Drug Usage in Children with Enterobiasis

By:

Group SGD B1
Luh Putu Widya Amritha Dewi / 2002511002
Karina Sih Nityani Kumar / 2002511003
Dewa Ayu Fony Prema Shanti / 2002511004
Ni Putu Ratih Cahaya Dewi / 2002511005
Williem Alexander Hartanto / 2002511011
Darren Junior / 2002511012
Mira Amba Grace Wrycza / 2002511018
Gede Raka Sutha Abdi Samudra / 2002511023
Winnie Chandra / 2002511027
Putu Nindya Krisnadewi Rahadi / 2002511028
I Kadek Sadam Wibawa / 2002511032
Sendi Aprilio / 2002511034

PROGRAM STUDI SARJANA KEDOKTERAN DAN PROFESI DOKTER

FAKULTAS KEDOKTERAN
UNIVERSITAS UDAYANA
2021
 FOREWORD

First and foremost, we would like to express our highest gratitude to the
Almighty God for his blessing that has enabled us to finish this student project
entitled “Drugs Usage in Children with Enterobiasis” on time. This student project
was made to complete our final project for the Basic Pharmaceutical and Drug Ethics
block. On this occasion, we would also like to say thanks to:
1. Prof. Dr. dr. I Ketut Suyasa, Sp. B., Sp. OT(K) as the Dean of the
Medical Faculty, Udayana University.
2. Dr. dr. Komang Januartha Putra Pinatih, M.Kes as the Head of the
Undergraduate Medical and Medical Profession Study Program, Medical
Faculty, Udayana University.
3. Apt. Dr. Ida Ayu Alit Widhiartini, as the head of the Basic
Pharmaceutical and Drug Ethics block, our lecturer and the evaluator of
this paper for examining our project.
4. Prof. dr. Ketut Tirtayasa, MS., AIF as our group facilitator, for guiding us
and giving us supportive remarks along the making of this project.
We understand that this project is far from perfect and has many rooms for
improvements. Therefore, we hope all readers are able to give us constructive
critiques and suggestions for the betterment of our future projects. Lastly, we do hope
that this student project can be useful for the readers.

Denpasar, Mei 2021

Writers

ii
 TABLE OF CONTENTS
Page
FOREWORD......................................................................................................................ii

TABLE OF CONTENTS...................................................................................................iii

LIST OF FIGURES.............................................................................................................v

CHAPTER I INTRODUCTION.........................................................................................1

1.1 Background................................................................................................................1

1.2 Problem Formulation.................................................................................................2

1.3 Purpose......................................................................................................................2

1.4 Benefit.......................................................................................................................2

CHAPTER II LITERATURE REVIEW.............................................................................3

2.1 Infection of Enterobius vermicularis.........................................................................3

2.2 Enterobiasis Drug Profile..........................................................................................4

2.2.1 Mebendazole...................................................................................................4

2.2.2 Piperazine........................................................................................................5

2.2.3 Pyrantel Pamoate.............................................................................................6

2.2.4 Albendazole.....................................................................................................7

2.3 Enterobiasis Drugs Theraphy for Children...............................................................8

2.3.1 Mebendazole...................................................................................................8

2.3.2 Piperazine........................................................................................................9

2.3.3 Pyrantel Pamoate...........................................................................................10

2.3.4 Albendazole...................................................................................................10

CHAPTER III SUMMARY..............................................................................................12

REFERENCES..................................................................................................................14

iii
 LIST OF FIGURES
Halaman

Tabel 2.1 Worm Count Before and After Treatment of Pirantel Pamoate..............7

iv
 CHAPTER I
INTRODUCTION

1.1 Background
Indonesia is a country with tropical climate, fertile lands, various economic
statuses, dense settlements, knowledge of health, and many of those factors are in low
category. Those phenomena cause a high number of diseases, especially worm
diseases like enterobiasis. Enterobiasis or also known as pinworm infection is a
parasitic infection commonly found in children. This disease is caused by Enterobius
vermicularis (parasitic pinworm). The infection can be transmitted to other people
through direct contact with contaminated food or objects (Kusumasari, Rizqiani.
2019). Worm infection patients can experience malnutrition, anemia, and digestive
tract disorders which in turn result in the decrease of body resistance. The decreased
stamina of the body will reduce the ability to learn in children. Children who often
spend their time outdoors playing or crowding with other children, making direct
contact with water and soil which has higher potential to be infected with Enterobius
vermicularis (Anjarsari, 2018).
The incidence of enterobiasis tends to be higher in children aged 6-8 years
and is still an important health problem in primary school age children. Most of the
countries in Asia have a fairly high rate of enterobiasis. One of the countries with
high incidence of enterobiasis in Asia is Nepal. Enterobiasis in Nepal (South Asia) in
110 children 1-12 years in Barbhan Village, Tanahun District found 14 children, that
means around 12.72% of children were infected with enterobiasis. The highest
incidence occurred in children aged 5-8 years, which was about 5.45% of the total
incidence. Then, followed by 5 children aged 9-12 years, finally 3 children 1-4 years.
There were more boys infected by 9 people than 5 girls (Adrianto & Wartiningsih,
2019). Several studies have also found that the incidence of enterobiasis in several
regions in Indonesia is still quite high. Based on Yulianti's report, the Minister of
Health said that around 60% -80% of school-age children in Indonesia have worm

1
infections. Hendratno S also reported that several areas in Central Java still had a
fairly high pre-

2
 2

valence rate of enterobiasis, namely around 58.93% to 74.31% (Anjarsari, 2018).

Based on the background, we are interested in discussing about “Drug Usage
in Children with Enterobiasis”.

1.2 Problem Formulation

1. How is the infection of Enterobiasis vermicularis?
2. How are the profiles of different enterobiasis drugs?
3. How are enterobiasis drugs prescribed as therapy for children?

1.3 Purpose
1. To give information about Enterobiasis vermicularis infection in general.
2. To give information about the profiles of different enterobiasis drugs.
3. To give information about enterobiasis drugs prescribed as therapy for
children.

1.4 Benefit
1. Give general information about Enterobiasis vermicularis infection,
especially in children.
2. Give general information about the profiles of different enterobiasis
drugs.
3. Give general information about enterobiasis drugs prescribed as therapy
for children.
 CHAPTER II
LITERATURE REVIEW

2.1 Infection of Enterobius vermicularis

Enterobiasis is a disease caused by parasitic pinworm infection, named
Enterobius vermicularis (Wendt et al., 2019). E. vermicularis is a nematode that has
a thread-like appearance, small, and whitish color. This worm has a characteristic pin-
like tail on the posterior side (CDC, 2020). Meanwhile, these worms’ eggs have two
layers and elongated-oval shape with a size of 50-60 × 20-30 µm (Kang & Jee, 2019).
Enterobiasis is often found in children, but it can also occur in adults. Tropical
climatic conditions and poor sanitation and hygiene also increase the risk factor of
enterobiasis transmission (Bharti et al., 2018; Fan et al., 2019). In accordance with its
life cycle, the infective stage of E. vermicularis is an embryonic egg. Transmission of
enterobiasis usually occurs by autoinfection via the fecal-oral route, where the
infective eggs from the anus are transferred to the person's mouth, either directly by
hand or through contaminated objects. Less commonly, transmission of the disease is
possible by inhalation or retroinfection, where the newly hatched larvae from the anus
move back into the rectum (Chen et al., 2018).
After a person swallows infective eggs, the larvae hatch in the small intestine,
then grow into adults and place themselves in the large intestine, usually in the
cecum. As adults, female worms are 8-13 mm in size, while male worms are 2-5 mm
in size (Fan et al., 2019). At night, female worms migrate to the anus and crawl on
the skin around the perianal area and lay their eggs there. The larvae contained in the
eggs develop and become infective within 4-6 hours under optimal conditions (CDC,
2020).
In general, this disease rarely causes any serious physical problems. The main
symptom of this disease is usually anal itching, mainly at night. It is caused by the
migration of female worms to the anus and deposition of eggs on the perianal area. If

3
the infection is severe, secondary bacterial infection may occur due to irritation and
sc-

4
 4

ratching of the anal area. Enterobiasis patients usually also complain of insomnia due
to disturbed sleep (Fan et al., 2019; Wendt et al., 2019).
Diagnosis of enterobiasis is carried out in two ways: identifying eggs in feces
and by perianal swab. Stool examination with a saline smear immediately detects the
presence of eggs. Meanwhile, the perianal area is wiped with tape, then placed on a
glass slide and examined for eggs. Swab should be done in the morning before taking
a bath and defecating. Adult worms can sometimes be seen on the skin near the anus
or underwear about 2-3 hours after sleeping (Bharti et al., 2018).
To treat enterobiasis, it is necessary to provide therapy with appropriate
antihelminthic drugs. Medications that can be used include mebendazole, piperazine,
pyrantel pamoate, and albendazole. Enterobiasis can lead to recurrent infections, so if
an infection occurs in a cluster group, treatment is mandatory for all members of the
cluster, whether symptomatic or not (Wendt et al., 2019).

2.2 Enterobiasis Drug Profile

2.2.1 Mebendazole
Mebendazole is a commonplace, wide range benzimidazole utilized for over
40 years in people to treat an assortment of parasitic invasions. It has FDA
endorsement for the treatment of patients more noteworthy than two years old with
gastrointestinal diseases brought about by Necator americanus or Ancylostoma
duodenale (hookworms), Ascaris lumbricoides (roundworms), Enterobius
vermicularis (pinworms), and Trichuris trichiura (whipworms) in single or blended
contaminations. Mebendazole acts by restraining the creation of microtubules through
restricting to colchicine restricting site of β-tubulin and in this way obstructing
polymerization of tubulin dimers in the intestinal cells of parasites. As an outcome,
glucose take-up, and the stomach related and conceptive limits of parasites are
intruded, bringing about immobilization, obstruction of egg creation and passing of
the helminth. Mebendazole is ineffectively invested in the stomach related plot
making it a viable prescription for overseeing intestinal helminthic diseases with not
very many results.
 5

The most widely recognized antagonistic impacts going with mebendazole use
are loss of appetite, stomach torment, diarrhea, flatulence, sickness, retching, cerebral
pain, tinnitus, and raised liver compounds. Some patients may encounter spasms, and
some may have excessive touchiness responses like rash, urticaria, and angioedema.
Mebendazole harmful effect is typically restricted to gastrointestinal disorder, yet
there are reports of other genuine results including neutropenia (counting
agranulocytosis) and additionally thrombocytopenia, especially in patients who have
taken higher measurements or had a more delayed treatment course than normally
suggested.
Mebendazole is contraindicated in children beneath the age of 1 year old for
the mass treatment of single or blended gastrointestinal invasions as a result of the
danger of spasm, which has been accounted for during post promoting use. The FDA
arranged mebendazole as a C class medication, which states either concentrates in
creatures have shown unfriendly results on the hatchling, and there are no accessible
checked examinations in women. Mebendazole is available in breastmilk. In a
restricted case arrangement report utilizing mebendazole during lactation, no
antagonistic results related with the medication happened in nursing babies.
In the condition of overdose, gastrointestinal manifestations (e.g., queasiness,
the runs, heaving, and stomach torment) may happen. In occasions of harmfulness,
actuate regurgitating and cleansing utilizing initiated charcoal if late ingestion has
happened, and just if the patient can secure their aviation route. There is no particular
remedy for mebendazole glut. Treatment is for the most part effective. Liquids and
electrolytes are used in patients who experience huge loose bowels or potentially
retching (Thakur and Patel, 2020).
2.2.2 Piperazine
Piperazine is an anthelmintic drug that is used to treat parasitic infections
caused by worm infections. Piperazine is very effective against Ascaris lumbricoides
which caused Ascariasis and Enterobius vermicularis which caused Enterobiasis.
Piperazine is an alternative treatment for Ascariasis with a cure rate for more than
90% if taken for 2 days but not recommended for other worm infections. However,
 6

piperazine is still an alternative treatment for Enterobiasis (Katzung, 2018; MIMS,

2021).
Using piperazine to treat Enterobiasis should be done by all family members
at home because Enterobius vermicularis is easily transmitted. Piperazine is available
in hexahydrate and various salts that is easily absorbed and can reached maximum
plasma levels in 2-4 hours. How piperazine works is exactly the same as pyrantel
pamoate. Piperazine works by paralyzing worms and expelling them alive with
normal peristalsis. Piperazine’s mechanism of action is by depolarizing the worm
muscles and increasing the frequency of impulses. Piperazine will act as an agonist at
GABA receptors and inhibit the acetylcholinesterase enzyme thereby blocking
acetylcholine at the neuromuscular junction. Therefore, the worms will die spastically
due to the increased contraction of the worm's muscles (Katzung, 2018; MIMS,
2021).
Mild side effects that sometimes occur are nausea, vomiting, diarrhea,
abdominal pain, dizziness, and headaches, while the most common side effect is mild
gastrointestinal irritation. Side effects that are rarely found are allergic reactions and
central nervous system disorders in the form of temporary ataxia and seizures. When
having a piperazine overdose, symptoms that will be experienced is incoordination or
muscle weakness, vertigo, difficulty speaking, and confusion, but these symptoms
will disappear when the treatment is stopped. Piperazine is a category B drug which
mean studies have not found any adverse effects on fetal development in the first
trimester and beyond. Nevertheless, piperazine should not be given to pregnant
women, patients with impaired kidney or liver function, or those with a history of
epilepsy or chronic neurological disease (MIMS, 2021).
2.2.3 Pyrantel Pamoate
The effective administration of pyrantel pamoate based on CVMP (Committee
for Medical Products) Summary Report EMEA/MRL/141/96 in 1998 is stated as a
single oral administration of blue labelled pyrantel pamoate (Health Products
Regulatory Authority, 2018). This drug is poorly absorbed from the intestinum tenue
(small intestine) so it is only use as a single dose (Raza et al., 2018). Pyrantel
 7

pamoate is divided into two dosages depending on its package, such as tablets of 720
mg (normally 250 mg) and as a suspension of 144 mg/mL (normally 50 mg/mL) in an
official drug’s brand name Pin-X or Anthelmintic agents/Antiminth. Otherwise the
dosage in both children and adults is 0,1 up to 1 g per kg as a single dose and used in
two weeks constantly (Shen et al., 2019). If the dosage does not work, consider
treating either family or relatives. Adverse effects are unusual, such as GI
(gastrointestinal) disorder, fatigue, and headache (Wijaya, 2017).

Figure 2.1
Worm count before and after treatment of pyrantel pamoate
(Sapulete et al., 2020)

Besides that, pyrantel pamoate is recommended for pinworm infection

because of Enterobius vermicularis or as we known as enterobiasis (Bethesda, 2020).
Pyrantel pamoate works as an agent that inhibits neuromuscular immature pinworm
(Enterobius vermicularis) to the other pinworm on the GI tract, therefore it will
release acetylcholine and suppress cholinesterase, giving a great impact in pinworm
weaknesses (Nurhasanah & Murlina, 2020).
2.2.4 Albendazole
The most common treatment for enterobiasis infection is albendazole, which
has been used as an anthelmintic for more than 30 years. Albendazole is safe but not
recommended for children under 2 years old or for women in the first trimester of
 8

pregnancy (Hong, 2018). The pharmacokinetics of albendazole are well absorbed in

the gastrointestinal tract when taken with high-fat meals because the solubility of the
drug is low in water. The drug is metabolized in the liver to form an active
metabolite, namely albendazole sulfoxide, which has potent anthelmintic activity.
The half-life of drugs in blood plasma varies widely between 4-15 hours.
Albendazole sulfoxide is excreted into the urine at a concentration less than 1% of the
dose of the drug that enters the body. Only a small amount of the drug is excreted into
the bile for excretion in the feces. The active metabolite of the drug albendazole,
namely albendazole sulfoxide, can inhibit tubulin polymerization causing selective
degeneration of the worm cytoplasmic microtubules. This degeneration results in
decreased glucose intake and glycogen stores, so that the production of adenosine
triphosphate (ATP) decreases which results in energy depletion, immobilization, and
death of worms (“Albendazole | DrugBank Online”, n.d.).
There are some side effects that have been reported after the used of
albendazole, such as vomiting, diarrhea, gastric pain, loss of hair, sore throat, cough,
chest pain, blurred vision, jaundice, anemia, hematoma, thrombocytopenia, pain in
muscles and joints, itching, fever, seizures, somnolence, allergic reactions, and so on.
Some drugs that can cause drug interactions with albendazole are dexamethasone,
praziquantel, cimetidine, theophylline, and ritonavir. Dexamethasone inhibits the
elimination of albendazole sulfoxide thereby increasing drug side effects.
Praziquantel increases the peak concentration of albendazole sulfoxide in the blood
plasma. In patients with hydatid cysts, cimetidine can increase the concentration of
albendazole sulfoxide in the bile and in the cyst fluid. Albendazole will inhibit the
metabolism of theophylline in the liver so that it has to be monitored during and after
the treatment. Ritonavir that taken in a long-term and also taken with albendazole can
decrease the effectiveness of albendazole (“Albendazole - Tablet (film coated) |
NIH”, n.d.).

2.3 Enterobiasis Drugs Theraphy for Children

2.3.1 Mebendazole
 9

Mebendazole is a medicine that is used to treat worm infection in the digestive

tract. Mebendazole has high effectiveness against intestinal nematode infections and
is mainly used to treat mixed worm infections. One of the conditions that can be
treated with Mebendazole is pinworm infection (Enterobius). Mebendazole
effectiveness in treating Enterobius vermicularis worm infections is >90% success.
Mebendazole is a drug that is recommended for adults and children over 2 years old
(Lubis et al., 2016).
Mebendazole dosage in Enterobius infection for adult patients and children
over 2 years of age is Mebendazole 100 mg orally as a single dose. If needed,
Mebendazole can be repeated 2-4 weeks later. Mebendazole usually takes about 3
days of treatment time and the times it takes to cure the infection depends on the
health condition of the patient’s response to the treatment. However, if the infection
has not cured within 3 weeks, it would be best to see the doctor. Therefore, the doctor
could recommend other worm medication that is more effective and safer for the
condition (Lubis et al., 2016).
2.3.2 Piperazine
The dosage of piperazine will be different for different patients. The number
of doses to be taken each day, the time allowed between doses, and the length of time
needed to take the medicine depends on the medical problem for which you are using
the medicine. The usage of piperazine for children with enterobiasis specifically can
be read down below:
For granules for oral solution, the dosage is based on the child’s age and/or body
weight and the treatment may need to be repeated in two weeks.
a. Up to 2 years of age: dose must be determined by your doctor.
b. For 2 to 8 years of age: 2 grams once a day for one day.
c. For 8 to 14 years of age: 2 grams two times a day for one day.
For oral suspension, the dosage is based on the child's age and the treatment
may need to be repeated in two weeks.
a. Up to 2 years of age: 600 milligrams (mg) every four hours for a total of
three doses in one day.
 10

b. For 2 to 8 years of age: 1.2 grams every six hours for a total of two doses in
one day.
c. For 8 to 14 years of age: 1.2 grams every four hours for a total of three
doses in one day.
For tablet dosage form, the dosage is based on body weight and must be
determined by the patient’s doctor. However, the usual dose is 65 mg (piperazine
hexahydrate) per kilogram (29.5 mg per pound) of body weight per day for seven
days in a row. The treatment may need to be repeated in one week (Mayoclinic,
2021).
If the child misses a dose of piperazine, it is advised to take it as soon as
possible. However, if it is almost time for the next dose, skip the missed dose and
directly go back to the regular dosing schedule. Do not let the child take double doses
(Mayoclinic, 2021).
2.3.3 Pyrantel Pamoate
Pyrantel pamoate is the therapy of choice besides albendazole and
mebendazole, works by blocking neuromuscular depolarization, inhibiting
cholinesterase, and causing spastic paralysis in worms (Ryan, 2018). Pyrantel
pamoate is the most widely used drug, is easily available, and is available at health
centers where patients seek treatment. This drug is known by the wider community in
Indonesia, as well as in several other countries, such as in Australia, Canada and
Europe, under the trade name Combantrin®. In case of enterobiasis, the treatment can
be repeated after a time interval of 2 weeks (Wendt et al., 2019).
Pyrantel pamoate is mainly used to treat ascaris lumbricoides, enterobius
vermicularis and ancylostoma duodenale. The recommended single dose is 10
mg/KgBW. Actually all products to treat intestinal worms in humans can only be
used to immobilize adult worms that are in the intestine when the drug is consumed.
These medicines do not disable eggs or immature worms and will not protect children
from recurring enterobius vermicularis infections. Therefore, it is advisable to check
yourself approximately 2-4 weeks after the initial dose of the drug is consumed, to
determine whether a second dose is needed or not (Friesen et al., 2019).
 11

2.3.4 Albendazole
Albendazole is one of many kind of drug that has a role as anthelmintic, that
can be used against many infections such as ascariasis, enterobiasis, tricuriasis,
strongyloidiasis, trichinellosis, and also hook worm infection caused by Ancylostoma
Duodenale and Necator Americanus (Melyer, 2016). However, the use of
Albendazole to cure enterobiasis also need guidance such as dosage, duration, and
frequency to ensure that the patient will get the therapeutic benefit from the drug. For
children under 6 months and adult, a 400 mg dose with single frequency need to be
administered, however, for children over 6 months but have weight under 10 kg, need
to be given 200 mg with single dose (WHO, 2021). The time span between the first
and second dose need to be at least 2 to 4 weeks in the event of using this drug to cure
enterobiasis (WHO, 2021).
 CHAPTER III
SUMMARY

Enterobiasis is a disease caused by a small, whitish-colored pinworm parasitic

infection called vermicular Enterobius. Cases of enterobiasis are found mainly in
children and rarely in adults with climatic conditions, poor sanitation and poor
hygiene are the risk factor for the disease. Someone who accidentally swallows the
infectious eggs will have their larvae in the small intestine and adult worms in the
large intestine. At night, the adult female worms will crawl into the anus and lay their
eggs around the perianal. The diagnosis of enterobiasis is carried out in two ways:
identification of eggs in the stool by a saline smear and a perianal swab using
adhesive tape. Enterobiasis rarely caused serious complication but only irritation and
anal scratching or insomnia, because the main symptom is only anal itching,
especially at night. Enterobiasis can be treated with antihelminthic drugs, such as
mebendazole, piperazine, pyrantel pamoate, and albendazole.
Mebendazole is a common benzimidazole widely used in humans to treat a
variety of parasitic invasions. Mebendazole works by limiting the formation of
microtubules by restricting the site of β-tubulin to the site of colchicine, thereby
preventing the polymerization of tubulin dimers in the intestinal cells of parasites.
Piperazine and pyrantel pamoate are another choice of drugs for enterobiasis with the
same mechanism by acting as a neuromuscular immature pinworm (Enterobius
vermicularis) inhibiting agent to other pinworms in the GI tract, thereby releasing
acetylcholine and suppressing cholinesterase in having a major impact on pinworm
laxity. Albendazole is the most common treatment for enterobiasis infection because
of the main active metabolite, Albendazole sulfoxide can inhibit tubulin
polymerization which causes selective degeneration of worm cytoplasmic
microtubules.
Mebendazole for enterobiasis is consumed orally for children over 2 years in
dose of 100 mg as a single dose and can be repeated 2-4 weeks later. Piperazine has
three type of drug forms, such as granules for oral solution, oral suspension, and

12
tablet. The dosage for each form is based on the child's age/ body weight and the
treatment

13
 13

may need to be repeated in one to two weeks. For pyrantel pamoate drug single dose
is 10 mg / Kg BW, but it only kills the adult worms in the intestines not the immature
eggs or worms hence it will not protect children from recurring enterobiasis.
Albendazole therapeutic treatment for children can be given in age under and over 6
months. For children under 6 months take a single dose of 400 mg and for children
over 6 months with weighing less than 10 kg need to take 200 mg in a single dose.
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