What is Learned from Cryptosporidiosis Outbreak Cases in Japan日本のクリプトスポリジウム集団感染事例から学んだこと

Takuro Endo, National Institute of Infectious Diseases, MHLW,
Japan
国立感染症研究所‑ 107 ‑

遠藤卓郎

What is Learned from Cryptosporidiosis Outbreak Cases in Japan
Takuro ENDO and Shinji IZUMIYAMA
Department of Parasitology
National Institute of Infectious Diseases
Toyama 1-23-1, Shinjuku-Ku Tokyo 162-8640, Japan
Whilst previous models used to explain the causal event(s) to induce large-scale
outbreak of cryptosporidiosis have studied the affects of turbidity increase either indrinking-water or in source water on the spread of the disease to consumers, a newmodel used in the current study tests the affects of other variables such as an increased
temperature and thus inducing changes in quantities of unboiled water consumed byindividuals.
All the data used in the present manuscript are those already reported elsewhere byother workers, some were in Japanese and others were in English.

1.

Case report

There have been three outbreaks of large-scale cryptosporidiosis in Japan(1-2).
1.1.

Hiratsuka Case:

The first recognized cryptosporidiosis outbreak was in August and September 1994.
As of September 3, Kanagawa Prefectural Health Department received informationthat 22 customers who visited either of 10 public houses in a building at Hiratsuka City,
which is located in Kanagawa prefecture complained of cholera-like or flu-like
symptoms. Epidemiological surveys by questionnaires revealed that 461 out of 736
individuals who visited one of the public houses/restaurants became ill with theclinical manifestations including mucous and/or watery diarrhea (96.7%), abdominal
cramps (61.6%), fever (54.2%: lower than 39℃ = 84.1%, higher than 39℃ = 15.9%),
malaise(37.1%), nausea (32.8%) and headache (29.3%). Five were hospitalized.

Interviews with the patients showed no evidence of food items served in the public
houses that might significantly be associated with risk for developing illness. Oocystsof C. parvum were identified in12 (48.0%) out of 25 stool specimens. Cryptosporidial
oocysts were also demonstrated in tap water and other water samples from a receivingtank, an elevated tank, a domestic sewage pit, a sanitary sewage pit and an artesian
well water tank. Tanks and pits were constructed adjacent to each other on a basement‑ 108 ‑

floor of the building and there were cross connections between tanks and pits at theupper part of the tanks to reduce inner pressure in the receiving tank. Accidental
malfunction of the drainage system, according to the owner of the building, caused
contamination of drinking water with sanitary sewage through the cross connection.
1.2.

Ogose case:

The second case of the waterborne outbreak of cryptosporidiosis was detected when
there was a sudden increase in absentees among school children due to severe diarrhea
and abdominal cramps during early June to the middle of July, 1996, in Ogose, which islocated in Saitama prefecture, approximately 50 km northwest from Tokyo. Routinestool, food or beverage cultures failed to yield a pathogen. Stools subsequently weresent to laboratories at Saitama Provincial Institute of Health, where C. parvum was
isolated one week after the onset of a large-scale outbreak. It took another one week to
identify the oocysts from the city's tap water.
Of the total population of 13,809, 12,345 (89%) were interviewed. Of those, 8,812(71.4%) had illnesses with watery diarrhea and abdominal cramps; 24 were admitted tohospital. None of the patients developed bloody stool. Average length of illness was
4.1 days. Illnesses had subsided by the beginning of July.
Around 75% of the city's total water supply came from a mixture of surface waters(including river-bed water) from the Oppe River, its tributary and from a ground water(deep well), and was treated with prechlorination, coagulation and sedimentation,
followed by rapid filtration. Approximately 0.4 km upstream from water intake, there
is an effluent opening for the treated domestic and sanitary sewage (Fig. 1). According
to the business log there, there was little rainfall during the middle of May to June,
1996 resulting in severe drought. Approximately one week before the onset of outbreak(on May 25), unusually high turbidity 92 Unit (1U≒0.65NTU) was recorded in
sedimentation tank water.
1.3.

Awaji case

The third case was reported in February, 2002. As of March 3, Hyougo Prefectural
Health Department received information that 31 high school students and the teaching
staff who went to Hokkaido on a school excursion complained of severe diarrhea.
Epidemiological surveys by questionnaires revealed that 129 out of 212 individuals
became ill with the clinical manifestations including watery diarrhea (96.7%) and othersymptoms.

‑ 109 ‑

2.

Persons with brief exposure
Study participants met the following criteria: (1) They were nonresidents of the cities(or buildings) where outbreaks occurred; (2) they had visited only once there during
outbreaks; and (3) they had either laboratory-confirmed cryptosporidiosis or waterydiarrhea (clinical cryptosporidiosis). For each of the following cases, threereconstructed the incubation distribution curves in lines are presented in Fig. 2.
2.1.

Hiratsuka caseAs the outbreak of diarrhea has occurred among customers who visited either of 10
public houses in a building at Hiratsuka City, 299 the patients met the above criteria.
The mean incubation period was 6.0 days (95% C.I. 5.9-6.2 days). The solid line in Fig. 2
corresponds to a log-logistic distribution with median 5.5 days and 95% quantile: 7.6
days.
2.2.

Ogose caseDuring the outbreak period, 16 individuals, 7 primary school boys and 9 adultvisitors, had stayed less than 24 hours and reported having consumed tap water orbeverages containing unboiled tap water while in the Ogose Water Work service area.
The mean incubation period was 6.4 days (95% C.I. 6.0-6.8 days). The dotted line in Fig.
2 corresponds to a log-logistic distribution with median 5.8 days and 95% quantile: 7.0
days.
2.3.

Awaji case

Altogether 126 individuals with severe diarrhea who went to Hokkaido on a school
excursion met the study participant criteria. The mean incubation period was 6.4 days
(95% C.I. 6.2-6.6 days). The broken line in Fig. 2 corresponds to a log-logistic
distribution with median 5.9 days and 95% quantile: 7.6 days.

3.

Water consumption
Recent questionnaire survey (n=859) on daily intake of unboiled tap water showedthat approximately 50% of the people did not use unboiled tap water or bottled waterat all for drinking, and the average quantity of water consumed by individuals was 209
ml (Fig. 3) (3). From our preliminary estimation, the daily intake of unboiled tap water
consumed automatically through dietary process, tooth brushing and others issomething around 20 ml or less.

‑ 110 ‑

According to a marketing survey done by one of the biggest beer companies, peoplechange their drinking items properly as temperature increases; at 23-25°C and below
they enjoy drinking coffee, tea or other liquid items just for their tastes; over 25°C theystop drinking hot drinks; at 28-30°C and beyond they consume plain water to quench
their thirst (personal communication). In summary, there is a threshold temperature, at
25 C, beyond which people start to have plain water and other cold liquid items torelieve their thirst.

4.

Causal event(s) leading up to the large-scale outbreak of cryptosporidiosis in
Ogose

4.1.

Trends by date of onset over time

In the current study, reported date of onset of illness identified by a questionnairefrom May 1 through July 15, 1996 (Fig. 4) was reexamined. The figure shows that thecounted number of diarrhea events among survey participants peaked periodicallyevery 5 days, starting from May 10 through June 20 (Fig 4, dotted line). This might
represent available approximation of the date of onset of those who had vague
recollection of the date of onset of the disease. To smooth a data series and to identify
changes in trends, the predicted number of cases with a 5-day moving average is
depicted in the same figure (solid line).
4.2.

Correlation between turbidity and illness

Like other cryptosporidiosis outbreak cases, the Ogose outbreak was preceded by a
sharp increase in the turbidity of source water to 92 KTU (1 KTU = 1.7NTU) for a shortperiod (Fig. 5). This was believed to have affected the treatment plant and resulted in
the high load of cryptosporidial oocysts in the tap water to a level high enough tocause a large-scale outbreak of cryptosporidiosis. However, there was no evidence that
supports this presumption of cause and effect. With a single exposure, even if it werehigh doses of the oocysts in drinking water due to elevated turbidity, onset of illness
would have ceased within a few days after initial onset of the event (Fig. 2), while theoutbreak continued for a month from June 1 to July 4, 1996. Time series of both daily
maximum and average turbidities of the source water before and during the outbreakand daily counts of illness are shown in Figs. 6a-f. No correlation was observed
between daily counts of onset of cryptosporidiosis and turbidity at given lag periods
from 7 to 9days; based on a distribution of incubation periods in the population of 6days (median incubation period) + days required for water treatment and distribution.

‑ 111 ‑

4.3.

Correlation between temperature and illness

Alternatively, the current analysis suggests that there may also have been a small
increase in transmission of gastroenteritis cases in 2-3 weeks before the large outbreak,regardless of elevation of turbidity (Fig. 5).
Since it was a time of seasonal transition from spring to summer when the Ogose
outbreak occurred, we drew attention to the correlation between temperature andillness. It is assumable that people drinks more water as temperature increased, whichmay, in turn, result in the increase in the risk of infection if water were polluted to acertain extent by cryptosporidial oocysts. The daily maximum temperature before May
21 was below 22 °C, then gradually increased to 25 °C in successive 3 days. From May
24, it exceeded 25°C, and reached to 28 °C on May 26, the 6 day before the first peak ofdate of onset (93 diarrhea cases) (Fig. 7).
Figure 8 shows the relation between the gastroenteritis events and the daily
maximum temperature with a lag of 6 days during pre-outbreak period. The daily
counts of illness increase markedly when daily maximum temperature exceeded at 25
C, the threshold temperature as was reported trend of water drinking habit. Provided
that people there started to drink a cup of unboiled tap water (200 ml) to relieve theirthirst as the daily maximum temperature exceeded the threshold temperature, and that
there was low level of contamination of Cryptosporidium oocysts in drinking water as
seen in Fig. 5, the risk of infection due to Cryptosporidium increased 10 times, resulting
in approximately 100 gastroenteritis cases in a day.
The daily estimated number of oocysts in tap water was calculated base on theumber of reported cases in each day using 20 ml (below 25°C) and 200ml (25°C andbeyond) for the amount of water consumed in accordance with the water drinking
habit, and were plotted with a lag of 6 days on the Fig. 9. The number of oocysts
remained to be around 0.5 oocysts/L in tap water during pre-outbreak and the initialstage of large outbreak from early May to May 29. Then the number of oocysts
increased to the order of 100 oocysts/L on May 31, in consequence of sewage recharge
system to put water back into the river (Fig. 1), leading up to the large-scalewaterborne outbreak of cryptosporidiosis in Ogose. In other words, 0.5 oocysts/L isenough to induce 100 diarrhea cases (cryptosporidiosis) when 14,000 residents in
Ogose drink a cap of unboiled tap water.
Although there are a number of data estimates being used in the present study as
substitutes for data that do not currently exist, it is sensible to note that there was clear
association between amount of drinking water consumed and cryptosporidiosis in‑ 112 ‑

Ogose case.
5.

References
1

Yamamoto N, Urabe K, Takaoka M, Nakazawa K, Gotoh A, Haga M, Fuchigami H,
Kimata I, Iseki M. Outbreak of cryptosporidiosis after contamination of the public
water supply in Saitama Prefecture, Japan, in 1996. Kansenshogaku Zasshi. 2000
Jun;74(6):518-26.

2

Kuroki T, Watanabe Y, Asai Y, Yamai S, Endo T, Uni S, Kimata I, Iseki M. [Anoutbreak of waterborne Cryptosporidiosis in Kanagawa, Japan] Kansenshogaku
Zasshi. 1996 Feb;70(2):132-40. (In Japanese)3

Yano K, Hosaka M, Otaki M, Tanaka A, Iyo T, Tosa K, Ichikawa H. Daily usage oftap water and bottled water for drinking in Japan. (2000) Japan Society on Water
Environment. (In Japanese)‑ 113 ‑

Distribution

1.0

House

0.9

House

Cumulative Probability

0.8

House

Water
treatment
plant

Oppegawa river

40

1000
800

140
120

600

100
80

400

60
200

20

7/5

6/30

0
6/25

0
6/20

200

6/15

20

6/10

400

6/5

40

5/31

600

5/26

60

5/21

800

Incident Cases

7/15

7/10

7/5

6/30

6/25

6/20

Fig. 4. A five days moving average view of onsetof illness and observed number of cases in Ogose.

80

5/16

6/15

Time in Days

1000

5/11

6/10

6/5

5/31

5/26

0
5/21

0

100

5/6

10

40

Fig. 3. Frequency of average daily intake of unboiled
water and its cumulative frequency. (Redrawn fromYano et al. 2000)

5/1

8

160

Quantity of water consumed (mL)

KTU (Kaorin Turbidity Unit)

6

180

5/16

1600

1400

1200

1000

800

0

600

0

400

20

200

10

4

200

5/1

20

2

Time in Days
Fig. 5. Time series of daily counts of illness and daily maximum
turbidity in source water of the Ogose water treatment plant.

‑ 114 ‑

Incident Cases

60

0.1

Fig. 2. Maximum likelihood fit of incubation distributionsof persons with brief exposure among 3 outbreak cases.

Incident Cases

30

0.2

Number of days since exposure

Cumulative Frequency (%)

800Frequency (%)

40

0.3

0

Fig. 1. Diagrammatic representation of sites ofwater and sewage treatment processes in Ogose.

100

0.4

0.0

Intake

50

0.5

5/6

Discharge

0.6

5/11

Sewagedisposal
plant

0.7

A) Maximum turbidity with a 7-day lag period.

B) Average turbidity with a 7-day lag period.

450

450

400
System 1

Incident Cases

350

400

System 2

350

300

300

250

250

200

200

150

150

100

100

50

50

0

0

0

20

40
60
Turbidity

80

0

100

C) Maximum turbidity with a 8-day lag period.

450

400

400

350

350

300

300

250

250

200

200

150

150

100

100

50

50

0

0
20

40

60

80

0

100

E) Maximum turbidity with a 9-day lag period.

10

15

20

25

30

D) Average turbidity with a 8-day lag period.

450

0

5

5

10

15

20

25

30

F) Average turbidity with a 9-day lag period.

450

450

400

400

350

350

300

300

250

250

200

200

150

150

100

100

50

50
0

0
0

20

40

60

80

0

100

5

10

15

20

25

Fig. 6. Correlations between both daily maximum and average turbidities of source
water and illness at lag periods of 7 - 9 days during pre-outbreak period.

‑ 115 ‑

30

30
25

150

20

100

15

6/10

6/5

5/31

5/26

5/21

5/16

5
5/11

0
5/6

10
5/1

50

500

Incident Cases

200

Maximum temperature (°C)

35

100
50

6/9

6/4

5/30

0

Estimated concentration of oocysts (/L)

150

5/25

100

20

25

30

35

Fig. 8.
Relation between daily counts of illness andmaximum temperature at a lag period of 6 days during
pre-outbreak period.

5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
5/20

200

Maximum temperature (°C)

200

5/15

300

15

Fig. 7. Time series of daily counts of illness anddaily maximum temperature.

5/10

400

0

Time in Days

Incident Cases

Incident Cases

250

Time in Days
Fig. 9. Daily counts of illness and estimated number ofoocysts in tap water at a lag period of 6 days during
pre-outbreak period.

‑ 116 ‑

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