anthelminthic drugs

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Antihelmintic Drugs

• Dr. Bashar Ibrahim
• Pediatrician

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Points to be highlighted

• What are helminths?
• Classification of helminths
• Two most common diseases
• Anthelmintics drugs

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Review

• Present 600 million years ago. gt 2 billion people
  worldwide
• Almost 350 species found in humans, and most
  colonize the GIT tract.
• They harm the host by depriving him from food,
  causing blood loss, injury to organs, intestinal
  or lymphatic obstruction and by secreting toxins.
• Infection may occur through many ways mouth by
  unpurified drinking water or in badly cooked
  meat from infected animals. through the skin
  following a cut, an insect bite or even after
  swimming or walking on infected soil.

Poor hygiene is a major contributory factor
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Anthelmintics are classified based upon their
chemical structures.

1. Piperazines Diethylcarbamazine citrate,
   Piperazine citrate.
2. Benzimidazoles Albendazole, Mebendazole,
   Thiabendazole, triclabendazole
3. Heterocyclics Oxamniquine, Praziquantel.
4. Natural products Ivermectin, Avermectin.
5. Vinyl pyrimidines Pyrantel, Oxantel
6. Amide Niclosamide .
7. Nitro derivative Niridazole
8. Imidazo thiazole Levamisole

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Position ?
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Helminth

• Helminth is a general term meaning worm
• macroscopic, multicellular,
• characterized by elongated, flat or round bodies
• Life cycles are complex
• Intermediate hosts are often needed to support
  larval stages

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Helminth forms
Larva Egg Cyst
Adults
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Classification of helminth
Taenia saginata. Taenia solium Echinococcus
Enterobius Vermicularis
Schistosoma haematobium
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ENTEROBIASIS

• The most common helminthic infection in the
  united states and western europe
• It infects 30 of children worldwide, and humans
  are the only known host
• The prevalence is highest in children 5-14 yrs.
  It is common in areas where children live, play,
  and sleep close together

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Life cycle
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• Autoinfection occurs by scratching the perianal
  area and transferring infective eggs to the
  mouth.
• Person-to-person eating food touched by
  contaminated hands or by handling contaminated
  clothes or bed linens.

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Clinical manifestations 

• Most are asymptomatic.

• The most common symptom is perianal itching. This
  is caused by an inflammatory reaction to the
  presence of adult worms and eggs on the perianal
  skin and occurs predominantly at night.
• abdominal pain, nausea, and vomiting.
• Adult pinworms may be found in normal and
  inflamed appendices following surgical removal,
  but whether or not they cause appendicitis is
  still debated
• Vaginal enterobiasis can occur with a wide range
  of clinical presentations

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Diagnosis

• The diagnosis can be established in one of the
  following ways
• Visual inspection of the anal verge, where mobile
  worms are sometimes visible.
• Visual inspection of undergarments and bed
  linens, where mobile worms are sometimes visible
• Paddle test The paddle test is performed by
  pressing a plastic paddle against the perianal
  region early in the morning and then placing onto
  a glass slide. Repeated examinations increase the
  chance of detecting ova 1 examination detects
  50, 3 examinations 90, and 5 examinations 99.
• Stool examination is not useful since worms and
  eggs are generally not passed in stool.

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Treatment

•  Nonpregnant adults and children  Options for
  treatment of enterobiasis include
• Albendazole (adults and children 400 mg orally
  once on empty stomach, repeat in two weeks)
• Mebendazole (adults and children 100 mg orally
  once, repeat in two weeks)
• Cure rates of 90 to 100
• Pregnant women  should be reserved for patients
  with significant symptoms. Pyrantel pamoate is
  favored over mebendazole or albendazole.
• Simultaneous treatment of the entire household is
  warranted. In addition,
• all bedding and clothes should be washed.
• Hygienic measures, such as clipping of
  fingernails, handwashing.

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Prevention

• Household contacts can be treated at the same
  time as the infected individual.
• Repeated treatments every 3-4 mo may be required
  in circumstances with repeated exposure, such as
  with institutionalized children.

Good hand hygiene is the most effective method
of prevention.
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Hydatid disease
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• Zoonotic disease
• Causative agents
• Echinococcus granulosus ( cystic echinococcus )
• Echinococcus multilocularis ( alveolar
  echinococcus )

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Sites of cyst
The cysts grow 2-3cm/yr
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Clinical features

• Mostly asymptomatic
• Most frequent sign is hepatomegaly palpable mass
• Most common symptoms abd.pain,vomiting,dyspepsi
  a
• Jaundice in 10 of pts- biliary tract
  obstruction
• Cysts larger than 5 cm in diameter pressure
  symptoms
• Rupture can result in disseminated
  echinococcosis anaphylactic reaction
• Pulmonary cyst, sudden onset of cough, fever,
  hemoptysis

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Diagnosis

• Routine blood invs are nonspecific 25
  esinophilia
• Indirect hemagglutination test and ELISA are the
  most widely used methods for detection of
  anti-Echinococcus IgG antibodies.
• false positive results- schistosomiasis and
  nematode infestations - not specific for
  diagnosing hydatidosis.

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• Plain X-ray specially for pulmonary hydatid cyst
• Ultrasound is the most valuable tool for both the
  diagnosis and treatment of
• cystic hydatid disease of the liver,
  accuracy 90
• CT findings are similar to those of
  ultrasonography and may at times be useful in
  distinguishing alveolar from cystic hydatid
  disease (98 )
• MRI

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Management of hydatid disease
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• There is no best treatment option for cystic
  echinococcus CE and no clinical trial has
  compared all the different treatment modalities.
  Treatment indications are complex and based on
• Cyst characteristics,
• Available medical/surgical expertise and
  equipment,
• Adherence of patients to long-term monitoring

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Surgical indications

• Rupture cyst, cysts with biliary fistulae, or
  compressing vital structures,
• Cysts with secondary infection or hemorrhage
• Cyst diameter gt10 cm,
• Superficial cyst at risk of rupture, and
• Extrahepatic disease
• Albendazole 1wk prior - 1 month post op. 15
  mg/kg/day/2 doses or
• Mebendazole 50 mg/kg/day in 3 divided doses. 3
  months post op.
• Recurrent occurs in 2 to 25 of cases. These
  rates depend on the location and size of the cyst
  and the surgeon's experience.

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Drug therapy

• Albendazole is the primary antiparasitic agent
  for treatment of E. granulosus. 
• Mebendazole and praziquantel are less effective
  in the absence of albendazole, mebendazole may be
  used as an alternative therapy
• The optimal duration is uncertain. Drug therapy
  for definitive treatment generally consists of
  1-3 months up to 6 months may be required.

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Monitoring

• CE can relapse years after treatment.
• Follow-up for up to 5 years is warranted to
  evaluate for recurrence
• Three years may be sufficient if there is no
  recurrence on imaging studies at 12, 24, and 36
  months.
• Ultrasonography Ultrasound findings that appear
  to correlate with effective therapy include
• Complete cyst disappearance
• Reduction in cyst size
• Increase in proportion of solid component of cyst
• Thickening and irregularity of the cyst wall
• Reduction in size and/or number of daughter cysts

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Mechanisms of action

• The mechanisms of action for many anthelminthic
  agents remain incompletely understood
• Benzimidazoles exert their anthelminthic effect
  by binding to free beta-tubulin and thus
  inhibiting the polymerization of tubulin and
  microtubule-dependent glucose uptake. 

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Mebendazole

• Benzimidazoles should be avoided in pregnant
• Mebendazole may enhance the adverse/toxic effect
  of Metronidazole (Systemic) Particularly the
  risk for Stevens-Johnson syndrome or toxic
  epidermal necrolysis.
• Mebendazole serum levels may be increased 5-10
  if taken with food
• Untreated soil-transmitted helminth infections
  during pregnancy are associated with adverse
  maternal outcomes (eg, maternal iron deficiency
  anemia, low birth weight, neonatal and maternal
  death).
• Periodic hematologic, and hepatic if treatment
  given for long time

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Dosing

• Ascariasis 100 mg x2 for 3 days or 500 mg once
  repeat in 3 weeks if not cured.
• Enterobiasis 100 mg x1, repeat in 2 weeks.
• Administer with or without food tablet can be
  crushed and mixed with food.

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Albendazole

• Consider discontinuing therapy if hepatic enzymes
  increase to twice the ULN while on therapy
• Administration Oral Administer with a high-fat
  meal to increase absorption (increases the oral
  bioavailability by up to 5 times). For patients
  who have difficulty swallowing whole tablets,
  tablet may be crushed or chewed and swallowed
  with a drink of water.

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Adverse Reactions

• Increased liver enzymes, Abdominal pain,
  Headache, Alopecia, Fever
• Bone marrow suppression Agranulocytosis,
  aplastic anemia, granulocytopenia, leukopenia,
  and pancytopenia have occurred
• Discontinue therapy in all patients who develop
  clinically significant decreases in blood cell
  counts.
• Use with caution in patients with hepatic
  impairment.
• Discontinue therapy if LFT elevations are gt2
  times the upper limit of normal.

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Albendazole Dosage

• Neurocysticercosis gt60 kg 400 mg PO BID x 8-30
  days
• lt60 kg 15 mg/kg/day divided BID PO x 8-30 days 
• Hydatid disease
• gt60 kg 400 mg PO BID x 28 days, THEN 14
  drug-free x 3 cycles
• lt60 kg 15 mg/kg/day divided BID PO,
• Ancylostoma, Ascariasis
• 400 mg PO once
• Larva Migrans, Cutaneous Trichuriasis
• 400 mg PO qDay x 3 days
• Enterobius (Pinworm)
• 400 mg PO once, repeat in 2 weeks

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Reproductive Considerations

• Effective contraception is recommended during
  chronic therapy and for 1 month after the last
  dose.
• Using a single dose of albendazole administered
  to women during the second or third trimester  
• Untreated infections during pregnancy are
  associated with adverse maternal outcomes (eg,
  maternal IDA, impaired nutrient absorption,
  maternal/fetal death) (WHO 2017).
• Use during the first trimester of pregnancy is
  not recommended (HHS OI Adult 2019 WHO 1996
  WHO 2017).

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Monitoring Parameters

• LFTs and CBC with differential at start of each
  28-day cycle and every 2 weeks during therapy
  (more frequent monitoring for patients with liver
  disease)

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Deworming strategies

• Have been associated with health benefits
  including improvements in
• Hemoglobin levels,
• Growth and physical fitness,
• Cognitive performance, and
• Nutritional status

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WHO recommendations

• Preventive chemotherapy (deworming), using annual
  or biannuala single-dose albendazole (400 mg) or
  mebendazole (500 mg) is recommended as a public
  health intervention for all young children 112
  years of age, living in areas where the baseline
  prevalence of any soil-transmitted infection is
  20 or more among children.

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Is it indicated to apply Deworming program in
Duhok?
Question ?
Thank you