Skip to main content
Download PDF

Health sequelae of human cryptosporidiosis in industrialised countries: a systematic review

Parasites & Vectors volume 13, Article number: 443 (2020) Cite this article

Abstract

Background

Cryptosporidium is a protozoan parasite which is a common cause of gastroenteritis worldwide. In developing countries, it is one of the most important causes of moderate to severe diarrhoea in young children; in industrialised countries it is a cause of outbreaks of gastroenteritis associated with drinking water, swimming pools and other environmental sources and a particular concern in certain immunocompromised patient groups, where it can cause severe disease. However, over recent years, longer-term sequelae of infection have been recognised and a number of studies have been published on this topic. The purpose of this systematic review was to examine the literature in order to better understand the medium- to long-term impact of cryptosporidiosis.

Methods

This was a systematic review of studies in PubMed, ProQuest and Web of Science databases, with no limitations on publication year or language. Studies from any country were included in qualitative synthesis, but only those in industrialised countries were included in quantitative analysis.

Results

Fifteen studies were identified for qualitative analysis which included 3670 Cryptosporidium cases; eight studies conducted in Europe between 2004–2019 were suitable for quantitative analysis, including five case-control studies. The most common reported long-term sequelae were diarrhoea (25%), abdominal pain (25%), nausea (24%), fatigue (24%) and headache (21%). Overall, long-term sequelae were more prevalent following infection with Cryptosporidium hominis, with only weight loss and blood in stool being more prevalent following infection with Cryptosporidium parvum. Analysis of the case-control studies found that individuals were 6 times more likely to report chronic diarrhoea and weight loss up to 28 months after a Cryptosporidium infection than were controls. Long-term abdominal pain, loss of appetite, fatigue, vomiting, joint pain, headache and eye pain were also between 2–3 times more likely following a Cryptosporidium infection.

Conclusions

This is the first systematic review of the long-term sequelae of cryptosporidiosis. A better understanding of long-term outcomes of cryptosporidiosis is valuable to inform the expectations of clinicians and their patients, and public health policy-makers regarding the control and prevention of this infection.

Systematic review registration PROSPERO Registration number CRD42019141311

Background

Cryptosporidiosis is a clinical disease, typically affecting the intestinal tract of humans and animals who have ingested the protozoan parasite Cryptosporidium in its oocyst (infective) stage [1]. Transmission of Cryptosporidium occurs predominantly via the faecal-oral route, or through consumption of contaminated food or water and therefore the prevalence of human Cryptosporidium infections is higher in low-resource settings [2]. However, Cryptosporidium infections are not infrequent in industrialized countries [3], with large outbreaks being reported in Sweden [4], the USA [5, 6] and the UK [7] following contamination of public water supplies.

While asymptomatic carriage is possible [8, 9], human cryptosporidiosis typically presents as an acute, gastroenteritis-like illness characterized by profuse, watery diarrhoea, frequently accompanied by abdominal pain/cramps, vomiting and weight loss, as well as more non-specific symptoms such as fatigue, low-grade fever, nausea and muscle weakness [10]. In immunocompetent hosts, cryptosporidiosis is generally self-limiting; however, disease severity can be influenced by host factors, such as age, immune status and nutritional status, as well as pathogen factors e.g. Cryptosporidium species and subtype [11].

Alongside ongoing interest in the acute symptomology of human cryptosporidiosis, there is also growing evidence to suggest that, rather like some bacterial causes of gastroenteritis and giardiasis [12,13,14], Cryptosporidium infection may have longer-term health consequences. Seven studies [15,16,17,18,19,20,21], with follow-up periods ranging from 2 months to 3 years, have investigated numerous potential post-Cryptosporidium infection sequelae including diarrhoea, abdominal pain, vomiting, loss of appetite, irritable bowel syndrome (IBS) [21], joint pain and fatigue, while case reports document incidences of reactive arthritis [22,23,24], Reiter’s syndrome [25], acute pancreatitis [26, 27] and haemolytic uremic syndrome [28], in the context of Cryptosporidium infection. There is also some emerging evidence, recently reviewed, of a possible association between cryptosporidiosis and cancer [29].

Due to resource limitations, public health professionals currently face the challenge of identifying and prioritising specific infectious diseases whose quantified burden of disease estimates justify the allocation of interventions and funding for research [30]. The Global Enteric Multicentre Study [31] identified Cryptosporidium as the second most common cause of moderate-to-severe diarrhoea (MSD; defined as diarrhoeal disease with presence of the suggestive features of sunken eyes, wrinkled skin, hospitalization, receipt of intravenous hydration, or dysentery) in children less than 2 years-old within sub-Saharan Africa and south Asia, while in 2016, the European Network for Foodborne Parasites (Euro-FBP) ranked Cryptosporidium spp. as the second highest priority foodborne parasite in northern and western Europe, and the eighth highest priority in eastern and south-western Europe [30]. However, actual burden of disease estimates for Cryptosporidium still vary widely [11] and it remains difficult to quantify the true burden of cryptosporidiosis, as current estimates only account for the morbidity and mortality associated with the acute illness, while the potential contributions of long-term manifestations are not included [32, 33]. A recent study from the Netherlands [2] found that long-term manifestations contributed nearly 10% of the total Disability-Adjusted Life Years (DALYs) and costs when included in burden of disease models for Cryptosporidium, suggesting a higher public heath burden and cost than previously estimated.

Accurate estimations of the burden of disease associated with Cryptosporidium will inform decisions regarding the allocation of diagnostic, surveillance and interventional measures to prevent and control Cryptosporidium infections. Due to the potential morbidity and mortality associated with long-term sequelae of human cryptosporidiosis, an accurate estimation of the proportion of cases that develop such sequelae is needed to quantify true burden of disease estimates for Cryptosporidium.

The objectives of this review were: (i) estimate the proportion of people that self-report health sequelae post-Cryptosporidium infection; (ii) estimate the risk of specific sequelae following Cryptosporidium infection; and (iii) explore potential risk factors associated with developing sequelae following Cryptosporidium infection in industrialised countries.

Methods

Search strategy

We searched for studies in PubMed, ProQuest and Web of Science databases, with no limitations on publication year or language. The reference lists from relevant papers identified during our electronic searches were also reviewed for additional relevant papers which may warrant inclusion in our review. Search terms were initially developed and piloted using PubMed and, to ensure consistency, the same search terms were used when searching ProQuest and Web of Science databases. Databases were searched using the following keywords: Cryptosporid*, Complications, Sequel*, Post-infecti*, Long term and Chronic. The full electronic search strategies are documented in Additional file 1: Table S1. The review was registered with PROSPERO, registration number CRD42019141311.

Selection of studies

All citations identified using the final search strategies were exported to Mendeley® reference managing software for organisation and removal of duplicates. The titles and abstracts of the remaining articles were screened for relevance by one reviewer (BC), after which, the remaining articles were independently screened by two reviewers (BC and APD) to ensure consistent application of the pre-determined inclusion/exclusion criteria (Additional file 1: Table S1).

Studies from any country were included in qualitative synthesis, but only those in industrialised countries were included in quantitative analysis. An industrialised country was defined using Organisation for Economic Co-operation & Development (OECD) membership.

Final inclusion of studies was decided by consensus, with any conflicts being reviewed by a third reviewer (RMC). The full text was retrieved and reviewed for articles where the title and abstract had been deemed relevant by reviewers.

Data extraction

Data were extracted from eligible studies and collated in a Microsoft Word document. We recorded post-Cryptosporidium infection health sequelae data as reported in the individual papers (e.g. prevalence, cumulative incidence, etc.). Relative risks or odds ratios were recorded where data were available. We also extracted the following study characteristics from each paper if available: name of authors, year of publication, study location/setting, study design, year(s) of study, study duration and duration of follow-up, number of included study participants, participation rate, study population demographics (including age and gender distributions), Cryptosporidium species data, the diagnostic method to ascertain Cryptosporidium infection and the types of sequelae reported. Additionally, where available, data on the incidence/prevalence of post-infectious IBS following Cryptosporidium infection and the IBS diagnostic criterion applied were collected.

Quality assessment

The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for nonrandomised studies [34]. NOS was used to score studies using three domains: (i) the selection of the study groups; (ii) the comparability of the groups; and (iii) the determination of either the exposure or outcome of interest in case-control or cohort studies, respectively. Scores ranged between 5–8 (Additional file 1: Table S2).

Statistical analysis

The proportion of Cryptosporidium cases that developed specific sequelae was calculated by dividing the number of individuals developing a sequela by the total number of Cryptosporidium cases. Where data were available from two or more appropriate studies, we used a random-effects meta-analysis model to obtain pooled estimates of prevalence for the outcomes of interest (i.e. sequelae) across the eligible studies. For this analysis, a study could be included more than once if sequelae data were reported longitudinally at different time periods. Data analyses were performed using Meta XI [35].

Assessment of heterogeneity and reporting biases

Forest plots and the I2 statistic were used to assess heterogeneity between the studies. Values of 0–40%, 30–60%, 50–90% and 75–100% were interpreted as; might not be important, may represent moderate heterogeneity, may represent substantial heterogeneity and considerable heterogeneity, respectively [36]. Funnel plots were used to assess for publication bias and small-study effects.

Stratified analysis was performed for the following subgroups; time (less than 6 months post-infection and more than 6 months post-infection) and Cryptosporidium sp. (e.g. C. parvum vs C. hominis).

Results

Data synthesis

The number of papers identified, included and excluded is presented according to the requirements of the PRISMA statement [37] in Fig. 1. Fifteen studies were identified for qualitative synthesis and eight of these were identified as being set in industrialised countries and of sufficient quality for additional quantitative synthesis.

Fig. 1
figure 1

PRISMA flowchart

Full size image

The qualitative synthesis is shown in Table 1. Quantitative synthesis results are shown in Tables 2, 3 and 4 and Figs. 2 and 3.

Table 1 Fifteen studies included in the qualitative synthesis
Full size table
Table 2 Pooled estimates for the prevalence of post-Cryptosporidium sequelae using a random effects model
Full size table
Table 3 Pooled prevalence of post-Cryptosporidium sequelae estimated by a random effects model, according to clinical manifestation by time period post-infection
Full size table
Table 4 Pooled risk ratio of individual post-Cryptosporidium sequelae
Full size table
Fig. 2
figure 2

Reported sequelae up to 36 months post-Cryptosporidium infection

Full size image
Fig. 3
figure 3

Reported sequelae up to 36 months post-Cryptosporidium infection by species (%)

Full size image

Qualitative synthesis

Electronic searching returned 1251 PubMed, 2161 ProQuest and 3227 Web of Science abstracts. After removal of duplicates, screening and assessment, 15 articles were suitable for inclusion in the qualitative synthesis and the data extracted from these studies are summarized in Table 1.

The 15 shortlisted studies included 3670 Cryptosporidium cases. The studies comprised 8 cohort studies and 7 case-control studies. Seven studies were conducted in children, with the remaining 8 studies including both adults and children. The length of duration of follow-up ranged from 2 months to 9 years. Studies were conducted in South America (3 studies), Africa (1 study), South Asia (2 studies) and Europe (9 studies) and were all based in a community setting. The selected studies were published between 1992 and 2019. The studies investigated a range of potential sequelae; diarrhoea (3 studies), developmental delay (2 studies), stunting of growth (4 studies) and multiple gastrointestinal and non-gastrointestinal symptoms (8 studies).

Quantitative synthesis

Adequate information to estimate post-Cryptosporidium infection sequelae was available in 8 of the 15 studies [4, 15,16,17,18,19,20,21]. The pooled estimates for each of the sequelae are shown in Table 2. Data for each individual sequela are available in Additional file 2.

The eight studies were conducted in Europe between 2004 and 2019; four in Sweden, three in the UK and one in the Netherlands. The sequelae investigated were mostly gastrointestinal, with some non-gastrointestinal symptoms such as joint pain and eye pain and most recruited cases were adults. This was in contrast to studies in non-industrialised countries which focused on growth, nutrition and cognitive detriment in children.

The most frequently investigated sequelae are listed in Table 2 and included diarrhoea, abdominal pain, vomiting, fatigue, joint pain, eye pain and headache.

The most common reported long-term sequelae were diarrhoea (25%), abdominal pain (25%), nausea (24%), fatigue (24%) and headache (21%). The distribution of gastrointestinal manifestations and non-gastrointestinal manifestations reported is shown in Fig. 2.

Subgroup analysis

Table 3 shows the pooled estimates for the prevalence of post-Cryptosporidium sequelae by time period post-infection. With the exception of eye pain and headache, all sequelae were more frequently reported within 6 months of Cryptosporidium infection.

In all eight studies included in the quantitative analysis, species identification of Cryptosporidium had been performed. Four were outbreak cohort follow-up studies so contained only one species (three contained C. hominis cases exclusively and one contained C. parvum exclusively). The other four studies contained both species; one of these four also contained a small number of other species (17/271 cases), but because of the low numbers, these have not been considered here. Figure 3 shows the pooled estimates for the prevalence of post-Cryptosporidium sequelae by Cryptosporidium species. Overall, long-term sequelae were more prevalent following infection with C. hominis, with only weight loss and blood in stool being more prevalent following infection with C. parvum. IBS was reported in 11% of cases, however, it should be noted that data for this outcome were only available from 2 studies, one of which only studied C. parvum cases.

Sequelae risk

Five of the 8 qualitative synthesis studies included a control group. A limited evaluation of risk of individual sequelae using the five case-control studies available was undertaken [4, 15, 17, 19, 20]. Data were available for 10 sequelae (Table 4).

Individuals were 6 times more likely to report chronic diarrhoea and weight loss up to 28 months after a Cryptosporidium infection than controls. Long-term abdominal pain, loss of appetite, fatigue, vomiting, joint pain, headache and eye pain were also 2–3 times more likely following a Cryptosporidium infection (Fig. 4).

Fig. 4
figure 4

Pooled risk ratio of individual post-Cryptosporidium sequelae showing 95% confidence intervals

Full size image

To view the PRISMA checklist relating to this work, please see Additional file 3.

Discussion

Of the 15 studies investigating long-term sequelae, just over half were set in industrialised countries. In contrast to those in non-industrialised settings, these involved mainly adult cases, with the inclusion of some children. Half were outbreak cohort studies, with the rest involving sporadic community cases. Studies from non-industrialised countries involved exclusively children, reflecting the greater clinical importance and recognition of paediatric infection in such settings. In industrialised countries there is more focus on detecting sporadic community cases of cryptosporidiosis in all age groups, partly in order to facilitate early detection of community outbreaks, for example from drinking water, swimming pools, or other environmental sources. The studies in non-industrialised countries also differed in that the children were recruited and tested as part of the specific studies, whilst the studies in industrialised countries relied on cases initially diagnosed routinely.

The eight studies suitable for inclusion in the quantitative analysis were all carried out in just three countries in Europe (UK, Sweden and the Netherlands), where species data are routinely generated and all except one [11] were relatively recent, dated between 2013–2019. In many non-industrialised countries, or in earlier European studies, species identification would not be routinely performed, and this is reflected in the study data. The geographical reach of the eight studies is somewhat limited, since they were all located in northwest Europe. Only five were case-control studies, and of these, only two included both C. hominis and C. parvum, with the other three limited to studying C. hominis alone following outbreaks. Since the bulk of the cryptosporidiosis burden is found in low-income countries, there is a need in future to conduct similar quantitative evaluations using data from developing countries, where obtaining suitable data may be more challenging.

There were some limitations to this review. The role of genotype in long-term outcomes could not be explored. Typing was undertaken by gp60 sequencing in three of the studies but was either not analysed with symptoms data [16], or was an outbreak where all had the same subtype [4, 18]. There were insufficient data to compare between studies. Another limitation was that since not all cases were necessarily tested for all gastrointestinal pathogens, or the results of such tests were not stated, long-term sequelae identified cannot be proven to be Cryptosporidium-specific and not due to other infectious agents.

Most of the studies examined quantitatively were concentrated on adult individuals, whereas cryptosporidiosis is commonest in young children. This over-representation of adults results from the fact that several of the studies followed large waterborne outbreaks involving many adults, rather than sporadic cases. Identifying and defining sometimes rather non-specific sequelae is more difficult in very young children. However, a study by Carter et al. [21] of sporadic cases did include children, and in fact this study found that the proportion developing IBS or IBS-like symptoms was higher in children than in adults, with 78% reporting it among 5–17 years-old and 63% at 6 months to 4 years-old.

The results indicate that sequelae are frequently reported after cryptosporidiosis lasting up to at least 2 years. Only one study investigated cases for longer, up to 36 months [11]. For both main infecting species, sequelae occur, but there are differences in the frequency of each depending on the species. Following the publication of the first study in 2004 [15], the evidence base surrounding post-Cryptosporidium infection sequelae has continued to expand [16,17,18,19,20,21]. Gastrointestinal sequelae such as continuing diarrhoea, nausea and abdominal pain appear particularly common, each reported by around a quarter of cases up to 36 months post-infection, with analysis of the case-control studies finding that persistent diarrhoea is around six times more likely than in controls and weight loss over three times more likely over 28 months. Fatigue and headache were also commonly reported and occurred in the case-control studies between two-three times more commonly in cases than controls over the same time period. Overall, the most commonly reported long-term sequelae were diarrhoea (25%), abdominal pain (25%), nausea (24%), fatigue (24%) and headache (21%). Where it was investigated, there was evidence that symptoms meeting the definition for IBS were described just over 10% of cases up to 36 months.

Conclusions

This is the first systematic review of the long-term sequelae of cryptosporidiosis. The proportion of cases self-reporting sequelae post-infection has been estimated and estimates of risk of specific sequelae presented. Risk factors for sequelae were less well identified. A better understanding of the long-term outcomes of cryptosporidiosis is valuable to inform the expectations of clinicians and their patients and public health policy makers regarding the control and prevention of this infection.

Availability of data and materials

All data generated or analysed during this study are included in this published article and its additional files.

References

  1. Chalmers RM, Davies AP. Minireview: clinical cryptosporidiosis. Exp Parasitol. 2010;124:138–46.

    PubMed  Google Scholar 

  2. Monge S, Pijnacker R, Van Pelt W, Franz E, Kortbeek LM, Mangen MJJ. Accounting for long-term manifestations of Cryptosporidium spp. infection in burden of disease and cost-of-illness estimations, the Netherlands (2013–2017). PLoS ONE. 2019;14:1–16.

    Google Scholar 

  3. Efstratiou A, Ongerth JE, Karanis P. Waterborne transmission of protozoan parasites: review of worldwide outbreaks—an update 2011–2016. Water Res. 2017;114:14–22.

    PubMed  Google Scholar 

  4. Widerström M, Schönning C, Lilja M, Lebbad M, Ljung T, Allestam G, et al. Large outbreak of Cryptosporidium hominis infection transmitted through the public water supply, Sweden. Emerg Infect Dis. 2014;20:581–9.

    PubMed  PubMed Central  Google Scholar 

  5. MacKenzie WR, Schell WL, Blair KA, Addiss DG, Peterson DE, Hoxie NJ, et al. Massive outbreak of waterborne Cryptosporidium infection in Milwaukee, Wisconsin: recurrence of illness and risk of secondary transmission. Clin Infect Dis. 1995;21:57–62.

    CAS  PubMed  Google Scholar 

  6. DeSilva MB, Schafer S, Kendall Scott M, Robinson B, Hills A, Buser GL, et al. Communitywide cryptosporidiosis outbreak associated with a surface water-supplied municipal water system—Baker City, Oregon, 2013. Epidemiol Infect. 2016;14:274–84.

    Google Scholar 

  7. Chalmers RM, Robinson G, Elwin K, Elson R. Analysis of the Cryptosporidium spp. and gp60 subtypes linked to human outbreaks of cryptosporidiosis in England and Wales, 2009 to 2017. Parasit Vectors. 2009;2019(12):95.

    Google Scholar 

  8. Davies AP, Campbell B, Evans MR, Bone A, Roche ACR. Asymptomatic carriage of protozoan parasites in children in day care centers in the United Kingdom. Pediatr Infect Dis J. 2009;28:838–40.

    PubMed  Google Scholar 

  9. Reh L, Muadica AS, Köster PC, Balasegaram S, Verlander NQ, Chércoles ER, et al. Substantial prevalence of enteroparasites Cryptosporidium spp., Giardia duodenalis and Blastocystis sp. in asymptomatic schoolchildren in Madrid, Spain, November 2017 to June 2018. Euro Surveill. 2019;24:1900241.

    PubMed Central  Google Scholar 

  10. Ehsan MA, Akter M, Ahammed M, Ali MA, Ahmed MU. Prevalence and clinical importance of Cryptosporidium and Giardia in humans and animals. Bangladesh J Vet Med. 2016;14:109–22.

    Google Scholar 

  11. Shirley DT, Moonah SN, Kotloff KL. Burden of disease from cryptosporidiosis. Curr Opin Infect Dis. 2015;25:555–63.

    Google Scholar 

  12. Halliez MCBA. Extra-intestinal and long term consequences of Giardia duodenalis infections. World J Gastroenterol. 2013;19:8974–85.

    PubMed  PubMed Central  Google Scholar 

  13. Litleskare S, Rortveit G, Eide GE, Hanevik K, Langeland NWK. Prevalence of irritable bowel syndrome and chronic fatigue 10 years after Giardia infection. Clin Gastroenterol Hepatol. 2018;16:1064–72.

    PubMed  Google Scholar 

  14. Mørch K, Hanevik K, Rivenes AC, Bødtker JE, Næss H, Stubhaug B, et al. Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course. BMC Gastroenterol. 2013;13:28.

    PubMed  PubMed Central  Google Scholar 

  15. Hunter PR, Hughes S, Woodhouse S, Nicholas R, Syed Q, Chalmers RM, et al. Health sequelae of human cryptosporidiosis in immunocompetent patients. Clin Infect Dis. 2004;39:504–10.

    PubMed  Google Scholar 

  16. Insulander M, Silverlås C, Lebbad M, Karlsson L, Mattsson JG, Svenungsson B. Molecular epidemiology and clinical manifestations of human cryptosporidiosis in Sweden. Epidemiol Infect. 2013;141:1009–20.

    CAS  PubMed  Google Scholar 

  17. Rehn M, Wallensten A, Widerström M, Lilja M, Grunewald M, Stenmark S, et al. Post-infection symptoms following two large waterborne outbreaks of Cryptosporidium hominis in northern Sweden, 2010–2011. BMC Public Health. 2015;15:529.

    PubMed  PubMed Central  Google Scholar 

  18. Stiff RE, Davies AP, Mason BW, Hutchings HA, Chalmers RM. Long-term health effects after resolution of acute Cryptosporidium parvum infection: a 1-year follow-up of outbreak-associated cases. J Med Microbiol. 2017;66:1607–11.

    PubMed  Google Scholar 

  19. Iglói Z, Mughini-Gras L, Nic Lochlainn L, Barrasa A, Sane J, Mooij S, et al. Long-term sequelae of sporadic cryptosporidiosis: a follow-up study. Eur J Clin Microbiol Infect Dis. 2018;37:1377–84.

    PubMed  PubMed Central  Google Scholar 

  20. Lilja M, Widerström M, Lindh J. Persisting post-infection symptoms 2 years after a large waterborne outbreak of Cryptosporidium hominis in northern Sweden. BMC Res Notes. 2018;11:625.

    PubMed  PubMed Central  Google Scholar 

  21. Carter BL, Stiff RE, Elwin K, Hutchings HA, Mason BW, Davies AP, et al. Health sequelae of human cryptosporidiosis—a 12-month prospective follow-up study. Eur J Clin Microbiol Infect Dis. 2019;38:1709–17.

    CAS  PubMed  Google Scholar 

  22. Hay E, Winfield W, McKendrick MW. Reactive arthritis associated with Cryptosporidium enteritis. Br Med J (Clin Res Ed). 1987;295:248.

    CAS  Google Scholar 

  23. Shepherd RC, Smail PJ, Sinha GP. Reactive arthritis complicating cryptosporidial infection. Arch Dis Child. 1989;64:743–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Sing A, Bechtold S, Heesemann J, Belohradsky BH, Schmidt H. Reactive arthritis associated with prolonged cryptosporidial infection. J Infect. 2003;47:181–4.

    PubMed  Google Scholar 

  25. Cron RQ, Sherry DD. Reiter’s syndrome associated with cryptosporidial gastroenteritis. J Rheumatol. 1995;22:1962–3.

    CAS  PubMed  Google Scholar 

  26. Hawkins SP, Thomas RP, Teasdale C. Acute pancreatitis: a new finding in Cryptosporidium enteritis. Br Med J (Clin Res Ed). 1987;294:483–4.

    CAS  Google Scholar 

  27. Norby SM, Bharucha AE, Larson MV, Temesgen Z. Acute pancreatitis associated with Cryptosporidium parvum enteritis in an immunocompetent man. Clin Infect Dis. 2008;27:223–4.

    Google Scholar 

  28. Printza N, Sapountzi E, Dotis J, Papachristou F. Hemolytic uremic syndrome related to Cryptosporidium infection in an immunocompetent child. Pediatr Int. 2013;55:788–90.

    PubMed  Google Scholar 

  29. Kalantari N, Gorgani-Firouzjaee T, Ghaffari S, Bayani M, Ghaffari T, Chehrazi M. Association between Cryptosporidium infection and cancer: a systematic review and meta-analysis. Parasitol Int. 2020;74:101979.

    PubMed  Google Scholar 

  30. Bouwknegt M, Devleesschauwer B, Graham H, Robertson LJ, van der Giessen JW, The Euro-Fbp Workshop participants. Prioritisation of food-borne parasites in Europe, 2016. Euro Surveill. 2018;23:17-00161.

    PubMed Central  Google Scholar 

  31. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013;382:209–22.

    PubMed  Google Scholar 

  32. Cassini A, Colzani E, Pini A, Mangen MJ, Plass D, McDonald SA, et al. Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the burden of communicable diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013. Euro Surveill. 2018;23:17–00454.

    PubMed Central  Google Scholar 

  33. Mangen MJJ, Bouwknegt M, Friesema IHM, Haagsma JA, Kortbeek LM, Tariq L, et al. Cost-of-illness and disease burden of food-related pathogens in the Netherlands, 2011. Int J Food Microbiol. 2015;196:84–93.

    PubMed  Google Scholar 

  34. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2012. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.%0A. Accessed 4 June 2020.

  35. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health. 2013;67:974–8.

    PubMed  Google Scholar 

  36. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. London: The Cochrane Collaboration; 2011. http://handbook-5-1.cochrane.org/.

  37. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    PubMed  PubMed Central  Google Scholar 

  38. Agnew DG, Lima AA, Newman RD, Wuhib T, Moore RD, Guerrant RL, et al. Cryptosporidiosis in northeastern Brazilian children: association with increased diarrhea morbidity. J Infect Dis. 1998;177:754–60.

    CAS  PubMed  Google Scholar 

  39. Ajjampur SSR, Koshy B, Venkataramani M, Sarkar R, Joseph AA, Jacob KS, et al. Effect of cryptosporidial and giardial diarrhoea on social maturity, intelligence and physical growth in children in a semi-urban slum in south India. Ann Trop Paediatr. 2011;31:205–12.

    CAS  PubMed  Google Scholar 

  40. Berkman DS, Lescano AG, Gilman RH, Lopez SL, Black MM. Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow-up study. Lancet. 2002;359:564–71.

    PubMed  Google Scholar 

  41. Delahoy MJ, Omore R, Ayers TL, Schilling KA, Blackstock AJ, Ochieng JB, et al. Clinical, environmental, and behavioral characteristics associated with Cryptosporidium infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008–2012: the Global Enteric Multicenter Study (GEMS). PLoS Negl Trop Dis. 2018;12:e0006640.

    PubMed  PubMed Central  Google Scholar 

  42. Guerrant DI, Moore SR, Lima AA, Patrick PD, Schorling JB, Guerrant RL. Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil. Am J Trop Med Hyg. 1999;61:707–13.

    CAS  PubMed  Google Scholar 

  43. Korpe PS, Haque R, Gilchrist C, Valencia C, Niu F, Lu M, et al. Natural history of cryptosporidiosis in a longitudinal study of slum-dwelling Bangladeshi children: association with severe malnutrition. PLoS Negl Trop Dis. 2016;10:e0004564.

    PubMed  PubMed Central  Google Scholar 

  44. Phillips AD, Thomas AG, Walker-Smith JA. Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa. Gut. 1992;33:1057–61.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This research received no grant from any funding agency in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Swansea University Medical School, Swansea University, Singleton Park, Swansea, UK

    Bethan L. Carter, Rachel M. Chalmers & Angharad P. Davies

  2. Cryptosporidium Reference Unit, Public Health Wales Microbiology, Singleton Hospital, Sketty Lane, Swansea, Wales, UK

    Rachel M. Chalmers & Angharad P. Davies

Authors
  1. Bethan L. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel M. Chalmers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angharad P. Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BC undertook the literature search and screened the titles and abstracts for relevance initially after which they were independently screened by BC and APD to ensure consistent application of the pre-determined inclusion/exclusion criteria. Final inclusion of studies was decided by consensus, with any conflicts being reviewed by RMC. BC wrote the first draft and AD and RC added to and reviewed it. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Angharad P. Davies.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Additional file 1: Table S1.

Full electronic search strategies. Table S2. Newcastle-Ottawa quality assessment scale.

Additional file 2.

Data for individual sequelae.

Additional file 3.

PRISMA checklist.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carter, B.L., Chalmers, R.M. & Davies, A.P. Health sequelae of human cryptosporidiosis in industrialised countries: a systematic review. Parasites Vectors 13, 443 (2020). https://doi.org/10.1186/s13071-020-04308-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13071-020-04308-7

Keywords

Parasites & Vectors

ISSN: 1756-3305

Contact us