Extended outbreak of cryptosporidiosis in a pediatric hospital, China.
Article Type: Report
Subject: Children (Health aspects)
Children's hospitals (Services)
Cryptosporidiosis (Risk factors)
Cryptosporidiosis (Research)
Cryptosporidiosis (Diagnosis)
Authors: Feng, Yaoyu
Wang, Lin
Duan, Liping
Gomez-Puerta, Luis A.
Zhang, Longxian
Zhao, Xukun
Hu, Jingjing
Zhang, Nan
Xiao, Lihua
Pub Date: 02/01/2012
Publication: Name: Emerging Infectious Diseases Publisher: U.S. National Center for Infectious Diseases Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 U.S. National Center for Infectious Diseases ISSN: 1080-6040
Issue: Date: Feb, 2012 Source Volume: 18 Source Issue: 2
Topic: Event Code: 360 Services information; 310 Science & research
Product: Product Code: E121920 Children
Geographic: Geographic Scope: China Geographic Code: 9CHIN China
Accession Number: 281175413
Full Text: Since the 1980s, [approximately equal to] 20 outbreaks of cryptosporidiosis have been reported in health care facilities (1-9). Thus far, to our knowledge, genotyping and subtyping tools have not been used in the investigation of this type of outbreak (10). We used subtyping in a molecular epidemiologic study of endemic cryptosporidiosis to retrospectively identify an extended outbreak among children in a hospital ward.

The Study

During September 2007-October 2009, fecal specimens were collected from children in hospitals I (3,245 patients), II (489), and III (2,550), in Shanghai, People's Republic of China. The children (1 month-19 years old, median 36 months) were hospitalized primarily for nongastrointestinal illnesses. For each patient, information was collected on age; sex; occurrence of diarrhea; and, later in the study, ward assignment in hospital I. The study was approved by the ethics committee of East China University of Science and Technology, Shanghai.

Cryptosporidium spp. were detected in the specimens and differentiated by PCR and restriction fragment length polymorphism analysis of the small subunit rRNA gene (11). C. hominis was subtyped by sequence analysis of the 60-kDa glycoprotein gene (12). Each specimen was analyzed at least 2x by PCR, with positive and negative controls in each run. Prevalence rates and 95% CIs were computed; the [chi square] test was used to test differences. Odds ratios (ORs) and 95% CIs were calculated.

Among the 6,284 patients, 102 were positive for Cryptosporidium spp.: 90 from hospital I (2.8%, 95% CI 2.2-3.3), 3 from hospital II (0.6%, 95% CI 0-1.3), and 9 from hospital III (0.4%, 95% CI 0.1-0.6) (p<0.01). Ward assignment was available for 1,592 of 3,245 patients in hospital I. In most of the 12 wards, the infection rate was 0%-2.3%; in ward A, it was 51.4% (p<0.01) (Table).

In hospital I, children <6 months old had a significantly higher positive rate (8.4%, 95% CI 5.6-11.2) than older children (1.9%, 95% CI 1.4-2.4) (p<0.01; data not shown). This was mainly because of a high infection rate among the age group in ward A (61.5%, 95% CI 36.9-86.2) versus those in other wards (40.0%, 95% CI 19.0-61.0). No age associated difference in infection rates was found in other wards (p = 0.80; data not shown).

Cryptosporidiosis was more prevalent during February-July 2008 (p<0.01). Prevalence rates remained at [approximately equal to] 6% in the monthly distribution of the 2 main C. hominis subtypes in hospital I; however, when adequate numbers of patients were sampled, rates of Cryptosporidium infection in ward A remained >28% in most study months.

C. hominis was identified in 90.2% (92/102) of Cryptosporidium-positive patients in the 3 hospitals, of whom 86 were patients in hospital I. In hospital I, C. hominis was detected only in ward A; C. meleagridis was isolated from 4 patients in other wards (Table). In contrast, C. canis (1 case) and C. hominis (2 cases) were identified in hospital II patients, and C. canis (1 case), C. hominis (4 cases), C. felis (2 cases), and C. meleagridis (2 cases) were identified in hospital III patients (Table).

Six C. hominis subtypes were found at the 3 hospitals; 4 were in 73 specimens from hospital I (Table). Of those 73 specimens, 71 (97.3%) were subtype IaA14R4 or IdA19, and they were mostly found in ward A and unknown wards (Table). Other subtypes (IbA19G2 and IdA14) were not found in ward A (Table). With 1 exception, subtypes in hospital I were not found in other hospitals; subtype IaA14R4 was found in 2 patients in hospital III. Likewise, subtypes IaA18R4 (in 1 patient in hospital II) and IgA14 (in 1 patient in hospital III) were not found in hospital I.

In hospital I, 44 of 1,084 patients with diarrhea (4.1%, 95% CI 2.9-5.3) and 46 of 2,161 without diarrhea (2.1%, 95% CI 1.5-2.7) were positive for Cryptosporidium spp. (p = 0.002, OR 1.95, 95% CI 1.28-2.96). C. hominis subtype IaA14R4 (21 diarrheic and 13 nondiarrheic cases) was significantly associated with diarrhea (p = 0.0004, OR 3.29, 95% CI 1.64-6.59), but subtype IdA19 (11 diarrheic and 26 nondiarrheic cases) was not (OR 0.86, 95% CI 0.42-1.75, p = 0.68).

Conclusions

Our data indicate that a cryptosporidiosis outbreak occurred among children in ward A of hospital I. This conclusion was supported by the following findings: the rate of Cryptosporidium-positive cases in ward A (51.4%) was significantly higher than the overall rates in hospitals I (2.8%), II (0.6%), and III (0.4%); less Cryptosporidium diversity was found in ward A (only C. hominis) than in other wards/hospitals (4 Cryptosporidium spp.); only C. hominis subtypes IaA14R4 and IdA19 were present among 38 ward A patients (vs. 6 subtypes in 12 patients in other wards/hospitals); and a high rate (61.5%) of Cryptosporidium-positive cases occurred in ward A among children <6 months old, an age that usually has a low prevalence of cryptosporidiosis (13).

The source of the cryptosporidiosis outbreak is unknown. Most of the 12 wards in hospital I were located in the main building; ward A, the smallest ward, was in an adjacent building and was for children from a welfare institute. Hired caregivers cared for children in ward A; family members were the primary caregivers for patients in other wards. Thus, poor diaper-changing and hand-washing practices by caregivers could be responsible for the persistence of C. hominis infections in ward A. However, the facts that most of the patients were examined for Cryptosporidium infection only once and that many of the specimens were not submitted immediately after patients were hospitalized prevented us from concluding with certainty whether the infections were acquired in the hospital or in the welfare institute. The likelihood for widespread foodborne and waterborne transmission of cryptosporidiosis in hospital I was small because children in ward A and other wards shared the same source for food and drinking water. The likelihood of direct transmission of cryptosporidiosis among ward A patients was also small because 80% of patients were <1 year old and mostly stayed in cribs and beds.

This cryptosporidiosis outbreak has several key features. First, it was lengthy, lasting [greater than or equal to] 14 months (November 2007-December 2008); only limited sampling was done before November 2007; and Cryptosporidium spp. were still present in December 2008. The longest previous outbreak was 4 months (14). Second, the number ([greater than or equal to] 38) of involved patients was high. Judged by the low occurrence of the 2 subtypes in other wards, most of the 32 IaA14R4-and IdA19-positive patients with missing ward information were probably also from ward A. Thus, >60 children might have been part of the outbreak. Third, this outbreak was caused concurrently by 2 C. hominis subtypes, of which IaA14R4, but not IdA19, was significantly associated with diarrhea. The observed difference in virulence is consistent with data from a community study in Peru (15), in which subtype family Ia, of which IaA14R4 is a member, was more virulent than Id, of which IdA19 is a member.

We retrospectively identified the outbreak by subtyping; the delay in detection prevented us from doing a thorough investigation, and continued sampling in the hospital and welfare institute and detailed epidemiologic and environmental investigation became impossible after we reported the outbreak to hospital I. Despite not knowing the source of infections, hospital I took measures to reduce hospital-acquired infections, including better training of caregivers and moving ward A to a new location. Thus, study data highlight the power of molecular epidemiologic tools in the surveillance and control of cryptosporidiosis and the need for prompt identification and investigation of outbreaks in health care facilities.

Acknowledgments

We thank the hospital personnel for assistance in specimen collection.

This work was supported in part by the National Natural Science Foundation of China (31110103901, 30928019 and 81041078); Fundamental Research Funds for the Central Universities, China (WB0914044); open funding projects of the State Key Laboratory of Bioreactor Engineering and the State Key Laboratory of Veterinary Etiological Biology.

Dr Feng is a professor at the East China University of Science and Technology. Her research interests are the molecular epidemiology, pathogenesis, transmission, and environmental ecology of waterborne and foodborne pathogens, such as Cryptosporidium and Giardia spp. and microsporidia.

References

(1.) Casemore DP, Gardner CA, O'Mahony C. Cryptosporidial infection, with special reference to nosocomial transmission of Cryptosporidium parvum: a review. Folia Parasitol (Praha). 1994;41:17-21.

(2.) Martino P, Gentile G, Caprioli A, Baldassarri L, Donelli G, Arcese W, et al. Hospital-acquired cryptosporidiosis in a bone marrow transplantation unit. J Infect Dis. 1988;158:647-8. http://dx.doi. org/10.1093/infdis/158.3.647

(3.) Neill MA, Rice SK, Ahmad NV, Flanigan TP. Cryptosporidiosis: an unrecognized cause of diarrhea in elderly hospitalized patients. Clin Infect Dis. 1996;22:168-70. http://dx.doi.org/10.1093/clinids/22.1.168

(4.) Pandak N, Zeljka K, Cvitkovic A. A family outbreak of cryptosporidiosis: probable nosocomial infection and person-to-person transmission. Wien Klin Wochenschr. 2006;118:485-7. http://dx.doi. org/10.1007/s00508-006-0637-7

(5.) el-Sibaei MM, Rifaat MM, Hameed DM, el-Din HM. Nosocomial sources of cryptosporidial infection in newly admitted patients in Ain Shams University Pediatric Hospital. J Egypt Soc Parasitol. 2003;33:177-88.

(6.) Weber DJ, Rutala WA. The emerging nosocomial pathogens Cryptosporidium, Escherichia coli O157:H7, Helicobacter pylori, and hepatitis C: epidemiology, environmental survival, efficacy of disinfection, and control measures. Infect Control Hosp Epidemiol. 2001;22:306-15. http://dx.doi.org/10.1086/501907

(7.) Bruce BB, Blass MA, Blumberg HM, Lennox JL, del Rio C, Horsburgh CR Jr. Risk of Cryptosporidium parvum transmission between hospital roommates. Clin Infect Dis. 2000;31:947-50. http://dx.doi. org/10.1086/318147

(8.) Navarrete S, Stetler HC, Avila C, Garcia Aranda JA, Santos-Preciado JI. An outbreak of Cryptosporidium diarrhea in a pedi atric hospital. Pediatr Infect Dis J. 1991;10:248-50. http://dx.doi. org/10.1097/00006454-199103000-00016

(9.) Sarabia-Arce S, Salazar-Lindo E, Gilman RH, Naranjo J, Miranda E. Case-control study of Cryptosporidium parvum infection in Peruvian children hospitalized for diarrhea: possible association with malnutrition and nosocomial infection. Pediatr Infect Dis J. 1990;9:627-31.

(10.) Xiao L, Ryan UM. Molecular epidemiology. In: Fayer R, Xiao L, editors. Cryptosporidium and cryptosporidiosis, 2nd ed. Boca Raton (FL): CRC Press and IWA Publishing; 2008. p. 119-71.

(11.) Jiang J, Alderisio KA, Xiao L. Distribution of Cryptosporidium genotypes in storm event water samples from three watersheds in New York. Appl Environ Microbiol. 2005;71:4446-54. http://dx.doi. org/10.1128/AEM.71.8.4446-4454.2005

(12.) Feng Y, Li N, Duan L, Xiao L. Cryptosporidium genotype and subtype distribution in raw wastewater in Shanghai, China: Evidence for possible unique Cryptosporidium hominis transmission. J Clin Microbiol. 2009;47:153-7. http://dx.doi.org/10.1128/JCM.0177708

(13.) Chen YG, Yao FB, Li HS, Shi WS, Dai MX, Lu M. Cryptosporidium infection and diarrhea in rural and urban areas of Jiangsu, People's Republic of China. J Clin Microbiol. 1992;30:492-4.

(14.) Ravn P, Lundgren JD, Kjaeldgaard P, Holten-Anderson W, Hojlyng N, Nielsen JO, et al. Nosocomial outbreak of cryptosporidiosis in AIDS patients. BMJ. 1991;302:277-80. http://dx.doi.org/10.1136/ bmj.302.6771.277

(15.) Cama VA, Bern C, Roberts J, Cabrera L, Sterling CR, Ortega Y, et al. Cryptosporidium species and subtypes and clinical manifestations in children, Peru. Emerg Infect Dis. 2008;14:1567-74. http://dx.doi. org/10.3201/eid1410.071273

Author affiliations: East China University of Science and Technology, Shanghai, People's Republic of China (Y. Feng, L. Wang, X. Zhao, J. Hu, N. Zhang); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (L. Wang, L. Duan, L.A. Gomez-Puerta, L. Xiao); and Henan Agricultural University, Zhengzhou, PRC (L. Zhang)

DOI: http://dx.doi.org/10.3201/eid1802.110666

Address for correspondence: Yaoyu Feng, State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China; email: yyfeng@ecust.edu.cn
Table. Distribution of Cryptosporidium spp. and subtypes among
wards in a hospital in Shanghai, People's Republic of China,
September 2007-October 2009 *

                                              No. patients positive
          No. patient      % Positive
Ward        samples         (95% CI)       C. meleagridis   C. hominis

A             74        51.4 (35.0-67.7)         0              38
B             348         0.6 (0-1.4)            1              1
C             283        1.8 (0.2-3.3)           2              3
D             216        2.3 (0.3-4.3)           1              4
E             266         1.1 (0-2.4)            0              3
F             56          1.8 (0-5.3)            0              1
Others        349              0                 0              0
Unknown      1653        2.2 (1.5-2.9)           0              36
Total        3,245        28 (2.2-3.3)           4              86

                 No. patients positive

Ward      IaA14R4   IdA19   IbA19G2   IdA14

A           19       14        0        0
B            0        1        0        0
C            0        1        0        1
D            2        1        1        0
E            0        1        0        0
F            0        0        0        0
Others       0        0        0        0
Unknown     13       19        0        0
Total       34       37        1        1

* Among 86 specimens positive for C. hominis, 78 were gp60
positive and 73 were subtyped. In 2 other hospitals, II and III,
among 6 C. hominis-specimens, 1 was IaA18R4 (hospital II), 1 was
IgA14 (hospital III), 2 were IaA14R4 (hospital III), and 2 were
gp60 negative (hospitals II and III); 2 patients each were
positive for C. meleagridis, C. canis, and C. felis.
Gale Copyright: Copyright 2012 Gale, Cengage Learning. All rights reserved.