Extended Outbreak of Cryptosporidiosis in a Pediatric Hospital, China

Four Cryptosporidium spp. and 6 C. hominis subtypes were isolated from 102 of 6,284 patients in 3 pediatric hospitals in People’s Republic of China. A cryptosporidiosis outbreak was identified retrospectively. The outbreak lasted >1 year and affected 51.4% of patients in 1 hospital ward, where 2 C. hominis subtypes with different virulence were found.

Four Cryptosporidium spp. and 6 C. hominis subtypes were isolated from 102 of 6,284 patients in 3 pediatric hospitals in People's Republic of China. A cryptosporidiosis outbreak was identifi ed retrospectively. The outbreak lasted >1 year and affected 51.4% of patients in 1 hospital ward, where 2 C. hominis subtypes with different virulence were found S ince the 1980s, ≈20 outbreaks of cryptosporidiosis have been reported in health care facilities (1)(2)(3)(4)(5)(6)(7)(8)(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 2× by PCR, with positive and negative controls in each run. Prevalence rates and 95% CIs were computed; the χ 2 test was used to test differences. Odds ratios (ORs) and 95% CIs were calculated.
Cryptosporidiosis was more prevalent during February-July 2008 (p<0.01). Prevalence rates remained at ≈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 identifi ed 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 identifi ed in hospital II patients, and C. canis (1 case), C. hominis (4 cases), C. felis (2 cases), and C. meleagridis (2 cases) were identifi ed 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

Conclusions
Our data indicate that a cryptosporidiosis outbreak occurred among children in ward A of hospital I. This conclusion was supported by the following fi ndings: the rate of Cryptosporidium-positive cases in ward A (51.4%) was signifi cantly 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 handwashing 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 >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 (>38) of involved patients was high. Judged by the low occurrence of the 2 subtypes in other wards, most of the 32 IaA14R4and 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 signifi cantly 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 identifi ed 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 identifi cation and investigation of outbreaks in health care facilities.