts/100 L), again suggestive of waste-
water contamination, but genotyping was unsuccessful. Of the
167 notified cases, most occurred among children, and playing
on previously overflowed floodplain was associated with
infection. Thus, this event indicated that public health
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476
Clinical Microbiology and Infection, Volume 22 Number 6, June 2016
TABLE 2. Selected outbreaks of cryptosporidiosis in Europe

No. of No. of
laboratory-confirmed estimated
Country and location Year Month Setting or vehicle Species and gp60 subtype cases cases Novel findings or key messages Reference

Spain, Granada 2014 September to Nursery school C. hominis IaA11R2 (5) and IbA10G2 7 Unknown Mixed infections may occur indicating multiple possible [32]
November (1); three children also had Giardia sources and/or high contamination and/or
transmission.
Germany, Halle 2013 August Playing on floodplain C. hominis IbA9G2v 167 Unknown Oocyst survival in the environment and adverse [33]
climatic events can increase the risk of
cryptosporidiosis.
England, Yorkshire 2013 April Open farm C. parvum IlaA19G1R1 35 46 Handwashing and provision of information about [30]
infection risks are important interventions in these
settings.
Sweden, Uppsala 2013 March Veterinary students C. parvum IIaA16G1R1b 6 13 Contact with calves and eating in clinic cars were risk [34]
(four cases) and IIdA24G1 factors, while handwashing was protective. Provision
(two cases) of information about infection risks is important,
even for occupationally exposed professional groups.
Finland; various 2012 October and Frisée salad C. parvum IIdA17G1 18 >250 Food trace-back identified possible causative factors for [35]
locations November contamination.
Europe 2012 Summer Community setting; C. hominis IbA10G2 1.8- to 4.9-fold increase Lack of routine diagnosis, reporting, species [9,36]
vehicle not known compared to previous identification and genotyping in some countries made
years it hard to define the extent of the outbreak.
England and Scotland 2012 May Precut mixed salad leaves C. parvum IIaA15G2R1 74 >300 Genotyping was important in case definition; [37]
improvements are needed in food trace-back.
Sweden 2011 June Bird contact C. meleagridis 1 3 Outbreak involving a species other than C. hominis or [38]
C. parvum; zoonotic source identified.
Sweden, Skellefteå 2011 May Drinking water C. hominis IbA10G2 Unknown ~20.000 High attack rate and postinfectious sequelae identified. [39]
Sweden, Östersund 2010 November Drinking water C. hominis IbA10G2 186 ~27.000 High attack rate and postinfectious sequelae identified. [39,40]
England, Greater 2010 September Swimming pool C. hominis 3 48 People with cryptosporidiosis continued to swim. [41]
Manchester
Norway 2009 and March and Holiday farm with two C. parvum IlaA19G1R1 11 and 15 55 and 40 Varying rates of secondary transmission were reported, [11]
2012 March outbreaks from both asymptomatic and symptomatic infections,
emphasising the importance of personal hygiene.
England, 2008 June Drinking water C. cuniculus VbA18 23 422 First outbreak involving a species other than C. parvum [42,43]
Northamptonshire or C. hominis. Syndromic surveillance indicated the
outbreak was larger than identified from diagnosed
cases.

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authorities should consider the potential health risks of long-
term surviving Cryptosporidium oocysts.
Finally, foodborne outbreaks of cryptosporidiosis have been
recently documented in several EU countries, and implicated
foods include fresh produce and unpasteurized or inadequately
pasteurized milk [49]. Of particular importance was the
outbreak in May 2012 that occurred across England and Scot-
land [37] (Table 2). To date, this is the largest documented
outbreak of cryptosporidiosis attributed to a food vehicle, with
>300 individuals involved. Although the precise source was not
identified, infection was strongly associated with the con-
sumption of precut mixed salad leaves sold by a single retailer,
and typing revealed the outbreak strain to be C. parvum gp60
subtype IIaA15G2R1, a worldwide-distributed subtype highly
prevalent in both livestock and humans. Also in 2012 an
outbreak occurred in Finland that was nearly as large as that in
the United Kingdom, caused by C. parvum IIdA17G1, and was
associated with consumption of frisée salad [35]. The trace-
back investigations revealed the source of the frisée salad as
an outdoor grower in the Netherlands, where there had been
heavy rainfall during the growing season. In recent years, con-
sumption of raw vegetables has been linked to outbreaks of
cryptosporidiosis in Denmark, Sweden and Finland, but this
trend is likely the result of good outbreak reporting and in-
depth case interviews [49].
In the second half of 2012, several countries (including the
United Kingdom, Germany, Belgium, Spain, Sweden, Finland and
the Netherlands) reported an unusual increase in the number
of cases of cryptosporidiosis [9,36]. The annual number of re-
ports to ECDC (excluding nonreporting countries and those
where national surveillance systems for cryptosporidiosis
reporting do not cover the whole population) was 68% higher
than in 2011, with 9591 cases reported, but no common
epidemiologic link could be identified [9,36]. Widespread out-
breaks raise the need for standardized subtyping schemes for
Cryptosporidium.
Analysis of outbreaks can provide information for future
prevention by identifying the main causes, understanding the
risks and ensuring effective interventions are in place. For
drinking water, catchment protection measures identified
through water safety plans, appropriate treatment (especially
the installation of filtration), secondary disinfection such as ul-
traviolet light, and protection of water in distribution are key
interventions [51]. In the United Kingdom, a demonstrable
reduction in the number of drinking water outbreaks and cases
attributed to mains water has been linked to improvements in
water quality through the closure of or installation of filtration
at unfiltered supplies [19,52]. Interestingly, one study in Scot-
land suggested that while oocyst removal from drinking water
supplies decreased the risk of waterborne cryptosporidiosis,
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 471–480
Cacciò and Chalmers Human cryptosporidiosis in Europe 477
the reduction in circulating antibody response may indicate
decreased protective immunity and that the population may
therefore be at increased infection risk from exposure to other
sources [53].
While outbreaks linked to drinking water have been shown
to have declined in the United Kingdom, those linked to rec-
reational waters, especially swimming pools, have not. Similarly,
in the United States, Cryptosporidium is the predominant cause
of outbreaks associated with recreational waters [54]. The
problem of Cryptosporidium resistance to chlorine at normal
pool water treatment levels (0.5 to 2.5 mg/L residual free
chlorine) means that treatment to deal with contamination
relies on good filtration practices, with an option for emer-
gency decontamination by superchlorination (http://pwtag.org/
technicalnotes/superchlorination-of-swimming-pool-water/).
Superchlorination, whereby the free chlorine is raised for a
sufficient time to provide a 3-log inactivation (20 mg/L for 13
hours for Cryptosporidium), provides no long-term protection,
and it must be carried out by correctly trained operators who
understand the procedure and that for subsequent dechlori-
nation to normal levels. Adverse effects include the generation
of potentially harmful by-products and the corrosive effect on
the treatment plant. However, prevention of contamination of
pools in the first place is preferable; this requires improved
hygiene by pool users, and communication of and adherence to
advice to patients not to swim for 2 weeks after symptoms
cease. It has been found that in some outbreaks symptomatic
people continued to use swimming pools [39]. Communicating
risk and appropriate preventative measures has also been found
to be important in reducing the risk of infection and outbreaks
at petting farms. One outbreak investigation found that lack of
verbal advice and noncompliance with handwashing were
significantly associated with the risk of acquiring cryptospo-
ridiosis at a petting farm [30]. The need for the provision and
reinforcement of similar preventive messages was also identi-
fied after an outbreak among veterinary students in Sweden
[34].
No major waterborne or foodborne outbreaks of crypto-
sporidiosis have occurred in some regions of Europe, particu-
larly in Southern Europe, thus implying a different
epidemiologic situation. However, this may be related to an
absence of notification and a lack of investigation rather than to
a truly different epidemiology.
Treatment
Treatment options for cryptosporidiosis are still limited. Spe-
cific treatment strategies for cryptosporidiosis have been pur-
sued for more than three decades, yet despite the evaluation of
478 Clinical Microbiology and Infection, Volume 22 Number 6, June 2016
nearly a thousand chemotherapeutic agents, therapies able to
clear the host of Cryptosporidium are lacking [55]. While
research on potential drug targets is ongoing and a number of
candidates have been identified, also through repurposing of
drugs developed for other indications [56], none has advanced
to clinical trials. This is of particular concern, considering the
benefit that an available treatment will have for risk groups such
as young children, the elderly, individuals with compromised T-
cell function and patients with primary T-cell deficiencies, such
as severe combined immunodeficiency and CD40 ligand defi-
ciency (hyper-IgM syndrome) [57]. The introduction of the
highly active antiretroviral therapy (HAART) has greatly
reduced the impact of cryptosporidiosis among HIV-infected
individuals [58]. This is due to an improvement in CD4 cell
count and the restoration of a degree of immunity, but also to a
direct effect of protease inhibitors on host cell invasion and
parasite development in vitro, an effect enhanced with paro-
momycin [59]. Unfortunately, HAART is costly and is thus not
readily available in poor regions of the world, where HIV/AIDS
and opportunistic cryptosporidiosis remains a major health
problem [56].
Currently nitazoxanide (NTZ) (Alinia, Romark Labora-
tories), a thiazolide drug with broad antiparasitic activities, is
the only US Food and Drug Administration–approved drug for
use against cryptosporidiosis in immunocompetent patients, but
it is not licensed in Europe. There is little evidence for efficacy
of NTZ in immunocompromised individuals and malnourished
children [60].
The lack of efficacious drug treatments indicates that the
development of strategies that prevent disease or reduce the
severity of infection, including vaccination, remains essential.
Progress in this field has been hampered by lack of systems for
continuous in vitro culture, cryopreservation of the parasite,
adequate animal models and tools for manipulation of the
parasite genome. However, a recent study has demonstrated
that genetic analysis and manipulation of the parasite is possible,
and that stable transgenes are obtained by delivering in vitro
transfected sporozoites directly into mouse intestine [61]. The
availability of luciferase reporter parasites will permit screening
of novel compounds in vitro or in animals, and gene deletion
experiments can be used to validate biologic targets. Attenu-
ated parasites may be obtained through genetic modification,
potentially leading to the development of an oral vaccine [62].
A better understanding the mechanisms underlying disease
and protection, however, remains crucially required to design
and produce a vaccine [63]. Furthermore, it needs to be
considered that the efficacy of a vaccine may be reduced in very
young children, also because of possible interference by
maternal antibodies, micronutrient deficiencies and persistent
exposure to other pathogens. Likewise, the use of a live,
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 471–480
CMI
attenuated vaccine might be feasible for immunocompetent
individuals, but serious complications exist for immunocom-
promised individuals.
The increasing availability of whole genome sequences from
different Cryptosporidium species, as well as functional genomics
and metabolomics data, will assist in the identification of new
drug targets [64].
Conclusions
The burden of cryptosporidiosis, including acute infection and
long-term sequelae, in Europe is currently unknown. Improved
monitoring and surveillance systems are necessary to define the
true epidemiologic situation and to ascertain possible differ-
ences among countries.
Interventions have been identified from epidemiologic and
outbreak investigations, and disease reduction can be achieved.
Proper risk communication, especially to vulnerable pop-
ulations, remains important.
Treatment options are still limited; no fully effective drug
treatment or vaccine is available for Cryptosporidium. The recently
demonstrated possibility to knock out genes and introduce
markers has opened new ways towards drug discovery and vac-
cine development. Interest in the development of new therapies
for paediatric cryptosporidiosis is growing, as witnessed by the
inclusion of Cryptosporidium in the last call for Global Grand
Challenges funded by the Bill and Melinda Gates Foundation.
Transparency Declaration
All authors report no conflicts of interest relevant to this
article.
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