Research Project

Incident Action Plan: Platyhelminthes Medical Response Plan for

Clonorchis sinensis​ Outbreak

Presented by

Chanatda Sareerat 1105 6161121

Chanya Goysookho 1102 6161213

Nutthunyawadee Suksodkiew 1105 6161008

Pimpichada Krittiyasrisumet 1102 6161084

Supawan Sangnuch 1104 6161041

Presented to

Mr. Andrew James Flipzack

Advanced Biology - A

Mahidol University International Demonstration School

AY 2019-2020
Table of Contents

Content Page

​Executive Summary (BLUF) ....................................................................... 2

Situation 3

Organism ……………………………………………………………. 3

Area ………………………………………………………………….... 4

Current Situation …………………………………………………….. 4

Health 6

Sign​s/symptoms, Diagnosis, Prognosis …………………………….... 6

Constraints & Restraints 7

Response Procedures 8

Organism control measures .....………………………………………. 8

Care for Sick …..……………………………………………………... 8

Projections …………………………………………………………… 10

Costs ………………………………………………………………....... 12

Prevention Steps 13

Bio/ Chem, Econ/Poli, Outreach/ Education ..………………………. 13

Conclusion 14

References 15

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Executive Summary (BLUF)

This IAP is a response plan to an outbreak of ​Clonorchis sinensis in the northern part of
Thailand. The area of the outbreak has 10,000 people in total. From the report, there is a total number
of 202 active cases and 34 deaths. If medical care is not given, the number will keep rising.

As we are a part of the Medical Disaster Assistance Response Team, or Med-DART, we want
to educate people about the disease. This will involve giving detailed information about the fluke: its
life cycle, prevention, and avoidance, also the outcomes if the preventive procedures are not followed.
To do this, we will have an educational team that would be able to move to different sub-communities
regularly. These knowledge will also be published in books, magazines, and newspapers to allow
many people to see. We would also set up sanitation systems for the whole region for waste
management, as well as sterilization of human feces before use in agricultural practices. This is one of
the important factors of the spreading of the disease. It will prevent the parasite from entering the life
cycle and into its hosts.

In cases of already infected patients, we will give medication treatments. To treat this disease,
25mg/kg of Praziquantel will be given as it is recommended for the most effective and safe. Though,
this could be either Albendazole or Praziquantel, depending on the situation and the health issues of
the patients. Pregnant and pediatrics patients may have to take more cautions with these medications.

Our economic-aiding measures involve distributing cooked food to the people in need for a
set amount of time; provide some funds to help with the development of technology for stool
examination. In terms of political measures, the local government should legislate the law that will
help reduce the rate of the disease. The law should concern the population’s health and safety, such as
encouraging the people to get some regular checkups of their blood to test for the fluke in their body.

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Situation

Organism

Clonorchis sinensis is a liver fluke of the Trematoda class and Platyhelminthes phylum. It is
found in specific regions which are eastern Asia and south Pacific Asia; mainly in China, Korea,
Vietnam, Taiwan, Japan and Thailand. Chinese liver flukes can live in aquatic and terrestrial habitats,
including grassland, rainforest, lakes, rivers, swamps, and etc. ​Clonorchis sinensis is hermaphroditic.
Each sexually mature adult fluke can produce around 4000 eggs daily for at least the first 6 months,
through the process of cross-fertilisation.

The flukes are born as eggs, produced by sexually mature flukes. The eggs have the length of
26-30 micrometers. They are surrounded with a thick yellow-brown shell which serves as a
protection. The eggs can be found in the definitive hosts or in the water where its population lives.
These eggs have high mortality because appropriate hosts are hard to find. As the eggs hatch, the ​C.
sinensis develops to the next stage: miracidium. This is the ciliated larval stage of the fluke that has
two eyespots and they could be detected in a microscopic sight. They use lateral papillae to sense their
surroundings. When miracidium grows, they enter the sporocyst stage where they can initially infect a
snail host. They look like a hollow body with sacs inside. Sometimes, the developing rediae can be
spotted in those sacs. The next stage of the fluke is the redia. The flukes start to shape like a worm
structure, but only contain pharynx, with no esophagus or intestine. The development of the next level
can be seen in their bodies: cercaria. In the next stage, they are like small adults with a tail which
helps it move. Unlike adults, they have two eyespots, penetration glands and a stylet at the anterior
end, and a cuticle with small spines. Metacercaria is the next phase the fluke enters. It loses all of its
larval organs which are the eyespots, the stylet, and the tail. Lastly, the river fluke reaches its last
stage becoming an adult. Flukes in this phase are very thin and short with only 10-25 millimeters
long. They develop many characteristics such as anterior sucker, vetal sucker, though they have no
blood circulatory system, and no body cavity.

The life cycle consists of three host-systems. Freshwater snails are the first intermediate hosts,
with a total of 10 species belonging to 3 families of freshwater snails that can serve as first
intermediate hosts. Freshwater snails are found in cool areas with slow-moving water, such as lakes,
streams, ponds, small ditches, etc. Followed by the second intermediate hosts which are freshwater

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fish and shrimps. Fishes that serve as second intermediate hosts are of the Cyphrinidae family, a
freshwater fish commonly used as food. An alternative second intermediate host would be freshwater
crustaceans, including some crabs and crayfishes. The definitive hosts are humans and carnivorous
animals.  

To sum up, the cycle starts when humans ingest the parasite from eating raw or uncooked
meat. The metacercariae exists in the duodenum and moves to the bile ducts. Once it grows, it releases
eggs that will be excreted through human feces. The eggs will later be ingested by freshwater snails,
the first intermediate host, then it will grow into a miracidium stage. In this phase, the flukes develop
themselves in sporocysts, radiae, and cercariae substages in the hosts’ intestines. The cercariae
substage of C. sinensis swims out of the body and enters the second intermediate host, freshwater fish
as metacercariae. These hosts are eaten by humans and in the case of being undercooked, the cycle
reloops.

Area

The area where the infections of Clonorchis sinensis are occurring is in the northern part of
Thailand. The total population of this rural region is 10,000. There is no mass transit and no system of
sanitation here, partly due to its geography. Northern Thailand has many mountains, hills, water sites,
and various kinds of forests: evergreen, mixed deciduous, rain forest, etc. These forests are homes for
all kinds of animals and insects such as mice, bats and snails. The major river sources of the people
there are Nan river, Mekong river, and Kok river. The population in the area mainly rely on these
rivers and some others since there is no sanitation. So, it is likely that people can ingest the flukes
without noticing.

Most of the people living here are Buddhist, 97.57%, followed by Muslims with 1.29%,
1.11% Christian and 0.03% are Hindus. Many popular dishes seem to be well cooked, but one of the
menu is Laab, which people sometimes tend to eat the meat rawly. Besides the popular dishes, there
are also a variety of foods which people would eat whether cooked or uncooked and their sources of
ingredients are forests and rivers. Vegetables are very common as the side dishes of every Thai menu.
However, in between the leaves of the plant could exist the parasite that comes from the soil along
with the water sources. This, basically, concludes that the flukes live in both flora and fauna.

The local economy here depends on agriculture. About ⅓ of the people raise animals, such as
cattles, pigs and sheep, for their living, which are directly in touch with the source of parasites. Meat
and other products from these animals can be transported to all major cities in Thailand.

Current Situation

Currently, the Chinese liver fluke is infecting the northern part of Thailand. As shown in the
table of Fig.1, the first start of the infection was in September with only one person having the
disease. However, the amount of new cases increases rapidly month by month. The current data
showed up to April with the total number of 202 known cases of Clonorchiasis and is reported with 34
deaths. Although, the local medical personnel believe that the actual number would be much higher
when included with the unknown number.

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 In the area of infection, there are 10,000 people with no mass transit between the
interconnected towns, but people would still move to other towns for jobs and other purposes. By
moving around, the rate of the spread will definitely increase to be much higher. There are great
hospitals in town, but right now, they are too small to accommodate the number of infected people.
Though, the law enforcement is good, people would follow every regulation given.

Month New Cases Total Cases

September 1 1

October 3 4

November 10 14

December 25 39

January 29 68

February 35 103

March 52 155

April 47 202
Fig.1 Table of current number of cases from the start of the outbreak

Fig.2 Line chart of current number of cases

It is predicted that the rate of infections will decrease by approximately 15 cases per month if
the situation is intervened now. The number of cases will eventually reach 0. On the other hand, if the
outbreak is waited three months before action, the case will be decreased by ten per month. Still,
within the range of three months, the case will keep rising.

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Health

 
Sign​s/symptoms

People who are infected with ​Clonorchis sinensis will usually not show any symptom.
However, in some cases, the patients will have the symptoms of having a fever, chills, nausea,
experience epigastric (upper abdominal) pain, mild jaundice; a condition in which skin and white eyes
turn yellow as a result of high bilirubin (yellow-orange bile pigment), and infection of bile stasis.

Diagnosis

The diagnosis of Clonorchiasis can be made by finding eggs in the feces or duodenum, which
can be done through ultrasound and MRI (magnetic resonance imaging scans). Other methods consist
of analysing surgical specimens for identification of adult flukes and performing percutaneous
transhepatic cholangiography (PTC), which involve an injection of a contrast medium into the bile
duct and taking an X-ray where the image will be examined. Confirmation of diagnosis can be made
several ways, including: parasitological techniques, immunological techniques, and molecular
techniques. Parasitological technique is the detection of ​Clonorchis eggs in stool samples and can
only be used with patients in the chronic phase. Immunological technique is the detection of
antibodies or antigens of a specific worm in serum or stool samples.

Prognosis

The prognosis consists of infection of the liver, gallbladder, and bile duct. Most infected
people wouldn’t show any symptoms at first, however, a long-time infection can lead to severe
conditions. If patients follow the medication plan, there will be no problem. Cases that require surgery
due to a severer condition will require a longer recovery period. Re-infection can lead to chronic
clonorchiasis, in which infected people will experience chronic inflammation. This results in fibrosis
of the ducts and destruction of the liver parenchyma. A common disease that rises from this is
Cholangiohepatitis. Moreover, Chronic clonorchiasis is linked with cholangiocarcinoma, a form of
bile duct cancer.

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Constraints & Restraints

Constraints

There are certain constraints which prevent some certain aspects of our response which could
have been effective. First of all, due to hospitals’ capacity, mass chemotherapy cannot be done.
Moreover, a lack of knowledge regarding the developmental cycle of the parasite in infected first and
second intermediate hosts limits us from taking the most effective measures to prevent further
infection of hosts. Another limitation has to do with the agricultural practices which should be
switched from using human feces to fertilization to reduce infections. However, because fertilizers are
more costly, this is most likely not possible. Detection of ​C. sinensis metacercariae in fish can be done
through PCR or LAMP, however due to time constraints and cost effectiveness, LAMP is more
preferable.

Restraints

Due to cultural and religious aspects, there are a few actions that would be absolutely
prohibited in this area. Firstly, domestic animals and other infected animals cannot be killed. Nearly
100% of the population here is Buddhism, so killing large living creatures is way too beyond the
limits of the religion. Along with the religious facet, livestocks are the main source of the
community’s income. People earn daily wages from farming and selling these animals’ products.
Secondly, even slaughtering animals is prohibited, hence, killing infected people is a lot worse, in
terms of both religion and culture. Lastly, mixing some chemicals into the water sites is too risky
since every citizen is dependent on these sources for their water, including daily uses and agricultural
uses. The chemicals could seriously affect the environment and the health of the reliance lives.

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Response Procedures

Organism control measures

As a response to prevent further infection, we must limit the chances of the parasite getting
into humans’ digestive system. This is because the situation takes place in the northern part of
Thailand, where people rely on the river for food and may eat it with some unsafe methods. Therefore,
we need to educate the people there to avoid them from eating raw fish that are processed through
pickled, salted, and smoked. To achieve this, we can start an educational organization who can move
to different sub-communities every now and then to give them knowledge regarding the ways to
prevent and the outcomes if they don’t follow the preventive procedures. This can be done with small
learning activities among the sub-communities, as well as in schools. To set an educational plan, we
may need to come up with the contents first. After we are done with the content creation, which will
consist of the basic information about the parasite, the life cycle of the parasite, the method that we
can stop each stage of the parasite development, etc. People will know the way to prevent themselves
from the parasite and they may stop their risky habits which will control the organism from infecting
humans. Another measure we can take is to set up a sanitation system for waste disposal, to prevent
the parasite from entering the first intermediate host, as well as other hosts and continue its life cycle.
Fishes is risky areas can be captured for PCR (polymerase chain reaction), a process which amplify
DNA samples, or through loop-mediated isothermal amplification (LAMP), which allow a sensitive
and rapid detection of C. sinensis metacercariae in fish, proved to be more efficient than PCR.
Immediate detection of parasites will make it easier to control further infections of later hosts.

Care for Sick

Prescription of medicine

For the treatment of Clonorchiasis, we can use Praziquantel (PZQ) 25 mg/kg among the
patients 3 times for 2 to 3 days. According to the World Health Organization, it is recommended as
one of the most effective and safe medicines. However, it also has some side effects such as headache,
vomiting, abdominal pain, poor coordination, and may also include allergic reactions. For pregnant
women, there have been no valid studies, but evidence has shown there is no difference in children
whose mothers were treated with Praziquantel. Moreover, treatment during lactation is recommended
because when breastfeeding, Praziquantel is excreted only at low concentrations. In pediatric patients
of children less than 4 years old, many children were reported to be treated with no negative effects.
For safety purposes, their risk of treatment has to be balanced with the risk of disease progression if
no treatment is taken. Another medicine for curing is Albendazole 10 mg/kg once a day for one week.
However, it is considered less safe as a skip in dosing can increase the risk of infection. There is
limited information on the use of Albendazole on pregnant women, therefore, great caution has to be
taken, especially when breastfeeding. According to past evidence, there has been no difference in
children whose mothers were prescribed with Praziquantel. For pediatric patients, it has been reported
safe for children less than 6 years old.

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Surgical treatments

Patients who are experiencing chronic pain may use the pain relievers for treating the
symptoms. Else, the patient could have the surgery for the biliary obstruction problem. People who
had a history of injection drug use were less likely to have been infected than those who had no
history of infection drug use.

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Projections

Intervene now (New cases)

Fig. 3.1 line chart of number of new cases if intervene now

Delay intervene (New cases)

Fig. 3.2 line chart of number of new cases if delay intervene by three months

Comparing the two graphs, there is a difference in the trend during the months of May, June
and July. While intervening now shows a decreasing pattern, delay intervention shows a constant rate
of new infections, then later decreases after the plan is intervened. Moreover, the project is extended
for another 5 months after intervening for delay intervention, while intervention now gives immediate
results of a decreasing number of new cases that requires 3 months to end the infection. Last but not
least, intervention now provides a steeper gradient which suggests a faster rate in reduction rate of
new infection.

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Intervene now (Total cases)

Fig. 3.3​ ​line chart of total number of cases if intervene now

Delay intervene (Total cases)

Fig. 3.4​ ​line chart of total number of cases if delay intervention by three months

Overall, the trends for both intervene now and delay intervention look similar. After
intervening, the gradient becomes less steep for both intervene now and delay intervention, which
suggests a slower rate of infection, until a point when it becomes constant, which is when there are no
new cases. However in the case of delaying intervention, the period of controlling the infection
extends for another five months. The total number of cases at the end of the response for delay
intervention is almost double of the total number for intervening now, having the value at 452 and
249, respectively.

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Costs

Total Cost (Immediate Intervention): ​249,000 ฿ [1,000 ฿ per person]

Month New Cases Total Cases
September 1 1
October 3 4
November 10 14
December 25 39
January 29 68
February 35 103
March 52 155
April 47 202
May 32 234
June 15 249
July 0 249
Fig.3.3.1 Table of total cases of immediate intervention (for total cost)

Total Cost (Delay Intervention): ​452,000 ฿ [1,000 ฿ per person]

Month New Cases Total Cases
September 1 1
October 3 4
November 10 14
December 25 39
January 29 68
February 35 103
March 52 155
April 47 202
May 50 252
June 54 306
July 49 355
August 39 394
September 30 424
October 18 442
November 10 452
December 0 452
Fig.3.4.1 Table of total cases of delay intervention (for total cost)

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Prevention Steps

Preventive measures (Biologically / Chemically)

A combination of different measures can be taken to provide the best control of clonorchiasis.
These measures include preventive chemotherapy, environmental reconstructions and certain
restrictions for the residents when it comes to consuming meat.

Chemotherapy through single administration of praziquantel (PZQ) at a dosage of 40 mg/kg

for infected people and selective for those at risk, because of hospital capacity, mass chemotherapy
cannot be done.

Residents should avoid eating undercooked or raw freshwater fish, this includes: raw, salted,
pickled, smoked, marinated, dried fish. Fish should have an internal temperature of more than 63 °C
before being consumed. Freezing fish at -20°C should be freezed for a minimum of 7 days. Or freeze
at -35°C or below until solid, then store at -35°C or -20°C, for at least 15 hours or 24 hours,
respectively.

Sanitation systems including toilets should be set up in areas with no freshwater snails and
fishponds to avoid ingestion of their early life stages by their intermediate hosts. Another measure that
would help prevent the flukes to enter its first intermediate host is to sterilize human feces. In the rural
area, human and domestic animal feces are quite important as they serve as a natural fertilizer that is
absolutely free. So, if the feces are sterilized beforehand, there would be no existing parasite in the
wastes.

Preventive measures (Economically / Politically)

In terms of economics, sales of fish may reduce as people who live near the imperiled area
will be limited to a certain degree in catching some marines until Clonorchis sinensis is controlled. At
the same time, the government can distribute some cooked foods as their substitutes toward the people
within both the sub-communities and the cities for a while. Moreover, governments should provide
funds for the technology in the area, in particular, for better measures of stool examination, where
results can be provided more immediately and accurately. For politics, the government should
legislate the law in the term to lessen the rate of Clonorchiasis​. In the law process, the government
should encourage people to go and have a medical check up for this disease every now and then. For
the medication, the patient may need to allow the technician to use their blood or even their stool to
investigate for the parasite.

Outreach / Education

Health education is necessary to maintain the control of clonorchiasis, therefore spreading

awareness of ​Clonorchis sinensis infection and the preventive steps they can take is vital. This can be
done through broadcasting and handing out health guide books. Moreover, billboards and posters can
also be used, and as mentioned earlier, an educational organisation can provide education every now
and then. With a lack of knowledge on the diseases concerning eating raw fish, preventive measures
won’t be so effective as they will continue their risky habits.

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Conclusion

In conclusion, the occurring outbreak right now can be prohibited and reduced over time if we
construct and follow the steps of recovery and prevention. The ongoing situation of infections is
caused by​ Clonorchis sinensis,​ and so far has infected 202 people in total out of 10,000 people. After
investigating its biological characteristic we conclude that we could reduce the infection rate from
altering the parasite life cycle or preventing it from infecting the hosts. Focusing on the organism, its
main reproduction depends on hatching water in freshwater environments which make all organisms
that are near the lake or river as a target host, such as snails, fish and mammals including humans. To
respond to this outbreak, we can provide health education to spread awareness and provide sanitation
systems, which include toilets in reasonable areas, away from water sources, as well as sterilizing
feces before use in agricultural practices.

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References

CDC - Clonorchis. (2019, June 3). Retrieved from  

https://www.cdc.gov/parasites/clonorchis/index.html 
 
Pearson, R. D., By, Pearson, R. D., & Last full review/revision Jan 2020| Content last modified Jan  
2020. (n.d.). Clonorchiasis - Infectious Diseases. Retrieved from 
https://www.msdmanuals.com/professional/infectious-diseases/trematodes-flukes/clonorchiasi
s 
 
Clonorchiasis. (2014, April 16). Retrieved from  
https://www.who.int/foodborne_trematode_infections/clonorchiasis/en/ 
 
Ze-Li Tang, Yan Huang, Xin-Bing Yu,.(2016, July 06). Current status and perspectives of Clonorchis  
sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control. 
Retrieved from ​https://idpjournal.biomedcentral.com/articles/10.1186/s40249-016-0166-1 
 
Liver Flukes Part 1: Clonorchis sinensis. (n.d.). Retrieved from  
http://www.infectionlandscapes.org/2012/06/liver-flukes-part-1-clonorchis-sinensis.html 

Huang, X.-H., Qian, M.-B., Zhu, G.-H., Fang, Y.-Y., Hao, Y.-T., & Lai, Y.-S. (2020, March 27).
Assessment of control strategies against Clonorchis sinensis infection based on a multi-group
dynamic transmission model. ​PLoS Neglected Tropical Diseases,​ ​14(​ 3).
https://doi.org/​10.1371/journal.pntd.0008152

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