Despite the clinical and public health importance of Cryptosporidium parvum, little is known about its transmission dynamics in cattle and other farm animals, especially in Iran and other Mideast countries. Currently, the maintenance of the parasites on cattle farms and the role of herd-to-herd transmission in cryptosporidiosis epidemiology are not clear (1).
Recent molecular epidemiologic studies of cryptosporidiosis have helped researchers to better understand the transmission of cryptosporidiosis in humans and the public health significance of Cryptosporidium spp. in animals and the environment (2, 3).
Because of the ability of Cryptosporidium spp. to infect humans and a wide variety of animals, and because of the ubiquitous presence of Cryptosporidium oocysts in the environment, humans can acquire Cryptosporidium infections through several transmission routes, such as direct contact with infected persons (person-to-person transmission) or animals (zoonotic transmission), and ingestion of contaminated food (foodborne transmission) and water (waterborne transmission). The relative importance of these transmission routes in the epidemiology of cryptosporidiosis is not entirely clear, largely due to the fact that traditional diagnostic tools do not have the ability to differentiate sources of parasites (3).
The use of molecular tools has been helpful in assessing the zoonotic potential of various Cryptosporidium species and the sources of human infection; it has begun to play a significant role in the characterization of transmission dynamics in different areas and in the determination of host specificity of various Cryptosporidium spp. The 60 kDa glycoprotein (gp60, also known as Cpgp15/45) gene encodes a precursor protein that is proteolytically cleaved to yield mature surface glycoproteins gp45 and gp15 (also known as Cp17), both of which are implicated in the attachment and invasion of enterocytes by sporozoites and merozoites.
An important feature of this gene is its high degree of sequence polymorphism in C. hominis, C. parvum, and C. meleagridis isolates. Several subtype families have been identified in these species: 7 subtype families in C. hominis (Ia–Ig), 2 zoonotic (IIa, IId) and 10 non-zoonotic (IIb, IIc, IIe–IIl) subtype families in C. parvum, and 6 subtype families in C. meleagridis (4). Within each subtype family, there are multiple subtypes based primarily on the number of tri-nucleotide repeats coding for the amino acid serine, as suggested by Sulaiman et al. (2005) (5).
The use of gp60 subtyping has allowed the identification of geographic and temporal differences in the transmission dynamics of cryptosporidiosis, the role of zoonotic infections in epidemiology, better appreciation of the public health significance of Cryptosporidium species/genotypes in ruminants and significance of parasite subtypes/strains in clinical manifestations and outbreak potentials, and the tracking of infection and contamination sources during outbreak and endemic investigations (1–5).
To our knowledge, there are several molecular epidemiological studies that have documented the presence of C. parvum and C. hominis In Iran (Table 1) (6–12). However, the distribution of subtypes of the two species in humans, animals and environmental is unclear. In the first characterization of Cryptosporidium subtypes in humans and cattle in Iran by sequence analysis of the gp60 gene, 47 samples of C. parvum (22 from children and 25 from cattle) and three of C. hominis (all from children) were characterized. Nine subtypes (two of C. hominis and seven of C. parvum) belonging to four subtype families were found. Cattle were mainly infected with C. parvum IIa subtypes and humans mostly with C. parvum IIa and IId subtypes (Table 2). The predominance of IIa and IId subtypes underlines the importance of zoonotic Cryptosporidium transmission in Iran. Thus, cattle could be a source of human infection with C. parvum IIa in Iran (13–15). Although the source of IId subtypes in humans is not yet clear, IId subtypes are known to be common in sheep and goats in some countries such as Spain (16) and in dairy cattle in some other countries such as Egypt (17) and China (18). Further molecular study in humans and animals is needed in order to determine the extent and animal source of zoonotic transmission of cryptosporidiosis in Iran.
Table 1.
Distribution of Cryptosporidium spp. in humans in Mideast countries
| Population | N | C. hominis | C. parvum | C. meleagridis | C. felis | C. canis | Mixed species | Reference |
|---|---|---|---|---|---|---|---|---|
| Iran | 15 | 4 | 12 | (9) | ||||
| Iran | 24 | 17 | 7 | (10) | ||||
| Iran | 21 | 15 | 6 | (11) | ||||
| Iran | 25 | 3 | 22 | (12) | ||||
| Turkey | 4 | 4 | (19) | |||||
| Kuwait | 62 | 3 | 58 | 2 | (5) | |||
| Kuwait | 83 | 22 | 61 | (20) | ||||
| Jordan | 44 | 20 | 22 | 1 | (21) | |||
| Saudi Arabia | 31 | 13 | 15 | 1 | 1 | (22) | ||
| Saudi Arabia | 53 | 9 | 43 | 1 | (23) | |||
| Egypt | 36 | 24 | 10 | 2 | (24) | |||
| Egypt | 15 | 9 | 3 | (25) |
Table 2.
Distribution of C. parvum subtypes in humans and cattle in Iran.
| subtype families | Subtype | No. of isolates | Source of Samples | Accession number |
|---|---|---|---|---|
| IIa | IIa A16G3R1 | 1 | Cattle | AB560739 |
| IId | IId A15G1 | 2 | Cattle | AB560740 |
| IIa | IIa A15G2R1 | 22 | Cattle | AB560741 |
| IId | IId A26G1 | 1 | Children with diarrhea | AB560742 |
| IId | IId A18G1 | 3 | Children with diarrhea | AB560743 |
| IIa | IIa A16G3R1 | 1 | Children with diarrhea | AB560744 |
| IId | IId A20G1a | 9 | Children with diarrhea | AB560745 |
| IId | IId A21G1a | 1 | Children with diarrhea | AB560746 |
| IIa | IIa A15G2R1 | 6 | Children with diarrhea | AB560747 |
| IId | IId A15G1 | 1 | Children with diarrhea | AB560748 |
The dominance of C. parvum and wide occurrence of IId C. parvum subtypes in humans in Iran is similar to the situation seen in other Mideast countries (9–12, 19–25) (Tables 1 and 3). Children in the Kuwait City are almost exclusively infected with IIa and IId subtypes, although they have little contact with farm animals. As the city uses desalinized sea water as drinking water, the C. parvum transmission appears to be anthroponotic in origin (5, 20). IId subtypes are also common in children in Saudi Arabia and Jordan (Table 3). In many industrialized nations in other areas, C. parvum infections are much less common in humans than C. hominis infections, with the exception of European countries and New Zealand, where both C. parvum and C. hominis are commonly seen in humans. In these industrialized nations, most C. parvum infections are caused by the IIa subtypes commonly found in cattle, indicating zoonotic transmission plays a significant role in cryptosporidiosis epidemiology. In contrast, humans in developing countries are much less commonly infected with C. parvum and most of the few C. parvum infections are caused by the anthroponotic IIc subtype family (2).
Table 3.
Distribution of C. parvum subtype families in humans in Mideast countries
In conclusion, preliminary molecular epidemiological studies have revealed some unique features of cryptosporidiosis transmission in humans in Iran and other Mideast countries. As the C. parvum subtype family IId was the dominant family causing cryptosporidiosis in humans in Iran (13–15), zoonotic transmission could possibly be involved. However, more extensive sampling of both humans and farm animals, especially sheep and goats, and collection of epidemiological data in case-control and longitudinal studies are needed for a better understanding of the sources of C. parvum infections in humans in Iran and other Mideast countries.
Acknowledgment
This work was supported in part by the National Natural science Foundation of China (grant no. 31110103901). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
References
- 1.Xiao L, Zhou L, Santin M, Yang W, Fayer R. Distribution of Cryptosporidium parvum subtypes in calves in eastern United States. Parasitol Res. 2007;100:701–706. doi: 10.1007/s00436-006-0337-2. [DOI] [PubMed] [Google Scholar]
- 2.Xiao L. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol. 2010;124:80–89. doi: 10.1016/j.exppara.2009.03.018. [DOI] [PubMed] [Google Scholar]
- 3.Xiao L, Bern C, Sulaiman IM, Lal AA. Molecular epidemiology of human cryptosporidiosis. In: Thompson M, editor. Cryptosporidium: from molecules to disease. Amsterdam: Elsevier; 2004. pp. 121–46. [Google Scholar]
- 4.Plutzer J, Karanis P. Genetic polymorphism in Cryptosporidium species: An update. Vet Parasitol. 2009;165:187–99. doi: 10.1016/j.vetpar.2009.07.003. [DOI] [PubMed] [Google Scholar]
- 5.Sulaiman IM, Hira PR, Zhou L, Al-Ali FM, Al-Shelahi FA, Shweiki HM, et al. Unique endemicity of cryptosporidiosis in children in Kuwait. J Clin Microbiol. 2005;43:2805–809. doi: 10.1128/JCM.43.6.2805-2809.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Keshavarz A, Athari A, Haghighi A, Kazami B, Abadi A, Nazemalhosseini-Mojarad E, et al. Genetic characterization of Cryptosporidium spp. among children with diarrhea in Tehran and Qazvin provinces, Iran. Iranian J Parasitol. 2008;3:30–36. [Google Scholar]
- 7.Keshavarz A, Haghighi A, Athari A, Kazemi B, Abadi A, Nazemalhosseini-Mojarad E. Prevalence and molecular characterization of bovine Cryptosporidium in Qazvin province, Iran. Vet Parasitol. 2009;160:316–18. doi: 10.1016/j.vetpar.2008.11.008. [DOI] [PubMed] [Google Scholar]
- 8.Keshavarz A, Nazemalhosseini-Mojarad E, Haghighi A, Taghipour N, Sahebekhtiari N, Nochi Z, Kazemi B. Survey of Cryptosporidium genetic diversity based on analysis of COWP, SSU-rRNA and TRAP-C2 polymorphic genes in children with diarrhea in provinces of Tehran and Qazvin. Pajohandeh. 2010;14:299–306. [In Persian] [Google Scholar]
- 9.Meamar AR, Rezaian M, Rezaie S, Mohraz M, Mohebali M, Mohammad K, et al. SSU-rRNA gene analysis of Cryptosporidium spp. in HIV positive and negative patients. Iranian J Publ Health. 2006;35:1–7. [Google Scholar]
- 10.Pirestani M, Sadraei J, Dalimi asl A, Zavvar M, Vaeznia H. Molecular characterization of Cryptosporidium isolates from human and bovine using 18s rRNA gene in Shahriar county of Tehran, Iran. Parasitol Res. 2008;103:467–72. doi: 10.1007/s00436-008-1008-2. [DOI] [PubMed] [Google Scholar]
- 11.Zavvar M, Sadraei J, Emadi H, Pirestani M. The use of a nested PCR-RFLP technique, based on the parasite's 18S ribosomal RNA, to characterise Cryptosporidium isolates from HIV/AIDS patients. Ann Trop Med Parasitol. 2008;102:597–601. doi: 10.1179/136485908X311876. [DOI] [PubMed] [Google Scholar]
- 12.Nazemalhosseini-Mojarad E, Keshavarz A, Taghipour N, Haghighi A, Kazemi B, Athari A. Genotyping of Cryptosporidium spp. in clinical samples: PCR-RFLP analysis of the TRAP-C2 gene. Gastroenterol Hepatol Bed Bench. 2011;4:29–33. [PMC free article] [PubMed] [Google Scholar]
- 13.Nazemalhosseini-Mojarad E, Haghighi A, Taghipour N, Keshavarz A, Mohebbi SR, Zali MR, Xiao L. Subtype analysis of Cryptosporidium parvum and C. hominis isolates from humans and cattle in Iran. Vet Parasitol. 2011;179:250–52. doi: 10.1016/j.vetpar.2011.01.051. [DOI] [PubMed] [Google Scholar]
- 14.Nazemalhosseini-Mojarad E, Taghipour N, Haghighi A, Keshavarz A, Rostami Nejad M, Zali MR. DNA fingerprinting of bovine Cryptosporidium isolates in Qazvin province. Iran koomesh. 2011;12:408–12. [Google Scholar]
- 15.Taghipour N, Nazemalhosseini-Mojarad E, Haghighi A, Rostami- Nejad M, Romani S, Keshavarz A, et al. Molecular Epidemiology of Cryptosporidiosis in Iranian children admitted to a Pediatric hospital in Tehran, Iran. Iranian J parasitol. 2011;6:41–45. [PMC free article] [PubMed] [Google Scholar]
- 16.Quilez J, Torres E, Chalmers RM, Hadfield SJ, Del Cacho E, Sanchez-Acedo C. Genotype and subtype characterization of Cryptosporidium in lambs and goat kids in Spain. Appl Environ Microbiol. 2008;74:6026–31. doi: 10.1128/AEM.00606-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Amer S, Honma H, Ikarashi M, Tada C, Fukuda Y, Suyama Y, Nakai Y. Cryptosporidium genotypes and subtypes in dairy calves in Egypt. Vet Parasitol. 2010;169:382–86. doi: 10.1016/j.vetpar.2010.01.017. [DOI] [PubMed] [Google Scholar]
- 18.Wang R, Wang H, Sun Y, Zhang L, Jian F, Qi M, et al. Characteristics of Cryptosporidium transmission in pre-weaned dairy cattle in Henan, China. J Clin Microbiol. 2011;49:1077–82. doi: 10.1128/JCM.02194-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Tamer GS, Turk M, Dagci H, Pektas B, Guy EC, Guruz AY, et al. The prevalence of cryptosporidiosis in Turkish children, and genotyping of isolates by nested polymerase chain reaction-restriction fragment length polymorphism. Saudi Med J. 2007;28:1243–46. [PubMed] [Google Scholar]
- 20.Iqbal J, Khalid N, Hira PR. Cryptosporidiosis in Kuwaiti children: association of clinical characteristics with Cryptosporidium species and subtypes. J Med Microbiol. 2011;60:647–52. doi: 10.1099/jmm.0.028001-0. [DOI] [PubMed] [Google Scholar]
- 21.Hijjawi N, Ng J, Yang R, Atoum MF, Ryan U. Identification of rare and novel Cryptosporidium GP60 subtypes in human isolates from Jordan. Exp Parasitol. 2010;125:161–64. doi: 10.1016/j.exppara.2010.01.011. [DOI] [PubMed] [Google Scholar]
- 22.Al-Brikan FA, Salem HS, Beeching N, Hilal N. Multilocus genetic analysis of Cryptosporidium isolates from Saudi Arabia. J Egypt Soc Parasitol. 2008;38:645–58. [PubMed] [Google Scholar]
- 23.Xiao L. Identification of Cryptosporidium GP60 subtypes in human isolates from Saudi Arabia; Unpublished data. [Google Scholar]
- 24.Abd El Kader NM, Blanco MA, Ali-Tammam M, Abd El Ghaffar AE, Osman A, El Sheikh N, et al. Detection of Cryptosporidium parvum and Cryptosporidium hominis in human patients in Cairo, Egypt. Parasitol Res. 2012;110:161–66. doi: 10.1007/s00436-011-2465-6. [DOI] [PubMed] [Google Scholar]
- 25.Eida AM, Eida MM, El-Desoky A. Pathological studies of different genotypes of human Cryptosporidium Egyptian isolates in experimentally mice. J Egypt Soc Parasitol. 2009;39:975–90. [PubMed] [Google Scholar]